Research ArticleDiscovery of Acupoints and Combinations with Potential toTreat Vascular Dementia A Data Mining Analysis
Shuwei Feng1 Yulan Ren1 Shilin Fan2 Minyu Wang1 Tianxiao Sun1
Fang Zeng1 Ping Li2 and Fanrong Liang1
1Chengdu University of Traditional Chinese Medicine Chengdu Sichuan 610075 China2Southwest Petroleum University Chengdu Sichuan 610500 China
Correspondence should be addressed to Ping Li dpingligmailcom and Fanrong Liang acuresearch126com
Received 18 December 2014 Revised 16 February 2015 Accepted 30 April 2015
Academic Editor Zhixiu Lin
Copyright copy 2015 Shuwei Feng et al This is an open access article distributed under the Creative Commons Attribution Licensewhich permits unrestricted use distribution and reproduction in any medium provided the original work is properly cited
The prevalence of vascular dementia (VaD) is high among the elderly Acupuncture a popular therapeutic method in Chinacan improve memory orientation calculation and self-managing ability in VaD patients However in clinical acupuncture andacupuncture research the selection of acupoints to treat VaD remains challenging This study aimed to discover acupoints andacupoint combinations with potential for VaD based on data mining After database searching and screening for articles on clinicaltrials evaluating the effects of acupuncture on VaD 238 acupuncture prescriptions were included for further analysis Baihui (GV20) Sishencong (EX-HN 1) Fengchi (GB 20) Shuigou (GV 26) and Shenting (GV 24) appeared most frequently in the modernliterature and are potential acupoints for VaD Combinations between Baihui (GV 20) Sishencong (EX-HN 1) Fengchi (GB 20)Shenting (GV 24) Shuigou (GV 26) and Zusanli (ST 36) were most frequent and represent potential combinations for VaDtreatment These results provide a reference for the selection and combination of acupoints to treat VaD in clinical acupunctureand acupuncture research
1 Introduction
Theselection of acupoints plays a critical role in the therapeu-tic effects of acupuncture However the selection of properacupoints remains challenging contributing to the limitedtherapeutic effects and application of acupuncture Datamining has been used to discover potential acupoints fromthe expansive relevant literature This method has been usedto suggest acupoints on the Shaoyang Meridian for migrainetreatment based on their high frequency in the literature [1]Based on the results of datamining a subsequent clinical trialconfirmed that acupuncture was effective for the treatmentof migraine and that acupoints on the Shaoyang Meridianwere more effective than acupoints on other meridians [2]Datamining has also been used to discover potential Chineseherbs for the effective treatment of specific diseases [3 4]These results support data mining as a promising method todiscover acupoints with potential for treating diseases
Vascular dementia (VaD) refers to cognitive impairmentcaused by changes in the blood circulation of the brain [5]Its clinical manifestations include confusion or short-termmemory problems wandering getting lost in familiar placeswalking with rapid and shuffling steps losing bladder orbowel control laughing or crying inappropriately difficultyin following instructions and problem with counting moneyand conductingmonetary transactions At the late stage VaDpatients may have severe impairment of basic activities ofdaily living and lack the capacity to make appropriate deci-sions regarding their choices and preferences [6] A recentpopulation-based survey reported that the prevalence of VaDamong individuals aged 65 years and older was 15 [7] Ithas been predicted that dementia will affect 80million peopleworldwide by 2040 [8] The annual cost of care per patientis estimated to be US$17000ndash55200 for severe dementiaplacing a heavy economic burden on families and society [9]
Hindawi Publishing CorporationEvidence-Based Complementary and Alternative MedicineVolume 2015 Article ID 310591 12 pageshttpdxdoiorg1011552015310591
2 Evidence-Based Complementary and Alternative Medicine
Acupuncture a primary therapeutic method in tradi-tional Chinese medicine (TCM) can improve memoryorientation calculation and self-managing ability in VaDpatients [10ndash12] The therapeutic effects of acupunctureare achieved via multiple pathways including antioxidativeeffects antiapoptotic effects and neurotrophic effects [1113ndash15] However acupoint selection remains a challenge inthe use of acupuncture to treat VaD According to ourpreliminary statistics more than 100 acupoints distributedin 13 meridians have been recorded in the modern literaturefor the treatment of VaD The most effective acupoints forthe treatment of VaD and the selection of acupoints forcombination remain to be elucidated representing a majorlimitation for clinical therapeutic effects and the applicationof acupuncture for VaD
To shed some light on the selection of acupoints andacupoint combinations to treat VaD in clinical acupunctureand acupuncture research this study aimed to discoveracupoints and acupoint combinations that have potential totreat VaD via data mining
2 Materials and Methods
The flow of information through the various phases of datamining is illustrated in Figure 1
21 Inclusion Criteria for Considering AcupointPrescriptions for Data Mining
211 Types of Studies Clinical trials evaluating the effect ofTCM acupuncture with or without randomization methodswere included Trials with or without controls were alsoincluded The control interventions included no treatmentsham acupuncture Western medicine TCM herbs non-traditional acupuncture and TCM acupuncture containinganother acupoint prescription which is different from the onein observation group Languagewas restricted toChinese andEnglish
212 Types of Participants Clinical trials involving adultparticipants diagnosed with VaD were included
213 Types of Interventions Clinical trials evaluating TCMacupuncture were included Acupuncture can be usedalone or in combination with other types of interventionsTCM acupuncture involves inserting needles into traditionalmeridian acupoints and extraordinary acupoints Electricalstimulation of the needles may be used Trials using moxi-bustion alone or as a cointervention with acupuncture werealso included
214 Effectiveness of Acupoint Prescriptions Acupoint pre-scriptions for the disease and not particular syndromesof VaD were included There should be statistical differ-ences in symptoms between before and after acupunctureIn a controlled trial patients treated with acupuncturealone or in combination should receive greater benefit thanpatients who do not receive acupuncture therapyThe controlinterventions included no treatment sham acupuncture
2121 records identified through database searching
(CNKI 892 CBM 1084 PubMed 145)
238 acupuncture prescriptions included in data
mining and network analysis after screening
Data preprocessing extraction of information about
titles journals interventions and main acupoints
and standardization of acupoint names
Data processing analysis of frequencies of
acupoints and meridians confidence of acupoint
combination and network properties
Figure 1 Flow of information through the different phases of datamining
Western medicine TCM herbs nontraditional acupunctureand TCM acupuncture containing another acupoint pre-scription which is different from the one in observationgroup If the studies compared the therapeutic effects ofdifferent acupoint prescriptions the most effective acupointprescription was included
22 Exclusion Criteria
221 Types of Studies Case reports reviews systematicreviews and meta-analyses were excluded
222 Types of Participants Trials evaluating the therapeuticeffect of acupuncture for Alzheimerrsquos disease traumaticdementia and other subtypes of dementia were excludedStudies on animals were also excluded
223 Types of Interventions Trials stimulating Ashi pointsalone were excluded Trials of dry needling or trigger pointtherapy therapies that are based on principles of westernanatomy and physiology were excluded Trials of laseracupuncture and noninvasive electrostimulation (eg using
Evidence-Based Complementary and Alternative Medicine 3
electrodes on the skin rather than needles or moxibustion tostimulate the acupoints) were excluded to limit the focus toTCM acupuncture Trials evaluating acupressure a form ofmassage were excluded as well Finally trials of micropunc-turewere excluded becausemicropuncture is a nontraditionalacupuncture practice that is based on the principle that thehead (or ear nose eye abdomen ankle etc) is amicrosystemof the entire body
224 Effectiveness of Acupoint Prescriptions Acupoint pre-scriptions for a particular syndrome of VaD were excludedAcupoint prescriptions with no statistical improvement ofsymptoms were also excluded When the therapeutic effectsof different acupoint prescriptions were compared in a studyall acupoint prescriptions except the most effective one wereexcluded
23 Searching Methods for Identification of Studies
231 Data Sources PubMed (httpwwwpubmedcom (1966to 2012)) the Chinese BioMedicine Database (CBM) (httpwwwsinomedaccn (1978 to 2012)) and China NationalKnowledge Infrastructure (CNKI) (httpwwwcnkinet (1912to 2012)) were searched formodern literature on acupuncturetreatment for VaD
232 Searching Strategy The searching strategy used thefollowing key words (I) ldquoacupuncturerdquo OR ldquoelectroacupunc-turerdquo OR ldquomoxibustionrdquo OR ldquomeridianrdquo OR ldquoacupointrdquo (II)ldquodementiardquoOR ldquovascular dementiardquoOR ldquoAlzheimerrsquos diseaserdquoThe searching strategy included literature on acupuncturetreatment for Alzheimerrsquos disease (AD) because the modernliterature on acupuncture for VaD overlaps with that on AD
24 Data Collection Two reviewers independently screenedthe title and abstract of every record retrieved from theliterature searches All potentially relevant articles wereinvestigated as full text in English or Chinese In cases ofdisagreement a trial was included or excluded based ondiscussion between the two reviewers or after a third reviewerreviewed the information For duplicate publications thefinal publication was used
25 Data Preprocessing Information about titles journalsinterventions and main acupoints was extracted using theself-established Data Excavation Platform of Acupoint Speci-ficity for data mining Because acupoints have aliases thenames of acupoints were standardized according to Funda-mentals of Acupuncture [16]
26 Data Processing
261 Frequencies of Acupoints The frequencies of acupointsmeridians and acupoints on different body parts wereanalyzed using the Data Excavation Platform of AcupointSpecificity
262AssociationRulesMiningAprioriAlgorithm for associa-tion rules mining [17] was adopted to analyze the frequencies
and support of acupoint combinations According to thedefinition of association rules mining [18] the followingcan be a statement of association rules mining for acupointcombination Let 119868 = 119894
1 1198942 119894
119898 be a set of acupoints
Let119863 be a set of acupoint prescriptions where each acupointprescription119879 is a set of acupoints such that119879 sube 119868 Associatedwith each acupoint prescription is a unique identifier calledTID An acupoint prescription 119879 contains 119883 a set of someacupoints in 119868 if 119883 sube 119879 The rule 119883-119884 has support 119904 in theacupoint prescription set119863 if 119904 of acupoint prescriptions in119863 contain119883 cup 119884
263 Measurement of Network PropertiesCommunity struc-ture is a common characteristic of complex networks andis characterized by more dense internal connections withingroups of nodes than with the rest of the network In thisstudy a hierarchical agglomeration was adopted to detectcommunity structure according to Clauset et al [19] We alsofocused on investigating the set of the most influential nodesin acupoint networks of VaD defined as the nodes with thehighest 119896-core value [20] The 119896-core method is predomi-nantly used in analyzing social networks We employed the119896-core method to obtain the cores of different acupoints The119896-coremethod was implemented as follows First all 1-degreenodeswere removed and the nodeswere further pruned untilno 1-degree nodes remained The remaining nodes formedthe 2-core node set The pruning process was repeated in asimilar manner for other nodes in the network assigned tothe corresponding cores (denoted by 119896s) The nodes with thelargest 119896-core value were defined as the network core Thedegree of each acupoint was also analyzed to measure theinvolvement of the node in the network The degree refers tothe number of nodes to which a focal node is connected [21]Betweenness centrality was also used to analyze an acupointrsquoscentrality in the network Centrality is an important conceptfor the analysis of networks and betweenness centrality isone of the most prominent measures of centrality It is usedto measure the degree to which a node is in a position ofbrokerage by summing up the fractions of shortest pathsbetween other pairs of vertices that pass through it [22]
3 Results
31 Overall Profile of Acupuncture Prescriptions Databasesearching identified 892 records in CNKI 1084 records inCBM and 145 records in PubMed After screening 238acupuncture prescriptions in 238 articles were includedAmong the 238 trials 185 are controlled clinical trials (CCTs)while the other 53 trials have no controls The whole view onthe study quality of the 185 CCTs were shown in Figure 2
32 Frequencies of Acupoints and Meridians Approximately109 meridian-acupoints distributed over 13 meridians and7 extraordinary acupoints have been recorded for 1400 and133 times respectively in modern literature on acupuncturetreatment for VaD The most frequently used meridianwas the Governor Meridian (477 times) Other frequentlyused meridians included the Gallbladder Meridian of Foot
4 Evidence-Based Complementary and Alternative Medicine
0 20 40 60 80 100()
Another bias
Selective reporting
Incomplete outcome data
Blinding of outcome assessment
Blinding of participants and personnel
Allocation concealment
Random sequence generation
Low riskUnclear riskHigh risk
Figure 2 Whole view on the study quality of the 185 CCTs
020406080
100120140160180200
Frequency
Baih
ui (G
V20
)
Sish
enco
ng (E
X-H
N1
)
Feng
chi (
GB20
)
Shui
gou
(GV26
)
Shen
ting
(GV24
)
Nei
guan
(PC6
)
Zusa
nli (
ST36
)
Sany
injia
o (S
P6
)
Shen
men
(HT7
)
Taix
i (KI
3)
Bens
hen
(GB13
)
Shen
shu
(BL23
)
Feng
long
(ST40
)
Taic
hong
(LV3
)
Daz
hui (
GV14
)
Xuan
zhon
g (G
B39
)
Feng
fu (G
V16
)
Heg
u (L
I4)
Quc
hi (L
I11
)
Yint
ang
(EX-
HN3
)
Figure 3 The 20 most frequent acupoints and their frequencies
Shaoyang and the Stomach Meridian of Foot Yangmingwhich were reported for 218 and 124 times respectivelyExtraordinary acupoints were also frequently used Baihui(GV 20) Sishencong (EX-HN 1) Fengchi (GB 20) Shuigou(GV 26) and Shenting (GV 24) which were among thetop five acupoints in frequency were recorded for 176 12493 86 and 84 times respectively The frequencies of eachmeridian and acupoint are shown in Table 1The twentymostfrequently used acupoints are shown in Figure 3
33 Frequencies of Acupoints on Different Body Parts Acu-points on the head face and neck were used most frequentlywith a total number of 42 acupoints and a total frequencyof 766 times followed by acupoints on the lower limbs (383
times) upper limbs (214 times) back and lumbar (127 times)and chest and abdomen (43 times) (Figures 4(a) and 4(b))
34 Frequencies of Specific Acupoints Specific acupoints rep-resented 78 of the 116 acupoints (6724) Specific acupointshave been used 1292 times representing 8428 of the totalfrequency of all acupoints (Figures 4(c) and 4(d))
35 Frequencies and Support of Acupoint Combinations Acu-point combinations between Baihui (GV 20) Sishencong(EX-HN 1) Fengchi (GB 20) Shenting (GV 24) Shuigou(GV 26) and Zusanli (ST 36) were used most frequentlyThe 15most frequently used acupoint combinations and theirsupport and confidence are shown in Table 2
Evidence-Based Complementary and Alternative Medicine 5
Table1Statisticso
fmeridians
andacup
ointsinthem
odernliteratureo
nacup
uncturetreatmentfor
VaD
Num
ber
Meridian
Frequency
Num
bero
facupo
ints
Acup
ointsa
ndtheirfrequ
encies
1GV
477
26
Baihui
(GV20)176Shu
igou
(GV26)8
6Sh
entin
g(G
V24)8
4Dazhu
i(GV14)2
7Feng
fu(G
V16)2
3Yintang(EX-
HN3)
16N
aohu
(GV17)13Shangxing(G
V23)11Mingm
en(G
V4)
8Yamen
(GV15)5
Qiang
jian(G
V18)5
Qiand
ing(G
V21)4
Yaoyang
guan
(GV3)
3Zh
iyang(G
V9)
3Jin
suo(G
V8)
2Shendao(G
V11)1Z
hong
shu(G
V7)
1Taod
ao(G
V13)1Lingtai(G
V10)1C
hangqiang(G
V1)1Xu
anshu
(GV5)
1Yaoshu
(GV2)
1Shenzhu(G
V12)1Jizho
ng(G
V6)
1Hou
ding
(GV19)1X
inhu
i(GV22)1
2GB
218
20
Fengchi(GB20)9
3Be
nshen(G
B13)4
7Xu
anzhon
g(G
B39)2
4Shuaigu(G
B8)
7Wangu
(GB12)6
To
ulinqi(G
B15)6
Qub
in(G
B7)
5Xu
anli(G
B6)
4Naokong
(GB19)4
Zuq
iaoyin
(GB44
)3Yanglingquan
(GB34)3
Yangbai(G
B14)3
Hanyan(G
B4)
2Qiuxu
(GB40
)2Fengshi
(GB31)2
Tou
qiaoyin(G
B11)2
Xu
anlu(G
B5)
2Muchu
ang(G
B16)1Z
heng
ying
(GB17)1Z
hongdu
(GB32)1
3EX
-HN
133
7Sishencong
(EX-
HN1)123Taiyang(EX-
HN5)
4Wailaogon
g(EX-
UE8)
2Sh
iqizhu
i(EX
-B8)
1Ba
xie
(EX-
UE9)
1Anm
ian(EX-
HN22)1Y
iming(EX-
HN14)1
4ST
124
7Zu
sanli(ST
36)7
2Feng
long
(ST40
)40To
uwei(ST8)
6Lidu
i(ST
45)2
Sibai(ST2)
2Fu
tu(ST32)1
Renying(ST9)
1
5BL
103
15Shenshu(BL23)4
3Ganshu(BL18)12Tianzhu(BL10)10Pishu(BL20)8
Feiyang
(BL58)8
Geshu
(BL17)
7Xinshu
(BL15)4
Zhiyin(BL67)2
Kun
lun(BL60)2
Yuzhen(BL9)
2To
ngtia
n(BL7)
1Ch
engjin
(BL56)
1Dazhu
(BL11)
1Weizhon
g(BL40
)1Q
ucha
(BL4)
16
SP96
5Sanyinjiao(SP6)
71X
uehai(SP
10)14Taibai(SP3)
8Yinb
ai(SP1)2Yinlingquan(SP9)
17
PC86
5Neigu
an(PC6)
73Z
hongchon
g(PC9)
4Daling(PC7)
4Jianshi
(PC5)
3Laogon
g(PC8)
28
KI83
5Taixi(KI
3)57D
azho
ng(K
I4)12Yo
ngqu
an(K
I1)10Zh
aohai(KI
6)8Ra
ngu(K
I2)2
9HT
673
Shenmen
(HT7)
62Shaocho
ng(H
T9)
3Jiq
uan(H
T1)2
10LI
457
Hegu(LI4
)20Quchi
(LI11)18Shang
yang
(LI1)2
Sho
usanli(LI10)
2Binao(LI14)
1Jianyu(LI15)
1Ying
xiang(LI2
0)1
11CV
435
Qihai(C
V6)
11Z
hong
wan
(CV12)10Guanyuan(C
V4)
9Danzhon
g(C
V17)9
Shenq
ue(C
V8)
412
LV40
2Taicho
ng(LV3)
37D
adun
(LV1)3
13TE
115
Waigu
an(TE5)
6Guancho
ng(TE1)2Sizhuk
ong(TE23)1Jiaosun
(TE20)1Sidu(TE9)
114
LU4
2Shaoshang(LU11)3
Liequ
e(LU
7)1
15SI
32
Shaoze
(SI1)2
Yanggu(SI5
)116
Total
1533
116GV
Governo
rMeridianGB
Gallbladd
erMeridianof
Foot
Shaoyang
EX-
HNextraordinary
acup
ointSTStom
achMeridianof
Foot
Yang
mingBL
Bladd
erMeridianof
Foot
TaiyangSPSpleenMeridianof
Foot
TaiyinP
CPeric
ardium
Meridianof
HandJueyinK
IKidn
eyMeridianof
Foot
Shaoyin
HTHeartMeridianof
HandSh
aoyin
CVC
onceptionVe
ssel
LIL
arge
Intestine
Meridianof
HandYang
mingLV
Liver
Meridianof
Foot
JueyinT
ETripleEn
ergizero
fHandSh
aoyang
LU
Lung
Meridianof
HandTaiyinSISm
allIntestin
eofH
andTaiyangFrequencieso
fmeridians
refertothetotalfre
quencies
ofacup
ointso
nthe
samem
eridian
Num
bero
facupo
intsrefertothetotalnu
mbero
facupo
intson
thes
amem
eridian
6 Evidence-Based Complementary and Alternative Medicine
Table 2 Statistics of the 15 most frequently used acupoint combinations in the treatment of VaD
Number Acupoint combination Frequency Support ()1 Baihui (GV 20) Sishencong (EX-HN 1) 98 41182 Baihui (GV 20) Fengchi (GB 20) 81 34033 Baihui (GV 20) Shuigou (GV 26) 72 29834 Baihui (GV 20) Shenting (GV 24) 70 29415 Baihui (GV 20) Zusanli (ST 36) 62 26056 Sishencong (EX-HN 1) Fengchi (GB 20) 60 25217 Baihui (GV 20) Sanyinjiao (SP 6) 57 23958 Baihui (GV 20) Neiguan (PC 6) 54 22699 Sishencong (EX-HN 1) Shuigou (GV 26) 51 214310 Sishencong (EX-HN 1) Baihui (GV 20) Fengchi (GB 20) 51 214311 Baihui (GV 20) Shenmen (HT 7) 51 214312 Sishencong (EX-HN 1) Shenting (GV 24) 49 205913 Sishencong (EX-HN 1) Neiguan (PC 6) 46 193314 Baihui (GV 20) Taixi (KI 3) 46 193315 Sishencong (EX-HN 1) Baihui (GV 20) Shuigou (GV 26) 43 1807Support refers to the percentage of acupoint prescriptions containing the acupoint combination
36 Community Structure Community detection resultedin the division of the 116 acupoints into 5 communitiesNodes of the same color belong to the same community Thecommunity structure is shown in Figure 5(a)
37 Acupoint 119870-Core Network The largest 119896-core value was19 At this value there were 28 nodes corresponding to Hegu(LI 4) Quchi (LI 11) Zusanli (ST 36) Fenglong (ST 40)Sanyinjiao (SP 6) Xuehai (SP 10) Shenmen (HT 7) Tianzhu(BL 10) Xinshu (BL 15) Ganshu (BL 18) Shenshu (BL 23)Taixi (KI 3) Dazhong (KI 4) Neiguan (PC 6) Benshen (GB13) Fengchi (GB 20) Xuanzhong (GB 39) Taichong (LV 3)Mingmen (GV 4) Dazhui (GV 14) Yamen (GV 15) Fengfu(GV 16) Baihui (GV20) Shenting (GV24) Shuigou (GV26)Guanyuan (CV 4) Sishencong (EX-HN 1) and Yintang (EX-HN 3) as shown in Figure 5(b)
38 Degree The top 20 acupoints in degree are shownin Figure 6(a) Baihui (GV 20) Sishencong (EX-HN 1)Fengchi (GB 20) Shenting (GV 24) and Neiguan (PC 6)had the highest degrees with values of 89 76 68 67 and 65respectively
39 Betweenness Centrality Thetop 20 acupoints in between-ness centrality are shown in Figure 6(b) Yongquan (KI 1)Baihui (GV 20) and Sishencong (EX-HN 1) had the highestbetweenness centrality
4 Discussion
41 Potential Acupoints and Combinations for VaD In thisstudy acupoints and combinations with potential for treat-ing VaD were discovered These results may provide somereference for the selection of acupoints in treatment forVaD which may promote the therapeutic effects in clinicalpractice The results suggest that Baihui (GV 20) Sishencong(EX-HN 1) Fengchi (GB 20) Shuigou (GV 26) and Shenting
(GV 24) are potential acupoints for treating VaD In terms ofmeridian acupoints on the Governor Meridian have poten-tial for treating VaD From the perspective of combinationscombinations between such acupoints as Baihui (GV 20)Sishencong (EX-HN 1) Fengchi (GB 20) Shenting (GV 24)Shuigou (GV 26) and Zusanli (ST 36) have potential fortreating VaD In addition acupoints on the head face andneck have more potential for VaD than acupoints on otherregions of the body Specific acupoints have more potentialthan nonspecific acupoints Specific acupoints with specificnames are a group of acupoints on fourteen meridians withspecific therapeutic effectsThere are ten types of specific acu-points Five-Shu acupoints Yuan-Primary acupoints Luo-Connecting acupoints Xi-Cleft acupoints Lower He-Seaacupoints Back-Shu acupoints Front-Mu acupoints eightinfluential acupoints eight confluent acupoints connectingthe eight extra meridians and convergent acupoints
Community detection divided the acupoints into 5 com-munities Acupoints within the same community have somecharacteristics in common Blue nodes (Community A) wereall Jing-Well acupoints Yellow nodes (Community B) were allacupoints on the face and head Most green nodes (Commu-nity C) were acupoints on the four limbs Most purple nodes(Community D) were acupoints belonging to Governor Ves-sel Most red nodes (Community E) were specific acupointsor acupoints with specific therapeutic effects and only thiscommunity contained Bach-Shu acupoints and acupointson the abdomen Acupoints within the same communitywere more densely connected with each other comparedwith acupoints from different communities indicating thatan acupoint was more often used with acupoints withinthe same community compared with acupoints within othercommunities
The 19-core network indicated that 28 acupoints includ-ing Hegu (LI 4) Quchi (LI 11) Zusanli (ST 36) Fenglong(ST 40) Sanyinjiao (SP 6) Xuehai (SP 10) Shenmen (HT 7)
Evidence-Based Complementary and Alternative Medicine 7
0
5
10
15
20
25
30
35
40
45
Head faceand neck
Lowerlimbs
Upperlimbs
Back andlumbar
Chest andabdomen
Number
(a) The numbers of acupoints in different parts
0
100
200
300
400
500
600
700
800
900
Head faceand neck
Lowerlimbs
Upperlimbs
Back andlumbar
Chest andabdomen
Frequency
(b) The frequencies of acupoints in different parts
0
5
10
15
20
25
30
35
40
Number
Con
verg
ent a
cupo
int
Five
-Shu
acup
oint
Yuan
-sou
rce p
oint
Luo-
Con
nect
ing
poin
t
Eigh
t infl
uent
ial p
oint
Shu-
Back
poi
nt
Eigh
t con
fluen
t acu
poin
ts
Fron
t-Mu
poin
t
Low
er H
e-Se
a poi
nt
Non
spec
ifc p
oint
(c) The numbers of different kinds of acupoints
0
100
200
300
400
500
600
700
800
Frequency
Con
verg
ent a
cupo
int
Five
-Shu
acup
oint
Yuan
-sou
rce p
oint
Luo-
Con
nect
ing
poin
t
Eigh
t infl
uent
ial p
oint
Shu-
Back
poi
nt
Eigh
t con
fluen
t acu
poin
ts
Fron
t-Mu
poin
t
Low
er H
e-Se
a poi
nt
Non
spec
ifc p
oint
(d) The frequencies of different kinds of acupoints
Figure 4 The frequencies and numbers of acupoints in different body parts and different types of acupoints
Tianzhu (BL 10) Xinshu (BL 15) Ganshu (BL 18) Shenshu(BL 23) Taixi (KI 3) Dazhong (KI 4) Neiguan (PC 6)Benshen (GB 13) Fengchi (GB 20) Xuanzhong (GB 39)Taichong (LV 3) Mingmen (GV 4) Dazhui (GV 14) Yamen(GV 15) Fengfu (GV 16) Baihui (GV 20) Shenting (GV 24)Shuigou (GV 26) Guanyuan (CV 4) Sishencong (EX-HN 1)and Yintang (EX-HN 3) are core acupoints in the network
Baihui (GV 20) Sishencong (EX-HN 1) Fengchi (GB20) Shenting (GV 24) and Neiguan (PC 6) had the highestdegreesThis result indicates that these 5 acupoints have beencombined with more acupoints than other acupoints Theseacupoints have specific therapeutic effects on VaDThereforethese acupoints can be used together with other acupoints toenhance therapeutic effects
Yongquan (KI 1) Baihui (GV 20) Sishencong (EX-HN1) Neiguan (PC 6) and Shenting (GV 24) which belonged
to 4 different communities had higher betweenness cen-trality Yongquan (KI 1) which had the highest betweennesscentrality did not have a relatively high degree However itconnects Jing-Well acupoints with other types of acupointsresulting in a high betweenness centrality Acupoints withhigher betweenness centrality play an important role inconnecting different types of acupoints Jing-Well acupointsexcept Yongquan (KI 1) were often used with other Jing-Wellacupoints only Yongquan (KI 1) was not only used with otherJing-Well acupoints but also with other types of acupointssuch as other types of specific acupoints nonspecific acu-points and acupoints on other parts The high betweennesscentrality suggested that Yongquan (KI 1) may have multipleeffects compared with other Jing-Well acupoints in treatmentof VaD From the perspective of TCM theory Jing-Wellacupoints can restore consciousness Yongquan (KI 1) was
8 Evidence-Based Complementary and Alternative Medicine
BL17
EX-HN22
BL7
LI1
GV13
SP9
GB11
EX-HN14
GB4
HT1
ST2
CV8
GB5
GV18
BL11
EX-UE8
LI20
GV1
ST36
BL20
CV17
BL58
BL9
GV17
GV14
GV15
GV11
GV12
GV10GV5
KI3
KI1
LU11
HT9
GV8
GV3
BL23
GV4
CV6
CV12
HT7GB20
GB17
GV24
GV16
CV4
GB8
GV21GV23GB13
SP10
BL10
ST32
GB34LI14
LI15
GB32
LI10
BL40
GB31
KI6
SI5
KI2
PC7
LI4
GB16
EX-HN5
GB12
PC8
PC6
BL18
BL15
BL56
GB40
TE9
EX-UE9SP6
TE5
SP3
LI11
GV22
BL60
GB6
GB14
GB15
GB19
ST9
GV7
GV2
GV6
EX-B8
BL4
SI1
PC9
TE1ST45
SP1
BL67
GB44
LV1
TE23
TE20
LU7
GV19
ST40
EX-HN3ST8
GV20
KI4
GB39
GB7
EX-HN1
PC5
LV3
GV9
GV26
(a) Network structure of acupoints for the treatment of VaD
GB13
EX-HN1
EX-HN3
LI4
KI3
KI4
HT7GB20
GV14
GV15
GV16
LV3
ST36
BL23
GV4
GV24
GV26GV20
ST40
SP6
LI11
GB39
SP10
PC6
BL10
CV4
BL18
BL15
(b) 19-core network
Figure 5 (a) Network structure of acupoints for the treatment of VaD Blue nodes (Community A) are all Jing-Well acupoints Yellow nodes(Community B) are all acupoints on the face and head Most green nodes (Community C) are acupoints on four limbs Most purple nodes(Community D) are acupoints belonging to Governor Vessel Most red nodes (Community E) are specific acupoints or acupoints withspecific therapeutic effects and only this community contains Bach-Shu acupoints and acupoints on the abdomen Acupoints within thesame community are more densely connected with each other than acupoints from different communities (b) 19-core network There are 28acupoints in the 19-core network They are core acupoints in the treatment of VaD
Evidence-Based Complementary and Alternative Medicine 9
0102030405060708090
100
GV
20
EX-H
N1
GB2
0
GV
24
PC6
SP6
GV
14
GV
26
GV
16
HT7 LI
4
KI3
ST36
ST40
LV3
GB1
3
EX-H
N3
BL10
GB3
9
LI 1
1
Degree
(a) The 20 acupoints with highest degree
0002004006008
01012014016
KI1
GV
20
EX-H
N1
PC6
GV
26
GB2
0
GV
24
GV
14 SP6
EX-H
N3
HT7 LI
4
KI3
GV
16
BL10
LV3
ST40
ST36
GB1
3
PC9
Betweenness centrality
(b) The 20 acupoints with highest betweenness centrality
Figure 6 The 20 acupoints with highest degree and the 20 acupoints with highest betweenness centrality
also used to tonify kidney in treatment of VaD ThereforeYongquan (KI 1) is used not only with other Jing-Wellacupoints but also with other types of acupoints such asother types of specific acupoints nonspecific acupoints andacupoints on other parts
42 UnderlyingMolecularMechanism of the Acupoint with theMost Potential to Treat VaD According to our results Baihui(GV 20) which had the highest frequency has the mostpotential to treat VaD A systematic review andmeta-analysisalso suggested that Baihui (GV 20) is a principal acupoint foracute intracerebral hemorrhage (ICH) in animal models ofacute ICH there was no difference in efficacy between Baihui(GV 20) alone and Baihui (GV 20) plus other acupoints [23]
Molecular biology studies have provided insights intothe mechanisms underlying the effects of Baihui (GV 20) inVaD treatment including antioxidant effects antiapoptoticeffects neurotrophic effects reduced blood-brain barrier(BBB) permeability and regulation of the cholinergic anddopaminergic systems Acupuncture at Baihui (GV 20) incombination with other acupoints decreases levels of 8-hydroxy-21015840-deoxyguanosine a product of oxidative damageto DNA induced by free radicals suggesting that the benefitof acupuncture is partly due to antioxidant effects [11]Acupuncture exerts therapeutic effects on VaD via antiapop-tosis The tumor suppressors p53 and Noxa are important inregulating apoptosis and mediate hypoxic cell death [24 25]
Electroacupuncture at Baihui (GV 20) Dazhui (GV 14) andShenshu (BL 23) blocks expression of p53 and Noxa in thehippocampal CA1 region of VaD rats [26] Acupuncture atBaihui (GV 20) can improve neurogenesis via regulatingbrain-derived neurotrophic factor (BDNF) and cyclic AMPresponse element-binding protein (CREB) BDNF whichis essential for synaptic plasticity and is coupled to CREBactivation [27] is important for long-term memory storage[28] CREB is required for the proliferation growth survivaland differentiation of all types of cells In the brain the CREBand CRE-mediated system is involved in memory learningsynaptic transmission neuron survival differentiation andaxon growth [29] Acupuncture at Baihui (GV 20) signifi-cantly increases the levels of BDNF [15 30] CREB proteinsCREB mRNA [30] and phosphorylated CREB the activeform of CREB [15] The molecular mechanism underlyingacupuncture at Baihui (GV 20) also involves cholinergicsystem regulation Decreased cholinergic function in thebrain can result in a decline in memory and cognitivefunction [31] Acupuncture at Baihui (GV 20) significantlyincreases the levels of choline acetyltransferase (ChAT) andrestores the expression of choline transporter 1 (CHT1)and vesicular acetylcholine transporter (VAChT) [30] Thedopaminergic system is also involved in the mechanismunderlying the treatment of VaD with acupuncture at Baihui(GV 20) Dopamine is a key regulator in specific synapticchanges observed at certain stages of learning and memory
10 Evidence-Based Complementary and Alternative Medicine
and of synaptic plasticity [32] Acupuncture at Baihui (GV20)increases dopamine levels in chronic cerebral hypoperfusionand ischemia-reperfusion injured rats [33] In additionacupuncture at Baihui (GV 20) and Zusanli (ST 36) preservesthe integrity of the BBB reducing BBB permeability TheBBB is constructed of tight conjunctions including occludinand claudin-5 which form the endothelial barrier Reducedexpression of ZO-1 claudin-5 and occludin mRNA andprotein contributes to BBB breakdown and edema in theischemic brain [34] Electroacupuncture at Baihui (GV 20)and Zusanli (ST 36) reduces brain damage and relatedbehavioral deficits via upregulation of tight conjunctionproteins including ZO-1 claudin-5 and occludin [35]Thesefindings reveal parts of the molecular mechanism underlyingacupuncture at Baihui (GV 20) to treat VaD
43 Acupoints Selection in Treatment for VaD The properselection of acupoints is essential for the therapeutic effectsof acupuncture because acupoints are specific with regard tomorphological structure biophysical properties pathologicalresponse and stimulating effects [36] This specificity dif-ferentiates acupoints from nonacupoints as well as differentacupoints from one another The specific therapeutic effectsof different acupoints have been reported for migraine [37]functional dyspepsia [38] ischemic stroke [39] and so forth
The specificity of acupoints for the treatment of VaDhas also been reported Phosphorylated CREB levels weresignificantly increased after acupuncture therapy of needlingBaihui (GV 20) and Zusanli (ST 36) compared to shamacupuncture therapy of needling nonacupoints [15] Baihui(GV 20) Shuigou (GV 26) and Shenmen (HT 7) are allamong the 10 acupoints with the most potential A clinicaltrial demonstrated that needling Baihui (GV 20) Shuigou(GV 26) and Shenmen (HT 7) were all effective in improvingthe symptoms of VaD However their therapeutic effects dif-fer Needling Baihui (GV 20) improved calculation ability andshort-term memory and corrected the personality changesof VaD patients while needling Shuigou (GV 26) improvednaming ability and short-term memory The therapeuticeffects of needling Baihui (GV 20) and Shuigou (GV 26)were superior to those of needling Shenmen (HT 7) [40]A PET and SPECT study revealed that needling these threedifferent acupoints in VaD patients affected different brainareas Needling Baihui (GV 20) activated the inner temporalsystem the thalamencephalon system and the prefrontalcortical system Needling Shuigou (GV 26) activated the pre-frontal cortical system Needling Shenmen (HT 7) generatedan effect similar to but weaker than the effect generated byneedling Shuigou (GV 26) [41] These findings demonstratethat different acupoints have different therapeutic effects inacupuncture treatment for VaD Consequently the selectionof acupoints which directly influences the therapeutic effectsof acupuncture should be considered carefully According toour results based on datamining Baihui (GV 20) Sishencong(EX-HN 1) Fengchi (GB 20) Shuigou (GV 26) and Shenting(GV 24) which have higher frequencies in the modernliterature may have better therapeutic effects on VaD
44 SingleAcupoint orAcupoint Combination Acupoint com-binations also influence the therapeutic effects of acupunc-ture An acupoint combination is considered to have asynergistic effect that enhances the therapeutic effect ofacupuncture For example a lower prevalence of postoper-ative nausea and vomiting in patients treated with Neiguan(PC 6) plus Hegu (LI 4) was observed compared with thosetreated with Neiguan (PC 6) only [42] In spite of extensiveevidence suggesting a synergistic effect of acupoint combi-nation and supporting its use some studies have reportedantagonistic effects [43ndash45] An antagonistic effect occurswhen one acupoint weakens the therapeutic effect of anotheracupoint [46] For example electroacupuncture can improvegastrointestinal movement in rats The effect of needlingPishu (BL 20) alone was better than the effect of needlingPishu (BL 20) and Zusanli (ST 36) at the same time [44]Therefore whether the effect of acupoint combination isbetter than a single acupoint still remains a question andneeds to be further studied
Some studies have compared single acupoints and anacupoint combination for the treatment of VaD The thera-peutic effect of needling Baihui (GV 20) Shuigou (GV 26)and Shenmen (HT 7) in combination was better than theeffects obtained by needling each alone [40] In additionneedling Baihui (GV 20) Shuigou (GV 26) and Shenmen(HT 7) simultaneously activated more brain areas relatedto intellectual activities compared with needling each alonegenerating a more extensive effect on the brain [41] Antago-nistic effects in acupuncture therapy for VaD have not beenreported but may occur Most acupuncture prescriptions forVaD contain acupoint combinations and the use of acupointcombinations is supported However acupoint combinationsshould be selected carefully to avoid antagonistic effects Itis hard to tell whether a combination of acupoints will exertantagonistic effects with current knowledge or TCM theoryAs abovementioned acupoints with similar functions canexert antagonistic effects There are many acupoints and thenumber of acupoint combinations will grow geometricallyTo test the antagonistic effects of each combination oneby one is an exhausting job To avoid antagonistic effectsas possible the acupoint prescriptions should be simplifiedas possible The general principle is to select acupointswith relatively better therapeutic effects and acupoints withmultiple indications and not to select many acupoints
45 Limitations This study has limitations as follows Firstother factors that influence acupuncture such as manipula-tion and treatment duration were not analyzed in this studyThese data can be further mined in future studies Secondlargely due to the lack of treatment based on syndrome differ-entiation and different methods of syndrome differentiationin modern literature potential acupoints and combinationsfor different syndromes of VaD were not analyzed Althoughtreatment based on syndrome differentiation is importantand is often emphasized in TCM treatment based on diseasedifferentiation is equally important Third the real therapeu-tic effects of acupoints and combinations on VaD cannotbe reflected by frequencies in the literature However theseresults suggest some potential acupoints and combinations to
Evidence-Based Complementary and Alternative Medicine 11
be explored in future clinical trials to validate the effects ofacupuncture on VaD To optimize the acupoint prescriptiondata may be extracted not only from literature but alsofrom clinical practice Further research can collect acupointprescriptions and symptom improvements in clinical practiceand optimize acupoint prescriptionwith dataminingMiningclinical data has been practiced to optimize prescriptionof Chinese herbal medicine for unstable angina by Fenget al [47] In their study five main symptoms of patientswith unstable angina the severity of each symptom andthe prescription of each patient were collected The levels ofaverage discounted reward (ADR) of different prescriptionswere calculated to evaluate the clinical efficacy of differ-ent treatment options with some optimized prescriptionsachieved Future studies can mine clinical data to optimizeacupoint prescription
5 Conclusions
In this study data mining was used to discover potentialacupoints and combinations for VaD Potential acupointsinclude Baihui (GV 20) Sishencong (EX-HN 1) Fengchi (GB20) Shuigou (GV 26) and Shenting (GV 24) In additioncombinations between Baihui (GV 20) Sishencong (EX-HN1) Fengchi (GB 20) Shenting (GV 24) Shuigou (GV 26) andZusanli (ST 36) were potential combinations Based on ourresults Baihui (GV 20) and Sishencong (EX-HN 1) shouldbe selected with priority Acupoints in head compared toacupoints in other parts should also be selected with priority
Conflict of Interests
The authors declare no conflict of interests
Authorsrsquo Contribution
Shuwei Feng and Yulan Ren contributed equally to this work
Acknowledgments
This study was supported by the National Basic ResearchProgram of China (no 2012CB518501) and the NationalScience Foundation of China (nos 81102742 and 61104224)
References
[1] Q Chen X Wu S F Lu et al ldquoMeridian acupoints selectionin acupuncture treatment for migraine the main charactersand relevant factors analysisrdquo Liaoning Journal of TraditionalChinese Medicine vol 36 no 9 pp 1477ndash1480 2009
[2] Y Li H Zheng C M Witt et al ldquoAcupuncture for migraineprophylaxis a randomized controlled trialrdquo Canadian MedicalAssociation Journal vol 184 no 4 pp 401ndash410 2012
[3] B H May C Lu L Bennett H M Hugel and C C LXue ldquoEvaluating the traditional Chinese literature for herbalformulae and individual herbs used for age-related dementiaand memory impairmentrdquo Biogerontology vol 13 no 3 pp299ndash312 2012
[4] L Zhang Y Li X Guo et al ldquoText mining of the classicalmedical literature for medicines that show potential in diabeticnephropathyrdquo Evidence-Based Complementary and AlternativeMedicine vol 2014 Article ID 189125 12 pages 2014
[5] Y Olsson A Brun and E Englund ldquoFundamental pathologicallesions in vascular dementiardquo Acta Neurologica Scandinavicavol 94 supplement 168 pp 31ndash38 1996
[6] S Davis M Shanahan A Campbell M Hegarty and BMcCarthy ldquoPalliative care for people with dementia aged carestaff perspectivesrdquo Alzheimerrsquos amp Dementia vol 7 no 4 p e502011
[7] J Jia F Wang C Wei et al ldquoThe prevalence of dementia inurban and rural areas of Chinardquo Alzheimerrsquos and Dementia vol10 no 1 pp 1ndash9 2014
[8] C P Ferri M Prince C Brayne et al ldquoGlobal prevalence ofdementia a Delphi consensus studyrdquo The Lancet vol 366 no9503 pp 2112ndash2117 2005
[9] W Quentin S G Riedel-Heller M Luppa A Rudolph andH-H Konig ldquoCost-of-illness studies of dementia a systematicreview focusing on stage dependency of costsrdquoActa PsychiatricaScandinavica vol 121 no 4 pp 243ndash259 2010
[10] J Yu X Zhang C Liu Y Meng and J Han ldquoEffect ofacupuncture treatment on vascular dementiardquo NeurologicalResearch vol 28 no 1 pp 97ndash103 2006
[11] G-X Shi C-Z Liu Q-Q Li H Zhu and L-P WangldquoInfluence of acupuncture on cognitive function and markersof oxidative DNA damage in patients with vascular dementiardquoJournal of Traditional Chinese Medicine vol 32 no 2 pp 199ndash202 2012
[12] X-Y Zhong X-X Su J Liu and G Q Zhu ldquoClinical effectsof acupuncture combined with nimodipine for treatment ofvascular dementia in 30 casesrdquo Journal of Traditional ChineseMedicine vol 29 no 3 pp 174ndash176 2009
[13] T Wang C-Z Liu J-C Yu W Jiang and J-X Han ldquoAcupunc-ture protected cerebral multi-infarction rats from memoryimpairment by regulating the expression of apoptosis relatedgenes Bcl-2 and Bax in hippocampusrdquo Physiology and Behaviorvol 96 no 1 pp 155ndash161 2009
[14] I K Hwang J Y Chung D Y Yoo et al ldquoComparing the effectsof acupuncture and electroacupuncture at Zusanli and Baihuion cell proliferation and neuroblast differentiation in the rathippocampusrdquo Journal of VeterinaryMedical Science vol 72 no3 pp 279ndash284 2010
[15] I K Hwang J Y Chung D Y Yoo et al ldquoEffects ofelectroacupuncture at Zusanli and Baihui on brain-derivedneurotrophic factor and cyclic AMP response element-bindingprotein in the hippocampal dentate gyrusrdquo Journal of VeterinaryMedical Science vol 72 no 11 pp 1431ndash1436 2010
[16] Y F Luo and J M Wu Fundamentals of Acupuncture SichuanUniversity Press Sichuan China 2008
[17] R Agrawal and R Srikant ldquoFast algorithms for mining associ-ation rulesrdquo in Proceedings of the 20th International Conferenceon Very Large Data Bases (VLDB rsquo94) pp 487ndash499 SantiagoChile 1994
[18] R Agrawal T Imielinski and A Swami ldquoMining associationrules between sets of items in large databasesrdquo ACM SIGMODRecord vol 22 no 2 pp 207ndash216 1993
12 Evidence-Based Complementary and Alternative Medicine
[19] A Clauset M E J Newman and C Moore ldquoFinding commu-nity structure in very large networksrdquo Physical Review E vol 70no 6 Article ID 066111 6 pages 2004
[20] G F de Arruda A L Barbieri P M Rodriguez et al ldquoRoleof centrality for the identification of influential spreaders incomplex networksrdquo Physical Review E Statistical Nonlinearand SoftMatter Physics vol 90 no 1ndash3 Article ID 032812 2014
[21] T Opsahl F Agneessens and J Skvoretz ldquoNode centrality inweighted networks generalizing degree and shortest pathsrdquoSocial Networks vol 32 no 3 pp 245ndash251 2010
[22] U Brandes ldquoOn variants of shortest-path betweenness central-ity and their generic computationrdquo Social Networks vol 30 no2 pp 136ndash145 2008
[23] H Q Li J H Li A J Liu M Y Ye and G Q ZhengldquoGV20-based acupuncture for animal models of acute intrac-erebral haemorrhage a preclinical systematic review and meta-analysisrdquo Acupuncture in Medicine vol 32 no 6 pp 495ndash5022014
[24] EOda ROhkiHMurasawa et al ldquoNoxa a BH3-onlymemberof the Bcl-2 family and candidate mediator of p53-inducedapoptosisrdquo Science vol 288 no 5468 pp 1053ndash1058 2000
[25] H Endo H Kamada C Nito T Nishi and P H Chan ldquoMito-chondrial translocation of p53 mediates release of cytochromec and hippocampal CA1 neuronal death after transient globalcerebral ischemia in ratsrdquo Journal of Neuroscience vol 26 no30 pp 7974ndash7983 2006
[26] Y Zhu and Y Zeng ldquoElectroacupuncture protected pyramidalcells in hippocampal CA1 region of vascular dementia rats byinhibiting the expression of P53 and Noxardquo CNS NeuroscienceandTherapeutics vol 17 no 6 pp 599ndash604 2011
[27] W J Tyler M Alonso C R Bramham and L D Pozzo-Miller ldquoFrom acquisition to consolidation on the role ofbrain-derived neurotrophic factor signaling in hippocampal-dependent learningrdquo Learning and Memory vol 9 no 5 pp224ndash237 2002
[28] P Bekinschtein M Cammarota C Katche et al ldquoBDNF isessential to promote persistence of long-termmemory storagerdquoProceedings of the National Academy of Sciences of the UnitedStates of America vol 105 no 7 pp 2711ndash2716 2008
[29] K Kitagawa ldquoCREB and cAMP response element-mediatedgene expression in the ischemic brainrdquo FEBS Journal vol 274no 13 pp 3210ndash3217 2007
[30] B Lee B Sur J Shim D Hahm and H Lee ldquoAcupuncturestimulation improves scopolamine-induced cognitive impair-ment via activation of cholinergic system and regulation ofBDNF andCREB expressions in ratsrdquoBMCComplementary andAlternative Medicine vol 14 no 1 article 338 2014
[31] M E Hasselmo ldquoThe role of acetylcholine in learning andmemoryrdquo Current Opinion in Neurobiology vol 16 no 6 pp710ndash715 2006
[32] T M Jay ldquoDopamine a potential substrate for synaptic plastic-ity andmemory mechanismsrdquo Progress in Neurobiology vol 69no 6 pp 375ndash390 2003
[33] C-M Chuang C-L Hsieh T-C Li and J-G Lin ldquoAcupunc-ture stimulation at Baihui acupoint reduced cerebral infarct andincreased dopamine levels in chronic cerebral hypoperfusionand ischemia-reperfusion injured Sprague-Dawley ratsrdquoAmeri-can Journal of ChineseMedicine vol 35 no 5 pp 779ndash791 2007
[34] H Jiao Z Wang Y Liu P Wang and Y Xue ldquoSpecific roleof tight junction proteins claudin-5 occludin and ZO-1 of theblood-brain barrier in a focal cerebral ischemic insultrdquo Journalof Molecular Neuroscience vol 44 no 2 pp 130ndash139 2011
[35] Y-M Zhang H Xu H Sun S Chen and F Wang ldquoElec-troacupuncture treatment improves neurological function asso-ciated with regulation of tight junction proteins in rats withcerebral ischemia reperfusion injuryrdquo Evidence-Based Comple-mentary and Alternative Medicine vol 2014 Article ID 98934010 pages 2014
[36] B-X Jin X-S Lai and C-Z Tang ldquoProgress in researches onthe specificity of acupointsrdquo Acupuncture Research vol 33 no2 pp 135ndash138 2008
[37] Y Li F Liang X Yang et al ldquoAcupuncture for treating acuteattacks of migraine a randomized controlled trialrdquo Headachevol 49 no 6 pp 805ndash816 2009
[38] T T Ma S Y Yu Y Li et al ldquoRandomised clinical trial anassessment of acupuncture on specific meridian or specific acu-point vs sham acupuncture for treating functional dyspepsiardquoAlimentary Pharmacology and Therapeutics vol 35 no 5 pp552ndash561 2012
[39] P-F Shen L Kong L-W Ni et al ldquoAcupuncture interventionin ischemic stroke a randomized controlled prospective studyrdquoThe American Journal of Chinese Medicine vol 40 no 4 pp685ndash693 2012
[40] Y Huang M H Win J Chen et al ldquoA comparative studyon the treatment of vascular dementia by puncturing Baihui(GV20) Shuigou (GV26) and Shenmen (HT7)rdquoWorld Journalof AcupuncturemdashMoxibustion no 1 pp 3ndash10 2005
[41] Y Huang X-S Lai and A-W Tang ldquoComparative study of thespecificities of needling acupoints DU20 DU26 and HT7 inintervening vascular dementia in different areas in the brain onthe basis of scale assessment and cerebral functional imagingrdquoChinese Journal of Integrative Medicine vol 13 no 2 pp 103ndash108 2007
[42] R Alizadeh S Esmaeili S Shoar S Bagheri-Hariri and NShoar ldquoAcupuncture in preventing postoperative nausea andvomiting efficacy of two acupuncture points versus a singleonerdquo Journal of Acupuncture and Meridian Studies vol 7 no2 pp 71ndash75 2014
[43] F M Xu and R X Chen ldquoThe antagonistic effect of acupointson oxygen consumption rate in ratsrdquo Journal of Jiangxi Collegeof Traditional Chinese Medicine vol 13 no 2 pp 60ndash61 2001
[44] F M Xu and R X Chen ldquoEffect of electroacupuncture ongastrointestinalmovement in rats with hypoactive gastrointesti-nal movement caused by greaserdquo Henan Traditional ChineseMedicine vol 20 no 2 pp 19ndash20 2000
[45] X H Li X Z Gao and L Hu ldquoExperimental study on syner-getic and antagonistic effects of acupoints Neiguan Shenmenand Xinshurdquo Chinese Acupuncture andMoxibustion vol 22 no12 pp 819ndash821 2002
[46] X H Li Q Y Wang X Z Gao et al ldquoStudy on cooperationand antagonism among acupointsrdquo Chinese Acupuncture andMoxibustion vol 22 no 6 pp 387ndash388 2002
[47] Y Feng Y Qiu X Zhou Y Wang H Xu and B Liu ldquoOpti-mizing prescription of Chinese herbal medicine for unstableangina based on partially observable Markov decision processrdquoEvidence-based Complementary and Alternative Medicine vol2013 Article ID 532534 6 pages 2013
Submit your manuscripts athttpwwwhindawicom
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Disease Markers
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Parkinsonrsquos Disease
Evidence-Based Complementary and Alternative Medicine
Volume 2014Hindawi Publishing Corporationhttpwwwhindawicom
2 Evidence-Based Complementary and Alternative Medicine
Acupuncture a primary therapeutic method in tradi-tional Chinese medicine (TCM) can improve memoryorientation calculation and self-managing ability in VaDpatients [10ndash12] The therapeutic effects of acupunctureare achieved via multiple pathways including antioxidativeeffects antiapoptotic effects and neurotrophic effects [1113ndash15] However acupoint selection remains a challenge inthe use of acupuncture to treat VaD According to ourpreliminary statistics more than 100 acupoints distributedin 13 meridians have been recorded in the modern literaturefor the treatment of VaD The most effective acupoints forthe treatment of VaD and the selection of acupoints forcombination remain to be elucidated representing a majorlimitation for clinical therapeutic effects and the applicationof acupuncture for VaD
To shed some light on the selection of acupoints andacupoint combinations to treat VaD in clinical acupunctureand acupuncture research this study aimed to discoveracupoints and acupoint combinations that have potential totreat VaD via data mining
2 Materials and Methods
The flow of information through the various phases of datamining is illustrated in Figure 1
21 Inclusion Criteria for Considering AcupointPrescriptions for Data Mining
211 Types of Studies Clinical trials evaluating the effect ofTCM acupuncture with or without randomization methodswere included Trials with or without controls were alsoincluded The control interventions included no treatmentsham acupuncture Western medicine TCM herbs non-traditional acupuncture and TCM acupuncture containinganother acupoint prescription which is different from the onein observation group Languagewas restricted toChinese andEnglish
212 Types of Participants Clinical trials involving adultparticipants diagnosed with VaD were included
213 Types of Interventions Clinical trials evaluating TCMacupuncture were included Acupuncture can be usedalone or in combination with other types of interventionsTCM acupuncture involves inserting needles into traditionalmeridian acupoints and extraordinary acupoints Electricalstimulation of the needles may be used Trials using moxi-bustion alone or as a cointervention with acupuncture werealso included
214 Effectiveness of Acupoint Prescriptions Acupoint pre-scriptions for the disease and not particular syndromesof VaD were included There should be statistical differ-ences in symptoms between before and after acupunctureIn a controlled trial patients treated with acupuncturealone or in combination should receive greater benefit thanpatients who do not receive acupuncture therapyThe controlinterventions included no treatment sham acupuncture
2121 records identified through database searching
(CNKI 892 CBM 1084 PubMed 145)
238 acupuncture prescriptions included in data
mining and network analysis after screening
Data preprocessing extraction of information about
titles journals interventions and main acupoints
and standardization of acupoint names
Data processing analysis of frequencies of
acupoints and meridians confidence of acupoint
combination and network properties
Figure 1 Flow of information through the different phases of datamining
Western medicine TCM herbs nontraditional acupunctureand TCM acupuncture containing another acupoint pre-scription which is different from the one in observationgroup If the studies compared the therapeutic effects ofdifferent acupoint prescriptions the most effective acupointprescription was included
22 Exclusion Criteria
221 Types of Studies Case reports reviews systematicreviews and meta-analyses were excluded
222 Types of Participants Trials evaluating the therapeuticeffect of acupuncture for Alzheimerrsquos disease traumaticdementia and other subtypes of dementia were excludedStudies on animals were also excluded
223 Types of Interventions Trials stimulating Ashi pointsalone were excluded Trials of dry needling or trigger pointtherapy therapies that are based on principles of westernanatomy and physiology were excluded Trials of laseracupuncture and noninvasive electrostimulation (eg using
Evidence-Based Complementary and Alternative Medicine 3
electrodes on the skin rather than needles or moxibustion tostimulate the acupoints) were excluded to limit the focus toTCM acupuncture Trials evaluating acupressure a form ofmassage were excluded as well Finally trials of micropunc-turewere excluded becausemicropuncture is a nontraditionalacupuncture practice that is based on the principle that thehead (or ear nose eye abdomen ankle etc) is amicrosystemof the entire body
224 Effectiveness of Acupoint Prescriptions Acupoint pre-scriptions for a particular syndrome of VaD were excludedAcupoint prescriptions with no statistical improvement ofsymptoms were also excluded When the therapeutic effectsof different acupoint prescriptions were compared in a studyall acupoint prescriptions except the most effective one wereexcluded
23 Searching Methods for Identification of Studies
231 Data Sources PubMed (httpwwwpubmedcom (1966to 2012)) the Chinese BioMedicine Database (CBM) (httpwwwsinomedaccn (1978 to 2012)) and China NationalKnowledge Infrastructure (CNKI) (httpwwwcnkinet (1912to 2012)) were searched formodern literature on acupuncturetreatment for VaD
232 Searching Strategy The searching strategy used thefollowing key words (I) ldquoacupuncturerdquo OR ldquoelectroacupunc-turerdquo OR ldquomoxibustionrdquo OR ldquomeridianrdquo OR ldquoacupointrdquo (II)ldquodementiardquoOR ldquovascular dementiardquoOR ldquoAlzheimerrsquos diseaserdquoThe searching strategy included literature on acupuncturetreatment for Alzheimerrsquos disease (AD) because the modernliterature on acupuncture for VaD overlaps with that on AD
24 Data Collection Two reviewers independently screenedthe title and abstract of every record retrieved from theliterature searches All potentially relevant articles wereinvestigated as full text in English or Chinese In cases ofdisagreement a trial was included or excluded based ondiscussion between the two reviewers or after a third reviewerreviewed the information For duplicate publications thefinal publication was used
25 Data Preprocessing Information about titles journalsinterventions and main acupoints was extracted using theself-established Data Excavation Platform of Acupoint Speci-ficity for data mining Because acupoints have aliases thenames of acupoints were standardized according to Funda-mentals of Acupuncture [16]
26 Data Processing
261 Frequencies of Acupoints The frequencies of acupointsmeridians and acupoints on different body parts wereanalyzed using the Data Excavation Platform of AcupointSpecificity
262AssociationRulesMiningAprioriAlgorithm for associa-tion rules mining [17] was adopted to analyze the frequencies
and support of acupoint combinations According to thedefinition of association rules mining [18] the followingcan be a statement of association rules mining for acupointcombination Let 119868 = 119894
1 1198942 119894
119898 be a set of acupoints
Let119863 be a set of acupoint prescriptions where each acupointprescription119879 is a set of acupoints such that119879 sube 119868 Associatedwith each acupoint prescription is a unique identifier calledTID An acupoint prescription 119879 contains 119883 a set of someacupoints in 119868 if 119883 sube 119879 The rule 119883-119884 has support 119904 in theacupoint prescription set119863 if 119904 of acupoint prescriptions in119863 contain119883 cup 119884
263 Measurement of Network PropertiesCommunity struc-ture is a common characteristic of complex networks andis characterized by more dense internal connections withingroups of nodes than with the rest of the network In thisstudy a hierarchical agglomeration was adopted to detectcommunity structure according to Clauset et al [19] We alsofocused on investigating the set of the most influential nodesin acupoint networks of VaD defined as the nodes with thehighest 119896-core value [20] The 119896-core method is predomi-nantly used in analyzing social networks We employed the119896-core method to obtain the cores of different acupoints The119896-coremethod was implemented as follows First all 1-degreenodeswere removed and the nodeswere further pruned untilno 1-degree nodes remained The remaining nodes formedthe 2-core node set The pruning process was repeated in asimilar manner for other nodes in the network assigned tothe corresponding cores (denoted by 119896s) The nodes with thelargest 119896-core value were defined as the network core Thedegree of each acupoint was also analyzed to measure theinvolvement of the node in the network The degree refers tothe number of nodes to which a focal node is connected [21]Betweenness centrality was also used to analyze an acupointrsquoscentrality in the network Centrality is an important conceptfor the analysis of networks and betweenness centrality isone of the most prominent measures of centrality It is usedto measure the degree to which a node is in a position ofbrokerage by summing up the fractions of shortest pathsbetween other pairs of vertices that pass through it [22]
3 Results
31 Overall Profile of Acupuncture Prescriptions Databasesearching identified 892 records in CNKI 1084 records inCBM and 145 records in PubMed After screening 238acupuncture prescriptions in 238 articles were includedAmong the 238 trials 185 are controlled clinical trials (CCTs)while the other 53 trials have no controls The whole view onthe study quality of the 185 CCTs were shown in Figure 2
32 Frequencies of Acupoints and Meridians Approximately109 meridian-acupoints distributed over 13 meridians and7 extraordinary acupoints have been recorded for 1400 and133 times respectively in modern literature on acupuncturetreatment for VaD The most frequently used meridianwas the Governor Meridian (477 times) Other frequentlyused meridians included the Gallbladder Meridian of Foot
4 Evidence-Based Complementary and Alternative Medicine
0 20 40 60 80 100()
Another bias
Selective reporting
Incomplete outcome data
Blinding of outcome assessment
Blinding of participants and personnel
Allocation concealment
Random sequence generation
Low riskUnclear riskHigh risk
Figure 2 Whole view on the study quality of the 185 CCTs
020406080
100120140160180200
Frequency
Baih
ui (G
V20
)
Sish
enco
ng (E
X-H
N1
)
Feng
chi (
GB20
)
Shui
gou
(GV26
)
Shen
ting
(GV24
)
Nei
guan
(PC6
)
Zusa
nli (
ST36
)
Sany
injia
o (S
P6
)
Shen
men
(HT7
)
Taix
i (KI
3)
Bens
hen
(GB13
)
Shen
shu
(BL23
)
Feng
long
(ST40
)
Taic
hong
(LV3
)
Daz
hui (
GV14
)
Xuan
zhon
g (G
B39
)
Feng
fu (G
V16
)
Heg
u (L
I4)
Quc
hi (L
I11
)
Yint
ang
(EX-
HN3
)
Figure 3 The 20 most frequent acupoints and their frequencies
Shaoyang and the Stomach Meridian of Foot Yangmingwhich were reported for 218 and 124 times respectivelyExtraordinary acupoints were also frequently used Baihui(GV 20) Sishencong (EX-HN 1) Fengchi (GB 20) Shuigou(GV 26) and Shenting (GV 24) which were among thetop five acupoints in frequency were recorded for 176 12493 86 and 84 times respectively The frequencies of eachmeridian and acupoint are shown in Table 1The twentymostfrequently used acupoints are shown in Figure 3
33 Frequencies of Acupoints on Different Body Parts Acu-points on the head face and neck were used most frequentlywith a total number of 42 acupoints and a total frequencyof 766 times followed by acupoints on the lower limbs (383
times) upper limbs (214 times) back and lumbar (127 times)and chest and abdomen (43 times) (Figures 4(a) and 4(b))
34 Frequencies of Specific Acupoints Specific acupoints rep-resented 78 of the 116 acupoints (6724) Specific acupointshave been used 1292 times representing 8428 of the totalfrequency of all acupoints (Figures 4(c) and 4(d))
35 Frequencies and Support of Acupoint Combinations Acu-point combinations between Baihui (GV 20) Sishencong(EX-HN 1) Fengchi (GB 20) Shenting (GV 24) Shuigou(GV 26) and Zusanli (ST 36) were used most frequentlyThe 15most frequently used acupoint combinations and theirsupport and confidence are shown in Table 2
Evidence-Based Complementary and Alternative Medicine 5
Table1Statisticso
fmeridians
andacup
ointsinthem
odernliteratureo
nacup
uncturetreatmentfor
VaD
Num
ber
Meridian
Frequency
Num
bero
facupo
ints
Acup
ointsa
ndtheirfrequ
encies
1GV
477
26
Baihui
(GV20)176Shu
igou
(GV26)8
6Sh
entin
g(G
V24)8
4Dazhu
i(GV14)2
7Feng
fu(G
V16)2
3Yintang(EX-
HN3)
16N
aohu
(GV17)13Shangxing(G
V23)11Mingm
en(G
V4)
8Yamen
(GV15)5
Qiang
jian(G
V18)5
Qiand
ing(G
V21)4
Yaoyang
guan
(GV3)
3Zh
iyang(G
V9)
3Jin
suo(G
V8)
2Shendao(G
V11)1Z
hong
shu(G
V7)
1Taod
ao(G
V13)1Lingtai(G
V10)1C
hangqiang(G
V1)1Xu
anshu
(GV5)
1Yaoshu
(GV2)
1Shenzhu(G
V12)1Jizho
ng(G
V6)
1Hou
ding
(GV19)1X
inhu
i(GV22)1
2GB
218
20
Fengchi(GB20)9
3Be
nshen(G
B13)4
7Xu
anzhon
g(G
B39)2
4Shuaigu(G
B8)
7Wangu
(GB12)6
To
ulinqi(G
B15)6
Qub
in(G
B7)
5Xu
anli(G
B6)
4Naokong
(GB19)4
Zuq
iaoyin
(GB44
)3Yanglingquan
(GB34)3
Yangbai(G
B14)3
Hanyan(G
B4)
2Qiuxu
(GB40
)2Fengshi
(GB31)2
Tou
qiaoyin(G
B11)2
Xu
anlu(G
B5)
2Muchu
ang(G
B16)1Z
heng
ying
(GB17)1Z
hongdu
(GB32)1
3EX
-HN
133
7Sishencong
(EX-
HN1)123Taiyang(EX-
HN5)
4Wailaogon
g(EX-
UE8)
2Sh
iqizhu
i(EX
-B8)
1Ba
xie
(EX-
UE9)
1Anm
ian(EX-
HN22)1Y
iming(EX-
HN14)1
4ST
124
7Zu
sanli(ST
36)7
2Feng
long
(ST40
)40To
uwei(ST8)
6Lidu
i(ST
45)2
Sibai(ST2)
2Fu
tu(ST32)1
Renying(ST9)
1
5BL
103
15Shenshu(BL23)4
3Ganshu(BL18)12Tianzhu(BL10)10Pishu(BL20)8
Feiyang
(BL58)8
Geshu
(BL17)
7Xinshu
(BL15)4
Zhiyin(BL67)2
Kun
lun(BL60)2
Yuzhen(BL9)
2To
ngtia
n(BL7)
1Ch
engjin
(BL56)
1Dazhu
(BL11)
1Weizhon
g(BL40
)1Q
ucha
(BL4)
16
SP96
5Sanyinjiao(SP6)
71X
uehai(SP
10)14Taibai(SP3)
8Yinb
ai(SP1)2Yinlingquan(SP9)
17
PC86
5Neigu
an(PC6)
73Z
hongchon
g(PC9)
4Daling(PC7)
4Jianshi
(PC5)
3Laogon
g(PC8)
28
KI83
5Taixi(KI
3)57D
azho
ng(K
I4)12Yo
ngqu
an(K
I1)10Zh
aohai(KI
6)8Ra
ngu(K
I2)2
9HT
673
Shenmen
(HT7)
62Shaocho
ng(H
T9)
3Jiq
uan(H
T1)2
10LI
457
Hegu(LI4
)20Quchi
(LI11)18Shang
yang
(LI1)2
Sho
usanli(LI10)
2Binao(LI14)
1Jianyu(LI15)
1Ying
xiang(LI2
0)1
11CV
435
Qihai(C
V6)
11Z
hong
wan
(CV12)10Guanyuan(C
V4)
9Danzhon
g(C
V17)9
Shenq
ue(C
V8)
412
LV40
2Taicho
ng(LV3)
37D
adun
(LV1)3
13TE
115
Waigu
an(TE5)
6Guancho
ng(TE1)2Sizhuk
ong(TE23)1Jiaosun
(TE20)1Sidu(TE9)
114
LU4
2Shaoshang(LU11)3
Liequ
e(LU
7)1
15SI
32
Shaoze
(SI1)2
Yanggu(SI5
)116
Total
1533
116GV
Governo
rMeridianGB
Gallbladd
erMeridianof
Foot
Shaoyang
EX-
HNextraordinary
acup
ointSTStom
achMeridianof
Foot
Yang
mingBL
Bladd
erMeridianof
Foot
TaiyangSPSpleenMeridianof
Foot
TaiyinP
CPeric
ardium
Meridianof
HandJueyinK
IKidn
eyMeridianof
Foot
Shaoyin
HTHeartMeridianof
HandSh
aoyin
CVC
onceptionVe
ssel
LIL
arge
Intestine
Meridianof
HandYang
mingLV
Liver
Meridianof
Foot
JueyinT
ETripleEn
ergizero
fHandSh
aoyang
LU
Lung
Meridianof
HandTaiyinSISm
allIntestin
eofH
andTaiyangFrequencieso
fmeridians
refertothetotalfre
quencies
ofacup
ointso
nthe
samem
eridian
Num
bero
facupo
intsrefertothetotalnu
mbero
facupo
intson
thes
amem
eridian
6 Evidence-Based Complementary and Alternative Medicine
Table 2 Statistics of the 15 most frequently used acupoint combinations in the treatment of VaD
Number Acupoint combination Frequency Support ()1 Baihui (GV 20) Sishencong (EX-HN 1) 98 41182 Baihui (GV 20) Fengchi (GB 20) 81 34033 Baihui (GV 20) Shuigou (GV 26) 72 29834 Baihui (GV 20) Shenting (GV 24) 70 29415 Baihui (GV 20) Zusanli (ST 36) 62 26056 Sishencong (EX-HN 1) Fengchi (GB 20) 60 25217 Baihui (GV 20) Sanyinjiao (SP 6) 57 23958 Baihui (GV 20) Neiguan (PC 6) 54 22699 Sishencong (EX-HN 1) Shuigou (GV 26) 51 214310 Sishencong (EX-HN 1) Baihui (GV 20) Fengchi (GB 20) 51 214311 Baihui (GV 20) Shenmen (HT 7) 51 214312 Sishencong (EX-HN 1) Shenting (GV 24) 49 205913 Sishencong (EX-HN 1) Neiguan (PC 6) 46 193314 Baihui (GV 20) Taixi (KI 3) 46 193315 Sishencong (EX-HN 1) Baihui (GV 20) Shuigou (GV 26) 43 1807Support refers to the percentage of acupoint prescriptions containing the acupoint combination
36 Community Structure Community detection resultedin the division of the 116 acupoints into 5 communitiesNodes of the same color belong to the same community Thecommunity structure is shown in Figure 5(a)
37 Acupoint 119870-Core Network The largest 119896-core value was19 At this value there were 28 nodes corresponding to Hegu(LI 4) Quchi (LI 11) Zusanli (ST 36) Fenglong (ST 40)Sanyinjiao (SP 6) Xuehai (SP 10) Shenmen (HT 7) Tianzhu(BL 10) Xinshu (BL 15) Ganshu (BL 18) Shenshu (BL 23)Taixi (KI 3) Dazhong (KI 4) Neiguan (PC 6) Benshen (GB13) Fengchi (GB 20) Xuanzhong (GB 39) Taichong (LV 3)Mingmen (GV 4) Dazhui (GV 14) Yamen (GV 15) Fengfu(GV 16) Baihui (GV20) Shenting (GV24) Shuigou (GV26)Guanyuan (CV 4) Sishencong (EX-HN 1) and Yintang (EX-HN 3) as shown in Figure 5(b)
38 Degree The top 20 acupoints in degree are shownin Figure 6(a) Baihui (GV 20) Sishencong (EX-HN 1)Fengchi (GB 20) Shenting (GV 24) and Neiguan (PC 6)had the highest degrees with values of 89 76 68 67 and 65respectively
39 Betweenness Centrality Thetop 20 acupoints in between-ness centrality are shown in Figure 6(b) Yongquan (KI 1)Baihui (GV 20) and Sishencong (EX-HN 1) had the highestbetweenness centrality
4 Discussion
41 Potential Acupoints and Combinations for VaD In thisstudy acupoints and combinations with potential for treat-ing VaD were discovered These results may provide somereference for the selection of acupoints in treatment forVaD which may promote the therapeutic effects in clinicalpractice The results suggest that Baihui (GV 20) Sishencong(EX-HN 1) Fengchi (GB 20) Shuigou (GV 26) and Shenting
(GV 24) are potential acupoints for treating VaD In terms ofmeridian acupoints on the Governor Meridian have poten-tial for treating VaD From the perspective of combinationscombinations between such acupoints as Baihui (GV 20)Sishencong (EX-HN 1) Fengchi (GB 20) Shenting (GV 24)Shuigou (GV 26) and Zusanli (ST 36) have potential fortreating VaD In addition acupoints on the head face andneck have more potential for VaD than acupoints on otherregions of the body Specific acupoints have more potentialthan nonspecific acupoints Specific acupoints with specificnames are a group of acupoints on fourteen meridians withspecific therapeutic effectsThere are ten types of specific acu-points Five-Shu acupoints Yuan-Primary acupoints Luo-Connecting acupoints Xi-Cleft acupoints Lower He-Seaacupoints Back-Shu acupoints Front-Mu acupoints eightinfluential acupoints eight confluent acupoints connectingthe eight extra meridians and convergent acupoints
Community detection divided the acupoints into 5 com-munities Acupoints within the same community have somecharacteristics in common Blue nodes (Community A) wereall Jing-Well acupoints Yellow nodes (Community B) were allacupoints on the face and head Most green nodes (Commu-nity C) were acupoints on the four limbs Most purple nodes(Community D) were acupoints belonging to Governor Ves-sel Most red nodes (Community E) were specific acupointsor acupoints with specific therapeutic effects and only thiscommunity contained Bach-Shu acupoints and acupointson the abdomen Acupoints within the same communitywere more densely connected with each other comparedwith acupoints from different communities indicating thatan acupoint was more often used with acupoints withinthe same community compared with acupoints within othercommunities
The 19-core network indicated that 28 acupoints includ-ing Hegu (LI 4) Quchi (LI 11) Zusanli (ST 36) Fenglong(ST 40) Sanyinjiao (SP 6) Xuehai (SP 10) Shenmen (HT 7)
Evidence-Based Complementary and Alternative Medicine 7
0
5
10
15
20
25
30
35
40
45
Head faceand neck
Lowerlimbs
Upperlimbs
Back andlumbar
Chest andabdomen
Number
(a) The numbers of acupoints in different parts
0
100
200
300
400
500
600
700
800
900
Head faceand neck
Lowerlimbs
Upperlimbs
Back andlumbar
Chest andabdomen
Frequency
(b) The frequencies of acupoints in different parts
0
5
10
15
20
25
30
35
40
Number
Con
verg
ent a
cupo
int
Five
-Shu
acup
oint
Yuan
-sou
rce p
oint
Luo-
Con
nect
ing
poin
t
Eigh
t infl
uent
ial p
oint
Shu-
Back
poi
nt
Eigh
t con
fluen
t acu
poin
ts
Fron
t-Mu
poin
t
Low
er H
e-Se
a poi
nt
Non
spec
ifc p
oint
(c) The numbers of different kinds of acupoints
0
100
200
300
400
500
600
700
800
Frequency
Con
verg
ent a
cupo
int
Five
-Shu
acup
oint
Yuan
-sou
rce p
oint
Luo-
Con
nect
ing
poin
t
Eigh
t infl
uent
ial p
oint
Shu-
Back
poi
nt
Eigh
t con
fluen
t acu
poin
ts
Fron
t-Mu
poin
t
Low
er H
e-Se
a poi
nt
Non
spec
ifc p
oint
(d) The frequencies of different kinds of acupoints
Figure 4 The frequencies and numbers of acupoints in different body parts and different types of acupoints
Tianzhu (BL 10) Xinshu (BL 15) Ganshu (BL 18) Shenshu(BL 23) Taixi (KI 3) Dazhong (KI 4) Neiguan (PC 6)Benshen (GB 13) Fengchi (GB 20) Xuanzhong (GB 39)Taichong (LV 3) Mingmen (GV 4) Dazhui (GV 14) Yamen(GV 15) Fengfu (GV 16) Baihui (GV 20) Shenting (GV 24)Shuigou (GV 26) Guanyuan (CV 4) Sishencong (EX-HN 1)and Yintang (EX-HN 3) are core acupoints in the network
Baihui (GV 20) Sishencong (EX-HN 1) Fengchi (GB20) Shenting (GV 24) and Neiguan (PC 6) had the highestdegreesThis result indicates that these 5 acupoints have beencombined with more acupoints than other acupoints Theseacupoints have specific therapeutic effects on VaDThereforethese acupoints can be used together with other acupoints toenhance therapeutic effects
Yongquan (KI 1) Baihui (GV 20) Sishencong (EX-HN1) Neiguan (PC 6) and Shenting (GV 24) which belonged
to 4 different communities had higher betweenness cen-trality Yongquan (KI 1) which had the highest betweennesscentrality did not have a relatively high degree However itconnects Jing-Well acupoints with other types of acupointsresulting in a high betweenness centrality Acupoints withhigher betweenness centrality play an important role inconnecting different types of acupoints Jing-Well acupointsexcept Yongquan (KI 1) were often used with other Jing-Wellacupoints only Yongquan (KI 1) was not only used with otherJing-Well acupoints but also with other types of acupointssuch as other types of specific acupoints nonspecific acu-points and acupoints on other parts The high betweennesscentrality suggested that Yongquan (KI 1) may have multipleeffects compared with other Jing-Well acupoints in treatmentof VaD From the perspective of TCM theory Jing-Wellacupoints can restore consciousness Yongquan (KI 1) was
8 Evidence-Based Complementary and Alternative Medicine
BL17
EX-HN22
BL7
LI1
GV13
SP9
GB11
EX-HN14
GB4
HT1
ST2
CV8
GB5
GV18
BL11
EX-UE8
LI20
GV1
ST36
BL20
CV17
BL58
BL9
GV17
GV14
GV15
GV11
GV12
GV10GV5
KI3
KI1
LU11
HT9
GV8
GV3
BL23
GV4
CV6
CV12
HT7GB20
GB17
GV24
GV16
CV4
GB8
GV21GV23GB13
SP10
BL10
ST32
GB34LI14
LI15
GB32
LI10
BL40
GB31
KI6
SI5
KI2
PC7
LI4
GB16
EX-HN5
GB12
PC8
PC6
BL18
BL15
BL56
GB40
TE9
EX-UE9SP6
TE5
SP3
LI11
GV22
BL60
GB6
GB14
GB15
GB19
ST9
GV7
GV2
GV6
EX-B8
BL4
SI1
PC9
TE1ST45
SP1
BL67
GB44
LV1
TE23
TE20
LU7
GV19
ST40
EX-HN3ST8
GV20
KI4
GB39
GB7
EX-HN1
PC5
LV3
GV9
GV26
(a) Network structure of acupoints for the treatment of VaD
GB13
EX-HN1
EX-HN3
LI4
KI3
KI4
HT7GB20
GV14
GV15
GV16
LV3
ST36
BL23
GV4
GV24
GV26GV20
ST40
SP6
LI11
GB39
SP10
PC6
BL10
CV4
BL18
BL15
(b) 19-core network
Figure 5 (a) Network structure of acupoints for the treatment of VaD Blue nodes (Community A) are all Jing-Well acupoints Yellow nodes(Community B) are all acupoints on the face and head Most green nodes (Community C) are acupoints on four limbs Most purple nodes(Community D) are acupoints belonging to Governor Vessel Most red nodes (Community E) are specific acupoints or acupoints withspecific therapeutic effects and only this community contains Bach-Shu acupoints and acupoints on the abdomen Acupoints within thesame community are more densely connected with each other than acupoints from different communities (b) 19-core network There are 28acupoints in the 19-core network They are core acupoints in the treatment of VaD
Evidence-Based Complementary and Alternative Medicine 9
0102030405060708090
100
GV
20
EX-H
N1
GB2
0
GV
24
PC6
SP6
GV
14
GV
26
GV
16
HT7 LI
4
KI3
ST36
ST40
LV3
GB1
3
EX-H
N3
BL10
GB3
9
LI 1
1
Degree
(a) The 20 acupoints with highest degree
0002004006008
01012014016
KI1
GV
20
EX-H
N1
PC6
GV
26
GB2
0
GV
24
GV
14 SP6
EX-H
N3
HT7 LI
4
KI3
GV
16
BL10
LV3
ST40
ST36
GB1
3
PC9
Betweenness centrality
(b) The 20 acupoints with highest betweenness centrality
Figure 6 The 20 acupoints with highest degree and the 20 acupoints with highest betweenness centrality
also used to tonify kidney in treatment of VaD ThereforeYongquan (KI 1) is used not only with other Jing-Wellacupoints but also with other types of acupoints such asother types of specific acupoints nonspecific acupoints andacupoints on other parts
42 UnderlyingMolecularMechanism of the Acupoint with theMost Potential to Treat VaD According to our results Baihui(GV 20) which had the highest frequency has the mostpotential to treat VaD A systematic review andmeta-analysisalso suggested that Baihui (GV 20) is a principal acupoint foracute intracerebral hemorrhage (ICH) in animal models ofacute ICH there was no difference in efficacy between Baihui(GV 20) alone and Baihui (GV 20) plus other acupoints [23]
Molecular biology studies have provided insights intothe mechanisms underlying the effects of Baihui (GV 20) inVaD treatment including antioxidant effects antiapoptoticeffects neurotrophic effects reduced blood-brain barrier(BBB) permeability and regulation of the cholinergic anddopaminergic systems Acupuncture at Baihui (GV 20) incombination with other acupoints decreases levels of 8-hydroxy-21015840-deoxyguanosine a product of oxidative damageto DNA induced by free radicals suggesting that the benefitof acupuncture is partly due to antioxidant effects [11]Acupuncture exerts therapeutic effects on VaD via antiapop-tosis The tumor suppressors p53 and Noxa are important inregulating apoptosis and mediate hypoxic cell death [24 25]
Electroacupuncture at Baihui (GV 20) Dazhui (GV 14) andShenshu (BL 23) blocks expression of p53 and Noxa in thehippocampal CA1 region of VaD rats [26] Acupuncture atBaihui (GV 20) can improve neurogenesis via regulatingbrain-derived neurotrophic factor (BDNF) and cyclic AMPresponse element-binding protein (CREB) BDNF whichis essential for synaptic plasticity and is coupled to CREBactivation [27] is important for long-term memory storage[28] CREB is required for the proliferation growth survivaland differentiation of all types of cells In the brain the CREBand CRE-mediated system is involved in memory learningsynaptic transmission neuron survival differentiation andaxon growth [29] Acupuncture at Baihui (GV 20) signifi-cantly increases the levels of BDNF [15 30] CREB proteinsCREB mRNA [30] and phosphorylated CREB the activeform of CREB [15] The molecular mechanism underlyingacupuncture at Baihui (GV 20) also involves cholinergicsystem regulation Decreased cholinergic function in thebrain can result in a decline in memory and cognitivefunction [31] Acupuncture at Baihui (GV 20) significantlyincreases the levels of choline acetyltransferase (ChAT) andrestores the expression of choline transporter 1 (CHT1)and vesicular acetylcholine transporter (VAChT) [30] Thedopaminergic system is also involved in the mechanismunderlying the treatment of VaD with acupuncture at Baihui(GV 20) Dopamine is a key regulator in specific synapticchanges observed at certain stages of learning and memory
10 Evidence-Based Complementary and Alternative Medicine
and of synaptic plasticity [32] Acupuncture at Baihui (GV20)increases dopamine levels in chronic cerebral hypoperfusionand ischemia-reperfusion injured rats [33] In additionacupuncture at Baihui (GV 20) and Zusanli (ST 36) preservesthe integrity of the BBB reducing BBB permeability TheBBB is constructed of tight conjunctions including occludinand claudin-5 which form the endothelial barrier Reducedexpression of ZO-1 claudin-5 and occludin mRNA andprotein contributes to BBB breakdown and edema in theischemic brain [34] Electroacupuncture at Baihui (GV 20)and Zusanli (ST 36) reduces brain damage and relatedbehavioral deficits via upregulation of tight conjunctionproteins including ZO-1 claudin-5 and occludin [35]Thesefindings reveal parts of the molecular mechanism underlyingacupuncture at Baihui (GV 20) to treat VaD
43 Acupoints Selection in Treatment for VaD The properselection of acupoints is essential for the therapeutic effectsof acupuncture because acupoints are specific with regard tomorphological structure biophysical properties pathologicalresponse and stimulating effects [36] This specificity dif-ferentiates acupoints from nonacupoints as well as differentacupoints from one another The specific therapeutic effectsof different acupoints have been reported for migraine [37]functional dyspepsia [38] ischemic stroke [39] and so forth
The specificity of acupoints for the treatment of VaDhas also been reported Phosphorylated CREB levels weresignificantly increased after acupuncture therapy of needlingBaihui (GV 20) and Zusanli (ST 36) compared to shamacupuncture therapy of needling nonacupoints [15] Baihui(GV 20) Shuigou (GV 26) and Shenmen (HT 7) are allamong the 10 acupoints with the most potential A clinicaltrial demonstrated that needling Baihui (GV 20) Shuigou(GV 26) and Shenmen (HT 7) were all effective in improvingthe symptoms of VaD However their therapeutic effects dif-fer Needling Baihui (GV 20) improved calculation ability andshort-term memory and corrected the personality changesof VaD patients while needling Shuigou (GV 26) improvednaming ability and short-term memory The therapeuticeffects of needling Baihui (GV 20) and Shuigou (GV 26)were superior to those of needling Shenmen (HT 7) [40]A PET and SPECT study revealed that needling these threedifferent acupoints in VaD patients affected different brainareas Needling Baihui (GV 20) activated the inner temporalsystem the thalamencephalon system and the prefrontalcortical system Needling Shuigou (GV 26) activated the pre-frontal cortical system Needling Shenmen (HT 7) generatedan effect similar to but weaker than the effect generated byneedling Shuigou (GV 26) [41] These findings demonstratethat different acupoints have different therapeutic effects inacupuncture treatment for VaD Consequently the selectionof acupoints which directly influences the therapeutic effectsof acupuncture should be considered carefully According toour results based on datamining Baihui (GV 20) Sishencong(EX-HN 1) Fengchi (GB 20) Shuigou (GV 26) and Shenting(GV 24) which have higher frequencies in the modernliterature may have better therapeutic effects on VaD
44 SingleAcupoint orAcupoint Combination Acupoint com-binations also influence the therapeutic effects of acupunc-ture An acupoint combination is considered to have asynergistic effect that enhances the therapeutic effect ofacupuncture For example a lower prevalence of postoper-ative nausea and vomiting in patients treated with Neiguan(PC 6) plus Hegu (LI 4) was observed compared with thosetreated with Neiguan (PC 6) only [42] In spite of extensiveevidence suggesting a synergistic effect of acupoint combi-nation and supporting its use some studies have reportedantagonistic effects [43ndash45] An antagonistic effect occurswhen one acupoint weakens the therapeutic effect of anotheracupoint [46] For example electroacupuncture can improvegastrointestinal movement in rats The effect of needlingPishu (BL 20) alone was better than the effect of needlingPishu (BL 20) and Zusanli (ST 36) at the same time [44]Therefore whether the effect of acupoint combination isbetter than a single acupoint still remains a question andneeds to be further studied
Some studies have compared single acupoints and anacupoint combination for the treatment of VaD The thera-peutic effect of needling Baihui (GV 20) Shuigou (GV 26)and Shenmen (HT 7) in combination was better than theeffects obtained by needling each alone [40] In additionneedling Baihui (GV 20) Shuigou (GV 26) and Shenmen(HT 7) simultaneously activated more brain areas relatedto intellectual activities compared with needling each alonegenerating a more extensive effect on the brain [41] Antago-nistic effects in acupuncture therapy for VaD have not beenreported but may occur Most acupuncture prescriptions forVaD contain acupoint combinations and the use of acupointcombinations is supported However acupoint combinationsshould be selected carefully to avoid antagonistic effects Itis hard to tell whether a combination of acupoints will exertantagonistic effects with current knowledge or TCM theoryAs abovementioned acupoints with similar functions canexert antagonistic effects There are many acupoints and thenumber of acupoint combinations will grow geometricallyTo test the antagonistic effects of each combination oneby one is an exhausting job To avoid antagonistic effectsas possible the acupoint prescriptions should be simplifiedas possible The general principle is to select acupointswith relatively better therapeutic effects and acupoints withmultiple indications and not to select many acupoints
45 Limitations This study has limitations as follows Firstother factors that influence acupuncture such as manipula-tion and treatment duration were not analyzed in this studyThese data can be further mined in future studies Secondlargely due to the lack of treatment based on syndrome differ-entiation and different methods of syndrome differentiationin modern literature potential acupoints and combinationsfor different syndromes of VaD were not analyzed Althoughtreatment based on syndrome differentiation is importantand is often emphasized in TCM treatment based on diseasedifferentiation is equally important Third the real therapeu-tic effects of acupoints and combinations on VaD cannotbe reflected by frequencies in the literature However theseresults suggest some potential acupoints and combinations to
Evidence-Based Complementary and Alternative Medicine 11
be explored in future clinical trials to validate the effects ofacupuncture on VaD To optimize the acupoint prescriptiondata may be extracted not only from literature but alsofrom clinical practice Further research can collect acupointprescriptions and symptom improvements in clinical practiceand optimize acupoint prescriptionwith dataminingMiningclinical data has been practiced to optimize prescriptionof Chinese herbal medicine for unstable angina by Fenget al [47] In their study five main symptoms of patientswith unstable angina the severity of each symptom andthe prescription of each patient were collected The levels ofaverage discounted reward (ADR) of different prescriptionswere calculated to evaluate the clinical efficacy of differ-ent treatment options with some optimized prescriptionsachieved Future studies can mine clinical data to optimizeacupoint prescription
5 Conclusions
In this study data mining was used to discover potentialacupoints and combinations for VaD Potential acupointsinclude Baihui (GV 20) Sishencong (EX-HN 1) Fengchi (GB20) Shuigou (GV 26) and Shenting (GV 24) In additioncombinations between Baihui (GV 20) Sishencong (EX-HN1) Fengchi (GB 20) Shenting (GV 24) Shuigou (GV 26) andZusanli (ST 36) were potential combinations Based on ourresults Baihui (GV 20) and Sishencong (EX-HN 1) shouldbe selected with priority Acupoints in head compared toacupoints in other parts should also be selected with priority
Conflict of Interests
The authors declare no conflict of interests
Authorsrsquo Contribution
Shuwei Feng and Yulan Ren contributed equally to this work
Acknowledgments
This study was supported by the National Basic ResearchProgram of China (no 2012CB518501) and the NationalScience Foundation of China (nos 81102742 and 61104224)
References
[1] Q Chen X Wu S F Lu et al ldquoMeridian acupoints selectionin acupuncture treatment for migraine the main charactersand relevant factors analysisrdquo Liaoning Journal of TraditionalChinese Medicine vol 36 no 9 pp 1477ndash1480 2009
[2] Y Li H Zheng C M Witt et al ldquoAcupuncture for migraineprophylaxis a randomized controlled trialrdquo Canadian MedicalAssociation Journal vol 184 no 4 pp 401ndash410 2012
[3] B H May C Lu L Bennett H M Hugel and C C LXue ldquoEvaluating the traditional Chinese literature for herbalformulae and individual herbs used for age-related dementiaand memory impairmentrdquo Biogerontology vol 13 no 3 pp299ndash312 2012
[4] L Zhang Y Li X Guo et al ldquoText mining of the classicalmedical literature for medicines that show potential in diabeticnephropathyrdquo Evidence-Based Complementary and AlternativeMedicine vol 2014 Article ID 189125 12 pages 2014
[5] Y Olsson A Brun and E Englund ldquoFundamental pathologicallesions in vascular dementiardquo Acta Neurologica Scandinavicavol 94 supplement 168 pp 31ndash38 1996
[6] S Davis M Shanahan A Campbell M Hegarty and BMcCarthy ldquoPalliative care for people with dementia aged carestaff perspectivesrdquo Alzheimerrsquos amp Dementia vol 7 no 4 p e502011
[7] J Jia F Wang C Wei et al ldquoThe prevalence of dementia inurban and rural areas of Chinardquo Alzheimerrsquos and Dementia vol10 no 1 pp 1ndash9 2014
[8] C P Ferri M Prince C Brayne et al ldquoGlobal prevalence ofdementia a Delphi consensus studyrdquo The Lancet vol 366 no9503 pp 2112ndash2117 2005
[9] W Quentin S G Riedel-Heller M Luppa A Rudolph andH-H Konig ldquoCost-of-illness studies of dementia a systematicreview focusing on stage dependency of costsrdquoActa PsychiatricaScandinavica vol 121 no 4 pp 243ndash259 2010
[10] J Yu X Zhang C Liu Y Meng and J Han ldquoEffect ofacupuncture treatment on vascular dementiardquo NeurologicalResearch vol 28 no 1 pp 97ndash103 2006
[11] G-X Shi C-Z Liu Q-Q Li H Zhu and L-P WangldquoInfluence of acupuncture on cognitive function and markersof oxidative DNA damage in patients with vascular dementiardquoJournal of Traditional Chinese Medicine vol 32 no 2 pp 199ndash202 2012
[12] X-Y Zhong X-X Su J Liu and G Q Zhu ldquoClinical effectsof acupuncture combined with nimodipine for treatment ofvascular dementia in 30 casesrdquo Journal of Traditional ChineseMedicine vol 29 no 3 pp 174ndash176 2009
[13] T Wang C-Z Liu J-C Yu W Jiang and J-X Han ldquoAcupunc-ture protected cerebral multi-infarction rats from memoryimpairment by regulating the expression of apoptosis relatedgenes Bcl-2 and Bax in hippocampusrdquo Physiology and Behaviorvol 96 no 1 pp 155ndash161 2009
[14] I K Hwang J Y Chung D Y Yoo et al ldquoComparing the effectsof acupuncture and electroacupuncture at Zusanli and Baihuion cell proliferation and neuroblast differentiation in the rathippocampusrdquo Journal of VeterinaryMedical Science vol 72 no3 pp 279ndash284 2010
[15] I K Hwang J Y Chung D Y Yoo et al ldquoEffects ofelectroacupuncture at Zusanli and Baihui on brain-derivedneurotrophic factor and cyclic AMP response element-bindingprotein in the hippocampal dentate gyrusrdquo Journal of VeterinaryMedical Science vol 72 no 11 pp 1431ndash1436 2010
[16] Y F Luo and J M Wu Fundamentals of Acupuncture SichuanUniversity Press Sichuan China 2008
[17] R Agrawal and R Srikant ldquoFast algorithms for mining associ-ation rulesrdquo in Proceedings of the 20th International Conferenceon Very Large Data Bases (VLDB rsquo94) pp 487ndash499 SantiagoChile 1994
[18] R Agrawal T Imielinski and A Swami ldquoMining associationrules between sets of items in large databasesrdquo ACM SIGMODRecord vol 22 no 2 pp 207ndash216 1993
12 Evidence-Based Complementary and Alternative Medicine
[19] A Clauset M E J Newman and C Moore ldquoFinding commu-nity structure in very large networksrdquo Physical Review E vol 70no 6 Article ID 066111 6 pages 2004
[20] G F de Arruda A L Barbieri P M Rodriguez et al ldquoRoleof centrality for the identification of influential spreaders incomplex networksrdquo Physical Review E Statistical Nonlinearand SoftMatter Physics vol 90 no 1ndash3 Article ID 032812 2014
[21] T Opsahl F Agneessens and J Skvoretz ldquoNode centrality inweighted networks generalizing degree and shortest pathsrdquoSocial Networks vol 32 no 3 pp 245ndash251 2010
[22] U Brandes ldquoOn variants of shortest-path betweenness central-ity and their generic computationrdquo Social Networks vol 30 no2 pp 136ndash145 2008
[23] H Q Li J H Li A J Liu M Y Ye and G Q ZhengldquoGV20-based acupuncture for animal models of acute intrac-erebral haemorrhage a preclinical systematic review and meta-analysisrdquo Acupuncture in Medicine vol 32 no 6 pp 495ndash5022014
[24] EOda ROhkiHMurasawa et al ldquoNoxa a BH3-onlymemberof the Bcl-2 family and candidate mediator of p53-inducedapoptosisrdquo Science vol 288 no 5468 pp 1053ndash1058 2000
[25] H Endo H Kamada C Nito T Nishi and P H Chan ldquoMito-chondrial translocation of p53 mediates release of cytochromec and hippocampal CA1 neuronal death after transient globalcerebral ischemia in ratsrdquo Journal of Neuroscience vol 26 no30 pp 7974ndash7983 2006
[26] Y Zhu and Y Zeng ldquoElectroacupuncture protected pyramidalcells in hippocampal CA1 region of vascular dementia rats byinhibiting the expression of P53 and Noxardquo CNS NeuroscienceandTherapeutics vol 17 no 6 pp 599ndash604 2011
[27] W J Tyler M Alonso C R Bramham and L D Pozzo-Miller ldquoFrom acquisition to consolidation on the role ofbrain-derived neurotrophic factor signaling in hippocampal-dependent learningrdquo Learning and Memory vol 9 no 5 pp224ndash237 2002
[28] P Bekinschtein M Cammarota C Katche et al ldquoBDNF isessential to promote persistence of long-termmemory storagerdquoProceedings of the National Academy of Sciences of the UnitedStates of America vol 105 no 7 pp 2711ndash2716 2008
[29] K Kitagawa ldquoCREB and cAMP response element-mediatedgene expression in the ischemic brainrdquo FEBS Journal vol 274no 13 pp 3210ndash3217 2007
[30] B Lee B Sur J Shim D Hahm and H Lee ldquoAcupuncturestimulation improves scopolamine-induced cognitive impair-ment via activation of cholinergic system and regulation ofBDNF andCREB expressions in ratsrdquoBMCComplementary andAlternative Medicine vol 14 no 1 article 338 2014
[31] M E Hasselmo ldquoThe role of acetylcholine in learning andmemoryrdquo Current Opinion in Neurobiology vol 16 no 6 pp710ndash715 2006
[32] T M Jay ldquoDopamine a potential substrate for synaptic plastic-ity andmemory mechanismsrdquo Progress in Neurobiology vol 69no 6 pp 375ndash390 2003
[33] C-M Chuang C-L Hsieh T-C Li and J-G Lin ldquoAcupunc-ture stimulation at Baihui acupoint reduced cerebral infarct andincreased dopamine levels in chronic cerebral hypoperfusionand ischemia-reperfusion injured Sprague-Dawley ratsrdquoAmeri-can Journal of ChineseMedicine vol 35 no 5 pp 779ndash791 2007
[34] H Jiao Z Wang Y Liu P Wang and Y Xue ldquoSpecific roleof tight junction proteins claudin-5 occludin and ZO-1 of theblood-brain barrier in a focal cerebral ischemic insultrdquo Journalof Molecular Neuroscience vol 44 no 2 pp 130ndash139 2011
[35] Y-M Zhang H Xu H Sun S Chen and F Wang ldquoElec-troacupuncture treatment improves neurological function asso-ciated with regulation of tight junction proteins in rats withcerebral ischemia reperfusion injuryrdquo Evidence-Based Comple-mentary and Alternative Medicine vol 2014 Article ID 98934010 pages 2014
[36] B-X Jin X-S Lai and C-Z Tang ldquoProgress in researches onthe specificity of acupointsrdquo Acupuncture Research vol 33 no2 pp 135ndash138 2008
[37] Y Li F Liang X Yang et al ldquoAcupuncture for treating acuteattacks of migraine a randomized controlled trialrdquo Headachevol 49 no 6 pp 805ndash816 2009
[38] T T Ma S Y Yu Y Li et al ldquoRandomised clinical trial anassessment of acupuncture on specific meridian or specific acu-point vs sham acupuncture for treating functional dyspepsiardquoAlimentary Pharmacology and Therapeutics vol 35 no 5 pp552ndash561 2012
[39] P-F Shen L Kong L-W Ni et al ldquoAcupuncture interventionin ischemic stroke a randomized controlled prospective studyrdquoThe American Journal of Chinese Medicine vol 40 no 4 pp685ndash693 2012
[40] Y Huang M H Win J Chen et al ldquoA comparative studyon the treatment of vascular dementia by puncturing Baihui(GV20) Shuigou (GV26) and Shenmen (HT7)rdquoWorld Journalof AcupuncturemdashMoxibustion no 1 pp 3ndash10 2005
[41] Y Huang X-S Lai and A-W Tang ldquoComparative study of thespecificities of needling acupoints DU20 DU26 and HT7 inintervening vascular dementia in different areas in the brain onthe basis of scale assessment and cerebral functional imagingrdquoChinese Journal of Integrative Medicine vol 13 no 2 pp 103ndash108 2007
[42] R Alizadeh S Esmaeili S Shoar S Bagheri-Hariri and NShoar ldquoAcupuncture in preventing postoperative nausea andvomiting efficacy of two acupuncture points versus a singleonerdquo Journal of Acupuncture and Meridian Studies vol 7 no2 pp 71ndash75 2014
[43] F M Xu and R X Chen ldquoThe antagonistic effect of acupointson oxygen consumption rate in ratsrdquo Journal of Jiangxi Collegeof Traditional Chinese Medicine vol 13 no 2 pp 60ndash61 2001
[44] F M Xu and R X Chen ldquoEffect of electroacupuncture ongastrointestinalmovement in rats with hypoactive gastrointesti-nal movement caused by greaserdquo Henan Traditional ChineseMedicine vol 20 no 2 pp 19ndash20 2000
[45] X H Li X Z Gao and L Hu ldquoExperimental study on syner-getic and antagonistic effects of acupoints Neiguan Shenmenand Xinshurdquo Chinese Acupuncture andMoxibustion vol 22 no12 pp 819ndash821 2002
[46] X H Li Q Y Wang X Z Gao et al ldquoStudy on cooperationand antagonism among acupointsrdquo Chinese Acupuncture andMoxibustion vol 22 no 6 pp 387ndash388 2002
[47] Y Feng Y Qiu X Zhou Y Wang H Xu and B Liu ldquoOpti-mizing prescription of Chinese herbal medicine for unstableangina based on partially observable Markov decision processrdquoEvidence-based Complementary and Alternative Medicine vol2013 Article ID 532534 6 pages 2013
Submit your manuscripts athttpwwwhindawicom
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Disease Markers
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Evidence-Based Complementary and Alternative Medicine
Volume 2014Hindawi Publishing Corporationhttpwwwhindawicom
Evidence-Based Complementary and Alternative Medicine 3
electrodes on the skin rather than needles or moxibustion tostimulate the acupoints) were excluded to limit the focus toTCM acupuncture Trials evaluating acupressure a form ofmassage were excluded as well Finally trials of micropunc-turewere excluded becausemicropuncture is a nontraditionalacupuncture practice that is based on the principle that thehead (or ear nose eye abdomen ankle etc) is amicrosystemof the entire body
224 Effectiveness of Acupoint Prescriptions Acupoint pre-scriptions for a particular syndrome of VaD were excludedAcupoint prescriptions with no statistical improvement ofsymptoms were also excluded When the therapeutic effectsof different acupoint prescriptions were compared in a studyall acupoint prescriptions except the most effective one wereexcluded
23 Searching Methods for Identification of Studies
231 Data Sources PubMed (httpwwwpubmedcom (1966to 2012)) the Chinese BioMedicine Database (CBM) (httpwwwsinomedaccn (1978 to 2012)) and China NationalKnowledge Infrastructure (CNKI) (httpwwwcnkinet (1912to 2012)) were searched formodern literature on acupuncturetreatment for VaD
232 Searching Strategy The searching strategy used thefollowing key words (I) ldquoacupuncturerdquo OR ldquoelectroacupunc-turerdquo OR ldquomoxibustionrdquo OR ldquomeridianrdquo OR ldquoacupointrdquo (II)ldquodementiardquoOR ldquovascular dementiardquoOR ldquoAlzheimerrsquos diseaserdquoThe searching strategy included literature on acupuncturetreatment for Alzheimerrsquos disease (AD) because the modernliterature on acupuncture for VaD overlaps with that on AD
24 Data Collection Two reviewers independently screenedthe title and abstract of every record retrieved from theliterature searches All potentially relevant articles wereinvestigated as full text in English or Chinese In cases ofdisagreement a trial was included or excluded based ondiscussion between the two reviewers or after a third reviewerreviewed the information For duplicate publications thefinal publication was used
25 Data Preprocessing Information about titles journalsinterventions and main acupoints was extracted using theself-established Data Excavation Platform of Acupoint Speci-ficity for data mining Because acupoints have aliases thenames of acupoints were standardized according to Funda-mentals of Acupuncture [16]
26 Data Processing
261 Frequencies of Acupoints The frequencies of acupointsmeridians and acupoints on different body parts wereanalyzed using the Data Excavation Platform of AcupointSpecificity
262AssociationRulesMiningAprioriAlgorithm for associa-tion rules mining [17] was adopted to analyze the frequencies
and support of acupoint combinations According to thedefinition of association rules mining [18] the followingcan be a statement of association rules mining for acupointcombination Let 119868 = 119894
1 1198942 119894
119898 be a set of acupoints
Let119863 be a set of acupoint prescriptions where each acupointprescription119879 is a set of acupoints such that119879 sube 119868 Associatedwith each acupoint prescription is a unique identifier calledTID An acupoint prescription 119879 contains 119883 a set of someacupoints in 119868 if 119883 sube 119879 The rule 119883-119884 has support 119904 in theacupoint prescription set119863 if 119904 of acupoint prescriptions in119863 contain119883 cup 119884
263 Measurement of Network PropertiesCommunity struc-ture is a common characteristic of complex networks andis characterized by more dense internal connections withingroups of nodes than with the rest of the network In thisstudy a hierarchical agglomeration was adopted to detectcommunity structure according to Clauset et al [19] We alsofocused on investigating the set of the most influential nodesin acupoint networks of VaD defined as the nodes with thehighest 119896-core value [20] The 119896-core method is predomi-nantly used in analyzing social networks We employed the119896-core method to obtain the cores of different acupoints The119896-coremethod was implemented as follows First all 1-degreenodeswere removed and the nodeswere further pruned untilno 1-degree nodes remained The remaining nodes formedthe 2-core node set The pruning process was repeated in asimilar manner for other nodes in the network assigned tothe corresponding cores (denoted by 119896s) The nodes with thelargest 119896-core value were defined as the network core Thedegree of each acupoint was also analyzed to measure theinvolvement of the node in the network The degree refers tothe number of nodes to which a focal node is connected [21]Betweenness centrality was also used to analyze an acupointrsquoscentrality in the network Centrality is an important conceptfor the analysis of networks and betweenness centrality isone of the most prominent measures of centrality It is usedto measure the degree to which a node is in a position ofbrokerage by summing up the fractions of shortest pathsbetween other pairs of vertices that pass through it [22]
3 Results
31 Overall Profile of Acupuncture Prescriptions Databasesearching identified 892 records in CNKI 1084 records inCBM and 145 records in PubMed After screening 238acupuncture prescriptions in 238 articles were includedAmong the 238 trials 185 are controlled clinical trials (CCTs)while the other 53 trials have no controls The whole view onthe study quality of the 185 CCTs were shown in Figure 2
32 Frequencies of Acupoints and Meridians Approximately109 meridian-acupoints distributed over 13 meridians and7 extraordinary acupoints have been recorded for 1400 and133 times respectively in modern literature on acupuncturetreatment for VaD The most frequently used meridianwas the Governor Meridian (477 times) Other frequentlyused meridians included the Gallbladder Meridian of Foot
4 Evidence-Based Complementary and Alternative Medicine
0 20 40 60 80 100()
Another bias
Selective reporting
Incomplete outcome data
Blinding of outcome assessment
Blinding of participants and personnel
Allocation concealment
Random sequence generation
Low riskUnclear riskHigh risk
Figure 2 Whole view on the study quality of the 185 CCTs
020406080
100120140160180200
Frequency
Baih
ui (G
V20
)
Sish
enco
ng (E
X-H
N1
)
Feng
chi (
GB20
)
Shui
gou
(GV26
)
Shen
ting
(GV24
)
Nei
guan
(PC6
)
Zusa
nli (
ST36
)
Sany
injia
o (S
P6
)
Shen
men
(HT7
)
Taix
i (KI
3)
Bens
hen
(GB13
)
Shen
shu
(BL23
)
Feng
long
(ST40
)
Taic
hong
(LV3
)
Daz
hui (
GV14
)
Xuan
zhon
g (G
B39
)
Feng
fu (G
V16
)
Heg
u (L
I4)
Quc
hi (L
I11
)
Yint
ang
(EX-
HN3
)
Figure 3 The 20 most frequent acupoints and their frequencies
Shaoyang and the Stomach Meridian of Foot Yangmingwhich were reported for 218 and 124 times respectivelyExtraordinary acupoints were also frequently used Baihui(GV 20) Sishencong (EX-HN 1) Fengchi (GB 20) Shuigou(GV 26) and Shenting (GV 24) which were among thetop five acupoints in frequency were recorded for 176 12493 86 and 84 times respectively The frequencies of eachmeridian and acupoint are shown in Table 1The twentymostfrequently used acupoints are shown in Figure 3
33 Frequencies of Acupoints on Different Body Parts Acu-points on the head face and neck were used most frequentlywith a total number of 42 acupoints and a total frequencyof 766 times followed by acupoints on the lower limbs (383
times) upper limbs (214 times) back and lumbar (127 times)and chest and abdomen (43 times) (Figures 4(a) and 4(b))
34 Frequencies of Specific Acupoints Specific acupoints rep-resented 78 of the 116 acupoints (6724) Specific acupointshave been used 1292 times representing 8428 of the totalfrequency of all acupoints (Figures 4(c) and 4(d))
35 Frequencies and Support of Acupoint Combinations Acu-point combinations between Baihui (GV 20) Sishencong(EX-HN 1) Fengchi (GB 20) Shenting (GV 24) Shuigou(GV 26) and Zusanli (ST 36) were used most frequentlyThe 15most frequently used acupoint combinations and theirsupport and confidence are shown in Table 2
Evidence-Based Complementary and Alternative Medicine 5
Table1Statisticso
fmeridians
andacup
ointsinthem
odernliteratureo
nacup
uncturetreatmentfor
VaD
Num
ber
Meridian
Frequency
Num
bero
facupo
ints
Acup
ointsa
ndtheirfrequ
encies
1GV
477
26
Baihui
(GV20)176Shu
igou
(GV26)8
6Sh
entin
g(G
V24)8
4Dazhu
i(GV14)2
7Feng
fu(G
V16)2
3Yintang(EX-
HN3)
16N
aohu
(GV17)13Shangxing(G
V23)11Mingm
en(G
V4)
8Yamen
(GV15)5
Qiang
jian(G
V18)5
Qiand
ing(G
V21)4
Yaoyang
guan
(GV3)
3Zh
iyang(G
V9)
3Jin
suo(G
V8)
2Shendao(G
V11)1Z
hong
shu(G
V7)
1Taod
ao(G
V13)1Lingtai(G
V10)1C
hangqiang(G
V1)1Xu
anshu
(GV5)
1Yaoshu
(GV2)
1Shenzhu(G
V12)1Jizho
ng(G
V6)
1Hou
ding
(GV19)1X
inhu
i(GV22)1
2GB
218
20
Fengchi(GB20)9
3Be
nshen(G
B13)4
7Xu
anzhon
g(G
B39)2
4Shuaigu(G
B8)
7Wangu
(GB12)6
To
ulinqi(G
B15)6
Qub
in(G
B7)
5Xu
anli(G
B6)
4Naokong
(GB19)4
Zuq
iaoyin
(GB44
)3Yanglingquan
(GB34)3
Yangbai(G
B14)3
Hanyan(G
B4)
2Qiuxu
(GB40
)2Fengshi
(GB31)2
Tou
qiaoyin(G
B11)2
Xu
anlu(G
B5)
2Muchu
ang(G
B16)1Z
heng
ying
(GB17)1Z
hongdu
(GB32)1
3EX
-HN
133
7Sishencong
(EX-
HN1)123Taiyang(EX-
HN5)
4Wailaogon
g(EX-
UE8)
2Sh
iqizhu
i(EX
-B8)
1Ba
xie
(EX-
UE9)
1Anm
ian(EX-
HN22)1Y
iming(EX-
HN14)1
4ST
124
7Zu
sanli(ST
36)7
2Feng
long
(ST40
)40To
uwei(ST8)
6Lidu
i(ST
45)2
Sibai(ST2)
2Fu
tu(ST32)1
Renying(ST9)
1
5BL
103
15Shenshu(BL23)4
3Ganshu(BL18)12Tianzhu(BL10)10Pishu(BL20)8
Feiyang
(BL58)8
Geshu
(BL17)
7Xinshu
(BL15)4
Zhiyin(BL67)2
Kun
lun(BL60)2
Yuzhen(BL9)
2To
ngtia
n(BL7)
1Ch
engjin
(BL56)
1Dazhu
(BL11)
1Weizhon
g(BL40
)1Q
ucha
(BL4)
16
SP96
5Sanyinjiao(SP6)
71X
uehai(SP
10)14Taibai(SP3)
8Yinb
ai(SP1)2Yinlingquan(SP9)
17
PC86
5Neigu
an(PC6)
73Z
hongchon
g(PC9)
4Daling(PC7)
4Jianshi
(PC5)
3Laogon
g(PC8)
28
KI83
5Taixi(KI
3)57D
azho
ng(K
I4)12Yo
ngqu
an(K
I1)10Zh
aohai(KI
6)8Ra
ngu(K
I2)2
9HT
673
Shenmen
(HT7)
62Shaocho
ng(H
T9)
3Jiq
uan(H
T1)2
10LI
457
Hegu(LI4
)20Quchi
(LI11)18Shang
yang
(LI1)2
Sho
usanli(LI10)
2Binao(LI14)
1Jianyu(LI15)
1Ying
xiang(LI2
0)1
11CV
435
Qihai(C
V6)
11Z
hong
wan
(CV12)10Guanyuan(C
V4)
9Danzhon
g(C
V17)9
Shenq
ue(C
V8)
412
LV40
2Taicho
ng(LV3)
37D
adun
(LV1)3
13TE
115
Waigu
an(TE5)
6Guancho
ng(TE1)2Sizhuk
ong(TE23)1Jiaosun
(TE20)1Sidu(TE9)
114
LU4
2Shaoshang(LU11)3
Liequ
e(LU
7)1
15SI
32
Shaoze
(SI1)2
Yanggu(SI5
)116
Total
1533
116GV
Governo
rMeridianGB
Gallbladd
erMeridianof
Foot
Shaoyang
EX-
HNextraordinary
acup
ointSTStom
achMeridianof
Foot
Yang
mingBL
Bladd
erMeridianof
Foot
TaiyangSPSpleenMeridianof
Foot
TaiyinP
CPeric
ardium
Meridianof
HandJueyinK
IKidn
eyMeridianof
Foot
Shaoyin
HTHeartMeridianof
HandSh
aoyin
CVC
onceptionVe
ssel
LIL
arge
Intestine
Meridianof
HandYang
mingLV
Liver
Meridianof
Foot
JueyinT
ETripleEn
ergizero
fHandSh
aoyang
LU
Lung
Meridianof
HandTaiyinSISm
allIntestin
eofH
andTaiyangFrequencieso
fmeridians
refertothetotalfre
quencies
ofacup
ointso
nthe
samem
eridian
Num
bero
facupo
intsrefertothetotalnu
mbero
facupo
intson
thes
amem
eridian
6 Evidence-Based Complementary and Alternative Medicine
Table 2 Statistics of the 15 most frequently used acupoint combinations in the treatment of VaD
Number Acupoint combination Frequency Support ()1 Baihui (GV 20) Sishencong (EX-HN 1) 98 41182 Baihui (GV 20) Fengchi (GB 20) 81 34033 Baihui (GV 20) Shuigou (GV 26) 72 29834 Baihui (GV 20) Shenting (GV 24) 70 29415 Baihui (GV 20) Zusanli (ST 36) 62 26056 Sishencong (EX-HN 1) Fengchi (GB 20) 60 25217 Baihui (GV 20) Sanyinjiao (SP 6) 57 23958 Baihui (GV 20) Neiguan (PC 6) 54 22699 Sishencong (EX-HN 1) Shuigou (GV 26) 51 214310 Sishencong (EX-HN 1) Baihui (GV 20) Fengchi (GB 20) 51 214311 Baihui (GV 20) Shenmen (HT 7) 51 214312 Sishencong (EX-HN 1) Shenting (GV 24) 49 205913 Sishencong (EX-HN 1) Neiguan (PC 6) 46 193314 Baihui (GV 20) Taixi (KI 3) 46 193315 Sishencong (EX-HN 1) Baihui (GV 20) Shuigou (GV 26) 43 1807Support refers to the percentage of acupoint prescriptions containing the acupoint combination
36 Community Structure Community detection resultedin the division of the 116 acupoints into 5 communitiesNodes of the same color belong to the same community Thecommunity structure is shown in Figure 5(a)
37 Acupoint 119870-Core Network The largest 119896-core value was19 At this value there were 28 nodes corresponding to Hegu(LI 4) Quchi (LI 11) Zusanli (ST 36) Fenglong (ST 40)Sanyinjiao (SP 6) Xuehai (SP 10) Shenmen (HT 7) Tianzhu(BL 10) Xinshu (BL 15) Ganshu (BL 18) Shenshu (BL 23)Taixi (KI 3) Dazhong (KI 4) Neiguan (PC 6) Benshen (GB13) Fengchi (GB 20) Xuanzhong (GB 39) Taichong (LV 3)Mingmen (GV 4) Dazhui (GV 14) Yamen (GV 15) Fengfu(GV 16) Baihui (GV20) Shenting (GV24) Shuigou (GV26)Guanyuan (CV 4) Sishencong (EX-HN 1) and Yintang (EX-HN 3) as shown in Figure 5(b)
38 Degree The top 20 acupoints in degree are shownin Figure 6(a) Baihui (GV 20) Sishencong (EX-HN 1)Fengchi (GB 20) Shenting (GV 24) and Neiguan (PC 6)had the highest degrees with values of 89 76 68 67 and 65respectively
39 Betweenness Centrality Thetop 20 acupoints in between-ness centrality are shown in Figure 6(b) Yongquan (KI 1)Baihui (GV 20) and Sishencong (EX-HN 1) had the highestbetweenness centrality
4 Discussion
41 Potential Acupoints and Combinations for VaD In thisstudy acupoints and combinations with potential for treat-ing VaD were discovered These results may provide somereference for the selection of acupoints in treatment forVaD which may promote the therapeutic effects in clinicalpractice The results suggest that Baihui (GV 20) Sishencong(EX-HN 1) Fengchi (GB 20) Shuigou (GV 26) and Shenting
(GV 24) are potential acupoints for treating VaD In terms ofmeridian acupoints on the Governor Meridian have poten-tial for treating VaD From the perspective of combinationscombinations between such acupoints as Baihui (GV 20)Sishencong (EX-HN 1) Fengchi (GB 20) Shenting (GV 24)Shuigou (GV 26) and Zusanli (ST 36) have potential fortreating VaD In addition acupoints on the head face andneck have more potential for VaD than acupoints on otherregions of the body Specific acupoints have more potentialthan nonspecific acupoints Specific acupoints with specificnames are a group of acupoints on fourteen meridians withspecific therapeutic effectsThere are ten types of specific acu-points Five-Shu acupoints Yuan-Primary acupoints Luo-Connecting acupoints Xi-Cleft acupoints Lower He-Seaacupoints Back-Shu acupoints Front-Mu acupoints eightinfluential acupoints eight confluent acupoints connectingthe eight extra meridians and convergent acupoints
Community detection divided the acupoints into 5 com-munities Acupoints within the same community have somecharacteristics in common Blue nodes (Community A) wereall Jing-Well acupoints Yellow nodes (Community B) were allacupoints on the face and head Most green nodes (Commu-nity C) were acupoints on the four limbs Most purple nodes(Community D) were acupoints belonging to Governor Ves-sel Most red nodes (Community E) were specific acupointsor acupoints with specific therapeutic effects and only thiscommunity contained Bach-Shu acupoints and acupointson the abdomen Acupoints within the same communitywere more densely connected with each other comparedwith acupoints from different communities indicating thatan acupoint was more often used with acupoints withinthe same community compared with acupoints within othercommunities
The 19-core network indicated that 28 acupoints includ-ing Hegu (LI 4) Quchi (LI 11) Zusanli (ST 36) Fenglong(ST 40) Sanyinjiao (SP 6) Xuehai (SP 10) Shenmen (HT 7)
Evidence-Based Complementary and Alternative Medicine 7
0
5
10
15
20
25
30
35
40
45
Head faceand neck
Lowerlimbs
Upperlimbs
Back andlumbar
Chest andabdomen
Number
(a) The numbers of acupoints in different parts
0
100
200
300
400
500
600
700
800
900
Head faceand neck
Lowerlimbs
Upperlimbs
Back andlumbar
Chest andabdomen
Frequency
(b) The frequencies of acupoints in different parts
0
5
10
15
20
25
30
35
40
Number
Con
verg
ent a
cupo
int
Five
-Shu
acup
oint
Yuan
-sou
rce p
oint
Luo-
Con
nect
ing
poin
t
Eigh
t infl
uent
ial p
oint
Shu-
Back
poi
nt
Eigh
t con
fluen
t acu
poin
ts
Fron
t-Mu
poin
t
Low
er H
e-Se
a poi
nt
Non
spec
ifc p
oint
(c) The numbers of different kinds of acupoints
0
100
200
300
400
500
600
700
800
Frequency
Con
verg
ent a
cupo
int
Five
-Shu
acup
oint
Yuan
-sou
rce p
oint
Luo-
Con
nect
ing
poin
t
Eigh
t infl
uent
ial p
oint
Shu-
Back
poi
nt
Eigh
t con
fluen
t acu
poin
ts
Fron
t-Mu
poin
t
Low
er H
e-Se
a poi
nt
Non
spec
ifc p
oint
(d) The frequencies of different kinds of acupoints
Figure 4 The frequencies and numbers of acupoints in different body parts and different types of acupoints
Tianzhu (BL 10) Xinshu (BL 15) Ganshu (BL 18) Shenshu(BL 23) Taixi (KI 3) Dazhong (KI 4) Neiguan (PC 6)Benshen (GB 13) Fengchi (GB 20) Xuanzhong (GB 39)Taichong (LV 3) Mingmen (GV 4) Dazhui (GV 14) Yamen(GV 15) Fengfu (GV 16) Baihui (GV 20) Shenting (GV 24)Shuigou (GV 26) Guanyuan (CV 4) Sishencong (EX-HN 1)and Yintang (EX-HN 3) are core acupoints in the network
Baihui (GV 20) Sishencong (EX-HN 1) Fengchi (GB20) Shenting (GV 24) and Neiguan (PC 6) had the highestdegreesThis result indicates that these 5 acupoints have beencombined with more acupoints than other acupoints Theseacupoints have specific therapeutic effects on VaDThereforethese acupoints can be used together with other acupoints toenhance therapeutic effects
Yongquan (KI 1) Baihui (GV 20) Sishencong (EX-HN1) Neiguan (PC 6) and Shenting (GV 24) which belonged
to 4 different communities had higher betweenness cen-trality Yongquan (KI 1) which had the highest betweennesscentrality did not have a relatively high degree However itconnects Jing-Well acupoints with other types of acupointsresulting in a high betweenness centrality Acupoints withhigher betweenness centrality play an important role inconnecting different types of acupoints Jing-Well acupointsexcept Yongquan (KI 1) were often used with other Jing-Wellacupoints only Yongquan (KI 1) was not only used with otherJing-Well acupoints but also with other types of acupointssuch as other types of specific acupoints nonspecific acu-points and acupoints on other parts The high betweennesscentrality suggested that Yongquan (KI 1) may have multipleeffects compared with other Jing-Well acupoints in treatmentof VaD From the perspective of TCM theory Jing-Wellacupoints can restore consciousness Yongquan (KI 1) was
8 Evidence-Based Complementary and Alternative Medicine
BL17
EX-HN22
BL7
LI1
GV13
SP9
GB11
EX-HN14
GB4
HT1
ST2
CV8
GB5
GV18
BL11
EX-UE8
LI20
GV1
ST36
BL20
CV17
BL58
BL9
GV17
GV14
GV15
GV11
GV12
GV10GV5
KI3
KI1
LU11
HT9
GV8
GV3
BL23
GV4
CV6
CV12
HT7GB20
GB17
GV24
GV16
CV4
GB8
GV21GV23GB13
SP10
BL10
ST32
GB34LI14
LI15
GB32
LI10
BL40
GB31
KI6
SI5
KI2
PC7
LI4
GB16
EX-HN5
GB12
PC8
PC6
BL18
BL15
BL56
GB40
TE9
EX-UE9SP6
TE5
SP3
LI11
GV22
BL60
GB6
GB14
GB15
GB19
ST9
GV7
GV2
GV6
EX-B8
BL4
SI1
PC9
TE1ST45
SP1
BL67
GB44
LV1
TE23
TE20
LU7
GV19
ST40
EX-HN3ST8
GV20
KI4
GB39
GB7
EX-HN1
PC5
LV3
GV9
GV26
(a) Network structure of acupoints for the treatment of VaD
GB13
EX-HN1
EX-HN3
LI4
KI3
KI4
HT7GB20
GV14
GV15
GV16
LV3
ST36
BL23
GV4
GV24
GV26GV20
ST40
SP6
LI11
GB39
SP10
PC6
BL10
CV4
BL18
BL15
(b) 19-core network
Figure 5 (a) Network structure of acupoints for the treatment of VaD Blue nodes (Community A) are all Jing-Well acupoints Yellow nodes(Community B) are all acupoints on the face and head Most green nodes (Community C) are acupoints on four limbs Most purple nodes(Community D) are acupoints belonging to Governor Vessel Most red nodes (Community E) are specific acupoints or acupoints withspecific therapeutic effects and only this community contains Bach-Shu acupoints and acupoints on the abdomen Acupoints within thesame community are more densely connected with each other than acupoints from different communities (b) 19-core network There are 28acupoints in the 19-core network They are core acupoints in the treatment of VaD
Evidence-Based Complementary and Alternative Medicine 9
0102030405060708090
100
GV
20
EX-H
N1
GB2
0
GV
24
PC6
SP6
GV
14
GV
26
GV
16
HT7 LI
4
KI3
ST36
ST40
LV3
GB1
3
EX-H
N3
BL10
GB3
9
LI 1
1
Degree
(a) The 20 acupoints with highest degree
0002004006008
01012014016
KI1
GV
20
EX-H
N1
PC6
GV
26
GB2
0
GV
24
GV
14 SP6
EX-H
N3
HT7 LI
4
KI3
GV
16
BL10
LV3
ST40
ST36
GB1
3
PC9
Betweenness centrality
(b) The 20 acupoints with highest betweenness centrality
Figure 6 The 20 acupoints with highest degree and the 20 acupoints with highest betweenness centrality
also used to tonify kidney in treatment of VaD ThereforeYongquan (KI 1) is used not only with other Jing-Wellacupoints but also with other types of acupoints such asother types of specific acupoints nonspecific acupoints andacupoints on other parts
42 UnderlyingMolecularMechanism of the Acupoint with theMost Potential to Treat VaD According to our results Baihui(GV 20) which had the highest frequency has the mostpotential to treat VaD A systematic review andmeta-analysisalso suggested that Baihui (GV 20) is a principal acupoint foracute intracerebral hemorrhage (ICH) in animal models ofacute ICH there was no difference in efficacy between Baihui(GV 20) alone and Baihui (GV 20) plus other acupoints [23]
Molecular biology studies have provided insights intothe mechanisms underlying the effects of Baihui (GV 20) inVaD treatment including antioxidant effects antiapoptoticeffects neurotrophic effects reduced blood-brain barrier(BBB) permeability and regulation of the cholinergic anddopaminergic systems Acupuncture at Baihui (GV 20) incombination with other acupoints decreases levels of 8-hydroxy-21015840-deoxyguanosine a product of oxidative damageto DNA induced by free radicals suggesting that the benefitof acupuncture is partly due to antioxidant effects [11]Acupuncture exerts therapeutic effects on VaD via antiapop-tosis The tumor suppressors p53 and Noxa are important inregulating apoptosis and mediate hypoxic cell death [24 25]
Electroacupuncture at Baihui (GV 20) Dazhui (GV 14) andShenshu (BL 23) blocks expression of p53 and Noxa in thehippocampal CA1 region of VaD rats [26] Acupuncture atBaihui (GV 20) can improve neurogenesis via regulatingbrain-derived neurotrophic factor (BDNF) and cyclic AMPresponse element-binding protein (CREB) BDNF whichis essential for synaptic plasticity and is coupled to CREBactivation [27] is important for long-term memory storage[28] CREB is required for the proliferation growth survivaland differentiation of all types of cells In the brain the CREBand CRE-mediated system is involved in memory learningsynaptic transmission neuron survival differentiation andaxon growth [29] Acupuncture at Baihui (GV 20) signifi-cantly increases the levels of BDNF [15 30] CREB proteinsCREB mRNA [30] and phosphorylated CREB the activeform of CREB [15] The molecular mechanism underlyingacupuncture at Baihui (GV 20) also involves cholinergicsystem regulation Decreased cholinergic function in thebrain can result in a decline in memory and cognitivefunction [31] Acupuncture at Baihui (GV 20) significantlyincreases the levels of choline acetyltransferase (ChAT) andrestores the expression of choline transporter 1 (CHT1)and vesicular acetylcholine transporter (VAChT) [30] Thedopaminergic system is also involved in the mechanismunderlying the treatment of VaD with acupuncture at Baihui(GV 20) Dopamine is a key regulator in specific synapticchanges observed at certain stages of learning and memory
10 Evidence-Based Complementary and Alternative Medicine
and of synaptic plasticity [32] Acupuncture at Baihui (GV20)increases dopamine levels in chronic cerebral hypoperfusionand ischemia-reperfusion injured rats [33] In additionacupuncture at Baihui (GV 20) and Zusanli (ST 36) preservesthe integrity of the BBB reducing BBB permeability TheBBB is constructed of tight conjunctions including occludinand claudin-5 which form the endothelial barrier Reducedexpression of ZO-1 claudin-5 and occludin mRNA andprotein contributes to BBB breakdown and edema in theischemic brain [34] Electroacupuncture at Baihui (GV 20)and Zusanli (ST 36) reduces brain damage and relatedbehavioral deficits via upregulation of tight conjunctionproteins including ZO-1 claudin-5 and occludin [35]Thesefindings reveal parts of the molecular mechanism underlyingacupuncture at Baihui (GV 20) to treat VaD
43 Acupoints Selection in Treatment for VaD The properselection of acupoints is essential for the therapeutic effectsof acupuncture because acupoints are specific with regard tomorphological structure biophysical properties pathologicalresponse and stimulating effects [36] This specificity dif-ferentiates acupoints from nonacupoints as well as differentacupoints from one another The specific therapeutic effectsof different acupoints have been reported for migraine [37]functional dyspepsia [38] ischemic stroke [39] and so forth
The specificity of acupoints for the treatment of VaDhas also been reported Phosphorylated CREB levels weresignificantly increased after acupuncture therapy of needlingBaihui (GV 20) and Zusanli (ST 36) compared to shamacupuncture therapy of needling nonacupoints [15] Baihui(GV 20) Shuigou (GV 26) and Shenmen (HT 7) are allamong the 10 acupoints with the most potential A clinicaltrial demonstrated that needling Baihui (GV 20) Shuigou(GV 26) and Shenmen (HT 7) were all effective in improvingthe symptoms of VaD However their therapeutic effects dif-fer Needling Baihui (GV 20) improved calculation ability andshort-term memory and corrected the personality changesof VaD patients while needling Shuigou (GV 26) improvednaming ability and short-term memory The therapeuticeffects of needling Baihui (GV 20) and Shuigou (GV 26)were superior to those of needling Shenmen (HT 7) [40]A PET and SPECT study revealed that needling these threedifferent acupoints in VaD patients affected different brainareas Needling Baihui (GV 20) activated the inner temporalsystem the thalamencephalon system and the prefrontalcortical system Needling Shuigou (GV 26) activated the pre-frontal cortical system Needling Shenmen (HT 7) generatedan effect similar to but weaker than the effect generated byneedling Shuigou (GV 26) [41] These findings demonstratethat different acupoints have different therapeutic effects inacupuncture treatment for VaD Consequently the selectionof acupoints which directly influences the therapeutic effectsof acupuncture should be considered carefully According toour results based on datamining Baihui (GV 20) Sishencong(EX-HN 1) Fengchi (GB 20) Shuigou (GV 26) and Shenting(GV 24) which have higher frequencies in the modernliterature may have better therapeutic effects on VaD
44 SingleAcupoint orAcupoint Combination Acupoint com-binations also influence the therapeutic effects of acupunc-ture An acupoint combination is considered to have asynergistic effect that enhances the therapeutic effect ofacupuncture For example a lower prevalence of postoper-ative nausea and vomiting in patients treated with Neiguan(PC 6) plus Hegu (LI 4) was observed compared with thosetreated with Neiguan (PC 6) only [42] In spite of extensiveevidence suggesting a synergistic effect of acupoint combi-nation and supporting its use some studies have reportedantagonistic effects [43ndash45] An antagonistic effect occurswhen one acupoint weakens the therapeutic effect of anotheracupoint [46] For example electroacupuncture can improvegastrointestinal movement in rats The effect of needlingPishu (BL 20) alone was better than the effect of needlingPishu (BL 20) and Zusanli (ST 36) at the same time [44]Therefore whether the effect of acupoint combination isbetter than a single acupoint still remains a question andneeds to be further studied
Some studies have compared single acupoints and anacupoint combination for the treatment of VaD The thera-peutic effect of needling Baihui (GV 20) Shuigou (GV 26)and Shenmen (HT 7) in combination was better than theeffects obtained by needling each alone [40] In additionneedling Baihui (GV 20) Shuigou (GV 26) and Shenmen(HT 7) simultaneously activated more brain areas relatedto intellectual activities compared with needling each alonegenerating a more extensive effect on the brain [41] Antago-nistic effects in acupuncture therapy for VaD have not beenreported but may occur Most acupuncture prescriptions forVaD contain acupoint combinations and the use of acupointcombinations is supported However acupoint combinationsshould be selected carefully to avoid antagonistic effects Itis hard to tell whether a combination of acupoints will exertantagonistic effects with current knowledge or TCM theoryAs abovementioned acupoints with similar functions canexert antagonistic effects There are many acupoints and thenumber of acupoint combinations will grow geometricallyTo test the antagonistic effects of each combination oneby one is an exhausting job To avoid antagonistic effectsas possible the acupoint prescriptions should be simplifiedas possible The general principle is to select acupointswith relatively better therapeutic effects and acupoints withmultiple indications and not to select many acupoints
45 Limitations This study has limitations as follows Firstother factors that influence acupuncture such as manipula-tion and treatment duration were not analyzed in this studyThese data can be further mined in future studies Secondlargely due to the lack of treatment based on syndrome differ-entiation and different methods of syndrome differentiationin modern literature potential acupoints and combinationsfor different syndromes of VaD were not analyzed Althoughtreatment based on syndrome differentiation is importantand is often emphasized in TCM treatment based on diseasedifferentiation is equally important Third the real therapeu-tic effects of acupoints and combinations on VaD cannotbe reflected by frequencies in the literature However theseresults suggest some potential acupoints and combinations to
Evidence-Based Complementary and Alternative Medicine 11
be explored in future clinical trials to validate the effects ofacupuncture on VaD To optimize the acupoint prescriptiondata may be extracted not only from literature but alsofrom clinical practice Further research can collect acupointprescriptions and symptom improvements in clinical practiceand optimize acupoint prescriptionwith dataminingMiningclinical data has been practiced to optimize prescriptionof Chinese herbal medicine for unstable angina by Fenget al [47] In their study five main symptoms of patientswith unstable angina the severity of each symptom andthe prescription of each patient were collected The levels ofaverage discounted reward (ADR) of different prescriptionswere calculated to evaluate the clinical efficacy of differ-ent treatment options with some optimized prescriptionsachieved Future studies can mine clinical data to optimizeacupoint prescription
5 Conclusions
In this study data mining was used to discover potentialacupoints and combinations for VaD Potential acupointsinclude Baihui (GV 20) Sishencong (EX-HN 1) Fengchi (GB20) Shuigou (GV 26) and Shenting (GV 24) In additioncombinations between Baihui (GV 20) Sishencong (EX-HN1) Fengchi (GB 20) Shenting (GV 24) Shuigou (GV 26) andZusanli (ST 36) were potential combinations Based on ourresults Baihui (GV 20) and Sishencong (EX-HN 1) shouldbe selected with priority Acupoints in head compared toacupoints in other parts should also be selected with priority
Conflict of Interests
The authors declare no conflict of interests
Authorsrsquo Contribution
Shuwei Feng and Yulan Ren contributed equally to this work
Acknowledgments
This study was supported by the National Basic ResearchProgram of China (no 2012CB518501) and the NationalScience Foundation of China (nos 81102742 and 61104224)
References
[1] Q Chen X Wu S F Lu et al ldquoMeridian acupoints selectionin acupuncture treatment for migraine the main charactersand relevant factors analysisrdquo Liaoning Journal of TraditionalChinese Medicine vol 36 no 9 pp 1477ndash1480 2009
[2] Y Li H Zheng C M Witt et al ldquoAcupuncture for migraineprophylaxis a randomized controlled trialrdquo Canadian MedicalAssociation Journal vol 184 no 4 pp 401ndash410 2012
[3] B H May C Lu L Bennett H M Hugel and C C LXue ldquoEvaluating the traditional Chinese literature for herbalformulae and individual herbs used for age-related dementiaand memory impairmentrdquo Biogerontology vol 13 no 3 pp299ndash312 2012
[4] L Zhang Y Li X Guo et al ldquoText mining of the classicalmedical literature for medicines that show potential in diabeticnephropathyrdquo Evidence-Based Complementary and AlternativeMedicine vol 2014 Article ID 189125 12 pages 2014
[5] Y Olsson A Brun and E Englund ldquoFundamental pathologicallesions in vascular dementiardquo Acta Neurologica Scandinavicavol 94 supplement 168 pp 31ndash38 1996
[6] S Davis M Shanahan A Campbell M Hegarty and BMcCarthy ldquoPalliative care for people with dementia aged carestaff perspectivesrdquo Alzheimerrsquos amp Dementia vol 7 no 4 p e502011
[7] J Jia F Wang C Wei et al ldquoThe prevalence of dementia inurban and rural areas of Chinardquo Alzheimerrsquos and Dementia vol10 no 1 pp 1ndash9 2014
[8] C P Ferri M Prince C Brayne et al ldquoGlobal prevalence ofdementia a Delphi consensus studyrdquo The Lancet vol 366 no9503 pp 2112ndash2117 2005
[9] W Quentin S G Riedel-Heller M Luppa A Rudolph andH-H Konig ldquoCost-of-illness studies of dementia a systematicreview focusing on stage dependency of costsrdquoActa PsychiatricaScandinavica vol 121 no 4 pp 243ndash259 2010
[10] J Yu X Zhang C Liu Y Meng and J Han ldquoEffect ofacupuncture treatment on vascular dementiardquo NeurologicalResearch vol 28 no 1 pp 97ndash103 2006
[11] G-X Shi C-Z Liu Q-Q Li H Zhu and L-P WangldquoInfluence of acupuncture on cognitive function and markersof oxidative DNA damage in patients with vascular dementiardquoJournal of Traditional Chinese Medicine vol 32 no 2 pp 199ndash202 2012
[12] X-Y Zhong X-X Su J Liu and G Q Zhu ldquoClinical effectsof acupuncture combined with nimodipine for treatment ofvascular dementia in 30 casesrdquo Journal of Traditional ChineseMedicine vol 29 no 3 pp 174ndash176 2009
[13] T Wang C-Z Liu J-C Yu W Jiang and J-X Han ldquoAcupunc-ture protected cerebral multi-infarction rats from memoryimpairment by regulating the expression of apoptosis relatedgenes Bcl-2 and Bax in hippocampusrdquo Physiology and Behaviorvol 96 no 1 pp 155ndash161 2009
[14] I K Hwang J Y Chung D Y Yoo et al ldquoComparing the effectsof acupuncture and electroacupuncture at Zusanli and Baihuion cell proliferation and neuroblast differentiation in the rathippocampusrdquo Journal of VeterinaryMedical Science vol 72 no3 pp 279ndash284 2010
[15] I K Hwang J Y Chung D Y Yoo et al ldquoEffects ofelectroacupuncture at Zusanli and Baihui on brain-derivedneurotrophic factor and cyclic AMP response element-bindingprotein in the hippocampal dentate gyrusrdquo Journal of VeterinaryMedical Science vol 72 no 11 pp 1431ndash1436 2010
[16] Y F Luo and J M Wu Fundamentals of Acupuncture SichuanUniversity Press Sichuan China 2008
[17] R Agrawal and R Srikant ldquoFast algorithms for mining associ-ation rulesrdquo in Proceedings of the 20th International Conferenceon Very Large Data Bases (VLDB rsquo94) pp 487ndash499 SantiagoChile 1994
[18] R Agrawal T Imielinski and A Swami ldquoMining associationrules between sets of items in large databasesrdquo ACM SIGMODRecord vol 22 no 2 pp 207ndash216 1993
12 Evidence-Based Complementary and Alternative Medicine
[19] A Clauset M E J Newman and C Moore ldquoFinding commu-nity structure in very large networksrdquo Physical Review E vol 70no 6 Article ID 066111 6 pages 2004
[20] G F de Arruda A L Barbieri P M Rodriguez et al ldquoRoleof centrality for the identification of influential spreaders incomplex networksrdquo Physical Review E Statistical Nonlinearand SoftMatter Physics vol 90 no 1ndash3 Article ID 032812 2014
[21] T Opsahl F Agneessens and J Skvoretz ldquoNode centrality inweighted networks generalizing degree and shortest pathsrdquoSocial Networks vol 32 no 3 pp 245ndash251 2010
[22] U Brandes ldquoOn variants of shortest-path betweenness central-ity and their generic computationrdquo Social Networks vol 30 no2 pp 136ndash145 2008
[23] H Q Li J H Li A J Liu M Y Ye and G Q ZhengldquoGV20-based acupuncture for animal models of acute intrac-erebral haemorrhage a preclinical systematic review and meta-analysisrdquo Acupuncture in Medicine vol 32 no 6 pp 495ndash5022014
[24] EOda ROhkiHMurasawa et al ldquoNoxa a BH3-onlymemberof the Bcl-2 family and candidate mediator of p53-inducedapoptosisrdquo Science vol 288 no 5468 pp 1053ndash1058 2000
[25] H Endo H Kamada C Nito T Nishi and P H Chan ldquoMito-chondrial translocation of p53 mediates release of cytochromec and hippocampal CA1 neuronal death after transient globalcerebral ischemia in ratsrdquo Journal of Neuroscience vol 26 no30 pp 7974ndash7983 2006
[26] Y Zhu and Y Zeng ldquoElectroacupuncture protected pyramidalcells in hippocampal CA1 region of vascular dementia rats byinhibiting the expression of P53 and Noxardquo CNS NeuroscienceandTherapeutics vol 17 no 6 pp 599ndash604 2011
[27] W J Tyler M Alonso C R Bramham and L D Pozzo-Miller ldquoFrom acquisition to consolidation on the role ofbrain-derived neurotrophic factor signaling in hippocampal-dependent learningrdquo Learning and Memory vol 9 no 5 pp224ndash237 2002
[28] P Bekinschtein M Cammarota C Katche et al ldquoBDNF isessential to promote persistence of long-termmemory storagerdquoProceedings of the National Academy of Sciences of the UnitedStates of America vol 105 no 7 pp 2711ndash2716 2008
[29] K Kitagawa ldquoCREB and cAMP response element-mediatedgene expression in the ischemic brainrdquo FEBS Journal vol 274no 13 pp 3210ndash3217 2007
[30] B Lee B Sur J Shim D Hahm and H Lee ldquoAcupuncturestimulation improves scopolamine-induced cognitive impair-ment via activation of cholinergic system and regulation ofBDNF andCREB expressions in ratsrdquoBMCComplementary andAlternative Medicine vol 14 no 1 article 338 2014
[31] M E Hasselmo ldquoThe role of acetylcholine in learning andmemoryrdquo Current Opinion in Neurobiology vol 16 no 6 pp710ndash715 2006
[32] T M Jay ldquoDopamine a potential substrate for synaptic plastic-ity andmemory mechanismsrdquo Progress in Neurobiology vol 69no 6 pp 375ndash390 2003
[33] C-M Chuang C-L Hsieh T-C Li and J-G Lin ldquoAcupunc-ture stimulation at Baihui acupoint reduced cerebral infarct andincreased dopamine levels in chronic cerebral hypoperfusionand ischemia-reperfusion injured Sprague-Dawley ratsrdquoAmeri-can Journal of ChineseMedicine vol 35 no 5 pp 779ndash791 2007
[34] H Jiao Z Wang Y Liu P Wang and Y Xue ldquoSpecific roleof tight junction proteins claudin-5 occludin and ZO-1 of theblood-brain barrier in a focal cerebral ischemic insultrdquo Journalof Molecular Neuroscience vol 44 no 2 pp 130ndash139 2011
[35] Y-M Zhang H Xu H Sun S Chen and F Wang ldquoElec-troacupuncture treatment improves neurological function asso-ciated with regulation of tight junction proteins in rats withcerebral ischemia reperfusion injuryrdquo Evidence-Based Comple-mentary and Alternative Medicine vol 2014 Article ID 98934010 pages 2014
[36] B-X Jin X-S Lai and C-Z Tang ldquoProgress in researches onthe specificity of acupointsrdquo Acupuncture Research vol 33 no2 pp 135ndash138 2008
[37] Y Li F Liang X Yang et al ldquoAcupuncture for treating acuteattacks of migraine a randomized controlled trialrdquo Headachevol 49 no 6 pp 805ndash816 2009
[38] T T Ma S Y Yu Y Li et al ldquoRandomised clinical trial anassessment of acupuncture on specific meridian or specific acu-point vs sham acupuncture for treating functional dyspepsiardquoAlimentary Pharmacology and Therapeutics vol 35 no 5 pp552ndash561 2012
[39] P-F Shen L Kong L-W Ni et al ldquoAcupuncture interventionin ischemic stroke a randomized controlled prospective studyrdquoThe American Journal of Chinese Medicine vol 40 no 4 pp685ndash693 2012
[40] Y Huang M H Win J Chen et al ldquoA comparative studyon the treatment of vascular dementia by puncturing Baihui(GV20) Shuigou (GV26) and Shenmen (HT7)rdquoWorld Journalof AcupuncturemdashMoxibustion no 1 pp 3ndash10 2005
[41] Y Huang X-S Lai and A-W Tang ldquoComparative study of thespecificities of needling acupoints DU20 DU26 and HT7 inintervening vascular dementia in different areas in the brain onthe basis of scale assessment and cerebral functional imagingrdquoChinese Journal of Integrative Medicine vol 13 no 2 pp 103ndash108 2007
[42] R Alizadeh S Esmaeili S Shoar S Bagheri-Hariri and NShoar ldquoAcupuncture in preventing postoperative nausea andvomiting efficacy of two acupuncture points versus a singleonerdquo Journal of Acupuncture and Meridian Studies vol 7 no2 pp 71ndash75 2014
[43] F M Xu and R X Chen ldquoThe antagonistic effect of acupointson oxygen consumption rate in ratsrdquo Journal of Jiangxi Collegeof Traditional Chinese Medicine vol 13 no 2 pp 60ndash61 2001
[44] F M Xu and R X Chen ldquoEffect of electroacupuncture ongastrointestinalmovement in rats with hypoactive gastrointesti-nal movement caused by greaserdquo Henan Traditional ChineseMedicine vol 20 no 2 pp 19ndash20 2000
[45] X H Li X Z Gao and L Hu ldquoExperimental study on syner-getic and antagonistic effects of acupoints Neiguan Shenmenand Xinshurdquo Chinese Acupuncture andMoxibustion vol 22 no12 pp 819ndash821 2002
[46] X H Li Q Y Wang X Z Gao et al ldquoStudy on cooperationand antagonism among acupointsrdquo Chinese Acupuncture andMoxibustion vol 22 no 6 pp 387ndash388 2002
[47] Y Feng Y Qiu X Zhou Y Wang H Xu and B Liu ldquoOpti-mizing prescription of Chinese herbal medicine for unstableangina based on partially observable Markov decision processrdquoEvidence-based Complementary and Alternative Medicine vol2013 Article ID 532534 6 pages 2013
Submit your manuscripts athttpwwwhindawicom
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Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
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Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
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Disease Markers
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
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OncologyJournal of
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Oxidative Medicine and Cellular Longevity
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PPAR Research
The Scientific World JournalHindawi Publishing Corporation httpwwwhindawicom Volume 2014
Immunology ResearchHindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Journal of
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Computational and Mathematical Methods in Medicine
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Research and TreatmentAIDS
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Gastroenterology Research and Practice
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Parkinsonrsquos Disease
Evidence-Based Complementary and Alternative Medicine
Volume 2014Hindawi Publishing Corporationhttpwwwhindawicom
4 Evidence-Based Complementary and Alternative Medicine
0 20 40 60 80 100()
Another bias
Selective reporting
Incomplete outcome data
Blinding of outcome assessment
Blinding of participants and personnel
Allocation concealment
Random sequence generation
Low riskUnclear riskHigh risk
Figure 2 Whole view on the study quality of the 185 CCTs
020406080
100120140160180200
Frequency
Baih
ui (G
V20
)
Sish
enco
ng (E
X-H
N1
)
Feng
chi (
GB20
)
Shui
gou
(GV26
)
Shen
ting
(GV24
)
Nei
guan
(PC6
)
Zusa
nli (
ST36
)
Sany
injia
o (S
P6
)
Shen
men
(HT7
)
Taix
i (KI
3)
Bens
hen
(GB13
)
Shen
shu
(BL23
)
Feng
long
(ST40
)
Taic
hong
(LV3
)
Daz
hui (
GV14
)
Xuan
zhon
g (G
B39
)
Feng
fu (G
V16
)
Heg
u (L
I4)
Quc
hi (L
I11
)
Yint
ang
(EX-
HN3
)
Figure 3 The 20 most frequent acupoints and their frequencies
Shaoyang and the Stomach Meridian of Foot Yangmingwhich were reported for 218 and 124 times respectivelyExtraordinary acupoints were also frequently used Baihui(GV 20) Sishencong (EX-HN 1) Fengchi (GB 20) Shuigou(GV 26) and Shenting (GV 24) which were among thetop five acupoints in frequency were recorded for 176 12493 86 and 84 times respectively The frequencies of eachmeridian and acupoint are shown in Table 1The twentymostfrequently used acupoints are shown in Figure 3
33 Frequencies of Acupoints on Different Body Parts Acu-points on the head face and neck were used most frequentlywith a total number of 42 acupoints and a total frequencyof 766 times followed by acupoints on the lower limbs (383
times) upper limbs (214 times) back and lumbar (127 times)and chest and abdomen (43 times) (Figures 4(a) and 4(b))
34 Frequencies of Specific Acupoints Specific acupoints rep-resented 78 of the 116 acupoints (6724) Specific acupointshave been used 1292 times representing 8428 of the totalfrequency of all acupoints (Figures 4(c) and 4(d))
35 Frequencies and Support of Acupoint Combinations Acu-point combinations between Baihui (GV 20) Sishencong(EX-HN 1) Fengchi (GB 20) Shenting (GV 24) Shuigou(GV 26) and Zusanli (ST 36) were used most frequentlyThe 15most frequently used acupoint combinations and theirsupport and confidence are shown in Table 2
Evidence-Based Complementary and Alternative Medicine 5
Table1Statisticso
fmeridians
andacup
ointsinthem
odernliteratureo
nacup
uncturetreatmentfor
VaD
Num
ber
Meridian
Frequency
Num
bero
facupo
ints
Acup
ointsa
ndtheirfrequ
encies
1GV
477
26
Baihui
(GV20)176Shu
igou
(GV26)8
6Sh
entin
g(G
V24)8
4Dazhu
i(GV14)2
7Feng
fu(G
V16)2
3Yintang(EX-
HN3)
16N
aohu
(GV17)13Shangxing(G
V23)11Mingm
en(G
V4)
8Yamen
(GV15)5
Qiang
jian(G
V18)5
Qiand
ing(G
V21)4
Yaoyang
guan
(GV3)
3Zh
iyang(G
V9)
3Jin
suo(G
V8)
2Shendao(G
V11)1Z
hong
shu(G
V7)
1Taod
ao(G
V13)1Lingtai(G
V10)1C
hangqiang(G
V1)1Xu
anshu
(GV5)
1Yaoshu
(GV2)
1Shenzhu(G
V12)1Jizho
ng(G
V6)
1Hou
ding
(GV19)1X
inhu
i(GV22)1
2GB
218
20
Fengchi(GB20)9
3Be
nshen(G
B13)4
7Xu
anzhon
g(G
B39)2
4Shuaigu(G
B8)
7Wangu
(GB12)6
To
ulinqi(G
B15)6
Qub
in(G
B7)
5Xu
anli(G
B6)
4Naokong
(GB19)4
Zuq
iaoyin
(GB44
)3Yanglingquan
(GB34)3
Yangbai(G
B14)3
Hanyan(G
B4)
2Qiuxu
(GB40
)2Fengshi
(GB31)2
Tou
qiaoyin(G
B11)2
Xu
anlu(G
B5)
2Muchu
ang(G
B16)1Z
heng
ying
(GB17)1Z
hongdu
(GB32)1
3EX
-HN
133
7Sishencong
(EX-
HN1)123Taiyang(EX-
HN5)
4Wailaogon
g(EX-
UE8)
2Sh
iqizhu
i(EX
-B8)
1Ba
xie
(EX-
UE9)
1Anm
ian(EX-
HN22)1Y
iming(EX-
HN14)1
4ST
124
7Zu
sanli(ST
36)7
2Feng
long
(ST40
)40To
uwei(ST8)
6Lidu
i(ST
45)2
Sibai(ST2)
2Fu
tu(ST32)1
Renying(ST9)
1
5BL
103
15Shenshu(BL23)4
3Ganshu(BL18)12Tianzhu(BL10)10Pishu(BL20)8
Feiyang
(BL58)8
Geshu
(BL17)
7Xinshu
(BL15)4
Zhiyin(BL67)2
Kun
lun(BL60)2
Yuzhen(BL9)
2To
ngtia
n(BL7)
1Ch
engjin
(BL56)
1Dazhu
(BL11)
1Weizhon
g(BL40
)1Q
ucha
(BL4)
16
SP96
5Sanyinjiao(SP6)
71X
uehai(SP
10)14Taibai(SP3)
8Yinb
ai(SP1)2Yinlingquan(SP9)
17
PC86
5Neigu
an(PC6)
73Z
hongchon
g(PC9)
4Daling(PC7)
4Jianshi
(PC5)
3Laogon
g(PC8)
28
KI83
5Taixi(KI
3)57D
azho
ng(K
I4)12Yo
ngqu
an(K
I1)10Zh
aohai(KI
6)8Ra
ngu(K
I2)2
9HT
673
Shenmen
(HT7)
62Shaocho
ng(H
T9)
3Jiq
uan(H
T1)2
10LI
457
Hegu(LI4
)20Quchi
(LI11)18Shang
yang
(LI1)2
Sho
usanli(LI10)
2Binao(LI14)
1Jianyu(LI15)
1Ying
xiang(LI2
0)1
11CV
435
Qihai(C
V6)
11Z
hong
wan
(CV12)10Guanyuan(C
V4)
9Danzhon
g(C
V17)9
Shenq
ue(C
V8)
412
LV40
2Taicho
ng(LV3)
37D
adun
(LV1)3
13TE
115
Waigu
an(TE5)
6Guancho
ng(TE1)2Sizhuk
ong(TE23)1Jiaosun
(TE20)1Sidu(TE9)
114
LU4
2Shaoshang(LU11)3
Liequ
e(LU
7)1
15SI
32
Shaoze
(SI1)2
Yanggu(SI5
)116
Total
1533
116GV
Governo
rMeridianGB
Gallbladd
erMeridianof
Foot
Shaoyang
EX-
HNextraordinary
acup
ointSTStom
achMeridianof
Foot
Yang
mingBL
Bladd
erMeridianof
Foot
TaiyangSPSpleenMeridianof
Foot
TaiyinP
CPeric
ardium
Meridianof
HandJueyinK
IKidn
eyMeridianof
Foot
Shaoyin
HTHeartMeridianof
HandSh
aoyin
CVC
onceptionVe
ssel
LIL
arge
Intestine
Meridianof
HandYang
mingLV
Liver
Meridianof
Foot
JueyinT
ETripleEn
ergizero
fHandSh
aoyang
LU
Lung
Meridianof
HandTaiyinSISm
allIntestin
eofH
andTaiyangFrequencieso
fmeridians
refertothetotalfre
quencies
ofacup
ointso
nthe
samem
eridian
Num
bero
facupo
intsrefertothetotalnu
mbero
facupo
intson
thes
amem
eridian
6 Evidence-Based Complementary and Alternative Medicine
Table 2 Statistics of the 15 most frequently used acupoint combinations in the treatment of VaD
Number Acupoint combination Frequency Support ()1 Baihui (GV 20) Sishencong (EX-HN 1) 98 41182 Baihui (GV 20) Fengchi (GB 20) 81 34033 Baihui (GV 20) Shuigou (GV 26) 72 29834 Baihui (GV 20) Shenting (GV 24) 70 29415 Baihui (GV 20) Zusanli (ST 36) 62 26056 Sishencong (EX-HN 1) Fengchi (GB 20) 60 25217 Baihui (GV 20) Sanyinjiao (SP 6) 57 23958 Baihui (GV 20) Neiguan (PC 6) 54 22699 Sishencong (EX-HN 1) Shuigou (GV 26) 51 214310 Sishencong (EX-HN 1) Baihui (GV 20) Fengchi (GB 20) 51 214311 Baihui (GV 20) Shenmen (HT 7) 51 214312 Sishencong (EX-HN 1) Shenting (GV 24) 49 205913 Sishencong (EX-HN 1) Neiguan (PC 6) 46 193314 Baihui (GV 20) Taixi (KI 3) 46 193315 Sishencong (EX-HN 1) Baihui (GV 20) Shuigou (GV 26) 43 1807Support refers to the percentage of acupoint prescriptions containing the acupoint combination
36 Community Structure Community detection resultedin the division of the 116 acupoints into 5 communitiesNodes of the same color belong to the same community Thecommunity structure is shown in Figure 5(a)
37 Acupoint 119870-Core Network The largest 119896-core value was19 At this value there were 28 nodes corresponding to Hegu(LI 4) Quchi (LI 11) Zusanli (ST 36) Fenglong (ST 40)Sanyinjiao (SP 6) Xuehai (SP 10) Shenmen (HT 7) Tianzhu(BL 10) Xinshu (BL 15) Ganshu (BL 18) Shenshu (BL 23)Taixi (KI 3) Dazhong (KI 4) Neiguan (PC 6) Benshen (GB13) Fengchi (GB 20) Xuanzhong (GB 39) Taichong (LV 3)Mingmen (GV 4) Dazhui (GV 14) Yamen (GV 15) Fengfu(GV 16) Baihui (GV20) Shenting (GV24) Shuigou (GV26)Guanyuan (CV 4) Sishencong (EX-HN 1) and Yintang (EX-HN 3) as shown in Figure 5(b)
38 Degree The top 20 acupoints in degree are shownin Figure 6(a) Baihui (GV 20) Sishencong (EX-HN 1)Fengchi (GB 20) Shenting (GV 24) and Neiguan (PC 6)had the highest degrees with values of 89 76 68 67 and 65respectively
39 Betweenness Centrality Thetop 20 acupoints in between-ness centrality are shown in Figure 6(b) Yongquan (KI 1)Baihui (GV 20) and Sishencong (EX-HN 1) had the highestbetweenness centrality
4 Discussion
41 Potential Acupoints and Combinations for VaD In thisstudy acupoints and combinations with potential for treat-ing VaD were discovered These results may provide somereference for the selection of acupoints in treatment forVaD which may promote the therapeutic effects in clinicalpractice The results suggest that Baihui (GV 20) Sishencong(EX-HN 1) Fengchi (GB 20) Shuigou (GV 26) and Shenting
(GV 24) are potential acupoints for treating VaD In terms ofmeridian acupoints on the Governor Meridian have poten-tial for treating VaD From the perspective of combinationscombinations between such acupoints as Baihui (GV 20)Sishencong (EX-HN 1) Fengchi (GB 20) Shenting (GV 24)Shuigou (GV 26) and Zusanli (ST 36) have potential fortreating VaD In addition acupoints on the head face andneck have more potential for VaD than acupoints on otherregions of the body Specific acupoints have more potentialthan nonspecific acupoints Specific acupoints with specificnames are a group of acupoints on fourteen meridians withspecific therapeutic effectsThere are ten types of specific acu-points Five-Shu acupoints Yuan-Primary acupoints Luo-Connecting acupoints Xi-Cleft acupoints Lower He-Seaacupoints Back-Shu acupoints Front-Mu acupoints eightinfluential acupoints eight confluent acupoints connectingthe eight extra meridians and convergent acupoints
Community detection divided the acupoints into 5 com-munities Acupoints within the same community have somecharacteristics in common Blue nodes (Community A) wereall Jing-Well acupoints Yellow nodes (Community B) were allacupoints on the face and head Most green nodes (Commu-nity C) were acupoints on the four limbs Most purple nodes(Community D) were acupoints belonging to Governor Ves-sel Most red nodes (Community E) were specific acupointsor acupoints with specific therapeutic effects and only thiscommunity contained Bach-Shu acupoints and acupointson the abdomen Acupoints within the same communitywere more densely connected with each other comparedwith acupoints from different communities indicating thatan acupoint was more often used with acupoints withinthe same community compared with acupoints within othercommunities
The 19-core network indicated that 28 acupoints includ-ing Hegu (LI 4) Quchi (LI 11) Zusanli (ST 36) Fenglong(ST 40) Sanyinjiao (SP 6) Xuehai (SP 10) Shenmen (HT 7)
Evidence-Based Complementary and Alternative Medicine 7
0
5
10
15
20
25
30
35
40
45
Head faceand neck
Lowerlimbs
Upperlimbs
Back andlumbar
Chest andabdomen
Number
(a) The numbers of acupoints in different parts
0
100
200
300
400
500
600
700
800
900
Head faceand neck
Lowerlimbs
Upperlimbs
Back andlumbar
Chest andabdomen
Frequency
(b) The frequencies of acupoints in different parts
0
5
10
15
20
25
30
35
40
Number
Con
verg
ent a
cupo
int
Five
-Shu
acup
oint
Yuan
-sou
rce p
oint
Luo-
Con
nect
ing
poin
t
Eigh
t infl
uent
ial p
oint
Shu-
Back
poi
nt
Eigh
t con
fluen
t acu
poin
ts
Fron
t-Mu
poin
t
Low
er H
e-Se
a poi
nt
Non
spec
ifc p
oint
(c) The numbers of different kinds of acupoints
0
100
200
300
400
500
600
700
800
Frequency
Con
verg
ent a
cupo
int
Five
-Shu
acup
oint
Yuan
-sou
rce p
oint
Luo-
Con
nect
ing
poin
t
Eigh
t infl
uent
ial p
oint
Shu-
Back
poi
nt
Eigh
t con
fluen
t acu
poin
ts
Fron
t-Mu
poin
t
Low
er H
e-Se
a poi
nt
Non
spec
ifc p
oint
(d) The frequencies of different kinds of acupoints
Figure 4 The frequencies and numbers of acupoints in different body parts and different types of acupoints
Tianzhu (BL 10) Xinshu (BL 15) Ganshu (BL 18) Shenshu(BL 23) Taixi (KI 3) Dazhong (KI 4) Neiguan (PC 6)Benshen (GB 13) Fengchi (GB 20) Xuanzhong (GB 39)Taichong (LV 3) Mingmen (GV 4) Dazhui (GV 14) Yamen(GV 15) Fengfu (GV 16) Baihui (GV 20) Shenting (GV 24)Shuigou (GV 26) Guanyuan (CV 4) Sishencong (EX-HN 1)and Yintang (EX-HN 3) are core acupoints in the network
Baihui (GV 20) Sishencong (EX-HN 1) Fengchi (GB20) Shenting (GV 24) and Neiguan (PC 6) had the highestdegreesThis result indicates that these 5 acupoints have beencombined with more acupoints than other acupoints Theseacupoints have specific therapeutic effects on VaDThereforethese acupoints can be used together with other acupoints toenhance therapeutic effects
Yongquan (KI 1) Baihui (GV 20) Sishencong (EX-HN1) Neiguan (PC 6) and Shenting (GV 24) which belonged
to 4 different communities had higher betweenness cen-trality Yongquan (KI 1) which had the highest betweennesscentrality did not have a relatively high degree However itconnects Jing-Well acupoints with other types of acupointsresulting in a high betweenness centrality Acupoints withhigher betweenness centrality play an important role inconnecting different types of acupoints Jing-Well acupointsexcept Yongquan (KI 1) were often used with other Jing-Wellacupoints only Yongquan (KI 1) was not only used with otherJing-Well acupoints but also with other types of acupointssuch as other types of specific acupoints nonspecific acu-points and acupoints on other parts The high betweennesscentrality suggested that Yongquan (KI 1) may have multipleeffects compared with other Jing-Well acupoints in treatmentof VaD From the perspective of TCM theory Jing-Wellacupoints can restore consciousness Yongquan (KI 1) was
8 Evidence-Based Complementary and Alternative Medicine
BL17
EX-HN22
BL7
LI1
GV13
SP9
GB11
EX-HN14
GB4
HT1
ST2
CV8
GB5
GV18
BL11
EX-UE8
LI20
GV1
ST36
BL20
CV17
BL58
BL9
GV17
GV14
GV15
GV11
GV12
GV10GV5
KI3
KI1
LU11
HT9
GV8
GV3
BL23
GV4
CV6
CV12
HT7GB20
GB17
GV24
GV16
CV4
GB8
GV21GV23GB13
SP10
BL10
ST32
GB34LI14
LI15
GB32
LI10
BL40
GB31
KI6
SI5
KI2
PC7
LI4
GB16
EX-HN5
GB12
PC8
PC6
BL18
BL15
BL56
GB40
TE9
EX-UE9SP6
TE5
SP3
LI11
GV22
BL60
GB6
GB14
GB15
GB19
ST9
GV7
GV2
GV6
EX-B8
BL4
SI1
PC9
TE1ST45
SP1
BL67
GB44
LV1
TE23
TE20
LU7
GV19
ST40
EX-HN3ST8
GV20
KI4
GB39
GB7
EX-HN1
PC5
LV3
GV9
GV26
(a) Network structure of acupoints for the treatment of VaD
GB13
EX-HN1
EX-HN3
LI4
KI3
KI4
HT7GB20
GV14
GV15
GV16
LV3
ST36
BL23
GV4
GV24
GV26GV20
ST40
SP6
LI11
GB39
SP10
PC6
BL10
CV4
BL18
BL15
(b) 19-core network
Figure 5 (a) Network structure of acupoints for the treatment of VaD Blue nodes (Community A) are all Jing-Well acupoints Yellow nodes(Community B) are all acupoints on the face and head Most green nodes (Community C) are acupoints on four limbs Most purple nodes(Community D) are acupoints belonging to Governor Vessel Most red nodes (Community E) are specific acupoints or acupoints withspecific therapeutic effects and only this community contains Bach-Shu acupoints and acupoints on the abdomen Acupoints within thesame community are more densely connected with each other than acupoints from different communities (b) 19-core network There are 28acupoints in the 19-core network They are core acupoints in the treatment of VaD
Evidence-Based Complementary and Alternative Medicine 9
0102030405060708090
100
GV
20
EX-H
N1
GB2
0
GV
24
PC6
SP6
GV
14
GV
26
GV
16
HT7 LI
4
KI3
ST36
ST40
LV3
GB1
3
EX-H
N3
BL10
GB3
9
LI 1
1
Degree
(a) The 20 acupoints with highest degree
0002004006008
01012014016
KI1
GV
20
EX-H
N1
PC6
GV
26
GB2
0
GV
24
GV
14 SP6
EX-H
N3
HT7 LI
4
KI3
GV
16
BL10
LV3
ST40
ST36
GB1
3
PC9
Betweenness centrality
(b) The 20 acupoints with highest betweenness centrality
Figure 6 The 20 acupoints with highest degree and the 20 acupoints with highest betweenness centrality
also used to tonify kidney in treatment of VaD ThereforeYongquan (KI 1) is used not only with other Jing-Wellacupoints but also with other types of acupoints such asother types of specific acupoints nonspecific acupoints andacupoints on other parts
42 UnderlyingMolecularMechanism of the Acupoint with theMost Potential to Treat VaD According to our results Baihui(GV 20) which had the highest frequency has the mostpotential to treat VaD A systematic review andmeta-analysisalso suggested that Baihui (GV 20) is a principal acupoint foracute intracerebral hemorrhage (ICH) in animal models ofacute ICH there was no difference in efficacy between Baihui(GV 20) alone and Baihui (GV 20) plus other acupoints [23]
Molecular biology studies have provided insights intothe mechanisms underlying the effects of Baihui (GV 20) inVaD treatment including antioxidant effects antiapoptoticeffects neurotrophic effects reduced blood-brain barrier(BBB) permeability and regulation of the cholinergic anddopaminergic systems Acupuncture at Baihui (GV 20) incombination with other acupoints decreases levels of 8-hydroxy-21015840-deoxyguanosine a product of oxidative damageto DNA induced by free radicals suggesting that the benefitof acupuncture is partly due to antioxidant effects [11]Acupuncture exerts therapeutic effects on VaD via antiapop-tosis The tumor suppressors p53 and Noxa are important inregulating apoptosis and mediate hypoxic cell death [24 25]
Electroacupuncture at Baihui (GV 20) Dazhui (GV 14) andShenshu (BL 23) blocks expression of p53 and Noxa in thehippocampal CA1 region of VaD rats [26] Acupuncture atBaihui (GV 20) can improve neurogenesis via regulatingbrain-derived neurotrophic factor (BDNF) and cyclic AMPresponse element-binding protein (CREB) BDNF whichis essential for synaptic plasticity and is coupled to CREBactivation [27] is important for long-term memory storage[28] CREB is required for the proliferation growth survivaland differentiation of all types of cells In the brain the CREBand CRE-mediated system is involved in memory learningsynaptic transmission neuron survival differentiation andaxon growth [29] Acupuncture at Baihui (GV 20) signifi-cantly increases the levels of BDNF [15 30] CREB proteinsCREB mRNA [30] and phosphorylated CREB the activeform of CREB [15] The molecular mechanism underlyingacupuncture at Baihui (GV 20) also involves cholinergicsystem regulation Decreased cholinergic function in thebrain can result in a decline in memory and cognitivefunction [31] Acupuncture at Baihui (GV 20) significantlyincreases the levels of choline acetyltransferase (ChAT) andrestores the expression of choline transporter 1 (CHT1)and vesicular acetylcholine transporter (VAChT) [30] Thedopaminergic system is also involved in the mechanismunderlying the treatment of VaD with acupuncture at Baihui(GV 20) Dopamine is a key regulator in specific synapticchanges observed at certain stages of learning and memory
10 Evidence-Based Complementary and Alternative Medicine
and of synaptic plasticity [32] Acupuncture at Baihui (GV20)increases dopamine levels in chronic cerebral hypoperfusionand ischemia-reperfusion injured rats [33] In additionacupuncture at Baihui (GV 20) and Zusanli (ST 36) preservesthe integrity of the BBB reducing BBB permeability TheBBB is constructed of tight conjunctions including occludinand claudin-5 which form the endothelial barrier Reducedexpression of ZO-1 claudin-5 and occludin mRNA andprotein contributes to BBB breakdown and edema in theischemic brain [34] Electroacupuncture at Baihui (GV 20)and Zusanli (ST 36) reduces brain damage and relatedbehavioral deficits via upregulation of tight conjunctionproteins including ZO-1 claudin-5 and occludin [35]Thesefindings reveal parts of the molecular mechanism underlyingacupuncture at Baihui (GV 20) to treat VaD
43 Acupoints Selection in Treatment for VaD The properselection of acupoints is essential for the therapeutic effectsof acupuncture because acupoints are specific with regard tomorphological structure biophysical properties pathologicalresponse and stimulating effects [36] This specificity dif-ferentiates acupoints from nonacupoints as well as differentacupoints from one another The specific therapeutic effectsof different acupoints have been reported for migraine [37]functional dyspepsia [38] ischemic stroke [39] and so forth
The specificity of acupoints for the treatment of VaDhas also been reported Phosphorylated CREB levels weresignificantly increased after acupuncture therapy of needlingBaihui (GV 20) and Zusanli (ST 36) compared to shamacupuncture therapy of needling nonacupoints [15] Baihui(GV 20) Shuigou (GV 26) and Shenmen (HT 7) are allamong the 10 acupoints with the most potential A clinicaltrial demonstrated that needling Baihui (GV 20) Shuigou(GV 26) and Shenmen (HT 7) were all effective in improvingthe symptoms of VaD However their therapeutic effects dif-fer Needling Baihui (GV 20) improved calculation ability andshort-term memory and corrected the personality changesof VaD patients while needling Shuigou (GV 26) improvednaming ability and short-term memory The therapeuticeffects of needling Baihui (GV 20) and Shuigou (GV 26)were superior to those of needling Shenmen (HT 7) [40]A PET and SPECT study revealed that needling these threedifferent acupoints in VaD patients affected different brainareas Needling Baihui (GV 20) activated the inner temporalsystem the thalamencephalon system and the prefrontalcortical system Needling Shuigou (GV 26) activated the pre-frontal cortical system Needling Shenmen (HT 7) generatedan effect similar to but weaker than the effect generated byneedling Shuigou (GV 26) [41] These findings demonstratethat different acupoints have different therapeutic effects inacupuncture treatment for VaD Consequently the selectionof acupoints which directly influences the therapeutic effectsof acupuncture should be considered carefully According toour results based on datamining Baihui (GV 20) Sishencong(EX-HN 1) Fengchi (GB 20) Shuigou (GV 26) and Shenting(GV 24) which have higher frequencies in the modernliterature may have better therapeutic effects on VaD
44 SingleAcupoint orAcupoint Combination Acupoint com-binations also influence the therapeutic effects of acupunc-ture An acupoint combination is considered to have asynergistic effect that enhances the therapeutic effect ofacupuncture For example a lower prevalence of postoper-ative nausea and vomiting in patients treated with Neiguan(PC 6) plus Hegu (LI 4) was observed compared with thosetreated with Neiguan (PC 6) only [42] In spite of extensiveevidence suggesting a synergistic effect of acupoint combi-nation and supporting its use some studies have reportedantagonistic effects [43ndash45] An antagonistic effect occurswhen one acupoint weakens the therapeutic effect of anotheracupoint [46] For example electroacupuncture can improvegastrointestinal movement in rats The effect of needlingPishu (BL 20) alone was better than the effect of needlingPishu (BL 20) and Zusanli (ST 36) at the same time [44]Therefore whether the effect of acupoint combination isbetter than a single acupoint still remains a question andneeds to be further studied
Some studies have compared single acupoints and anacupoint combination for the treatment of VaD The thera-peutic effect of needling Baihui (GV 20) Shuigou (GV 26)and Shenmen (HT 7) in combination was better than theeffects obtained by needling each alone [40] In additionneedling Baihui (GV 20) Shuigou (GV 26) and Shenmen(HT 7) simultaneously activated more brain areas relatedto intellectual activities compared with needling each alonegenerating a more extensive effect on the brain [41] Antago-nistic effects in acupuncture therapy for VaD have not beenreported but may occur Most acupuncture prescriptions forVaD contain acupoint combinations and the use of acupointcombinations is supported However acupoint combinationsshould be selected carefully to avoid antagonistic effects Itis hard to tell whether a combination of acupoints will exertantagonistic effects with current knowledge or TCM theoryAs abovementioned acupoints with similar functions canexert antagonistic effects There are many acupoints and thenumber of acupoint combinations will grow geometricallyTo test the antagonistic effects of each combination oneby one is an exhausting job To avoid antagonistic effectsas possible the acupoint prescriptions should be simplifiedas possible The general principle is to select acupointswith relatively better therapeutic effects and acupoints withmultiple indications and not to select many acupoints
45 Limitations This study has limitations as follows Firstother factors that influence acupuncture such as manipula-tion and treatment duration were not analyzed in this studyThese data can be further mined in future studies Secondlargely due to the lack of treatment based on syndrome differ-entiation and different methods of syndrome differentiationin modern literature potential acupoints and combinationsfor different syndromes of VaD were not analyzed Althoughtreatment based on syndrome differentiation is importantand is often emphasized in TCM treatment based on diseasedifferentiation is equally important Third the real therapeu-tic effects of acupoints and combinations on VaD cannotbe reflected by frequencies in the literature However theseresults suggest some potential acupoints and combinations to
Evidence-Based Complementary and Alternative Medicine 11
be explored in future clinical trials to validate the effects ofacupuncture on VaD To optimize the acupoint prescriptiondata may be extracted not only from literature but alsofrom clinical practice Further research can collect acupointprescriptions and symptom improvements in clinical practiceand optimize acupoint prescriptionwith dataminingMiningclinical data has been practiced to optimize prescriptionof Chinese herbal medicine for unstable angina by Fenget al [47] In their study five main symptoms of patientswith unstable angina the severity of each symptom andthe prescription of each patient were collected The levels ofaverage discounted reward (ADR) of different prescriptionswere calculated to evaluate the clinical efficacy of differ-ent treatment options with some optimized prescriptionsachieved Future studies can mine clinical data to optimizeacupoint prescription
5 Conclusions
In this study data mining was used to discover potentialacupoints and combinations for VaD Potential acupointsinclude Baihui (GV 20) Sishencong (EX-HN 1) Fengchi (GB20) Shuigou (GV 26) and Shenting (GV 24) In additioncombinations between Baihui (GV 20) Sishencong (EX-HN1) Fengchi (GB 20) Shenting (GV 24) Shuigou (GV 26) andZusanli (ST 36) were potential combinations Based on ourresults Baihui (GV 20) and Sishencong (EX-HN 1) shouldbe selected with priority Acupoints in head compared toacupoints in other parts should also be selected with priority
Conflict of Interests
The authors declare no conflict of interests
Authorsrsquo Contribution
Shuwei Feng and Yulan Ren contributed equally to this work
Acknowledgments
This study was supported by the National Basic ResearchProgram of China (no 2012CB518501) and the NationalScience Foundation of China (nos 81102742 and 61104224)
References
[1] Q Chen X Wu S F Lu et al ldquoMeridian acupoints selectionin acupuncture treatment for migraine the main charactersand relevant factors analysisrdquo Liaoning Journal of TraditionalChinese Medicine vol 36 no 9 pp 1477ndash1480 2009
[2] Y Li H Zheng C M Witt et al ldquoAcupuncture for migraineprophylaxis a randomized controlled trialrdquo Canadian MedicalAssociation Journal vol 184 no 4 pp 401ndash410 2012
[3] B H May C Lu L Bennett H M Hugel and C C LXue ldquoEvaluating the traditional Chinese literature for herbalformulae and individual herbs used for age-related dementiaand memory impairmentrdquo Biogerontology vol 13 no 3 pp299ndash312 2012
[4] L Zhang Y Li X Guo et al ldquoText mining of the classicalmedical literature for medicines that show potential in diabeticnephropathyrdquo Evidence-Based Complementary and AlternativeMedicine vol 2014 Article ID 189125 12 pages 2014
[5] Y Olsson A Brun and E Englund ldquoFundamental pathologicallesions in vascular dementiardquo Acta Neurologica Scandinavicavol 94 supplement 168 pp 31ndash38 1996
[6] S Davis M Shanahan A Campbell M Hegarty and BMcCarthy ldquoPalliative care for people with dementia aged carestaff perspectivesrdquo Alzheimerrsquos amp Dementia vol 7 no 4 p e502011
[7] J Jia F Wang C Wei et al ldquoThe prevalence of dementia inurban and rural areas of Chinardquo Alzheimerrsquos and Dementia vol10 no 1 pp 1ndash9 2014
[8] C P Ferri M Prince C Brayne et al ldquoGlobal prevalence ofdementia a Delphi consensus studyrdquo The Lancet vol 366 no9503 pp 2112ndash2117 2005
[9] W Quentin S G Riedel-Heller M Luppa A Rudolph andH-H Konig ldquoCost-of-illness studies of dementia a systematicreview focusing on stage dependency of costsrdquoActa PsychiatricaScandinavica vol 121 no 4 pp 243ndash259 2010
[10] J Yu X Zhang C Liu Y Meng and J Han ldquoEffect ofacupuncture treatment on vascular dementiardquo NeurologicalResearch vol 28 no 1 pp 97ndash103 2006
[11] G-X Shi C-Z Liu Q-Q Li H Zhu and L-P WangldquoInfluence of acupuncture on cognitive function and markersof oxidative DNA damage in patients with vascular dementiardquoJournal of Traditional Chinese Medicine vol 32 no 2 pp 199ndash202 2012
[12] X-Y Zhong X-X Su J Liu and G Q Zhu ldquoClinical effectsof acupuncture combined with nimodipine for treatment ofvascular dementia in 30 casesrdquo Journal of Traditional ChineseMedicine vol 29 no 3 pp 174ndash176 2009
[13] T Wang C-Z Liu J-C Yu W Jiang and J-X Han ldquoAcupunc-ture protected cerebral multi-infarction rats from memoryimpairment by regulating the expression of apoptosis relatedgenes Bcl-2 and Bax in hippocampusrdquo Physiology and Behaviorvol 96 no 1 pp 155ndash161 2009
[14] I K Hwang J Y Chung D Y Yoo et al ldquoComparing the effectsof acupuncture and electroacupuncture at Zusanli and Baihuion cell proliferation and neuroblast differentiation in the rathippocampusrdquo Journal of VeterinaryMedical Science vol 72 no3 pp 279ndash284 2010
[15] I K Hwang J Y Chung D Y Yoo et al ldquoEffects ofelectroacupuncture at Zusanli and Baihui on brain-derivedneurotrophic factor and cyclic AMP response element-bindingprotein in the hippocampal dentate gyrusrdquo Journal of VeterinaryMedical Science vol 72 no 11 pp 1431ndash1436 2010
[16] Y F Luo and J M Wu Fundamentals of Acupuncture SichuanUniversity Press Sichuan China 2008
[17] R Agrawal and R Srikant ldquoFast algorithms for mining associ-ation rulesrdquo in Proceedings of the 20th International Conferenceon Very Large Data Bases (VLDB rsquo94) pp 487ndash499 SantiagoChile 1994
[18] R Agrawal T Imielinski and A Swami ldquoMining associationrules between sets of items in large databasesrdquo ACM SIGMODRecord vol 22 no 2 pp 207ndash216 1993
12 Evidence-Based Complementary and Alternative Medicine
[19] A Clauset M E J Newman and C Moore ldquoFinding commu-nity structure in very large networksrdquo Physical Review E vol 70no 6 Article ID 066111 6 pages 2004
[20] G F de Arruda A L Barbieri P M Rodriguez et al ldquoRoleof centrality for the identification of influential spreaders incomplex networksrdquo Physical Review E Statistical Nonlinearand SoftMatter Physics vol 90 no 1ndash3 Article ID 032812 2014
[21] T Opsahl F Agneessens and J Skvoretz ldquoNode centrality inweighted networks generalizing degree and shortest pathsrdquoSocial Networks vol 32 no 3 pp 245ndash251 2010
[22] U Brandes ldquoOn variants of shortest-path betweenness central-ity and their generic computationrdquo Social Networks vol 30 no2 pp 136ndash145 2008
[23] H Q Li J H Li A J Liu M Y Ye and G Q ZhengldquoGV20-based acupuncture for animal models of acute intrac-erebral haemorrhage a preclinical systematic review and meta-analysisrdquo Acupuncture in Medicine vol 32 no 6 pp 495ndash5022014
[24] EOda ROhkiHMurasawa et al ldquoNoxa a BH3-onlymemberof the Bcl-2 family and candidate mediator of p53-inducedapoptosisrdquo Science vol 288 no 5468 pp 1053ndash1058 2000
[25] H Endo H Kamada C Nito T Nishi and P H Chan ldquoMito-chondrial translocation of p53 mediates release of cytochromec and hippocampal CA1 neuronal death after transient globalcerebral ischemia in ratsrdquo Journal of Neuroscience vol 26 no30 pp 7974ndash7983 2006
[26] Y Zhu and Y Zeng ldquoElectroacupuncture protected pyramidalcells in hippocampal CA1 region of vascular dementia rats byinhibiting the expression of P53 and Noxardquo CNS NeuroscienceandTherapeutics vol 17 no 6 pp 599ndash604 2011
[27] W J Tyler M Alonso C R Bramham and L D Pozzo-Miller ldquoFrom acquisition to consolidation on the role ofbrain-derived neurotrophic factor signaling in hippocampal-dependent learningrdquo Learning and Memory vol 9 no 5 pp224ndash237 2002
[28] P Bekinschtein M Cammarota C Katche et al ldquoBDNF isessential to promote persistence of long-termmemory storagerdquoProceedings of the National Academy of Sciences of the UnitedStates of America vol 105 no 7 pp 2711ndash2716 2008
[29] K Kitagawa ldquoCREB and cAMP response element-mediatedgene expression in the ischemic brainrdquo FEBS Journal vol 274no 13 pp 3210ndash3217 2007
[30] B Lee B Sur J Shim D Hahm and H Lee ldquoAcupuncturestimulation improves scopolamine-induced cognitive impair-ment via activation of cholinergic system and regulation ofBDNF andCREB expressions in ratsrdquoBMCComplementary andAlternative Medicine vol 14 no 1 article 338 2014
[31] M E Hasselmo ldquoThe role of acetylcholine in learning andmemoryrdquo Current Opinion in Neurobiology vol 16 no 6 pp710ndash715 2006
[32] T M Jay ldquoDopamine a potential substrate for synaptic plastic-ity andmemory mechanismsrdquo Progress in Neurobiology vol 69no 6 pp 375ndash390 2003
[33] C-M Chuang C-L Hsieh T-C Li and J-G Lin ldquoAcupunc-ture stimulation at Baihui acupoint reduced cerebral infarct andincreased dopamine levels in chronic cerebral hypoperfusionand ischemia-reperfusion injured Sprague-Dawley ratsrdquoAmeri-can Journal of ChineseMedicine vol 35 no 5 pp 779ndash791 2007
[34] H Jiao Z Wang Y Liu P Wang and Y Xue ldquoSpecific roleof tight junction proteins claudin-5 occludin and ZO-1 of theblood-brain barrier in a focal cerebral ischemic insultrdquo Journalof Molecular Neuroscience vol 44 no 2 pp 130ndash139 2011
[35] Y-M Zhang H Xu H Sun S Chen and F Wang ldquoElec-troacupuncture treatment improves neurological function asso-ciated with regulation of tight junction proteins in rats withcerebral ischemia reperfusion injuryrdquo Evidence-Based Comple-mentary and Alternative Medicine vol 2014 Article ID 98934010 pages 2014
[36] B-X Jin X-S Lai and C-Z Tang ldquoProgress in researches onthe specificity of acupointsrdquo Acupuncture Research vol 33 no2 pp 135ndash138 2008
[37] Y Li F Liang X Yang et al ldquoAcupuncture for treating acuteattacks of migraine a randomized controlled trialrdquo Headachevol 49 no 6 pp 805ndash816 2009
[38] T T Ma S Y Yu Y Li et al ldquoRandomised clinical trial anassessment of acupuncture on specific meridian or specific acu-point vs sham acupuncture for treating functional dyspepsiardquoAlimentary Pharmacology and Therapeutics vol 35 no 5 pp552ndash561 2012
[39] P-F Shen L Kong L-W Ni et al ldquoAcupuncture interventionin ischemic stroke a randomized controlled prospective studyrdquoThe American Journal of Chinese Medicine vol 40 no 4 pp685ndash693 2012
[40] Y Huang M H Win J Chen et al ldquoA comparative studyon the treatment of vascular dementia by puncturing Baihui(GV20) Shuigou (GV26) and Shenmen (HT7)rdquoWorld Journalof AcupuncturemdashMoxibustion no 1 pp 3ndash10 2005
[41] Y Huang X-S Lai and A-W Tang ldquoComparative study of thespecificities of needling acupoints DU20 DU26 and HT7 inintervening vascular dementia in different areas in the brain onthe basis of scale assessment and cerebral functional imagingrdquoChinese Journal of Integrative Medicine vol 13 no 2 pp 103ndash108 2007
[42] R Alizadeh S Esmaeili S Shoar S Bagheri-Hariri and NShoar ldquoAcupuncture in preventing postoperative nausea andvomiting efficacy of two acupuncture points versus a singleonerdquo Journal of Acupuncture and Meridian Studies vol 7 no2 pp 71ndash75 2014
[43] F M Xu and R X Chen ldquoThe antagonistic effect of acupointson oxygen consumption rate in ratsrdquo Journal of Jiangxi Collegeof Traditional Chinese Medicine vol 13 no 2 pp 60ndash61 2001
[44] F M Xu and R X Chen ldquoEffect of electroacupuncture ongastrointestinalmovement in rats with hypoactive gastrointesti-nal movement caused by greaserdquo Henan Traditional ChineseMedicine vol 20 no 2 pp 19ndash20 2000
[45] X H Li X Z Gao and L Hu ldquoExperimental study on syner-getic and antagonistic effects of acupoints Neiguan Shenmenand Xinshurdquo Chinese Acupuncture andMoxibustion vol 22 no12 pp 819ndash821 2002
[46] X H Li Q Y Wang X Z Gao et al ldquoStudy on cooperationand antagonism among acupointsrdquo Chinese Acupuncture andMoxibustion vol 22 no 6 pp 387ndash388 2002
[47] Y Feng Y Qiu X Zhou Y Wang H Xu and B Liu ldquoOpti-mizing prescription of Chinese herbal medicine for unstableangina based on partially observable Markov decision processrdquoEvidence-based Complementary and Alternative Medicine vol2013 Article ID 532534 6 pages 2013
Submit your manuscripts athttpwwwhindawicom
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Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
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Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
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Disease Markers
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OncologyJournal of
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Oxidative Medicine and Cellular Longevity
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Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Parkinsonrsquos Disease
Evidence-Based Complementary and Alternative Medicine
Volume 2014Hindawi Publishing Corporationhttpwwwhindawicom
Evidence-Based Complementary and Alternative Medicine 5
Table1Statisticso
fmeridians
andacup
ointsinthem
odernliteratureo
nacup
uncturetreatmentfor
VaD
Num
ber
Meridian
Frequency
Num
bero
facupo
ints
Acup
ointsa
ndtheirfrequ
encies
1GV
477
26
Baihui
(GV20)176Shu
igou
(GV26)8
6Sh
entin
g(G
V24)8
4Dazhu
i(GV14)2
7Feng
fu(G
V16)2
3Yintang(EX-
HN3)
16N
aohu
(GV17)13Shangxing(G
V23)11Mingm
en(G
V4)
8Yamen
(GV15)5
Qiang
jian(G
V18)5
Qiand
ing(G
V21)4
Yaoyang
guan
(GV3)
3Zh
iyang(G
V9)
3Jin
suo(G
V8)
2Shendao(G
V11)1Z
hong
shu(G
V7)
1Taod
ao(G
V13)1Lingtai(G
V10)1C
hangqiang(G
V1)1Xu
anshu
(GV5)
1Yaoshu
(GV2)
1Shenzhu(G
V12)1Jizho
ng(G
V6)
1Hou
ding
(GV19)1X
inhu
i(GV22)1
2GB
218
20
Fengchi(GB20)9
3Be
nshen(G
B13)4
7Xu
anzhon
g(G
B39)2
4Shuaigu(G
B8)
7Wangu
(GB12)6
To
ulinqi(G
B15)6
Qub
in(G
B7)
5Xu
anli(G
B6)
4Naokong
(GB19)4
Zuq
iaoyin
(GB44
)3Yanglingquan
(GB34)3
Yangbai(G
B14)3
Hanyan(G
B4)
2Qiuxu
(GB40
)2Fengshi
(GB31)2
Tou
qiaoyin(G
B11)2
Xu
anlu(G
B5)
2Muchu
ang(G
B16)1Z
heng
ying
(GB17)1Z
hongdu
(GB32)1
3EX
-HN
133
7Sishencong
(EX-
HN1)123Taiyang(EX-
HN5)
4Wailaogon
g(EX-
UE8)
2Sh
iqizhu
i(EX
-B8)
1Ba
xie
(EX-
UE9)
1Anm
ian(EX-
HN22)1Y
iming(EX-
HN14)1
4ST
124
7Zu
sanli(ST
36)7
2Feng
long
(ST40
)40To
uwei(ST8)
6Lidu
i(ST
45)2
Sibai(ST2)
2Fu
tu(ST32)1
Renying(ST9)
1
5BL
103
15Shenshu(BL23)4
3Ganshu(BL18)12Tianzhu(BL10)10Pishu(BL20)8
Feiyang
(BL58)8
Geshu
(BL17)
7Xinshu
(BL15)4
Zhiyin(BL67)2
Kun
lun(BL60)2
Yuzhen(BL9)
2To
ngtia
n(BL7)
1Ch
engjin
(BL56)
1Dazhu
(BL11)
1Weizhon
g(BL40
)1Q
ucha
(BL4)
16
SP96
5Sanyinjiao(SP6)
71X
uehai(SP
10)14Taibai(SP3)
8Yinb
ai(SP1)2Yinlingquan(SP9)
17
PC86
5Neigu
an(PC6)
73Z
hongchon
g(PC9)
4Daling(PC7)
4Jianshi
(PC5)
3Laogon
g(PC8)
28
KI83
5Taixi(KI
3)57D
azho
ng(K
I4)12Yo
ngqu
an(K
I1)10Zh
aohai(KI
6)8Ra
ngu(K
I2)2
9HT
673
Shenmen
(HT7)
62Shaocho
ng(H
T9)
3Jiq
uan(H
T1)2
10LI
457
Hegu(LI4
)20Quchi
(LI11)18Shang
yang
(LI1)2
Sho
usanli(LI10)
2Binao(LI14)
1Jianyu(LI15)
1Ying
xiang(LI2
0)1
11CV
435
Qihai(C
V6)
11Z
hong
wan
(CV12)10Guanyuan(C
V4)
9Danzhon
g(C
V17)9
Shenq
ue(C
V8)
412
LV40
2Taicho
ng(LV3)
37D
adun
(LV1)3
13TE
115
Waigu
an(TE5)
6Guancho
ng(TE1)2Sizhuk
ong(TE23)1Jiaosun
(TE20)1Sidu(TE9)
114
LU4
2Shaoshang(LU11)3
Liequ
e(LU
7)1
15SI
32
Shaoze
(SI1)2
Yanggu(SI5
)116
Total
1533
116GV
Governo
rMeridianGB
Gallbladd
erMeridianof
Foot
Shaoyang
EX-
HNextraordinary
acup
ointSTStom
achMeridianof
Foot
Yang
mingBL
Bladd
erMeridianof
Foot
TaiyangSPSpleenMeridianof
Foot
TaiyinP
CPeric
ardium
Meridianof
HandJueyinK
IKidn
eyMeridianof
Foot
Shaoyin
HTHeartMeridianof
HandSh
aoyin
CVC
onceptionVe
ssel
LIL
arge
Intestine
Meridianof
HandYang
mingLV
Liver
Meridianof
Foot
JueyinT
ETripleEn
ergizero
fHandSh
aoyang
LU
Lung
Meridianof
HandTaiyinSISm
allIntestin
eofH
andTaiyangFrequencieso
fmeridians
refertothetotalfre
quencies
ofacup
ointso
nthe
samem
eridian
Num
bero
facupo
intsrefertothetotalnu
mbero
facupo
intson
thes
amem
eridian
6 Evidence-Based Complementary and Alternative Medicine
Table 2 Statistics of the 15 most frequently used acupoint combinations in the treatment of VaD
Number Acupoint combination Frequency Support ()1 Baihui (GV 20) Sishencong (EX-HN 1) 98 41182 Baihui (GV 20) Fengchi (GB 20) 81 34033 Baihui (GV 20) Shuigou (GV 26) 72 29834 Baihui (GV 20) Shenting (GV 24) 70 29415 Baihui (GV 20) Zusanli (ST 36) 62 26056 Sishencong (EX-HN 1) Fengchi (GB 20) 60 25217 Baihui (GV 20) Sanyinjiao (SP 6) 57 23958 Baihui (GV 20) Neiguan (PC 6) 54 22699 Sishencong (EX-HN 1) Shuigou (GV 26) 51 214310 Sishencong (EX-HN 1) Baihui (GV 20) Fengchi (GB 20) 51 214311 Baihui (GV 20) Shenmen (HT 7) 51 214312 Sishencong (EX-HN 1) Shenting (GV 24) 49 205913 Sishencong (EX-HN 1) Neiguan (PC 6) 46 193314 Baihui (GV 20) Taixi (KI 3) 46 193315 Sishencong (EX-HN 1) Baihui (GV 20) Shuigou (GV 26) 43 1807Support refers to the percentage of acupoint prescriptions containing the acupoint combination
36 Community Structure Community detection resultedin the division of the 116 acupoints into 5 communitiesNodes of the same color belong to the same community Thecommunity structure is shown in Figure 5(a)
37 Acupoint 119870-Core Network The largest 119896-core value was19 At this value there were 28 nodes corresponding to Hegu(LI 4) Quchi (LI 11) Zusanli (ST 36) Fenglong (ST 40)Sanyinjiao (SP 6) Xuehai (SP 10) Shenmen (HT 7) Tianzhu(BL 10) Xinshu (BL 15) Ganshu (BL 18) Shenshu (BL 23)Taixi (KI 3) Dazhong (KI 4) Neiguan (PC 6) Benshen (GB13) Fengchi (GB 20) Xuanzhong (GB 39) Taichong (LV 3)Mingmen (GV 4) Dazhui (GV 14) Yamen (GV 15) Fengfu(GV 16) Baihui (GV20) Shenting (GV24) Shuigou (GV26)Guanyuan (CV 4) Sishencong (EX-HN 1) and Yintang (EX-HN 3) as shown in Figure 5(b)
38 Degree The top 20 acupoints in degree are shownin Figure 6(a) Baihui (GV 20) Sishencong (EX-HN 1)Fengchi (GB 20) Shenting (GV 24) and Neiguan (PC 6)had the highest degrees with values of 89 76 68 67 and 65respectively
39 Betweenness Centrality Thetop 20 acupoints in between-ness centrality are shown in Figure 6(b) Yongquan (KI 1)Baihui (GV 20) and Sishencong (EX-HN 1) had the highestbetweenness centrality
4 Discussion
41 Potential Acupoints and Combinations for VaD In thisstudy acupoints and combinations with potential for treat-ing VaD were discovered These results may provide somereference for the selection of acupoints in treatment forVaD which may promote the therapeutic effects in clinicalpractice The results suggest that Baihui (GV 20) Sishencong(EX-HN 1) Fengchi (GB 20) Shuigou (GV 26) and Shenting
(GV 24) are potential acupoints for treating VaD In terms ofmeridian acupoints on the Governor Meridian have poten-tial for treating VaD From the perspective of combinationscombinations between such acupoints as Baihui (GV 20)Sishencong (EX-HN 1) Fengchi (GB 20) Shenting (GV 24)Shuigou (GV 26) and Zusanli (ST 36) have potential fortreating VaD In addition acupoints on the head face andneck have more potential for VaD than acupoints on otherregions of the body Specific acupoints have more potentialthan nonspecific acupoints Specific acupoints with specificnames are a group of acupoints on fourteen meridians withspecific therapeutic effectsThere are ten types of specific acu-points Five-Shu acupoints Yuan-Primary acupoints Luo-Connecting acupoints Xi-Cleft acupoints Lower He-Seaacupoints Back-Shu acupoints Front-Mu acupoints eightinfluential acupoints eight confluent acupoints connectingthe eight extra meridians and convergent acupoints
Community detection divided the acupoints into 5 com-munities Acupoints within the same community have somecharacteristics in common Blue nodes (Community A) wereall Jing-Well acupoints Yellow nodes (Community B) were allacupoints on the face and head Most green nodes (Commu-nity C) were acupoints on the four limbs Most purple nodes(Community D) were acupoints belonging to Governor Ves-sel Most red nodes (Community E) were specific acupointsor acupoints with specific therapeutic effects and only thiscommunity contained Bach-Shu acupoints and acupointson the abdomen Acupoints within the same communitywere more densely connected with each other comparedwith acupoints from different communities indicating thatan acupoint was more often used with acupoints withinthe same community compared with acupoints within othercommunities
The 19-core network indicated that 28 acupoints includ-ing Hegu (LI 4) Quchi (LI 11) Zusanli (ST 36) Fenglong(ST 40) Sanyinjiao (SP 6) Xuehai (SP 10) Shenmen (HT 7)
Evidence-Based Complementary and Alternative Medicine 7
0
5
10
15
20
25
30
35
40
45
Head faceand neck
Lowerlimbs
Upperlimbs
Back andlumbar
Chest andabdomen
Number
(a) The numbers of acupoints in different parts
0
100
200
300
400
500
600
700
800
900
Head faceand neck
Lowerlimbs
Upperlimbs
Back andlumbar
Chest andabdomen
Frequency
(b) The frequencies of acupoints in different parts
0
5
10
15
20
25
30
35
40
Number
Con
verg
ent a
cupo
int
Five
-Shu
acup
oint
Yuan
-sou
rce p
oint
Luo-
Con
nect
ing
poin
t
Eigh
t infl
uent
ial p
oint
Shu-
Back
poi
nt
Eigh
t con
fluen
t acu
poin
ts
Fron
t-Mu
poin
t
Low
er H
e-Se
a poi
nt
Non
spec
ifc p
oint
(c) The numbers of different kinds of acupoints
0
100
200
300
400
500
600
700
800
Frequency
Con
verg
ent a
cupo
int
Five
-Shu
acup
oint
Yuan
-sou
rce p
oint
Luo-
Con
nect
ing
poin
t
Eigh
t infl
uent
ial p
oint
Shu-
Back
poi
nt
Eigh
t con
fluen
t acu
poin
ts
Fron
t-Mu
poin
t
Low
er H
e-Se
a poi
nt
Non
spec
ifc p
oint
(d) The frequencies of different kinds of acupoints
Figure 4 The frequencies and numbers of acupoints in different body parts and different types of acupoints
Tianzhu (BL 10) Xinshu (BL 15) Ganshu (BL 18) Shenshu(BL 23) Taixi (KI 3) Dazhong (KI 4) Neiguan (PC 6)Benshen (GB 13) Fengchi (GB 20) Xuanzhong (GB 39)Taichong (LV 3) Mingmen (GV 4) Dazhui (GV 14) Yamen(GV 15) Fengfu (GV 16) Baihui (GV 20) Shenting (GV 24)Shuigou (GV 26) Guanyuan (CV 4) Sishencong (EX-HN 1)and Yintang (EX-HN 3) are core acupoints in the network
Baihui (GV 20) Sishencong (EX-HN 1) Fengchi (GB20) Shenting (GV 24) and Neiguan (PC 6) had the highestdegreesThis result indicates that these 5 acupoints have beencombined with more acupoints than other acupoints Theseacupoints have specific therapeutic effects on VaDThereforethese acupoints can be used together with other acupoints toenhance therapeutic effects
Yongquan (KI 1) Baihui (GV 20) Sishencong (EX-HN1) Neiguan (PC 6) and Shenting (GV 24) which belonged
to 4 different communities had higher betweenness cen-trality Yongquan (KI 1) which had the highest betweennesscentrality did not have a relatively high degree However itconnects Jing-Well acupoints with other types of acupointsresulting in a high betweenness centrality Acupoints withhigher betweenness centrality play an important role inconnecting different types of acupoints Jing-Well acupointsexcept Yongquan (KI 1) were often used with other Jing-Wellacupoints only Yongquan (KI 1) was not only used with otherJing-Well acupoints but also with other types of acupointssuch as other types of specific acupoints nonspecific acu-points and acupoints on other parts The high betweennesscentrality suggested that Yongquan (KI 1) may have multipleeffects compared with other Jing-Well acupoints in treatmentof VaD From the perspective of TCM theory Jing-Wellacupoints can restore consciousness Yongquan (KI 1) was
8 Evidence-Based Complementary and Alternative Medicine
BL17
EX-HN22
BL7
LI1
GV13
SP9
GB11
EX-HN14
GB4
HT1
ST2
CV8
GB5
GV18
BL11
EX-UE8
LI20
GV1
ST36
BL20
CV17
BL58
BL9
GV17
GV14
GV15
GV11
GV12
GV10GV5
KI3
KI1
LU11
HT9
GV8
GV3
BL23
GV4
CV6
CV12
HT7GB20
GB17
GV24
GV16
CV4
GB8
GV21GV23GB13
SP10
BL10
ST32
GB34LI14
LI15
GB32
LI10
BL40
GB31
KI6
SI5
KI2
PC7
LI4
GB16
EX-HN5
GB12
PC8
PC6
BL18
BL15
BL56
GB40
TE9
EX-UE9SP6
TE5
SP3
LI11
GV22
BL60
GB6
GB14
GB15
GB19
ST9
GV7
GV2
GV6
EX-B8
BL4
SI1
PC9
TE1ST45
SP1
BL67
GB44
LV1
TE23
TE20
LU7
GV19
ST40
EX-HN3ST8
GV20
KI4
GB39
GB7
EX-HN1
PC5
LV3
GV9
GV26
(a) Network structure of acupoints for the treatment of VaD
GB13
EX-HN1
EX-HN3
LI4
KI3
KI4
HT7GB20
GV14
GV15
GV16
LV3
ST36
BL23
GV4
GV24
GV26GV20
ST40
SP6
LI11
GB39
SP10
PC6
BL10
CV4
BL18
BL15
(b) 19-core network
Figure 5 (a) Network structure of acupoints for the treatment of VaD Blue nodes (Community A) are all Jing-Well acupoints Yellow nodes(Community B) are all acupoints on the face and head Most green nodes (Community C) are acupoints on four limbs Most purple nodes(Community D) are acupoints belonging to Governor Vessel Most red nodes (Community E) are specific acupoints or acupoints withspecific therapeutic effects and only this community contains Bach-Shu acupoints and acupoints on the abdomen Acupoints within thesame community are more densely connected with each other than acupoints from different communities (b) 19-core network There are 28acupoints in the 19-core network They are core acupoints in the treatment of VaD
Evidence-Based Complementary and Alternative Medicine 9
0102030405060708090
100
GV
20
EX-H
N1
GB2
0
GV
24
PC6
SP6
GV
14
GV
26
GV
16
HT7 LI
4
KI3
ST36
ST40
LV3
GB1
3
EX-H
N3
BL10
GB3
9
LI 1
1
Degree
(a) The 20 acupoints with highest degree
0002004006008
01012014016
KI1
GV
20
EX-H
N1
PC6
GV
26
GB2
0
GV
24
GV
14 SP6
EX-H
N3
HT7 LI
4
KI3
GV
16
BL10
LV3
ST40
ST36
GB1
3
PC9
Betweenness centrality
(b) The 20 acupoints with highest betweenness centrality
Figure 6 The 20 acupoints with highest degree and the 20 acupoints with highest betweenness centrality
also used to tonify kidney in treatment of VaD ThereforeYongquan (KI 1) is used not only with other Jing-Wellacupoints but also with other types of acupoints such asother types of specific acupoints nonspecific acupoints andacupoints on other parts
42 UnderlyingMolecularMechanism of the Acupoint with theMost Potential to Treat VaD According to our results Baihui(GV 20) which had the highest frequency has the mostpotential to treat VaD A systematic review andmeta-analysisalso suggested that Baihui (GV 20) is a principal acupoint foracute intracerebral hemorrhage (ICH) in animal models ofacute ICH there was no difference in efficacy between Baihui(GV 20) alone and Baihui (GV 20) plus other acupoints [23]
Molecular biology studies have provided insights intothe mechanisms underlying the effects of Baihui (GV 20) inVaD treatment including antioxidant effects antiapoptoticeffects neurotrophic effects reduced blood-brain barrier(BBB) permeability and regulation of the cholinergic anddopaminergic systems Acupuncture at Baihui (GV 20) incombination with other acupoints decreases levels of 8-hydroxy-21015840-deoxyguanosine a product of oxidative damageto DNA induced by free radicals suggesting that the benefitof acupuncture is partly due to antioxidant effects [11]Acupuncture exerts therapeutic effects on VaD via antiapop-tosis The tumor suppressors p53 and Noxa are important inregulating apoptosis and mediate hypoxic cell death [24 25]
Electroacupuncture at Baihui (GV 20) Dazhui (GV 14) andShenshu (BL 23) blocks expression of p53 and Noxa in thehippocampal CA1 region of VaD rats [26] Acupuncture atBaihui (GV 20) can improve neurogenesis via regulatingbrain-derived neurotrophic factor (BDNF) and cyclic AMPresponse element-binding protein (CREB) BDNF whichis essential for synaptic plasticity and is coupled to CREBactivation [27] is important for long-term memory storage[28] CREB is required for the proliferation growth survivaland differentiation of all types of cells In the brain the CREBand CRE-mediated system is involved in memory learningsynaptic transmission neuron survival differentiation andaxon growth [29] Acupuncture at Baihui (GV 20) signifi-cantly increases the levels of BDNF [15 30] CREB proteinsCREB mRNA [30] and phosphorylated CREB the activeform of CREB [15] The molecular mechanism underlyingacupuncture at Baihui (GV 20) also involves cholinergicsystem regulation Decreased cholinergic function in thebrain can result in a decline in memory and cognitivefunction [31] Acupuncture at Baihui (GV 20) significantlyincreases the levels of choline acetyltransferase (ChAT) andrestores the expression of choline transporter 1 (CHT1)and vesicular acetylcholine transporter (VAChT) [30] Thedopaminergic system is also involved in the mechanismunderlying the treatment of VaD with acupuncture at Baihui(GV 20) Dopamine is a key regulator in specific synapticchanges observed at certain stages of learning and memory
10 Evidence-Based Complementary and Alternative Medicine
and of synaptic plasticity [32] Acupuncture at Baihui (GV20)increases dopamine levels in chronic cerebral hypoperfusionand ischemia-reperfusion injured rats [33] In additionacupuncture at Baihui (GV 20) and Zusanli (ST 36) preservesthe integrity of the BBB reducing BBB permeability TheBBB is constructed of tight conjunctions including occludinand claudin-5 which form the endothelial barrier Reducedexpression of ZO-1 claudin-5 and occludin mRNA andprotein contributes to BBB breakdown and edema in theischemic brain [34] Electroacupuncture at Baihui (GV 20)and Zusanli (ST 36) reduces brain damage and relatedbehavioral deficits via upregulation of tight conjunctionproteins including ZO-1 claudin-5 and occludin [35]Thesefindings reveal parts of the molecular mechanism underlyingacupuncture at Baihui (GV 20) to treat VaD
43 Acupoints Selection in Treatment for VaD The properselection of acupoints is essential for the therapeutic effectsof acupuncture because acupoints are specific with regard tomorphological structure biophysical properties pathologicalresponse and stimulating effects [36] This specificity dif-ferentiates acupoints from nonacupoints as well as differentacupoints from one another The specific therapeutic effectsof different acupoints have been reported for migraine [37]functional dyspepsia [38] ischemic stroke [39] and so forth
The specificity of acupoints for the treatment of VaDhas also been reported Phosphorylated CREB levels weresignificantly increased after acupuncture therapy of needlingBaihui (GV 20) and Zusanli (ST 36) compared to shamacupuncture therapy of needling nonacupoints [15] Baihui(GV 20) Shuigou (GV 26) and Shenmen (HT 7) are allamong the 10 acupoints with the most potential A clinicaltrial demonstrated that needling Baihui (GV 20) Shuigou(GV 26) and Shenmen (HT 7) were all effective in improvingthe symptoms of VaD However their therapeutic effects dif-fer Needling Baihui (GV 20) improved calculation ability andshort-term memory and corrected the personality changesof VaD patients while needling Shuigou (GV 26) improvednaming ability and short-term memory The therapeuticeffects of needling Baihui (GV 20) and Shuigou (GV 26)were superior to those of needling Shenmen (HT 7) [40]A PET and SPECT study revealed that needling these threedifferent acupoints in VaD patients affected different brainareas Needling Baihui (GV 20) activated the inner temporalsystem the thalamencephalon system and the prefrontalcortical system Needling Shuigou (GV 26) activated the pre-frontal cortical system Needling Shenmen (HT 7) generatedan effect similar to but weaker than the effect generated byneedling Shuigou (GV 26) [41] These findings demonstratethat different acupoints have different therapeutic effects inacupuncture treatment for VaD Consequently the selectionof acupoints which directly influences the therapeutic effectsof acupuncture should be considered carefully According toour results based on datamining Baihui (GV 20) Sishencong(EX-HN 1) Fengchi (GB 20) Shuigou (GV 26) and Shenting(GV 24) which have higher frequencies in the modernliterature may have better therapeutic effects on VaD
44 SingleAcupoint orAcupoint Combination Acupoint com-binations also influence the therapeutic effects of acupunc-ture An acupoint combination is considered to have asynergistic effect that enhances the therapeutic effect ofacupuncture For example a lower prevalence of postoper-ative nausea and vomiting in patients treated with Neiguan(PC 6) plus Hegu (LI 4) was observed compared with thosetreated with Neiguan (PC 6) only [42] In spite of extensiveevidence suggesting a synergistic effect of acupoint combi-nation and supporting its use some studies have reportedantagonistic effects [43ndash45] An antagonistic effect occurswhen one acupoint weakens the therapeutic effect of anotheracupoint [46] For example electroacupuncture can improvegastrointestinal movement in rats The effect of needlingPishu (BL 20) alone was better than the effect of needlingPishu (BL 20) and Zusanli (ST 36) at the same time [44]Therefore whether the effect of acupoint combination isbetter than a single acupoint still remains a question andneeds to be further studied
Some studies have compared single acupoints and anacupoint combination for the treatment of VaD The thera-peutic effect of needling Baihui (GV 20) Shuigou (GV 26)and Shenmen (HT 7) in combination was better than theeffects obtained by needling each alone [40] In additionneedling Baihui (GV 20) Shuigou (GV 26) and Shenmen(HT 7) simultaneously activated more brain areas relatedto intellectual activities compared with needling each alonegenerating a more extensive effect on the brain [41] Antago-nistic effects in acupuncture therapy for VaD have not beenreported but may occur Most acupuncture prescriptions forVaD contain acupoint combinations and the use of acupointcombinations is supported However acupoint combinationsshould be selected carefully to avoid antagonistic effects Itis hard to tell whether a combination of acupoints will exertantagonistic effects with current knowledge or TCM theoryAs abovementioned acupoints with similar functions canexert antagonistic effects There are many acupoints and thenumber of acupoint combinations will grow geometricallyTo test the antagonistic effects of each combination oneby one is an exhausting job To avoid antagonistic effectsas possible the acupoint prescriptions should be simplifiedas possible The general principle is to select acupointswith relatively better therapeutic effects and acupoints withmultiple indications and not to select many acupoints
45 Limitations This study has limitations as follows Firstother factors that influence acupuncture such as manipula-tion and treatment duration were not analyzed in this studyThese data can be further mined in future studies Secondlargely due to the lack of treatment based on syndrome differ-entiation and different methods of syndrome differentiationin modern literature potential acupoints and combinationsfor different syndromes of VaD were not analyzed Althoughtreatment based on syndrome differentiation is importantand is often emphasized in TCM treatment based on diseasedifferentiation is equally important Third the real therapeu-tic effects of acupoints and combinations on VaD cannotbe reflected by frequencies in the literature However theseresults suggest some potential acupoints and combinations to
Evidence-Based Complementary and Alternative Medicine 11
be explored in future clinical trials to validate the effects ofacupuncture on VaD To optimize the acupoint prescriptiondata may be extracted not only from literature but alsofrom clinical practice Further research can collect acupointprescriptions and symptom improvements in clinical practiceand optimize acupoint prescriptionwith dataminingMiningclinical data has been practiced to optimize prescriptionof Chinese herbal medicine for unstable angina by Fenget al [47] In their study five main symptoms of patientswith unstable angina the severity of each symptom andthe prescription of each patient were collected The levels ofaverage discounted reward (ADR) of different prescriptionswere calculated to evaluate the clinical efficacy of differ-ent treatment options with some optimized prescriptionsachieved Future studies can mine clinical data to optimizeacupoint prescription
5 Conclusions
In this study data mining was used to discover potentialacupoints and combinations for VaD Potential acupointsinclude Baihui (GV 20) Sishencong (EX-HN 1) Fengchi (GB20) Shuigou (GV 26) and Shenting (GV 24) In additioncombinations between Baihui (GV 20) Sishencong (EX-HN1) Fengchi (GB 20) Shenting (GV 24) Shuigou (GV 26) andZusanli (ST 36) were potential combinations Based on ourresults Baihui (GV 20) and Sishencong (EX-HN 1) shouldbe selected with priority Acupoints in head compared toacupoints in other parts should also be selected with priority
Conflict of Interests
The authors declare no conflict of interests
Authorsrsquo Contribution
Shuwei Feng and Yulan Ren contributed equally to this work
Acknowledgments
This study was supported by the National Basic ResearchProgram of China (no 2012CB518501) and the NationalScience Foundation of China (nos 81102742 and 61104224)
References
[1] Q Chen X Wu S F Lu et al ldquoMeridian acupoints selectionin acupuncture treatment for migraine the main charactersand relevant factors analysisrdquo Liaoning Journal of TraditionalChinese Medicine vol 36 no 9 pp 1477ndash1480 2009
[2] Y Li H Zheng C M Witt et al ldquoAcupuncture for migraineprophylaxis a randomized controlled trialrdquo Canadian MedicalAssociation Journal vol 184 no 4 pp 401ndash410 2012
[3] B H May C Lu L Bennett H M Hugel and C C LXue ldquoEvaluating the traditional Chinese literature for herbalformulae and individual herbs used for age-related dementiaand memory impairmentrdquo Biogerontology vol 13 no 3 pp299ndash312 2012
[4] L Zhang Y Li X Guo et al ldquoText mining of the classicalmedical literature for medicines that show potential in diabeticnephropathyrdquo Evidence-Based Complementary and AlternativeMedicine vol 2014 Article ID 189125 12 pages 2014
[5] Y Olsson A Brun and E Englund ldquoFundamental pathologicallesions in vascular dementiardquo Acta Neurologica Scandinavicavol 94 supplement 168 pp 31ndash38 1996
[6] S Davis M Shanahan A Campbell M Hegarty and BMcCarthy ldquoPalliative care for people with dementia aged carestaff perspectivesrdquo Alzheimerrsquos amp Dementia vol 7 no 4 p e502011
[7] J Jia F Wang C Wei et al ldquoThe prevalence of dementia inurban and rural areas of Chinardquo Alzheimerrsquos and Dementia vol10 no 1 pp 1ndash9 2014
[8] C P Ferri M Prince C Brayne et al ldquoGlobal prevalence ofdementia a Delphi consensus studyrdquo The Lancet vol 366 no9503 pp 2112ndash2117 2005
[9] W Quentin S G Riedel-Heller M Luppa A Rudolph andH-H Konig ldquoCost-of-illness studies of dementia a systematicreview focusing on stage dependency of costsrdquoActa PsychiatricaScandinavica vol 121 no 4 pp 243ndash259 2010
[10] J Yu X Zhang C Liu Y Meng and J Han ldquoEffect ofacupuncture treatment on vascular dementiardquo NeurologicalResearch vol 28 no 1 pp 97ndash103 2006
[11] G-X Shi C-Z Liu Q-Q Li H Zhu and L-P WangldquoInfluence of acupuncture on cognitive function and markersof oxidative DNA damage in patients with vascular dementiardquoJournal of Traditional Chinese Medicine vol 32 no 2 pp 199ndash202 2012
[12] X-Y Zhong X-X Su J Liu and G Q Zhu ldquoClinical effectsof acupuncture combined with nimodipine for treatment ofvascular dementia in 30 casesrdquo Journal of Traditional ChineseMedicine vol 29 no 3 pp 174ndash176 2009
[13] T Wang C-Z Liu J-C Yu W Jiang and J-X Han ldquoAcupunc-ture protected cerebral multi-infarction rats from memoryimpairment by regulating the expression of apoptosis relatedgenes Bcl-2 and Bax in hippocampusrdquo Physiology and Behaviorvol 96 no 1 pp 155ndash161 2009
[14] I K Hwang J Y Chung D Y Yoo et al ldquoComparing the effectsof acupuncture and electroacupuncture at Zusanli and Baihuion cell proliferation and neuroblast differentiation in the rathippocampusrdquo Journal of VeterinaryMedical Science vol 72 no3 pp 279ndash284 2010
[15] I K Hwang J Y Chung D Y Yoo et al ldquoEffects ofelectroacupuncture at Zusanli and Baihui on brain-derivedneurotrophic factor and cyclic AMP response element-bindingprotein in the hippocampal dentate gyrusrdquo Journal of VeterinaryMedical Science vol 72 no 11 pp 1431ndash1436 2010
[16] Y F Luo and J M Wu Fundamentals of Acupuncture SichuanUniversity Press Sichuan China 2008
[17] R Agrawal and R Srikant ldquoFast algorithms for mining associ-ation rulesrdquo in Proceedings of the 20th International Conferenceon Very Large Data Bases (VLDB rsquo94) pp 487ndash499 SantiagoChile 1994
[18] R Agrawal T Imielinski and A Swami ldquoMining associationrules between sets of items in large databasesrdquo ACM SIGMODRecord vol 22 no 2 pp 207ndash216 1993
12 Evidence-Based Complementary and Alternative Medicine
[19] A Clauset M E J Newman and C Moore ldquoFinding commu-nity structure in very large networksrdquo Physical Review E vol 70no 6 Article ID 066111 6 pages 2004
[20] G F de Arruda A L Barbieri P M Rodriguez et al ldquoRoleof centrality for the identification of influential spreaders incomplex networksrdquo Physical Review E Statistical Nonlinearand SoftMatter Physics vol 90 no 1ndash3 Article ID 032812 2014
[21] T Opsahl F Agneessens and J Skvoretz ldquoNode centrality inweighted networks generalizing degree and shortest pathsrdquoSocial Networks vol 32 no 3 pp 245ndash251 2010
[22] U Brandes ldquoOn variants of shortest-path betweenness central-ity and their generic computationrdquo Social Networks vol 30 no2 pp 136ndash145 2008
[23] H Q Li J H Li A J Liu M Y Ye and G Q ZhengldquoGV20-based acupuncture for animal models of acute intrac-erebral haemorrhage a preclinical systematic review and meta-analysisrdquo Acupuncture in Medicine vol 32 no 6 pp 495ndash5022014
[24] EOda ROhkiHMurasawa et al ldquoNoxa a BH3-onlymemberof the Bcl-2 family and candidate mediator of p53-inducedapoptosisrdquo Science vol 288 no 5468 pp 1053ndash1058 2000
[25] H Endo H Kamada C Nito T Nishi and P H Chan ldquoMito-chondrial translocation of p53 mediates release of cytochromec and hippocampal CA1 neuronal death after transient globalcerebral ischemia in ratsrdquo Journal of Neuroscience vol 26 no30 pp 7974ndash7983 2006
[26] Y Zhu and Y Zeng ldquoElectroacupuncture protected pyramidalcells in hippocampal CA1 region of vascular dementia rats byinhibiting the expression of P53 and Noxardquo CNS NeuroscienceandTherapeutics vol 17 no 6 pp 599ndash604 2011
[27] W J Tyler M Alonso C R Bramham and L D Pozzo-Miller ldquoFrom acquisition to consolidation on the role ofbrain-derived neurotrophic factor signaling in hippocampal-dependent learningrdquo Learning and Memory vol 9 no 5 pp224ndash237 2002
[28] P Bekinschtein M Cammarota C Katche et al ldquoBDNF isessential to promote persistence of long-termmemory storagerdquoProceedings of the National Academy of Sciences of the UnitedStates of America vol 105 no 7 pp 2711ndash2716 2008
[29] K Kitagawa ldquoCREB and cAMP response element-mediatedgene expression in the ischemic brainrdquo FEBS Journal vol 274no 13 pp 3210ndash3217 2007
[30] B Lee B Sur J Shim D Hahm and H Lee ldquoAcupuncturestimulation improves scopolamine-induced cognitive impair-ment via activation of cholinergic system and regulation ofBDNF andCREB expressions in ratsrdquoBMCComplementary andAlternative Medicine vol 14 no 1 article 338 2014
[31] M E Hasselmo ldquoThe role of acetylcholine in learning andmemoryrdquo Current Opinion in Neurobiology vol 16 no 6 pp710ndash715 2006
[32] T M Jay ldquoDopamine a potential substrate for synaptic plastic-ity andmemory mechanismsrdquo Progress in Neurobiology vol 69no 6 pp 375ndash390 2003
[33] C-M Chuang C-L Hsieh T-C Li and J-G Lin ldquoAcupunc-ture stimulation at Baihui acupoint reduced cerebral infarct andincreased dopamine levels in chronic cerebral hypoperfusionand ischemia-reperfusion injured Sprague-Dawley ratsrdquoAmeri-can Journal of ChineseMedicine vol 35 no 5 pp 779ndash791 2007
[34] H Jiao Z Wang Y Liu P Wang and Y Xue ldquoSpecific roleof tight junction proteins claudin-5 occludin and ZO-1 of theblood-brain barrier in a focal cerebral ischemic insultrdquo Journalof Molecular Neuroscience vol 44 no 2 pp 130ndash139 2011
[35] Y-M Zhang H Xu H Sun S Chen and F Wang ldquoElec-troacupuncture treatment improves neurological function asso-ciated with regulation of tight junction proteins in rats withcerebral ischemia reperfusion injuryrdquo Evidence-Based Comple-mentary and Alternative Medicine vol 2014 Article ID 98934010 pages 2014
[36] B-X Jin X-S Lai and C-Z Tang ldquoProgress in researches onthe specificity of acupointsrdquo Acupuncture Research vol 33 no2 pp 135ndash138 2008
[37] Y Li F Liang X Yang et al ldquoAcupuncture for treating acuteattacks of migraine a randomized controlled trialrdquo Headachevol 49 no 6 pp 805ndash816 2009
[38] T T Ma S Y Yu Y Li et al ldquoRandomised clinical trial anassessment of acupuncture on specific meridian or specific acu-point vs sham acupuncture for treating functional dyspepsiardquoAlimentary Pharmacology and Therapeutics vol 35 no 5 pp552ndash561 2012
[39] P-F Shen L Kong L-W Ni et al ldquoAcupuncture interventionin ischemic stroke a randomized controlled prospective studyrdquoThe American Journal of Chinese Medicine vol 40 no 4 pp685ndash693 2012
[40] Y Huang M H Win J Chen et al ldquoA comparative studyon the treatment of vascular dementia by puncturing Baihui(GV20) Shuigou (GV26) and Shenmen (HT7)rdquoWorld Journalof AcupuncturemdashMoxibustion no 1 pp 3ndash10 2005
[41] Y Huang X-S Lai and A-W Tang ldquoComparative study of thespecificities of needling acupoints DU20 DU26 and HT7 inintervening vascular dementia in different areas in the brain onthe basis of scale assessment and cerebral functional imagingrdquoChinese Journal of Integrative Medicine vol 13 no 2 pp 103ndash108 2007
[42] R Alizadeh S Esmaeili S Shoar S Bagheri-Hariri and NShoar ldquoAcupuncture in preventing postoperative nausea andvomiting efficacy of two acupuncture points versus a singleonerdquo Journal of Acupuncture and Meridian Studies vol 7 no2 pp 71ndash75 2014
[43] F M Xu and R X Chen ldquoThe antagonistic effect of acupointson oxygen consumption rate in ratsrdquo Journal of Jiangxi Collegeof Traditional Chinese Medicine vol 13 no 2 pp 60ndash61 2001
[44] F M Xu and R X Chen ldquoEffect of electroacupuncture ongastrointestinalmovement in rats with hypoactive gastrointesti-nal movement caused by greaserdquo Henan Traditional ChineseMedicine vol 20 no 2 pp 19ndash20 2000
[45] X H Li X Z Gao and L Hu ldquoExperimental study on syner-getic and antagonistic effects of acupoints Neiguan Shenmenand Xinshurdquo Chinese Acupuncture andMoxibustion vol 22 no12 pp 819ndash821 2002
[46] X H Li Q Y Wang X Z Gao et al ldquoStudy on cooperationand antagonism among acupointsrdquo Chinese Acupuncture andMoxibustion vol 22 no 6 pp 387ndash388 2002
[47] Y Feng Y Qiu X Zhou Y Wang H Xu and B Liu ldquoOpti-mizing prescription of Chinese herbal medicine for unstableangina based on partially observable Markov decision processrdquoEvidence-based Complementary and Alternative Medicine vol2013 Article ID 532534 6 pages 2013
Submit your manuscripts athttpwwwhindawicom
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Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
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Disease Markers
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OncologyJournal of
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Oxidative Medicine and Cellular Longevity
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PPAR Research
The Scientific World JournalHindawi Publishing Corporation httpwwwhindawicom Volume 2014
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Research and TreatmentAIDS
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Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Parkinsonrsquos Disease
Evidence-Based Complementary and Alternative Medicine
Volume 2014Hindawi Publishing Corporationhttpwwwhindawicom
6 Evidence-Based Complementary and Alternative Medicine
Table 2 Statistics of the 15 most frequently used acupoint combinations in the treatment of VaD
Number Acupoint combination Frequency Support ()1 Baihui (GV 20) Sishencong (EX-HN 1) 98 41182 Baihui (GV 20) Fengchi (GB 20) 81 34033 Baihui (GV 20) Shuigou (GV 26) 72 29834 Baihui (GV 20) Shenting (GV 24) 70 29415 Baihui (GV 20) Zusanli (ST 36) 62 26056 Sishencong (EX-HN 1) Fengchi (GB 20) 60 25217 Baihui (GV 20) Sanyinjiao (SP 6) 57 23958 Baihui (GV 20) Neiguan (PC 6) 54 22699 Sishencong (EX-HN 1) Shuigou (GV 26) 51 214310 Sishencong (EX-HN 1) Baihui (GV 20) Fengchi (GB 20) 51 214311 Baihui (GV 20) Shenmen (HT 7) 51 214312 Sishencong (EX-HN 1) Shenting (GV 24) 49 205913 Sishencong (EX-HN 1) Neiguan (PC 6) 46 193314 Baihui (GV 20) Taixi (KI 3) 46 193315 Sishencong (EX-HN 1) Baihui (GV 20) Shuigou (GV 26) 43 1807Support refers to the percentage of acupoint prescriptions containing the acupoint combination
36 Community Structure Community detection resultedin the division of the 116 acupoints into 5 communitiesNodes of the same color belong to the same community Thecommunity structure is shown in Figure 5(a)
37 Acupoint 119870-Core Network The largest 119896-core value was19 At this value there were 28 nodes corresponding to Hegu(LI 4) Quchi (LI 11) Zusanli (ST 36) Fenglong (ST 40)Sanyinjiao (SP 6) Xuehai (SP 10) Shenmen (HT 7) Tianzhu(BL 10) Xinshu (BL 15) Ganshu (BL 18) Shenshu (BL 23)Taixi (KI 3) Dazhong (KI 4) Neiguan (PC 6) Benshen (GB13) Fengchi (GB 20) Xuanzhong (GB 39) Taichong (LV 3)Mingmen (GV 4) Dazhui (GV 14) Yamen (GV 15) Fengfu(GV 16) Baihui (GV20) Shenting (GV24) Shuigou (GV26)Guanyuan (CV 4) Sishencong (EX-HN 1) and Yintang (EX-HN 3) as shown in Figure 5(b)
38 Degree The top 20 acupoints in degree are shownin Figure 6(a) Baihui (GV 20) Sishencong (EX-HN 1)Fengchi (GB 20) Shenting (GV 24) and Neiguan (PC 6)had the highest degrees with values of 89 76 68 67 and 65respectively
39 Betweenness Centrality Thetop 20 acupoints in between-ness centrality are shown in Figure 6(b) Yongquan (KI 1)Baihui (GV 20) and Sishencong (EX-HN 1) had the highestbetweenness centrality
4 Discussion
41 Potential Acupoints and Combinations for VaD In thisstudy acupoints and combinations with potential for treat-ing VaD were discovered These results may provide somereference for the selection of acupoints in treatment forVaD which may promote the therapeutic effects in clinicalpractice The results suggest that Baihui (GV 20) Sishencong(EX-HN 1) Fengchi (GB 20) Shuigou (GV 26) and Shenting
(GV 24) are potential acupoints for treating VaD In terms ofmeridian acupoints on the Governor Meridian have poten-tial for treating VaD From the perspective of combinationscombinations between such acupoints as Baihui (GV 20)Sishencong (EX-HN 1) Fengchi (GB 20) Shenting (GV 24)Shuigou (GV 26) and Zusanli (ST 36) have potential fortreating VaD In addition acupoints on the head face andneck have more potential for VaD than acupoints on otherregions of the body Specific acupoints have more potentialthan nonspecific acupoints Specific acupoints with specificnames are a group of acupoints on fourteen meridians withspecific therapeutic effectsThere are ten types of specific acu-points Five-Shu acupoints Yuan-Primary acupoints Luo-Connecting acupoints Xi-Cleft acupoints Lower He-Seaacupoints Back-Shu acupoints Front-Mu acupoints eightinfluential acupoints eight confluent acupoints connectingthe eight extra meridians and convergent acupoints
Community detection divided the acupoints into 5 com-munities Acupoints within the same community have somecharacteristics in common Blue nodes (Community A) wereall Jing-Well acupoints Yellow nodes (Community B) were allacupoints on the face and head Most green nodes (Commu-nity C) were acupoints on the four limbs Most purple nodes(Community D) were acupoints belonging to Governor Ves-sel Most red nodes (Community E) were specific acupointsor acupoints with specific therapeutic effects and only thiscommunity contained Bach-Shu acupoints and acupointson the abdomen Acupoints within the same communitywere more densely connected with each other comparedwith acupoints from different communities indicating thatan acupoint was more often used with acupoints withinthe same community compared with acupoints within othercommunities
The 19-core network indicated that 28 acupoints includ-ing Hegu (LI 4) Quchi (LI 11) Zusanli (ST 36) Fenglong(ST 40) Sanyinjiao (SP 6) Xuehai (SP 10) Shenmen (HT 7)
Evidence-Based Complementary and Alternative Medicine 7
0
5
10
15
20
25
30
35
40
45
Head faceand neck
Lowerlimbs
Upperlimbs
Back andlumbar
Chest andabdomen
Number
(a) The numbers of acupoints in different parts
0
100
200
300
400
500
600
700
800
900
Head faceand neck
Lowerlimbs
Upperlimbs
Back andlumbar
Chest andabdomen
Frequency
(b) The frequencies of acupoints in different parts
0
5
10
15
20
25
30
35
40
Number
Con
verg
ent a
cupo
int
Five
-Shu
acup
oint
Yuan
-sou
rce p
oint
Luo-
Con
nect
ing
poin
t
Eigh
t infl
uent
ial p
oint
Shu-
Back
poi
nt
Eigh
t con
fluen
t acu
poin
ts
Fron
t-Mu
poin
t
Low
er H
e-Se
a poi
nt
Non
spec
ifc p
oint
(c) The numbers of different kinds of acupoints
0
100
200
300
400
500
600
700
800
Frequency
Con
verg
ent a
cupo
int
Five
-Shu
acup
oint
Yuan
-sou
rce p
oint
Luo-
Con
nect
ing
poin
t
Eigh
t infl
uent
ial p
oint
Shu-
Back
poi
nt
Eigh
t con
fluen
t acu
poin
ts
Fron
t-Mu
poin
t
Low
er H
e-Se
a poi
nt
Non
spec
ifc p
oint
(d) The frequencies of different kinds of acupoints
Figure 4 The frequencies and numbers of acupoints in different body parts and different types of acupoints
Tianzhu (BL 10) Xinshu (BL 15) Ganshu (BL 18) Shenshu(BL 23) Taixi (KI 3) Dazhong (KI 4) Neiguan (PC 6)Benshen (GB 13) Fengchi (GB 20) Xuanzhong (GB 39)Taichong (LV 3) Mingmen (GV 4) Dazhui (GV 14) Yamen(GV 15) Fengfu (GV 16) Baihui (GV 20) Shenting (GV 24)Shuigou (GV 26) Guanyuan (CV 4) Sishencong (EX-HN 1)and Yintang (EX-HN 3) are core acupoints in the network
Baihui (GV 20) Sishencong (EX-HN 1) Fengchi (GB20) Shenting (GV 24) and Neiguan (PC 6) had the highestdegreesThis result indicates that these 5 acupoints have beencombined with more acupoints than other acupoints Theseacupoints have specific therapeutic effects on VaDThereforethese acupoints can be used together with other acupoints toenhance therapeutic effects
Yongquan (KI 1) Baihui (GV 20) Sishencong (EX-HN1) Neiguan (PC 6) and Shenting (GV 24) which belonged
to 4 different communities had higher betweenness cen-trality Yongquan (KI 1) which had the highest betweennesscentrality did not have a relatively high degree However itconnects Jing-Well acupoints with other types of acupointsresulting in a high betweenness centrality Acupoints withhigher betweenness centrality play an important role inconnecting different types of acupoints Jing-Well acupointsexcept Yongquan (KI 1) were often used with other Jing-Wellacupoints only Yongquan (KI 1) was not only used with otherJing-Well acupoints but also with other types of acupointssuch as other types of specific acupoints nonspecific acu-points and acupoints on other parts The high betweennesscentrality suggested that Yongquan (KI 1) may have multipleeffects compared with other Jing-Well acupoints in treatmentof VaD From the perspective of TCM theory Jing-Wellacupoints can restore consciousness Yongquan (KI 1) was
8 Evidence-Based Complementary and Alternative Medicine
BL17
EX-HN22
BL7
LI1
GV13
SP9
GB11
EX-HN14
GB4
HT1
ST2
CV8
GB5
GV18
BL11
EX-UE8
LI20
GV1
ST36
BL20
CV17
BL58
BL9
GV17
GV14
GV15
GV11
GV12
GV10GV5
KI3
KI1
LU11
HT9
GV8
GV3
BL23
GV4
CV6
CV12
HT7GB20
GB17
GV24
GV16
CV4
GB8
GV21GV23GB13
SP10
BL10
ST32
GB34LI14
LI15
GB32
LI10
BL40
GB31
KI6
SI5
KI2
PC7
LI4
GB16
EX-HN5
GB12
PC8
PC6
BL18
BL15
BL56
GB40
TE9
EX-UE9SP6
TE5
SP3
LI11
GV22
BL60
GB6
GB14
GB15
GB19
ST9
GV7
GV2
GV6
EX-B8
BL4
SI1
PC9
TE1ST45
SP1
BL67
GB44
LV1
TE23
TE20
LU7
GV19
ST40
EX-HN3ST8
GV20
KI4
GB39
GB7
EX-HN1
PC5
LV3
GV9
GV26
(a) Network structure of acupoints for the treatment of VaD
GB13
EX-HN1
EX-HN3
LI4
KI3
KI4
HT7GB20
GV14
GV15
GV16
LV3
ST36
BL23
GV4
GV24
GV26GV20
ST40
SP6
LI11
GB39
SP10
PC6
BL10
CV4
BL18
BL15
(b) 19-core network
Figure 5 (a) Network structure of acupoints for the treatment of VaD Blue nodes (Community A) are all Jing-Well acupoints Yellow nodes(Community B) are all acupoints on the face and head Most green nodes (Community C) are acupoints on four limbs Most purple nodes(Community D) are acupoints belonging to Governor Vessel Most red nodes (Community E) are specific acupoints or acupoints withspecific therapeutic effects and only this community contains Bach-Shu acupoints and acupoints on the abdomen Acupoints within thesame community are more densely connected with each other than acupoints from different communities (b) 19-core network There are 28acupoints in the 19-core network They are core acupoints in the treatment of VaD
Evidence-Based Complementary and Alternative Medicine 9
0102030405060708090
100
GV
20
EX-H
N1
GB2
0
GV
24
PC6
SP6
GV
14
GV
26
GV
16
HT7 LI
4
KI3
ST36
ST40
LV3
GB1
3
EX-H
N3
BL10
GB3
9
LI 1
1
Degree
(a) The 20 acupoints with highest degree
0002004006008
01012014016
KI1
GV
20
EX-H
N1
PC6
GV
26
GB2
0
GV
24
GV
14 SP6
EX-H
N3
HT7 LI
4
KI3
GV
16
BL10
LV3
ST40
ST36
GB1
3
PC9
Betweenness centrality
(b) The 20 acupoints with highest betweenness centrality
Figure 6 The 20 acupoints with highest degree and the 20 acupoints with highest betweenness centrality
also used to tonify kidney in treatment of VaD ThereforeYongquan (KI 1) is used not only with other Jing-Wellacupoints but also with other types of acupoints such asother types of specific acupoints nonspecific acupoints andacupoints on other parts
42 UnderlyingMolecularMechanism of the Acupoint with theMost Potential to Treat VaD According to our results Baihui(GV 20) which had the highest frequency has the mostpotential to treat VaD A systematic review andmeta-analysisalso suggested that Baihui (GV 20) is a principal acupoint foracute intracerebral hemorrhage (ICH) in animal models ofacute ICH there was no difference in efficacy between Baihui(GV 20) alone and Baihui (GV 20) plus other acupoints [23]
Molecular biology studies have provided insights intothe mechanisms underlying the effects of Baihui (GV 20) inVaD treatment including antioxidant effects antiapoptoticeffects neurotrophic effects reduced blood-brain barrier(BBB) permeability and regulation of the cholinergic anddopaminergic systems Acupuncture at Baihui (GV 20) incombination with other acupoints decreases levels of 8-hydroxy-21015840-deoxyguanosine a product of oxidative damageto DNA induced by free radicals suggesting that the benefitof acupuncture is partly due to antioxidant effects [11]Acupuncture exerts therapeutic effects on VaD via antiapop-tosis The tumor suppressors p53 and Noxa are important inregulating apoptosis and mediate hypoxic cell death [24 25]
Electroacupuncture at Baihui (GV 20) Dazhui (GV 14) andShenshu (BL 23) blocks expression of p53 and Noxa in thehippocampal CA1 region of VaD rats [26] Acupuncture atBaihui (GV 20) can improve neurogenesis via regulatingbrain-derived neurotrophic factor (BDNF) and cyclic AMPresponse element-binding protein (CREB) BDNF whichis essential for synaptic plasticity and is coupled to CREBactivation [27] is important for long-term memory storage[28] CREB is required for the proliferation growth survivaland differentiation of all types of cells In the brain the CREBand CRE-mediated system is involved in memory learningsynaptic transmission neuron survival differentiation andaxon growth [29] Acupuncture at Baihui (GV 20) signifi-cantly increases the levels of BDNF [15 30] CREB proteinsCREB mRNA [30] and phosphorylated CREB the activeform of CREB [15] The molecular mechanism underlyingacupuncture at Baihui (GV 20) also involves cholinergicsystem regulation Decreased cholinergic function in thebrain can result in a decline in memory and cognitivefunction [31] Acupuncture at Baihui (GV 20) significantlyincreases the levels of choline acetyltransferase (ChAT) andrestores the expression of choline transporter 1 (CHT1)and vesicular acetylcholine transporter (VAChT) [30] Thedopaminergic system is also involved in the mechanismunderlying the treatment of VaD with acupuncture at Baihui(GV 20) Dopamine is a key regulator in specific synapticchanges observed at certain stages of learning and memory
10 Evidence-Based Complementary and Alternative Medicine
and of synaptic plasticity [32] Acupuncture at Baihui (GV20)increases dopamine levels in chronic cerebral hypoperfusionand ischemia-reperfusion injured rats [33] In additionacupuncture at Baihui (GV 20) and Zusanli (ST 36) preservesthe integrity of the BBB reducing BBB permeability TheBBB is constructed of tight conjunctions including occludinand claudin-5 which form the endothelial barrier Reducedexpression of ZO-1 claudin-5 and occludin mRNA andprotein contributes to BBB breakdown and edema in theischemic brain [34] Electroacupuncture at Baihui (GV 20)and Zusanli (ST 36) reduces brain damage and relatedbehavioral deficits via upregulation of tight conjunctionproteins including ZO-1 claudin-5 and occludin [35]Thesefindings reveal parts of the molecular mechanism underlyingacupuncture at Baihui (GV 20) to treat VaD
43 Acupoints Selection in Treatment for VaD The properselection of acupoints is essential for the therapeutic effectsof acupuncture because acupoints are specific with regard tomorphological structure biophysical properties pathologicalresponse and stimulating effects [36] This specificity dif-ferentiates acupoints from nonacupoints as well as differentacupoints from one another The specific therapeutic effectsof different acupoints have been reported for migraine [37]functional dyspepsia [38] ischemic stroke [39] and so forth
The specificity of acupoints for the treatment of VaDhas also been reported Phosphorylated CREB levels weresignificantly increased after acupuncture therapy of needlingBaihui (GV 20) and Zusanli (ST 36) compared to shamacupuncture therapy of needling nonacupoints [15] Baihui(GV 20) Shuigou (GV 26) and Shenmen (HT 7) are allamong the 10 acupoints with the most potential A clinicaltrial demonstrated that needling Baihui (GV 20) Shuigou(GV 26) and Shenmen (HT 7) were all effective in improvingthe symptoms of VaD However their therapeutic effects dif-fer Needling Baihui (GV 20) improved calculation ability andshort-term memory and corrected the personality changesof VaD patients while needling Shuigou (GV 26) improvednaming ability and short-term memory The therapeuticeffects of needling Baihui (GV 20) and Shuigou (GV 26)were superior to those of needling Shenmen (HT 7) [40]A PET and SPECT study revealed that needling these threedifferent acupoints in VaD patients affected different brainareas Needling Baihui (GV 20) activated the inner temporalsystem the thalamencephalon system and the prefrontalcortical system Needling Shuigou (GV 26) activated the pre-frontal cortical system Needling Shenmen (HT 7) generatedan effect similar to but weaker than the effect generated byneedling Shuigou (GV 26) [41] These findings demonstratethat different acupoints have different therapeutic effects inacupuncture treatment for VaD Consequently the selectionof acupoints which directly influences the therapeutic effectsof acupuncture should be considered carefully According toour results based on datamining Baihui (GV 20) Sishencong(EX-HN 1) Fengchi (GB 20) Shuigou (GV 26) and Shenting(GV 24) which have higher frequencies in the modernliterature may have better therapeutic effects on VaD
44 SingleAcupoint orAcupoint Combination Acupoint com-binations also influence the therapeutic effects of acupunc-ture An acupoint combination is considered to have asynergistic effect that enhances the therapeutic effect ofacupuncture For example a lower prevalence of postoper-ative nausea and vomiting in patients treated with Neiguan(PC 6) plus Hegu (LI 4) was observed compared with thosetreated with Neiguan (PC 6) only [42] In spite of extensiveevidence suggesting a synergistic effect of acupoint combi-nation and supporting its use some studies have reportedantagonistic effects [43ndash45] An antagonistic effect occurswhen one acupoint weakens the therapeutic effect of anotheracupoint [46] For example electroacupuncture can improvegastrointestinal movement in rats The effect of needlingPishu (BL 20) alone was better than the effect of needlingPishu (BL 20) and Zusanli (ST 36) at the same time [44]Therefore whether the effect of acupoint combination isbetter than a single acupoint still remains a question andneeds to be further studied
Some studies have compared single acupoints and anacupoint combination for the treatment of VaD The thera-peutic effect of needling Baihui (GV 20) Shuigou (GV 26)and Shenmen (HT 7) in combination was better than theeffects obtained by needling each alone [40] In additionneedling Baihui (GV 20) Shuigou (GV 26) and Shenmen(HT 7) simultaneously activated more brain areas relatedto intellectual activities compared with needling each alonegenerating a more extensive effect on the brain [41] Antago-nistic effects in acupuncture therapy for VaD have not beenreported but may occur Most acupuncture prescriptions forVaD contain acupoint combinations and the use of acupointcombinations is supported However acupoint combinationsshould be selected carefully to avoid antagonistic effects Itis hard to tell whether a combination of acupoints will exertantagonistic effects with current knowledge or TCM theoryAs abovementioned acupoints with similar functions canexert antagonistic effects There are many acupoints and thenumber of acupoint combinations will grow geometricallyTo test the antagonistic effects of each combination oneby one is an exhausting job To avoid antagonistic effectsas possible the acupoint prescriptions should be simplifiedas possible The general principle is to select acupointswith relatively better therapeutic effects and acupoints withmultiple indications and not to select many acupoints
45 Limitations This study has limitations as follows Firstother factors that influence acupuncture such as manipula-tion and treatment duration were not analyzed in this studyThese data can be further mined in future studies Secondlargely due to the lack of treatment based on syndrome differ-entiation and different methods of syndrome differentiationin modern literature potential acupoints and combinationsfor different syndromes of VaD were not analyzed Althoughtreatment based on syndrome differentiation is importantand is often emphasized in TCM treatment based on diseasedifferentiation is equally important Third the real therapeu-tic effects of acupoints and combinations on VaD cannotbe reflected by frequencies in the literature However theseresults suggest some potential acupoints and combinations to
Evidence-Based Complementary and Alternative Medicine 11
be explored in future clinical trials to validate the effects ofacupuncture on VaD To optimize the acupoint prescriptiondata may be extracted not only from literature but alsofrom clinical practice Further research can collect acupointprescriptions and symptom improvements in clinical practiceand optimize acupoint prescriptionwith dataminingMiningclinical data has been practiced to optimize prescriptionof Chinese herbal medicine for unstable angina by Fenget al [47] In their study five main symptoms of patientswith unstable angina the severity of each symptom andthe prescription of each patient were collected The levels ofaverage discounted reward (ADR) of different prescriptionswere calculated to evaluate the clinical efficacy of differ-ent treatment options with some optimized prescriptionsachieved Future studies can mine clinical data to optimizeacupoint prescription
5 Conclusions
In this study data mining was used to discover potentialacupoints and combinations for VaD Potential acupointsinclude Baihui (GV 20) Sishencong (EX-HN 1) Fengchi (GB20) Shuigou (GV 26) and Shenting (GV 24) In additioncombinations between Baihui (GV 20) Sishencong (EX-HN1) Fengchi (GB 20) Shenting (GV 24) Shuigou (GV 26) andZusanli (ST 36) were potential combinations Based on ourresults Baihui (GV 20) and Sishencong (EX-HN 1) shouldbe selected with priority Acupoints in head compared toacupoints in other parts should also be selected with priority
Conflict of Interests
The authors declare no conflict of interests
Authorsrsquo Contribution
Shuwei Feng and Yulan Ren contributed equally to this work
Acknowledgments
This study was supported by the National Basic ResearchProgram of China (no 2012CB518501) and the NationalScience Foundation of China (nos 81102742 and 61104224)
References
[1] Q Chen X Wu S F Lu et al ldquoMeridian acupoints selectionin acupuncture treatment for migraine the main charactersand relevant factors analysisrdquo Liaoning Journal of TraditionalChinese Medicine vol 36 no 9 pp 1477ndash1480 2009
[2] Y Li H Zheng C M Witt et al ldquoAcupuncture for migraineprophylaxis a randomized controlled trialrdquo Canadian MedicalAssociation Journal vol 184 no 4 pp 401ndash410 2012
[3] B H May C Lu L Bennett H M Hugel and C C LXue ldquoEvaluating the traditional Chinese literature for herbalformulae and individual herbs used for age-related dementiaand memory impairmentrdquo Biogerontology vol 13 no 3 pp299ndash312 2012
[4] L Zhang Y Li X Guo et al ldquoText mining of the classicalmedical literature for medicines that show potential in diabeticnephropathyrdquo Evidence-Based Complementary and AlternativeMedicine vol 2014 Article ID 189125 12 pages 2014
[5] Y Olsson A Brun and E Englund ldquoFundamental pathologicallesions in vascular dementiardquo Acta Neurologica Scandinavicavol 94 supplement 168 pp 31ndash38 1996
[6] S Davis M Shanahan A Campbell M Hegarty and BMcCarthy ldquoPalliative care for people with dementia aged carestaff perspectivesrdquo Alzheimerrsquos amp Dementia vol 7 no 4 p e502011
[7] J Jia F Wang C Wei et al ldquoThe prevalence of dementia inurban and rural areas of Chinardquo Alzheimerrsquos and Dementia vol10 no 1 pp 1ndash9 2014
[8] C P Ferri M Prince C Brayne et al ldquoGlobal prevalence ofdementia a Delphi consensus studyrdquo The Lancet vol 366 no9503 pp 2112ndash2117 2005
[9] W Quentin S G Riedel-Heller M Luppa A Rudolph andH-H Konig ldquoCost-of-illness studies of dementia a systematicreview focusing on stage dependency of costsrdquoActa PsychiatricaScandinavica vol 121 no 4 pp 243ndash259 2010
[10] J Yu X Zhang C Liu Y Meng and J Han ldquoEffect ofacupuncture treatment on vascular dementiardquo NeurologicalResearch vol 28 no 1 pp 97ndash103 2006
[11] G-X Shi C-Z Liu Q-Q Li H Zhu and L-P WangldquoInfluence of acupuncture on cognitive function and markersof oxidative DNA damage in patients with vascular dementiardquoJournal of Traditional Chinese Medicine vol 32 no 2 pp 199ndash202 2012
[12] X-Y Zhong X-X Su J Liu and G Q Zhu ldquoClinical effectsof acupuncture combined with nimodipine for treatment ofvascular dementia in 30 casesrdquo Journal of Traditional ChineseMedicine vol 29 no 3 pp 174ndash176 2009
[13] T Wang C-Z Liu J-C Yu W Jiang and J-X Han ldquoAcupunc-ture protected cerebral multi-infarction rats from memoryimpairment by regulating the expression of apoptosis relatedgenes Bcl-2 and Bax in hippocampusrdquo Physiology and Behaviorvol 96 no 1 pp 155ndash161 2009
[14] I K Hwang J Y Chung D Y Yoo et al ldquoComparing the effectsof acupuncture and electroacupuncture at Zusanli and Baihuion cell proliferation and neuroblast differentiation in the rathippocampusrdquo Journal of VeterinaryMedical Science vol 72 no3 pp 279ndash284 2010
[15] I K Hwang J Y Chung D Y Yoo et al ldquoEffects ofelectroacupuncture at Zusanli and Baihui on brain-derivedneurotrophic factor and cyclic AMP response element-bindingprotein in the hippocampal dentate gyrusrdquo Journal of VeterinaryMedical Science vol 72 no 11 pp 1431ndash1436 2010
[16] Y F Luo and J M Wu Fundamentals of Acupuncture SichuanUniversity Press Sichuan China 2008
[17] R Agrawal and R Srikant ldquoFast algorithms for mining associ-ation rulesrdquo in Proceedings of the 20th International Conferenceon Very Large Data Bases (VLDB rsquo94) pp 487ndash499 SantiagoChile 1994
[18] R Agrawal T Imielinski and A Swami ldquoMining associationrules between sets of items in large databasesrdquo ACM SIGMODRecord vol 22 no 2 pp 207ndash216 1993
12 Evidence-Based Complementary and Alternative Medicine
[19] A Clauset M E J Newman and C Moore ldquoFinding commu-nity structure in very large networksrdquo Physical Review E vol 70no 6 Article ID 066111 6 pages 2004
[20] G F de Arruda A L Barbieri P M Rodriguez et al ldquoRoleof centrality for the identification of influential spreaders incomplex networksrdquo Physical Review E Statistical Nonlinearand SoftMatter Physics vol 90 no 1ndash3 Article ID 032812 2014
[21] T Opsahl F Agneessens and J Skvoretz ldquoNode centrality inweighted networks generalizing degree and shortest pathsrdquoSocial Networks vol 32 no 3 pp 245ndash251 2010
[22] U Brandes ldquoOn variants of shortest-path betweenness central-ity and their generic computationrdquo Social Networks vol 30 no2 pp 136ndash145 2008
[23] H Q Li J H Li A J Liu M Y Ye and G Q ZhengldquoGV20-based acupuncture for animal models of acute intrac-erebral haemorrhage a preclinical systematic review and meta-analysisrdquo Acupuncture in Medicine vol 32 no 6 pp 495ndash5022014
[24] EOda ROhkiHMurasawa et al ldquoNoxa a BH3-onlymemberof the Bcl-2 family and candidate mediator of p53-inducedapoptosisrdquo Science vol 288 no 5468 pp 1053ndash1058 2000
[25] H Endo H Kamada C Nito T Nishi and P H Chan ldquoMito-chondrial translocation of p53 mediates release of cytochromec and hippocampal CA1 neuronal death after transient globalcerebral ischemia in ratsrdquo Journal of Neuroscience vol 26 no30 pp 7974ndash7983 2006
[26] Y Zhu and Y Zeng ldquoElectroacupuncture protected pyramidalcells in hippocampal CA1 region of vascular dementia rats byinhibiting the expression of P53 and Noxardquo CNS NeuroscienceandTherapeutics vol 17 no 6 pp 599ndash604 2011
[27] W J Tyler M Alonso C R Bramham and L D Pozzo-Miller ldquoFrom acquisition to consolidation on the role ofbrain-derived neurotrophic factor signaling in hippocampal-dependent learningrdquo Learning and Memory vol 9 no 5 pp224ndash237 2002
[28] P Bekinschtein M Cammarota C Katche et al ldquoBDNF isessential to promote persistence of long-termmemory storagerdquoProceedings of the National Academy of Sciences of the UnitedStates of America vol 105 no 7 pp 2711ndash2716 2008
[29] K Kitagawa ldquoCREB and cAMP response element-mediatedgene expression in the ischemic brainrdquo FEBS Journal vol 274no 13 pp 3210ndash3217 2007
[30] B Lee B Sur J Shim D Hahm and H Lee ldquoAcupuncturestimulation improves scopolamine-induced cognitive impair-ment via activation of cholinergic system and regulation ofBDNF andCREB expressions in ratsrdquoBMCComplementary andAlternative Medicine vol 14 no 1 article 338 2014
[31] M E Hasselmo ldquoThe role of acetylcholine in learning andmemoryrdquo Current Opinion in Neurobiology vol 16 no 6 pp710ndash715 2006
[32] T M Jay ldquoDopamine a potential substrate for synaptic plastic-ity andmemory mechanismsrdquo Progress in Neurobiology vol 69no 6 pp 375ndash390 2003
[33] C-M Chuang C-L Hsieh T-C Li and J-G Lin ldquoAcupunc-ture stimulation at Baihui acupoint reduced cerebral infarct andincreased dopamine levels in chronic cerebral hypoperfusionand ischemia-reperfusion injured Sprague-Dawley ratsrdquoAmeri-can Journal of ChineseMedicine vol 35 no 5 pp 779ndash791 2007
[34] H Jiao Z Wang Y Liu P Wang and Y Xue ldquoSpecific roleof tight junction proteins claudin-5 occludin and ZO-1 of theblood-brain barrier in a focal cerebral ischemic insultrdquo Journalof Molecular Neuroscience vol 44 no 2 pp 130ndash139 2011
[35] Y-M Zhang H Xu H Sun S Chen and F Wang ldquoElec-troacupuncture treatment improves neurological function asso-ciated with regulation of tight junction proteins in rats withcerebral ischemia reperfusion injuryrdquo Evidence-Based Comple-mentary and Alternative Medicine vol 2014 Article ID 98934010 pages 2014
[36] B-X Jin X-S Lai and C-Z Tang ldquoProgress in researches onthe specificity of acupointsrdquo Acupuncture Research vol 33 no2 pp 135ndash138 2008
[37] Y Li F Liang X Yang et al ldquoAcupuncture for treating acuteattacks of migraine a randomized controlled trialrdquo Headachevol 49 no 6 pp 805ndash816 2009
[38] T T Ma S Y Yu Y Li et al ldquoRandomised clinical trial anassessment of acupuncture on specific meridian or specific acu-point vs sham acupuncture for treating functional dyspepsiardquoAlimentary Pharmacology and Therapeutics vol 35 no 5 pp552ndash561 2012
[39] P-F Shen L Kong L-W Ni et al ldquoAcupuncture interventionin ischemic stroke a randomized controlled prospective studyrdquoThe American Journal of Chinese Medicine vol 40 no 4 pp685ndash693 2012
[40] Y Huang M H Win J Chen et al ldquoA comparative studyon the treatment of vascular dementia by puncturing Baihui(GV20) Shuigou (GV26) and Shenmen (HT7)rdquoWorld Journalof AcupuncturemdashMoxibustion no 1 pp 3ndash10 2005
[41] Y Huang X-S Lai and A-W Tang ldquoComparative study of thespecificities of needling acupoints DU20 DU26 and HT7 inintervening vascular dementia in different areas in the brain onthe basis of scale assessment and cerebral functional imagingrdquoChinese Journal of Integrative Medicine vol 13 no 2 pp 103ndash108 2007
[42] R Alizadeh S Esmaeili S Shoar S Bagheri-Hariri and NShoar ldquoAcupuncture in preventing postoperative nausea andvomiting efficacy of two acupuncture points versus a singleonerdquo Journal of Acupuncture and Meridian Studies vol 7 no2 pp 71ndash75 2014
[43] F M Xu and R X Chen ldquoThe antagonistic effect of acupointson oxygen consumption rate in ratsrdquo Journal of Jiangxi Collegeof Traditional Chinese Medicine vol 13 no 2 pp 60ndash61 2001
[44] F M Xu and R X Chen ldquoEffect of electroacupuncture ongastrointestinalmovement in rats with hypoactive gastrointesti-nal movement caused by greaserdquo Henan Traditional ChineseMedicine vol 20 no 2 pp 19ndash20 2000
[45] X H Li X Z Gao and L Hu ldquoExperimental study on syner-getic and antagonistic effects of acupoints Neiguan Shenmenand Xinshurdquo Chinese Acupuncture andMoxibustion vol 22 no12 pp 819ndash821 2002
[46] X H Li Q Y Wang X Z Gao et al ldquoStudy on cooperationand antagonism among acupointsrdquo Chinese Acupuncture andMoxibustion vol 22 no 6 pp 387ndash388 2002
[47] Y Feng Y Qiu X Zhou Y Wang H Xu and B Liu ldquoOpti-mizing prescription of Chinese herbal medicine for unstableangina based on partially observable Markov decision processrdquoEvidence-based Complementary and Alternative Medicine vol2013 Article ID 532534 6 pages 2013
Submit your manuscripts athttpwwwhindawicom
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Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
MEDIATORSINFLAMMATION
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Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
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Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
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Disease Markers
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
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OncologyJournal of
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Oxidative Medicine and Cellular Longevity
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
PPAR Research
The Scientific World JournalHindawi Publishing Corporation httpwwwhindawicom Volume 2014
Immunology ResearchHindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Journal of
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Computational and Mathematical Methods in Medicine
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Research and TreatmentAIDS
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
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Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Parkinsonrsquos Disease
Evidence-Based Complementary and Alternative Medicine
Volume 2014Hindawi Publishing Corporationhttpwwwhindawicom
Evidence-Based Complementary and Alternative Medicine 7
0
5
10
15
20
25
30
35
40
45
Head faceand neck
Lowerlimbs
Upperlimbs
Back andlumbar
Chest andabdomen
Number
(a) The numbers of acupoints in different parts
0
100
200
300
400
500
600
700
800
900
Head faceand neck
Lowerlimbs
Upperlimbs
Back andlumbar
Chest andabdomen
Frequency
(b) The frequencies of acupoints in different parts
0
5
10
15
20
25
30
35
40
Number
Con
verg
ent a
cupo
int
Five
-Shu
acup
oint
Yuan
-sou
rce p
oint
Luo-
Con
nect
ing
poin
t
Eigh
t infl
uent
ial p
oint
Shu-
Back
poi
nt
Eigh
t con
fluen
t acu
poin
ts
Fron
t-Mu
poin
t
Low
er H
e-Se
a poi
nt
Non
spec
ifc p
oint
(c) The numbers of different kinds of acupoints
0
100
200
300
400
500
600
700
800
Frequency
Con
verg
ent a
cupo
int
Five
-Shu
acup
oint
Yuan
-sou
rce p
oint
Luo-
Con
nect
ing
poin
t
Eigh
t infl
uent
ial p
oint
Shu-
Back
poi
nt
Eigh
t con
fluen
t acu
poin
ts
Fron
t-Mu
poin
t
Low
er H
e-Se
a poi
nt
Non
spec
ifc p
oint
(d) The frequencies of different kinds of acupoints
Figure 4 The frequencies and numbers of acupoints in different body parts and different types of acupoints
Tianzhu (BL 10) Xinshu (BL 15) Ganshu (BL 18) Shenshu(BL 23) Taixi (KI 3) Dazhong (KI 4) Neiguan (PC 6)Benshen (GB 13) Fengchi (GB 20) Xuanzhong (GB 39)Taichong (LV 3) Mingmen (GV 4) Dazhui (GV 14) Yamen(GV 15) Fengfu (GV 16) Baihui (GV 20) Shenting (GV 24)Shuigou (GV 26) Guanyuan (CV 4) Sishencong (EX-HN 1)and Yintang (EX-HN 3) are core acupoints in the network
Baihui (GV 20) Sishencong (EX-HN 1) Fengchi (GB20) Shenting (GV 24) and Neiguan (PC 6) had the highestdegreesThis result indicates that these 5 acupoints have beencombined with more acupoints than other acupoints Theseacupoints have specific therapeutic effects on VaDThereforethese acupoints can be used together with other acupoints toenhance therapeutic effects
Yongquan (KI 1) Baihui (GV 20) Sishencong (EX-HN1) Neiguan (PC 6) and Shenting (GV 24) which belonged
to 4 different communities had higher betweenness cen-trality Yongquan (KI 1) which had the highest betweennesscentrality did not have a relatively high degree However itconnects Jing-Well acupoints with other types of acupointsresulting in a high betweenness centrality Acupoints withhigher betweenness centrality play an important role inconnecting different types of acupoints Jing-Well acupointsexcept Yongquan (KI 1) were often used with other Jing-Wellacupoints only Yongquan (KI 1) was not only used with otherJing-Well acupoints but also with other types of acupointssuch as other types of specific acupoints nonspecific acu-points and acupoints on other parts The high betweennesscentrality suggested that Yongquan (KI 1) may have multipleeffects compared with other Jing-Well acupoints in treatmentof VaD From the perspective of TCM theory Jing-Wellacupoints can restore consciousness Yongquan (KI 1) was
8 Evidence-Based Complementary and Alternative Medicine
BL17
EX-HN22
BL7
LI1
GV13
SP9
GB11
EX-HN14
GB4
HT1
ST2
CV8
GB5
GV18
BL11
EX-UE8
LI20
GV1
ST36
BL20
CV17
BL58
BL9
GV17
GV14
GV15
GV11
GV12
GV10GV5
KI3
KI1
LU11
HT9
GV8
GV3
BL23
GV4
CV6
CV12
HT7GB20
GB17
GV24
GV16
CV4
GB8
GV21GV23GB13
SP10
BL10
ST32
GB34LI14
LI15
GB32
LI10
BL40
GB31
KI6
SI5
KI2
PC7
LI4
GB16
EX-HN5
GB12
PC8
PC6
BL18
BL15
BL56
GB40
TE9
EX-UE9SP6
TE5
SP3
LI11
GV22
BL60
GB6
GB14
GB15
GB19
ST9
GV7
GV2
GV6
EX-B8
BL4
SI1
PC9
TE1ST45
SP1
BL67
GB44
LV1
TE23
TE20
LU7
GV19
ST40
EX-HN3ST8
GV20
KI4
GB39
GB7
EX-HN1
PC5
LV3
GV9
GV26
(a) Network structure of acupoints for the treatment of VaD
GB13
EX-HN1
EX-HN3
LI4
KI3
KI4
HT7GB20
GV14
GV15
GV16
LV3
ST36
BL23
GV4
GV24
GV26GV20
ST40
SP6
LI11
GB39
SP10
PC6
BL10
CV4
BL18
BL15
(b) 19-core network
Figure 5 (a) Network structure of acupoints for the treatment of VaD Blue nodes (Community A) are all Jing-Well acupoints Yellow nodes(Community B) are all acupoints on the face and head Most green nodes (Community C) are acupoints on four limbs Most purple nodes(Community D) are acupoints belonging to Governor Vessel Most red nodes (Community E) are specific acupoints or acupoints withspecific therapeutic effects and only this community contains Bach-Shu acupoints and acupoints on the abdomen Acupoints within thesame community are more densely connected with each other than acupoints from different communities (b) 19-core network There are 28acupoints in the 19-core network They are core acupoints in the treatment of VaD
Evidence-Based Complementary and Alternative Medicine 9
0102030405060708090
100
GV
20
EX-H
N1
GB2
0
GV
24
PC6
SP6
GV
14
GV
26
GV
16
HT7 LI
4
KI3
ST36
ST40
LV3
GB1
3
EX-H
N3
BL10
GB3
9
LI 1
1
Degree
(a) The 20 acupoints with highest degree
0002004006008
01012014016
KI1
GV
20
EX-H
N1
PC6
GV
26
GB2
0
GV
24
GV
14 SP6
EX-H
N3
HT7 LI
4
KI3
GV
16
BL10
LV3
ST40
ST36
GB1
3
PC9
Betweenness centrality
(b) The 20 acupoints with highest betweenness centrality
Figure 6 The 20 acupoints with highest degree and the 20 acupoints with highest betweenness centrality
also used to tonify kidney in treatment of VaD ThereforeYongquan (KI 1) is used not only with other Jing-Wellacupoints but also with other types of acupoints such asother types of specific acupoints nonspecific acupoints andacupoints on other parts
42 UnderlyingMolecularMechanism of the Acupoint with theMost Potential to Treat VaD According to our results Baihui(GV 20) which had the highest frequency has the mostpotential to treat VaD A systematic review andmeta-analysisalso suggested that Baihui (GV 20) is a principal acupoint foracute intracerebral hemorrhage (ICH) in animal models ofacute ICH there was no difference in efficacy between Baihui(GV 20) alone and Baihui (GV 20) plus other acupoints [23]
Molecular biology studies have provided insights intothe mechanisms underlying the effects of Baihui (GV 20) inVaD treatment including antioxidant effects antiapoptoticeffects neurotrophic effects reduced blood-brain barrier(BBB) permeability and regulation of the cholinergic anddopaminergic systems Acupuncture at Baihui (GV 20) incombination with other acupoints decreases levels of 8-hydroxy-21015840-deoxyguanosine a product of oxidative damageto DNA induced by free radicals suggesting that the benefitof acupuncture is partly due to antioxidant effects [11]Acupuncture exerts therapeutic effects on VaD via antiapop-tosis The tumor suppressors p53 and Noxa are important inregulating apoptosis and mediate hypoxic cell death [24 25]
Electroacupuncture at Baihui (GV 20) Dazhui (GV 14) andShenshu (BL 23) blocks expression of p53 and Noxa in thehippocampal CA1 region of VaD rats [26] Acupuncture atBaihui (GV 20) can improve neurogenesis via regulatingbrain-derived neurotrophic factor (BDNF) and cyclic AMPresponse element-binding protein (CREB) BDNF whichis essential for synaptic plasticity and is coupled to CREBactivation [27] is important for long-term memory storage[28] CREB is required for the proliferation growth survivaland differentiation of all types of cells In the brain the CREBand CRE-mediated system is involved in memory learningsynaptic transmission neuron survival differentiation andaxon growth [29] Acupuncture at Baihui (GV 20) signifi-cantly increases the levels of BDNF [15 30] CREB proteinsCREB mRNA [30] and phosphorylated CREB the activeform of CREB [15] The molecular mechanism underlyingacupuncture at Baihui (GV 20) also involves cholinergicsystem regulation Decreased cholinergic function in thebrain can result in a decline in memory and cognitivefunction [31] Acupuncture at Baihui (GV 20) significantlyincreases the levels of choline acetyltransferase (ChAT) andrestores the expression of choline transporter 1 (CHT1)and vesicular acetylcholine transporter (VAChT) [30] Thedopaminergic system is also involved in the mechanismunderlying the treatment of VaD with acupuncture at Baihui(GV 20) Dopamine is a key regulator in specific synapticchanges observed at certain stages of learning and memory
10 Evidence-Based Complementary and Alternative Medicine
and of synaptic plasticity [32] Acupuncture at Baihui (GV20)increases dopamine levels in chronic cerebral hypoperfusionand ischemia-reperfusion injured rats [33] In additionacupuncture at Baihui (GV 20) and Zusanli (ST 36) preservesthe integrity of the BBB reducing BBB permeability TheBBB is constructed of tight conjunctions including occludinand claudin-5 which form the endothelial barrier Reducedexpression of ZO-1 claudin-5 and occludin mRNA andprotein contributes to BBB breakdown and edema in theischemic brain [34] Electroacupuncture at Baihui (GV 20)and Zusanli (ST 36) reduces brain damage and relatedbehavioral deficits via upregulation of tight conjunctionproteins including ZO-1 claudin-5 and occludin [35]Thesefindings reveal parts of the molecular mechanism underlyingacupuncture at Baihui (GV 20) to treat VaD
43 Acupoints Selection in Treatment for VaD The properselection of acupoints is essential for the therapeutic effectsof acupuncture because acupoints are specific with regard tomorphological structure biophysical properties pathologicalresponse and stimulating effects [36] This specificity dif-ferentiates acupoints from nonacupoints as well as differentacupoints from one another The specific therapeutic effectsof different acupoints have been reported for migraine [37]functional dyspepsia [38] ischemic stroke [39] and so forth
The specificity of acupoints for the treatment of VaDhas also been reported Phosphorylated CREB levels weresignificantly increased after acupuncture therapy of needlingBaihui (GV 20) and Zusanli (ST 36) compared to shamacupuncture therapy of needling nonacupoints [15] Baihui(GV 20) Shuigou (GV 26) and Shenmen (HT 7) are allamong the 10 acupoints with the most potential A clinicaltrial demonstrated that needling Baihui (GV 20) Shuigou(GV 26) and Shenmen (HT 7) were all effective in improvingthe symptoms of VaD However their therapeutic effects dif-fer Needling Baihui (GV 20) improved calculation ability andshort-term memory and corrected the personality changesof VaD patients while needling Shuigou (GV 26) improvednaming ability and short-term memory The therapeuticeffects of needling Baihui (GV 20) and Shuigou (GV 26)were superior to those of needling Shenmen (HT 7) [40]A PET and SPECT study revealed that needling these threedifferent acupoints in VaD patients affected different brainareas Needling Baihui (GV 20) activated the inner temporalsystem the thalamencephalon system and the prefrontalcortical system Needling Shuigou (GV 26) activated the pre-frontal cortical system Needling Shenmen (HT 7) generatedan effect similar to but weaker than the effect generated byneedling Shuigou (GV 26) [41] These findings demonstratethat different acupoints have different therapeutic effects inacupuncture treatment for VaD Consequently the selectionof acupoints which directly influences the therapeutic effectsof acupuncture should be considered carefully According toour results based on datamining Baihui (GV 20) Sishencong(EX-HN 1) Fengchi (GB 20) Shuigou (GV 26) and Shenting(GV 24) which have higher frequencies in the modernliterature may have better therapeutic effects on VaD
44 SingleAcupoint orAcupoint Combination Acupoint com-binations also influence the therapeutic effects of acupunc-ture An acupoint combination is considered to have asynergistic effect that enhances the therapeutic effect ofacupuncture For example a lower prevalence of postoper-ative nausea and vomiting in patients treated with Neiguan(PC 6) plus Hegu (LI 4) was observed compared with thosetreated with Neiguan (PC 6) only [42] In spite of extensiveevidence suggesting a synergistic effect of acupoint combi-nation and supporting its use some studies have reportedantagonistic effects [43ndash45] An antagonistic effect occurswhen one acupoint weakens the therapeutic effect of anotheracupoint [46] For example electroacupuncture can improvegastrointestinal movement in rats The effect of needlingPishu (BL 20) alone was better than the effect of needlingPishu (BL 20) and Zusanli (ST 36) at the same time [44]Therefore whether the effect of acupoint combination isbetter than a single acupoint still remains a question andneeds to be further studied
Some studies have compared single acupoints and anacupoint combination for the treatment of VaD The thera-peutic effect of needling Baihui (GV 20) Shuigou (GV 26)and Shenmen (HT 7) in combination was better than theeffects obtained by needling each alone [40] In additionneedling Baihui (GV 20) Shuigou (GV 26) and Shenmen(HT 7) simultaneously activated more brain areas relatedto intellectual activities compared with needling each alonegenerating a more extensive effect on the brain [41] Antago-nistic effects in acupuncture therapy for VaD have not beenreported but may occur Most acupuncture prescriptions forVaD contain acupoint combinations and the use of acupointcombinations is supported However acupoint combinationsshould be selected carefully to avoid antagonistic effects Itis hard to tell whether a combination of acupoints will exertantagonistic effects with current knowledge or TCM theoryAs abovementioned acupoints with similar functions canexert antagonistic effects There are many acupoints and thenumber of acupoint combinations will grow geometricallyTo test the antagonistic effects of each combination oneby one is an exhausting job To avoid antagonistic effectsas possible the acupoint prescriptions should be simplifiedas possible The general principle is to select acupointswith relatively better therapeutic effects and acupoints withmultiple indications and not to select many acupoints
45 Limitations This study has limitations as follows Firstother factors that influence acupuncture such as manipula-tion and treatment duration were not analyzed in this studyThese data can be further mined in future studies Secondlargely due to the lack of treatment based on syndrome differ-entiation and different methods of syndrome differentiationin modern literature potential acupoints and combinationsfor different syndromes of VaD were not analyzed Althoughtreatment based on syndrome differentiation is importantand is often emphasized in TCM treatment based on diseasedifferentiation is equally important Third the real therapeu-tic effects of acupoints and combinations on VaD cannotbe reflected by frequencies in the literature However theseresults suggest some potential acupoints and combinations to
Evidence-Based Complementary and Alternative Medicine 11
be explored in future clinical trials to validate the effects ofacupuncture on VaD To optimize the acupoint prescriptiondata may be extracted not only from literature but alsofrom clinical practice Further research can collect acupointprescriptions and symptom improvements in clinical practiceand optimize acupoint prescriptionwith dataminingMiningclinical data has been practiced to optimize prescriptionof Chinese herbal medicine for unstable angina by Fenget al [47] In their study five main symptoms of patientswith unstable angina the severity of each symptom andthe prescription of each patient were collected The levels ofaverage discounted reward (ADR) of different prescriptionswere calculated to evaluate the clinical efficacy of differ-ent treatment options with some optimized prescriptionsachieved Future studies can mine clinical data to optimizeacupoint prescription
5 Conclusions
In this study data mining was used to discover potentialacupoints and combinations for VaD Potential acupointsinclude Baihui (GV 20) Sishencong (EX-HN 1) Fengchi (GB20) Shuigou (GV 26) and Shenting (GV 24) In additioncombinations between Baihui (GV 20) Sishencong (EX-HN1) Fengchi (GB 20) Shenting (GV 24) Shuigou (GV 26) andZusanli (ST 36) were potential combinations Based on ourresults Baihui (GV 20) and Sishencong (EX-HN 1) shouldbe selected with priority Acupoints in head compared toacupoints in other parts should also be selected with priority
Conflict of Interests
The authors declare no conflict of interests
Authorsrsquo Contribution
Shuwei Feng and Yulan Ren contributed equally to this work
Acknowledgments
This study was supported by the National Basic ResearchProgram of China (no 2012CB518501) and the NationalScience Foundation of China (nos 81102742 and 61104224)
References
[1] Q Chen X Wu S F Lu et al ldquoMeridian acupoints selectionin acupuncture treatment for migraine the main charactersand relevant factors analysisrdquo Liaoning Journal of TraditionalChinese Medicine vol 36 no 9 pp 1477ndash1480 2009
[2] Y Li H Zheng C M Witt et al ldquoAcupuncture for migraineprophylaxis a randomized controlled trialrdquo Canadian MedicalAssociation Journal vol 184 no 4 pp 401ndash410 2012
[3] B H May C Lu L Bennett H M Hugel and C C LXue ldquoEvaluating the traditional Chinese literature for herbalformulae and individual herbs used for age-related dementiaand memory impairmentrdquo Biogerontology vol 13 no 3 pp299ndash312 2012
[4] L Zhang Y Li X Guo et al ldquoText mining of the classicalmedical literature for medicines that show potential in diabeticnephropathyrdquo Evidence-Based Complementary and AlternativeMedicine vol 2014 Article ID 189125 12 pages 2014
[5] Y Olsson A Brun and E Englund ldquoFundamental pathologicallesions in vascular dementiardquo Acta Neurologica Scandinavicavol 94 supplement 168 pp 31ndash38 1996
[6] S Davis M Shanahan A Campbell M Hegarty and BMcCarthy ldquoPalliative care for people with dementia aged carestaff perspectivesrdquo Alzheimerrsquos amp Dementia vol 7 no 4 p e502011
[7] J Jia F Wang C Wei et al ldquoThe prevalence of dementia inurban and rural areas of Chinardquo Alzheimerrsquos and Dementia vol10 no 1 pp 1ndash9 2014
[8] C P Ferri M Prince C Brayne et al ldquoGlobal prevalence ofdementia a Delphi consensus studyrdquo The Lancet vol 366 no9503 pp 2112ndash2117 2005
[9] W Quentin S G Riedel-Heller M Luppa A Rudolph andH-H Konig ldquoCost-of-illness studies of dementia a systematicreview focusing on stage dependency of costsrdquoActa PsychiatricaScandinavica vol 121 no 4 pp 243ndash259 2010
[10] J Yu X Zhang C Liu Y Meng and J Han ldquoEffect ofacupuncture treatment on vascular dementiardquo NeurologicalResearch vol 28 no 1 pp 97ndash103 2006
[11] G-X Shi C-Z Liu Q-Q Li H Zhu and L-P WangldquoInfluence of acupuncture on cognitive function and markersof oxidative DNA damage in patients with vascular dementiardquoJournal of Traditional Chinese Medicine vol 32 no 2 pp 199ndash202 2012
[12] X-Y Zhong X-X Su J Liu and G Q Zhu ldquoClinical effectsof acupuncture combined with nimodipine for treatment ofvascular dementia in 30 casesrdquo Journal of Traditional ChineseMedicine vol 29 no 3 pp 174ndash176 2009
[13] T Wang C-Z Liu J-C Yu W Jiang and J-X Han ldquoAcupunc-ture protected cerebral multi-infarction rats from memoryimpairment by regulating the expression of apoptosis relatedgenes Bcl-2 and Bax in hippocampusrdquo Physiology and Behaviorvol 96 no 1 pp 155ndash161 2009
[14] I K Hwang J Y Chung D Y Yoo et al ldquoComparing the effectsof acupuncture and electroacupuncture at Zusanli and Baihuion cell proliferation and neuroblast differentiation in the rathippocampusrdquo Journal of VeterinaryMedical Science vol 72 no3 pp 279ndash284 2010
[15] I K Hwang J Y Chung D Y Yoo et al ldquoEffects ofelectroacupuncture at Zusanli and Baihui on brain-derivedneurotrophic factor and cyclic AMP response element-bindingprotein in the hippocampal dentate gyrusrdquo Journal of VeterinaryMedical Science vol 72 no 11 pp 1431ndash1436 2010
[16] Y F Luo and J M Wu Fundamentals of Acupuncture SichuanUniversity Press Sichuan China 2008
[17] R Agrawal and R Srikant ldquoFast algorithms for mining associ-ation rulesrdquo in Proceedings of the 20th International Conferenceon Very Large Data Bases (VLDB rsquo94) pp 487ndash499 SantiagoChile 1994
[18] R Agrawal T Imielinski and A Swami ldquoMining associationrules between sets of items in large databasesrdquo ACM SIGMODRecord vol 22 no 2 pp 207ndash216 1993
12 Evidence-Based Complementary and Alternative Medicine
[19] A Clauset M E J Newman and C Moore ldquoFinding commu-nity structure in very large networksrdquo Physical Review E vol 70no 6 Article ID 066111 6 pages 2004
[20] G F de Arruda A L Barbieri P M Rodriguez et al ldquoRoleof centrality for the identification of influential spreaders incomplex networksrdquo Physical Review E Statistical Nonlinearand SoftMatter Physics vol 90 no 1ndash3 Article ID 032812 2014
[21] T Opsahl F Agneessens and J Skvoretz ldquoNode centrality inweighted networks generalizing degree and shortest pathsrdquoSocial Networks vol 32 no 3 pp 245ndash251 2010
[22] U Brandes ldquoOn variants of shortest-path betweenness central-ity and their generic computationrdquo Social Networks vol 30 no2 pp 136ndash145 2008
[23] H Q Li J H Li A J Liu M Y Ye and G Q ZhengldquoGV20-based acupuncture for animal models of acute intrac-erebral haemorrhage a preclinical systematic review and meta-analysisrdquo Acupuncture in Medicine vol 32 no 6 pp 495ndash5022014
[24] EOda ROhkiHMurasawa et al ldquoNoxa a BH3-onlymemberof the Bcl-2 family and candidate mediator of p53-inducedapoptosisrdquo Science vol 288 no 5468 pp 1053ndash1058 2000
[25] H Endo H Kamada C Nito T Nishi and P H Chan ldquoMito-chondrial translocation of p53 mediates release of cytochromec and hippocampal CA1 neuronal death after transient globalcerebral ischemia in ratsrdquo Journal of Neuroscience vol 26 no30 pp 7974ndash7983 2006
[26] Y Zhu and Y Zeng ldquoElectroacupuncture protected pyramidalcells in hippocampal CA1 region of vascular dementia rats byinhibiting the expression of P53 and Noxardquo CNS NeuroscienceandTherapeutics vol 17 no 6 pp 599ndash604 2011
[27] W J Tyler M Alonso C R Bramham and L D Pozzo-Miller ldquoFrom acquisition to consolidation on the role ofbrain-derived neurotrophic factor signaling in hippocampal-dependent learningrdquo Learning and Memory vol 9 no 5 pp224ndash237 2002
[28] P Bekinschtein M Cammarota C Katche et al ldquoBDNF isessential to promote persistence of long-termmemory storagerdquoProceedings of the National Academy of Sciences of the UnitedStates of America vol 105 no 7 pp 2711ndash2716 2008
[29] K Kitagawa ldquoCREB and cAMP response element-mediatedgene expression in the ischemic brainrdquo FEBS Journal vol 274no 13 pp 3210ndash3217 2007
[30] B Lee B Sur J Shim D Hahm and H Lee ldquoAcupuncturestimulation improves scopolamine-induced cognitive impair-ment via activation of cholinergic system and regulation ofBDNF andCREB expressions in ratsrdquoBMCComplementary andAlternative Medicine vol 14 no 1 article 338 2014
[31] M E Hasselmo ldquoThe role of acetylcholine in learning andmemoryrdquo Current Opinion in Neurobiology vol 16 no 6 pp710ndash715 2006
[32] T M Jay ldquoDopamine a potential substrate for synaptic plastic-ity andmemory mechanismsrdquo Progress in Neurobiology vol 69no 6 pp 375ndash390 2003
[33] C-M Chuang C-L Hsieh T-C Li and J-G Lin ldquoAcupunc-ture stimulation at Baihui acupoint reduced cerebral infarct andincreased dopamine levels in chronic cerebral hypoperfusionand ischemia-reperfusion injured Sprague-Dawley ratsrdquoAmeri-can Journal of ChineseMedicine vol 35 no 5 pp 779ndash791 2007
[34] H Jiao Z Wang Y Liu P Wang and Y Xue ldquoSpecific roleof tight junction proteins claudin-5 occludin and ZO-1 of theblood-brain barrier in a focal cerebral ischemic insultrdquo Journalof Molecular Neuroscience vol 44 no 2 pp 130ndash139 2011
[35] Y-M Zhang H Xu H Sun S Chen and F Wang ldquoElec-troacupuncture treatment improves neurological function asso-ciated with regulation of tight junction proteins in rats withcerebral ischemia reperfusion injuryrdquo Evidence-Based Comple-mentary and Alternative Medicine vol 2014 Article ID 98934010 pages 2014
[36] B-X Jin X-S Lai and C-Z Tang ldquoProgress in researches onthe specificity of acupointsrdquo Acupuncture Research vol 33 no2 pp 135ndash138 2008
[37] Y Li F Liang X Yang et al ldquoAcupuncture for treating acuteattacks of migraine a randomized controlled trialrdquo Headachevol 49 no 6 pp 805ndash816 2009
[38] T T Ma S Y Yu Y Li et al ldquoRandomised clinical trial anassessment of acupuncture on specific meridian or specific acu-point vs sham acupuncture for treating functional dyspepsiardquoAlimentary Pharmacology and Therapeutics vol 35 no 5 pp552ndash561 2012
[39] P-F Shen L Kong L-W Ni et al ldquoAcupuncture interventionin ischemic stroke a randomized controlled prospective studyrdquoThe American Journal of Chinese Medicine vol 40 no 4 pp685ndash693 2012
[40] Y Huang M H Win J Chen et al ldquoA comparative studyon the treatment of vascular dementia by puncturing Baihui(GV20) Shuigou (GV26) and Shenmen (HT7)rdquoWorld Journalof AcupuncturemdashMoxibustion no 1 pp 3ndash10 2005
[41] Y Huang X-S Lai and A-W Tang ldquoComparative study of thespecificities of needling acupoints DU20 DU26 and HT7 inintervening vascular dementia in different areas in the brain onthe basis of scale assessment and cerebral functional imagingrdquoChinese Journal of Integrative Medicine vol 13 no 2 pp 103ndash108 2007
[42] R Alizadeh S Esmaeili S Shoar S Bagheri-Hariri and NShoar ldquoAcupuncture in preventing postoperative nausea andvomiting efficacy of two acupuncture points versus a singleonerdquo Journal of Acupuncture and Meridian Studies vol 7 no2 pp 71ndash75 2014
[43] F M Xu and R X Chen ldquoThe antagonistic effect of acupointson oxygen consumption rate in ratsrdquo Journal of Jiangxi Collegeof Traditional Chinese Medicine vol 13 no 2 pp 60ndash61 2001
[44] F M Xu and R X Chen ldquoEffect of electroacupuncture ongastrointestinalmovement in rats with hypoactive gastrointesti-nal movement caused by greaserdquo Henan Traditional ChineseMedicine vol 20 no 2 pp 19ndash20 2000
[45] X H Li X Z Gao and L Hu ldquoExperimental study on syner-getic and antagonistic effects of acupoints Neiguan Shenmenand Xinshurdquo Chinese Acupuncture andMoxibustion vol 22 no12 pp 819ndash821 2002
[46] X H Li Q Y Wang X Z Gao et al ldquoStudy on cooperationand antagonism among acupointsrdquo Chinese Acupuncture andMoxibustion vol 22 no 6 pp 387ndash388 2002
[47] Y Feng Y Qiu X Zhou Y Wang H Xu and B Liu ldquoOpti-mizing prescription of Chinese herbal medicine for unstableangina based on partially observable Markov decision processrdquoEvidence-based Complementary and Alternative Medicine vol2013 Article ID 532534 6 pages 2013
Submit your manuscripts athttpwwwhindawicom
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Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
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Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
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Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
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Disease Markers
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
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OncologyJournal of
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Oxidative Medicine and Cellular Longevity
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PPAR Research
The Scientific World JournalHindawi Publishing Corporation httpwwwhindawicom Volume 2014
Immunology ResearchHindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Journal of
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Computational and Mathematical Methods in Medicine
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Research and TreatmentAIDS
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
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Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Parkinsonrsquos Disease
Evidence-Based Complementary and Alternative Medicine
Volume 2014Hindawi Publishing Corporationhttpwwwhindawicom
8 Evidence-Based Complementary and Alternative Medicine
BL17
EX-HN22
BL7
LI1
GV13
SP9
GB11
EX-HN14
GB4
HT1
ST2
CV8
GB5
GV18
BL11
EX-UE8
LI20
GV1
ST36
BL20
CV17
BL58
BL9
GV17
GV14
GV15
GV11
GV12
GV10GV5
KI3
KI1
LU11
HT9
GV8
GV3
BL23
GV4
CV6
CV12
HT7GB20
GB17
GV24
GV16
CV4
GB8
GV21GV23GB13
SP10
BL10
ST32
GB34LI14
LI15
GB32
LI10
BL40
GB31
KI6
SI5
KI2
PC7
LI4
GB16
EX-HN5
GB12
PC8
PC6
BL18
BL15
BL56
GB40
TE9
EX-UE9SP6
TE5
SP3
LI11
GV22
BL60
GB6
GB14
GB15
GB19
ST9
GV7
GV2
GV6
EX-B8
BL4
SI1
PC9
TE1ST45
SP1
BL67
GB44
LV1
TE23
TE20
LU7
GV19
ST40
EX-HN3ST8
GV20
KI4
GB39
GB7
EX-HN1
PC5
LV3
GV9
GV26
(a) Network structure of acupoints for the treatment of VaD
GB13
EX-HN1
EX-HN3
LI4
KI3
KI4
HT7GB20
GV14
GV15
GV16
LV3
ST36
BL23
GV4
GV24
GV26GV20
ST40
SP6
LI11
GB39
SP10
PC6
BL10
CV4
BL18
BL15
(b) 19-core network
Figure 5 (a) Network structure of acupoints for the treatment of VaD Blue nodes (Community A) are all Jing-Well acupoints Yellow nodes(Community B) are all acupoints on the face and head Most green nodes (Community C) are acupoints on four limbs Most purple nodes(Community D) are acupoints belonging to Governor Vessel Most red nodes (Community E) are specific acupoints or acupoints withspecific therapeutic effects and only this community contains Bach-Shu acupoints and acupoints on the abdomen Acupoints within thesame community are more densely connected with each other than acupoints from different communities (b) 19-core network There are 28acupoints in the 19-core network They are core acupoints in the treatment of VaD
Evidence-Based Complementary and Alternative Medicine 9
0102030405060708090
100
GV
20
EX-H
N1
GB2
0
GV
24
PC6
SP6
GV
14
GV
26
GV
16
HT7 LI
4
KI3
ST36
ST40
LV3
GB1
3
EX-H
N3
BL10
GB3
9
LI 1
1
Degree
(a) The 20 acupoints with highest degree
0002004006008
01012014016
KI1
GV
20
EX-H
N1
PC6
GV
26
GB2
0
GV
24
GV
14 SP6
EX-H
N3
HT7 LI
4
KI3
GV
16
BL10
LV3
ST40
ST36
GB1
3
PC9
Betweenness centrality
(b) The 20 acupoints with highest betweenness centrality
Figure 6 The 20 acupoints with highest degree and the 20 acupoints with highest betweenness centrality
also used to tonify kidney in treatment of VaD ThereforeYongquan (KI 1) is used not only with other Jing-Wellacupoints but also with other types of acupoints such asother types of specific acupoints nonspecific acupoints andacupoints on other parts
42 UnderlyingMolecularMechanism of the Acupoint with theMost Potential to Treat VaD According to our results Baihui(GV 20) which had the highest frequency has the mostpotential to treat VaD A systematic review andmeta-analysisalso suggested that Baihui (GV 20) is a principal acupoint foracute intracerebral hemorrhage (ICH) in animal models ofacute ICH there was no difference in efficacy between Baihui(GV 20) alone and Baihui (GV 20) plus other acupoints [23]
Molecular biology studies have provided insights intothe mechanisms underlying the effects of Baihui (GV 20) inVaD treatment including antioxidant effects antiapoptoticeffects neurotrophic effects reduced blood-brain barrier(BBB) permeability and regulation of the cholinergic anddopaminergic systems Acupuncture at Baihui (GV 20) incombination with other acupoints decreases levels of 8-hydroxy-21015840-deoxyguanosine a product of oxidative damageto DNA induced by free radicals suggesting that the benefitof acupuncture is partly due to antioxidant effects [11]Acupuncture exerts therapeutic effects on VaD via antiapop-tosis The tumor suppressors p53 and Noxa are important inregulating apoptosis and mediate hypoxic cell death [24 25]
Electroacupuncture at Baihui (GV 20) Dazhui (GV 14) andShenshu (BL 23) blocks expression of p53 and Noxa in thehippocampal CA1 region of VaD rats [26] Acupuncture atBaihui (GV 20) can improve neurogenesis via regulatingbrain-derived neurotrophic factor (BDNF) and cyclic AMPresponse element-binding protein (CREB) BDNF whichis essential for synaptic plasticity and is coupled to CREBactivation [27] is important for long-term memory storage[28] CREB is required for the proliferation growth survivaland differentiation of all types of cells In the brain the CREBand CRE-mediated system is involved in memory learningsynaptic transmission neuron survival differentiation andaxon growth [29] Acupuncture at Baihui (GV 20) signifi-cantly increases the levels of BDNF [15 30] CREB proteinsCREB mRNA [30] and phosphorylated CREB the activeform of CREB [15] The molecular mechanism underlyingacupuncture at Baihui (GV 20) also involves cholinergicsystem regulation Decreased cholinergic function in thebrain can result in a decline in memory and cognitivefunction [31] Acupuncture at Baihui (GV 20) significantlyincreases the levels of choline acetyltransferase (ChAT) andrestores the expression of choline transporter 1 (CHT1)and vesicular acetylcholine transporter (VAChT) [30] Thedopaminergic system is also involved in the mechanismunderlying the treatment of VaD with acupuncture at Baihui(GV 20) Dopamine is a key regulator in specific synapticchanges observed at certain stages of learning and memory
10 Evidence-Based Complementary and Alternative Medicine
and of synaptic plasticity [32] Acupuncture at Baihui (GV20)increases dopamine levels in chronic cerebral hypoperfusionand ischemia-reperfusion injured rats [33] In additionacupuncture at Baihui (GV 20) and Zusanli (ST 36) preservesthe integrity of the BBB reducing BBB permeability TheBBB is constructed of tight conjunctions including occludinand claudin-5 which form the endothelial barrier Reducedexpression of ZO-1 claudin-5 and occludin mRNA andprotein contributes to BBB breakdown and edema in theischemic brain [34] Electroacupuncture at Baihui (GV 20)and Zusanli (ST 36) reduces brain damage and relatedbehavioral deficits via upregulation of tight conjunctionproteins including ZO-1 claudin-5 and occludin [35]Thesefindings reveal parts of the molecular mechanism underlyingacupuncture at Baihui (GV 20) to treat VaD
43 Acupoints Selection in Treatment for VaD The properselection of acupoints is essential for the therapeutic effectsof acupuncture because acupoints are specific with regard tomorphological structure biophysical properties pathologicalresponse and stimulating effects [36] This specificity dif-ferentiates acupoints from nonacupoints as well as differentacupoints from one another The specific therapeutic effectsof different acupoints have been reported for migraine [37]functional dyspepsia [38] ischemic stroke [39] and so forth
The specificity of acupoints for the treatment of VaDhas also been reported Phosphorylated CREB levels weresignificantly increased after acupuncture therapy of needlingBaihui (GV 20) and Zusanli (ST 36) compared to shamacupuncture therapy of needling nonacupoints [15] Baihui(GV 20) Shuigou (GV 26) and Shenmen (HT 7) are allamong the 10 acupoints with the most potential A clinicaltrial demonstrated that needling Baihui (GV 20) Shuigou(GV 26) and Shenmen (HT 7) were all effective in improvingthe symptoms of VaD However their therapeutic effects dif-fer Needling Baihui (GV 20) improved calculation ability andshort-term memory and corrected the personality changesof VaD patients while needling Shuigou (GV 26) improvednaming ability and short-term memory The therapeuticeffects of needling Baihui (GV 20) and Shuigou (GV 26)were superior to those of needling Shenmen (HT 7) [40]A PET and SPECT study revealed that needling these threedifferent acupoints in VaD patients affected different brainareas Needling Baihui (GV 20) activated the inner temporalsystem the thalamencephalon system and the prefrontalcortical system Needling Shuigou (GV 26) activated the pre-frontal cortical system Needling Shenmen (HT 7) generatedan effect similar to but weaker than the effect generated byneedling Shuigou (GV 26) [41] These findings demonstratethat different acupoints have different therapeutic effects inacupuncture treatment for VaD Consequently the selectionof acupoints which directly influences the therapeutic effectsof acupuncture should be considered carefully According toour results based on datamining Baihui (GV 20) Sishencong(EX-HN 1) Fengchi (GB 20) Shuigou (GV 26) and Shenting(GV 24) which have higher frequencies in the modernliterature may have better therapeutic effects on VaD
44 SingleAcupoint orAcupoint Combination Acupoint com-binations also influence the therapeutic effects of acupunc-ture An acupoint combination is considered to have asynergistic effect that enhances the therapeutic effect ofacupuncture For example a lower prevalence of postoper-ative nausea and vomiting in patients treated with Neiguan(PC 6) plus Hegu (LI 4) was observed compared with thosetreated with Neiguan (PC 6) only [42] In spite of extensiveevidence suggesting a synergistic effect of acupoint combi-nation and supporting its use some studies have reportedantagonistic effects [43ndash45] An antagonistic effect occurswhen one acupoint weakens the therapeutic effect of anotheracupoint [46] For example electroacupuncture can improvegastrointestinal movement in rats The effect of needlingPishu (BL 20) alone was better than the effect of needlingPishu (BL 20) and Zusanli (ST 36) at the same time [44]Therefore whether the effect of acupoint combination isbetter than a single acupoint still remains a question andneeds to be further studied
Some studies have compared single acupoints and anacupoint combination for the treatment of VaD The thera-peutic effect of needling Baihui (GV 20) Shuigou (GV 26)and Shenmen (HT 7) in combination was better than theeffects obtained by needling each alone [40] In additionneedling Baihui (GV 20) Shuigou (GV 26) and Shenmen(HT 7) simultaneously activated more brain areas relatedto intellectual activities compared with needling each alonegenerating a more extensive effect on the brain [41] Antago-nistic effects in acupuncture therapy for VaD have not beenreported but may occur Most acupuncture prescriptions forVaD contain acupoint combinations and the use of acupointcombinations is supported However acupoint combinationsshould be selected carefully to avoid antagonistic effects Itis hard to tell whether a combination of acupoints will exertantagonistic effects with current knowledge or TCM theoryAs abovementioned acupoints with similar functions canexert antagonistic effects There are many acupoints and thenumber of acupoint combinations will grow geometricallyTo test the antagonistic effects of each combination oneby one is an exhausting job To avoid antagonistic effectsas possible the acupoint prescriptions should be simplifiedas possible The general principle is to select acupointswith relatively better therapeutic effects and acupoints withmultiple indications and not to select many acupoints
45 Limitations This study has limitations as follows Firstother factors that influence acupuncture such as manipula-tion and treatment duration were not analyzed in this studyThese data can be further mined in future studies Secondlargely due to the lack of treatment based on syndrome differ-entiation and different methods of syndrome differentiationin modern literature potential acupoints and combinationsfor different syndromes of VaD were not analyzed Althoughtreatment based on syndrome differentiation is importantand is often emphasized in TCM treatment based on diseasedifferentiation is equally important Third the real therapeu-tic effects of acupoints and combinations on VaD cannotbe reflected by frequencies in the literature However theseresults suggest some potential acupoints and combinations to
Evidence-Based Complementary and Alternative Medicine 11
be explored in future clinical trials to validate the effects ofacupuncture on VaD To optimize the acupoint prescriptiondata may be extracted not only from literature but alsofrom clinical practice Further research can collect acupointprescriptions and symptom improvements in clinical practiceand optimize acupoint prescriptionwith dataminingMiningclinical data has been practiced to optimize prescriptionof Chinese herbal medicine for unstable angina by Fenget al [47] In their study five main symptoms of patientswith unstable angina the severity of each symptom andthe prescription of each patient were collected The levels ofaverage discounted reward (ADR) of different prescriptionswere calculated to evaluate the clinical efficacy of differ-ent treatment options with some optimized prescriptionsachieved Future studies can mine clinical data to optimizeacupoint prescription
5 Conclusions
In this study data mining was used to discover potentialacupoints and combinations for VaD Potential acupointsinclude Baihui (GV 20) Sishencong (EX-HN 1) Fengchi (GB20) Shuigou (GV 26) and Shenting (GV 24) In additioncombinations between Baihui (GV 20) Sishencong (EX-HN1) Fengchi (GB 20) Shenting (GV 24) Shuigou (GV 26) andZusanli (ST 36) were potential combinations Based on ourresults Baihui (GV 20) and Sishencong (EX-HN 1) shouldbe selected with priority Acupoints in head compared toacupoints in other parts should also be selected with priority
Conflict of Interests
The authors declare no conflict of interests
Authorsrsquo Contribution
Shuwei Feng and Yulan Ren contributed equally to this work
Acknowledgments
This study was supported by the National Basic ResearchProgram of China (no 2012CB518501) and the NationalScience Foundation of China (nos 81102742 and 61104224)
References
[1] Q Chen X Wu S F Lu et al ldquoMeridian acupoints selectionin acupuncture treatment for migraine the main charactersand relevant factors analysisrdquo Liaoning Journal of TraditionalChinese Medicine vol 36 no 9 pp 1477ndash1480 2009
[2] Y Li H Zheng C M Witt et al ldquoAcupuncture for migraineprophylaxis a randomized controlled trialrdquo Canadian MedicalAssociation Journal vol 184 no 4 pp 401ndash410 2012
[3] B H May C Lu L Bennett H M Hugel and C C LXue ldquoEvaluating the traditional Chinese literature for herbalformulae and individual herbs used for age-related dementiaand memory impairmentrdquo Biogerontology vol 13 no 3 pp299ndash312 2012
[4] L Zhang Y Li X Guo et al ldquoText mining of the classicalmedical literature for medicines that show potential in diabeticnephropathyrdquo Evidence-Based Complementary and AlternativeMedicine vol 2014 Article ID 189125 12 pages 2014
[5] Y Olsson A Brun and E Englund ldquoFundamental pathologicallesions in vascular dementiardquo Acta Neurologica Scandinavicavol 94 supplement 168 pp 31ndash38 1996
[6] S Davis M Shanahan A Campbell M Hegarty and BMcCarthy ldquoPalliative care for people with dementia aged carestaff perspectivesrdquo Alzheimerrsquos amp Dementia vol 7 no 4 p e502011
[7] J Jia F Wang C Wei et al ldquoThe prevalence of dementia inurban and rural areas of Chinardquo Alzheimerrsquos and Dementia vol10 no 1 pp 1ndash9 2014
[8] C P Ferri M Prince C Brayne et al ldquoGlobal prevalence ofdementia a Delphi consensus studyrdquo The Lancet vol 366 no9503 pp 2112ndash2117 2005
[9] W Quentin S G Riedel-Heller M Luppa A Rudolph andH-H Konig ldquoCost-of-illness studies of dementia a systematicreview focusing on stage dependency of costsrdquoActa PsychiatricaScandinavica vol 121 no 4 pp 243ndash259 2010
[10] J Yu X Zhang C Liu Y Meng and J Han ldquoEffect ofacupuncture treatment on vascular dementiardquo NeurologicalResearch vol 28 no 1 pp 97ndash103 2006
[11] G-X Shi C-Z Liu Q-Q Li H Zhu and L-P WangldquoInfluence of acupuncture on cognitive function and markersof oxidative DNA damage in patients with vascular dementiardquoJournal of Traditional Chinese Medicine vol 32 no 2 pp 199ndash202 2012
[12] X-Y Zhong X-X Su J Liu and G Q Zhu ldquoClinical effectsof acupuncture combined with nimodipine for treatment ofvascular dementia in 30 casesrdquo Journal of Traditional ChineseMedicine vol 29 no 3 pp 174ndash176 2009
[13] T Wang C-Z Liu J-C Yu W Jiang and J-X Han ldquoAcupunc-ture protected cerebral multi-infarction rats from memoryimpairment by regulating the expression of apoptosis relatedgenes Bcl-2 and Bax in hippocampusrdquo Physiology and Behaviorvol 96 no 1 pp 155ndash161 2009
[14] I K Hwang J Y Chung D Y Yoo et al ldquoComparing the effectsof acupuncture and electroacupuncture at Zusanli and Baihuion cell proliferation and neuroblast differentiation in the rathippocampusrdquo Journal of VeterinaryMedical Science vol 72 no3 pp 279ndash284 2010
[15] I K Hwang J Y Chung D Y Yoo et al ldquoEffects ofelectroacupuncture at Zusanli and Baihui on brain-derivedneurotrophic factor and cyclic AMP response element-bindingprotein in the hippocampal dentate gyrusrdquo Journal of VeterinaryMedical Science vol 72 no 11 pp 1431ndash1436 2010
[16] Y F Luo and J M Wu Fundamentals of Acupuncture SichuanUniversity Press Sichuan China 2008
[17] R Agrawal and R Srikant ldquoFast algorithms for mining associ-ation rulesrdquo in Proceedings of the 20th International Conferenceon Very Large Data Bases (VLDB rsquo94) pp 487ndash499 SantiagoChile 1994
[18] R Agrawal T Imielinski and A Swami ldquoMining associationrules between sets of items in large databasesrdquo ACM SIGMODRecord vol 22 no 2 pp 207ndash216 1993
12 Evidence-Based Complementary and Alternative Medicine
[19] A Clauset M E J Newman and C Moore ldquoFinding commu-nity structure in very large networksrdquo Physical Review E vol 70no 6 Article ID 066111 6 pages 2004
[20] G F de Arruda A L Barbieri P M Rodriguez et al ldquoRoleof centrality for the identification of influential spreaders incomplex networksrdquo Physical Review E Statistical Nonlinearand SoftMatter Physics vol 90 no 1ndash3 Article ID 032812 2014
[21] T Opsahl F Agneessens and J Skvoretz ldquoNode centrality inweighted networks generalizing degree and shortest pathsrdquoSocial Networks vol 32 no 3 pp 245ndash251 2010
[22] U Brandes ldquoOn variants of shortest-path betweenness central-ity and their generic computationrdquo Social Networks vol 30 no2 pp 136ndash145 2008
[23] H Q Li J H Li A J Liu M Y Ye and G Q ZhengldquoGV20-based acupuncture for animal models of acute intrac-erebral haemorrhage a preclinical systematic review and meta-analysisrdquo Acupuncture in Medicine vol 32 no 6 pp 495ndash5022014
[24] EOda ROhkiHMurasawa et al ldquoNoxa a BH3-onlymemberof the Bcl-2 family and candidate mediator of p53-inducedapoptosisrdquo Science vol 288 no 5468 pp 1053ndash1058 2000
[25] H Endo H Kamada C Nito T Nishi and P H Chan ldquoMito-chondrial translocation of p53 mediates release of cytochromec and hippocampal CA1 neuronal death after transient globalcerebral ischemia in ratsrdquo Journal of Neuroscience vol 26 no30 pp 7974ndash7983 2006
[26] Y Zhu and Y Zeng ldquoElectroacupuncture protected pyramidalcells in hippocampal CA1 region of vascular dementia rats byinhibiting the expression of P53 and Noxardquo CNS NeuroscienceandTherapeutics vol 17 no 6 pp 599ndash604 2011
[27] W J Tyler M Alonso C R Bramham and L D Pozzo-Miller ldquoFrom acquisition to consolidation on the role ofbrain-derived neurotrophic factor signaling in hippocampal-dependent learningrdquo Learning and Memory vol 9 no 5 pp224ndash237 2002
[28] P Bekinschtein M Cammarota C Katche et al ldquoBDNF isessential to promote persistence of long-termmemory storagerdquoProceedings of the National Academy of Sciences of the UnitedStates of America vol 105 no 7 pp 2711ndash2716 2008
[29] K Kitagawa ldquoCREB and cAMP response element-mediatedgene expression in the ischemic brainrdquo FEBS Journal vol 274no 13 pp 3210ndash3217 2007
[30] B Lee B Sur J Shim D Hahm and H Lee ldquoAcupuncturestimulation improves scopolamine-induced cognitive impair-ment via activation of cholinergic system and regulation ofBDNF andCREB expressions in ratsrdquoBMCComplementary andAlternative Medicine vol 14 no 1 article 338 2014
[31] M E Hasselmo ldquoThe role of acetylcholine in learning andmemoryrdquo Current Opinion in Neurobiology vol 16 no 6 pp710ndash715 2006
[32] T M Jay ldquoDopamine a potential substrate for synaptic plastic-ity andmemory mechanismsrdquo Progress in Neurobiology vol 69no 6 pp 375ndash390 2003
[33] C-M Chuang C-L Hsieh T-C Li and J-G Lin ldquoAcupunc-ture stimulation at Baihui acupoint reduced cerebral infarct andincreased dopamine levels in chronic cerebral hypoperfusionand ischemia-reperfusion injured Sprague-Dawley ratsrdquoAmeri-can Journal of ChineseMedicine vol 35 no 5 pp 779ndash791 2007
[34] H Jiao Z Wang Y Liu P Wang and Y Xue ldquoSpecific roleof tight junction proteins claudin-5 occludin and ZO-1 of theblood-brain barrier in a focal cerebral ischemic insultrdquo Journalof Molecular Neuroscience vol 44 no 2 pp 130ndash139 2011
[35] Y-M Zhang H Xu H Sun S Chen and F Wang ldquoElec-troacupuncture treatment improves neurological function asso-ciated with regulation of tight junction proteins in rats withcerebral ischemia reperfusion injuryrdquo Evidence-Based Comple-mentary and Alternative Medicine vol 2014 Article ID 98934010 pages 2014
[36] B-X Jin X-S Lai and C-Z Tang ldquoProgress in researches onthe specificity of acupointsrdquo Acupuncture Research vol 33 no2 pp 135ndash138 2008
[37] Y Li F Liang X Yang et al ldquoAcupuncture for treating acuteattacks of migraine a randomized controlled trialrdquo Headachevol 49 no 6 pp 805ndash816 2009
[38] T T Ma S Y Yu Y Li et al ldquoRandomised clinical trial anassessment of acupuncture on specific meridian or specific acu-point vs sham acupuncture for treating functional dyspepsiardquoAlimentary Pharmacology and Therapeutics vol 35 no 5 pp552ndash561 2012
[39] P-F Shen L Kong L-W Ni et al ldquoAcupuncture interventionin ischemic stroke a randomized controlled prospective studyrdquoThe American Journal of Chinese Medicine vol 40 no 4 pp685ndash693 2012
[40] Y Huang M H Win J Chen et al ldquoA comparative studyon the treatment of vascular dementia by puncturing Baihui(GV20) Shuigou (GV26) and Shenmen (HT7)rdquoWorld Journalof AcupuncturemdashMoxibustion no 1 pp 3ndash10 2005
[41] Y Huang X-S Lai and A-W Tang ldquoComparative study of thespecificities of needling acupoints DU20 DU26 and HT7 inintervening vascular dementia in different areas in the brain onthe basis of scale assessment and cerebral functional imagingrdquoChinese Journal of Integrative Medicine vol 13 no 2 pp 103ndash108 2007
[42] R Alizadeh S Esmaeili S Shoar S Bagheri-Hariri and NShoar ldquoAcupuncture in preventing postoperative nausea andvomiting efficacy of two acupuncture points versus a singleonerdquo Journal of Acupuncture and Meridian Studies vol 7 no2 pp 71ndash75 2014
[43] F M Xu and R X Chen ldquoThe antagonistic effect of acupointson oxygen consumption rate in ratsrdquo Journal of Jiangxi Collegeof Traditional Chinese Medicine vol 13 no 2 pp 60ndash61 2001
[44] F M Xu and R X Chen ldquoEffect of electroacupuncture ongastrointestinalmovement in rats with hypoactive gastrointesti-nal movement caused by greaserdquo Henan Traditional ChineseMedicine vol 20 no 2 pp 19ndash20 2000
[45] X H Li X Z Gao and L Hu ldquoExperimental study on syner-getic and antagonistic effects of acupoints Neiguan Shenmenand Xinshurdquo Chinese Acupuncture andMoxibustion vol 22 no12 pp 819ndash821 2002
[46] X H Li Q Y Wang X Z Gao et al ldquoStudy on cooperationand antagonism among acupointsrdquo Chinese Acupuncture andMoxibustion vol 22 no 6 pp 387ndash388 2002
[47] Y Feng Y Qiu X Zhou Y Wang H Xu and B Liu ldquoOpti-mizing prescription of Chinese herbal medicine for unstableangina based on partially observable Markov decision processrdquoEvidence-based Complementary and Alternative Medicine vol2013 Article ID 532534 6 pages 2013
Submit your manuscripts athttpwwwhindawicom
Stem CellsInternational
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
MEDIATORSINFLAMMATION
of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Behavioural Neurology
EndocrinologyInternational Journal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Disease Markers
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
BioMed Research International
OncologyJournal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Oxidative Medicine and Cellular Longevity
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
PPAR Research
The Scientific World JournalHindawi Publishing Corporation httpwwwhindawicom Volume 2014
Immunology ResearchHindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Journal of
ObesityJournal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Computational and Mathematical Methods in Medicine
OphthalmologyJournal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Diabetes ResearchJournal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Research and TreatmentAIDS
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Gastroenterology Research and Practice
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Parkinsonrsquos Disease
Evidence-Based Complementary and Alternative Medicine
Volume 2014Hindawi Publishing Corporationhttpwwwhindawicom
Evidence-Based Complementary and Alternative Medicine 9
0102030405060708090
100
GV
20
EX-H
N1
GB2
0
GV
24
PC6
SP6
GV
14
GV
26
GV
16
HT7 LI
4
KI3
ST36
ST40
LV3
GB1
3
EX-H
N3
BL10
GB3
9
LI 1
1
Degree
(a) The 20 acupoints with highest degree
0002004006008
01012014016
KI1
GV
20
EX-H
N1
PC6
GV
26
GB2
0
GV
24
GV
14 SP6
EX-H
N3
HT7 LI
4
KI3
GV
16
BL10
LV3
ST40
ST36
GB1
3
PC9
Betweenness centrality
(b) The 20 acupoints with highest betweenness centrality
Figure 6 The 20 acupoints with highest degree and the 20 acupoints with highest betweenness centrality
also used to tonify kidney in treatment of VaD ThereforeYongquan (KI 1) is used not only with other Jing-Wellacupoints but also with other types of acupoints such asother types of specific acupoints nonspecific acupoints andacupoints on other parts
42 UnderlyingMolecularMechanism of the Acupoint with theMost Potential to Treat VaD According to our results Baihui(GV 20) which had the highest frequency has the mostpotential to treat VaD A systematic review andmeta-analysisalso suggested that Baihui (GV 20) is a principal acupoint foracute intracerebral hemorrhage (ICH) in animal models ofacute ICH there was no difference in efficacy between Baihui(GV 20) alone and Baihui (GV 20) plus other acupoints [23]
Molecular biology studies have provided insights intothe mechanisms underlying the effects of Baihui (GV 20) inVaD treatment including antioxidant effects antiapoptoticeffects neurotrophic effects reduced blood-brain barrier(BBB) permeability and regulation of the cholinergic anddopaminergic systems Acupuncture at Baihui (GV 20) incombination with other acupoints decreases levels of 8-hydroxy-21015840-deoxyguanosine a product of oxidative damageto DNA induced by free radicals suggesting that the benefitof acupuncture is partly due to antioxidant effects [11]Acupuncture exerts therapeutic effects on VaD via antiapop-tosis The tumor suppressors p53 and Noxa are important inregulating apoptosis and mediate hypoxic cell death [24 25]
Electroacupuncture at Baihui (GV 20) Dazhui (GV 14) andShenshu (BL 23) blocks expression of p53 and Noxa in thehippocampal CA1 region of VaD rats [26] Acupuncture atBaihui (GV 20) can improve neurogenesis via regulatingbrain-derived neurotrophic factor (BDNF) and cyclic AMPresponse element-binding protein (CREB) BDNF whichis essential for synaptic plasticity and is coupled to CREBactivation [27] is important for long-term memory storage[28] CREB is required for the proliferation growth survivaland differentiation of all types of cells In the brain the CREBand CRE-mediated system is involved in memory learningsynaptic transmission neuron survival differentiation andaxon growth [29] Acupuncture at Baihui (GV 20) signifi-cantly increases the levels of BDNF [15 30] CREB proteinsCREB mRNA [30] and phosphorylated CREB the activeform of CREB [15] The molecular mechanism underlyingacupuncture at Baihui (GV 20) also involves cholinergicsystem regulation Decreased cholinergic function in thebrain can result in a decline in memory and cognitivefunction [31] Acupuncture at Baihui (GV 20) significantlyincreases the levels of choline acetyltransferase (ChAT) andrestores the expression of choline transporter 1 (CHT1)and vesicular acetylcholine transporter (VAChT) [30] Thedopaminergic system is also involved in the mechanismunderlying the treatment of VaD with acupuncture at Baihui(GV 20) Dopamine is a key regulator in specific synapticchanges observed at certain stages of learning and memory
10 Evidence-Based Complementary and Alternative Medicine
and of synaptic plasticity [32] Acupuncture at Baihui (GV20)increases dopamine levels in chronic cerebral hypoperfusionand ischemia-reperfusion injured rats [33] In additionacupuncture at Baihui (GV 20) and Zusanli (ST 36) preservesthe integrity of the BBB reducing BBB permeability TheBBB is constructed of tight conjunctions including occludinand claudin-5 which form the endothelial barrier Reducedexpression of ZO-1 claudin-5 and occludin mRNA andprotein contributes to BBB breakdown and edema in theischemic brain [34] Electroacupuncture at Baihui (GV 20)and Zusanli (ST 36) reduces brain damage and relatedbehavioral deficits via upregulation of tight conjunctionproteins including ZO-1 claudin-5 and occludin [35]Thesefindings reveal parts of the molecular mechanism underlyingacupuncture at Baihui (GV 20) to treat VaD
43 Acupoints Selection in Treatment for VaD The properselection of acupoints is essential for the therapeutic effectsof acupuncture because acupoints are specific with regard tomorphological structure biophysical properties pathologicalresponse and stimulating effects [36] This specificity dif-ferentiates acupoints from nonacupoints as well as differentacupoints from one another The specific therapeutic effectsof different acupoints have been reported for migraine [37]functional dyspepsia [38] ischemic stroke [39] and so forth
The specificity of acupoints for the treatment of VaDhas also been reported Phosphorylated CREB levels weresignificantly increased after acupuncture therapy of needlingBaihui (GV 20) and Zusanli (ST 36) compared to shamacupuncture therapy of needling nonacupoints [15] Baihui(GV 20) Shuigou (GV 26) and Shenmen (HT 7) are allamong the 10 acupoints with the most potential A clinicaltrial demonstrated that needling Baihui (GV 20) Shuigou(GV 26) and Shenmen (HT 7) were all effective in improvingthe symptoms of VaD However their therapeutic effects dif-fer Needling Baihui (GV 20) improved calculation ability andshort-term memory and corrected the personality changesof VaD patients while needling Shuigou (GV 26) improvednaming ability and short-term memory The therapeuticeffects of needling Baihui (GV 20) and Shuigou (GV 26)were superior to those of needling Shenmen (HT 7) [40]A PET and SPECT study revealed that needling these threedifferent acupoints in VaD patients affected different brainareas Needling Baihui (GV 20) activated the inner temporalsystem the thalamencephalon system and the prefrontalcortical system Needling Shuigou (GV 26) activated the pre-frontal cortical system Needling Shenmen (HT 7) generatedan effect similar to but weaker than the effect generated byneedling Shuigou (GV 26) [41] These findings demonstratethat different acupoints have different therapeutic effects inacupuncture treatment for VaD Consequently the selectionof acupoints which directly influences the therapeutic effectsof acupuncture should be considered carefully According toour results based on datamining Baihui (GV 20) Sishencong(EX-HN 1) Fengchi (GB 20) Shuigou (GV 26) and Shenting(GV 24) which have higher frequencies in the modernliterature may have better therapeutic effects on VaD
44 SingleAcupoint orAcupoint Combination Acupoint com-binations also influence the therapeutic effects of acupunc-ture An acupoint combination is considered to have asynergistic effect that enhances the therapeutic effect ofacupuncture For example a lower prevalence of postoper-ative nausea and vomiting in patients treated with Neiguan(PC 6) plus Hegu (LI 4) was observed compared with thosetreated with Neiguan (PC 6) only [42] In spite of extensiveevidence suggesting a synergistic effect of acupoint combi-nation and supporting its use some studies have reportedantagonistic effects [43ndash45] An antagonistic effect occurswhen one acupoint weakens the therapeutic effect of anotheracupoint [46] For example electroacupuncture can improvegastrointestinal movement in rats The effect of needlingPishu (BL 20) alone was better than the effect of needlingPishu (BL 20) and Zusanli (ST 36) at the same time [44]Therefore whether the effect of acupoint combination isbetter than a single acupoint still remains a question andneeds to be further studied
Some studies have compared single acupoints and anacupoint combination for the treatment of VaD The thera-peutic effect of needling Baihui (GV 20) Shuigou (GV 26)and Shenmen (HT 7) in combination was better than theeffects obtained by needling each alone [40] In additionneedling Baihui (GV 20) Shuigou (GV 26) and Shenmen(HT 7) simultaneously activated more brain areas relatedto intellectual activities compared with needling each alonegenerating a more extensive effect on the brain [41] Antago-nistic effects in acupuncture therapy for VaD have not beenreported but may occur Most acupuncture prescriptions forVaD contain acupoint combinations and the use of acupointcombinations is supported However acupoint combinationsshould be selected carefully to avoid antagonistic effects Itis hard to tell whether a combination of acupoints will exertantagonistic effects with current knowledge or TCM theoryAs abovementioned acupoints with similar functions canexert antagonistic effects There are many acupoints and thenumber of acupoint combinations will grow geometricallyTo test the antagonistic effects of each combination oneby one is an exhausting job To avoid antagonistic effectsas possible the acupoint prescriptions should be simplifiedas possible The general principle is to select acupointswith relatively better therapeutic effects and acupoints withmultiple indications and not to select many acupoints
45 Limitations This study has limitations as follows Firstother factors that influence acupuncture such as manipula-tion and treatment duration were not analyzed in this studyThese data can be further mined in future studies Secondlargely due to the lack of treatment based on syndrome differ-entiation and different methods of syndrome differentiationin modern literature potential acupoints and combinationsfor different syndromes of VaD were not analyzed Althoughtreatment based on syndrome differentiation is importantand is often emphasized in TCM treatment based on diseasedifferentiation is equally important Third the real therapeu-tic effects of acupoints and combinations on VaD cannotbe reflected by frequencies in the literature However theseresults suggest some potential acupoints and combinations to
Evidence-Based Complementary and Alternative Medicine 11
be explored in future clinical trials to validate the effects ofacupuncture on VaD To optimize the acupoint prescriptiondata may be extracted not only from literature but alsofrom clinical practice Further research can collect acupointprescriptions and symptom improvements in clinical practiceand optimize acupoint prescriptionwith dataminingMiningclinical data has been practiced to optimize prescriptionof Chinese herbal medicine for unstable angina by Fenget al [47] In their study five main symptoms of patientswith unstable angina the severity of each symptom andthe prescription of each patient were collected The levels ofaverage discounted reward (ADR) of different prescriptionswere calculated to evaluate the clinical efficacy of differ-ent treatment options with some optimized prescriptionsachieved Future studies can mine clinical data to optimizeacupoint prescription
5 Conclusions
In this study data mining was used to discover potentialacupoints and combinations for VaD Potential acupointsinclude Baihui (GV 20) Sishencong (EX-HN 1) Fengchi (GB20) Shuigou (GV 26) and Shenting (GV 24) In additioncombinations between Baihui (GV 20) Sishencong (EX-HN1) Fengchi (GB 20) Shenting (GV 24) Shuigou (GV 26) andZusanli (ST 36) were potential combinations Based on ourresults Baihui (GV 20) and Sishencong (EX-HN 1) shouldbe selected with priority Acupoints in head compared toacupoints in other parts should also be selected with priority
Conflict of Interests
The authors declare no conflict of interests
Authorsrsquo Contribution
Shuwei Feng and Yulan Ren contributed equally to this work
Acknowledgments
This study was supported by the National Basic ResearchProgram of China (no 2012CB518501) and the NationalScience Foundation of China (nos 81102742 and 61104224)
References
[1] Q Chen X Wu S F Lu et al ldquoMeridian acupoints selectionin acupuncture treatment for migraine the main charactersand relevant factors analysisrdquo Liaoning Journal of TraditionalChinese Medicine vol 36 no 9 pp 1477ndash1480 2009
[2] Y Li H Zheng C M Witt et al ldquoAcupuncture for migraineprophylaxis a randomized controlled trialrdquo Canadian MedicalAssociation Journal vol 184 no 4 pp 401ndash410 2012
[3] B H May C Lu L Bennett H M Hugel and C C LXue ldquoEvaluating the traditional Chinese literature for herbalformulae and individual herbs used for age-related dementiaand memory impairmentrdquo Biogerontology vol 13 no 3 pp299ndash312 2012
[4] L Zhang Y Li X Guo et al ldquoText mining of the classicalmedical literature for medicines that show potential in diabeticnephropathyrdquo Evidence-Based Complementary and AlternativeMedicine vol 2014 Article ID 189125 12 pages 2014
[5] Y Olsson A Brun and E Englund ldquoFundamental pathologicallesions in vascular dementiardquo Acta Neurologica Scandinavicavol 94 supplement 168 pp 31ndash38 1996
[6] S Davis M Shanahan A Campbell M Hegarty and BMcCarthy ldquoPalliative care for people with dementia aged carestaff perspectivesrdquo Alzheimerrsquos amp Dementia vol 7 no 4 p e502011
[7] J Jia F Wang C Wei et al ldquoThe prevalence of dementia inurban and rural areas of Chinardquo Alzheimerrsquos and Dementia vol10 no 1 pp 1ndash9 2014
[8] C P Ferri M Prince C Brayne et al ldquoGlobal prevalence ofdementia a Delphi consensus studyrdquo The Lancet vol 366 no9503 pp 2112ndash2117 2005
[9] W Quentin S G Riedel-Heller M Luppa A Rudolph andH-H Konig ldquoCost-of-illness studies of dementia a systematicreview focusing on stage dependency of costsrdquoActa PsychiatricaScandinavica vol 121 no 4 pp 243ndash259 2010
[10] J Yu X Zhang C Liu Y Meng and J Han ldquoEffect ofacupuncture treatment on vascular dementiardquo NeurologicalResearch vol 28 no 1 pp 97ndash103 2006
[11] G-X Shi C-Z Liu Q-Q Li H Zhu and L-P WangldquoInfluence of acupuncture on cognitive function and markersof oxidative DNA damage in patients with vascular dementiardquoJournal of Traditional Chinese Medicine vol 32 no 2 pp 199ndash202 2012
[12] X-Y Zhong X-X Su J Liu and G Q Zhu ldquoClinical effectsof acupuncture combined with nimodipine for treatment ofvascular dementia in 30 casesrdquo Journal of Traditional ChineseMedicine vol 29 no 3 pp 174ndash176 2009
[13] T Wang C-Z Liu J-C Yu W Jiang and J-X Han ldquoAcupunc-ture protected cerebral multi-infarction rats from memoryimpairment by regulating the expression of apoptosis relatedgenes Bcl-2 and Bax in hippocampusrdquo Physiology and Behaviorvol 96 no 1 pp 155ndash161 2009
[14] I K Hwang J Y Chung D Y Yoo et al ldquoComparing the effectsof acupuncture and electroacupuncture at Zusanli and Baihuion cell proliferation and neuroblast differentiation in the rathippocampusrdquo Journal of VeterinaryMedical Science vol 72 no3 pp 279ndash284 2010
[15] I K Hwang J Y Chung D Y Yoo et al ldquoEffects ofelectroacupuncture at Zusanli and Baihui on brain-derivedneurotrophic factor and cyclic AMP response element-bindingprotein in the hippocampal dentate gyrusrdquo Journal of VeterinaryMedical Science vol 72 no 11 pp 1431ndash1436 2010
[16] Y F Luo and J M Wu Fundamentals of Acupuncture SichuanUniversity Press Sichuan China 2008
[17] R Agrawal and R Srikant ldquoFast algorithms for mining associ-ation rulesrdquo in Proceedings of the 20th International Conferenceon Very Large Data Bases (VLDB rsquo94) pp 487ndash499 SantiagoChile 1994
[18] R Agrawal T Imielinski and A Swami ldquoMining associationrules between sets of items in large databasesrdquo ACM SIGMODRecord vol 22 no 2 pp 207ndash216 1993
12 Evidence-Based Complementary and Alternative Medicine
[19] A Clauset M E J Newman and C Moore ldquoFinding commu-nity structure in very large networksrdquo Physical Review E vol 70no 6 Article ID 066111 6 pages 2004
[20] G F de Arruda A L Barbieri P M Rodriguez et al ldquoRoleof centrality for the identification of influential spreaders incomplex networksrdquo Physical Review E Statistical Nonlinearand SoftMatter Physics vol 90 no 1ndash3 Article ID 032812 2014
[21] T Opsahl F Agneessens and J Skvoretz ldquoNode centrality inweighted networks generalizing degree and shortest pathsrdquoSocial Networks vol 32 no 3 pp 245ndash251 2010
[22] U Brandes ldquoOn variants of shortest-path betweenness central-ity and their generic computationrdquo Social Networks vol 30 no2 pp 136ndash145 2008
[23] H Q Li J H Li A J Liu M Y Ye and G Q ZhengldquoGV20-based acupuncture for animal models of acute intrac-erebral haemorrhage a preclinical systematic review and meta-analysisrdquo Acupuncture in Medicine vol 32 no 6 pp 495ndash5022014
[24] EOda ROhkiHMurasawa et al ldquoNoxa a BH3-onlymemberof the Bcl-2 family and candidate mediator of p53-inducedapoptosisrdquo Science vol 288 no 5468 pp 1053ndash1058 2000
[25] H Endo H Kamada C Nito T Nishi and P H Chan ldquoMito-chondrial translocation of p53 mediates release of cytochromec and hippocampal CA1 neuronal death after transient globalcerebral ischemia in ratsrdquo Journal of Neuroscience vol 26 no30 pp 7974ndash7983 2006
[26] Y Zhu and Y Zeng ldquoElectroacupuncture protected pyramidalcells in hippocampal CA1 region of vascular dementia rats byinhibiting the expression of P53 and Noxardquo CNS NeuroscienceandTherapeutics vol 17 no 6 pp 599ndash604 2011
[27] W J Tyler M Alonso C R Bramham and L D Pozzo-Miller ldquoFrom acquisition to consolidation on the role ofbrain-derived neurotrophic factor signaling in hippocampal-dependent learningrdquo Learning and Memory vol 9 no 5 pp224ndash237 2002
[28] P Bekinschtein M Cammarota C Katche et al ldquoBDNF isessential to promote persistence of long-termmemory storagerdquoProceedings of the National Academy of Sciences of the UnitedStates of America vol 105 no 7 pp 2711ndash2716 2008
[29] K Kitagawa ldquoCREB and cAMP response element-mediatedgene expression in the ischemic brainrdquo FEBS Journal vol 274no 13 pp 3210ndash3217 2007
[30] B Lee B Sur J Shim D Hahm and H Lee ldquoAcupuncturestimulation improves scopolamine-induced cognitive impair-ment via activation of cholinergic system and regulation ofBDNF andCREB expressions in ratsrdquoBMCComplementary andAlternative Medicine vol 14 no 1 article 338 2014
[31] M E Hasselmo ldquoThe role of acetylcholine in learning andmemoryrdquo Current Opinion in Neurobiology vol 16 no 6 pp710ndash715 2006
[32] T M Jay ldquoDopamine a potential substrate for synaptic plastic-ity andmemory mechanismsrdquo Progress in Neurobiology vol 69no 6 pp 375ndash390 2003
[33] C-M Chuang C-L Hsieh T-C Li and J-G Lin ldquoAcupunc-ture stimulation at Baihui acupoint reduced cerebral infarct andincreased dopamine levels in chronic cerebral hypoperfusionand ischemia-reperfusion injured Sprague-Dawley ratsrdquoAmeri-can Journal of ChineseMedicine vol 35 no 5 pp 779ndash791 2007
[34] H Jiao Z Wang Y Liu P Wang and Y Xue ldquoSpecific roleof tight junction proteins claudin-5 occludin and ZO-1 of theblood-brain barrier in a focal cerebral ischemic insultrdquo Journalof Molecular Neuroscience vol 44 no 2 pp 130ndash139 2011
[35] Y-M Zhang H Xu H Sun S Chen and F Wang ldquoElec-troacupuncture treatment improves neurological function asso-ciated with regulation of tight junction proteins in rats withcerebral ischemia reperfusion injuryrdquo Evidence-Based Comple-mentary and Alternative Medicine vol 2014 Article ID 98934010 pages 2014
[36] B-X Jin X-S Lai and C-Z Tang ldquoProgress in researches onthe specificity of acupointsrdquo Acupuncture Research vol 33 no2 pp 135ndash138 2008
[37] Y Li F Liang X Yang et al ldquoAcupuncture for treating acuteattacks of migraine a randomized controlled trialrdquo Headachevol 49 no 6 pp 805ndash816 2009
[38] T T Ma S Y Yu Y Li et al ldquoRandomised clinical trial anassessment of acupuncture on specific meridian or specific acu-point vs sham acupuncture for treating functional dyspepsiardquoAlimentary Pharmacology and Therapeutics vol 35 no 5 pp552ndash561 2012
[39] P-F Shen L Kong L-W Ni et al ldquoAcupuncture interventionin ischemic stroke a randomized controlled prospective studyrdquoThe American Journal of Chinese Medicine vol 40 no 4 pp685ndash693 2012
[40] Y Huang M H Win J Chen et al ldquoA comparative studyon the treatment of vascular dementia by puncturing Baihui(GV20) Shuigou (GV26) and Shenmen (HT7)rdquoWorld Journalof AcupuncturemdashMoxibustion no 1 pp 3ndash10 2005
[41] Y Huang X-S Lai and A-W Tang ldquoComparative study of thespecificities of needling acupoints DU20 DU26 and HT7 inintervening vascular dementia in different areas in the brain onthe basis of scale assessment and cerebral functional imagingrdquoChinese Journal of Integrative Medicine vol 13 no 2 pp 103ndash108 2007
[42] R Alizadeh S Esmaeili S Shoar S Bagheri-Hariri and NShoar ldquoAcupuncture in preventing postoperative nausea andvomiting efficacy of two acupuncture points versus a singleonerdquo Journal of Acupuncture and Meridian Studies vol 7 no2 pp 71ndash75 2014
[43] F M Xu and R X Chen ldquoThe antagonistic effect of acupointson oxygen consumption rate in ratsrdquo Journal of Jiangxi Collegeof Traditional Chinese Medicine vol 13 no 2 pp 60ndash61 2001
[44] F M Xu and R X Chen ldquoEffect of electroacupuncture ongastrointestinalmovement in rats with hypoactive gastrointesti-nal movement caused by greaserdquo Henan Traditional ChineseMedicine vol 20 no 2 pp 19ndash20 2000
[45] X H Li X Z Gao and L Hu ldquoExperimental study on syner-getic and antagonistic effects of acupoints Neiguan Shenmenand Xinshurdquo Chinese Acupuncture andMoxibustion vol 22 no12 pp 819ndash821 2002
[46] X H Li Q Y Wang X Z Gao et al ldquoStudy on cooperationand antagonism among acupointsrdquo Chinese Acupuncture andMoxibustion vol 22 no 6 pp 387ndash388 2002
[47] Y Feng Y Qiu X Zhou Y Wang H Xu and B Liu ldquoOpti-mizing prescription of Chinese herbal medicine for unstableangina based on partially observable Markov decision processrdquoEvidence-based Complementary and Alternative Medicine vol2013 Article ID 532534 6 pages 2013
Submit your manuscripts athttpwwwhindawicom
Stem CellsInternational
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
MEDIATORSINFLAMMATION
of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Behavioural Neurology
EndocrinologyInternational Journal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Disease Markers
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
BioMed Research International
OncologyJournal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Oxidative Medicine and Cellular Longevity
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
PPAR Research
The Scientific World JournalHindawi Publishing Corporation httpwwwhindawicom Volume 2014
Immunology ResearchHindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Journal of
ObesityJournal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Computational and Mathematical Methods in Medicine
OphthalmologyJournal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Diabetes ResearchJournal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Research and TreatmentAIDS
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Gastroenterology Research and Practice
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Parkinsonrsquos Disease
Evidence-Based Complementary and Alternative Medicine
Volume 2014Hindawi Publishing Corporationhttpwwwhindawicom
10 Evidence-Based Complementary and Alternative Medicine
and of synaptic plasticity [32] Acupuncture at Baihui (GV20)increases dopamine levels in chronic cerebral hypoperfusionand ischemia-reperfusion injured rats [33] In additionacupuncture at Baihui (GV 20) and Zusanli (ST 36) preservesthe integrity of the BBB reducing BBB permeability TheBBB is constructed of tight conjunctions including occludinand claudin-5 which form the endothelial barrier Reducedexpression of ZO-1 claudin-5 and occludin mRNA andprotein contributes to BBB breakdown and edema in theischemic brain [34] Electroacupuncture at Baihui (GV 20)and Zusanli (ST 36) reduces brain damage and relatedbehavioral deficits via upregulation of tight conjunctionproteins including ZO-1 claudin-5 and occludin [35]Thesefindings reveal parts of the molecular mechanism underlyingacupuncture at Baihui (GV 20) to treat VaD
43 Acupoints Selection in Treatment for VaD The properselection of acupoints is essential for the therapeutic effectsof acupuncture because acupoints are specific with regard tomorphological structure biophysical properties pathologicalresponse and stimulating effects [36] This specificity dif-ferentiates acupoints from nonacupoints as well as differentacupoints from one another The specific therapeutic effectsof different acupoints have been reported for migraine [37]functional dyspepsia [38] ischemic stroke [39] and so forth
The specificity of acupoints for the treatment of VaDhas also been reported Phosphorylated CREB levels weresignificantly increased after acupuncture therapy of needlingBaihui (GV 20) and Zusanli (ST 36) compared to shamacupuncture therapy of needling nonacupoints [15] Baihui(GV 20) Shuigou (GV 26) and Shenmen (HT 7) are allamong the 10 acupoints with the most potential A clinicaltrial demonstrated that needling Baihui (GV 20) Shuigou(GV 26) and Shenmen (HT 7) were all effective in improvingthe symptoms of VaD However their therapeutic effects dif-fer Needling Baihui (GV 20) improved calculation ability andshort-term memory and corrected the personality changesof VaD patients while needling Shuigou (GV 26) improvednaming ability and short-term memory The therapeuticeffects of needling Baihui (GV 20) and Shuigou (GV 26)were superior to those of needling Shenmen (HT 7) [40]A PET and SPECT study revealed that needling these threedifferent acupoints in VaD patients affected different brainareas Needling Baihui (GV 20) activated the inner temporalsystem the thalamencephalon system and the prefrontalcortical system Needling Shuigou (GV 26) activated the pre-frontal cortical system Needling Shenmen (HT 7) generatedan effect similar to but weaker than the effect generated byneedling Shuigou (GV 26) [41] These findings demonstratethat different acupoints have different therapeutic effects inacupuncture treatment for VaD Consequently the selectionof acupoints which directly influences the therapeutic effectsof acupuncture should be considered carefully According toour results based on datamining Baihui (GV 20) Sishencong(EX-HN 1) Fengchi (GB 20) Shuigou (GV 26) and Shenting(GV 24) which have higher frequencies in the modernliterature may have better therapeutic effects on VaD
44 SingleAcupoint orAcupoint Combination Acupoint com-binations also influence the therapeutic effects of acupunc-ture An acupoint combination is considered to have asynergistic effect that enhances the therapeutic effect ofacupuncture For example a lower prevalence of postoper-ative nausea and vomiting in patients treated with Neiguan(PC 6) plus Hegu (LI 4) was observed compared with thosetreated with Neiguan (PC 6) only [42] In spite of extensiveevidence suggesting a synergistic effect of acupoint combi-nation and supporting its use some studies have reportedantagonistic effects [43ndash45] An antagonistic effect occurswhen one acupoint weakens the therapeutic effect of anotheracupoint [46] For example electroacupuncture can improvegastrointestinal movement in rats The effect of needlingPishu (BL 20) alone was better than the effect of needlingPishu (BL 20) and Zusanli (ST 36) at the same time [44]Therefore whether the effect of acupoint combination isbetter than a single acupoint still remains a question andneeds to be further studied
Some studies have compared single acupoints and anacupoint combination for the treatment of VaD The thera-peutic effect of needling Baihui (GV 20) Shuigou (GV 26)and Shenmen (HT 7) in combination was better than theeffects obtained by needling each alone [40] In additionneedling Baihui (GV 20) Shuigou (GV 26) and Shenmen(HT 7) simultaneously activated more brain areas relatedto intellectual activities compared with needling each alonegenerating a more extensive effect on the brain [41] Antago-nistic effects in acupuncture therapy for VaD have not beenreported but may occur Most acupuncture prescriptions forVaD contain acupoint combinations and the use of acupointcombinations is supported However acupoint combinationsshould be selected carefully to avoid antagonistic effects Itis hard to tell whether a combination of acupoints will exertantagonistic effects with current knowledge or TCM theoryAs abovementioned acupoints with similar functions canexert antagonistic effects There are many acupoints and thenumber of acupoint combinations will grow geometricallyTo test the antagonistic effects of each combination oneby one is an exhausting job To avoid antagonistic effectsas possible the acupoint prescriptions should be simplifiedas possible The general principle is to select acupointswith relatively better therapeutic effects and acupoints withmultiple indications and not to select many acupoints
45 Limitations This study has limitations as follows Firstother factors that influence acupuncture such as manipula-tion and treatment duration were not analyzed in this studyThese data can be further mined in future studies Secondlargely due to the lack of treatment based on syndrome differ-entiation and different methods of syndrome differentiationin modern literature potential acupoints and combinationsfor different syndromes of VaD were not analyzed Althoughtreatment based on syndrome differentiation is importantand is often emphasized in TCM treatment based on diseasedifferentiation is equally important Third the real therapeu-tic effects of acupoints and combinations on VaD cannotbe reflected by frequencies in the literature However theseresults suggest some potential acupoints and combinations to
Evidence-Based Complementary and Alternative Medicine 11
be explored in future clinical trials to validate the effects ofacupuncture on VaD To optimize the acupoint prescriptiondata may be extracted not only from literature but alsofrom clinical practice Further research can collect acupointprescriptions and symptom improvements in clinical practiceand optimize acupoint prescriptionwith dataminingMiningclinical data has been practiced to optimize prescriptionof Chinese herbal medicine for unstable angina by Fenget al [47] In their study five main symptoms of patientswith unstable angina the severity of each symptom andthe prescription of each patient were collected The levels ofaverage discounted reward (ADR) of different prescriptionswere calculated to evaluate the clinical efficacy of differ-ent treatment options with some optimized prescriptionsachieved Future studies can mine clinical data to optimizeacupoint prescription
5 Conclusions
In this study data mining was used to discover potentialacupoints and combinations for VaD Potential acupointsinclude Baihui (GV 20) Sishencong (EX-HN 1) Fengchi (GB20) Shuigou (GV 26) and Shenting (GV 24) In additioncombinations between Baihui (GV 20) Sishencong (EX-HN1) Fengchi (GB 20) Shenting (GV 24) Shuigou (GV 26) andZusanli (ST 36) were potential combinations Based on ourresults Baihui (GV 20) and Sishencong (EX-HN 1) shouldbe selected with priority Acupoints in head compared toacupoints in other parts should also be selected with priority
Conflict of Interests
The authors declare no conflict of interests
Authorsrsquo Contribution
Shuwei Feng and Yulan Ren contributed equally to this work
Acknowledgments
This study was supported by the National Basic ResearchProgram of China (no 2012CB518501) and the NationalScience Foundation of China (nos 81102742 and 61104224)
References
[1] Q Chen X Wu S F Lu et al ldquoMeridian acupoints selectionin acupuncture treatment for migraine the main charactersand relevant factors analysisrdquo Liaoning Journal of TraditionalChinese Medicine vol 36 no 9 pp 1477ndash1480 2009
[2] Y Li H Zheng C M Witt et al ldquoAcupuncture for migraineprophylaxis a randomized controlled trialrdquo Canadian MedicalAssociation Journal vol 184 no 4 pp 401ndash410 2012
[3] B H May C Lu L Bennett H M Hugel and C C LXue ldquoEvaluating the traditional Chinese literature for herbalformulae and individual herbs used for age-related dementiaand memory impairmentrdquo Biogerontology vol 13 no 3 pp299ndash312 2012
[4] L Zhang Y Li X Guo et al ldquoText mining of the classicalmedical literature for medicines that show potential in diabeticnephropathyrdquo Evidence-Based Complementary and AlternativeMedicine vol 2014 Article ID 189125 12 pages 2014
[5] Y Olsson A Brun and E Englund ldquoFundamental pathologicallesions in vascular dementiardquo Acta Neurologica Scandinavicavol 94 supplement 168 pp 31ndash38 1996
[6] S Davis M Shanahan A Campbell M Hegarty and BMcCarthy ldquoPalliative care for people with dementia aged carestaff perspectivesrdquo Alzheimerrsquos amp Dementia vol 7 no 4 p e502011
[7] J Jia F Wang C Wei et al ldquoThe prevalence of dementia inurban and rural areas of Chinardquo Alzheimerrsquos and Dementia vol10 no 1 pp 1ndash9 2014
[8] C P Ferri M Prince C Brayne et al ldquoGlobal prevalence ofdementia a Delphi consensus studyrdquo The Lancet vol 366 no9503 pp 2112ndash2117 2005
[9] W Quentin S G Riedel-Heller M Luppa A Rudolph andH-H Konig ldquoCost-of-illness studies of dementia a systematicreview focusing on stage dependency of costsrdquoActa PsychiatricaScandinavica vol 121 no 4 pp 243ndash259 2010
[10] J Yu X Zhang C Liu Y Meng and J Han ldquoEffect ofacupuncture treatment on vascular dementiardquo NeurologicalResearch vol 28 no 1 pp 97ndash103 2006
[11] G-X Shi C-Z Liu Q-Q Li H Zhu and L-P WangldquoInfluence of acupuncture on cognitive function and markersof oxidative DNA damage in patients with vascular dementiardquoJournal of Traditional Chinese Medicine vol 32 no 2 pp 199ndash202 2012
[12] X-Y Zhong X-X Su J Liu and G Q Zhu ldquoClinical effectsof acupuncture combined with nimodipine for treatment ofvascular dementia in 30 casesrdquo Journal of Traditional ChineseMedicine vol 29 no 3 pp 174ndash176 2009
[13] T Wang C-Z Liu J-C Yu W Jiang and J-X Han ldquoAcupunc-ture protected cerebral multi-infarction rats from memoryimpairment by regulating the expression of apoptosis relatedgenes Bcl-2 and Bax in hippocampusrdquo Physiology and Behaviorvol 96 no 1 pp 155ndash161 2009
[14] I K Hwang J Y Chung D Y Yoo et al ldquoComparing the effectsof acupuncture and electroacupuncture at Zusanli and Baihuion cell proliferation and neuroblast differentiation in the rathippocampusrdquo Journal of VeterinaryMedical Science vol 72 no3 pp 279ndash284 2010
[15] I K Hwang J Y Chung D Y Yoo et al ldquoEffects ofelectroacupuncture at Zusanli and Baihui on brain-derivedneurotrophic factor and cyclic AMP response element-bindingprotein in the hippocampal dentate gyrusrdquo Journal of VeterinaryMedical Science vol 72 no 11 pp 1431ndash1436 2010
[16] Y F Luo and J M Wu Fundamentals of Acupuncture SichuanUniversity Press Sichuan China 2008
[17] R Agrawal and R Srikant ldquoFast algorithms for mining associ-ation rulesrdquo in Proceedings of the 20th International Conferenceon Very Large Data Bases (VLDB rsquo94) pp 487ndash499 SantiagoChile 1994
[18] R Agrawal T Imielinski and A Swami ldquoMining associationrules between sets of items in large databasesrdquo ACM SIGMODRecord vol 22 no 2 pp 207ndash216 1993
12 Evidence-Based Complementary and Alternative Medicine
[19] A Clauset M E J Newman and C Moore ldquoFinding commu-nity structure in very large networksrdquo Physical Review E vol 70no 6 Article ID 066111 6 pages 2004
[20] G F de Arruda A L Barbieri P M Rodriguez et al ldquoRoleof centrality for the identification of influential spreaders incomplex networksrdquo Physical Review E Statistical Nonlinearand SoftMatter Physics vol 90 no 1ndash3 Article ID 032812 2014
[21] T Opsahl F Agneessens and J Skvoretz ldquoNode centrality inweighted networks generalizing degree and shortest pathsrdquoSocial Networks vol 32 no 3 pp 245ndash251 2010
[22] U Brandes ldquoOn variants of shortest-path betweenness central-ity and their generic computationrdquo Social Networks vol 30 no2 pp 136ndash145 2008
[23] H Q Li J H Li A J Liu M Y Ye and G Q ZhengldquoGV20-based acupuncture for animal models of acute intrac-erebral haemorrhage a preclinical systematic review and meta-analysisrdquo Acupuncture in Medicine vol 32 no 6 pp 495ndash5022014
[24] EOda ROhkiHMurasawa et al ldquoNoxa a BH3-onlymemberof the Bcl-2 family and candidate mediator of p53-inducedapoptosisrdquo Science vol 288 no 5468 pp 1053ndash1058 2000
[25] H Endo H Kamada C Nito T Nishi and P H Chan ldquoMito-chondrial translocation of p53 mediates release of cytochromec and hippocampal CA1 neuronal death after transient globalcerebral ischemia in ratsrdquo Journal of Neuroscience vol 26 no30 pp 7974ndash7983 2006
[26] Y Zhu and Y Zeng ldquoElectroacupuncture protected pyramidalcells in hippocampal CA1 region of vascular dementia rats byinhibiting the expression of P53 and Noxardquo CNS NeuroscienceandTherapeutics vol 17 no 6 pp 599ndash604 2011
[27] W J Tyler M Alonso C R Bramham and L D Pozzo-Miller ldquoFrom acquisition to consolidation on the role ofbrain-derived neurotrophic factor signaling in hippocampal-dependent learningrdquo Learning and Memory vol 9 no 5 pp224ndash237 2002
[28] P Bekinschtein M Cammarota C Katche et al ldquoBDNF isessential to promote persistence of long-termmemory storagerdquoProceedings of the National Academy of Sciences of the UnitedStates of America vol 105 no 7 pp 2711ndash2716 2008
[29] K Kitagawa ldquoCREB and cAMP response element-mediatedgene expression in the ischemic brainrdquo FEBS Journal vol 274no 13 pp 3210ndash3217 2007
[30] B Lee B Sur J Shim D Hahm and H Lee ldquoAcupuncturestimulation improves scopolamine-induced cognitive impair-ment via activation of cholinergic system and regulation ofBDNF andCREB expressions in ratsrdquoBMCComplementary andAlternative Medicine vol 14 no 1 article 338 2014
[31] M E Hasselmo ldquoThe role of acetylcholine in learning andmemoryrdquo Current Opinion in Neurobiology vol 16 no 6 pp710ndash715 2006
[32] T M Jay ldquoDopamine a potential substrate for synaptic plastic-ity andmemory mechanismsrdquo Progress in Neurobiology vol 69no 6 pp 375ndash390 2003
[33] C-M Chuang C-L Hsieh T-C Li and J-G Lin ldquoAcupunc-ture stimulation at Baihui acupoint reduced cerebral infarct andincreased dopamine levels in chronic cerebral hypoperfusionand ischemia-reperfusion injured Sprague-Dawley ratsrdquoAmeri-can Journal of ChineseMedicine vol 35 no 5 pp 779ndash791 2007
[34] H Jiao Z Wang Y Liu P Wang and Y Xue ldquoSpecific roleof tight junction proteins claudin-5 occludin and ZO-1 of theblood-brain barrier in a focal cerebral ischemic insultrdquo Journalof Molecular Neuroscience vol 44 no 2 pp 130ndash139 2011
[35] Y-M Zhang H Xu H Sun S Chen and F Wang ldquoElec-troacupuncture treatment improves neurological function asso-ciated with regulation of tight junction proteins in rats withcerebral ischemia reperfusion injuryrdquo Evidence-Based Comple-mentary and Alternative Medicine vol 2014 Article ID 98934010 pages 2014
[36] B-X Jin X-S Lai and C-Z Tang ldquoProgress in researches onthe specificity of acupointsrdquo Acupuncture Research vol 33 no2 pp 135ndash138 2008
[37] Y Li F Liang X Yang et al ldquoAcupuncture for treating acuteattacks of migraine a randomized controlled trialrdquo Headachevol 49 no 6 pp 805ndash816 2009
[38] T T Ma S Y Yu Y Li et al ldquoRandomised clinical trial anassessment of acupuncture on specific meridian or specific acu-point vs sham acupuncture for treating functional dyspepsiardquoAlimentary Pharmacology and Therapeutics vol 35 no 5 pp552ndash561 2012
[39] P-F Shen L Kong L-W Ni et al ldquoAcupuncture interventionin ischemic stroke a randomized controlled prospective studyrdquoThe American Journal of Chinese Medicine vol 40 no 4 pp685ndash693 2012
[40] Y Huang M H Win J Chen et al ldquoA comparative studyon the treatment of vascular dementia by puncturing Baihui(GV20) Shuigou (GV26) and Shenmen (HT7)rdquoWorld Journalof AcupuncturemdashMoxibustion no 1 pp 3ndash10 2005
[41] Y Huang X-S Lai and A-W Tang ldquoComparative study of thespecificities of needling acupoints DU20 DU26 and HT7 inintervening vascular dementia in different areas in the brain onthe basis of scale assessment and cerebral functional imagingrdquoChinese Journal of Integrative Medicine vol 13 no 2 pp 103ndash108 2007
[42] R Alizadeh S Esmaeili S Shoar S Bagheri-Hariri and NShoar ldquoAcupuncture in preventing postoperative nausea andvomiting efficacy of two acupuncture points versus a singleonerdquo Journal of Acupuncture and Meridian Studies vol 7 no2 pp 71ndash75 2014
[43] F M Xu and R X Chen ldquoThe antagonistic effect of acupointson oxygen consumption rate in ratsrdquo Journal of Jiangxi Collegeof Traditional Chinese Medicine vol 13 no 2 pp 60ndash61 2001
[44] F M Xu and R X Chen ldquoEffect of electroacupuncture ongastrointestinalmovement in rats with hypoactive gastrointesti-nal movement caused by greaserdquo Henan Traditional ChineseMedicine vol 20 no 2 pp 19ndash20 2000
[45] X H Li X Z Gao and L Hu ldquoExperimental study on syner-getic and antagonistic effects of acupoints Neiguan Shenmenand Xinshurdquo Chinese Acupuncture andMoxibustion vol 22 no12 pp 819ndash821 2002
[46] X H Li Q Y Wang X Z Gao et al ldquoStudy on cooperationand antagonism among acupointsrdquo Chinese Acupuncture andMoxibustion vol 22 no 6 pp 387ndash388 2002
[47] Y Feng Y Qiu X Zhou Y Wang H Xu and B Liu ldquoOpti-mizing prescription of Chinese herbal medicine for unstableangina based on partially observable Markov decision processrdquoEvidence-based Complementary and Alternative Medicine vol2013 Article ID 532534 6 pages 2013
Submit your manuscripts athttpwwwhindawicom
Stem CellsInternational
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
MEDIATORSINFLAMMATION
of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Behavioural Neurology
EndocrinologyInternational Journal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Disease Markers
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
BioMed Research International
OncologyJournal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Oxidative Medicine and Cellular Longevity
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
PPAR Research
The Scientific World JournalHindawi Publishing Corporation httpwwwhindawicom Volume 2014
Immunology ResearchHindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Journal of
ObesityJournal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Computational and Mathematical Methods in Medicine
OphthalmologyJournal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Diabetes ResearchJournal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Research and TreatmentAIDS
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Gastroenterology Research and Practice
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Parkinsonrsquos Disease
Evidence-Based Complementary and Alternative Medicine
Volume 2014Hindawi Publishing Corporationhttpwwwhindawicom
Evidence-Based Complementary and Alternative Medicine 11
be explored in future clinical trials to validate the effects ofacupuncture on VaD To optimize the acupoint prescriptiondata may be extracted not only from literature but alsofrom clinical practice Further research can collect acupointprescriptions and symptom improvements in clinical practiceand optimize acupoint prescriptionwith dataminingMiningclinical data has been practiced to optimize prescriptionof Chinese herbal medicine for unstable angina by Fenget al [47] In their study five main symptoms of patientswith unstable angina the severity of each symptom andthe prescription of each patient were collected The levels ofaverage discounted reward (ADR) of different prescriptionswere calculated to evaluate the clinical efficacy of differ-ent treatment options with some optimized prescriptionsachieved Future studies can mine clinical data to optimizeacupoint prescription
5 Conclusions
In this study data mining was used to discover potentialacupoints and combinations for VaD Potential acupointsinclude Baihui (GV 20) Sishencong (EX-HN 1) Fengchi (GB20) Shuigou (GV 26) and Shenting (GV 24) In additioncombinations between Baihui (GV 20) Sishencong (EX-HN1) Fengchi (GB 20) Shenting (GV 24) Shuigou (GV 26) andZusanli (ST 36) were potential combinations Based on ourresults Baihui (GV 20) and Sishencong (EX-HN 1) shouldbe selected with priority Acupoints in head compared toacupoints in other parts should also be selected with priority
Conflict of Interests
The authors declare no conflict of interests
Authorsrsquo Contribution
Shuwei Feng and Yulan Ren contributed equally to this work
Acknowledgments
This study was supported by the National Basic ResearchProgram of China (no 2012CB518501) and the NationalScience Foundation of China (nos 81102742 and 61104224)
References
[1] Q Chen X Wu S F Lu et al ldquoMeridian acupoints selectionin acupuncture treatment for migraine the main charactersand relevant factors analysisrdquo Liaoning Journal of TraditionalChinese Medicine vol 36 no 9 pp 1477ndash1480 2009
[2] Y Li H Zheng C M Witt et al ldquoAcupuncture for migraineprophylaxis a randomized controlled trialrdquo Canadian MedicalAssociation Journal vol 184 no 4 pp 401ndash410 2012
[3] B H May C Lu L Bennett H M Hugel and C C LXue ldquoEvaluating the traditional Chinese literature for herbalformulae and individual herbs used for age-related dementiaand memory impairmentrdquo Biogerontology vol 13 no 3 pp299ndash312 2012
[4] L Zhang Y Li X Guo et al ldquoText mining of the classicalmedical literature for medicines that show potential in diabeticnephropathyrdquo Evidence-Based Complementary and AlternativeMedicine vol 2014 Article ID 189125 12 pages 2014
[5] Y Olsson A Brun and E Englund ldquoFundamental pathologicallesions in vascular dementiardquo Acta Neurologica Scandinavicavol 94 supplement 168 pp 31ndash38 1996
[6] S Davis M Shanahan A Campbell M Hegarty and BMcCarthy ldquoPalliative care for people with dementia aged carestaff perspectivesrdquo Alzheimerrsquos amp Dementia vol 7 no 4 p e502011
[7] J Jia F Wang C Wei et al ldquoThe prevalence of dementia inurban and rural areas of Chinardquo Alzheimerrsquos and Dementia vol10 no 1 pp 1ndash9 2014
[8] C P Ferri M Prince C Brayne et al ldquoGlobal prevalence ofdementia a Delphi consensus studyrdquo The Lancet vol 366 no9503 pp 2112ndash2117 2005
[9] W Quentin S G Riedel-Heller M Luppa A Rudolph andH-H Konig ldquoCost-of-illness studies of dementia a systematicreview focusing on stage dependency of costsrdquoActa PsychiatricaScandinavica vol 121 no 4 pp 243ndash259 2010
[10] J Yu X Zhang C Liu Y Meng and J Han ldquoEffect ofacupuncture treatment on vascular dementiardquo NeurologicalResearch vol 28 no 1 pp 97ndash103 2006
[11] G-X Shi C-Z Liu Q-Q Li H Zhu and L-P WangldquoInfluence of acupuncture on cognitive function and markersof oxidative DNA damage in patients with vascular dementiardquoJournal of Traditional Chinese Medicine vol 32 no 2 pp 199ndash202 2012
[12] X-Y Zhong X-X Su J Liu and G Q Zhu ldquoClinical effectsof acupuncture combined with nimodipine for treatment ofvascular dementia in 30 casesrdquo Journal of Traditional ChineseMedicine vol 29 no 3 pp 174ndash176 2009
[13] T Wang C-Z Liu J-C Yu W Jiang and J-X Han ldquoAcupunc-ture protected cerebral multi-infarction rats from memoryimpairment by regulating the expression of apoptosis relatedgenes Bcl-2 and Bax in hippocampusrdquo Physiology and Behaviorvol 96 no 1 pp 155ndash161 2009
[14] I K Hwang J Y Chung D Y Yoo et al ldquoComparing the effectsof acupuncture and electroacupuncture at Zusanli and Baihuion cell proliferation and neuroblast differentiation in the rathippocampusrdquo Journal of VeterinaryMedical Science vol 72 no3 pp 279ndash284 2010
[15] I K Hwang J Y Chung D Y Yoo et al ldquoEffects ofelectroacupuncture at Zusanli and Baihui on brain-derivedneurotrophic factor and cyclic AMP response element-bindingprotein in the hippocampal dentate gyrusrdquo Journal of VeterinaryMedical Science vol 72 no 11 pp 1431ndash1436 2010
[16] Y F Luo and J M Wu Fundamentals of Acupuncture SichuanUniversity Press Sichuan China 2008
[17] R Agrawal and R Srikant ldquoFast algorithms for mining associ-ation rulesrdquo in Proceedings of the 20th International Conferenceon Very Large Data Bases (VLDB rsquo94) pp 487ndash499 SantiagoChile 1994
[18] R Agrawal T Imielinski and A Swami ldquoMining associationrules between sets of items in large databasesrdquo ACM SIGMODRecord vol 22 no 2 pp 207ndash216 1993
12 Evidence-Based Complementary and Alternative Medicine
[19] A Clauset M E J Newman and C Moore ldquoFinding commu-nity structure in very large networksrdquo Physical Review E vol 70no 6 Article ID 066111 6 pages 2004
[20] G F de Arruda A L Barbieri P M Rodriguez et al ldquoRoleof centrality for the identification of influential spreaders incomplex networksrdquo Physical Review E Statistical Nonlinearand SoftMatter Physics vol 90 no 1ndash3 Article ID 032812 2014
[21] T Opsahl F Agneessens and J Skvoretz ldquoNode centrality inweighted networks generalizing degree and shortest pathsrdquoSocial Networks vol 32 no 3 pp 245ndash251 2010
[22] U Brandes ldquoOn variants of shortest-path betweenness central-ity and their generic computationrdquo Social Networks vol 30 no2 pp 136ndash145 2008
[23] H Q Li J H Li A J Liu M Y Ye and G Q ZhengldquoGV20-based acupuncture for animal models of acute intrac-erebral haemorrhage a preclinical systematic review and meta-analysisrdquo Acupuncture in Medicine vol 32 no 6 pp 495ndash5022014
[24] EOda ROhkiHMurasawa et al ldquoNoxa a BH3-onlymemberof the Bcl-2 family and candidate mediator of p53-inducedapoptosisrdquo Science vol 288 no 5468 pp 1053ndash1058 2000
[25] H Endo H Kamada C Nito T Nishi and P H Chan ldquoMito-chondrial translocation of p53 mediates release of cytochromec and hippocampal CA1 neuronal death after transient globalcerebral ischemia in ratsrdquo Journal of Neuroscience vol 26 no30 pp 7974ndash7983 2006
[26] Y Zhu and Y Zeng ldquoElectroacupuncture protected pyramidalcells in hippocampal CA1 region of vascular dementia rats byinhibiting the expression of P53 and Noxardquo CNS NeuroscienceandTherapeutics vol 17 no 6 pp 599ndash604 2011
[27] W J Tyler M Alonso C R Bramham and L D Pozzo-Miller ldquoFrom acquisition to consolidation on the role ofbrain-derived neurotrophic factor signaling in hippocampal-dependent learningrdquo Learning and Memory vol 9 no 5 pp224ndash237 2002
[28] P Bekinschtein M Cammarota C Katche et al ldquoBDNF isessential to promote persistence of long-termmemory storagerdquoProceedings of the National Academy of Sciences of the UnitedStates of America vol 105 no 7 pp 2711ndash2716 2008
[29] K Kitagawa ldquoCREB and cAMP response element-mediatedgene expression in the ischemic brainrdquo FEBS Journal vol 274no 13 pp 3210ndash3217 2007
[30] B Lee B Sur J Shim D Hahm and H Lee ldquoAcupuncturestimulation improves scopolamine-induced cognitive impair-ment via activation of cholinergic system and regulation ofBDNF andCREB expressions in ratsrdquoBMCComplementary andAlternative Medicine vol 14 no 1 article 338 2014
[31] M E Hasselmo ldquoThe role of acetylcholine in learning andmemoryrdquo Current Opinion in Neurobiology vol 16 no 6 pp710ndash715 2006
[32] T M Jay ldquoDopamine a potential substrate for synaptic plastic-ity andmemory mechanismsrdquo Progress in Neurobiology vol 69no 6 pp 375ndash390 2003
[33] C-M Chuang C-L Hsieh T-C Li and J-G Lin ldquoAcupunc-ture stimulation at Baihui acupoint reduced cerebral infarct andincreased dopamine levels in chronic cerebral hypoperfusionand ischemia-reperfusion injured Sprague-Dawley ratsrdquoAmeri-can Journal of ChineseMedicine vol 35 no 5 pp 779ndash791 2007
[34] H Jiao Z Wang Y Liu P Wang and Y Xue ldquoSpecific roleof tight junction proteins claudin-5 occludin and ZO-1 of theblood-brain barrier in a focal cerebral ischemic insultrdquo Journalof Molecular Neuroscience vol 44 no 2 pp 130ndash139 2011
[35] Y-M Zhang H Xu H Sun S Chen and F Wang ldquoElec-troacupuncture treatment improves neurological function asso-ciated with regulation of tight junction proteins in rats withcerebral ischemia reperfusion injuryrdquo Evidence-Based Comple-mentary and Alternative Medicine vol 2014 Article ID 98934010 pages 2014
[36] B-X Jin X-S Lai and C-Z Tang ldquoProgress in researches onthe specificity of acupointsrdquo Acupuncture Research vol 33 no2 pp 135ndash138 2008
[37] Y Li F Liang X Yang et al ldquoAcupuncture for treating acuteattacks of migraine a randomized controlled trialrdquo Headachevol 49 no 6 pp 805ndash816 2009
[38] T T Ma S Y Yu Y Li et al ldquoRandomised clinical trial anassessment of acupuncture on specific meridian or specific acu-point vs sham acupuncture for treating functional dyspepsiardquoAlimentary Pharmacology and Therapeutics vol 35 no 5 pp552ndash561 2012
[39] P-F Shen L Kong L-W Ni et al ldquoAcupuncture interventionin ischemic stroke a randomized controlled prospective studyrdquoThe American Journal of Chinese Medicine vol 40 no 4 pp685ndash693 2012
[40] Y Huang M H Win J Chen et al ldquoA comparative studyon the treatment of vascular dementia by puncturing Baihui(GV20) Shuigou (GV26) and Shenmen (HT7)rdquoWorld Journalof AcupuncturemdashMoxibustion no 1 pp 3ndash10 2005
[41] Y Huang X-S Lai and A-W Tang ldquoComparative study of thespecificities of needling acupoints DU20 DU26 and HT7 inintervening vascular dementia in different areas in the brain onthe basis of scale assessment and cerebral functional imagingrdquoChinese Journal of Integrative Medicine vol 13 no 2 pp 103ndash108 2007
[42] R Alizadeh S Esmaeili S Shoar S Bagheri-Hariri and NShoar ldquoAcupuncture in preventing postoperative nausea andvomiting efficacy of two acupuncture points versus a singleonerdquo Journal of Acupuncture and Meridian Studies vol 7 no2 pp 71ndash75 2014
[43] F M Xu and R X Chen ldquoThe antagonistic effect of acupointson oxygen consumption rate in ratsrdquo Journal of Jiangxi Collegeof Traditional Chinese Medicine vol 13 no 2 pp 60ndash61 2001
[44] F M Xu and R X Chen ldquoEffect of electroacupuncture ongastrointestinalmovement in rats with hypoactive gastrointesti-nal movement caused by greaserdquo Henan Traditional ChineseMedicine vol 20 no 2 pp 19ndash20 2000
[45] X H Li X Z Gao and L Hu ldquoExperimental study on syner-getic and antagonistic effects of acupoints Neiguan Shenmenand Xinshurdquo Chinese Acupuncture andMoxibustion vol 22 no12 pp 819ndash821 2002
[46] X H Li Q Y Wang X Z Gao et al ldquoStudy on cooperationand antagonism among acupointsrdquo Chinese Acupuncture andMoxibustion vol 22 no 6 pp 387ndash388 2002
[47] Y Feng Y Qiu X Zhou Y Wang H Xu and B Liu ldquoOpti-mizing prescription of Chinese herbal medicine for unstableangina based on partially observable Markov decision processrdquoEvidence-based Complementary and Alternative Medicine vol2013 Article ID 532534 6 pages 2013
Submit your manuscripts athttpwwwhindawicom
Stem CellsInternational
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
MEDIATORSINFLAMMATION
of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Behavioural Neurology
EndocrinologyInternational Journal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Disease Markers
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
BioMed Research International
OncologyJournal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Oxidative Medicine and Cellular Longevity
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
PPAR Research
The Scientific World JournalHindawi Publishing Corporation httpwwwhindawicom Volume 2014
Immunology ResearchHindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Journal of
ObesityJournal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Computational and Mathematical Methods in Medicine
OphthalmologyJournal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Diabetes ResearchJournal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Research and TreatmentAIDS
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Gastroenterology Research and Practice
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Parkinsonrsquos Disease
Evidence-Based Complementary and Alternative Medicine
Volume 2014Hindawi Publishing Corporationhttpwwwhindawicom
12 Evidence-Based Complementary and Alternative Medicine
[19] A Clauset M E J Newman and C Moore ldquoFinding commu-nity structure in very large networksrdquo Physical Review E vol 70no 6 Article ID 066111 6 pages 2004
[20] G F de Arruda A L Barbieri P M Rodriguez et al ldquoRoleof centrality for the identification of influential spreaders incomplex networksrdquo Physical Review E Statistical Nonlinearand SoftMatter Physics vol 90 no 1ndash3 Article ID 032812 2014
[21] T Opsahl F Agneessens and J Skvoretz ldquoNode centrality inweighted networks generalizing degree and shortest pathsrdquoSocial Networks vol 32 no 3 pp 245ndash251 2010
[22] U Brandes ldquoOn variants of shortest-path betweenness central-ity and their generic computationrdquo Social Networks vol 30 no2 pp 136ndash145 2008
[23] H Q Li J H Li A J Liu M Y Ye and G Q ZhengldquoGV20-based acupuncture for animal models of acute intrac-erebral haemorrhage a preclinical systematic review and meta-analysisrdquo Acupuncture in Medicine vol 32 no 6 pp 495ndash5022014
[24] EOda ROhkiHMurasawa et al ldquoNoxa a BH3-onlymemberof the Bcl-2 family and candidate mediator of p53-inducedapoptosisrdquo Science vol 288 no 5468 pp 1053ndash1058 2000
[25] H Endo H Kamada C Nito T Nishi and P H Chan ldquoMito-chondrial translocation of p53 mediates release of cytochromec and hippocampal CA1 neuronal death after transient globalcerebral ischemia in ratsrdquo Journal of Neuroscience vol 26 no30 pp 7974ndash7983 2006
[26] Y Zhu and Y Zeng ldquoElectroacupuncture protected pyramidalcells in hippocampal CA1 region of vascular dementia rats byinhibiting the expression of P53 and Noxardquo CNS NeuroscienceandTherapeutics vol 17 no 6 pp 599ndash604 2011
[27] W J Tyler M Alonso C R Bramham and L D Pozzo-Miller ldquoFrom acquisition to consolidation on the role ofbrain-derived neurotrophic factor signaling in hippocampal-dependent learningrdquo Learning and Memory vol 9 no 5 pp224ndash237 2002
[28] P Bekinschtein M Cammarota C Katche et al ldquoBDNF isessential to promote persistence of long-termmemory storagerdquoProceedings of the National Academy of Sciences of the UnitedStates of America vol 105 no 7 pp 2711ndash2716 2008
[29] K Kitagawa ldquoCREB and cAMP response element-mediatedgene expression in the ischemic brainrdquo FEBS Journal vol 274no 13 pp 3210ndash3217 2007
[30] B Lee B Sur J Shim D Hahm and H Lee ldquoAcupuncturestimulation improves scopolamine-induced cognitive impair-ment via activation of cholinergic system and regulation ofBDNF andCREB expressions in ratsrdquoBMCComplementary andAlternative Medicine vol 14 no 1 article 338 2014
[31] M E Hasselmo ldquoThe role of acetylcholine in learning andmemoryrdquo Current Opinion in Neurobiology vol 16 no 6 pp710ndash715 2006
[32] T M Jay ldquoDopamine a potential substrate for synaptic plastic-ity andmemory mechanismsrdquo Progress in Neurobiology vol 69no 6 pp 375ndash390 2003
[33] C-M Chuang C-L Hsieh T-C Li and J-G Lin ldquoAcupunc-ture stimulation at Baihui acupoint reduced cerebral infarct andincreased dopamine levels in chronic cerebral hypoperfusionand ischemia-reperfusion injured Sprague-Dawley ratsrdquoAmeri-can Journal of ChineseMedicine vol 35 no 5 pp 779ndash791 2007
[34] H Jiao Z Wang Y Liu P Wang and Y Xue ldquoSpecific roleof tight junction proteins claudin-5 occludin and ZO-1 of theblood-brain barrier in a focal cerebral ischemic insultrdquo Journalof Molecular Neuroscience vol 44 no 2 pp 130ndash139 2011
[35] Y-M Zhang H Xu H Sun S Chen and F Wang ldquoElec-troacupuncture treatment improves neurological function asso-ciated with regulation of tight junction proteins in rats withcerebral ischemia reperfusion injuryrdquo Evidence-Based Comple-mentary and Alternative Medicine vol 2014 Article ID 98934010 pages 2014
[36] B-X Jin X-S Lai and C-Z Tang ldquoProgress in researches onthe specificity of acupointsrdquo Acupuncture Research vol 33 no2 pp 135ndash138 2008
[37] Y Li F Liang X Yang et al ldquoAcupuncture for treating acuteattacks of migraine a randomized controlled trialrdquo Headachevol 49 no 6 pp 805ndash816 2009
[38] T T Ma S Y Yu Y Li et al ldquoRandomised clinical trial anassessment of acupuncture on specific meridian or specific acu-point vs sham acupuncture for treating functional dyspepsiardquoAlimentary Pharmacology and Therapeutics vol 35 no 5 pp552ndash561 2012
[39] P-F Shen L Kong L-W Ni et al ldquoAcupuncture interventionin ischemic stroke a randomized controlled prospective studyrdquoThe American Journal of Chinese Medicine vol 40 no 4 pp685ndash693 2012
[40] Y Huang M H Win J Chen et al ldquoA comparative studyon the treatment of vascular dementia by puncturing Baihui(GV20) Shuigou (GV26) and Shenmen (HT7)rdquoWorld Journalof AcupuncturemdashMoxibustion no 1 pp 3ndash10 2005
[41] Y Huang X-S Lai and A-W Tang ldquoComparative study of thespecificities of needling acupoints DU20 DU26 and HT7 inintervening vascular dementia in different areas in the brain onthe basis of scale assessment and cerebral functional imagingrdquoChinese Journal of Integrative Medicine vol 13 no 2 pp 103ndash108 2007
[42] R Alizadeh S Esmaeili S Shoar S Bagheri-Hariri and NShoar ldquoAcupuncture in preventing postoperative nausea andvomiting efficacy of two acupuncture points versus a singleonerdquo Journal of Acupuncture and Meridian Studies vol 7 no2 pp 71ndash75 2014
[43] F M Xu and R X Chen ldquoThe antagonistic effect of acupointson oxygen consumption rate in ratsrdquo Journal of Jiangxi Collegeof Traditional Chinese Medicine vol 13 no 2 pp 60ndash61 2001
[44] F M Xu and R X Chen ldquoEffect of electroacupuncture ongastrointestinalmovement in rats with hypoactive gastrointesti-nal movement caused by greaserdquo Henan Traditional ChineseMedicine vol 20 no 2 pp 19ndash20 2000
[45] X H Li X Z Gao and L Hu ldquoExperimental study on syner-getic and antagonistic effects of acupoints Neiguan Shenmenand Xinshurdquo Chinese Acupuncture andMoxibustion vol 22 no12 pp 819ndash821 2002
[46] X H Li Q Y Wang X Z Gao et al ldquoStudy on cooperationand antagonism among acupointsrdquo Chinese Acupuncture andMoxibustion vol 22 no 6 pp 387ndash388 2002
[47] Y Feng Y Qiu X Zhou Y Wang H Xu and B Liu ldquoOpti-mizing prescription of Chinese herbal medicine for unstableangina based on partially observable Markov decision processrdquoEvidence-based Complementary and Alternative Medicine vol2013 Article ID 532534 6 pages 2013
Submit your manuscripts athttpwwwhindawicom
Stem CellsInternational
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
MEDIATORSINFLAMMATION
of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Behavioural Neurology
EndocrinologyInternational Journal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Disease Markers
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
BioMed Research International
OncologyJournal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Oxidative Medicine and Cellular Longevity
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
PPAR Research
The Scientific World JournalHindawi Publishing Corporation httpwwwhindawicom Volume 2014
Immunology ResearchHindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Journal of
ObesityJournal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Computational and Mathematical Methods in Medicine
OphthalmologyJournal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Diabetes ResearchJournal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Research and TreatmentAIDS
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Gastroenterology Research and Practice
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Parkinsonrsquos Disease
Evidence-Based Complementary and Alternative Medicine
Volume 2014Hindawi Publishing Corporationhttpwwwhindawicom
Submit your manuscripts athttpwwwhindawicom
Stem CellsInternational
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
MEDIATORSINFLAMMATION
of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Behavioural Neurology
EndocrinologyInternational Journal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Disease Markers
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
BioMed Research International
OncologyJournal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Oxidative Medicine and Cellular Longevity
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
PPAR Research
The Scientific World JournalHindawi Publishing Corporation httpwwwhindawicom Volume 2014
Immunology ResearchHindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Journal of
ObesityJournal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Computational and Mathematical Methods in Medicine
OphthalmologyJournal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Diabetes ResearchJournal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Research and TreatmentAIDS
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Gastroenterology Research and Practice
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Parkinsonrsquos Disease
Evidence-Based Complementary and Alternative Medicine
Volume 2014Hindawi Publishing Corporationhttpwwwhindawicom