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Hindawi Publishing CorporationEvidence-Based Complementary and Alternative MedicineVolume 2013 Article ID 235969 9 pageshttpdxdoiorg1011552013235969

Review ArticleZHENG-Omics Application in ZHENG Classification andTreatment Chinese Personalized Medicine

Jianye Dai1 Junwei Fang1 Shujun Sun1 Qiwen Chen2 Huijuan Cao1 Ningning Zheng1

Yongyu Zhang1 and Aiping Lu3

1 Center for Traditional Chinese Medicine and Systems Biology Shanghai University of Traditional Chinese MedicineShanghai 201203 China

2Department of Integrated Oncology Shanghai Cancer Center Fudan University Shanghai 200032 China3 School of Chinese Medicine Hong Kong Baptist University Hong Kong

Correspondence should be addressed to Yongyu Zhang dryyzsinacom and Aiping Lu lap64067611126com

Received 10 January 2013 Revised 22 February 2013 Accepted 27 February 2013

Academic Editor Zhaoxiang Bian

Copyright copy 2013 Jianye Dai 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

With the hope to provide an effective approach for personalized diagnosis and treatment clinically traditional chinese medicine(TCM) is being paid increasing attention as a complementary and alternative medicine It performs treatment based on ZHENG(TCMsyndrome) classification which could be identified clinical special phenotypes by symptoms and signs of patients even if theyhave a different disease However it caused controversy because ZHENG classification only depends on observation knowledgeand clinical experience of TCM practitioners which lacks objectivity and repeatability Although researchers and scientists ofTCM have done some work with a lot of beneficial methods the results could not reach satisfactory with the shortcomings ofgeneralizing the entire state of the body or ignoring the patientsrsquo feelings By total summary mining and integration of existingresearches the present paper attempts to introduce a novel macro-microconcept of ZHENG-omics with the prospect of brightfuture in providing an objective and repeatable approach for Chinese personalized medicine in an effective way In this paper wegive the brief introduction and preliminary validation and discuss strategies and system-oriented technologies for achieving thisgoal

1 Introduction

After the accomplishment of the Human Genome Projectpersonalized medicine is looming in the horizon Recogniz-ing continuous genetic variation and expensive cost it seemsthat it would be difficult to perform personalized drug ther-apy for a wide range of major diseases using genomic know-ledge alone although it is clearly important [1] Alternativelya holistic approach attempting to bring the body mind andspirit into harmony [2 3] traditional chinese medicine(TCM) combined with the principle of ldquoZHENG (TCM Syn-drome) Classification and Treatmentrdquo (ZCT bian zheng lunzhi in Chinese) may bring personalized medicine to light inan efficient way Researches have been conducted by He et al[4] and Lu et al [5] to illustrate that the effective rate of treat-ment based on ZHENG classification may improve thespecificity and efficiency in bothTCMandWesternmedicine

The success of personalized medicine relies on having accu-rate diagnostic tests that identify patients who can benefitfrom targeted therapies [6] While in TCM ZHENG classi-fication is performed by four diagnostic methods lookinglistening and smelling asking and touching Still it is arguedas it depended on clinical observation andTCMpractitionerrsquosexperience which would be subjective and unrepeatable Soa great breakthrough in TCM diagnosis with objectivity re-peatability and comprehensiveness is needed

Actually researchers and scientists of TCM have donesome work with a lot of beneficial methods such as physiol-ogy and biochemistry [7] molecular biology [8] and tongueimage digitization [9 10] to classify ZHENGs and evaluatethe treatment based on ZHENG classification Though theresearches are beneficial they are far from satisfactory Themain reason accounting for the results may be that thesemethods only focus on one or several indicators which

2 Evidence-Based Complementary and Alternative Medicine

cannot generalize the entire state of the body However withthe advent of the era of systems biology a broader technologyplatform was established for the study of TCM The omictechnologies provide integral systemic and dynamic tech-nology platforms and lay the foundation for the systemicstudy at a higher level The system point of view provides uswith an important idea to sweep aside the fog of mysteriousTCMandmay be a breakthrough point of incorporating East-ern medicine with Western medicine Though the researchesbased on system biology have had great progresses recentlythere is a little flaw of ignoring patientsrsquo feelings in the onlyomic data

So through existing researches of system biology applica-tion in ZCT we would like to propose further a new macro-microconcept namely ldquoZHENG-Omicsrdquo which is defined asldquoa systematic approach for targeting individual patient guid-ing treatment and predicting the outcome of personalizedtreatment by global NET-Markers (combination of genesproteins metabolites symptoms and others based on themathematicalmodel) on the basis of ZCTrdquo In this paper aftercomprehensive reviewed recent researches we will graduallyshow you brief introduction and preliminary validationand discuss strategies and system-oriented technologies forachieving the goal of providing an objective and repeatableapproach for Chinese personalized medicine in an effectiveway

2 Research Status of System BiologyApplication in ZCT

TCM researchers have attempted some beneficial works Re-search in the area of Yin-Yang sets a good example Yin-Yang (two opposite complementary interdependent and ex-changeable aspects of nature) the general principles in eightare used to categorize natural phenomena which helped usunderstand prevent and cure disease The classification ofYin-Yang usually is the first step in the ZHENG classificationSystems biology was proved to be a useful tool for the studyof Yin-Yang although the concept of Yin-Yang is abstractmysterious and obscure So far the most researches of Yin-Yang syndrome are concentrated on Yin-deficiency syn-drome andYang-deficiency syndrome Genomic informationshowed that Yang-deficiency patients had significant differ-ence in Haplotype 25 (Hap25) of APM1 rs7627128 rs1063539PSMB7 and CXCR4 compared to control group howeverHaplotype13 of PPARG in Yin-deficiency patients [11 12]At the proteomic level it was found that CRP CRH IL10ACE PTH MPO CRH PTH PRL BRCA1 BRCA2 [13]transthyretin plasma retinol-binding protein precursor andchain A-prealbumin [14] liver protein and protein of thelivermitochondria [15] levels correlatedwith Yang-deficiencysyndrome It is especially worth noting that metabonomics iswidely and deeply utilized in Yin-Yang classification Wanget al [16] and Lu et al [17] have respectively found differentmetabolites between Kidney-Yin and Kidney-Yang defi-ciency syndrome which are estrone creatinine uric acidindoxyl sulfate and so on demonstrating the notable differ-ences of these two ZHENGs From these previous researches

we realized that it is possible to establish a group of prelimi-nary global net-markers to identify the Yin-Yang deficiencysyndrome Though there has been no research on Net-Markers of Yin-Yang syndrome the combination of networkbiology and Bioinformatics has been used by Li et al toinvestigate novel biomarkers for cold-heat syndrome whichpartly represents the Yin-Yang syndrome in TCM [18 19]

However ZHENG classification is not the ultimate goalbut a progression towards treatment and curing of diseasesUnfortunately current evaluation methods are conductedignoring theories of TCM and are unable to bring this tradi-tional medicine which has been validated in clinical practiceto light This may cripple public confidence in the effective-ness of TCM To counter this an objective method on thebasis of holistic TCM must be developed What is gratify-ing systems biology especially metabonomics has shownpromising application prospect in its practice For exampleit was demonstrated in our previous experiment that if dif-ferent ZHENGs of hepatitis-B-caused cirrhosis patients weretreated by the same therapy they would show various res-ponses [20] Similar research has been performed by Chenet al [21] to study the biochemical profiles of hydrocortisone-induced animal models which evaluated the effectiveness ofHerba Cistanches Deserticolae that is formulated to warm andreinforce kidney Yang to intervene Kidney-Yang deficiencyrats A good correlation between the chemical profile and theprogress of treatment was observed In addition to this studyWang et al [16] and Lu et al [17] evaluated the effectivenessof Liuwei Dihuang Pill and Rhizoma Drynariae respectivelyin Kidney-Yin and Kidney-Yang syndromes and satisfactoryresults were obtained as well

Due to space limitation and insufficient research otherresearch has not been touched upon To systematically noteZHENG research as being performed presently clinical andexperimental studies have been summarized in Tables 1 and2 with respect to the combination of ZHENG in TCM anddisease in western medicine

3 Brief Introduction ofthe Origin of lsquolsquoZHENG-Omicsrsquorsquo

Our thought is not groundless but derived from formerresearches althoughmost of whichwere discrete andwithouta systemic and consistent research strategy ZHENG-Omics isnot simple combination of systems biology and ZCT Theirassociation could play bigger roles in helping mutually toremedy deficiencies One the systems biology research andphilosophy of TCM coincide in many ways They sharesimilar attributes in many aspects especially in a holisticapproach Two the strategy employing a dynamic noninva-sive approach is very important for the acquisition of long-term large-scale samples The thorough knowledge ofZHENGsrsquo connotation and intervention may evolve to adynamic classification approach Three a nontargeting con-cept may provide freedom for exploration of unknown classi-fications of disease states without being bound by the exist-ing methods familiar to Western medicine Finally digitalresults can be integrated for ZHENG classification through

Evidence-Based Complementary and Alternative Medicine 3

Table 1 Clinical researches of TCM ZHENGs with systems biology

Syndromes Disease Researchers Omics

Liver-gallbladder dampness-heat Hypertension Chu et al [22] ProteomicsChronic hepatitis B Guo et al [23]

Liver Yang transforming into wind Cerebral infarction Zeng et al [24] Proteomics

Liver stagnation Depression premenstrual syndromemenopausal syndrome Tan et al [25] Proteomics

Rheumatoid arthritis Lu et al [26] GenomicsCold and heat pattern Cold-syndrome genealogy Wang et al [27] Genomics

Rheumatoid arthritis Gu et al [28] MetabolomicsColorectal cancer Yang et al [29] Genomics

Spleen deficiency Chronic superficial gastritis Yang et al [30] GenomicsGastritis Liu et al [31] ProteomicsDiabetes Weng et al [32] Genomics

Wu et al [11] GenomicsKidney deficiency Normal Ni et al [12] Genomics

Normal Liu et al [14] ProteomicsChronic heart failure Zheng et al [33] Metabolomics

Dampness syndrome Chronic hepatitis B Guan et al [34] GenomicsChronic gastritis Wang et al [35] Proteomics

Dampness-phlegm Obesity Wang et al [36] GenomicsCoronary heart disease Ma et al [37] GenomicsCoronary heart disease Yuan et al [38] Genomics

Blood stasis Coronary heart disease Yuan et al [39] GenomicsCoronary heart disease Wu et al [40] Proteomics

Unstable angina Wang et al [41] MetabolomicsHepatitis B cirrhosis Li et al [42] GenomicsChronic hepatitis B Song et al [43] Proteomics

Deficiency syndrome Primary liver cancer Chen et al [44] MetabolomicsDiabetes mellitus Wu et al [45] MetabolomicsHypertension Yang et al [46] Metabolomics

Liver-kidney Yin deficiency syndrome Hepatocellular carcinoma Weng et al [47] GenomicsAscendant hyperactivity of Ganyang syndrome Hypertension Jiang et al [48] Metabolomics

statistical analysis and database building andmodeling Mostimportantly digitalization of information can be absorbedfrom scholars without a TCM background into this field ofresearch

The scope of ZHENG-omics can be illustrated as followsFirstly clinical symptoms are classified into several groupsaccording to the principle of ZHENG classification and thedifference in biological markers including DNA RNA pro-teins and metabolites are identified among these groupsSecondly by integrating of genes proteins metabolitessymptoms and others NET-Markers of ZHENG will beobtained from former differences by bioinformatics and othermathematical analysis The markers could then be used toprovide the basis in developing a possible population-screen-ing tool for selecting target individuals and creating eval-uation index for personalized treatment based on ZHENGclassification Finally ZHENG-Omics will give an objectiveand practical evaluation to the classical ZCT

4 Preliminary Validation

To explore the feasibility of our thought process a prelimi-nary case study was performed The study was performed inaccordance with the principles contained in the Declarationof Helsinki and was approved by the local ethics committeeUrine samples from 12 healthy volunteers (control group CG)and 17 patients (Hepatitis-B-caused cirrhosis group HBCG)were analyzed by gas chromatography mass spectrometry(GCMS) andmultivariate statistical analysis was performedby Simca-P 120 Software package (Umetrics Umea Sweden)[68] Though the patients were treated by Fuzheng Huayutablets (FZHY tablets Chinese patent medicine) in the sameway as lacking significant deviation inChild-Pugh Score theywere classified into 2 ZHENG types by the TCM practitioneraccording to the recording symptoms liver-gallbladderdampness-heat syndrome (LGDHS 119899 = 7) and liver-kidneyYin deficiency syndrome (LKYDS 119899 = 10) [69] The TCM


Table 2 Experimental researches of TCM ZHENGs with systems biology


Ascendant hyperactivity of liver Yang

Migraine headache Hu et al [49] ProteomicsMigraine headache Zhong et al [50] Proteomics

Hypertension Zhou et al [51] ProteomicsHypertension Zhang et al [52] Proteomics

Liver depression Zhong et al [53] Proteomics

Spleen deficiency Wang et al [54] ProteomicsLuo et al [55] MetabolomicsShen et al [56] GenomicsTang et al [15] Proteomics

Kidney deficiency Chronic heart failure Zheng et al [33] MetabolomicsLu et al [17] Metabolomics

Wang et al [16] MetabolomicsChen et al [57] Metabonomics

Blood stasis-phlegm Coronary heart disease Liu et al [58] ProteomicsBlood deficiency Tong et al [59] Genomics

Blood stasis Coronary heart disease Jian et al [60] MetabolomicsCoronary heart disease Wang et al [61] Metabolomics

Yang Qi deficiency H22 tumor-bearing Pan et al [62] Genomics

ZHENG types were identified by three chief or deputy physi-cians according to ldquoevaluation criteria of the clinical diag-nosis drug efficacy and ZHENG classification for cirrhosis(pilot program)rdquo [70] This classification was then verified bymetabonomics (Figure 1)

Furthermore there was a significant difference in meta-bolites between CG and two ZHENGs which were selectedby OPLS loading plot analysis The differentiated metabolitescombined with classic symptoms and feelings (bitter tastehypochondriac pain slimy fur of tongue and yellow fur oftongue in LGDHS while drymouth lack of strength withoutfur of tongue and red tongue in LKYDS) were chosen as thepotential markers for each ZHENG The reversions of thesemetabolites and hierarchical corresponding symptoms wereused as indicators of the therapeutic effect of FZHY tabletsand found that FZHY tablets are more effective for LKYDSthan for LGDHS which coincides with the treatment prin-ciples of TCM (Figure 2) This section relates to theFZHY study only Further details are provided in the Supple-mentary Methods available online at httpdxdoiorg1011552013235969

Because every ldquo-Omicsrdquo has the similar features in Sys-temsBiology as holistic aspects noninvasive integritymulti-target high-throughput and digitalization the similarthought could be applied to other ldquo-Omicsrdquo It is to say thatgene sequences or proteins could be combined with clinicalinformation to provide the NET-Marker of the specialZHENG Thus our initial exploration provided strong evi-dence of the feasibility and robustness of ZHENG-Omicseven though we did not obtain a full validation

5 Discussion and Prospect

The outcome of our exploration is inspiriting us to assessthe curative effect based on ZCT by ZHENG-omics that

10

5

0

minus5

minus10

minus20 minus10 0 10 20

119905[2]

119905[1]

Figure 1 PLS-DA score plots between healthy subjects and Hep-atitis B caused Cirrhosis subjects Black dots Red boxes blue tri-angles refer to healthy subjects Liver-Gallbladder Dampness-HeatSyndrome and Liver-Kidney Yin Deficiency Syndrome of HepatitisB caused Cirrhosis subjects respectively

combines omic data with clinical symptoms and feelings Wehope this approach will narrow the gap between mainstreammedicine and TCM

Compared with pharmaco-omics [1] and other ldquo-OmicsrdquoZHENG-omics may show some promise as a new methodhaving distinct advantages First of all ZHENG-omics maygive the guide to pharmaco-omic performance with the cli-nical experience of 3000 years based on ZCT though lackingenough evident ascertainments The ZHENG classificationmay guide patient classification of predose phenotype andprescribe drugs according to the phenotype FurthermoreZHENG-Omics could provide the profound connotation ofthe disease which consists of not only genetic and environ-mental factors but also emotional and spiritual factors Thisnotion resembles the new treatment concept of modernmedicine that a treatment should not only relieve symptomsbut should also take care of the mental health of a patient In


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115

225

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ate

Vani

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Paro

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Pipe

rona

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edio

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Hyp

ocho

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c pai

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tter t

aste

Slim

y fu

r of t

ongu

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llow

fur o

f ton

gue

22998400-B

ithio

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(a)

005

115

225

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)-na

phth

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Acet

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Acet

ic ac

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deBe

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hol

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Vani

llin

Ethy

lben

zene

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spar

tic ac

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rolin

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alin

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glyc

ine e

thyl

este

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Hyd

roxy

prop

ioph

enon

ePh

enol

Pipe

rona

lPr

opan

edio

ic ac

idPy

ridin

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uino

line

Dry

mou

thLa

ck o

f stre

ngth

With

out f

ur o

f ton

gue

Red

tong

ue

dl-T

rypt

opha

n

(b)

10

5

0

()

minus5

minus10

minus15

minus20

minus25

minus30

minus35

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)-na

phth

alen

one

2-M

ethy

lant

hran

ilic a

cid

Acet

ic ac

idBe

nzoi

c aci

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Citr

ate

Vani

llin

Gly

cine

l-Pro

line

l-Val

ine

N-B

enzo

ylgl

ycin

e eth

yl es

ter

Paro

xypr

opio

nePh

enol

Pipe

rona

lPr

opan

edio

ic ac

idPy

ridin

eQ

uino

line

Hyp

ocho

ndria

c pai

nBi

tter t

aste

Slim

y fu

r of t

ongu

eYe

llow

fur o

f ton

gue

22998400-B

ithio

phen

e

dl-T

rypt

opha

n

(c)

0102030405060

1(2H

)-na

phth

alen

one

14-

Buta

nedi

oic a

cid

4-Fl

uoro

benz

oic a

cid

5-M

ethy

lant

hran

ilic a

cid

Acet

ate

Acet

ic ac

idBe

nzal

dehy

deBe

nzen

amin

eBe

nzen

emet

hana

min

eBe

nzyl

alco

hol

Buta

nedi

oic a

cid

dl-T

rypt

opha

nVa

nilli

nEt

hylb

enze

neL-

Asp

artic

acid

l-Pro

line

l-Val

ine

N-B

enzo

ylgl

ycin

e eth

yl es

ter

o-H

ydro

xypr

opio

phen

one

Phen

olPi

pero

nal

Prop

aned

ioic

acid

Pyrid

ine

Qui

nolin

eD

ry m

outh

Lack

of s

treng

thW

ithou

t fur

of t

ongu

eRe

d to

ngue

()

minus10

(d)

Figure 2 The reversion maps reveal the therapeutic effects of two TCM ZHENG types in hepatitis-B-caused cirrhosis (a) and (b)Histogramof the therapeutic effects of FZHYTablet for liver-gallbladder dampness-heat syndrome and liver-kidney Yin deficiency syndromerespectively by the changing trend of significantly differential metabolites and classic symptoms Blue red and green bars stand for controlgroup before intervention and 12-week intervention of FZHY tablet The 119909-axis represents the changed metabolites and symptoms and the119910-axis is fold change of mean ranks calculated by the Mann-Whitney test compared with the control group (c) and (d) Curve diagram ofregression trend of significantly differential metabolites and classic symptoms in liver-gallbladder dampness-heat syndrome and liver-kidneyYin deficiency syndrome respectively for 12-week intervention of FZHY tabletThe 119909-axis represents the changedmetabolites and symptomsand the 119910-axis is the rate of reversion representing the therapeutic effect of FZHY tablet for different ZHENGs

this respect ZHENG-omics may provide some new revela-tions for personalized medicine

However every coin has two sides so as to currentldquoOmicsrdquo Every ldquoOmicrdquo has the advantages and disadvantages(Table 3) If using only one ldquoOmicsrdquo for study of ZHENG theshortcomings such as deficiency of cross-reference and scien-tific discrimination overloading information and excessivesimplification will show up On the other side one can carryout ZHENG-omics at different levels in multiple researchcenters Such research can find those specific and meaning-ful markers distinguishing primary factors from secondaryfactors With the multidimensional studies of DNA proteinsand metabolites the variability integrity and complexity ofTCM ZHENGs will be annotated commendably and can beused as basis for understanding and differentiating them Fur-thermore we should combine microscopic omic data with

macroscopic symptomswith themethods such as associationrules [71] and bioinformatics [72] Yet for ZHENG-omicsstudy one should pay special attention to the followingaspects

First of all careful screening and data collection of sam-ples from patients with the most classic ZHENGs are neces-sary Before this can be initialized the patients with classicZHENG should be targeted according to the most typicalsyndromes getting out from literature retrieval and datamining of a lot of clinical cases [73 74] Patient samples fora special ZHENG can be found based on these typical symp-tomsThemore samples that are collected themore precisionwill be developed to the essence of ZHENG leading to moreaccurate and objective classification

Second the existing strategy should be refined Since oneZHENG (one syndrome) can change to another ZHENG


Black boxZHENG-

omicsOmics datasymptoms BioinformaticsSufficient

classic samples

On the basis of holism and

dynamic

Integration of

information

TCM(ZHENG)Network

studyand so on

17501500125010007505002500

Cnt

4 6 8 150 300 450 600 750119898119911

Figure 3 Schematic diagram of research approach for ZHENG-omics Traditional Chinese medicine is mysterious and obscure like a fuzzypicture It is difficult to obtain systematic knowledge from the whole directly yet the partial information is much easier to be acquired andunderstood such as nucleic acids proteins and metabolites Combined with classic symptoms and feelings the former could be obtainedby ZHENG-omics from sufficient classic samples on the basis of holism The integration of omic data and symptoms will be performed bybioinformatics and so on which further provide the multilevel information like small lights in the big black box Then a vivid picture mayemerge in our sights just like getting the systematic connotation of TCM or ZHENG

Table 3 Brief introduction of ldquo-omicsrdquo and bioinformatics

Omics Advantages Disadvantages Literatures

Genomics(transcriptomics)

Gene polymorphismSusceptibility for prognosis and treatmentCompleted databaseHigh throughput

Nonassociation to regulation oflife activitiesNonconsistent strictly withmRNA expression

Wu et al [11]Lu et al [63]

Proteomics Performer of life function InstabilityVariability

Liu et al [64]Lu et al [65]

Metabonomics

Amplified actionSimplicity to detectLess numbersSimilarities in different species

Lack of beneficial supportsInterferences by physiologicalfactors

van Wietmarschen et al [66]Sun et al [67]Liu et al [31]

BioinformaticsTotally holismExploration the potential of informationFocusing on function relation

Needing of self-development Li et al [18]

dynamically the current static study cannot meet the needsof deep research and clinical application Luckily ZHENG-omics provides a high-throughput and noninvasive clinicalresearch tool and enables study on the dynamical ZHENGclassification in an extending period Particularly we advo-cate that initiative and passive intervention could be used tostudy development and dynamic Classification of ZHNEGwith the help of tracer techniques such as fluorescencelabeling Nowadays most attention is paid to preliminaryintervention by inducers [1 21] and environmental factors[75] while purposeful further continuous intervention willprovide deeper vision into the regularity of ZHENG classifi-cation

Since ZHENGs are frequently considered as phenotypesof a disease researchers are mostly focused on the differentZHENGs of the same disease However we should pay moreattention to the formerly mentioned phenomenon that the

same syndrome appears in different diseases This part willbring another look to old drugs as treatments for otherdiseases

6 Conclusion

Just like a blindfold boy will feel an elephant snake treewall and rope would be in his mind when he touched thesquirming trunk grossus knee broad body and swinging tailrespectively He may perceive the whole elephant from com-bination of these incomplete parts Huge and metaphysicalTCM especially ZHENG is corresponding to the elephantwhile ZHENG-omicswill provide themultilevel informationjust like omic data and symptoms compared to tusk kneeand tail It is important to note that dynamic and interventionwill also paint a vivid picture (Figure 3) Under the strategy of


ldquoblack box-partial system-whole systemrdquo the connotation ofsystematic TCM will emerge in our sights

Furthermore the ZHENG-omics possesses and inte-grates the characteristics of both ZHENG and systems biol-ogy andmay advance TCM to a new level It would overcomethe shortcomings of current methods for evaluating per-sonal diagnosis complex intervention and patientsrsquo feelingsThrough ZHENG-omic study personal medicine in TCMmay emerge eventually and may change the current medicalsystem We believe that the advantage of TCM in theory andexperience will overcome the limitations of current personalmedicine and contribute to the overall world healthcare

Data Bases

Elsevier Science httpwwwsciencedirectcom CNKIhttpwwwcnkinet Traditional Chinese Medicine |Syndrome | Pattern | Zheng | Systems Biology | Genomics |Transcriptomics | Proteomics |Metabolomics

Conflict of Interests

The authors declared that they have no conflicts of interest tothis work And they did not have a direct financial relationwith the commercial identity mentioned in this paper

Authorsrsquo Contribution

J Dai J Fang S Sun and Q Chen contributed equally to thiswork and should be considered co-first authors

Acknowledgments

This work was supported by the Shanghai InterdisciplinaryCultivation Platform of Outstanding and Innovative Post-graduates National Science and Technology Major Project(2012ZX10005001-004) and Shanghai ldquo085rdquo Science andTechnology Innovation Supporting Project for Top-GradeDiscipline Construction

References

[1] T A Clayton J C Lindon O Cloarec et al ldquoPharmaco-metabonomic phenotyping and personalized drug treatmentrdquoNature vol 440 no 7087 pp 1073ndash1077 2006

[2] Huangdirsquos Internal Classic[3] J L Tang B Y Liu and K W Ma ldquoTraditional Chinese

medicinerdquoThe Lancet vol 372 no 9654 pp 1938ndash1940 2008[4] Y T He A P Lu Y L Zha and I Tsang ldquoDifferential effect

on symptoms treated with traditional Chinese medicine andWestern combination therapy in RA patientsrdquo ComplementaryTherapies in Medicine vol 16 no 4 pp 206ndash211 2008

[5] C Lu Q I Zha A I Chang Y T He and A P LuldquoPattern differentiation in traditional chinese medicine canhelp define specific indications for biomedical therapy in thetreatment of rheumatoid arthritisrdquo Journal of Alternative andComplementary Medicine vol 15 no 9 pp 1021ndash1025 2009

[6] M A Hamburg and F S Collins ldquoThe path to personalizedmedicinerdquo The New England Journal of Medicine vol 363 no4 pp 301ndash304 2011

[7] J L YuanH Zhang LWang et al ldquoBiochemical characteristicsof traditional Chinese medicine syndromes and their elementsin patients with hepatitis B cirrhosisrdquo Journal of ChineseIntegrative Medicine vol 9 no 4 pp 374ndash381 2011

[8] Y Q Xie H Wang Y P Wu D H Yin Z S Wang and YH Huang ldquoAssociation of APOE polymorphisms and insulinresistance with TCM syndromes in type 2 diabetes patients withmacroangiopathyrdquoMolecular Medicine Reports vol 4 no 6 pp1219ndash1223 2011

[9] X Q Yue andQ Liu ldquoAnalysis of studies on pattern recognitionof tongue image in traditional Chinese medicine by computertechnologyrdquo Journal of Chinese Integrative Medicine vol 2 no5 pp 326ndash329 2004

[10] B Pang D Zhang N Li and K Wang ldquoComputerized tonguediagnosis based on Bayesian networksrdquo IEEE Transactions onBiomedical Engineering vol 51 pp 1803ndash1810 2004

[11] Y Wu Y Cun J Dong et al ldquoPolymorphisms in PPARDPPARGandAPM1 associatedwith four types of traditional Chi-nese medicine constitutionsrdquo Journal of Genetics and Genomicsvol 37 no 6 pp 371ndash379 2010

[12] H M Ni Y P Wu and Y M He ldquoDifferential expressiongenes in teenagers with kidney-Yang sthenia constitution bygenechiptechniquerdquoActa Univ Tradit Med Sin Pharm Shanghaivol 38 pp 3ndash5 2004 (Chinese)

[13] Y Feng Z H Wu X Z Zhou Z M Zhou and W Y FanldquoKnowledge discovery in traditional Chinese medicine state ofthe art and perspectivesrdquo Artificial Intelligence in Medicine vol38 no 3 pp 219ndash236 2006

[14] X C Liu H Liang Z Tian Y Chen and L Zhang ldquoCompar-ative proteomic analysis of human kidney-Yang deficiency syn-drome serumrdquo Chinese Journal of Biochemistry and MolecularBiology vol 23 no 7 pp 592ndash599 2007 (Chinese)

[15] L H Tang X D Wo D Z Lu M R Shi Y Li and LK Wo ldquoEffects of warm and tonify kidney-Yang herbs onliver mitochondria proteome of kidney-Yang deficiency ratsrdquoChinese Pharmaceutical Journal vol 42 no 3 pp 169ndash175 2007

[16] P Wang H Sun H T Lv et al ldquoThyroxine and reserpine-induced changes in metabolic profiles of rat urine and thetherapeutic effect of LiuWei Di HuangWan detected by UPLC-HDMSrdquo Journal of Pharmaceutical and Biomedical Analysis vol53 no 3 pp 631ndash645 2010

[17] X M Lu Z L Xiong J L Li S N Zheng T G Huo andF M Li ldquoMetabonomic study on ldquoKidney-Yang deficiencysyndromerdquo and intervention effects of Rhizoma Drynariaeextracts in rats using ultra performance liquid chromatographycoupled with mass spectrometryrdquo Talanta vol 83 no 3 pp700ndash708 2011

[18] S Li Z Q Zhang L JWu X G Zhang Y D Li andY YWangldquoUnderstanding Zheng in traditional Chinese medicine in thecontext of neuro-endocrine-immune networkrdquo IET SystemsBiology vol 1 no 1 pp 51ndash60 2007

[19] T Ma C G Tan H Zhang M Q Wang W J Ding and S LildquoBridging the gap between traditional Chinese medicine andsystems biology the connection of Cold syndrome and NEInetworkrdquoMolecular BioSystems vol 6 no 4 pp 613ndash619 2010

[20] S J Sun J Y DaiW YWang et al ldquoMetabonomic evaluation ofZHENG differentiation and treatment by Fuzhenghuayu tablet


in hepatitis-B-caused cirrhosisrdquo Evidence-Based Complemen-tary and Alternative Medicine vol 2012 Article ID 453503 8pages 2012

[21] M Chen L Zhao and W Jia ldquoMetabonomics study onthe biochemical profiles of a hydrocortisone-induced animalrdquoJournal of Proteome Research vol 4 no 6 pp 2391ndash2396 2005

[22] Y G Chu J Shi and Y H Hu ldquoSerum proteomic study onhypertension patients with Gan-Dan damp-heat syndromerdquoChinese Journal of Integrative Medicine vol 30 no 1 pp 37ndash412010

[23] Z Z Guo S H Yu Y Guan et al ldquoMolecular mechanismsof same TCM syndrome for different diseases and differentTCM syndrome for same disease in chronic hepatitis B andliver cirrhosisrdquo Evidence-Based Complementary and AlternativeMedicine vol 2012 Article ID 120350 9 pages 2012

[24] N J Zeng Q H Liang X G Xiong et al ldquoProteomicsanalysis and identification on a peripheral blood lymphocyteof Ganyang Huafeng syndrome of cerebral infarctionrdquo ChineseJournal of Information on Traditional Chinese Medicine vol 15no 4 pp 11ndash15 2008 (Chinese)

[25] Q X Tan Z P Lu X L Zhong and X G Zhang ldquoPreliminarystudy on change of serum proteome in liver stagnation syn-dromerdquo Liaoning Journal of Traditional Chinese Medicine vol33 pp 157ndash158 2006 (Chinese)

[26] C Lu C Xiao L H Zhao et al ldquoComparison of gene profileof peripheral CD4+ lymphocytes in rheumatoid arthritis withcold and heat syndromerdquo Chinese Journal of Basic Medicine inTraditional Chinese Medicine vol 12 no 2 pp 130ndash133 2006(Chinese)

[27] Y Q Wang L P Yang W J Ding H Gao and Q G WangldquoA report on 15 differential expression genes found in a cold-syndrome genealogyrdquo Journal of Traditional Chinese Medicinevol 47 pp 131ndash133 2006

[28] Y Gu C Lu Q L Cha et al ldquoPlasma metabonomics studyof rheumatoid arthritis and its Chinese medicine subtypes byusing liquid chromatography and gas chromatography coupledwith mass spectrometryrdquo Molecular Systems Biology vol 8 no5 pp 1535ndash1543 2012

[29] C B Yang J Xue P S Yin J S Zuo and K C Xu ldquoExpressionof blc-2 gene in spleen deficiency syndrome in colorectalcarcinoma and the regulatory effect of Jianpikangfu decoctionrdquoAcademic Journal of FirstMilitaryMedical University vol 25 pp1268ndash1269 2005 (Chinese)

[30] Z M Yang W W Chen and Y F Wang ldquoStudy on genedifferential expressions of substance and energy metabolism inchronic superficial gastritis patients of Pi deficiency syndromeand of Pi-Wei hygroyrexia syndromerdquo Chinese Journal of Inte-grative Medicine vol 32 no 9 pp 1180ndash1187 2012

[31] P Liu Y Y Zhang and J Qiao ldquoEstablishment and analy-sis of serum two-dimensional gel electrophoresis profiles ofmyasthenia gravis patients with spleen and kidney deficiencysyndromerdquo Journal of Chinese Integrative Medicine vol 5 no 2pp 150ndash154 2007

[32] L Weng J Du W T He and C Q Ling ldquoCharacteristicgenomics of peripheral blood mononuclear cells of hepato-cellular carcinoma patients with liver-kidney yin deficiencysyndromerdquo Chinese Journal of Integrative Medicine vol 10 no4 pp 406ndash415 2012

[33] H S Zheng J Jiang W Jia et al ldquoResearch on metabolomicsin chronic heart failure with kidney-Yang deficiencyrdquo ChinaJournal of Traditional Chinese Medicine and Pharmacy vol 25no 2 pp 198ndash201 2010 (Chinese)

[34] Y GuanH ZhangW Zhang and S B Su ldquoAnalysis of differen-tial gene expression profile in peripheral blood of patients withchronic hepatitis B and syndromes of dual deficiency of liverand kidney yin and accumulation of dampness heatrdquo ChineseJournal of Integrative Medicine vol 10 no 7 pp 751ndash756 2012

[35] Y Q Wang F F Li W J Wang L Y Zhao L Guo and HF Wang ldquoSerum proteomics study of chronic gastritis withdampness syndrome in traditional Chinese medicinerdquo Journalof Chinese Integrative Medicine vol 5 no 5 pp 514ndash516 2007

[36] Q Wang H Y Xi and J H Gao ldquoStudy on characteristics ofperipheral blood gene expression profile in the obesity withphlegm-dampness constitutionrdquo Journal of Traditional ChineseMedicine vol 47 pp 851ndash858 2006

[37] X J Ma H J Yin and K J Chen ldquoDifferential gene expressionprofiles in coronary heart disease patients of blood stasissyndrome in traditional Chinese medicine and clinical role oftarget generdquo Chinese Journal of Integrative Medicine vol 15 no2 pp 101ndash106 2009

[38] Z K Yuan X P Huang G B Tan et al ldquoDetective analysison polymorphism of apolipoprotein E gene in blood-stasis syn-drome of coronary heart diseaserdquo Journal of Beijing University ofTraditional Chinese Medicine vol 31 no 12 pp 830ndash834 2008(Chinese)

[39] Z K Yuan L P Wang and X P Huang ldquoThe screening andthe functional pathway analysis of differential genes correlatedwith coronary heart disease of blood stasis syndromerdquo ChineseJournal of Integrative Medicine vol 32 no 10 pp 1313ndash13182012

[40] H J Wu Z C Ma Y Gao and S Q Wang ldquoStudy onGAP in blood-stasis type of coronary heart disease by usingproteomic techniquerdquo Chinese Journal of Integrative Medicineon CardioCerebrovascular Disease vol 3 pp 189ndash191 2005(Chinese)

[41] J Wang Z F Li H H Zhao et al ldquoCharacteristics of urinemetabonomics in patients with blood stasis syndrome of CHNunstable anginardquo Journal of Beijing University of TraditionalChinese Medicine vol 35 no 4 pp 284ndash288 2012

[42] Q Y Li Z Z Guo J Liang et al ldquoInterleukin-10 genotypecorrelated to deficiency syndrome in hepatitis B cirrhosisrdquoEvidence-Based Complementary and Alternative Medicine vol2012 Article ID 298925 6 pages 2012

[43] Y N Song H Zhang Y Guan et al ldquoClassification of tradi-tional Chinese medicine syndromes in patients with chronichepatitis B by SELDI-based proteinchip analysisrdquo Based Com-plementary and Alternative Medicine vol 2012 Article ID626320 10 pages 2012

[44] QW Chen X Q Huang G J Yang et al ldquoPreliminary study ofserum metabonomics on Yang deficiency syndrome of patientswith primary liver cancerrdquo Chin Arch Tradit Chin Med vol 30no 3 pp 526ndash529 2012

[45] T Wu M Yang H F Wei S H He S C Wang and G JildquoApplication of metabolomics in traditional Chinese medicinedifferentiation of deficiency and excess syndromes in patientswith diabetes mellitusrdquo Evidence-Based Complementary andAlternativeMedicine vol 2012 Article ID968083 11 pages 2012

[46] C H Yang J M Lin and J Xie ldquoStudy on the metabolicdifference of hypertension patients of Gan-Yang hyperactivitysyndrome and Yin-Yang deficiency syndromerdquo Chinese Journalof Integrative Medicine vol 32 no 9 pp 1204ndash1207 2012

[47] L Weng J Du W T He and C Q Ling ldquoCharacteristicgenomics of peripheral blood monouclear cells of hepato-cellular carcinoma patients with liver-kidney yin deficiency


syndromerdquo Chinese Journal of Integrative Medicine vol 10 no4 pp 406ndash415 2012

[48] H Q Jiang Y L Li and J Xie ldquoUrine metabonomic studyon hypertension patients of ascendant hyperactivity of GanYang syndrome by high performance liquid chromatographycoupled with time of flight mass spectrometryrdquo Chinese Journalof Integrative Medicine vol 32 no 3 pp 333ndash337 2012

[49] J J Hu Z Q Chen G W Zhong W Li and T H YinldquoComparative proteomics analysis on splenic lymphocytes inmigraine rat model with hyperactivity of liver-yangrdquo ChineseJournal of Information on Traditional Chinese Medicine vol 15pp 34ndash37 2008 (Chinese)

[50] G W Zhong J Hu Z Chen et al ldquoEffect of the formulaefor calming the liver and suppressing YANG on lymphocyteproteome in migraine rats with syndrome of hyperactivityof liver-YANGrdquo Journal of Central South University (MedicalSciences) vol 35 no 1 pp 70ndash76 2010 (Chinese)

[51] L Y Zhou Z Q Chen and W Li ldquoObservation of differentialprotein of hypothalamus in the hyperthyroidlsm rats withhyperactivity of liver-yangrdquo Chinese Journal of Information onTraditional Chinese Medicine vol 14 pp 18ndash20 2007

[52] X Zhang X Zeng X J Duan and R M Ou ldquoReproductionof a rat model of liver-yang hyperactivity syndrome withessential hypertension and analysis of protein expression inliverrdquo Sichuan Journal of Traditional Chinese Medicine vol 26pp 9ndash11 2008

[53] X L Zhong Z P Lu L J Qian X H Liu Q X Tan andX G Zhang ldquoDifferential expression of serum proteome onstagnation on liver-Qi syndrome model ratsrdquo China Journal ofTraditional Chinese Medicine and Pharmacy vol 21 no 5 pp399ndash401 2006

[54] SWang S J Zou X Y Chen andW J Gang ldquoPrimary study onchanges of gene expression profile in hippocampl of reserpineanimal models with spleen-astheniardquo Mod J Integr Tradit ChinWest Med vol 13 pp 841ndash844 2004

[55] H G Luo J Ding G X Yue and J X Chen ldquoMetabonomicstudy of syndrome of liver Qi stagnation and spleen deficiencyin ratsrdquo Journal of Chinese Integrative Medicine vol 5 pp 307ndash313 2007

[56] Z Y Shen Y Chen J H Huang and Z W Hu ldquoThegene expression profile in hypothalamus-pituitary-adrenal-thymus(HPAT) axis from EF-treated old ratsrdquo Chinese Journalof Immunology vol 20 pp 59ndash62 2004 (Chinese)

[57] M J Chen L P Zhao and W Jia ldquoMetabonomic study onthe biochemical profiles of a hydrocortisone-induced animalmodelrdquo Journal of Proteome Research vol 4 no 6 pp 2391ndash2396 2005

[58] J X Liu LMiao X Z Li andYH Pan ldquoProteomics research ofserum of Chinese experimental mini-pig model with syndromeof phlegm and blood stasis of coronaryrdquo Pharmacology andClinics of Chinese Materia Medica vol 26 pp 73ndash76 2010

[59] L Tong SH Chen Z CMa J Huang YDing and SQWangldquoAccessing gene expression profile of blood deficiency miceusing hematopoietic-ralated cytokine oligonucleotide microar-raysrdquo Chinese Traditional and Herbal Drugs vol 34 no 7 pp625ndash629 2003 (Chinese)

[60] W X Jian Z K Yuan and X P Huang ldquoDetection andanalysis on plasmametabolomics in patient with coronary heartdisease of xin-blood stasis syndrome patternrdquo Chinese Journalof Integrative Medicine vol 30 pp 579ndash584 2010

[61] Y Wang Z F Li J X Chen et al ldquoStudy of mini-pig serumof coronary heart disease (chronic myocardial ischemia) with

syndrome of blood stasis based on nuclearrdquo Chinese Journalof Analytical Chemistry vol 39 no 8 pp 1274ndash1278 2011(Chinese)

[62] Z Q Pan Z Q Fang W L Lu et al ldquoDifference of geneexpression in adrenal gland of H22 tumor mice of Yang-Qideficiency syndrome and Qi-Yin-Yang deficiency syndromerdquoActa Univ Tradit Med Sin Pharm Shanghai vol 22 no 3 pp45ndash50 2008 (Chinese)

[63] C Lu C Xiao G Chen et al ldquoCold and heat pattern ofrheumatoid arthritis in traditional Chinese medicine distinctmolecular signatures indentified by microarray expression pro-files in CD4-positive T cellrdquo Rheumatology International vol32 no 1 pp 61ndash68 2012

[64] Y Liu P Liu R Dai et al ldquoAnalysis of plasma proteome fromcases of the different traditional Chinese medicine syndromesin patients with chronic hepatitis Brdquo Journal of Pharmaceuticaland Biomedical Analysis vol 59 pp 173ndash178 2012

[65] C L Lu X Y Qu and J G Jiang ldquoProteomics and syndrome ofChinese medicinerdquo Journal of Cellular and Molecular Medicinevol 14 no 12 pp 2721ndash2728 2010

[66] H van Wietmarschen K Yuan C Lu et al ldquoSystems biologyguided byChinesemedicine reveals newmarkers for sub-typingrheumatoid arthritis patientsrdquo Journal of Clinical Rheumatologyvol 15 no 7 pp 330ndash337 2009

[67] P Sun G A Luo M Q Qiao et al ldquoStudies on the metabo-nomics of premenstrual syndrome liver-Qi invasion patientinterfered by Jingqianping granulesrdquoWorld Science andTechnol-ogyModernization of Traditional ChineseMedicine andMateriaMedica vol 12 no 2 pp 195ndash201 2010

[68] Y Qiu M Su Y Liu et al ldquoApplication of ethyl chlorofor-mate derivatization for gas chromatography-mass spectrometrybasedmetabonomic profilingrdquoAnalyticaChimicaActa vol 583no 2 pp 277ndash283 2007

[69] Chinese Society of Hepatology and Chinese Medical Associa-tion ldquoThe guidelines of prevention and treatment for chronichepatitis Brdquo Chinese Journal of Hepatology vol 13 pp 881ndash8912005 (Chinese)

[70] Y X Zhang and B H Wei ldquoEvaluation criteria of the clinicaldiagnosis drug efficacy and TCM syndrome differentiationfor cirrhosis (pilot program)rdquo Chinese Journal of IntegrativeMedicine vol 14 pp 237ndash238 1994 (Chinese)

[71] J F Boulicaut F Esposito F Giannotti and D Pedreschi EdsProceedings of the 8th European Conference on Principles andPractice of Knowledge Discovery in Databases Springer BerlinGermany 2004

[72] S Li ldquoComputational Systems Biology-based TCM Research acase study of coldheat zheng and associated formulardquo WorldScience and TechnologyModernization of Traditional ChineseMedicine and Materia Medica vol 9 no 1 pp 105ndash111 2007

[73] H L Wu X M Ruan and W J Luo ldquoCluster analysis onTCM syndromes in 319 coronary artery disease patients forestablishment of syndrome diagnostic figurerdquo Chinese Journalof Integrative Medicine vol 27 pp 616ndash618 2007

[74] C T Shen H Q Zhang andXH Zhu ldquoInvestigation and anal-ysis on diagnostic standard for TCM syndrome differentiationin 400 patients with climacteric syndromerdquo Chinese Journal ofIntegrative Medicine vol 24 pp 517ndash520 2004

[75] W H Liu X Z Yan L Zhang Q Zhang L H Wang and F HYu ldquoMetabonomics study on phlegm and blood stasis evolutionof hyperlipidemia and atherosclerosisrdquo Liaoning Journal ofTraditional Chinese Medicine vol 49 no 5 pp 738ndash741 2008(Chinese)

Submit your manuscripts athttpwwwhindawicom

Stem CellsInternational

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014


MEDIATORSINFLAMMATION

of


Behavioural Neurology

EndocrinologyInternational Journal of



Disease Markers


BioMed Research International

OncologyJournal of



Oxidative Medicine and Cellular Longevity


PPAR Research

The Scientific World JournalHindawi Publishing Corporation httpwwwhindawicom Volume 2014

Immunology ResearchHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Journal of

ObesityJournal of



Computational and Mathematical Methods in Medicine

OphthalmologyJournal of


Diabetes ResearchJournal of



Research and TreatmentAIDS


Gastroenterology Research and Practice


Parkinsonrsquos Disease

Evidence-Based Complementary and Alternative Medicine

Volume 2014Hindawi Publishing Corporationhttpwwwhindawicom


cannot generalize the entire state of the body However withthe advent of the era of systems biology a broader technologyplatform was established for the study of TCM The omictechnologies provide integral systemic and dynamic tech-nology platforms and lay the foundation for the systemicstudy at a higher level The system point of view provides uswith an important idea to sweep aside the fog of mysteriousTCMandmay be a breakthrough point of incorporating East-ern medicine with Western medicine Though the researchesbased on system biology have had great progresses recentlythere is a little flaw of ignoring patientsrsquo feelings in the onlyomic data

So through existing researches of system biology applica-tion in ZCT we would like to propose further a new macro-microconcept namely ldquoZHENG-Omicsrdquo which is defined asldquoa systematic approach for targeting individual patient guid-ing treatment and predicting the outcome of personalizedtreatment by global NET-Markers (combination of genesproteins metabolites symptoms and others based on themathematicalmodel) on the basis of ZCTrdquo In this paper aftercomprehensive reviewed recent researches we will graduallyshow you brief introduction and preliminary validationand discuss strategies and system-oriented technologies forachieving the goal of providing an objective and repeatableapproach for Chinese personalized medicine in an effectiveway

2 Research Status of System BiologyApplication in ZCT

TCM researchers have attempted some beneficial works Re-search in the area of Yin-Yang sets a good example Yin-Yang (two opposite complementary interdependent and ex-changeable aspects of nature) the general principles in eightare used to categorize natural phenomena which helped usunderstand prevent and cure disease The classification ofYin-Yang usually is the first step in the ZHENG classificationSystems biology was proved to be a useful tool for the studyof Yin-Yang although the concept of Yin-Yang is abstractmysterious and obscure So far the most researches of Yin-Yang syndrome are concentrated on Yin-deficiency syn-drome andYang-deficiency syndrome Genomic informationshowed that Yang-deficiency patients had significant differ-ence in Haplotype 25 (Hap25) of APM1 rs7627128 rs1063539PSMB7 and CXCR4 compared to control group howeverHaplotype13 of PPARG in Yin-deficiency patients [11 12]At the proteomic level it was found that CRP CRH IL10ACE PTH MPO CRH PTH PRL BRCA1 BRCA2 [13]transthyretin plasma retinol-binding protein precursor andchain A-prealbumin [14] liver protein and protein of thelivermitochondria [15] levels correlatedwith Yang-deficiencysyndrome It is especially worth noting that metabonomics iswidely and deeply utilized in Yin-Yang classification Wanget al [16] and Lu et al [17] have respectively found differentmetabolites between Kidney-Yin and Kidney-Yang defi-ciency syndrome which are estrone creatinine uric acidindoxyl sulfate and so on demonstrating the notable differ-ences of these two ZHENGs From these previous researches

we realized that it is possible to establish a group of prelimi-nary global net-markers to identify the Yin-Yang deficiencysyndrome Though there has been no research on Net-Markers of Yin-Yang syndrome the combination of networkbiology and Bioinformatics has been used by Li et al toinvestigate novel biomarkers for cold-heat syndrome whichpartly represents the Yin-Yang syndrome in TCM [18 19]

However ZHENG classification is not the ultimate goalbut a progression towards treatment and curing of diseasesUnfortunately current evaluation methods are conductedignoring theories of TCM and are unable to bring this tradi-tional medicine which has been validated in clinical practiceto light This may cripple public confidence in the effective-ness of TCM To counter this an objective method on thebasis of holistic TCM must be developed What is gratify-ing systems biology especially metabonomics has shownpromising application prospect in its practice For exampleit was demonstrated in our previous experiment that if dif-ferent ZHENGs of hepatitis-B-caused cirrhosis patients weretreated by the same therapy they would show various res-ponses [20] Similar research has been performed by Chenet al [21] to study the biochemical profiles of hydrocortisone-induced animal models which evaluated the effectiveness ofHerba Cistanches Deserticolae that is formulated to warm andreinforce kidney Yang to intervene Kidney-Yang deficiencyrats A good correlation between the chemical profile and theprogress of treatment was observed In addition to this studyWang et al [16] and Lu et al [17] evaluated the effectivenessof Liuwei Dihuang Pill and Rhizoma Drynariae respectivelyin Kidney-Yin and Kidney-Yang syndromes and satisfactoryresults were obtained as well

Due to space limitation and insufficient research otherresearch has not been touched upon To systematically noteZHENG research as being performed presently clinical andexperimental studies have been summarized in Tables 1 and2 with respect to the combination of ZHENG in TCM anddisease in western medicine

3 Brief Introduction ofthe Origin of lsquolsquoZHENG-Omicsrsquorsquo

Our thought is not groundless but derived from formerresearches althoughmost of whichwere discrete andwithouta systemic and consistent research strategy ZHENG-Omics isnot simple combination of systems biology and ZCT Theirassociation could play bigger roles in helping mutually toremedy deficiencies One the systems biology research andphilosophy of TCM coincide in many ways They sharesimilar attributes in many aspects especially in a holisticapproach Two the strategy employing a dynamic noninva-sive approach is very important for the acquisition of long-term large-scale samples The thorough knowledge ofZHENGsrsquo connotation and intervention may evolve to adynamic classification approach Three a nontargeting con-cept may provide freedom for exploration of unknown classi-fications of disease states without being bound by the exist-ing methods familiar to Western medicine Finally digitalresults can be integrated for ZHENG classification through








































10

5

0

minus5

minus10


119905[2]

119905[1]





005

115

225

3

1(2H

)-na

phth

alen

one

2-M

ethy

lant

hran

ilic a

cid

Acet

ic ac

idBe

nzoi

c aci

ddl

-Try

ptop

han

Citr

ate

Vani

llin

Gly

cine

l-Pro

line

l-Val

ine

N-B

enzo

ylgl

ycin

e eth

yl es

ter

Paro

xypr

opio

nePh

enol

Pipe

rona

lPr

opan

edio

ic ac

idPy

ridin

eQ

uino

line

Hyp

ocho

ndria

c pai

nBi

tter t

aste

Slim

y fu

r of t

ongu

eYe

llow

fur o

f ton

gue

22998400-B

ithio

phen

e

(a)

005

115

225

3

1(2H

)-na

phth

alen

one

14-

Buta

nedi

oic a

cid

4-Fl

uoro

benz

oic a

cid

5-M

ethy

lant

hran

ilic a

cid

Acet

ate

Acet

ic ac

idBe

nzal

dehy

deBe

nzen

amin

eBe

nzen

emet

hana

min

eBe

nzyl

alco

hol

Buta

nedi

oic a

cid

Vani

llin

Ethy

lben

zene

L-A

spar

tic ac

idl-P

rolin

el-V

alin

eN

-Ben

zoyl

glyc

ine e

thyl

este

ro-

Hyd

roxy

prop

ioph

enon

ePh

enol

Pipe

rona

lPr

opan

edio

ic ac

idPy

ridin

eQ

uino

line

Dry

mou

thLa

ck o

f stre

ngth

With

out f

ur o

f ton

gue

Red

tong

ue

dl-T

rypt

opha

n

(b)

10

5

0

()

minus5

minus10

minus15

minus20

minus25

minus30

minus35

1(2H

)-na

phth

alen

one

2-M

ethy

lant

hran

ilic a

cid

Acet

ic ac

idBe

nzoi

c aci

d

Citr

ate

Vani

llin

Gly

cine

l-Pro

line

l-Val

ine

N-B

enzo

ylgl

ycin

e eth

yl es

ter

Paro

xypr

opio

nePh

enol

Pipe

rona

lPr

opan

edio

ic ac

idPy

ridin

eQ

uino

line

Hyp

ocho

ndria

c pai

nBi

tter t

aste

Slim

y fu

r of t

ongu

eYe

llow

fur o

f ton

gue

22998400-B

ithio

phen

e

dl-T

rypt

opha

n

(c)

0102030405060

1(2H

)-na

phth

alen

one

14-

Buta

nedi

oic a

cid

4-Fl

uoro

benz

oic a

cid

5-M

ethy

lant

hran

ilic a

cid

Acet

ate

Acet

ic ac

idBe

nzal

dehy

deBe

nzen

amin

eBe

nzen

emet

hana

min

eBe

nzyl

alco

hol

Buta

nedi

oic a

cid

dl-T

rypt

opha

nVa

nilli

nEt

hylb

enze

neL-

Asp

artic

acid

l-Pro

line

l-Val

ine

N-B

enzo

ylgl

ycin

e eth

yl es

ter

o-H

ydro

xypr

opio

phen

one

Phen

olPi

pero

nal

Prop

aned

ioic

acid

Pyrid

ine

Qui

nolin

eD

ry m

outh

Lack

of s

treng

thW

ithou

t fur

of t

ongu

eRe

d to

ngue

()

minus10

(d)








Black boxZHENG-


classic samples


dynamic

Integration of

information

TCM(ZHENG)Network

studyand so on

17501500125010007505002500

Cnt

4 6 8 150 300 450 600 750119898119911










Metabonomics









6 Conclusion





Data Bases






Acknowledgments


References






















































































of






Disease Markers



OncologyJournal of





PPAR Research



Journal of

ObesityJournal of























































10

5

0

minus5

minus10


119905[2]

119905[1]





005

115

225

3

1(2H

)-na

phth

alen

one

2-M

ethy

lant

hran

ilic a

cid

Acet

ic ac

idBe

nzoi

c aci

ddl

-Try

ptop

han

Citr

ate

Vani

llin

Gly

cine

l-Pro

line

l-Val

ine

N-B

enzo

ylgl

ycin

e eth

yl es

ter

Paro

xypr

opio

nePh

enol

Pipe

rona

lPr

opan

edio

ic ac

idPy

ridin

eQ

uino

line

Hyp

ocho

ndria

c pai

nBi

tter t

aste

Slim

y fu

r of t

ongu

eYe

llow

fur o

f ton

gue

22998400-B

ithio

phen

e

(a)

005

115

225

3

1(2H

)-na

phth

alen

one

14-

Buta

nedi

oic a

cid

4-Fl

uoro

benz

oic a

cid

5-M

ethy

lant

hran

ilic a

cid

Acet

ate

Acet

ic ac

idBe

nzal

dehy

deBe

nzen

amin

eBe

nzen

emet

hana

min

eBe

nzyl

alco

hol

Buta

nedi

oic a

cid

Vani

llin

Ethy

lben

zene

L-A

spar

tic ac

idl-P

rolin

el-V

alin

eN

-Ben

zoyl

glyc

ine e

thyl

este

ro-

Hyd

roxy

prop

ioph

enon

ePh

enol

Pipe

rona

lPr

opan

edio

ic ac

idPy

ridin

eQ

uino

line

Dry

mou

thLa

ck o

f stre

ngth

With

out f

ur o

f ton

gue

Red

tong

ue

dl-T

rypt

opha

n

(b)

10

5

0

()

minus5

minus10

minus15

minus20

minus25

minus30

minus35

1(2H

)-na

phth

alen

one

2-M

ethy

lant

hran

ilic a

cid

Acet

ic ac

idBe

nzoi

c aci

d

Citr

ate

Vani

llin

Gly

cine

l-Pro

line

l-Val

ine

N-B

enzo

ylgl

ycin

e eth

yl es

ter

Paro

xypr

opio

nePh

enol

Pipe

rona

lPr

opan

edio

ic ac

idPy

ridin

eQ

uino

line

Hyp

ocho

ndria

c pai

nBi

tter t

aste

Slim

y fu

r of t

ongu

eYe

llow

fur o

f ton

gue

22998400-B

ithio

phen

e

dl-T

rypt

opha

n

(c)

0102030405060

1(2H

)-na

phth

alen

one

14-

Buta

nedi

oic a

cid

4-Fl

uoro

benz

oic a

cid

5-M

ethy

lant

hran

ilic a

cid

Acet

ate

Acet

ic ac

idBe

nzal

dehy

deBe

nzen

amin

eBe

nzen

emet

hana

min

eBe

nzyl

alco

hol

Buta

nedi

oic a

cid

dl-T

rypt

opha

nVa

nilli

nEt

hylb

enze

neL-

Asp

artic

acid

l-Pro

line

l-Val

ine

N-B

enzo

ylgl

ycin

e eth

yl es

ter

o-H

ydro

xypr

opio

phen

one

Phen

olPi

pero

nal

Prop

aned

ioic

acid

Pyrid

ine

Qui

nolin

eD

ry m

outh

Lack

of s

treng

thW

ithou

t fur

of t

ongu

eRe

d to

ngue

()

minus10

(d)








Black boxZHENG-


classic samples


dynamic

Integration of

information

TCM(ZHENG)Network

studyand so on

17501500125010007505002500

Cnt

4 6 8 150 300 450 600 750119898119911










Metabonomics









6 Conclusion





Data Bases






Acknowledgments


References






















































































of






Disease Markers



OncologyJournal of





PPAR Research



Journal of

ObesityJournal of


































10

5

0

minus5

minus10


119905[2]

119905[1]





005

115

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3

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ic ac

idPy

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Slim

y fu

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22998400-B

ithio

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(a)

005

115

225

3

1(2H

)-na

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Buta

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Buta

nedi

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cid

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tic ac

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alin

eN

-Ben

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ine e

thyl

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prop

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Pipe

rona

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idPy

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Dry

mou

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ngth

With

out f

ur o

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Red

tong

ue

dl-T

rypt

opha

n

(b)

10

5

0

()

minus5

minus10

minus15

minus20

minus25

minus30

minus35

1(2H

)-na

phth

alen

one

2-M

ethy

lant

hran

ilic a

cid

Acet

ic ac

idBe

nzoi

c aci

d

Citr

ate

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ter

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nBi

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aste

Slim

y fu

r of t

ongu

eYe

llow

fur o

f ton

gue

22998400-B

ithio

phen

e

dl-T

rypt

opha

n

(c)

0102030405060

1(2H

)-na

phth

alen

one

14-

Buta

nedi

oic a

cid

4-Fl

uoro

benz

oic a

cid

5-M

ethy

lant

hran

ilic a

cid

Acet

ate

Acet

ic ac

idBe

nzal

dehy

deBe

nzen

amin

eBe

nzen

emet

hana

min

eBe

nzyl

alco

hol

Buta

nedi

oic a

cid

dl-T

rypt

opha

nVa

nilli

nEt

hylb

enze

neL-

Asp

artic

acid

l-Pro

line

l-Val

ine

N-B

enzo

ylgl

ycin

e eth

yl es

ter

o-H

ydro

xypr

opio

phen

one

Phen

olPi

pero

nal

Prop

aned

ioic

acid

Pyrid

ine

Qui

nolin

eD

ry m

outh

Lack

of s

treng

thW

ithou

t fur

of t

ongu

eRe

d to

ngue

()

minus10

(d)








Black boxZHENG-


classic samples


dynamic

Integration of

information

TCM(ZHENG)Network

studyand so on

17501500125010007505002500

Cnt

4 6 8 150 300 450 600 750119898119911










Metabonomics









6 Conclusion





Data Bases






Acknowledgments


References






















































































of






Disease Markers



OncologyJournal of





PPAR Research



Journal of

ObesityJournal of

















005

115

225

3

1(2H

)-na

phth

alen

one

2-M

ethy

lant

hran

ilic a

cid

Acet

ic ac

idBe

nzoi

c aci

ddl

-Try

ptop

han

Citr

ate

Vani

llin

Gly

cine

l-Pro

line

l-Val

ine

N-B

enzo

ylgl

ycin

e eth

yl es

ter

Paro

xypr

opio

nePh

enol

Pipe

rona

lPr

opan

edio

ic ac

idPy

ridin

eQ

uino

line

Hyp

ocho

ndria

c pai

nBi

tter t

aste

Slim

y fu

r of t

ongu

eYe

llow

fur o

f ton

gue

22998400-B

ithio

phen

e

(a)

005

115

225

3

1(2H

)-na

phth

alen

one

14-

Buta

nedi

oic a

cid

4-Fl

uoro

benz

oic a

cid

5-M

ethy

lant

hran

ilic a

cid

Acet

ate

Acet

ic ac

idBe

nzal

dehy

deBe

nzen

amin

eBe

nzen

emet

hana

min

eBe

nzyl

alco

hol

Buta

nedi

oic a

cid

Vani

llin

Ethy

lben

zene

L-A

spar

tic ac

idl-P

rolin

el-V

alin

eN

-Ben

zoyl

glyc

ine e

thyl

este

ro-

Hyd

roxy

prop

ioph

enon

ePh

enol

Pipe

rona

lPr

opan

edio

ic ac

idPy

ridin

eQ

uino

line

Dry

mou

thLa

ck o

f stre

ngth

With

out f

ur o

f ton

gue

Red

tong

ue

dl-T

rypt

opha

n

(b)

10

5

0

()

minus5

minus10

minus15

minus20

minus25

minus30

minus35

1(2H

)-na

phth

alen

one

2-M

ethy

lant

hran

ilic a

cid

Acet

ic ac

idBe

nzoi

c aci

d

Citr

ate

Vani

llin

Gly

cine

l-Pro

line

l-Val

ine

N-B

enzo

ylgl

ycin

e eth

yl es

ter

Paro

xypr

opio

nePh

enol

Pipe

rona

lPr

opan

edio

ic ac

idPy

ridin

eQ

uino

line

Hyp

ocho

ndria

c pai

nBi

tter t

aste

Slim

y fu

r of t

ongu

eYe

llow

fur o

f ton

gue

22998400-B

ithio

phen

e

dl-T

rypt

opha

n

(c)

0102030405060

1(2H

)-na

phth

alen

one

14-

Buta

nedi

oic a

cid

4-Fl

uoro

benz

oic a

cid

5-M

ethy

lant

hran

ilic a

cid

Acet

ate

Acet

ic ac

idBe

nzal

dehy

deBe

nzen

amin

eBe

nzen

emet

hana

min

eBe

nzyl

alco

hol

Buta

nedi

oic a

cid

dl-T

rypt

opha

nVa

nilli

nEt

hylb

enze

neL-

Asp

artic

acid

l-Pro

line

l-Val

ine

N-B

enzo

ylgl

ycin

e eth

yl es

ter

o-H

ydro

xypr

opio

phen

one

Phen

olPi

pero

nal

Prop

aned

ioic

acid

Pyrid

ine

Qui

nolin

eD

ry m

outh

Lack

of s

treng

thW

ithou

t fur

of t

ongu

eRe

d to

ngue

()

minus10

(d)








Black boxZHENG-


classic samples


dynamic

Integration of

information

TCM(ZHENG)Network

studyand so on

17501500125010007505002500

Cnt

4 6 8 150 300 450 600 750119898119911










Metabonomics









6 Conclusion





Data Bases






Acknowledgments


References






















































































of






Disease Markers



OncologyJournal of





PPAR Research



Journal of

ObesityJournal of

















Black boxZHENG-


classic samples


dynamic

Integration of

information

TCM(ZHENG)Network

studyand so on

17501500125010007505002500

Cnt

4 6 8 150 300 450 600 750119898119911










Metabonomics









6 Conclusion





Data Bases






Acknowledgments


References






















































































of






Disease Markers



OncologyJournal of





PPAR Research



Journal of

ObesityJournal of



















Data Bases






Acknowledgments


References






















































































of






Disease Markers



OncologyJournal of





PPAR Research



Journal of

ObesityJournal of

















































































of






Disease Markers



OncologyJournal of





PPAR Research



Journal of

ObesityJournal of




















































of






Disease Markers



OncologyJournal of





PPAR Research



Journal of

ObesityJournal of





















of






Disease Markers



OncologyJournal of





PPAR Research



Journal of

ObesityJournal of
















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Review Article ZHENG-Omics Application in ZHENG ...downloads.hindawi.com › journals › ecam › 2013 › 235969.pdf · Review Article ZHENG-Omics Application in ZHENG Classification