EffectofTongluozhitongPrescription-AssistedIntra-Articular

Research ArticleEffect of Tongluozhitong Prescription-Assisted Intra-ArticularInjection of SodiumHyaluronate onVAS Score andKnee LysholmScore in Patients with Knee Osteoarthritis

Jianfang Gong ,1 Qiang Li,2 Mengling Wei,1 Liangliang Xue,3 Yinlian Liu,4 Jun Gao,1

and Tiantian Qin1

1Department of Traditional Chinese Medicine, Bethune Hospital, Taiyuan, Shanxi 030032, China2Department of Orthopaedics, Bethune Hospital, Taiyuan, Shanxi 030032, China3Department of Radiology, Bethune Hospital, Taiyuan, Shanxi 030032, China4Department of Rehabilitation, Bethune Hospital, Taiyuan, Shanxi 030032, China

Correspondence should be addressed to Jianfang Gong; [email protected]

Received 8 September 2021; Accepted 11 October 2021; Published 28 October 2021

Academic Editor: Songwen Tan

Copyright © 2021 Jianfang Gong et al.+is is an open access article distributed under the Creative Commons Attribution License,which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Knee osteoarthritis (KOA) has become one of the leading causes of workforce loss in the middle-aged and elderly population and aglobal public health problem second only to cardiovascular disease, so we need to findmore effective treatments for this disease. In thisstudy, we selected 120 patients with KOA admitted to our hospital from June 2018 to December 2020 and divided them into treatmentgroup 1, treatment group 2, and joint group according to the random number table method, with 40 patients in each group. Treatmentgroup 1was treated with Tongluozhitong prescription dip-soaking therapy, treatment 2 groupwas treated with intra-articular injectionof sodium hyaluronate, and the joint group was treated with a combination of both modalities for 4 weeks in all three groups. Clinicalefficacy, visual analogue scale (VAS), Lysholm knee score (LKS), activity of daily living score (ADL), the levels of bone metabolicmarkers such as cartilage oligomeric matrix protein (COMP), type II collagen degradation maker (CTX-II), and matrix metal-loproteinase-3 (MMP-3), and the levels of inflammatory mediators such as interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α),and hypersensitive C-reactive protein (hs-CRP) were used as observations to compare and analyze the therapeutic effects of the threetreatment regimens in KOA patients. +e results showed that the clinical excellence rates of the joint group, treatment group 1, andtreatment group 2 were 72.50%, 50.00%, and 90.00%, respectively, with statistically significant differences between any two com-parisons. After treatment, VAS scores, serumCOMP, CTX-II, MMP-3, IL-1β, TNF-α, and hs-CRP levels decreased in all three groups,and the levels of each index were as follows: joint group< treatment group 1< treatment group 2, and the difference between any twocomparisons was statistically significant.+e LKS score and ADL score increased in all three groups, and the levels of each index wereas follows: joint group> treatment group 1> treatment group 2, with statistically significant differences in any two groups compared.None of the patients in the three groups experienced any significant adverse effects during treatment.+is suggests that the dip-soakingtherapy of Tongluozhitong prescription is more advantageous than intra-articular sodium hyaluronate injection treatment insuppressing the level of serum bone metabolic markers and inflammatory mediators, reducing pathological joint damage, relievingsymptoms of pain, alleviating degenerative joint symptoms, and improving knee function in KOA patients. +e combination of thetwo in KOA patients can significantly improve the efficacy and has a good safety profile.

1. Introduction

Knee osteoarthritis (KOA) is a chronic joint disease char-acterized by deformation and destruction of articular car-tilage and osteophytes, which can cause joint pain and

dysfunction and seriously affect the quality of life of patients,and is one of the chronic diseases commonly seen in middle-aged and elderly people [1]. +e incidence of KOA is in-creasing year by year with the aging trend of our population,which brings about a great economic burden to the patients

HindawiEvidence-Based Complementary and Alternative MedicineVolume 2021, Article ID 3210494, 9 pageshttps://doi.org/10.1155/2021/3210494

mailto:[email protected]

https://orcid.org/0000-0002-0912-2907

https://creativecommons.org/licenses/by/4.0/

https://doi.org/10.1155/2021/3210494

themselves, their families, and the society [2]. +e patho-genesis of KOA is not well understood and clinical man-agement of the disease focuses on controlling pain, reducingdisability, improving knee function, and improving qualityof life [3]. +ere are various treatment modalities for KOA,including oral drugs, topical drugs, intravenous input, andintra-articular injection of drugs, among which intra-ar-ticular injection of sodium hyaluronate is currently the mostwidely used clinical treatment method [4].

Sodium hyaluronate is the main component of synovialfluid and one of the components of cartilage matrix. It canplay a lubricating role to reduce the friction between thetissues in the joint cavity after the injection into the jointcavity; it can also promote synovial cells to synthesizepolymeric hyaluronic acid to increase the concentration andmolecular weight of sodium citrate in the joint fluid andchange the viscosity of the joint fluid. In addition to pro-tecting joint cartilage and promoting healing and regener-ation of joint cartilage, sodium hyaluronate can alsosignificantly improve the inflammatory response of tissues,relieve pain, and improve joint function [5, 6]. KOA belongsto the category of “rheumatism” in traditional Chinesemedicine. Sweating when wind, sitting on wet ground,wading through water and rain, etc., can cause wind, coldand dampness, and other evils to invade the body’s me-ridians and stay in joints, vitrous resulting in obstruction ofmeridian qi and blood. +erefore, Chinese medicine oftenuses the principle of warming the meridians, dispersing cold,and relieving pain as treatment [7]. +e external treatmentmethod of Chinese medicine emphasizes internal and ex-ternal application to the organism through different ways,which can achieve the purpose of supporting the righteousenergy and eliminating the evil energy, and has extensiveclinical experience in the treatment of rheumatism. Chinesemedicine dip-soaking therapy is a kind of wet compressionmethod, which is a method to grind the drug and put it in abag and soak it in the liquid, warm it, and then take it out andapply it wet on the affected area and maintain the tem-perature by heating it with electromagnetic wave therapeuticapparatus. It has the advantages of exact efficacy, simplicity,and ease of use, as well as few side effects, and is widely usedin clinical practice [8].

In this study, we selected the dip-soaking therapy ofTongluozhitong prescription, intra-articular injection ofsodium hyaluronate, and the combined application of thetwo treatments and conducted a comparative analysis ofthe efficacy of different treatment methods to clarify theeffect of combined treatment on the clinical efficacy ofKOA patients and provide some reference for the selec-tion of more appropriate treatment methods for KOApatients.

2. Materials and Methods

2.1.Materials. 120 patients with KOA who were admitted toour hospital from June 2018 to December 2020 were se-lected; among them, 51males and 69 females were aged from41 to 70 years, and the mean age was 54.23± 7.78 years; theduration of the disease ranged from 5 months to 7 years,

with a mean of 3.21± 1.36 years. After enrollment, eachsubject was numbered sequentially (1 to 120). +e totalnumber of cases was set at 120 and the number of treatmentgroups was set at 3 by the random number table method, andthe patients were divided into treatment group 1, treatmentgroup 2, and joint group, with 40 cases in each group. +ecomparison of general data such as gender, age, diseaseduration, and lesion site in the three groups is shown inTable 1.

2.2. Diagnostic Criteria [9]. +e diagnostic criteria were asfollows: ① recurrent knee pain within the last 1 monthwhich prevents normal work or labor;② X-ray examinationshowing that the knee joint space became narrow, osteo-phytes formed on the edges of the joints, and bone sclerosisor cystic changes appeared under the cartilage; ③ middle-aged and elderly people aged ≥40 years; ④ joint stiffness inthe morning ≤30min; and ⑤ existence of a distinct sen-sation of bone friction at the affected joint when moving. If①+② or ①+③+④+⑤ of the diagnostic criteria weremet, the diagnosis of KOA was made.

2.3. InclusionCriteria. +e inclusion criteria were as follows:① patients who met the above diagnostic criteria and werediagnosed with KOA; ② patients with joint pain and dys-function caused by KOA; ③ patients without significantheart, brain, kidney, or lung insufficiency; ④ exclusion ofrheumatoid arthritis and other diseases by laboratory tests;⑤ patients who voluntarily participated in the trial andsigned an informed consent form; and⑥ patients in the agerange of 40 to 70 years.

2.4. Exclusion Criteria. +e exclusion criteria were as fol-lows: ① patients combined with sprains or other traumas;② those with coexisting severe visceral pathologies or othercomorbidities affecting the knee joint, such as psoriasis,syphilitic neuropathy, metabolic bone disease, and goutlesions; ③ patients with serious organic diseases, pregnantwomen, patients with coagulation disorders, and patientswith diabetes mellitus; ④ those with skin problems at theknee joint and poor skin sensation; and ⑤ those who wereunable to adhere to the treatment or dropped out in themiddle of the treatment for various other reasons and couldnot judge the efficacy of the treatment.

2.5. Treatment Methods

(1) Treatment group 1 was treated by dip-soaking withTongluozhitong prescription, and the specific op-erations were as follows: 30 g of frankincense, 30 g ofmyrrh, 30 g of garden balsam stem, 30 g of Zan-thoxylum bungeanum Maxim., 30 g of radix puer-ariae, and so forth were put into a cloth bag of about15× 20 cm sewn with a towel and soaked in athermostat for 1 hour and heat to about 40°C andthen taken out and wet-applied to the knee joint, andthe treatment was administered for 30 minutes

2 Evidence-Based Complementary and Alternative Medicine

under the thermostatic control of the electromag-netic therapy instrument at a temperature of 32 to45°C (the temperature should be comfortable andtolerable to the patient), 1 time per day for 4 weeks asa course of treatment.

(2) Treatment group 2 was treated with intra-articularinjection of sodium hyaluronate, and the specificoperations were as follows: the patient was treated ina supine position, keeping the knee joint flexed at 45°,and the Neixiyan point (the Neixiyan point is locatedat the inner depression of the anterior patellar lig-ament of the knee joint) was selected for routinedisinfection and anesthesia. A 5mL disposable sy-ringe was inserted into the joint cavity to completelyextract the fluid from the cavity, without removingthe needle, a sodium hyaluronate syringe was at-tached directly, and 2mL of sodium hyaluronate wasinjected slowly and evenly. After the injection wascompleted, the needle was removed, a band-aid wasapplied externally, and the patient was allowed tomove the knee joint several times to evenly distributethe injection solution, 1 time per week, for a total of 4treatments.

(3) +e joint group was treated with a regimen of dip-soaking with Tongluozhitong prescription-assistedintra-articular injection of sodium hyaluronate: thepatients in this group were treated for the sameduration as the other two groups, for a total of 4weeks. On the first day of each week, patients weretreated by dip-soaking with Tongluozhitong pre-scription for 30 minutes (same operation as treat-ment group 1), followed by intra-articular injectionof sodium hyaluronate (same operation as treatmentgroup 2), and, starting from the second day of thisweek, the traditional Chinese medicine dip-soakingtherapy treatment was performed only once a dayuntil the end of this week. +is cycle was used tocomplete the subsequent three weeks of treatment.

2.6. Observation Indicators

(1) Visual analogue scale (VAS) was rated before andafter treatment in the three groups, and the scoringcriteria were as follows: the VAS score was based on11 numbers from 0 to 10 representing different levelsof pain, where 0 means no pain and 10 means ex-treme pain, and patients were asked to select anumber from the table to represent their pain level

before treatment and after 4 weeks of treatment,respectively. A score of 0 indicated that the patientdid not feel any pain; 1∼3 indicated mild pain, andthe patient’s activities were not restricted and did notaffect work and life; 4∼6 indicated moderate pain,and the patient’s activities were slightly restrictedand affected general work and life; 7∼10 indicatedsevere pain, and the patient’s activities were signif-icantly restricted and significantly affected work andlife.

(2) Patients were rated on knee function before and aftertreatment using the Lysholm knee scale (LKS): thisscale included eight entries for claudication, inter-locking, pain, bracing, instability, swelling, stairclimbing, and squatting, with a total score of 0 to 100,and the score was proportional to the patient’s jointfunction. +e patients’ knee function was evaluatedbefore treatment and after 4 weeks of treatment,respectively; a score of >84 indicated normal jointfunction; a score of 66–84 indicated fair jointfunction; and a score of ≤65 indicated poor jointfunction.

(3) +e activities of daily living (ADL) scale: patients’ADL was assessed before and after treatment usingthe Barthel Index, one of the most commonmethodsused to assess ADL, which includes 10 items such aseating, bowel control, activity, transfer, bathing, anddressing. +e scores for bathing and grooming were0 and 5; for eating, dressing, bowel control, urinecontrol, toileting, and stairs they were 0, 5, and 10;and for transfer and activities they were 0, 5, 10, and15. 10 items were scored out of 100, with higherscores indicating higher ability to perform activitiesof daily living.

(4) +e levels of serum bone metabolic markers andinflammatory mediators were compared before andafter treatment in the three groups: patients wereinstructed not to eat or drink after 22 : 00 on the firstday before the test, and 5ml of venous blood wasdrawn in the early morning of the second day on anempty stomach for the test. We measured the levelsof bone metabolism markers such as cartilage olig-omeric matrix protein (COMP), type II collagencarboxy-terminal peptide (CTX-II), matrix metal-loproteinase-3 (MMP-3), and serum inflammatorymediators such as interleukin-1β (IL-1β), tumornecrosis factor-α (TNF-α), and hypersensitiveC-reactive protein (hs-CRP) by enzyme-linked

Table 1: Comparison of basic information of treatment group 1, treatment group 2, and joint group.

Information Treatment group 1 (n� 40) Treatment group 2 (n� 40) Joint group (n� 40) P value

Gender (case, %) Male 17 (42.50) 18 (45.00) 16 (40.00) 0.903Female 23 (57.50) 22 (55.00) 24 (60.00)

Lesion site (case, %) Unilateral 26 (65.00) 28 (70.00) 29 (72.50) 0.761Bilateral 14 (35.00) 12 (30.00) 11 (27.50)Age, mean (SD), years 53.96± 7.26 54.35± 8.01 54.12± 7.46 0.974Disease duration, mean (SD), years 3.29± 1.29 3.18± 1.38 3.24± 1.34 0.934

Evidence-Based Complementary and Alternative Medicine 3

immunosorbent assay (ELISA), Serum COMPELISA Kit, Serum CTX-II ELISA Kit, SerumMMP-3ELISA Kit, Serum IL-1β ELISA Kit, Serum TNF-αELISA Kit, and Serum hs-CRP ELISA Kit which werepurchased from Shanghai Xitang Biotechnology Co.+e specific operation steps were carried out inaccordance with the instructions of the ELISA kit.

2.7. Judgment of Efficacy. +e efficacy criteria were devel-oped with reference to the “Guidelines for Clinical Researchof New Chinese Medicine (Trial)” [10] and combined withknee X-ray examination. ① After treatment, the patient’sclinical symptoms and signs mostly disappeared, the jointmovement returned to normal, the X-ray indicated that thejoint returned to normal, and the LKS score increased bymore than 90% and was considered as healed. ② +e pa-tient’s symptoms and signs improved significantly, and he/she could carry out normal life and work, the X-ray filmindicated that the joint pathology was significantly im-proved, and the LKS increased by 71% to 90% and wasconsidered as marked effect.③+e patient’s symptoms andsigns were relieved after treatment, but the joint movementwas still limited to a certain extent, the X-ray showed someimprovement of the joint pathology, and an increase of 31%to 70% in the LKS was considered as valid. ④ +e patient’sclinical symptoms and signs did not improve after treat-ment, his/her daily life was limited, X-rays showed noimprovement in the joint pathology, and the LKS increasedby less than 31% and was considered as invalid. Excellentrate� number of (healed +marked effect) cases/total num-ber of cases× 100%.

2.8. Statistical Method. All data were processed with SPSS22.0 statistical software, and GraghPad prism 8 was used tomake statistical graphs. +e count data was expressed ascase, %, and chi-square (χ2) test was performed. +e mea-surement data were tested according to normality, t-test wasused between two groups conforming to normality, andOne-Way ANOVA (F-test) was used between multiplegroups, expressed as mean± standard deviation (mean,(SD)). P< 0.05 indicated that the difference was statisticallysignificant.

3. Results

3.1. Comparison of Clinical Efficacy. After 4 weeks, 14 cases(35.00%) were healed, 15 cases (37.50%) were marked effect,9 cases (22.50%) were valid, and 2 cases (5.00%) were invalidin treatment group 1, with an excellent treatment rate of72.50%. +ere were 10 cases (25.00%) healed, 10 cases(25.00%) with marked effect, 15 cases (37.50%) with valideffect, and 5 cases (12.50%) with invalid effect in treatmentgroups 2, with an excellent treatment rate of 50.00%. In thejoint group, 23 cases (57.50%) were healed, 13 cases (32.50%)were marked effect, 4 cases (10.00%) were valid, and 0 caseswere invalid, with an excellent treatment rate of 90.00%. Weconducted a statistical analysis of the excellent rates oftreatment in the three groups. +e results showed that the

excellent efficacy rate of the three groups was as follows: jointgroup> treatment group 1> treatment group 2, and thedifference between any two groups was statistically signifi-cant (P< 0.05) (Figure 1).

3.2. Comparison of VAS, LKS, andADLScores before and afterTreatment. +ere was no significant difference in the scoresof VAS, LKS, and ADL in the three groups before treatment(P> 0.05).+eVAS scores decreased and Lysholm scores andADL scores increased in all three groups after treatment(P< 0.05). Among them, the VAS scores were as follows:joint group< treatment group 1< treatment group 2, and thedifference between any two comparisons was statisticallysignificant (P< 0.05). +e Lysholm scores and ADL scoreswere as follows: combined group< treatment 1 group-< treatment 2 group, and the difference between any twocomparisons was statistically significant (P< 0.05) (Figure 2).

3.3. Comparison of Serum Bone Metabolism Marker Levelsbefore and after Treatment. +e differences in the levels ofserum COMP, CTX-II, and MMP-3 in the three groupsbefore treatment were not statistically significant (P> 0.05).In contrast, the levels of serum COMP, CTX-II, and MMP-3decreased significantly in all three groups after treatment(P< 0.05). +e levels of the above indexes in the joint groupwere lower than those in treatment groups 1 and 2, whiletreatment group 1 was lower than treatment group 2, and thedifference was statistically significant (P< 0.05) (Figure 3).

3.4. Comparison of Serum Inflammatory Mediator Levelsbefore and after Treatment. +ere was no statistically sig-nificant difference in the pretreatment levels of serum IL-1β,TNF-α, and hs-CRP among the three groups (P> 0.05).After treatment, serum IL-1β, TNF-α, and hs-CRP levelsdecreased in all three groups (P< 0.05). Among them, thelevels of serum IL-1β, TNF-α, and hs-CRP in the joint groupwere lower than those in treatment group 1 and treatmentgroup 2, while the levels of the above indexes in treatmentgroup 1 were lower than those in treatment group 2, and thedifferences were statistically significant (P< 0.05) (Figure 4).

3.5. Safety. +e three cohorts underwent routine blood,urine, and stool tests, liver and kidney function tests, andelectrocardiograms before and after treatment, and none ofthe results were significantly abnormal. No severe skinitching, red rash, or burns were observed in any of thepatients treated with Tongluozhitong prescription dip-soaking therapy, which indicates that Chinese medicinetreatment, western medicine treatment, and combinedtreatment regimens have a good safety profile.

4. Discussion

Total knee arthroplasty is the best treatment for patients withend-stage KOA, but this surgical treatment can be traumaticto the patient’s body and has the disadvantages of high costand high risk of postoperative infection. +erefore, effective


Healed Marked effect Valid Invalid Excellent rate0

20

40

60

80

100

Clin

ical

effic

acy

(%)

Treatment group 1Treatment group 2Joint group

^

^*

Figure 1: Comparison of clinical efficacy between treatment group 1, treatment group 2, and joint group. Excellent rate: compared withtreatment group 1, ∧P< 0.05; compared with treatment group 2, ∗P< 0.05.

Pre-treatment Post-treatment0

2

4

6

8

VA

S sc

ore

#

#^

#^*


(a)


20

40

60

80

100LK

S sc

ore

# #^*#^


(b)


20

40

60

80

100

AD

L sc

ore

##^*

#^


(c)

Figure 2: Comparison of VAS, LKS, and ADL scores before and after treatment between treatment group 1, treatment group 2, and jointgroup. (a) Mean VAS scores. (b) Mean LKS scores. (c) Mean ADL scores. Compared to the same group before treatment, #P< 0.05;compared with treatment group 1 in the same time period, ∧P< 0.05; compared with treatment group 2 in the same time period, ∗P< 0.05.


options to delay or even reverse the degenerative changes inthe knee joint before the patient’s disease becomes advancedare always the key to clinical treatment [11, 12]. +epathogenesis of the disease is not fully understood, andnumerous studies [13, 14] have shown that inflammatoryfactors play an important role in the production of KOA. IL-1β and TNF-α are common inflammatory cytokines withmultiple biological functions, both of which can induce thesynthesis of matrix metalloproteinases (MMPs), therebyincreasing the degradation of chondrocytes and eventuallyleading to the destruction of articular cartilage and theformation of osteoarthritis. In addition, TNF-α can alsodamage cartilage and stimulate chondrocytes by stimulatingthe production of prostaglandin E2 by anterior synovialcells, causing them to release large amounts of fibrinolyticactivators and ultimately aggravate joint damage by con-verting fibrinogen [15].

+e KOA patients included in the study were treatedwith dip-soaking of Tongluozhitong prescription, sodiumhyaluronate injection, and a combination of both, re-spectively. +e results showed that the clinical efficacy oftreatmen group 1 was significantly higher than that oftreatment group 2, and the improvement of pain, jointfunction, and activity scores and serum inflammatoryfactors were significantly better in treatment group 1 thanin treatment group 2 after treatment, while, compared withthese two groups, the joint group showed better efficacyand improvement in each index. Currently, sodium hya-luronate is a commonly used drug in the clinical treatmentof KOA patients. +e decreased synthesis of hyaluronicacid by the synovial membrane in patients with KOA canlead to damage to knee cartilage. +us, intra-articularinjection of exogenous sodium hyaluronate into the kneejoint cavity can increase the content of macromolecular


2

4

6CO

MP

(μg/

L)

##^

#^*


(a)

CTX-

II (μ

g/L)


200

400

600

800

# #^#^*


(b)

0

1

2

3

4

5

MM

P-3

(μg/

L) ##^

#^*

Pre-treatment Post-treatment


(c)

Figure 3: Comparison of serum bone metabolism marker levels before and after treatment between treatment group 1, treatment group 2,and joint group. (a) Mean COMN levels. (b) Mean CTX-II levels. (c) Mean MMP-3 levels. Compared to the same group before treatment,#P< 0.05; compared with treatment group 1 in the same time period, ∧P< 0.05; compared with treatment group 2 in the same time period,∗P< 0.05.


hyaluronic acid to restore the viscoelasticity of the jointfluid and reconstruct the articular cartilage. In addition,this drug can inhibit the release of inflammatory mediatorsto eliminate swelling symptoms, reduce joint pressure andcartilage friction, and delay arthrosis [16]. Chinese medi-cine dip-soaking therapy has also been gradually applied tothe treatment of KOA in recent years, and its mechanism ofaction in the treatment of KOA is divided into two mainaspects [17, 18]. +e first is the efficacy of the drugsthemselves; the drugs used in herbal dip-soaking can beselected according to the patient’s disease evidence andspecific performance. Among the drugs selected in thisstudy, myrrh and frankincense have the function of in-vigorating blood, promoting qi, dredging collaterals, andrelieving pain; garden balsam stem has the effects of dis-pelling wind and dampness, relaxing muscles and acti-vating blood, and detoxifying and relieving pain;Zanthoxylum bungeanum Maxim. warms the middle and

disperses cold to relieve pain, and radix puerariae is cold-natured, which can avoid excessive pungency and warmthin the whole prescription. +e whole prescription has theeffects of dispelling wind and dampness, promoting bloodcirculation and dredging collaterals, dispelling cold, andrelieving pain. +e second is the warming effect producedby the heating of the drug. +e efficacy of the drug com-bined with the heat can promote the expansion of bloodvessels in the affected area and accelerate blood circulation,so that the drug can reach the lesion directly through theexpanded pores and thus play a therapeutic role. Modernpharmacological studies have confirmed that myrrh [19],frankincense [20], and Zanthoxylum bungeanum Maxim.[21] have strong anti-inflammatory effects, in addition tosignificant analgesic effects; the dip-soaking therapy ofTongluozhitong prescription takes into account anti-in-flammatory and pain-relieving effects and treats the root ofthe disease, which is more conducive to the relief of

0

50

100

150

200

250IL

-1β

(ng/

L)

# #^#^*



(a)

0

50

100

150

TNF-α

(pg/

mL)

#^*# #^



(b)

0

5

10

15

20

hs-C

RP (μ

g/m

L)

##^

#^*



(c)

Figure 4: Comparison of serum inflammatory mediator levels before and after treatment between treatment group 1, treatment group 2,and joint group. (a) Mean IL-1β levels. (b) Mean TNF-α levels. (c) Mean hs-CRP levels. Compared to the same group before treatment,#P< 0.05; compared with treatment group 1 in the same time period, ∧P< 0.05; compared with treatment group 2 in the same time period,∗P< 0.05.


patients’ symptoms. Tongluozhitong prescription treats theroot cause by exerting the effect of dispersing cold andrelieving pain, activating blood circulation, and treating thesymptoms by nourishing and moisturizing anti-inflam-mation with sodium hyaluronate. +e combination of thetwo drugs achieves the purpose of treating both principaland secondary aspects of disease so that the combination ofherbal collapse treatment can lead to further improvementin the clinical outcome of KOA patients. However, as mostKOA patients are middle-aged and elderly, they are sus-ceptible subjects and should be closely monitored duringtreatment, with continuous improvement of the formula,enhanced communication between doctors and patients,and timely management of adverse reactions duringtreatment to improve treatment effectiveness.

COMP, CTX-II, and MMP-3 are all markers of cartilagemetabolism. COMP is a component of cartilage non-collagenous protein and is a sensitive indicator for clinicalevaluation of the degree of articular cartilage damage, and anincrease in its level usually indicates increased damage toknee cartilage [22]. CTX-II is a small molecule peptideproduced by the stimulation of type II collagen by protease,and its level reflects the degradation ability of type II col-lagen, which is involved in the degeneration of articularcartilage and the formation of osteoarthritis [23]. MMP-3 ismainly secreted by chondrocytes and synovial cells, and itsexpression level is closely related to articular cartilagedamage and can be used as a sensitive indicator for thediagnosis of osteoarthritic conditions [24]. In this study, thelevels of COMP, CTX-II, and MMP-3 were significantlylower in the joint group after treatment than in the other twogroups, while treatment 1 group was lower than treatment 2group. It is suggested that the dip-soaking therapy ofChinese medicine is more effective in regulating the bonemetabolic index of KOA patients to slow down the process ofarticular cartilage degeneration, and the combination ofChinese medicine dip-soaking therapy is an effective solu-tion in the clinical treatment of patients with KOA, orpatients with low tolerance to multiple solutions can betreated with herbal impregnation, which can also achievebetter therapeutic results.

5. Conclusion

In a word, the dip-soaking therapy of Tongluozhitongprescription is more advantageous than intra-articular so-dium hyaluronate injection treatment in suppressing thelevel of serum bone metabolic markers and inflammatorymediators, reducing pathological joint damage, relievingsymptoms of pain, alleviating degenerative joint symptoms,and improving knee function in KOA patients. +e com-bination of the two in KOA patients can significantly im-prove the efficacy and has a good safety profile.

Data Availability

+e datasets used and/or analyzed during this study areavailable from the corresponding author upon reasonablerequest.

Ethical Approval

+is study was approved by the Ethics Committee ofBethune Hospital (2017006).

Conflicts of Interest

+e authors declare no conflicts of interest, financial orotherwise.

Acknowledgments

+is study was supported by the Project of Shanxi Ad-ministration of Traditional Chinese Medicine (Project no.2020ZYYC048).

References

[1] M. N. Turner, D. O. Hernandez, W. Cade, C. P. Emerson,J. M. Reynolds, and T. M. Best, “+e role of resistance trainingdosing on pain and physical function in individuals with kneeosteoarthritis: a systematic review,” Sports Health: a Multi-disciplinary Approach, vol. 12, no. 2, pp. 200–206, 2020.

[2] H. Chen, X. Zheng, H. Huang, C. Liu, Q. Wan, and S. Shang,“+e effects of a home-based exercise intervention on elderlypatients with knee osteoarthritis: a quasi-experimental study,”BMC Musculoskeletal Disorders, vol. 20, no. 1, p. 160, 2019.

[3] D. Primorac, V. Molnar, E. Rod et al., “Knee osteoarthritis: areview of pathogenesis and state-of-the-art non-operativetherapeutic consideration,” Genes, vol. 11, no. 8, p. 854, 2020.

[4] T. Georgiev and A. K. Angelov, “Modifiable risk factors inknee osteoarthritis: treatment implications,” RheumatologyInternational, vol. 39, no. 7, pp. 1145–1157, 2019.

[5] K. Xie, X. Pan, F. Huang et al., “Needle knife therapy plussodium hyaluronate injection for knee osteoarthritis: a pro-tocol for a systematic review and meta-analysis,” Medicine,vol. 99, no. 46, Article ID E23242, 2020.

[6] C. Cooper, F. Rannou, P. Richette et al., “Use of intraarticularhyaluronic acid in the management of knee osteoarthritis inclinical practice,” Arthritis Care and Research (Hoboken),vol. 69, no. 9, pp. 1287–1296, 2017.

[7] M. Yang, L. Jiang, Q. Wang, H. Chen, and G. Xu, “TraditionalChinese medicine for knee osteoarthritis: an overview ofsystematic review,” PLoS One, vol. 12, no. 12, Article IDe0189884, 2017.

[8] B. F. Zhu, “[Observation on 17 patients of radio-ulcer withcombined traditional Chinese medicine and westernmedicinetherapy],” Zhongguo Zhong Xi Yi Jie He Za Zhi, vol. 14, no. 2,pp. 89–91, 1994.

[9] T. E. McAlindon, R. R. Bannuru, M. C. Sullivan et al., “OARSIguidelines for the non-surgical management of knee osteo-arthritis,” Osteoarthritis Cartilage, vol. 22, no. 3, pp. 363–388,2014.

[10] X. Y. Zheng, Guidelines for Clinical Research of New ChineseMedicine (Trial), China Medical Science and TechnologyPress, Beijing, China, 2002.

[11] X. Yang, G. H. Li, H. J. Wang, and C. Y. Wang, “Continuouspassive motion after total knee arthroplasty: a systematicreview and meta-analysis of associated effects on clinicaloutcomes,” Archives of Physical Medicine and Rehabilitation,vol. 100, no. 9, pp. 1763–1778, 2019.

[12] A. Perlman, S. G. Fogerite, O. Glass et al., “Efficacy and safetyof massage for osteoarthritis of the knee: a randomized clinical


trial,” Journal of General Internal Medicine, vol. 4, no. 3,pp. 379–386, 2019.

[13] C. Du, A. Smith, M. Avalos et al., “Blueberries improve pain,gait performance, and inflammation in individuals withsymptomatic knee osteoarthritis,” Nutrients, vol. 11, no. 2,p. 290, 2019.

[14] M. N. Wang, L. Liu, L. P. Zhao et al., “[Research of in-flammatory factors and signaling pathways in knee osteoar-thritis],” Zhong Guo Gu Shang, vol. 33, no. 4, pp. 38–392,2020.

[15] C. R. Liao, S. N. Wang, S. Y. Zhu et al., “Advanced oxidationprotein products increase TNF-α and IL-1β expression inchondrocytes via NADPH oxidase 4 and accelerate cartilagedegeneration in osteoarthritis progression,” Redox Biology,vol. 28, Article ID 101306, 2020.

[16] J. W. Belk, M. J. Kraeutler, D. A. Houck, J. A. Goodrich,J. L. Dragoo, and E. C. McCarty, “Platelet-rich plasma versushyaluronic acid for knee osteoarthritis: a systematic reviewand meta-analysis of randomized controlled trials,” AmericanJournal of Sports Medicine, vol. 49, no. 1, pp. 249–260, 2021.

[17] X. Ding, J. Wu, Q. Shen, J. Xu, and W. Mo, “Clinical controlstudy of traditional Chinese medicine hot compress combinedwith traction in the treatment of cervical spondylotic radi-culopathy: study protocol,” Medicine (Baltimore), vol. 100,no. 4, Article ID E23880, 2021.

[18] M. Zhu, N. Xu, Q. H. He, J. N. Xun, F. Dai, and Z. L. Zhao,“[Effect of shirexiao waist hot-compress on the expressions of+17/treg-specific factors in the mouse model of experimentalautoimmune prostatitis with damp heat syndrome],”Zhonghua Nan Ke Xue, vol. 23, no. 3, pp. 243–250, 2017.

[19] R. Lamichhane, K. H. Lee, P. R. Pandeya et al., “Subcutaneousinjection of myrrh essential oil in mice: acute and subacutetoxicity study,” Evidence Based Complement AlternativeMedicine, vol. 2019, Article ID 8497980, 13 pages, 2019.

[20] A. R. Al-Yasiry and B. Kiczorowska, “Frankincense--thera-peutic properties,” Postepy Higieny i MedycynyDoswiadczalnej (Online), vol. 70, pp. 380–391, 2016.

[21] M. Zhang, J. Wang, L. Zhu et al., “Zanthoxylum bungeanummaxim. (rutaceae): a systematic review of its traditional uses,botany, phytochemistry, pharmacology, pharmacokinetics,and toxicology,” International Journal of Molecular Science,vol. 18, no. 10, p. 2172, 2017.

[22] X. Bi, “Correlation of serum cartilage oligomeric matrixprotein with knee osteoarthritis diagnosis: a meta-analysis,”Journal of Orthopaedic Surgery and Research, vol. 13, no. 1,p. 262, 2018.

[23] H. Cheng, B. Hao, J. Sun, and M. Yin, “C-terminal cross-linked telopeptides of type II collagen as biomarker for ra-diological knee osteoarthritis: a meta-analysis,” Cartilage,vol. 11, no. 4, pp. 512–520, 2020.

[24] T. Georgiev, M. Ivanova, T. Velikova, and R. Stoilov, “Serumlevels of matrix metalloproteinase-3 as a prognostic markerfor progression of cartilage injury in patients with knee os-teoarthritis,” Acta Reumatologica Portuguesa, vol. 45, no. 3,pp. 207–213, 2020.


Documents

EffectofTongluozhitongPrescription-AssistedIntra-Articular