Zhuifeng Tougu capsules in the treatment of knee osteoarthritis (cold dampness obstruction syndrome): a randomized, double blind, multicenter clinical study.

BACKGROUND: In Traditional Chinese Medicine (TCM) theory, cold dampness obstruction is one of the common syndromes of osteoarthritis. Therefore, in clinical practice, the main treatment methods are to dispel wind, remove dampness, and dissipate cold, used to treat knee osteoarthritis (KOA). This report describes a mulitercenter clinical study to assess Zhuifeng Tougu Capsule's efficacy and safety in the treatment of patients who are cold dampness obstruction syndrome in KOA, and to provide evidence-based medical for the rational use of Zhuifeng Tougu Capsules in clinical practice. METHODS: This randomized, parallel group controlled, double-blind, double dummy trial will include a total of 215 KOA patients who meet the study criteria. 215 patients underwent 1:1 randomisation, with 107 cases assigned the experimental group (Zhuifeng Tougu Capsules + Glucosamine Sulfate Capsules Simulator) and 108 assigned the control group (Glucosamine Sulfate Capsules + Zhuifeng Tougu Capsules Simulator). After enrolment, patients received 12 weeks of treatment. The main efficacy measure is the Western Ontario and McMaster University Osteoarthritis Index (WOMAC) pain score. Visual analogue scale (VAS) pain score, Self-condition assessment VAS score, WOMAC KOA score, TCM syndrome score and TCM syndrome efficacy, ESR level, CRP level, suprapatellar bursa effusion depth, use of rescue drugs, and safety indicators are secondary efficacy indicators. RESULTS: Compared with before treatment, WOMAC pain score, VAS pain score, Self-condition assessment VAS score, WOMAC KOA score, and TCM syndrome score decreased significantly in both groups (P < 0.01). Also, the experimental group showed significant differences in the above indicators compared to control (P < 0.01). However, after treatment, no significant differences were showed in the ESR level, CRP level, and suprapatellar bursa effusion depth between the two groups (P > 0.05). No any serious adverse effects showed in the experimental group and control group. CONCLUSIONS: Zhuifeng Tougu Capsules can effectively improve knee joint function and significantly alleviate the pain of KOA. TRIAL REGISTRATION: Clinical trial registration was completed with the China Clinical Trial Registration Center for this research protocol (No. ChiCTR2000028750) on January 2, 2020.

Wangbi granule as a combination therapy to achieve clinical deep remission in rheumatoid arthritis: protocol for a multicenter, triple-blind, randomised, placebo-controlled trial.

INTRODUCTION: Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease that may lead to bone erosion and disability. Although there are many biological therapies in RA treatment nowadays, such as etanercept and tofacitinib, there are still a considerable number of patients who cannot achieve clinical deep remission, which makes patients feel pain and stiffness of joints. As a traditional Chinese medicine preparation, Wangbi granule showed a synergistic role with methotrexate in the treatment of RA patients with "kidney deficiency and dampness" or "stasis blocking channels". Therefore, it is a promising therapeutic strategy for the clinical deep remission of RA. In this study, Wangbi granule will be used as the test drug. The investigators conduct this study to evaluate the efficacy and safety of Wangbi granule in the treatment of patients who have not achieved deep remission despite the use of methotrexate and tofacitinib. METHODS AND ANALYSIS: Two parallel randomized, triple-blind, placebo-controlled trials will be conducted. In six study centers, 340 eligible RA patients will be recruited and randomly allocated to either the intervention group or the control group (in a 1:1 ratio). They will receive Wangbi granule or Wangbi placebo 12.0 g each time, three times a day for 12 weeks. The primary outcome is the disease activity score derivative for 28 joints (DAS28). Secondary outcomes are patient-reported outcomes, American College of Rheumatology 50% response criteria (ACR50), fatigue scale-14 (FS-14), visual analogue scale for pain (VAS), health assessment questionnaire disability index (HAQ-DI) and biomarkers such as C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR). EXPECTED OUTCOMES: The success of this study will provide strong evidence to confirm the efficacy and safety of Wangbi granule in the treatment of RA. Trial registration The trial has been registered in the ClinicalTrials Registry (NCT05540938, Date: 09/15/2022, https://clinicaltrials.gov/ct2/show/NCT05540938 ).

Molecular mechanism of ovarian toxicity of Hook.F. a study based on network pharmacology and molecular docking.

To explore the mechanism of ovarian toxicity of Hook. F. (TwHF) by network pharmacology and molecular docking. The candidate toxic compounds and targets of TwHF were collected by the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) and the Comparative Toxicogenomics Database (CTD). Then, the potential ovarian toxic targets were obtained from CTD, and the target genes of ovarian toxicity of TwHF were analyzed using the STRING database. The protein-protein interaction (PPI) network was established by Cytoscape and analyzed by the cytoHubba plug-in to identify hub genes. Additionally, the target genes of ovarian toxicity of TwHF were subjected to Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses by using the R software. Finally, Discovery Studio software was used for molecular docking verification of the core toxic compounds and the hub genes. Nine candidate toxic compounds of TwHF and 56 potential ovarian toxic targets were identified in this study. Further network analysis showed that the core ovarian toxic compounds of TwHF were triptolide, kaempferol and tripterine, and the hub ovarian toxic genes included , , , , , , , , and . Besides, the GO and KEGG analysis indicated that TwHF caused ovarian toxicity through oxidative stress, reproductive system development and function, regulation of cell cycle, response to endogenous hormones and exogenous stimuli, apoptosis regulation and aging. The docking studies suggested that 3 core ovarian toxic compounds of TwHF were able to fit in the binding pocket of the 10 hub genes. TwHF may cause ovarian toxicity by acting on 10 hub genes and 140 signaling pathways.

The Impact of Traditional Chinese Medicine QingreHuoxue Treatment and the Combination of Methotrexate and Hydroxychloroquine on the Radiological Progression of Active Rheumatoid Arthritis: A 52-Week Follow-Up of a Randomized Controlled Clinical Study.

Traditional Chinese medicine (TCM) has been used successfully to treat rheumatoid arthritis (RA). QingreHuoxue treatment (QingreHuoxue decoction [QRHXD]/QingreHuoxue external preparation [QRHXEP]) is a Chinese medicine treatment for RA. To date, very few studies have compared the long-term effects of QRHXD with those of conventional disease-modifying antirheumatic drugs on RA disease activity and radiological progression. QRHXD delayed the radiological progression and showed long-term clinical efficacy of RA. In clinical experiments, the clinical evidence of delaying the radiological progression of RA patients was obtained. A portion of the patients who participated in the "Traditional Chinese Medicine QingreHuoxue Treatment vs. the Combination of Methotrexate and Hydroxychloroquine for Active Rheumatoid Arthritis" study were followed up for 52 weeks, and intention-to-treat (ITT) and compliance protocol (PP) analyses were used to collect and compare the clinical indicators and imaging data between baseline and week 52. Two radiologists who were blind to treatment scored the images independently. Of the 468 subjects, 141 completed the 52-week follow-up. There were no significant differences among the three groups: the traditional Chinese medicine comprehensive treatment group, the Western medicine treatment group, and the integrated traditional Chinese and Western medicine treatment group. There were no differences in the total Sharp score, joint space stenosis score, and joint erosion score at baseline or 52 weeks. In the comparison of the estimated annual radiographic progression (EARP) and the actual annual Sharp total score changes among the three groups, the actual changes were much lower than the EARP at baseline. The radiological progress in all three groups was well controlled. Results of the ITT and PP data sets showed that the disease activity score 28 level of the three groups at 52 weeks was significantly lower than that at baseline. During the 52-week treatment period, the clearance of heat and promotion of blood circulation controlled disease activity and delayed the radiological progress of active RA.

Traditional Chinese Medicine Qingre Huoxue Treatment vs. the Combination of Methotrexate and Hydroxychloroquine for Active Rheumatoid Arthritis: A Multicenter, Double-Blind, Randomized Controlled Trial.

Traditional Chinese medicine (TCM) has been used successfully to treat rheumatoid arthritis (RA). Qingre Huoxue treatment (Qingre Huoxue decoction (QRHXD)/Qingre Huoxue external preparation (QRHXEP)) is a therapeutic scheme of TCM for RA. To date, there have been few studies comparing the efficacy and safety of QRHXD and conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) for the treatment of active RA. This was investigated in a multicenter, double-blind, randomized controlled trial involving 468 Chinese patients with active RA [disease activity score (DAS)-28 > 3.2] treated with QRHXD/QRHXEP (TCM group), methotrexate plus hydroxychloroquine [Western medicine (WM) group], or both [integrative medicine (IM) group]. Patients were followed up for 24 weeks. The primary outcome measure was the change in DAS-28 from baseline to 24 weeks. The secondary outcome measures were treatment response rate according to American College of Rheumatology 20, 50, and 70% improvement criteria (ACR-20/50/70) and the rate of treatment-related adverse events (TRAEs). The trial was registered at ClinicalTrials.gov (NCT02551575). DAS-28 decreased in all three groups after treatment (p < 0.0001); the score was lowest in the TCM group (p < 0.05), while no difference was observed between the WM and IM groups (p > 0.05). At week 24, ACR-20 response was 73.04% with TCM, 80.17% with WM, and 73.95% with IM (based on the full analysis set [FAS], p > 0.05); ACR-50 responses were 40.87, 47.93, and 51.26%, respectively, (FAS, p > 0.05); and ACR-70 responses were 20.87, 22.31, and 25.21%, respectively, (FAS, p > 0.05). Thus, treatment efficacy was similar across groups based on ACR criteria. On the other hand, the rate of TRAEs was significantly lower in the TCM group compared to the other groups (p < 0.05). Thus, QRHXD/QRHXEP was effective in alleviating the symptoms of active RA-albeit to a lesser degree than csDMARDs-with fewer side effects. Importantly, combination with QRHXD enhanced the efficacy of csDMARDs. These results provide evidence that QRHXD can be used as an adjunct to csDMARDs for the management of RA, especially in patients who experience TRAEs with standard drugs. Clinical Trial Registration: ClinicalTrials.gov, identifier NCTNCT025515.

Clinical Practice Guideline for Tripterygium Glycosides/Tripterygium wilfordii Tablets in the Treatment of Rheumatoid Arthritis.

Tripterygium wilfordii Hook F (TwHF) is one of the most commonly used and effective traditional Chinese herbal medicines against rheumatoid arthritis (RA). Both Tripterygium Glycoside Tablets (TGT) and Tripterygium wilfordii Tablets (TWT) are the representative TwHF-based agents enrolled into the 2019 edition of Medicine Catalog for National Basic Medical Insurance, Injury Insurance, and Maternity Insurance. However, individual differences in TGT/TWT response across patients usually exist in the process of treating RA, implying that the clinical application of the two agents may not be standardized leading to the ineffective treatment and the risk of side effects. Growing evidence show that the bioactive constituents of TwHF may often have toxicity, the package insert of TGT and TWT may not be described in detail, and the therapeutic windows of the two agents are narrow. Thus, it is an urgent task to develop a standardized clinical practice guideline for TGT and TWT in the treatment of RA. In the current study, a group of clinical experts of traditional Chinese medicine and Western medicine in the research field of rheumatism diseases, pharmacists, and methodologists of evidence-based medicine were invited to select the clinical questions, to determine the levels of the evidence and the strength of the recommendations, and to develop the recommendations and good practice points. The guideline is formed based on the combination of clinical research evidence and expert experience (evidence-based, consensus, supplemented by experience). The clinical problems which are supported by clinical evidence may form recommendations, and the clinical problems without clinical evidence may form experts' suggestions. Both recommendations and experts' suggestions in this guideline summarized the clinical indications, usage, dosage, combined medication, and safety of TGT and TWT against RA systematically and comprehensively, which may offer a professional guidance in the context of the clinical application of the two TwHF-based agents.

Intervention of integrative medicine treatment has impact on serum levels of ET-1, TNF-α, MLT in RA-CVD.

Rheumatoid arthritis (RA) is a systemic autoimmune disease that can destroy peripheral joints. However, very little is known regarding specific biological marker for RA in Chinese patients. In this study, we determined the serum biomarkers and clinical features of RA-CVD. We also evaluated the short-term efficacy of routine RA treatment combined with integrative medicine treatment on RA-CVD. We found that anti-cyclic citrullinated peptide (CCP) and disease activity score in 28 joints (DAS28) are associated with risks of cardiovascular disease (CVD) in RA. And, melatonin (MLT) may play a negative regulatory role in cardiovascular damage in patients with RA. Furthermore, endothelin (ET-1) and inflammatory markers may be subclinical cardiovascular damages in RA. Moreover, of the 17 patients with RA-CVD, test results of ET-1, TNF-α and OSCAR after integrative medicine treatment were significantly decreased than before treatment. Collectively, our results provide a therapeutic potential of integrative medicine to the treatment of RA-CVD.

Comparison of the impact of Tripterygium wilfordii Hook F and Methotrexate treatment on radiological progression in active rheumatoid arthritis: 2-year follow up of a randomized, non-blinded, controlled study.

BACKGROUND: Tripterygium wilfordii Hook F (TwHF) alone or in combination with methotrexate (MTX) has been shown to be more effective than MTX monotherapy in controlling the manifestations in subjects with disease-modifying antirheumatic drug (DMARD)-naïve active rheumatoid arthritis (RA) over a 6-month period. The long-term impact of these therapies on disease activity and radiographic progression in RA has not been examined. METHODS: Patients with DMARD-naïve RA enrolled in the "Comparison of Tripterygium wilfordii Hook F with methotrexate in the Treatment of Active Rheumatoid Arthritis" (TRIFRA) study were randomly allocated into three arms with TwHF or MTX or the two in combination. Clinical indexes and radiographic data at baseline and year 2 was collected and compared using an intent-to-treat (ITT) and a per-protocol (PP) analysis. Two radiologists blinded to the treatment scored the images independently. RESULTS: Of 207 subjects 109 completed the 2-year follow up. The number of subjects withdrawing from the study and the number adhering to the initial regimens were similar among the three groups (p > = 0.05). In the ITT analysis, proportions of patients reaching American College of Rheumatology 50% (ACR50) response criteria were 46.4%, 58.0% and 50.7% in the MTX, TwHF and MTX + TwHF groups (TwHF vs MTX monotherapy, p = 0.004). Similar patterns were found in ACR20, ACR70, Clinical Disease Activity Index good responses, European League Against Rheumatism good response, remission rate and low disease activity rate at year 2. The results of the PP analysis agreed with those in the ITT analysis. The changes in total Sharp scores and joint erosion and joint space narrowing during the 2 years were associated with changes in disease activity measured by the 28-joint count Disease Activity Score and were comparable among the three groups (p > 0.05). Adverse events were similar in the three treatment groups. CONCLUSIONS: During the 2-year therapy period, TwHF monotherapy was not inferior to MTX monotherapy in controlling disease activity and retarding radiological progression in patients with active RA. TRIAL REGISTRATION: This is a follow-up study. Original trial registration: ClinicalTrials.gov , NCT01613079 . Registered on 4 June 2012.

Comparison of Tripterygium wilfordii Hook F with methotrexate in the treatment of active rheumatoid arthritis (TRIFRA): a randomised, controlled clinical trial.

OBJECTIVES: To compare the efficacy and safety of Tripterygium wilfordii Hook F (TwHF) with methotrexate (MTX) in the treatment of active rheumatoid arthritis (RA). METHODS: Design: a multicentre, open-label, randomised controlled trial. All patients were assessed by trained investigators who were unaware of the therapeutic regimen. INTERVENTION: 207 patients with active RA were randomly allocated (1:1:1) to treatment with MTX 12.5 mg once a week, or TwHF 20 mg three times a day, or the two in combination. At week 12, if reduction of the 28-joint count Disease Activity Score (DAS28) was <30% in the monotherapy groups, the patient was switched to MTX+TwHF. The primary efficacy point was the proportion of patients achieving an American College of Rheumatology (ACR) 50 response at week 24. RESULTS: 174/207 (84.1%) patients completed 24 weeks of the trial. In an intention-to-treat analysis, the proportion of patients reaching the ACR50 response criteria was 46.4% (32/69), 55.1% (38/69) and 76.8% (53/69), respectively, in the MTX, TwHF and MTX+TwHF groups (TwHF vs MTX monotherapy, p=0.014; MTX+TwHF vs MTX monotherapy, p<0.001). Similar statistically significant patterns at week 24 were found for ACR20, ACR70, clinical Disease Activity Index good responses, EULAR good response, remission rate and low disease activity rate. Significant improvement in the Health Assessment Questionnaire and 36-item Short-Form Health Survey questionnaire scores from baseline to week 24 was seen in each treatment arm (p<0.05), though no significant difference was found among the treatment arms (p>0.05). The result of per-protocol analysis agreed with that seen in the intention-to-treat analysis. Seven, three and five women in the TwHF, MTX and combination groups, respectively, developed irregular menstruation (TwHF vs MTX monotherapy, p=0.216). CONCLUSIONS: TwHF monotherapy was not inferior to, and MTX+TwHF was better than, MTX monotherapy in controlling disease activity in patients with active RA. TRIAL REGISTRATION NUMBER: NCT01613079.

Societal costs of rheumatoid arthritis in China: a hospital-based cross-sectional study.

OBJECTIVE: To estimate the annual direct and indirect costs of rheumatoid arthritis (RA) in China and identify the predictors for cost of illness. METHODS: A cross-sectional study of cost of illness from the societal perspective was conducted on 829 patients with RA in 21 tertiary care hospitals in China between July 2009 and December 2010. Data on demographics, clinical variables, and components of costs were collected by physician interview. Costs were represented in 2009 US dollars using purchasing power parity estimates. Univariate and multivariate linear regression analyses were performed to identify the predictors for cost of illness. RESULTS: The mean ± SD total cost of RA in China was $3,826 ± $5,659 per patient-year, given a gross domestic product per capita of $6,798 in China in 2009. Direct costs and indirect costs comprised 90.0% and 10.0% of the total costs, respectively. Drug expense represented approximately half of the total costs, dominated by biologic agents (48.2%) and disease-modifying antirheumatic drugs (23.5%). Additionally, the cost of extracted herbal drugs and traditional Chinese medicine comprised ∼17.6% of the drug expense. Higher education level, noninsured status, longer disease duration, more extraarticular manifestations, and higher Health Assessment Questionnaire score independently predicted higher total costs. CONCLUSION: Our results provide the first study of costs of RA in China. This study not only demonstrates the economic burden of RA, but also identifies the predictors that could be interventional factors to reduce the societal costs of RA in China.

[Clinical effect analysis of ankylosing spondylitis treated by Chinese medical syndrome differentiation].

OBJECTIVE: To evaluate the curative effect and safety of Bushen Qiangji Decoction (BQD) and Qingre Qiangji Decoction (QQD) in treating ankylosing spondylitis (AS) patients, and to verify the clinical utility of AS syndrome differentiation and treatment scheme [Shen-deficiency induced stasis obstruction syndrome (SDISOS) and dampness-heat obstruction syndrome (DHOS) being two basic syndrome types, Shen invigorating blood activating method (SIBAM) and heat clearing dampness resolving method (HCDRM) being two basic treatment methods]. METHODS: Totally 354 AS patients of SDISOS and DHOS were randomly assigned to the treatment group and the control group using a multi-center randomized, positive drug parallel-controlled clinical trail. Patients in treatment group were treated by BQD or QQD according to syndrome typing, while those in the control group took Sulfasalazine enteric-coated tablet (SECT), 24 weeks as one therapeutic course. After treatment, the clinical efficacy was evaluated by using ASAS20 standard (set by Asessment in Ankylosing Spondylitis working group), Chinese medical efficacy evaluation standards, and BASDAI, BASFI, BASMI, night-pain index, spinal pain index, PGA, C-reactive protein (CRP), and erythrocyte sedimentation rate (ESR). RESULTS: After 24 weeks of treatment by BQD or QQD, ASAS20 standard rate was 86.75% in the treatment group, and the total effective rate of Chinese medical syndrome was 85.47%. They could significantly reduce patients' integrals of Chinese medical syndrome, BASDAI, BASFI, BASMI, night-pain index, spinal pain index, and PGA (all P < 0.01). CONCLUSIONS: QQD and BQD got confirmable clinical effects in treating AS, providing strong evidence of evidence-based medicine for syndrome differentiation and treatment of AS.

[Protective mechanism on the vascular pathological process in diabetes mellitus rats by Rheum officeinale].

OBJECTIVE: To explore the protective mechanism of officeihale on the vascular pathological process in diabetes mellitus (DM) rats. METHOD: After the DM rat model was established, 24 DM rats were randomly divided into model group (12 DM rats) and Rheum officeinale group (12 DM rats). Rheum officeinale was orally given in 10 g kg(-1) per day, and the other two groups were given equal pure water. 8 weeks later, blood samples were collected to determine the level of nitric oxide (NO) and endothelin-1 (ET-1). Thoracic aortic rings was prepared to observe the inhibiting effect of Ach with different concentration on contraction caused by NE. Another part of aorta was made to observe the expression of ICAM-1 and VCAM-1 by method of SP immunohistochemistry staining, RESULT: Rheum officeinale group obviously decreased the level of ET-1 and increased the NO compared with model group (P <0.05). The expression of ICAM-1 and VCAM-1 could be obviously inhibited in Rheum officeinale group compared with model group. (P <0.05). CONCLUSION: Rheum officeinale could decrease the level of ET-1 with increased the NO in diabetes rats, and inhibit the expression of ICAM-1 and VCAM-1, which may be mechanisms of protecting the endothelium of vessel in diabetes rats.

[An animal model of alcoholic fatty liver and the prevention and treatment with New Qinggan Decoction].

OBJECTIVE: To establish an animal model of alcoholic fatty liver (AFL) and to observe the prevention and treatment with New Qinggan Decoction (NQGD). METHODS: Female SD rats were exposed to the mixture of white spirit and corn oil continuously for up to 6 weeks via an intragastric feeding protocol. The pathologic alteration of the liver and the changes of serum lipid were observed, and the effect of NQGD for preventing and treating AFL was studied. RESULTS: Wide hepatic steatosis was induced in model group rats. Serum triglyceride (TG) and total cholesterol (TC) of the model group were higher than those of the normal group (P<0.01). Serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) of the model group were higher than those of the normal group (P<0.05). In NQGD group, hepatic steatosis was milder than that in the model group, and serum TG, TC, AST, ALT descended significantly as compared with the model group (P<0.01). CONCLUSION: AFL model of rats established by feeding the mixture of white spirit and corn oil is similar to the episode of the human AFL, and is easy to intervene with medicine. NQGD can prevent the occurrence of AFL in this model.