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Objective: To investigate the inhibition effect of dexamethasone with different concentration gradients on the expression of MMP-1, -3, and -13 in a bone joint cell model of IL-1β-induced SW1353 cells. Methods: The SW1353 cells were placed in a culture medium containing 101-108 nmol/L dexamethasone, and after 12 hours of culture, the appropriate intervention concentration range of dexamethasone was screened by the MTS for subsequent experiments. After SW1353 cells were induced with 10 ng/mL IL-1β, 101-107 nmol/L dexamethasone was given for intervention, and RT-PCR was used to detect the mRNA expression of MMP-1, -3, and -13. The protein was extracted after the intervention of 104 nmol/L dexamethasone, and western blot was used to detect the protein expression of MMP-1, -3, and -13. Results: MTS proliferation experiment results showed that 101-107 nmol/L dexamethasone had no significant effect on SW1353 cell viability, while 108 nmol/L dexamethasone had a significant inhibitory effect on SW1353 (p

OBJECTIVES A cross-sectional study was conducted in 270 Chinese patients with ankylosing spondylitis (AS) in order to identify potential risk factors for severity of spinal structural damage. METHODS Two hundred seventy AS patients fulfilled the Modified New York Criteria. Computed tomography (CT) was used to scan sacroiliac and hip joints, and radiography was used to scan anteroposterior and lateral lumbar spine, as well as lateral cervical spine. Bath Ankylosing Spondylitis Radiology Index and modified Stoke Ankylosing Spondylitis Spine Score (mSASSS) were scored in duplicate. RESULTS One hundred eighty-three patients had low mSASSS (mSASSS

To summarize the evidence from systematic reviews (SRs) on the benefits and safety of Tripterygium glycosides (TG) and total glucosides of paeony (TGP), commonly used to treat rheumatoid arthritis (RA) in China, for patients with RA. SRs of randomized controlled trials (RCTs) on TG or TGP in treating RA were included, by searching 8 databases from their inception until December 2017. Two authors extracted data independently. We assessed the quality of SRs using AMSTAR and graded the quality of evidence according to the GRADE approach. Eleven SRs containing an average of 7.6 RCTs, involving a total of 7,012 participants were included in this overview. On the basis of included SRs, TG and TGP could improve the following indexes for RA patients: American College of Rheumatology (ACR) 20 response rate, ACR50 response rate and ACR70 response rate, swollen joint count, tender joint count, erythrocyte sedimentation rate and C-reactive protein. Moreover, TGP could reduce incidence of hepatotoxicity. The most common adverse effects of TG were gastrointestinal discomfort and gonad toxicity, while for TGP was mild to moderate diarrhea. The overall quality of evidence for these findings ranged from “low” to “moderate”. TG and TGP might be 2 potentially effective complementary and alternative drugs for patients with RA. Nevertheless, due to gonad toxicity, TG should only be considered in elderly patients or patients without reproductive needs. More evidence from high quality RCTs and SRs is warranted to support the use of TG and TGP for RA patients.

Tripterygiumwilfordii 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.

Total flavonoids of Rhizoma Drynariae (TFRD) have been shown to have beneficial effects on osteoarthritis (OA) clinically, but the mechanisms have not been elucidated. In this study, we investigated the effect of TFRD on articular cartilage in an OA rat model established by the Hulth method and in SW1353 chondrocytes induced by the proinflammatory factor interleukin-1β (IL-1β). The results showed that TFRD could alleviate the pathological changes in knee cartilage in OA model rats. In vivo, the qPCR analysis indicated that the mRNA levels of matrix metalloproteinases, MMP-1, MMP-3, and MMP-13, were decreased, while tissue inhibitor of matrix metalloproteinases- (TIMP-) 4 was increased in cartilage, and these changes could be partially prevented by TFRD. In vitro experiments showed that IL-1β could significantly increase the expression of MMP-1, MMP-3, and MMP-13 and decrease the expression of TIMP-4 in SW1353 cells at the mRNA and protein levels. TFRD could increase the expression of MMP-3 and MMP-13 and decrease the expression of TIMP-4. Transfection of siRNA and addition of pathway inhibitors were used to clarify that inhibition of NF- κ B and PI3K/AKT pathway decreased MMP-1, MMP-3, and MMP-13 and increased TIMP-4 expression. We also found that in IL-1β-induced SW1353 cells, TFRD pretreatment had a modest inhibitory effect on p-AKT (Ser473) and reversed the increase of nuclear factor kappa-B (NF- κ B ) p65 in nuclear fraction and the decrease of inhibitor of NF- κ B I κ B - α in the cytosolic fraction. Further immunofluorescence confirmed that TFRD can inhibit IL-1β-induced NF- κ B p65 translocation to the nucleus to some extent. In conclusion, TFRD showed chondroprotective effects by restoring the MMP/TIMP balance in OA models by suppressing the activation of the NF- κ B and PI3K/AKT pathways.

Objectives: We quantified the expression of six well-characterized microRNAs (miRNAs) in peripheral blood mononuclear cells to see whether they can predispose to syndesmophytes in ankylosing spondylitis (AS) patients. Methods: This is a cross-sectional study involving 46 AS patients (23/23 with/without syndesmophytes) and 22 healthy controls. miRNAs expression was quantified by real-time PCR. Results: Six examined miRNAs were comparably expressed between AS patients without syndesmophytes and healthy controls (p > .05). Relative to AS patients without syndesmophytes, patients with syndesmophytes had significantly higher levels of miR-29a, miR-335-5p, miR-27a and let-7i (p = .001, .002, .013 and .029, respectively). Nine significant contributors associated with syndesmophytes in AS, including smoking, AS duration, human leukocyte antigen B27, erythrocyte sedimentation rate, C-reactive protein, miR-335-5p, miR-27a, miR-218 and sacroiliitis, were identified. The addition of miR-335-5p, miR-27a and miR-218 can significantly improve the accuracy of baseline risk factors. Based on the nine significant contributors, a nomogram was constructed, with good prediction accuracy (C-index: 0.86, p Conclusion: We provide evidence for the predisposition of miR-335-5p, miR-27a and miR-218 to syndesmophytes in AS patients, indicating a contributory role of miRNAs in the pathogenesis of syndesmophytes. Further validation is warranted.

Background Total glucosides of paeony (TGP) is commonly used to treat rheumatoid arthritis (RA) in China. However, clinical practice hasn’t been well informed by evidence from appropriately conducted systematic reviews. This PRISMA-compliant systematic review aims at examining the effectiveness and safety of TGP for RA. Methods Randomized controlled trials (RCTs) comparing TGP with placebo, no treatment, or disease-modifying antirheumatic drugs (DMARDs) for patients with RA were retrieved by searching seven databases. Primary outcomes included disease improvement and disease remission. Secondary outcomes included adverse effects, pain, health-related quality of life, C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR). Data extraction and analyses were conducted according to the Cochrane standards. We assessed risk of bias for each included studies and quality of evidence on pre-specified outcomes. Results Eight studies enrolling 1209 patients with active RA were included in this systematic review. On the basis of traditional DMARD(s), TGP might be beneficial for patients with RA in improvement of American College of Rheumatology (ACR) 20 response rate, ACR 50 response rate, ACR70 response rate, and in reduction of adverse effects, compared with no treatment. The overall methodological quality of included studies and the quality of evidence for each outcome were limited. Conclusions Current trials suggested potential benefits of TGP for RA on the basis of traditional DMARD(s). Therefore, TGP may be a good choice for RA as an adjuvant therapy. However, considering the limited methodological quality and strength of evidence, high-quality RCTs are warranted to support the use of TGP for RA.

To observe the therapeutic efficacy and safety of Gubitong Recipe (骨痹通方, GBT) in treating osteoarthritis (OA) of knee joint. Ninety patients with knee osteoarthritis were equally assigned, according to a randomizing digital table, to the treatment group and the control group. The treatment group was treated with GBT Decoction one dose every day and the control group with glucosamine sulfate 500 mg thrice a day, respectively, for eight successive weeks. Besides, diclofenac sodium could be given as supplementary dugs with the dosage used recorded if necessary. Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC, an index reflecting the degree of joint pain, stiffness, and dysfunction) in patients was assessed before and after treatment, and the patients’ symptoms were evaluated by visual analogue scale (VAS) as well. Moreover, erythrocyte sedimentation rate (ESR), blood C-reactive protein (CRP), blood and urinary routine tests, liver and kidney function examination, and the adverse reaction that occurred during the treatment period were observed. WOMAC index and integral VAS value were lowered in both groups after treatment, showing significant statistical difference as compared with before treatment (P

Introduction: Total glucosides of paeony (TGP) is a natural plant extract, which is widely used in China for treating rheumatoid arthritis (RA). Many relevant randomised controlled trials (RCTs) of TGP for RA are available, but they have not been systematically reviewed. This systematic review aims to examine the effectiveness and safety of TGP in patients with RA. Methods and analyses: We will search for RCTs of TGP in the treatment of RA, performed up until February 2016, in PubMed, Embase, Cochrane Central Register of Controlled Trials, and four Chinese databases (Chinese Biomedical Database, China National Knowledge Infrastructure, Wanfang Database and Chinese Scientific Journal Database). Trial registers and reference lists of retrieved articles will also be searched to identify potential articles. RCTs comparing TGP with placebo, no treatment, or disease-modifying antirheumatic drugs for patients with RA will be retrieved. The primary outcomes will be disease improvement and disease remission. The secondary outcomes will be surrogate outcomes, symptoms, adverse effects, and quality of life. Two reviewers will independently extract data on participants, interventions, comparisons, outcomes, etc. The methodological quality of each included study will be evaluated using the Cochrane risk of bias tool, and the strength of evidence on prespecified outcomes will be assessed in accordance with the GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach. Review Manager 5.3 software will be used for data analyses. Meta-analyses will be performed if the data are sufficiently homogeneous, both statistically and clinically. Possible publication bias will also be checked using funnel plots once the number of included studies is sufficient. Ethics and dissemination: Ethics approval is not required, as this study will not involve patients. The results of this study will be submitted to a peerreviewed journal for publication, to inform both clinical practice and further research. Trial registration number: CRD42015026345.