Publications by authors named "Dong-Yi He"

20 Publications

  • Page 1 of 1

Epidemiology of Takayasu arteritis in Shanghai: A hospital-based study and systematic review.

Int J Rheum Dis 2021 Jul 27. Epub 2021 Jul 27.

Department of Renal and Rheumatology, Xinhua Hospital Affiliated To Shanghai JiaoTong University School of Medicine, Shanghai, China.

Background: Takayasu arteritis (TAK) is a rare large vessel vasculitis, and epidemiological data on TAK are lacking in China. Thus, we designed this study to estimate the TAK prevalence and incidence in residential Shanghai, China.

Methods: Data on diagnosed TAK cases aged over 16 years were retrieved from 22 tertiary hospitals in Shanghai through hospital electronic medical record systems between January 1, 2015 and December 31, 2017 to estimate the prevalence and incidence. A systematic literature review based on searches in PubMed, Ovid-Medline, Excerpta Medica Database (EMBASE), Web of Science, and China National Knowledge Infrastructure (CNKI) was performed to summarize TAK distribution across the world.

Results: In total 102 TAK patients, with 64% female, were identified. The point prevalence (2015-2017) was 7.01 (95% CI 5.65-8.37) cases per million, and the mean annual incidence was 2.33 (1.97-3.21) cases per million. The average age of TAK patients was 44 ± 16 years, with the highest prevalence (11.59 [9.23-19.50] cases per million) and incidence (3.55 [0.72 3.74] cases per million) in the 16 to 34 years population. Seventeen reports were included in the system review, showing that the epidemiology of TAK varied greatly across the world. The incidence and prevalence were both relatively higher in Asian countries, with the prevalence ranging 3.3-40 cases per million and annual incidence ranging 0.34-2.4 cases per million.

Conclusions: The prevalence and incidence of TAK in Shanghai was at moderate to high levels among the previous reports. The disease burden varied globally among racial populations.
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http://dx.doi.org/10.1111/1756-185X.14183DOI Listing
July 2021

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

Front Pharmacol 2021 25;12:679588. Epub 2021 May 25.

Guang'anmen Hospital China Academy of Chinese Medical Sciences, Beijing, China.

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 ( < 0.0001); the score was lowest in the TCM group ( < 0.05), while no difference was observed between the WM and IM groups ( > 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], > 0.05); ACR-50 responses were 40.87, 47.93, and 51.26%, respectively, (FAS, > 0.05); and ACR-70 responses were 20.87, 22.31, and 25.21%, respectively, (FAS, > 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 ( < 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.
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http://dx.doi.org/10.3389/fphar.2021.679588DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8186316PMC
May 2021

A double-blind, double-dummy, randomized controlled, multicenter trial of 99Tc-methylene diphosphonate in patients with moderate to severe rheumatoid arthritis.

Chin Med J (Engl) 2021 May 19;134(12):1457-1464. Epub 2021 May 19.

Department of Rheumatology, Renji Hospital of Shanghai Jiaotong University School of Medicine, Shanghai 200000, China.

Background: Clinical observational studies revealed that 99Tc-methylene diphosphonate (99Tc-MDP) could reduce joint pain and swollenness in rheumatoid arthritis (RA) patients. This multicenter, randomized, double-blind, double-dummy study aimed to evaluate the effects of 99Tc-MDP plus methotrexate (MTX) vs. MTX alone or 99Tc-MDP alone on disease activity and structural damage in MTX-naïve Chinese patients with moderate to severe RA.

Methods: Eligible patients with moderate to severely active RA were randomized to receive 99Tc-MDP plus MTX (n = 59) vs. MTX (n = 59) alone or 99Tc-MDP (n = 59) alone for 48 weeks from six study sites across four provinces in China. The primary outcomes were the American College of Rheumatology 20% improvement (ACR20) response rates at week 24 and changes in modified total Sharp score at week 48.

Results: At week 24, the proportion of participants achieving ACR20 was significantly higher in the MTX + 99Tc-MDP combination group (69.5%) than that in the MTX group (50.8%) or 99Tc-MDP group (47.5%) (P = 0.03 for MTX + 99Tc-MDP vs. MTX, and MTX + 99Tc-MDP vs.99Tc-MDP, respectively). The participants in the MTX + 99Tc-MDP group and the 99Tc-MDP group had significantly less important radiographic progression than the participants in the MTX group over the 48 weeks (MTX + 99Tc-MDP vs. MTX: P = 0.03, 99Tc-MDP vs. MTX: P = 0.03, respectively). There was no significant difference in terms of adverse events (AEs) among the groups. No serious AEs were observed.

Conclusions: This study demonstrated that the combination of 99Tc-MDP with MTX inhibited structural damage and improved disease activity in RA patients compared with MTX and 99Tc-MDP monotherapies, without increasing the rate of AEs. Additional clinical studies of 99Tc-MDP therapy in patients with RA are warranted.

Trial Registration: Chictr.org, ChiCTR-IPR-14005684; http://www.chictr.org.cn/showproj.aspx?proj=10088.
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http://dx.doi.org/10.1097/CM9.0000000000001527DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8213301PMC
May 2021

Pharmacological Treatment of Osteoporosis in Elderly People: A Systematic Review and Meta-Analysis.

Gerontology 2021 Apr 6:1-11. Epub 2021 Apr 6.

Hospital Infection Control Center, The Second Xiangya Hospital of Central South University, Changsha, China.

Background: The evidence supporting the use of antiresorptive and anabolic agents for fracture prevention in elderly patients is still inconclusive. Whether it is too late to alter the course of the disease in this age-group has remained uncertain.

Objectives: The objective of this study was to determine the efficacy and safety of antiresorptive and anabolic agents in elderly patients.

Methods: PubMed, Web of Science, MEDLINE, and the Cochrane Central Register of Controlled Trials were searched for randomized controlled trials (RCTs) and post hoc analyses of RCTs reporting efficacy outcomes or adverse events of antiresorptive and anabolic agents in elderly patients. Statistical heterogeneity was assessed with the Cochran Q χ2 test and I2 statistic. All results were expressed as relative risk (RR) with 95% confidence intervals (CIs).

Results: The meta-analysis included 1 RCT and 11 post hoc analyses of data from 10 double-blind placebo-controlled RCTs. Antiresorptive therapy significantly reduced the pooled incidence of vertebral fractures (RR = 0.43; 95% CI = 0.35-0.53; and p < 0.001). It was also associated with lower risk of nonvertebral and hip fractures (RR = 0.84; 95% CI = 0.74-0.96; and p = 0.009 and RR = 0.75; 95% CI = 0.58-0.97; and p = 0.028, respectively). For any adverse events, no difference was observed between antiresorptive agents and placebo groups (RR = 1.01; 95% CI = 1.00-1.02; and p = 0.23).

Conclusions: Both antiresorptive and anabolic agents represented potentially important osteoporosis treatments, showing significant effects on reducing vertebral, nonvertebral, or hip fracture risk, and were well-tolerated by elderly patients. Even in the elderly, maybe it is not too late to alter the course of the disease.
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http://dx.doi.org/10.1159/000514449DOI Listing
April 2021

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

Front Pharmacol 2020 14;11:608703. Epub 2021 Jan 14.

Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, China.

Hook F (HF) is one of the most commonly used and effective traditional Chinese herbal medicines against rheumatoid arthritis (RA). Both Tripterygium Glycoside Tablets (TGT) and Tablets (TWT) are the representative HF-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 HF 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 HF-based agents.
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http://dx.doi.org/10.3389/fphar.2020.608703DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7845140PMC
January 2021

Rapid Onset of Efficacy of Baricitinib in Chinese Patients with Moderate to Severe Rheumatoid Arthritis: Results from Study RA-BALANCE.

Adv Ther 2021 01 25;38(1):772-781. Epub 2020 Nov 25.

Eli Lilly and Company, Shanghai, China.

Introduction: Baricitinib is an oral, selective inhibitor of Janus kinase which demonstrates clinical efficacy in patients with rheumatoid arthritis (RA). This report aims to analyze the onset time of baricitinib in Chinese patients with moderately to severely active RA who had an inadequate response to methotrexate.

Methods: This post hoc analysis evaluated clinical improvements of Chinese patients treated with baricitinib 4 mg once daily compared with placebo, based on data from a phase 3 study RA-BALANCE. Efficacy measures including American College of Rheumatology 20% (ACR20) response, ACR core set values, Disease Activity Score modified to include the 28 diarthrodial joint count (DAS28) using high-sensitivity C-reactive protein (hsCRP), DAS28-erythrocyte sedimentation rate, Simplified Disease Activity Index, Clinical Disease Activity Index, DAS28-hsCRP ≤ 3.2 response (low disease activity), and Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) were evaluated at weeks 1, 2, 4, 8, 12, 14, 16, 20, and 24 (except for FACIT-F evaluated every 4 weeks). A logistic regression model and an analysis of covariance model were used to analyze treatment comparisons of categorical and continuous measures, respectively.

Results: Statistically significant (p ≤ 0.05) improvements were observed as early as week 1 or 2 for the baricitinib group compared to placebo in almost all main efficacy measures. For other outcomes including 66 swollen joint count, 68 tender joint count, FACIT-F, and DAS28-hsCRP ≤ 3.2 response rate, differences were evident (p ≤ 0.05) by week 4 in the baricitinib group compared with placebo. Significant improvements in all efficacy measures were sustained through 24 weeks.

Conclusions: Baricitinib demonstrated a rapid onset of efficacy on ACR20 response, ACR core set values, disease activity, and patient-reported outcome improvements in Chinese patients from RA-BALANCE.

Trial Registration: ClinicalTrials.gov identifier, NCT02265705.
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http://dx.doi.org/10.1007/s12325-020-01572-yDOI Listing
January 2021

Efficacy and Safety of Baricitinib in Chinese Rheumatoid Arthritis Patients and the Subgroup Analyses: Results from Study RA-BALANCE.

Rheumatol Ther 2020 Dec 2;7(4):851-866. Epub 2020 Sep 2.

Peking University People's Hospital, Beijing, China.

Introduction: Baricitinib is an oral selective inhibitor of Janus kinase (JAK) 1 and JAK 2, which has demonstrated significant efficacy in patients with moderately to severely active rheumatoid arthritis (RA). This analysis aims to describe the efficacy and safety of baricitinib in Chinese RA patients with an inadequate response to methotrexate (MTX-IR), and to analyze the effects of baseline characteristics on the efficacy of baricitinib treatment.

Methods: In this 52-week, randomized, double-blind, placebo-controlled study, 231 Chinese patients with moderately to severely active RA who had MTX-IR were randomly assigned to placebo (n = 115) or baricitinib 4 mg once daily (n = 116). The primary endpoint was American College of Rheumatology 20% (ACR20) response at week 12. Other efficacy measures included ACR50, ACR70, Physician's Global Assessment of Disease Activity, Patient's Global Assessment of Disease Activity, patient's assessment of pain, Disease Activity Score in 28 joints using high-sensitivity C-reactive protein, remission and low disease activity rates according to Simplified Disease Activity Index or Clinical Disease Activity Index, Health Assessment Questionnaire-Disability Index, and mean duration and severity of morning joint stiffness, worst tiredness and worst joint pain were analyzed. Additionally, subgroup analyses were performed across baseline characteristics.

Results: Statistically significant improvement in ACR20 response was achieved with baricitinib at week 12 (53.4 vs. 22.6%, p = 0.001) in Chinese patients, compared to placebo. Most of the secondary objectives were met with statistically significant improvements. Efficacy of baricitinib was irrespective of patient demographics and baseline characteristics. Safety events were similar between the baricitinib and placebo groups.

Conclusions: The efficacy of baricitinib 4 mg in Chinese patients with moderately to severely active RA and prior MTX-IR was clinically significant compared to placebo regardless of baseline characteristics. Baricitinib was well tolerated with an acceptable safety profile during the full study period.

Trial Registration: NCT02265705.
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http://dx.doi.org/10.1007/s40744-020-00231-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7695798PMC
December 2020

Anti-cyclic citrullinated peptide antibody predicts the development of rheumatoid arthritis in patients with undifferentiated arthritis.

Chin Med J (Engl) 2019 Dec;132(24):2899-2904

Department of Rheumatology and Immunology, Hebei General Hospital, Shijiazhuang, Hebei 050051, China.

Background: Clinical outcomes of undifferentiated arthritis (UA) are diverse, and only 40% of patients with UA develop rheumatoid arthritis (RA) after 3 years. Discovering predictive markers at disease onset for further intervention is critical. Therefore, our objective was to analyze the clinical outcomes of UA and ascertain the predictors for RA development.

Methods: We performed a prospective, multi-center study from January 2013 to October 2016 among Chinese patients diagnosed with UA in 22 tertiary-care hospitals. Clinical and serological parameters were obtained at recruitment. Follow-up was undertaken in all patients every 12 weeks for 2 years. Predictive factors of disease progression were identified using multivariate Cox proportional hazards regression.

Results: A total of 234 patients were recruited in this study, and 17 (7.3%) patients failed to follow up during the study. Among the 217 patients who completed the study, 83 (38.2%) patients went into remission. UA patients who developed RA had a higher rheumatoid factor (RF)-positivity (42.9% vs. 16.8%, χ = 8.228, P = 0.008), anti-cyclic citrullinated peptide (CCP) antibody-positivity (66.7% vs. 10.7%, χ = 43.897, P < 0.001), and double-positivity rate of RF and anti-CCP antibody (38.1% vs. 4.1%, χ = 32.131, P < 0.001) than those who did not. Anti-CCP antibody but not RF was an independent predictor for RA development (hazard ratio 18.017, 95% confidence interval: 5.803-55.938; P < 0.001).

Conclusion: As an independent predictor of RA, anti-CCP antibody should be tested at disease onset in all patients with UA.
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http://dx.doi.org/10.1097/CM9.0000000000000570DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6964957PMC
December 2019

Regulatory effect of anti-gp130 functional mAb on IL-6 mediated RANKL and Wnt5a expression through JAK-STAT3 signaling pathway in FLS.

Oncotarget 2018 Apr 4;9(29):20366-20376. Epub 2018 Jan 4.

Shanghai Institute of Immunology, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

We investigated the effect on rheumatoid arthritis (RA) of an anti-gp130 monoclonal antibody (mAb) and its mechanism using RA fibroblast-like synoviocytes (FLS) and a collagen antibody-induced arthritis (CAIA) mouse model. We determined the interleukin 6 (IL-6), IL-6 receptor α (IL-6Rα), gp130, receptor activator of nuclear factor κB ligand (RANKL), matrix metalloproteinase 3 (MMP3), TIMP metallopeptidase inhibitor 1 (TIMP1), and Bcl-2 levels in RA and osteoarthritis (OA) serum and synovial fluid. RA FLS were cultured with or without IL-6/IL-6Rα; WNT5A and RANKL levels were detected. We generated an anti-gp130 mAb (M10) with higher affinity and specificity, blocked IL-6 signaling with it, and assessed its effects on the CAIA model, and expression, and signal transducer and activator of transcription 3 (STAT3) phosphorylation. The IL-6 signaling system in patients with RA was increased; RANKL, MMP3, TIMP1, and Bcl-2 in RA bone were elevated. IL-6/IL-6Rα increased RA FLS and expression. M10 ameliorated arthritis in the CAIA model, and inhibited RANKL, WNT5A, and Bcl-2 expression in RA FLS by blocking IL-6 signaling, likely via Janus kinase-STAT3 pathway downregulation. The IL-6-soluble IL-6Rα-gp130 complex is hyperactive in RA and OA. M10 may be the basis for a novel RA treatment drug.
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http://dx.doi.org/10.18632/oncotarget.23917DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5945543PMC
April 2018

Genome-wide DNA methylation patterns in CD4+ T cells from Chinese Han patients with rheumatoid arthritis.

Mod Rheumatol 2017 May 1;27(3):441-447. Epub 2016 Sep 1.

a Department of Rheumatology , Shanghai Guanghua Hospital of Integrated Traditional and Western Medicine , Shanghai , China.

Introduction: Rheumatoid arthritis (RA) is an autoimmune disease that causes chronic inflammation of the joints. Recent evidence indicated the epigenetic changes may contribute to the pathogenesis of RA.

Method: To understand the extent and nature of dysregulated DNA methylation in RA CD4T cells, we performed a genome-wide DNA methylation study in CD4 + T cells in 12 RA patients compared to 12 matched normal healthy controls. Cytosine methylation status was quantified with Illumina methylation 450K microarray.

Result: The DNA methylation profiling showed 383 hyper- and 785 hypo-methylated genes in the CD4 + T cells of the RA patients (p < 3.4 × 10). Gene ontology analysis indicated transcript alternative splicing and protein modification mediated by DNA methylation might play an important role in the pathogenesis of RA. In addition, the result showed that human leukocyte antigen (HLA) region including HLA-DRB6, HLA-DQA1 and HLA-E was frequently hypomethylated, but HLA-DQB1 hypermethylated in CpG island region and hypomethylated in CpG shelf region in RA patients. Outside the MHC region, HDAC4, NXN, TBCD and TMEM61 were the most hypermethylated genes, while ITIH3, TCN2, PRDM16, SLC1A5 and GALNT9 are the most hypomethylated genes.

Conclusion: Genome-wide DNA methylation profile revealed significant DNA methylation change in CD4 + T cells from patients with RA.
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http://dx.doi.org/10.1080/14397595.2016.1218595DOI Listing
May 2017

The effects of dopamine receptor 2 expression on B cells on bone metabolism and TNF-α levels in rheumatoid arthritis.

BMC Musculoskelet Disord 2016 08 19;17:352. Epub 2016 Aug 19.

Department of Rheumatology, Zhongshan Hospital, Fudan University, No. 180, Road Fenglin, Shanghai, 200032, People's Republic of China.

Background: Dopamine receptor 2 (DR2) expressions on B cells from Rheumatoid arthritis (RA) patients has been found to be negatively correlated with disease activity and can potentially predict the response to treatment. This study aimed to investigate the role of B cell DR2 expression on bone remodeling in RA.

Methods: Patients with RA (n = 14) or osteoarthritis (OA; n = 12), and healthy controls (n = 12) were recruited for this study. Dopamine receptor (DR) 2 expression was assessed using flow cytometry. Pro-inflammatory cytokines, including interleuin(IL)-1β, IL-6, IL-17, and tumor necrosis factor(TNF)-α, and bone turnovers, including osteocalcin (OC),serum procollagen type I N propeptide (PINP), C-terminal telopeptide of type I collagen (β-CTX), collagen type I cross-linked telopeptide (ICTP), as well as matrix metalloproteinase-3 (MMP-3) and osteoprotegerin (OPG) were measured by electrochemiluminescence, chemiluminescence, or enzyme-linked immunosorbent assay. DR2 expression on synovial B cells from 4 RA patients and 3 OA patients was detected by immunofluorescence.

Results: There were more DR2(+)CD19(+) B cells in synovial tissues from RA patients than in those from OA patients. The frequency of peripheral B cells that expressed DR2 was positively correlated with plasma TNF-α level. Levels of ICTP and MMP-3 were significantly higher, and OPG were lower in RA patients compared to those in the OA group and healthy controls (all P < 0.05).

Conclusion: The frequency of B cells that expressed DR2 showed a correlation with levels of the pro-inflammatory cytokine TNF-α. DR2(+)CD19(+) B cells in synovial tissues might have a role in bone metabolism and TNF-α production.
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http://dx.doi.org/10.1186/s12891-016-1220-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4992283PMC
August 2016

Good response to infliximab in rheumatoid arthritis following failure of interleukin-1 receptor antagonist.

Int J Rheum Dis 2016 Apr 5;19(4):370-6. Epub 2014 May 5.

Department of Pediatrics, Xinhua Hospital Shanghai Jiaotong University School of Medicine, Shanghai, China.

Aim: To evaluate the efficacy of tumor necrosis factor inhibitor infliximab in patients with rheumatoid arthritis (RA) who were disease-resistant to recombinant human interleukin-1 receptor antagonist (IL-1Ra).

Methods: A total of 104 patients with active RA despite methotrexate (MTX) treatment were enrolled in the open trial. Among them, 27 IL-1Ra nonresponders 'Switchers' and 51 biologic-naive patients 'Naivers' received an infusion of 3 mg/kg infliximab at weeks 0, 2, 6 and 14, combined with concurrent MTX therapy, while the other 26 patients who had never received any biologics 'Controls' continued MTX monotherapy. Clinical outcomes and safety were assessed at weeks 0, 2 and every 4 weeks thereafter for 18 weeks with the American College of Rheumatology (ACR) core set criteria, the Disease Activity Score in 28 joints, and records of adverse events (AEs) and abnormal laboratory findings.

Results: At week 18, an ACR20 response was achieved in 56% of Switchers and 61% of Naivers, compared with 23% of Controls (P = 0.0013 and 0.0126, respectively). Compared with Controls, both Switchers and Naivers achieved a significant improvement in tender-joint count, swollen-joint count, patient's assessment of pain, patient's and physician's global assessment of disease activity, erythrocyte sedimentation rate and C-reactive protein. Switchers even achieved a greater benefit from health assessment questionnaire (HAQ) scores than Naivers. Infliximab was well tolerated, with a similar incidence of AEs across all study groups.

Conclusion: Switching from IL-1Ra to infliximab is effective in improving disease activity and maintaining joint function.
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http://dx.doi.org/10.1111/1756-185X.12387DOI Listing
April 2016

Expression of cannabinoid receptor 2 and its inhibitory effects on synovial fibroblasts in rheumatoid arthritis.

Rheumatology (Oxford) 2014 May 17;53(5):802-9. Epub 2014 Jan 17.

Department of Rheumatology and Immunology, Changhai Hospital, Second Military Medical University, 168 Changhai Road, Shanghai 200433, China.

Objective: Recent studies have suggested immunomodulatory and anti-inflammatory effects of cannabinoid receptor 2 (CB2R) activation, which shows no psychoactivity. However, it is still unclear whether CB2R is expressed in fibroblast-like synoviocytes (FLS) of RA. In this study we investigated whether CB2R is expressed in FLS of RA, and whether CB2R activation modulates the function of RA-FLS.

Methods: Expression of CB2R in synovial tissue and FLS was studied by immunohistochemistry, western blotting and RT-PCR. mRNA expression levels of CB2R, IL-6 and MMPs were analysed by quantitative real-time RT-PCR. The protein concentrations of IL-6 and MMPs in culture supernatants were determined by ELISA. The protein levels of signal transducing molecules were assayed by western blotting.

Results: Both mRNA and protein expression of CB2R were found in synovial tissue and cultured FLS with slightly higher levels in RA patients than in OA patients. In cultured RA-FLS, the expression level of CB2R was up-regulated by stimulation with IL-1β, TNF-α or lipopolysaccharide. In vitro, HU-308, a selective CB2R agonist, inhibited IL-1β-induced proliferation of RA-FLS as well as IL-1β-induced production of MMP-3, MMP-13 and IL-6 in RA-FLS in a dose-dependent manner. HU-308 also suppressed IL-1β-induced activation of extracellular signal-regulated kinase 1/2 and p38 mitogen-activated protein kinase in FLS.

Conclusion: In RA-FLS, proinflammatory mediators up-regulate the expression of CB2R, which negatively regulates the production of proinflammatory cytokines and MMPs. These data suggest that CB2R may be a potential therapeutic target of RA.
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http://dx.doi.org/10.1093/rheumatology/ket447DOI Listing
May 2014

[Effect of icariin on bone destruction and serum RANKL/OPG levels in type II collagen-induced arthritis rats].

Zhongguo Zhong Xi Yi Jie He Za Zhi 2013 Sep;33(9):1221-5

Basic Medicine Department of Rehabilitation, Rehabilitation College, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.

Objective: To observe the effect of Icariin (ICA) on serum receptor activator of NFkappaB-ligand (RANKL)/osteoprotegerin (OPG) production and bone destruction in type II collagen-induced arthritis (CIA) rats.

Methods: The CIA rat model was established in all rats, except those in the normal group (n = 8) using bovine type II collagen and complete Freund's adjuvant. Totally 24 CIA rats with arthritis index (AI) > or = 6 were selected and divided into the model group, the methotrexate (MTX) group, and the ICA group according to the AI score, 8 in each group. Normal saline was given to rats in the normal group and the model group by gastrogavage. MTX at the weekly dose of 5 mg/kg was given to rats in the MTX group. ICA at the daily dose of 20 mg/kg was given to rats in the ICA group. All medication lasted for 4 weeks. The AI scores were recorded once a week. Histomorphologic changes of the ankle joint were observed by HE staining. The bone destruction and the osteoporosis of the foot phalanx were detected by X-ray. Serum levels of RANKL and OPG were determined by enzyme-linked immunosorbent assay (ELISA).

Results: After 4-week intervention, when compared with the model group, AI score and Larsen score were significantly lower, the serum RANKL concentration and the RANKL/OPG ratio obviously decreased, while the serum OPG concentration obviously increased in the CIA group (P < 0.05, P < 0.01). In the MTX group, the aforesaid indices decreased, but without statistical difference (P > 0.05). Results of HE staining indicated that hyperplasia of joint synovium, infiltration of inflammatory cells, and the degree of articular cartilage destruction were obviously alleviated in the ICA group.

Conclusion: ICA could alleviate or lessen the degree of articular cartilage destruction in CIA rats, and its mechanism might be associated with reducing serum levels of RANKL and elevating levels of OPG, thus further decreasing the ratio of RANKL/OPG.
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September 2013

IL-18 upregulates the production of key regulators of osteoclastogenesis from fibroblast-like synoviocytes in rheumatoid arthritis.

Inflammation 2013 Feb;36(1):103-9

Changzheng Hospital, Second Military Medical University, Shanghai, China.

Recent data have demonstrated the importance of IL-18 in the induction and perpetuation of chronic inflammation in experimental arthritis. The aim of the present study was to elucidate whether IL-18 has any indirect effects on osteoclastogenesis by regulating the production of molecules from fibroblast-like synoviocytes (FLS) in rheumatoid arthritis (RA). Human FLS were isolated from RA synovial tissue and cultured in vitro for three to five passages. The expression of IL-18 receptor was determined by RT-PCR. The levels of soluble receptor activator of nuclear factor κB ligand (RANKL), osteoprotegerin (OPG), macrophage colony-stimulating factor (M-CSF), and granulocyte-macrophage colony-stimulating factor (GM-CSF) in culture supernatants were determined by ELISA. Membrane-bound RANKL expression was analyzed by flow cytometry. Both α and β chains of IL-18 receptor were confirmed in cultured FLS. IL-18 upregulated membrane-bound RANKL expression and soluble RANKL production by FLS in both time- and dose-dependent manners. In addition, IL-18 enhanced production of M-CSF, GM-CSF, and OPG from cultured FLS in a dose-dependent manner. IL-18 also increased the ratio of RANKL/OPG, suggesting that the net effect of IL-18 on FLS favors for the induction of osteoclast formation and bone resorption. In conclusion, IL-18 upregulates the production of key regulators of osteoclastogenesis from FLS in RA.
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http://dx.doi.org/10.1007/s10753-012-9524-8DOI Listing
February 2013

The risk factors for nosocomial infection in chinese patients with active rheumatoid arthritis in shanghai.

ISRN Rheumatol 2012 19;2012:215692. Epub 2012 Mar 19.

Department of Rheumatology and Immunology, Changhai Hospital, Second Military Medical University, Shanghai 200433, China.

Objective. To analyse the potential risk factors of nosocomial infections in patients with active rheumatoid arthritis (RA). Methods. A total of 2452 active RA patients at Hospitals in Shanghai between January 2009 and February 2011 were analyzed. Their demographic and clinical characteristics were compared with those without infection, and the potential risk factors were determined by logistic regression analysis. Results. Multivariate analysis indicated the gender (OR = 0.70, 95% CI 0.53-0.92), duration in hospital (OR = 1.03 , 95%CI 1.01-1.05), number of organs involved (OR = 0.82, 95%CI 0.72-0.92), number of disease-modifying antirheumatic drugs ((DMARDs) (OR = 1.22, 95%CI 1.061-1.40)), corticosteroid therapy (OR = 1.02, 95%CI 1.01-1.03), peripheral white blood cell counts ((WBC) (OR = 1.04, 95%CI 1.00-1.08)), levels of serum albumin (OR = 0.98, 95%CI 0.97-0.99), and C-reactive protein ((CRP) (OR = 1.03 , 95%CI 1.01-1.04)) that were significantly associated with the risk of infections. Conclusion. The female patients, longer hospital stay, more organs involved, more DMARDs, corticosteroid usage, high counts of WBC, lower serum albumin, and higher serum CRP were independent risk factors of infections in active RA patients.
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http://dx.doi.org/10.5402/2012/215692DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3328155PMC
August 2012

[Significance of anti-cyclic citrullinated peptide antibody and magnetic resonance imaging of metacarpophalangeal joints and wrist in early rheumatoid arthritis].

Zhonghua Yi Xue Za Zhi 2011 Jun;91(23):1633-6

Department of Rheumatology, Shanghai Guanghua Hospital of Integrated Chinese & Western Medicine, Shanghai, China.

Objective: To study the diagnostic value of anti-cyclic citrullinated peptide antibody (anti-CCP) and magnetic resonance imaging (MRI) of metacarpophalangeal joints (MCP) and wrist in early rheumatoid arthritis (RA).

Methods: MRI of MCP and wrist joint, laboratory indices of anti-CCP and rheumatic factor (RF) were performed and recorded in the 94 early-stage RA patients, 24 non-typical monoarthritis and 35 other arthritis. The MRI findings and OMERACT (outcome measures in rheumatoid arthritis clinical trials) score were analyzed in comparison with their clinical and laboratory indices.

Results: The sensitivity of anti-CCP, synovitis, bone erosion and bone erosion was 55.3%, 100%, 25.5% and 88.3% respectively in early-stage RA patients. The specificity was 88.6%, 71.4%, 94.3% and 65.7% respectively. There was significant difference between early-stage RA group and other arthritis group (P < 0.05). Bone erosion was found to be the most specific among MRI findings. And bone erosion of wrist joint had a positive correlation with anti-CCP. MRI was a more efficient supplemental modality in diagnosing early-stage RA as compared with conventional radiological films. Among 94 early-stage RA, their MRI findings and OMERACT scores of wrist joint appeared more obvious.

Conclusion: Anti-CCP has a better specificity for early-stage RA than RF. But MRI may visualize the disorder of RA earlier while it is often missed by radiological films. Both have prominent diagnostic values in early RA patients. Bone erosion of wrist joint has a positive correlation with anti-CCP. MRI may help to differentiate those RA patients with negative anti-CCP.
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June 2011

Anti-inflammatory and immunomodulatory effects of paeonia lactiflora pall., a traditional chinese herbal medicine.

Front Pharmacol 2011 25;2:10. Epub 2011 Feb 25.

Department of Rheumatology, Shanghai Guanghua Hospital Shanghai, China.

In China, Korea, and Japan, a decoction of the dried root without bark of Paeonia lactiflora Pall. has been used in the treatment of rheumatoid arthritis, systemic lupus erythematosus, hepatitis, dysmenorrhea, muscle cramping and spasms, and fever for more than 1200 years. A water/ethanol extract of the root is now known as total glucosides of peony (TGP), which contains more than 15 components. Paeoniflorin is the most abundant ingredient and accounts for the pharmacological effects observed with TGP in both in vitro and in vivo studies. The analgesic effect of TGP was confirmed in various animal models of pain, which may be mediated partly by adenosine A1 receptor. The direct anti-inflammatory effects of TGP were observed in animal models of both acute and subacute inflammation, by inhibiting the production of prostaglandin E2, leukotriene B4, and nitric oxide, and by suppressing the increase of intracellular calcium ion concentration. TGP was also reported to have protective effects of cells against oxidative stress. In vitro, dual effects of TGP were noted on the proliferation of lymphocytes, differentiation of Th/Ts lymphocytes, and the production of proinflammatory cytokines and antibodies. In vivo, TGP inhibited the delayed-type hypersensitivity in immuno-activated mice, and enhanced the delayed-type hypersensitivity in immuno-suppressed mice. In adjuvant arthritis rats, paeoniflorin exerted immunosuppressive effects. The beneficial effects of TGP in treating rheumatoid arthritis were verified by randomized controlled trials. The adverse events of TGP were mainly gastrointestinal tract disturbances, mostly mild diarrhea.
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http://dx.doi.org/10.3389/fphar.2011.00010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3108611PMC
July 2011

[Treatment of gout by integrative medicine].

Zhongguo Zhong Xi Yi Jie He Za Zhi 2011 Apr;31(4):465

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April 2011

[Efficacy and safety of infliximab in patients with rheumatoid arthritis].

Zhonghua Yi Xue Za Zhi 2009 Jul;89(27):1876-80

Department of Rheumatology and Immunology, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100730, China.

Objective: To investigate the efficacy and safety of Infliximab (IFX) plus methotrexate (MTX) combination therapy in patients with rheumatoid arthritis (RA).

Methods: Prospectively observe refractory RA patients who were treated with combination therapy of MTX and IFX. IFX was infused at the dosage of 3 mg/kg, in week 0, 2, 6, and then every 8 weeks. During treatment, clinical variables, disease activity and adverse effects were evaluated.

Results: After treatment, 69.8%, 52.4%, 29.5% and 7.2% RA patients achieved ACR20, ACR50, ACR70 and ACR90 respectively. There were significant statistical differences in the changes of swollen joint counts, tender joint counts, VAS scale, patient' s global assessment, and physician's global assessment before and after therapy.

Conclusion: Infliximab plus MTX achieved significant efficacy and safety in refractory RA patients.
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July 2009
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