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Chinese registry of rheumatoid arthritis: IV. Correlation and consistency of rheumatoid arthritis disease activity indices in China

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Chinese Medical Journal 2021年第12期134卷 1465-1470页

作者： Xing Song Yan-Hong Wang Meng-Tao Li Xin-Wang Duan Hong-Bin Li Xiao-Feng Zeng the Co-authors of CREDIT Peking Union Medical College and Chinese Academy of Medical Sciences Beijing 100730China Department of Epidemiology and Bio-statistics Institute of Basic Medical SciencesChinese Academy of Medical Sciences&Peking Union Medical CollegeBeijing 100005China Department of Rheumatology Peking Union Medical College Hospital(PUMCH)Peking Union Medical College&Chinese Academy of Medical SciencesNational Clinical Research Center for Dermatologic and Immunologic Diseases(NCRC-DID)Ministry of Science&TechnologyKey Laboratory of Rheumatology and Clinical ImmunologyMinistry of EducationState Key Laboratory of Complex Severe and Rare DiseasesMinistry of Science&TechnologyBeijing 100730China Department of Rheumatology The Second Affiliated Hospital of Nanchang UniversityNanchangJiangxi 330006China Department of Rheumatology The Affiliated Hospital of Inner Mongolia Medical CollegeHohhotInner Mongolia 010050China 不详

Background:Disease activity indices(DAIs)including disease activity score 28(DAS28),simplified disease activity index(SDAI),and clinical disease activity index(CDAI)have been widely used in clinical practice and research studies of rheumatoid arthritis(RA).The objective of our study was to evaluate the correlation and concordance among different DAIs in Chinese patients with ***:A cross-sectional study,including patients enrolled in the Chinese registry of rheumatoid arthritis from November 2016 to August 2018,was *** correlations were evaluated using Spearman correlation coefficient and concordance with Bland-Altman plots,quadratic weighted kappa,and discordance rates in the *** other indices,the optimal cutoff points corresponding to SDAI remission were explored through receiver operating characteristic curve ***:A total of 30,501 patients were included,of whom 80.46%were *** individuals were with moderate disease activity or high disease *** correlations among DAS28-erythrocyte sedimentation rate(ESR)and DAS28-C-reactive protein(CRP),SDAI and CDAI were ***,the weighted kappa value among the indices was *** Bland-Altman plots,a positive difference between DAS28-ESR and DAS28-CRP was observed,with an absolute difference of>1.2 in 3079(10.09%)*** crosstab,approximately 30%of the patients were classified into different *** values between SDAI remission and the optimal cutoff points of DAS28-ESR,DAS28-CRP,and CDAI were 3.06,2.37,and 3.20,***:Although DAIs had high correlations and weighted kappa values,the discordance between DAIs was significant in Chinese patients with *** four DAIs are not interchangeable.

关键词： Disease activity indices rheumatoid arthritis Chinese registry of rheumatoid arthritis

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Chemokines and Chemokine Receptors as Novel Therapeutic Targets in rheumatoid arthritis (RA):Inhibitory Effects of Traditional Chinese Medicinal Components

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Cellular & Molecular Immunology 2004年第5期1卷 336-342页

作者： XinChen JoostJ.Oppenheim O.M.ZackHoward BasicResearchProgram SAIC-FrederickIncUSA. LaboratoryofMolecularImmunoregulation CenterforCancerResearchNationalCancerInstitute-FrederickFrederickMaryland21702-1201USA.

Chemokines belong to a large family of inflammatory cytokines responsible for migration and accumulation of leukocytes at inflammatory *** the past decade,accumulating evidence indicated a crucial role for chemokines and chemokine receptors in the pathophysiology of rheumatoid arthritis(RA).RA is a chronic autoimmune disease in which the synovial tissue is heavily infiltrated by *** play an important role in the infiltration,localization,retention of infiltrating leukocytes and generation of ectopic germinal centers in the inflamed *** evidence also suggests that identification of inhibitors directly targeting chemokines or their receptors may provide a novel therapeutic strategy in *** Chinese medicines(TCMs) have a long history in the treatment of inflammatory joint *** basis for the clinical benefits of TCM remains largely *** studies have led to the identification of numerous novel chemokine/chemokine receptor inhibitors present in anti-inflammatory *** of these inhibitors were previously reported by other researchers to have anti-arthritic effect,which may be attributable,at least in part,to their inhibitory effect on chemokine and/or chemokine ***,identification of agents capable of targeting chemokine/chemokine receptor interactions has suggested a mechanism of action for several TCM components and provided a means of identifying additional anti-RA ***,this approach may lead to the discovery of new inhibitors of chemokines or chemokine receptors that can be used to treat diseases associated with inappropriately overactive chemokine mediated inflammatory *** & Molecular Immunology.2004;1(5):336-342.

关键词： chemokine receptor rheumatoid arthritis traditional Chinese medicine

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Impaired brachial artery flow-mediated dilation and increased carotid intima-media thickness in rheumatoid arthritis patients

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Chinese Medical Journal 2012年第5期125卷 832-837页

作者： FAN Chun-yan ZHANG Zhi-yi MEI Yi-fang WU Chang-jun SHEN Bao-zhong Department of Medical Imaging and Nuclear Medicine FourthAffiliated Hospital Harbin Medical University HarbinHeilongjiang 150001 China Department of Rheumatology First Affiliated Hospital Harbin Medical University Harbin Heilongjiang 150001 China Department of Ultrasonography First Affiliated Hospital Harbin Medical University Harbin Heilongjiang 150001 China

Background Carotid artery intima-media thickness （CIMT） and brachial artery flow-mediated dilation percentage （FMD%） are common parameters used for detecting subclinical atherosclerosis. This study compared subclinical atherosclerosis of the carotid and brachial arteries in rheumatoid arthritis （RA） patients and healthy controls using high resolution ultrasonography. We also investigated their correlation with clinical factors and the association between FMD% and CIMT.

关键词： rheumatoid arthritis flow-mediated dilation intima-media thickness atherosclerosis

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Glucose-6-phosphate isomerase is associated with disease activity and declines in response to infliximab treatment in rheumatoid arthritis

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Chinese Medical Journal 2020年第8期133卷 886-891页

作者： Jing Xu Xiao-Ying Zhang Ru Li Jing Liu Hua Ye Xue-Wu Zhang Zhan-Guo Li Department of Rheumatology and Immunology Peking University People’s HospitalBeijing 100044China Department of Rheumatology and Immunology Peking University International HospitalBeijing 102206China Beijing Key Laboratory for Rheumatism Mechanism and Immune Diagnosis(BZ0135) Beijing 100044China

Background:rheumatoid arthritis (RA), a systemic autoimmune disease characterized by synovial inflammation, can cause cartilage and bone damage as well as disability. The aim of this study was to explore whether serum glucose-6-phosphate isomerase (GPI) is correlated with disease activity and the value of GPI in the evaluation of infliximab treatment in patients with ***:Sixty-two patients with RA who had an inadequate response to methotrexate (MTX) were enrolled in Peking University People’s Hospital from July 1, 2016 to July 31, 2018. Infliximab (3 mg/kg, intravenous at weeks 0, 2, and 6 and then every 8 weeks) was administered to patients with stable background MTX therapy. Serum samples were obtained at baseline and week 18. Serum GPI levels were determined using enzyme-linked immunosorbent assay. The associations between serum GPI levels and clinical features were ***:Serum GPI was positively correlated with Disease Activity Score in 28 joints (DAS28), swollen joint count, tender joint count and C-reactive protein level ( P < 0.001, P < 0.001, P < 0.001, and P = 0.033, respectively). The change of DAS28 in GPI-positive patients was greater than that in GPI-negative patients ( P < 0.001). Compared with those for patients receiving MTX monotherapy at baseline, the GPI levels were significantly declined when MTX was combined with infliximab ( P < 0.001). Conclusion:Serum GPI is related to disease activity and clinical response to infliximab treatment.

关键词： Glucose-6-phosphate isomerase rheumatoid arthritis Treatment

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Effect of sustained intensive therapy with disease modifying anti-rheumatic drugs in rheumatoid arthritis:a 5-year real-world consecutive study

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Chinese Medical Journal 2020年第12期133卷 1397-1403页

作者： Yue-Ming Cai Ru Li Hua Ye Jing He Xiao-Lin Sun Jia-Yang Jin Jia-Jia Liu Yu-Zhou Gan Xu-Jie You Jing Xu Lian-Jie Shi Gong Cheng Qing-Wen Wang Zhan-Guo Li Department of Rheumatology and Immunology Peking University People’s HospitalBeijing 100044China Department of Rheumatology and Immunology Peking University Shenzhen HospitalShenzhenGuangdong 518035China Beijing Key Laboratory for Rheumatism Mechanism and Immune Diagnosis(BZ0135) Beijing 100044China Peking-Tsinghua Center for Life Sciences Peking UniversityBeijing 100044China Department of Rheumatology and Immunology Peking University International HospitalBeijing 102206China

Background:Intensive therapy with disease modifying anti-rheumatic drugs(DMARDs)has been reported to improve the outcomes of rheumatoid arthritis(RA).However,real-world study on the effect of intensive therapy on RA sustained remission is still *** study aimed to investigate the outcome of sustained intensive DMARD therapy(SUIT)for RA in a real-world 5-year consecutive ***:Based on a consecutive cohort of 610 out-patients with RA,remission of RA was assessed in 541 patients from 2012 to 2017,by dividing into SUIT,non-SUIT,and intermittent SUIT(Int-SUIT)*** in the disease activity scores were evaluated by 28-joint disease activity score based on erythrocyte sedimentation rate(DAS28-ESR),28-joint disease activity score based on C-reactive protein(DAS28-CRP),and clinical deep remission criteria(CliDR).Cumulative remission rates between different groups were compared using Kaplan-Meier curves and predictive factors of sustained remission were identified by univariate and multivariate logistic regression ***:The remission rates of the SUIT group decreased from 12.0%(65/541)to 5.6%(20/359)based on DAS28-ESR,from 14.0%(76/541)to 7.2%(26/359)based on DAS28-CRP,and from 8.5%(46/541)to 3.1%(11/359)based on CliDR,respectively,with a gradually decreasing trend during the 5 *** SUIT regimen led to a significantly higher cumulative remission rate than non-SUIT regimen based on DAS28-ESR(39.7%vs.19.5%,P=0.001),DAS28-CRP(42.0%vs.19.6%,P=0.001),and CliDR(24.5%vs.8.7%,P=0.001).The cumulative remission rates of patients treated with SUIT regimen were significantly higher than those treated with Int-SUIT regimen based on DAS28-ESR(39.7%vs.25.7%,P=0.043)and CliDR(24.5%vs.14.2%,P=0.047),but there was no significant difference between the two groups based on DAS28-CRP(42.0%vs.27.4%,P=0.066).Multivariate logistic regression analysis showed that the use of SUIT regimen was an independent favorable predictor according to different remission d

关键词： rheumatoid arthritis Remission Sustained intensive therapy Cohort study

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Inhibition of smoothened decreases proliferation of Synoviocytes in rheumatoid arthritis

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Cellular & Molecular Immunology 2017年第2期14卷 214-222页

作者： Shang-ling Zhu Jian-lin Huang Wei-xiang Peng Dan-chun Wu Min-qi Luo Qiu-xia Li Zhao-xia Li Xiao-xue Feng Fang Liu Ming-xia Wang Wei-qian Chen Nancy Olsen Song Guo Zheng Division of Rheumatology Department of Internal Medicine the Third Affiliated Hospital Sun Yat-sen University Guangzhou Guangdong Province People's Republic of China Center for Clinic Immunology the Third Affiliated Hospital Sun Yat-sen University Guangzhou Guangdong Province People's Republic of China Division of Rheumatology Penn State University Hershey College of Medicine Hershey PA USA Both Shang-ling Zhu and Jian-lin Huang equally contributed to this work

Fibroblast-like synoviocytes （FLSs） contribute to synovial hyperplasia in rheumatoid arthritis （RA）. Smoothened （Smo） is a key component of sonic hedgehog （Shh） signaling and contributes to tumor cell proliferation. The objective of this study was to investigate the role of Smo in RA synoviocyte proliferation. FLSs were isolated from RA synovium. Shh signaling was studied using a Smo antagonist （GDC-0449） and small interfering RNA （siRNA） targeting the Smo gene in FLSs. Cell proliferation was quantified by using kit-8 assay and cell cycle distribution and apoptosis were evaluated by flow cytometry. Cell cycle-related genes and proteins were detected by real-time PCR and western blot. FLSs treated with GDC-0449 or Smo-siRNA showed significantly decreased proliferation compared to controls （P〈0.05）. Incubation with GDC-0449 or transfection with Smo-siRNA resulted in a significant increase of G1 phase cells compared to controls （P 〈 0.05）. Cell cycle arrest was validated by the significant increase in cyclin D1 and E1 mRNA expression, decrease in cyclin-dependent kinase p21 mRNA expression in Smo-siRNA transfected cells （P 〈 0.05）. Protein expression of cyclin D1 was also downregulated after Smo gene knockdown （P 〈0.05）.The results suggest that Shh signaling plays an important role in RA-FLSs proliferation in a Smo-dependent manner and may contribute to synovial hyperplasia. Targeting Shh signaling may help control joint damage in patients with RA.

关键词： cell proliferation rheumatoid arthritis smoothened protein sonic hedgehog signaling synoviocyte

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Elevated levels of serum antibodies against alpha-1,6-glucan in patients with systemic lupus erythematosus or rheumatoid arthritis

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Protein & Cell 2011年第9期2卷 739-744页

作者： Hui Dai Xiao-Ming Gao Department of Immunology Peking University Health Science CenterPeking UniversityBeijing 100083China Institute of Biology and Medical Sciences Soochow UniversitySuzhou 215123China

This study was undertaken to investigate whether levels of anti-alpha-1,6-glucan antibodies in human sera correlate with rheumatoid arthritis(RA)and systemic lupus erythematosus(SLE).Serum samples were collected from patients with SLE(n=30),RA(n=30)and healthy adult ***,IgA and IgM levels against alpha-1,6-glucan were measured using enzyme linked immunosorbent ***-alpha-1,6-glucan IgG prevalence was raised in patients with active SLE(73.3%)and RA(60%)compared with healthy controls(13.3%).Strong correlation between anti-alpha-1,6-glucan-IgG levels and anti-perinuclear factor(r=0.642;p<0.05)in RA patients or anti-nuclear antibodies(r=0.675;p<0.05)in SLE patients was *** significant differences in anti-alpha-1,6-glucan-IgA or-IgM levels were noted between different *** conclude that anti-alpha-1,6-glucan-IgG levels were significantly elevated in patients with SLE or RA and positively correlated with disease activity.

关键词： autoantibody anti-alpha-1 6-glucan autoimmune diseases systemic lupus erythematosus rheumatoid arthritis

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

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Chinese Medical Journal 2021年第12期134卷 1457-1464页

作者： Qiong Fu Ping Feng Ling-Yun Sun Xiao-Xia Zuo Dong-Bao Zhao Dong-Yi He Hua-Xiang Wu Wei Zhang Wei Zhang Fang Du Chun-De Bao Department of Rheumatology Renji Hospital of Shanghai Jiaotong University School of MedicineShanghai 200000China National Medical Products Administration Key Laboratory for Clinical Research and Evaluation of Innovative Drugs Institute of Clinical TrialsWest China HospitalSichuan UniversityChengduSichuan 610041China Department of Rheumatology Nanjing Drum Tower HospitalNanjing University Medical SchoolNanjingJiangsu 210008China Department of Rheumatology Xiangya HospitalCentral South UniversityChangshaHunan 410008China Department of Rheumatology and Immunology Changhai HospitalShanghai 200433China Department of Rheumatology Shanghai Guanghua Hospital of Integrated Traditional Chinese and Western MedicineShanghai 200052China Department of Rheumatology The Second Affiliated Hospital of Zhejiang University School of MedicineHangzhouZhejiang 310009China Department of Quality Control Cheng Fei HospitalChengduSichuan 610091China

Background:Clinical observational studies revealed that ^(99)Tc-methylene diphosphonate(^(99)Tc-MDP)could reduce joint pain and swollenness in rheumatoid arthritis(RA)*** multicenter,randomized,double-blind,double-dummy study aimed to evaluate the effects of ^(99)Tc-MDP plus methotrexate(MTX)*** alone or ^(99)Tc-MDP alone on disease activity and structural damage in MTX-naïve Chinese patients with moderate to severe ***:Eligible patients with moderate to severely active RA were randomized to receive ^(99)Tc-MDP plus MTX(n=59)***(n=59)alone or ^(99)Tc-MDP(n=59)alone for 48 weeks from six study sites across four provinces in *** 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 ***:At week 24,the proportion of participants achieving ACR20 was significantly higher in the MTX+^(99)Tc-MDP combination group(69.5%)than that in the MTX group(50.8%)or ^(99)Tc-MDP group(47.5%)(P=0.03 for MTX+^(99)Tc-MDP ***,and MTX+^(99)Tc-MDP vs.^(99)Tc-MDP,respectively).The participants in the MTX+^(99)Tc-MDP group and the ^(99)Tc-MDP group had significantly less important radiographic progression than the participants in the MTX group over the 48 weeks(MTX+^(99)Tc-MDP ***:P=0.03,^(99)Tc-MDP ***:P=0.03,respectively).There was no significant difference in terms of adverse events(AEs)among the *** serious AEs were ***:This study demonstrated that the combination of ^(99)Tc-MDP with MTX inhibited structural damage and improved disease activity in RA patients compared with MTX and ^(99)Tc-MDP monotherapies,without increasing the rate of *** clinical studies of ^(99)Tc-MDP therapy in patients with RA are *** Registration:***,ChiCTR-IPR-14005684;http://***/***?proj=10088.

关键词： rheumatoid arthritis Methotrexate ^(99)Tc-MDP Efficacy Safety

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Nanomedicines for the treatment of rheumatoid arthritis:State of art and potential therapeutic strategies

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Acta Pharmaceutica Sinica B 2021年第5期11卷 1158-1174页

作者： Qin Wang Xianyan Qin Jiyu Fang Xun Sun Key Laboratory of Advanced Technologies of Materials Ministry of Education and School of Materials Science and EngineeringSouthwest Jiaotong UniversityChengdu 610031China Advanced Materials Processing and Analysis Center and Department of Materials Science and Engineering University of Central FloridaOrlandoFL 32816USA Key Laboratory of Drug Targeting and Drug Delivery Systems Ministry of EducationWest China School of PharmacySichuan UniversityChengdu 610041China

Increasing understanding of the pathogenesis of rheumatoid arthritis(RA)has remarkably promoted the development of effective therapeutic regimens of ***,the inadequate response to current therapies in a proportion of patients,the systemic toxicity accompanied by longterm administration or distribution in non-targeted sites and the comprised efficacy caused by undesirable bioavailability,are still unsettled problems lying across the full remission of *** far,these existing limitations have inspired comprehensive academic researches on nanomedicines for RA treatment.A variety of versatile nanocarriers with controllable physicochemical properties,tailorable drug release pattern or active targeting ability were fabricated to enhance the drug delivery efficiency in RA *** review aims to provide an up-to-date progress regarding to RA treatment using nanomedicines in the last 5 years and concisely discuss the potential application of several newly emerged therapeutic strategies such as inducing the antigen-specific tolerance,pro-resolving therapy or regulating the immunometabolism for RA treatments.

关键词： Nanomedicines rheumatoid arthritis Targeted drug delivery Liposome Micelle Stimulus-responsive delivery systems Immune tolerance Inflammation resolution

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miR-573 is a negative regulator in the pathogenesis of rheumatoid arthritis

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Cellular & Molecular Immunology 2016年第6期13卷 839-848页

作者： Lin Wang Guanhua Song Yabing Zheng Dan Wang Hongyan Dong Jihong Pan Xiaotian Chang Research Center for Medicinal Biotechnology Key Laboratory for Rare & Uncommon Diseases of Shandong Province Shandong Academy of Medicinal Sciences Jinan People's Republic of China Institute of Basic Medicine Shandong Academy of Medical Sciences Jinan People's Republic of China Medical Research Center of Shandong Provincial Qianfoshan Hospital Shandong University Jinan People's Republic of China Department of pathology Linyi People's Hospital Linyi People's Republic of China

rheumatoid arthritis （RA） is a chronic autoimmune disease characterized by abnormal inflammation, angiogenesis, and cartilage destruction. Our previous study demonstrated an increased expression of thioredoxin domain containing 5 （TXNDC5） in the synovial tissues of RA, and its overexpression was implicated in RA pathology. Although TXNDC5 variation is linked to genetic susceptibility to RA, the regulation of its abnormal expression has not been well defined. Here, we show that TXNDC5 is directly targeted by microRNA （miR）-573, and TXNDC5, in turn, mediates the suppressive effect of miR-573 on the invasion of synovial fibroblasts of RA （RASFs）. miR-573 overexpression suppressed the expression of interleukin 6 （I L-6） and cyclooxygenase 2 in RASFs, as well as the production of tumor necrosis factor-alpha and interleukin- 1 beta by activated THP-1 cells in response to lipopolysaccharide （LPS） stimulation. Moreover, treatment with conditioned medium of RASFs transfected with miR-573 mimic inhibited the angiogenic ability of human umbilical vein endothelial cells （HUVECs）. Of note, epidermal growth factor receptor and Toll-like receptor 2 were validated as new direct targets of miR-573, and mediate the regulation of miR-573 on IL-6 production as well as the angiogenesis of HUVECs. In addition, exogenous miR-573 expression suppressed the activation of mitogen-activated protein kinase （MAPK）, signal transducer and activator of transcription 3, and phosphatidylinositol-3 kinase/activate protein kinase B in RASFs in response to LPS. Indeed, MAPK signaling was essential to ensure the function of miR-573. Taken together, our study points toward the protective roles of miR-573 in the pathological process of RA and suggests a potential target in the treatment of RA.

关键词： EGFR miR-573 rheumatoid arthritis TLR2 TXNDC5

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