类风湿性关节炎临床治疗方案的研究进展

类风湿性关节炎(RA)是一种临床上常见的全身性自身免疫性疾病,患者临床表现主要为对称性、涉及多个关节、慢性的关节疾病和滑膜关节炎,其发病相关因素主要涉及遗传、滑膜中T细胞、B细胞及细胞因子等免疫细胞等,但具体机制现仍不完全明确。目前,RA的临床治疗效果尚不理想,主要的治疗方法为常规药物、中医中药、外科手术及新技术疗法等。     

类风湿性关节炎治疗经验

对类风湿性关节炎进行详细的病因病机探讨,通过总结个人临床经验,对症施治,治以祛风除湿、活血化瘀、补益肝肾之法,收效满意,值得临床推广。     

类风湿关节炎新靶点药物治疗进展

类风湿关节炎(RA)是一种异质性疾病,多种细胞参与发病并最终导致关节破坏,但其病理生理过程尚不明确,可能涉及遗传和(或)环境因素。近年来,随着基础研究深入,RA治疗有了显著进展,除传统抗风湿药物(DMARDs),生物制剂已扩展了RA治疗手段。笔者主要综述近年来该领域药物治疗现状。     

RF、CRP和抗CCP抗体联合检测对类风湿关节炎的诊断意义

目的：通过分析类风湿关节炎的临床资料及进行类风湿因子（RF）、C反应蛋白（CRF）及抗环瓜氨酸肽抗体（抗CCP抗体）的检查,探讨RF、CRP及抗CCP抗体联合检测在诊断类风湿关节炎患者的临床应用价值。方法对本院的115例类风湿关节炎的患者及131例非类风湿性患者的血清,用酶联免疫吸附试验检测抗CCP抗体、免疫比浊法对RF、CRP进行定量检测,然后对RF、CRP及抗CCP抗体检查结果进行分析。结果类风湿关节炎组RF、CRP及抗CCP抗体检测的阳性率显著高于非类风湿关节炎组,抗CCP抗体对类风湿关节炎的敏感性为64.5%, CRP对类风湿关节炎的敏感性为69.9%, RF对类风湿关节炎的敏感性为60.5%,略低于抗CCP抗体和CRP;RF对类风湿关节炎的特异性为79.3%,抗CCP抗体的特异性最高94.0%, CRP较低为55%;抗CCP抗体和RF、CRP联合检测时对RA诊断的敏感性为73.5%,特异性为98.9%。经统计学检验, RF、CRP及抗CCP抗体联合检测的灵敏性与单独应用时差异无统计学意义;RF、CRP及抗CCP抗体联合检测特异性比抗CCP抗体、RF、CRP高,差异有统计学意义。结论临床单独将RF、CRP或抗CCP抗体的检查用于类风湿关节炎的诊断敏感性和特异性一般,为提高类风湿关节炎诊断的敏感性和特异性,应该将RF、CRP和抗CCP抗体检测进行联合应用。     

针对类风湿关节炎分子靶点的治疗药物研究进展

治疗类风湿关节炎(rheum atoid arthritis,RA)的药物虽有很多,但由于RA的发病机制和病因还没有完全阐明,目前还没有一种药物能够根治RA。随着对炎症过程的认识不断深入,特别对信号转导路径的认识,人们一直努力找寻一些调理疾病进程的具有特异性的干扰信号转导路径新的治疗药物。TNF-α阻断剂和IL-1受体拮抗剂等细胞因子拮抗剂在临床试验中治疗RA起到明显的效果。调节滑膜细胞G蛋白-AC-cAMP和Ras-MAPKs信号通路是中药白芍总苷和木瓜总苷发挥抗滑膜细胞增殖的重要分子机制。该文将对一些以细胞因子、炎症介质、细胞表面抗原、信号转导为靶点的药物研究情况进行综述。     

JAK-STAT inhibitors: Immersing therapeutic approach for management of rheumatoid arthritis

Rheumatoid arthritis is a world leading cause of musculoskeletal disease. With the introduction of biological agents as treatment alternatives the clinical possibilities have grown exponentially. Currently most common Disease-modifying anti-rheumatic drugs (DMARDs) treatment option involves intravenous or subcutaneous injection, and some patients struggle to respond to DMARDs or lose their primary reaction. An oral drug formulation with lowered costs of manufacturing and flexibility for healthcare workers to preferably perform treatment will result in decreased healthcare expenditures and increased medication compliance. The JAK-STAT inhibitors, a new class of small molecules drugs, fulfills these criteria and has recently shown efficacy in rheumatoid arthritis. Here we give a summary of how JAK-STAT inhibitors function and a detailed review of current clinical trials. Convincing clinical results suggest that therapeutic inhibition of the JAK proteins can effectively modulate a complex cytokine-driven inflammation.     

The potential of PTPN22 as a therapeutic target for rheumatoid arthritis

ABSTRACT

Introduction: PTPN22 encodes a lymphoid-specific tyrosine phosphatase (LYP) that is a master regulator of the immune response. This gene is a major susceptibility factor for a wide range of autoimmune conditions, including rheumatoid arthritis (RA) for which it represents the strongest non-HLA contributor to disease risk. A missense PTPN22 allele (R620W) affecting the protein-protein interaction of LYP with other relevant players was described as the functional variant of the association. This review will focus on the role of PTPN22 in the pathogenic mechanisms underlying RA predisposition and discuss the possibility of developing LYP-based treatment strategies with a potential application in clinical practice.

Areas covered: This review covers the literature showing how PTPN22 is implicated in signalling pathways involved in the autoimmune and autoinflammatory processes underlying RA. Insights obtained from studies aimed at developing novel selective LYP suppressors for treating RA are summarized.

Expert opinion: Targeting key risk factors during the early steps of the disease may represent a good strategy to accomplish complete disease remission. As cumulating evidences suggest that PTPN22 R620W is a gain-of-function variant, a growing interest in developing LYP inhibitors has arisen. The potential efficacy and possible application of such compounds are discussed.     

二仙益肾饮治疗类风湿性关节炎临床效果观察

目的：观察二仙益肾饮治疗类风湿性关节炎（RA）的临床疗效。方法：将101例RA患者随机分为2组,治疗组57例,对照组44例。治疗组使用二仙益肾饮进行治疗。比较两组患者的治愈率及其相关情况。统计方法采用软件包SPSS for windows 12．0,用χ^2检验比较两组资料间的显著性差异。结果：治疗组与对照组比较,治愈率及总有效率明显高于对照组（P〈0．05）。结论：二仙益肾饮对RA疗效显著,适合于临床使用。     

免疫抑制剂治疗类风湿关节炎的研究进展

类风湿关节炎（rheumatoid arthritis,RA）是风湿免疫科一种常见的全身性自身免疫性疾病。根据病情进展的不同程度,治疗方案亦不同,包括改善病情抗风湿药（disease-modifying anti-rheumatic drugs,DMARDs）、非甾体抗炎药（non-steroidal anti-inflammatory drugs,NSAIDs）、生物制剂、植物制剂等药物治疗以及辅助疗法,如针对性的锻炼、改善膳食、热敷冷敷等。目前的治疗方法对于RA的病情是有明显改善的,其中免疫抑制剂（immunosupressive agents,ISA）起到了不可忽视的作用,故从免疫抑制的角度论述,它能够有效控制病情进展,达到缓解疾病、提高生活质量的目标,得到了广泛的应用和发展。本文简述了选择性免疫抑制剂和非选择性免疫抑制剂治疗类风湿关节炎的作用机制以及临床应用,为免疫抑制剂治疗RA方面提供理论依据。     

维生素对类风湿关节炎防治作用的研究进展

类风湿关节炎（RheumatoidArthritis,RA）是以非化脓性增生性滑膜炎为特征的一种自身免疫性疾病,我国患病率为0．32％～0．36％。RA发病过程中存在维生素的不足,补充维生素有可能为防治RA提供新的思路。现将维生素对RA防治作用的研究进展作-综述。     

全膝关节置换治疗类风湿性关节炎临床分析

目的探讨膝关节全膝关节置换治疗类风湿性关节炎的临床效果。方法对12例类风湿性关节炎患者(16膝)进行全膝关节置换。根据软组织平衡情况采用后稳定型膝关节非限制性假体(12膝)或者限制性假体(4膝),记录骨缺损、手术时间、出血量、关节稳定性、髌骨轨迹和术后功能恢复情况。结果所有病例均顺利度过围手术期,手术时间(125±15)min,术中出血量(150±25)mL,术后出血量(650±75)mL。所有关节获得良好的稳定性,平均活动度为(120±25)°。经过3～42个月随访,HSS评分由手术前平均25分提高至手术后平均95分,无一例感染及深静脉血栓。结论类风湿性关节炎病理改变复杂,手术的难度大,需要很好的软组织平衡技术,韧带损伤严重者需要采用限制性假体才能取得满意的疗效。     

Altered expression of microRNAs may predict therapeutic response in rheumatoid arthritis patients

BackgroundEpigenetic alternations of microRNAs (miRNAs) can contribute to the pathogenesis and progression of rheumatoid arthritis (RA). This study aimed to measure the expression level of peripheral blood miRNAs, as well as their target mRNAs, in RA patients and healthy controls (HCs), and to evaluate the potential of miRNAs as promising non-invasive biomarkers of treatment response.MethodsThe peripheral expression of miRNAs, including miR-146a, miR-146b, miR-150, miR-155, miR-125a-5p, miR-223, miR-26a, and miR-21, as well as their target mRNAs, was analyzed in 90 RA patients and 30 HCs via quantitative real-time polymerase chain reaction (RT-PCR) assay. We compared differences between the patients in terms of good response (GR; n = 55) and poor response (PR; n = 35) to the conventional therapeutic approach.ResultsAll miRNAs were significantly overexpressed in RA patients. The expression of miR-155, miR-150, miR-146a, miR-146b, miR-125a-5p, and miR-223 increased in both groups of RA patients, compared to HCs, and miR-26a and miR-21 were the only upregulated miRNAs in the GR group versus HCs. Among the upregulated miRNAs, miR-125a-5p expression significantly changed in GR and PR patients (P = 0.047). The ROC curve analysis indicated the potential involvement of miR-125a-5p in the pathogenesis of RA. We also observed the downregulated expression of GATA3, RORC, FOXP3, TBX21, STAT1, and TRAF6 in RA patients versus HCs.ConclusionOur findings indicated that different expression levels of miR-125a-5p in the GR and PR groups of patients may serve as a therapeutic response biomarker, which can be also used as a target for therapeutic interventions.     

类风湿关节炎常用免疫诊断指标的优选

目的 对目前临床常用的免疫指标进行优选,以期能更快、更准确、更经济地诊断与监测类风湿性关节炎.方法 同步检测类风湿关节炎患者血液的类风湿因子（RF）、C反应蛋白（CRP）、红细胞沉降率（ESR）、抗环瓜氨酸肽抗体（anti-CCP）、抗角蛋白抗体（AKA）、葡萄糖-6-磷酸异构酶抗原（CPI）、抗突变型瓜氨酸化波形蛋白抗体（anti-MCV）,比较其敏感性与特异性.结果 anti-MCV敏感性76.8%,特异性90.6% anti-CCP 67.2%,90.3% AKA 75.2%,84.7% RF 72.8%,79.1% GPI特异性（92.1%）较好,但敏感性（46.4%）较差 其他项目特异性和敏感性均不好.结论 anti-MCV、anti-CCP、AKA、RF可作为临床对类风湿性关节炎的诊断、治疗和疗效监控的优选指标.     

英夫利昔单抗治疗类风湿关节炎的临床研究

目的探讨英夫利昔单抗治疗类风湿关节炎的临床疗效,为临床合理用药提供参考。方法回顾性分析我院风湿免疫科2013年10月至2015年6月收治的30例患者应用英夫利昔单抗治疗类风湿关节炎的情况,观察患者治疗前后症状、体征及实验室检查等情况。结果治疗后患者的血沉和CRP明显降低,病情活动情况明显减轻。30例患者中,1例出现局部注射反应,2 d内可自动消失。其余患者未发现明显不良反应。结论英夫利昔单抗能明显改善RA等风湿免疫疾病的炎症反应,抑制关节破坏进展,改善患者的临床表现及预后。     

软骨细胞在类风湿性关节炎中的研究进展

类风湿性关节炎(Rheumatoid arthritis,RA)是一种慢性进行性的自身免疫系统疾病,其病理特征主要是滑膜长期的慢性炎症,进而造成对软骨及骨关节的破坏。类风湿性关节炎的发病机制涉及免疫系统中的多种细胞因子、酶等。本文对软骨细胞在抑制RA的软骨破坏方面可能存在的机制作一综述。     

Prediction of triptolide targets in rheumatoid arthritis using network pharmacology and molecular docking

Network pharmacology is a novel approach that uses bioinformatics to predict and identify multiple drug targets and interactions in disease. Here, we used network pharmacology to investigate the mechanism by which triptolide acts in rheumatoid arthritis (RA). We first searched public databases for genes and proteins known to be associated with RA, as well as those predicted to be targets of triptolide, and then used Ingenuity Pathway Analysis (IPA) to identify enriched gene pathways and networks. Networks and pathways that overlapped between RA-associated proteins and triptolide target proteins were then used to predict candidate protein targets of triptolide in RA. The following proteins were found to occur in both RA-associated networks and triptolide target networks: CD274, RELA, MCL1, MAPK8, CXCL8, STAT1, STAT3, c-JUN, JNK, c-Fos, NF-κB, and TNF-α. Docking studies suggested that triptolide can fit in the binding pocket of the six top candidate triptolide target proteins (CD274, RELA, MCL1, MAPK8, CXCL8 and STAT1). The overlapping pathways were activation of Th1 and Th2 cells, macrophages, fibroblasts and endothelial cells in RA, while the overlapping networks were involved in cellular movement, hematological system development and function, immune cell trafficking, cell-to-cell signaling and interaction, inflammatory response, cellular function and maintenance, and cell death and survival. These results show that network pharmacology can be used to generate hypotheses about how triptolide exerts therapeutic effects in RA. Network pharmacology may be a useful method for characterizing multi-target drugs in complex diseases.     

Acetylator polymorphism in rheumatoid arthritis

Summary Acetylator phenotype has been determined with sulphamethazine (sulphadimidine) in 69 Spanish patients with rheumatoid arthritis (48 females), all of whom were on second line therapy, and in 96 age-matched normal controls (54 females).Thirty-two patients (46.4%) and 56 controls (58.3%) were classified as slow acetylators. On analysing separately the females in both groups, 37.5% of patients and 63% of controls were found to be slow acetylators.No difference was found in the males (patients 66.3% and controls 52.4% slow acetylators).Rapid acetylator phenotype may be a risk factor for the development of severe rheumatoid arthritis in women.     

糖皮质激素治疗类风湿关节炎的初步临床分析

目的初步探讨糖皮质激素（glucocorticoids,GCs）在类风湿关节炎（rheumatoid arthritis,RA）中使用的利弊。方法随机调查53例RA患者使用GCs的情况（非激素组25例,激素组28例）,详细记录GCs使用的剂量、时间,同时测定所有患者的临床及相关实验室指标,比较非激素组和激素组RA患者间上述指标的差异。结果两组患者间年龄、BM I、病程、性别构成以及是否使用改变病情抗风湿药物等基本情况比较显示,差异无统计学意义（P〉0.05）。非激素组与激素组在关节压痛指数（21.92±15.52）vs（35.39±17.53）、关节肿胀指数（8.88±6.21）vs（12.61±6.66）、HAQ积分（0.83±0.69）vs（1.76±0.80）、患者评价（5.44±1.80）vs（6.61±1.50）、关节功能分级构成比（1∶13∶10∶1）vs（0∶5∶12∶11）、关节X线分期构成比（6∶14∶4∶1）vs（1∶12∶8∶7）及骨质疏松发生率（5/25vs13/28）的比较显示,差异有统计学意义（P〈0.05）。服用激素的总量与关节压痛指数（r=0.308,P=0.025）、HAQ积分（r=0.549,P=0.0001）、患者评价（r=0.301,P=0.028）、双手平均握力（r=-0.337,P=0.014）和桡骨远端骨密度（r=-0.362,P=0.008）呈直线相关。结论不适当使用GCs治疗的RA患者关节压痛和肿胀数更多,HAQ积分更高,患者评价、关节功能和关节X线分期更差,骨质疏松的发生率亦更高;但每日3片左右的强的松使用1.5年对RA血压、血糖和血脂的影响并不大。     

雪莲治疗类风湿性关节炎疗效系统评价

目的系统评价雪莲治疗类风湿性关节炎的临床疗效。方法计算机检索MEDLINE（1996年至2005年11月）、EMBASE（1984年至2005年11月）、Cochrane临床对照试验资料库（2005年第4期）、中国Cochrane中心临床对照实验资料数据库、中国生物医学文献数据库（1978年至2005年11月）,手工检索纳入试验的所有中文及外文文献及相关文献,并逐个进行方法学质量评价,采用RevMan4.2.7软件进行Meta分析。结果共纳入2个半随机对照试验（198例患者）,结果显示,①治愈率：1个研究报道了与湿热麻痹剂比较,治疗前后差异无统计学意义[RR1.81,95%CI（0.40,8.81）];②总有效率：2个研究,与湿热麻痹剂或吲哚美辛比较,治疗前后差异无统计学意义[RR1.21,95%CI（1.00,1.46）;RR 1.23,95%CI（1.02,1.48）]。结论现有的有限证据表明,无法得出其能改善类风湿性关节炎的治愈率、总有效率或病死率等的结论;需要更多设计良好的随机、双盲、安慰剂对照试验加以证实。