诱导性共刺激分子靶点用于小鼠佐剂诱导型关节炎模型的可行性

目的 观察诱导性共刺激分子(ICOS)靶点用于小鼠佐剂诱导型关节炎(AIA)模型的可行性。方法 选取20只BALB/c小鼠,于右后爪分别注射等剂量完全弗氏佐剂(AIA组,n=10)或磷酸盐缓冲液(对照组,n=10),之后经尾静脉分别注射ICOS-IRD680 mAb探针(AIA组)或IgG-IRD680 mAb探针对照组,比较24及48 h后2组近红外荧光成像右爪与左爪荧光强度比值;提取小鼠总RNA行转录组测序,筛选并分析差异表达基因。针对对照组提取脾脏原代T细胞并分选磁珠阴性T细胞,以佛波酯/离子霉素刺激、诱导活化T细胞形成,检测其表面ICOS蛋白表达水平,并进行安全性评价。结果 相比对照组,AIA组ICOS基因表达显著上调、T细胞占比增高,FoxP3+调节性T细胞、CD8+T细胞及CD4+T细胞中ICOS分布较多。对照组分选磁珠阴性T细胞前、后CD3+T细胞纯度分别为65.31%和90.14%;其中,ICOS蛋白阳性小鼠CD4+T细胞在活化前、后占比分别为7.14%及31.20%,且活化CD4+T细胞ICOS蛋白平均荧光强度(586±25)显著高于未活化者(161±31)(t=25.390,P<0.001)。注射探针后24及48 h,AIA组右爪/左爪荧光强度比值均高于对照组(t=34.600、P<0.001;t=23.380、P<0.001)。相比对照组,AIA组小鼠心、肝、肾组织未见明显病理改变,且组间血清谷丙转氨酶、谷草转氨酶及肌酐无明显差异(P均>0.05)。结论 ICOS靶点用于小鼠AIA模型安全、可行。     

复方丹参注射液对实验性大鼠类风湿关节炎的病理学影响

Rheumatoidarthritis（RA）isakindofautoimmunitydiseases，intheearlyphase，itmainlyaffectssynoviumandthengraduallyextendtojoints．Large－dosedcompoundsagerootinjectioniseffectiveintreatingRAinclinic，therapeuticeffectissatisfying．Inordertostudytheinvolvedmechanism，weestablishedCIAmodelsinducedbycol－lagenIItoinvestigatemechanismspathologically．１Materialsandmethod１．１ExperimentalanimalsNormalWistarratsweighting（１２０±２０）gwereprovidedbyCenterofExperimentalAnimalsofFirstMili－tar…     

大鼠胶原诱导性关节炎模型的制备及评价

目的：制备型胶原诱导性关节炎大鼠模型（CIA模型）。方法：将40只大鼠随机分为正常组和模型组。以酶联免疫吸附测定法（ELISA法）检测模型组和正常组大鼠血清中炎性细胞因子肿瘤坏死因子-α（TNF-α）水平,同时采用组织病理学和X线摄片的方法显示关节炎大鼠的发病程度和病理学特征。结果：与正常组相比,模型组在免疫后第36天关节肿胀达到最高峰。ELISA法检测结果显示模型组TNF-α的水平均较正常组大鼠明显增高（P〈0.05）。组织病理学和X射线摄片结果显示,关节软骨组织、骨组织和滑膜组织呈典型的关节炎病变。结论：胶原诱导的大鼠关节炎模型,其病理特征和人类类风湿关节炎（RA）极为相似,为进一步深入研究人类RA的发病机制及其临床治疗提供了有价值的实验材料。     

电针治疗实验性大鼠类风湿性关节炎的可能机制

目的研究电针治疗实验性大鼠类风湿性关节炎的可能机制。方法建立大鼠Freund氏完全佐剂类风湿性关节炎模型,随机分为4组,观察一般情况,体重的变化,足爪肿胀度,血清中SOD活力及MDA含量等的变化。结果与对照组比较,模型组SOD活力增强,而针灸组与模型组相比MDA含量明显降低,有显著性差异(P<0.05)。结论电针治疗类风湿性关节炎的机理与降低代偿性增高的SOD活力,清除MDA的含量有关。     

Efficacy of etanercept and complete decongestive physical therapy in bilateral lower-limb lymphoedema associated with rheumatoid arthritis: A case report

A 54-y-old patient with rheumatoid arthritis (RA) and bilateral lower-limb lymphoedema is presented. Complete decongestive physical therapy (CDP) is the cornerstone of the management programme in all patients suffering from lymphoedema associated with RA, but it is not clear which therapy is the most effective in decreasing the oedema. We report on a patient with bilateral lower-limb lymphoedema associated with RA who, after receiving etanercept and CDP, showed moderate improvement. There is little information on the benefit of etanercept therapy for the extra-articular manifestations of RA. Further research is necessary to confirm the beneficial effect of etanercept and CDP.     

Selective antihyperalgesic effect of [Ser1] histogranin on complete Freund's adjuvant-induced hyperalgesia in rats.

The search for alternative pharmacotherapies that target abnormal pain has focused on N-methyl-D-aspartate glutamate receptor (NMDAR) antagonists, since they are efficacious in various chronic pain models. However, adverse effects of currently available agents limit their therapeutic usefulness. The naturally derived NMDAR antagonist peptide, histogranin, is thought to interact at a novel site on the NMDAR subunit. Previous studies in our laboratory have suggested the potential for histogranin analogs to attenuate neuropathic pain. The ability of this peptide derivative to reduce inflammatory pain was evaluated in the present study. The effect of intrathecal (i.t.) injection of the stable analog [Ser(1)] histogranin (SH) was evaluated in rats with a unilateral hind paw inflammation. Following injection of complete Freund's adjuvant into the hind paw, responsiveness to noxious thermal and mechanical stimuli were greatly enhanced (hyperalgesia). The i.t. injection of SH partially attenuated mechanical hyperalgesia for up to 2 h post-injection, with no effect on withdrawal thresholds of the non-inflamed paw. In contrast, SH had no effect on thermal hyperalgesia. No attendant motor abnormalities were noted. These results indicate that SH has selective and modest antinociceptive effects on inflammatory pain and suggests that novel histogranin analogs may be safe and useful adjuncts in the management of chronic pain.     

类风湿关节炎相关实验室指标的诊断性能评价

目的：分析评价类风湿关节炎（RA）患者抗环瓜氨酸抗体（Anti-CCP）、类风湿因子（RF）、C 反应蛋白（CRP）、红细胞沉降率（SR）等4个实验室指标的临床诊断意义。方法采用电化学发光法定量测定 Anti-CCP,免疫速率散射比浊法定量检测RF、CRP,仪器法检测 SR,分别将2013年来该院就诊的90例 RA 患者、93例非 RA 患者的血清进行检测,通过 ROC 曲线对测定结果进行统计和综合分析评价。结果经检测,RA 组与非 RA 组比较 Anti-CCP、RF 水平差异具有统计学意义（P ＜0.05）,CRP、SR 水平差异不具有统计学意义（P ＞0.05）。Anti-CCP、RF、CRP、SR 曲线下面积（AUC）分别为94.0％、84.0％、51.7％和56.5％;Anti-CCP 和 RF 的敏感度分别为90.0％和74.4％,特异度分别为94.6％和86.0％,Youden 指数分别为84.6％和60.4％;CRP 诊断敏感度仅为52.2％,SR 诊断特异度仅为50.5％。结论 Anti-CCP、RF 对 RA 具有良好的诊断价值,且 Anti-CCP诊断性能优于 RF;CRP 和 SR 诊断性能差,仅可作为疾病进展辅助参考,联合检测以上指标对类风湿关节炎的诊断更具临床意义。     

Indian herbal medicines: possible potent therapeutic agents for rheumatoid arthritis

Rheumatoid arthritis (RA) is an autoimmune disease of unknown etiology and is mainly characterized by the progressive erosion of cartilage leading to chronic polyarthritis and joint distortion. Although the exact pathogenesis of the disease has yet not been elucidated, however, studies suggest that cellular proliferation of synoviocytes result in pannus formation which damages the cartilage and bone. Recent reports also support the role of free radicals in its pathogenesis. Apart from the conventional treatment strategies using nonsteroidal anti-inflammatory drugs, disease modifying antirheumatic drugs and glucocorticoids, newer and safer drugs are continuously being searched, as long term usage of these drugs have resulted in adverse effects. Alternative medicine provides another approach for treatment of RA and currently a number of medicinal plants are under scientific evaluation to develop a novel drug. There is a dire need to investigate the complete therapeutic potential and adverse effects, if any, of these herbals for providing newer and safer treatment options with minimum side effects. In this review we have tried to explore various Indian ancient Ayurvedic, Unani and Tibbi, as also some Chinese and Korean, herbals for their potential to treat RA.     

腕部MRI体积定量分析评价类风湿关节炎疗效

目的探讨腕部MRI体积定量分析对于评价类风湿关节炎(RA)疗效的价值。方法收集30例活动期RA并接受规律治疗1年患者,应用MRI体积定量分析软件测量治疗前后同一腕关节滑膜炎、骨髓水肿体积,并获取同期患者红细胞沉降率(ESR)和C反应蛋白(CRP),计算28关节疾病活动度(DAS28)。分析治疗前后滑膜炎、骨髓水肿、CRP、ESR、DAS28变化,并将滑膜炎、骨髓水肿变化量与CRP、ESR、DAS28变化量进行相关性分析。结果治疗后滑膜炎体积、骨髓水肿范围、CRP、ESR、DAS28均显著降低(P均<0.05)。滑膜炎与骨髓水肿变化量呈正相关(r=0.61,P<0.01)。滑膜炎、骨髓水肿变化量与ESR、CRP变化量均无明显相关(P均>0.05),滑膜炎、骨髓水肿变化量均与DAS28变化量呈正相关(r=0.50、0.56,P=0.01、<0.01)。结论 MRI定量分析可作为量化指标,准确客观监测RA病情和评价疗效。     

两种类风湿关节炎治疗方案的疗效及安全性比较

目的比较小剂量激素联合甲氨蝶呤(MTX)及雷公藤多甙方案(TMP方案)和MTX联合来氟米特方案(ML方案)治疗类风湿关节炎(RA)的效果及安全性。方法选择符合1987年诊断标准的类风湿关节炎患者纳入研究。TMP方案选择使用小剂量激素联合甲氨蝶呤及雷公藤多甙;ML方案选择使用甲氨蝶呤联合来氟米特。评估2组治疗4、12周疗效及副反应。结果 2组患者治疗第4、12周的ACR20、ACR50、ACR70组内比较均有显著差异(P0.05)。2组患者治疗4、12周后关节压痛、关节肿胀数、晨僵、血沉、CRP、VAS等指标较用药前显著改善(P0.05)。2组患者不良反应均以肝功能损害为主。结论小剂量激素联合甲氨蝶呤及雷公藤多甙能够显著改善类风湿关节炎患者的症状。     

肌肉骨骼超声对类风湿关节炎疾病活动度的评估价值

目的探索肌肉骨骼超声对类风湿关节炎疾病活动度的评估价值。方法以2018年2月14日至2020年2月21日收治的172例疑似类风湿关节炎患者为研究对象,以病理诊断为金标准将患者分为类风湿关节炎组(阳性组,86例)和非类风湿关节炎组(阴性组,86例),均进行肌肉骨骼超声检查。分析肌肉骨骼超声的诊断效能。结果阳性组的血流信号分级总异常率显著高于阴性组(P<0.05)。高度活动障碍组的血流信号分级高于轻度活动障碍组、中度活动障碍组,滑膜厚度厚于轻度活动障碍组、中度活动障碍组(P<0.05)。肌肉骨骼超声对关节积液诊断准确率为95.24%,对滑膜肥厚/增生诊断准确率为96.15%。肌肉骨骼超声诊断的灵敏度、特异度、漏诊率、误诊率分别为96.51%、97.67%、3.49%、2.33%。结论在评估类风湿关节炎疾病活动度时,应用肌肉骨骼超声检查可提高诊断的准确率。     

Immunoadsorption with tryptophan columns: A therapeutic option for the treatment of rheumatoid arthritis with septic complications

Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease affecting multiple organs and tissues. Although there is a wide range of therapeutic applications, the coexistence of severe side effects and contraindications outlines the necessity of new therapeutic options in the treatment of severe RA. We report on the case of a 71‐year‐old patient with successful treatment of a complicated RA with tryptophan immunoadsorption combined with low‐dose steroids. Bacterial spondylitis developed in this patient during long‐term treatment with infliximab and methotrexate. Weekly immunoadsorption sessions with tryptophan columns resulted in continuous suppression of RA activity over a period of more than 5 months, as indicated by laboratory findings, the disease activity score, and the visual analog scale. This is the first report of successful treatment of a refractory and complicated RA using tryptophan immunoadsorption columns. In conclusion, immunoadsorption is a safe and effective therapeutic alternative, which should be considered to bridge infectious complications in patients with severe RA. J. Clin. Apheresis, 2009. © 2009 Wiley‐Liss, Inc.     

临床护理路径在类风湿性关节炎治疗和康复护理中的效果评价

目的探讨临床路径在类风湿性关节炎康复护理中的应用。方法将172例收治入院的类风湿性关节炎患者随机分为对照组和治疗组,各86例。对照组实施传统护理方法,治疗组采用临床护理路径进行护理,比较2组临床效果。结果观察组临床治愈率、缓解率、健康知识知晓率、满意率均高于对照组,平均康复时间较对照组短,观察组躯体化、强迫症状、人际关系敏感度、抑郁及焦虑评分低于对照组,精神状态优于对照组,2组比较差异有统计学意义(P0.05)。结论临床路径应用于类风湿性关节炎康复护理能显著提高护理质量,缩短住院时间,值得在临床推广应用。     

脐带间充质干细胞移植治疗大鼠胶原诱导关节炎模型的疗效观察

目的探讨脐带间充质干细胞(UCMSCs)移植治疗大鼠胶原诱导关节炎(CIA)模型的疗效。方法 40只造模成功的Wistar大鼠随机分为MSCs移植治疗组(MSC组,n=20)、细胞对照组(FLS组,n=10)、疾病对照组(CIA组,n=10),10只正常的Wistar大鼠作为正常对照组。采用AI评分来评价CIA大鼠关节肿胀程度。第17天予MSC组CIA大鼠尾静脉注射1×106UCMSCs,FLSs组CIA大鼠尾静脉注射等量成纤维样滑膜细胞。第42天处死所有大鼠,外周血分离血清,踝关节HE染色。ELISA法检测血清中TNF-α、TGF-β、IL-1β、IL-6水平。踝关节病理评价关节间隙狭窄程度。结果 MSC组大鼠关节AI低于FLS组和CIA组(P0.05);HE染色示CIA大鼠造模后踝关节出现炎性细胞浸润及关节腔狭窄,但MSC治疗组关节间隙明显好于CIA组和FLS组;CIA组和FLS组TNF-α、IL-1β、IL-6水平均高于正常对照组,MSC治疗组TNF-α、IL-1β、IL-6水平较CIA组和FLS组均有显著下降(P0.05);TGF-β在对照组与CIA组间差异无统计学意义,但输注MSC后TGF-β得到上调(P0.01)。结论 UCMSCs移植能通过抑制炎性细胞因子TNF-α、IL-1β、IL-6,上调抑炎细胞因子TGF-β来减轻CIA大鼠关节炎症和软骨破坏。     

Synovial biopsies in inflammatory arthritis: precision medicine in rheumatoid arthritis

ABSTRACT

Introduction: Synovial tissue (ST) is composed of a lining and sublining layer and is the target tissue involved in the inflammatory arthritides (IA), in which there is lining layer hyperplasia, inflammatory cell influx, macrophage recruitment and change in number and behavior of lining fibroblasts. Understanding synovial pathology has been critical in providing insights into pathogenetic mechanisms of disease and therapeutics. Pathobiological insights into ST have been underpinned by progress in molecular analytic methods; research in this area holds promise in individualizing treatment and optimizing response.

Areas covered: We explore ST in IA and cover in-depth the utility of synovial biopsy and ST heterogeneity. We review recent advances in ST research and discuss implications with regards to therapeutic response. Finally, we provide perspectives on the identification of new drug targets and new diagnostic and prognostic markers.

Expert opinion: ST holds the potential to individualize therapy by detecting biomarkers of diagnosis, therapeutic choice, and treatment modification in IA. Advances in molecular biology including high-throughput omics are likely to provide information that has hitherto remained unknown. ST analyzes pre- and post-treatment needs to be standard of care; only by routinely collecting and analyzing ST will we achieve the precision medicine outcomes described herein.     

热矿泥浴对大鼠佐剂性关节炎的作用及机制

目的观察热矿泥浴对大鼠佐剂性关节炎( AIA)的治疗效果及作用机制. 方法 Wistar大鼠按 AIA造模后,随机分为 3组,分别给予热矿泥浴、普通黄泥浴共 19 d,空白对照组则不予处理.连续观察关节炎症积分,第 30天取标本,检测血清肿瘤坏死因子( TNF α)含量,关节的组织病理学改变,原位杂交法观察基质金属蛋白酶-1( MMP-1)和细胞间黏附分子( ICAM-1) mRNA在关节滑膜和软骨中的表达. 结果热矿泥浴能显著降低 AIA的关节炎症程度,包括炎症积分,以及组织切片的滑膜细胞增生和软骨侵袭.热矿泥浴还能显著降低血液中的 TNF α含量,抑制滑膜和软骨细胞的 MMP-1 mRNA以及软骨细胞 ICAM-1 mRNA的表达.普通黄泥浴也能抑制软骨细胞的 ICAM-1 mRNA的表达. 结论热矿泥浴能显著抑制大鼠 AIA的关节炎症,其机制与抑制 TNF α的产生以及 MMP-1和 ICAM-1在滑膜和软骨中的表达有关,且这种作用不单纯是泥浴的物理作用,可能主要是热矿泥浴的化学和生物学作用所致.     

Incidence of rheumatoid arthritis,psoriatic arthritis and polymyalgia rheumatica in an inland area of central Italy: results of the CAMPO-RHE study

Objective: The aim of the CAMPO-RHE study was to determine the incidence of rheumatoid arthritis (RA), psoriatic arthritis (PsA) and polymyalgia rheumatica (PMR) in patients attending a rheumatologic outpatient’s clinic of a new institution in Campobasso, Italy.

Methods: Campobasso is a small town of approximately 50,000 inhabitants located in the inland territory of central Italy (Molise), and Public Health is managed from a single health authority. In Italy, all citizens are registered with a National Health System of General Practitioner (GP) Physicians. Between the 1^st of June 2014 and the 31^st of May 2016, all consecutive adult patients, sent by a GP, of Campobasso with any diagnosis of musculoskeletal symptoms/signs/complaints were evaluated in a single rheumatology outpatient clinic of our Academic Unit. The clinic represents the first and unique reference for GPs about rheumatic diseases in the territory. Subjects were classified using the 2010 EULAR criteria for RA, the CASPAR criteria for PsA and the 2012 ACR classification criteria for PMR.

Results: 1003 adult patients, sent by GPs, with articular or musculoskeletal complaints visited our clinic. Of these, 409 inhabitants of the municipality of Campobasso were evaluated for the study. During the 2-year study period we diagnosed 18, 19 and 12 new cases of RA, PsA and PMR respectively, with a new incident cases rate of 21.4, 22.59 and 27.43/100,000/year on the population at risk.

Conclusion: The results of our study could contribute to better define the incidence of these rheumatic diseases classified with the new classification criteria.     

抗环瓜氨酸肽抗体在类风湿关节炎中的应用

目的类风湿关节炎(RA)是一种致畸性较高的自身免疫性疾病,本实验探讨抗环瓜氨酸肽抗体(抗-CCP)和类风湿因子(RF)对RA的诊断作用。方法用酶联免疫吸附试验法测定抗-CCP,用速率散射免疫比浊检测RF。结果 380例RA患者抗-CCP和RF阳性率分别为63.4%、68.2%;152例非RA患者抗-CCP和RF阳性率2.0%、15.1%;抗-CCP和RF对RA诊断的灵敏度分别为63.4%、68.9%,特异性分别为98%、84.9%,二者联合时特异性达到97.4%。结论抗-CCP在RA诊断中有良好的灵敏度和特异性,二者联合能极大地提高RA诊断的准确性。     

iTRAQ‐based proteomic analysis of differentially expressed proteins in sera of seronegative and seropositive rheumatoid arthritis patients

ObjectiveThe diagnosis of seronegative rheumatoid arthritis (SNRA) is often difficult due to the unavailability of reliable laboratory markers. The aim of this study was to identify differentially expressed proteins in sera of SNRA, seropositive RA (SPRA), and healthy donors (HD).MethodsA total of 32 seropositive RA patients, 32 SNRA patients, and 35 HD were enrolled in our study. Differentially expressed proteins between 3 groups were identified via isobaric tags for relative and absolute quantitation (iTRAQ)‐based proteomic analysis, and an ELISA test was used for the validation test. Correlation analysis was conducted by GraphPad Prism.ResultsUsing iTRAQ quantitative proteomics, we identified 14 proteins were significantly different between SPRA and SNRA, including 4 upregulated proteins and 10 downregulated proteins. Four differentially expressed proteins were validated by ELISA test, and the results showed that SAA1 protein was significantly higher in SPRA and SNRA patients compared with HD, and PSME1 was elevated in SPRA patients. What''s more, SAA1 was increased in the anti‐CCP or RF high‐level group in RA patients, and PSME1 was increased in the RF high‐level group. Alternatively, SAA1 was positively correlated with inflammation indicators in RA patients, while PSME1 showed no correlation with inflammation indicators.ConclusionsiTRAQ proteomic approaches revealed variations in serum protein composition among SPRA patients, SNRA patients, and HD and provided new idea for advanced diagnostic methods and precision treatment of RA.     

Paraneoplastic syndrome, infection or arthritis: Difficulties in diagnosis

Many different diseases have overlapping clinical symptoms. A major challenge in daily clinical practice is to differentiate between diseases associated with systemic inflammation, such as neoplasia, infection and autoimmune disease. We report on a 46-year-old Caucasian male with a 3-month history of rheumatoid arthritis presenting with dramatic weight loss and dysphagia. Computer tomography revealed multiple lesions in the liver and the spleen, strongly suggesting malignant disease of unknown origin. Surprisingly, on biopsy, the liver lesions drained pus. Workup revealed that the abscesses resulted from gastric perforation, which was the consequence of NSAR therapy for rheumatoid arthritis. Antibiotic therapy was initiated, abscesses diminished and dysfunctional deglutition improved. This unique case demonstrates in a dramatic way the difficulties in daily clinical practice to differentiate between paraneoplasia, infection and autoimmune disease and the potentially life-threatening consequences of their therapy.