穴位埋药线对难治性癫痫大鼠癫痫样波的发放及大脑海马和颞叶皮质多药耐药相关蛋白MRP1、P-gp表达的影响

目的：探讨穴位埋药线对难治性癫痫大鼠癫痫样波的发放及大脑海马和皮质中多药耐药相关蛋白 MRP1、P-gp表达的影响。方法（1）造模：大鼠海马区注射红藻氨酸（KA）,经过点燃和再次亚惊厥剂量点燃造模,且脑电图检测有癫痫样波发放者筛选为造模成功耐药难治性癫痫模型鼠。（2）分组与处理：普通线组（PTX组）与药线组（YX组）,先埋一侧穴位,间隔15 d后埋对侧穴位。拉莫三嗪组（LTG组）按照人用拉莫三嗪剂量换算灌胃大鼠,每日2次;空白对照组（Normal组）和模型组（Model组）给予灌胃同等体积的蒸馏水,均灌胃30 d。（3）采用VEEG-1518K型数字化视频脑电监测分析系统检测脑波基本节律的波幅与频率变化。（4）标本处理与检测：采用免疫组织化学技术,检测多药耐药相关蛋白MRP1、P-gp在海马与颞叶皮层不同部位的表达。结果各组治疗前比较差异无统计学意义（P＞0.05）;各组治疗后,YX组、LTG 组分别与Model 组、PTX组比较差异有统计学意义（P＜0.05）,YX组与LTG组比较差异无统计学意义（P＞0.05）;与Model组相比,LTG组和YX组干预后能降低致痫鼠EEG 痫波放电持续时间与发放频率以及海马区和颞叶皮质区多药耐药蛋白 MRP1、P-gp 的表达水平（P<0.05或P<0.01）;YX组与PTG组比较差异无统计学意义(P<0.05)。结论（1）埋药线使KA致痫鼠EEG痫波放电持续时间缩短,发放频率减少。（2）KA点燃难治性癫痫模型大鼠大脑海马区存在多药耐药蛋白MRP1、P-gp的表达较皮质区明显升高。（3）埋药线逆转与降低致痫鼠海马区多药耐药蛋白MRP1、P-gp的表达水平,可能是其抗癫痫生物学作用机制之一。     

塞来昔布联合正清风痛宁片对类风湿关节炎的疗效分析

目的:探讨塞来昔布联合正清风痛宁片对类风湿关节炎患者外周淋巴细胞的影响及疗效。方法:类风湿关节炎患者122例,随机分为两组:对照组57例,单用塞来昔布治疗;观察组65例,塞来昔布联合正清风痛宁片治疗,疗程4周。比较两组患者治疗前后IL-1、IL-6、TNF-α水平及类风湿因子(RF);肿胀疼痛关节数、VAS疼痛评分及疗效。结果:(1)总有效率观察组高于对照组(66.15%vs.52.63%,P<0.05);(2)治疗后观察组RF、IL-6、TNF-α水平均低于对照组[(19.27±3.81)vs.(36.64±4.11)]U/m L、[(10.34±1.64)vs.(14.37±3.21)]ng/L、[(8.54±2.47)vs.(12.58±1.69)]μg/L,均P<0.05;(3)治疗后观察组与对照组比较,肿胀疼痛关节数差异有统计学意义(P<0.05),但VAS疼痛评分比较差异无统计学意义(P>0.05)。结论:塞来昔布联合正清风痛宁片治疗类风湿关节炎,能够显著改善患者症状,缓解疼痛,减轻炎症反应,其疗效优于单用塞来昔布治疗。     

类风湿关节炎发病运气分析

<正>类风湿关节炎(rheumatoid arthritis,RA)是一种发病机制不明的以侵蚀性、对称性多关炎为主要临床表现的慢性、全身性自身免疫性疾病~[1]。RA归属中医"痹证"范畴。《素问·痹论》云:"风寒湿三气杂至,合而为痹也。"风湿病的发病与"乘年之虚,失时之和"有着密切的关系~[2]。年运的太过不及、司天在泉、运气同化、主客气以及客主加临等因素对风湿病的发病起着一定的影响。本文将通过回顾性病例研究     

The role of Bruton’s tyrosine kinase in autoimmunity and implications for therapy

Bruton’s tyrosine kinase (BTK) mediates B cell signaling and is also present in innate immune cells but not T cells. BTK propagates B cell receptor (BCR) responses to antigen-engagement as well as to stimulation via CD40, toll-like receptors (TLRs), Fc receptors (FCRs) and chemokine receptors. Importantly, BTK can modulate signaling, acting as a “rheostat” rather than an “on-off” switch; thus, overexpression leads to autoimmunity while decreased levels improve autoimmune disease outcomes. Autoreactive B cells depend upon BTK for survival to a greater degree than normal B cells, reflected as loss of autoantibodies with maintenance of total antibody levels when BTK is absent. This review describes contributions of BTK to immune tolerance, including studies testing BTK-inhibitors for treatment of autoimmune diseases.     

Social participation in early and established rheumatoid arthritis patients

Purpose: The aim of the study was to examine whether rheumatoid arthritis (RA) patients with different levels of restriction in social participation differ in disease related as well as psychosocial variables and whether a similar pattern can be found among early and established RA patients.

Method: Two samples of RA patients with early (n?=?97; age?=?53?±?12.3 years; disease duration?= 2.8?±?1.2 years; 76% women) and established (n?=?143; age?=?58?±?10.3 years; disease duration?= 16.1?±?3.6 years; 86% women) were collected. The pattern of differences for the patients with different level of participation restriction (no restriction, mild, moderate or high restriction) was explored by the Jonckheere–Terpstra test. Results: Significant differences were found between patients with different levels of social participation restrictions in both samples in pain, fatigue, functional disability, anxiety, depression and mastery. Generally, it was found that patients with higher restrictions experienced more pain and fatigue, more anxiety and depression and reported lower mastery. Similar pattern of differences concerning disease activity and self-esteem was found mainly in the established group. Conclusions: The study shows that the level of perceived restrictions in social participation are highly relevant regarding the disease related variables such as pain, fatigue and functional disability as well as psychological status and personal resources in both early and established RA.

• Implications for Rehabilitation

• Supporting involvement and participation of individuals with rheumatoid arthritis is important for decreasing the impact of RA symptoms on everyday life.

• Recognition and empowerment of individual resources such a mastery and self-esteem of RA patients could be beneficial for overcoming restrictions in participation.

     

Upper cervical instability associated with rheumatoid arthritis: a case report

Rheumatoid arthritis (RA) affects between 1 and 2 million individuals in the United States. Atlantoaxial instability (AAI) has been shown to have 40–85% prevalence among individuals with RA. Despite the high incidence of craniovertebral involvement, overt symptoms of instability are rare. The high risk of AAI and limited symptomology should increase therapist suspicion of potential contraindications and precautions to initiation of therapy for the cervical spine without prior diagnostic imaging. The purpose of this case study is to describe the historical, clinical, and diagnostic imaging complexity of AAI associated with RA, and to illustrate the use of these factors in the clinical reasoning within a patient case.     

Unconventional T‐cell recognition of an arthritogenic epitope of proteoglycan aggrecan released from degrading cartilage

It has been proposed that peptide epitopes bind to MHC class II molecules to form distinct structural conformers of the same MHC II–peptide complex termed type A and type B, and that the two conformers of the same peptide–MHC II complex are recognized by distinct CD4 T cells, termed type A and type B T cells. Both types recognize short synthetic peptides but only type A recognize endosomally processed intact antigen. Type B T cells that recognize self peptides from exogenously degraded proteins have been shown to escape negative selection during thymic development and so have the potential to contribute to the pathogenesis of autoimmunity. We generated and characterized mouse CD4 T cells specific for an arthritogenic epitope of the candidate joint autoantigen proteoglycan aggrecan. Cloned T‐cell hybridomas specific for a synthetic peptide containing the aggrecan epitope showed two distinct response patterns based on whether they could recognize processed intact aggrecan. Fine mapping demonstrated that both types of T‐cell recognized the same core epitope. The results are consistent with the generation of aggrecan‐specific type A and type B T cells. Type B T cells were activated by supernatants released from degrading cartilage, indicating the presence of antigenic extracellular peptides or fragments of aggrecan. Type B T cells could play a role in the pathogenesis of proteoglycan‐induced arthritis in mice, a model for rheumatoid arthritis, by recognizing extracellular peptides or protein fragments of joint autoantigens released by inflamed cartilage.     

PTPN22 polymorphisms,but not R620W,were associated with the genetic susceptibility of systemic lupus erythematosus and rheumatoid arthritis in a Chinese Han population

ObjectivesThe present study aimed to detect a possible association between PTPN22 gene polymorphisms and rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) in a Chinese Han population.Methods7 PTPN22 SNPs were genotyped in 358 patients with RA and 713 patients with SLE, as well as 564 RA controls and 672 SLE controls by Restriction Fragment Length Polymorphism (RFLP). Association analyses were conducted on the whole data set. Significant relationships were also examined between clinical features and SNPs for both RA and SLE.ResultsRs2476601 was lack of polymorphism with a ⩽0.1% frequency in both SLE and RA patients and healthy controls in our study. The two SNPs rs1217414 and rs3811021 of PTPN22 shown strong association with both SLE (rs1217414T: p_adj = 6.07e−004, OR = 0.57; rs3811021C: p_adj = 4.68e−005, OR = 0.65) and RA (rs1217414T: p_adj = 2.01e−008, OR = 0.26; rs3811021C: p_adj = 0.028, OR = 0.70). And the rs3765598 revealed a strong risk factor for SLE (p = 9.38e−009, p_adj = 6.57e−008, OR = 1.93), but not for RA (p = 0.48, OR = 1.12). Moreover, protective haplotype ACTTC in RA (p = 7.73e−016, p_adj = 5.51−015, OR[95%CI] = 0.02[0.002–0.10]) and SLE (p = 8.29e−018, p_adj = 5.80e−017, OR[95%CI] = 0.11[0.06–0.21]) were observed. In addition, the distribution of risk haplotypes ACGTC and GCTTT in RA (ACGTC: p = 0.0006, p_adj = 0.004, OR[95%CI] = 1.85[1.29–2.63]; GCTTT: p = 2.62e−005, p_adj = 1.85e−004, OR[95%CI] = 2.40[1.57–3.65]) and SLE (ACGTC: p = 0.0006, p_adj = 0.004, OR[95%CI] = 1.85[1.29–2.63]; ACGTC: p = 7.74e−011, p_adj = 6.81e−010, OR[95%CI] = 2.21[1.12–3.34]; GCTTT: p = 2.40[1.57–3.65], p_adj = 2.26e−006, OR[95%CI] = 2.64[1.79–3.87]) were significant different from that in controls. Furthermore, significant association was observed between the PTPN22 rs3765598 and antinuclear antibodies 1 (ANA1) in SLE.ConclusionsOur data provide strong evidence that the rs1217414 and rs3811021 in PTPN22 gene might be common protective factors contributed to SLE and RA susceptibility in the Chinese Han population. While, the rs3765598 might increase the genetic susceptibility of SLE, but not RA.     

进行性假性类风湿性发育不良症并双侧股骨髁上骨折1例

正患者,女,12岁。5岁开始逐渐出现行走不稳,左右摇摆,未予重视。2013年出现双髋关节疼痛,逐渐加重,5个月前发展为无法行走,需要坐轮椅。曾被诊断为"脑炎"、"先天发育异常"、"幼年性类风湿"等疾病,均未确诊,症状无改善。1 d前不慎从轮椅上摔下,双膝着地,双膝关节上方处剧烈疼痛,活动不能,为进一步治疗来我院就诊。急诊X线片(图1a,1b)示股骨远端及胫骨近端骨骺及干骺端扩大,双侧股     

香砂六君颗粒治疗抗风湿药及非甾体抗炎药相关胃肠道不良反应的疗效观察

目的 观察香砂六君颗粒治疗抗风湿药(DMARDs)及非甾体抗炎药(NSAIDs)所致胃肠道不良反应的疗效.方法 选择57例服用DMARDs及NSAIDs后出现胃肠道反应的类风湿性关节炎患者,按随机数字表法将其分为观察组29例、对照组28例,对照组给予叶酸片及质子泵抑制剂治疗,观察组在对照组治疗基础上给予香砂六君颗粒治疗,两组疗程均为4周.观察两组治疗前后胃肠道症状评分、血浆胃动素(MTL)及胃泌素(GAS)水平.结果 治疗后,观察组食少纳呆、体倦乏力、食后腹胀、大便异常、恶心呕吐等症状评分及总积分明显降低(P＜0.05),并且食少纳呆、体倦乏力、食后腹胀、大便异常评分及总积分明显低于对照组(P＜0.05).观察组有效率为96.55％,对照组为82.14％,观察组疗效优于对照组(P＜0.05).治疗后观察组MTL及GAS水平较前升高,且高于对照组(P＜0.05).结论 香砂六君颗粒治疗DMARDs及NSAIDs所致胃肠道反应效果好,可明显改善类风湿性关节炎患者临床症状.