Prevalence of overlap of antineutrophil cytoplasmic antibody associated vasculitis with systemic autoimmune diseases: an unrecognized example of poliautoimmunity

Clinical Rheumatology - We aimed to estimate the frequency of overlap of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) with systemic autoimmune diseases. Retrospective...     

Necroptotic TNFα-Syndecan 4-TNFα Vicious Cycle as a Therapeutic Target for Preventing Temporomandibular Joint Osteoarthritis

Temporomandibular joint osteoarthritis (TMJOA) is a chronic degenerative disease for which the underlying mechanism still remains unclear. Compared with apoptosis and autophagy, necroptosis causes greater harm to tissue homeostasis by releasing damage-associated molecular patterns (DAMPs). However, the role of necroptosis and downstream key DAMPs in TMJOA is unknown. Here, rodent models of TMJOA were established by the unilateral anterior crossbite (UAC). Transmission electron microscopy (TEM) and immunohistochemistry of receptor interacting protein kinase 3 (RIPK3)/phosphorylation of mixed lineage kinase domain-like protein (pMLKL) were conducted to evaluate the occurrence of necroptosis in vivo. The therapeutic effects of blocking necroptosis were achieved by intra-articularly injecting RIPK3 or MLKL inhibitors and using RIPK3 or MLKL knockout mice. In vitro necroptosis of condylar chondrocyte was induced by combination of tumor necrosis factor alpha (TNFα), second mitochondria-derived activator of caspases (SMAC) mimetics and carbobenzoxy-valyl-alanyl-aspartyl-[O-methyl]- fluoromethylketone (z-VAD-fmk). The possible DAMPs released by necroptotic chondrocytes were screened by quantitative proteomics and blocked by specific antibody. Translucent cytosol, swollen organelles, and ruptured cell membranes, features of necroptosis, were frequently manifested in chondrocytes at the early stage of condylar cartilage degeneration in TMJOA, which was accompanied by upregulation of RIPK3/pMLKL. Inhibiting or knocking out RIPK3/MLKL significantly prevented cartilage degeneration. DAMPs released by necroptotic condylar chondrocytes, such as syndecan 4 (SDC4) and heat shock protein 90 (HSP90), were verified. Furthermore, blocking the function of SDC4 significantly attenuated the expression of TNFα in cartilage and synovium, and accordingly increased cartilage thickness and reduced synovial inflammation. Thus, the necroptotic vicious cycle of TNFα-SDC4-TNFα contributes to cartilage degeneration and synovitis, and can serve as a potential therapeutic target for treating TMJOA. © 2022 American Society for Bone and Mineral Research (ASBMR).     

浅低温心脏不停搏心内手术对心肌保护效果的比较

目的:探讨浅低温体外循环(CPB)心脏搏动中心内直视手术对心肌保护的效果.方法:40例患者随机分为观察组(浅低温心不停搏组)和对照组(中低温心停搏组).分别在术前、转机、停机及术后6 h、12 h、24 h、48 h、72 h,取冠状静脉窦或中心静脉血样,测定血气分析及血清中肌酸磷酸激酶(CK)及其同功酶(CK-MB)、天门冬氨酸氨基转换酶(AST)、乳酸脱氢酶(LDH)、丙二醛(MDA)、超氧化物歧化酶(SOD)的含量.并取心房间隔肌观察心肌含水量及心肌超微结构的改变.临床观察CPB时间、脱机、呼吸支持、多巴胺应用、严重心律失常和血红蛋白尿等指标.结果:冠脉循环血气、电解质、酸碱水平与体循环的组内组间对比基本一致.CK、CK-MB、AST、LDH两组在CPB和术后均有增加,且以对照组升高显著,与观察组相同时点相比,差异均有显著性(P＜0.01).对照组术后MDA明显升高,SOD明显降低(P＜0.01),而观察组变化不大.心肌含水量和超微结构观察,对照组变化显著,而观察组轻微改变.临床指标观察,观察组优于对照组.结论:浅低温体外循环心脏不停搏心内直视手术对心肌损伤很轻,有很好的心肌保护效果.     

B细胞淋巴瘤TIL-T的IL-2Rα基因突变及蛋白表达检测

目的 :检测B细胞淋巴瘤 (B NHL)中肿瘤浸润T细胞 (TIL T)的活化标记IL 2Rα(CD2 5 )的基因及蛋白表达 ,寻找TIL T在B NHL肿瘤微环境中存在意义的实验依据。方法 :将 19例B NHL提取RNA ,采用RT PCR和SSCP检测其IL 2Rα的Ⅳ Ⅷ外显子基因突变与否 ;19例B NHL采用细胞免疫化学染色进行CD3、CD4、CD8、CD2 0、CD2 5细胞免疫表型的分析 ;2 9例B NHL和 2 0例良性淋巴组织 ,采用冰冻切片免疫组化方法进行IL 2Rα(CD2 5 )蛋白表达的检测。结果 :SSCP显示 19例TIL -T的IL 2Rα未发现异常泳动条带。细胞免疫化学染色示B NHL中 5 2 .6 3% (10 /19例 )的CD2 5 +细胞少于 10 % ,TIL T(CD3+)与CD4相关 (r =0 .5 7,P <0 .0 1)并与CD2 5相关 (r =0 .5 0 ,P <0 .0 5 )。免疫组化示 86 .2 % (2 5 /2 9例 )的B NHL中CD2 5表达 (+/- )和 (+) ,且主要表达在TIL T细胞上 ,呈散在分布 ,阳性细胞少于T标记细胞。结论 :19例TIL T的IL 2Rα在RNA水平未发现基因异常 ;CD2 5蛋白在B NHL中呈弱表达趋势。提示部分TIL T不表达CD2 5 ,推测TIL T的IL 2Rα的表达在转录后机制中可能出现异常或TIL T存在活化障碍。     

Involvement of ADAM10 in axonal outgrowth and myelination of the peripheral nerve

The disintegrin and metalloproteinase 10 (ADAM10) is a membrane‐anchored metalloproteinase with both proteolytic and disintegrin characteristics. Here, we investigate the expression, regulation, and functional role of ADAM10 in axonal outgrowth and myelination of the peripheral nerve. Expression pattern analysis of 11 ADAM family members in co‐cultures of rat dorsal root ganglia (DRG) neurons and Schwann cells (SCs) demonstrated the most pronounced mRNA expression for ADAM10. In further studies, ADAM10 was found to be consistently upregulated in DRG‐SC co‐cultures before the induction of myelination. Neurons as well as SCs widely expressed ADAM10 at the protein level. In neurons, the expression of ADAM10 was exclusively limited to the axons before the induction of myelination. Inhibition of ADAM10 activity by the hydroxamate‐based inhibitors GI254023X and GW280264X resulted in a significant decrease in the mean axonal length. These data suggest that ADAM10 represents a prerequisite for myelination, although its activity is not required during the process of myelination itself as demonstrated by expression analysis of myelin protein zero (P0) and Sudan black staining. Hence, during the process of myelin formation, ADAM10 is highly upregulated and appears to be critically involved in axonal outgrowth that is a requirement for myelination in the peripheral nerve. © 2009 Wiley‐Liss, Inc.     

心房充血分数评价高血压患者左室舒张功能的临床研究

目的探讨心房充血分数(AFF)在评价高血压患者左室舒张功能方面的临床应用价值。方法应用声学定量技术(AQ)对40名高血压患者及40名正常人的AAF值,快充血率峰值(PRFR)进行测定,并兼测了二尖瓣口E峰峰值速度与A峰峰值速度比(EV/AV)。结果高血压患者的AFF值明显高于正常人(P<0·001);而PRFR、EV/AV值明显低于正常人(P<0·001~P<0·05)。且所有受试者的AFF值与EV/AV值、PRFR值分别呈负相关(r=-0·51;r=-0·61)。结论AFF能够客观的反映高血压患者的左室舒张功能变化,对鉴别左室舒张功能异常有一定的诊断意义。     

石刻雕塑作业劳动卫生学调查及实验研究

测定了石雕作业粉尘浓度，几何平均浓度为８２．３５～３．６７ｍｇ／ｍ３。工人职业性健康检查结果，接尘工人的咽部充血、咳嗽、咯痰检出率高于对照组；肺功能低下的检出率也高于对照组。该厂自１９７２年以来发生尘肺患者１７例，其病情发展和晋期缓慢，发病工龄长。动物实验研究表明，石雕粉尘有轻微的致纤维化作用。