简介：AbstractSystemic lupus erythematosus (SLE) is an autoimmune disease with extreme heterogeneity and potentially involvement of any organ or system. Numerous unanswered questions and challenges in SLE always prompt further exploration. In 2019, great progress in various aspects of SLE emerged. Both the classification criteria and management recommendation for SLE were updated. New promising medications have been widely developed and tested, although subsequent clinical studies are warranted. As an emerging number of most notable studies in SLE were published in both clinical area and basic research in 2019, we aim to summarize the highest quality data on SLE regarding novel insights of pathogenesis, updated recommendations, hot-spot issues on clinical manifestations, new understanding of disease prognosis, and most importantly, the therapeutic advances in SLE in this review.

简介：AutoreactiveB房间是在全身的豺狼座erythematosus(SLE)的致病被含有的关键有免疫力的房间之一。除了有害自身抗体(auto-Abs)的生产，B房间作为介绍抗原的房间告知autoreactiveT房间并且分泌大量支持inflammatorycytokines有autocrine和paracrine效果。调制B房间的代理人可能因此具有潜在的治疗学的价值。当前的策略包括指向B房间表面抗原，cytokines支持B房间生长和功能，和B房间和T房间相互作用。在这篇文章，我们在动物和人的研究在SLE考察B细胞的角色，并且我们检验为这个条件的处理作为有希望的策略支持B房间调整的以前的报告。另外，我们在场评估了在人的SLE反对CD20，CD22和B淋巴细胞激发器(BLyS)的代理人的治疗学的功效和安全的临床的试用上的更改。当这些研究的许多的结果仍然保持不确定时，belimumab，对BLyS的人的monoclonal抗体，显示出诺言并且最近被US食物药品管理局为病人作为显示的治疗同意了与对中等SLE温和。无疑，在B房间免疫学的进展将继续带我们到SLE致病的更好的理解和指向B房间的新奇特定的治疗的发展。

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简介：AbstractIntroduction:Pterygium inversum unguis (PIU) refers to a disorder that distal portion of the nail bed adheres to ventral surface of the nail plate, leading to the absence of the distal groove. This is not a common condition in existing literature, thus its pathogenesis has not been elucidated. The occurrence can be congenital, idiopathic, or secondary. Here we present a case of PIU associated with systemic lupus erythematosus (SLE).Case presentation:A 33-year-old woman presented with distal nail bed of the bilateral fingers (excluding the thumbs) adheres to the ventral surface of the nail plate, associated with a malar rash, photosensitivity, and arthritis, whose further laboratory examinations confirmed immunologic disorders. All these clinical characteristics and laboratory results point to the diagnosis of PIU secondary to SLE. Treatment of SLE and topical application of tretinoin 0.025% were performed and resulted in the improvement of most discomforts but PIU. There has no aggravation or alleviation of the PIU during a year of follow-up.Discussion:Acquired form of PIU is reportedly associated with connective tissue diseases or other conditions, which may be caused by abnormal distal circulation or exposure to certain chemical stimuli. Some therapies may be available, while the most effective strategy is to treat potential disorder. Clinicians should be vigilant to find out the underlying causes of PIU, so as to obtain better therapeutic efficacy.Conclusion:We observed a rare disorder of PIU associated with SLE. Hence when identifying a patient of PIU, comprehensive evaluations and long-term follow-up are imperative to to detect the development of connective tissus diseases, such as SLE.

简介：AbstractBackground:Systemic lupus erythematosus (SLE) is a multisystem autoimmune disease characterized by complex and various clinical manifestations. The study aimed to analyze clinical features and cerebral magnetic resonance imaging (MRI) changes of hyperintense white matter (WM) lesions in SLE patients.Methods:This was a retrospective study based on a consecutive cohort of 1191 SLE patients; 273 patients for whom cerebral MRI data were available were enrolled to assess hyperintense WM lesions associated with SLE. Patients were assigned to two groups, ie, with or without hyperintense WM lesions. The MRI assessment showed that the hyperintense WM lesions could be classified into three categories: type A, periventricular hyperintense WM lesions; type B, subcortical hyperintense WM lesions; and type C, multiple discrete hyperintense WM lesions. The clinical and MRI characteristics were analyzed. Factors related to hyperintense WM lesions were identified by multivariate logistic regression analysis.Results:Among the 273 SLE patients with available cerebral MRI scans, 35.9% (98/273) had hyperintense WM lesions associated with SLE. The proportions of types A, B, and C were 54.1% (53/98), 11.2% (11/98), and 92.9% (91/98), respectively. Fifty-one percents of the patients showed an overlap of two or three types. Type C was the most common subgroup to be combined with other types. Compared with those without hyperintense WM lesions, the patients with hyperintense WM lesions were associated with neuropsychiatric SLE (NPSLE), lupus nephritis (LN), hypertension, and hyperuricemia (P = 0.002, P = 0.018, P = 0.045, and P = 0.036, respectively). Significantly higher rates of polyserous effusions and cardiac involvement were found in the patients with hyperintense WM lesions (P = 0.029 and P = 0.027, respectively), and these patients were more likely to present with disease damage (P < 0.001). In addition, the patients with hyperintense WM lesions exhibited a higher frequency of proteinuria (P = 0.009) and higher levels of CD8+ T cells (P = 0.005). In the multivariate logistic analysis, hyperuricemia and higher CD8+ T cells percentages were significantly correlated with hyperintense WM lesions in SLE patients (P= 0.019; OR 2.129, 95% confidence interval [CI] 1.313-4.006 and P < 0.001; OR 1.056, 95% CI 1.023-1.098, respectively).Conclusions:Hyperintense WM lesions are common in SLE patients and significantly associated with systemic involvement, including NPSLE, LN, polyserous effusions, cardiac involvement, and disease damage. Hyperuricemia and a higher number of CD8+ T cells were independent factors associated with hyperintense WM lesions in SLE.

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简介：AbstractBackground:Systemic lupus erythematosus (SLE) is a complex autoimmune disease, and the mechanism of SLE is yet to be fully elucidated. The aim of this study was to explore the role of two-pore segment channel 2 (TPCN2) in SLE pathogenesis.Methods:Quantitative reverse transcription polymerase chain reaction (qRT-PCR) was used to detect the expression of TPCN2 in SLE. We performed a loss-of-function assay by lentiviral construct in Jurkat and THP-1 cell. Knockdown of TPCN2 were confirmed at the RNA level by qRT-PCR and protein level by Western blotting. Cell Count Kit-8 and flow cytometry were used to analyze the cell proliferation, apoptosis, and cell cycle of TPCN2-deficient cells. In addition, gene expression profile of TPCN2-deficient cells was analyzed by RNA sequencing (RNA-seq).Results:TPCN2 knockdown with short hairpin RNA (shRNA)-mediated lentiviruses inhibited cell proliferation, and induced apoptosis and cell-cycle arrest of G2/M phase in both Jurkat and THP-1 cells. We analyzed the transcriptome of knockdown- TPCN2-Jurkat cells, and screened the differential genes, which were enriched for the G2/M checkpoint, complement, and interleukin-6-Janus kinase-signal transducer and activator of transcription pathways, as well as changes in levels of forkhead box O, phosphatidylinositol 3-kinase/protein kinase B/mechanistic target of rapamycin, and T cell receptor pathways; moreover, TPCN2 significantly influenced cellular processes and biological regulation.Conclusion:TPCN2 might be a potential protective factor against SLE.

简介：热吃惊蛋白质90的提高的表示(HSP90)在全身的豺狼座erythematosus(SLE)的肾和浆液被发现了病人和MRL/Mp-Faslpr/Faslpr(MRL/lpr)自体免疫的老鼠。如果HSP90的抑制将在MRL/lpr老鼠减少疾病，我们调查了。在在vivo的vitro，有在IL-6的有免疫力刺激的显示出的减少的表示以前的HSP90禁止者Geldanamycin的mesangial房间的预告的处理，IL-12和号码，我们发现当与C57BL/6相比鼠标和MRL/lpr鼠标与HSP90禁止者17-DMAG对待时，HSP90表示在MRL/lpr肾被提高。与17-DMAG对待的MRL/lpr老鼠显示出减少的proteinuria并且减少了浆液anti-dsDNA抗体生产。Glomerulonephritis和glomerularIgG和C3没被17-DMAG的管理显著地在MRL/lpr影响。17-DMAG增加了CD8+T房间，减少的双negativeT房间，减少CD4/CD8比率和减少的小囊的B房间。这些研究建议HSP90可以在调整T房间区别和激活起一个作用并且HSP90抑制可以在豺狼座减少发炎。

简介：全身的豺狼座erythematosus(SLE)是B房间hyperreactivity描绘的自体免疫的疾病。像使用费的受体7(TLR7)表明小径反常地在SLEB房间被激活。CyclinD3(CCND3)在B房间增长，开发，和区别起一个重要作用。尽管以前的研究为自发的幼芽的中心的发展集中了于TLR7的B房间内在的角色，在SLEB房间的CCND3上的TLR7的影响仍然不是清楚的。这里，我们使用了介绍薄片的B房间并且发现CCND3与SLE有关并且显著地在SLEB房间提高了。而且，我们决定CCND3的表示水平更高，当miR-15b与正常题目相比在从SLE病人和B6.MRL-Faslpr/J豺狼座老鼠的B房间是显著地更低的时。而且，我们证明TLR7的激活戏剧性地增加了CCND3表示，但是显著地减少了在在vitro的B房间的miR-15b并且我们鉴别CCND3是miR-15b的一个直接目标。为了推进，证实我们的结果，我们由谈论地对待C57BL/6(B6)建立了另一个豺狼座模型有为8个星期的TLR-7收缩筋imiquimod(IMQ)的老鼠根据以前描述的协议。Expectedly，有IMQ的热门治疗显著地也增加了CCND3并且减少在B6老鼠的B房间的miR-15b。一起拿，我们的结果鉴别TLR7的激活在Bcells;经由miR-15b的downregulation增加了CCND3表示；因此，这些调查结果建议那外来的导致因素的CCND3表情可以在SLE贡献B房间的反常。

简介：系统科学和控制论在二次世界大战以后出现在年里。这些地创造了许多新途径到工程和管理并且贡献了新想法到存在的学术地。新地也越过地的一个范围识别了类似的概念并且开始创造了系统的一个一般理论。另外，系统科学为管理复杂系统创造了许多方法，例如后勤，运筹学和计算机模拟。在1970年代，关于人口和环境平衡有担心。当前与统治正在增加担心，后来，问题的表示的率似乎比我们的机构的能力很好管理他们。这篇论文将讨论系统科学的历史，控制论，提出的问题和答案求婚，困难在在当代的大学和现在在进行之中的研究的一些令人激动的线以内发现一个家遇到了。

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简介：数据是清楚的：人类正在面对一个全球社会经济的危机。全球身体在结束neoliberal寻找答案独占性，而非自由的市场，经济，并且在在社会责任的标签下面的全身的行为的介绍。支持这个努力，在这贡献被报导关于的研究，建议社会责任的全身的感觉引起滥用的结束，社会责任，并且合适的经济前提的提升的策略，由行动的几根线支持了，所有人能触发它。

简介：AbstractSystemic sclerosis (SSc) is characterized by immune dysfunction, vasculopathy, chronic fibrosis of skin and internal organs with complex etiology. With the rapid development and the application in biomedicine of epigenetics, accumulating evidence has shown that epigenetics plays an important role in the pathogenesis of SSc. Environmental factors via epigenetics are needed to trigger and maintain for the disease in the subjects with genetic predisposition to SSc. The role of epigenetics in the pathogenesis of SSc includes hypermethylation of the promoter region of nitric oxide synthase and bone morphogenetic protein receptors II, up-regulation of histone deacetylases 4 and 5 expression, and down-regulation of miR-193b and miR-152 in endothelial cells inducing vascular dysfunction; DNA hypermethylation and hypoacetylation of histone H3 and H4 in Friend leukemia virus integration 1 and Kruppel-like factor 5 genes, and the abnormal expression of miR-29, miR-129-5p and miR-135b in fibroblasts causing excessive fibrosis; DNA hypomethylation in the promoter regions of CD11a and CD70 genes in CD4+T cells resulting in immune dysfunction. Studies on the role of epigenetics in SSc are of great significance for better understanding the pathogenic machanism of SSc, which is helpful to find new molecular targets for treating SSc, and consequently, improve the prognosis of SSc.

简介：Theworldpost-9/11ischaracterisedbyuncertainty,fearandsuspicion.Psychologicalconfrontationsamplifiedbythemassmediahaveevencometodominatephysicalengagementsbetweenwarringparties.Dramatheoryprovidesapowerfulframeworkforunderstandingtheseinteractionsinmuchthewaythatgametheorywasabletosupportstrategymakingbyautonomousplayersinalessinter-connectedera.Amodelofthe'normal'processleadingtodramaticresolutionisanessentialfeatureofthedramatheoryapproachandisdescribedhere.Howeverthisprocesscanbederailedorfailinmanyways.Thispaperreviewsmanyofthesesystemicpathologiesandillustratessomeofthemthroughconsiderationofthreehigh-profilecases.Theconclusionisthatitisimportanttorecogniseandpossiblytousepathologicalbehaviorasanelementofacharacter'sinteractionstrategy.