自发性狼疮鼠模型的研究近况

自发性红斑狼疮鼠模型主要包括NZB、NZB×NZWF1、BXSB和MRL/lpr,这些模型表现出与人类系统性红斑狼疮相似的临床症状,包括多种自身抗体产生、血管炎、淋巴结炎、免疫复合物沉积引起的狼疮肾炎等.由于这些模型之间也存在相应的差异,对其研究近况及异同进行总结,将会为其正确应用提供一定借鉴意义.     

系统性红斑狼疮伴自发性细菌性腹膜炎1例

自发性细菌性腹膜炎是在无腹腔内邻近器官直接细菌感染来源的情况下发生于腹腔的感染,是肝硬化腹水患者的一种常见而严重的并发症。系统性红斑狼疮是一种累及多个器官和系统的自身免疫病,它可引起腹痛、恶心、呕吐等消化道表现,也可并发自发性细菌性腹膜炎。当系统性红斑狼疮并发自发性细菌性腹膜炎时极易引起误诊,病死率高,须引起注意。     

系统红斑狼疮应用糖皮质激素致骨质疏松的流行情况及发病机制研究进展

骨质疏松症是系统性红斑狼疮患者常见的,也是可预防的并发症之一。随着红斑狼疮治疗手段的增多,红斑狼疮患者的生存率逐渐升高,但如何防治系统性红斑狼疮的并发症是研究重点之一,例如骨质疏松症。随着糖皮质激素在系统性红斑狼疮治疗中的广泛应用,它已成为导致系统性红斑狼疮患者发生骨质疏松的主要原因,该文就其流行情况及发病机制作一综述。     

治疗系统性红斑狼疮常用中药的实验研究进展

摘 要系统回顾近年来中药治疗系统性红斑狼疮的实验研究相关文献,主要从单味中药和其有效成分治疗、中药复方制剂治疗等方面来阐述中药对系统性红斑狼疮的治疗效果。结果表明中药具有确切的治疗系统性红斑狼疮的作用,且其作用是多靶点的。     

基于CiteSpace的贝利尤单抗治疗系统性红斑狼疮研究文献的可视化分析

目的研究近10年国际上贝利尤单抗治疗系统性红斑狼疮的现状及热点。方法检索Web of Science数据库中发表于2011—2020年贝利尤单抗治疗系统性红斑狼疮的相关文献,采用CiteSpace 5.7.R2软件对文献进行可视化分析,从发文量、作者和被引作者、机构、国家、期刊、研究领域分析贝利尤单抗治疗系统性红斑狼疮的研究现状、通过文献共被引及关键词的知识图谱分析该领域的知识基础、研究热点及研究前沿变化。结果共纳入文献457篇,发文量呈逐年递增趋势,发文量靠前的国家有美国、英国、意大利、德国、瑞典,发文量最多的机构为英国葛兰素史克,作者是美国南加州大学凯克医学院的Stohl W,被引频次最多的作者是美国纽约扎克医学院的学者Furie R,期刊是Arthritis Rheum-US。该领域主要研究热点是贝利尤单抗治疗系统性红斑狼疮有效性研究、长期疗效及安全性研究、皮下剂型研究、与利妥昔单抗联用相关研究、特殊人群疗效与安全性研究等。研究前沿趋势变化为由贝利尤单抗治疗系统性红斑狼疮有效性和安全性研究转向特殊人群(如儿童患者、狼疮肾炎患者、重度活动度患者、神经狼疮患者等)临床应用研究。结论近10年来贝利尤单抗治疗系统性红斑狼疮的研究越来越受到临床医师和学者的重视,研究主要集中在贝利尤单抗治疗系统性红斑狼疮的有效性、长期疗效和安全性等方面,未来应更多地关注在特殊人群中的疗效和安全性研究。     

系统性红斑狼疮中医理法及药理分析

目的通过中医手段对系统性红斑狼疮进行治疗,从中医理论角度出发,系统研究红斑狼疮的病因及相关治疗方案对策。方法以中国古典医学典籍为研究蓝本,详细发现系统性红斑狼疮的发病起因、病情病理、治疗手段等中医模板对策。结果利用中医模板治疗为基本理论,辅以中草药治疗手段,治疗效果显著。结论中医结合治疗手段应用于系统性红斑狼疮,可最大限度的减轻患者的病症蔓延情况,保证患者能够在无较大副作用的前提下,更好更稳定的进行治疗,有利于临床医学上的推广与应用。     

夏日炎炎，“狼肾”患者要注意防晒

正系统性红斑狼疮是一种自身免疫性疾病,以多脏器、多系统受累为主要特点。而狼疮性肾炎就是由系统性红斑狼疮累及肾脏所致,是系统性红斑狼疮最严重的并发症,也是导致患者死亡的主要原因之一。狼疮性肾炎最常见的临床表现为蛋白尿、血尿和肾小管损伤。     

生物技术药物治疗系统性红斑狼疮的研究进展

系统性红斑狼疮是一种侵犯身体多脏器的典型的自体免疫疾病,对人体危害极大。严重肾脏受累的系统性红斑狼疮患者如果不给予适当治疗会进展到末期肾病,甚至死亡。系统性红斑狼疮的治疗是现今研究关注的热点。现有的激素治疗由于副作用以及对病程恶化无显著改善而限制了其临床应用。生物技术药物因其良好的靶向性为治疗系统性红斑狼疮提供了新的思路,其安全性和有效性已在临床试验中证明。本文对生物技术药物用于治疗系统性红斑狼疮的研究作一综述。     

炎性介质在LN发病中的机制

系统性红斑狼疮(SLE)是一种常见的伴随多系统器官损害的自身免疫性疾病。临床上以皮肤损害和血管炎为主要表现,肾脏是该病最常累及的靶器官。当系统性红斑狼疮伴发肾脏损害(主要累及肾小球)时,称为狼疮肾炎(LN),常表现为肾病综合征,可见肾炎综合征,临床上表现为大量蛋白尿、血尿、病理管型。目前系统性红斑狼疮和狼疮肾炎的发病机制尚不十分清楚,大多数专家学者倾向于遗传、环境、雌激素三者共同作用的结果。随着医疗水平的提高和科学技术的飞速发展,特别是SLE基因水平的研究,使人类对SLE和LN的发病机制有了更深入的了解,其中免疫炎性介质在SLE和LN发病中的作用是SLE研究中的重大发现,也是研究热点,对SLE和LN的治疗产生了深远影响。现就这些炎性介质作用机理做一综述,拟进一步探讨SLE和LN的发病机制。     

超声诊断腹壁与腹内脏器粘连

腹内脏器随呼吸或手法推挤而在腹壁深层下滑动，分别称为自发性或诱导性内脏滑动。经手术证实的１９例无腹壁粘连和１８例有腹壁粘连病人比较，前者自发性和诱导性内脏滑动的距离均显著大于后者（Ｐ＜０．０１）。以自发性和诱导性内脏滑动＜１ｃｍ作为内脏滑动减弱的指标，诊断腹壁粘连完全正确。超声检查内脏滑动，提供了一种非创性诊断腹壁粘连有用的方法。     

雷公藤治疗系统性红斑狼疮免疫机制的研究

目的：探讨雷公藤治疗系统性红斑狼疮的免疫作用机制。方法：用系统性红斑狼疮（ＳＬＥ）的外周血单个核细胞（ＰＢＭＣ）体外培养观察雷公藤对于ＳＬＥ的Ｔ,Ｂ细胞功能的影响。结果;雷公藤不仅能抑制ＳＬＥ病人ＰＢＭＣ对ＰＨＡ诱导的增殖反应,也能抑制ＳＬＥ病人活化Ｂ细胞的自发增殖以及ＳＡＣ诱导的静止期Ｂ细胞的增殖反应。另外雷公藤还能明显的抑制ＳＬＥ病人ＰＢＭＣ的自发性ＩｇＧ分泌以及ｒ－ＩＬ２诱导的ＰＢＭＣ的Ｉｇ     

A possible utilization of the mice forced swim test for modeling manic-like increase in vigor and goal-directed behavior

IntroductionThe lack of appropriate animal models for bipolar disorder (BPD) is a major factor hindering the research of its pathophysiology and the development of new drug treatments. In line with the notion that BPD might represent a heterogeneous group of disorders, it was suggested that models for specific domains of BPD should be developed. The present study tested the possible utilization of the forced swim test (FST) as a model for the heightened vigor and goal-directed behavior domain of mania, using mice with low baseline immobility.MethodsBlack Swiss mice were previously identified to have low immobility in the FST but similar spontaneous activity levels compared with several other mice strains. Thus, spontaneous activity and behavior in the FST were evaluated following treatment with the mood stabilizer valproate and the antidepressant imipramine.ResultsThe results indicated that valproate increased immobility in the FST without affecting spontaneous activity whereas imipramine had no effect in the FST but increased spontaneous activity.DiscussionThese findings suggest that in mice with low baseline immobility scores, the FST might be a useful model for the elevated vigor and goal-directed behavior domain of mania. As such, this test might be well integrated into a battery of models for different domains of BPD.     

上海市系统性红斑狼疮患者的治疗依从性及经济负担状况分析

目的 调查上海市系统性红斑狼疮（systemic lupus erythematosus,SLE）患者的治疗依从性与经济负担的现状,分析影响患者用药和治疗依从性的相关因素。方法 研究纳入于上海交通大学附属仁济医院南院风湿免疫科门诊就诊的SLE患者,进行问卷调查。内容包括患者个人情况、治疗依从性以及经济负担情况,采用风湿病治疗依从性问卷（CQR）和基于访谈的自我报告调查综合评价患者治疗依从性,最后用逐步回归模型进行相关性分析。结果 2017年1-2月,121例就诊于门诊的SLE患者中依从患者为59例（48.7%）,直接医疗支出为每年33 899元;多因素回归分析显示SLE的治疗依从性主要与用药提醒工具、可选择性药物、工作强度有关。结论 上海市SLE患者的治疗依从性差,经济负担重。亟需采取有效干预措施提高SLE患者治疗依从性（如有效的提醒工具）,改善健康状态,以及减轻经济负担。     

Proteomic approaches for novel systemic lupus erythematosus (SLE) drug discovery

Introduction: Systemic lupus erythematosus (SLE) is a complex autoimmune disease with a high risk of morbidity and mortality; however, there is no cure and the current medications are far from optimal in addressing efficacy and safety concerns. Over the past decade, various emerging technologies have been used in the search for novel drug targets of SLE which have resulted in numerous promising data. However, the systematic review and careful digestion of this information have been lacking.

Areas covered: In this review, the authors summarize promising biomarkers and drug targets which have been identified via various multiplexing and high-throughput proteomic strategies. The authors also introduce emerging technologies which are hopeful to be used for the discovery of novel biomarkers and therapeutic targets of SLE in the near future.

Expert opinion: Emerging proteomic technologies and genome-wide association studies (GWAS) have been the new driving forces in the discovery of novel biomarkers and promising therapeutic targets of SLE. Careful validation of these potential targets in lupus mouse models and clinical trials are urgently needed so that the next generation of target-specific medications can be developed for SLE patients.     

Drugs in early clinical development for Systemic Lupus Erythematosus

Introduction: While immunosuppressive therapy has positively impacted the prognosis of systemic lupus erythematosus (SLE), many patients still do not respond to traditional therapy. Thus, active SLE disease remains a significant problem. Furthermore, conventional immunosuppressive treatments for SLE are associated a high risk of side effects. These issues call for improvement in our current therapeutic armamentarium.

Areas covered: In this review, the authors highlight the recent developments in therapies for SLE, and present an overview of drugs which are in early clinical development for SLE. There are many new therapeutic approaches being developed, including those focused on B-cell targets, T-cell downregulation, co-stimulatory blockade, anti-cytokine agents, and kinase inhibition, and Toll-like receptor inhibition. They also discuss peptide therapy as a potential method to re-establish immune tolerance, and some of the challenges ahead in developing and testing novel agents for SLE.

Expert opinion: Many novel agents are currently in development for SLE, but this encouraging news is tempered by several disappointments in clinical trials and provides a timely moment to reflect on the future of therapeutic development in SLE. It seems likely that biological heterogeneity between patients is a major contributor to difficulty in drug design in SLE.     

Novel approaches to lupus drug discovery using stem cell therapy. Role of mesenchymal-stem-cell-secreted factors

Introduction: Patients with systemic lupus erythematosus (SLE) are at increased risk for premature death, particularly among young adults, and present dilemmas regarding drug efficacy versus toxicity. Novel therapeutic strategies have included the use of mesenchymal stem cell (MSC) therapies that are promising but still have limitations. In several disease models, it has become apparent that MSCs do not necessarily replace diseased tissues but rather exert complex paracrine effects that are mediated by their extracellular-secreted products.

Areas covered: In this review, the authors highlight the data on MSC treatment of SLE and related mechanisms of actions. This data includes the recent evidence that MSC-secreted factors such as extracellular microvesicles (MVs) are important mediators of MSC therapy. Among MVs, the authors delineate the role of exosomes as triggers of regenerative effects in target cells, mediated by transfer of proteins, mRNAs or microRNAs. The authors also outline some of the biological and regulatory restraints encountered by MSC therapy, in contrast to the potential advantages of MSC-derived exosomes as new therapeutic tools in SLE.

Expert opinion: There is concern about reproducible data on the use of MSC therapy in rheumatic diseases and specifically SLE. Although most experts consider MSCs to be safe, there are still worries over donor variability, immune-mediated rejection, culture-induced senescence, loss of functional properties and genetic instability or eventual malignant transformation. MSC-released factors could avoid most limiting factors associated with cell therapy and are therefore expected to provide a new and safe therapeutic option at an affordable cost.     

Emerging biological therapies for systemic lupus erythematosus

Introduction: Systemic lupus erythematosus (SLE) is a systemic autoimmune disease with unpredictable disease course, intermingled with periods of remission and exacerbation. Current therapies for SLE are not ideal in terms of efficacy and toxicity. Although the prognosis of the disease has improved in the past decades, further improvement is hindered by the occurrence of organ damage as a result of persistent disease activity and treatment-related complications. Novel biological therapies targeting at higher treatment efficacy and fewer adverse effects are being developed.

Areas covered: This review summarizes recent data on novel biological therapies for SLE. The pitfalls of clinical trial design and future directions of the development of SLE therapeutics are discussed.

Expert opinion: The variable therapeutic response observed in SLE reflects the clinical and immunological heterogeneity of the disease. The treatment plan of SLE patients should be individualized, with the target of quenching out disease activity, minimizing disease flares, and treatment related morbidities. Despite the disappointment of recent clinical trials, avenues are being opened for novel agents that intervene at different levels of the pathophysiological cascade of SLE. With the availability of a new treatment armamentarium, it is hoped that the survival rate and quality of life of SLE patients can continue to improve.     

Association of omentin-1, adiponectin,and resistin genetic polymorphisms with systemic lupus erythematosus in a Chinese population

ObjectiveAn increasing number of studies have demonstrated the roles of adipokines in systemic lupus erythematosus (SLE). We aimed to investigate the association of genetic variations of omentin-1, adiponectin, and resistin with SLE susceptibility.MethodsWe selected 623 SLE patients and 665 normal controls in the present study. Genotyping of omentin-1 rs2274907, rs35779394, rs79209815, and rs13376023; adiponectin rs16861194 and rs266729; and resistin rs1862513, rs3745368, and rs3745367 was conducted by TaqMan SNP genotyping assays.ResultsOverall, we found no significant differences in the allele or genotype frequencies of the nine studied SNPs between the SLE patients and controls. However, an increased frequency of the resistin rs3745368 variant was observed in the SLE patients under the dominant model (P = 0.024). In omentin-1, the rs13376023 A allele was found to be related to oral ulcers in SLE patients (P = 0.013), and the rs35779394 C and rs13376023 A allele frequencies were significantly lower in SLE patients with BMI ≥ 24 kg/m² (P = 0.019, P = 0.033, respectively). For resistin, the frequencies of the rs3745368 AA genotype and A allele were lower in SLE patients with discoid rash (P = 0.036, P = 0.011), and the rs3745368 A allele frequency was higher in SLE patients with lupus nephritis (P = 0.018). The resistin rs3745367 AA genotype and A allele frequencies were related to the occurrence of renal disorder in SLE patients (P = 0.024, P = 0.009). The haplotype analysis showed that the CGA haplotype of resistin was associated with susceptibility to SLE (P = 0.005). No significant associations of plasma omentin-1, adiponectin or resistin levels with their respective genotypes were found in SLE patients.ConclusionsIn summary, omentin-1, adiponectin and resistin SNPs are not associated with the genetic background of SLE in Chinese patients. However, omentin-1 and resistin genetic variations might contribute to several clinical phenotypes of SLE.     

Alterations in peripheral blood B cells in systemic lupus erythematosus patients with renal insufficiency

ObjectiveSystemic lupus erythematosus (SLE) is one of the autoimmune diseases, believed to be closely related to hyperactivity of B cells, overproduction of autoantibodies and immune complex formation and deposition in affected tissue. The autoreactive inflammation leads to multiorgan damage with kidney dysfunction in the forefront. Studies on lupus nephritis (LN), affecting the majority of SLE patients, are mainly focused on cells causing local inflammation. The aim of our work was to detect alterations in more accessible peripheral blood B cells in the course of SLE focusing on the influence of renal insufficiency (RI) on those parameters.MethodsWe performed a comprehensive flow cytometry analysis of B cell subpopulations, analyzed gene expression patterns with qPCR, and examined serum cytokine levels with multiplex cytokine/chemokine assay.ResultsWe discovered distribution of specific B cell subsets, especially CD38⁺ cells, plasmablasts, associated with the presence and severity of the disease. Changes in expression of MBD2, DNMT1 and APRIL genes were not only associated with activity of SLE but also were significantly changed in patients with RI.ConclusionsAll these results shed new light on the role of circulating B cells, their subpopulations, function, and activity in the SLE with kidney manifestation.     

延胡索甲素与左旋延胡索乙素抗吗啡躯体依赖和精神依赖的作用研究

目的 观察并比较延胡索甲素(corydaline,Cor)与左旋延胡索乙素(l-tetrahydropalmatine,l-THP)抗吗啡躯体依赖和精神依赖的作用。方法 SD大鼠随机分为对照组、模型组、Cor组、l-THP组。连续递增sc吗啡9 d后,纳洛酮促瘾,制备吗啡依赖大鼠催促戒断模型,促瘾前30 min ip Cor(40、80 mg/kg)或l-THP(5.0、10.0 mg/kg),观察大鼠戒断症状和体质量的降低;应用旷场实验,观察Cor(5、10 mg/kg)和l-THP(2.5、5.0 mg/kg)对吗啡诱导的大鼠自发活动的影响、对吗啡连续递增给药致大鼠行为敏化效应的影响,以及Cor(10、20、40 mg/kg)和l-THP(2.5、5.0、10.0 mg/kg)对大鼠自发活动的影响。结果 Cor(40、80 mg/kg)、l-THP(5.0 mg/kg)对吗啡催促戒断症状无显著改善作用,10 mg/kg l-THP显著改善大鼠戒断症状(P<0.05);Cor和l-THP对吗啡降低大鼠体质量效应有改善趋势,但差异不显著;Cor 40 mg/kg以下剂量、l-THP 10 mg/kg以下剂量对大鼠自发活动无显著影响;Cor(5、10 mg/kg)和l-THP(2.5、5.0 mg/kg)均可显著降低吗啡诱发的大鼠高活动性行为、行为敏化的形成(P<0.05、0.01)。结论 Cor和l-THP对吗啡所致的大鼠躯体依赖和精神依赖均有不同程度的调节作用,l-THP的起效剂量明显低于Cor。