The lack of diagnostic markers limits the window of effectiveness for rheumatoid arthritis (RA) therapies. Here, we isolated exosomes of serum samples from four distinct groups RA patients, according to disease activity and with/without medication. Then, total RNA of exosomes was extracted for whole-transcriptome sequencing. Focusing on lncRNA sequencing, gene ontology (GO) and kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment analyses were performed. We found that the number of upregulated lncRNAs were significantly higher than that of downregulated lncRNAs in each four RA groups. And most importantly, we identified two specific lncRNAs from differentially expressed lncRNAs, TCONS_I2_00013502 (up-regulated) and ENST00000363624 (down-regulated) in RA. Receiver Operating Characteristic (ROC) curve analysis showed that the two lncRNAs were promising biomarkers for RA diagnosis. These findings highlight lncRNAs of the serum exosome are important biomarkers and provide application potential for diagnosis of RA.

Objective To investigate the treatment outcomes,prognosis,and risk factors of treatment failure of peritoneal dialysis associated peritonitis (PDAP) caused by Klebsiella pneumoniae,and thus provide clinical evidence for the prevention and treatment of this disease. Methods The clinical data of PDAP patients at four peritoneal dialysis centers from January 1,2014 to December 31,2019 were collected retrospectively.The treatment outcomes and prognosis were compared between the patients with PDAP caused by Klebsiella.pneumoniae and that caused by Escherichia coli.Kaplan-Meier method was employed to establish the survival curve of technical failure,and multivariate Logistic regression to analyze the risk factors of the treatment failure of PADP caused by Klebsiella pneumoniae. Results In the 4 peritoneal dialysis centers,1034 cases of PDAP occurred in 586 patients from 2014 to 2019,including 21 cases caused by Klebsiella pneumoniae and 98 cases caused by Escherichia coli.The incidence of Klebsiella pneumoniae caused PDAP was 0.0048 times per patient per year on average,ranging from 0.0024 to 0.0124 times per patient per year during 2014-2019.According to the Kaplan-Meier survival curve,the technical failure rate of Klebsiella pneumoniae caused PDAP was higher than that of Escherichia coli caused PDAP (P=0.022).The multivariate Logistic regression model showed that long-term dialysis was an independent risk factor for the treatment failure of Klebsiella pneumoniae caused PDAP (OR=1.082,95%CI=1.011-1.158,P=0.023).Klebsiella pneumoniae was highly sensitive to amikacin,meropenem,imipenem,piperacillin,and cefotetan,and it was highly resistant to ampicillin (81.82%),cefazolin (53.33%),tetracycline (50.00%),cefotaxime (43.75%),and chloramphenicol (42.86%). Conclusion The PDAP caused by Klebsiella pneumoniae had worse prognosis than that caused by Escherichia coli,and long-term dialysis was an independent risk factor for the treatment failure of Klebsiella pneumoniae caused PDAP.

目的 探讨外周血外泌体与类风湿关节炎(RA)辅助性T细胞-17/调节性T细胞(Th17/Treg)应答失衡的相关性,为临床提供参考.方法 回顾性分析2020年1月至2022年1月广东医科大学附属医院收治的90例类风湿关节炎(RA)患者的临床资料,根据疾病活动度(DAS28)积分将其分为轻度组(2.6分5.1分),各30例;另回顾性分析同期广东医科大学附属医院院内30例健康体检者的临床资料,将其作为对照组.分别对其外周血外泌体中miR-223、miR-155表达水平及Th17细胞/调节性T细胞(Th17/Treg)含量进行检测,并分析外泌体与Th17/Treg细胞的相关性.结果 重度组、中度组及轻度组患者Th17、Th17/Treg水平明显高于对照组,Treg亚群水平明显低于对照组(P<0.05).重度组、中度组及轻度组患者miR-223、miR-155表达水平显著高于对照组(P<0.05).Th17细胞、Treg亚群、Th17/Treg、miR-223、miR-155预测RA的敏感度分别为87.04％、88.89％、94.59％、87.04％、88.89％,特异度分别为75.00％、75.00％、81.25％、68.75％、81.25％.外泌体miR-223、miR-155水平与Th17细胞、Th17/Treg均呈正相关性,与Treg亚群呈负相关性(P<0.05).结论 外泌体与RA Th17/Treg细胞应答失衡存在一定关联,根据外泌体miR-223、miR-155表达水平可判断RA患者的Th17/Treg细胞应答失衡状态,从而有效评估其疾病严重程度.

睡眠对于维持机体的新陈代谢、细胞免疫、精力体力的恢复发挥着重要的作用.但随着社会压力的增大以及年龄的增长,睡眠障碍在当代社会变得越来越常见,已有的研究表明,睡眠障碍会增加不良健康事件的风险,近年来,有研究发现睡眠障碍对自身免疫性疾病的发生也产生了重要的影响,但是针对睡眠障碍如何影响系统性红斑狼疮等自身免疫性疾病的发生发展的机制仍未明确,本文就综合国内外现有研究对睡眠障碍如何影响系统性红斑狼疮的发生发展做一综述.

系统性红斑狼疮(SLE)是一种有多系统受累的自身免疫性疾病,SLE与妊娠可相互影响,妊娠可引起SLE复发,SLE可致不良妊娠结局,使有生育需求的女性及家庭的生活质量受到影响;同时,患有SLE的女性患者是否会影响后代的健康和发育问题仍未确定,本文对妊娠合并SLE围生期管理进行综述.

Acute lethal inflammation, especially that related to liver injury, is an important clinical issue. To date, however, there is no model that can be used to assess this serious condition. This study was designed to establish a novel lipopolysaccharide (LPS)/D-galactosamine (D-GalN)-induced acute lethal liver injury model in nuclear factor-κB (NF-κB) transgenic mice. The results show that a high dose of LPS (500 μg/kg) plus D-GalN (800 mg/kg) successfully established a novel mouse model of acute lethal liver injury with a lifespan of 8-10 h. Significantly increased NF-κB activity, detected with an in vivo imaging system (IVIS), peaked at approximately 4 h post-LPS/D-GalN challenge in NF-κB transgenic mice. Moreover, the serum levels of tumor necrosis factor (TNF)-α, interleukin (IL)-6, and monocyte chemoattractant protein (MCP)-1 were significantly increased and peaked at approximately 4 h post-i.p. injection of LPS/D-GalN. The serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) also sharply increased. Correlation analyses showed that NF-κB activity was significantly correlated with serum levels of ALT and AST. The mouse model livers showed marked congestion and hemorrhage, and hematoxylin and eosin (H&E) staining confirmed the destruction of the lobular structure and severe hepatocyte necrosis and hemorrhage. None of these changes were observed in the control mice. In summary, a novel LPS/D-GalN-induced acute lethal liver injury model with visualization of NF-κB activity was established in NF-κB transgenic mice. This model will provide the technology for developing new therapeutic strategies for treatment of severe acute liver injury complicated by endotoxemia or septicemia.

We set out this study to investigate the activation of peripheral basophils of rheumatoid arthritis(RA) patients and analyze its relationship with the pathogenesis of RA,The activation of peripheral basophils and expression of inflammatory cytokines and lymph node homing receptors,by basophils from RA patients and healthy controls were detected by flow cytometry.The results showed that the expression of CD203c by basophils from RA patients were higher than that of healthy controls (P＜0,05),The proportion of IL-4,IL-6 and IL-13 positive basophils,and expression levels of CD62L and CCR7 on basophils from RA patients were significantly higher than those of the healthy controls(all P＜0.05).In conclusion,basophils are activated in RA patients with high expression of inflammatory cytokines and lymph node homing receptors,thus provides the possibility for basophils to migrate into local sites and maybe involved in the pathogenesis of RA.

目的 研制具有中国特色的第一版类风湿关节炎患者报告结局测定量表PROISCD-RA(V1.0)特异模块.方法 采用议题小组和核心小组讨论、程序化决策方式及借鉴国内外量表开发的经验,通过定性访谈和定量调查相结合的方法对提出的条目进行再筛选,初步形成量表特异模块.对2015年3月至2016年8月经确诊的类风湿关节炎门诊或住院患者进行调查,采用变异度法、相关系数法、因子分析法及内部一致性系数法(Cron-bach′sα)进行统计分析.结果 共调查符合条件的类风湿关节炎患者279例,经统计学分析及小组讨论结果,最终得出的特异模块共含13个条目,含关节症状、活动受限及其他症状等3个侧面.结论 类风湿关节炎患者报告结局测定量表特异模块所有条目严格按条目再筛选原则得出,具有较好的内容效度和代表性.

Objective:To discuss the current status of life quality of patients with systemic lupus erythematosus in Zhanjiang and analyze its influential factors,so as to provide a theoretical basis to improve the patients' life quality,advocate effective medical measures and realize the objective of Health China.Methods:The method of convenience sampling was used to investigate 248 patients with systemic lupus erythematosus who received treatment in department of rheumatism and immunology in our hospital,and then received transfusion treatment in emergency transfusion room from March 2015 to August 2016,questionnaire investigation form and short form health survey (SF-36) were used for questionnaire investigation,and the patients' objective clinical indicators were collected.Results:Except for the score of physiological function (77.36±19.55) and score of social function SF (72.04±23.72),the patients with systemic lupus erythematosus had lower scores (47.28-66.61) of life quality in other fields,with a poor life quality.The single factor analysis result showed that the scores of one or more dimensions of the patients' different ages,occupations,education backgrounds,marriage statuses,family economic conditions,clinical staging and treatment methods in SF-36 scale (P<0.05),with an influence on the life quality.The multiple linear regression showed that when the comprehensive score of trunk was used as the dependent variable,education background,blood sedimentation and family economic condition entered the equation,with an adjusted coefficient of determination of R2a=0.409;when the comprehensive psychological score was used as the independent variable,blood glucose and family economic condition entered the equation,with an adjusted coefficient of determination of R2a=0.252.Conclusion:The life quality of patients with systemic lupus erythematosus was affected by many factors,developing economy and improve the diagnosis,treatment and nursing could improve the patients' life quality.

Objective:To investigate the activation of peripheral basophils from patients with rheumatoid arthritis ( RA) and its mechanisms. Methods:The activation markers including CD203c and the proportion of IL-4 positive rate of peripheral basophils from RA patients and healthy controls were detected by flow cytometry. Serum levels of IgE in RA patients and healthy controls were detected by electrochemilu minescence immunoassay. Basophils were negatively isolated and co-cultured with or without purified IgE,anti-IgE as positive control,then,the expression of CD203c and propotion of IL-4 positive basophils were detected by flow cytometry. Results:The expression of CD203c and IL-4 positive rate of basophils from RA patients were higher than that of healthy controls (P<0. 05). Serum levels of IgE in RA were higher than that of healthy controls (P<0. 05). After co-cultured with isolated IgE from RA patients,basophils negatively isolated from healthy controls were activated,and higher expression of CD203c and proportion of IL-4 (P<0.05). Conclusion:Basophil activation is related with development of RA,and its activation is mainly mediated by IgE. Targeting basophil and its activation pathway would be expected to provide new strategies for the treatment of RA.

记忆性B细胞( Memory B cells)是成熟的初始B细胞被抗原激活分化为具有记忆功能并持续存在于宿主的一类细胞。当再次遇到相同抗原时,该细胞可迅速增殖分化为浆细胞,产生高亲和力的抗原特异性抗体,介导体液免疫应答,从而保护机体免受再次入侵的抗原感染[1,2]。

目的：研究系统性红斑狼疮患者生命质量／患者报告结局的关联因素，为提升患者生命质量和改善预后提供依据。方法：采用系统性红斑狼疮患者生命质量／患者报告结局测定量表（QLICD-SLE V2．0），对143例住院患者进行测定并记录其客观指标。采用 t 检验、方差分析、多元逐步回归等统计方法进行分析。结果：单因素分析结果显示，不同医疗形式对生命质量总分及各领域得分差异有影响（P ＜0．05）；除特异模块外，家庭经济状况对生命质量总分及各领域得分差异有影响（P ＜0．05）；不同职业状况在生理功能和社会功能领域得分有差异（P ＜0．05）；不同文化程度在社会功能领域得分及量表总分有差异（P ＜0．05）。多因素分析：天门冬氨酸氨基转移酶、文化程度、激素停药情况及 SLEDIA 评分4个变量进入回归方程，决定系数R2＝0．440。结论：医疗形式、家庭经济状况、文化程度、职业状况、天门冬氨酸氨基转移酶及SLEDIA评分是系统性红斑狼疮患者生命质量／患者报告结局的关联因素。发展经济、缓解症状及降低治疗副作用利于提高类风湿关节炎患者的生命质量／患者报告结局。

Background: There are recent reports on several anesthetics that have anti-inflammatory and anti-infective effects apart from their uses for pain relief and muscle relaxation. Chloral hydrate is a clinical anesthetic drug and sedative that has also been reported to attenuate inflammatory response, but the mechanisms are not clearly understood.Material/Methods: This study investigated the effect of chloral hydrate treatment on the apoptosis of macrophages and explored the underlying mechanisms. RAW264.7 macrophages were treated with various concentrations of chloral hydrate for various lengths of time. Morphological changes were observed under a light microscope and apoptosis was detected with annexin-V-FITC/PI double-staining assay, Hochest 33258 and DNA ladder assay, the expression of Fas/FasL was detected with a flow cytometer, and the Fas signaling pathway was assessed by Western blotting.Results: The results showed that chloral hydrate treatment induced the morphology of RAW264.7 macrophages to change shape from typical fusiform to round in a concentration-and time-dependent manner, and was finally suspended in the supernatant. For the induction of apoptosis, chloral hydrate treatment induced the apoptosis of RAW264.7 macrophages from early-to-late stage apoptosis in a concentration-and time-dependent manner. For the mechanism, chloral hydrate treatment induced higher expression of Fas on RAW264.7 macrophages, and was also associated with changes in the expression of proteins involved in Fas signaling pathways.Conclusions: Chloral hydrate treatment can induce the apoptosis of RAW264.7 macrophages through the Fas signaling pathway, which may provide new options for adjunctive treatment of acute inflammation.

Specific blocking strategies of TLR2-mediated inflammatory signaling and hypersensitivity reactions may offer novel therapeutic strategies to prevent a variety of diseases. In this study, we investigated the blocking effects of a new anti-TLR2 antibody anti-T20 against a 20 mer peptide T20 located in the extracellular specific domain of mouse TLR2. In addition, the effects of the anti-T20in vitro, measuring the inhibition of the IL-6 and TNF-αproduction in response to PGN, LTA, and Pam3CSK4-stimulated RAW264.7 cells, were determined.In vivo, the effects of anti-T20 on a lethal anaphylaxis model using PGN-challenged OVA allergic mice, including the rectal temperature and mortality, and serum levels of TNF-α, IL-6, and LTC4 were assayed. The results showed that anti-T20 specifically bound to TLR2 and significantly inhibited PGN, LTA, and Pam3CSK4-driven TNF-αand IL-6 production by RAW264.7 cells. Also, anti-T20 protected OVA allergic mice from PGN-induced lethal anaphylaxis, and the serum levels of TNF-α, IL-6, and LTC4 of anti-T20 treated PGN-challenged OVA allergic mice were decreased as compared to isotype control of anti-T20 treated mice. In summary, this study produced a new antibody against the specific extracellular domain of TLR2 which has protective effect on TLR2 agonists-driven inflammatory and allergic response.

目的 建立中国痛风患者生命质量量表的特异模块.方法 采用议题组、核心组的程序化决策方式,通过定量调查和定性访谈相结合办法,对条目进行初步评价、修改和筛选,制定出痛风生命质量量表特异模块的初量表.之后,对30例痛风患者和20名医护工作者进行访谈和相应问卷调查,用变异系数法、医生重要性评分、患者重要性评分、因子分析、相关分析对结果进行分析.结果 按以上5种方法分别选出4、8、11、13和11个条目,最终选定了12个条目为痛风患者的特异性模块,包含生理症状、常用药物的副作用、特异性心理反应、疾病所致影响等方面.结论 形成了符合中国痛风患者生命质量量表的特异性模块.

目的 探究影响类风湿关节炎患者生命质量/患者报告结局的因素,为提高患者生命质量提供科学依据.方法 应用类风湿关节炎生命质量测定量表(quality of life instruments for chronic diseases in rheumatoid arthritis(version 2.0),QLICD-RA(V 2.0))调查100例住院患者的生命质量,并记录临床相关客观指标.应用t检验、方差分析、多元逐步回归等统计学方法分析影响类风湿关节炎患者生命质量/患者报告结局的因素.结果 单因素分析中,不同文化程度和家庭经济状况的患者生命质量总分及各领域得分差异均有统计学意义(均有P＜0.05).多元逐步回归分析中,筛选出28关节中的关节肿胀得分(disease activity score-28,DAS28)、家庭经济状况(economy conditions,EC)和天门冬氨酸氨基转移酶(aspartate aminotransferase,AST)与丙氨酸氨基转移酶(alanine aminotransferase,ALT)比值(AST/ALT)这3个变量进入回归方程,其回归方程为:Y=55.239-1.390DAS28+12.729EC-4.491AST/ALT,调整决定系数R2a=0.558.结论 类风湿关节炎患者生命质量/患者报告结局受多种因素影响,缓解患者症状、提高经济水平对提高类风湿关节炎患者的生命质量/患者报告结局有重要意义.

用鸡Ⅱ型胶原免疫C57BL/6小鼠,制备胶原诱导性关节炎(collagen induced arthritis,CIA)小鼠模型.用MAR-1抗体清除嗜碱粒细胞,以同型抗体为对照.记录各组小鼠关节炎指数(arthritis index,AI)的变化.ELISA法检测血清抗Ⅱ型胶原抗体、IL-4、IL-6和IFN-γ水平.小鼠关节标本用HE染色进行病理分析.探讨嗜碱粒细胞在胶原诱导性关节炎小鼠发病早期中的作用.结果显示,成功建立CIA小鼠模型.清除嗜碱粒细胞组、模型对照组和MAR-1抗体同型对照组相比,清除嗜碱粒细胞可显著抑制关节炎指数的升高,显著降低抗Ⅱ型胶原的抗体水平以及血清IL-4的水平,但对IL 6和IFN-γ的水平无影响.同时,清除嗜碱粒细胞可显著改善CIA模型小鼠的关节外观和关节病理改变.研究表明,靶向清除嗜碱粒细胞可减轻CIA模型小鼠的早期发病症状,可能与其介导IL-4生成和自身抗体产生相关.

The T helper (Th)1/Th2 imbalance plays a crucial role in the development of rheumatoid arthritis (RA). It is well known that basophils can affect the Th1/Th2 balance by enhancing the Th2 response, while impairing the Th1 response, which is known to be involved in the development of a number of diseases. However, limited information is available with regard to the role of basophils in RA. Decreased levels of circulating basophils and a dominant Th1 response have been reported in adult patients with RA, while children with juvenile RA have been largely found to have increased levels of circulating basophils and a dominant Th2 response. Furthermore, the circulating basophils in the two conditions have an activated phenotype and are associated with disease activity. In addition, a longitudinal study found the Th2 response was dominant in the early stages of RA, while the Th1 response was dominant in long-term chronic RA. These observations indicate that basophils may be involved in the development of RA by affecting the Th1/Th2 balance, particularly in the early stages of RA. Therefore, targeting basophils may be a novel therapeutic strategy for the treatment of RA; however, further investigation is required.

类风湿关节炎（ Rheumatoid arthritis，RA）是一种常见的自身免疫性疾病，世界范围内发病率约0．3％～1％［1］。其特征以慢性关节炎症为主，易反复发作最终出现关节畸形甚至不同程度的残疾［2，3］，目前仍无较好的根治方法。既往发现RA与免疫异常、遗传背景、环境差异、细胞凋亡、病毒感染和酶代谢异常等因素相关，但其发病机制仍未完全解析［4－6］。

细胞微粒（ Microparticles，MPs）是一类在某些生理或病理状况下，从血管内皮细胞或循环血细胞出芽脱落的富含磷脂的直径约为0.1～1.0μm的颗粒，具有生物活性可参与多种免疫性疾病（Immune diseases）的发病［1］。微粒被认为是多功能的亚细胞结构，通过释放生物活性分子和表面抗原与靶细胞的受体相互作用，介导细胞内信号转导，传递分子物质和诱导细胞内信号［2，3］。因此，细胞微粒可能作为自身免疫性疾病新的潜在治疗靶标。