目的 探讨特发性膜性肾病(IMN)患者血清T细胞免疫球蛋白黏蛋白分子-3(Tim-3)及其配体癌胚抗原相关细胞黏附分子1(CEACAM1)与其肾功能进展的相关性.方法 选取2019年7月至2022年8月于该院住院并经肾组织活检确诊为IMN的80例患者作为IMN组,另选取77例同期体检健康者作为对照组.根据估算肾小球滤过率(eGFR)水平将IMN组分为肾功能正常组[eGFR>90 mL/(min·1.73 m2)],肾功能下降组[eGFR≤90 mL/(min·1.73 m2)].采用酶联免疫吸附试验比较各组血清Tim-3、CEACAM1水平,分析IMN患者血清Tim-3、CEACAM1水平与一般临床指标的相关性,采用多因素Logistic回归分析影响IMN患者肾功能下降的危险因素.结果 与对照组比较,IMN组血清Tim-3、CEACAM1水平升高(P<0.05);肾功能下降组血清Tim-3水平高于肾功能正常组(P<0.05);血清Tim-3水平与白蛋白、总蛋白、eGFR呈负相关(r=-0.266、-0.229、-0.374,P<0.05),与肌酐呈正相关(r=0.289,P<0.05);多因素Logistic回归分析结果显示,Tim-3水平升高是影响IMN患者肾功能下降的独立危险因素.结论 IMN患者血清Tim-3、CEACAM1水平升高,Tim-3/CEACAM1可能在IMN的发生发展中发挥重要作用,血清Tim-3水平可为IMN患者治疗及预后提供一定依据.

BACKGROUND:M1/M2 macrophage polarization affects patient outcomes after myocardial infarction (MI). The relationship between milk fat globule-epidermal growth factor 8 (MFG-E8) and Ca2+/calmodulin-dependent protein kinase II (CaMKII) on macrophage polarization after MI is unknown. To investigate the functional role of MFG-E8 in modulating cardiac M1/M2 macrophage polarization after MI, especially its influence on CaMKII signaling. METHODS:Human ventricular tissue and blood were obtained from patients with MI and controls. MFG-E8-KO mice were constructed (C57BL/6). The mice were randomized to WT-sham, sham-MFG-E8-KO, WT-PBS, rmMFG-E8 (WT injected with rmMFG-E8 10 min after MI), and MFG-E8-KO. The mouse macrophage cell line RAW264.7 was obtained. CaMKII, p-CaMKII, Akt, and NF-κB p65 were determined by qRT-PCR, western blot, and immunofluorescence. RESULTS:The MFG-E8 levels were significantly enhanced after MI in the hearts and plasma of patients with MI compared with controls. The MFG-E8 levels were significantly increased in the hearts and plasma of mice after MI. MFG-E8 was derived from cardiac fibroblasts. The administration of rmMFG-E8 improved ventricular remodeling and cardiac function after MI. rmMFG-E8 did not suppress infiltrating monocyte/macrophages into the peri-infarct area. rmMFG-E8 suppressed the polarization of macrophages to the M1 phenotype and promoted the polarization of macrophages to the M2 phenotype. rmMFG-E8 suppressed CaMKII-dependent signaling in macrophages. CONCLUSIONS:MFG-E8 and CaMKII appear to collaboratively regulate myocardial remodeling and M1/M2 macrophage polarization after MI. These observations suggest new roles for MFG-E8 in inhibiting M1 but promoting M2 macrophage polarization.

Although C-type lectin domain family 9A (Clec9A) on conventional type 1 dendritic cells (cDC1s) plays a critical role in cytotoxic CD8+ T cell response in cancers and viral infections, its role in chronic obstructive pulmonary disease (COPD) is unknown. We measured the expression of Clec9A in sera, bronchoalveolar lavage fluid (BALF), and peripheral blood mononuclear cells (PBMCs) from controls and COPD patients. The percentages of Clec9A+ DC and cytotoxic CD8+ T cell in the BALF were determined by flow cytometry between patients with COPD and non-obstructive chronic bronchitis (NOCB). Compared with healthy individuals, the serum levels of Clec9A were increased at different stages of COPD patients, and the mRNA and protein levels of Clec9A were both increased in COPD patients at GOLD stages III-IV. The percentage of Clec9A+ DCs was also increased in the BALF of COPD patients compared with NOCB patients. Moreover, enhanced Clec9A+ DCs recruitment was positively correlated with cytotoxic CD8+ T cell response in the BALF of COPD patients. This study suggests that Clec9A+ DCs participate in the CD8+ T cell-mediated chronic airway inflammation in COPD.

机体免疫系统通过识别自身组织或细胞释放的危险信号做出免疫应答.损伤相关分子模式(DAMPs)是受损组织或死亡细胞释放的内源性分子,即危险信号,与模式识别受体(PRRs)结合后,激活免疫应答,诱导炎症反应.除感染、损伤外,活细胞在伤害应激、代谢失衡等情况下也能主动释放DAMPs.最近研究发现,DAMPs在急性损伤后的组织修复中发挥重要作用.本文将对已知DAMPs的分类及其在组织修复中的应用进行简要综述.

Immunoglobulin G4 autoimmune diseases (IgG4-AID) is the general name of a series of autoimmune diseases, including membranous nephropathy, pemphigus and myasthenia gravis. It is mainly characterized by the existence of IgG4 autoantibodies in patients. At present, a variety of IgG4-AID-related autoantigens have been found, which mainly exist in kidney, skin, central and peripheral nervous system, blood circulation or vascular system. Compared with IgG autoantibodies, various IgG4 autoantibodies have better clinical significance or clinical-laboratory value in the diagnosis, differential diagnosis, treatment and prognosis judgment of some IgG4-AID. This article reviews the research progress of IgG4 autoantibodies in IgG4-AID.

机体在病毒感染、肿瘤等病理因素下产生的大量坏死细胞需要细胞毒性T淋巴细胞(CTL)的靶向杀伤作用来清除.人外周血BDCA3+树突状细胞上的Clec9A能特异性识别与结合坏死细胞暴露的纤维状肌动蛋白(F-actin),激活胞内脾酪氨酸激酶Syk.Clec9A作为F-actin的受体,不仅内吞坏死细胞,同时将坏死细胞相关抗原交叉提呈至CD8+T细胞,活化CTL,启动机体获得性免疫应答.CTL释放的穿孔素及颗粒酶特异性杀伤靶细胞,导致体内感染细胞或肿瘤细胞进一步被清除.因此,Clec9A在机体抗病毒感染、肿瘤治疗中具有潜在的应用前景.

目的:探讨Flt3配体（Flt3L）和生长停滞特异性蛋白6（Gas6）对非霍奇金淋巴瘤（NHL）患者化疗后感染的诊断价值。方法:收集2019年7月至2020年10月在武汉市第一医院就诊的NHL化疗患者94例，其中男62例，女32例，年龄（53.50±13.70）岁。根据化疗后是否感染，分为感染组40例，未感染组54例。另选择同期健康者50例为对照组。比较3组间血清Flt3L、Gas6和一般炎症指标的表达水平，相关性分析采用Spearman法，受试者工作特征（ROC）曲线分析血清Flt3L和Gas6对NHL患者化疗后感染的预测价值，采用Kaplan-Meier曲线分析血清Flt3L和Gas6水平对NHL化疗患者发生医院感染的影响。结果:NHL患者化疗后感染组血清Flt3L［807.80（215.10，1 232.00）pg/ml］和Gas6［20.04（13.14，27.52）ng/ml］水平均高于未感染组和对照组，差异均有统计学意义（ P均<0.05）；NHL患者化疗后重度感染组血清Flt3L［887.30（321.60，1 367.00）pg/ml］和Gas6［25.24（17.61，42.86）ng/ml］水平均高于轻度感染组，差异均有统计学意义（ P均<0.05）。血清Flt3L浓度与WBC呈负相关（ r=-0.375， P<0.05），与IL-6呈正相关（ r=0.341， P<0.05）；血清Gas6浓度与WBC呈负相关（ r=-0.461， P<0.05）。ROC曲线分析表示血清Flt3L和Gas6预测诊断感染的曲线下面积及95% CI分别为0.811（0.719~0.902）和0.643（0.526~0.759），血清Flt3L与hsCRP、PCT和IL-6联合应用后，曲线下面积分别为0.956、0.923和0.865。Kaplan-Meier曲线分析表示NHL化疗患者血清Flt3L≥649.80 pg/ml及血清Gas6≥21.50 ng/ml时，医院感染率显著升高（ P均<0.05）。 结论:NHL化疗后感染患者血清Flt3L和Gas6水平明显升高并与感染严重程度有关。早期检测血清Flt3L浓度有助于预测NHL患者化疗后感染及病情判断。

OBJECTIVEST cell immunoglobulin and mucin domain 3 (TIM-3) has been reported as an important regulatory molecule on T cells and plays a pivotal role in autoimmune diseases, but the impact on dendritic cells (DCs) is poorly explored. The formation of neutrophil extracellular traps (NETs) is considered as strongly implicated in the pathogenesis of autoimmune diseases, such as in myeloperoxidase-antineutrophil cytoplasmic autoantibody associated vasculitis (MPO-AAV). This study thus aimed to investigate the potential regulation roles of TIM-3 in the regulation of NETs-mediated DC activation in MPO-AAV.METHODSTwenty untreated patients with MPO-AAV and 20 healthy controls were enrolled in this study. The expressions of TIM-3 and toll-like receptor 4 (TLR4) in peripheral blood dendritic cells were analysed by flow cytometry, and the release of NETs by neutrophils was evaluated by immunofluorescence. In animal experiments, we measured the DC activation markers after the stimulation of NETs. Furthermore, we detected the NETs-mediated DC activation after TIM-3 blockade.RESULTSHere we found an increased spontaneous NET production in MPOAAV patients. We also revealed a markedly reduced expression of TIM-3 and an increased expression of TLR4 on DCs of active MPO-AAV patients. We found the NETs could induce the activation of DCs and promote Toll-like receptor 4 expression on DC surface. More interestingly, the blockade of TIM-3 could further enhance the NETs-mediated DC cytokine expression.CONCLUSIONSOur results demonstrated DC surface TIM-3 plays an important role in maintaining the NETs mediated immune homeostasis in MPO-AAV, suggesting an important role in MPOAAV development.

『目的]评价乳腺癌患者血清可溶性T细胞免疫球蛋白及黏蛋白分子-3 (souble T cell im-munoglobulin and mucin-domain containing molecule-3,sTim-3)及其配体半乳糖凝集素-9(galactose lectin-9,Galectin-9)、癌胚抗原相关细胞黏附分子1(carcino-embryonic antigen related cellular adhesion molecule-1,CEACAM-1)表达水平,并探讨其临床意义.[方法]收集2019年7月至2020年10月武汉市中西医结合医院甲乳外科住院的乳腺癌患者90例血清,同期选择选择60名年龄相应匹配的健康体检者血清为对照组.酶联免疫吸附法检测乳腺癌患者和对照组血清sTim-3、Galectin-9、CEACAM-1表达水平.ROC曲线分析血清sTim-3、Galectin-9对乳腺癌的诊断学效能.[结果]乳腺癌患者血清sTim-3[2.59(1.78～4.03) ng/ml]和Galectin-9 [2.20(1.55～3.05) ng/ml]表达水平显著性高于对照组sTim-3 [1.79(1.19～2.45) ng/ml]和Galeetin-9『1.59 (1.18～2.15) ng/ml](P＜0.05),乳腺癌患者血清CEACAM-1水平与对照组相比无显著性差异(P=0.622).乳腺癌患者血清sTim-3表达水平与年龄、肿瘤大小、临床分期、腋窝淋巴结转移显著性相关(P＜0.05),与组织学分级、Ki-67表达无显著性相关(P＞0.05).Galectin-9表达水平与临床病理学特征无显著性相关(P＞0.05).乳腺癌患者血清CEACAM-1表达水平随组织学分级的升高而增高(P=-0.025),与其他临床病理学特征无显著性相关(P＞0.05).sTim-3和Galectin-9诊断乳腺癌的曲线下面积分别为0.741 (95％CI:0.666～0.816),0.692 (95％CI:0.599～0.785).[结论]乳腺癌患者血清sTim-3及其配体Galectin-9表达水平显著性上调,血清sTim-3与多个临床病理学特征相关,对乳腺癌的诊断具有一定价值.CEACAM-1在乳腺癌患者血清中表达未见升高,但与组织学分级存在一定关联,其与乳腺癌的关系有待进一步研究.

细胞因子是调控免疫应答及介导炎症反应的关键分子,在防御病原体感染和自身免疫性疾病发生机制中起重要作用.机体内细胞因子免疫耐受不完全,可产生相应的抗细胞因子自身抗体(anti?cytokine autoantibodies,ACAA).ACAA通过阻断靶细胞因子的生物学功能诱导获得性免疫缺陷,被认为是"原发性免疫缺陷的自身免疫表型".研究发现ACAA的存在不仅引发特殊感染表型,还与多种自身免疫性疾病的发展及预后相关.研究发现中和性I型干扰素自身抗体可能是导致危重症新型冠状病毒肺炎(COVID?19)的诱因.该文将对ACAA相关的特殊感染表型及自身免疫性疾病中的临床意义进行简要综述.

Viruses infect host cells by binding to receptors on their surfaces of cells. Receptor is an important factor affecting host range and interspecific transmission. In December 2019, an outbreak of unexplained pneumonia occurred in Wuhan, Hubei province. The pathogen was a new coronavirus, named 2019 novel coronavirus (2019-nCoV) by WHO. Angiotensin-converting enzyme 2 (ACE2) was found to be the receptor of 2019-nCoV. This review provides a brief overview of human coronavirus receptors and their applications, with a view to providing references for the tracing, cross-species transmission, epidemiological analysis and antiviral and vaccine studies of 2019-nCoV.

目的 观察不同性别的冠心病(coronary heart disease,CHD)患者脂质代谢特征,制定个性化的诊疗方案,提高防治水平.方法 回顾性分析2007年至2017年在武汉市第一医院体检中心进行常规体检的1200例(男性600例,女性600例)脂代谢异常并于6月内在我院心内科行冠脉造影检查确诊CHD患者的病历资料,包括中医体质辨识资料、血脂水平等临床资料,研究不同性别CHD患者体质与脂质代谢特征.结果 不同性别CHD患者体质不同,脂质代谢的种类和水平也不同.女性冠心病患者TC水平整体高于男性患者,男性冠心病患者整体TG水平高于女性患者,女性痰湿质、气郁质和血瘀质患者TC水平高于男性患者,男性阳虚质患者TG水平高于女性患者,男性阴虚质患者HDL水平高于女性患者,女性痰湿质和血瘀质患者HDL水平低于男性患者,女性平和质、气虚质和特禀质患者LDL水平高于男性性患者.结论 CHD患者脂质代谢与性别和体质相关,针对不同人群和体质制定个性化的防治方案具有重要的临床价值.

目的:研究脂质代谢与体质和冠心病(CHD)发生的关系.方法:选择2007-2017年在我院体检中心进行常规体检的脂代谢异常的CHD患者1 200例,其中男600例,女600例.收集体检档案中1个月内在我院心内科行冠状动脉造影检查并确诊CHD患者的病历资料,包括中医体质辨识资料、血脂水平以及年龄、性别等临床资料,对其进行分析,研究不同体质患者脂质代谢与CHD发生的关系.结果:男性群体中湿热型体质CHD的发病率最高,女性群体中气郁型体质CHD的发病率最高,在全部人群中,湿热型体质CHD的发病率最高;不同性别CHD患者中医体质类型与脂代谢水平比较有差异.结论:不同性别特征的男女群体的体质特征与脂质代谢相关,男女存在一定的差异,CHD的发生具有体质易感性,体质调理预防CHD具有一定的临床价值.

目的 繁殖和鉴定Mfge8基因敲除C57BL/6小鼠,获取纯合子(Mfge8-/-)小鼠,并比较Mfge8-/-小鼠血清学及组织学改变.方法 对幼鼠剪尾抽提基因组DNA,用PCR法和琼脂糖凝胶电泳法鉴定幼鼠基因型;利用TUNEL法分别检测12周龄野生型(WT)和Mfge8-/-小鼠肺组织中凋亡细胞;并且利用免疫荧光法分别检测36周龄WT和Mfge8-/-小鼠血清中ANA和AECA含量.结果 构建的基因敲除小鼠已成功繁育保种,并得到纯合基因缺失型小鼠.同时,12周龄Mfge8-/-小鼠肺组织中凋亡细胞数量明显多于WT小鼠;36周龄Mfge8-/-小鼠血清中ANA抗体及AECA抗体阳性,而WT小鼠血清中呈现阴性.结论 C57BL/6背景小鼠敲除Mfge8基因后,更易发生自身免疫疾病.

肌动蛋白是细胞骨架微丝系统的主要组成成分,在细胞膜完整性受损的情况下,肌动蛋白被释放到细胞外成为危险相关分子模式的一员.目前已发现的胞外肌动蛋白有三种存在形式:与细胞膜外表面连接、存在于细胞外基质或是游离于循环体液中.胞外肌动蛋白参与多种疾病病理生理过程,作为一种自身抗原也参与许多自身免疫性疾病的发生发展.循环游离肌动蛋白、抗肌动蛋白免疫球蛋白以及肌动蛋白清除系统相关组分均可以作为生物标志物,用于多种疾病的预后判断.

Alarmins known as danger associated molecular patterns(DAMPs) are released into the extracellular endogenous bi-ological mediate by white blood cells and epithelial cells when body in a state of tissue injury and inflammation or physiological stress. Immunological and adaptive immune responses are activated and strengthened by chemotaxis and activation of antigen presenting cells(APC). They are closely associated with the disease development and outcome,and have important guiding significance for clinical diagnosis and treatment.

Objective To investigate the value of F-actin autoantibodies in the serum of patients with systemic lupus erythematosus (SLE),and to explore the relationships between F-actin autoantibodies and other clinical indicators.Methods ELISA was established to detect serum levels of F-actin autoantibodies in 93 inpatients with SLE from March 2017 to January 2018 (case group,n=93),72 patients with rheumatoid arthritis (RA) (disease control group) and 83 healthy subjects (healthy control group) were included during the same period.The positive rates of F-actin autoantibodies between the case group and the two control group were compared.Clinical data including SLE disease activity index (SLEDAI),immuno-globulin (lg)G,erythrocyte sedimentation rate (ESR),anti-dsDNA,and antinuclear antibody (ANA) of 93 patients with SLE were collected and the correlation analysis between F-actin autoantibodies units was applied respectively.The diagnostic performance of F-actin autoantibodies in SLE was analyzed by using the receiver operating characteristic curve (ROC).T test,Chi-square test and Spearman/Pearson correlation analysis were applied for statistical analysis.Results The serum levels of F-actin autoantibodies in the SLE case group,disease control group,and healthy control group were (18±13),(12±6),and (11±5) U,respectively,the differences between SLE case group and disease control group,and healthy control group were significant (t=3.163,P=0.001 9;t=4.436,P＜0.01).The positive rates of F-actin autoantibodies were 33％(31/93) in patients with SLE,10％(7/72) in disease control group,and 4％(3/83) in healthy control group.The F-actin autoanti-bodies units in SLE were correlated with SLEDAI,IgG,ESR,anti-dsDNA,and ANA (r=0.273 7,P=0.008 3;r=0.558 7,P＜0.01;r=0.419 9,P=0.000 1,r=0.351 4,P=0.001 1,r=0.460 9,P＜0.01),in which F-actin autoantibodies units showed significant correlation with IgG and ANA.In the ROC curve,the area under the curve(AUC) was 0.62 [95％CI(0.54,0.70)],P=0.001 3.which was statistically significant.When the cut-off value of the F-actin autoantibodies was 14.04 U,the Youden's index (YI) was the largest (YI=0.30),and the sen-sitivity for the diagnosis of SLE was 0.77,the specificity was 0.53.Conclusion The positive rate of F-actin autoantibodies in the serum of patients with SLE is higher than that of RA and healthy controls,so it has certain diagnostic value for SLE.The F-actin autoantibodies units is correlated with both SLEDAI,ESR,and anti-dsDNA,suggesting that F-actin autoantibodies units may be a new biomarker for disease activity assessment of SLE patients.

The IL-36,which is a member of IL-1 family,consists of three ligands IL-36α,IL-36β and IL-36γ. The cytokines exert their proinflammatory effects through a specific IL-36 receptor(IL-36R),IL-36Ra is an antagonist of IL-36R.IL-36 acts as a helper,involved in dendritic cell and T cell activation, maturation, polarization, antigen presentation and stimulating inflammatory factor production,and so on.IL-36,as a new proinflammatory factor,plays a very important role in many inflammation diseases, including psoriasis,inflammatory bowel disease,arthritis,SLE,lung diseases and so on.

目的 探讨肝功能异常患者血清F-肌动蛋白表达水平变化及临床意义.方法 肝功能异常患者71例(观察组),体检健康者83例(对照组),检测2组血清F-肌动蛋白、谷丙转氨酶(glutamic pyruvic transaminase,GPT)、谷草转氨酶(glutamic oxaloacetic transaminase,GOT)、γ-谷氨酰转移酶(γ-glutamyl transferase,γ-GT)、碱性磷酸酶(alkaline phosphatase,ALP)水平;Spearman法分析观察组血清F-肌动蛋白与GPT、GOT、γ-GT、ALP水平的相关性;绘制ROC曲线分析血清F-肌动蛋白诊断肝功能异常的效能.结果 观察组血清F-肌动蛋白[1.48(1.08,2.39)μg/L]、GPT[105.00(75.00,177.00) u/L]、GOT[81.00(59.00,163.00) u/L]、γ-GT[127.50 (50.25,314.75) u/L]、ALP[131.50(97.25,152.32)u/L]水平均高于对照组[1.17(0.89,1.93) μg/L、19.00(14.50,22.00) u/L、20.00(18.00,22.00) u/L、17.00(13.00,24.50) u/L、84.00(74.50,98.75) u/L] (P＜0.05);血清F-肌动蛋白与GOT、ALP呈正相关(r=0.273,P=0.033;r=0.322,P=0.011),与GPT、γ-GT无相关性(r=0.217,P=0.094;r=0.112,P=0.392);血清F-肌动蛋白值以1.042 9为最佳截断值,诊断肝功能异常的AUC为0.624(95％CI:0.535～0.713,P=0.009),灵敏度为80.3％,特异度为43.2％.结论 肝功能异常患者血清F-肌动蛋白表达明显上调,检测血清F-肌动蛋白水平有助于肝功能异常的诊断.

Smoking is considered to be the main source of indoor pollution, and it has been identified as an important environmental factor contributing to asthma onset. We know that T helper 2 (Th2) response plays a crucial role in the process of asthma disease. We have investigated the reaction of cigarette smoke extract (CSE) on Th polarization which is controlled by dendritic cells (DCs). Stimulated by CSE, immature DCs from murine bone marrow showed upregulated levels of TIM4. Cocultured with CD4+ T cells, stimulated DCs increased the ratio of IL-4+ versus IFN-γ+ of CD4+ T cells. This suggests a differentiation towards Th2 response. Moreover, antibodies against TIM4 reversed the upexpression of the IL-4+/IFN-γ+ ratio provoked by CSE, indicating that the Th2 polarization which was induced by CSE is via TIM4 mechanisms. CSE could activate mitogen-activated protein kinase pathways like ERK and p38. Upregulation of TIM4 expression by CSE stimulation was found to be inhibited by an ERK inhibitor but not p38 and JNK. In conclusion, DC-induced Th2 polarization is a hallmark of CSE allergy, and this aspect can be explained by CSE-induced TIM4 expression.