过敏性哮喘患儿外周血T细胞免疫球蛋白及黏蛋白域4和血清免疫球蛋白G4的水平变化及意义

目的 研究过敏性哮喘患儿外周血T细胞免疫球蛋白及黏蛋白域4(TIM4)、血清免疫球蛋白G4(IgG4)的水平变化及诊断价值.方法 选取2016年12月至2019年2月广东省第二人民医院收治的过敏性哮喘患儿80例,按照病情严重程度将入选患者分为轻度哮喘组(24例)、中度哮喘组(29例)和重度哮喘组(27例).另取同期于我...     

初诊急性髓系白血病患者T细胞免疫球蛋白黏液素3和程序性死亡分子1的表达及临床意义

目的 探索初诊急性髓系白血病患者T细胞免疫球蛋白黏液素3(Tim-3)和程序性死亡分子1(PD-1)的表达水平及其临床意义。方法 回顾性选取2018年7月至2020年4月在聊城市第二人民医院住院及门诊初诊的34例急性髓系白血病患者和20例良性血液病患者作为研究对象,根据不同疾病分为观察组(急性髓系白血病,34例)和对照组(良性血液病,20例)。应用流式细胞术分别检测外周血CD3⁺T细胞Tim-3和细胞程序性死亡-配体1(PD-L1)的表达水平,以及应用实时荧光定量PCR检测骨髓Tim-3 mRNA和PD-L1 mRNA的相对表达量,并进行对比分析。结果 观察组患者的外周血CD3⁺细胞Tim-3的表达、骨髓Tim-3 mRNA均高于对照组,差异有统计学意义(P<0.001);观察组患者的外周血CD3⁺细胞PD-L1的表达、骨髓PD-L1 mRNA均高于对照组,差异有统计学意义(P<0.001)。结论 初诊急性髓系白血病患者Tim-3和PD-L1表达水平升高,在急性髓系白血病免疫抑制微环境的形成中起到了一定作用。     

FOXP3及调节性T细胞与支气管哮喘的相关性研究

目的检测支气管哮喘患者外周血CD4+T细胞、CD4+ CD25+T细胞、CD4+ FOXP3+T细胞三类亚群,分析其在支气管哮喘患者的表达。方法选择112例支气管哮喘患者和56例正常人作为对照,采用流式细胞术检侧患者外周血的CD4+T细胞、CD4+ CD25+ T细胞、CD4+ FOXP3+T细胞。结果 FOXP3主要表达在CD4+ CD25+T细胞上,CD4+ CD25+T细胞、CD4+FOXP3+T细胞与对照组相比均明显降低(P<0.01),急性发作期哮喘患者外周血中CD4+ CD25+ T细胞、CD4+ FOXP3+T细胞明显低于非急性发作期(P<0.01),与疾病的活动性相关。结论支气管哮喘患者存在明显的免疫功能失调,CD4+ CD25+T细胞、CD4+ FOXP3+ T细胞在疾病活动中起着重要作用,是导致患者细胞免疫功能失调的重要原因。     

靶向T细胞免疫球蛋白黏蛋白3的免疫检查点抑制剂——Sabatolimab

T淋巴细胞免疫球蛋白黏蛋白3(TIM-3)是新兴免疫检查点中的一种重要抑制性受体。Sabatolimab(研发代号:MBG453)是诺华制药公司开发的一款新型抗TIM-3单克隆抗体,其能够靶向抑制白血病干细胞的更新并激活免疫细胞,最终实现对恶性血液病的免疫治疗。此外,Sabatolimab与程序性死亡受体1(PD-1)抑制剂联用有望进一步激活肿瘤免疫疗效并改善耐药性。目前该药已进入Ⅲ期临床研究阶段,Sabatolimab单药和联合治疗恶性血液病均表现出良好的疗效与安全性。本文就Sabatolimab的基本信息、作用机制、临床前研究及临床研究等作简要概述。     

呼吸系统疾病潜在治疗靶点半乳糖凝集素-3的研究进展

半乳糖凝集素-3属于半乳糖凝集素家族,是一种广泛分布于人体内的内源性β-半乳糖苷结合凝集素,在细胞的增殖、分化、凋亡、细胞黏附、免疫反应以及信号转导等多种功能中发挥重要作用.越来越多的证据表明,半乳糖凝集素-3参与了呼吸系统多种疾病的发生发展,涉及特发性肺纤维化、肺癌、肺动脉高压和支气管哮喘等疾病.本综述总结并分析了半...     

哮喘患儿血清免疫球蛋白和T淋巴细胞亚群检测

笔者对30例确诊为哮喘的患儿进行了血清免疫球蛋白和T淋巴细胞亚群的检测，以探讨哮喘发作期患儿血清免疫球蛋白和T淋巴细胞亚群与哮喘发病的关系。     

支气管哮喘患儿血清可溶性细胞间黏附分子-1的测定

目的 :探讨可溶性细胞间黏附分子 -1(sICAM -1)与哮喘的关系及激素对其的影响。方法 :采用放射免疫法测定30例哮喘患儿 (哮喘组 ) ,30例健康小学生 (正常对照组 )的血清sICAM -1。结果 :(1)哮喘组急性发作期及缓解期血清sICAM -1水平均较正常对照组高 (均P<0.01)。(2)哮喘患儿在缓解期血清sICAM -1水平较急性发作期明显下降 (P<0.01) ;9例服强的松的哮喘患者 ,其血清ICAM -1水平在服药期间低于停用激素1周后 ,差异有统计学意义 (P<0.05)。结论 :(1)黏附分子可能参与了哮喘的发生与发作 ,其水平的高低可能与哮喘的活动度有关。 (2)激素可能通过抑制血清ICAM -1的升高而起到控制及预防哮喘发作的作用     

激活的T细胞与嗜酸细胞在哮喘中的作用

激活的Ｔ细胞与嗜酸细胞在哮喘中的作用山西医学院第二附属医院（０３０００１）孙春香李黎宋涛太原铁路中心医院王红卫传统观点认为哮喘为Ⅰ型变态反应所致支气管痉挛所致，但现代医学证实这种观点不全面，哮喘的本质是由多种细胞参与的气道变应性炎症，尤其与嗜酸细胞不...     

可溶性细胞间黏附分子-1与支气管哮喘病情程度的关系

目的探讨可溶性细胞间黏附分子－1（sICAM－1）与支气管哮喘发作及其病情严重程度的相关性。方法采用ELISA方法测定134例不同时期支气管哮喘患者及健康志愿者血清sICAM-1水平,同时对支气管哮喘急性发作期患者进行肺功能测定。结果63例急性发作期支气管哮喘患者血清sICAM-1[（298．05±52．33）ng／L]水平较缓解期患者[（213．36±16．88）．g／L]及健康志愿者[（117．83±13．23）ng／L]明显升高,并且随哮喘病情加重其值有明显升高;急性发作期患者肺功能第一秒用力呼吸量（FEV．％）值与血清slCAM-1呈明显负相关。结论slCAM-1是支气管哮喘发病中重要的黏附分子,可作为判断病情严重程度的指标之一。     

调节性T细胞、免疫球蛋白G4对支气管哮喘急性发作患儿再次发作的预测价值

目的 分析调节性T细胞(Treg)、免疫球蛋白G4(IgG4)对支气管哮喘(BA)急性发作患儿再次发作的预测价值。方法 选取2019年1月至2021年9月景德镇市妇幼保健院收治的86例BA急性发作患儿作为研究对象,对所有患儿均开展为期1年的随访观察,按照再次发作情况与否分成再次发作组(40例)与未再次发作组(46例)。比较两组治疗前的外周血Treg、IgG4水平,一般资料以及肺功能指标,并以受试者工作特征(ROC)曲线分析明确外周血Treg、IgG4水平预测BA急性发作患儿再次发作的效能。结果 再次发作组外周血Treg、IgG4水平低于未再次发作组,差异有统计学意义(P<0.05)。再次发作组年龄低于未再次发作组,治疗前哮喘严重程度重于未再次发作组,合并过敏性鼻炎以及合并慢性鼻窦炎人数占比均高于未再次发作组,差异有统计学意义(P<0.05)。再次发作组各项肺功能指标水平低于未再次发作组,差异有统计学意义(P<0.05)。外周血Treg、IgG4水平联合检测预测BA急性发作患儿再次发作的曲线下面积优于上述两项指标单独预测效能(P<0.05)。结论 Treg、IgG...     

T cell immunoglobulin-3 as a new therapeutic target for rheumatoid arthritis

T cell immunoglobulin-3 (Tim-3) is a surface molecule expressed on various cell types of the immune system which plays a central role in immune regulation. Recently, identi?cation of galectin-9 (Gal-9) as a ligand for Tim-3 has established the Tim-3–Gal-9 pathway as an important regulator of Th1 immunity and induction of tolerance. The interaction of Tim-3 with Gal-9 induces cell death; the in vivo blockade of this interaction results in exacerbated autoimmunity and abrogation of tolerance in experimental models, thus establishing Tim-3 as a negative regulatory molecule. A number of previous studies have demonstrated that Tim-3 in?uences chronic autoimmune diseases, such as multiple sclerosis and systemic lupus erythematosus. In addition, an association between Tim-3 polymorphisms and susceptibility to several autoimmune diseases has been identi?ed in various autoimmune diseases, including rheumatoid arthritis (RA). Recent work has focused on the role of Tim-3 in RA, and the results indicate that Tim-3 may represent a novel target for the treatment of RA. In this article we will discuss the Tim-3 pathway and the therapeutic potential of modulating the Tim-3 pathway in RA.     

防治血管再狭窄的新靶点——缝隙连接蛋白43

缝隙连接是介导相邻细胞间离子和小分子信号物质直接交换的跨膜通道,血管平滑肌细胞中主要表达连接蛋白43(connexin43,CX43)。研究表明,CX43表达上调与平滑肌细胞的增殖、迁移及细胞外基质生成密切相关,促使血管损伤后新内膜生成,引起血管再狭窄,提示CX43可能成为血管性疾病治疗的新靶点。本文综述CX43与血管再狭窄之间关系及以CX43为靶点的药物和基因治疗的研究进展。     

Isoforms of human B7-H3 co-signalling molecule for T cell activation as potential immunoregulatory agents

B7 family molecules, which are expressed on antigen-presenting cells and display extracellular regions containing immunoglobulin (Ig) variable (V)- and constant (C)-like domains, are known to modulate T cell receptor (TCR)-mediated T cell activation by providing co-signals that are either stimulatory or inhibitory. One of the most recently identified members of this family is B7-H3 (B7 homologue 3). Here, evidence is presented that human B7-H3 exists as two isoforms: B7-H3 VC, which contains one IgV- and IgC-like domain, and B7-H3 VCVC, which contains two such domains. The latter represents the predominant B7-H3 molecule detectable in various human tissues. Both B7-H3 isoforms are shown to decrease the proliferation and cytokine production induced by TCR activation of human T cells in vitro. It is therefore claimed that B7-H3 molecules may provide tools to modulate immune responses for therapeutic purpose.     

BALB/c 3T3 cell transformation assay for the prediction of carcinogenic potential of chemicals and environmental mixtures

The prediction of the carcinogenic risk for humans is mostly based on animal experiments. For the last 20 years, however, the scientific community has paid great attention to alternative strategies in compliance with common moral and ethical values. The new European chemical regulation REACH (Reg. EC 1907/2006) requires the performance of new studies in vertebrates only as a last resort. REACH asks for the development of validated in vitro protocols that can replace, in the medium to the long term, animal bioassays. An in vitro cell transformation assay (CTA) is proposed as an alternative to in vivo carcinogenicity testing. This assay is reported in the list of accepted methods for REACH (Reg. EC 440/2008).The BALB/c 3T3 model represents one of the most well-known CTAs and is regarded as a useful tool to screen single chemicals or complex mixtures for carcinogenicity prediction. In this study we used a modified protocol to highlight the transforming potential of three single compounds, ethinylestradiol (EE), azathioprine (AZA-T), melphalan, and two polychlorinated biphenyls (PCBs) mixtures, which are known or suspected to be human carcinogens. We also evaluated the activity of the antioxidant alpha-lipoic acid (ALA), a promising tumor chemopreventive. A significant increase in transformation frequency was observed when the BALB/c 3T3 cells were exposed to EE, AZA-T or melphalan as well as after PCBs treatment. On the contrary, ALA did not induce any increase of foci occurrence. Our results confirm the suitability of the improved protocol to discriminate carcinogenic compounds and support the use of BALB/c 3T3 cell transformation assay as a possible alternative to predict carcinogenic risk to humans.     

IL-17-expressing cells as a potential therapeutic target for treatment of immunological disorders

IL-17 is a multifunctional cytokine produced by activated CD4+ and CD8+ lymphocytes as well as stimulated unconventional Tγδ and natural killer T cells. IL-17 induces expression of chemokines, proinflammatory cytokines and metalloproteinases, thereby stimulating the inflammation and chemotaxis of neutrophils. Elevation of proinflammatory cytokines is associated with asthma and autoimmune disorders, such as multiple sclerosis, rheumatoid arthritis and psoriasis. Although the role of IL-17 in these disorders is not always easy to define, extensive research has demonstrated an aggravating influence of IL-17 in some animal models. Thus, the development of therapeutics to reduce IL-17 levels is a promising strategy for ameliorating inflammatory diseases. This review briefly summarizes recent knowledge about stimulants and intracellular signaling pathways that induce development and maturation of IL-17-expressing cells. Its positive and negative roles on disease progression and its importance in vaccine-induced memory are also discussed. Finally, recent literature describing potential therapeutic approaches for targeting IL-17 is presented.     

Budesonide/formoterol dry powder in asthma: an option for control as maintenance and reliever therapy

Importance of the field: Asthma is a heterogeneous disease with various components that may contribute to symptoms. Obtaining global control of is one of the fundamental parts of the management of this disease.

Areas covered in this review: The Cochrane trial database, Medline and Embase, were searched systematically, and approximately 20 respiratory journals and conference abstracts were searched manually. The search was limited to publications in English language of last 20 years and which included the keywords ‘budesonide’, ‘formoterol’, ‘asthma’ and ‘control’.

What the reader will gain: The purposes of this review are: i) to discuss the rationale about possibility of using combination therapy administered with a single inhaler for both daily maintenance and relief as needed of breakthrough symptoms in asthma management; ii) to give readers the current status of clinical pharmacological treatment of asthma; iii) to discuss the evidence on the use of budesonide/formoterol dry powder in one inhaler.

Take home message: Among the various inhalatory drugs, budesonide and formoterol can be conveniently delivered in one dry powder inhaler and simplify treatment by providing immediate step-up when symptoms increase. Alongside the anti-inflammatory component, formoterol provides both short- and long-acting bronchodilator effects with maintenance and reliever properties. The option of using one inhaler simplifies treatment by simultaneously providing bronchodilator and anti-inflammatory activity, thus enhancing compliance. As indicated in guidelines, all these characteristics are essential for optimizing asthma treatment and control.     

槲皮素对PDGF诱导的NIH 3T3细胞增殖的影响

目的研究酪氨酸蛋白激酶抑制剂槲皮素对ＰＤＧＦ诱导的ＮＩＨ３Ｔ３细胞增殖的影响。方法采用ＭＴＴ比色法、Ｇｉｅｍｓａ染色、流式细胞术（测定ＤＮＡ含量的变化及增殖细胞核抗原的表达）、及ＷｅｓｔｅｒｎＢｌｏｔ分析技术对ＰＤＧＦ诱导的ＮＩＨ３Ｔ３细胞增殖进行分析。结果与对照组相比，槲皮素处理可显著地抑制ＰＤＧＦ诱导的ＮＩＨ３Ｔ３细胞增殖，而且主要是细胞周期Ｓ期抑制，ＷｅｓｅｔｅｒｎＢｌｏｔ分析提示槲皮素可明显地抑制ＰＤＧＦ诱导的ＮＩＨ３Ｔ３细胞酪氨酸磷酸化程度。结论酪氨酸蛋白激酶抑制剂可显著地抑制ＰＤＧＦ诱导的ＮＩＨ３Ｔ３细胞增殖，可能是通过抑制酪氨酸蛋白激酶活性来完成。     

Survivin基因在鼻型NK／T细胞淋巴瘤的表达及其与肿瘤细胞增殖的关系

目的探讨Survivin基因在鼻型NK／T细胞淋巴瘤中的表达,并初步分析肿瘤组织中Survivin基因表达与肿瘤细胞增殖的关系及其在鼻型NK／T细胞淋巴瘤发生发展中的意义。方法应用免疫组化Envision System检测鼻型NK／T细胞淋巴瘤和正常淋巴结组织中Survivin和ki-67的表达情况,计算肿瘤组织ki-67增殖指数,并对Survivin表达阳性组和阴性组ki-67增殖指数的差异进行分析。结果50例肿瘤组织中Survivin阳性表达率为60％（30／50）,12例正常淋巴结组织中Survivin阳性表达率为16．7％（2／12）,且主要局限于少数生发中心细胞（χ^2=7．28,P〈0．05）。Survivin基因阳性组ki-67增殖指数明显高于Survivin基因阴性组（t=2．80,P〈0．05）。结论Survivin高表达在鼻型NK／T细胞淋巴瘤的发生发展中可能有一定的作用。Survivin与增殖指数呈正相关,Survivin可能促进肿瘤细胞的增殖。