巨噬细胞与结核分枝杆菌的免疫反应的研究进展

巨噬细胞是结核分枝杆菌在机体内的主要宿主细胞.细胞介导的免疫反应是机体抗结核分枝杆菌的主要免疫保护机制,巨噬细胞可通过吞噬、溶酶体融合,提呈结核分枝杆菌抗原,产生多种细胞因子、反应氧中间产物和反应氮中间产物,以及细胞凋亡等多种途径来杀灭结核分枝杆菌;同时,结核分枝杆菌也可采取各种方式来逃逸巨噬细胞的免疫作用.本文就巨噬细胞与结核分枝杆菌的免疫反应的研究进展作一综述.     

Increased frequency and cell death of CD16+ monocytes with Mycobacterium tuberculosis infection

Monocytes from tuberculosis patients exhibit functional and phenotypical alterations compared with healthy controls. To determine whether these discrepancies can be explained by changes in monocyte subsets, the expression of CD14 and CD16 was evaluated in tuberculosis patients and healthy controls; additionally, some markers related to the mononuclear phagocytes maturation, differentiation and function, such as CD1a, CD1c, CD11b, CD11c, CD13, CD33, CD36, CD40, CD64, CD68, CD80, CD83, CD86, HLA-DR, CCR2, CCR5, and non-specific esterases (NSE) were determined in monocyte subsets. Patients had increased percentage of circulating CD14^HiCD16⁺ and CD14^LoCD16⁺ monocytes. The percentage of monocytes expressing CD11b, CD36, CD64, CD68, CD80, CD86, CCR2 and NSE was lower in CD14^HiCD16⁺ and CD14^LoCD16⁺ cells than in CD14^HiCD16⁻ monocytes. M. tuberculosis infected CD16⁺ monocytes produced more TNF-α and less IL-10 than CD16⁻ cells at 6 h post-infection. Isolated CD16⁺ monocytes spontaneously underwent apoptosis during differentiation into macrophages; in contrast to CD16⁻ monocytes that became differentiated into monocyte-derived macrophages (MDM) with a minimal induction of cell death. In addition, there were more Annexin V and propidium iodide positive monocytes in the CD16⁺ subset infected with live M. tuberculosis at 24 h than CD16⁻ monocytes. Under the culture conditions established for this study, the monocyte subsets did not differentiate into dendritic cells. These results show that tuberculosis patients have an augmented frequency of CD16⁺ circulating monocytes which are more prone to produce TNF-α and to undergo cell death in response to M. tuberculosis infection.     

对2型糖尿病患者肺功能变化及其相关因素的临床分析

目的 分析2型糖尿病患者肺功能变化的影响因素.方法 选取该院2018年10月—2019年5月期间收治的62例2型糖尿病患者以及同期于该院接受体检的60名健康体检者作为研究对象,分别作为观察组和对照组,对比两组受检者各项肺功能指标的差异,分析糖化血红蛋白(HbA1c)水平、微血管并发症积分以及胰岛素抵抗指数(HOMA-I...     

5种结核分枝杆菌Rpf样蛋白的活性鉴定及促生长作用

目的探讨结核分枝杆菌5种Rpf样蛋白(RpfA、RpfB、RpfC、RpfD、RpfE)的生物学活性及其促生长作用。方法根据GenBank中结核分枝杆菌H37Rv基因组核酸序列分别设计5种Rpf样蛋白特异性引物序列,采用PCR技术扩增目的片段,克隆、表达及纯化结核分枝杆菌的5种Rpf样蛋白,应用获得的Rpf样蛋白对藤黄微球菌、BCG和结核分枝杆菌标准菌株H37Rv的促生长活性观察。结果成功获得了纯化的五种Rpf重组蛋白,其浓度分别为374.76μg/mL、300μg/mL、116.27μg/mL、306.9μg/mL、349.8μg/mL;促生长效果观察,其中RpfC无明显的促生长活性,RpfE的促生长活性最明显;A、B和D均有一定程度的促进这三种菌生长增殖的作用。结论Rpf样蛋白具有促进结核分枝杆菌增殖的作用,有可能成为一种新型的培养基添加剂,为结核菌的快速培养及相关研究奠定基础。     

三种细胞因子在肺结核与肺癌胸腔积液中的诊断价值

目的 分析肺结核患者(TB)和肺癌患者胸腔积液中巨噬细胞迁移抑制因子(MIF)、孤核受体α(RORα)和孤核受体γ(RORγ)水平的差异,探讨其在肺结核与肺癌鉴别诊断中的价值。 方法 通过简单随机抽样,将已确诊为肺结核和肺癌的冻存胸腔积液样本进行编号,抽取样本各80例,总结研究对象的基本信息,采用酶联免疫吸附法检测各样本中的MIF、RORα及RORγ水平。采用SPSS 20.0软件进行统计学对比分析,本研究中两组计量资料不符合正态分布,采用“Mann-Whitney U检验”,以P<0.05为差异有统计学意义。 结果 肺结核组和肺癌组胸腔积液中的MIF水平中位数(四分位数)[M(Q₁,Q₃)]分别为5.83(2.41,16.43)、2.79(0.91,11.12)ng/L,差异有统计学意义(U=2314.50,P<0.01);肺结核组和肺癌组胸腔积液中RORα水平[M(Q₁,Q₃)]分别为0.63(0.37,1.66)、0.63(0.57,2.16)ng/L,差异无统计学意义(U=3525.00,P>0.05);肺结核组和肺癌组胸腔积液中RORγ水平[M(Q₁,Q₃)]分别为3.23(1.82,5.26)、3.44(1.94,7.11)ng/L,差异无统计学意义(U=3431.50,P>0.05)。 结论 肺结核患者胸腔积液中MIF水平高于肺癌患者, 检测胸腔积液中MIF水平对肺结核与肺癌的鉴别有一定诊断价值;而胸腔积液中RORα及RORγ水平检测的价值仍有待进一步验证。     

肺癌患者血清癌胚抗原、神经元特异性烯醇化酶、细胞角蛋白21-1变化及其临床意义

目的观察肺癌患者血清癌胚抗原(CEA)、神经元特异性烯醇化酶(NSE)、细胞角蛋白21-1(CYFRA21-1)水平变化,探讨其临床意义。方法选取海安县肿瘤医院2012—2013年收治的经病理检查确诊的肺癌患者35例为肺癌组,肺部良性疾病患者38例为良性病变组,同期50例体检健康者为对照组,检测其血清CEA、NSE、CYFRA21-1水平。结果肺癌组患者血清CEA、NSE、CYFRA21-1水平均高于良性病变组、对照组(P0.05);良性病变组与对照组受试者血清CEA、NSE、CYFRA21-1水平比较,差异均无统计学意义(P0.05)。35例肺癌患者治疗后血清CEA、NSE、CYFRA21-1水平均低于治疗前(P0.05)。结论肺癌患者血清CEA、NSE、CYFRA21-1水平明显升高,血清CEA、NSE、CYFRA21-1水平检测可用于肺癌治疗疗效判断及预后评估。     

Safe Concurrent Use of Anti-tuberculosis Drugs and Pembrolizumab in a Patient with Non-small-cell Lung Cancer Who Was Infected with Mycobacterium tuberculosis

A 68-year-old Japanese man was diagnosed with lung adenocarcinoma stage IVB. We introduced a first-line chemotherapy of four cycles of carboplatin and pemetrexed and pembrolizumab, followed by pemetrexed and pembrolizumab maintenance therapy. Approximately four months after anticancer therapy, a small nodule appeared in the right peripheral S3 lesion. After five months, the nodule was confirmed as a Mycobacterium tuberculosis (TB) nodule. We initiated anti-TB therapy without stopping pembrolizumab, and the right S3 nodule shrank immediately. This report supports the concurrent use of anti-TB treatment with an immune checkpoint inhibitor when the TB infection area is limited.