肺结核患者外周血单个核细胞MCP-1表达上升

目的 研究肺结核患者血浆单核细胞趋化蛋白（MCP-1）的浓度特点及外周血单核细胞（PBMCs）经结核分枝杆菌特异性抗原肽刺激后MCP-1和IFN-γ的表达及相关性.方法 20例活动期肺结核患者和16位PPD阳性健康对照,采集EDTA抗凝血,用结核分枝杆菌特异性抗原肽刺激PBMCs,采用FlowCytomix流式技术检测血浆和细胞培养液上清上中MCP-1和IFN-γ的表达.结果 肺结核患者血浆MCP-1浓度与对照组比较差异无统计学意义[肺结核组（263.8±25.31）pg/ml,对照组（212.1±18.04）pg/ml,P＞0.05],但肺结核患者的血浆MCP-1水平偏高,尤其是呼吸道症状明显的患者.肺结核患者的PBMCs经结核分枝杆菌特异性抗原肽刺激后,培养液上清中MCP-1的水平比血浆显著升高,肺结核患者与对照组比较差异有统计学意义[（21460±3376）pg/ml vs 10910±2141）pg/ml,P＜0.01],与IFN-γ的分泌无关（spearman r=0.1835,P＞0.05）.结论 肺结核患者血浆MCP-1浓度可能与病情发展相关;结核分枝杆菌特异性抗原肽刺激外周血单个核细胞产生的MCP-1可能成为新的诊断指标之一.     

肺结核患者外周血单个核细胞MCP-1表达上升

Objective To study the feature of MCP-1 in plasma of active pulmonary tuberculosis patients and the correlation of MCP-1 obtained from PBMCs stimulated with specific Mtb peptides with IFNγ.Methods 20 patients with active pulmonary tuberculosis and 16 healthy controls with positive PPD were enrolled.The concentration of MCP-1 and IFN-γwas analyzed with Bender Flowcytomix on flow cytometry.Results No statistical difference of MCP-1 concentration in plasma was found between TB patients and controls [(263.8 ± 25.31)pg/ml and(212.1 ± 18.04)pg/ml,P ＞ 0.05].But TB patients with continuous respiratory symptoms showed higher MCP-1 in plasma.The concentration of MCP-1 and IFN-γwas significantly elevated in PBMCs culture supernatants.It was significantly higher in TB patients than in controls [(21460 ±3376)pg/ml vs(10910 ±2141)pg/ml,P ＜0.01].There was no correlation between the concentration of MCP-1 and IFN-γ.Conclusions The concentration of MCP-1 in plasma may be related to the progress of the pulmonary tuberculosis.MCP-1 stimulated by Mtb-specific peptides may be one of the biomarkers for TB diagnosis.     

基质衍生因子1等基因多态性在人群中的分布

目的　探讨SDF1-3’A、CCR2 -64I、-2 518MCP -1基因多态性在皖籍汉族人群中的分布。方法　运用PCR -RFLP方法确定SDF1-3 /A和 -2 518MCP -1基因多态性 ,运用ARMS方法确定CCR2 -64I基因多态性。结果　皖籍汉族人 -2 518MCP -1G等位基因突变频率为 64% ,高于西班牙人、美国黑人、高加索人 ,均有显著性差异(P <0 0 1)。CCR2 -64I等位基因突变频率为 2 5% ,高于美国黑人和高加索人 (P <0 0 1)。SDF1-3’A等位基因突变频率为 2 2 % ,高于美国黑人 ,但与国内其他地区均无显著性差异 (P <0 0 5)。结论　皖籍汉族人 -2 518MCP -1、CCR2 -64I、SDF1-3’A等位基因突变频率有别于其他人种     

Poor performance status is associated with early death in patients with pulmonary tuberculosis

The objective of this study was to determine whether poor performance status at the start of anti-tuberculous (anti-TB) treatment is associated with early death in patients admitted to hospital with pulmonary tuberculosis (PTB). During 3 months in 2001, all adult patients admitted to eight hospitals in Limpopo Province, South Africa, and diagnosed with PTB were eligible for inclusion. At initiation of anti-TB treatment, a performance status between 0 and 4 was estimated for each patient using a modified version of the Eastern Cooperative Oncology Group scoring system. Hospital records and local TB registers were reviewed to identify patients who had died during the first 2 months of treatment. In addition, it was ascertained whether a death notification had been received by the provincial administration. Fifty-three of 295 (18%) patients died within 2 months. Mortality increased from 6% in patients with the best performance status to 51% in patients with the poorest performance status. Univariate and multivariate Cox regression analysis showed that the hazard ratio for dying was significantly higher for patients with a performance status of 3 or 4. Poor performance status shows a strong association with early death in patients with PTB and has the potential to be a useful clinical, epidemiological and research tool.     

Factors associated with mortality in HIV-infected and uninfected patients with pulmonary tuberculosis

Background  

HIV has fuelled the TB epidemic in sub-Saharan Africa. Mortality in patients co-infected with TB and HIV is high. Managing factors influencing mortality in TB patients might help reducing it. This study investigates factors associated with mortality including patients' HIV sero-status, CD4 cell count, laboratory, nutritional and demographic characteristics in AFB smear positive pulmonary TB patients.     

The combined polymorphisms of interleukin-6-174GG genotype and interleukin-10 ATA haplotype are associated with a poor quality of life in patients with chronic hepatitis C

Quality of Life Research - Chronic hepatitis C (CHC) is associated with a decreased health-related quality of life (HRQOL). More recent studies have pointed toward a genetic basis of...     

肺结核患者血清Th1/Th2细胞因子浓度变化及影响因素研究

目的 探讨Th1型细胞因子γ-干扰素(IFN-γ)、白介素-2(IL-2)和Th2型细胞因子白介素-4(IL-4)、白介素-10(IL-10)在肺结核患者抗结核治疗前后血清浓度的变化及治疗前血清浓度的影响因素。方法 以上海市5个结核病示范区的8家定点医院为研究现场,连续纳入2013年5月-2015年8月诊断的上海市户籍肺结核患者,使用自制问卷对患者进行问卷调查,并于抗结核治疗前、治疗2个月末留取血液样本,采用酶联免疫吸附法(ELISA)分别检测IFN-γ、IL-2、IL-4、IL-10的血清浓度。结果 共纳入患者309例,其中痰涂片结核分枝杆菌阳性患者占80.6%,男女比例为2.64,平均年龄为(51.43±18.29)岁。治疗2个月末痰涂片转阴率为72.69%。IFN-γ(治疗前45.11 pg/mL,2个月末36.17 pg/mL)、IL-2(治疗前15.12 pg/mL,2个月末9.96 pg/mL)、IL-10(治疗前28.72 pg/mL,2个月末12.28 pg/mL)血清浓度治疗前后差异有统计学意义,治疗2个月末显著下降;IL-4浓度治疗前后差异无统计学意义。Th1/Th2比值(IFN-γ/IL-4)在治疗前后分别为3.59和2.17,差异有统计学意义(t=4.715,P<0.01)。结论 肺结核患者体内存在明显的免疫紊乱,抗结核治疗后,IFN-γ、IL-2、IL-10血清浓度下降,Th1/Th2比值下降。监测Th1/Th2相关细胞因子血清浓度有助于判断肺结核的病程及治疗效果。     

N-乙酰基转移酶2基因型与结核病患者发生药物性肝损害的关系

目的 研究N-乙酰基转移酶2(N-acetyltransferase 2,NAT2)基因型与抗结核药物性肝损害的关系,阐明抗结核药物性肝损害的分子机制.方法 通过病例-对照研究和聚合酶链反应-直接测序(PCR-DS)技术,收集抗结核药物所致肝损害患者101例和无药物性肝损害的结核患者107例,分别作为肝损害组和对照组,...     

A variant in the promoter of MBL2 is associated with protection against visceral leishmaniasis in Morocco

Progressive visceral leishmaniasis (VL) is fatal if not treated; yet, most infections with the causative agents are asymptomatic. We hypothesized that genetic factors contribute to this variable response to infection. The mannose-binding lectin 2 gene (MBL2) is a candidate that merits examination in the context of VL because it enhances infection with intracellular pathogens. Four functional MBL2 polymorphisms at codons 52, 54, 57 and in the promoter at the -221 position (X/Y) are known to be associated with the outcome of several diseases. The aim of the present study was to investigate whether these functional variants were associated with VL in Moroccan children.Here, we genotyped polymorphisms by sequencing and PCR-RFLP in 112 individuals with VL, 97 asymptomatic subjects and 42 healthy individuals who had no evidence of present or past infection.Regression analysis showed no significant association between polymorphisms in exon 1 genotypes and outcome of infection with Leishmania infantum. However, the genotype XY in −221 conferred a protective role against VL in our study population with a significant difference (OR = 0.291; CI [0.158–0.538]; p = 0.0006). Subjects with YY genotypes in -221 had a higher risk to developing VL.We concluded that MBL2 polymorphism at the -221 promoter region plays a protective role in L. infantum infection.     

2005-2014年北京市肺结核流行特征分析

目的 分析2005-2014年北京市肺结核流行病学特征,为北京市结核病防控提供依据.方法 采用描述性流行病学研究方法,对2005-2014年北京市报告发病的肺结核患者资料进行分析.结果 2005-2014年北京市共报告发病肺结核患者85 605例,报告发病率呈逐年下降趋势(Cochran-Armitage趋势检验,Z=-53.22,P＜0.01);全年各月报告发病数以3月最高,之后缓慢下降;全市16个区均有肺结核病例的报告,年均报告发病率前5位的分别为门头沟区、丰台区、昌平区、西城区、和通州区.男女比例为1.93:1;报告病例主要集中在15～59岁年龄段,占病例总数79.05％;15～岁和≥65岁为高发年龄,报告发病率分别为61.24/10万和83.58/10万;职业分布居前5位的分别为家务及待业、农牧渔民、离退人员、学生和教师、工人,分别占患者总数的20.20％、16.04％、12.88％、9.50％和9.23％.结论 北京市结核病报告发病率总体呈逐年下降趋势,各区之间发病率有差异,男性、青壮年和老年人、家务及待业等是结核高发因素,应有针对性的加强重点人群的防控措施.     

肺结核病新患者发现延误及影响因素分析

目的 了解浙江省新发肺结核患者发现延误的影响因素,为肺结核的早期控制提供科学依据。方法 采用回顾性研究方法收集浙江省2009年1月1日-12月31日确诊登记的31 287例新发肺结核患者病案资料,分析患者发现延误的影响因素。结果 浙江省新发肺结核患者就诊延误、诊断延误和发现延误时间中位数分别为17、1和21 d,就诊延误、诊断延误和发现延误率分别为55.66%、7.06%和62.91%;多因素logistic回归分析结果表明,羁押人群、发现地区地形为山地/岛屿、涂阳和重症患者是浙江省新发肺结核患者发现延误的危险因素;男性、15~59岁、学生/儿童、教师/医务人员/职员、服务行业人员、其他职业人员、省外流动户籍、患者来源为健康检查/转诊/追踪、发现地区地形为盆地/丘陵、诊治单位为定点医院是浙江省新发肺结核患者发现延误的保护因素。结论 新发肺结核患者就诊延误时间明显较诊断延误长;性别、年龄、职业、户籍、是否羁押人群、患者来源、发现地区地形、诊治单位类型、诊断结果、是否重症是浙江省新发肺结核患者发现延误的影响因素。     

BCG sub-strains induce variable protection against virulent pulmonary Mycobacterium tuberculosis infection, with the capacity to drive Th2 immunity

The hallmark of a vaccine is to induce long-term protective immunity against the pathogen. The use of Mycobacterium bovis BCG as a vaccine against tuberculosis has been problematic in that immunity induced by BCG wanes over time and it may be less effective against more virulent strains of Mycobacterium tuberculosis. Thus it is important to determine what factors might be associated with waning or inefficient immunity. One such factor has been associated with the difference in many types of BCG that are used around the world, or more specifically due to the loss of genomic material in the various sub-strains used in vaccination programs. To address this issue we investigated the long-term immune response generated by 3 sub-strains BCG in the C57BL/6 mouse model of experimental tuberculosis. Mice vaccinated with these diverse strains of BCG were assessed at 6 and 12 months post-vaccination. All BCG sub-strain induced elevated levels of IFN-γ-producing cells at each time point as determined by ELISpot assay. However, when mice were challenged at 6 and 12 months with either M. tuberculosis H37Rv or HN878 the ability of the BCG sub-strains to protect vaccinated mice varied, depending on the time of challenge and on the strain used to infect mice. BCG Pasteur was then used to vaccinate guinea pigs, which were subsequently infected with either H37Rv or HN878. Data showed that BCG Pasteur prolonged the survival of guinea pigs against infection with both strains. Taken together these data suggest that longevity of the immune response generated by BCG is not related to the loss of genetic material and that BCG can induce a protective immune response to infection with a clinical strain of M. tuberculosis.     

Genetic polymorphisms of CCL2, CCL5, CCR2 and CCR5 genes in Sahariya tribe of North Central India: an association study with pulmonary tuberculosis

The association of genetic variants of chemokines, CCL2 [MCP-1 (monocyte chemoattractant protein-1)], CCL5 [RANTES (regulated on activation, normal T-cell expressed and secreted)] and their receptors CCR2 and CCR5, respectively, earlier reported to be associated with susceptibility to pulmonary tuberculosis (PTB) in certain ethnic populations, were explored in Sahariya tribe, a primitive tribe of North Central India having a high prevalence of TB. We genotyped 215 cases and 215 controls of Sahariya tribe for polymorphisms in CCL2 (-2518A/G, -362G/C) by PCR-RFLP method and in CCR2 (V64I), CCL5 (-403G/A, -28C/G) and CCR5 (-59029G/A) by ARMS-PCR method. The frequencies of 'AA' genotype and 'A' allele of -403G/A were found significantly higher in cases than in controls (OR, 2.616 [95%CI, 1.302-5.320] and OR, 1.348 [95%CI, 0.980-1.853], respectively). Conversely, the frequencies of 'AA' genotype and 'A' allele of V64I were significantly (p=0.05 and 0.04, respectively) higher in controls than in cases. Also, the "AA" genotype of V64I was found to provide significant (p=0.05) protection against high bacillary load (3+). Likewise, the comparison of frequencies of different combinations of these polymorphisms further strengthens the association of -403G/A with susceptibility and V64I with resistance to TB in Sahariya tribe. However, no significant association of other polymorphisms with either resistance or susceptibility to TB was found. Thus, our findings support the association of -403G/A and V64I polymorphisms with genetic susceptibility and resistance to TB, respectively , alone or in combination with other polymorphisms in Sahariya tribe.     

Swine influenza matrix 2 (M2) protein contributes to protection against infection with different H1 swine influenza virus (SIV) isolates

A swine influenza virus (SIV) vaccine-challenge pig model was used to study the potential of a conserved matrix 2 (M2) protein vaccine alone or in combination with an inactivated H1N1-vaccine to protect against H1N1 and H1N2 viruses. The H1N1-vaccine and heterologous H1N2-challenge virus model has previously been shown to prolong fever and increase SIV-associated pneumonic lesions. The M2 vaccine in combination with the H1N1-vaccine reduced the H1N2 induced fever but not virus shedding. The M2 vaccine alone reduced respiratory signs and pneumonic lesions to levels similar to the negative control pigs following H1N2 infection. This study found that the M2 protein has potential as a vaccine for SIV-associated disease prevention. However, development of an immune response towards the major envelope HA protein was required to reduce SIV shedding.     

HTLV-1 infection is associated with a history of active tuberculosis among family members of HTLV-1-infected patients in Peru

The purpose of this study was to assess the association between human T-lymphotropic virus 1 (HTLV-1) and a lifetime history of active tuberculosis (TB) among relatives of HTLV-1-infected patients. We reviewed clinical charts of all relatives of HTLV-1-infected index cases who attended our institute in Lima from 1990-2004. The data of 1233 relatives was analysed; 394 (32.0%) were HTLV-1 positive. Eighty-one subjects (6.6%) had a history of active TB, including 45/394 (11.4%) HTLV-1-positive and 36/839 (4.3%) HTLV-1-negative relatives (P<0.001). On multivariate analysis, three factors were associated with TB history: HTLV-1 infection (adjusted OR 2.5, 95% CI 1.6-3.9), age (adjusted OR 1.3, 95% CI 1.1-1.5 per 10-year age increase) and relation to the index case (adjusted OR 2.6, 95% CI 1.3-5.1, for siblings vs. spouses of index cases). In conclusion, HTLV-1 infection may increase the susceptibility to active TB. In populations where both infections are frequent, such an association could affect the dynamics of TB.     

可溶性白细胞介素-2受体测定在肺结核病中的应用

本文应用ＥＬＩＳＡ技术，对４２名正常对照和８９名肺结核患者（包括结核性胸膜炎患者）的血清可溶性白细胞介素－２受体（ＳＩＬ－２Ｒ）进行测定。结果表明，肺结核及结核性胸膜炎患者血清ＳＩＬ－２Ｒ明显高于正常人（Ｐ＜００１），且与病变部位大小和机体是否产生结核抗体有关（Ｐ＜００５），与病程长短无显著性差异（Ｐ＞００５）。     

VEGF、RANTES、sflt-1及MCP-1在子宫内膜异位症合并代谢综合征的表达及意义

目的 探究血管内皮生长因子（VEGF）、T细胞表达和分泌的调节性激活因子（RANTES）、血管内皮生长因子可溶性受体（sflt-1）及单核细胞趋化蛋白-1（MCP-1）在子宫内膜异位症合并代谢综合征的表达及意义。方法 选取2012年1月至2015年4月期间内在江汉大学附属医院妇产科接受治疗的子宫内膜异位症合并代谢综合征240例患者作为研究组,同时选择输卵管系膜囊肿、卵巢良性肿瘤或是宫颈病变患者210例作为对照组。研究组患者根据病变部位、大小以及病灶粘连程度,分为Ⅰ~Ⅳ期,Ⅰ~Ⅱ期患者130例,Ⅲ~Ⅳ期患者110例。采用ELISA对患者血清及腹腔液中sflt-1、VEGF、MCP-1、RANTES表达表达水平进行检测,对比不同组别患者各项指标。结果 研究组患者血清及腹腔液内VEGF、sflt-1、MCP-1和RANTES表达水平均高于对照组,组间数据差异有统计学意义（血清：t值分别为119.385、32.115、13.521、104.776,腹腔液内：t值分别为94.576、42.023、14.762、35.738,均P=0.000〈0.05）;在Ⅰ-Ⅱ期组与Ⅲ-Ⅳ期组指标对比中,前者VEGF、sflt-1和R A NTES指标在血清和腹腔液中表达水平均低于后者,数据有显著统计学差异（血清：t值分别为78.152、6.151、49.337,腹腔液内：t值分别为73.424、8.424、23.385,均P=0.000〈0.05）;但MCP-1数据比较无统计学意义（P〉0.05）。结论 在子宫内膜异位症合并代谢综合征与检测指标包括sflt-1、VEGF、MCP-1、RANTES的表达水平存在密切关系,表明上述因子与疾病发生发展机制存在关联,因此可以在临床上将上述指标作为子宫内膜异位症合并代谢综合征的辅助检测生化指标。