环境外暴露及GSTT_1、GSTM_1基因型对1-羟基芘作为多环芳烃暴露标志物的影响

目的研究多环芳烃(PAHs)暴露(环境空气暴露和吸烟)、GSTT1、GSTM1基因型对1-羟基芘(1-OHP)作为PAHs暴露标志物的影响。方法选取51名巡警作为研究组,48名内勤警察作为对照组,测定两组人群环境空气中的PAHS浓度以及尿中的1-OHP浓度,采用HPLC方法分析环境空气中PAHs浓度和研究对象尿样中的1-OHP;PCR方法测定GSTT1、GSTM1基因型。结果对照组环境PAHs浓度为12.79ng/m3,研究组为20.85ng/m3。研究组、对照组内部相同吸烟条件下GSTT1、GSTM1不同基因型人群尿中1-OHP浓度没有差别,相同基因型下的非吸烟人群中,对照组尿中1-OHP浓度均小于研究组,吸烟人群中没有发现同样的规律。按吸烟分层后,研究组、对照组内部吸烟者尿中的1-OHP浓度均大于非吸烟者,并且对照组吸烟者尿中1-OHP浓度大于研究组非吸烟者。结论PAHs暴露及吸烟是影响尿中1-OHP浓度的重要因素;在环境空气中PAHs浓度较低的情况下,吸烟对尿中1-OHP浓度的贡献更大。但GSTT1、GSTM1基因型不是影响尿中1-OHP浓度的主要因素。     

焦炉工GSTM1、GSTT1基因多态性和外周血淋巴细胞DNA损伤的关系

[目的]探讨GSTM1和GSTT1基因多态性与外周血淋巴细胞DNA损伤的关系。[方法]选择某焦化厂248名焦炉作业工人,其中炉顶区作业工人99人,炉侧作业78人,炉底作业71人。120名与之相匹配的对照人群选自该厂非职业多环芳烃(PAHs)暴露者。采用单细胞凝胶电泳实验观察外周血淋巴细胞DNA损伤;运用多重PCR方法检测GSTM1、GSTT1基因多态性。同时,通过问卷调查的方式了解被调查者的年龄、吸烟、饮酒和个人职业暴露史。[结果]炉顶和炉侧区作业工人外周血淋巴细胞的Olive尾矩(OliveTailMoment,OTM)经对数转换后分别为1.37±1.16和1.46±0.97,均明显高于炉底区和对照组(OTM分别为0.98±1.18、0.56±0.99),差异显著(P<0.05)。经调整年龄、吸烟、暴露等级等因素后,焦炉作业组中GSTM1(-)基因型和GSTM1( )基因型的外周血淋巴细胞DNA损伤分别为1.36±1.15和1.15±1.10,差异无显著性(P>0.05)。其中炉顶区作业工人GSTM1(-)基因型OTM明显高于GSTM1( )基因型(分别为1.56±1.08、1.09±1.25,P<0.05)。此外,在焦炉作业组中,GSTM1(-)GSTT1( )基因型OTM为1.44±1.13,明显高于GSTM1( )GSTT1( )基因型0.94±1.06,差异具有显著性(P<0.05);GSTM1( )GSTT1(-)和GSTM1(-)GSTT1(-)基因型OTM分别为1.36±1.10、1.28±1.17,两者差异无显著性。[结论]在炉顶作业工人中,GSTM1基因型可以明显影响外周血淋巴细胞DNA损伤程度。GSTM1和GSTT1基因存在交互作用,同时携带GSTM1( )和GSTT1( )基因型的焦炉作业工人淋巴细胞DNA损伤水平较低。     

焦炉工血清GST活力与尿1-羟基芘和GSTM1、GSTT1基因多态的关系

目的研究血清谷胱甘肽硫转移酶(GST)能否作为焦炉工人多环芳烃的暴露评价指标,同时探讨GSTM1、GSTI1基因多态性与血清GST活力的关系.方法选择某焦化厂39名男性焦炉工人和44名男性对照工人,采用统一的调查表调查一般情况.采集静脉血分析血清GST活力和GSTM1、GSTT1基因型,采集尿样分析尿1-羟基芘(1-OHP)浓度.血清GST活力用试剂盒检测;尿1-羟基芘(1-OHP)浓度作为多环芳烃内暴露剂量,用碱水解-高效液相色谱方法测定;GSTM1和GSTT1基因多态性分析采用PCR方法.结果焦炉工人尿1-OHP浓度(中位数为5.60μmol/mol肌酐)和血清GST活力(中位数25.75 U/ml)分别高于对照组(尿1-OHP浓度:中位数1.32 μmol/mol肌酐,血清GST活力:14.54 U/ml),差异均有统计学意义(均P＜0.001).GSTM1(-/-)和GSTT1(-/-)型工人的血清GST活力分别与GSTM1(-/ , / )和GSTT1(-/ , / )型工人的血清GST活力相比,差异均无统计学意义(均P＞0.05).广义线性回归分析显示,尿1-OHP对血清GST的影响具有统计学意义(P＜0.01).血清GST活力和尿1-OHP浓度存在统计学正相关(r=0.357,P＜0.001,n=83).结论焦炉工人血清GST有可能作为多环芳烃暴露评价的参数;未见GSTM1和GSTT1基因缺失对血清GST活力的影响.     

谷胱甘肽硫转移酶M1和T1基因多态性与噪声性听力损失易感性的关系研究

目的探讨谷胱甘肽硫转移酶M1和T1(GSTM1和GSTT1)的基因多态性与噪声性听力损失易感性之间的关系。方法采用横断面流行病学研究方法,对194名噪声暴露作业工人进行调查和听力测试,按听力学评价的结果将其分为听力损失组和听力正常组。用多重PCR方法检测其GSTM1和GSTT1的存在空白基因多态性。结果GSTM1和GSTT1的存在空白基因型分布在93名噪声性听力损失与101名听力正常工人之间差异无显著性(P>0.05)。采用多元Logistic回归分析对两组间年龄、性别、吸烟状况、爆震史和累积噪声暴露量等因素进行校正后,发现GSTT1空白基因型组与GSTT1存在基因型组相比噪声性听力损失的危险度显著性升高(P<0.05),调整OR值为1.952(95%可信区间为1.017～3.746);GSTM1存在与空白基因型之间发生噪声性听力损失的相对危险度差异无显著性(P>0.05)。结论谷胱甘肽硫转移酶T1基因多态性可能在噪声性听力损失的发病过程中起一定作用,携带GSTT1空白基因型的个体对噪声性听力损失的易感性升高。     

GSTM1和GSTT1基因多态性与噪声性听力损失易感性的关系

目的探讨GSTM1和GSTT1基因多态性与噪声性听力损失易感性的关系。方法采用病例对照研究方法和多重聚合酶链反应(PCR)技术检测听损组123(118)例和对照组123(114)例的GSTM1和GSTT1基因缺失型频率,以2检验检测听损组和对照组基因型频率的差异。结果GSTM1基因在听损组和正常组的缺失率分别为69.1%和56.1%,差异具有统计学意义(P<0.05)。GSTM1(-)基因型携带者发生噪声性听力损失的危险性是携带GSTM1( )基因型者的1.75倍。GSTT1基因在听损组和正常组的缺失率为50.8%和57.9%,差异没有统计学意义(P>0.05)。联合分析表明,携带GSTM1(-)和GSTT1(-)基因型者发生噪声性听力损失的危险性虽稍高于携带GSTM1( )和GSTT1( )基因型者(OR=1.11,2=0.16,P>0.05),但差异无统计学意义,由此认为GSTM1和GSTT1基因之间可能不存在联合作用。结论GSTM1基因缺失可能是发生噪声性听力损失的易感因素之一。     

外周血谷胱甘肽S转移酶M1和T1基因多态性与乙型肝炎肝硬化易感性及肝功能的关联

目的 探讨外周血谷胱甘肽S转移酶M1(GSTM1)和T1基因(GSTT1)与乙型肝炎肝硬化易感性及肝功能的关系。方法 选取2018年3月-2021年3月医院收治的乙型肝炎肝硬化患者110例(研究组)、乙型肝炎患者45例(对照组)为研究对象,检测患者外周血GSTM1和GSTT1基因分型,Child Pugh分级标准评估患者肝功能,并检测血清肝功能指标[谷丙转氨酶(ALT)、总胆红素(TBiL)、谷草转氨酶(AST)],比较两组外周血GSTM1、GSTT1基因型分布情况,分析不同临床特征乙型肝炎肝硬化患者GSTM1及GSTT1基因暴露水平,明确GSTM1和GSTT1与乙型肝炎肝硬化易感性及肝功能的关系。结果 研究组肝功能指标、肝功能分级较对照组高(P<0.05)。研究组GSTM1空白基因占比、GSTT1非空白基因占比高于对照组(P<0.05)。乙型肝炎肝硬化患者Child Pugh分级为C级的GSTM1空白基因分布频率较GSTM1非空白基因高,GSTT1非空白基因分布频率较GSTT1空白基因高(P<0.05)。多因素非条件Logistic回归结果显示GSTM1空白基因、G...     

海南汉族健康人群GSTT1、GSTM1基因多态性分析

目的 探讨海南汉族人群谷胱甘肽S转移酶GSTM1基因和GSTT1基因多态性分布情况.方法 应用多重PCR扩增方法检测147名汉族健康人群GSTM1基因型和GSTT1基因型.结果 147名海南汉族人群中,GSTM1-基因型频率为56.5％(83/147),GSTT1-基因型频率为40.8％(60/147),GSTM1-/GSTT1-基因型频率为25.2％ (37/147),2基因在正常人群中分布与年龄、性别无关,且相互独立无关联.结论 海南汉族健康人群GSTM1基因和GSTT1基因多态性与不同地区正常人群之间存在一定差异性(P＜0.01).     

GSTT1和GSTM1基因多态性与砷中毒易感性的相关性研究

目的 探讨GSTT1、GSTM1基因多态性与砷中毒易感性的相关性.方法 选择某工业性砷污染区常住居民中的174名砷中毒患者(病例组)和92名正常人(对照组)作为研究对象.应用多重PCR技术检测GSTM1和GSTT1基因多态性.结果 病例组GSTM1( )的百分比(39.66%)高于对照组(27.17%),两组间差异有统计学意义(P＜0.05);GSTM1( )人群患砷中毒的危险性是GSTM1(-)的人群的1.7611倍(95%CI为1.0154～3.0546).病例组GSTT1( )的百分比(60.34%)高于对照组(45.65%),两组差异有统计学意义(P＜0.05);GSTY1( )人群患砷中毒的危险性是GSTT1(-)的人群的1.811 6倍(95%CI为1.087 4～3.018 2).GSTM1和GSTY1同时为非空白基因型人群患砷中毒的危险性是GSTM1和GSTT1同时为空白基因型人群的3.083 3倍(95%CI为1,414 8～6.719 6).结论 GSTT1和GSTM1基因多态性与砷中毒的发生可能有关,在相同砷暴露环境下,GSTT1和GSTM1空白基因型个体患砷中毒的危险性可能更低.     

GSTT1和GSTM1基因多态性与人体砷甲基化代谢水平关系探讨

目的探讨GSTT1、GSTM1基因多态性与人体砷甲基化代谢水平之间的关系。方法选择某工业性砷污染区的247名成年常住居民为研究对象。采用多重PCR法检测GSTM1和GSTT1基因多态性。离子色谱氢化物发生原子荧光法(IC-HG-AFS)测定尿中无机砷(iAs)、一甲基胂酸(MMA)和二甲基胂酸(DMA)。结果GSTT1缺失基因型人群与GSTT1非缺失基因型人群尿中iAs比例、DMA比例和MMA比例相比较,差异均无统计学意义(P>0.05)。GSTM1缺失基因型人群与GSTM1非缺失基因型人群尿中iAs比例、DMA比例和MMA比例相比较,差异均无统计学意义(P>0.05)。四组不同GSTT1和GSTM1联合基因型人群尿中iAs比例、DMA比例和MMA比例相比较,四组间差异也均无统计学意义(P>0.05)。结论本研究未发现GSTT1、GSTM1基因多态性与砷代谢水平之间存在显著关联。     

新疆地区肺结核病患者GSTM1、GSTT1多态性位点的基因型分布

目的了解GSTM1、GSTT1基因多态性在新疆肺结核患者中的分布。方法采用多重聚合酶链式反应(PCR)检测1 675例肺结核患者的GSTM1、GSTT1的基因型。结果 GSTM1、GSTT1纯合缺失基因型的频率分别为53.91%、29.25%;GSTM1/GSTT1联合基因型GSTM1(-)/GSTT1(-)、GSTM1(-)/GSTT1(+)、GSTM1(+)/GSTT1(-)和GSTM1(+)/GSTT1(+)的分布频率分别为16.72%、37.19%、12.54%和33.55%。结论肺结核患者的GSTM1、GSTT1基因不受年龄、性别、吸烟、饮酒的影响,但具有种族、地区差异性。     

H1N1 vaccination

Early results (January to April) from the 2010 Canadian Community Health Survey show that an estimated 41% of Canadians (excluding those in the territories) aged 12 or older had been vaccinated for H1N1 by April 2010. The percentages were higher in the Atlantic provinces, Quebec and Saskatchewan than in Canada overall. Relatively high percentages of females and people aged 45 or older were vaccinated; the percentage of immigrants who had done so was relatively low. Being in a priority group (health-care worker, having children younger than 5 in the household, or having a chronic condition that could increase the risk for complications from H1N1) increased the likelihood of vaccination. A history of seasonal flu vaccination and having a regular doctor were also associated with H1N1 vaccination. Nearly three-quarters of those who had not been vaccinated reported that they did not think it was necessary.     

被动吸烟与cyp1b1、gstp1、sult1a1基因多态性对乳腺癌发病的影响

目的 探讨被动吸烟、cyp1b1、gstp1、sult1a1基因多态性及其联合作用对乳腺癌发病的影响。方法 2014 - 2015年间,采用病例-对照研究方法,收集病例794例,对照805例。问卷调查收集研究对象信息。采用飞行质谱技术,进行cyp1b1、gstp1、sult1a1基因单核苷酸多态性分型检测。采用多因素非条件 logistic 回归,分析环境烟草烟雾暴露及cyp1b1、gstp1、sult1a1基因多态性与乳腺癌发病风险的关系。结果 调整年龄、教育程度、家庭年总收入、职业、婚姻状况后,环境烟草烟雾暴露与gstp1基因多态性未发现协同作用。以环境烟草烟雾低暴露且携带 cyp1b1 rs1056836 C等位基因为参照,环境烟草烟雾高暴露且携带 GG 基因在绝经前女性中乳腺癌风险明显增高（OR = 1.678,95%CI:1.039～2.711）。以环境烟草烟雾组合低暴露且携带sult1a1 rs9282861GG基因型为参照,环境烟草烟雾高暴露且携带A等位基因绝经前乳腺癌风险明显增高（OR = 2.389,95%CI:1.157～4.931）,但交互作用系数无统计学意义。结论 环境烟草烟雾高暴露与cyp1b1 及sult1a1基因对乳腺癌发病风险可能存在协同作用,但尚扩大样本进行验证。     

Echo-AM1-1 encephaloscope]

A new miniature model of the A-mode ultrasonic echoencephaloscope, 0.88 MHz, has been developed and adopted to practical use in neurology. The device contains a detector for amplitude determination of echopulsation and curve (echopulsograms) recording. It is highly sensitive, cost-effective, which enhances the quality of rapid diagnosis of central nervous diseases, including those of vascular genesis, in in- and outpatient settings.     

接种甲型H1N1流感疫苗后患甲型H1N1流感分析

目的 分析接种甲型H1N1流感疫苗后发生甲型H1N1流感感染的病例,探讨发病原因,为进一步提高疫苗预防效果提供参考依据.方法 对接种甲型H1N1流感疫苗后发生甲型H1N1流感感染148例,进行回顾性调查分析.结果 接种甲型H1N1流感疫苗11176例.发生甲型H1N1感染148例,感染率1.32%,其中1～14 d感染81例,感染率0.72%,＞15 d感染67例,感染率0.60%.结论 甲型H1N1流感病毒裂解疫苗是一种安全高效的疫苗,不足之处尚待进一步探讨、完善.     

NF1 gene and neurofibromatosis 1

Neurofibromatosis 1 (NF1), also known as von Recklinghausen disease, is an autosomal dominant condition caused by mutations of the NF1 gene, which is located at chromosome 17q11.2. NF1 is believed to be completely penetrant, but substantial variability in expression of features occurs. Diagnosis of NF1 is based on established clinical criteria. The presentation of many of the clinical features is age dependent. The average life expectancy of patients with NF1 is probably reduced by 10-15 years, and malignancy is the most common cause of death. The prevalence of clinically diagnosed NF1 ranges from 1/2,000 to 1/5,000 in most population-based studies. A wide variety of NF1 mutations has been found in patients with NF1, but no frequently recurring mutation has been identified. Most studies have not found an obvious relation between particular NF1 mutations and the resulting clinical manifestations. The variability of the NF1 phenotype, even in individuals with the same NF1 gene mutation, suggests that other factors are involved in determining the clinical manifestations, but the nature of these factors has not yet been determined. Laboratory testing for NF1 mutations is difficult. A protein truncation test is commercially available, but its sensitivity, specificity, and predictive value have not been established. No general, population-based molecular studies of NF1 mutations have been performed. At this time, it appears that the benefits of population-based screening for clinical features of NF1 would not outweigh the costs of screening.     

GSTM1及GSTT1和GSTP1基因多态性对尿中1-羟基芘水平的影响

目的 研究GSTM1、GSTT1和GSTP1基因多态性对多环芳烃接触工人尿中1-羟基芘(1-OHP)水平的影响.方法 分别选取2个炼焦厂共447名多环芳烃职业接触工人(接触组)和某线材厂220名非职业接触工人(对照组)作为研究对象,采用高效液相色谱法测定尿中1-OHP水平,采用线性回归统计模型分析GSTM1和GSTT1缺失型及GSTP1 I105V位点的多态性对不同人群尿中1-OHP水平的修饰作用.结果 接触组工人尿中1-OHP浓度为4.61 μmol/mol Cr,明显高于对照组(0.34μmol/mol Cr),差异有统计学意义(P＜0.05).接触类别和吸烟分别是影响尿中1-OHP水平的主要因素,在控制各混杂因素的影响后,线性回归分析显示,接触组尿中1-OHP水平和GSTP1 I105V位点多态性有关(单基因分析,P=0.012;多基因分析,P=0.011),对总体样本,单基因模型和多基因模型均显示,尿中1-OHP水平可能和GSTT1缺失型多态有关(P=0.055),多基因交互作用分析显示,GSTT1和GSTP1基因多态对接触组尿中1-OHP水平具有交互作用.结论 谷胱甘肽硫转移酶(GSTs)基因的多态性对接触多环芳烃工人尿中1-OHP水平有影响.

Abstract：

Objective To investigate the modification of GSTM1, GSTT1 and GSTP1 gene polymorphisms on urinary 1-hydroxypyrene (1-OHP) excretions in workers under different exposure levels. Methods Four hundred and forty-seven occupationally exposed workers from two coking plants and 220 control workers from a wire rod plant were genotyped to analyze the modification of GSTM1, GSTT1 and GSTP1 gene polymorphisms on urinary 1-OHP excretions. Results The urinary 1-OHP concentration in exposed group was much higher than that in control group (4.61 vs 0.34 μmol/mol Cr, P＜0.05). Occupational exposure levels and cigarette smoking were of the dominating factors affecting 1-OHP excretions in urine. After controlling potential confounders, decreased excretion of urinary 1-OHP was associated with GSTP1 I105V AG + GG genotype in coke oven workers (single-gene model, P=0.012; multi-gene model, P=0.011 ) and with GSTT1 null type in the analysis including all subjects (P=0.055 in both single-gene and multi-gene models). GSTT1 and GSTP1 were interacted on the urinary concentrations of 1-OHP. Conclusion Urinary 1-OHP concentrations can be modified by GSTM1, GSTT1 and GSTP1 gene polymorphisms, indicating that these genes are involved in the metabolism of polycyclic aromatic hydrocarbons.     

Co-circulation of pandemic 2009 H1N1, classical swine H1N1 and avian-like swine H1N1 influenza viruses in pigs in China

The pandemic A/H1N1 influenza viruses emerged in both Mexico and the United States in March 2009, and were transmitted efficiently in the human population. They were transmitted occasionally from humans to other mammals including pigs, dogs and cats. In this study, we report the isolation and genetic analysis of novel viruses in pigs in China. These viruses were related phylogenetically to the pandemic 2009 H1N1 influenza viruses isolated from humans and pigs, which indicates that the pandemic virus is currently circulating in swine populations, and this hypothesis was further supported by serological surveillance of pig sera collected within the same period. Furthermore, we isolated another two H1N1 viruses belonging to the lineages of classical swine H1N1 virus and avian-like swine H1N1 virus, respectively. Multiple genetic lineages of H1N1 viruses are co-circulating in the swine population, which highlights the importance of intensive surveillance for swine influenza in China.