Association of Gene Polymorphisms of CYP1B1 Ala119Ser with Breast Cancer Risk in Zhuang Nationality Women in Guangxi

目的 探讨CYP1B1基因Ala119Ser与乳腺癌易感性的关联性.方法 采用聚合酶链反应-限制性片断长度多态性(PCR-RFLP)技术对88例广西壮族女性乳腺癌患者和106例健康对照者进行CYP1B1 Ala119Ser基因分型,并分析其与乳腺癌患病的关系.结果 病例组CYP1B1 Ala119Ser T等位基因分布频率(30.7％)明显高于对照组(19.3％),差异有统计学意义(P＜0.05).病例组3种基因型(GG、GT、TT)分布频率与对照组相比,差异有统计学意义(P＜0.05)；病例组CYP1B1 Ala119Ser突变型纯合子(TT)的分布频率为10.2％,明显高于对照组(2.8％)；与野生型纯合子(GC)相比,病例组TT基因型能增加乳腺癌患病风险(0R=4.74,95％ CI为1.22～18.51).结论 CYP1B1 Ala119Ser突变可能增加广西壮族妇女乳腺癌易感性.     

广西壮族人群CYP1B1基因Leu 432 Va1多态性分析

目的研究CYP1B1第432密码子在广西壮族人群中遗传特征,为进一步研究CYP1B1基因多态性与疾病的发生易感性奠定基础。方法采用人工修饰双等位基因特异性引物扩增法(diASA-AMP)技术对288名广西壮族正常成人进行CYP1B1 Leu 432 Va1基因分型,探讨性别间差异及与国内外其他人群分布频率差异。结果广西壮族女性和男性人群CYP1B1 Leu 432 Va1均以C等位基因为主,分别为89.1%和91.4%;CC野生纯合子型、CG杂合子型和GG突变纯合型在女性人群中分别为78.3%、21.3%和0,男性人群则为83.6%、15.6%和0.8%;统计分析表明,广西壮族CYP1B1 Leu 432 Va1等位基因和基因型分布频率无性别差异,与朝鲜人群相应位点基因型分布频率无差异,但与国内江苏汉族、上海和四川女性相比具有统计学差异(P<0.05),与日本、印度、波兰、尼日利亚、美国白人和美国黑人等人群相应位点基因型分布频率有明显差异(P<0.01)。结论广西壮族人群CYP1B1基因Leu 432 Va1呈多态性分布,基因型分布频率无性别差异,存在种族差异。     

CYP1B1基因多态性与异常体液型乳腺癌易感性

目的 探讨细胞色素氧化酶p450(cytochrome,CYP)1B1基因外显子3密码子432亮氨酸(Leu)-缬氨酸(Val)位点多态性与乳腺癌(BC)及其异常体液型乳腺癌(BCAH)的相关性.方法 按维吾尔医学将乳腺癌病例组分为4种体液型,应用聚合酶链反应-限制性片断长度多态性(PCR-RFLP)技术检测84例BC患者和131例对照组的CYP1B1基因Leu432Val位点多态性的分布频率.结果 CYP1 B1各基因型及等位基因分布频率在BC、BCAH与对照组之间差异均无统计学意义(P＞0.05);在BC病例组中Leu/Val和Val/Val合并后其发生BC的风险是野生型Leu/Leu个体的2.137倍(95%CI=0.969 ～4.717,P=0.056),在BCABH病例组中其发生BC的风险是野生型Leu/Leu个体的3.636倍(95% CI =0.996～13.157,P=0.062).结论 CYP1B1突变基因型(Leu/Val+ Val/Val)可能与新疆汉族人群BC和BCABH易感性有关.     

CYP19和CYP1B1基因多态性与妊娠期肝内胆汁淤积症易感性的研究

目的:探讨P450酶系的CYP19和CYP1B1基因多态性与妊娠期肝内胆汁淤积症(ICP)发病的关系。方法:应用聚合酶链反应-限制性片段多态性技术(PCR-RFLP)和等位基因特异性PCR技术(AS-PCR)对100例ICP患者和100例正常对照孕妇CYP19基因第3外显子Rsal酶切多态和CYP1B1基因外显子3密码子432(C-G)多态性进行分析。结果:①对照组CYP19的基因型AA、AG、GG频率分别为30.0%、50.0%、20.0%,ICP组分别为38.0%、45.0%、17.0%,两组比较差异无统计学意义(P>0.05);对照组等位基因A、G频率分别为55.0%、45.0%,ICP组分别为60.5%、39.5%,两组比较差异也无统计学意义(P>0.05)。②对照组CYP1B1的基因型CC、CG频率分别为80.0%、20.0%,ICP组分别为70.0%、30.0%,两组均无突变纯合子(GG),两组比较差异无统计学意义(P>0.05);对照组等位基因C、G频率分别为90%、10%,ICP组分别为85%、15%,两组比较差异也无统计学意义(P>0.0S)。结论:CYP19外显子3基因多态性和CYP1B1外显子3密码子432基因多态性与ICP发病无关。     

PARP-1基因Val762Ala多态性与乳腺癌易感性的关系

目的探讨DNA修复基因聚腺苷二磷酸核糖聚合酶-1(PARP-1)单核苷酸多态性位点Val762Ala基因多态性与中国人群乳腺癌易感性的关系。方法采用Sequenom MassARRAY单核苷酸多态性(SNP)基因型分析技术对经病理确诊的原发性乳腺癌女性患者837例(病例组)和健康对照组865例进行PARP-1基因单核苷酸位点Val762Ala基因分型。以非条件logistic回归计算优势比(odds ratio,OR)及其95%可信区间(CI)评价各基因型与乳腺癌发病风险的关系。数据均由SPSS13.0统计软件分析。结果病例组和对照组中TT、TC、CC和TC+CC 4种基因型的分布分别差异无统计学意义,OR[95%CI]值分别为1、1.07(0.83～1.39)、1.03(0.70～1.36)、1.08(0.82～1.33)。结论 Val762Ala基因型与乳腺癌易感性无显著相关性。PARP-1基因Val762Ala多态性在乳腺癌发病过程中无作用。     

CYP 1B1基因A119S多态性与妊娠期肝内胆汁淤积症风险关系的研究

目的:探讨CYP1B1基因A119S多态性与妊娠期肝内胆汁淤积症(ICP)发生危险性的关系。方法:用等位基因特异性PCR(AS-PCR)法,对73例妊娠期肝内胆汁淤积症患者和90例正常女性的CYP1B1 A119S多态位点进行检测分析,确定出多态性的3种基因型,即野生型G/G、杂合型G/T、突变型T/T。结果:CYP1B1基因A119S多态性G/G、G/T、T/T 3种基因型分布频率,ICP组分别为3.8%、39.7%和16.5%,对照组分别为64.4%、26.7%和8.9%;ICP组G、T等位基因频率为63.7%,36.3%,对照组为77.8%,22.2%。CYP1B1 A119S多态性基因型及等位基因型在两组间分布频率的差别有统计学意义(P<0.05)。基因型T/T与G/G比较、G/T与G/G比较,OR值分别为2.719(1.007～7.341)倍和2.190(1.096～4.375)倍;等位基因T使ICP危险性增加了1.995(1.226～3.246)倍。结论:CYP1B1 A119S多态位点3种基因型的分布与ICP发病风险有一定关联,突变基因型增加了ICP的发病风险。     

CYP2E1和CYP1A1及白细胞介素-4基因多态性与三氯乙烯药疹样皮炎的关系

目的 研究代谢酶基因CYP2E1和CYP1A1以及白细胞介素(IL)-4的基因多态性与三氯乙烯(TCE)药疹样皮炎易感性的关系.方法 选择35例TCE药疹样皮炎病例作为病例组,选无皮肤损害的35名健康工人作为对照组.应用实时荧光定量聚合酶链反应(PCR)和TaqMan MGB探针技术,检测病例组和对照组CYP2E1、CYP1A1和IL-4基因的单核苷酸多态性(SNP),计算病例组和对照组的基因型与等位基因型频率.结果 CYP1A1基因(rs1048943)的SNP多态性检测结果显示,病例组G等位基因频率(37.1%)明显高于对照组,差异有统计学意义(P＜0.01);检测发现,病例组CYP2E1基因-1053 C→岬位点T等位基因频率(41.4%)明显高于对照组,差异有统计学意义(P＜0.01);对IL4基因588 C→岬位点(rs2243250)检测发现,病例组TT纯合突变频率(75.0%)明显高于对照组,差异有统计学意义(P＜0.01),T等位基因频率(87.5%)明显高于对照组,差异有统计学意义(P＜0.01).结论 CYP1A1、CYP2E1和IL-4基因的某些位点的改变可能与少数TCE敏感个体对接触TCE引起的超敏反应存在密切关系,CYP1A1、CYP2E1和IL-4的基因多态性可能是TCE药疹样皮炎患者易感性差异相关的遗传学因素之一.     

CYP2E1 5′侧翼区基因多态性与职业性锰中毒易感性病例对照研究

[目的]探讨CYP2E1 5′侧翼区基因多态性与职业性慢性锰中毒易感性的关系。[方法]本研究以51例职业性锰中毒患者为病例,以相同环境锰暴露而未发病、匹配条件相当者为对照,进行1∶1配对病例-对照研究,应用PCR-RFLP方法进行CYP2E1 5′侧翼区基因PstI/RsaI位点和DraI位点多态性分析。[结果]CYP2E1基因RsaI位点基因型及等位基因的分布在病例组和对照组之间差异无统计学意义。CYP2E1DraI位点基因型分布在病例组和对照组有差别。CYP2E1基因DraI位点野生型纯合子(DD)在病例组的分布明显高于对照组,突变型纯合子(CC)在病例组的分布明显低于对照组。[结论]携带野生型CYP2E1基因者,其DraI位点更易突变,对锰的神经毒性可能更敏感,推测CYP2E1基因的多态性可能与锰中毒的易感性有关。     

CYP1A1基因多态性与吉林籍汉族女性子宫内膜异位症易感性的研究

目的:探讨在吉林市汉族妇女中CYP1A1基因Exon7位点即Ile-Val位点的多态性与子宫内膜异位症易感性的相关关系。方法:以病例对照的研究方法,采用PCR技术检测在216例子宫内膜异位症患者和216例对照人群中CYP1A1基因Ile-Val位点多态性的表达。结果:Ile-Val 3种多态基因型在病例组和对照组分布有统计学意义(P<0.05),Ile/Val、Val/Val基因型在病例组的分布频率明显高于对照组(P<0.05);Ile/Val、Val/Val基因型患子宫内膜异位症的危险分别是Ile/Ile基因型的1.901倍和3.056倍。结论:CYP1A1Exon7的Ile/Val、Val/Val基因型与子宫内膜异位症的易感性有关,可望作为子宫内膜异位症易感人群筛选的重要指标。     

XRCC1基因单核苷酸多态性与铅毒性遗传易感性的关系

目的研究DNA修复基因XRCC1单核苷酸多态性与铅毒性易感性的关系。方法采集326名某蓄电池企业铅作业工人外周静脉血样品,检测血铅和血锌原卟啉(ZPP),采用聚合酶链式反应-限制性片段长度多态(PCR-RFLP)检测XRCC1基因型,分析不同基因型铅作业工人与铅毒性易感性的关系。结果 326名铅作业工人XRCC1基因分布呈现多态现象,各基因型的分布频率符合遗传学的Hardy-Weinberg平衡(P>0.05);不同基因型组(XRCC1-194CC/CT+TT、XRCC1-280 GG/GA+AA、XRCC1-399GG/GA+AA)工人ZPP差异无统计学意义(P>0.05);XRCC1-194CT+TT基因型组工人平均血铅值高于XRCC1-241CC基因型组(P<0.05),而XRCC1-280GG/GA+AA、XRCC1-399GG/GA+AA基因型组工人平均血铅值差异无统计学意义(P>0.05);以血铅水平1.90μmol/L为界,经χ2检验、logistic回归分析显示,高铅组XRCC1-194CT+TT基因型的比例大于低铅组(P<0.05),XRCC1-194CT+TT基因型组工人较XRCC1-194CC基因型组工人高血铅发生率的风险明显增高(OR=2.78,95%CI=1.49～5.28)。结论XRCC1 Arg194Trp基因单核苷酸多态性与血铅升高有一定关联性,C→T多态性提高了接铅工人对铅毒性易感的风险性,XRCC1-194CT/TT基因型可能是铅毒性易感基因型;XRCC1 Arg280His和XRCC1 Arg399Gln多态性可能与铅毒性易感性无关。     

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.     

工作场所空气中1,1-二氯-1-硝基乙烷的气相色谱测定法

目的 建立工作场所空气中1,1-二氯-1-硝基乙烷的气相色谱测定方法.方法 活性炭管采集工作场所空气中的1,1-二氯-1-硝基乙烷,以二硫化碳解吸后毛细管柱气相色谱法测定.结果 方法的测定范围为4.0～858.2μg/ml;回归方程Y=283X-1076,相关系数r=0.9999;最低检出浓度为0.4 mg/m3(以采集3L空气样品计);不同浓度测定的相对标准偏差(RSD)为1.8%～4.1%(批内精密度试验的RSD分别为2.9%、1.8%和2.0%;批间精密度试验的RSD分别为4.1%、3.5%和3.2%);解吸效率为88.5%～90.6%;穿透容量大于0.7 mg;采样效率100%;样品在室温下至少可保存7 d.结论 方法的各项指标均符合GBZ/T210.4-2008<职业卫生标准制订指南-工作场所空气中化学物质测定方法>要求,可用于工作场所空气中1,1-二氯-1-硝基乙烷的测定.     

苗族人群细胞色素及GSTMI基因多态性分布

目的 了解细胞色素P4501A1(CYP1A1)与谷胱甘肽硫转移酶(GST)M1基因多态性在贵州苗族人群中的分布.方法 采用聚合酶链反应(PCR)和聚合酶链反应-限制性片断长度多态性(PCR-RFLP)技术检测CYP1A1和GSTM1基因的多态性.结果 97人中CYP1A1基因型为野生型、杂合型、突变型的分别有69,18,10人,分别占71.13%,18.56%,10.31%;野生型等位基因频率为0.805,突变型等位基因频率为0.195.97人中有67人为GSTM1基因缺陷型,GSTM1缺陷型占69%.结论 贵州苗族CYP1A1m1突变型等位基因频率明显低于亚洲人.而高于欧洲人群;贵州苗族GSTM1基因缺陷率与中国汉族人相比无明显差异,但明显高于日本人、韩国人、德国人和波兰人.     

PD-1/PD-L1在肝细胞癌中免疫调节作用的研究进展

肝细胞癌是世界上最常见的致死性肿瘤之一,程序性死亡蛋白-1(PD-1)和程序性死亡配体-1(PD-L1)这对免疫共抑制分子在肝癌细胞中广泛表达。目前以抗PD-1/PD-L1为靶点的免疫治疗在多种肿瘤中取得了良好而持久的疗效。然而PD-1/PD-L1在肝细胞癌微环境中的免疫调节机制尚待完善,是否对抗PD-1/PD-L1治疗敏感及如何联合其他治疗目前尚无定论。笔者主要对PD-1/PD-L1通路在肝细胞癌中的免疫调节及抗PD-1/PD-L1在肝细胞癌治疗方面的研究进展进行综述。     

妊娠合并重症新型甲型H1N1流感患者抗H1N1抗体IgG亚类的分布

目的探讨妊娠合并重症甲型H1N1流感患者抗H1N1抗体各IgG亚类在血清中的分布特点。方法收集2009年11月14日-12月31日,确诊的女性甲型H1N1流感患者,分为妊娠病例组,非妊娠病例组,同时收集抗甲型H1N1抗体阳性的健康妊娠女性作为妊娠对照组,采用ELISA法检测各组血清特异性IgG及亚类的百分结合率。结果妊娠病例组的IgG2I、gG3I、gG4亚类的百分结合率中位数分别为53.0%、65.0%、61.6%,均低于妊娠对照组,差异有统计学意义(P<0.05);各组的特异性抗甲型H1N1 IgG均以IgG1亚类为主,为>70.0%,妊娠病例组的IgG2亚类占5.0%,低于非妊娠病例组的10.0%和妊娠对照组的8.0%,(P<0.05)。结论妊娠合并甲型H1N1流感患者中,特异性抗甲型H1N1 IgG以IgG1亚类为主,IgG2亚类的绝对及相对下降与甲型H1N1感染相关。     

中磺酸抑制人单核细胞系THP-1细胞ACAT-1表达

目的观察牛磺酸对人单核细胞系THP-1细胞酰基辅酶A、胆固醇酰基转移酶-1（ACAT-1）表达的影响，以期为牛磺酸用于临床治疗动脉粥样硬化提供实验依据。方法在有或无干扰素-γ（IFN—γ）的条件下，用不同浓度的牛磺酸与THP-1持续孵育不同的时间，RT-PCR检测ACAT—1mRNA水平，Western Blot检测其蛋白表达。结果牛磺酸显著下调THP-1的ACAT-1mRNA和蛋白表达水平（P〈0．05～0．0l，n=3），并呈时间和剂量依赖性效应。IFN-γ促进ACAT-1mRNA和蛋白表达（P〈0．05），该作用被牛磺酸部分抑制（P〈0．01）。结论牛磺酸抑制ACAT-1的基础表达和由IFN-γ诱导的表达，这可能是其抗动脉粥样硬化的机制之一。     

Detection of equine herpesvirus 1 genome 1B in Argentina

To determine the genomic variation of equine herpesviruses (EHVs) isolated in Argentina between 1979 and the first half of 2004, DNA sequences from all 69 strains isolated were analysed. Sixty strains were recovered from aborted fetuses, one from leucocyte-rich plasma from a horse with respiratory signs and eight from cases of neonatal disease. The DNA was extracted from rabbit kidney epithelial (RK13) cells infected with each strain and digested with three restriction endonucleases (BamHI, Bg/II and KpnI). Two strains could be differentiated using BamHI restriction and were assigned to the EHV-1 1B prototype group. Only one of these two strains was typed EHV-1 1B with Bg/II. DNA digestion with KpnI was ineffective. The results obtained in this study demonstrate that the EHV-1 1B genome has been present in Argentina since at least 1996. The finding of two strains with this electropherotype suggests that there is genomic heterogeneity among Argentinian isolates.     

Detection of CYP1A1 gene polymorphism using designed RFLP and distributions of CYP1A1 genotypes in Japanese

Isoleucine (Ile)-valine (Val) polymorphism, which is caused by a point mutation from A to G in exon 7, is reported to be associated with an elevated risk of lung cancer among Japanese. Because CYP1A1 catalyzes bioactivation of environmental procarcinogens, such as benzo[a]pyrene, it is very important to study the clinical meaning of Ile-Val polymorphism using an epidemiological study. In an epidemiological study, easy, economical, rapid and reliable identification of the CYP1A1 genotype is necessary. The present study shows that the new method, designed restriction fragment length polymorphism (designed RFLP), can detect Ile-Val polymorphism of CYP1A1 The Ile-Val polymorphism detected using this new method was consistent with that found by the allele-specific PCR amplifications (ASA) method in six cases tested. This new method detected Ile-Va1 polymorphism of CYP1A1 using 240 healthy Japanese who lived in the northern Kyusyu region. The frequency of the genotypes was as follows: Ile/Ile, 159 (66.2%); Ile/Val, 65 (27.1%); Val/Val, 16 (6.7%). The frequency of the Ile gene was 0.798 and that of the Val gene, 0.202. There was no difference in Ile-Val polymorphism based on sex or age. Racial differences influenced the distribution of this polymorphism, but Japanese regional differences did not. Since this new method, designed RFLP, is rapid, reliable and suitable for large-scale screening of polymorphisms, it may be used routinely to detect Ile-Val polymorphism of CYP1A1 Furthermore, it will help to evaluate the relationship between CYP1A1 polymorphism and individual sensitivity to xenobiotics that may affect the incidence of lung cancer.     

郴州市甲型H1N1流感流行态势研究

目的了解郴州市甲型H1N1流感流行特征,分析流行原因,为防控工作提供科学依据。方法收集郴州市2009-2010年甲型H1N1流感疫情、监测资料,运用描述性流行病学进行分析。结果郴州市2009-2010年报告甲型H1N1流感病例4 459例,发病率95.61/10万,其中重症病例17例（占0.38%）,死亡3例,病死率0.67‰;疫情从2009年8月上旬发生输入性病例开始,发病数快速上升,11月份达到发病高峰,2010年1月份快速下降,并维持在较低水平;病例多为在校学生,占病例数的95.70%,男性发病数明显多于女性;发生暴发疫情38起,其中发生在学校36起,续发率3.98%;流感监测显示：9月份以后甲型H1N1流感病毒迅速取代季节性流感病毒,成为流行优势病毒株;甲型H1N1流感病毒感染状况调查IgG抗体阳性率32.28%。结论郴州市甲型H1N1流感疫情通过综合措施得到有效防控;通过加强监测,积极开展疫苗接种,能够有效遏制甲型H1N1流感快速传播。     

HbA1c in the monitoring of type 1 diabetic patients

We conducted this study to determine quality of glycemic control in patients with type 1 diabetes, based on evaluation of mean HbA1c. We enrolled 125 patients with type 1 diabetes who were hospitalized during the period from December 1998 to December 2001. Glycemic control was evaluated on mean of HbA1c in 82 patients and on mean of fasting glycemia values in 43 patients. Mean HbA1c was 9.9%. Mean of plasma fasting glycemia was 11 mmol/l. 22% of patients were perfectly or good controlled (HbA1c < or = 7% or HbA1c 7-7.5%). 12% had a moderate control (HbA1c 7.5 et 9%) and finally 66% of patients had a worse control (HbA1c > 9%). There was an excellent correlation between HbA1c and mean fasting glycemic values (p = 0.00028). Most of patients had unsatifactory control. We stressed on the absolute necessity of intensified insulin therapy and self-monitoring blood glucose.