rs11362基因多态性和HIV-1发病风险关联性研究的Meta分析

目的 目前有很多关于rs11362基因多态性和HIV-1发病风险的关联性研究,但是结论并不一致,所以本文用meta分析的方法对现有的研究进行分析,以探索rs11362基因多态性和HIV-1发病风险的关联性。方法 搜索Pubmed网站、Web of Science网站、中国生物医学文献数据库（CBM）、Embase网站、维普、万方及中国知网数据库截至2022年9月30日之前发表的所有关于rs11362基因多态性和HIV-1发病风险关联性研究的文章,关联性强度用比值比（OR）和95%可信区间（CI）来评估。结果 最终有9篇文章符合纳入标准。病例数总计2 565例。显性模型显示,与携带GG基因型相比,携带AA/GA基因型增加了HIV-1的发病风险（OR=1.583,95%CI:1.054～2.376）。等位基因模型显示,和G等位基因相比,携带A等位基因增加了HIV-1的发病风险（OR=1.220,95%CI:1.013～1.469）。分层分析发现,同样的效应见于种族为混合人种的人群,包括显性模型（OR=2.337,95%CI:1.392～3.924）和等位基因模型（OR=1.465,95%C...     

HLA-DP基因多态性与肺癌遗传易感性研究

目的 探讨人类白细胞抗原（Human Leukocyte Antigens,HLA）DP基因多态性与中国汉族人群肺癌遗传易感性的关联。方法 应用TaqMan探针方法检测401例肺癌患者和843例对照者 rs3077和rs9277535位点基因型,比较不同基因型与肺癌患病风险的关系。结果 采用多因素Logistic回归分析,结果显示rs3077和rs9277535位点突变基因型AA显著增加肺癌的发病风险（调整OR = 1.69,95%CI = 1.16～2.51;调整OR = 1.58,95%CI = 1.10～2.25）;单倍型分析显示,与GG单倍型相比,携带AA单倍型的个体可增加肺癌发病风险（调整OR = 1.41,95%CI = 1.61～1.71）;与携带rs3077 GG+GA and rs9377357 GG基因型的个体相比,携带1～4个危险等位基因的个体发生肺癌的风险显著（P趋势 ＜0.01）。结论 HLA基因多态性与中国汉族人群肺癌的发病风险存在关联。     

女性脑卒中与纤溶酶原激活物抑制剂1基因关系

摘要:目的　探讨口服避孕药（Oral Contraceptive,OC）暴露、纤溶酶原激活物抑制剂1（Plasminogen Activator Inhibitor-1,PAI-1）基因多态性联合作用与中国女性脑卒中发病风险的关系。方法　采用Taqman-MGB方法和普通聚合酶链式反应（Polymerase Chain Reaction,PCR）方法检测PAI-1位点各基因型频率。结果　服用OC女性脑卒中发病风险明显升高（OR＝1.31;95%CI:1.01～1.71）。与4G4G基因型相比,携带rs1799889位点5G/5G基因型显著降低梗塞型脑卒中的发病风险（OR＝0.35;95%CI:0.18～0.67）。与未服用OC且不携带4G等位基因的妇女相比,服用OC同时携带rs1799889位点5G等位基因可降低梗塞型脑卒中的发病风险（OR＝0.53;95%CI:0.34～0.83）。结论　服用OC会显著增加中国女性脑卒中的发病风险;PAI-1基因多态性与中国女性梗塞型脑卒中发病有关;OC与PAI-1基因多态性之间的联合作用会与女性脑卒中的发病风险存在关联。     

雌激素相关基因多态性和流产对乳腺癌发病风险的影响

目的 探索雌激素合成/代谢相关基因CYP1B1rs1056836 (C＞G)、COMTrs4680 (G＞A)、ESR1rs2046210 (G＞A)多态性和流产对乳腺癌发病风险的影响。方法 采用病例对照设计,序贯收集2014年4月 - 2015 年6月间的乳腺癌新发病例794 例,健康体检女性805 例。采用统一编制结构化问卷收集信息,提取外周血DNA检测基因型,t/χ2检验筛选危险因素,广义多因素降维(GMDR)和非条件多因素logistic回归分析基因多态性与流产对乳腺癌发病风险的影响。结果 绝经前女性基因CYP1B1rs1056836 (C＞G)多态性、COMTrs4680 (G＞A)多态性对乳腺癌的发病危险度分别为ORCYP1B1 = 5.96(95%CI:1.20～29.64),ORCOMT = 0.69 (95%CI:0.52～0.92), ESR1rs2046210 (G＞A)多态性可能增加绝经前/后乳腺癌的罹患风险 (OR = 1.53,95%CI: 1.14～2.05;OR = 1.49,95%CI: 1.07～2.07)。有药流史可能增加绝经前/后乳腺癌的发病风险(OR = 3.63,95%CI:1.71～7.68;OR = 6.53,95%CI:1.83～23.32)。绝经前女性COMTrs4680 (G＞A)和药流相乘交互系数ORmulti = 0.16(95%CI:0.33～0.82)。结论 ESR1rs2046210 (G＞A)多态性、药流史可能增加乳腺癌罹患风险。     

着色性干皮病基因多态性及单体型与肺癌遗传易感的关联

目的探讨DNA的修复基因着色性干皮病基因B(XPB)、XPD、XPG的单核苷酸多态性和单体型与肺癌遗传易感的关联。方法用病例-对照研究的方法,选择海南省有吸烟暴露史、诊断明确的肺癌患者100例为病例组,与其有相近吸烟暴露史、胸外科其他疾病(如胸外伤、支气管扩张、肺结核等)患者100例为对照组。采用质谱法检测XPB基因rs4150441和rs4150434,XPD基因rs171140和rs11878544,XPG基因rs4771436、rs2094258、rs17655位点的多态性,采用Halopview软件进行单体型构建,探讨XP基因多态性及单体型与肺癌遗传易感性的关联。结果 XPB基因的rs4150434位点,携带GA基因型个体患肺癌的易感性是携带GG基因型个体的2. 071倍(OR=2. 071,95%CI 1. 055～4. 067),携带AA基因型个体患肺癌的易感性是携带GG基因型个体的2. 535倍(OR=2. 535,95%CI 1. 063～6. 044)。XPG基因的rs4771436位点,携带GG基因型个体患肺癌的风险是携带TT基因型个体的2. 494倍(OR=2. 494,95%CI 1. 038～5. 992)。XPG基因的rs2094258位点,携带AA基因型个体对肺癌的易感性是携带GG基因型个体的3. 020倍(OR=3. 020,95%CI1. 015～8. 980)。单体型结果显示,XPB基因rs4150441位点(G> A)和XPB rs4150434位点(G>A)所构成的单体型中,GA单体型的肺癌易感性是GG单体型的3. 643倍(OR=3. 643,95%CI 1. 113～11. 921)。XPG基因rs2094258位点(G>A)、rs4771436位点(T>G)和rs17655位点(C>G)所构成的单体型中,ATC单体型的肺癌易感性是GTC单体型的3. 800倍(OR=3. 800,95%CI 1. 073～13. 459)。结论XPB rs4150434、XPG rs4771436、XPG rs2094258位点多态性与肺癌的遗传易感性相关联,XPB基因的GA单体型和XPG基因的ATC单体型可能增加肺癌的发病风险。     

亚洲人群MDM2基因SNP309多态性与乳腺癌易感性的Meta分析

目的综合评价MDM2基因SNP309多态性与亚洲人群乳腺癌易感性的关系。方法电子检索PubMed、Embase、VIP、CNKI和万方数据库中关于MDM2基因多态性与乳腺癌关系的病例对照研究,按照纳入与排除标准筛选文献,提取数据、评价纳入研究质量后进行Meta分析,计算合并OR值及95%CI,并进行敏感性分析和发表偏倚评估。结果共纳入11篇文献,涉及3 439例乳腺癌患者和3 499例对照。Meta分析结果显示,与携带TT基因型个体相比,携带GG基因型个体与乳腺癌风险增高相关(OR=1.37,95%CI:1.00~1.88),而携带GT基因型个体乳腺癌发病风险并未明显增高(OR=1.21,95%CI:0.99~1.49);与携带TT基因型个体相比,携带GT、GG基因型个体的乳腺癌发病风险增加(OR=1.26,95%CI:1.01~1.59);与携带GT、TT基因型个体相比,携带GG基因型个体的乳腺癌发病风险未明显增高(OR=1.18,95%CI:0.95~1.47)。结论在亚洲人群中,MDM2基因SNP309G可能是乳腺癌易感性增加的危险因素。     

HLA-DP基因多态性与卵巢癌临床病理参数的关联研究

目的探讨人类白细胞抗原(Human Leukocyte Antigens,HLA)DP基因多态性与卵巢癌临床病理参数的关联性。方法应用TaqMan探针方法,检测rs3077和rs9277535位点基因型,比较卵巢癌患者和健康对照者,探讨不同基因型与卵巢癌患病风险以及卵巢癌临床病理参数的关系。结果 rs3077和rs9277353位点突变纯合基因型AA病例组中占比均显著高于对照组(调整OR=1.82,95%CI:1.11~3.01;调整OR=1.89,95%CI:1.26~2.97);与携带rs3077 GG+GA和rs9377357GG+GA基因型的个体相比,携带1~2个危险基因型的个体发生卵巢癌的风险显著(P0.01);尚未发现HLADP基因遗传多态性与卵巢癌临床病理参数存在关联。结论 HLA-DP基因多态性与卵巢癌的发病风险存在关联。     

外周血SULF1基因多态性与不明原因复发性流产的关系研究

目的探究外周血硫酸酯酶1(SULF1)基因多态性与不明原因复发性流产(URSA)的关系。方法选取2016年1月-2017年1月该院196例诊断为URSA的患者作为研究组,以无不良妊娠史的健康妇女167例作为对照组,采用聚合酶链反应-限制性片段长度多态性分析(PCR-RFLP)技术,分析SULF1 rs6990375基因多态性与URSA相关性。结果 SULF1基因rs6990375检测到3种基因型:GG、GA、AA,3种基因型及等位基因频率在研究组和对照组中的分布均符合Hardy-Weinberg平衡定律(P0.05)。与对照组相比,研究组GG基因型频率显著增加(P0.05)。两组间GA、AA基因频率分布差异无统计学意义(P0.05)。与对照组相比,研究组G等位基因频率显著增加而A等位基因频率显著降低(P0.05)。以AA等位基因作为参照(OR=1.00),GA(OR=1.794)和GG(OR=2.418)携带者发病风险的相对危险度分别为1.794和2.418,差异有统计学意义(P0.05);以A等位基因作为参照(OR=1.00),G等位基因携带者OR为2.517,差异有统计学意义(P0.05)。SULF1基因rs6690375 GG、GA、AA基因型频率与自然流产次数明显相关(P0.05)。Logistic回归分析发现,GG基因型频率与自然流产次数增多的发生风险显著相关(OR=2.417,95%CI=1.386～2.899)。结论 SULF1基因rs6990375多态性与URSA发生风险有关,具有GG基因型的妇女URSA发生风险增加。     

MPO、NQO1、GSTP1和UGT1A6基因多态与慢性苯中毒遗传易感性关系

目的探讨MPO、NQO1、GSTP1和UGT1A6基因多态与慢性苯中毒易感性的关系。方法采用病例-对照研究,以268名苯中毒工人为病例组,268名接触苯而没有中毒表现的工人为对照组。应用TaqManPCR分析技术判定MPO(rs7208693),NQO1(rs1800566),GSTP1(rs947894)和UGT1A6(rs6759892,rs1105879,rs4124874,rs3755319,rs887829和rs4148323)基因型。结果携带GSTP1基因rs947894G等位基因个体患慢性苯中毒的危险性比AA基因型个体降低0.657倍(95%CI0.434~0.994,P=0.046);携带MPO基因rs7208693A等位基因人群中,UGT1 A6 rs6759892G等位基因个体发生慢性苯中毒的危险性是TT基因型的2.702倍(P=0.024),UGT1 A6 rs1105879C等位基因个体发生慢性苯中毒的危险性是TT型的2.619倍(P=0.035)。在饮酒人群中,携带NQO1基因rs1800566TT基因型个体慢性苯中毒的发病风险较携带CC和CT基因型个体增加9.000倍(95%CI1.460~55.478,P=0.021);在吸烟人群中,带NQO1基因rs1800566TT基因型个体慢性苯中毒的发病风险较携带CC和CT基因型个体增加7.000倍(95%CI1.555~31.575,P=0.012)。单倍型分析显示,本人群携带UGT1A6基因TACGGG单倍型个体慢性苯中毒的发病风险是携带TAATGG单倍型个体的1.446倍(OR=1.446,95%CI1.005~2.080,P=0.046)。结论同时携带MPO基因rs7208693A和UGT1A6基因rs6759892G或rs1105879C等位基因型个体对苯中毒易感;携带NQO1基因rs1800566TT基因型且同时吸烟或饮酒的个体对苯中毒易感;携带UGT1A6基因TAATGG单倍型个体可增加慢性苯中毒的发病风险;GSTP1基因多态与慢性苯中毒遗传易感性的关系仍需进一步研究。     

ESRα和VDR基因多态性与乳腺癌易感性关系

目的探讨雌激素受体α(ESRα)、维生素D受体(VDR)基因多态性与乳腺癌发病风险关系。方法选取189例乳腺癌患者和374名非癌女性对照人群为研究对象,应用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)和测序检测ESRα基因rs2234693和rs9340799位点、VDR基因rs10735810位点的多态性。结果 ESRα基因rs9340799位点等位基因G在病例组的分布频率(15.08%)明显低于对照组(22.46%)(P=0.002),与等位基因A相比,经年龄校准的OR=0.580(95%CI=0.413~0.815);ESRα基因单体型CG在病例组的分布频率(13.7%)明显低于对照组(20.6%)(P=0.005),复合基因型CCGG在病例组的分布频率(1.59%)也明显低于对照组(5.61%)(P=0.025),其OR值分别为0.614(95%CI=0.436~0.864)和0.271(95%CI=0.080~0.921)。结论 ESRα基因rs9340799位点多态性与乳腺癌发病紧密相关,携带有等位基因G,单体型CG或复合基因型CCGG的个体患乳腺癌的风险较低。     

Arsenic methylation, GSTT1, GSTM1, GSTP1 polymorphisms, and skin lesions

OBJECTIVE: We investigated whether primary and secondary arsenic methylation ratios were associated with skin lesions and whether GSTT1, GSTP1, and GSTM1 polymorphisms modify these relationships. METHODS: A case-control study of 600 cases and 600 controls that were frequency matched on age and sex was conducted in Pabna, Bangladesh, in 2001-2002. Individual well water, urine, and blood samples were collected. Water arsenic concentration was determined using inductively coupled plasma mass spectrometry (ICP-MS). Urinary arsenic speciation was determined using high performance liquid chromatography hydride with generator atomic absorption spectrometry and ICP-MS. Genotyping was conducted using multiplex polymerase chain reaction and TaqMan. RESULTS: A 10-fold increase in primary methylation ratio [monomethylarsonic acid (MMA)/(arsenite + arsenate] was associated with a 1.50-fold increased risk of skin lesions (multivariate odds ratio = 1.50; 95% confidence interval, 1.00-2.26). We observed significant interaction on the multiplicative scale between GSTT1 wildtype and secondary methylation ratio [dimethylarsinic acid/MMA; likelihood ratio test (LRT), p = 0.01]. No significant interactions were observed for GSTM1 or GSTP1 or for primary methylation ratios. CONCLUSION: Our findings suggest that increasing primary methylation ratios are associated with an increase in risk of arsenic-related skin lesions. The interaction between GSTT1 wildtype and secondary methylation ratio modifies risk of skin lesions among arsenic-exposed individuals.     

老年呼吸机相关肺炎患者死亡的危险因素

目的分析老年呼吸机相关肺炎(VAP)患者死亡的危险因素。方法调查2011年4月—2017年2月某院年龄≥60岁且发生VAP的患者,收集患者的临床资料,包括基本情况、感染情况、预后等,并对其死亡的危险因素进行分析。结果共有老年VAP患者682例,198例患者死亡,病死率为29.03%。APACHEⅡ评分15分(OR=2.482,95%CI=1.473~4.183)、机械通气时间15 d(OR=2.526,95%CI=1.661~3.840)、多重耐药菌感染(OR=3.379,95%CI=2.008~5.686)、真菌感染(OR=3.414,95%CI=1.830~6.370)、使用糖皮质激素(OR=2.075,95%CI=1.265~3.403)、血清清蛋白浓度35 g/L(OR=2.129,95%CI=1.386~3.268)、器官损伤数目≥3个(OR=3.438,95%CI=2.165~5.459)、血糖≥10 mmol/L(OR=1.744,95%CI=1.106~2.751)等8个因素均为老年VAP患者死亡的独立危险因素。结论老年VAP患者死亡与多种因素有关,临床应采取以干预主要危险因素为主的综合防控措施,降低其病死率。     

脑循环分析仪的研制

介绍脑循环分析仪的基本结构、工作原理、软件设计和临床应用等内容,该仪器运用超声多普勒、超声脉冲和压力变送器,在心电同步信号监测下检测血液流速、压力波形和血管管径管数据,然后通过分析计算得到脑血管阻力,代偿血流量和血管壁弹性等脑循环血流动力学参数。     

Association of genetic polymorphisms in CYP2E1, MPO,NQO1, GSTM1, and GSTT1 genes with benzene poisoning

Metabolic enzymes involved in benzene activation or detoxification, including NAD(P)H, quinone oxidoreductase 1 (NQO1), cytochrome P450 2E1 (CYP2E1), myeloperoxidase (MPO), glutathione-S-transferase mu-1 (GSTM1), and glutathione-S-transferase theta-1 (GSTT1), were studied for their roles in human susceptibility to benzene poisoning. The potential interactions of these metabolic enzymes with lifestyle factors such as cigarette smoking and alcohol consumption were also explored. We studied 156 benzene-poisoning patients and 152 workers occupationally exposed to benzene in South China. Sequencing, denaturing HPLC, restriction fragment-length polymorphism, and polymerase chain reaction were used to detect polymorphisms on the promoters and complete coding regions of NQO1, CYP2E1, MPO, and the null genotypes of GSTM1 and GSTT1. Seventeen single nucleotide polymorphisms (SNPs) were identified in NQO1, CYP2E1, and MPO genes, including 6 novel SNPs in CYP2E1 and MPO. Of the subjects who smoked and drank alcohol, an 8.15-fold [95% confidence interval (CI), 1.43-46.50] and a 21.50-fold (95% CI, 2.79-165.79) increased risk of benzene poisoning, respectively, were observed among the subjects with two copies of NQO1 with a C-to-T substitution in cDNA at nucleotide 609 (c.609 C>T variation; i.e., NQO1 c.609 T/T) compared to those with the heterozygous or wild (NQO1 c.609 C/T and c.609 C/C) genotypes. Our data also indicated that individuals with CYP2E1 c.-1293 C/C and c.-1293 G/C, and NQO1 c.609 T/T, and GSTT1 null genotypes tended to be more susceptible to benzene toxicity. Our results suggest that the combined effect of polymorphisms in NQO1, CYP2E1, and GSTT1 genes and lifestyle factors might contribute to benzene poisoning.     

GSTM1, GSTT1, GSTP1, and GSTA1 polymorphisms and urinary isothiocyanate metabolites following broccoli consumption in humans

Isothiocyanates (ITC) are potentially anticarcinogenic phytochemicals formed from the metabolism of glucosinolates and are found in cruciferous vegetables as well as a select number of other foods. ITC are both substrates for and inducers of glutathione S-transferase (GST) phase II metabolizing enzymes involved in carcinogen detoxification as well as effectors of phase I pathways. Previous studies report mixed results on the interaction between cruciferous vegetable intake, GST polymorphisms, and risk of cancer. We conducted a study of 114 healthy human subjects between 18 and 50 y of age to examine the biologic mechanism underlying the associations, specifically, to assess whether GST genotype is associated with urinary ITC metabolites following a known dose of broccoli. After 48 h of abstaining from all sources of glucosinolates, participants provided a blood sample, consumed 1 meal containing 2.5 g broccoli/kg body weight, and collected urine for 24 h. ITC metabolites were measured in the urine using a HPLC cyclocondensation assay. DNA was extracted from blood samples, and GSTM1 deletion, GSTT1 deletion, GSTP1 Ile105Val, and GSTA1*A/*B were genotyped by matrix-assisted laser desorption/ionization time-of-flight. A chi-square test was used to compare high and low ITC excretion levels across genotypes. ITC levels were regressed on genotype, adjusting for gender. There were no substantial differences in ITC levels among genotypes, either individually or in combination. Contrary to our hypothesis, a higher proportion of GSTM1 null individuals had high ITC excretion (62%) compared with the proportion of GSTM1 present with high ITC excretion (39%) (P = 0.03). These results are in agreement with another feeding study, and lend support to the idea of alternative routes of ITC metabolism.     

Genetic polymorphisms of MnSOD, GSTM1, GSTT1, and OGG1 in coal workers' pneumoconiosis

Little is known about the genetic susceptibility to coal workers' pneumoconiosis (CWP). We investigated the association between genetic polymorphisms of MnSOD, GSTM1, GSTT1, or OGG1 and susceptibility to CWP. The study population was composed of 259 Chinese retired coal miners who had similar dust exposure histories. Of these, there were 99 cases with International Labor Organization chest radiologic criteria for CWP and 160 controls (with no radiologic criteria for CWP). Individual dust exposure variables were estimated from work histories, and smoking information was obtained from interviews. Polymerase chain reaction-based techniques evaluated the genotypes of all study subjects. There were no differences in genotype frequency of MnSOD, GSTM1, GSTT1, and OGG1 between miners with CWP and miners without CWP, by logistic regression analysis. Cumulative dust exposures, but not genetic polymorphisms, were associated significantly with the presence of CWP. This study illustrates the complexity of factors that may contribute to the development of CWP.