女性人乳头瘤病毒感染的相关因素分析

目的 分析女性人乳头瘤病毒(human papilloma virus,HPV)感染率、HPV亚型分布及影响感染的相关因素,为女性宫颈癌的防治提供科学指导.方法 以2009年3-11月在哈尔滨医科大学附属肿瘤医院接受子宫颈HPV检测的605例女性为观察对象,取其宫颈脱落细胞标本,采用快速导流杂交技术HPV DNA检测法进行HPV的基因型分型,采用单因素和多因素非条件Logistic回归模型分析年龄、婚姻、受教育程度、收入、职业、初次性生活年龄、避孕方式、妊娠次数、分娩方式、吸烟等因素与HPV感染的关系.结果 女性HPV总感染率为21.49%(130/605),其中高危亚型感染率为15.70%(95/605),中国人常见亚型感染率为5.29%(32/605).在单因素分析中,危险因素为初次性生活年龄,HPV感染率随初次性生活年龄增高而减低(X2=4.4618,P<0.05),而年龄、婚姻、受教育程度、收入、职业、避孕方式、妊娠次数、分娩方式、吸烟因素组内比较差异无统计学意义(X2值分别为0.0525、1.8510、1.0348、0.2592、1.1176、1.5664、2.8835、1.4597、2.6161,P均>0.05).在多因素非条件Logistic回归中,危险因素主要有初次性生活年龄、婚姻和妊娠次数(X2值分别为21.6637、8.0574、15.7573,P均<0.05).结论 初次性生活年龄、婚姻及妊娠次数与HPV感染高度相关,应尽量避免高危因素的发生,同时应重视HPV的筛查,尽可能做到早期发现及时进行规范性治疗.     

The molecular epidemiology of hepatitis E virus infection

Molecular characterization of various hepatitis E virus (HEV) strains circulating among humans and animals (particularly swine, deer and boars) in different countries has revealed substantial genetic heterogeneity. The distinctive four-genotype distribution worldwide of mammalian HEV and varying degrees of genetic relatedness among local strains suggest a long and complex evolution of HEV in different geographic regions. The population expansion likely experienced by mammalian HEV in the second half of the 20th century is consistent with an extensive genetic divergence of HEV strains and high prevalence of HEV infections in many parts of the world, including developed countries. The rate and mechanisms of human-to-human transmission and zoonotic transmission to humans vary geographically, thus contributing to the complexity of HEV molecular evolution.     

Alcohol dehydrogenase genetic polymorphisms, low-to-moderate alcohol consumption, and risk of breast cancer

BACKGROUND: In vitro, human isoenzymes encoded by genes homozygous for the ADH1C*1 or ADH1B*2 alleles metabolize ethanol to acetaldehyde at a faster rate than those homozygous for the ADH1C*2 or ADH1B*1 allele. Because alcohol is a known risk factor for breast cancer, we evaluated the joint association of genetic variants in ADH and alcohol consumption in relation to breast cancer. METHODS: A nested case-control study of 321 cases and matched controls was conducted. Five single nucleotide polymorphisms (SNPs) in the ADH1C and ADH1B genes were genotyped. Logistic regression was used to assess odds ratios (ORs) and 95% confidence limits (CIs) for each SNP. Haplotype analysis of all 5 SNPs was also undertaken. RESULTS: Among drinkers, the median intake of total alcohol was 13 g/wk (10th-90th percentiles; 4.5-135.9) in cases and 18 g/wk (10th-90th percentiles; 4.5-104.1) in controls. Women who drank alcohol tended to be at an increased risk of developing breast cancer compared with those who did not drink (OR=1.40%, 95% CI 0.97-2.03), particularly those who were premenopausal at the time of breast cancer diagnosis (OR=2.69%, 95% CI: 1.00-7.26). Of the known functional alleles, breast cancer risk was not significantly increased among carriers of at least 1 ADH1C*1 or ADH1B*2 allele, when compared with those homozygous for the genotype at each locus. However, breast cancer risk tended to be lower among women who inherited the G allele at ADH1B IVS1+896A>G (OR=0.62, 95% CI 0.37-1.04). Overall haplotype frequencies were not significantly different between cases and controls. CONCLUSIONS: In this study low levels of alcohol are associated with a modest increase in breast cancer risk that is not altered by known functional allelic variants of the ADH1B and 1C gene. The protective association conferred by the G allele at ADH1B IVS1+896A>G needs further evaluation.     

广西三城市7岁以下儿童13地中海贫血发生率及其基因突变类型的研究

目的 对广西南宁、柳州、百色地区7岁以下儿童进行β地中海贫血发生率及基因突变类型分析.方法 按分层整群随机抽样方法,抽取南宁、柳州和百色地区7岁以下儿童共2261名,进行血常规检测、血红蛋白(Hb)分析和β珠蛋白基因分析.结果 2261名儿童中,Hb分析显示125名HbA2升高,经基因分析诊断为β地中海贫血杂合子.β地中海贫血的发生率为5.53%.共检出CD41-42基因突变59例,CD17基因突变33例,TATA box nt-28基因突变18例,IVS-Ⅱ-654基因突变7例,CD43基因突变3例,HbE基因突变3例,CD71-72基因突变1例,及TATAbox nt-29基因突变1例.基因型频率依次为:CD41-42为47.20%、CD17为26.40%、TATAbox nt-28为14.40%、IVS-Ⅱ-654为5.60%、CD43为2.40%、HbE为2.40%、CD71-72为0.80%和TATAbox nt-29为0.80%.结论 研究显示调查的3个地区地中海贫血发生率较高;7岁以下儿童中存在β地中海贫血基因突变携带者.     

Phenotype–genotype interactions on renal function in type 2 diabetes: an analysis using structural equation modelling

Aims/hypothesis  Cardiovascular and renal diseases share common risk factors. We used structural equation modelling (SEM) to evaluate the independent and combined effects of phenotypes and genotypes implicated in cardiovascular diseases on renal function in type 2 diabetes. Methods  1,188 type 2 diabetic patients were stratified into high-risk and low-risk groups according to bimodal distributions of the logarithmically transformed (log_e) urinary albumin:creatinine ratio and plasma creatinine levels. Models for these groups, comprising continuous and non-ranking categorical data, were developed separately to evaluate the inter-relationships among measured variables and latent factors using non-linear SEMs, Bayesian estimation and model selection as assessed by a goodness-of-fit statistic. Results  Inter-correlated measured variables (obesity, glycaemia, lipid, blood pressure) and variants of the genes encoding endothelial nitric oxide synthase (NOS), β-adrenergic receptor (ADRB), components of the renin–angiotensin system (RAS) and lipid metabolism were loaded onto their respective latent factors of phenotypes and genotypes. In addition to direct and indirect effects, latent factors of obesity, lipid and BP interacted with latent factors of ADRB and RAS genotypes to influence renal function. Together with variants of the genes encoding peroxisome proliferator-activated receptor γ, atrial natriuretic peptide, adducin, G protein β₃ subunit, epithelial sodium channel α subunit and matrix metallopeptidase 3, these parameters explained 39–80% of the variance in renal function in the high-risk and low-risk models. Conclusions/interpretation  SEM is a useful tool for confirming and quantifying multiple interactions of biological pathways with genetic determinants. The combined and interactive effects of blood pressure, lipid and obesity on renal function may have therapeutic implications, especially in type 2 diabetic individuals with genetic risk factors. Electronic supplementary material  The online version of this article (doi:) contains supplementary material, which is available to authorised users.     

Classifying genotype F of hepatitis B virus into F1 and F2 subtypes

AIM: To explore the propriety of providing hepatitis B virus (HBV) genotypes F and H with two distinct genotypes. METHODS: Eleven HBV isolates of genotype F (HBV/F) were recovered from patients living in San Francisco, Japan, Panama, and Venezuela, and their full-length sequences were determined. Phylogenetic analysis was carried out among them along with HBV isolates previously reported. RESULTS: Seven of them clustered with reported HBV/F isolates in the phylogenetic tree constructed on the entire genomic sequence. The remaining four flocked on another branch along with three HBV isolates formerly reported as genotype H. These seven HBV isolates, including the four in this study and the three reported, had a sequence divergence of 7.3-9.5% from the other HBV/F isolates, and differed by > 13.7% from HBV isolates of the other six genotypes (A-E and G). Based on a marked genomic divergence, falling just short of > 8% separating the seven genotypes, these seven HBV/F isolates were classified into F2 subtype and the former seven into F1 subtype provisionally. In a pairwise comparison of the S-gene sequences among the 7 HBV/F2 isolates and against 47 HBV/F1 isolates as well as 136 representing the other six genotypes (A-E and G), two clusters separated by distinct genetic distances emerged. CONCLUSION: Based on these analyses, classifying HBV/F isolates into two subtypes (F1 and F2) would be more appropriate than providing them with two distinct genotypes (F and H).     

厦门地区儿科患者分离的产超广谱β-内酰胺酶大肠埃希菌耐药及基因型分析

目的了解厦门地区儿科患者分离的产超广谱β-内酰胺酶(ESBLs)大肠埃希菌耐药及基因型情况,为临床防治提供对策。方法分析2011年1-12月解放军第174医院儿科住院患者中分离的产ESBLs大肠埃希菌的耐药情况,并采用特定引物PCR扩增的方法进行ESBLs基因亚型分析。结果 2011年全年共分离产ESBLs的大肠埃希菌189株,阳性率为19.73%(189/958),药敏结果显示除碳氢酶烯类抗生素、加酶抑制剂复合抗生素类、头霉素类抗生素等不同程度敏感外,其余抗生素均耐药;基因亚型主要为CTX-M-13,还有TEM型。结论厦门地区儿童患者产ES-BLs情况较为严重,应尽量避免不适当地应用三代头孢菌素、长期预防应用抗生素等。一旦发生感染,应有针对性地选用碳青霉烯类和头霉素类等使感染得以控制。     

云南地区乙型肝炎病毒基因型分布与临床的相关性

目的: 了解云南地区乙型肝炎病毒基因型分布特征, 探讨其与慢性HBV感染者的性别和年龄、不同临床疾病谱、病毒复制水平的关系.方法:选择云南地区慢性HBV感染者117例, 其中慢性无症状乙型肝炎表面抗原携带者(ASC)26例、慢性乙型肝炎(CHB)55例(轻度21例、中度24例、重度10例)、慢性重型肝炎(CLF)18例、乙肝后肝硬化(LC)11例及原发性肝细胞肝癌(HCC)7例, 采用反向杂交技术(RDB)检测HBV基因型, 并对与其性别年龄、临床分型和病毒复制水平的关系进行分析.结果: 云南地区HBV基因型以B型和C型为主, 分别为41.0%(48/117)和54.7%(64/117) , 并以C型为最多(χ2 = 4.38, P = 0.036);D型1例(0.86%), B、C混合型2例(1.71%), A、C混合型2例(1.71%). B基因型在轻度慢乙肝组所占的比例显著高于中、重度慢乙肝组(χ2 = 8.27、11.98, P = 0.004、0.001)、ASC组(χ2 = 5.46, P = 0.02)、CLF组(χ2 = 4.13, P = 0.042)和LC/HCC组(χ2 = 11.3, P = 0.001). C基因型在LC/HCC组和重度慢乙肝组所占的比例均显著高于轻度慢乙肝组(χ2 = 11.3, P = 0.001;χ2 = 8.78, P = 0.003), 与其他各临床型组间的比较则无显著性差异(P>0.05). C基因型在HBV DNA( )组和HBeAg(-)组r所占的比例均分别显著高于HBV DNA(-)组(χ2 = 6.63, P = 0.01)和HBeAg( )组(χ2 = 7.12, P = 0.008). B基因型在HBV DNA低水平复制组中所占的比例显著高于高水平复制组(χ2 = 4.12, P = 0.042). C基因型在HBV DNA高水平复制组中所占的比例显著高于B基因型(χ2 = 3.89, P<0.05). C基因型在年龄≥30岁组中所占的比例(63.3%)高于年龄<30岁组(45.6%)(χ2 = 3.7, P = 0.05). HBV基因型在性别间的分布无统计学差异(P>0.05)结论:云南地区存在HBV的B、C、D、B C和A C基因型, 以B型和C型为主要基因型, 并以C型为最多. B基因型在轻度慢乙肝的比例显著高于其他各临床型HBV感染者, 并且与HBV的低水平复制和低年龄有关. C基因型主要分布于重度慢乙肝和LC/HCC、HBV DNA高水平复制、年龄≥30岁的患者中. 提示C基因型与慢乙肝重度、肝硬化、肝细胞肝癌及HBV DNA高水平复制关系密切.     

The use of molecular assays in the management of viral hepatitis

Molecular assays are instrumental in the clinical management of viral hepatitis. During the past years, a wide variety of molecular assays have been developed and implemented. This considerably improved the understanding of the natural history and pathogenesis of Hepatitis B virus (HBV), Hepatitis C virus (HCV) or Hepatitis delta virus (HDV) hepatitis, but also caused uncertainties in the selection of the most appropriate assays for clinical requirements. Indeed, a rational choice and application of these assays requires adequate knowledge of the performance of the single test. Moreover, the choice of the most accurate assay for patients’ needs and physicians’ objectives, needs to be oriented to specific contexts, such as diagnosis, management or treatment. In the past, a hurdle in the routine use of assays for hepatitis viruses nucleic acid quantification was represented by the availability of only “home brew” methods which lacked standardization. Major improvement in addressing the use of molecular assays for viral hepatitis has been derived from recent standardization procedures that allowed a comparison between different tests after results were given as International Units. In addition, it should be reminded that, before getting into the market, molecular assays should be approved by European regulation authorities and validated using internationally recognized standards. A subsequent clinical validation should address the diagnostic accuracy of the assay. These proceedings have the aim of identifying which molecular tests, among those currently available, meet clinical requirements for each specific application.