构建7q32区域鼻咽癌和正常鼻咽上皮细胞部分基因的表达图谱

目的构建７ｑ３２区域鼻咽癌细胞和组织及原代培养人正常鼻咽上皮细胞的部分基因表达图谱。方法通过差异ＲＴ－ＰＣＲ和Ｎｏｒｔｈｅｒｎ杂交的方法检测定位于７ｑ３２区域的２０个ＥＳＴ在鼻咽癌细胞和鼻咽癌组织及原代培养人正常鼻咽上皮细胞ｍＲＮＡ的表达水平。结果８个ＥＳＴ在鼻咽癌细胞ＨＮＥ１和原代培养人正常鼻咽上皮细胞中表达量较一致，７个ＥＳＴ在两种细胞中均无表达，３个ＥＳＴ（Ｗ７２６８８、Ｈ１９８３０、ＡＡ１３０６３０）在鼻咽癌细胞株中表达上调，而２个ＥＳＴ（ＡＡ０７０４３７、Ｈ９０８８２）在原代培养人鼻咽上皮细胞中表达上调。在１３例鼻咽癌活检组织中３０．７％（４／１３）的ＡＡ０７０４３７表达下调，７７％（１０／１３）的Ｗ７２６８８和７７％（１０／１３）的Ｈ１９８３０表达上升。结论构建了７ｑ３２区域鼻咽癌细胞和组织及原代培养人正常鼻咽上皮细胞部分基因表达图谱，并初步认为Ａ０７０４３７的表达下调和Ｗ７２６８８、Ｈ１９８３０的过表达与鼻咽癌的发生有关。     

左肝管全程剖开胆肠吻合术的应用解剖学研究

左肝管全程剖开手术,必须熟悉左肝管与邻近血管的局部解剖关系.为此我们用 ABS 丙酮溶液灌注塑型了6具新鲜成人尸肝脏,解剖40例(成人30,儿童10)肝脏标本,测量了左肝管长度和管径,左肝管与肝总管夹角。全程剖开左肝管与右肝管,并观察左肝管与右肝管、左肝动脉、门静脉左干和肝圆韧带的关系,提出了右肝管全程剖开手术方法和注意事项。     

未培养羊水荧光原位杂交快速检测60例胎儿常见染色体数目异常

目的 应用细菌人工染色体(bacterial artificial chromosome,BAC)克隆自行制备荧光探针,对胎儿常见染色体数目异常(13,18,21,X,Y)行快速产前诊断.方法 利用中国医学遗传学国家重点实验室BAC库中相应染色体特异位点克隆,自行制备荧光探针.经外周血淋巴细胞染色体杂交验证后,用于胎儿未培养羊水的快速荧光原位杂交fluorescence in situ hybridization,FISH)检测,已检测60例羊水标本.结果 所有探针特异性均为100%,杂交成功率为97.86%;FISH结果与常规核型分析一致,检出21三体2例,18三体1例.有两例涉及其它染色体的结构异常未能检出.结论 自制探针用于未培养羊水快速FISH,使用标本量少、快速、简便,可有效检出上述5种染色体的数目异常,但本法不能检出其他染色体的数目异常和结构异常,其应用仍有一定局限性.     

湖南汉族人群HLA-DP、-DQ位点等位基因多态性与鼻咽癌的相关性

目的 探讨湖南汉族人群HLA—DP、HLA—DQ位点等位基因多态性与鼻咽癌遗传易感性之间的关系。方法 应用聚合酶链反应—特异性寡核苷酸探针基因分型技术对87例湖南汉族鼻咽癌患者与91名健康对照作HLA—DPAl、—DPBl、—DQAl及—DQBl的基因分型，采用x^2检验比较两组各位点等位基因频率，单倍型频率分布的差异。结果 发现鼻咽癌组DPAl*0201、DPBl*1901、DQAl*0201较对照组明显降低，DPBl*0402、DQAl*0101较对照组明显升高；单倍型DPAl*0201—DPBl*1401及DQAl*0201—DQBl*0201较对照明显降低；但P值经Bonferroni校正后，差异均无显著性(Pc＞0．05)。结论 湖南汉族人群HLA—DP和—DQ位点与鼻咽癌无明显相关，与以往用受累同胞对方法在鼻咽癌家系中未能证实鼻咽癌易感基因与HLA—DP和—DQ位点连锁的结果一致。     

Polymorphisms of four microsatellite DNA markers from telomeric HLA I region (D6S1624, D6S258, M6S211 and D6S510) and their linkage disequilibrium with HLA-A in a southern Chinese Han population]

OBJECTIVE: To explore the genetic polymorphisms of four microsatellite DNA markers from telomeric HLA I region (D6S1624, D6S258, M6S211 and D6S510) and their linkage disequilibrium with HLA-A in a southern Chinese Han population residing in Hunan province. METHODS: Fluorescent PCR/Size-sequencing was carried out to analyze the polymorphisms of D6S1624, D6S258, M6S211 and D6S510 loci, and polymerase chain reaction-sequence specific priming (PCR-SSP) technique was used for HLA-A typing. RESULTS: The genotypic distributions at the 5 loci were consistent with Hardy-Weinberg equilibrium (P> 0.05). The number of allelic variants for D6S1624, D6S258, M6S211 and D6S510 loci were 10, 10, 12 and 9, respectively. Each locus had several main alleles and the dominant alleles were D6S1624-*199, D6S258-*195, M6S211-*261 and D6S510-*186. All of the 4 microsatellite markers exhibited high heterozygosity values (0.7142-0.8316) and polymorphism information content values (0.6686-0.811). No global linkage disequilibrium (LD) was detected between D6S1624 and HLA-A (P= 0.2646), or between D6S258 and HLA-A (P= 0.3481). In contrast, very significant global LD was found between M6S211 and HLA-A (P< 0.0001), and between D6S510 and HLA-A(P< 0.0001). Subsequent analysis for haplotypes with an observed frequency of > or = 3% revealed that only 2 of the 10 D6S1624-HLA-A haplotypes and 3 of the 9 D6S258-HLA-A haplotypes displayed weak or moderate LD, while 7 out of the 8 M6S211-HLA-A haplotypes, 6 among the 7 D6S510-HLA-A haplotypes were in tight LD. CONCLUSION: Authors have characterized four microsatellite DNA markers, D6S1624, D6S258, M6S211 and D6S510 in a southern Chinese Han population. Findings shown here can be helpful for those studies mainly addressing the association between HLA I sub-region and diseases. The data also provide basis for future study in forensics, HLA matching in clinical transplantation and anthropology.     

两个遗传性非患肉性结直肠癌家系中MLH1和MSH2基因的突变检测

目的 确定两个遗传性非息肉性结直肠癌(hereditary nonpolyposis colorectal cancer,HNPCC)家系的致病基因,选择MLH1基因和MSH2基因进行突变检测.方法 采用聚合酶链反应结合DNA直接测序法,对两个遗传性非息肉性结直肠癌家系的患者进行MLH1基因和MSH2基因的突变检测;发现变异后,采用PCR-限制性片段长度多态性或直接测序法鉴定此变异是否属于突变.结果 在家系A的患者中发现了位于MLH1基因第3外显子内的新突变c.243_244 insA;在家系B的患者中发现了MSH2基因第7外显子内的c.1215_1218dupCCGA突变,这两个突变都导致了编码蛋白的提前终止.结论 MLH1基因的c.243_244insA突变和MSH2基因的c.1215_1218dupCCGA突变分别是导致家系A和家系B发生遗传性非息肉性结直肠癌的致病突变.     

A novel locus for autosomal dominant nonsyndromic hearing loss identified at 5q31.1-32 in a Chinese pedigree

 Hearing impairment is an extremely heterogeneous disorder. A total of 35 loci and 17 related genes for autosomal dominant nonsyndromic hearing loss have been identified. In a Chinese pedigree characterized by autosomal dominant inheritance with bilateral, postlingual, progressive, and sensorineural nonsyndromic hearing impairment, the putative disease gene locus was localized to chromosome 5q31.1-32 by a genome-wide scan. Fine mapping indicated that the disease gene was located within an 8.8-cM region between markers D5S2056 and D5S638, with a maximum two-point logarithm of differences (LOD) score of 6.89 (θ = 0) at D5S2017. By the candidate gene approach, mutation screening of the DIAPH1 and POU4F3 genes at 5q31 was performed. No mutation was found, suggesting that this is a novel deafness locus, which has been named DFNA42. Received: May 8, 2002 / Accepted: October 1, 2002     

2017—2020年2 426株肺炎克雷伯菌临床分布及耐药性变迁回顾性分析

目的 了解湖南中医药大学第一附属医院肺炎克雷伯菌(Klebsiella pneumoniae, KP)的临床分布和耐药性特征,并对耐碳青霉烯肺炎克雷伯菌(carbapenem resistant Klebsiella pneumoniae,CRKP)的耐药性变迁进行分析,为临床合理选用抗菌药物提供依据。 方法 回顾性分析2017年1月—2020年12月临床分离KP的标本来源、科室来源,整体药敏试验结果,对不同年度、主要科室来源CRKP分离率及常用抗菌药物的耐药性变迁进行统计学分析。 结果 2017—2020年共分离非重复KP 2 426株,其中1 825株(75.23%)来自下呼吸道,246株(10.14%)来自尿液,164株(6.76%)来自全血。呼吸内科、老年病科和中心ICU分离占比居前三位,共分离924株(38.09%)。所有分离株对头孢曲松、亚胺培南、阿米卡星和替加环素的耐药率分别为34.36%、20.02%、7.79%和2.31%。共分离CRKP 500株,2017—2020年分离出CRKP比率分别为23.34%、25.30%、18.52%和13.94%,中心ICU和烧伤创伤整形外科分离出CRKP比率高达61.82%和59.26%。2017—2020年各年度CRKP对阿米卡星的耐药率分别为49.64%、30.36%、31.75%、23.19%,对替加环素耐药率分别为7.30%、7.74%、6.35%和8.70%,CRKP对其余常用抗菌药物均表现为高度耐药。 结论 该院临床分离的KP主要来自老年和重症患者呼吸道、泌尿系统和血流感染,耐药情况比较严峻。近两年CRKP分离率呈现下降趋势,有待进一步观察。临床应重视CRKP联合治疗方案的应用,院感科应加强对多重耐药KP和抗菌药物的管控,预防院内感染并对CRKP的院内获得性传播引起高度重视。     

浏阳市居民新鲜水果摄入频率与脑卒中发病的关联

目的 了解湖南省浏阳市居民新鲜水果摄入频率情况,探讨新鲜水果摄入频率与脑卒中发病关联。 方法 利用中国慢性病前瞻性研究湖南省浏阳市项目点30～79岁常住居民基线调查数据和随访获得的脑卒中发病数据,利用Cox比例风险模型,在调整混杂因素后,评估新鲜水果摄入频率与脑卒中发病的关联。 结果 共57 288名研究对象纳入分析,浏阳市仅7.38%的研究对象每周有4 d及以上吃新鲜水果 。男性、家庭年收入水平低、文化程度低、吸烟、饮酒人群新鲜水果摄入频率较低(P<0.001)。2015—2019年共随访观察到2 720例脑卒中发病。增加新鲜水果摄入频率对脑卒中的发病有保护作用,与不吃或极少吃新鲜水果相比,每周有4 d及以上吃新鲜水果脑卒中的发病风险降低了28%(HR=0.72,95%CI:0.61~0.85),缺血性脑卒中的发病风险降低了25%(HR=0.75,95%CI:0.60~0.94),出血性脑卒中的发病风险降低了51%(HR=0.49,95%CI:0.35~0.76)。 结论 新鲜水果摄入频率增加能降低脑卒中发病风险。浏阳市居民新鲜水果摄入频率情况不容乐观,针对这一问题,需要采取适当措施以增加居民新鲜水果摄入频率。