多囊蛋白-1的研究进展

多囊蛋白-1（polycystin-1,PC-1）是由多囊肾病基因-1（PKD1）编码的跨膜蛋白,属多囊蛋白家族成员,主要在上皮细胞、内分泌细胞、心肌细胞和骨骼肌细胞上表达。PC-1可与多囊蛋白-2（polycystin-2,PC-2）、踝蛋白、纽蛋白等蛋白结合,参与细胞-细胞、细胞-基质黏附和细胞间信号转导。PC-1可调节肾小管上皮细胞的增殖和分化、介导细胞间的黏附,在肾脏的正常发育和常染色体显性遗传性多囊肾病（ADPKD）发病起重要作用。     

GRIN1突变相关发育迟缓患儿临床特征和基因突变特点分析

目的 对GRIN1基因突变相关发育迟缓患儿的临床特征及基因突变特点进行分析.方法 收集2例发育迟缓患儿的临床资料,对2例患儿及其父母进行靶向基因测序(TGS).结合文献分析发育迟缓患儿的临床特征和基因突变特点.结果 2例患儿均表现为精神发育迟缓、语言落后、运动落后,无特殊面容,无癫痫,其中1例合并矮小症.TGS结果显示...     

原发性肝癌患者乙型肝炎病毒C基因启动子变异与HBV DNA关系的探讨

目的研究原发性肝癌患者乙型肝炎病毒C基因启动子变异(HBVBCP)与HBVDNA关系。方法(1)采用PCR微板核酸杂交结合ELISA检测显示技术,对患者血清进行检测HBVBCP区核苷酸(nt)1762碱基A→T和1764G→A联合突变。(2)采用PCR结合荧光探针检测技术,检测患者血清HBVDNA含量。结果(1)HBVBCP变异在原发性肝癌组的阳性率为70.0%(14/20),显著高于慢性肝病组的阳性率37.8%(59/156)(P=0.008)。(2)原发性肝癌组的血清HBVDNA含量(107.6414±1.3398拷贝/ml)明显高于慢性肝病组的HBVDNA含量(106.7672±1.7669拷贝/ml)(P=0.034)。结论HBVBCP变异与原发性肝癌关系密切,且血清HBVDNA复制水平在原发性肝癌的发生中可能也起到主要的作用。     

NSCLC非经典EGFR突变患者临床特点及治疗预后分析

目的 了解表皮生长因子受体酪氨酸激酶抑制剂(epidermal growth factor receptor-tyrosine kinase inhibitor,EGFR-TKI)对非经典突变非小细胞肺癌(non-small-cell lung cancer,NSCLC)的治疗疗效,为非经典突变患者选择最合适的靶向药物...     

骨关节炎关节软骨中软骨细胞线粒体DNA缺失突变的分析

目的：分析骨关节炎病人关节软骨组织中软骨细胞线粒体DNA序列变化,探讨骨关节炎发病的潜在病理机制。方法：应用gap—PCR扩增方法检测10例骨关节炎病人和3例正常关节软骨中软骨细胞线粒体DNA的4977bp缺失突变。采用2轮PCR扩增,第1轮PCR反应以骨关节炎病人的关节软骨中软骨细胞线粒体DNA为模板;第2轮PCR扩增反应以第1轮PCR扩增反应的产物为模板,再次进行扩增。结果：第1轮PCR反应结果显示,mtDNA524bp扩增产物呈阴性,而533bp扩增产物均呈阳性;第2轮PCR扩增反应结果显示,10例骨关节炎病人病例标本中有2例出现524bp区带,而533bp扩增产物均呈阳性。两次扩增,正常关节软骨中软骨细胞和外周血对照524bp扩增产物全部为阴性。结论：骨关节炎病人关节软骨组织中软骨细胞线粒体DNA有8470～13447nt之间4977bp大片段缺失,提示骨关节炎的发病与关节软骨中软骨细胞线粒体DNA的突变关系密切。     

豫医无毛小鼠无毛基因部分内含子突变研究

目的 研究豫医无毛小鼠突变的分子机制。方法 对豫医无毛小鼠和昆明小鼠的基因组DNA进行PCR扩增,对二者扩增片段克隆后测序,对结果进行比较,以确定豫医无毛小鼠无毛基因的特异性程度。结果 本实验共测出豫医无毛小鼠DNA序列1746bp和昆明小鼠DNA序列1733bp,两者不同之处有32处,均位于内含子,突变形式包括插入、缺失和点突变。结论 无毛性状的产生可能与内含子中的插入、缺失和点突变有关。     

Influence of Strain Gradient on Fatigue Life of Carbon Steel for Pressure Vessels in Low-Cycle and High-Cycle Fatigue Regimes

This paper discusses how the strain gradient influences the fatigue life of carbon steel in the low-cycle and high-cycle fatigue regimes. To obtain fatigue data under different strain distributions, cyclic alternating bending tests using specimens with different thicknesses and cyclic tension–compression tests were conducted on carbon steel for pressure vessels (SPV235). The crack initiation life and total failure life were evaluated via the strain-based approach. The experimental results showed that the crack initiation life became short with decreasing strain gradient from 10² to 10⁶ cycles in fatigue life. On the other hand, the influence of the strain gradient on the total failure life was different from that on the crack initiation life: although the total failure life of the specimen subjected to cyclic tension–compression was also the shortest, the strain gradient did not affect the total failure life of the specimen subjected to cyclic bending from 10² to 10⁶ cycles in fatigue life. This was because the crack propagation life became longer in a thicker specimen. Hence, these experimental results implied that the fatigue crack initiation life could be characterized by not only strain but also the strain gradient in the low-cycle and high-cycle fatigue regimes.     

CYP17基因新的突变导致两姐妹17α羟化酶/17,20裂链酶联合缺乏

目的分析一家庭中患17α羟化酶／17,20裂链酶联合缺乏症的两姐妹及其父母的CYP17基因序列。方法外周血中提取基因组DNA。设计引物行PCR反应并对PCR产物进行序列测定。结果两姐妹均表现为典型的17α羟化酶／17,20裂链酶联合缺乏,其CYP17基因均为985缺失TAC插入AA的纯合子突变,而其父母是杂合子突变。结论985缺失TAC插入AA杂合子仅是一遗传标志,并不能引起疾病,但这种纯合子突变或在此基础上再发生另一突变可导致疾病的发生。     

p53 alterations in chemically induced hamster cheek-pouch lesions

To confirm that the hamster cheek-pouch carcinogenesis model reflects development of human squamous cell carcinoma (SCC), we determined if and when p53 mutations occur in the development of SCC in this model by using immunohistochemical staining and polymerase chain reaction (PCR)-single-strand conformation polymorphism (SSCP) analysis plus direct DNA sequencing. Twenty-four hamster cheek-pouches were treated with a solution of 0.5% 7,12-dimethylbenz[a]anthracene in mineral oil three times a week for 16 wk. The malignant endophytic and exophytic tumors induced with this protocol are preceded by a sequence of premalignant lesions such as hyperplasia with or without dysplasia and carcinoma in situ, similar to the development of this cancer in humans. For this study, p53 protein accumulation was evaluated by immunostaining of various hamster cheek-pouch exophytic and endophytic SCCs as well as flat dysplastic hyperplasia and carcinomas in situ. A moderate percentage (33.3%) of exophytic lesions and most endophytic carcinomas (90%) showed positive p53 staining. In addition we also found p53-positive staining in a number of preneoplastic lesions, including areas of focal hyperplasia, dysplastic hyperplasia, and carcinomas in situ. To determine whether the alterations in p53 staining were due to p53 gene mutation, we used PCR-SSCP analysis and direct sequencing. PCR products corresponding to exons 5a, 6, 7, and 8 from 40 tumors with the highest percentage of p53-stained cells were analyzed. We detected shifted bands in 17 lesions. Direct sequencing of eight selected shifted bands revealed four mutations, including two G→T transversions in codons 216 (tumor #1) and 252 (tumor #2) and one G→C transversion in codon 282 (tumor #3). Tumor #4 contained a frameshift mutation in codon 251. These mutations are consistent with those reported in many human cancers. Therefore, we concluded that in the hamster cheek-pouch model, p53 protein accumulation occurs frequently and early in carcinogenesis, as it does in human SCCs, and some of these p53 alterations are due to p53 gene mutations. These findings may help us better define the mechanisms of carcinogenesis in the hamster cheek-pouch model, and p53 alterations may be an early biomarker of progression for chemoprevention studies. © 1996 Wiley-Liss, Inc.