BRCA1在胃癌中的研究进展

化疗在胃癌的治疗中占有重要地位,铂类药物是常用的胃癌化疗药物之一,不同个体对铂类药物的敏感性差异很大.乳腺癌易感基因1(breast cancer susceptibility gene1,BRCA1)是一种抑癌基因,与铂类药物的敏感性有关.目前针对BRCA1的研究多集于乳腺癌方面,而在胃癌中的研究很少.本文就BRCA1的结构与功能,BRCA1与胃癌关系的相关研究进展进行综述.     

烧伤小鼠肝组织糖皮质激素受体的变化

目的 观察烧伤小鼠24h内肝糖皮质激素受体在蛋白及mRNA水平的时相变化特点。方法 将60只BALB／C小鼠随机分为正常对照组和实验组，实验组给予背部Ⅲ度15％－20％烧伤。分别于伤后2、4、6、12、24h测定血清皮质酮浓度，用Westernblotting、RF－PCR蛋白质和mRNA水平测定肝组织糖皮质激素受体。结果 烧伤小鼠血清皮质酮浓度2－4h达到高峰，24h仍未恢复正常；肝组织糖皮质激素受体在蛋白质水平4－6h降至最低；而mRNA水平仅仅在伤后2h有短暂降低。结论 烧伤应激引起小鼠血清皮质酮水平明显升高，其受体在蛋白质及mRNA水平均可降低，但蛋白的降低不仅仅发生在mRNA水平。     

转染外源性FasL的CD34+细胞诱导同种抗原特异性T细胞凋亡的实验研究

为探讨通过Fas/FasL途径选择性去除移植物中成熟T细胞的可能性 ,本研究借助反转录病毒途径 ,以FasL基因转染骨髓CD34+ 细胞 ,与经过富集的T细胞进行单向混合培养 (刺激细胞 /效应细胞比例为 5∶1) ,加入或不加入IFN γ ,IL 2 ,应用原位末端标记法 (TUNEL)和流式细胞术 (FCM)检测培养 5天后的细胞凋亡率 ,并比较两种细胞因子对移植物中CD34+ 细胞的影响。以转染外源FasL的CD34+ 细胞为刺激细胞 ,T细胞凋亡率为 (12 .1±1.5 ) %〔对照组为 (3.2± 1.1) % ,P <0 .0 1〕 ;经IFN γ或IL 2作用后 ,转染细胞诱导T细胞的凋亡率分别上升至(2 0 .1± 2 .3) % ,(17.6± 1.3) % (P <0 .0 1) ;且IL 2对CD34+ 细胞Fas抗原的表达无明显影响。上述结果表明 ,转染外源FasL的骨髓CD34+ 细胞可诱导同种抗原特异性T细胞凋亡 ,IFN γ和IL 2增强上述致细胞凋亡作用 ,且IL 2更有利于临床应用 ;提示该方案可选择性清除移植物中同种抗原特异性T细胞 ,可望为临床上防治移植物抗宿主病 (GVHD)提供新的途径     

脊髓型颈椎病髓内MRI对称性T2延长病变的研究

目的　探讨脊髓型颈椎病 MRI颈髓内 2个对称性 T2 高信号影像特点。方法　临床明确诊断为脊髓型颈椎病者 17例 ,对其颈髓内两个眼样 T2 高信号 snake eye sign MRI表现进行回顾性分析。结果　位置以椎体 4 /5、5 /6各5例为最多 ,颈髓腹侧者 6例中 4例有肌力下降 ,无法判定者 5例 ,腹背均涉及者 4例。发病 6个月以内 5例。 13例以上肢症状为主诉 ,snake eye sign位置与临床神经病理检查反映的病变节段一致。结论　MRI对显示脊髓型颈椎病髓内snake eye sign有价值。     

宫颈癌血管生成与癌细胞增殖及浸润转移的关系

目的　探讨早期宫颈癌血管生成与癌细胞增殖及浸润转移的关系。方法　采用免疫组织化学 SP法检测75例早期宫颈癌、18例宫颈上皮内瘤样病变 (CIN)和 15例癌旁正常宫颈上皮中微血管密度 (MVD,CD34 标记 )及 Ki- 6 7抗原的表达情况 ,探讨宫颈癌血管生成与癌细胞增殖及浸润转移的关系。结果　 CD34 主要表达于宫颈癌巢间质血管内皮细胞 ,而 Ki- 6 7主要表达于宫颈癌细胞核。从正常宫颈上皮→ CIN→宫颈浸润癌 ,MVD和 Ki- 6 7表达均显著升高 (P<0 .0 5 )。宫颈癌 MVD与盆腔淋巴结转移、脉管浸润、间质浸润和 Ki- 6 7表达有关 (P<0 .0 5 ) ;而与年龄、FIGO分期、组织学分级和组织学类型无关 (P>0 .0 5 )。有盆腔淋巴结转移、脉管浸润、≥深层间质浸润及 Ki- 6 7呈高度表达者 ,其 MVD分别显著高于无盆腔淋巴结转移、无脉管浸润、<深层间质浸润及 Ki- 6 7<高度表达者 (P<0 .0 5 )。结论　肿瘤血管生成可能在宫颈癌发生发展、癌细胞增殖和浸润转移中起重要作用。宫颈癌伴 MVD显著升高者 ,其癌细胞增殖活跃 ,易发生浸润转移 ,但并非唯一决定因素。检测宫颈癌 MVD对进一步了解宫颈癌生物学行为具有一定的临床应用价值。     

^99mTc-hIgG在炎症性肠病诊断与随访中的临床应用

评价^99mTc-hIgG象法在炎症性肠病定位、疗效随访和预测复发中的临床价值。方法：对54例临床确诊的炎症性肠病病人在正规治疗前、41例经治疗症状得“控制和16例随访过程中症状复发者分别作^99mTc-hIgG核素显象检查。结果：①54例炎症性肠病病人中,50例出现阳性改变,其中2例假阳性,2例因发现新的放射性异常浓集修正丁诊断,4例假阴性,总灵敏度925％,特异性902％,准确率为88.9％;②41例临床缓解病人中,同位素显象出现相应减轻者38例,总符合率92．6％：④16例症状复发者中核素有异常浓集者15例,与临床的符台率为91．6％。结论：在炎症性肠病的诊断方法中,^99mTc-hIgG是一种非创伤性的辅助性方法,具灵敏度高、特异性好的优点,在疗效随访和预测复发方面有良好的实用价值。     

高原老年人QT离散度正常参考值的探讨

目的探讨高原老年人ＱＴ间期离散度（ＱＴｄ）正常参考值。方法选择海拔３０００～３３００ｍ高原居住的老年人１２０例,常规记录３导同步１２导联心电图,测定ＱＴ离散度（ＱＴｄ）、校正的ＱＴ离散度（ＱＴｃｄ）、ＪＴ离散度（ＪＴｄ）、校正的ＪＴ离散度（ＪＴｃｄ）４项参数,对不同年龄组、不同性别组与同海拔非老年组进行比较,判定其统计学意义。结果（１）高原老年人ＱＴｄ、ＪＴｄ均值分别为（４９±９）及（５１±１０）ｍｓ;（２）高原人进入老年阶段后ＱＴｄ各参数随增龄呈递增趋势,然其进程相对缓慢,仅６０～６４与８０～８４岁组间差异有极显著性（Ｐ＜０．０１）;（３）不同性别间差异无显著性。结论高原老年人ＱＴｄ、ＱＴｃｄ、ＪＴｄ、ＪＴｃｄ上限值分别为６４、６７、７０、７２ｍｓ,较同海拔非老年人显著延长。建议以≤上述各值作为高原老年人的正常参考值。     

Sodium thiosulfate protects human aortic smooth muscle cells from osteoblastic transdifferentiation via high-level phosphate

Vascular calcification is recognized as a common complication in some patients, such as chronic renal failure. The purpose of this study was to investigate the role of sodium thiosulfate (STS) for the transdifferentiation of human aortic vascular smooth muscle cells into osteoblast-like cells induced by high-level phosphate. All human aortic vascular smooth muscle cells were divided into STS group 1 (treatment with STS) and STS group 2 (culture in a medium containing a high level of phosphate). STS group 1 included a normal group, a high-level phosphate group, and other subgroups based on treatment with different concentrations of STS. Cells of STS group 2 were cultured in a medium containing a high level of phosphate for 72 hours, and then divided into a high-phosphate control group and other subgroups based on treatment with different concentrations of STS. The mRNA and protein expressions of bone morphogenetic protein-2 (BMP-2), core binding factor α-1 (Cbfα-1), and matrix Gla protein (MGP) were detected. Meanwhile, calcium concentration and alkaline phosphatase (ALP) activation were measured. In STS group 1, the mRNA levels of BMP-2 and Cbfα-1 were elevated significantly in the high-level phosphate group compared with the normal group (p < 0.05). However, both gene expressions were attenuated in the STS-treated groups (vs. normal group, p < 0.05). MGP mRNA levels were reduced in the high-level phosphate group (vs. normal group, p < 0.05). In the STS-treated groups, mRNA expression of MGP was elevated compared to the high-level phosphate group (p < 0.05). In STS group 2, expression of MGP was enhanced significantly (vs. high-phosphate control group, p < 0.05) with both BMP-2 and Cbfα-1 reducing in the STS-treated groups (vs. high-phosphate-control group, p < 0.05). STS attenuates calcium concentration and ALP activation. It can reverse osteoblast differentiation of vascular smooth muscle cells and modulate the expressions of calcification-related factors.     

Association of the six transmembrane protein of prostate 2 gene polymorphisms with metabolic syndrome in Han Chinese population

AimThe six-transmembrane protein of prostate 2 (STAMP2) has been demonstrated to play a potential role in the pathogenesis of metabolic syndrome (MetS). The present study was designed to investigate the association of STAMP2 gene polymorphisms with MetS in Han Chinese population.MethodsA case-control study enrolled 350 Han Chinese subjects in two groups: 182 MetS patients and 168 control subjects. The clinical and biochemical characteristics were determined. Three single nucleotide polymorphisms (SNPs), rs1981529, rs12386756 and rs10263111 in STAMP2 gene were genotyped. The association of STAMP2 gene polymorphisms with MetS was analyzed.ResultsSNPs rs1981529 and rs10263111 were found to be significantly associated with MetS phenotype in male population (P = 0.014 and 0.025). Moreover, SNP rs1981529 was found to be associated with high density lipoprotein-cholesterol in male cases and with body mass index in female cases (P = 0.014 and 0.049). SNP rs10263111 was found to be associated with both waist circumference and diastolic blood pressure in total cases (P = 0.044 and 0.033). Haplotype analysis yielded significant association of STAMP2 gene with MetS in total (global P = 0.0109) and male population (global P = 0.0004).ConclusionOur findings revealed that STAMP2 gene polymorphisms are likely to significantly contribute to the risk of MetS in male Han Chinese population.     

Systematic profiling of Caenorhabditis elegans locomotive behaviors reveals additional components in G-protein Gαq signaling

Genetic screens have been widely applied to uncover genetic mechanisms of movement disorders. However, most screens rely on human observations of qualitative differences. Here we demonstrate the application of an automatic imaging system to conduct a quantitative screen for genes regulating the locomotive behavior in Caenorhabditis elegans. Two hundred twenty-seven neuronal signaling genes with viable homozygous mutants were selected for this study. We tracked and recorded each animal for 4 min and analyzed over 4,400 animals of 239 genotypes to obtain a quantitative, 10-parameter behavioral profile for each genotype. We discovered 87 genes whose inactivation causes movement defects, including 50 genes that had never been associated with locomotive defects. Computational analysis of the high-content behavioral profiles predicted 370 genetic interactions among these genes. Network partition revealed several functional modules regulating locomotive behaviors, including sensory genes that detect environmental conditions, genes that function in multiple types of excitable cells, and genes in the signaling pathway of the G protein Gαq, a protein that is essential for animal life and behavior. We developed quantitative epistasis analysis methods to analyze the locomotive profiles and validated the prediction of the γ isoform of phospholipase C as a component in the Gαq pathway. These results provided a system-level understanding of how neuronal signaling genes coordinate locomotive behaviors. This study also demonstrated the power of quantitative approaches in genetic studies.