我国食管癌发病危险因素的Meta分析

目的：评价我国食管癌发病的危险因素。方法：通过Meta分析对国内13篇公开发表的有关食管癌发病危险因素的病例-对照研究进行定量综合分析，共对12个因素进行评价，计算每个因素的综合OR值．结果：共有9个因素有显意义，分别为：吸烟(ORs=1．69)、饮酒(ORs=1．81)、酸菜(0Rs=2．22)、烫食(ORs=2．41)、家族史(ORs=4．00)、精神因素(ORs=3．06)、干硬食物(ORs=2．07)、吃饭快(ORs=1．82)、水果(ORs=0．39)．结论：吸烟、饮酒、酸菜、烫食、家族史、精神因素、干硬食物及吃饭快为食管癌发病的危险因素，水果为保护因素，而蔬菜、饮茶以及肉类对食管癌发病的作用尚不能确定。     

羊膜建库及其临床应用研究

目的 :制备与保存羊膜 (Amnioticmembrane,AM ) ,为临床移植治疗眼表泪液 (Ocularsur face&Teardisease ,OSTD)提供新鲜羊膜 (Freshamnioticmembrane ,FSAM )、冻干羊膜 (Frozenam nioticmembrane ,FZAM )并观察其眼表重建的特点与临床疗效。方法 :采用目前国际公认的羊膜制备与保存方法 ,制备FSAM、FZAM并进行保存研究 ,经组织染色和电子显微镜检查 ,观察保存羊膜的形态及其活性 ;并将FSAM、FZAM应用于 12例OSTD患者 ,行患眼FSAM或FZAM移植术。通过术后印迹细胞学追踪观察移植后AM上皮细胞存活与移行、替代时间 ,评估AM移植重建眼表的临床疗效。结果 :FSAM、FZAM在光镜和电镜下均与正常球结膜组织结构相近 ,主要结构为胶原纤维和网状纤维。 12例OSTD患者行羊膜移植术 (Amnioticmembranetransplantation ,AMT)后均未见明显急性排斥反应 ,术后 1～ 2周可见少量新生血管长入植片 ,AMT后印迹细胞学追踪检查 ,术后 3个月为阴性 ,4个月出现阳性反应。所有患者术后随访 5～ 18个月 ,平均 11个月 ,AM在术后 4～ 9个月逐渐溶解、消失 ,移植区眼表的色泽与结构基本恢复正常。结论 :FSAM、FZAM是目前理想的结膜替代材料并可有效地用于重建角、结膜表面 ,减轻炎症反应 ,减少新生血管的生成 ,抑制纤维组织增生 ,防止     

巨噬细胞炎性蛋白4的突变和原核表达

目的 探索如何抑制嗜酸细胞的趋化作用，选择β-趋化因子巨噬细胞炎性蛋白4（MIP4）的突变性（Met-MIP4)作为趋化因子受体3的拮抗剂，将Met-MIP4基因在原核细胞中进行表达。方法 设计MIP4基因的PCR引物并进行氨基酸突变，将MIP4N末端的丙氨酸突变为蛋氨酸，以正常人肺酸突变，将MIP4N末端的丙氨酸突变为蛋氨酸。以正常人肺cDNA文库为模板，PCR方法获取Met-MIP4基因，克隆入载体pUC19，测序验证序列已得到突变，将正确的基因插入到GST融合表达载体pGEX-4T中，以IPTG诱导表达。结果 PCR产物为220bp左右的片段，连接入pUC19质粒后测序验证获得正确突变，构建的pGEX-4T融合表达载体在大肠杆菌中表达，经SDS-PAGE凝胶电泳显示有大小约34kU的新生融合蛋白表达。结论 成功突变并克隆了β-趋化因子MIP4基因，SDS-PAGE表明，与GST融合的Met-MIP4突变体已得到表达，为进一步研究其生物学活性奠定了基础。     

Proteolytic Processing Mechanisms in the Biosynthesis of Neuroendocrine Peptides: The Subtilisin-like Proprotein Convertases

The recent discovery of a novel family of precursor processing endoproteases has greatly accelerated progress in understanding the complex mechanisms underlying the maturation of prohormones, neuropeptides, and many other precursor-derived proteins. At least six members of this family have been found thus far in mammalian species, several having alternatively spliced isoforms, and related enzymes have been identified in many invertebrates, including molluscs, insects, nematodes, and coelenterates. The proprotein convertases are all dependent on calcium for activity and all possess highly conserved subtilisin-like domains with the characteristic catalytic triad of this serine protease (ordered Asp, His, and Ser along the polypeptide chain). Two members of this family, PC2(SPC2) and PC1/PC3(SPC3), appear to play a preeminent role in neuroendocrine precursor processing. Both convertases are expressed only in the brain and in the extended neuroendocrine system, while another important family member—furin/PACE (SPC1)—is expressed more ubiquitously, in almost all tissues, and at high levels in liver. SPC2 and SPC3 exhibit acidic pH optima and other properties which enhance their activity in the acidic, calcium-enriched environment of the dense-core secretory granules of the regulated pathway in neuroendocrine cells, while furin has a neutral pH optimum and is localized predominantly to the trans Golgi network where it is retained by a C-terminal transmembrane domain. Furin processes a wide variety of precursors in the constitutive pathway, such as those of growth factors, receptors, coagulation factors, and viral glycoproteins. Recent findings on the processing of proopiomelanocortin, proinsulin, proglucagon, and several other neuroendocrine precursors by SPC2 and SPC3 are discussed, along with information on the structure, properties, evolution, developmental expression, and regulation or the convertases. An inherited defect in the fat/fat mouse which affects the processing of proinsulin, and probably also many other prohormones, due to a point mutation in carboxypeptidase E has recently been identified and has begun to provide new insights into the functional integration of the individual processing steps.     

Changes in ultrastructure and Ca2+ distribution in the isolated working rabbit heart after ischemia. A time-related study.

Ultrastructural changes in cardiac muscle of isolated working rabbit hearts after various periods of ischemia are described and compared with distributional changes in calcium. The effects of reperfusion on these structural parameters were also investigated. The purposes of this study were to relate the role of calcium in the degeneration of cardiac muscle; to determine whether Ca2+ localizations could serve as additional criteria to determine more closely the point of no return; and to investigate the contributory role of reoxygenation to the development of myocardial damage. This study shows the existence of topographic differences in the tolerance to ischemia in the mid area, subendocardium, and subepicardium; that the sequestration of Ca2+ by mitochondria is an energy-requiring (active) process that occurs only during reperfusion; the loss of the sarcolemma's ability to bind Ca2+ during ischemia to coincide with increased Ca2+ entry during postischemic reperfusion (this Ca2+ is scavenged by mitochondria as long as sufficient energy remains available; these changes are interpreted as being at the edge of irreversibility); and the lack of additional damage and and lack of Ca2+ accumulation in mitochondria during reperfusion in cells that are damaged to such an extent that mitochondria possess flocculent densities already at the end of the ischemic insult.     

Somatic mitochondrial mutation in gastric cancer.

Likely hot spots for mutations are mitochondrial sequences as there is less repair and more damage by carcinogens compared with nuclear sequences. A somatic 50-bp mitochondrial D-loop deletion was detected in four gastric adenocarcinomas. The deletion included the CSB2 region and was flanked by 9-bp direct repeats. The deletion was more frequent in adenocarcinomas arising from the gastroesophageal junction (4/32, 12.5%) compared with more distal tumors (0/45). Topographical analysis revealed the absence of the deletion from normal tissues except in focal portions of smooth muscle in one case. In two cases, apparent mutant homoplasmy was present throughout two tumors, including their metastases. In the two other cases, the mutation was present in only minor focal portions ( < 5%) of their primary tumors. These findings document the presence of somatic mitochondrial alterations in gastric cancer, which may reflect the environmental and genetic influences operative during tumor progression.     

肝脏血管瘤的手术指征和手术方法选择（附46例报告）

目的 探讨肝脏血管瘤的手术指征和手术方法。方法 回顾性分析采用手术治疗46例肝脏血管瘤病人资料，判断其手术指征，评价不同手术方法的治疗效果厦其手术并发症发生情况。结果 46例病人中，19例采用肝叶或肝段切除术，17例出现并发症，以胸腔积液和膈下积液多见，采用血管瘤摘除术的27例病人无并发症。结论 对肝脏血管瘤直径大于5cm并有明显临床症状，或不能除外恶性肿瘤的病人可以采用手术治疗。血管瘤摘除术是安全有效、并发症少的手术方法。     

Impaired hepatocyte survival and liver regeneration in Atm-deficient mice

Atm is a stress-induced DNA damage checkpoint protein kinase with multiple roles in cell-cycle progression. Recent evidence indicates that Atm also plays a role in stem cell maintenance and self-renewal. It is not known whether Atm has a role during tissue regeneration. Using liver regeneration as a model system, we examined the role of Atm in this process. Here, we show that the expression levels of Atm protein were gradually increased during liver regeneration and this was correlated with the onset of DNA replication. The induction of Stat3 and JNK signaling, which are essential processes in normal regeneration response, was attenuated during the early phases of liver regeneration in Atm-deficient mice. P53 was transiently phosphorylated at serine 23 during liver regeneration in an Atm-dependent manner. In addition, we found that cyclin A induction was delayed and p21 was over-expressed, both of these processes were correlated with reduced and delayed DNA replication in Atm(-/-) mice during liver regeneration. Finally, we show that increased apoptosis was observed in Atm(-/-) mice in response to partial hepatectomy, indicating that Atm is required for the survival of hepatocytes. Collectively, these data indicate that liver regeneration is impaired in Atm-deficient mice. Given that liver is the first line of defense against environmental toxins, the elucidation of the function of Atm and Atm-mediated signaling pathways in liver metabolism and in response to environmental toxins is of fundamental interest.