绵羊二尖瓣置换动物模型的制作

目的:探索人工二尖瓣置换绵羊动物模型制作的外科技术。方法:实验于2006-01/04在南方医科大学动物实验中心完成。①选用健康雄性绵羊6只,制作人工机械心脏瓣膜置换动物模型;另外取6只羊每只采血1500mL后处死。②人工机械心脏瓣膜由兰州飞控医疗仪器厂生产,为C-LⅠ型短柱人工机械心脏瓣膜,瓣架为高强度耐酸铬镍合金,瓣片的内部为石墨基体,表面为沉积热解碳,瓣环为涤纶长丝织物。③二尖瓣置换模型制备:术中右颈静脉建立通路用于测静脉压、输液等;右股动脉置管连续监测动脉压;连续监测心电图、血氧饱和度;检测血气分析、血钾和全血激活凝血时间;监测鼻咽及肛温,计尿量。麻醉后气管内插管接麻醉机。降主动脉插供血管,右心耳或者上、下腔静脉插引流管,升主动脉根部插灌注管和左肺静脉插左心引流管,建立体外循环。主动脉阻断,灌注心肌保护液;阻断上下腔静脉。体外循环为新鲜羊血预充,转流降温至鼻咽温度27～30℃。经左心耳切口显露二尖瓣,切除瓣叶、腱索及部分乳头肌。放置人工瓣膜,连续缝合二尖瓣环。开放循环,心脏自动复跳,循环稳定后脱离体外循环并拔管,放置左胸引流后常规关胸。术后常规使用血管活性药,麻醉清醒后拔除气管插管,青霉素预防感染,华法令口服抗凝治疗。结果:6只羊手术过程均顺利,心脏全部自动复跳,术后全部存活且超过1个月。术中体外循环过程平稳,监测血气分析无大的波动;平均手术时间为(129±11)min,平均转流时间为(61±7)min,平均主动脉阻断时间为(30±6)min,预充血量为(700±89)mL,转流中鼻咽温为(28.7±1.3)℃。术后呼吸机辅助时间12～30h,术后血管活性药使用时间6～37h,均在24h内拔除胸腔引流管。3只羊并发肺部感染经抗炎治疗后治愈。术后口服华法令抗凝治疗,剂量6.0～12mg,国际标准化比值控制在2.1～3.2之间。结论:经左心耳入路行二尖瓣置换制作绵羊动物模型是可行的。采用同种新鲜羊血预充、术中保持良好的引流和组织灌注、术后加强呼吸道管理以及抗凝治疗是提高手术成功率的重要保证。     

体外培养新生大鼠心肌细胞的形态及其增殖能力

目的:心脏组织中心肌细胞增殖分化转变发生于出生后3～4d,有细胞周期调控机制的参与。观察新生大鼠心室肌细胞培养过程中细胞形态学和细胞周期素E表达的变化规律。方法:实验于2005-01/2006-03在新乡医学院解剖学与组织胚胎学重点学科实验室完成。①实验材料:1日龄Wistar大鼠20只,体质量7～10g。②实验方法及评估:心肌细胞分离、纯化及培养后用倒置显微镜观察其形态变化,免疫细胞化学染色及图像分析方法检测培养第1～53天新生大鼠心室肌细胞周期素E的表达。结果:纳入大鼠20只,均进入结果分析。①培养心肌细胞4h后贴壁,偶见单个细胞开始自发性搏动,部分细胞为梭形;以后细胞变为双核细胞,三角形或柱形细胞。第3天细胞聚集成片并同步搏动,第10天搏动频率最快,之后搏动频率逐渐减慢。②心肌细胞周期素E位于细胞核和核周的胞浆中。培养1～3d染色较深,以后逐渐变浅。③心肌细胞核内细胞周期素E表达量逐渐下降,第2天与第1天比较,差异无显著性(P>0.05)。从第3天开始差异有显著性(P<0.05,P<0.01)。结论:新生大鼠心肌细胞出生后早期体外培养的前3天有一定增殖能力,但以后呈下降趋势。细胞周期素E表达下调与心肌细胞增殖能力降低呈正相关。     

肠易激综合征重叠功能性消化不良患者的临床症状、生存质量及精神心理状态分析

目的 研究肠易激综合征（IBS）重叠功能性消化不良（FD）患者的临床症状、生存质量、焦虑抑郁状态及就医情况,为临床诊治提供依据。 方法 选取2012年9月至2013年5月就诊于四川大学华西医院消化门诊的IBS患者,根据是否重叠FD症状分为2组,选10名健康志愿者作为正常对照组。通过发放胃肠道症状评估量表（GSRS）、汉化版IBS-生存质量量表（ChIBS-QOL）以及汉密尔顿焦虑量表（HAMA）14项及汉密尔顿抑郁量表（HAMD）17项版本,比较所有受试者的临床症状、生存质量、焦虑抑郁状态及就医情况。 结果 60例IBS患者中25例（41.7%）重叠FD症状（IBS-FD）。IBS-FD患者的GSRS评分高于单纯IBS患者及健康志愿者,差异有统计学意义（P<0.05）;IBS-FD患者就医次数多于单纯IBS患者,差异有统计学意义（P<0.05）。健康志愿者无焦虑及抑郁发生,单纯IBS患者多见轻度焦虑及抑郁,IBS-FD患者多见中-重度焦虑及抑郁;IBS-FD患者焦虑及抑郁发病率高于单纯IBS患者（分别为80.0%比51.4%,76.0%比48.6%）,差异有统计学意义（P<0.05）。进一步分型提示重叠FD症状的便秘型IBS（IBS-C-FD）患者的GSRS评分最高、焦虑发病率最高及ChIBS-QOL评分最高。 结论 IBS-FD患者尤其IBS-C-FD患者较单纯IBS患者的胃肠道症状更严重、焦虑抑郁程度更重,生存质量更差。     

Localization of the gene for rapidly progressive autosomal dominant parkinsonism and dementia with pallido-ponto-nigral degeneration to chromosome 17q21

Rapidly progressive autosomal dominant parkinsonism and dementia with pallido-ponto-nigral degeneration (PPND) is a neurodegenerative disorder which begins later in life (> 30 years of age) and is characterized by rapidly progressive parkinsonism, dystonia, dementia, perservative vocalizations and pyramidal tract dysfunction. The disease is observed in a large American family that includes almost 300 members in nine generations with 34 affected individuals. In this kindred evidence for linkage to chromosome 17q21 was obtained with a maximum lod score of 9.08 for the D17S958 locus. Multilocus analysis positions the disease gene in an approximately 10 cM region between D17S250 and D17S943. Notably, the disease locus for a clinically distinct familial neurodegenerative disease named 'disinhibition-dementia-parkinsonism- amyotrophy complex' (DDPAC) was recently mapped to the same region of chromosome 17, suggesting that PPND and DDPAC may possibly originate from mutations in the same gene.      

Sarcomatous transformation in diaphyseal aclasis

Multiple hereditary exostosis (or diaphyseal aclasis) is a condition characterized by the development of multiple osteochondromas. The tendency for malignant transformation into chondrosarcoma is well known. Malignancy typically arises from the cartilaginous cap of the osteochondroma. Radiographs supplemented by computed tomography have an important role in the diagnosis of this condition. Magnetic resonance imaging shows the features of sarcomatous change and aids in differentiating malignancy from pseudotumours.     

年龄及人参皂甙 Rg1 对大鼠大脑皮层 NO 释放的影响

探讨了NO与衰老的关系及与Rg1抗衰老机制的关系。用Griess法,³H-L-精氨酸转化法分别研究大鼠大脑皮层细胞NO含量及NOS活性,观察其随龄变化及人参皂甙Rg1(Rg1)对老年鼠NO及NOS的影响。实验表明,成年鼠(9月龄)与青年鼠(3月龄)NO含量及NOS活性无显著性差异。老年鼠(27月龄)脑皮层NO含量明显高于青年鼠和成年鼠,NOS活性也明显增高。老年鼠给予Rg1后可显著减少大脑皮层NO含量和降低NOS活性。结果提示,NO与衰老关系密切,Rg1的抗衰老作用与其对NOS活性的抑制有关。     

芳香酶抑制剂依西美坦(Exemestane)的合成

目的：合成依西美坦并改进合成工艺。方法：以雄甾烯一酮为原料，经Mannich反应、溴化、脱溴等数步反应制得依西美坦。结果：所得产物经元素分析。柴外光谱，红外光谱，核磁共振谱及质谱等确证了结构。结论：此路线是可行的。     

抗有机磷酸酯药物的合成及其构效关系的研究

本文报道一类双吡啶季铵盐化合物,对抗小鼠有机磷酸酯化合物中毒有效,其中一些化合物的抗毒效价超过了文献报道的HI-6,HGG-42的水平。为探讨其构效关系,用EHMO方法计算了23个化合物的分子轨道指数,从中发现吡啶环Ⅱ和羰基可能是化合物的活性部位,影响抗毒作用的因素有二个,并再次设计合成了二个新化合物,量化计算预测的抗毒效价与药理结果一致。化合物与胆碱N受体结合有较强的选择性,根据计算,提出了其可能的作用模式,推测N受体活性部位除有文献报道的阴离子部位、亲酯中心、疏水区域外,还可能有轨道作用部位。     

Deficiency in BRCA2 leads to increase in non-conservative homologous recombination

The BRCA2 tumor suppressor has been implicated in the maintenance of genomic integrity through a function in cellular responses to DNA damage. The BRCA2 protein directly associates with Rad51, that is essential for repair of double-strand breaks (DSBs) by homologous recombination (HR). In this report, we study the BRCA2-defective Chinese hamster cell mutant V-C8 for its ability to perform homology-directed repair (HDR) between repeated sequences. V-C8 cells were recently shown to be defective in Rad51 foci formation in response to DNA damage. Strikingly, we find that these BRCA2 mutant cells exhibit a strong stimulation of HDR activity compared to the V79 parental cells, which harbor a wild-type BRCA2. Furthermore, molecular characterization of the HDR products shows that loss of BRCA2 in V-C8 cells leads to significant reduction in Rad51-dependent gene conversion but strong enhancement of Rad51-independent single-strand annealing (SSA) events frequency. These data imply that, when HDR by conservative gene conversion is impaired, DSBs usually repaired by this pathway are instead resolved by other non-conservative HDR subpathways. Therefore, high chromosomal instability in BRCA2-deficient cells presumably results from enhancement of error-prone repair mechanisms, such as SSA.