大黄素-8-O-β-D-葡萄糖苷的体内外遗传毒性评价

目的:评价大黄素-8-O-β-D-葡萄糖苷(EG)的体内外遗传毒性,并比较体外细胞试验及大鼠体内实验评价结果的差异。方法:采用体外二维(2D)、三维(3D)细胞培养法分别构建2D、3D HepaRG细胞模型,造模成功后,分别将2D、3D HepaRG细胞分为空白对照组[0.5%二甲基亚砜(DMSO)]、丝裂霉素C组(阳性对照,0.1μg/mL)和EG低、中、高剂量组(10、50、200μg/mL),然后检测各组HepaRG细胞的微核形成率和尾DNA百分含量。将SD大鼠分为空白对照组(0.5%羧甲基纤维素钠)、甲磺酸乙酯组(阳性对照,200 mg/kg)和EG低、中、高剂量组(100、300、1 000 mg/kg),每组6只,连续灌胃给药15 d,每天1次;15 d后检测各组大鼠骨髓嗜多染红细胞、肝细胞的微核形成率及外周血淋巴细胞、肝细胞的尾DNA百分含量、尾距。结果:在体外2D HepaRG细胞模型中,与空白对照组比较,丝裂霉素C组HepaRG细胞的微核形成率和尾DNA百分含量均显著升高(P<0.01),EG各剂量组HepaRG细胞的微核形成率和尾DNA百分含量差异无统计学意义(P>0.05);在3D HepaRG细胞模型中,与空白对照组比较,丝裂霉素C组HepaRG细胞的微核形成率和尾DNA百分含量均显著升高(P<0.01或P<0.001),EG高剂量组HepaRG细胞的尾DNA百分含量显著升高(P<0.01)。在大鼠体内实验中,与空白对照组比较,甲磺酸乙酯组大鼠骨髓嗜多染红细胞、肝细胞的微核形成率和外周血淋巴细胞、肝细胞的尾DNA百分含量、尾距均显著升高(P<0.01),EG高剂量组大鼠外周血淋巴细胞尾DNA百分含量显著升高(P<0.01),EG各剂量组大鼠骨髓嗜多染红细胞、肝细胞的微核形成率和肝细胞尾DNA百分含量、尾距差异无统计学意义(P>0.05),但随剂量增加有升高趋势。结论:本研究结果提示在2D细胞模型中,EG未导致染色体断裂及DNA损伤,但3D细胞模型长期给药和体内重复给药结果均显示EG存在一定DNA损伤风险,故3D HepaRG细胞模型的评价结果更接近大鼠体内实验结果。     

植入式心律转复除颤器手术前后患者确定感、焦虑与性格乐观状态的研究

目的研究比较植入式心律转复除颤器(ICD)作为心源性猝死的一级预防(primary prevention,PP)和二级预防(secondary prevention,SP),在植入前、植入后1周以及植入后1个月对患者情绪的不同影响。方法选择15例患者应用植入式心律转复除颤器作为心源性猝死的PP,15例患者应用植入式心律转复除颤器作为心源性猝死的SP,应用描述性横断面调查法,利用Mishel-疾病不确定感量表(Mishel’s Uncertainty in Illness Scale,MUIS-C),特质状态焦虑量表(State-Trait Anxiety Inventory,STAI)和生活目标量表(the Life Orientation Test,LOT-R),通过晤谈行半结构访问。结果在植入式心律转复除颤器植入前,两组患者的MUIS-C分值都较高(PP=67.67±13.36;SP=70.27±6.80,P=0.507);LOT-R分值为PP=15.67±3.8,SP=16.47±3.6,P=0.557;STAI分值为PP=37.40±10.0,SP=37.73±13.6,P=0.940。在植入式心律转复除颤器植入后1个月,PP患者的MUIS-C分值明显低于SP患者(PP=62.33±4.17,SP=67.87±4.61,P=0.002)。结论利用植入式心律转复除颤器作为SP的患者护理时更应该引起护士的重视。     

维生素E微胶囊的制备工艺研究

目的:通过正交实验优化包合工艺参数,研究超声法制备维生素E油β-环糊精包合物的最佳工艺条件。方法:采用β-环糊精为壁材,运用包结络合法对维生素E进行微胶囊化。结果:得到超声法制备最佳工艺条件为:包合时间20 min、包合温度30℃、超声功率150 W、m(VE)∶m(β-CD)=1∶9。在优选的条件下包合得包合率为83.5%,产物收率达到71.3%。结论:在此条件下维生素E油β-环糊精包合物成功解决了维生素E易氧化、遇光和热不稳定的难题,提高了其稳定性。     

A catalogue of genes in the cardiovascular system as identified by expressed sequence tags.

The heart, which is composed of all the cellular components of the circulatory system, is a representative organ for obtaining genes expressed in the cardiovascular system in normal and disease states. We used partial sequences of cDNA clones, or expressed sequence tags, to identify and tag genes expressed in this organ. More than 3500 partial sequences representing > 3000 cDNA clones have been obtained from either the 5' or 3' end of inserts derived from human heart cDNA libraries. Of 3132 cDNA clones analyzed by sequence similarity searching against the GenBank/EMBL data bases, 1485 (47.4%) were found to represent additional, previously undiscovered genes, whereas 267 clones were matched to human brain expressed sequence tags. Clones matching to known genes were catalogued according to their putative structural and cellular functions. cDNA probes from reverse-transcribed mRNAs of fetal and adult hearts were used to study differential expression of selected clones in cardiac development. Cataloguing genes expressed in the heart may provide insight into the genes involved in health and cardiovascular disease.     

结核性胸膜炎内科胸腔镜下表型及其诊断价值

目的观察结核性胸膜炎患者胸腔镜下表现特征,探讨结核性胸膜炎镜下不同表型对诊断的价值。方法回顾分析2011年4月-2013年7月60例确诊结核性胸膜炎患者内科胸腔镜下表现特征。结果 60例结核性胸膜炎患者胸腔镜下主要表现为4种类型:胸膜弥漫性充血水肿、糜烂;粟粒性结节型(多发或散在的小结节型,个别融合成大结节,直径1~2 cm);胸膜肥厚、胸膜腔呈多房改变;纤维苔素沉积及粘连。结论结核性胸膜炎患者内科胸腔镜下表现形态多样,以结节、弥漫性充血水肿为主,内科胸腔镜检查安全,创伤小,诊断率高,对结核性胸腔积液具有重要应用价值。     

Profiling of β-Lactam Selectivity for Penicillin-Binding Proteins in Streptococcus pneumoniae D39

Selective fluorescent β-lactam chemical probes enable the visualization of the transpeptidase activity of penicillin-binding proteins (PBPs) at different stages of bacterial cell division. To facilitate the development of new fluorescent probes for PBP imaging, we evaluated 20 commercially available β-lactams for selective PBP inhibition in an unencapsulated derivative of the D39 strain of Streptococcus pneumoniae. Live cells were treated with β-lactam antibiotics at different concentrations and subsequently incubated with Bocillin FL (Boc-FL; fluorescent penicillin) to saturate uninhibited PBPs. Fluorophore-labeled PBPs were visualized by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and fluorescence scanning. Among 20 compounds tested, carbapenems (doripenem and meropenem) were coselective for PBP1a, PBP2x, and PBP3, while six of the nine penicillin compounds were coselective for PBP2x and PBP3. In contrast, the seven cephalosporin compounds tested display variability in their PBP-binding profiles. Three cephalosporin compounds (cefoxitin, cephalexin, and cefsulodin) and the monobactam aztreonam exhibited selectivity for PBP3, while only cefuroxime (a cephalosporin) was selective for PBP2x. Treatment of S. pneumoniae cultures with a sublethal concentration of cefuroxime that inhibited 60% of PBP2x activity and less than 20% of the activity of other PBPs resulted in formation of elongated cells. In contrast, treatment of S. pneumoniae cultures with concentrations of aztreonam and cefoxitin that inhibited up to 70% of PBP3 activity and less than 30% of other PBPs resulted in no discernible morphological changes. Additionally, correlation of the MIC and IC₅₀s for each PBP, with the exception of faropenem, amdinocillin (mecillinam), and 6-APA, suggests that pneumococcal growth inhibition is primarily due to the inhibition of PBP2x.     

监测中心动脉压对预防颈动脉斑块形成的研究进展

颈动脉斑块能够有效预测心脑血管疾病的发生,故寻找其相关危险因素、防止斑块形成对心脑血管疾病的预防有非同寻常的作用。本文将详细说明颈动脉斑块形成发展过程中各种影响因素及中心动脉压的病理生理特点,两者之间的联系及监测中心动脉压对预防劲动脉斑块形成的意义。     

健康老年人群血浆可溶性血栓调节蛋白和肾小球滤过率的关系

目的：探讨老年人群血浆可溶性血栓调节蛋白（sTM）与估算的肾小球滤过率（eGFR）的相关性。方法采用整群随机抽样的方法对北京市9个社区283名≥65岁健康老年人进行研究,酶联免疫吸附法测定血浆可溶性血栓调节蛋白水平,应用CKD-EPI公式评估eGFR,同时行人体学测量及血清生化指标测定,并做相关和回归分析。结果北京社区健康老年人群eGFR水平与sTM、年龄、尿素氮、肌酐、C反应蛋白（CRP）及收缩压呈负相关,与白蛋白、高密度脂蛋白胆固醇（HDL-C）、低密度脂蛋白胆固醇（LDL-C）水平呈正相关;在校正了年龄、血压、血糖（GLU）、CRP、血脂、尿酸（UA）等指标后,健康老年人血浆sTM仍然和eGFR呈负相关（B＝-3.340,P＝0.000）。在进一步的研究中,将入组的北京社区健康老年人分为老年（65～80岁）和高龄老年（＞80岁）两组;两组之间eGFR和sTM水平差异均无统计学意义（P＞0.05）,老年组和高龄老年组eGFR均与sTM水平呈负相关（r＝-0.229,P＝0.000;r＝-0.3613,P＝0.02）,校正了年龄、血压、GLU、CRP、血脂、UA等指标后差异仍有统计学意义（B＝-3.26,P＝0.000;B＝-4.45,P＝0.013）。结论 sTM可作为判断老年人群肾功能下降的指标。     

经皮颈内静脉长期导管在老年维持性血液透析患者中的临床应用

目的：探讨经皮颈内静脉长期导管在老年维持性血液透析患者中的应用及其常见并发症的防治。方法对2009年12月至2012年12月在中南大学湘雅医院行经皮颈内静脉长期置管的15例维持性血液透析老年患者的临床资料进行回顾性分析,观察置管术后情况、导管的使用情况、常见并发症的防治、透析充分性评价等。结果（1）实施颈内静脉长期置管18例次,其中3例为重新置管,置管成功率100%。（2）导管相关并发症：2例患者术后1周内出现置管处局部渗血;1例出现导管出口感染,2例发生导管相关性血流感染;3例患者出现导管血栓形成;2例诊断导管纤维鞘形成;1例因人为损坏出现导管破裂。经过相应处理后均使问题得到解决。（3）导管使用期限：本组患者长期导管使用时间为4～41个月,除1例死亡（原因为脑出血）,3例为重新置管,余患者仍继续使用。（4）透析充分性评价：15例患者平均尿素下降率为72%,平均尿素清除指数达1.54。结论对于血管条件差无法建立动静脉内瘘的老年血透患者,使用颈内静脉长期导管行血液透析可以达到充分透析;提高置管及导管护理技术、加强健康宣教,能延长导管使用年限,减少导管并发症。