凝血酶引起人支气管上皮细胞内活性氧及血小板源生长因子-AB分泌的改变

目的 探讨凝血酶对永生化人支气管上皮细胞(BEP2D细胞)内活性氧产生及血小板源生长因子-AB(PDGF-AB)分泌的影响.方法 不同浓度凝血酶刺激指数生长期的BEP2D细胞,通过检测氧化型氢化乙啶及二氯荧光素荧光强度测定活性氧簇含量变化.采用双抗体夹心ELISA法检测BEP2D细胞分泌PDGF-AB的变化.结果 随着凝血酶浓度增加,反应体系中活性氧明显升高,且有明显的剂量反应关系.凝血酶处理组BEP2D细胞上清液中PDGF-AB含量较对照组上清液显著升高[(770.33+24.29)ng/L vs(117.42±10.85)ng/L,P＜0.01].凝血酶在一定范围内有剂量反应关系.10 U/ml凝血酶刺激48 h后BEP2D细胞分泌PDGF-AB量最大[(817.63+22.53)ng/L].结论 凝血酶既可以引起细胞内氧化应激导致基因毒性,又可以通过刺激BEP2D细胞分泌PDGF-AB发挥自分泌及旁分泌作用.

Abstract：

Objective To investigate the effects of thrombin on reactive oxygen species and plateletderived growth factor-AB (PDGF-AB) in immortalized human bronchial epithelial cells (BEP2D cells).Methods BEP2D cells at exponential growth phase were stimulated by different concentrations of thrombin. The content of active oxygen species was determined by detecting the fluorescence intensity of hydroxyethidium and dichlorofluorescein. The changes of PDGF-AB were measured by double antibody sandwich ELISA assay. Results With the increase of the thrombin concentration, reactive oxygen species significantly increased, and there was a dose-response relationship. The concentration of PDGF-AB in culture supematants in thrombin-treated group was higher than that in control group [(770. 33 +24. 29 )ng/L vs (117. 42+ 10.85) ng/L, P ＜ 0. 01], and there was a dose-response relationship. The concentration of PDGF-AB was maximal [(817.63 +22.53) ng/L] when BEP2D cells were stimulated with 10 U/ml thrombin for 48 hours. Conclusions Thrombin can induce cellular oxidative stress to lead to genotoxicity,and play autocrine and paracrine role by stimulating the secretion of PDGF-AB in BEP2D cells.     

环丙沙星联合妥布霉素对兔铜绿假单胞菌环丙沙星耐药突变选择窗的影响

目的 以兔组织笼感染模型观察环丙沙星联合妥布霉素,能否缩小环丙沙星对铜绿假单胞菌的耐药突变选择窗.方法 体外测定环丙沙星与妥布霉素对铜绿假单胞菌标准菌株ATCC27853的最低抑菌浓度(MIC)、防耐药突变浓度(MPC)、突变选择窗(MSW,MPC～MIC)、突变选择指数(SI,MPC/M1C),同时棋盘格法测定联合后的MIC.建立兔组织笼模型6只,高效液相色谱法测定环丙沙星在兔组织液中药代动力学参数.兔组织笼感染模型55只,随机平均分为11组,1组为牛理盐水组(对照组),5组单用环丙沙星(环丙沙星组),5组为环丙沙星联合妥布霉素(联合组).环丙沙星10次/d给药,每次给药间隔2 h,使兔组织液环丙沙星稳态浓度分别达到0.25、0.5、1.0、2.0和4.0 mg/L,即5个亚组;妥布霉素2.0 mg·kg～·d-1,其组织液峰浓度达到2.0 mg/L左右.3 d后抽取组织液,涂布于含有0.25 ms/L浓度环丙沙星的琼脂平板,有细菌生长者为耐药突变体.结果 体外环丙沙星与妥布霉素对铜绿假单胞菌的MIC、MPC、S1分别为0.25 mg/L、4.0 mg/L、16与0.25 mg/L、8.0 mg/L、32.环丙沙星组中环丙沙星浓度0.25、0.5、1.0及2.0 mg/L亚组组织液中均有耐药突变体生长,4.0 mg/L亚组无耐药突变体牛长;即体内环丙沙星MPC与体外相同,SI为16.联合组中环丙沙星浓度0.25 mg/L业组有耐药突变体生长,0.5、1.O、2.0及4.0 mg/L亚组无耐药突变体生长;即联合妥布霉素后环丙沙星的MPC为0.5 mg/L,MIC为0.125 mg/L,因此SI为4.结论 环丙沙星联合妥布霉素可缩小环丙沙星对铜绿假单胞菌的耐药突变选择窗,减少耐药突变体的产生,有利于减少细菌耐药.

Abstract：

Objective To observe whether the mutant selective windows(MSW)of ciprofloxacin would be reduced after its combination against Pseudomonas aeruginosa in rabbits. Methods Firstly the minimal inhibitory concentration(MIC),mutant prevention concentration(MPC),mutant selective windows (MSW,MPC-MIC)and selective indices(SI,MPC/MIC)of ciprofloxacin and tobramycin were measured in vitro respectively with standard strain ATCC27853. And the MIC was detected for the combination of ciprofloxacin and tobramycin. The rabbit tissue cage model was constructed to determine the pharmacokinetic parameters of ciprofloxacin by HPLC(high performance liquid chromatography). Fifty-five rabbits were randomly divided by a random number table into 11 groups:physiological saline in 1 group,ciprofloxacin alone in 5 groups and ciprofloxacin plus tobramycin in another 5 groups. The rabbits received ciprofloxacin 10 times a day at a 2-hour dosing interval. In 2 dosing groups. the steady state concentrations of ciprofloxacin reached to 0. 25,0. 5,1. 0,2. 0 and 4. 0 me,/L respectively. The dose of tobramycin was 2. 0 mg·kg-1·d-1and its peak concentration reached around 2.0 mg/L. At Day 3,the tissue juice was extracted, diluted and coated on agar plates with ciprofloxacin at a concentration of 0. 25 ms/L so as toobserve the growing condition of mutants. Results Against Pseudomonas aeruginosa,the values of MIC,MPC and SI of ciprofloxacin were 0. 25 mr,/L,4. 0 mg/L and 16 while 0. 25 mg/L,8. 0 mg/L and 32 for tobramycin respectively. Single groups:the mutants were found in 0. 25,0. 5,1. 0 and 2. 0 mg/L groups,but none in 4. 0 mg/L group. The MPC of cipmfloxacin was the same for in vivo and in vitro. Both were at 16. Combination groups: the mutants were only found in the group with a concentration of ciprofloxacin at 0. 25 mg/L while no mutants in the other groups. And MPC was 0. 5 mg/L and MIC 0. 125 mg/L for ciprofloxacin plus tobramycin. And the value of SI was 4. Conclusion The combined use of ciprofloxacin and tobramycin may reduce the mutant selective windows of ciprofloxacin against P. aeruginosa in rabbits so as to reduce the occurrence of mutants to control its drug resistance.     

别把流感当感冒

前不久,李大爷的孙子凡凡咳嗽了,李大爷以为是普通感冒,想到这马上就是期末考试,学习不能耽误,给孙子服了点止咳药,还是把孩子送到了学校。可没到下午放学,李大爷就接到班主任周老师的电话,说孩子发烧,希望家长马上接回家。李大爷匆匆赶到学校,把孙子接了回来。回家后,李大爷一测孩子的体温:39℃,这下李大爷可急了,急急忙忙把孩子送到医院。没想到的是,在医院里,凡凡竟然遇到了4个相识的同学,而且症状类似,都是高烧、头痛、咳嗽、全身酸痛、疲倦无力、咽痛。医生说,这些小孩患的可不是普通感冒,而是流感。     

大剂量EGFR-TKI治疗非小细胞肺癌脑转移的研究进展

非小细胞肺癌(non-small cell lung cancer,NSCLC)患者发生脑转移在肺癌中常见,预后较差,除了标准的全脑放射治疗,化疗在NSCLC脑转移患者中的治疗作用有限.表皮生长因子受体(epidermal growth factor receptor,EGFR)-酪氨酸激酶抑制剂(tyrosine kinase inhibitor,TKI)由于脑脊液药物浓度低,疗效不佳.近来个案报道大剂量EGFR-TKI为存在EGFR突变的NSCLC脑转移患者带来了很大获益.本文对NSCLC脑转移治疗现状、EGFR-TKI应用于NSCLC脑转移与存在的困惑、大剂量TKI治疗NSCLC脑转移药代动力学基础以及安全性和有效性进行综述.     

成人支气管扩张症的临床特点

目的 分析成人支气管扩张症的临床特点, 并探索不同影像学类型的差异。方法 选取从2011年9月至2014年8月, 于山东省2家三甲综合性医院收治、经高分辨率CT确诊为支气管扩张症的成人患者313例。分析其病因、临床表现、影像学、肺功能及痰培养等, 并比较不同影像学类型的临床表现的差异。结果 特发性(217例, 69.3%)是支气管扩张症最常见的病因, 其次为结核后(57例, 18.2%)。最常见的病变部位为左肺下叶(219例, 70.0%)。咳嗽(296例, 94.6%)、咯痰(285例, 91.1%)、咯血(127例, 40.6%)及湿罗音(195例, 62.3%)是支气管扩张症的特征表现。218例(69.6%)患者的肺功能异常, 最常见的是阻塞性通气功能障碍(136例, 62.4%)。144例(46.0%)患者的痰培养阳性, 最常见的病原菌为铜绿假单胞菌(106例, 73.6%)。囊状支气管扩张症患者更易出现咯痰、呼吸困难、发热及乏力症状(P均<0.001)。结论 特发性支气管扩张症最常见, 咳嗽、咯痰、咯血及固定湿罗音是支气管扩张症的特征表现, 囊状支气管扩张症的临床表现较严重。     

Twist基因在非小细胞肺癌中的研究进展

Twist作为碱性螺旋-环-螺旋转录因子的家族成员,在胚胎发育过程中通过转录激活或抑制下游靶基因对细胞的迁移和分化发挥重要的调节作用.Twist基因在多种肿瘤中存在高表达,参与多种信号通路及肿瘤上皮-间质转化的调控,与肿瘤的发生、侵袭转移、血管生成、凋亡抵抗及肿瘤细胞耐药等密切相关,是多种肿瘤的不良预后因子.本文对Twist基因在非小细胞肺癌发生发展、侵袭转移及肿瘤细胞耐药等方面的研究进展作一综述.     

三叶因子家族肽在呼吸道中的作用研究

三叶因子家族 (trefoilfactorfamily ,TFF)肽是一类具有特殊结构 P结构域的蛋白质家族 ,其在哺育动物的表达具有相对的组织特异性和高度的细胞特异性。在呼吸道中主要表达于杯状细胞、纤毛上皮细胞和黏膜下腺体 ,以TFF3表达最为丰富 ,且其表达与气道黏蛋白相匹配。TFF家族与气道黏蛋白一起保护气道上皮、影响上皮细胞的迁移及调节气道炎症反应 ,可能在呼吸道的防御和修复过程中具有重要的作用。     

胸腔积液VEGF和Endostatin检测的鉴别诊断价值

目的:探讨血管内皮生长因子(VEGF)和Endostatin联合检测在肺癌患者胸腔积液中的诊断价值.方法:采用ELISA方法检测70例肺癌和46例结核性胸膜炎并胸腔积液患者胸腔积液中VEGF和Endostatin表达水平,同时采用电化学发光法测定CEA、CYFRA211和NSE表达水平.结果:肺癌胸腔积液中VEGF和Endostatin表达水平明显高于结核性胸膜炎组,差异有统计学意义,P<0.01.VEGF在诊断恶性胸腔积液中的灵敏度、特异性和准确率分别为74.28%、67.39%和71.55%;Endostatin的评价指标分别为70.00%、82.61%和75.00%;而VEGF和Endostatin联合检测时各项评价指标均有很大提高,分别为82.86%、95.65%和87.93%.结论:胸腔积液中VEGF和Endostatin水平的增高有助于恶性胸腔积液的诊断,两者联合检测能提高灵敏度、特异性和准确性.     

高剂量左氧氟沙星静脉制剂治疗呼吸道感染的临床研究

目的在中国人群验证左氧氟沙星500mg静脉制剂治疗呼吸道感染的安全性和有效性。方法前瞻性、多中心临床研究。结果研究共纳入49所医院的1746例下呼吸道感染的患者,左氧氟沙星的用法用量为500mgIVOD,平均疗程8.9天。左氧氟沙星500mg每日一次给药治疗常见下呼吸道感染的临床有效率为91.55%,细菌清除率为72.28%,临床不良反应发生率为7.67%,主要为轻度胃肠道反应和中枢神经系统反应,3.78%的患者出现实验室检查异常,主要为白细胞一过性减少和肝功能一过性异常。结论左氧氟沙星500mg/d能有效地治疗下呼吸道感染,患者耐受性好、安全性高。