泛耐药肺炎克雷伯菌株的医院内流行特性的研究

目的 了解华山医院泛耐药肺炎克雷伯菌株及其流行的特点.方法 收集2006年8月-2009年12月对CLSI推荐常规检测药物均耐药的肺炎克雷们菌临床分离株,共57株.所有菌株都进行药物敏感试验、超广谱β-内酰胺酶(ESBLs)初筛及表型确证试验、改良Hodge试验、等电聚焦电泳,聚合酶链反应及其产物测序、接合试验、肠杆菌基因间重复共有序列PCR(ERIC-PCR)和多位点序列分型(MLST).结果 所有菌株都携带blaKPC-2、blaCTX-M-14、blaSHV12和blaTEM-1及qnrB和aac(6')-I b-cr基因.57株细菌中ST423型5株,MIST ST11型52株.ST423型散发,而ST11型呈医院内流行.57株细菌都对替加环素耐药,对多黏菌素、米诺环素和多西环素部分敏感.结论 本次泛耐药肺炎克雷们流行主要为ST11型菌株;不同的肺炎克雷伯菌株,播散能力不同;检出泛耐药肺炎克雷伯菌时应增加检测药物的种类.     

811例酵母样真菌感染的临床分布及药敏分析

目的分析临床酵母样真菌感染的分布情况,结合真菌的鉴定及药敏,指导临床合理用药。方法回顾性分析真菌感染者的临床资料、检出的酵母样真菌的分布及对抗真菌药物的耐药特点。结果真菌感染以60岁以上老年人居多,占69.4%,感染部位主要为呼吸道、泌尿道及肠道;基本都有抗生素使用史,多有创伤性介入治疗。检出真菌主要为白色假丝酵母菌,共526例,另有热带假丝酵母菌117例,光滑假丝酵母菌86例,近平滑假丝酵母菌57例,其他酵母菌25例。10种抗真菌药物中,耐药性较高的为特比奈芬、制霉菌素和两性霉素B,比较敏感的为5-氟胞嘧啶和酮康唑。两性霉素B33.9%和氟康唑22.6%的耐药率,大大高于以往熟知的程度,这与临床大量常规使用其预防真菌感染有密切联系。结论应加强真菌检测,指导临床合理使用抗生素,减少多重耐药出现。     

肿瘤多药耐药逆转中药活性成分的研究进展

肿瘤多药耐药（multi-drug resistance,MDR）的客观存在是肿瘤化疗失败的主要原因,因此,寻找低毒高效的肿瘤耐药逆转剂已是肿瘤化疗药物领域研究的热点,目前进入临床应用研究的化学药物逆转剂因作用机制单一、选择性差、中毒剂量与有效剂量接近等原因,     

吉西他滨联合多烯紫杉醇治疗蒽环类耐药转移性乳腺癌的疗效观察

目的：观察吉西他滨（GEM）联合多烯紫杉醇（DXL）治疗蒽环类耐药转移性乳腺癌的临床疗效。方法：49例确诊为蒽环类耐药转移性乳腺癌患者,随机分为2组,联合组25例采用吉西他滨（GEM）联合多烯紫杉醇（DXL）治疗,对照组24例单纯使用多烯紫杉醇治疗。结果：2组近期疗效结果比较,GD联合组有效率为68.0%,对照组有效率为41.7%,2组在临床疗效上有统计学意义。49例患者2年随访率比较无显著性差异。2组患者的不良反应以血液学为主,其次为恶心、呕吐、腹泻、手足综合征等,患者均可以耐受这些不良反应。结论：吉西他滨（GEM）联合多烯紫杉醇（DXL）是治疗蒽环类耐药转移性乳腺癌的有效方案,且患者耐受性良好。     

慢性化脓性中耳炎病原菌对氟喹诺酮类耐药机制的研究进展

慢性化脓性中耳炎是耳鼻喉科常见病,非手术治疗主要以全身和局部应用抗菌药为主,在目前应用的药物中,以氟喹诺酮类疗效最好,但随着该药物的广泛应用,耐药率逐渐上升,本文介绍了慢性化脓性中耳炎常见病原菌对氟喹诺酮类药物耐药机制的相关研究.     

肝移植后泛耐药鲍曼不动杆菌感染者的细胞免疫功能监测和免疫抑制方案调整

目的 探讨肝移植后泛耐药鲍曼不动杆菌(PDR-Ab)感染者的细胞免疫功能监测及免疫抑制方案的调整.方法 回顾性总结2008年1月至2010年5月299例尸体肝移植病例并发PDR-Ab的感染和预后情况.监测肝移植后T淋巴细胞亚群及绝对计数、CD4+T淋巴细胞ATP含量,进行T淋巴细胞免疫功能评分.将14例发生PDR-Ab感染者根据免疫抑制方案的调整不同分为2组,常规治疗组(6例)的他可莫司用量不变,停用吗替麦考酚酯和泼尼松,给予头孢哌酮钠/舒巴坦钠静脉滴注;免疫调节组(8例)在常规治疗的基础上,根据受者的T淋巴细胞免疫功能评分(TCIFS)的动态变化进行免疫抑制方案的调整.结果 两组间受者的年龄、终末期肝病模型评分、Child-Pugh评分的差异均无统计学意义(P＞0.05);术中出血量的差异有统计学意义(P＜0.01);术后1周、发生PDR-Ab感染时TCIFS的差异无统计学意义(P＞0.05),但在治疗终点,免疫调节组的TCIFS明显高于常规治疗组(P＜0.05);两组间治愈率的差异有统计学意义(P＜0.05).2个组均未发生排斥反应.结论 肝移植后并发PDR-Ab感染时,根据T淋巴细胞亚群计数和CD4+T淋巴细胞ATP值对肝移植受者的细胞免疫功能进行量化评分,以进行免疫抑制方案的调整,是降低肝移植后PDR-Ab感染病死率的有效方法.

Abstract：

Objective To explore the monitoring and the individualized adjustment of cellular immunology function in the recipients infected with pan-drug resistant Acinetobacter baumannii(PDR-Ab)after liver transplantation.Methods We retrospectively summarized the infection and the prognosis of PDR-Ab in 299 cases of liver transplantation performed from Jan.2008 to May 2010.The absolute number of T lymphocytes and ATP level within CD4+ T cells were monitored,and T cell immunology function(TCIFS)was scored.According to different immunology adjusting proposals,14 cases of PDR-Ab infection were divided into 2 groups:(1)traditional group,routine anti-infective therapy;(2)individualized group.Individualized immunology adjustment was made according to the score of TCIFS besides routine therapy.Results There was no significant difference in age,MELD and Child-pugh score between two groups.The peri-operative bleeding volume in individualized group was more than that in traditional group(P<0.01).There was no significant difference in TCIFS score between two groups at 1st week after transplantation and the onset of the PDR-Ab infection.However,the score in individualized group was apparently higher than that in traditional group when anti-infection therapy ended(P<0.05).The difference in the recovery rate between two groups was significant(P<0.05).No rejection happened in two groups.Conclusion It is an effective way to decrease the mortality of PDR-Ab infection after liver transplantation that the individualized adjustment of immunosuppression protocols is guided by grading quantitatively the cellular immunology function according to the absolute number of T lymphocytes and ATP level within CD4+ T cells.     

非小细胞肺癌K-ras突变小分子对吉非替尼耐药细胞的作用

目的 观察针对K-ras突变小分子NSC-741909是否可特异性杀伤吉非替尼原发耐药细胞,并探讨其机制.方法 选取吉非替尼耐药细胞;观察NSC-741909作用后细胞增殖与凋亡的变化;共聚焦显微镜观察细胞骨架改变;Western blot检测K-ras、JNK、P-JNK的改变.结果 NSC-741909可使耐药细胞在作用24 h后,在1 μmol/L和2 μmol/L时,FITC-A+/PE-A+细胞增加至(6.9±0.6)%和(21.1±3.2)%(P＜0.01);作用30 min后,K-ras表达在2 h下降达70%;p-JNK表达增加,并持续至少15 h,而总JNK蛋白表达无改变;细胞骨架蛋白F-actin呈稀疏、不规则、发散状排列.结论 针对K-ras突变的小分子NSC-741909可特异性杀伤吉非替尼原发耐药细胞,这是通过持续激活JNK途径从而导致细胞凋亡实现的.

Abstract：

Objective To study whether a recently identified novel anticancer agent NSC-741909 can suppresses the growth of non-small cell lung cancer cell line ( NSCLC) which has primary resistance to Gefitinib and explore its molecular mechanisms. Methods Select NSCLC cell line which is resistant to Gefitinib. Observe the cell growth supression effect of NSC-741909 to the cell line, apoptosis and actin cytoskeleton changement. Observe K-ras, JNK, p-JNK protein expression by Western blotting. Results NSC-741909 can induce apoptosis of Gefitinib resistant cell lines at 24 h. At that time point, FITC-A +/ PE-A + increased to (6. 9 ±0.6)% and (21. 1 ±3.2)% (P ＜0. 01) at 1 and 2 μmol/L;K-ras protein decreased to 70% at 2 h; p-JNK expression was increased and lasted for at least 15 h and total JNK remained the same. Cell cytoskeleton F-actin presented as loose, irregular and radiation arrangement. Conclusion NSC-741909 which supress the mutant K-ras expression can induce the apoptosis of the NSCLC which is primary resistant to Gefitinib. This inhibition was mediated by sustained JNK activation.     

人乳腺癌多西他赛耐药细胞株MCF7/Docetaxel的建立及其生物学特征

目的 建立人乳腺癌多西他赛耐药细胞株MCFT/Doeetaxel,探讨其生物学特征.方法 采用多西他赛中等浓度、间歇作用法建立耐药细胞株MCF7/Docetaxel,采用噻唑蓝(MTT)比色法测定其对Doeetaxel的耐药指数,观察冻存、撤药对耐药性的影响,比较耐药细胞株与亲本细胞株生长曲线、群体倍增时间及贴壁率的不同,流式细胞仪检测细胞周期,软琼脂实验检测细胞的恶性增殖能力,罗丹明实验检测其对药物的摄入、排出能力.结果 人乳腺癌耐药细胞株MCF7/Docetaxel的耐药指数为16.2,冻存对耐药性无明显影响,撤药培养可使耐药性降低,MCF7/Docetaxel与MCF7细胞的群体倍增时间分别为(39.89±0.43)、(27.51±0.55)h(P＜0.05),耐药细胞株倍增时间延长,生长缓慢,G2、M期细胞比例增加(39.50±3.83)%、(23.59±2.51)%(P＜0.05),克隆形成率明显高于亲本细胞67%、23%(P＜0.05),对罗丹明的摄入减少,排出增多.结论 成功建立人乳腺癌多烯紫杉醇耐药细胞株MCF7/Docetaxel,生长及耐药性稳定.

Abstract：

Objective To establish a docetaxel-induced human breast carcinoma drug-resistant cell line MCF7/Docetaxel and study its biological characteristics. Methods The drug-resistant cell line MCF7/Docetaxel was established in culture by exposing MCF7 parent cells to moderate concentration of docetaxel over a period of 11 months. The resistance index to docetaxel was determined by methyl thiazol tetrazolium (MTT) assay. Cell growth curve was drawed and the doubling time was accounted. Flow cytometry (FCM) was performed to determine cell cycle. Fluorescence activated cell analysis (FACS) was employed to determine the concentration of fluorescence dye of rhodamine 123 ( Rh123) in the cells for the evaluation of drug-absorptive and expelling capacity. Results The resistant index of MCF7/Docetaxel was 16. 2. When MCF7/Docetaxel was stored with docetaxel at - 196℃ for 3 months and then went back to the normal environment, its characteristic of anti-tumor drug resistance was still maintained. But after being cultured in RPMI 1640 without docetaxel for a period of 1 month, MCF7/Docetaxel showed a decrease in the resistant index. As compared with the parent cells, MCF7/Docetaxel exhibited a prolonged doubling time [(39. 89 ±0. 43 vs 27. 51 ±0. 55 h,P＜0. 05] and lower growth rate. The percentages of cells in G2 and M phases were significantly increased in MCF7/Docetaxel in comparison with those in MCF7 [(39. 50 ± 3. 83) % vs (23. 59 ± 2. 51) % , P ＜ 0.05]. In soft agar growth test, MCF7/Docetaxel cells formed more cell clones than MCF7 cells (67% vs 23% ,P ＜0. 05). Finally, the concentration of Rh123 in MCF7/Docetaxel was lower than that in MCF7. Conclusion The newly established stable cell line MCF7/Docetaxel possesses typical drug-resistant characteristics and its drug-resistant phenotype is stable.     

可溶性耐药相关钙结合蛋白同肿瘤多药耐药关系的研究进展

可溶性耐药相关钙结合蛋白（sorcin）是一种广泛存在于多种正常组织细胞及肿瘤细胞中的胞浆蛋白。sorcin可在多种耐药细胞中高表达,其耐药机制可能是它可以与细胞中钙离子结合,也可能与其阻断内质网膜上钙离子通道引起的细胞凋亡相关,但sorcin表达的量与耐药程度之间的关系还不明了。本文主要对sorcin的结构及其在耐药肿瘤细胞中的表达和导致耐药的机制进行综述。