胆绿素改善大鼠脑缺血再灌注损伤的作用机制

  目的  探讨胆绿素对大鼠脑缺血再灌注损伤的保护作用以及机制。  方法  采用线栓法建立大鼠大脑中动脉栓塞模型（middle cerebral artery occlusion model，MCAO），给予胆绿素治疗后，采用改良版神经功能缺损评分评价大鼠神经功能缺损情况，干湿重法测定脑组织含水量，TTC染色测定脑梗死面积，Iba-1/DAPI染色标记缺血侧脑组织小胶质细胞活化情况，免疫荧光染色检测脑组织炎症因子TNF-α表达，Western blot测定脑组织Iba-1/CD68的蛋白表达。  结果  和IR组比较，胆绿素治疗可改善MCAO大鼠的神经功能缺损（P < 0.05），同时，还能减轻脑组织含水量（P < 0.05），降低大脑梗死面积（P < 0.05），以及降低缺血侧脑组织中小胶质细胞的表达和Iba-1/CD68蛋白的表达（P < 0.05）。此外，胆绿素治疗还能减少缺血侧脑组织中炎症因子TNF-α的表达（P < 0.05）。  结论  胆绿素在MCAO大鼠中可能通过抑制小胶质细胞活化而减轻大鼠脑缺血再灌注损伤。     

Transferrin-conjugated polymeric nanomedicine to enhance the anticancer efficacy of edelfosine in acute myeloid leukemia

In this study, transferrin (Tf)-conjugated polyethylene glycol (PEG)-poly-l-lysine (PLL)-poly(lactic-co-glycolic acid) (PLGA) (PEG-PLL-PLGA)-based micellar formulations were successfully prepared for the delivery of edelfosine (EDS) in leukemia treatment. The micelles were nanosized and presented spherical shaped particles. Our in vitro data suggest that the nanoformulations maintain the biological activity of drugs for longer periods and lead to a continuous release of active drug. The enhanced cellular uptake of EDS-TM resulted in significantly higher cytotoxic effect in K562 leukemia cells. Cell cycle analysis further demonstrated the significantly higher G2/M phase arrest of cancer cells. Immunoblot analysis clearly revealed the potential of EDS-TM in inducing apoptosis of cancer cells which could improve the anticancer efficacy in leukemia. Importantly, EDS-M and EDS-TM significantly prolonged the circulation profile of EDS throughout until 24 h, indicating the potential of targeted nanoparticulate delivery system. The prolonged blood circulation potential of micellar formulations might improve the therapeutic potential of drug by increasing its bioavailability in the serum. It would be worthwhile evaluating the effects of the EDS-loaded micelles on cancer cells in vivo for clinical application.     

产超广谱β-内酰胺酶肠杆菌科细菌感染患者使用抗菌药物的药物评价

  目的  评价云南省第一人民医院产超广谱β-内酰胺酶（ESBLs）肠杆菌科细菌患者应用抗菌药物使用的合理性。  方法  采用药物利用评价（DUR）和药物利用评估（ DUE）法,分析评价云南省第一人民医院2017年1月至2017年6月出院的135例 ESBLs肠杆菌科细菌感染患者的药物利用指数（DUI）、抗菌药物选用、给药方案及临床治疗结果。  结果  纳入DUR和DUE分析的抗菌药有14种,其中8种药物的药物利用指数（DUI） < 1,5种药物的药物利用指数（DUI） = 1,3种药物DUI > 1; DDDs居前5位的药物分别为头孢甲肟、头孢哌酮舒巴坦、美罗培南、左氧氟沙星和头孢曲松。DUE标准评价结果显示仅药品不良反应处理及监测为100%,而符合标准率较低的为有产ESBLs的危险因素且为轻中度感染选用的抗菌药物（28.87%）并正确降阶梯治疗（30.00%）。  结论  联合应用DUR和DUE可以更全面的对ESBLs肠杆菌科细菌患者的用药情况。仍需加强对ESBLs肠杆菌科细菌感染患者分层选择抗菌药物及选择合理的给药方案。     

RYR1-related congenital myopathy with fatigable weakness,responding to pyridostigimine

The spectrum of RYR1 mutation associated disease encompasses congenital myopathies, exercise induced rhabdomyolysis, malignant hyperthermia susceptibility and King-Denborough syndrome. We report the clinical phenotype of two siblings who presented in infancy with hypotonia and striking fatigable ptosis. Their response to pyridostigimine was striking, but genetic screening for congenital myasthenic syndromes was negative, prompting further evaluation. Muscle MRI was abnormal with a selective pattern of involvement evocative of RYR1-related myopathy. This directed sequencing of the RYR1 gene, which revealed two heterozygous c.6721C>T (p.Arg2241X) nonsense mutations and novel c.8888T>C (p.Leu2963Pro) mutations in both siblings. These cases broaden the RYR1-related disease spectrum to include a myasthenic-like phenotype, including partial response to pyridostigimine. RYR1-related myopathy should be considered in the presence of fatigable weakness especially if muscle imaging demonstrates structural abnormalities. Single fibre electromyography can also be helpful in cases like this.     

2型糖尿病患者血小板活化与肾病的关系

目的探索血小板活化异常与糖尿病肾病（DN）的关系。方法我们采用流式细胞术检测116例2型糖尿病（DM）患者周围血中CD62p^＋，CD63^＋，CD31^＋，CD41^＋及血浆α-颗粒膜蛋白（GMP140）含量测定（ELISA法），并依据24h尿白蛋白排出率（UAER）将其分为正常白蛋白尿组（DM1）、微量白蛋白尿组（DM2）、大量白蛋白尿组（DM3），并与40例正常人对照（NC）。结果周围血中CD62p^＋，CD63^＋，CD31^＋，CD41^＋及血浆GMP140在DM各组均较Nc组升高。特别是DM2，DM3组较NC组明显升高。DM合并高血压者周围血中CD62p^＋，CD63^＋，CD31^＋，CD41^＋及血浆GMP140均较无高血压者为高（P〈0．05）。结论血小板活化的增强可能与DN的发生、发展相关。     

硫代乙酰胺诱导大鼠肝纤维化的研究

目的研究硫代乙酰胺对大鼠肝纤维化模型的诱导作用。方法采用0．03％的硫代乙酰胺腹腔注射,每周2次,构建大鼠肝纤维化模型;观察大鼠肝纤维化形成情况。结果与空白组比较,模型组大鼠血清谷丙转氨酶（ALT）、谷草转氨酶（AST）、透明质酸（HA）明显升高（P〈0．01）;层粘连蛋白（LN）升高（P〈0．05）。组织病理提示模型组大鼠肝细胞大量坏死,假小叶形成。结论硫代乙酰胺能诱导大鼠形成肝纤维化。     

新型口服碳青酶烯类抗生素法罗培南治疗急性细菌感染性疾病临床对照研究

目的评价口服碳青酶烯类抗生素法罗培南片治疗临床常见致病菌引起的呼吸、泌尿系统细菌感染性疾病的疗效和安全性。方法用多中心随机单盲阳性药平行对照试验方法,共入选有效病例226例,试验组(法罗培南钠)入选114例,对照组(头孢泊肟酯)入选112例,法罗培南钠片600mg/d,头孢泊肟酯片200mg/d,疗程均为7~14d。结果试验组与对照组临床痊愈率分别为83.33%和80.36%,总有效率分别为95.61%和95.54%;细菌清除率均为98.94%。药物不良反应发生率分别为6.84%和6.14%。结论法罗培南钠片治疗临床常见急性细菌感染性疾病安全、有效。