托烷司琼预防全身麻醉术后恶心呕吐的Meta分析

目的评价托烷司琼对预防全身麻醉术后恶心呕吐（PONV）发生的疗效和安全性。方法检索PubMed、EBSCO、Cochrane、CNKI和维普等数据库,检索托烷司琼预防PONV的随机对照试验（RCT）,收集符合纳入标准的文献,提取资料,评价纳入研究的文献方法学质量,并且提取出有效数据进行Meta分析,统计学分析采用Rev Man5.0软件。结果符合纳入标准的文章18篇,共包括2 901例试验者。Meta分析结果显示：（1）托烷司琼能有效降低全身麻醉PONV发生率[OR=0.43,95%CI（0.33~0.57）],相对早期[OR=0.66,95%CI（0.44~0.98）]而言,托烷司琼更能有效降低后期[OR=0.41,95%CI（0.25~0.65）]PONV发生率;（2）托烷司琼联合地塞米松与单用托烷司琼相比较,能更有效降低PONV发生率[OR=0.37,95%CI（0.22~0.64）]。（3）托烷司琼与格拉司琼和昂丹司琼比较差异无统计学意义（P〉0.05）,分别为[OR=1.08,95%CI（0.68~1.73）],[OR=0.77,95%CI（0.27~2.21）]。（4）托烷司琼与地塞米松相比差异无统计学意义[OR=1.06,95%CI（0.49~2.30）]。结论托烷司琼能明显降低全身麻醉患者PONV的发生率,与其他非5-HT3拮抗剂类止吐药如地塞米松联合用药效果更佳。

托烷斯琼预防全麻术后恶心呕吐有效性和安全性的Meta分析

目的系统评价托烷斯琼预防全麻术后恶心呕吐的临床效果和安全性。方法电子检索PubMed、EBSCO、Springer、Ovid、CNKI等数据库,并查阅所获文献的参考文献,收集1995～2009年发表的有关托烷斯琼预防全麻术后恶心呕吐的随机对照试验(RCT)。按Cochrane Handbook 5.0.1对纳入文献进行质量评价和资料提取,统计学分析采用RavMan 4.2.10软件。结果共纳入17个RCT,包括4?678例患者。Meta分析结果显示:①有效性:托烷司琼单次静注能降低全麻术后恶心呕吐的发生率[RR=0.41,95%CI(0.29,0.60)]和全麻术后应用阿片类药物镇痛患者恶心呕吐的发生率[RR=0.30,95%CI(0.15,0.60)];单次静注或分次泵注均能降低全麻术后应用曲马多镇痛患者恶心呕吐的发生率[RR(95%CI)分别为0.41(0.29,0.56)和0.10(0.06,0.19)];托烷司琼与地塞米松联用较托烷司琼单用能更有效降低全麻术后患者恶心呕吐的发生率[RR=0.27,95%(0.13,0.57)]。②安全性:托烷司琼静注能减少头晕头迷的发生率[RR=0.35,95%CI(0.16,0.75)],但在减少术后瘙痒、嗜睡方面差异无统计学意义;所有纳入研究患者均未出现椎体外系、排尿困难等症状。结论托烷司琼能明显降低全麻患者术后恶心呕吐的发生率,且不增加瘙痒、嗜睡等不良反应,并可减少头晕头迷的发生。

2-脱氧葡萄糖可增强TRAIL诱导的口腔癌细胞凋亡的敏感性

目的探讨糖基化抑制剂2-脱氧葡萄糖(2-DG)对肿瘤坏死因子相关凋亡诱导配体(TRAIL)诱导肿瘤细胞凋亡作用的影响。方法 MTT法检测不同浓度(0、0.625、1.25、2.5、5、10 mmol/L)2-DG及不同浓度2-DG与TRAIL(200 ng/ml)合用对口腔癌细胞KB的增殖抑制作用。集落克隆法检测2-DG及TRAIL对口腔癌细胞KB的增殖抑制作用。溴化丙啶(PI)单染法检测2-DG(5 mmol/L)对TRAIL诱导口腔癌细胞KB凋亡的影响;Western blot检测2-DG(5 mmol/L)处理口腔癌细胞KB不同时间(0、6、16、24 h),DR5的表达以及联合TRAIL处理后Caspase-3的表达。结果 5 mmol/L 2-DG作用于口腔癌细胞KB 24、48、72 h细胞存活率分别为75.25%、69.06%、59.19%,但24 h细胞凋亡率仅为15.9%。5 mmol/L 2-DG与TRAIL联合作用于口腔癌细胞KB 24 h的凋亡率为72.5%,高于TRAIL本身诱导凋亡率45.3%,并且2-DG可增强TRAIL抑制口腔癌细胞KB的集落克隆形成的作用。2-DG上调DR5的表达并且增强Caspase-3的激活。结论 2-DG能增强TRAIL诱导口腔癌细胞的凋亡,其机制可能是上调DR5的表达及增强Caspase-3的激活。

The antiemetic effects of magnetotherapy plus granisetron hydrochloride versus granisetron hydrochloride in patients with chemotherapy

Objective:The aim of this study was to observe and compare the antiemetic effectiveness and adverse events of magnetotherapy plus 5-hydroxytryptamine (5-HT3) receptor inhibitor granisetron hydrochloride vs granisetron hydrochloride alone in patients with chemotherapy.Methods:Sixty-four patients were randomized to receive either granisetron hydrochloride alone (control group:granisetron hydrochloride 3 mg intervenous infusion before chemotherapy, from the 1st day of chemotherapy course until the day after chemotherapy course completed) or magnetotherapy plus granisetron hydrochloride (treatment group:the same granisetron hydrochloride regimen plus rotatory magnetotherapy of 1 every day after chemotherapy for 5 begin with chemotherapy).Baseline characteristics were similar in both groups.The patients' emesia was evaluated according to WHO's criteria.The density of 5-HT3 was detected by enzyme-linked immunosorbent assay (ELISA).Results:In the treatment of acute vomiting, there was no significant difference between two groups (P>0.05), but in the treatment of tardive vomiting, the effectiveness in treatment group was better than that in control group (P<0.05).The density of 5-HT3 in treatment group and control group were (225.32±57.29) ng/mL vs (213.00 ±53.29) ng/mL before chemotherapy and (273.88 ±75.42) ng/mL vs (313.17±76.36) ng/mL after chemotherapy (P<0.01); the rate of adverse events was 36.36% and 48.39% respectively in treatment group and control group (P>0.05).Conclusion:Magnetotherapy plus granisetron hydrochloride provide better effectiveness than granisetron hydrochloride alone, and both therapies have synergistic effect.The adverse events didn't raised in treatment group.

nNOS抑制剂亚胺基烯丁基-L-鸟氨酸对心肌缺血再灌注损伤的影响及机制

目的探讨nNOS选择性抑制剂亚胺基烯丁基-L-鸟氨酸(L-VNIO)对心肌缺血再灌注(I/R)损伤的影响及机制。方法构建SD大鼠离体心脏I/R模型和H9c2细胞缺氧/复氧(H/R)模型;nNOS抑制剂L-VNIO(10μmol·L^(−1))持续给药整个再灌注或复氧过程。TTC染色测定心肌梗死面积;流式细胞术检测H9c2细胞凋亡率;Fluo-3/AM Ca^(2+)荧光探针通过流式细胞仪检测H9c2细胞内Ca^(2+)浓度;试剂盒法测定离体心脏灌流液乳酸脱氢酶(LDH)、丙二醛(MDA)水平以及H9c2细胞MDA水平和超氧化物歧化酶(SOD)活性;离体心脏提取肌浆网,试剂盒法检测肌浆网Ca^(2+)-ATP酶(SERCA)活性,Western blotting检测肌浆网SERCA蛋白表达;Western blotting检测离体心脏中受磷蛋白(PLB)和兰尼碱受体2(RyR2)蛋白表达水平和磷酸化水平。结果与I/R或H/R模型组相比,L-VNIO显著降低细胞凋亡率,减少心肌梗死面积,降低LDH、MDA水平,提高SOD活性,差异均有统计学意义(P<0.05);此外,与I/R或H/R模型组相比,L-VNIO组明显降低细胞内Ca^(2+)超载,增高PLB磷酸化水平,降低RyR2磷酸化水平,增强SERCA活性(P<0.05)。结论nNOS抑制剂L-VNIO可以减轻I/R损伤,机制与调节Ca^(2+)转运相关蛋白而降低I/R引起的Ca^(2+)超载相关。

Androgen-AR axis in primary and metastatic prostate cancer: chasing steroidogenic enzymes for therapeutic intervention

Androgens play an important role in prostate cancer(PCa)development and progression.Although androgen deprivation therapy remains the front-line treatment for advanced prostate cancer,patients eventually relapse with the lethal form of the disease.The prostate tumor microenvironment is characterised by elevated tissue androgens that are capable of activating the androgen receptor(AR).Inhibiting the steroidogenic enzymes that play vital roles in the biosynthesis of testosterone(T)and dihydrotestosterone(DHT)seems to be an attractive strategy for PCa therapies.Emerging data suggest a role for the enzymes mediating pre-receptor control of T and DHT biosynthesis by alternative pathways in controlling intratumoral androgen levels,and thereby influencing PCa progression.This supports the idea for the development of multi-targeting strategies,involving both dual and multiple inhibitors of androgen-metabolising enzymes that are able to affect androgen synthesis and signalling at different points in the biosynthesis.In this review,we will focus on CYP17A1,AKR1C3,HSD17B3 and SRD5A,as these enzymes play essential roles in all the three androgenic pathways.We will review also the AR as an additional target for the design of bifunctional drugs.Targeting intracrine androgens and AKR1C3 have potential to overcome enzalutamide and abiraterone resistance and improve survival of advanced prostate cancer patients.