罗氟司特对亚洲慢性阻塞性肺疾病患者肺功能影响的Meta分析

目的:系统评价罗氟司特对亚洲慢性阻塞性肺疾病(COPD)患者肺功能的影响,为临床合理用药提供循证参考。方法:计算机检索Cochrane图书馆、PubMed、Embase、中国生物医学文献数据库、中国知网、维普数据库和万方数据库,收集罗氟司特或罗氟司特联合常规治疗或安慰剂(试验组)对比常规治疗或安慰剂治疗(对照组)治疗亚洲人群COPD的随机对照试验(RCT)。筛选文献,提取资料并按照Cochrane偏倚风险评估工具评价文献质量后,采用Rev Man 5.2软件进行Meta分析。结果:共纳入6项RCT,包括1 494例患者。Meta分析结果显示,试验组患者支气管扩张药使用前第1秒用力呼气容积[MD=75.19,95%CI(53.21,97.17),P<0.000 01]、支气管扩张药使用后第1秒用力呼气容积[MD=56.60,95%CI(27.56,85.63),P=0.000 1]、用力肺活量[MD=43.67,95%CI(15.91,71.43),P=0.002]、支气管扩张药使用后25%～75%用力肺活量的平均流速[MD=14.58,95%CI(8.43,20.73),P<0.001]、腹泻发生率[RR=5.06,95%CI(1.26,20.27),P=0.02]、呼吸道感染发生率[RR=1.94,95%CI(1.30,2.90),P=0.001]、食欲下降发生率[RR=7.43,95%CI(2.94,18.79),P=0.001]、体质量下降发生率[RR=5.46,95%CI(2.12,14.03),P=0.001]、头痛发生率[RR=7.73,95%CI(1.42,42.16),P=0.02]、头晕发生率[RR=3.44,95%CI(1.28,9.27),P=0.01]、胃炎发生率[RR=5.09,95%CI(1.49,17.45),P=0.01]、厌食症发生率[RR=5.06,95%CI(1.97,13.00),P=0.001]均显著高于对照组;圣乔治呼吸问卷总评分[MD=-5.82,95%CI(-7.77,-3.87),P<0.001]、呼吸症状评分[MD=-1.67,95%CI(-2.51,-0.84),P<0.001]、活动受限评分[MD=-1.55,95%CI(-2.14,-0.97),P<0.001]、疾病影响评分[MD=-2.59,95%CI(-3.40,-1.79),P<0.001]均显著低于对照组。结论:罗氟司特可改善亚洲COPD患者的肺功能及呼吸困难症状,但会增加不良反应的发生风险。     

消渴丸对比格列本脲治疗2型糖尿病疗效与安全性的系统评价

目的:系统评价消渴丸对比格列本脲治疗2型糖尿病的疗效和安全性,以为临床治疗提供循证参考。方法:计算机检索Medline、Pub Med、EMBase、Cochrane图书馆、中国生物医学文献数据库、中国期刊全文数据库、万方数据库和中文科技期刊数据库,纳入消渴丸(试验组)对比格列本脲(对照组)治疗2型糖尿病的随机对照试验(RCT),按Cochrane系统评价方法筛选文献、提取资料、评价质量后采用Rev Man 5.2统计软件对数据进行Meta分析。结果:共纳入15项RCT,合计3 319例患者。Meta分析结果显示,试验组患者糖化血红蛋白(Hb A1c)水平[MD=-0.39,95%CI(-0.75,-0.02),P=0.04]、空腹血糖(FPG)水平[MD=-0.70,95%CI(-1.27,-0.12),P=0.02]、餐后2 h血糖(2 h PG)水平[MD=-0.87,95%CI(-1.55,-0.20),P=0.01]、口渴喜饮治疗有效率[RR=3.35,95%CI(1.92,5.85),P<0.001]、倦怠乏力治疗有效率[RR=5.74,95%CI(3.52,9.36),P<0.001]均显著优于对照组,低血糖发生率[RR=0.67,95%CI(0.49,0.91),P=0.01]显著低于对照组,差异均有统计学意义。结论:消渴丸治疗2型糖尿病的疗效和安全性均优于格列本脲,可显著改善患者Hb A1c、FPG、2 h PG水平和中医症状。     

噻托溴铵治疗慢性阻塞性肺疾病有效性和安全性的Meta分析

目的:系统评价噻托溴铵治疗慢性阻塞性肺疾病(COPD)的有效性和安全性,以为临床治疗提供循证参考。方法:计算机检索Pub Med、EMBase、Medline、Cochrane图书馆、中国期刊全文数据库、万方数据库和中文科技期刊数据库,收集噻托溴铵(试验组)对比安慰剂(对照组)治疗COPD的随机对照试验(RCT),提取资料并评价质量后,采用Rev Man 5.0统计软件进行分析。结果:共纳入19项RCT,合计16 318例患者。Meta分析结果显示,试验组患者第1秒用力呼气容积(FEV1)[MD=0.13,95%CI(0.12,0.14),P<0.001]、用力肺活量(FVC)[MD=0.20,95%CI(0.20,0.25),P<0.001]显著高于对照组,圣乔治呼吸问卷得分(SGRQ)[MD=-2.94,95%CI(-3.38,-2.49),P<0.001]和COPD急性加重率[RR=0.83,95%CI(0.77,0.90),P<0.001]显著低于对照组,口干发生率亦显著高于对照组[RR=2.07,95%CI(1.34,3.20),P<0.001],差异均有统计学意义。结论:噻托溴铵治疗COPD疗效较好,但易引起口干的不良反应。受纳入研究方法学的限制,该结论有待大样本、高质量的RCT进一步验证。     

垂体后叶素联合酚妥拉明对比单用垂体后叶素治疗支气管扩张咯血疗效与安全性的系统评价

目的:系统评价垂体后叶素联合酚妥拉明对比单用垂体后叶素治疗支气管扩张咯血的疗效与安全性,以为临床治疗提供循证参考。方法:计算机检索Pub Med、Cochrane图书馆、EMBase、中国期刊全文数据库、万方数据库、中文科技期刊数据库,收集垂体后叶素联合酚妥拉明(试验组)对比单用垂体后叶素(对照组)治疗支气管扩张咯血疗效与安全性的随机对照试验(RCT),对符合纳入标准的临床研究进行资料提取和质量评价后,采用Rev Man 5.2.3统计软件进行Meta分析。结果:共纳入43项RCT,合计3 094例患者。Meta分析结果显示,试验组患者显效率[RR=1.50,95%CI(1.38,1.62),P<0.001]、有效率[RR=1.25,95%CI(1.20,1.30),P<0.001]显著高于对照组,无效率[RR=0.29,95%CI(0.23,0.36),P<0.001]、咯血停止或缓解的时间[MD=-2.00,95%CI(-2.43,-1.57),P<0.001]、头痛发生率[RR=0.36,95%CI(0.22,0.59),P<0.001]、胸闷发生率[RR=0.41,95%CI(0.26,0.63),P<0.001]、腹痛发生率[RR=0.26,95%CI(0.16,0.43),P<0.001]、血压升高发生率[RR=0.28,95%CI(0.14,0.56),P<0.001]显著低于对照组,差异均有统计学意义。结论:垂体后叶素联合酚妥拉明治疗支气管扩张咯血疗效与安全性优于单用垂体后叶素。受纳入研究方法学质量和样本量限制,该结论有待更多设计严格、长期随访的大样本RCT加以验证。     

海昆肾喜胶囊治疗慢性肾功能衰竭的Meta分析

目的:系统评价海昆肾喜胶囊治疗慢性肾功能衰竭(CRF)的疗效,为临床提供循证参考。方法:计算机检索Central、Pub Med、EMBase、中国期刊全文数据库(CJFD)、中国生物医学文献数据库(CBM)、中文科技期刊数据库(VIP)和万方数据库,收集海昆肾喜胶囊联合常规方案(试验组)对比单纯常规方案(对照组)治疗CRF的随机对照试验(RCT),筛选文献、提取资料并采用Cochrane协作网提供的风险偏倚评估图评价质量后,采用Rev Man 5.3统计软件进行Meta分析。结果:共纳入10项RCT,合计704例患者。Meta分析结果显示,试验组患者总有效率显著高于对照组[RR=4.42,95%CI(2.70,7.22),P<0.001],血肌酐[MD=-140.37,95%CI(-191.72,-89.03),P<0.001]、血尿素氮[MD=-5.49,95%CI(-8.36,-2.63),P<0.001]和24 h尿蛋白定量[MD=-0.43,95%CI(-0.62,-0.23),P<0.001]均显著低于对照组,差异均有统计学意义。结论:海昆肾喜胶囊治疗CRF疗效较好,可以显著改善患者相关肾功能指标。     

阿戈美拉汀治疗抑郁症急性期疗效的系统评价

目的:系统评价阿戈美拉汀治疗抑郁症急性期的疗效,以为临床治疗提供循证参考。方法:计算机检索Cochrane图书馆、Medline、EMBase、中国期刊全文数据库、中文科技期刊数据库、中国生物医学数据库、万方数据库以及世界卫生组织(WHO)临床试验注册平台和美国临床试验注册平台,收集阿戈美拉汀对比安慰剂治疗抑郁症急性期的随机对照试验(RCT),对符合纳入标准的临床研究进行质量评价和资料提取后,采用Rev Man 5.2统计软件进行Meta分析。结果:共纳入7项RCT,合计2 378例患者。Meta分析结果显示,阿戈美拉汀组患者有效率[RR=1.43,95%CI(1.29,1.59),P<0.001]、缓解率[RR=1.27,95%CI(1.03,1.57),P=0.02]均显著高于安慰剂组,抑郁量表终点评分值显著低于安慰剂组[MD=-2.92,95%C(I-3.65,-2.20),P<0.001],两组比较差异均有统计学意义。结论:阿戈美拉汀治疗抑郁症急性期的疗效显著。但受纳入研究方法学质量和样本量限制,该结论有待更多设计严格、长期随访的大样本RCT加以验证。     

阿托伐他汀对稳定期COPD患者肺功能、肺动脉压及相关指标影响的Meta分析

目的:系统评价阿托伐他汀对稳定期慢性阻塞性肺疾病(COPD)患者肺功能、肺动脉压及相关指标的影响,为临床提供循证参考。方法:计算机检索Cochrane图书馆、PubMed、EMBase、中国期刊全文数据库、中文科技期刊数据库,收集阿托伐他汀联合常规基础方案(试验组)对比单纯常规基础方案(对照组)治疗稳定期COPD的随机对照试验(RCT),提取资料并按照Cochrane系统评价员手册5.1.0评价质量后,采用Rev Man 5.3统计软件进行Meta分析。结果:共纳入7项RCT,合计371例患者。Meta分析结果显示,试验组患者第1秒用力呼气容积[MD=0.07,95%CI(0.04,0.09),P<0.001]、第1秒用力呼气容积占预计值百分比[MD=6.18,95%CI(2.23,10.12),P=0.002]、6分钟步行距离[MD=55.31,95%CI(36.44,74.18),P<0.001]均显著高于/长于对照组,肺动脉收缩压[MD=-6.78,95%CI(-11.62,-1.94),P=0.006]、平均肺动脉压[MD=-6.61,95%CI(-7.26,-5.96),P<0.001]、圣乔治呼吸问卷评分[MD=-13.21,95%CI(-23.90,-2.52),P=0.02]均显著低于对照组,差异均有统计学意义;两组患者第1秒用力呼气容积占用力肺活量比值[MD=3.73,95%CI(-2.08,9.55),P=0.21]和高敏C反应蛋白水平[MD=0.29,95%CI(-1.37,1.95),P=0.73]比较,差异均无统计学意义。结论:阿托伐他汀用于稳定期COPD患者可以显著改善患者肺功能和肺动脉压,提高患者生活质量。     

艾塞那肽治疗2型糖尿病疗效及安全性的Meta分析

目的:评价人胰高血糖素样肽-1(GLP-1)抑制剂艾塞那肽治疗2型糖尿病的疗效及安全性。方法:计算机检索EMBase、PubMed、Coehrane、中国期刊网数据库(CNKI)、万芳数据库(VIP)、中国生物医学文献数据库(CBM)数据库,纳入相关随机对照试验(RCT),对纳入的RCT进行质量评价并提取相关资料。应用RevMan 5.2软件进行Meta分析,计算均数差(MD)、相对风险度(RR)和95%置信区间(CI)。结果:共纳入8个RCT进行分析。Meta分析结果显示:艾塞那肽组在改善2型糖尿病患者糖化血红蛋白和空腹血糖水平方面显著优于安慰剂[MD=-0.86,95%CI(-0.95,-0.77),P<0.01;MD=-1.06,95%CI(-1.52,-0.59),P<0.01]。在不良反应发生率方面,艾塞那肽组发生恶心和呕吐的相对风险度显著增高[RR=3.91,95%CI(2.36,6.47),P<0.01;RR=3.73,95%CI(1.67,8.34),P=0.01]。合用磺酰脲类治疗时,艾塞那肽组发生低血糖的相对风险度较安慰剂显著增高[RR=3.55,95%CI(1.55,8.16),P<0.01];未合用磺酰脲类治疗时,则与安慰剂组无显著性差异[RR=1.03,95%CI(0.74,1.43),P=0.87]。结论:艾塞那肽可显著改善2型糖尿病患者糖化血红蛋白和空腹血糖水平,但恶心和呕吐不良反应发生风险增高,同时与磺酰脲类药物合用可能会增加低血糖风险。     

鼻内给予右美托咪定对比口服水合氯醛用于儿童程序化镇静有效性和安全性的Meta分析

目的:系统评价鼻内给予右美托咪定对比口服水合氯醛用于儿童程序化镇静的有效性和安全性。方法:计算机检索Cochrane图书馆、PubMed、Embase、中国生物医学文献数据库、中国知网数据库和万方数据库,收集鼻内给予右美托咪定(试验组)对比口服水合氯醛(对照组)用于儿童程序化镇静的随机对照试验(RCT)。筛选文献、提取资料后采用Cochrane 5.1.0偏倚风险评估工具对纳入文献质量进行评价,采用Rev Man 5.3软件进行Meta分析。结果:共纳入8项RCT,共计1 413例患儿。Meta分析结果显示,试验组患儿镇静成功率[RR=1.13,95%CI(1.02,1.25),P=0.02]、镇静起效时间[MD=-1.07,95%CI(-1.82,-0.31),P=0.006]、镇静持续时间[MD=-8.25,95%CI(-14.02,-2.47),P=0.005]、苏醒时间[MD=-9.63,95%CI(-15.40,-3.86),P=0.001]、恶心呕吐发生率[RR=0.05,95%CI(0.02,0.14),P<0.000 01]均显著优于对照组;两组患儿血氧饱和度<95%发生率[RR=0.60,95%CI(0.24,1.54),P=0.29]、低血压发生率[RR=1.18,95%CI(0.51,2.74),P=0.71]、心动过缓发生率[RR=1.33,95%CI(0.18,9.88),P=0.78]比较,差异均无统计学意义。结论:鼻内给予右美托咪定相较于口服水合氯醛用于儿童程序化镇静的效果更优,且安全性较好。     

六味五灵片联合恩替卡韦治疗慢性乙型肝炎的Meta分析

目的:系统评价六味五灵片联合恩替卡韦治疗慢性乙型肝炎的有效性,为临床提供循证参考。方法:计算机检索Cochrane图书馆、PubMed、Web of Science、中国期刊全文数据库(CJFD)、万方数据库和中文科技期刊数据库(VIP),收集六味五灵片联合恩替卡韦(试验组)对比恩替卡韦单用(对照组)治疗慢性乙型肝炎的随机对照试验(RCT),提取数据并按照Cochrane系统评价员手册5.1.0评价质量后,采用Rev Man 5.3统计软件进行Meta分析。结果:最终纳入8项RCT,共计728例患者。Meta分析结果显示,试验组患者血清丙氨酸转氨酶[MD=-16.67,95%CI(-19.83,-13.51),P<0.001]、天冬氨酸转氨酶[MD=-20.52,95%CI(-25.65,-15.39),P<0.001]、总胆红素[MD=-5.85,95%CI(-11.31,-0.38),P=0.04]水平显著低于对照组,临床总有效率[RR=1.23,95%CI(1.03,1.46),P=0.02]和乙肝e抗原(HBe Ag)转阴率[RR=1.26,95%CI(1.03,1.54),P=0.02]显著高于对照组,差异均有统计学意义。两组患者血清乙肝病毒基因转阴率比较,差异无统计学意义[RR=1.22,95%CI(0.99,1.52),P=0.07]。结论:与恩替卡韦单用相比,六味五灵片联合恩替卡韦治疗慢性乙型肝炎疗效较好,可以显著改善患者肝功能生化指标。     

Quantitative in vivo and in vitro sex differences in artemisinin metabolism in rat

1. The pharmacokinetics of the antimalarial compound artemisinin were compared in the male and female Sprague-Dawley rat after single dose i.v. (20 mg.kg) or i.p. (50 mg.kg) administration of an emulsion formulation. 2. Plasma clearance of artemisinin was 12.0 (95% confidence interval: 10.4, 13.0) l.h. kg in the male rat and 10.6 (95% CI: 7.5, 15.0) l.h. kg in the female rat suggesting high hepatic extraction in combination with erythrocyte uptake or clearance. Artemisinin half-life was 0.5 h after both routes of administration in both sexes. Values for plasma clearance and half-lives did not statistically differ between the sexes. 3. After i.p. administration artemisinin AUCs were 2-fold higher in the female compared with male rat (p 0.001). Artemisinin disappearance was 3.9-fold greater in microsomes from male compared with female livers and it was inhibited in male microsomes by goat or rabbit serum containing antibodies against CYP2C11 and CYP3A2 but not CYP2B1 or CYP2E1. 4. The unbound fraction of artemisinin in plasma was lower (p 0.001) in plasma obtained from the male (8.8 2.0%) compared with the female rat (11.7 2.2%). 5. The possibility of a marked sex difference, dependent on the route of administration, has to be taken into account in the design and interpretation of toxicological studies of artemisinin in this species.     

Quantitative in vivo and in vitro sex differences in artemisinin metabolism in rat

1. The pharmacokinetics of the antimalarial compound artemisinin were compared in the male and female Sprague-Dawley rat after single dose i.v. (20 mg x kg(-1)) or i.p. (50 mg x kg(-1)) administration of an emulsion formulation. 2. Plasma clearance of artemisinin was 12.0 (95% confidence interval: 10.4, 13.0) 1 x h(-1) x kg(-1) in the male rat and 10.6 (95% CI: 7.5, 15.0) 1 x h(-1) x kg(-1) in the female rat suggesting high hepatic extraction in combination with erythrocyte uptake or clearance. Artemisinin half-life was approximately 0.5 h after both routes of administration in both sexes. Values for plasma clearance and half-lives did not statistically differ between the sexes. 3. After i.p. administration artemisinin AUCs were 2-fold higher in the female compared with male rat (p < 0.001). Artemisinin disappearance was 3.9-fold greater in microsomes from male compared with female livers and it was inhibited in male microsomes by goat or rabbit serum containing antibodies against CYP2C11 and CYP3A2 but not CYP2B1 or CYP2E1. 4. The unbound fraction of artemisinin in plasma was lower (p < 0.001) in plasma obtained from the male (8.8 +/- 2.0%) compared with the female rat (11.7 +/- 2.2%). 5. The possibility of a marked sex difference, dependent on the route of administration, has to be taken into account in the design and interpretation of toxicological studies of artemisinin in this species.     

Interindividual variability in metabolic activation in humans in vivo

In assessing interindividual variability in metabolic activation, the toxic metabolite is often too unstable for conventional analysis. Possible alternatives include a stable product of the reactive metabolite e.g. cysteinyl derivatives of N-acetyl-4-benzoquinoneimine, the toxic metabolite of paracetamol, adducts with DNA or protein, and indirect measurement of the activity of the enzyme(s) producing the active metabolite. An example of the last approach is the use of furafylline, a highly specific inhibitor of human CYP1A2, to determine the extent of the metabolic activation of the cooked food mutagens PhIP and MeIQx. The extent of inhibition, determined from levels of unchanged amine in urine, is an indirect measure of the activity of the activation pathway. Further refinement of this approach, allied to improved measures of the biological process of interest should prove of value in evaluating interindividual variability and its role in the risk assessment process.     

Theophylline kinetics in peripheral tissues in vivo in humans

Several biochemical and cellular effects have been described for methylxanthines under in vitro conditions. However, it is unknown, whether threshold concentrations required to exert these effects are attained in target tissues in vivo. We therefore employed the microdialysis technique for measuring theophylline concentrations in peripheral tissues under in vivo conditions.Following in vitro and in vivo calibration, microdialysis probes were inserted into the medial vastus muscle and into the periumbilical subcutaneous adipose layer of healthy volunteers. Following single oral dose administration of 300 mg or i.v. infusion of 240 mg theophylline, in vivo time courses of theophylline concentrations were monitored in tissues and plasma. Major pharmacokinetic parameters (c_max, t_max, AUC) were calculated for plasma and tissue time courses. The mean AUC_tissue /AUC_plasma-ratio was 0.56 (p.o.) and 0.55 (i.v.) for muscle and 0.55 (p.o.) and 0.72 (i.v.) for subcutaneous adipose tissue.We conclude that microdialysis provides important information on the distribution and the tissue pharmacokinetics of theophylline.Abbreviations FPIA Fluorescence polarisation immuno assay - AUC Area under the curve - t_max Time to peak concentration - c_max Peak concentration     

休克时血中氧自由基的变化

本实验测定10名休克患者血浆和红细胞的丙二醛(MDA)、血浆总抗的氧化活性(AOA)的含量。结果表明:休克病人红细胞膜和血浆 MDA 含量(4.298±0.722;5.348±0.834)与对照组(3.235±0.682;4.356±1.081)比较明显增高(P<0.05);血浆 AOA(39.65±7.858)与对照组(48.21±10.81)比较明显降低(P<0.01)。提示:休克时,患者机体内自由基反应增强是引起组织细胞损伤的原因之一。     

Changes in angiopoietin expression in glomeruli involved in glomerulosclerosis in rats with daunorubicin-induced nephrosis

AIM: To study the potential pathological role of endogenous angiopoietins in daunorubicin-induced progressive glomerulosclerosis in rats. METHODS: Seventy male Wistar rats were allocated randomly into a daunorubicin group (DRB; n=40) or a control group (n=30). The rats in the DRB group were injected with DRB (15 mg/kg), in their tails. Subsequently, at intervals of 1, 2, 4, 6, 8, and 12 weeks, 5 male Wistar rats in each group were chosen randomly for 24 h urinary protein quantitative measurements (24 h UPQM), and determination of plasma tumor necrosis factor alpha (TNF-alpha), angiopoietin-1 (Ang1), and angiopoietin-2 (Ang2) levels. Kidney sections were examined by electron microscopy, Periodic Acid Schiff (PAS) staining, immunohistochemical staining and in situ hybridization histochemistry. RESULTS: As glomerulosclerosis progressed in the DRB group, expression of Ang1 mRNA and protein in glomeruli decreased and expression of TNF-alpha protein, Ang2 mRNA and protein in glomeruli increased. Expression of Ang1 mRNA and protein in glomeruli were negatively correlated with 24 h UPQM, Fn protein expression, and mean area of extracellular matrix (MAECM). In comparison, expression of Ang2 mRNA and protein in glomeruli were positively correlated with 24 h UPQM, Fn protein expression and MAECM; furthermore, there was a positive correlation between plasma Ang2 and 24 h UPQM. Plasma TNF-alpha and expression of TNF-alpha in glomeruli were positively correlated with expression of Ang2 mRNA and protein in glomeruli. There was a negative correlation between Ang1 protein expression and Ang2 protein expression in glomeruli. CONCLUSION: During DRB-induced glomerulosclerosis, podocyte injury led to a shift in the balance of Ang1 and Ang2 in glomeruli. Increased TNF-alpha in plasma and glomeruli may upregulate Ang2 expression in glomeruli. Elevated Ang2 in both plasma and glomeruli may mediate protein permeability through the glomerular filtration barrier. Moreover, local expression of Ang2 may facilitate the progress of glomerulosclerosis by upregulating a component expression of extracellular matrix.     

Trichinellosis in immigrants in Switzerland

We describe a case of trichinellosis diagnosed at the Division of Infectious Diseases, Hospital of Lugano, in January 2009. This case was associated with a cluster of cases and was traced to the consumption of contaminated meat after a wild boar hunt in Bosnia.