七叶皂苷联合依达拉奉治疗脑出血有效性和安全性的Meta分析

摘 要 目的：采用Meta分析方法评价七叶皂苷联合依达拉奉治疗脑出血的有效性与安全性。方法：计算机检索PubMed、Embase、the Cochrane Library、CNKI、WangFang Data、SinoMed和VIP,检索时限均从各数据库建库至2016年4月,纳入七叶皂苷联合依达拉奉治疗脑出血的随机对照试验（RCT）,进行数据提取和质量评价后,使用RevMan 5.3软件进行Meta分析。结果以均数差（MD）、相对危险度（RR）、比值比（OR）、95%置信区间（CI）等指标进行分析。结果：共纳入13个RCT,共计1 046例患者。Meta分析结果显示：七叶皂苷联合依达拉奉能够提高临床疗效（RR=1.38, 95%CI：1.27~1.49, P<0.000 01）,减少NIHSS评分（MD=-4.98, 95%CI：-6.85~-3.21, P<0.000 01）和NDS评分（MD=-7.98, 95%CI：-12.03~-3.93, P=0.000 1）,有效地减少脑水肿体积（MD=-2.61, 95%CI：-3.99~-1.22, P=0.000 2）与脑出血体积（MD=-6.03, 95%CI：-11.35~-0.70, P<0.03）;安全性方面因仅1项研究报道了不良反应发生情况,故无法评价。结论：七叶皂苷联合依达拉奉能够有效地提高临床疗效,减少NIHSS评分或NDS评分缩小患者的脑水肿、脑血肿的体积,但是其安全性仍需要进一步的探讨。     

基于Meta分析的复方苦参注射液联合FOLFOX化疗方案治疗大肠癌临床评价研究

摘 要 目的：系统评价复方苦参注射液联合FOLFOX化疗方案治疗大肠癌临床疗效及安全性。方法：EMBASE、PubMed、Cochrane Library、CancerLit、中国期刊全文数据库（CNKI）、中文科技期刊全文数据库（VIP）、中国生物医学文献数据库（SinoMed）、万方数据库等数据库1979~2016年文献,全面搜集复方苦参注射液联合FOLFOX化疗方案治疗大肠癌的随机对照试验,对纳入文献进行质量评价,提取资料并通过RevMan 5.3软件进行数据分析。结果：共纳入26 篇文献,累计2 269例受试者。Meta 分析结果显示：在FOLFOX化疗方案基础上联用复方苦参注射液治疗大肠癌的临床疗效优于对照组仅用FOLFOX化疗方案 （RR=1.35, 95%CI：1.23~1.40, P＜0.000 01）, 生存质量明显改善（RR=1.58, 95%CI: 1.37~1.83, P<0.000 01）。此外,复方苦参注射液还可降低化疗引起的不良反应的发生率,如白细胞减少（RR=0.62,95%CI：0.42~0.93,P=0.02）,恶心呕吐（RR=0.63, 95%CI: 0.50~0.80, P=0.000 2）。 结论：〖JP〗复方苦参注射液联合FOLFOX化疗方案在治疗大肠癌方面具有较好的疗效。     

基于Meta分析的参麦注射剂辅助治疗急性白血病临床评价研究

摘 要 目的：采用Meta分析方法评价参麦注射剂辅助化疗药物治疗急性白血病的有效性及安全性。方法：计算机检索the Cochrane library、PubMed、Embase、SinoMed、中国知网、维普期刊数据库和万方数据库有关参麦注射剂治疗急性白血病的随机对照临床试验文献,检索时限为各数据库建库至2016年9月1日。采用Cochrane风险评价表评价其研究质量,提取资料通过RevMan5.3软件进行Meta分析。结果：共纳入12个随机对照试验,累计患者775例。Meta分析结果显示,与仅采用化疗药物治疗的对照组比较,参麦注射剂辅助化疗药物治疗可提高临床总有效率（RR=1.15,95% CI：1.06~1.25,P=0.001）;此外,参麦注射剂辅助化疗药物治疗还可以缓解化疗药物引起的不良反应,如恶心呕吐（RR=0.63,95%CI：0.49~0.81,P=0.000 4）、白细胞减少（RR=0.58,95%CI：0.41~0.82,P=0.002）及心脏毒性（RR=0.36,95%CI：0.22~0.60,P<0.0001）的发生率低于对照组。结论：参麦注射剂辅助化疗药物治疗急性白血病具有较好的疗效,且能缓解化疗引起的不良反应,值得临床推广。但受纳入文献方法学质量的限制,本研究结论有待大样本、多中心的随机对照试验进一步验证。     

替格瑞洛用于急性冠脉综合征的卫生技术评估

摘 要 目的：评估新型血小板P2Y12受体抑制药替格瑞洛治疗急性冠脉综合征（ACS）的有效性、安全性和经济性,为临床用药和决策提供证据支持。方法：计算机检索PubMed、Embase、the Cochrane Library、Web of Science、CNKI和SinoMed等数据库,按照纳入排除标准筛选已发表的HTA报告、系统评价/Meta分析、RCT、药物经济学分析,并评价其研究质量。对RCT研究结果进行Meta分析,对其他研究结果进行定性分析。结果：在有效性上,与氯吡格雷相比,替格瑞洛可显著降低主要心脏不良事件的发生率（RR=0.86,95%CI：0.79~0.94,P=0.000 4）、心血管死亡率（RR=0.77,95%CI：0.68~0.88,P＜0.000 1）、全因死亡率（RR=0.81,95%CI：0.71~0.91,P=0.000 8）、心肌梗死发生率（RR=0.82,95%CI：0.73~0.91,P=0.000 2）、支架内血栓发生率（RR=0.74,95%CI：0.61~0.91,P=0.004）。在安全性上,与氯吡格雷相比,替格瑞洛对主要出血发生率（RR=1.04,95%CI：0.96~1.13,P=0.30）和心动过缓发生率（RR=1.12,95%CI：0.98~1.28,P=0.08）无明显影响,但增加了主要或次要出血的发生率（RR=1.28,95%CI：1.04~1.58,P=0.02）和呼吸困难的发生率（RR=1.76,95%CI：1.62~1.91,P<0.000 01）。在经济性上,替格瑞洛比氯吡格雷和基因检测指导的抗血小板治疗更具有经济性。结论：替格瑞洛用于ACS具有有效性、安全性和经济性。     

抑酸药预防术后应激性溃疡出血的系统评价

摘 要 目的：评价抑酸药［包括质子泵抑制药（PPI）和H2受体阻断药（H2RA）］对比安慰剂（或空白对照）预防术后应激性溃疡出血（SUB）的疗效和安全性,为临床提供循证依据。方法: 检索Cochrane图书馆临床对照试验数据库、MEDLINE光盘数据库、EMbase光盘数据库、中国知网中国期刊全文数据库、中国生物医学文献数据库、中国科技期刊全文数据库、万方数字化期刊全文数据库、临床实验注册网站（clinicaltrials.gov, ISRCTN Register和WHO ICTRP）,收集抑酸药与安慰剂（或空白对照）比较用于预防术后SUB,以出血发生率、病死率、不良反应发生率、胃液pH和住院天数中任何一项作为研究终点的随机对照试验（RCT）。对纳入研究进行资料提取和偏倚风险评价,采用 Stata12.0软件进行Meta分析,结果以相对危险度（RR）以及95% 置信区间（CI）表示,并应用Grade分别评价终点指标的证据质量等级,漏斗图和Eggers test 检验判断是否存在发表偏倚。 结果: 15项RCT（971例）用于Meta分析。Meta分析结果显示抑酸药在预防SUB、显性出血和临床大出血发生率方面均优于安慰剂或空白对照（RR 0.29,95%CI：0.19～0.45;RR 0.25,95%CI：0.10～0.64;RR 0.36,95%CI：0.17～0.77）（中等证据强度）,两组在隐性出血、病死率和不良反应发生率方面差异无统计学意义（RR 0.79,95%CI：0.41～1.50;RR 0.49,95%CI：0.17～1.38;RR 0.78,95%CI：0.33～1.85）（极低强度证据）。亚组分析显示预防使用PPI的研究,术后SUB发生率（RR=0.27）低于使用H2RA的研究（RR=0.33）;心脏科手术后SUB发生率（RR=0.20）分别低于普通外科（RR=0.23）和神经外科（RR=0.37）的研究;术前给药的术后SUB发生率（RR=0.31）高于术后给药的研究（RR=0.26）。 结论:预防用抑酸药可有效降低术后SUB的发生率,且不增加不良反应发生率和死亡率。但纳入研究方法学质量普遍偏低,部分文献的结局指标不全面,缺乏肺炎、难辨梭菌感染等安全性指标。今后尚需进一步开展高质量、大样本的临床研究验证其临床效果。     

基于Meta分析的红花注射液治疗不稳定型心绞痛临床评价研究

摘 要 目的：运用Meta分析方法评价红花注射液联合西医常规治疗不稳定型心绞痛的临床疗效及安全性。方法：系统检索 Embase、PubMed、the Cochrane Library、中国期刊全文数据库（CNKI）、中文科技期刊全文数据库（VIP）、中国生物医学文献数据库（SinoMed）、万方数据库,检索时间从各数据库建库至2016年6月1日,全面搜集红花注射液联合西医常规治疗不稳定型心绞痛的随机对照试验,对纳入文献进行质量评价,提取资料并通过RevMan 5.3软件进行数据分析。结果：共纳入9篇文献,累计876例受试者。Meta分析结果显示：在常规用药的基础上,联合使用红花注射液可提高心绞痛疗效（RR＝1.31, 95%CI: 1.22~1.40, P<0.000 01）和心电图疗效(RR=1.40, 95%CI:1.24~1.59,P<0.000 01);但红花注射液不能明显改善不稳定型心绞痛患者的血浆黏度。仅4篇文献记录了药品不良反应发生情况,未发生严重不良反应。结论：在西医常规治疗的基础上联合使用红花注射液对不稳定型心绞痛有较好的疗效,但其安全性仍需进一步探讨。     

艾迪注射液辅助治疗肝癌的Meta分析

摘 要 目的：运用Meta分析方法评价艾迪注射液联合肝动脉栓塞化疗治疗肝癌的临床疗效及安全性。方法：计算机检索PubMed、The Cochrane Library、Embase、中国期刊全文数据库（CNKI）、中国生物医学文献服务系统（SinoMed）、中文科技期刊数据库（VIP）、万方数据库,检索时间为各数据建库至2016年10月8日,全面搜集艾迪注射液联合肝动脉栓塞化疗治疗肝癌的随机对照试验,对纳入文献进行质量评价,提取资料并通过RevMan 5.3软件进行数据分析。结果：本研究共纳入33篇文献,累计2 306例受试者。Meta 分析结果显示：在肝动脉栓塞化疗基础上联用艾迪注射液治疗肝癌可以提高临床总有效率（RR=1.31,95%CI：1.20~1.43,P<0.000 01）,改善生存质量（RR=1.86,95%CI：1.65~2.09,P<0.000 01）。此外,艾迪注射液还可改善化疗引起的不良反应、提高肝癌患者生存率。结论：现有临床证据表明,在肝动脉栓塞化疗基础上联用艾迪注射液对肝癌有一定的辅助治疗作用。但本研究结论尚需更多设计良好、严格执行的大样本随机对照双盲试验加以证实。     

冠心病抗血小板治疗加用口服Ⅹa因子抑制药有效性及安全性的Meta分析

摘 要 目的：采用Meta分析方法评价冠心病抗血小板治疗基础上加用口服Ⅹa因子抑制药的有效性及安全性。方法：计算机检索PubMed、the Cochrane Library、Embase、Clinical Trials.gov、CNKI、WanFang Data数据库,搜集关于冠心病患者加用口服Ⅹa因子抑制药的随机对照试验（RCTs）,检索时限均为建库至2018年2月,由两名研究者独立筛选文献、提取资料并评价纳入研究的偏倚风险后,采用RevMan 5.0软件进行Meta分析。 结果：共纳入7项研究,共有50 044例患者。Meta分析结果显示：加用口服Ⅹa因子抑制药可减少缺血复合终点事件发生率[RR=0.84,95%CI（0.79,0.91）,P<0.001]、全因死亡率[RR=0.88,95%CI（0.79,0.97）,P=0.01]、心肌梗死发生率[RR=0.89,95%CI（0.80,0.98）,P=0.02]及缺血性卒中发生率[RR=0.63,95%CI（0.51,0.78）,P<0.001];然而却明显增加TIMI大出血的风险[RR=3.22,95%CI（2.35,4.42）,P<0.001]、TIMI小出血的风险[RR=2.40,95%CI（1.69,3.41）,P<0.001]及颅内出血的风险[RR=1.83,95%CI（1.20,2.81）,P=0.005]。加用Ⅹa因子抑制药对增加致命性出血风险的差异无统计学意义[RR=1.63,95%CI（0.96,2.78),P=0.07]。结论：冠心病标准抗血小板治疗基础上加用口服Ⅹa因子抑制药是有效的,可以减少缺血复合终点事件、全因死亡、心肌梗死、缺血性卒中的发生风险,但安全性方面,口服Ⅹa因子抑制药会增加出血风险。     

基于Meta分析的参芪扶正注射剂辅助治疗大肠癌临床评价研究

摘 要 目的：采用Meta分析方法评价参芪扶正注射剂联合FOLFOX化疗方案治疗大肠癌临床疗效及安全性。方法：计算机检索Embase、PubMed、the Cochrane Library、中国期刊全文数据库（CNKI）、中文科技期刊全文数据库（VIP）、中国生物医学文献数据库（SinoMed）、万方数据库有关参芪扶正注射剂联合FOLFOX化疗方案治疗大肠癌的随机对照试验,对纳入文献进行质量评价,提取资料并通过RevMan 5.3软件进行数据分析。结果：共纳入11 篇文献,累计943例受试者。Meta 分析结果显示：在FOLFOX化疗方案基础上,联用参芪扶正注射剂可以提高临床总有效率（RR=1.40,95%CI：1.21~1.61,P=0.000 01）,改善患者生存质量（RR=1.76,95%CI：1.40~2.23,P<0.000 01）,此外,参芪扶正注射剂还可改善化疗引起的不良反应,如消化道反应（RR=0.61,95%CI：0.51~0.74,P<0.000 01）,白细胞减少（RR=0.60,95%CI：0.49~0.74,P<0.000 01）,血小板减少（RR=0.51,95%CI：0.37~0.71,P<0.000 01）,肝功能异常（RR=0.54,95%CI：0.36~0.80,P=0.002）。 结论：参芪扶正注射剂联合FOLFOX化疗方案在治疗大肠癌方面具有较好的疗效,但本研究结论还需要进一步大样本严格的随机对照试验来证实。     

基于Meta分析的醒脑静注射剂治疗急性脑梗死临床评价研究

摘 要 目的：采用Meta分析方法评价醒脑静注射剂辅助西医常规治疗急性脑梗死的有效性及安全性。方法：计算机检索the Cochrane Library、PubMed、Embase、SinoMed、中国期刊全文数据库（CNKI）、中文科技期刊全文数据库（VIP）、万方数据库中有关醒脑静注射剂治疗急性脑梗死的随机对照试验,文献检索年限为各数据库建库至2016年9月。采用Cochrane风险评估表评价其质量,通过RevMan 5.3软件提取资料并进行Meta分析。结果：共纳入24个随机对照试验,累计2 514名患者。Meta分析结果显示,醒脑静注射剂辅助西医常规治疗与仅用西医常规治疗方法相比,可提高临床总有效率（RR＝1.22, 95%CI：1.18~1.27, P<0.000 01)。此外,醒脑静注射剂也可改善神经功能缺损情况（MD＝-3.93, 95%CI：-5.04~-2.82, P<0.000 01）,影响血液流变学指标。有8个随机对照试验共报告发生了38例不良反应,7个随机对照试验报告未发生明显不良反应。结论：醒脑静注射剂辅助西医常规治疗急性脑梗死具有较好的疗效,但其安全性需进一步探讨。     

Affective and Anxiety Disorders and Alcohol and Drug Dependence:

Depression and anxiety frequently coexist in patients with substance use disorders. This clinically-oriented article examiens the relationship between these conditions and emphasizes data showing that substances of abuse can cause signs and symptoms of both depression and anxiety. These substance-related syndromes appear to have a different course and prognosis than uncomplicated, independent anxiety and major depressive disorders, and clinicians should consider the role of alcohol and other drugs in all patients presenting with these complaints. The authors will also outline an approach for diagnosing and managing patients with the combination of a substance use and depressive or anxiety disorder.     

Synthesis and anti-nociceptive and anti-inflammatory effects of gaultherin and its analogs

The synthesis of gaultherin (1) and its analogs was carried out to provide 11 glycosides under phase-transfer catalytic conditions. The activities of all synthesized compounds were evaluated by nitric oxide production inhibitory assay in vitro. Methyl 2-O-(4-O-β-d-galactopyranosyl)-β-d-glucopyranosylbenzoate (5f) showed significantly anti-nociceptive and anti-inflammatory effects by the evaluation in vivo. Structure–activity relationships within these compounds were discussed.     

Modelling and simulation of variability and uncertainty in toxicokinetics and pharmacokinetics

Two important methodological issues within the framework of the variability and uncertainty analysis of toxicokinetic and pharmacokinetic systems are discussed: (i) modelling and simulation of the existing physiologic variability in a population; and (ii) modelling and simulation of variability and uncertainty when there is insufficient or not well defined (e.g. small sample, semiquantitative, qualitative and vague) information available. Physiologically based pharmacokinetic models are especially suited for separating and characterising the physiologic variability from the overall variability and uncertainty in the system. Monte Carlo sampling should draw from multivariate distributions, which reflect all levels of existing dependencies in the intact organism. The population characteristics should be taken into account. A fuzzy simulation approach is proposed to model variability and uncertainty when there is semiquantitative, qualitative and vague information about the model parameters and their statistical distributions cannot be defined reliably.     

成骨细胞的功能与损伤和骨质疏松的防治

骨质疏松是一种全身性骨骼疾病,导致骨折风险增加。成人的骨量通过破骨细胞的骨吸收和成骨细胞的骨形成作用来维持动态平衡,治疗骨质疏松症的理想策略是抑制破骨细胞的骨吸收和/或增强成骨细胞的骨形成功能。目前针对保护成骨细胞及增强其功能的骨质疏松疗法相对较少。因此,本文针对成骨细胞相关功能蛋白、各种细胞损伤机制（内质网应激、氧化应激、机械过载、微小RNA和长链非编码RNA的影响等）及骨质疏松的治疗与预防作一综述,以期为针对增强成骨细胞功能的骨质疏松治疗策略提供新思路。     

Self-stimulation and amphetamine: Tolerance to d and l isomers and cross tolerance to cocaine and methylphenidate

The effects of the d and l isomers of amphetamine on self-stimulation responding were tested following acute and chronic administration. Tolerance and post-drug depression of responding occurred in tests with both isomers, indicating no role for p-hydroxynorephedrine (PHN) which is one of the metabolites of d-amphetamine. In the second experiment, d-amphetamine, methylphenidate and cocaine all produced quantitatively and qualitatively similar effects on self-stimulation responding following acute administration. Following chronic administration of d-amphetamine, animals showed tolerance to all three drugs, indicating cross-tolerance among them. These data are consistent with an hypothesis that tolerance and post-drug depression following chronic amphetamine treatment are the result of decreases in postsynaptic receptor sensitivity, which would lead to a decreased effectiveness of all three drugs, regardless of their pre-synaptic mechanisms.     

益生菌与肿瘤防治

益生菌广泛存在于自然界中,通过维持宿主体内菌群平衡、影响肠屏障功能和调节免疫应答等作用,提高宿主健康水平,被公认为"肠道健康卫士".一些益生菌可以增强机体的免疫功能,抑制致癌物质,影响肿瘤细胞的基因表达,对肿瘤具有拮抗作用.大量研究表明,益生菌在未来的肿瘤防治中有很好的应用和发展前景.     

Acamprosate and naltrexone treatment effects on ethanol and sucrose seeking and intake in ethanol-dependent and nondependent rats

Rationale  Two pharmacotherapies are approved for treating alcohol craving (acamprosate and naltrexone), but both have shown mixed findings in animals and humans. Objectives  The present experiments utilized a “reinforcer blocking” approach (i.e., rats were able to consume ethanol during treatment) to better understand the efficacy of these treatments for ethanol seeking and drinking using ethanol-dependent and nondependent rats. Materials and methods  In “nondependent” experiments, drugs (acamprosate 50, 100, and 200 mg/kg; naltrexone 0.1, 0.3, and 1.0 mg/kg) were administered over 3-week periods prior to operant sessions with a low response requirement to gain access to reinforcers for 20 min. For “dependent” experiments, rats were made dependent in vapor/inhalation chambers. Results  Acamprosate and naltrexone had similar effects on intake in nondependent and dependent rats; neither drug was selective for ethanol over sucrose drinking. In nondependent animals, naltrexone was more efficacious at more doses than acamprosate, and acamprosate’s effects were limited to a dose that also had adverse effects on body weight. Both pharmacotherapies showed more selectivity when examining reinforcer seeking. In nondependent rats, acamprosate and naltrexone had response-attenuating effects in ethanol, but not sucrose, groups. In dependent animals, acamprosate had selective effects limited to a decrease in sucrose seeking. Naltrexone, however, selectively decreased ethanol-seeking in nondependent rats. Conclusions  The naltrexone-induced decreases in seeking suggested a change in incentive motivation which was selective for ethanol in nondependent rats. The “nondependent” paradigm may model early stages of “problem drinking” in humans, and the findings suggest that naltrexone could be a good intervention for this level of alcohol abuse and relapse prevention.     

Antiinfective and encrustation-inhibiting materials--myth and facts

Catheters, urethral and ureteral stents and other urological implants are frequently affected by encrustration and infection due to their permanent contact with urine. Indwelling urinary catheters provide a haven for microorganisms and thus require extensive monitoring. Several surface modification techniques have been proposed to improve the performance of devices including the immobilization of biomolecules, the incorporation of hydrophilic grafts to reduce protein adsorption, the creation of hydrophobic surfaces, the creation of microdomains to regulate cellular and protein adhesion, new polymers and antimicrobial coatings. Physico-chemical explanation to elucidate the mechanism of such encrustation or infection inhibiting materials is still not available. Our series of experiments showed a marked decrease of silver-activity in biological fluids which corresponds with the controversial clinical results obtained with silver coated urinary catheters. Rifampicin/minocycline coated catheters had very low activity against Gram-negative rods, enterococci and Candida spp., the main causing organisms of urinary catheter infection. Surface engineered materials and antimicrobial drug delivery systems will be the next generation of sophisticated urinary catheters and stents, if both efficacy as well as efficiency has been proved clinically.     

Alprazolam and lorazepam single and multiple-dose effects on psychomotor skills and sleep

Summary The effects of alprazolam 0.5 mg and lorazepam 2 mg on cognitive and psychomotor skills were assessed in twelve normal volunteer subjects in a randomised, double-blind, crossover design. Single and multiple dose effects were monitored using a battery of tests comprising critical flicker fusion threshold (CFFT), choice reaction time (CRT), simulated car tracking, and subjective ratings of perceived sedation (LARS) and of sleep behaviour (LSEQ). Compared with placebo baseline scores, treatment with lorazepam 2 mg (both single and multiple doses) resulted in a widespread impairment of CRT, tracking accuracy, and CFFT. Single doses of alprazolam 0.5 mg reduced CFFT with respect to the placebo baseline. Single and multiple dose treatment with both drugs resulted in subjective reports of sedation, a reduction of sleep onset latency, and improved sleep quality. Only lorazepam 2 mg significantly disrupted the integrity of behaviour on waking from sleep. These results suggest important pharmacodynamic differences between the two drugs in the doses used.