雷替曲塞治疗中晚期原发性肝癌的疗效与安全性的Meta分析

摘 要 目的：采用Meta分析方法评价雷替曲塞治疗中晚期原发性肝癌的疗效及安全性。方法: 计算机检索 PubMed、Web of Science、Embase、The Cochrane Library、SinoMed、CNKI、VIP、WanFang Data数据库,收集雷替曲塞治疗中晚期原发性肝癌的随机对照试验（RCTs）,检索年限均为建库开始至2017年12月,由两位研究者独立进行文献筛选、资料提取和方法学质量评价后,采用RevMan 5.2软件进行 Meta 分析。结果: 共纳入8项研究,合计821例患者。Meta分析显示,在疗效方面,试验组（雷替曲塞治疗）患者总有效率[OR=2.09,95%CI（1.48,2.93）,P<0.001]、疾病控制率[OR=2.63,95%CI（1.90,3.64）,P<0.001]、1年生存率［OR=2.12,95%CI（1.34,3.34）,P=0.001］、2年生存率［OR=2.93,95%CI（1.76,4.88）,P<0.001］、甲胎蛋白下降率［OR=3.36,95%CI（1.98,5.69）,P<0.001］、转氨酶下降率［OR=2.99,95%CI（1.65,5.43）,P<0.001］、胆红素下降率［OR=3.07,95%CI（1.70,5.55）,P<0.001］,均显著高于对照组（非雷替曲塞治疗）,且差异有统计学意义。在安全性方面,试验组不良反应的发生率均低于对照组,其中胃肠道反应的有统计学意义［OR=0.62,95%CI（0.41,0.93）,P<0.05］。结论: 当前证据显示,雷替曲塞能提高中晚期原发性肝癌的临床疗效,同时减少不良反应发生,该结论有待高质量、大样本的RCTs进一步验证。     

酪氨酸激酶抑制药用于抗肿瘤治疗致肝毒性的Meta分析

摘 要 目的：综合评价肿瘤患者使用酪氨酸激酶抑制药（TKI）导致肝毒性的风险,为临床治疗提供循证参考。方法：计算机检索PubMed、EMBase、SinoMed、Cochrane图书馆、中国期刊全文数据库、万方数据库,搜集TKI对比安慰剂治疗肿瘤的随机对照试验（RCT）,筛选文献,提取资料,采用RevMan 5.2统计软件进行Meta分析。结果：共纳入13篇文献,合计3 931例受试者。Meta分析结果显示,TKI组丙氨酸氨基转氨酶（ALT）升高≥3级的发生率 （OR=3.77,95%CI：2.08~6.83,P<0.000 1）,天门冬氨酸氨基转氨酶（AST）升高≥3级的发生率（OR=3.85,95%CI：2.55~5.82,P<0.000 1）显著高于对照组,而血清总胆红素（TB）升高≥3级的发生率（OR=1.89,95%CI：0.90~3.96,P=0.09）与对照组相比差异无统计学意义。结论：现有的证据表明肿瘤患者使用TKI发生肝毒性的风险显著升高,提示在临床用药过程中,需对患者肝功能进行定期检查及监护。     

法舒地尔注射液治疗动脉瘤术后脑血管痉挛的Meta分析

摘 要 目的：利用Meta分析方法对法舒地尔注射液防治动脉瘤术后脑血管痉挛的疗效和安全性评价分析。方法: 计算机检索PubMed、EMbase、The Cochrane Library、维普、万方、CNKI等数据库公开发表的随机对照研究文献。筛选符合纳入标准的文献进行研究,采用RevMan 5.0软件统计Meta分析。结果: 初检出418篇文献,最终纳入11篇,共786例患者。在治疗动脉瘤性蛛网膜下腔出血的脑血管痉挛的有效率方面,尼莫地平组与法舒地尔组的差异无统计学意义（OR=1.56,95%CI:0.95～2.58,P＞0.05）,法舒地尔组脑血管痉挛的发生率低于尼莫地平组（OR=0.43,95%CI:0.23～0.81,P=0.008）,法舒地尔组不良反应的发生率高于尼莫地平组（OR=0.43,95%CI:0.25～0.75,P=0.003）。结论:与尼莫地平注射液预防动脉瘤性蛛网膜下腔出血的脑血管痉挛的发生率相比,法舒地尔可能有更好的效果,但对于已发生的脑血管痉挛的治疗有效率无明显差异,相反法舒地尔发生不良反应相对较多。     

非洛地平对比硝苯地平治疗中国人原发性高血压的Meta分析及其GRADE证据质量评价

摘 要 目的：采用Meta分析方法评价非洛地平对比硝苯地平治疗中国人原发性高血压的疗效和安全性。方法：计算机检索the Cochrane Library（2016年第11期）、PubMed、MEDLINE、Embase、CNKI、WanFang Data、VIP、SinoMed,检索时限均为建库至2016年11月15日,全面收集非洛地平对比硝苯地平治疗中国人原发性高血压的随机对照试验（RCTs）。采用Cochrane系统评价手册进行严格质量评价,经RevMan 5.3统计软件对符合标准的RCTs进行Meta分析,并用GRADE profiler 3.6软件进行证据质量评价。结果：共纳入14个RCTs,包括1 909例患者。Meta分析结果显示,与硝苯地平相比,非洛地平能提高原发性高血压患者的总有效率（OR=3.58,95%CI：2.08~6.18,P＜0.05）和显效率（OR=2.24,95%CI：1.52~3.31,P＜0.05）,增加收缩压降低值（ΔSBP,MD=5.83,95%CI：0.70~10.97,P＜0.05）和舒张压降低值（ΔDBP,MD=3.63,95%CI：-0.02~7.29,P=0.05）,降低药品不良反应发生率（RR=0.41,95%CI：0.31~0.55,P＜0.05）。证据等级显示,总有效率、ΔSBP和ΔDBP为极低级,显效率和ADR发生率为低级,推荐强度均为弱推荐。结论：基于现有临床证据,与硝苯地平比较,非洛地平疗效和安全性均更好,值得临床推广。由于纳入研究的质量不高,该结论有待高质量的RCTs进一步验证。     

耐碳青霉烯类铜绿假单胞菌感染危险因素的Meta分析

摘 要 目的：采用Meta分析方法评价耐碳青霉烯类铜绿假单胞菌（CRPA）感染的危险因素。方法：计算机检索PubMed、The Cochrane Library、Embase、CNKI、WanFang Data和VIP数据库中有关CRPA感染危险因素的研究,检索时限均从建库至2018年1月。采用RevMan 5.3软件对纳入的研究进行Meta分析。根据不同区域研究人群进行亚组分析,发现纳入研究的异质性来源。结果：22篇研究（6 097例患者）符合纳入标准。Meta分析结果显示,病例组（发生CRPA感染）的机械通气[OR=1.64,95%CI（1.42,1.89）],使用碳青霉烯类[OR=7.15,95%CI（3.52,14.52）]、亚胺培南[OR=7.89,95%CI（3.90,15.93）]、氟喹诺酮类[OR=2.88,95%CI（2.12,3.90）]、哌拉西林/他唑巴坦[OR=4.46,95%CI（2.33,8.53）]、万古霉素[OR=5.39,95%CI（3.94,7.37）],入住ICU [OR=2.88,95%CI（2.12,3.90）],住院天数[WMD=6.53,95%CI（1.33,11.73）]等8个危险因素的分布与未发生CRPA感染的对照组比较,差异均有统计学意义（P＜0.05）。亚组分析不同区域研究人群使用碳青霉烯类、亚胺培南的结果,其中亚洲人群存在高度异质性分别为（P≤0.1,I2=87%）、（P≤0.1,I2=85%）。结论：针对存在高危因素的患者,应结合危险因素及早采取预防措施,降低CRPA感染的发生率。     

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。     

泮托拉唑不良反应的Meta分析

摘 要 目的：系统评价泮托拉唑的不良反应,分析其临床应用的安全性,为泮托拉唑的合理使用提供参考。 方法: 计算机检索PubMed、Embase、The Cochrane Library、Clinicaltrials.gov、CNKI、WanFang Data和SinoMed数据库,搜集单用泮托拉唑或在对照组（使用其他药物）基础上加用泮托拉唑的随机对照试验（RCTs）,检索时限均为建库至2018年5月31日。两名研究者独立筛选文献、提取资料并进行偏倚风险评价后,采用RevMan 5.3软件进行Meta分析。 结果: 共纳入26个RCTs,合计6 396例患者。Meta分析结果显示,两组患者总体不良反应发生率的差异无统计学意义[OR=0.91,95%CI（0.77,1.08）,P＞0.05]。亚组分析显示,适应证为食管炎时,泮托拉唑组总的不良反应发生率高于对照组,差异无统计学意义[OR=1.19,95%CI（0.80,1.76）,P＞0.05];适应证为消化性溃疡[OR=0.56,95%CI（0.33,0.94）,P=0.03]、口服用药[OR=0.68,95%CI（0.48,0.96）,P=0.03]、单独用药[OR=0.60,95%CI（0.37,0.98）,P=0.04]时,泮托拉唑组胃肠系统损害发生率低于对照组,两组的差异有统计学意义;疗程>8周时,泮托拉唑组总的不良反应发生率高于对照组,但差异无统计学意义[OR=1.07,95%CI（0.79,1.45）,P＞0.05];与奥美拉唑比较,泮托拉唑胃肠系统损害发生率更低,差异有统计学意义[OR=0.60,95%CI（0.44,0.83）,P=0.002]。结论: 泮托拉唑不良反应主要累及中枢及外周神经系统、胃肠系统、皮肤及其附件。治疗食管炎时、疗程>8周时,应特别注意其不良反应的发生。在治疗消化性溃疡、口服用药、单独用药或与其他药物比较时,泮托拉唑胃肠系统损害发生率更低,适合胃肠功能障碍的患者。     

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。     

中药复方治疗青春期多囊卵巢综合征疗效及安全性的Meta分析

摘 要 目的：采用Meta分析的方法评价中药复方治疗青春期多囊卵巢综合征（PCOS）有效性。方法：计算机检索SinoMed、CNKI、VIP、WanFang Data、PubMed、Cochrane Library、Embase数据库中有关中药复方治疗青春期PCOS的随机对照试验（RCTs）,检索时限均为1989年1月~2018年4月。由两名研究人员独立筛选文献、提取资料并评价纳入研究的偏倚风险后,采用RevMan 5.3软件进行Meta分析。结果：共纳入10个RCTs,共698例患者,其中中药复方组350例,单纯西药组348例。Meta分析结果显示,中药复方治疗青春期PCOS临床总有效率优于单纯西药组[OR=4.56,95%CI（2.68,7.76）,P＜0.000 01],中药复方在提高青春期PCOS患者月经周期恢复率[OR=4.73,95%CI（2.31,9.69）,P＜0.000 1]、排卵率[OR=4.14,95%CI（1.77,9.67）,P=0.001]优于西药组。并可有效改善患者卵巢平均体积[MD=-2.55,95%CI（-3.02,-2.08）,P＜0.000 01]以及降低BMI指数[MD=-2.51,95%CI（-3.13,-1.90）,P＜0.000 01]。中药复方组在治疗青春期PCOS患者时药品不良反应发生率低于单纯西药组[OR=0.03, 95%CI（0.01,0.10）,P＜0.000 01],但两者在改善青春期PCOS患者多毛症状无明显差异[MD=-3.63,95%CI（-7.79,0.53）,P=0.09]。结论：中药复方治疗青春期PCOS患者临床有效率优于单纯西药治疗,可有效恢复其月经周期、促进排卵、缩小卵巢平均体积,以及降低其BMI指数,且中药复方有着更好的药物安全性。但在改善其多毛症状时,两者无明显差异。受纳入研究数量和质量所限,本研究结论尚待更多高质量研究予以验证。     

紫杉醇联合奈达铂治疗卵巢癌的Meta分析

摘 要 目的：系统评价紫杉醇联合奈达铂对卵巢癌患者进行治疗的安全性和有效性。方法：计算机检索PubMed、Cochrane Library、Embase、CNKI、WanFang Data、SinoMed数据库,搜集有关紫杉醇联合奈达铂治疗卵巢癌的随机对照试验（RCTs）。检索时限均为建库至2018年4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 5.3软件进行分析。 结果：共纳入12 项研究,包括1 219 例患者。Meta分析结果显示,紫杉醇联合奈达铂治疗卵巢癌的总有效率与其他化疗方案相比,差异无统计学意义[OR=1.14,95%CI （0.88,1.48）,P=0.16],但紫杉醇联合奈达铂可提高患者1年生存率[OR=3.37,95%CI（1.47,7.71）,P=0.004]和2年生存率[OR=2.24,95%CI（1.27,3.97）,P=0.006],并且该方案显著减少了不良反应的发生率：血小板降低[OR=0.49,95%CI（0.36,0.66）,P=0.000 01]、恶心呕吐[OR=0.65,95%CI（0.47,0.89）,P=0.007]、外周神经毒性[OR=0.43,95%CI（0.28,0.67）,P=0.000 2]及肝功能损伤[OR=0.39,95%CI（0.20,0.77）,P=0.006]等不良反应的发生率。 结论：紫杉醇联合奈达铂治疗卵巢癌可延长患者1年及2年生存率且不良反应较轻,受研究数量和质量的限制,结论还需更多高质量的RCTs进行验证。     

Efficacy of gut lavage,hemodialysis, and hemoperfusion in the therapy of paraquat or diquat intoxication

Clinical and in vitro investigations were carried out to test the efficacy of gut lavage, hemodialysis, and hemoperfusion in the treatment of poisoning with paraquat or diquat. In a patient suffering from diquat intoxication 130 times more diquat was removed by gut lavage 30 h after ingestion than was removed by complete aspiration of the gastric contents.Determination of in vitro clearances for paraquat and diquat by hemodialysis showed that, at serum concentrations of 1–2 ppm, such as are frequently encountered in poisoning in man, toxicologically relevant quantities of herbicide cannot be removed from the body. At a concentration of 20 ppm, on the other hand, hemodialysis proved to be effective, the clearance being 70 ml/min at a blood flow rate of 100 ml/min. The efficacy of hemoperfusion with coated activated charcoal was on the whole better. Especially at concentrations around 1–2 ppm, the clearance values for hemoperfusion were some 5–7 times higher than those for hemodialysis.In a patient suffering from paraquat poisoning, both hemodialysis as well as hemoperfusion were carried out. The in vitro results could be confirmed: At serum concentrations of paraquat less than 1 ppm no clearance could be obtained by hemodialysis while by hemoperfusion with activated charcoal quite high clearance values were measured and the serum level dropped down to zero.

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Zusammenfassung Klinische Untersuchungen und Laboratoriumsversuche wurden durchgeführt, um die Wirksamkeit von Darmspülung, Hämodialyse und Hämoperfusion bei Paraquat- und Deiquat-Vergiftungen zu prüfen.Bei einem Patienten wurde 30 Std nach Deiquat-Aufnahme durch Darmspülung 130mal mehr Deiquat entfernt als durch vollständige Aspiration des Mageninhaltes. In vitro-Versuche ergaben, daß bei Blutserumkonzentrationen von 1–2 ppm, die bei Vergiftungen oft gemessen werden, durch Hämodialyse keine toxikologisch relevanten Paraquat- oder Deiquat-Mengen entfernt werden können. Dagegen erwies sich die Hämodialyse bei 20 ppm und einer Blutumlaufgeschwindigkeit von 100 ml/min mit einer Clearance von 70 ml/min als wirksam. Die Hämoperfusion mit beschicheter Aktivkohle war in diesen Versuchen aber eindeutig überlegen, denn insbesondere bei Konzentrationen um 1–2 ppm waren die Clearance-Werte 5–7mal höher als bei der Hämodialyse.Die in vitro-Ergebnisse wurden bei einem Patienten mit einer Paraquat-Vergiftung bestätigt: Bei Konzentrationen unter 1 ppm war die Hämodialyse wirkungslos, während durch Hämoperfusion relativ hohe Clearance-Werte erreicht wurden, so daß der Serumspiegel rasch unter die Nachweisgrenze abfiel.

     

In vitro studies on sterically stabilized liposomes (SL) as enzyme carriers in organophosphorus (OP) antagonism

This study describes a new approach for organophosphorous (OP) antidotal treatment by encapsulating an OP hydrolyzing enzyme, OPA anhydrolase (OPAA), within sterically stabilized liposomes. The recombinant OPAA enzyme was derived from Alteromonas strain JD6. It has broad substrate specificity to a wide range of OP compounds: DFP and the nerve agents, soman and sarin. Liposomes encapsulating OPAA (SL)* were made by mechanical dispersion method. Hydrolysis of DFP by (SL)* was measured by following an increase of fluoride ion concentration using a fluoride ion selective electrode. OPAA entrapped in the carrier liposomes rapidly hydrolyze DFP, with the rate of DFP hydrolysis directly proportional to the amount of (SL)* added to the solution. Liposomal carriers containing no enzyme did not hydrolyze DFP. The reaction was linear and the rate of hydrolysis was first order in the substrate. This enzyme carrier system serves as a biodegradable protective environment for the recombinant OP-metabolizing enzyme, OPAA, resulting in prolongation of enzymatic concentration in the body. These studies suggest that the protection of OP intoxication can be strikingly enhanced by adding OPAA encapsulated within (SL)* to pralidoxime and atropine.     

Aquatic Insects and Trace Metals: Bioavailability,Bioaccumulation, and Toxicity

Abstract

The uptake of metals from food and water sources by insects is thought to be additive. For a given metal, the proportions taken up from water and food will depend both on the bioavailable concentration of the metal associated with each source and the mechanism and rate by which the metal enters the insect. Attempts to correlate insect trace metal concentrations with the trophic level of insects should be made with a knowledge of the feeding relationships of the individual taxa concerned. Pathways for the uptake of essential metals, such as copper and zinc, exist at the cellular level, and other nonessential metals, such as cadmium, also appear to enter via these routes. Within cells, trace metals can be bound to proteins or stored in granules. The internal distribution of metals among body tissues is very heterogeneous, and distribution patterns tend to be both metal and taxon specific. Trace metals associated with insects can be both bound on the surface of their chitinous exoskeleton and incorporated into body tissues. The quantities of trace meals accumulated by an individual reflect the net balance between the rate of metal influx from both dissolved and particulate sources and the rate of metal efflux from the organism. The toxicity of metals has been demonstrated at all levels of biological organization: cell, tissue, individual, population, and community. Much of the literature pertaining to the toxic effects of metals on aquatic insects is based on laboratory observations and, as such, it is difficult to extrapolate the data to insects in nature. The few experimental studies in nature suggest that trace metal contaminants can affect both the distribution and the abundance of aquatic insects. Insects have a largely unexploited potential as biomonitors of metal contamination in nature. A better understanding of the physico-chemical and biological mechanisms mediating trace metal bioavailability and exchange will facilitate the development of general predictive models relating trace metal concentrations in insects to those in their environment. Such models will facilitate the use of insects as contaminant biomonitors.     

Steroidal sapogenin contents in some domestic plants

In order to find out the values of the steroid resources for the future use. the compositions and contents of steroidal sapogenins from 13 domestic plants have been investigated. As a result,Dioscorea nipponica, D. quinqueloba andSmilax china were found to have large amount of diosgenin. And pennogenin inTrillium kamtschaticum andParis verticillata, yuccagenin inAllium fistulosum, hecogenin inAgave americana and neochlorogenin inSolanum nigum were appeared to be major steroidal sapogenins.     

Alzheimer’s disease – current trends in basic and clinical research. Highlights from the 16th ECNP

Advances in the molecular biological knowledge of neuronal nicotinic acetylcholine receptors (nAChRs) have led to a growing interest by the pharmaceutical industry in the development of novel compounds that selectively modulate nAChR function. The ability of (-)-nicotine, an activator of nAChRs, to enhance attentional aspects of cognition in animals and humans, to exert neuroprotective and anxiolytic-like effects, and presumably to mediate the negative correlation between smoking and Alzheimer's (and Parkinson's) Disease, has focused interest on the potential therapeutic utility of modulators of nAChR function for treatment of some of the deficits associated with these progressive, neurodegenerative conditions. Numerous compounds are known which activate nAChRs and which might serve as lead compounds toward the development of such agents. The pharmacologic diversity of neuronal nAChR subtypes suggests the possibility of developing selective compounds which would have more favourable side-effect profiles than existing agents. This broader class of agents, collectively called cholinergic channel modulators (ChCMs), is anticipated to encompass compounds which would have more favourable side-effect profiles than existing agents, which generally exhibit low selectivity. This selectivity may be achieved by preferentially activating some subtypes of nAChRs (i.e., Cholinergic Channel Activators, ChCAs) or inhibiting the function of other subtypes (Cholinergic Channel Inhibitors, ChCIs). An overview of the biology of nAChRs and the rationale for the use of ChCMs for the treatment of dementia related to neurodegenerative diseases are presented, followed by a discussion of lead compounds and compounds under consideration for clinical evaluation.