TLR4基因Asp299Gly多态性与脑膜炎球菌病易感性的Meta分析

目的 探讨TLR4基因Asp299Gly基因多态性与脑膜炎球菌病易感性的关系。方法 检索Pubmed,embase,Cohrance,CNKI,维普,万方数据平台从建库到2015 年12 月的文献,对符合本实验纳入标准和排除标准的随机对照临床研究,运用RevMan5.0.0软件进行Meta分析。结果 共纳入4 篇文献,累计样本量为3707例,其中病例组1681例,对照组2026例。Meta分析未见TLR4基因Asp299Gly多态性与脑膜炎球菌病易感性相关(等位基因A vs G：OR=1.01,95% CI=0.84~1.23,P=0.89;基因型AA/AG vs GG：OR=1.05,95% CI=0.55~2.02,P=0.87;基因型AA vs AG/GG：OR=1.01,95% CI=0.82~1.24,P=0.95)。结论 未见TLR4基因Asp299Gly多态性与脑膜炎球菌病易感性相关。     

Toll样受体4基因Asp299Gly多态性与肺炎链球菌病易感性的Meta分析

目的系统评价Toll样受体4(TLR4)基因Asp299Gly基因多态性与肺炎链球菌病易感性的相关性。方法计算机检索Pubmed,Cohrance,Embase,CNKI,维普,万方等网站,检索时限均为各数据库建库到2016年7月31日,搜寻符合纳入和排除条件的随机对照研究,采用Rev Man5.3软件进行Meta分析及相关统计学分析。结果共纳入5篇文献,样本量总计为1456例,其中研究组501例,对照组955例。Meta分析未见TLR4基因Asp299Gly多态性与肺炎链球菌病易感性相关(等位基因A vs G:OR=1.01,95%CI=0.49~2.07,P=0.98;基因型AA/AG vs GG:OR=0.67,95%CI=0.18~2.48,P=0.55;基因型AA vs AG/GG:OR=1.01,95%CI=0.47~2.19,P=0.98)。结论未见TLR4基因Asp299Gly多态性与肺炎链球菌病易感性相关。     

Toll样受体4(896A/G)基因多态性与溃疡性结肠炎易感性的Meta分析

目的 研究Toll样受体4(TLR4)896A>G位点基因多态性与溃疡性结肠炎(UC)发病风险的关系.方法 检索相关英文及中文数据库筛选文献,以OR值及95％CI为效应指标,运用RevMan 5.2和Stata 11.0进行Meta分析和敏感性分析,并采用Egger′s test评价发表偏倚.结果 研究共纳入14篇文献,包括2174例UC患者和3134例对照者.Meta分析结果表明携带等位基因G的人群较携带等位基因A的人群患UC的风险性增加,在各个基因模型下均差异有统计学意义[等位基因模型G/A:OR=1.41,95％CI(1.21～1.66),P<0.0001;显性模型AG+GG/AA:OR=1.37,95％CI(1.16～1.62),P=0.0002;隐性模型GG/AA+AG:OR=3.74,95％CI(1.78～7.86),P=0.0005;共显性模型AG/AA:OR=1.42,95％CI(1.07～1.87),P=0.01;共显性模型GG/AA:OR=3.85,95％CI(1.82～8.12),P=0.0004].亚组分析结果表明,在等位基因模型G/A、显性模型AG+GG/AA、共显性模型AG/AA下,差异仅在白种人中存在.结论 TLR4896A>G基因多态性与UC易感性相关,携带等位基因G会增加白种人患UC的发病风险.由于该研究纳入有关亚洲人群及非洲人群的文献数量较少,相关结果需要更多研究予以验证.     

中国人群非小细胞肺癌GSTP1基因多态性与铂类药物敏感性Meta分析

目的 系统评价中国人群中非小细胞肺癌(NSCLC)患者GSTP1基因多态性与铂类药物化学治疗(简称化疗)敏感性的相关性。方法计算机检索Cochrane Library,Pub Med,EMBASE数据库和中国生物医学文献数据库(CBM)、中国学术期刊全文数据库(CNKI)和中文科技期刊全文数据库维普(VIP)、万方等数据库中有关GSTP1基因多态性与铂类药物化疗敏感性的研究,由2名研究者独立筛选提取资料和评价质量,采用Rev Man 5.2软件进行Meta分析。结果 有6篇文献符合要求,纳入研究,共527例患者。Meta分析结果显示,GSTP1 313 GG基因型(GG vs AA,OR为4.80,95%CI为1.57~14.69)和AG基因型(AG vs AA,OR为3.42,95%CI为1.99~5.86)的患者化疗有效率明显高于AA基因型患者,而且变异基因型G携带者(AG+GG基因型)的化疗有效率明显高于野生型AA基因型患者(AG+GG vs AA,OR为2.38,95%CI为1.61~3.53)。结论 中国人群中非小细胞肺癌患者的GSTP1基因多态性与铂类药物化疗敏感性相关。     

中国人群非小细胞肺癌XRCC1基因多态性与铂类药物敏感性的Meta分析

目的系统评价非小细胞肺癌患者中XRCCl基因多态性与铂类药物化学治疗敏感性的相关性。方法计算机检索中国生物医学文献数据库（CBM）、中国学术期刊全文数据库（CNKI）和中文科技期刊全文数据库维普（VIP）、万方数据库、Pubmed和EMBASE等数据库,检索时间为1978年1月至2012年6月。在提取资料和评价质量后,用RevMan5．1．4软件进行Meta分析。结果共纳入17个研究,合计l807例患者。Meta分析结果显示,XRCCl基因194位点｜rr基因型【1rrvs．CC,OR=2．08,95％cI（1．40—3．09）1和CT基因型[CTVSCC,OR=2．12,95％CI（1．62—2．76）】的患者化学治疗有效率都明显高于CC基因型的患者,而且变异型（CT＋1Tr基因型）的患者化学治疗有效率明显高于野生型（CC）基因型的患者【1rr＋CTvsCC,OR=2．14;95％c,（1．67—2．75）】;XRCCl399位点的AA基因型化学治疗敏感性低于GG基因型[AAvsGG,OR=0．52,95％CI（0．33—0．83）】,而且XRCCl399位点变异型（AA＋AG基因型）化学治疗敏感性低于野生型（GG基因型）【AA＋AGVSGG,OR=0．53,95％Cl（0．34—0．81）】。然而,XRCCl399位点的AG基因型与GG基因型之间没有显著性差异【AGVSGG,OR：0．69,95％CI（0．45—1．06）】。结论非小细胞肺癌患者中XRCCl基因多态性与铂类药物化学治疗敏感性相关。     

中国人群的AXIN2 rs2240308多态性与肺癌易感性的关系研究

目的旨在探讨AXIN2外显子1-148(rs2240308)多态性与肺癌易感性在中国汉族人群的关系。方法在555例对照组和520例肺癌患者中使用TaqMan SNP基因分型方法对AXIN2外显子1-148SNP进行基因分型。使用非条件Logistic回归分析来计算调整后的比值(OR)和95%可信区间(95%CI)的。结果 AG、AA和GG基因型出现频率在对照组和病例组之间存在显著差异,相比于那些携带GG基因型的患者,携带A等位基因(AG+AA基因型)患者其肺癌易感性较高。结论在中国人群中AXIN2外显子1-148 G->A多态性(rs2240308)患者其肺癌易感性较高。进一步表明AXIN2可作为肺癌相关基因。     

髓过氧化物酶基因G-463A多态性与脑梗死易感性的研究

目的 探讨髓过氧化物酶(MPO)基因G-463A位点多态性与颈动脉斑块患者易发脑梗死的相关性.方法 用二维超声测量97例颈动脉斑块患者和68名健康者内-中膜厚度(IMT)及颈动脉斑块指数(PI),限制性片段长度多态性-聚合酶链反应(RFLP-PCR)技术检测MPO基因G-463A多态性.结果 MPO-463位点G/A多态性有3种基因型(GG,GA,AA),2组间基因型分布和等位基因频率分布差异有统计学意义(P＜0.05).具有GG基因型者发生脑梗死的危险性较具有AA基因型者显著增高[x2=6.925,P=0.008,相对危险度(OR)=4.030,95％可信区间(CI):1.465～11.236];杂合子GA发生脑梗死的危险性较纯合子AA仍有升高趋势(x2=3.43,P=0.006,OR=2.748,95％CI:0.952～7.800);将GA和GG基因型合并计算,发现携带至少1个等位基因G者其患脑梗死的风险仍显著增高(x2=6.20,P=0.013,OR=3.488,95％CI:1.302～9.468).结论 MPO基因G-463A位点多态性与颈动脉斑块程度关系明显.MPO基因G-463A位点多态性与颈动脉斑块患者易发脑梗死的关系明显.     

中国人群载脂蛋白E基因多态性与阿尔茨海默病相关性的Meta分析

目的 探讨中国人群载脂蛋白E基因多态性与阿尔茨海默病（AD）的相关性.方法 检索相关文献,按纳入排除标准筛选后提取相关数据.应用RevMan 5.0软件进行异质性检验和数据合并,并进行敏感性分析.应用Stata 12.0软件评估发表偏倚.结果 共纳入11篇合格文献（13项研究）,累计2 577例,其中AD组l 209例,对照组1 368例.Meta分析结果显示,ApoE ε4等位基因及e3/4、ε4/4基因型携带者AD易感性明显升高,差异有统计学意义[ε4 vs ε3：比值比（OR）=2.88,95％置信区间（CI）为2.41 ～3.44;ε3/4 vs e3/3：OR =2.62,95％ CI为2.11 ～3.25; ε4/4 vs ε3/3：OR =7.98,95％ CI为4.21～15.13];ApoE e2等位基因及ε2/3基因型携带者AD易感性降低,差异有统计学意义（e2 vs ε3：OR =0.77,95％ CI为0.62 ～ 0.96;e2/3 vs ε3/3：OR=0.76,95％ CI为0.58～0.98）.结论 中国人群ApoE基因多态性与AD密切相关.     

中国汉族人群5-HT_（2A）受体基因1438A/G多态性与海洛因依赖的Meta分析

目的：探讨中国汉族人群5-羟色胺2A受体（Serotonin 2A receptor,5-HT2A受体）基因1438A/G多态性与海洛因依赖的关联性。方法：检索中国知网、万方、维普、Pub Med等中外数据库于建库至2014年3月公开发表的文献,收集有关中国汉族人群5-HT2A受体基因1438A/G（rs6311）多态性与海洛因依赖的病例对照研究,在评价纳入文献质量,提取有效数据后,使用Stata12.0软件进行Meta分析。结果：共纳入9项关于5-HT2A受体基因1438A/G（rs6311）多态性与海洛因依赖的病例对照研究,其中病例组2654人,对照组2089人。Meta分析结果显示：中国汉族人群5-HT2A受体基因1438A/G多态性与海洛因依赖之间无显著相关性（A VS.G：OR=1.05,95%CI=0.89-1.25;AA＋AG VS.GG：OR=1.11,95%CI=0.84-1.47;AA VS.GG：OR=1.10,95%CI=0.57-1.57;AG VS.GG：OR=0.92,95%CI=0.71-1.18;AA VS.AG＋GG：OR=1.02,95%CI=0.66-1.58）。Meta回归对异质性来源分析发现异质性主要来源于出版年份,基于地域的亚组分析显示：5-HT2A受体基因1438A/G多态性对于南方和北方人群的海洛因依赖风险无明显相关（南方：OR=0.95,95%CI=0.68-1.33;北方：OR=0.82,95%CI=0.49-1.37）,敏感性分析显示Meta分析结果稳定,可信度较高。结论：中国汉族人群5-HT2A受体基因1438A/G多态性与海洛因依赖之间不存在关联性。     

DDAH基因多态性影响格列苯脲治疗妊娠期糖尿病效果及其相关性分析

目的：探讨DDAH基因多态性对格列苯脲治疗妊娠期糖尿病(Gestational diabetes mellitus,GDM)疗效的影响及其与人类软骨糖蛋白-39(YKL-40)、视黄醇结合蛋白4(Retinol binding protein,RBP4)水平的相关性研究。方法：选择山西省儿童医院妇幼保健院于2019年1月至2022年1月收治的346例GDM患者为研究对象,根据DDAH rs1241321位点基因多态性分为AA基因型组、AG基因型组及GG基因型组。三组患者给予格列本脲联合门冬胰岛素治疗8周后对比三组患者的血糖指标、临床疗效及治疗前后血清YKL-40、RBP4表达水平差异;并通过相对风险度（OR）分析DDAH1基因与格列苯脲降糖效应之间的相关性。结果：格列本脲联合门冬胰岛素治疗后,AA基因型组餐后血糖指标2-h PG、HOMA-IR、FPG与血清YKL-40、RBP4浓度均高于GG基因型组、AG基因型组,且AG基因型组高于GG基因型组,差异具有统计学意义（P<0.001)。相对风险度（OR）分析结果显示DDAH1基因rs1241321位点基因型（AA、AG、GG）与Y...     

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.     

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.     

Synthesis,Cytotoxicity and Antileishmanial Activity of Some N-(2-(indol-3-yl)ethyl)-7-chloroquinolin-4-amines

We report herein the condensation of 4,7-dichloroquinoline (1) with tryptamine (2) and D-tryptophan methyl ester (3) . Hydrolysis of the methyl ester adduct (5) yielded the free acid (6) . The compounds were evaluated in vitro for activity against four different species of Leishmania promastigote forms and for cytotoxic activity against Kb and Vero cells. Compound (5) showed good activity against the Leishmania species tested, while all three compounds displayed moderate activity in both Kb and Vero cells.     

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.