肾移植受者中ABCC2基因多态性与环孢素导致肝损伤的相关性研究

摘 要 目的：探讨肾移植受者中ABCC2基因多态性与环孢素致肝损伤易感性的相关性。方法: 将入组的肾移植受者分为肝损伤组和对照组,利用高通量技术对ABCC2基因的五个单核苷酸多态性位点（rs4919395、rs2804398、rs4148394、rs4148397和rs3740065）进行基因分型,分析这些位点在两组间分布差异。结果:在35例肝损伤组和182例对照组间,ABCC2基因的5个SNP等位基因和基因型差异均无统计学意义（P>0.05）,且所选取的SNP单倍型组间也无显著差异（P>0.05）。结论:ABCC2的rs4919395,rs2804398,rs4148394,rs4148397和rs3740065位点与环孢素致肝损伤并无关联。     

ABCB1 3435C>T基因多态性对急性淋巴细胞白血病患儿大剂量甲氨蝶呤血药浓度及不良反应的影响

摘 要 目的：研究急性淋巴细胞白血病（ALL）患儿多药耐药基因1（ABCB1）基因多态性与使用大剂量甲氨蝶呤（MTX）化疗期间的血药浓度及不良反应的关系。方法: 70例ALL患儿外周血,提取DNA,采用PCR技术和直接测序的方法分析ABCB1基因的基因型;采用酶放大免疫法（EMIT）测定MTX给药后48h的血药浓度;2.华中科技大学同济医学院同济医院药学部,统计不良反应相关信息。分析ABCB1基因多态性与MTX血药浓度及不良反应的关系。结果: ABCB1 C3435T位点存在多态性,ABCB1 C3435T位点患儿CC、CT和TT基因型的分布频率分别为31.43%,47.14%,21.43%。ABCB1 C3435T位点各基因型MTX 48h C/D值由低到高依次为CC型患儿、CT型患儿、TT型患儿,其中TT型与CC型之间差异具有统计学意义(P＜0.05)。ABCB1 C3435T位点不同基因型患者中,口腔黏膜损害、肝脏损害发生率差异有统计学意义（P＜0.05）。结论:ABCB1 C3435T位点基因多态性与ALL患儿大剂量MTX化疗后的血药浓度及不良反应（口腔黏膜炎、肝脏损害）有关。     

MTHFR基因单核苷酸多态性与下肢动脉粥样硬化的关联研究

摘 要 目的：研究汉族人群中亚甲基四氢叶酸还原酶 (methylene tetrahydrofolate reductase,MTHFR)基因多态性与下肢动脉粥样硬化(lower extremity atherosclerotic disease,LEAD)的相关性。方法: 收集福建省闽南地区384例 (LEAD者224例,健康者160例)的临床资料及外周血;LEAD检查采用踝肱指数(ABI)、趾肱指数(TBI)、多普勒彩超和其他影像学检查等手段;选取MTHFR基因rs1801133、rs1801131、rs2274976、rs4846048、rs3737966、rs1537515、rs4846049、rs3834044、rs13306561和rs3737964等10个单核苷酸多态性 (single nucleotide polymorphisms,SNP)位点进行基质辅助激光解吸电离飞行时间质谱分析技术 (matrix assisted laser desorption ionization time of flight, MALDI TOF)的基因分型。结果: 10个SNP位点均符合Hardy Weinberg平衡;rs4846048与rs3737966等37个位点之间存在明显连锁不平衡现像 (D′均大于0.9);MTHFR基因GCCTCGGAAT单倍型在LEAD和正常组的分布差异有统计学意义 (P=0.02);等位基因频率的χ² 检验显示rs1801131 (OR＝1.287);rs4846048 (OR＝1.844,P＝0.02);rs3737966 (OR＝1.339);rs4846049 (OR＝1.314)和rs3737964 (OR＝1.522);且rs4846048位点的趋势χ² 检验 (cochran armitage trend test,TREND)、显性基因检验 (Dominant gene action test,DOM)均显示LEAD与正常组之间分布频率的差异有统计学意义 (P＜0.05)。结论:MTHFR基因rs1801131、rs4846048、rs3737966、rs4846049和rs3737964等5个位点可能与LEAD的易感性相关,其中rs4846048基因突变可能是LEAD致病性的危险因素之一。     

ABCB1基因多态性与五酯胶囊对他克莫司增效作用的相关性研究

摘 要 目的：研究五酯胶囊对他克莫司增效作用与 ABCB1基因多态性的相关性研究。方法: 通过聚合酶链反应 限制性片段长度多态性(PCR RFLP)方法测定ABCB1 1236C>T(rs1128503)、ABCB1 2677G>T/A(rs2032582)和ABCB1 3435C>T(rs1045642)基因型,使用化学发光微粒子免疫分析技术(CMIA)检测他克莫司C0。采用协方差分析考察不同组别患者他克莫司C0/D的差异。结果: 无论是单独使用他克莫司,还是他克莫司与五酯胶囊合用,ABCB1 1236C>T、ABCB1 2677G>T/A、ABCB1 3435C>T 不同基因型及单倍型组的他克莫司C0/D均无显著差异（P>0.05）。结论: 五酯胶囊对他克莫司的增效作用与ABCB1 1236C>T、ABCB1 2677G>T/A、ABCB1 3435C>T基因多态性无关。     

双环醇和多烯磷酯酰胆碱治疗甲亢性肝损伤疗效观察

摘 要 目的： 观察双环醇片和多烯磷酯酰胆碱胶囊治疗甲亢性肝损伤临床疗效和安全性。方法: 112例甲亢性肝损伤患者随机分为两组,在常规使用甲巯咪唑治疗同时,观察组56例加用双环醇片,对照组56例加用多烯磷酯酰胆碱胶囊,疗程均为4周。比较两组患者治疗前后丙氨酸转氨酶（ALT）、血清天冬氨酸转氨酶（AST）、总胆红素(TBIL)、碱性磷酸酶（ALP）等指标的变化,观察两组疗效与药品不良反应。结果: 治疗后两组ALT、AST、TBIL、ALP水平均较治疗前显著下降（P<0.05）,且观察组ALT、AST水平明显低于对照组（P<0.05）,而TBIL、ALP水平无差异（P>0.05）。观察组总有效率明显高于对照组（P<0.05）。两组药品不良反应均较轻微。结论: 双环醇片能有效治疗甲亢性肝损伤,且疗效优于多烯磷酯酰胆碱。     

自拟经验方联合降糖药治疗2型糖尿病94例

摘 要 目的: 探讨中医药治疗糖尿病的疗效。方法: 180例2型糖尿病患者随机分为治疗组94例和对照组86例,两组均使用基础降糖西药,治疗组加用自拟经验方。比较两组疗效。结果: 治疗组总有效率96.8%,对照组总有效率84.9%。治疗组明显优于对照组（P＜0.05）。治疗组联合胰岛素治疗例数,以及低血糖发生例数均少于对照组（P＜0.05）。结论:自拟经验方联合降糖药治疗2型糖尿病效果显著,值得临床推广。     

ABCG2 421C>A基因多态性与肾移植患者术后吗替麦考酚酯所致不良反应的相关性研究

摘 要 目的：研究肾移植术后患者ABCG2 421C>A基因多态性对吗替麦考酚酯（MMF）所致不良反应的影响。方法: 对236例患者按不良反应类型分为骨髓抑制组、胃肠道反应组、感染组和对照组,并对患者的肾源、年龄、性别、身高、体质量、体质指数（BMI）、透析时间、移植年月等临床资料以及患者移植术后3,6,12,24,36个月时的MMF剂量进行统计学分析;采用高效液相 荧光检测器法测定肾移植受者的MMF血药浓度;采用限制性片段长度多态性（PCR RFLP）法检测236例患者的ABCG2 421C>A位点多态性,并将PCR产物送测序公司直接测序以验证结果的准确性。结果: 有36例骨髓抑制,15例胃肠道反应,26例感染,124例未发生不良反应,ABCG2 421C>A基因突变频率为34.32%,野生纯合子（CC）构成比为43.64%,突变杂合子（CA）为44.07%,突变纯合子（AA）为12.29%,胃肠道反应组AA基因型分布明显高于对照组（26.67% vs. 9.43%,P=0.041）,ABCG2 421 AA基因型组与CC、CA基因型组在性别上分布的差异有统计学意义（PCC=0.002、PCA=0.036）;Logistic回归分析显示,ABCG2 421AA基因型是肾移植术后发生MMF所致胃肠道反应的独立危险因素。结论: 肾移植术后患者ABCG2 421C>A基因多态性与MMF所致不良反应有关,ABCG2 421AA基因型患者更容易发生MMF所致胃肠道反应。     

右美托咪定与丙泊酚联用于老年患者无痛胃镜麻醉的临床观察

摘 要 目的： 观察右美托咪定与丙泊酚联用在老年患者无痛胃镜麻醉中的效果及安全性。方法: 拟行无痛胃镜检查的老年患者70例随机分为观察组（35例）和对照组（35例）;观察组给予右美托咪定联合丙泊酚麻醉,对照组给予丙泊酚麻醉。比较两组患者的麻醉诱导时间、苏醒时间,患者不同时点的生命体征,术中并发症、药品不良反应等指标。结果: 观察组麻醉诱导时间、苏醒时间均短于对照组（P<0.01）。两组患者平均动脉压（MAP）在T2、T3、T4阶段均明显低于T1阶段（P<0.05或P<0.01）;对照组的HR在T3阶段、R在T2阶段均低于T1阶段（P<0.05）;观察组的RR在T2阶段明显低于T1阶段（P<0.05）;观察组MAP在T2、T3阶段明显高于对照组（P<0.01）,在T4阶段低于对照组（P<0.05）;观察组的HR在T3阶段明显高于对照组（P<0.05）。观察组患者术中并发症显著低于对照组（P<0.05）。结论:右美托咪定联合丙泊酚的麻醉效果与安全性均高于单用丙泊酚,值得临床推广应用。     

甲氨蝶呤联合米非司酮治疗异位妊娠疗效观察

摘 要 目的:观察甲氨蝶呤联合米非司酮治疗异位妊娠的临床疗效。方法：58例异位妊娠患者按入院前后次序分为观察组及对照组各29例。对照组予甲氨蝶呤50 mg·m-2,im bid;观察组在对照组基础上,加用米非司酮片50 mg,po bid。两组疗程均为3 d。治疗后比较两组治愈率、二次用药率及不良反应发生率。结果：观察组治愈率为93.1%,高于对照组的69.0%（P<0.05）;二次用药率为10.3%,明显低于对照组的48.4%（P<0.05）;两组不良反应发生差异无统计学意义（P>0.05）。结论：甲氨蝶呤联合米非司酮治疗异位妊娠效果确切,能明显降低二次用药率,值得临床推广使用。     

脑心通胶囊治疗后循环缺血眩晕46例回顾性分析

摘 要 目的:探讨脑心通胶囊在治疗后循环缺血（PCI）眩晕中的价值与治疗效果。方法： 采用回顾性研究方法,收集83例PCI患者病历资料,其中采用常规治疗加氟桂利嗪治疗的37例（对照组）;采用常规治疗加脑心通治疗的46例（观察组）,比较两组GCS评分、血液流变学指标、临床疗效,观察治疗过程中的不良反应。结果：治疗后,两组患者GCS评分与血液流变学指标均有一定改善,且观察组优于对照组（P<0.05）;观察组总有效率91.30%,明显高于对照组（P<0.05）;两组间不良反应发生率差异无统计学意义（P＞0.05）。结论：脑心通胶囊治疗PCI患者疗效显著。     

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.     

Pharmacological treatment of COVID-19: an opinion paper

The precocity and efficacy of the vaccines developed so far against COVID-19 has been the most significant and saving advance against the pandemic. The development of vaccines has not prevented, during the whole period of the pandemic, the constant search for therapeutic medicines, both among existing drugs with different indications and in the development of new drugs. The Scientific Committee of the COVID-19 of the Illustrious College of Physicians of Madrid wanted to offer an early, simplified and critical approach to these new drugs, to new developments in immunotherapy and to what has been learned from the immune response modulators already known and which have proven effective against the virus, in order to help understand the current situation.     

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.     

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.