二甲双胍临床不合理用药调查

摘 要 目的:了解我院住院患者二甲双胍使用情况,总结二甲双胍的不合理用药现象,促进临床合理用药。方法：收集2014年应用二甲双胍的住院患者病历,对二甲双胍临床应用的适应证、用法用量、禁忌证、不良反应及药物相互作用等进行系统的回顾性调查分析。结果：二甲双胍主要应用于2型糖尿病患者。使用最多的剂型为缓释片,约占65.17%。二甲双胍用药不合理率为38.87%,其中用法用量不合理59.83%、存在用药禁忌39.3%和无适应证用药0.87%。用法用量不合理主要表现为肠溶片餐中或餐后服用,占83.45%。二甲双胍的应用禁忌证主要为应用碘造影剂前后未停用二甲双胍（47.47%）,肝、肾功能不全（21.21%）。二甲双胍的不良反应发生率为6.98%。结论：目前二甲双胍在临床应用中仍存在一些不合理现象,应积极开展二甲双胍临床药学服务,加强其合理用药,降低临床用药风险。     

某院病区口服抗糖尿病药物用药的规范性评价

摘 要 目的：评价某院病区口服抗糖尿病药物医嘱的规范性,为合理用药提供依据。方法: 采取回顾性调查方法,查阅2017年1～3月病区口服抗糖尿病药物的长期医嘱,统计分析药物使用情况,评价医嘱规范性。结果:病区口服抗糖尿病药物13个品种,医嘱4 397条,医嘱方案886条,盐酸二甲双胍片和阿卡波糖片使用频率最高;医嘱用药不规范率70.54%,其中“未标注准确的用药时间”占66.03%,“标注错误的用药时间” 占4.51%。12种药品存在不规范问题(>50%)。结论:医嘱开具的主要问题是未考虑到抗糖尿病药物的服用时间点,既影响最佳疗效,也不利依从性用药,因此必须规范此类药物的医嘱开具,提高药物治疗方案的规范性。     

艾塞那肽在中青年2型糖尿病合并非酒精性脂肪肝治疗中的作用及对患者各项指标的影响

摘 要 目的：观察艾塞那肽在中青年2型糖尿病合并非酒精性脂肪肝治疗中的作用,及对患者体质量、血糖、血脂、胰岛素抵抗及脂肪肝病变程度的影响。方法: 口服降糖药治疗不达标的中青年2型糖尿病合并非酒精性脂肪肝患者70例随机分为两组,每组35例。观察组在原降糖方案基础上加用艾塞那肽,对照组在原方案基础上加用精蛋白生物合成人胰岛素注射液,干预时间3个月。比较患者治疗前后的体质量、体质指数（BMI）、腰围、胰岛素抵抗指数 (HOMA IR)、空腹血糖 (FPG)、餐后2 h血糖 (2hPG)、糖化血红蛋白 (HbA1c)、血脂(TG、TC、LDL C、HDL C)、肝功能指标 (ALT、AST、GGT), 及脂肪肝治疗疗效。结果:治疗3个月后,观察组的血糖控制与对照组无显著差异(P>0.05)。但观察组患者的体质量、BMI、腰围、HOMA IR、TG、ALT、AST、GGT均较治疗前显著下降 (P<0.05),且显著优于对照组 (P<0.05);而对照组上述指标治疗前后差异无统计学意义 (P>0.05)。观察组治疗脂肪肝的总有效率显著高于对照组 (P<0.05)。结论:艾塞那肽在有效降糖的基础上,可明显减低体质量、降低TG、改善胰岛素抵抗,同时能降低肝酶并显著改善脂肪肝,有望成为中青年2型糖尿病合并非酒精性脂肪肝患者治疗的新选择。     

阿卡波糖与2型糖尿病患者冠心病发病风险的回顾性队列研究

摘 要 目的：探究使用阿卡波糖对新发2型糖尿病（T2DM）人群冠心病发病风险的影响。 方法：使用2012~2015年北京市城镇职工基本医疗保险数据库进行回顾性队列研究,共1 627例新发T2DM患者纳入分析。以患者首次诊断为糖尿病的时间为随访起点,直到出现研究结局、或最后一次就诊日期为观察终点。按照随访期间有无使用阿卡波糖将研究对象分为暴露组与对照组,使用时间依赖的Cox比例风险回归模型分析阿卡波糖用药对冠心病发病的影响;并根据累积暴露水平（累积用药时间/剂量）进行亚组分析。 结果：对研究对象随访4年,发生冠心病共计918例（56.42%）,其中暴露组379例（47.55%）,对照组539例（64.94%）,差异有统计学意义（P<0.05）。与对照组相比,累积用药天数＜60 d、60~180 d和＞180 d组发生冠心病的调整后HR（95%CI）分别为2.08（1.77,2.45）、0.79（0.65,0.97）和0.29（0.22,0.39）;累积用药剂量＜14 000 mg、14 000~48 000 mg和＞48 000 mg组发生冠心病的调整后HR（95%CI）分别为2.02（1.73,2.37）、0.72（0.58,0.89）和0.23（0.17,0.32）。 〖HTH〗结论：〖HTK〗长期使用阿卡波糖（累积用药达一定的天数或者剂量）可以降低新发T2DM患者冠心病的发病风险。     

4种预混胰岛素治疗新诊断2型糖尿病的最小成本分析

摘 要 目的：评价4种预混胰岛素用于新诊断2型糖尿病的短期经济学效果。方法: 选择120例新诊断2型糖尿病住院患者,根据所用胰岛素分为A组（门冬胰岛素30注射液）、B组（赖脯胰岛素25注射液）、C组[精蛋白生物合成人胰岛素注射液（预混30R）]和D组（精蛋白锌重组人胰岛素混合注射液）,观察疗程均为3个月,以3个月内病情缓解率为效果测量指标,运用最小成本法评价短期经济学效果。结果: A、B、C、D组的缓解率分别为48.39%,48.28%,51.61%,51.72%,差异无统计学意义（P＞0.05）;4组治疗平均总成本为1 195.52,1 202.41,1 220.69,1 258.84元/人,药品平均成本为750.52,689.41,754.69,764.34元/人,差异无统计学意义（P＞0.05）。B组药物成本相对较低。结论:4种预混胰岛素在总成本上差异不明显,均为可选择的起始胰岛素;相对而言,门冬胰岛素30注射液和赖脯胰岛素25注射液是较好的糖尿病起始治疗方案。     

达格列净联合二甲双胍治疗2型糖尿病疗效观察

摘 要 目的：观察单用二甲双胍控制不佳的2型糖尿病患者,分别加用格列美脲或达格列净的疗效以及安全性。 方法：90例2型糖尿病患者随机分为两组各45例。观察组予达格列净联合二甲双胍,对照组予格列美脲联合二甲双胍。治疗24周后,比较两组患者治疗前后空腹血糖（FBG）、餐后2 h血糖（2hPG）、糖化血红蛋白（HbA1c）、体重指数（BMI）等指标变化,以及低血糖事件发生率和药品不良反应。结果：治疗后,两组FBG、2hPG、HbA1c均较治疗前明显下降（P＜0.05）,两组间比较差异无统计学意义（P＞0.05）。观察组BMI较前明显下降（P＜0.05）,对照组则下降不明显（P＞0.05）,两组比较差异有统计学意义（P＜0.05）。观察组低血糖发生率明显低于对照组（P＜0.05）。〖HTH〗结论：〖HTK〗使用二甲双胍控制不佳的2型糖尿病患者加用格列美脲或达格列净治疗24周后可使血糖控制得到相似程度的改善,与使用格列美脲联合二甲双胍治疗相比较,使用达格列净联合二甲双胍治疗的患者出现低血糖的风险更低,且在体重控制方面有明显优势。因此,达格列净联合二甲双胍治疗2型糖尿病疗效可靠,且有良好的安全性。     

恩格列净治疗2型糖尿病有效性和安全性的Meta分析

摘 要 目的：采用Meta分析方法评价恩格列净治疗2型糖尿病的有效性和安全性,为其临床应用提供依据。方法：计算机检索 PubMed、EMbase、MEDLINE、Cochrane 图书馆、CNKI、WanFang Data、VIP、SinoMed 数据库有关恩格列净治疗2型糖尿病的随机临床对照试验,检索时间为建库至2017年6月。按Cochrane系统评价的方法评价纳入研究的方法学质量并提取相应数据,采用 RevMan 5.3软件进行 Meta分析。结果：纳入符合标准的随机对照试验14个,2型糖尿病患者共计5 003例。Meta分析结果显示,与安慰剂相比,使用恩格列净治疗后糖化血红蛋白（HbA1c）水平改善较好[MD=-0.66,95%CI（-0.73,-0.58）,P＜0.000 01],空腹血糖水平改善较好[MD=-1.50,95%CI（-1.63,-1.37）,P＜0.000 01]。安全性分析结果显示恩格列净组与安慰剂组不良反应发生率差异无统计学意义（P=0.05）。结论：与安慰剂相比,恩格列净治疗能更加有效地降低糖化血红蛋白以及空腹血糖水平。受纳入研究方法学限制,该结论尚长期RCT进一步验证。     

西格列汀治疗初发2型糖尿病伴非酒精性脂肪肝的疗效及对患者血糖、血脂的影响

摘 要 目的： 比较西格列汀联合二甲双胍与格列美脲联合二甲双胍治疗初发2型糖尿病伴非酒精性脂肪肝的临床疗效及安全性。方法: 160例初发2型糖尿病伴非酒精性脂肪肝患者随机分为对照组与观察组各80例。两组均采用二甲双胍片0.5 g,po,bid基础治疗,对照组同时给予格列美脲片2 mg,po,qd,观察组同时给予西格列汀片100 mg,po,qd。分别于治疗前、治疗16周后检测两组患者空腹血糖、餐后2 h血糖、肝功能、血脂等指标,比较两组临床疗效与药品不良反应。结果: 观察组患者脂肪肝改善总有效率为88.75%,明显高于对照组的61.25%（P<0.05）;治疗16周后,两组患者肝功能和胰岛素抵抗指数均较治疗前明显改善（P<0.05）,且观察组较对照组改善更显著（P<0.05）;两组血糖及血脂水平较治疗前明显下降（P<0.05）,但组间比较差异无统计学意义（P>0.05）。治疗期间两组患者均未发生严重不良反应。结论: 西格列汀联合二甲双胍治疗初发2型糖尿病伴非酒精性脂肪肝,相比格列美脲联合二甲双胍效果更显著,且安全。     

延伸药学服务对糖尿病患者用药依从性的影响观察

摘 要 目的： 探讨依托短信平台进行个体化用药指导对糖尿病患者用药依从性的改变。方法: 100例门诊糖尿病患者按照顺序号分组,单号归入观察组,双号归入对照组,两组各50例,观察组由药师依托短信技术平台为患者提供药学指导和用药提醒服务等延伸药学服务;对照组电话随访,了解用药情况。分别在入组时和3个月后,评价两组用药依从性,并比较两组血糖控制情况。结果: 入组时,两组血糖水平及用药依从性良好率比较,差异无统计学意义(P>0.05)。3个月后,观察组血糖水平降低,用药依从性良好率明显提升,与对照组比较,差异均有统计学意义(P<0.01)。结论: 依托手机短信技术平台对患者进行个体化临床药学指导的延伸药学服务能显著提高糖尿病患者的用药依从性。     

利拉鲁肽治疗2型糖尿病合并肥胖疗效观察

摘 要 目的：观察利拉鲁肽治疗2型糖尿病（T2DM）合并肥胖患者的降糖及减重作用,探讨合并肥胖的T2DM新的治疗思路。方法: 超重和肥胖的T2DM患者38例,入组前口服降糖药物或应用胰岛素治疗血糖控制不达标,按体质指数（BMI）分为两组,A组为超重组（BMI 24～28 kg·m-2)18例、B组为肥胖组（BMI≥28 kg·m-2)20例,两组均加用利拉鲁肽治疗12周,观察治疗前后两组患者身高、体质量和BMI;2 h空腹和餐后2 h血糖（FPG,2hPG）、糖化血红蛋白（HbA1c）,空腹(FINS)和餐后2 h胰岛素(2hINS)、空腹(FCP)和餐后2 hC肽(2hCP);以及胰岛素抵抗指数(HOMA IR)和胰岛β细胞分泌功能指数(HOMA β）。结果: 治疗后两组患者的HbA1c、FBG、2hPG、FCP、2hCP及HOMA β、HOMA IR等指标均较治疗前明显改善(P＜0.01);两组上述指标组间比较无明显差异(P＞0.05)。治疗后B组患者体质量和BMI较治疗前下降明显(P＜0.01),而A组体质量和BMI无明显改变(P＞0.05)。结论: 超重和肥胖T2DM患者,加用利拉鲁肽治疗后,可有效地控制血糖,改善胰岛素抵抗,而肥胖患者体质量较治疗前有明显下降。     

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.