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目前中药研究的难点之一是如何将数学方法科学地运用到具体的中药复方研究中。《运用直接试验设计优化复方丹参片处方的探索性研究》以复方丹参片为研究对象,运用以直接试验设计为指导思想的试验方案筛选计算机软件安排拆方试验,以大鼠冠脉结扎模型为试验载     

基于文献分析法的药物临床试验信息化建设

目的:梳理药物临床试验信息化建设研究脉络,了解并掌握药物临床试验信息化建设研究热点和发展趋势。方法:本研究采用知识图谱CiteSpaceⅤ软件,在2000年至2020年中国知网数据库391条文献的基础上,从文献数量分析、研究机构分析、作者分析、研究热点主题以及研究趋势分析等角度进行了深入探讨,并绘制知识图谱,梳理药物临床试验信息化建设研究脉络。结果:分析表明近20年来药物临床信息化建设相关研究论文发表数量波动上升,主要研究机构在该领域大都有较强的研究能力,但研究机构间的联系还较为松散,学者间的学术交流还有待加强。在热点研究上的转变体现了该领域更加注重系统化和保护受试者权益。结论:药物临床试验信息化建设研究热点主要集中于临床试验、药物临床试验、质量控制等方面。通过信息化建设进一步提高试验管理效能,保证药物临床试验可靠规范,有效降低药物临床试验风险隐患是未来研究趋势。     

新药评价中彗星试验方法学研究及发展趋势

彗星试验是一项检测单细胞损伤的试验方法,近年来在毒理学研究中发展很快。对彗星试验的原理和方法,及其在新药评价遗传毒性研究、生殖毒性研究和靶器官毒理学研究中的应用进行了分析和介绍,并提出了彗星试验技术的发展趋势。     

简约稳定性研究设计介绍

稳定性研究设计分为完全试验设计和简约试验设计2种。完全试验设计是指在全部的时间点考察全部批次的样品，简约试验设计指在部分时间点考察全部批次的样品。简约试验设计常用的有括弧法和矩阵法。简约设计的稳定性研究数据的处理与完全设计的稳定性研究数据的处理相同。     

统计学在药物临床试验中的应用

药物临床试验与在实验室开展的动物研究不同,研究者不能完全支配病人的行为,很多无法控制的因素影响对试验药物作用的评价。在临床试验中,通常是根据研究的目的,通过观察足够数量的受试者来研究药物对疾病的作用,因此,临床试验设计必须应用统计学原理对试验相关的因素做出合理的、有效的安排,控制试验误差和提高试验质量以及对试验数据进行科学的分析,保证试验结果的真实性和科学性。     

研究机构疫苗临床试验质量管理体系建设探讨

摘要：目的:建立完善的研究机构疫苗临床试验质量管理体系,规范临床试验全过程,保证疫苗临床试验质量。方法:收集相关文献并结合本机构近10年疫苗临床试验实践经验,从研究机构质量保证体系的建立与质控活动的实施入手,探讨研究机构疫苗临床试验质量管理体系建设。结果:研究机构建立的质量管理体系通常由质量管理人员、系统标准文件、现场设施设备、质量控制活动组成。在临床试验实施过程中需要质量管理人员之间密切配合、严格遵守系统标准文件,并按照质量控制计划的要求实施,才能有效保证临床试验过程的规范性和真实性。结论:质量管理是保证临床试验结果科学、可靠、真实的重要手段,应贯穿于整个临床试验过程。研究机构建立完善的质量管理体系对疫苗临床试验的质量及试验结果的可靠性有重要作用。     

医疗器械临床前动物试验研究的考虑要点

目的：医疗器械安全性和有效性评价中动物试验是重要手段之一,医疗器械临床前动物试验研究是许多Ⅲ类医疗器械,特别是创新型医疗器械进行临床试验研究之前需要开展的重要项目。本综述为规范开展医疗器械临床前动物试验研究提供参考。方法：本文在归纳国内外医疗器械临床前动物试验研究领域的法规、标准的基础上,参考了《药物非临床研究质量管理规范》的框架对医疗器械临床前动物试验研究的考虑要点进行了归纳整理。结果：本文从人员、设施、仪器设备和实验材料、试验系统、标准操作规程、研究工作的实施、总结报告以及质量保证和资料档案等几个方面,归纳总结了医疗器械临床前动物试验研究的考虑要点。结论：本文为医疗器械临床前动物试验研究提供更全面的理解,为开展动物试验研究提供参考。     

药物临床试验技术服务合同专家共识(中国药理学会药物临床试验专业委员会)

药物临床试验是指任何在人体(病人或健康志愿者)进行药物的系统性研究,目的是确定试验药物的疗效与安全性。当药物研发单位(药企、研究所等)不具备实施试验药物的临床条件和资质时,就需要作为发起该药临床试验的申办方(Sponsor),委托具有资质的研究机构参与药物的临床评价过程,因此,药物临床试验技术服务合同是申办方与研究机构间专门针对特定药物临床试验项目中特定任务所签订的委托服务协议。药物临床试验合同是申办方、研究机构、主     

我国生殖毒理学研究进展

我国生殖毒理学研究在 60年代以评价化学物致畸效应为主 ;70年代有关刊物详尽描述了致畸和繁殖试验的方法 ;80年代制定的法规将喂养繁殖试验、喂养致畸试验和传统致畸试验列为必做试验 ,并在致突变试验项目中列出睾丸生殖细胞染色体畸变分析和精子畸形试验 ;90年代的研究内容已由单纯致畸研究扩大至男 (雄 )性和女 (雌 )性生殖和发育毒理 ,在研究手段上由整体动物实验扩大至全胚胎培养、组织培养、细胞培养 ,并运用了分子生物学理论和技术。现从生殖毒性测试的发展、观测生殖毒性指标的进展、化学物生殖毒性研究进展等几个角度对我国生殖毒理领域的研究作一概述 ,并提出今后的研究动向将会以生殖细胞遗传毒性研究、拓宽研究对象以及开展环境内分泌干扰物的研究为主     

程序变湿变温药物稳定性试验

目的建立一种研究湿度对药物稳定性影响的简便实验方法。方法用程序变湿和程序变温加速试验方法,以青霉素钾为例进行药物稳定性试验。结果程序变湿和程序变温加速试验与恒温恒湿对照试验得到的青霉素钾的降解动力学参数基本一致。结论程序变湿变温加速试验可以应用于药物稳定性研究。     

Nicotine addiction: a re-analysis of the arguments

This paper evaluates the arguments put forward by Robinson and Pritchard (R&P, this volume) that the conclusions of the US Surgeon General (USDHHS 1988) that nicotine is addictive were ill founded. R&P state that nicotine does not cause intoxication, that many smokers do not exhibit compulsive use, that nicotine is not a euphoriant, that nicotine is a weak reinforcer in other species, that non-pharmacological aspects of smoking are important and that negative affect control accounts for more of the variance in questionnaire measures of smoking motives than does habit. This paper points out that intoxication and a euphoriant effect are not normally considered to be central to dependence potential, that no addictive drug results in compulsive use in all users in all situations, that animals do reliably self-administer nicotine, that evidence concerning the apparent importance of non-pharmacological components of smoking do not diminish the importance of pharmacological aspects and that variance accounted for of self-report measures of smoking motivation do not bear on the issue of the importance of those motives. The paper concludes with a summary of the essence of the argument that cigarettes are addictive and that nicotine is the primary focus of that addiction.     

Importance of delta opioid receptors in maintaining high alcohol drinking

We have previously reported that naloxone, a nonspecific opioid receptor antagonist, suppresses alcohol but not water consumption by male rats that have been genetically selected for high voluntary alcohol drinking. However, the identity of the specific opioid receptor subtype that may mediate alcohol drinking is not known. This paper reports that a selective delta opioid receptor antagonist is as effective as naloxone in suppressing alcohol consumption and that an enkephalinase inhibitor, which potentiates the action of endogenous enkephalins, increases alcohol intake. These results suggest that alcohol-induced activation of the endogenous enkephalinergic system, and occupation of delta opioid receptors, are involved in the maintenance of continued alcohol drinking.     

Integrating heterogeneous data to facilitate COVID-19 drug repurposing

In the COVID-19 pandemic, drug repositioning has presented itself as an alternative to the time-consuming process of generating new drugs. This review describes a drug repurposing process that is based on a new data-driven approach: we put forward five information paths that associate COVID-19-related genes and COVID-19 symptoms with drugs that directly target these gene products, that target the symptoms or that treat diseases that are symptomatically or genetically similar to COVID-19. The intersection of the five information paths results in a list of 13 drugs that we suggest as potential candidates against COVID-19. In addition, we have found information in published studies and in clinical trials that support the therapeutic potential of the drugs in our final list.     

Medical Specialization,Profession, and Mediating Beliefs That Predict Stated Likelihood of Alcohol Screening and Brief Intervention: Targeting Educational Interventions

Practitioner-level educational approaches that promote screening and brief intervention (SBI) seldom consider providers' profession and medical specialization. Strategies that consider these variables may be better equipped to affect change in beliefs and behavior. The aim of this study was to identify beliefs that predict stated likelihood of practicing SBI by specialty and health profession in order to guide the direction of educational strategies. Physicians and nurse practitioners were studied that specialized in family, internal, obstetric gynecology (ObGyn), and pediatric medicine. The results indicated that independent of amount of previous postgraduate alcohol education and knowledge, self-rated competence mediated between specialty and likelihood of practicing SBI. For instance, low self-rated competence for ObGyn was a barrier that suppressed likelihood of practicing SBI. Other findings were that role legitimacy mediated the association between profession and likelihood of SBI, so that lack of role legitimacy was a barrier for physicians but not for nurse practitioners. We suggest that targeted educational strategies for ObGyn and pediatric clinicians may prove more effective than the prevalent one-size-fits all approaches aimed at general adult populations.     

Design and synthesis of nonpeptide mimetics of jaspamide

Jaspamide is a novel metabolite of mixed peptide/polyketide biosynthesis that was isolated from sponges of the genus Jaspis, and that has been reported to exhibit both insecticidal and antifungal activity. We have evaluated three nonpeptide mimetic designs, and have synthesized a nonpeptide mimic of the proposed bioactive region to investigate the structure activity relationship. Structural investigations of potential mimetics, utilizing molecular modeling in conjunction with spectroscopic and crystallographic data, indicate that positioning of the critical functional groups in two mimetics corresponds closely to that observed in jaspamide, and that the flexibility of mimetic 4 approximates that of jaspamide. Initial biological evaluation suggests that lactam mimetic 4 exhibits a biological profile similar to jaspamide.     

彩色多普勒在无损伤性肝循环中的应用

本研究应用彩色多普勒超声对于３０例正常肝脏，３０例慢性肝病，２５例肝硬化，２２例原发性肝癌症的门静脉，脾静脉及肝静脉进行多种数据测量。结果显示慢肝时门脉血流量显著少于正常，慢肝，肝硬化，肝癌时门脉内径明显增宽，血流速度明显减低，肝静脉内径变窄，最大流速比平均流速增高显著，充血指数小于正常、笔者认为，应用彩色多普勒为无创伤性测量肝脏循环确定一种新的诊断标准，门脉血流量的测定，可作为慢肝和肝硬化的鉴别     

Evidence for a cholinergic role in haloperidol-induced catalepsy

Experiments in mice tested previous evidence that activation of cholinergic systems promotes catalepsy and that cholinergic mechanisms need to be intact for full expression of neuroleptic-induced catalepsy. Large doses of the cholinomimetic, pilocarpine, could induce catalepsy when peripheral cholinergic receptors were blocked. Low doses of pilocarpine caused a pronounced enhancement of the catalepsy that was induced by the dopaminergic blocker, haloperidol. A muscarinic receptor blocker, atropine, disrupted haloperidol-induced catalepsy. Intracranial injection of an acetylcholine-synthesis inhibitor, hemicholinium, prevented the catalepsy that is usually induced by haloperidol. These findings suggest the hypothesis that the catalepsy that is produced by neuroleptics such as haloperidol is actually mediated by intrinsic central cholinergic systems. Alternatively, activation of central cholinergic systems could promote catalepsy by suppression of dopaminergic systems.     

Co-occurring mental health and drug dependency disorders: work-force development challenges for the AOD field

In this paper it is argued that the sheer extent of the co-occurrence of mental health and drug dependency disorders means inevitably that alcohol and other drug (AOD) staff encounter such problems. However, it is contended that the AOD work-force has a number of characteristics that often act as impediments to people with co-occurring disorders receiving, in that sector, appropriate, integrated, 'one-stop-shop' care. Nevertheless, because of the configuration of mental health services in Australia, as essentially acute services for people with severe mental illnesses, there has been, and will continue to be, an overspill of people with mental health disorders and drug problems disorders into the AOD sector. It is there absolutely necessary that initiatives are put into place that support and enable the AOD sector to respond more effectively to people with co-occurring disorders.     

Pharmacological manipulation of human working memory

Rationale The goal of this paper is to briefly overview human studies that have examined pharmacological agents designed to enhance working memory function, with the idea of providing clues as to promising avenues to follow for the development of drugs likely to enhance working memory and other cognitive processes in individuals with schizophrenia.Objectives We reviewed the studies that have used pharmacological agents designed to target the dopamine system, the noradrenergic system, the acetycholine system, the serotonin system, and the glycine site on NMDA receptors.Results There are a large number of studies suggesting that dopamine agents can enhance working memory, though there remain conflicting issues regarding the role that baseline performance plays in modulating the influence of drug and the importance of different dopamine receptors. There is also consistent evidence that cholinesterase inhibitors can enhance working memory function, potentially through improved encoding of the information. There is less consistent evidence that noradrenergic alpha-2 agonists consistently improve working memory in humans, despite the large animal literature suggesting that these agents should have a beneficial effect on memory. As of yet, there is little evidence that agents targeting the glycine site of the NMDA receptor improve working memory, and data to suggest that enhancement of the serotonin system impairs working memory.Conclusions Compounds geared towards enhancing the dopamine system and the acetycholine system remain promising avenues for the development of pro-cognitive drugs, though further work is clearly needed on developing agents that may more selectively target specific receptors.     

肿瘤新生血管生成抑制剂的研究进展

肿瘤血管生成柳制剂一类能破坏或抑制血管生成,有效地阻止肿瘤生长和转移的药物。按作用机制可分为5大类：①抑制基底膜降解。②直接抑制内皮细胞增殖。③抑制血管生长因子活化。④抑制内皮细胞特异性整合素／生存信号。⑤其他非特异性作用机制的药物。本文主要简介正在进行临床试验的肿瘤血管生成抑制剂的最新研究进展。