酸枣仁总皂苷抗抑郁作用的实验研究

目的研究酸枣仁总皂苷对行为绝望小鼠抑郁模型的影响。方法采用小鼠强迫游泳实验和悬尾实验抑郁模型,小鼠行为绝望的不动时间作为指标,考察酸枣仁总皂苷抗抑郁活性。结果酸枣仁总皂苷中、高剂量组均能减少小鼠强迫游泳和悬尾不动时间,与空白对照组比较差异有统计学意义(P<0.05,P<0.01)。结论酸枣仁总皂苷具有一定的抗抑郁作用。     

槟榔壳总酚类提取物抗抑郁作用研究

目的:探讨槟榔壳总酚类提取物对抑郁模型小鼠的抗抑郁作用。方法:采用小鼠悬尾、强迫游泳等抑郁模型,以小鼠行为绝望的不动时间作为指标,考察槟榔壳总酚类抗抑郁活性。结果:槟榔壳总酚类320,160 mg.kg-1剂量组均能显著减少小鼠悬尾和强迫游泳的不动时间。结论:槟榔壳总酚类可以改善小鼠的绝望行为,具有明显的抗抑郁作用。     

积雪草总三萜酸及其主要成分的抗抑郁活性研究

目的:探讨积雪草总三萜酸和其主要成分积雪草酸、羟基积雪草酸的抗抑郁作用.方法:采用小鼠强迫游泳实验、小鼠悬尾实验、开野实验和拮抗利血平所致的小鼠眼睑下垂实验,分别以小鼠不动时间、自主活动数和拮抗率作为评价指标.结果:在强迫游泳实验中积雪草总三萜酸、积雪草酸、羟基积雪草酸60 mg/kg、120 mg/kg剂量均能显著缩短小鼠不动时间,在悬尾实验中30 mg/kg、60 mg/kg、120 mg/kg剂量均能显著缩短小鼠不动时间,开野实验结果表明给药后小鼠的自主活动无明显变化,在利血平拮抗实验中积雪草总三萜酸、积雪草酸、羟基积雪草酸均可减少小鼠眼睑下垂.结论:积雪草总三萜酸、积雪草酸、羟基积雪草酸有抗抑郁作用.     

豆腐果苷抗抑郁作用的初步研究

目的初步探讨豆腐果苷的抗抑郁作用。方法采用小鼠悬尾实验及小鼠强迫游泳实验方法观察豆腐果苷的抗抑郁作用。结果在小鼠悬尾实验和小鼠强迫游泳实验中,豆腐果苷在20、30mg/kg剂量下能明显缩短小鼠的悬尾不动时间,在30、40mg/kg剂量下能明显缩短小鼠强迫游泳的不动时间。结论豆腐果苷在“行为绝望”动物模型中呈现抗抑郁作用,且量效曲线呈现行为学特有的U型曲线特征。     

柴芪口服液抗抑郁作用实验研究

摘要目的：实验观察柴芪口服液的抗抑郁作用。方法：将动物随机分为空白对照组、阳性对照（氟西汀）组、柴芪口服液高、中、低剂量组,分别灌胃给予同等容积的相应药物,qd,连续给予14d,末次给药后40min,采用小鼠悬尾实验、强迫游泳实验及开场实验等方法观察柴芪口服液的抗抑郁作用。结果：在小鼠强迫游泳实验和小鼠悬尾实验中,柴芪口服液大剂量（生药6．4g·kg^-1）能明显缩短两种“行为绝望”模型小鼠的不动时间;在小鼠开场实验中,柴芪口服液6．4g·kg^-1使小鼠水平方向活动次数显著提高,与对照组比较有显著性差异（P＜0．05）。结论：柴芪口服液具有抗抑郁作用。     

醒神开郁方抗抑郁作用的实验研究

目的：研究醒神开郁方的抗抑郁作用及其可能的作用机制。方法：采用小鼠悬尾、强迫游泳实验观察小鼠悬尾、游泳不动时间;自主活动实验测定小鼠自主活动次数;利血平诱导小鼠体温下降实验考察小鼠肛温、眼睑下垂度以及脑内单胺类神经递质含量等指标。采用SPSS 13.0软件对上述观察指标进行统计分析。结果：醒神开郁方对小鼠自主活动行为无显著影响;在小鼠悬尾和强迫游泳实验中,醒神开郁方低、中、高剂量组可明显缩短小鼠悬尾和强迫游泳不动时间（P〈0.05,P〈0.01,P〈0.01）。利血平诱导小鼠体温下降实验中,与模型组比较,醒神开郁方中、高剂量组可显著拮抗利血平所致小鼠的体温下降和眼睑下垂（P〈0.05,P〈0.01）;与模型组比较,醒神开郁方中、高剂量组均能显著增加小鼠脑组织内NE、5-HT含量（P〈0.01）以及DA含量（P〈0.05,P〈0.01）。结论：醒神开郁方具有显著的抗抑郁作用,其作用机制与增强脑组织内NE、5-HT、DA调节神经系统作用有关,且醒神开郁方无中枢兴奋作用。     

低剂量氯胺酮联用丁苯酞对急性抑郁小鼠行为的影响

目的探讨低剂量氯胺酮(ketamine)与丁苯酞(NBP)联用对抑郁行为的影响。方法采用悬尾实验、强迫游泳实验观察低剂量氯胺酮与丁苯酞联用的抗抑郁作用。强迫游泳和悬尾实验分别采用50只小鼠,随机分成5组,分别为溶剂对照组(Control组)、NBP 30 mg·kg~(-1)组(N组)、低剂量氯胺酮1 mg·kg~(-1)(LK组)、联用组(N+LK)、高剂量氯胺酮组15 mg·kg~(-1)(HK组)。强迫游泳实验需在实验前24 h进行15 min预游泳。给予相应的药物30 min后进行行为学测试。结果在悬尾实验中,与Control组相比,N+LK组和HK组均能明显降低小鼠的累积不动时间(P<0.01,P<0.05),而其他2组对降低小鼠累积不动时间无显著差异;在强迫游泳实验中,N+LK组和HK组均能显著降低小鼠的累积不动时间(P<0.01),其余组与Control组相比无差异;在自主活动实验中,与Control组相比,HK组能明显增加小鼠的直立次数(P<0.05),其余组在水平移动格数和直立次数均无明显差异。结论低剂量氯胺酮与丁苯酞联用较两者单用对急性抑郁小鼠的抗抑郁作用更强,与HK组抗抑郁作用相似,且未出现高剂量氯胺酮引起的不自主活动。     

芍药内酯苷抗抑郁作用的实验研究

目的:研究芍药内酯苷的抗抑郁作用.方法:采用小鼠悬尾、小鼠强迫游泳、小鼠自主活动实验,观察芍药内酯苷对小鼠游泳不动时间、悬尾不动时间及自主活动的影响.结果:芍药内酯苷14、7mg/kg均可显著缩短小鼠悬尾( P＜0.01,P＜0.05)及强迫游泳不动时间(P＜0.05),实验各剂量芍药内酯苷对小鼠自主活动无明显影响.结论:芍药内酯苷具有明显的抗抑郁作用.     

隐丹参酮对小鼠抑郁样行为的影响

目的 观察隐丹参酮的抗抑郁作用.方法 KM小鼠随机分为正常对照组、隐丹参酮低(10 mg·kg-1)、中(20 mg·kg-1)、高(30 mg·kg-1)剂量组及阳性药对照药组.采用小鼠悬尾实验、强迫游泳实验、利血平拮抗实验、5-HTP增强实验,考察隐丹参酮的抗抑郁作用.结果 隐丹参酮能够显著缩短悬尾和强迫游泳实验小...     

花椒多酚类化合物急性给药的抗抑郁作用及机制研究

目的探讨花椒多酚类化合物总提取物（ZPPC）急性给药对ICR小鼠抑郁模型的拮抗作用及可能的机制。方法采用经典的行为绝望抑郁模型,即小鼠悬尾实验和强迫游泳实验,观察ZPPC急性给药对应激小鼠绝望不动时间的影响;同时观察ZPPC对小鼠自主活动的影响,采用荧光分光光度法测定ZPPC对小鼠脑内单胺氧化酶活性的影响。结果与空白组比较,ZPPC（50,100,200mg·kg-1,i.g.）明显缩短小鼠悬尾和强迫游泳实验中的不动时间,其作用类似于阳性对照药丙咪嗪（10mg·kg-1,i.p.）;ZPPC还明显抑制脑内单胺氧化酶的活性。结论 ZPPC急性给药在小鼠行为绝望模型中显示出明显的抗抑郁作用,其作用机制可能与抑制脑内单胺氧化酶活性有关。     

对临床试验中显著性检验、区间检验及置信区间检验之间关系一致性的认识

显著性检验是最基本的统计假设检验,它的基本思想是小概率原理;区间检验是传统显著性检验的延伸,它用来检验两个总体的差异是否在某范围之内;置信区间检验是先找到药物疗效差值的置信区间,通过置信区间下限或(和)上限与界值的关系来判断两种药物非劣效、等效、优效的关系。通过公式推导发现,区间检验与显著性检验的主要区别是前者的假设中包含了有临床意义的界值△,而区间检验和置信区间检验是一致的,可以用置信区间检验实现区间检验的目的。     

谈谈两总体比较的非参数检验方法

针对不同的数据类型,探讨选用不同的非参数检验方法,并通过实例说明这些非参数检验方法的应用。     

A Comparison of Two-Sample Tests of Significance When Used With Variable Treatment Effects

This article compares the performance of many two-sample tests of significance that might be used to test the equality of means when the effect of the treatment is variable. Of the 19 tests that were compared, the normal scores test is recommended for general use in testing the null hypothesis of no treatment effect against the alternative that the distributions are stochastically ordered when the ratio of the larger standard deviation to the smaller standard deviation does not exceed 1.3. The Baumgartner-Weiß-Schindler tests and an adaptive test also have higher power than the pooled t-test, the unequal variance t-test, and the rank-sum test for many distributions. In the simulation studies, data in the first sample are generated from nine distributions, including long-tailed and skewed distributions. Data in the second sample are generated by adding a random treatment effect to a random variable that was generated from the same distribution that was used in the first sample. Because we restricted our power studies to treatment effects that are positive or zero, the population distributions will be stochastically ordered. The results of these studies demonstrate that the normal scores test is often more powerful than the t-tests and the rank-sum test. If the ratio of the standard deviations does exceed 1.3, then one of the t-tests is recommended.     

Testing equality of proportions for correlated binary data in ophthalmologic studies

In ophthalmologic studies, bilateral correlated data often arise when information involving paired organs (e.g., eyes) are measured from each subject. Adjusted chi-square approach for testing the equality of proportions has been proposed in the literature. In this article, we investigate and derive three alter- native testing procedures for the problem. Our simulation results show the score testing procedure usually produces satisfactory type I error control with higher power, and therefore is recommended. Examples from ophthalmologic studies are used to illustrate our proposed methods.     

中国药品上市后抽验模式现状及问题

目的在综合分析中国药品上市后抽验模式现状及问题的基础上,提出药品上市后抽验的建议。方法通过文献研究的方法,发现中国药品上市后抽验模式中存在的问题,并提出相关建议。结果与结论在药品抽验中引入以风险为基础的抽验模式,将药品上市后抽验结果与药品监管相衔接。     

Mutagenicity testing of quinine with submammalian and mammalian systems

Quinine hydrochloride was assayed for genotoxic activity by using 4 different test systems with distinct genetic endpoints. No indications for point mutations were observed in the Ames system. In 3 cytogenetic tests performed on small rodents, Chinese hamsters showed no genotoxic activity, while inbred strains of mice revealed a dose dependent increase of SCEs, enhanced incidence of micronuclei and elevated chromatid breaks.     

刹毒草口服液的药理作用研究

目的:研究刹毒草口服液对小鼠的药理作用。方法:用小鼠分别进行爬杆实验、炭粒廓清实验、耳肿胀实验和墨汁推进实验,观察刹毒草口服液对小鼠的抗疲劳作用、非特异性免疫功能的影响、抗炎作用和抗腹泻作用。结果:刹毒草口服液能显著延长小鼠爬杆时间,有较好的抗疲劳作用;高剂量刹毒草口服液能显著提高小鼠对惰性炭粒的吞噬指数及吞噬活性,可提高小鼠免疫功能;刹毒草口服液3个剂量组均对二甲苯致小鼠耳炎症有较好的抑制作用,且能显著降低墨汁推进的速率,有较好的抗腹泻作用。结论:刹毒草口服液具有一定抗疲劳、抗炎、提高非特异性免疫功能和抗腹泻作用。     

Simultaneous Test for Superiority and Noninferiority Hypotheses in Active-Controlled Clinical Trials∗

The primary objective of the dose-escalation trial for NGX267 was to estimate the maximally tolerated dose (MTD) and to gather detailed clinical and pharmacokinetic observations near the MTD. The MTD was defined based on the weighted average of moderate and severe adverse events. An adaptive design was employed to concentrate dosage assignments at or near the MTD. Favoring the acquisition of data near the MTD, at the expense of information at lower dosage levels, resulted in a shorter trial and no loss of the type of information required to inform subsequent studies where larger normal volunteer or patient samples are evaluated.     

氢溴酸山莨菪碱注射液细菌内毒素检查法的建立

目的:建立氢溴酸山莨菪碱注射液的细菌内毒素检查方法。方法:按《中国药典》2010年版(二部)附录相关方法确定本品细菌内毒素限值,分别进行细菌内毒素检查凝胶法和动态浊度法的干扰试验。结果:凝胶法结果表明,样品稀释2倍(5 mg/ml)时对试验无干扰作用;动态浊度法结果表明,本品稀释2倍(5 mg/ml)时外加内毒素的回收率在50%²00%之间。每1 mg氢溴酸山莨菪碱中含内毒素应小于0.35 EU。结论 :本文初步建立的氢溴酸山莨菪碱注射液细菌内毒素检查方法,可为《中国药典》增订该制剂的细菌内毒素检查项提供参考。     

Bootstrap inference in a linear equation estimated by instrumental variables

Summary We study several tests for the coefficient of the single right‐hand‐side endogenous variable in a linear equation estimated by instrumental variables. We show that writing all the test statistics—Student's t, Anderson–Rubin, the LM statistic of Kleibergen and Moreira (K), and likelihood ratio (LR)—as functions of six random quantities leads to a number of interesting results about the properties of the tests under weak‐instrument asymptotics. We then propose several new procedures for bootstrapping the three non‐exact test statistics and also a new conditional bootstrap version of the LR test. These use more efficient estimates of the parameters of the reduced‐form equation than existing procedures. When the best of these new procedures is used, both the K and conditional bootstrap LR tests have excellent performance under the null. However, power considerations suggest that the latter is probably the method of choice.