爱宁的致突变作用研究

目的检测爱宁的致突变性,以提供有关致突变的遗传毒性安全评价数据。方法设1.6,8,40,200和1000μg/皿5个剂量组,进行Am es试验;设0.3,1,3和9μg.mL-14个剂量组,进行仓鼠肺成纤维细胞染色体畸变试验;设15,100和250 mg.kg-13个剂量组,观察其对小鼠骨髓细胞微核的影响。结果Am es试验表明,爱宁在加和不加S9的条件下,对TA97,TA98,TA100和TA102菌株回复突变菌落结果为阴性。仓鼠肺成纤维细胞染色体畸变试验表明,爱宁对中国仓鼠肺成纤维细胞体外培养染色体无畸变作用。小鼠骨髓细胞微核试验表明,爱宁三个剂量组的微核出现率与阴性对照组比较无显著性差异。结论在本实验条件下,爱宁无致突变性。     

爱宁的致突变作用研究

目的检测爱宁的致突变性,以提供有关致突变的遗传毒性安全评价数据。方法设1.6,8,40,200和1000μg/皿5个剂量组,进行Am es试验;设0.3,1,3和9μg·mL^-14个剂量组,进行仓鼠肺成纤维细胞染色体畸变试验;设15,100和250 mg·kg^-13个剂量组,观察其对小鼠骨髓细胞微核的影响。结果Am es试验表明,爱宁在加和不加S9的条件下,对TA97,TA98,TA100和TA102菌株回复突变菌落结果为阴性。仓鼠肺成纤维细胞染色体畸变试验表明,爱宁对中国仓鼠肺成纤维细胞体外培养染色体无畸变作用。小鼠骨髓细胞微核试验表明,爱宁三个剂量组的微核出现率与阴性对照组比较无显著性差异。结论在本实验条件下,爱宁无致突变性。     

塑身胶囊的安全性毒理学研究

目的了解塑身减肥胶囊毒理学安全性,确保其食用安全。方法按《保健食品安全性毒理学评价程序和检验方法规范》进行小鼠急性毒性试验、Am es试验、小鼠骨髓嗜多染红细胞微核试验、小鼠精子畸变试验。结果受试物对小鼠经口LD 50>10g.kg-1,为实际无毒物;在Am es试验、小鼠骨髓嗜多染红细胞微核试验和小鼠精子畸变试验中均显示呈阴性反应,未显示致突变作用。结论塑身胶囊经口急性毒性LD 50>10g.kg-1;根据急性毒性分级,属实际无毒,且无致突变性,在正常摄入情况下对人体是安全的。     

聚乙二醇修饰降纤酶的遗传毒性评价

目的检测聚乙二醇修饰降纤酶的遗传毒性。方法应用鼠伤寒沙门菌回复突变试验(Ames试验)、体外培养CHO细胞染色体畸变试验和小鼠骨髓微核试验检测聚乙二醇修饰降纤酶的遗传毒性。结果 Ames试验结果显示每平皿100、20、4、0.8、0.16 U各个剂量组,在加或不加S9代谢活化系统时对组氨酸缺陷型鼠伤寒沙门菌TA97、TA98、TA100、TA102及TA1535所诱发的回复突变菌落数均与溶剂对照的突变菌落数相近。体外培养CHO细胞染色体畸变试验结果显示2.5、5.0和10.0 U.mL-1各个剂量组在加S9代谢活化系统于24 h和不加S9代谢活化系统于24 h、48 h培养的CHO细胞染色体畸变率与溶剂对照组比较均无显著差异(P>0.05)。小鼠骨髓微核试验显示425、850、1700 U.kg-1各个剂量组对ICR小鼠的微核诱发率与溶剂对照组比较均无显著差异(P>0.05)。结论聚乙二醇修饰降纤酶对鼠伤寒沙门菌无致突变性,对哺乳动物培养细胞的染色体无致畸变作用,对ICR小鼠无诱发骨髓嗜多染红细胞微核的效应。表明聚乙二醇修饰降纤酶在本实验条件下无遗传毒性。     

赤苷脉通注射液的致突变研究

目的探讨中药制剂赤苷脉通注射液的致突变性。方法采用鼠伤寒沙门氏组氨酸营养缺陷型菌株回复突变实验(Ames实验)、中国仓鼠肺成纤维细胞(CHL)染色体畸变实验和小鼠骨髓微核实验来检测赤苷脉通注射液的致突变作用。结果 Ames实验中,赤苷脉通注射液在312.5～5 000μg.皿-1剂量范围内,无论加或不加S9,鼠伤寒沙门氏菌组氨酸缺陷型TA97,TA98,TA100,TA102和TA1535 5株菌的回复突变菌落数均未出现剂量依赖性的增加;染色体畸变实验中,非活化条件或代谢活化条件下,药物质量浓度为1 200,600和300μg.mL-1时,细胞的染色体畸变率均未出现剂量依赖性增加;微核实验中,在1 150,575和287.5mg.kg-1剂量组中均未见骨髓中含微核的嗜多染红细胞数增加。结论在该实验室条件下,Ames实验、CHL细胞染色体畸变实验和小鼠骨髓微核实验结果均为阴性,即中药制剂赤苷脉通注射液无潜在的遗传毒性。     

藿莲香Ⅱ号复方的致突变性研究

目的根据《食品安全性毒理学评价程序和方法》(GB15193-2003)对中药复方藿莲香Ⅱ号进行相关的毒理学评价。方法应用急性毒性试验、小鼠骨髓嗜多染红细胞微核试验、小鼠骨髓细胞染色体畸变试验和Ames试验检测该复方的急性毒性和致突变性。结果急性经口毒性试验:雌性、雄性小鼠经口最大无毒浓度(MTD)为10g/kg体质量,属实际无毒;致突变实验:小鼠骨髓嗜多染红细胞微核试验、小鼠骨髓细胞染色体畸变试验和Ames试验结果均为阴性,显示在本实验条件下,该配伍未见有致突变性作用。结论藿莲香Ⅱ号未见有致突变性作用。     

中药复方藿莲香Ⅰ号的遗传毒理学研究

目的：根据前期藿莲香Ⅰ号药效学研究结果,进一步研究该复方的急性毒性和致突变作用,为其进一步应用的安全性提供理论依据。方法应用急性毒性实验、小鼠骨髓嗜多染红细胞微核试验、小鼠骨髓细胞染色体畸变试验和Ames试验检测该组分配伍复方的急性毒性和致突变性。结果急性经口毒性试验：雌性、雄性小鼠经口MTD均大于10g＆#183;kg-1,属实际无毒。致突变实验：小鼠骨髓嗜多染红细胞微核试验、小鼠骨髓细胞染色体畸变试验和Ames试验结果均为阴性,显示在本实验条件下,该中药复方未见有致突变性作用。结论中药复方藿莲香Ⅰ号未见有明显的急性毒性和致突变作用,表明该药物安全性良好。     

喹烯酮遗传毒性的研究

喹烯酮由中国农科院兰州畜牧与兽药研究所研制的一类低毒的抗菌促生长药物。为了探讨其遗传毒性,采用Ames试验、小鼠骨髓细胞微核试验和体外哺乳动物细胞染色体畸变试验,预测其遗传危害和潜在致癌的可能性。方法在Ames试验中,以1.0、2.6、6.9、18.2和50.0μg/皿的剂量,对TA97、TA98、TA100、TA102、TA1535、TA1537等6个菌株,采用直接掺入法进行试验;在微核试验中,以1700、3600和7200mg/kg的剂量,采用30h2次给药法制片观察,并计算微核率;在体外染色体畸变试验中,以1.25、2.5、5.0和10.0μg/ml的剂量为终浓度,采用V79细胞株,进行制片观察,并计算染色体畸变率。在Ames试验中,除TA102、TA1535为阴性外,各剂量组在18.2μg/皿时加和不加代谢活化系统都为阳性,且呈现一定的剂量-反应关系;在微核试验中,各剂量组微核率与阴性对照组比较差异无统计学意义(P>0.05);在体外染色体畸变试验,各剂量组加和不加代谢活化系统时染色体畸变率均小于5%,为阴性。本研究首次进行了6种菌株的Ames试验、微核试验和体外哺乳动物细胞染色体畸变试验,结果表明,喹烯酮对Ames试验菌株具有一定的致突变性,提示喹烯酮具有一定的遗传毒性。     

银参胶囊遗传毒性研究

目的探讨银参胶囊的遗传毒性。方法选用SPF级健康ICR小鼠,通过Ames试验、小鼠骨髓细胞微核试验、小鼠睾丸染色体畸变试验等遗传毒性试验验证银参胶囊的安全性。结果 Ames试验中,银参胶囊在8~5 000μg/皿剂量范围内,无论是否加入哺乳动物肝脏微粒体酶(S9),鼠伤寒沙门菌TA97,TA98,TA100,TA102等4株菌的回复突变菌落数均未出现剂量依赖性增加;微核试验中,2 500,5 000,10 000 mg/kg剂量组均未见骨髓中含微核的嗜多染红细胞数增加;小鼠睾丸染色体畸变试验中,药物质量分数为2 500,5 000,10 000 mg/kg时,细胞的染色体畸变率均未出现剂量依赖性增加。结论银参胶囊未显示致突变作用,可初步判定其在遗传毒性方面是安全的。     

3-甲氧基槲皮素的致突变性

目的　 3 甲氧基槲皮素是从植物中提取的药物 ,研究发现有很好的抗病毒作用。该文研究了 3 甲氧基槲皮素致突变性效应。方法　采用Ａｍｅｓ试验 ,ＣＨＬ细胞体外染色体畸变试验 ,小鼠骨髓微核试验 ,小鼠睾丸初级精母细胞染色体畸变试验进行检测。结果　Ａｍｅｓ试验 :在加或不加肝微粒体代谢活化酶系 (Ｓ9)的条件下 ,各菌株对最高浓度 3 75 0 μｇ 皿均呈现不同程度的抑菌作用 ,4个标准菌株各浓度组结果均阴性。ＣＨＬ细胞体外染色体畸变试验 :3 甲氧基槲皮素致染色体畸变类型以断片为主 ,未加代谢活化的 2 4ｈ染色体畸变率为 9% ,在 5 0 %…     

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.