除草剂毒莠定原药的致突变性

目的　研究除草剂毒莠定原药的致突变性。方法　采用小鼠骨髓多染红细胞微核试验,剂量设为雄性13 1、2 61、5 2 2mg/kg、雌性2 3 0、460、92 0mg/kg ;小鼠睾丸精母细胞染色体畸变试验,剂量设为3 2 6、65 3、13 0 5mg/kg。Ames试验用TA97、TA98、TA10 0、TA10 2菌株,加与不加S9试验,剂量设为5、5 0、5 0 0、10 0 0、5 0 0 0 μg/皿。结果　小鼠骨髓多染红细胞微核试验和小鼠睾丸精母细胞染色体畸变试验,各剂量组和阴性对照组比较,差异无显著性(P >0 0 5 ) ;Ames试验中各测试浓度的回变菌落数均末超过自然回变菌落数的2倍。结论　该试验范围内,未见毒莠定原药有致突变性。     

新型农用杀菌剂氰菌胺致突变实验研究

目的探讨氰菌胺原药的致突变作用。方法小鼠骨髓嗜多染红细胞微核试验分别以1000、500、250mg/kg剂量经口给药2d,小鼠睾丸初级精母细胞染色体畸变试验分别以2000、1000、500mg/kg剂量经口给药5d,观察骨髓嗜多染红细胞微核率及睾丸初级精母细胞染色体畸变率。鼠伤寒沙门杆菌回复突变试验(Ames试验),选用TA97、TA98、TA100和TA102菌株,试验剂量为5000、1000、200、40μg/皿,观察各菌株的回变菌落数。结果小鼠骨髓嗜多染红细胞微核率及小鼠睾丸初级精母细胞染色体畸变率与阴性对照组比较,差异均无统计学意义(P0.05)。Ames试验,氰菌胺原药各剂量组的回变菌落数均未超过自发回变菌落数的2倍,亦未见剂量-反应关系,Ames试验结果为阴性。结论上述致突变试验结果表明氰菌胺原药无致突变作用。     

对二氯苯致突变性的实验研究

目的　研究对二氯苯的致突变性。方法　Ames试验用TA97、TA98、TA10 0和TA10 2菌株 ,加与不加S 9试验 (剂量设为 0 2 5、0 5、1 0、2 0、5 0mg/皿 ) ;小鼠骨髓多染红细胞微核试验 (剂量设为 10 0、2 0 0、40 0、80 0mg/kg)和小鼠睾丸细胞染色体畸变试验 (剂量设为 2 5 0、5 0 0、10 0 0mg/kg)。结果　Ames试验中各测试浓度的回变菌落数均未超过自然回变菌落数 2倍 ;小鼠骨髓多染红细胞微核试验和小鼠睾丸细胞染色体畸变试验 ,各剂量组和阴性对照组差异无显著性 (P >0 0 5 )。结论　该试验范围内 ,未见对二氯苯有致突变性。     

沙蚕毒农药杀虫单原药的致突变作用

目的 探讨杀虫单原药的致突变作用.方法 取ICR小鼠60只,随机分为6组.剂量组分别以0.56、2.81、5.62、11.24mg/kg杀虫单原药灌胃染毒,连续2天,每天1次;阳性对照腹腔注射环磷酰胺(40mg/kg);阴性对照给予蒸馏水灌胃.取雄性ICR小鼠25只,随机分为5组.剂量组分别以6.875、13.75、27.50mg/kg杀虫单原药灌胃染毒,连续5天,每天1次;阳性对照给予环磷酰胺(40mg/kg);阴性对照给予蒸馏水.分别取胸骨、睾丸组织,常规制片,镜下观察骨髓多染红细胞微核和睾丸精母细胞染色体畸变细胞.分别以杀虫单原药40、200、1 000、5 000μg/,进行鼠伤寒沙门氏菌回复突变(Ames)试验.结果 各剂量组小鼠骨髓嗜多染红细胞微核率、睾丸精母细胞染色体畸变率与阴性对照组比较,差异均无统计学意义(P＞0.05);Ames试验显示各菌株各剂量组的回变菌落数均未超过自发回变菌落数的2倍.结论 在该试验条件下,未发现杀虫单原药的致突变性.     

阿维菌素原药的蓄积毒性和致突变性研究

研究新型农药阿维菌素原药的蓄积毒性和致突变性。对KM小鼠进行蓄积毒性试验、睾丸精母细胞染色体畸变试验和骨髓多染红细胞微核试验,以及鼠伤寒沙门氏菌回复突变(Am es)试验。结果表明:阿维菌素原药的蓄积毒性为轻度蓄积性;染色体畸变试验和骨髓微核试验阿维菌素组和阴性对照组差异无统计学意义(P>0.05),Am es试验阿维菌素组的回变菌落数均未超过自发回变菌落数的2倍,未呈现致突变性。 更多还原     

吡虫啉原药致突变实验研究

为探讨吡虫啉原药的致突变性,预测其遗传危害性和潜在致癌作用的可能性.采用昆明种健康小鼠经口灌胃染毒吡虫啉原药,小鼠骨髓多染红细胞微核实验的染毒剂量分别为90、45、23 mg/kg,睾丸细胞染色体畸变实验的剂量分别为150、75、38 mg/kg.取其股骨或睾丸组织,常规制片,观察分散良好的中期分裂相.鼠伤寒沙门氏菌回复突变(Ames)实验采用平板掺入法,染毒荆量分别为5 000、1 000、200、40 μg/皿.结果小鼠骨髓多染红细胞微核实验、小鼠睾丸细胞染色体畸变实验显示,吡虫啉原药组与阴性对照组相比,差异无统计学意义(P>0.05);Ames实验显示,不同测试浓度下各菌株的回变菌落数均未超过自发回变菌落数的2倍.提示在本实验条件下吡虫啉原药无致突变性.     

扑灭津原药致突变性实验研究

扑灭津原药致突变实验结果显示,小鼠骨髓嗜多染红细胞微核率及睾丸精母细胞染色体畸变率,染毒组与阴性对照组的差异均无统计学意义。Ames实验中各剂量组的回变菌落数均未超过自发回变菌落数的2倍。表明在本实验条件下,未发现扑灭津原药有明显的致突变性。     

FE-50致突变作用研究

目的　研究FE - 5 0是否具有致突变性。方法　以国家技术监督局《农药登记毒理学试验方法》GBl5 6 70 1995 [1] 为实验依据。选择小鼠骨髓嗜多染红细胞微核试验、小鼠睾丸染色体畸变试验和Ames试验进行研究。结果　Ames试验中 ,在不加S9条件下 ,TA98在剂量为 5 0、5 0 0ug/皿时的回变菌落数均高于空白和溶剂对照组的回变菌落数 (MR >2 ) ,且有剂量反应关系。在加S9条件下 ,TA98、TA10 0 在剂量为 5 0 0ug/皿时的回变菌落数均超过空白和溶剂对照组的回变菌落数的两倍。各剂量组小鼠骨髓嗜多染红细胞微核试验微核率、小鼠睾丸染色体畸变试验畸变细胞率和对照组比较 ,差异无显著性。结论　农药FE - 5 0具有潜在致突变作用。     

异丙草胺原药致突变性试验研究

目的探讨异丙草胺原药的致突变性,预测其遗传危害和潜在致癌作用的可能性。方法用昆明种小鼠经口灌胃染毒,骨髓微核试验的剂量分别为5000、2500、1250、625mg/kg,睾丸细胞染色体畸变试验的剂量为625.00、312.50、156.25mg/kg,分别取胸骨、睾丸组织,常规制片,镜下观察。鼠伤寒沙门氏菌回复突变(Ames)试验采用平板掺入法,剂量分别为0.5、1.0、2.0、5.0mg/皿。结果小鼠骨髓微核、睾丸细胞染色体畸变试验显示:异丙草胺原药染毒组与阴性对照组比较,差异无显著性(P>0.05);Ames试验显示各菌株的各剂量组的回变菌落数均未超过自发回变菌落数的两倍。结论在本试验条件下,未发现异丙草胺原药的致突变性。     

除草剂乙氧氟草醚原药致突变性实验研究

目的 探讨乙氧氟草醚原药的致突变作用.方法 将昆明种小鼠60只,雌雄各半,随机分为6组,每组10只.实验组分别以625、1 250、2 500、5 000 mg/kg乙氧氟草醚原药灌胃染毒,连续2 d,每天1次;阳性对照给予环磷酰胺（50 mg/kg）;阴性对照给予植物油灌胃.将雄性昆明种小鼠25只,随机分为5组,每组5只.实验组分别以250、500、1 000 mg/kg乙氧氟草醚原药灌胃染毒,连续5d,每天1次;阳性对照给予环磷酰胺（50 mg/kg）;阴性对照给予植物油.分别取胸骨、睾丸组织,常规制片,镜下观察骨髓多染红细胞微核率及睾丸精母细胞畸变细胞率.以乙氧氟草醚分别为500、1000、2 000、5 000 μg/皿,进行鼠伤寒沙门菌回复突变（Ames）试验.结果各剂量实验组小鼠骨髓多染红细胞微核率、睾丸精母细胞染色体畸变细胞率与阴性对照组比较,差异均无统计学意义（P＞0.05）;Ames实验显示各菌株各剂量组的回变菌落数均未超过自发回变菌落数的2倍.结论 在该试验条件下,未发现乙氧氟草醚原药的致突变性.     

A Wilcoxon-type test for trend

An extension of the Wilcoxon rank-sum test is developed to handle the situation in which a variable is measured for individuals in three or more (ordered) groups and a non-parametric test for trend across these groups is desired. The uses of the test are illustrated by two examples from cancer research.     

乙烷硒啉致突变试验研究

目的观察乙烷硒啉是否存在遗传毒性。方法应用Ames试验、中国仓鼠肺细胞体外培养染色体畸变试验和小鼠骨髓嗜多染红细胞微核试验,研究乙烷硒啉的致突变作用。结果Ames试验在〈400μg/皿浓度下未见回复突变菌落数显著增加;中国仓鼠肺细胞体外培养染色体畸变试验在〈3.3μg/ml浓度下未出现细胞染色体畸变率显著增高;小鼠骨髓嗜多染红细胞微核试验在〈20.0g/kg剂量下未诱发微核细胞率的增高。结论乙烷硒啉在试验剂量范围内无致突变作用。     

Adaptive testing for association between two random vectors in moderate to high dimensions

Testing for association between two random vectors is a common and important task in many fields, however, existing tests, such as Escoufier's RV test, are suitable only for low‐dimensional data, not for high‐dimensional data. In moderate to high dimensions, it is necessary to consider sparse signals, which are often expected with only a few, but not many, variables associated with each other. We generalize the RV test to moderate‐to‐high dimensions. The key idea is to data adaptively weight each variable pair based on its empirical association. As the consequence, the proposed test is adaptive, alleviating the effects of noise accumulation in high‐dimensional data, and thus maintaining the power for both dense and sparse alternative hypotheses. We show the connections between the proposed test with several existing tests, such as a generalized estimating equations‐based adaptive test, multivariate kernel machine regression (KMR), and kernel distance methods. Furthermore, we modify the proposed adaptive test so that it can be powerful for nonlinear or nonmonotonic associations. We use both real data and simulated data to demonstrate the advantages and usefulness of the proposed new test. The new test is freely available in R package aSPC on CRAN at https://cran.r-project.org/web/packages/aSPC/index.html and https://github.com/jasonzyx/aSPC .     

多中心多组临床试验的设计入路

目的本文提出一种用于多中心多组临床试验的设计入路,并同Cochran入路以至Mantel-Haenszel入路作以比较.方法以四格表卡方统计量为起点,将组数由2推广到大于2,层数由1到大干1,得到多层多组非中心参数表达式和检验统计量.结果本文入路计算简便,设计灵活,层数组数不受限制,可作非等层非等样本设计.相比之下,Cochran入路几乎不能用于3组以上,Mantel-Haenszel入路更限于等层设计.对于3中心3组等层设计,本文入路结果比Cochran入路大0到4,至于Mantel-Haenszel入路,为-3到1.本文入路结果多介于后二者之间.结论本文入路可用于多中心多组临床试验的设计.     

大肠癌非侵入性诊断试验的评价

本文以临床流行病学观点对大肠癌患者30例及正常人34名进行四种非侵入性诊断试验的评价,结果如下:CH_4、NQT、BT、LAT敏感度分别为80%,90%,70%,80%;特异度分别为70.6%,97%,91.1%100%;准确度分别为75%,93.7%,81.2%,90.6%.联合试验可提高诊断的敏感度与特异度,有助于对大肠癌作出正确的诊断.     

古尼拟青霉的致突变研究

古尼拟青霉为可代替名贵中药——冬虫夏草的新药。通过Ames试验、微核、姊妹染色单体互换(SCE)及精子畸形试验对古尼拟青霉进行诱变研究。试验结果均为阴性。初步认为古尼拟青霉无诱变性。     

某种含葛根黄酮的保健食品的急性毒性和遗传毒性研究

[目的]研究某种含葛根黄酮的保健食品的急性毒性和遗传毒性,为葛根黄酮的开发利用提供依据。[方法]应用小鼠急性经口毒性试验、Ames试验、小鼠骨髓嗜多染红细胞微核试验和小鼠精子畸形试验对该含葛根黄酮的保健食品的毒性进行了试验观察。[结果]该含葛根黄酮的保健食品对雌雄小鼠LD50均大于10 000 mg/kg.bw,属实际无毒物质;Ames试验中受试物各剂量组回变菌落数均未超过自发回变菌落数的2倍,亦无剂量-反应关系,结果为阴性;小鼠骨髓嗜多染红细胞微核试验和小鼠精子畸形试验中各剂量组微核率、精子畸形率与阴性对照组之间差异无统计学意义(P>0.05),而环磷酰胺阳性对照组与阴性对照组之间差异有统计学意义(P<0.01),证明实验结果均为阴性。[结论]本次实验条件下,该含葛根黄酮的保健食品属实际无毒物质,未显示有遗传毒性作用。     

Likelihood ratio and score tests to test the non‐inferiority (or equivalence) of the odds ratio in a crossover study with binary outcomes

We consider the non‐inferiority (or equivalence) test of the odds ratio (OR) in a crossover study with binary outcomes to evaluate the treatment effects of two drugs. To solve this problem, Lui and Chang (2011) proposed both an asymptotic method and a conditional method based on a random effects logit model. Kenward and Jones (1987) proposed a likelihood ratio test (LRT_M) based on a log linear model. These existing methods are all subject to model misspecification. In this paper, we propose a likelihood ratio test (LRT) and a score test that are independent of model specification. Monte Carlo simulation studies show that, in scenarios considered in this paper, both the LRT and the score test have higher power than the asymptotic and conditional methods for the non‐inferiority test; the LRT, score, and asymptotic methods have similar power, and they all have higher power than the conditional method for the equivalence test. When data can be well described by a log linear model, the LRT_M has the highest power among all the five methods (LRT_M, LRT, score, asymptotic, and conditional) for both non‐inferiority and equivalence tests. However, in scenarios for which a log linear model does not describe the data well, the LRT_M has the lowest power for the non‐inferiority test and has inflated type I error rates for the equivalence test. We provide an example from a clinical trial that illustrates our methods. Copyright © 2016 John Wiley & Sons, Ltd.     

医疗费用效果分析中的检验方法及其应用

目的：借用生存分析的方法，将“医疗费用”视为生存分析中的“生存时间”，“治愈和未治愈”视为生存分析中的“死亡和仍活着”，探讨该考察指标的统计检验问题。方法：给出了每治愈一例，两种治疗方案的平均费用的显著性检验方法（指数分布均数检验法）以及数据应满足的条件，进一步介绍了用非参数检验方法ｌｏｇｒａｎｋ进行分析和检验。结果：对每治愈一例，两组平均费用进行显著性差异检验。发现两种检验方法的结果接近，结论相同。结论：治愈一例患者的平均费用的显著性检验可以采用指数分布均数检验法进行分析，但要求资料近似服从指数分布；非参数方法ｌｏｇｒａｎｋ方法也可以分析和比较两种治疗方案每治愈一例患者的期望费用     

Testing the utility of mod scores and sib-pair analysis to detect presence of disease susceptibility loci

Linkage analyses and association studies were employed to detect disease susceptibility loci leading to elevated Q1 levels in Problem 2B. Phenotypes were defined to be the dichotomous affection status, the quantitative value for Q1, and Q1 adjusted for covariates. The method of mod-scores (for the dichotomous phenotype) and the Haseman-Elston sib-pair test on the dichotomous and quantitative phenotypes were used to screen for linkage of disease susceptibilitygenes to 367 markers. These analyses were performed on a sample ascertained from the first 60 replicates. The mod-score method detected linkage to MG1, MG2, and MG3 with scores of 1.5,5.0, and 1.6 respectively. Sib-pair analysis using quantitative phenotypes signaled linkage only to the area surrounding MG1; the dichotomous phenotype detected linkage only to MG2. Association studies used ANOVA on all founders in the first 60 replicates and ASSOC on the ascertained families and on a subset of families from the 60 replicates but only confirmed an association to MG1. In conclusion, the mod-score method may be a useful tool for genomic screens. © 1997 Wiley-Liss, Inc.