目的:基于国际疾病分类(International Classification of Diseases,ICD)第10版(ICD-10),通过分子流行病学的方法探索心血管疾病(cardiovascular diseases,CVD)主要亚型分类的分子生物学依据。方法:研究所采用的表型数据和基因型数据均...目的:基于国际疾病分类(International Classification of Diseases,ICD)第10版(ICD-10),通过分子流行病学的方法探索心血管疾病(cardiovascular diseases,CVD)主要亚型分类的分子生物学依据。方法:研究所采用的表型数据和基因型数据均来源于英国生物样本库(UK Biobank,UKB)。共纳入年龄在40~69岁的380083个样本,其中对照组是没有任何心血管疾病(不具有以字母I开头的ICD-10代码)的246437个样本,心血管疾病五大亚型分别为:(1)缺血性心脏病(ischaemic heart diseases,IHD);(2)肺源性心脏病和肺循环疾病(pulmonary heart disease and diseases of pulmonary circulation,PHD);(3)脑血管疾病(cerebrovascular diseases,CRB);(4)动脉、小动脉和毛细血管疾病(diseases of arteries,arterioles and capillaries,AAC);(5)静脉、淋巴管和淋巴结疾病,不可归类在他处者(diseases of veins,lymphatic vessels and lymph nodes,not elsewhere classified,VLL)。本研究首先对五大亚型分别进行全基因组关联分析(genome-wide association study,GWAS);然后,基于GWAS分析结果对五大亚型两两之间进行连锁不平衡回归分析(linkage disequilibrium score regression,LDSC)来计算亚型之间的遗传相关性;最后,对每一对亚型进行孟德尔随机化分析(Mendelian randomizatoin,MR)来评估亚型之间的因果联系。结果:GWAS研究新发现28个显著性基因位点。LDSC分析显示IHD分别和VLL(P=2.52×10-7)、PHD(P=3.77×10-3)、AAC(P=4.90×10-3)这3个亚型具有显著的遗传相关性。MR分析显示IHD对VLL(P=7.40×10-5)和AAC(P=1.50×10-3)这两个疾病的风险增加有正向因果关系,而反向因果皆不成立。结论:通过分子流行病学的方法,本研究发现基于ICD-10分类的一部分心血管疾病亚型之间存在遗传相关性和因果关联,对新版ICD标准的制定提供依据。展开更多
AIM To investigate the chemopreventive effect of sulindac, one of the nonstroidal anti inflammatory drugs (NSAIDs), on the growth of N methyl N nitrosourea (MNU) induced mouse colonic tumors.
All known subtypes of influenza A viruses are maintained in wild waterfowl, the natural reservoir of these viruses. Influenza A viruses are isolated from a variety of animal species with varying morbidity and mortalit...All known subtypes of influenza A viruses are maintained in wild waterfowl, the natural reservoir of these viruses. Influenza A viruses are isolated from a variety of animal species with varying morbidity and mortality rates. More importantly, influenza A viruses cause respiratory disease in humans with potentially fatal outcome. Local or global outbreaks in humans are typically characterized by excess hospitalizations and deaths. In 1997, highly pathogenic avian influenza viruses of the H5N1 subtype emerged in Hong Kong that transmitted to humans, resulting in the first documented cases of human death by avian influenza virus infection. A new outbreak started in July 2003 in poultry in Vietnam, Indonesia, and Thailand, and highly pathogenic avian H5N1 influenza viruses have since spread throughout Asia and into Europe and Africa. These viruses continue to infect humans with a high mortality rate and cause worldwide concern of a looming pandemic. Moreover, H5N1 virus outbreaks have had devastating effects on the poultry industries throughout Asia. Since H5N1 virus outbreaks appear to originate from Southern China, we here examine H5N1 influenza viruses in China, with an emphasis on their biological properties.展开更多
文摘目的:基于国际疾病分类(International Classification of Diseases,ICD)第10版(ICD-10),通过分子流行病学的方法探索心血管疾病(cardiovascular diseases,CVD)主要亚型分类的分子生物学依据。方法:研究所采用的表型数据和基因型数据均来源于英国生物样本库(UK Biobank,UKB)。共纳入年龄在40~69岁的380083个样本,其中对照组是没有任何心血管疾病(不具有以字母I开头的ICD-10代码)的246437个样本,心血管疾病五大亚型分别为:(1)缺血性心脏病(ischaemic heart diseases,IHD);(2)肺源性心脏病和肺循环疾病(pulmonary heart disease and diseases of pulmonary circulation,PHD);(3)脑血管疾病(cerebrovascular diseases,CRB);(4)动脉、小动脉和毛细血管疾病(diseases of arteries,arterioles and capillaries,AAC);(5)静脉、淋巴管和淋巴结疾病,不可归类在他处者(diseases of veins,lymphatic vessels and lymph nodes,not elsewhere classified,VLL)。本研究首先对五大亚型分别进行全基因组关联分析(genome-wide association study,GWAS);然后,基于GWAS分析结果对五大亚型两两之间进行连锁不平衡回归分析(linkage disequilibrium score regression,LDSC)来计算亚型之间的遗传相关性;最后,对每一对亚型进行孟德尔随机化分析(Mendelian randomizatoin,MR)来评估亚型之间的因果联系。结果:GWAS研究新发现28个显著性基因位点。LDSC分析显示IHD分别和VLL(P=2.52×10-7)、PHD(P=3.77×10-3)、AAC(P=4.90×10-3)这3个亚型具有显著的遗传相关性。MR分析显示IHD对VLL(P=7.40×10-5)和AAC(P=1.50×10-3)这两个疾病的风险增加有正向因果关系,而反向因果皆不成立。结论:通过分子流行病学的方法,本研究发现基于ICD-10分类的一部分心血管疾病亚型之间存在遗传相关性和因果关联,对新版ICD标准的制定提供依据。
文摘AIM To investigate the chemopreventive effect of sulindac, one of the nonstroidal anti inflammatory drugs (NSAIDs), on the growth of N methyl N nitrosourea (MNU) induced mouse colonic tumors.
基金Acknowledgments We thank Susan Watson for editing the manuscript and those in our laboratories who contributed to the data cited in this review. We also thank Ryo Takano for the preparation of figures. Research in HC＇s group is supported by the Ministry of Science and Technology, China （2004BA519A-57, 2006BAD06A05）. Research in GFG＇s group is supported by the Ministry of Science and Technology, China （MOST, 2005CB523001 and 2006BAD06A01）, the National Natural Science Foundation of China （NSFC, Grant #3059934, #30525010） and the US National Institutes of Health （U19 AI051915-05S1）. Research in YS＇s group is supported by the Ministry of Science and Technology, China （MOST, 2005CB523006 and 2006BAD06A15）, and the National Natural Science Foundation of China （NSFC, Grant #30599433）. Research in YK＇s group is supported by National Institute of Allergy and Infectious Diseases Public Health Service research grants by CREST and ERATO （Japan Science and Technology Agency）, and by grants-in-aid and a contract research fund for the Program of Founding Research Centers for Emerging and Reemerging Infectious Diseases from the Ministry of Education, Culture, Sports, Science, and Technology of Japan.
文摘All known subtypes of influenza A viruses are maintained in wild waterfowl, the natural reservoir of these viruses. Influenza A viruses are isolated from a variety of animal species with varying morbidity and mortality rates. More importantly, influenza A viruses cause respiratory disease in humans with potentially fatal outcome. Local or global outbreaks in humans are typically characterized by excess hospitalizations and deaths. In 1997, highly pathogenic avian influenza viruses of the H5N1 subtype emerged in Hong Kong that transmitted to humans, resulting in the first documented cases of human death by avian influenza virus infection. A new outbreak started in July 2003 in poultry in Vietnam, Indonesia, and Thailand, and highly pathogenic avian H5N1 influenza viruses have since spread throughout Asia and into Europe and Africa. These viruses continue to infect humans with a high mortality rate and cause worldwide concern of a looming pandemic. Moreover, H5N1 virus outbreaks have had devastating effects on the poultry industries throughout Asia. Since H5N1 virus outbreaks appear to originate from Southern China, we here examine H5N1 influenza viruses in China, with an emphasis on their biological properties.
