Aim Idiopathic pulmonary arterial hypertension(IPAH) and pulmonary veno-occlusive disease (PVOD) are undistinguished on clinical practice. We proposed that gene test might be a promising and feasible method in the fut...Aim Idiopathic pulmonary arterial hypertension(IPAH) and pulmonary veno-occlusive disease (PVOD) are undistinguished on clinical practice. We proposed that gene test might be a promising and feasible method in the future.Methods A 20-year-old woman was diagnosed as IPAH in 2013while a diagnosis of PVOD was also suspected. The genomic DNA was extracted from peripheral blood and gene panel testing was performed.展开更多
Objective Obesity is becoming a worldwide health problem. The genome wide association （GWA） study particularly for body mass index （BMI） has not been successfully conducted in the Chinese. In order to identify nov...Objective Obesity is becoming a worldwide health problem. The genome wide association （GWA） study particularly for body mass index （BMI） has not been successfully conducted in the Chinese. In order to identify novel genes for BMI variation in the Chinese, an initial GWA study and a follow up replication study were performed. Methods Affymetrix 500K SNPs were genotyped for initial GWA of 597 Northern Chinese. After quality control, 281 533 SNPs were included in the association analysis. Three SNPs were genotyped in a Southern Chinese replication sample containing 2 955 Chinese Han subjects. Association analyses were performed by Plink software. Results Eight SNPs were significantly associated with BMI variation after false discovery rate （FDR） correction （P=5.45×10-7-7.26×106, FDR q=0.033-0.048）. Two adjacent SNPs （rs4432245 ＆ rs711906） in the eukaryotic translation initiation factor 2 alpha kinase 4 （EIF2AK4） gene were significantly associated with BMI （P=6.38×10-6＆ 4.39×106, FDR q=0.048）. In the follow-up replication study, we confirmed the associations between BMI and rs4432245, rs711906 in the EIF2AKE gene （P=0.03 ＆ 0.01, respectively）. Conclusion Our study suggests novel mechanisms for BMI, where EIF2AK4 has exerted a profound effect on the synthesis and storage of triglycerides and may impact on overall energy homeostasis associated with obesity. The minor allele frequencies for the two SNPs in the EIF2AK4 gene have marked ethnic differences between Caucasians and the Chinese. The association of the EIF2AK4 gene with BMI is suggested to be ＇ethnic specific＇ in the Chinese.展开更多
Dermatophytes and other members of Onygenales are unique in their ability to degrade keratin,affecting hair and nails,and in the case of human hosts,causing skin infections.Subtillisins are essential proteases in kera...Dermatophytes and other members of Onygenales are unique in their ability to degrade keratin,affecting hair and nails,and in the case of human hosts,causing skin infections.Subtillisins are essential proteases in keratin assimilation,and subtilisin-like protease 1(SUB1)and SUB3-7 are specific for dermatophytes.eIF2αkinases are serine-threonine kinases that perform essential functions in response to infection,proteotoxicity,and nutrient scavenging.The relatively conserved nature of EIF2AK4 among fungi makes them potential evolutionary markers,which may contribute to a deeper understanding of der-matophyte taxonomy and evolution.This study aimed to assess the phylogeny of dermatophytes by examining the EIF2AK4 and SUB1 genes compared to the ITS gene marker.The phylogenetic trees generated from the EIF2AK4 and SUB1 genes exhibited a similar topology,which differed from that observed in the ITS tree.Our preliminary findings with a limited dataset suggest that the EIF2AK4 and SUB1 genes provide a reasonably correct reflection of the evolution of Arthrodermataceae.In addition,the study analyzed in vitro keratinolytic responses of 19 dermatophyte species using hairs of a broad range of mammals,including ancestral as well as derived species,as substrates.Trichophyton mentagrophytes and Nannizzia gypsea were the most active in degrading hair,while Trichophyton verrucosum,Trichophyton tonsurans and Epidermophyton floc-cosum showed low response.Hairs of Hyracoidea and Rodentia were most affected of all mammal hairs,while in contrast,bat hairs were difficult to degrade by nearly all tested dermatophyte species.Zoophilic species showed more activity than anthropophilic dermatophytes,but hair degradation profiles were not diagnostic for particular dermatophyte species.展开更多
文摘Aim Idiopathic pulmonary arterial hypertension(IPAH) and pulmonary veno-occlusive disease (PVOD) are undistinguished on clinical practice. We proposed that gene test might be a promising and feasible method in the future.Methods A 20-year-old woman was diagnosed as IPAH in 2013while a diagnosis of PVOD was also suspected. The genomic DNA was extracted from peripheral blood and gene panel testing was performed.
基金supported by grants from Natural Science Foundation of China(30600364,30470534,30771222,30731160618,30230210,and 81101655)the grant from the China Postdoctoral Science Foundation(2011M501282)
文摘Objective Obesity is becoming a worldwide health problem. The genome wide association （GWA） study particularly for body mass index （BMI） has not been successfully conducted in the Chinese. In order to identify novel genes for BMI variation in the Chinese, an initial GWA study and a follow up replication study were performed. Methods Affymetrix 500K SNPs were genotyped for initial GWA of 597 Northern Chinese. After quality control, 281 533 SNPs were included in the association analysis. Three SNPs were genotyped in a Southern Chinese replication sample containing 2 955 Chinese Han subjects. Association analyses were performed by Plink software. Results Eight SNPs were significantly associated with BMI variation after false discovery rate （FDR） correction （P=5.45×10-7-7.26×106, FDR q=0.033-0.048）. Two adjacent SNPs （rs4432245 ＆ rs711906） in the eukaryotic translation initiation factor 2 alpha kinase 4 （EIF2AK4） gene were significantly associated with BMI （P=6.38×10-6＆ 4.39×106, FDR q=0.048）. In the follow-up replication study, we confirmed the associations between BMI and rs4432245, rs711906 in the EIF2AKE gene （P=0.03 ＆ 0.01, respectively）. Conclusion Our study suggests novel mechanisms for BMI, where EIF2AK4 has exerted a profound effect on the synthesis and storage of triglycerides and may impact on overall energy homeostasis associated with obesity. The minor allele frequencies for the two SNPs in the EIF2AK4 gene have marked ethnic differences between Caucasians and the Chinese. The association of the EIF2AK4 gene with BMI is suggested to be ＇ethnic specific＇ in the Chinese.
文摘目的基于生物信息学与机器学习方法探讨多囊卵巢综合征(polycystic ovary syndrome,PCOS)关键基因,并在临床水平进行验证,同时筛选对相关基因起调控作用的中药。方法应用GEO数据库获取4个数据集,使用R软件包“Limma”和加权基因共表达网络分析(weighted gene co-expression network analysis,WGCNA)筛选PCOS组与健康对照组的差异表达基因,并对其进行功能富集和细胞免疫浸润分析。应用机器学习算法获取PCOS关键基因,绘制列线图,建立受试者工作特征(receiver operator characteristic,ROC)曲线评估列线图与每个关键基因识别PCOS的能力及特异性和敏感性。收集临床PCOS患者外周血单个核细胞,对关键基因表达量与PCOS识别情况进行临床验证。通过COREMINE数据库、古今医案云平台预测潜在调控PCOS的中药,并分析其性味归经及功效。结果4个数据集共获得42个样本,其中PCOS组21个样本,健康对照组21个样本。共获得差异基因127个,基因本体(gene ontology,GO)分析显示差异基因与肾上腺髓质素受体信号过程、细胞间桥、类固醇结合等有关;京都基因与基因组百科全书(Kyoto encyclopedia of genes and genomes,KEGG)分析显示差异基因与核因子-κB(nuclear factor-κB,NF-κB)介导的肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)信号传导、血管生成、白细胞介素-2(interleukin-2,IL-2)-信号转导和转录激活因子5(signal transducer and activator of transcription 5,STAT5)信号等相关。进一步进行细胞免疫浸润,发现PCOS组γδT细胞、单核细胞、激活的肥大细胞水平升高,浆细胞、CD4初始T细胞、激活的自然杀伤(natural killer,NK)细胞水平降低。最小绝对收缩和选择算子(logistic least absolute shrinkage and selection operator,LASSO)-Cox比例风险模型(Cox proportional-hazards model,COX)回归筛选11个关键靶点,包括AK4、DEPP1、DUOX2、FGG、GAREM1、PLOD2、SLC41A2、SPIN4、THNSL1、TMEM187、ZNF443,PCOS组关键基因的表达量均低于对照组(P<0.05),单个关键基因识别PCOS的曲线下面积(area under urve,AUC)为0.76~0.90,诺莫图识别PCOS的AUC为0.98。临床数据验证共纳入PCOS组12例,健康对照组12例,PCOS组AK4、ZNF443、DUOX2、DEPP1、FGG、SLC41A2、SPIN4与TMEM187的基因表达量均低于健康对照组(P<0.05),应用诺莫图验证对PCOS的识别,AUC为1。预测到与差异基因相关的中药85味,中药的四气以寒、温、平为主,五味以苦、甘、辛味为主,归经以肝、肺、胃经为主,功效以清热解毒、理气为主。结论AK4、DEPP1、DUOX2、FGG、GAREM1、PLOD2、SLC41A2、SPIN4、THNSL1、TMEM187、ZNF443可能是识别PCOS的潜在关键生物标志物以及对潜在治疗中药的预测二者为PCOS的诊断和治疗提供了新思路。
基金supported by China Scholarship Council(Number 201808520089)This work was supported by the 111 Project(D20009)+4 种基金National Natural Science Foundation of China(NSFCNo.32060034)Talent Base Project of Guizhou Province,China[RCJD2018-22]High-level Innovation Talent Project of Guizhou Province(GCC[2022]036-1)Major Science and Technology Projects of China Tobacco[No.110202101048(LS-08)].
文摘Dermatophytes and other members of Onygenales are unique in their ability to degrade keratin,affecting hair and nails,and in the case of human hosts,causing skin infections.Subtillisins are essential proteases in keratin assimilation,and subtilisin-like protease 1(SUB1)and SUB3-7 are specific for dermatophytes.eIF2αkinases are serine-threonine kinases that perform essential functions in response to infection,proteotoxicity,and nutrient scavenging.The relatively conserved nature of EIF2AK4 among fungi makes them potential evolutionary markers,which may contribute to a deeper understanding of der-matophyte taxonomy and evolution.This study aimed to assess the phylogeny of dermatophytes by examining the EIF2AK4 and SUB1 genes compared to the ITS gene marker.The phylogenetic trees generated from the EIF2AK4 and SUB1 genes exhibited a similar topology,which differed from that observed in the ITS tree.Our preliminary findings with a limited dataset suggest that the EIF2AK4 and SUB1 genes provide a reasonably correct reflection of the evolution of Arthrodermataceae.In addition,the study analyzed in vitro keratinolytic responses of 19 dermatophyte species using hairs of a broad range of mammals,including ancestral as well as derived species,as substrates.Trichophyton mentagrophytes and Nannizzia gypsea were the most active in degrading hair,while Trichophyton verrucosum,Trichophyton tonsurans and Epidermophyton floc-cosum showed low response.Hairs of Hyracoidea and Rodentia were most affected of all mammal hairs,while in contrast,bat hairs were difficult to degrade by nearly all tested dermatophyte species.Zoophilic species showed more activity than anthropophilic dermatophytes,but hair degradation profiles were not diagnostic for particular dermatophyte species.
