Limitations of monolayer culture conditions have motivated scientists to explore new models that can recapitulate the architecture and function of human organs more accurately.Recent advances in the improvement of pro...Limitations of monolayer culture conditions have motivated scientists to explore new models that can recapitulate the architecture and function of human organs more accurately.Recent advances in the improvement of protocols have resulted in establishing three-dimensional(3D)organ-like architectures called‘organoids’that can display the characteristics of their corresponding real organs,including morphological features,functional activities,and personalized responses to specific pathogens.We discuss different organoid-based 3D models herein,which are classified based on their original germinal layer.Studies of organoids simulating the complexity of real tissues could provide novel platforms and opportunities for generating practical knowledge along with preclinical studies,including drug screening,toxicology,and molecular pathophysiology of diseases.This paper also outlines the key challenges,advantages,and prospects of current organoid systems.展开更多
Klinefelter syndrome(KS)is the most common sex chromosome disorder in men.It is characterized by germ cell loss and other variable clinical features,including autoimmunity.The sex-determining region of Y(SRY)-box 13(S...Klinefelter syndrome(KS)is the most common sex chromosome disorder in men.It is characterized by germ cell loss and other variable clinical features,including autoimmunity.The sex-determining region of Y(SRY)-box 13(Sox13)gene is expressed in mouse spermatogonia.In addition,it has been identified as islet cell autoantigen 12(ICA12),which is involved in the pathogenesis of autoimmune diseases,including type 1 diabetes mellitus(DM)and primary biliary cirrhosis.SOX13 expression has never been investigated in patients with KS.In this age-matched,case-control study performed on ten patients with KS and ten controls,we found that SOX13 is significantly downregulated in peripheral blood mononuclear cells of patients with KS compared to controls.This finding might be consistent with the germ cell loss typical of patients with KS.However,the role of SOX13 in the pathogenesis of germ cell loss and humoral autoimmunity in patients with KS deserves to be further explored.展开更多
背景与目的原发性纵隔生殖细胞瘤(primary mediastinal germ cell tumor,PMGCT)是一种相对罕见且偶尔会具有高度侵袭性的纵隔肿瘤。目前对PMGCT的疾病特异性生存期(disease special survival,DSS)的相关研究报道较少,大数据分析亦相对较...背景与目的原发性纵隔生殖细胞瘤(primary mediastinal germ cell tumor,PMGCT)是一种相对罕见且偶尔会具有高度侵袭性的纵隔肿瘤。目前对PMGCT的疾病特异性生存期(disease special survival,DSS)的相关研究报道较少,大数据分析亦相对较少,DSS预后模型也较为少见。本研究旨在探讨影响PMGCT DSS的预后相关因素,并构建简便、有效、可对PMGCT患者DSS预后情况进行预测的列线图。方法回顾性分析从监测、流行病学和最终结果(Surveillance,Epidemiology,and End Results,SEER)数据库提取的1975年-2019年共347例PMGCT患者的临床病理资料。采用Kaplan-Meier法及Log-rank检验估计DSS。执行Cox比例风险回归模型筛选影响预后的独立危险因素,构建个体化列线图预测PMGCT患者的3年、5年、8年DSS。通过受试者工作特征(receiver operating characteristic,ROC)曲线、校正曲线及决策曲线分析(decision curve analysis,DCA)评估模型的预测精度。结果PMGCT患者的3年、5年、8年生存率分别为84.6%、83.6%、83.3%。单因素Cox回归分析显示组织学分型、手术与否、年龄、肿瘤大小、肿瘤转移情况及肿瘤分期6项因素可影响PMGCT的预后(P<0.05),多因素Cox回归分析显示组织学分型、手术与否、年龄、肿瘤大小是PMGCT患者预后的独立危险因素(P<0.05),利用这些独立危险因素构建了列线图模型。ROC的曲线下面积(area under the curve,AUC)为0.824,3年、5年、8年生存时间的校正曲线以及DCA曲线,三者结果提示本研究的列线图评估预测结果与真实结果之间有良好的一致性。结论PMGCT中组织学分型为精原细胞瘤的患者比非精原细胞瘤患者预后更佳,年龄>40岁、肿瘤大小≥15 cm且未进行过手术治疗的患者预后不佳。列线图模型可以对PMGCT患者的DSS进行准确直观的预测。展开更多
Von Hippel-Lindau （VHL） disease is a rare autosomal dominant disorder caused by germ line mutations of the VHL tumour suppressor gene. it predisposes affected individuals to develop a variety of neoplasms, including...Von Hippel-Lindau （VHL） disease is a rare autosomal dominant disorder caused by germ line mutations of the VHL tumour suppressor gene. it predisposes affected individuals to develop a variety of neoplasms, including haemangioblastomas of the central nervous system, retinal angiomas, renal cell carcinomas （RCCs）, pheochromocytomas and cysts of the kidneys and epididymis. Germ line VHL mutations have been found in all VHL disease families. RCC occurs in 25% to 45% of patients with VHL disease and is one of the leading causes of death.展开更多
基金supported by the National Cancer Control Charity Foundation(Registration Number 41476,Grant Number,235)Iran National Science Foundation,INSF(Grant Number,97014445)by the Ministry of Science and Higher Education of the Russian Federation within the framework of state support for the creation and development of World-Class Research Centers"Digital biodesign and personalized healthcare"(No.075-15-2020-926).
文摘Limitations of monolayer culture conditions have motivated scientists to explore new models that can recapitulate the architecture and function of human organs more accurately.Recent advances in the improvement of protocols have resulted in establishing three-dimensional(3D)organ-like architectures called‘organoids’that can display the characteristics of their corresponding real organs,including morphological features,functional activities,and personalized responses to specific pathogens.We discuss different organoid-based 3D models herein,which are classified based on their original germinal layer.Studies of organoids simulating the complexity of real tissues could provide novel platforms and opportunities for generating practical knowledge along with preclinical studies,including drug screening,toxicology,and molecular pathophysiology of diseases.This paper also outlines the key challenges,advantages,and prospects of current organoid systems.
文摘Klinefelter syndrome(KS)is the most common sex chromosome disorder in men.It is characterized by germ cell loss and other variable clinical features,including autoimmunity.The sex-determining region of Y(SRY)-box 13(Sox13)gene is expressed in mouse spermatogonia.In addition,it has been identified as islet cell autoantigen 12(ICA12),which is involved in the pathogenesis of autoimmune diseases,including type 1 diabetes mellitus(DM)and primary biliary cirrhosis.SOX13 expression has never been investigated in patients with KS.In this age-matched,case-control study performed on ten patients with KS and ten controls,we found that SOX13 is significantly downregulated in peripheral blood mononuclear cells of patients with KS compared to controls.This finding might be consistent with the germ cell loss typical of patients with KS.However,the role of SOX13 in the pathogenesis of germ cell loss and humoral autoimmunity in patients with KS deserves to be further explored.
文摘背景与目的原发性纵隔生殖细胞瘤(primary mediastinal germ cell tumor,PMGCT)是一种相对罕见且偶尔会具有高度侵袭性的纵隔肿瘤。目前对PMGCT的疾病特异性生存期(disease special survival,DSS)的相关研究报道较少,大数据分析亦相对较少,DSS预后模型也较为少见。本研究旨在探讨影响PMGCT DSS的预后相关因素,并构建简便、有效、可对PMGCT患者DSS预后情况进行预测的列线图。方法回顾性分析从监测、流行病学和最终结果(Surveillance,Epidemiology,and End Results,SEER)数据库提取的1975年-2019年共347例PMGCT患者的临床病理资料。采用Kaplan-Meier法及Log-rank检验估计DSS。执行Cox比例风险回归模型筛选影响预后的独立危险因素,构建个体化列线图预测PMGCT患者的3年、5年、8年DSS。通过受试者工作特征(receiver operating characteristic,ROC)曲线、校正曲线及决策曲线分析(decision curve analysis,DCA)评估模型的预测精度。结果PMGCT患者的3年、5年、8年生存率分别为84.6%、83.6%、83.3%。单因素Cox回归分析显示组织学分型、手术与否、年龄、肿瘤大小、肿瘤转移情况及肿瘤分期6项因素可影响PMGCT的预后(P<0.05),多因素Cox回归分析显示组织学分型、手术与否、年龄、肿瘤大小是PMGCT患者预后的独立危险因素(P<0.05),利用这些独立危险因素构建了列线图模型。ROC的曲线下面积(area under the curve,AUC)为0.824,3年、5年、8年生存时间的校正曲线以及DCA曲线,三者结果提示本研究的列线图评估预测结果与真实结果之间有良好的一致性。结论PMGCT中组织学分型为精原细胞瘤的患者比非精原细胞瘤患者预后更佳,年龄>40岁、肿瘤大小≥15 cm且未进行过手术治疗的患者预后不佳。列线图模型可以对PMGCT患者的DSS进行准确直观的预测。
基金This study was supported by a grant from the Doctoral Foundation of Shanghai Jiaotong University Medical School(No.BXJ0615)
文摘Von Hippel-Lindau （VHL） disease is a rare autosomal dominant disorder caused by germ line mutations of the VHL tumour suppressor gene. it predisposes affected individuals to develop a variety of neoplasms, including haemangioblastomas of the central nervous system, retinal angiomas, renal cell carcinomas （RCCs）, pheochromocytomas and cysts of the kidneys and epididymis. Germ line VHL mutations have been found in all VHL disease families. RCC occurs in 25% to 45% of patients with VHL disease and is one of the leading causes of death.
