目的探讨组织尾侧型同源转录因子2(Caudal type homeobox transcription factor 2,CDX2)、肝细胞核因子4α(Hepatocyte nuclear factor 4 alpha,HNF4α)、腺苷酸环化酶相关蛋白2(Adenylate cyclase related protein 2,CAP2)联合检测对...目的探讨组织尾侧型同源转录因子2(Caudal type homeobox transcription factor 2,CDX2)、肝细胞核因子4α(Hepatocyte nuclear factor 4 alpha,HNF4α)、腺苷酸环化酶相关蛋白2(Adenylate cyclase related protein 2,CAP2)联合检测对幽门螺杆菌(Hp)感染相关高危胃癌患者的诊断价值。方法收集2017年2月-2019年1月胜利油田中心医院收治的47例萎缩性胃炎及59例胃癌患者胃黏膜组织标本;免疫组化染色测定组织CDX2、HNF4α、CAP2蛋白表达情况,快速银染法检测Hp感染情况,分析三者在Hp感染相关胃部炎症恶性转化过程中的作用,受试者工作曲线(Receiver operator characteristic curve,ROC)分析三者联合检测对Hp感染相关胃癌的诊断价值。结果胃癌患者组织标本CDX2阳性率低于萎缩性胃癌患者(P<0.05),HNF4α、CAP2阳性率高于萎缩性胃炎患者(P<0.05);胃癌患者Hp感染率为79.66%,高于萎缩性胃炎Hp感染率42.55%(P<0.05),Hp阳性胃癌、萎缩性胃炎组织标本CDX2、HNF4α、CAP2阳性率皆高于Hp阴性病例组织标本(P<0.05);胃癌患者组织CDX2、HNF4α、CAP2表达与Hp感染率呈正相关(P<0.05);HNF4α阳性染色评分>3分预测Hp相关高危胃癌价值最高,曲线下面积(Area under the curve,AUC)为0.870,敏感度、特异性分别为91.49%、75.00%;其次为CAP2,AUC为0.860,敏感度、特异性为89.36%、75.00%;三者联合预测Hp相关高危胃癌综合效能最高,AUC为0.891,敏感度、特异性分别为89.36%、91.67%。结论组织CDX2、HNF4α、CAP2异常表达与Hp感染有关,参与胃炎向胃癌恶性转化过程;联合检测组织CDX2、HNF4α、CAP2对Hp感染相关高危胃癌有较高的预测价值。展开更多
青少年的成年起病型糖尿病(maturity-onset diabetes of the young, MODY)是一种异质性的单基因糖尿病,其中MODY1、MODY2和MODY3是常见的MODY亚型。近年来胰升糖素样肽1受体激动剂(GLP-1RA)、二肽基肽酶4抑制剂(DPP-4i)、钠-葡萄糖共转...青少年的成年起病型糖尿病(maturity-onset diabetes of the young, MODY)是一种异质性的单基因糖尿病,其中MODY1、MODY2和MODY3是常见的MODY亚型。近年来胰升糖素样肽1受体激动剂(GLP-1RA)、二肽基肽酶4抑制剂(DPP-4i)、钠-葡萄糖共转运蛋白2抑制剂(SGLT2i)与葡萄糖激酶激动剂(GKA)等新型降糖药物在治疗糖尿病方面取得了良好的进展,本文结合目前最新的基础及临床证据,对上述三种MODY的发病机制、临床特征、关于新型降糖药物的诊疗进展作一综述,旨在为MODY的诊疗开拓更为安全有效的新方法。展开更多
A recent work of Iliopoulos et al published in Cell highlighted a circuit orchestrated by microRNAs (miRNAs) that results in liver tumorigenesis and inflammation. This feedback loop, governed by miR-24 and miR-629, pr...A recent work of Iliopoulos et al published in Cell highlighted a circuit orchestrated by microRNAs (miRNAs) that results in liver tumorigenesis and inflammation. This feedback loop, governed by miR-24 and miR-629, promotes a hepatocyte nuclear factor-4α transient inhibition resulting in miR-124 induction and signal transducer and activator of transcription 3 activation. These promising data support the use of miRNA mimics or inhibitors as potent therapeutic approaches in liver cancer.展开更多
目的:研究肝细胞核因子-4α(hepatocyte nuclear factor-4α,HNF-4α)基因的P2启动子区域的2个单核苷酸多态性(SNP)位点rs1884614和rs2144908与2型糖尿病的相关性。方法:收集2型糖尿病患者328例和非糖尿病患者196例,应用Taq Man SNP Gen...目的:研究肝细胞核因子-4α(hepatocyte nuclear factor-4α,HNF-4α)基因的P2启动子区域的2个单核苷酸多态性(SNP)位点rs1884614和rs2144908与2型糖尿病的相关性。方法:收集2型糖尿病患者328例和非糖尿病患者196例,应用Taq Man SNP Genotyping系统进行rs1884614和rs2144908的基因型多态性分析。并分析它们与患者有关临床代谢指标的关系。结果:两组的基因型分布及等位基因频率差异无统计学意义(P>0.05);但在非肥胖(BMI<25 kg/m^2)患者的OGTT检测中,rs1884614 T/T基因型与较小的血浆胰岛素曲线下面积存在相关性(P<0.05)。结论:HNF-4α基因的P2启动子区的SNP rs1884614可能影响江苏地区非肥胖型2型糖尿病患者的胰岛素分泌。展开更多
AIM: To investigate the effect of hepatocyte nuclear factor 4α(HNF4α) on the differentiation and transformation of hepatic stellate cells(HSCs).METHODS: By constructing the recombinant adenovirus vector expressing H...AIM: To investigate the effect of hepatocyte nuclear factor 4α(HNF4α) on the differentiation and transformation of hepatic stellate cells(HSCs).METHODS: By constructing the recombinant adenovirus vector expressing HNF4α and HNF4αshRNA vector, and manipulating HNF4α expression in HSC-T6 cells, we explored the influence of HNF4α and its induction capacity in the differentiation of rat HSCs into hepatocytes.RESULTS: With increased expression of HNF4αmediated by AdHNF4α, the relative expression of Nanog was downregulated in HSC-T6 cells(98.33 ±12.33 vs 41.33 ± 5.67, P < 0.001). Consequently, the expression of G-P-6 and PEPCK was upregulated(G-P-6:14.34 ± 3.33 vs 42.53 ± 5.87, P < 0.01; PEPCK: 10.10± 4.67 vs 56.56 ± 5.25, P < 0.001), the expression of AFP and ALB was positive, and the expression of Nanog, Type Ⅰ collagen, α-SMA, and TIMP-1 was significantly decreased. HNF4α also downregulated vimentin expression and enhanced E-cadherin expression. The ultrastructure of HNF4α-induced cells had more mitochondria and ribosomes compared with the parental cells. After silencing HNF4α expression,EPCK, E-cadherin, AFP, and ALB were downregulated and α-SMA and vimentin were upregulated.CONCLUSION: HNF4α can induce a tendency of differentiation of HSCs into hepatocyte-like cells. These findings may provide an effective way for the treatmentof liver diseases.展开更多
文摘目的探讨组织尾侧型同源转录因子2(Caudal type homeobox transcription factor 2,CDX2)、肝细胞核因子4α(Hepatocyte nuclear factor 4 alpha,HNF4α)、腺苷酸环化酶相关蛋白2(Adenylate cyclase related protein 2,CAP2)联合检测对幽门螺杆菌(Hp)感染相关高危胃癌患者的诊断价值。方法收集2017年2月-2019年1月胜利油田中心医院收治的47例萎缩性胃炎及59例胃癌患者胃黏膜组织标本;免疫组化染色测定组织CDX2、HNF4α、CAP2蛋白表达情况,快速银染法检测Hp感染情况,分析三者在Hp感染相关胃部炎症恶性转化过程中的作用,受试者工作曲线(Receiver operator characteristic curve,ROC)分析三者联合检测对Hp感染相关胃癌的诊断价值。结果胃癌患者组织标本CDX2阳性率低于萎缩性胃癌患者(P<0.05),HNF4α、CAP2阳性率高于萎缩性胃炎患者(P<0.05);胃癌患者Hp感染率为79.66%,高于萎缩性胃炎Hp感染率42.55%(P<0.05),Hp阳性胃癌、萎缩性胃炎组织标本CDX2、HNF4α、CAP2阳性率皆高于Hp阴性病例组织标本(P<0.05);胃癌患者组织CDX2、HNF4α、CAP2表达与Hp感染率呈正相关(P<0.05);HNF4α阳性染色评分>3分预测Hp相关高危胃癌价值最高,曲线下面积(Area under the curve,AUC)为0.870,敏感度、特异性分别为91.49%、75.00%;其次为CAP2,AUC为0.860,敏感度、特异性为89.36%、75.00%;三者联合预测Hp相关高危胃癌综合效能最高,AUC为0.891,敏感度、特异性分别为89.36%、91.67%。结论组织CDX2、HNF4α、CAP2异常表达与Hp感染有关,参与胃炎向胃癌恶性转化过程;联合检测组织CDX2、HNF4α、CAP2对Hp感染相关高危胃癌有较高的预测价值。
文摘青少年的成年起病型糖尿病(maturity-onset diabetes of the young, MODY)是一种异质性的单基因糖尿病,其中MODY1、MODY2和MODY3是常见的MODY亚型。近年来胰升糖素样肽1受体激动剂(GLP-1RA)、二肽基肽酶4抑制剂(DPP-4i)、钠-葡萄糖共转运蛋白2抑制剂(SGLT2i)与葡萄糖激酶激动剂(GKA)等新型降糖药物在治疗糖尿病方面取得了良好的进展,本文结合目前最新的基础及临床证据,对上述三种MODY的发病机制、临床特征、关于新型降糖药物的诊疗进展作一综述,旨在为MODY的诊疗开拓更为安全有效的新方法。
文摘A recent work of Iliopoulos et al published in Cell highlighted a circuit orchestrated by microRNAs (miRNAs) that results in liver tumorigenesis and inflammation. This feedback loop, governed by miR-24 and miR-629, promotes a hepatocyte nuclear factor-4α transient inhibition resulting in miR-124 induction and signal transducer and activator of transcription 3 activation. These promising data support the use of miRNA mimics or inhibitors as potent therapeutic approaches in liver cancer.
文摘目的:研究肝细胞核因子-4α(hepatocyte nuclear factor-4α,HNF-4α)基因的P2启动子区域的2个单核苷酸多态性(SNP)位点rs1884614和rs2144908与2型糖尿病的相关性。方法:收集2型糖尿病患者328例和非糖尿病患者196例,应用Taq Man SNP Genotyping系统进行rs1884614和rs2144908的基因型多态性分析。并分析它们与患者有关临床代谢指标的关系。结果:两组的基因型分布及等位基因频率差异无统计学意义(P>0.05);但在非肥胖(BMI<25 kg/m^2)患者的OGTT检测中,rs1884614 T/T基因型与较小的血浆胰岛素曲线下面积存在相关性(P<0.05)。结论:HNF-4α基因的P2启动子区的SNP rs1884614可能影响江苏地区非肥胖型2型糖尿病患者的胰岛素分泌。
基金Supported by National Natural Science Foundation of China,No.81070359
文摘AIM: To investigate the effect of hepatocyte nuclear factor 4α(HNF4α) on the differentiation and transformation of hepatic stellate cells(HSCs).METHODS: By constructing the recombinant adenovirus vector expressing HNF4α and HNF4αshRNA vector, and manipulating HNF4α expression in HSC-T6 cells, we explored the influence of HNF4α and its induction capacity in the differentiation of rat HSCs into hepatocytes.RESULTS: With increased expression of HNF4αmediated by AdHNF4α, the relative expression of Nanog was downregulated in HSC-T6 cells(98.33 ±12.33 vs 41.33 ± 5.67, P < 0.001). Consequently, the expression of G-P-6 and PEPCK was upregulated(G-P-6:14.34 ± 3.33 vs 42.53 ± 5.87, P < 0.01; PEPCK: 10.10± 4.67 vs 56.56 ± 5.25, P < 0.001), the expression of AFP and ALB was positive, and the expression of Nanog, Type Ⅰ collagen, α-SMA, and TIMP-1 was significantly decreased. HNF4α also downregulated vimentin expression and enhanced E-cadherin expression. The ultrastructure of HNF4α-induced cells had more mitochondria and ribosomes compared with the parental cells. After silencing HNF4α expression,EPCK, E-cadherin, AFP, and ALB were downregulated and α-SMA and vimentin were upregulated.CONCLUSION: HNF4α can induce a tendency of differentiation of HSCs into hepatocyte-like cells. These findings may provide an effective way for the treatmentof liver diseases.
