目的分析血清乙型肝炎病毒(hepatitis B virus,HBV)前S1蛋白(precursor S1 protein,preS1)与慢性乙型肝炎(chronic hepatitis B,CHB)肝纤维化及癌变进展的相关性。方法对2019年10月—2021年10月期间在青海红十字医院接受检查的228例乙...目的分析血清乙型肝炎病毒(hepatitis B virus,HBV)前S1蛋白(precursor S1 protein,preS1)与慢性乙型肝炎(chronic hepatitis B,CHB)肝纤维化及癌变进展的相关性。方法对2019年10月—2021年10月期间在青海红十字医院接受检查的228例乙肝表面抗原(hepatitis B surface antigen,HBsAg)阳性慢性HBV感染者进行回顾性分析,其中CHB患者75例、肝硬化(liver cirrhosis,LC)患者93例(LC组)、肝细胞癌(hepatocellular carcinoma,HCC)患者60例(HCC组)。根据LC和HCC组肝组织活检分析肝脏炎症活动及肝纤维化程度。结果HCC组血清preS1水平[496.32(457.63,988.0)ng/mL]和LC组[338.72(247.93,554.61)ng/mL]血清preS1水平均显著高于CHB组[113.69(87.09,177.40)ng/mL],且差异具有统计学意义(P均<0.05)。HCC组血清preS1水平亦高于LC组(P=0.002)。经受试者工作特征曲线分析,血清preS1水平鉴别诊断CHB与LC的曲线下面积(area under the curve,AUC)是0.881(95%CI:0.830~0.932),鉴别诊断CHB/LC与HCC的AUC是0.861(95%CI:0.815~0.908)。3组患者的血清preS1水平与HBsAg(rs=0.799,P<0.001)呈强正相关和Log HBV DNA(rs=0.262,P<0.001)呈弱正相关。此外LC组和HCC组血清preS1水平与肝脏炎症活动分级(rs=0.201,P=0.009)及肝纤维化分期也呈弱正相关性(rs=0.295,P<0.001)。结论血清preS1水平与血清HBsAg、HBV DNA水平和肝脏炎症和纤维化进展呈正相关,有可能成为鉴别诊断HBV相关慢性肝病肝硬化或癌变的候选标志物。展开更多
Sortilin-related receptor 1(SORL1)is a critical gene associated with late-onset Alzheimer’s disease.SORL1 contributes to the development and progression of this neurodegenerative condition by affecting the transport ...Sortilin-related receptor 1(SORL1)is a critical gene associated with late-onset Alzheimer’s disease.SORL1 contributes to the development and progression of this neurodegenerative condition by affecting the transport and metabolism of intracellularβ-amyloid precursor protein.To better understand the underlying mechanisms of SORL1 in the pathogenesis of late-onset Alzheimer s disease,in this study,we established a mouse model of SorI1 gene knockout using cluste red regularly inters paced short palindro mic repeats-associated protein 9 technology.We found that Sorl1-knocko ut mice displayed deficits in learning and memory.Furthermore,the expression of brain-derived neurotrophic factor was significantly downregulated in the hippocampus and co rtex,and amyloidβ-protein deposits were observed in the brains of 5orl1-knockout mice.In vitro,hippocampal neuronal cell synapses from homozygous Sorl1-knockout mice were impaired.The expression of synaptic proteins,including Drebrin and NR2B,was significantly reduced,and also their colocalization.Additionally,by knocking out the Sorl1 gene in N2a cells,we found that expression of the N-methyl-D-aspartate receptor,NR2B,and cyclic adenosine monophosphate-response element binding protein was also inhibited.These findings suggest that SORL1 participates in the pathogenesis of late-onset Alzheimer s disease by regulating the N-methyl-D-aspartate receptor NR2B/cyclic adenosine monophosphate-response element binding protein signaling axis.展开更多
目的研究G_(2)/S期应答相关蛋白1(G_(2) and S phase-expressed protein 1,GTSE1)在肝细胞癌(hepatocellular carcinoma,HCC)中的表达、免疫学作用和预后分析,及其潜在作用机制。方法使用公共数据库癌症基因组图谱(The Cancer Genome At...目的研究G_(2)/S期应答相关蛋白1(G_(2) and S phase-expressed protein 1,GTSE1)在肝细胞癌(hepatocellular carcinoma,HCC)中的表达、免疫学作用和预后分析,及其潜在作用机制。方法使用公共数据库癌症基因组图谱(The Cancer Genome Atlas,TCGA)提供的数据,用Kaplan-Meier、肿瘤免疫评估资源(Tumor Immune Estimation Resource,TIMER)数据库和基因表达谱交互分析(Gene Expression Profiling Interactive Analysis,GEPIA)数据库进行GTSE1基因表达、免疫学作用及预后分析,通过免疫组化实验验证GTSE1在临床样本中的表达,应用R软件对GTSE1相关差异基因进行基因本体(gene ontology,GO)和京都基因与基因组百科全书(Kyoto Encyclopedia of Genes and Genomes,KEGG)富集分析。结果GTSE1在人类癌组织中显著高表达,且与肝细胞癌预后不良显著相关(P<0.05);GTSE1基因表达与HCC中浸润性免疫细胞的丰度显著相关(P<0.001)。GTSE1相关的差异表达基因主要富集于核分裂、细胞器裂变、离子通道活性等基因模块;其参与的信号通路主要包括神经活性配体-受体的相互作用、细胞周期等。结论GTSE1在HCC中的表达显著上调并与患者预后不良显著相关,且在免疫细胞浸润中发挥重要作用,可作为HCC的预后标志物和免疫治疗靶点。展开更多
文摘目的分析血清乙型肝炎病毒(hepatitis B virus,HBV)前S1蛋白(precursor S1 protein,preS1)与慢性乙型肝炎(chronic hepatitis B,CHB)肝纤维化及癌变进展的相关性。方法对2019年10月—2021年10月期间在青海红十字医院接受检查的228例乙肝表面抗原(hepatitis B surface antigen,HBsAg)阳性慢性HBV感染者进行回顾性分析,其中CHB患者75例、肝硬化(liver cirrhosis,LC)患者93例(LC组)、肝细胞癌(hepatocellular carcinoma,HCC)患者60例(HCC组)。根据LC和HCC组肝组织活检分析肝脏炎症活动及肝纤维化程度。结果HCC组血清preS1水平[496.32(457.63,988.0)ng/mL]和LC组[338.72(247.93,554.61)ng/mL]血清preS1水平均显著高于CHB组[113.69(87.09,177.40)ng/mL],且差异具有统计学意义(P均<0.05)。HCC组血清preS1水平亦高于LC组(P=0.002)。经受试者工作特征曲线分析,血清preS1水平鉴别诊断CHB与LC的曲线下面积(area under the curve,AUC)是0.881(95%CI:0.830~0.932),鉴别诊断CHB/LC与HCC的AUC是0.861(95%CI:0.815~0.908)。3组患者的血清preS1水平与HBsAg(rs=0.799,P<0.001)呈强正相关和Log HBV DNA(rs=0.262,P<0.001)呈弱正相关。此外LC组和HCC组血清preS1水平与肝脏炎症活动分级(rs=0.201,P=0.009)及肝纤维化分期也呈弱正相关性(rs=0.295,P<0.001)。结论血清preS1水平与血清HBsAg、HBV DNA水平和肝脏炎症和纤维化进展呈正相关,有可能成为鉴别诊断HBV相关慢性肝病肝硬化或癌变的候选标志物。
基金supported by the Community Development Office of Hunan Provincial Science and Technology DepartmentChina,Nos.2020SK53613(to DH),21JJ31006(to DH)the Fundamental Research Funds of Central South University,Nos.CX20220375(to TX),2023zzts215(to MZ)。
文摘Sortilin-related receptor 1(SORL1)is a critical gene associated with late-onset Alzheimer’s disease.SORL1 contributes to the development and progression of this neurodegenerative condition by affecting the transport and metabolism of intracellularβ-amyloid precursor protein.To better understand the underlying mechanisms of SORL1 in the pathogenesis of late-onset Alzheimer s disease,in this study,we established a mouse model of SorI1 gene knockout using cluste red regularly inters paced short palindro mic repeats-associated protein 9 technology.We found that Sorl1-knocko ut mice displayed deficits in learning and memory.Furthermore,the expression of brain-derived neurotrophic factor was significantly downregulated in the hippocampus and co rtex,and amyloidβ-protein deposits were observed in the brains of 5orl1-knockout mice.In vitro,hippocampal neuronal cell synapses from homozygous Sorl1-knockout mice were impaired.The expression of synaptic proteins,including Drebrin and NR2B,was significantly reduced,and also their colocalization.Additionally,by knocking out the Sorl1 gene in N2a cells,we found that expression of the N-methyl-D-aspartate receptor,NR2B,and cyclic adenosine monophosphate-response element binding protein was also inhibited.These findings suggest that SORL1 participates in the pathogenesis of late-onset Alzheimer s disease by regulating the N-methyl-D-aspartate receptor NR2B/cyclic adenosine monophosphate-response element binding protein signaling axis.
文摘目的研究G_(2)/S期应答相关蛋白1(G_(2) and S phase-expressed protein 1,GTSE1)在肝细胞癌(hepatocellular carcinoma,HCC)中的表达、免疫学作用和预后分析,及其潜在作用机制。方法使用公共数据库癌症基因组图谱(The Cancer Genome Atlas,TCGA)提供的数据,用Kaplan-Meier、肿瘤免疫评估资源(Tumor Immune Estimation Resource,TIMER)数据库和基因表达谱交互分析(Gene Expression Profiling Interactive Analysis,GEPIA)数据库进行GTSE1基因表达、免疫学作用及预后分析,通过免疫组化实验验证GTSE1在临床样本中的表达,应用R软件对GTSE1相关差异基因进行基因本体(gene ontology,GO)和京都基因与基因组百科全书(Kyoto Encyclopedia of Genes and Genomes,KEGG)富集分析。结果GTSE1在人类癌组织中显著高表达,且与肝细胞癌预后不良显著相关(P<0.05);GTSE1基因表达与HCC中浸润性免疫细胞的丰度显著相关(P<0.001)。GTSE1相关的差异表达基因主要富集于核分裂、细胞器裂变、离子通道活性等基因模块;其参与的信号通路主要包括神经活性配体-受体的相互作用、细胞周期等。结论GTSE1在HCC中的表达显著上调并与患者预后不良显著相关,且在免疫细胞浸润中发挥重要作用,可作为HCC的预后标志物和免疫治疗靶点。
