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
The inflammasome is a multiprotein complex involved in innate immunity that mediates the inflammatory response leading to pyroptosis,which is a lytic,inflammatory form of cell death.There is accumulating evidence that...The inflammasome is a multiprotein complex involved in innate immunity that mediates the inflammatory response leading to pyroptosis,which is a lytic,inflammatory form of cell death.There is accumulating evidence that nucleotide-binding domain and leucine-rich repeat pyrin domain containing 3(NLRP3)inflammasome-mediated microglial pyroptosis and NLRP1 inflammasome-mediated neuronal pyroptosis in the brain are closely associated with the pathogenesis of Alzheimer’s disease.In this review,we summarize the possible pathogenic mechanisms of Alzheimer’s disease,focusing on neuroinflammation.We also describe the structures of NLRP3 and NLRP1 and the role their activation plays in Alzheimer’s disease.Finally,we examine the neuroprotective activity of small-molecule inhibitors,endogenous inhibitor proteins,microRNAs,and natural bioactive molecules that target NLRP3 and NLRP1,based on the rationale that inhibiting NLRP3 and NLRP1 inflammasome-mediated pyroptosis can be an effective therapeutic strategy for Alzheimer’s disease.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 Natural Science Foundation of Zhejiang Province of China,Nos.LQ22H090003(to JJ),LTGY23C090001(to XZ),LY23H020008(to BH)Sci-Tech Planning Project of Jiaxing,Nos.2021AY30001(to XZ)and 2022AY30020(to JJ).
文摘The inflammasome is a multiprotein complex involved in innate immunity that mediates the inflammatory response leading to pyroptosis,which is a lytic,inflammatory form of cell death.There is accumulating evidence that nucleotide-binding domain and leucine-rich repeat pyrin domain containing 3(NLRP3)inflammasome-mediated microglial pyroptosis and NLRP1 inflammasome-mediated neuronal pyroptosis in the brain are closely associated with the pathogenesis of Alzheimer’s disease.In this review,we summarize the possible pathogenic mechanisms of Alzheimer’s disease,focusing on neuroinflammation.We also describe the structures of NLRP3 and NLRP1 and the role their activation plays in Alzheimer’s disease.Finally,we examine the neuroprotective activity of small-molecule inhibitors,endogenous inhibitor proteins,microRNAs,and natural bioactive molecules that target NLRP3 and NLRP1,based on the rationale that inhibiting NLRP3 and NLRP1 inflammasome-mediated pyroptosis can be an effective therapeutic strategy for Alzheimer’s disease.
