目的探讨血清前Ⅲ型胶原氨基端肽(typeⅢprocollagen,PRO-C3)与高尔基体蛋白73(golgi protein 73,GP73)动态变化对人工肝治疗乙型肝炎慢加急性肝衰竭(hepatitis B virus-related acute-on-chronic liver failure,HBV-ACLF)患者短期预后...目的探讨血清前Ⅲ型胶原氨基端肽(typeⅢprocollagen,PRO-C3)与高尔基体蛋白73(golgi protein 73,GP73)动态变化对人工肝治疗乙型肝炎慢加急性肝衰竭(hepatitis B virus-related acute-on-chronic liver failure,HBV-ACLF)患者短期预后的评估价值。方法回顾性分析138例接受≥3次人工肝治疗的HBV-ACLF患者(生存组85例,死亡组53例)。检测基线及治疗2周后血清PRO-C3、GP73水平及常规肝肾功能指标,分析其与临床预后的相关性。血清PRO-C3采用罗氏cobas®分析仪(ECLIA法)检测;血清GP73采用ELISA法(北京热景生物试剂盒)检测。通过多因素Cox回归构建联合预测模型,并采用ROC曲线评估预测效能。结果对两组基线情况进行对比分析,结果显示,死亡组的总胆红素、肌酐、MELD水平均显著高于生存组(总胆红素535.5±118.7 vs 380.9±108.0μmol/L、肌酐96.6±29.6 vs 66.9±28.6μmol/L、MELD评分33.5±5.5 vs 20.7±4.3,均P<0.001);生存组PRO-C3与GP73降幅显著大于死亡组(P<0.001);多因素Cox回归显示,MELD评分为独立危险因素,PRO-C3降幅和GP73降幅为保护因素;联合动态指标(ΔPRO-C3%+ΔGP73%+MELD)的AUC达0.993,阴性预测值89.8%;按标志物降幅分组(良好/部分/无应答),3个月生存率分别为95.2%、65.5%、11.4%(P<0.001)。结论PRO-C3联合GP73的动态监测可精准评估人工肝治疗应答,其构建的预测模型对HBV-ACLF患者3个月预后具有显著的判别价值,尤其阴性预测效能突出。展开更多
Inborn errors of metabolism(IEMs)are a large group of disorders resulting from deficient activities in several metabolic pathways due to the dysfunction of a distinct enzyme associated with a biochemical pathway[1,2]....Inborn errors of metabolism(IEMs)are a large group of disorders resulting from deficient activities in several metabolic pathways due to the dysfunction of a distinct enzyme associated with a biochemical pathway[1,2].Toxic intermediates will be produced due to the dysfunction of biochemical pathways.The liver is responsible for many essential metabolic processes,therefore it becomes one of the most severely affected organ by metabolic diseases[3].Early onset of liver disorders in IEMs includes jaundice,hepatomegaly,splenomegaly,ascites,hepatic encephalopathy,and liver failure[4].In infants and young children under 3 years old with acute liver failure(ALF),IEMs account for 18.9%-43%[5].展开更多
Background:High-mobility group box 1(HMGB1)is a critical damage-associated molecular pattern protein that participates in diverse physiological and pathological processes.However,its relevance to the prognosis of arti...Background:High-mobility group box 1(HMGB1)is a critical damage-associated molecular pattern protein that participates in diverse physiological and pathological processes.However,its relevance to the prognosis of artificial liver support therapy in patients with acute liver injury(ALF)remains unclear.Methods:Bioinformatics analyses were performed to identify HMGB1-interacting proteins and associated inflammatory signaling pathways.Peripheral blood samples were collected from ALF patients before and after artificial liver support therapy,and serum HMGB1 concentrations were quantified using ELISA.Primary mouse hepatocytes were stimulated with lipopolysaccharide(LPS)in vitro and HMGB1 expression was verified by western blot.Results:Single-cell transcriptomic profiling showed that HMGB1 is widely expressed across tissues and predominantly localized in the nucleus.In the liver,HMGB1 was primarily expressed in hepatocytes and hepatic stellate cells.STRING database analysis revealed that human HMGB1 interacts with multiple proteins,including TLR4,TP53,and BECN1.The constructed interaction network comprised 11 nodes with an average local clustering coefficient of 0.888,and the protein–protein interaction enrichment P-value was 1.42×10^(-5),indicating significant enrichment.Gene Ontology and KEGG pathway enrichment analyses demonstrated that HMGB1 is closely linked to inflammatory and injury-related signaling pathways,including the TLR and NLR pathways.Metabolomic profiling revealed significant metabolic alterations between patients with ALF and healthy controls under both positive and negative ion modes and functional analysis showed necroptosis was activated.The cell viability gradually decreased with time and dose under LPS treatment and extracellular HMGB1 was upregulated in LPS induced ALF model and patients(P<0.05).Serum HMGB1/RIPK3/MLKL levels were markedly elevated in ALF patients compared with controls(P<0.05)and progressively declined following artificial liver support therapy.Furthermore,elevated HMGB1 concentrations were positively correlated with unfavorable clinical outcomes.Conclusion:Peripheral blood HMGB1 levels are significantly increased in patients with acute liver failure,decrease following artificial liver support therapy,and are positively associated with poor clinical prognosis.展开更多
文摘目的探讨血清前Ⅲ型胶原氨基端肽(typeⅢprocollagen,PRO-C3)与高尔基体蛋白73(golgi protein 73,GP73)动态变化对人工肝治疗乙型肝炎慢加急性肝衰竭(hepatitis B virus-related acute-on-chronic liver failure,HBV-ACLF)患者短期预后的评估价值。方法回顾性分析138例接受≥3次人工肝治疗的HBV-ACLF患者(生存组85例,死亡组53例)。检测基线及治疗2周后血清PRO-C3、GP73水平及常规肝肾功能指标,分析其与临床预后的相关性。血清PRO-C3采用罗氏cobas®分析仪(ECLIA法)检测;血清GP73采用ELISA法(北京热景生物试剂盒)检测。通过多因素Cox回归构建联合预测模型,并采用ROC曲线评估预测效能。结果对两组基线情况进行对比分析,结果显示,死亡组的总胆红素、肌酐、MELD水平均显著高于生存组(总胆红素535.5±118.7 vs 380.9±108.0μmol/L、肌酐96.6±29.6 vs 66.9±28.6μmol/L、MELD评分33.5±5.5 vs 20.7±4.3,均P<0.001);生存组PRO-C3与GP73降幅显著大于死亡组(P<0.001);多因素Cox回归显示,MELD评分为独立危险因素,PRO-C3降幅和GP73降幅为保护因素;联合动态指标(ΔPRO-C3%+ΔGP73%+MELD)的AUC达0.993,阴性预测值89.8%;按标志物降幅分组(良好/部分/无应答),3个月生存率分别为95.2%、65.5%、11.4%(P<0.001)。结论PRO-C3联合GP73的动态监测可精准评估人工肝治疗应答,其构建的预测模型对HBV-ACLF患者3个月预后具有显著的判别价值,尤其阴性预测效能突出。
文摘Inborn errors of metabolism(IEMs)are a large group of disorders resulting from deficient activities in several metabolic pathways due to the dysfunction of a distinct enzyme associated with a biochemical pathway[1,2].Toxic intermediates will be produced due to the dysfunction of biochemical pathways.The liver is responsible for many essential metabolic processes,therefore it becomes one of the most severely affected organ by metabolic diseases[3].Early onset of liver disorders in IEMs includes jaundice,hepatomegaly,splenomegaly,ascites,hepatic encephalopathy,and liver failure[4].In infants and young children under 3 years old with acute liver failure(ALF),IEMs account for 18.9%-43%[5].
基金supported by the National Natural Science Foundation of China(No.82360120)the Kunming Medical University Joint Special Project on Applied Basic Research(202401AY070001-134),and project iGandanF-1082022-RGG049+2 种基金the Open Project of Yunnan Provincial Clinical Medical Center for Digestive System Diseases(2022LCZXXF-XH07/17)the 14th Undergraduate Scientific Research Project of Mudanjiang Medical University(2024057)Yunnan Provincial Key Laboratory of Clinical Virology(No.2023A4010403-04).
文摘Background:High-mobility group box 1(HMGB1)is a critical damage-associated molecular pattern protein that participates in diverse physiological and pathological processes.However,its relevance to the prognosis of artificial liver support therapy in patients with acute liver injury(ALF)remains unclear.Methods:Bioinformatics analyses were performed to identify HMGB1-interacting proteins and associated inflammatory signaling pathways.Peripheral blood samples were collected from ALF patients before and after artificial liver support therapy,and serum HMGB1 concentrations were quantified using ELISA.Primary mouse hepatocytes were stimulated with lipopolysaccharide(LPS)in vitro and HMGB1 expression was verified by western blot.Results:Single-cell transcriptomic profiling showed that HMGB1 is widely expressed across tissues and predominantly localized in the nucleus.In the liver,HMGB1 was primarily expressed in hepatocytes and hepatic stellate cells.STRING database analysis revealed that human HMGB1 interacts with multiple proteins,including TLR4,TP53,and BECN1.The constructed interaction network comprised 11 nodes with an average local clustering coefficient of 0.888,and the protein–protein interaction enrichment P-value was 1.42×10^(-5),indicating significant enrichment.Gene Ontology and KEGG pathway enrichment analyses demonstrated that HMGB1 is closely linked to inflammatory and injury-related signaling pathways,including the TLR and NLR pathways.Metabolomic profiling revealed significant metabolic alterations between patients with ALF and healthy controls under both positive and negative ion modes and functional analysis showed necroptosis was activated.The cell viability gradually decreased with time and dose under LPS treatment and extracellular HMGB1 was upregulated in LPS induced ALF model and patients(P<0.05).Serum HMGB1/RIPK3/MLKL levels were markedly elevated in ALF patients compared with controls(P<0.05)and progressively declined following artificial liver support therapy.Furthermore,elevated HMGB1 concentrations were positively correlated with unfavorable clinical outcomes.Conclusion:Peripheral blood HMGB1 levels are significantly increased in patients with acute liver failure,decrease following artificial liver support therapy,and are positively associated with poor clinical prognosis.
