BACKGROUND Acute liver failure(ALF)has a high mortality with widespread hepatocyte death involving ferroptosis and pyroptosis.The silent information regulator sirtuin 1(SIRT1)-mediated deacetylation affects multiple b...BACKGROUND Acute liver failure(ALF)has a high mortality with widespread hepatocyte death involving ferroptosis and pyroptosis.The silent information regulator sirtuin 1(SIRT1)-mediated deacetylation affects multiple biological processes,including cellular senescence,apoptosis,sugar and lipid metabolism,oxidative stress,and inflammation.AIM To investigate the association between ferroptosis and pyroptosis and the upstream regulatory mechanisms.METHODS This study included 30 patients with ALF and 30 healthy individuals who underwent serum alanine aminotransferase(ALT)and aspartate aminotransferase(AST)testing.C57BL/6 mice were also intraperitoneally pretreated with SIRT1,p53,or glutathione peroxidase 4(GPX4)inducers and inhibitors and injected with lipopolysaccharide(LPS)/D-galactosamine(D-GalN)to induce ALF.Gasdermin D(GSDMD)^(-/-)mice were used as an experimental group.Histological changes in liver tissue were monitored by hematoxylin and eosin staining.ALT,AST,glutathione,reactive oxygen species,and iron levels were measured using commercial kits.Ferroptosis-and pyroptosis-related protein and mRNA expression was detected by western blot and quantitative real-time polymerase chain reaction.SIRT1,p53,and GSDMD were assessed by immunofluorescence analysis.RESULTS Serum AST and ALT levels were elevated in patients with ALF.SIRT1,solute carrier family 7a member 11(SLC7A11),and GPX4 protein expression was decreased and acetylated p5,p53,GSDMD,and acyl-CoA synthetase long-chain family member 4(ACSL4)protein levels were elevated in human ALF liver tissue.In the p53 and ferroptosis inhibitor-treated and GSDMD^(-/-)groups,serum interleukin(IL)-1β,tumour necrosis factor alpha,IL-6,IL-2 and C-C motif ligand 2 levels were decreased and hepatic impairment was mitigated.In mice with GSDMD knockout,p53 was reduced,GPX4 was increased,and ferroptotic events(depletion of SLC7A11,elevation of ACSL4,and iron accumulation)were detected.In vitro,knockdown of p53 and overexpression of GPX4 reduced AST and ALT levels,the cytostatic rat展开更多
Based on the general requirements of the coordinated development of"ecological livable"and"affluent life"in the rural revitalization strategy,the evaluation index system of desertification control ...Based on the general requirements of the coordinated development of"ecological livable"and"affluent life"in the rural revitalization strategy,the evaluation index system of desertification control was constructed,the interaction between desertification control and regional social economy and the internal space-time coordination mechanism were explored,and the quality of desertification control and its coordination degree with regional economic development were quantitatively analyzed.The decoupling mechanism of desertification governance society economy system were analyzed,and the high level for the government to promote desertification governance,constructing ecological economy coordinated development pattern to provide decision basis to Xizang desertification governance-social economic system interaction and coupling coordination development as the research object,introducing the coupling decoupling model to measure the coupling coordination model and system coordination and decoupling decoupling.Desertification control in Xizang shows a trend of gradual improvement,but the overall level is still not high and there is a lot of room for optimization.The coupling coordination degree of desertification control-social and economic system is in a steady fluctuation trend,rising from D value less than 0.55 in 2004 to 0.87 in 2018,in a state of coordinated development(good),and grey prediction analysis shows that D value is in a continuous rise.The coupling coordination degree of the six prefecture-level cities in Xizang and Ngari region is different in time and space,but the overall development trend is coordinated.The development index of desertification control and the socio-economic development index show the interaction of strong decoupling,strong negative decoupling and weak decoupling,and there are interaction effects of desertification control,economic development and social development at different scales.展开更多
BACKGROUND Autoimmune hepatitis(AIH)and primary biliary cholangitis(PBC)are two common clinical autoimmune liver diseases,and some patients have both diseases;this feature is called AIH-PBC overlap syndrome.Autoimmune...BACKGROUND Autoimmune hepatitis(AIH)and primary biliary cholangitis(PBC)are two common clinical autoimmune liver diseases,and some patients have both diseases;this feature is called AIH-PBC overlap syndrome.Autoimmune thyroid disease(AITD)is the most frequently overlapping extrahepatic autoimmune disease.Immunoglobulin(IgG)4-related disease is an autoimmune disease recognized in recent years,characterized by elevated serum IgG4 levels and infiltration of IgG4-positive plasma cells in tissues.CASE SUMMARY A 68-year-old female patient was admitted with a history of right upper quadrant pain,anorexia,and jaundice on physical examination.Laboratory examination revealed elevated liver enzymes,multiple positive autoantibodies associated with liver and thyroid disease,and imaging and biopsy suggestive of pancreatitis,hepatitis,and PBC.A diagnosis was made of a rare and complex overlap syndrome of AIH,PBC,AITD,and IgG4-related disease.Laboratory features improved on treatment with ursodeoxycholic acid,methylprednisolone,and azathioprine.CONCLUSION This case highlights the importance of screening patients with autoimmune diseases for related conditions.展开更多
基金Supported by National Natural Science Foundation of China,No.82060123Doctoral Start-up Fund of Affiliated Hospital of Guizhou Medical University,No.gysybsky-2021-28+1 种基金Fund Project of Guizhou Provincial Science and Technology Department,No.[2020]1Y299Guizhou Provincial Health Commission,No.gzwjk2019-1-082。
文摘BACKGROUND Acute liver failure(ALF)has a high mortality with widespread hepatocyte death involving ferroptosis and pyroptosis.The silent information regulator sirtuin 1(SIRT1)-mediated deacetylation affects multiple biological processes,including cellular senescence,apoptosis,sugar and lipid metabolism,oxidative stress,and inflammation.AIM To investigate the association between ferroptosis and pyroptosis and the upstream regulatory mechanisms.METHODS This study included 30 patients with ALF and 30 healthy individuals who underwent serum alanine aminotransferase(ALT)and aspartate aminotransferase(AST)testing.C57BL/6 mice were also intraperitoneally pretreated with SIRT1,p53,or glutathione peroxidase 4(GPX4)inducers and inhibitors and injected with lipopolysaccharide(LPS)/D-galactosamine(D-GalN)to induce ALF.Gasdermin D(GSDMD)^(-/-)mice were used as an experimental group.Histological changes in liver tissue were monitored by hematoxylin and eosin staining.ALT,AST,glutathione,reactive oxygen species,and iron levels were measured using commercial kits.Ferroptosis-and pyroptosis-related protein and mRNA expression was detected by western blot and quantitative real-time polymerase chain reaction.SIRT1,p53,and GSDMD were assessed by immunofluorescence analysis.RESULTS Serum AST and ALT levels were elevated in patients with ALF.SIRT1,solute carrier family 7a member 11(SLC7A11),and GPX4 protein expression was decreased and acetylated p5,p53,GSDMD,and acyl-CoA synthetase long-chain family member 4(ACSL4)protein levels were elevated in human ALF liver tissue.In the p53 and ferroptosis inhibitor-treated and GSDMD^(-/-)groups,serum interleukin(IL)-1β,tumour necrosis factor alpha,IL-6,IL-2 and C-C motif ligand 2 levels were decreased and hepatic impairment was mitigated.In mice with GSDMD knockout,p53 was reduced,GPX4 was increased,and ferroptotic events(depletion of SLC7A11,elevation of ACSL4,and iron accumulation)were detected.In vitro,knockdown of p53 and overexpression of GPX4 reduced AST and ALT levels,the cytostatic rat
基金supported by the Beijing Social Science Foundation Project(Grant No.18YJB011)the Ministry of Education Humanities and Social Science Research Fund for Youth Project(Grant No.20YJA790059)+2 种基金the National Social Science Foundation of China(Grant No.20FGLB022)the General Project of National Social Science Foundation of China(Grant No.19BGL052)the Innovation and Entrepreneurship Project of Beijing Forestry University(Grant No.X202110022111).
文摘Based on the general requirements of the coordinated development of"ecological livable"and"affluent life"in the rural revitalization strategy,the evaluation index system of desertification control was constructed,the interaction between desertification control and regional social economy and the internal space-time coordination mechanism were explored,and the quality of desertification control and its coordination degree with regional economic development were quantitatively analyzed.The decoupling mechanism of desertification governance society economy system were analyzed,and the high level for the government to promote desertification governance,constructing ecological economy coordinated development pattern to provide decision basis to Xizang desertification governance-social economic system interaction and coupling coordination development as the research object,introducing the coupling decoupling model to measure the coupling coordination model and system coordination and decoupling decoupling.Desertification control in Xizang shows a trend of gradual improvement,but the overall level is still not high and there is a lot of room for optimization.The coupling coordination degree of desertification control-social and economic system is in a steady fluctuation trend,rising from D value less than 0.55 in 2004 to 0.87 in 2018,in a state of coordinated development(good),and grey prediction analysis shows that D value is in a continuous rise.The coupling coordination degree of the six prefecture-level cities in Xizang and Ngari region is different in time and space,but the overall development trend is coordinated.The development index of desertification control and the socio-economic development index show the interaction of strong decoupling,strong negative decoupling and weak decoupling,and there are interaction effects of desertification control,economic development and social development at different scales.
基金Supported by National Natural Science Foundation of China,No.82060123National Health Commission of Guizhou Province,No.gzwjk2019-1-082.
文摘BACKGROUND Autoimmune hepatitis(AIH)and primary biliary cholangitis(PBC)are two common clinical autoimmune liver diseases,and some patients have both diseases;this feature is called AIH-PBC overlap syndrome.Autoimmune thyroid disease(AITD)is the most frequently overlapping extrahepatic autoimmune disease.Immunoglobulin(IgG)4-related disease is an autoimmune disease recognized in recent years,characterized by elevated serum IgG4 levels and infiltration of IgG4-positive plasma cells in tissues.CASE SUMMARY A 68-year-old female patient was admitted with a history of right upper quadrant pain,anorexia,and jaundice on physical examination.Laboratory examination revealed elevated liver enzymes,multiple positive autoantibodies associated with liver and thyroid disease,and imaging and biopsy suggestive of pancreatitis,hepatitis,and PBC.A diagnosis was made of a rare and complex overlap syndrome of AIH,PBC,AITD,and IgG4-related disease.Laboratory features improved on treatment with ursodeoxycholic acid,methylprednisolone,and azathioprine.CONCLUSION This case highlights the importance of screening patients with autoimmune diseases for related conditions.
