Chronic liver injury leads to progressive liver fibrosis and ultimately cirrhosis,a major cause of morbidity and mortality worldwide.However,there are currently no effective anti-fibrotic therapies available,especiall...Chronic liver injury leads to progressive liver fibrosis and ultimately cirrhosis,a major cause of morbidity and mortality worldwide.However,there are currently no effective anti-fibrotic therapies available,especially for latestage patients,which is partly attributed to the major knowledge gap regarding liver cell heterogeneity and cellspecific responses in different fibrosis stages.To reveal the multicellular networks regulating mammalian liver fibrosis from mild to severe phenotypes,we generated a single-nucleus transcriptomic atlas encompassing 49919nuclei corresponding to all main liver cell types at different stages of murine carbon tetrachloride(CCl_(4))-induced progressive liver fibrosis.Integrative analysis distinguished the sequential responses to injury of hepatocytes,hepatic stellate cells and endothelial cells.Moreover,we reconstructed the cell-cell interactions and gene regulatory networks implicated in these processes.These integrative analyses uncovered previously overlooked aspects of hepatocyte proliferation exhaustion and disrupted pericentral metabolic functions,dysfunction for clearance by apoptosis of activated hepatic stellate cells,accumulation of pro-fibrotic signals,and the switch from an anti-angiogenic to a pro-angiogenic program during CCl_(4)-induced progressive liver fibrosis.Our dataset thus constitutes a useful resource for understanding the molecular basis of progressive liver fibrosis using a relevant animal model.展开更多
We present a female patient with preterm labor, severe viral hepatitis B of acute phase, hepatic encephalopathy stage Ⅲ and coma.After delivery, the illness was exacerbated and the patient presented with clinical sig...We present a female patient with preterm labor, severe viral hepatitis B of acute phase, hepatic encephalopathy stage Ⅲ and coma.After delivery, the illness was exacerbated and the patient presented with clinical signs of vital organ dysfunctions such as acute respiratory distress syndrome, cerebral edema and hypoxemia that needed mechanical ventilation.Emergency liver transplantation was recommended after multidisciplinary panel consultations.The donor, her mother, consented to donate her right liver.Auxiliary partial orthotopic living donor liver transplantion(APOLDLT) was performed.After operation, the patient was on triple medication of tacrolimus plus mofetil mycophenolate and prednisone for immunosuppression.The combination of antihepatitis B virus(HBV) immunoglobulin and entecavir was initiated for anti-HBV therapy.Both the patient and the donor recovered well without any complications.The patient was followed up regularly.Her liver function, clinical signs and symptoms improved significantly.Until now, the recipient has been living for more than 78 mo free of any complications.The APOLDLT is a life-saving modality for rescuing patients with high-risk acute liver failure following HBV infection without available donor and hence is recommended under standardized antiviral therapy coverage as stated above.展开更多
基金supported by the National Natural Science Foundation of China(32200688,92068106,U20A2015,32211530050)Guangdong Basic and Applied Basic Research Foundation(2021B1515120075,2021A1515110180)Science and Technology Program of Guangzhou(202201010408,202201011037)。
文摘Chronic liver injury leads to progressive liver fibrosis and ultimately cirrhosis,a major cause of morbidity and mortality worldwide.However,there are currently no effective anti-fibrotic therapies available,especially for latestage patients,which is partly attributed to the major knowledge gap regarding liver cell heterogeneity and cellspecific responses in different fibrosis stages.To reveal the multicellular networks regulating mammalian liver fibrosis from mild to severe phenotypes,we generated a single-nucleus transcriptomic atlas encompassing 49919nuclei corresponding to all main liver cell types at different stages of murine carbon tetrachloride(CCl_(4))-induced progressive liver fibrosis.Integrative analysis distinguished the sequential responses to injury of hepatocytes,hepatic stellate cells and endothelial cells.Moreover,we reconstructed the cell-cell interactions and gene regulatory networks implicated in these processes.These integrative analyses uncovered previously overlooked aspects of hepatocyte proliferation exhaustion and disrupted pericentral metabolic functions,dysfunction for clearance by apoptosis of activated hepatic stellate cells,accumulation of pro-fibrotic signals,and the switch from an anti-angiogenic to a pro-angiogenic program during CCl_(4)-induced progressive liver fibrosis.Our dataset thus constitutes a useful resource for understanding the molecular basis of progressive liver fibrosis using a relevant animal model.
基金Supported by Beijing Municipal Commission of Education,Grant No.KM201110025026Projects of State Commission of Science and Technology of China,Grant No.2012BAI06B01Organ Transplantation Research Fund from the Ministry of Health,Grant No.RHECC08-2012-08
文摘We present a female patient with preterm labor, severe viral hepatitis B of acute phase, hepatic encephalopathy stage Ⅲ and coma.After delivery, the illness was exacerbated and the patient presented with clinical signs of vital organ dysfunctions such as acute respiratory distress syndrome, cerebral edema and hypoxemia that needed mechanical ventilation.Emergency liver transplantation was recommended after multidisciplinary panel consultations.The donor, her mother, consented to donate her right liver.Auxiliary partial orthotopic living donor liver transplantion(APOLDLT) was performed.After operation, the patient was on triple medication of tacrolimus plus mofetil mycophenolate and prednisone for immunosuppression.The combination of antihepatitis B virus(HBV) immunoglobulin and entecavir was initiated for anti-HBV therapy.Both the patient and the donor recovered well without any complications.The patient was followed up regularly.Her liver function, clinical signs and symptoms improved significantly.Until now, the recipient has been living for more than 78 mo free of any complications.The APOLDLT is a life-saving modality for rescuing patients with high-risk acute liver failure following HBV infection without available donor and hence is recommended under standardized antiviral therapy coverage as stated above.
