BACKGROUND Hepatorenal syndrome(HRS)is a severe complication of cirrhosis with high mortality,which necessitates accurate clinical decision.However,studies on prognostic factors and scoring systems to predict overall ...BACKGROUND Hepatorenal syndrome(HRS)is a severe complication of cirrhosis with high mortality,which necessitates accurate clinical decision.However,studies on prognostic factors and scoring systems to predict overall survival of HRS are not enough.Meanwhile,a multicenter cohort study with a long span of time could be more convincing.AIM To develop a novel and effective prognostic model for patients with HRS and clarify new prognostic factors.METHODS We retrospectively enrolled 1667 patients from four hospitals,and 371 eligible patients were finally analyzed to develop and validate a novel prognostic model for patients with HRS.Characteristics were compared between survivors and non-survivors,and potential prognostic factors were selected according to the impact on 28-d mortality.Accuracy in predicting 28-d mortality was compared between the novel and other scoring systems,including Model for End-Stage Liver Disease(MELD),Chronic Liver Failure-Sequential Organ Failure Assessment(CLIF-SOFA),and Chinese Group on the Study of Severe Hepatitis BAcute-on-Chronic Liver Failure(COSSH-ACLF).RESULTS Five prognostic factors,comprised of gender,international normalized ratio,mean corpuscular hemoglobin concentration,neutrophil percentage,and stage,were integrated into a new score,GIMNS;stage is a binary variable defined by the number of failed organs.GIMNS was positively correlated with MELD,CLIFSOFA,and COSSH-ACLF.Additionally,it had better accuracy[area under the receiver operating characteristic curve(AUROC):0.830]than MELD(AUROC:0.759),CLIF-SOFA(AUROC:0.767),and COSSH-ACLF(AUROC:0.759)in the derivation cohort(P<0.05).It performed better than MELD and CLIF-SOFA in the validation cohort(P<0.050)and had a higher AUROC than COSSH-ACLF(P=0.122).CONCLUSION We have developed a new scoring system,GIMNS,to predict 28-d mortality of HRS patients.Mean corpuscular hemoglobin concentration and stage were first proposed and found to be related to the mortality of HRS.Additionally,the GIMNS score showed better accuracy than MELD and CLIF-SOFA,and the AUROC was higher than that of COSSH-ACLF.展开更多
Drug-induced liver injury(DILI),which refers to liver damage caused by a drug or its metabolites,has emerged as an important cause of acute liver failure(ALF)in recent years.Chemically-induced ALF in animal models mim...Drug-induced liver injury(DILI),which refers to liver damage caused by a drug or its metabolites,has emerged as an important cause of acute liver failure(ALF)in recent years.Chemically-induced ALF in animal models mimics the pathology of DILI in humans;thus,these models are used to study the mechanism of potentially effective treatment strategies.Mesenchymal stromal cells(MSCs)possess immunomodulatory properties,and they alleviate acute liver injury and decrease the mortality of animals with chemically-induced ALF.Here,we summarize some of the existing research on the interaction between MSCs and immune cells,and discuss the possible mechanisms underlying the immunomodulatory activity of MSCs in chemically-induced ALF.We conclude that MSCs can impact the phenotype and function of macrophages,as well as the differentiation and maturation of dendritic cells,and inhibit the proliferation and activation of T lymphocytes or B lymphocytes.MSCs also have immunomodulatory effects on the production of cytokines,such as prostaglandin E2 and tumor necrosis factor-alpha-stimulated gene 6,in animal models.Thus,MSCs have significant benefits in the treatment of chemically-induced ALF by interacting with immune cells and they may be applied to DILI in humans in the near future.展开更多
The electrochemical oxidation of small molecules is a promising approach in chemical synthesis,but catalyst deactivation due to the accumulation of poorly soluble products on the surface remains a significant challeng...The electrochemical oxidation of small molecules is a promising approach in chemical synthesis,but catalyst deactivation due to the accumulation of poorly soluble products on the surface remains a significant challenge.To address this,we propose an in situ cleaning method using an additional oxygen evolution reaction(OER)to regenerate degraded catalysts.The OER facilitates the removal of insoluble products,thereby restoring active sites.Taking the electrochemical oxidation of tetrahydroisoquinoline(THIQ)to dihydroisoquinoline(DHIQ)as an example,we develop a highly activeγ-Ni(Co)OOH anode.The OER generates oxygen,promoting the oxidation of DHIQ to IQ,which is more soluble,thus effectively removing DHIQ from the catalyst surface.After 120 cycles in a small-scale pilot test,the current stability exceeds 98%,and the product selectivity reaches 95%.This method demonstrates the highest stability to date,outperforming previous catalysts 15-fold,and can be applied to other electrocatalytic systems facing similar deactivation issues.展开更多
基金Chinese High Tech Research&Development(863)Program,No.2013AA020102.
文摘BACKGROUND Hepatorenal syndrome(HRS)is a severe complication of cirrhosis with high mortality,which necessitates accurate clinical decision.However,studies on prognostic factors and scoring systems to predict overall survival of HRS are not enough.Meanwhile,a multicenter cohort study with a long span of time could be more convincing.AIM To develop a novel and effective prognostic model for patients with HRS and clarify new prognostic factors.METHODS We retrospectively enrolled 1667 patients from four hospitals,and 371 eligible patients were finally analyzed to develop and validate a novel prognostic model for patients with HRS.Characteristics were compared between survivors and non-survivors,and potential prognostic factors were selected according to the impact on 28-d mortality.Accuracy in predicting 28-d mortality was compared between the novel and other scoring systems,including Model for End-Stage Liver Disease(MELD),Chronic Liver Failure-Sequential Organ Failure Assessment(CLIF-SOFA),and Chinese Group on the Study of Severe Hepatitis BAcute-on-Chronic Liver Failure(COSSH-ACLF).RESULTS Five prognostic factors,comprised of gender,international normalized ratio,mean corpuscular hemoglobin concentration,neutrophil percentage,and stage,were integrated into a new score,GIMNS;stage is a binary variable defined by the number of failed organs.GIMNS was positively correlated with MELD,CLIFSOFA,and COSSH-ACLF.Additionally,it had better accuracy[area under the receiver operating characteristic curve(AUROC):0.830]than MELD(AUROC:0.759),CLIF-SOFA(AUROC:0.767),and COSSH-ACLF(AUROC:0.759)in the derivation cohort(P<0.05).It performed better than MELD and CLIF-SOFA in the validation cohort(P<0.050)and had a higher AUROC than COSSH-ACLF(P=0.122).CONCLUSION We have developed a new scoring system,GIMNS,to predict 28-d mortality of HRS patients.Mean corpuscular hemoglobin concentration and stage were first proposed and found to be related to the mortality of HRS.Additionally,the GIMNS score showed better accuracy than MELD and CLIF-SOFA,and the AUROC was higher than that of COSSH-ACLF.
基金National Natural Science Foundation of China,No.81971756and Stem Cell and Translational Research from National Key Research and Development Program of China,No.2016YFA0101001.
文摘Drug-induced liver injury(DILI),which refers to liver damage caused by a drug or its metabolites,has emerged as an important cause of acute liver failure(ALF)in recent years.Chemically-induced ALF in animal models mimics the pathology of DILI in humans;thus,these models are used to study the mechanism of potentially effective treatment strategies.Mesenchymal stromal cells(MSCs)possess immunomodulatory properties,and they alleviate acute liver injury and decrease the mortality of animals with chemically-induced ALF.Here,we summarize some of the existing research on the interaction between MSCs and immune cells,and discuss the possible mechanisms underlying the immunomodulatory activity of MSCs in chemically-induced ALF.We conclude that MSCs can impact the phenotype and function of macrophages,as well as the differentiation and maturation of dendritic cells,and inhibit the proliferation and activation of T lymphocytes or B lymphocytes.MSCs also have immunomodulatory effects on the production of cytokines,such as prostaglandin E2 and tumor necrosis factor-alpha-stimulated gene 6,in animal models.Thus,MSCs have significant benefits in the treatment of chemically-induced ALF by interacting with immune cells and they may be applied to DILI in humans in the near future.
基金the National Natural Science Foundation of China(22275001)the Anhui Provincial Department of Education(2022AH010004,KJ2021ZD0002).
文摘The electrochemical oxidation of small molecules is a promising approach in chemical synthesis,but catalyst deactivation due to the accumulation of poorly soluble products on the surface remains a significant challenge.To address this,we propose an in situ cleaning method using an additional oxygen evolution reaction(OER)to regenerate degraded catalysts.The OER facilitates the removal of insoluble products,thereby restoring active sites.Taking the electrochemical oxidation of tetrahydroisoquinoline(THIQ)to dihydroisoquinoline(DHIQ)as an example,we develop a highly activeγ-Ni(Co)OOH anode.The OER generates oxygen,promoting the oxidation of DHIQ to IQ,which is more soluble,thus effectively removing DHIQ from the catalyst surface.After 120 cycles in a small-scale pilot test,the current stability exceeds 98%,and the product selectivity reaches 95%.This method demonstrates the highest stability to date,outperforming previous catalysts 15-fold,and can be applied to other electrocatalytic systems facing similar deactivation issues.
