The Electro-Hydrostatic Actuator(EHA)is a typical hydro-mechatronic control system.Due to the limited accuracy of measurement,inadequate knowledge,and vague judgments,hybrid uncertainties,including aleatory and episte...The Electro-Hydrostatic Actuator(EHA)is a typical hydro-mechatronic control system.Due to the limited accuracy of measurement,inadequate knowledge,and vague judgments,hybrid uncertainties,including aleatory and epistemic uncertainties,inevitably exist in the performance assessment of EHA systems.Existing methods ignored the hybrid uncertainties which can hardly obtain a satisfactory result while wasting a lot of time on the experimental design.To overcome this drawback,a metamodeling method for hybrid uncertainty propagation of EHA systems is developed via an active learning Gaussian Process(GP)model.The proposed method is bifurcated into three pillars:(A)Initializing the GP model and generating the optimum candidate sampling set by an Optimized Max-Minimize Distance(OMMD)algorithm,which aims to maximize the minimum distance between the added samples and original samples,(B)maximizing the learning function and generating new samples by a developed farthest or nearest judgment strategy,while updating the original GP model,and(C)judging the convergence by three uncertainty metrics,i.e.,the area metric,maximum variance metric,and the mean value metric.A numerical example is exemplified to evaluate the effectiveness and efficiency of the proposed method.Meanwhile,the EHA system of aircrafts is examined to show the application of the proposed method for high-dimensional problems.The effects of the uncertainties in the Proportional-Integral-Differential(PID)of the EHA system are also examined.展开更多
Background:The Global Leadership Initiative on Malnutrition(GLIM)criteria were published to build a global consensus on nutritional diagnosis.Reduced muscle mass is a phenotypic criterion with strong evidence to suppo...Background:The Global Leadership Initiative on Malnutrition(GLIM)criteria were published to build a global consensus on nutritional diagnosis.Reduced muscle mass is a phenotypic criterion with strong evidence to support its inclusion in the GLIM consensus criteria.However,there is no consensus regarding how to accurately measure and define reduced muscle mass in clinical settings.This study aimed to investigate the optimal reference values of skeletal muscle mass index for diagnosing sarcopenia and GLIM-defined malnutrition,as well as the prevalence of GLIM-defined malnutrition in hospitalized cirrhotic patients.Methods:This retrospective study was conducted on 1002 adult patients with liver cirrhosis between January 1,2018,and February 28,2022,at Beijing You-An Hospital,Capital Medical University.Adult patients with a clinical diagnosis of liver cirrhosis and who underwent an abdominal computed tomography(CT)examination during hospitalization were included in the study.These patients were randomly divided into a modeling group(cohort 1,667 patients)and a validation group(cohort 2,335 patients).In cohort 1,optimal cut-off values of skeletal muscle index at the third lumbar skeletal muscle index(L3-SMI)were determined using receiver operating characteristic analyses against in-hospital mortality in different gender groups.Next,patients in cohort 2 were screened for nutritional risk using the Nutritional Risk Screening 2002(NRS-2002),and malnutrition was diagnosed by GLIM criteria.Additionally,the reference values of reduced muscle mass in GLIM criteria were derived from the L3-SMI values from cohort 1.Multivariate logistic regression analysis was used to analyze the association between GLIM-defined malnutrition and clinical outcomes.Results:The optimal cut-off values of L3-SMI were 39.50 cm 2/m 2 for male patients and 33.06 cm 2/m 2 for female patients.Based on the cut-off values,31.63%(68/215)of the male patients and 23.3%(28/120)of the female patients had CT-determined sarcopenia in cohort 2.The prevalence of GLIM-defined malnutrition in cirrhotic patients was 34.3%(115/335)and GLIM-defined malnutrition was an independent risk factor for in-hospital mortality in patients with liver cirrhosis(Wald=6.347,P=0.012).Conclusions:This study provided reference values for skeletal muscle mass index and the prevalence of GLIM-defined malnutrition in hospitalized patients with liver cirrhosis.These reference values will contribute to applying the GLIM criteria in cirrhotic patients.展开更多
Background:Acute-on-chronic liver failure(ACLF)is a severe liver disease with complex pathogenesis.Clinical hypoglycemia is common in patients with ACLF and often predicts a worse prognosis.Accumulating evidence sugge...Background:Acute-on-chronic liver failure(ACLF)is a severe liver disease with complex pathogenesis.Clinical hypoglycemia is common in patients with ACLF and often predicts a worse prognosis.Accumulating evidence suggests that glucose metabolic disturbance,especially gluconeogenesis dysfunction,plays a critical role in the disease progression of ACLF.Lon protease-1(LONP1)is a novel mediator of energy and glucose metabolism.However,whether gluconeogenesis is a potential mechanism through which LONP1 modulates ACLF remains unknown.Methods:In this study,we collected liver tissues from ACLF patients,established an ACLF mouse model with carbon tetrachloride(CCl 4),lipopolysaccharide(LPS),and D-galactose(D-gal),and constructed an in vitro hypoxia and hyperammonemia-triggered hepatocyte injury model.LONP1 overexpression and knockdown adenovirus were used to assess the protective effect of LONP1 on liver injury and gluconeogenesis regulation.Liver histopathology,biochemical index,mitochondrial morphology,cell viability and apoptosis,and the expression and activity of key gluconeogenic enzymes were detected to explore the underlying protective mechanisms of LONP1 in ACLF.Results:We found that LONP1 and the expressions of gluconeogenic enzymes were downregulated in clinical ACLF liver tissues.Furthermore,LONP1 overexpression remarkably attenuated liver injury,which was characterized by improved liver histopathological lesions and decreased serum alanine aminotransferase(ALT)and aspartate aminotransferase(AST)in ACLF mice.Moreover,mitochondrial morphology was improved upon overexpression of LONP1.Meanwhile,the expression and activity of the key gluconeogenic enzymes were restored by LONP1 overexpression.Similarly,the hepatoprotective effect was also observed in the hepatocyte injury model,as evidenced by improved cell viability,reduced cell apoptosis,and improved gluconeogenesis level and activity,while LONP1 knockdown worsened liver injury and gluconeogenesis disorders.Conclusion:We demonstrated that gluconeogenesis dysfunction exists in ACLF,and LONP1 could ameliorate liver injury and improve gluconeogenic dysfunction,which would provide a promising therapeutic target for patients with ACLF.展开更多
基金the National Natural Science Foundation of China(Nos.72301057,72271044,72331002,and 52305010)the Sichuan Science and Technology Program,China(No.2023YFG0157).
文摘The Electro-Hydrostatic Actuator(EHA)is a typical hydro-mechatronic control system.Due to the limited accuracy of measurement,inadequate knowledge,and vague judgments,hybrid uncertainties,including aleatory and epistemic uncertainties,inevitably exist in the performance assessment of EHA systems.Existing methods ignored the hybrid uncertainties which can hardly obtain a satisfactory result while wasting a lot of time on the experimental design.To overcome this drawback,a metamodeling method for hybrid uncertainty propagation of EHA systems is developed via an active learning Gaussian Process(GP)model.The proposed method is bifurcated into three pillars:(A)Initializing the GP model and generating the optimum candidate sampling set by an Optimized Max-Minimize Distance(OMMD)algorithm,which aims to maximize the minimum distance between the added samples and original samples,(B)maximizing the learning function and generating new samples by a developed farthest or nearest judgment strategy,while updating the original GP model,and(C)judging the convergence by three uncertainty metrics,i.e.,the area metric,maximum variance metric,and the mean value metric.A numerical example is exemplified to evaluate the effectiveness and efficiency of the proposed method.Meanwhile,the EHA system of aircrafts is examined to show the application of the proposed method for high-dimensional problems.The effects of the uncertainties in the Proportional-Integral-Differential(PID)of the EHA system are also examined.
基金supported by grants from the National Natural Science Foundation of China(No.82170643)Internal Project of Beijing Youan Hospital Capital Medical University(No.YNKTLC2021005)
文摘Background:The Global Leadership Initiative on Malnutrition(GLIM)criteria were published to build a global consensus on nutritional diagnosis.Reduced muscle mass is a phenotypic criterion with strong evidence to support its inclusion in the GLIM consensus criteria.However,there is no consensus regarding how to accurately measure and define reduced muscle mass in clinical settings.This study aimed to investigate the optimal reference values of skeletal muscle mass index for diagnosing sarcopenia and GLIM-defined malnutrition,as well as the prevalence of GLIM-defined malnutrition in hospitalized cirrhotic patients.Methods:This retrospective study was conducted on 1002 adult patients with liver cirrhosis between January 1,2018,and February 28,2022,at Beijing You-An Hospital,Capital Medical University.Adult patients with a clinical diagnosis of liver cirrhosis and who underwent an abdominal computed tomography(CT)examination during hospitalization were included in the study.These patients were randomly divided into a modeling group(cohort 1,667 patients)and a validation group(cohort 2,335 patients).In cohort 1,optimal cut-off values of skeletal muscle index at the third lumbar skeletal muscle index(L3-SMI)were determined using receiver operating characteristic analyses against in-hospital mortality in different gender groups.Next,patients in cohort 2 were screened for nutritional risk using the Nutritional Risk Screening 2002(NRS-2002),and malnutrition was diagnosed by GLIM criteria.Additionally,the reference values of reduced muscle mass in GLIM criteria were derived from the L3-SMI values from cohort 1.Multivariate logistic regression analysis was used to analyze the association between GLIM-defined malnutrition and clinical outcomes.Results:The optimal cut-off values of L3-SMI were 39.50 cm 2/m 2 for male patients and 33.06 cm 2/m 2 for female patients.Based on the cut-off values,31.63%(68/215)of the male patients and 23.3%(28/120)of the female patients had CT-determined sarcopenia in cohort 2.The prevalence of GLIM-defined malnutrition in cirrhotic patients was 34.3%(115/335)and GLIM-defined malnutrition was an independent risk factor for in-hospital mortality in patients with liver cirrhosis(Wald=6.347,P=0.012).Conclusions:This study provided reference values for skeletal muscle mass index and the prevalence of GLIM-defined malnutrition in hospitalized patients with liver cirrhosis.These reference values will contribute to applying the GLIM criteria in cirrhotic patients.
基金supported by grants from the Municipal Natural Science Foundation of Beijing,China(No.7192085)the National Natural Science Foundation of China(No.82170643)
文摘Background:Acute-on-chronic liver failure(ACLF)is a severe liver disease with complex pathogenesis.Clinical hypoglycemia is common in patients with ACLF and often predicts a worse prognosis.Accumulating evidence suggests that glucose metabolic disturbance,especially gluconeogenesis dysfunction,plays a critical role in the disease progression of ACLF.Lon protease-1(LONP1)is a novel mediator of energy and glucose metabolism.However,whether gluconeogenesis is a potential mechanism through which LONP1 modulates ACLF remains unknown.Methods:In this study,we collected liver tissues from ACLF patients,established an ACLF mouse model with carbon tetrachloride(CCl 4),lipopolysaccharide(LPS),and D-galactose(D-gal),and constructed an in vitro hypoxia and hyperammonemia-triggered hepatocyte injury model.LONP1 overexpression and knockdown adenovirus were used to assess the protective effect of LONP1 on liver injury and gluconeogenesis regulation.Liver histopathology,biochemical index,mitochondrial morphology,cell viability and apoptosis,and the expression and activity of key gluconeogenic enzymes were detected to explore the underlying protective mechanisms of LONP1 in ACLF.Results:We found that LONP1 and the expressions of gluconeogenic enzymes were downregulated in clinical ACLF liver tissues.Furthermore,LONP1 overexpression remarkably attenuated liver injury,which was characterized by improved liver histopathological lesions and decreased serum alanine aminotransferase(ALT)and aspartate aminotransferase(AST)in ACLF mice.Moreover,mitochondrial morphology was improved upon overexpression of LONP1.Meanwhile,the expression and activity of the key gluconeogenic enzymes were restored by LONP1 overexpression.Similarly,the hepatoprotective effect was also observed in the hepatocyte injury model,as evidenced by improved cell viability,reduced cell apoptosis,and improved gluconeogenesis level and activity,while LONP1 knockdown worsened liver injury and gluconeogenesis disorders.Conclusion:We demonstrated that gluconeogenesis dysfunction exists in ACLF,and LONP1 could ameliorate liver injury and improve gluconeogenic dysfunction,which would provide a promising therapeutic target for patients with ACLF.
