1.USP29 alleviates the progression of MASLD by stabilizing ACSL5 through K48 deubiquitination
Sha HU ; Zhouxiang WANG ; Kun ZHU ; Hongjie SHI ; Fang QIN ; Tuo ZHANG ; Song TIAN ; Yanxiao JI ; Jianqing ZHANG ; Juanjuan QIN ; Zhigang SHE ; Xiaojing ZHANG ; Peng ZHANG ; Hongliang LI
Clinical and Molecular Hepatology 2025;31(1):147-165
Background/Aims:
Metabolic dysfunction–associated steatotic liver disease (MASLD) is a chronic liver disease characterized by hepatic steatosis. Ubiquitin-specific protease 29 (USP29) plays pivotal roles in hepatic ischemiareperfusion injury and hepatocellular carcinoma, but its role in MASLD remains unexplored. Therefore, the aim of this study was to reveal the effects and underlying mechanisms of USP29 in MASLD progression.
Methods:
USP29 expression was assessed in liver samples from MASLD patients and mice. The role and molecular mechanism of USP29 in MASLD were assessed in high-fat diet-fed and high-fat/high-cholesterol diet-fed mice and palmitic acid and oleic acid treated hepatocytes.
Results:
USP29 protein levels were significantly reduced in mice and humans with MASLD. Hepatic steatosis, inflammation and fibrosis were significantly exacerbated by USP29 deletion and relieved by USP29 overexpression. Mechanistically, USP29 significantly activated the expression of genes related to fatty acid β-oxidation (FAO) under metabolic stimulation, directly interacted with long-chain acyl-CoA synthase 5 (ACSL5) and repressed ACSL5 degradation by increasing ACSL5 K48-linked deubiquitination. Moreover, the effect of USP29 on hepatocyte lipid accumulation and MASLD was dependent on ACSL5.
Conclusions
USP29 functions as a novel negative regulator of MASLD by stabilizing ACSL5 to promote FAO. The activation of the USP29-ACSL5 axis may represent a potential therapeutic strategy for MASLD.
2.Epidemiological burden of tetanus in China from 1990 to 2021
Ji XU ; Guoqing HUANG ; Ning YANG ; Liping ZHOU ; Xiaoye MO ; Shanshan HU ; Ping WU ; Changshou SHE
Chinese Journal of Infection Control 2025;24(7):923-931
Objective Tetanus is a serious infectious diseases with high mortality,which is an important global public health issue.This study aims to analyze the epidemiological burden and changing trends of tetanus in China from 1990 to 2021,providing a basis for disease prevention and control.Methods Epidemiological indicators and global socio-demographic index(SDI)related to tetanus in China were retrieved and collected from the 2021 Global Burden of Disease database(GBD 2021).The trend analysis of the incidence rate,mortality rate and disability-ad-justed life years(DALYs)rate of tetanus in China from 1990 to 2021 was conducted by Joinpoint 5.3 software.Results From 1990 to 2021,the age-standardized incidence rate(ASIR),age-standardized mortality rate(ASMR),and age-standardized disability-adjusted life years(DALYs)rate of tetanus in China decreased significantly(average annual percent change[AAPC]<0,P<0.001),with males being significantly higher than females.The crude incidence rate,crude mortality rate,and crude DALYs rate for all age groups showed overall declining trends,with the lar-gest decline in the 0-14 years age group.In 2021,the crude incidence rate,crude mortality rate,and crude DALYs rate of tetanus in the population aged 70-years were higher than those in the population aged 0-14,15-49,and 50-69 years groups.The ASIR,ASMR,and age-standardized DALYs rate of tetanus in China in 2021 were lower than the global level,only higher than those in the high SDI regions.Conclusion From 1990 to 2021,the disease burden of tetanus in China varied with gender and age,with an overall declining trend over time.It is necessary to strengthen tetanus health education for males and the ≥70 years population,and to improve the overall level of pri-mary prevention measures for tetanus.
3.USP29 alleviates the progression of MASLD by stabilizing ACSL5 through K48 deubiquitination
Sha HU ; Zhouxiang WANG ; Kun ZHU ; Hongjie SHI ; Fang QIN ; Tuo ZHANG ; Song TIAN ; Yanxiao JI ; Jianqing ZHANG ; Juanjuan QIN ; Zhigang SHE ; Xiaojing ZHANG ; Peng ZHANG ; Hongliang LI
Clinical and Molecular Hepatology 2025;31(1):147-165
Background/Aims:
Metabolic dysfunction–associated steatotic liver disease (MASLD) is a chronic liver disease characterized by hepatic steatosis. Ubiquitin-specific protease 29 (USP29) plays pivotal roles in hepatic ischemiareperfusion injury and hepatocellular carcinoma, but its role in MASLD remains unexplored. Therefore, the aim of this study was to reveal the effects and underlying mechanisms of USP29 in MASLD progression.
Methods:
USP29 expression was assessed in liver samples from MASLD patients and mice. The role and molecular mechanism of USP29 in MASLD were assessed in high-fat diet-fed and high-fat/high-cholesterol diet-fed mice and palmitic acid and oleic acid treated hepatocytes.
Results:
USP29 protein levels were significantly reduced in mice and humans with MASLD. Hepatic steatosis, inflammation and fibrosis were significantly exacerbated by USP29 deletion and relieved by USP29 overexpression. Mechanistically, USP29 significantly activated the expression of genes related to fatty acid β-oxidation (FAO) under metabolic stimulation, directly interacted with long-chain acyl-CoA synthase 5 (ACSL5) and repressed ACSL5 degradation by increasing ACSL5 K48-linked deubiquitination. Moreover, the effect of USP29 on hepatocyte lipid accumulation and MASLD was dependent on ACSL5.
Conclusions
USP29 functions as a novel negative regulator of MASLD by stabilizing ACSL5 to promote FAO. The activation of the USP29-ACSL5 axis may represent a potential therapeutic strategy for MASLD.
4.USP29 alleviates the progression of MASLD by stabilizing ACSL5 through K48 deubiquitination
Sha HU ; Zhouxiang WANG ; Kun ZHU ; Hongjie SHI ; Fang QIN ; Tuo ZHANG ; Song TIAN ; Yanxiao JI ; Jianqing ZHANG ; Juanjuan QIN ; Zhigang SHE ; Xiaojing ZHANG ; Peng ZHANG ; Hongliang LI
Clinical and Molecular Hepatology 2025;31(1):147-165
Background/Aims:
Metabolic dysfunction–associated steatotic liver disease (MASLD) is a chronic liver disease characterized by hepatic steatosis. Ubiquitin-specific protease 29 (USP29) plays pivotal roles in hepatic ischemiareperfusion injury and hepatocellular carcinoma, but its role in MASLD remains unexplored. Therefore, the aim of this study was to reveal the effects and underlying mechanisms of USP29 in MASLD progression.
Methods:
USP29 expression was assessed in liver samples from MASLD patients and mice. The role and molecular mechanism of USP29 in MASLD were assessed in high-fat diet-fed and high-fat/high-cholesterol diet-fed mice and palmitic acid and oleic acid treated hepatocytes.
Results:
USP29 protein levels were significantly reduced in mice and humans with MASLD. Hepatic steatosis, inflammation and fibrosis were significantly exacerbated by USP29 deletion and relieved by USP29 overexpression. Mechanistically, USP29 significantly activated the expression of genes related to fatty acid β-oxidation (FAO) under metabolic stimulation, directly interacted with long-chain acyl-CoA synthase 5 (ACSL5) and repressed ACSL5 degradation by increasing ACSL5 K48-linked deubiquitination. Moreover, the effect of USP29 on hepatocyte lipid accumulation and MASLD was dependent on ACSL5.
Conclusions
USP29 functions as a novel negative regulator of MASLD by stabilizing ACSL5 to promote FAO. The activation of the USP29-ACSL5 axis may represent a potential therapeutic strategy for MASLD.
5.Epidemiological burden of tetanus in China from 1990 to 2021
Ji XU ; Guoqing HUANG ; Ning YANG ; Liping ZHOU ; Xiaoye MO ; Shanshan HU ; Ping WU ; Changshou SHE
Chinese Journal of Infection Control 2025;24(7):923-931
Objective Tetanus is a serious infectious diseases with high mortality,which is an important global public health issue.This study aims to analyze the epidemiological burden and changing trends of tetanus in China from 1990 to 2021,providing a basis for disease prevention and control.Methods Epidemiological indicators and global socio-demographic index(SDI)related to tetanus in China were retrieved and collected from the 2021 Global Burden of Disease database(GBD 2021).The trend analysis of the incidence rate,mortality rate and disability-ad-justed life years(DALYs)rate of tetanus in China from 1990 to 2021 was conducted by Joinpoint 5.3 software.Results From 1990 to 2021,the age-standardized incidence rate(ASIR),age-standardized mortality rate(ASMR),and age-standardized disability-adjusted life years(DALYs)rate of tetanus in China decreased significantly(average annual percent change[AAPC]<0,P<0.001),with males being significantly higher than females.The crude incidence rate,crude mortality rate,and crude DALYs rate for all age groups showed overall declining trends,with the lar-gest decline in the 0-14 years age group.In 2021,the crude incidence rate,crude mortality rate,and crude DALYs rate of tetanus in the population aged 70-years were higher than those in the population aged 0-14,15-49,and 50-69 years groups.The ASIR,ASMR,and age-standardized DALYs rate of tetanus in China in 2021 were lower than the global level,only higher than those in the high SDI regions.Conclusion From 1990 to 2021,the disease burden of tetanus in China varied with gender and age,with an overall declining trend over time.It is necessary to strengthen tetanus health education for males and the ≥70 years population,and to improve the overall level of pri-mary prevention measures for tetanus.
6.Analysis on factors affecting the enhancement quality of head and neck CTA images based on bolus-tracking technology
Jun FU ; Wen-tao TANG ; Ji SHE ; De-chuan ZHANG
Journal of Regional Anatomy and Operative Surgery 2025;34(6):525-529
Objective To explore the factors affecting the enhancement quality of head and neck computed tomography angiography(CTA)images based on bolus-tracking technology,and provide a basis for quantitatively controlling image quality.Methods The general information,injection parameters,scanning parameters and analysis data of enhancement quality of images of 500 subjects who underwent head and neck CTA examinations in our hospital from January to June 2024 were prospectively collected.A comprehensive evaluation of enhancement quality of head and neck CTA images of the examinees was conducted,and the relevant examination data of the examinees with qualified and unqualified enhancement quality of images were compared.Multivariate Logistic regression analysis was used to analyze the independent factors influencing the enhancement quality of image.Results Among 500 CTA images of head and neck,262 cases had qualified enhancement quality of images and 238 cases were unqualified.There were statistically significant differences in gender,height,body weight,tube voltage,scanning direction,trigger threshold,diagnostic delay time,iodine contrast agent concentration,iodine contrast agent dosage,and iodine contrast agent flow rate between the examinees with qualified and unqualified enhancement quality of images(P<0.05).Multivariate Logistic analysis showed that the examinees were male(95%CI:0.22 to 0.75,P=0.004),body weight(95%CI:0.92 to 0.97,P<0.01),and head-foot direction scanning(95%CI:0.03 to 0.43,P=0.002),diagnostic delay time(95%CI:0.44 to 0.92,P=0.017),iodine contrast agent dosage(95%CI:1.21 to 1.34,P<0.001),iodine contrast agent flow rate(95%CI:0.14 to 0.59,P<0.001)were all the independent influencing factors of enhancement quality of image;Among them,the iodine contrast agent dosage(β=0.24,OR=1.27)was positively correlated with the enhancement quality of image,the examinees were male(β=-0.89,OR=0.41),body weight(β=-0.06,OR=0.94),head-foot direction scanning(β=-2.23,OR=0.11),diagnostic delay time(β=-0.45,OR=0.64),and iodine contrast agent flow rate(β=-1.26,OR=0.28)were negatively correlated with the enhancement quality of image.Conclusion In the application of bolus-tracking technology for head and neck CTA,individual factors,scanning parameters,and injection regimens are the key control elements that affect the positive results of enhancement quality of head and neck CTA images.In clinical practice,technicians can establish personalized scanning protocols by integrating artificial intelligence-assisted decision-making systems to achieve precise,standardized and personalized imaging.
7.Analysis on factors affecting the enhancement quality of head and neck CTA images based on bolus-tracking technology
Jun FU ; Wen-tao TANG ; Ji SHE ; De-chuan ZHANG
Journal of Regional Anatomy and Operative Surgery 2025;34(6):525-529
Objective To explore the factors affecting the enhancement quality of head and neck computed tomography angiography(CTA)images based on bolus-tracking technology,and provide a basis for quantitatively controlling image quality.Methods The general information,injection parameters,scanning parameters and analysis data of enhancement quality of images of 500 subjects who underwent head and neck CTA examinations in our hospital from January to June 2024 were prospectively collected.A comprehensive evaluation of enhancement quality of head and neck CTA images of the examinees was conducted,and the relevant examination data of the examinees with qualified and unqualified enhancement quality of images were compared.Multivariate Logistic regression analysis was used to analyze the independent factors influencing the enhancement quality of image.Results Among 500 CTA images of head and neck,262 cases had qualified enhancement quality of images and 238 cases were unqualified.There were statistically significant differences in gender,height,body weight,tube voltage,scanning direction,trigger threshold,diagnostic delay time,iodine contrast agent concentration,iodine contrast agent dosage,and iodine contrast agent flow rate between the examinees with qualified and unqualified enhancement quality of images(P<0.05).Multivariate Logistic analysis showed that the examinees were male(95%CI:0.22 to 0.75,P=0.004),body weight(95%CI:0.92 to 0.97,P<0.01),and head-foot direction scanning(95%CI:0.03 to 0.43,P=0.002),diagnostic delay time(95%CI:0.44 to 0.92,P=0.017),iodine contrast agent dosage(95%CI:1.21 to 1.34,P<0.001),iodine contrast agent flow rate(95%CI:0.14 to 0.59,P<0.001)were all the independent influencing factors of enhancement quality of image;Among them,the iodine contrast agent dosage(β=0.24,OR=1.27)was positively correlated with the enhancement quality of image,the examinees were male(β=-0.89,OR=0.41),body weight(β=-0.06,OR=0.94),head-foot direction scanning(β=-2.23,OR=0.11),diagnostic delay time(β=-0.45,OR=0.64),and iodine contrast agent flow rate(β=-1.26,OR=0.28)were negatively correlated with the enhancement quality of image.Conclusion In the application of bolus-tracking technology for head and neck CTA,individual factors,scanning parameters,and injection regimens are the key control elements that affect the positive results of enhancement quality of head and neck CTA images.In clinical practice,technicians can establish personalized scanning protocols by integrating artificial intelligence-assisted decision-making systems to achieve precise,standardized and personalized imaging.
8.Value of atherogenic index of plasma combined with Bedside Index for Severity in Acute Pancreatitis in the early prediction of severe hypertriglyceridemic acute pancreatitis
Qi JI ; Xi HUANG ; Chenyi SHE ; Song ZHANG ; Weitian XU ; Qingming WU
Journal of Clinical Hepatology 2023;39(6):1398-1403
Objective To investigate the correlation between atherogenic index of plasma (AIP) and the severity of hypertriglyceridemic acute pancreatitis (HTG-AP) and the value of AIP combined with Bedside Index for Severity in Acute Pancreatitis (BISAP) score in the early prediction of severe HTG-AP (sHTG-AP). Methods A retrospective analysis was performed for the clinical data of 170 patients with HTG-AP who were hospitalized in The General Hospital of Central Theater Command from January 2017 to December 2021, and according to related guidelines, they were divided into the sHTG-AP group with 28 patients and non-sHTG-AP group with 142 patients. Peripheral blood samples were collected from all patients within 24 hours after admission, and the two groups were compared in terms of sex, age, laboratory test results, AIP, BISAP score, and modified CT severity index (MCTSI) score. The chi-square test or the Fisher's exact test was used for comparison of categorical data between groups; the Mann-Whitney U test was used for comparison of continuous data between groups. The Spearman rank correlation test was used to investigate the correlation between each factor and the severity of HTG-AP, and the binary logistic regression analysis were used to investigate the independent risk factors for sHTG-AP. The receiver operating characteristic (ROC) curve was plotted to assess the predictive efficacy of each indicator. Results There were significant differences between the two groups in the medical history of diabetes, lymphocyte count, albumin, Ca 2+ , triglyceride, high-density lipoprotein cholesterol, AIP, BISAP score, MCTSI score, length of hospital stay, and hospital costs (all P < 0.05). The sHTG-AP group had a longer length of hospital stay, higher hospital costs, and a higher AIP value. AIP (odds ratio [ OR ]=1.244, 95% confidence interval [ CI ]: 1.062-1.458, P =0.007), BISAP score ( OR =5.525, 95% CI : 1.646-18.543, P =0.006), and MCTSI score ( OR =2.029, 95% CI : 1.245-3.305, P =0.004) were risk factors for sHTG-AP. AIP, BISAP score, and MCTSI score were positively correlated with the severity of HTG-AP ( r =0.291, 0.631, and 0.649, all P < 0.001), and AIP was positively correlated with BISAP score and MCTSI score ( r =0.190 and 0.215, both P < 0.05). AIP had an optimal cut-off value of 1.095 in predicting sHTG-AP, and AIP, BISAP score, and AIP combined with BISAP score had an area under the ROC curve of 0.759, 0.887, 0.925, respectively, a sensitivity of 0.821, 0.857, and 0.786, respectively, and a specificity of 0.627, 0.817, and 0.937, respectively (all P < 0.001). Conclusion AIP is a risk factor for sHTG-AP and is correlated with disease severity, and AIP combined with BISAP score has a relatively high value in the early prediction of sHTG-AP.
9.Genetic diagnosis of microcephaly
Xiaofeng LIAO ; Baojian LIAO ; Weihe TAN ; Li WANG ; Dandan WANG ; Erfang TANG ; Fuguang LI ; Xiufeng PAN ; Linghua JI ; Qin SHE
Chinese Journal of Obstetrics and Gynecology 2023;58(3):178-184
Objective:To explore the diagnostic value of chromosome karyotype analysis, chromosomal microarray analysis (CMA) and whole exome sequencing (WES) in microcephaly.Methods:A total of 9 cases of microcephaly fetuses diagnosed by prenatal ultrasound or children with microcephaly diagnosed after birth were selected from the Sixth Affiliated Hospital of Guangzhou Medical University from January 2014 to August 2022.Karyotype analysis and/or CMA were used to detect. The cases with negative karyotype analysis and CMA results were further sequenced by trio-based WES (Trio-WES). Then the coding genes contained in the pathogenic copy number variation (CNV) fragments were analyzed by gene ontology (GO) enrichment. The genes related to the development of the central nervous system contained in the pathogenic CNV and the pathogenic genes found by Trio-WES were combined for gene interaction network analysis.Results:In this study, 9 cases of microcephaly were recruited, with the time of diagnosis ranged from 23 weeks of gestation to 7 years after birth, and the head circumference of fetus or children ranged from 18.3 to 42.5 cm (-7SD to -2SD). Karyotype analysis was detected in all 9 cases and no abnormality result was found. Eight cases were detected by CMA, and one abnormal was found. Five cases were detected by Trio-WES, and two cases were detected with likely pathogenic genes. The GO enrichment analysis of the coding gene in the 4p16.3 microdeletion (pathogenic CNV) region showed that: in biological process, it was mainly concentrated in phototransduction, visible light; in terms of molecular function, it was mainly concentrated in fibroblast growth factor binding; in terms of cell components, it was mainly concentrated in rough endoplasmic reticulum. Gene interaction network analysis suggested that CDC42 gene could interact with CTBP1, HTT and ASPM gene.Conclusions:CMA could be used as a first-line detection technique for microcephaly. When the results of chromosome karyotype analysis and/or CMA are negative, Trio-WES could improve the detection rate of pathogenicity of microcephaly.
10.Risk factors for bleeding and thrombotic events in critically ill patients undergoing extracorporeal membrane oxygenation
Liping ZHOU ; Guoqing HUANG ; Xiangmin LI ; Ning YANG ; Ping WU ; Changshou SHE ; Shanshan HU ; Ji XU ; Xiaogang LI ; Xiaoye MO
Chinese Journal of Emergency Medicine 2023;32(9):1226-1234
Objective:To investigate the risk factors for bleeding and thrombosis during extracorporeal membrane oxygenation (ECMO) therapy in critically ill patients and determine the best predictors of coagulation-related complications.Methods:A retrospective analysis was performed on patients who received ECMO for respiratory or circulatory failure at Xiangya Hospital of Central South University from January 2020 to December 2022. The outcome was whether bleeding or thrombosis occurred from 24 h after ECMO insertion to before weaning. The differences in demographic characteristics, weaning conditions, prognosis, routine blood tests, organ function, coagulation and blood product transfusion of each group were compared. Logistic regression analysis was used to evaluate the risk factors for bleeding and thrombosis, and ROC curve evaluation was used to assess their capacity to predict complications.Results:A total of 61 patients with ECMO were enrolled, with 21 cases of bleeding and 14 cases of thrombosis during ECMO. Compared with the nonbleeding group, the activated partial thromboplastin time, thromboplastin time (TT), and transfusions of frozen plasma and red blood cells were higher in the bleeding group (all P<0.05). Compared with the nonthrombotic group, the increase in body weight, D-dimer (DD), fibrinogen degradation product (FDP), and improvement of arterial oxygen partial pressure (ΔPO 2) within 24 h were significantly higher in the thrombotic group (all P<0.05). Logistic regression analysis revealed that TT ( OR=1.039, 95% CI: 1.006~1.072, P=0.018) and frozen plasma transfusion volume ( OR=1.046, 95% CI: 1.010-1.083, P=0.012) were risk factors for bleeding events. FDP ( OR=1.030, 95% CI: 1.009-1.051, P=0.005), DD ( OR=1.181, 95% CI: 1.044-1.336, P=0.008), and ΔPO 2 ( OR=1.007, 95% CI: 1.002-1.012, P=0.006) were risk factors for thrombosis. According to ROC curve analysis, the AUCs of TT, frozen plasma transfusion, and combined indexes for predicting bleeding were 0.712, 0.690, and 0.816, respectively. The combined indices had a cut-off value of 0.273, a sensitivity of 75.61%, and a specificity of 80.00%. The AUCs of FDP, DD, ΔPO 2, and combined FDP with ΔPO 2 for predicting thrombosis were 0.778, 0.748, 0.786, and 0.868, respectively. The cut-off value of the combined index was 0.157, the sensitivity was 68.09%, and the specificity was 92.86%. Conclusions:TT combined with frozen plasma transfusion volume predicted bleeding optimally, while FDP plus ΔPO 2 predicted thrombotic events better during ECMO treatment in critically ill patients.

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