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.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.
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.Adjuvant strategies for patients with T1b invasion after endoscopic submucosal dissection for esophageal squamous cell carcinoma
Kaiyuan ZHU ; Yuchen SU ; Zhichao LIU ; Hong ZHANG ; Chunguang LI ; Jie ZHANG ; Zhigang LI
Journal of Shanghai Jiaotong University(Medical Science) 2024;44(1):116-123
Objective·To compare the prognostic effects of radical resection of esophageal cancer,concurrent chemoradiotherapy and simple follow-up observation on the prognosis of patients with T1b invasion of superficial esophageal squamous cell carcinoma after endoscopic submucosal dissection(ESD).Methods·From May 2016 to May 2021,the clinical data of 67 patients with esophageal squamous cell carcinoma who were pathologically confirmed as pT1b after ESD and treated in Shanghai Chest Hospital were retrospectively analyzed.According to the additional treatment after ESD,the patients were divided into additional surgery group(S group),chemoradio-therapy group(CRT group)and observation group(O group).χ2 test was used to compare the clinical baseline data and pathological information of the three groups of patients.The Kaplan-Meier survival curve and log-rank test were used to compare the disease free survival(DFS)and recurrence free survival(RFS)of the three groups of patients,and the Cox proportional hazards regression model was used on DFS and RFS by univariate and multivariate analysis.Results·Among all 67 patients,there were 23 cases in the S group,19 cases in the CRT group,and 25 cases in the O group.There was no significant difference in age(P=0.080),gender(P=0.078),tumor length(P=0.485),tumor location(P=0.655),lesion circumferential ratio(P= 0.310),histological grading(P=0.084),depth of tumor invasion(P=0.066)and lymphovascular invasion(P=0.279)among the three groups.During(42.6±16.7)months of follow-up,tumor recurrence was observed in 10 cases(14.9%),including 6 patients(60%)with local recurrence,2 patients(20%)with regional lymph recurrence and 2 patients(20%)with distant metastasis.The median recurrence time of group S,group CRT,and group O was 40.1,36.6,and 22.1 months,and the 3-year DFSs were 100%,89.5%,and 74.5%(P-trend=0.040).Multivariate Cox analysis showed that additional esophagectomy was the key to improving independent protective factors of RFS(HR=0.097,95%CI 0.010?0.956,P=0.046).Conclusion·For patients with superficial esophageal squamous cell carcinoma confirmed as pT1b after ESD,additional surgery can significantly reduce the possibility of long-term recurrence.
5.Application of standardized family in pediatric clinical teaching
Binbin YANG ; Yueling ZHU ; Wei LI ; Zhigang GAO ; Yunxia HONG
Chinese Journal of Medical Education Research 2024;23(3):332-337
Standardized patient (SP) has been widely used for medical teaching and assessment in medical colleges at home and abroad. Pediatric consultations are mostly directed toward parents, so in pediatric education, SP is usually referred to as standardized family (Sfam), which is trained to portray the patient's family members. At present, the development of Sfam in pediatric teaching in China is relatively slow. Based on the characteristics of pediatric teaching, the paper summarizes the necessity of Sfam, the application of different types of Sfam, the integration of Sfam with other clinical teaching methods, and the value of Sfam in pediatric teaching, and also discusses the future direction and prospects of Sfam combined with artificial intelligence in pediatric teaching. After years of development, Sfam has been proved to be an effective teaching model. We hope this paper can help more pediatric clinical educators gain a deeper understanding of the Sfam teaching method, and promote the application of Sfam in pediatric teaching to maximize its role in advancing the development of pediatric education.
6.Efficacy of recombinant human interferon α-2b spray, administered under medication guidance, in the treatment of herpangina
Minqing TONG ; Zhigang LIN ; Lili ZHU ; Shunxin XU
Chinese Journal of Primary Medicine and Pharmacy 2024;31(4):505-509
Objective:To investigate the efficacy of recombinant human interferon α-2b spray, administered under medication guidance, in the clinical treatment of herpangina.Methods:A total of 76 children with herpangina who were treated at The First People's Hospital of Yongkang between October 2020 and October 2022 were included in this study. Using the random number table method, these patients were randomly assigned to an observation group ( n = 42) and a control group ( n = 34). The control group received conventional treatment, whereas the observation group was administered recombinant human interferon α-2b spray under medication guidance. A comparative analysis was conducted between the two groups, evaluating clinical efficacy, inflammatory factor levels, treatment compliance, and the negative conversion rate of throat swab virology. Results:After treatment, the overall response rate of the observation group [95.24% (40/42)] and treatment compliance [97.62% (41/42)] were significantly higher than those of the control group [76.47% (26/34), 79.41% (27/34), χ2 = 4.27, 4.82, P = 0.040, 0.030]. The levels of C-reactive protein [(6.28 ± 1.64) mg/L], white blood cell count [(6.11 ± 1.10) × 10 9], and serum amyloid A [(3.47 ± 0.89) mg/L] in the observation group were significantly lower than those in the control group [(7.51 ± 1.16) mg/L, (7.51 ± 1.16) × 10 9, (7.82 ± 1.30) mg/L, t = 3.69, 6.46, 17.27, all P < 0.001]. The positive conversion rate of throat swab virology in the observation group [4.76% (2/42)] was lower than that in the control group [26.47% (9/34), χ2 = 5.51, P = 0.190]. Conclusion:The use of recombinant human interferon α-2b spray under medication guidance in the treatment of herpangina can improve treatment compliance, rapidly alleviate clinical symptoms, and significantly improve the prognosis.
7.Self-management and family support among elderly patients with type 2 diabetes in community: based on semi-structured interviews
Lan ZHU ; Zhigang PAN ; Fulai SHEN
Chinese Journal of General Practitioners 2024;23(2):126-131
Objective:To investigate the status of self-management and family support among elderly diabetic patients in community.Methods:Eight elderly patients with type 2 diabetes were interviewed in Xietu Community Health Service Center in Shanghai by semi-structured interviews from March 1st to March 15th, 2022. The interview outline focused on the impact of the disease on the patients' daily life, the status of disease self-management, and the support provided by their family. The contents of interviews were analyzed and extracted by Colaizz 7-step analysis method.Results:Of the 8 interviewees, there were 2 males and 6 females, aged (75.25±3.01)years old, with a disease course of (17.50±8.50)years. The interviews showed that there were three themes in the area of family support: difficulties in disease management (in terms of diet, exercise, medication, disease surveillance, health knowledge and quitting unhealthy habits), helpfulness of family support in management of above behaviors, differences between family support and support from others (including eating habits, information sharing, emotional support, patient trust, and continuity of support).Conclusions:The elderly diabetic patients in the community have some awareness of health management, but there is still much room for improvement. The supervision and support from family members can help patients improve their self-management and quality of life.
8.Diagnostic efficacy of AI in rib fracture under CT images with different reconstruction slice thickness
Ping AO ; Li ZHU ; Zhigang XIU ; Han XIAO ; Weimin LI
Chongqing Medicine 2024;53(5):723-726
Objective To investigate the diagnostic efficiency of artificial intelligence(AI)in rib frac-ture under the computed tomography(CT)images with different reconstruction slice thickness.Methods The first CT images of 100 patients with rib fractures were selected,and the interval-free recon-struction was carried out with the thickness of 0.625 mm,1.250 mm,2.500 mm and 5.000 mm,respectively.The rib fracture screening function of AI was used to automatically detect the CT images of four groups,and the diagnostic efficiency of AI for rib fracture under different reconstruction thickness conditions was com-pared.Results The sensitivity of AI in the diagnosis of rib fracture at 0.625 mm,1.250 mm,2.500 mm and 5.000 mm thickness was 99.32%(436/439),98.41%(432/439),89.52%(393/439)and 83.60%(367/439),respectively.The false positive rate was 4.80%(22/458),0.92%(4/436),0.76%(3/396)and 0.27%(1/368).The diagnostic sensitivity of AI in 0.625 mm and 1.250 mm thickness was higher than that in 2.500 mm and 5.000 mm,and the difference was statistically significant(P<0.05),while there was no significant difference in the thickness of 0.625 mm and 1.250 mm.The false positive rate of AI in the diagnosis of 0.625 mm slice thickness was higher than that of 1.250 mm,2.500 mm and 5.000 mm,and the difference was sta-tistically significant(P<0.05),while there was no significant difference in the thickness of 1.250 mm,2.500 mm and 5.000 mm(P>0.05).Conclusion The diagnostic efficiency of AI in 1.250 mm CT images is better than that in 0.625 mm,2.500 mm and 5.000 mm CT images.
9.Heparin-binding protein as a predictor of mortality in patients with diabetes mellitus and community-acquired pneumonia in intensive care unit:a propensity score matched study
Sun YUHAN ; Sun BAOQING ; Ren ZHIGANG ; Xue MINGSHAN ; Zhu CHANGJU ; Liu QI
World Journal of Emergency Medicine 2024;15(4):263-272
BACKGROUND:Patients with diabetes mellitus(DM)are vulnerable to community-acquired pneumonia(CAP),which have a high mortality rate.We aimed to investigate the value of heparin-binding protein(HBP)as a prognostic marker of mortality in patients with DM and CAP. METHODS:This retrospective study included CAP patients who were tested for HBP at intensive care unit(ICU)admission from January 2019 to April 2020.Patients were allocated to the DM or non-DM group and paired with propensity score matching.Baseline characteristics and clinical outcomes up to 90 days were evaluated.The primary outcome was the 10-day mortality.Receiver operating characteristic(ROC)curves,Kaplan-Meier analysis,and Cox regression were used for statistical analysis. RESULTS:Among 152 enrolled patients,60 pairs were successfully matched.There was no significant difference in 10-day mortality,while more patients in the DM group died within 28 d(P=0.024)and 90 d(P=0.008).In the DM group,HBP levels at ICU admission were higher in 10-day non-survivors than in 10-day survivors(median 182.21[IQR:55.43-300]ng/ml vs.median 66.40[IQR:34.13-107.85]ng/mL,P=0.019),and HBP levels could predict the 10-day mortality with an area under the ROC curve of 0.747.The cut-offvalue,sensitivity,and specificity were 160.6 ng/mL,66.7%,and 90.2%,respectively.Multivariate Cox regression analysis indicated that HBP was an independent prognostic factor for 10-day(HR 7.196,95%CI:1.596-32.455,P=0.01),28-day(HR 4.381,95%CI:1.449-13.245,P=0.009),and 90-day mortality(HR 4.581,95%CI:1.637-12.819,P=0.004)in patients with DM. CONCLUSION:Plasma HBP at ICU admission was associated with the 10-day,28-day,and 90-day mortality,and might be a prognostic factor in patients with DM and CAP.
10.A multicenter study on the impact of the early infusion rate on prognosis and the factors of influencing the infusion rate in patients with severe burns and inhalation injury
Shengyu HUANG ; Qimin MA ; Yusong WANG ; Wenbin TANG ; Zhigang CHU ; Haiming XIN ; Liu CHANG ; Xiaoliang LI ; Guanghua GUO ; Feng ZHU
Chinese Journal of Burns 2024;40(11):1024-1033
Objective:To investigate the impact of the early infusion rate on prognosis and the factors of influencing the infusion rate in patients with severe burns and inhalation injury.Methods:This study was a retrospective case series research. From January 2015 to December 2020, 220 patients with severe burns and inhalation injury meeting the inclusion criteria were admitted to 7 burn treatment centers in China, including 13 cases in the Fourth People's Hospital of Dalian, 26 cases in the First Affiliated Hospital of Naval Medical University, 73 cases in Guangzhou Red Cross Hospital of Jinan University, 21 cases in the 924 th Hospital of PLA, 30 cases in the First Affiliated Hospital of Jiangxi Medical College of Nanchang University, 30 cases in Tongren Hospital of Wuhan University & Wuhan Third Hospital, and 27 cases in Zhengzhou First People's Hospital. There were 163 males and 57 females, and their ages ranged from 18 to 91 years. The patients were divided into survival group and death group according to the survival within 28 d post injury. The following data of patients in the 2 groups were collected, including basic information (gender, age, body weight, body temperature, etc.), the injury characteristics (total burn area, post-injury admission time, etc.), the underlying diseases, the post-injury fluid resuscitation condition (infusion rate and ratio of infused electrolyte solution to colloid solution in the first 24 h post injury, etc.), the results of laboratory tests on admission (blood urea nitrogen, blood creatinine, albumin, pH value, base excess, blood lactate, oxygenation index, etc.), and treatment condition (inhaled oxygen volume fraction, hospitalization day, renal replacement therapy, etc.). After adjusting covariates using univariate Cox regression analysis, the multivariate Cox regression analysis was performed to evaluate the impact of infusion rate in the first 24 h post injury on patient death. The receiver operator characteristic curve for the infusion rate in the first 24 h post injury to predict the risk of death was plotted, and the maximum Youden index was calculated. Patients were divided into 2 groups according to the cutoff value (2.03 mL·kg -1·% total body surface area (TBSA) -1) for predicting risk of death by the infusion rate in the first 24 h post injury determined by the maximum Youden index, and the risk of death was compared between the 2 groups. The correlation between the previously mentioned clinical data and the infusion rate in the first 24 h post injury was analyzed; after the univariate linear regression analysis was used to screen the independent variables, the multivariate linear regression analysis was performed to screen the independent influential factors on the infusion rate in the first 24 h post injury. Results:Compared with those in survival group, patients in death group had significantly higher age and total burn area (with Z values of 12.08 and 23.71, respectively, P<0.05), the infusion rate in the first 24 h post injury, inhaled oxygen volume fraction, and blood urea nitrogen, blood creatinine, blood lactic acid on admission (with Z values of 7.99, 4.01, 11.76, 23.24, and 5.97, respectively, P<0.05), and the proportion of patients treated with renal replacement therapy ( P<0.05) were significantly higher, the albumin, pH value, and base excess on admission were significantly lower ( t=2.72, with Z values of 8.18 and 9.70, respectively, P<0.05), and the hospitalization day was significantly reduced ( Z=85.47, P<0.05). After adjusting covariates, the infusion rate in the first 24 h post injury was the independent influential factor on death (with standardized hazard ratio of 1.69, 95% confidence interval of 1.21-2.37, P<0.05). Patients in infusion rate ≥2.03 mL·kg -1·%TBSA -1 group had a significantly higher risk of death than those in infusion rate <2.03 mL·kg -1·% TBSA -1 group (with hazard ratio of 3.47, 95% confidence interval of 1.48-8.13, P<0.05). There was a significant correlation between total burn area, body weight, inhaled oxygen volume fraction, body temperature, post-injury admission time, the ratio of infused electrolyte solution to colloid solution in the first 24 h post injury, and oxygenation index <300 on admission and the infusion rate in the first 24 h post injury (with r values of -0.192, -0.215, 0.137, -0.162, -0.252, and 0.314, respectively, Z=4.48, P<0.05). After screening the independent variables, total burn area, body weight, post-injury admission time, and oxygenation index <300 on admission were the independent influential factors on the infusion rate in the first 24 h post injury (with standardized β values of -0.22, -0.22, -0.19, and 0.46, respectively, 95% confidence intervals of -0.34 to 0.09, -0.34 to 0.10, -0.32 to 0.06, and 0.22 to 0.71, respectively, P<0.05). Conclusions:The infusion rate in the first 24 h post injury in patients with severe burns and inhalation injury is the independent factor of influencing death, and patients with infusion rate ≥2.03 mL·kg -1·%TBSA -1 in the first 24 h post injury have a significantly increased risk of death. The total burn area, body weight, post-injury admission time, and oxygenation index <300 on admission were the independent factors of influencing the infusion rate in the first 24 h post injury in patients with severe burns and inhalation injury.

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