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.Clinical observation of free palmaris longus tendon graft reconstruction in treatment of gouty tophus erosion lesions in flexor tendon of wrist and hand.
Guozhong WANG ; Chao LU ; Zhigang QU ; Yuejuan ZHANG ; Benjun BI ; Fei GAO ; Zhao ZHANG ; Yuehai PAN ; Enxia ZHU ; Heng HUANG
Chinese Journal of Reparative and Reconstructive Surgery 2025;39(3):278-283
OBJECTIVE:
To investigate the effectiveness of free palmaris longus tendon graft reconstruction in the treatment of gouty tophus erosion lesions in flexor tendon of wrist and hand.
METHODS:
A retrospective analysis was conducted on 8 patients with gouty tophus erosion lesions in flexor tendon of wrist and hand who underwent free palmaris longus tendon graft reconstruction between June 2017 and December 2023. All patients were male, aged 22-65 years, with an average of 45.9 years. The duration of gout history ranged from 2 to 18 years, with an average of 8.8 years. The duration from the discovery of gouty tophus to operation ranged from 12 to 26 months, with an average of 17.6 months. The gouty tophus eroded the flexor pollicis longus tendon in 4 cases, with Verdan flexor tendon zones being Ⅰ-Ⅱ in 1 case and Ⅳ-Ⅴ in 3 cases. The flexor digitorum profundus tendons were affected in 2 cases for the index finger, 1 for the middle finger, and 1 for the ring finger, all located in zone Ⅳ-Ⅴ. The long axis of the gouty tophus ranged from 2.3 to 4.5 cm, with an average of 3.4 cm. All 8 patients presented with limited finger flexion and extension. Among them, 4 cases were accompanied by median nerve compression symptoms, and 1 case had associated bone and joint destruction in the hand. The total active motion (TAM) of the affected finger was (81.3±30.2)° before operation according to the hand function evaluation criteria for tendon repair by the Chinese Society of Hand Surgery of the Chinese Medical Association, and the functional evaluation was poor. The harvested palmaris longus tendon intraoperatively was 7-9 cm in length.
RESULTS:
Surgical incisions in all 8 patients healed by first intention, with no infections, graft non-union, or significant adhesion complications. All patients were followed up 8-25 months, with an average of 14.8 months. Numbness symptoms resolved in all 4 patients who presented with median nerve compression symptoms. Patients did not experience wrist pain or other discomfort, and function was not compromised. At last follow-up, according to the hand function evaluation criteria for tendon repair by the Chinese Society of Hand Surgery of the Chinese Medical Association, the TAM of 8 patients was (197.5±55.8)°, which significantly improved when compared with that before operation ( t=11.638, P<0.001); the hand function of 1 patient with gouty tophus in zone Ⅰ-Ⅱ flexor pollicis longus tendon was good, and the other 7 patients were excellent.
CONCLUSION
Free palmaris longus tendon graft reconstruction demonstrates good effectiveness in treating gouty tophus erosion lesions in flexor tendon of wrist and hand.
Humans
;
Middle Aged
;
Male
;
Adult
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Tendons/surgery*
;
Retrospective Studies
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Aged
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Gout/complications*
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Wrist/surgery*
;
Plastic Surgery Procedures/methods*
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Hand/surgery*
;
Treatment Outcome
;
Young Adult
5.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.
6.Mechanism of Chinese Medicine Against Diabetic Gastroparesis: A Review
Long LI ; Zhifeng TANG ; Wenjing SONG ; Fangyi CHEN ; Yuting YUE ; Xia YANG ; Zhigang WANG ; Wanxin ZHU ; Shengfang WAN
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(17):256-266
Diabetic gastroparesis (DGP) is a common diabetic neuropathy that affects the normal function of gastric motility and emptying. Clinically, it often manifests as abdominal distension, nausea and vomiting, early satiety, dyspepsia, etc. The pathogenesis of DGP is multifactorial, closely related to many factors, such as chronic hyperglycemia, neuropathy, autonomic nervous system disorders, inflammation, and oxidative stress. These factors can interact with each other, leading to delayed gastric emptying and the occurrence of related symptoms. Traditional Chinese medicine (TCM) has significant advantages in the prevention and treatment of DGP, including a long history, remarkable efficacy, individualized treatment, diverse therapeutic formulations, and improvement in the quality of life. Additionally, TCM is known for its low adverse reactions, good tolerance, and multi-targeted effects, making it an important approach in the management of DGP. Previous research has found that the main mechanisms of Chinese medicine in the prevention and treatment of DGP include the regulation of gastrointestinal hormones, inhibition of inflammatory responses, reduction of oxidative stress, enhancement of interstitial cells of Cajal activity, inhibition of pyroptosis, and modulation of related signaling pathways such as stem cell factor (SCF)/cellular growth factor receptor (c-Kit), adenosine monophosphate-activated protein kinase (AMPK), Ras homologous genome member A (RhoA)/Rho-associated coiled-coil forming kinase (ROCK). This article primarily summarized the research progress on Chinese medicine in preventing and treating DGP through the inhibition of inflammatory responses, reduction of oxidative stress, enhancement of interstitial cells of Cajal activity, inhibition of pyroptosis, and regulation of related signaling pathways, aiming to provide a reference and basis for further research on the application value of Chinese medicine in the prevention and treatment of DGP.
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.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.
9.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.
10.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.

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