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*
;
Hand/surgery*
;
Treatment Outcome
;
Young Adult
5.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.
6.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.
7.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.
8.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.
9.Clinical efficacy evaluation of modified posterior pharyngeal flap surgery in the treatment of velopharyngeal insufficiency
Lanrui LUO ; Shuang YANG ; Xia ZHOU ; Changjiang DU ; Zhigang CAI ; Hongping ZHU
Chinese Journal of Plastic Surgery 2024;40(8):857-865
Objective:To evaluate the clinical effect of modified posterior pharyngeal flap surgery in the treatment of velopharyngeal insufficiency.Methods:Clinical data of patients with cleft lip and palate diagnosed with velopharyngeal insufficiency and undergoing modified posterior pharyngeal flap surgery in Peking University School and Hospital of Stomatology from January 2018 to May 2022 were retrospectively analyzed. The traditional posterior pharyngeal flap surgery was improved by combining the modern concept and method of soft palate muscle reconstruction, and performed modified posterior pharyngeal flap surgery to correct velopharyngeal insufficiency. Preoperative and postoperative follow-up were performed including speech evaluation (classifying as none, mild, moderate, moderate to severe hypernasality and nasal emission), nasopharyngeal fiberscope (classifying velopharyngeal insufficiency as mild, moderate, or severe), lateral cephalometric radiographs (resting position and /i/ position), and the Nasal Obstruction Symptom Evaluation (NOSE) scale. The recovery of velopharyngeal function and nasal ventilation after the operation were statistically analyzed. The difference of resting velar length (RVL), effective working length (EWL) and angel of velar lifting (AVL) before and after the operation was compared by paired t-test to evaluate the clinical effect of surgery. P<0.05 indicates a statistically significant difference. Results:A total of 83 patients with velopharyngeal insufficiency were enrolled, including 44 males and 39 females, aged (13.04±11.31) years (4-53 years). 83 patients were followed up for 6-18 months after surgery, and all patients had primary wound healing without postoperative bleeding, perforation, or posterior pharyngeal flap detachment; 78 cases achieved complete velopharyngeal closure, the surgical success rate was 94%, three patients still had mild hypernasality and nasal emission after surgery, one patient still had moderate hypernasality and nasal emission after surgery, and one patient had severe hypernasality after surgery. The RVL was (29.27±6.01) mm before the operation and (36.88±6.51) mm after the operation.The EWL of the soft palate was (18.53±5.04) mm before the operation and (25.76±5.17) mm after the operation.The angel of velar lifting was 11.42°±11.65° before the operation and 15.91°±8.54° after operation. The differences were statistically significant ( P<0.01). 98%(81/83) patients had subjective nasal obstruction symptom in the short period after surgery (within one month), the nasal obstruction symptom evaluation (NOSE) score was 8.61±3.64. The long-term postoperative follow-up showed that the NOSE score was 3.06±2.92, and the difference was statistically significant ( P<0.01). Conclusion:Modified posterior pharyngeal flap surgery can significantly increase the resting velar length and effective working length, improve the movement ability of the soft palate, acquire functional reconstruction of velopharyngeal closure, improve speech function and achieve effectively surgical results.
10.Clinical Validation of a Prototype Smart Non-Invasive Pregnancy Glucose Monitor
Heqing LU ; Lirui CHENG ; Qiaoling DU ; Xiaofeng ZHANG ; Zhenzhen SUN ; Zhigang ZHU
Chinese Journal of Medical Instrumentation 2024;48(5):539-543
The aim of this study is to evaluate the effectiveness of a smart non-invasive blood glucose monitor prototype during pregnancy through clinical validation.The monitor utilizes near-infrared spectroscopy combined with AI big data analysis of photoelectric volumetric pulse wave data to achieve non-invasive monitoring of blood glucose in women during pregnancy.The research team developed a monitor that employs a sensing chip,effectively overcoming the problems of weak signals and individual differences in non-invasive blood glucose monitoring.The user experience is enhanced by visualizing the test results on the accompanying cell phone APP(application)of the smart non-invasive pregnancy blood glucose monitor.Clinical validation revealed that the non-invasive monitoring data for pregnant women aged 20~30 years significantly differed from those obtained via traditional blood glucose measurement methods,whereas no significant difference(P<0.05)was observed for pregnant women aged 31~42 years.The study concluded that further calibration of the monitor and an expansion of the sample size are necessary to enhance consistency with invasive glucose monitoring results.

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