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
;
Tendons/surgery*
;
Retrospective Studies
;
Aged
;
Gout/complications*
;
Wrist/surgery*
;
Plastic Surgery Procedures/methods*
;
Hand/surgery*
;
Treatment Outcome
;
Young Adult
5.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.
6.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.
7.Key Environment Factors and Regionalization of the Ecological Suitability of the Original Species of Chinese Medicine Cremastrae Pseudobulbus/Pleiones Pseudobulbus
Yujie CHI ; Mingyu ZHU ; Yifei LIU ; Di LIU ; Lin SEN ; Zhigang HU ; Jingjing ZHANG
World Science and Technology-Modernization of Traditional Chinese Medicine 2024;26(5):1254-1260
Objective In order to offer a theoretical foundation for Cremastae Pseudobulbus/Pleiones Pseudobulbus original species scientific introduction and site selection for expansion.Methods We gathered sample distribution information for the original species of Cremastae Pseudobulbus/Pleiones Pseudobulbus nationwide by consulting various databases and conducting field investigations.A total of 257 effective distribution data were gathered.Altitude,temperature,solar radiation,precipitation,and water vapor pressure were among the 68 environment factors that were chosen from 5 categories.The ecological suitability of Cremastae Pseudobulbus/Pleiones Pseudobulbus original species was investigated using Maxent and ArcGIS.Results The investigation revealed that precipitation,solar radiation,and altitude were the core environment factors influencing the ecological suitability of Cremastae Pseudobulbus/Pleiones Pseudobulbus.The most important environment factors varied significantly between diverse original species.The most suitable potential areas for the growth of Cremastra appendicutata,Pleione bulbocodioides,and Pleione yunnanensis were concentrated in Taiwan,South China,and the adjacent areas of Yunnan and Sichuan,respectively.Conclusion Further ecological suitability levels were classified for their potential distribution areas,providing a scientific basis for the rational introduction,cultivation,and artificial stanhbzyydxdardized expansion of the Cremastae Pseudobulbus/Pleiones Pseudobulbus.
8.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.
9.Efficacy and safety of modified VIALE-A regimen for treatment of elderly patients with intermediate or high risk myelodysplastic syndromes
Qixin SUN ; Zhenzhen WEN ; Xiaoyan CHEN ; Ahui WANG ; Guiping CHEN ; Ziyuan ZHAO ; Zhigang ZHU
Journal of Leukemia & Lymphoma 2024;33(8):462-465
Objective:To explore the efficacy and safety of the modified VIALE-A regimen in the treatment of elderly (>75 years old) patients with intermediate or high risk myelodysplastic syndromes (MDS).Methods:A retrospective case series analysis was conducted. Clinical data were collected from 7 MDS patients aged >75 years who were continuously treated with the modified VIALE-A regimen (azacytidine 75 mg/m 2 per day from day 1 to day 7 + venetoclax 200 mg per day from day 8 to day 28) from May 2021 to August 2023, and the patients were diagnosed according to the World Health Organization 2016 staging criteria and were determined to be at intermediate or high risk according to the revised International Prognostic Scoring System. The patients' efficacy and common adverse reactions were analyzed, and the Kaplan-Meier method was used for survival analysis. Results:Of the 7 patients, 5 were female and 2 were male; the median age [ M ( Q1, Q3)] was 84 years old (80 years old, 90 years old). One patient failed the initial treatment, and the remaining 6 achieved complete remission or complete remission in bone marrow after induction therapy with the modified VIALE-A regimen in 1-2 courses. By the follow-up cut-off date of December 31st, 2023, the median follow-up was 10 months (5 months, 18 months) and the median overall survival time was 18 months (95% CI: 0-39 months). Grade 3-4 myelosuppression occurred in all 7 patients during the induction phase, with granulocytopenia lasting 7-10 d; Of the 64 courses of maintenance treatment, 54 (84%) had grade 1-3 myelosuppression; non-hematologic adverse reactions were mild; no treatment interruptions occurred in the cumulative 73 courses. Conclusions:The modified VIALE-A regimen is moderately efficacious in elderly patients with intermediate or high risk MDS, with controllable adverse reactions.
10.Correlation between systemic immune-inflammation index and lower extremity vascular disease in patients with type 2 diabetes mellitus
Ruomei YANG ; Yushuang LIU ; Nan JIANG ; Hexuan ZHANG ; Qing ZHOU ; Liqin YANG ; Qiang LI ; Hua YANG ; Zhigang ZHAO ; Hongbo HE ; Zhiming ZHU ; Zhencheng YAN
Journal of Army Medical University 2024;46(18):2138-2144
Objective To investigate the relationship between systemic immune-inflammation index (SII)and lower extremity vascular disease in patients with type 2 diabetes mellitus (T2DM).Methods A cross-sectional study was conducted on 390 T2DM patients admitted in our department from January 2013 to January 2024.According to the diagnostic criteria for lower extremity vascular disease in T2DM patients,they were divided into a lower extremity vascular disease group (n=158)and a control group (n=232).General data and results of laboratory tests were compared between the 2 groups.Spearman correlation analysis was used to identify the related factors for lower extremity vascular diseases in T2DM patients.The correlation between SII and lower extremity vascular diseases in T2DM patients was analyzed using the Row Mean Scores and Cochran-Armitage Trend analysis.Multivariate logistic regression analysis was applied to identify the risk factors for lower limb vascular lesions in T2DM patients.Receiver operating characteristic (ROC)curve was plotted to evaluate the diagnostic efficacy of SII for lower extremity vascular disease in the patients.Results Compared with T2DMpatients without lower extremity vascular disease,those with lower extremity vascular disease were older,had higher levels of total cholesterol (TC),low-density lipoprotein cholesterol (LDL-C),SII,larger proportion of carotid vascular lesions,and increased proportion of no-taking statins.The lower extremity vascular disease in T2DM patients was positively correlated with SII/100 (r=0.429,P<0.001),age (r=0.517,P<0.001),TC (r=0.161,P=0.001),LDL-C (r=0.117,P=0.021),carotid artery lesions (r=0.101,P=0.047),no-taking statins (r=0.266,P<0.001).Logistic regression analysis showed that SII,age,LDL-C,and no-taking statins were the risk factors for lower extremity vascular lesions in T2DM patients (P<0.01).The area under the curve (AUC)value of SII combined with age,LDL-C,and no-taking statins in predicting lower extremity vascular disease in T2DM patients was 0.896.Conclusion SII is not only a risk factor,but also a simple marker for lower extremity vascular disease in T2DM patients,suggesting that inflammatory response plays an important role in the occurrence and development of lower extremity vascular disease in T2DM.

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