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.Summary of best evidence for prevention and management of radiation esophagitis in patients with chest tumors
Lei LEI ; Xiaojing XUE ; Lan WANG ; Fang HE ; Xiaoyan WANG ; Yuan JIANG ; Wenxi LI ; Xiaoying ZHONG
Chinese Journal of Modern Nursing 2024;30(24):3318-3325
Objective:To summarize the best evidence for the prevention and management of radiation esophagitis in patients with chest tumors, so as to provide basis for the prevention and management of radiation esophagitis in patients.Methods:The research question was proposed based on the population, intervention, professional, outcome, setting and type of evidence (PIPOST) model, and guidelines, expert consensus, clinical decision-making, evidence summary, systematic review, and randomized controlled trials on the prevention and management of radiation esophagitis in chest tumor patients were systematically searched on UpToDate, BMJ Best Practice, Cochrane Library, PubMed, American Society of Clinical Oncology, China National Knowledge Infrastructure, WanFang Data, and other databases and websites based on the "6S" model. The search period was from database establishment to August 1, 2023. Two researchers independently evaluated the quality of the literature and extracted and integrated evidence from the literature that met the quality standards.Results:A total of ten articles were included, including three guidelines, one expert consensus, one systematic review, two systematic evaluations, and three randomized controlled trials. Twenty-three pieces of evidence were summarized from six dimensions of building multidisciplinary teams, screening and evaluation, nutritional support, drug and non-drug prevention, integrated traditional Chinese and western medicine treatment, and health education.Conclusions:The included evidence can provide a theoretical basis for the prevention and management of radiation esophagitis in patients undergoing chest tumor radiotherapy. Clinical medical and nursing personnel can provide personalized interventions to patients based on clinical practice.
5.Diagnostic value of magnetically controlled capsule gastroscope in elderly patients with suspected upper gastrointestinal bleeding
Xiaoxiong WANG ; Fang WANG ; Yufeng GUO ; Ting YE ; Jingjing WANG ; Xiaojing GU ; Shaoqi YANG
Chinese Journal of Digestive Endoscopy 2024;41(9):702-706
Objective:To investigate the diagnostic value of magnetically controlled capsule gastroscope in elderly patients with suspected upper gastrointestinal bleeding.Methods:A total of 102 patients with suspected upper gastrointestinal bleeding who underwent magnetically controlled capsule gastroscopy (MCCG) in General Hospital of Ningxia Medical University from October 2020 to September 2022 were enrolled. Patients were divided into two groups according to age: 38 patients in group A (≤65 years old) and 64 patients in group B (> 65 years old). The case data, changes of vital signs, detection of lesions and adverse reactions of the two groups were compared.Results:There were significant differences in combined diseases between group A and group B. The stomach examination time in group A was significantly shorter than that of group B (15.49±2.04 min VS 16.61±2.02 min, t=-2.685, P=0.009). There was significant difference in small intestine examination time between the two groups (331.69±14.96 min VS 337.83±14.28 min, t=-1.229, P=0.227). The incidence of adverse reactions in group A was significantly lower than that in group B [0.00%(0/38) VS 6.25%(4/64), χ2=6.186, P=0.013]. The changes of vital signs before, during and after examination were not statistically different. The detection rates of upper gastrointestinal lesions were 92.1% (35/38) and 98.4% (63/64), respectively. The positive rates of upper gastrointestinal bleeding under MCCG were 60.0% (21/35) and 50.8% (32/63), respectively. Patients with unexplained upper gastrointestinal bleeding under MCCG received small intestine examination. The detection rates of small intestinal lesions by small intestine examination were 84.6% (11/13) and 91.7% (22/24), respectively. Conclusion:MCCG demonstrates excellent diagnostic accuracy in elderly patients with suspected upper gastrointestinal bleeding. Additionally, it is safe and suitable for use in elderly patients with multiple comorbidities, allowing for concurrent small intestine examination.
6.Relationship between serum P-glycoprotein and claudin-5 levels with epilepsy and cognitive impairment in children
Guosheng XIE ; Na ZHANG ; Yanling ZHANG ; Fang WANG ; Xiaojing YAN
Chinese Pediatric Emergency Medicine 2024;31(11):841-845
Objective:To explore the relationship between the levels of serum P-glycoprotein(P-gp)and claudin-5 with epilepsy and cognitive impairment in children.Methods:A total of 120 children with epilepsy admitted to Xingtai People's Hospital from June 2020 to June 2022 were retrospectively selected as the epilepsy group,and divided into the general tonic-clonic seizure group( n=44)and the focal seizure group( n=76)according to the type of epilepsy,and also divided into the cognitive normal group( n=88)and the cognitive impairment group( n=32)according to the cognitive function of the children. Another 100 healthy children in the hospital were selected as the control group. Serum P-gp and claudin-5 levels were detected by enzyme-linked immunosorbent assay and compared between the two groups. Pearson correlation was used to analyze the relationship between serum P-gp,claudin-5 levels and epilepsy condition in children. Receiver operating characteristic (ROC) curve was used to analyze the diagnostic value of serum P-gp and claudin-5 for cognitive impairment in children with epilepsy. Results:The serum P-gp level in the epilepsy group was higher than that in the control group[(3.11±0.34) ng/L vs. (1.33±0.17) ng/L],and the serum claudin-5 level was lower than that in the control group[(0.66±0.12) ng/mL vs. (1.66±0.28) ng/mL] , and the differences were statistically significant (all P<0.05). The serum P-gp level in the generalized tonic-clonic seizure group was higher than that in the focal seizure group [(5.62±1.02) ng/mL vs. (2.55±0.28) ng/mL],and the serum claudin-5 level was lower than that in the focal seizure group[(0.40±0.05) ng/mL vs. (1.10±0. 25) ng/mL] , and the differences were all statistically significant (all P<0.05). Pearson correlation analysis showed that serum P-gp was positively correlated with negatively correlated with national hospital seizure severity scale(NHS3) score in pediatric epilepsy( r=0.447, P<0.05),and serum claudin-5 was NHS3 score in pediatric epilepsy( r=-0.485, P<0.05). The serum P-gp level in the cognitive impairment group was higher than that in the cognitive normal group [(5.87±1.05) ng/L vs. (2.44±0.26) ng/L],and the serum claudin-5 level was lower than that in the cognitive normal group [(0.32±0.03) ng/mL vs. (0.86±0.08) ng/mL], and the differences were all statistically significant (all P<0.05). ROC curve analysis showed that the area under the curve(AUC)of serum P-gp for evaluating cognitive impairment in children with epilepsy was 0.831(95% CI 0.781-0.881),the AUC of serum claudin-5 for evaluating cognitive impairment was 0.854(95% CI 0.804-0.904),and the AUC of the combination was 0.905(95% CI 0.855-0.955). Conclusion:Serum P-gp level is increased and claudin-5 level is decreased in children with epilepsy,and both levels are closely associated with the disease condition and cognitive impairment,with the combination of the two indexes more effective than either indicator in diagnosing cognitive impairment in pediatric epilepsy.
7.Laxation Atherosclerosis of Guizhi Tongluo Tablets by Inhibiting Neutrophil Extracellular Trapping Nets
Qiuyun LYU ; Lin YANG ; Dong SHEN ; Xiaojing HUANG ; Xianmei PAN ; Senjie ZHONG ; Jie CHEN ; Lingjun WANG ; Shaoxiang XIAN ; Wenhua XU ; Hongcheng FANG
Herald of Medicine 2024;43(12):1898-1903
Objective To investigate the mechanism of Guizhi Tongluo Tablets(GZTLP)on improving atherosclerosis in APOE knockout mice by regulating neutrophil extracellular trapping nets(NETs).Methods After modeling,24 APOE knockout mice aged 8 weeks were randomly divided into 4 groups:GZTLP high-dose group,low-dose group,model control group and normal control group,with 6 mice in each group.GZTLP was given 1.87 mg·g-1 and 0.47 mg·g-1 intragastric administration in high-dose group and low-dose group,respectively.The normal control group and model control group were given 0.9%sodium chloride solution intragastric administration for 6 weeks,and the lipid plaque deposition in aorta was observed by gross oil red O staining.Lipid deposition in aortic root was observed by oil red O staining.The pathological changes of lipid plaques in aortic root were observed by HE staining.The levels of interleukin-1β(IL-1β)and tumor necrosis factor α(TNF-α)in peripheral blood of mice were detected by enzyme-linked immunosorbent assay(ELISA).The expression of lymphocyte antigen 6G(Ly6G),myeloperoxidase(MPO)and citrulinated histone(Cit-H3)in plaques of the aortic arch and the colocalization of Ly6G,MPO and Cit-H3 were detected by immunofluorescence assay.Results Compared with the normal control group,the aorta of mice in the model control group showed serious lipid plaque deposition,morphological damage,and a large number of inflammatory cells infiltration,the contents of serum inflammatory factors IL-1β and TNF-α were increased,and the protein expressions of Ly6G,Cit-H3 and MPO were significantly increased.Compared with model control group,GZTLP group reduced the amount of lipid plaque deposition in aorta,the arrangement of aortic cells was more regular,the inflammatory cell infiltration was improved,and the contents of serum inflammatory factors IL-1β and TNF-α were significantly decreased(P<0.05).The colocalization and the protein expression of Ly6G,MPO and Cit-H3 were significantly decreased in aortic tissues(P<0.01).Conclusions GZTLP can improve atherosclerosis,and its mechanism may be related to the inhibition of neutrophil extracellular trapping nets.
8.Dosage of 4-Vinylcyclohexene Diepoxide in Induction of Premature Ovarian Insufficiency in Rats
Weixin LI ; Pengfei DU ; Yaoyao ZHU ; Chenchen SU ; Huanfang XU ; Li YANG ; Xiaojing SONG ; Yigong FANG
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(18):72-79
ObjectiveTo compare the effects of different doses and withdrawal time of 4-vinylcyclohexene diepoxide (VCD) on the reproductive endocrine levels of female rats, and to explore the effective, stable, and safe dosage of VCD for constructing a premature ovarian insufficiency (POI) rat model. MethodSD rats with regular estrous cycles were randomly divided into three groups: blank group, low-dose VCD group (80 mg·kg-1·d-1), and high-dose VCD group (160 mg·kg-1·d-1), with 24 rats in each group. After drug intervention, samples were collected on the 15th day (D15) and the 45th day (D45) after intervention. The general condition, rate of estrous cycle disturbance, serum hormone levels, ovarian histomorphology, follicle count, pregnancy outcome, and the protein and mRNA expression of transforming growth factor (TGF)-β and Smad2/3 were assessed. ResultCompared with the blank group, the low-dose VCD group showed no significant differences in the rate of estrous cycle disturbance or serum follicle-stimulating hormone (FSH), luteinizing hormone (LH), and estradiol (E2) levels. Ovarian tissue was damaged. Specifically, the number of primordial and primary follicles decreased on D15 (P<0.01), and the number of secondary follicles (P<0.01) and antral follicles (P<0.05) further decreased on D45. The litter number decreased on D15 (P<0.05), but there was no significant difference on D45. Furthermore, TGF-β protein levels increased on D15 (P<0.05) and D45 (P<0.01). The Smad2/3 levels increased on D45 (P<0.01), and TGF-β and Smad2/3 mRNA levels increased on D45 (P<0.05). Compared with the results in the blank group, the disturbance rate of the estrous cycle increased on D45 in the high-dose VCD group (P<0.01). The serum of FSH and LH increased (P<0.01), while E2 decreased (P<0.05). Ovarian tissue was damaged, and the downward trend of follicles at all levels was similar to that in the low-dose VCD group. The litter number significantly decreased on D15 and D45. TGF-β and Smad2/3 protein levels increased (P<0.05,P<0.01), and TGF-β mRNA increased on D45 (P<0.05). ConclusionHigh-dose VCD is an ideal method for constructing a POI rat model, being effective, stable, and safe.
9.Echocardiography evaluation of the short-term efficacy of interventional and surgical treatment for severe aortic valve stenosis
Wei CHENG ; Yingying ZHANG ; Qin XIA ; Jiaojiao HU ; Xiaojing YAO ; Jingqin FANG
Journal of Interventional Radiology 2024;33(5):479-482
Objective To discuss the clinical value of echocardiographic indicators in assessing the short-term efficacy of transcatheter aortic valve replacement(TAVR)and surgical aortic valve replacement(SAVR)in treating patients with severe aortic valve stenosis(AS).Methods The clinical data of 70 patients with severe AS,who received treatment at the Daping Hospital of Army Military Medical University of China between June 2019 and September 2022 were retrospectively analyzed.The patients were divided into SAVR group(n=40)and TAVR group(n=30).The preoperative one-week and postoperative one-month echocardiographic indicators were compared between the two groups.Results In both groups,the postoperative one-month peak aortic valve velocity(Vmax),aortic valve mean transvalvular pressure gradient(mPG),relative thickness of chamber wall(RWT),and left ventricular mass index(LVMI)were decreased when compared with preoperative values(all P<0.05);in TAVR group the left ventricular ejection fraction(LVEF),LVMI and incidence of perivalvular leakage were remarkably higher than those in SAVR group,while the Vmax and mPG were obviously lower than those in SAVR group(all P<0.05).In TAVR group,the mitral regurgitation decreased from preoperative 12 patients(40%)to postoperative 2 patients(6.7%)and the over-moderate tricuspid regurgitation decreased from preoperative 7 patients(23.3%)to postoperative one patient(3.3%)(all P<0.05).In SAVR group,the mitral regurgitation decreased from preoperative 15 patients(37.5%)to postoperative 2 patients(5.0%)and the over-moderate tricuspid regurgitation decreased from preoperative 9 patients(22.5%)to postoperative one patient(2.5%)(all P<0.05).The pulmonary artery hypertension in TAVR group decreased from preoperative 17 patients(56.7%)to postoperative 4 patients(13.3%),which in SAVR group decreased from preoperative 22 patients(55.0%)to postoperative 5 patients(12.5%)(P<0.05),but the differences in the above indexes between the two groups were not statistically significant(all P>0.05).Conclusion TAVR and SAVR have similar efficacy in improving secondary valve regurgitation and pulmonary artery hypertension caused by severe AS.TAVR is superior to SAVR in improving postoperative ventricular reverse remodeling and hemodynamics,although the incidence of paravalvular leakage in TAVR is higher than that in SAVR.(J Intervent Radiol,2024,33:479-482)
10.Exploration and practice of the blended teaching model based on BOPPPS classroom reconstruction in Diagnostic Radiology
Ting CHEN ; Dajing GUO ; Yangyang LIU ; Zheng FANG ; Xiaojing HE
Chinese Journal of Medical Education Research 2023;22(8):1163-1167
Objective:To investigate the feasibility and effectiveness of the blended teaching model for diagnostic radiology based on BOPPPS classroom reconstruction, i.e., bridge-in, objective, pre-assessment, participatory-learning, post-assessment, and summary.Methods:The undergraduate students in the classes of 2017 and 2018 in Department of Medical Imaging were selected as research subjects. The students in the class of 2018 were established as observation group and received the innovative blended teaching model based on BOPPPS classroom reconstruction, and those in the class of 2017 were established as control group and received teaching with traditional theoretical lectures. At the end of the course, 80 students were randomly selected from the observation group and the control group for performance analysis and teaching evaluation. SPSS 26.0 was used to perform the t-test. Results:The observation group had a total score of (82.66±6.18), while the control group had a total score of (76.47±5.42), and compared with the control group, the observation group had significantly higher scores of homework score, course discussion, and final examination ( P<0.05). Compared with the control group, the observation group had significantly higher scores of "understanding of the basic knowledge of imaging", "improvement of comprehensive diagnostic thinking ability", "stimulating the interest in learning and expanding horizons", and "cultivating clinical competence" in the self-evaluation survey ( P<0.05). Conclusion:The blended teaching model based on BOPPPS classroom reconstruction is suitable for the teaching of radiology diagnostics. It not only enriches teaching means and methods and enhances classroom participation and interaction, but also expands teaching space and teaching content.

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