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.Observation on the therapeutic effect of a modified Devine procedure with subcutaneous sliding fixation method for concealed penis.
Mohammed Abdulkarem AL-QAISI ; Hai-Fu TIAN ; Jia-Jin FENG ; Ke-Ming CHEN ; Jin ZHANG ; Yun-Shang TUO ; Xue-Hao WANG ; Bin-Cheng HUANG ; Muhammad Arslan Ul HASSAN ; Rui HE ; Guang-Yong LI
Asian Journal of Andrology 2025;27(4):470-474
To evaluate the therapeutic effect of a modified Devine procedure with a subcutaneous sliding fixation method for the treatment of congenital concealed penis, we retrospectively selected 45 patients with congenital concealed penises who were admitted to General Hospital of Ningxia Medical University (Yinchuan, China) between September 2020 and November 2023. In all cases, the penis was observed to be short, and retracting the skin at the base revealed a normal penile body, which immediately returned to its original position upon release. All patients underwent the modified Devine procedure with subcutaneous sliding fixation and completed a 12-week postoperative follow-up. A statistically significant increase in penile length was observed postoperatively, with the median length increasing from 4.0 (interquartile range [IQR]: 3.5-4.8; 95% confidence interval [CI]: 3.9-4.4) cm to 8.0 (IQR: 7.8-8.0; 95% CI: 7.7-7.9) cm, with P < 0.001. The parents were satisfied with the outcomes, including increased penile length, improved hygiene, and enhanced esthetics. Except for mild foreskin edema in all cases, no complications (such as infections, skin necrosis, or penile retraction) were observed. The edema was resolved within 4 weeks after the operation. This study demonstrates that the modified Devine procedure utilizing the subcutaneous sliding fixation method yields excellent outcomes with minimal postoperative complications, reduced penile retraction, and high satisfaction rates among patients and their families.
Humans
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Male
;
Penis/abnormalities*
;
Retrospective Studies
;
Urologic Surgical Procedures, Male/methods*
;
Treatment Outcome
;
Child
;
Plastic Surgery Procedures/methods*
5.The current situation and the future of pediatric blood transfusion.
Chinese Journal of Contemporary Pediatrics 2024;26(12):1245-1248
With advancements in clinical medicine, pediatric blood transfusion has evolved from traditional empirical practices to evidence-based approaches grounded in clinical research data. To better guide pediatric blood transfusion practices and improve clinical outcomes for pediatric patients, the National Health Commission has developed and issued "Guideline for pediatric transfusion". This article summarizes the unique aspects of pediatric blood transfusion, the application of blood component therapy in treating pediatric patients, the significance of interpreting the "Guideline for pediatric transfusion", and anticipates future developments in pediatric blood transfusion medicine.
Humans
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Blood Transfusion
;
Child
6.p53 regulates primordial follicle activation through the mTOR signaling pathway.
Huan LIN ; Tian-He REN ; Yun-Tong TONG ; Gui-Feng WU ; Tuo ZHANG ; Teng-Xiang CHEN ; Guo-Qiang XU
Acta Physiologica Sinica 2023;75(3):339-350
This paper aimed to investigate the role and potential mechanism of p53 on primordial follicle activation. Firstly, the p53 mRNA expression in the ovary of neonatal mice at 3, 5, 7 and 9 days post-partum (dpp) and the subcellular localization of p53 were detected to confirm the expression pattern of p53. Secondly, 2 dpp and 3 dpp ovaries were cultured with p53 inhibitor Pifithrin-μ (PFT-μ, 5 μmol/L) or equal volume of dimethyl sulfoxide for 3 days. The function of p53 in primordial follicle activation was determined by hematoxylin staining and whole ovary follicle counting. The proliferation of cell was detected by immunohistochemistry. The relative mRNA levels and protein levels of the key molecules involved in the classical pathways associated with the growing follicles were examined by immunofluorescence staining, Western blot and real-time PCR, respectively. Finally, rapamycin (RAP) was used to intervene the mTOR signaling pathway, and ovaries were divided into four groups: Control, RAP (1 μmol/L), PFT-μ (5 μmol/L), PFT-μ (5 μmol/L) + RAP (1 μmol/L) groups. The number of follicles in each group was determined by hematoxylin staining and whole ovary follicle counting. The results showed that the expression of p53 mRNA was decreased with the activation of primordial follicles in physiological condition. p53 was expressed in granulosa cells and oocyte cytoplasm of the primordial follicles and growing follicles, and the expression of p53 in the primordial follicles was higher than that in the growing follicles. Inhibition of p53 promoted follicle activation and reduced the primordial follicle reserve. Inhibition of p53 promoted the proliferation of the granulosa cells and oocytes. The mRNA and protein expression levels of key molecules in the PI3K/AKT signaling pathway including AKT, PTEN, and FOXO3a were not significantly changed after PFT-μ treatment, while the expression of RPS6/p-RPS6, the downstream effectors of the mTOR signaling pathway, was upregulated. Inhibition of both p53 and mTOR blocked p53 inhibition-induced primordial follicle activation. Collectively, these findings suggest that p53 may inhibit primordial follicle activation through the mTOR signaling pathway to maintain the primordial follicle reserve.
Female
;
Animals
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Mice
;
Tumor Suppressor Protein p53/metabolism*
;
Proto-Oncogene Proteins c-akt/metabolism*
;
Phosphatidylinositol 3-Kinases/metabolism*
;
Hematoxylin
;
Signal Transduction/physiology*
;
TOR Serine-Threonine Kinases
;
Sirolimus
;
RNA, Messenger
7.Treatment options for patients with osteoporotic thoracolumbar injury classification and severity score of 4 points after acute symptomatic osteoporotic thoracolumbar compression fracture
Qingda LI ; Junsong YANG ; Lin GAO ; Jianan ZHANG ; Baorong HE ; Tuanjiang LIU ; Changjun HE ; Mingyi YANG ; Chao JIANG ; Xin TIAN ; Yuan TUO ; Dingjun HAO
Chinese Journal of Trauma 2021;37(1):15-21
Objective:To explore the treatment options for patients with osteoporotic thoracolumbar injury classification and severity score (OTLICS) of 4 points following acute symptomatic osteoporotic vertebral compression fracture (OVCF) .Methods:A retrospective case-control study was conducted to analyze the clinical data of 108 patients with acute symptomatic OVCF admitted to Honghui Hospital, Xi'an Jiaotong University Faculty of Medicine from February 2016 to February 2018. There were 21 males and 87 females, aged 55-92 years [(71.6±5.3)years]. All patients had OTLICS score of 4 points. Of all, 76 patients were treated operatively (surgery group) and 32 patients were treated non-operatively (non-surgery group). The visual analogue scale (VAS), Oswestry disability index (ODI) and quality of life score (SF-36) were compared between the two groups before treatment, at 1 week, 3 months, 6 months after treatment, and at the last follow-up. The recovery of the injured vertebrae before and after treatment (Cobb angle of the injured vertebra, relative height of the anterior edge of the injured vertebrae), adjacent vertebral body fractures, and complications were compared between the two groups.Results:All patients were followed up for 12-18 months [(13.4±4.2)months]. At 1 week, 3 months and 6 months after treatment, the VAS in surgery group [(3.5±1.0)points, (2.1±0.6)points, (2.0±0.4)points] was better than that in non-surgery group [(6.4±1.7)points, (5.3±1.5)points, (3.3±0.6)points] ( P<0.05), the ODI in surgery group [(45.8±10.3)points, (35.3±8.6)points, (26.5±7.1)points] was better than that in non-surgery group [(65.7±12.1)points, (58.3±10.7)points, (45.6±9.3)points] ( P<0.05), the SF-36 in surgery group [(82.8±1.4)points, (85.0±1.5)points, (88.0±1.3)points] was better than that in non-surgery group [(80.4±1.3)points, (81.5±1.4)points, (85.6±1.1)points] ( P<0.05). At the last follow-up, there were no significant differences in VAS, ODI and SF-36 between the two groups ( P>0.05). At 3 months, 6 months and the last follow-up, the Cobb angle in surgery group [(18.3±3.9)°, (17.5±3.0)°, (17.8±1.6)°] was better than that in non-surgery group [(22.4±2.2)°, (22.5±1.7)°, (22.1±1.3)°] ( P<0.05), and the relative height of the anterior edge of the injured vertebra in surgery group [(75.4±8.6)%, (76.6±8.6)%, (75.2±8.3)%] was better than that in non-surgery group [(63.5±7.6)%, (65.2±7.4)%, (62.8±7.2)%] ( P<0.05). The adjacent vertebral fractures occurred in 6 patients (8%) in surgery group, and in 2 patients (6%)in non-surgey group ( P>0.05). Postoperative complications occurred in 8 patients (11%) in surgery group, and occurred in 6 patients (19%) in non-surgery group ( P>0.05). Conclusion:When applying the OTLICS scoring system to treat acute symptomatic OVCF, patients with OTLICS score of 4 points should be promptly treated with operatively, which can quick relieve pain, correct deformities promote functional recovery, and improve quality of life.
8.Foundation of acute symptomatic osteoporotic thoracolumbar fracture classification system and its validity examination and clinical application evaluation
Dingjun HAO ; Jianan ZHANG ; Junsong YANG ; Tuanjiang LIU ; Xiaohui WANG ; Peng LIU ; Liang YAN ; Yuanting ZHAO ; Qinpeng ZHAO ; Dageng HUANG ; Jijun LIU ; Shichang LIU ; Yunfei HUANG ; Yuan TUO ; Ye TIAN ; Lulu BAI ; Heng LI ; Zilong ZHANG ; Peng ZOU ; Pengtao WANG ; Qingda LI ; Xin CHAI ; Baorong HE
Chinese Journal of Trauma 2021;37(3):250-260
Objective:To establish the acute symptomatic osteoporotic thoracolumbar fracture (ASOTLF) classification system, and to examine the reliability and evaluate the effect of clinical application.Methods:A retrospective case series study was conducted to analyze the clinical data of 1 293 patients with osteoporotic thoracolumbar fracture(OTLF) admitted to Honghui Hospital from January 2016 to December 2018. There were 514 males and 779 females, aged 57-90 years [(71.4±6.3)years]. The T value of bone mass density was -5.0--2.5 SD [(-3.1±-0.4)SD]. According to the clinical symptoms a and fracture morphology, OTLF was divided into 4 types, namely type I(I occult fracture), type II(compressed fracture), type III (burst fracture) and type IV(unstable fracture). The type II was subdivided into three subtypes (type IIA, IIB, IIC), and the Type III into two subtypes (type IIIA, IIIB). of all patients, 75 patients (5.8%) were with type I, 500 (38.7%) with type II A, 134 (10.4%) with type IIB, 97 (7.5%) with type IIC, 442 (34.2%) with type IIIA, 27(2.1%) with type IIIB and 18 (1.4%) with type IV. After testing the validity of the classification, different treatment methods were utilized according to the classification, including percutaneous vertebroplasty (PVP) for Type I, PVP after postural reduction for Type II, percutaneous kyphoplasty (PKP) for Type IIIA, posterior reduction and decompression, bone graft fusion and bone cement-augmented screw fixation for Type IIIB, and posterior reduction, bone graft fusion and bone cement-augmented screw fixation for Type IV. The visual analog score (VAS), Oswestry disability index (ODI), Frankel grade of spinal cord injury, local Cobb Angle, and vertebral body angle (vertebral body angle) were recorded in all patients and in each type of patients before surgery, at 1 month after surgery and at the last follow-up. The neurological function recovery and complications were also recorded.Results:The patients were followed up for 24-43 months [(29.9±5.1)months]. A total of 3 000 assessments in two rounds were conducted by three observers. The overall κ value of inter-observer credibility was 0.83, and the overall κ value of intra-observer credibility was 0.88. The VAS and ODI of all patients were (5.8±0.7)points and 72.5±6.6 before surgery, (1.8±0.6)points and 25.0±6.3 at 1 month after surgery, and (1.5±0.6)points and 19.5±6.2 at the last follow-up, respectively (all P<0.05). The Cobb angle and vertebral body angle of all patients were (13.0±9.1)° and (8.0±4.6)° before surgery, (7.9±5.2)° and (4.6±2.9)° at 1 month after surgery, and (9.1±6.0)° and (5.8±3.0)° at the last follow-up, respectively (all P<0.05). At the last follow-up, VAS, ODI, Cobb Angle and VBA of each type of patients were significantly improved compared with those before surgery (all P<0.05). The spinal cord compression symptoms were found 1 patient with type IV and 5 patients with type IIIB preoperatively. At the last follow-up, neurological function improved from grade C to grade E in 1 patient and from grade D to grade E in 5 patients ( P<0.05). The lower limb radiation pain or numbness in 3 patients with type IV and 22 patients with type III preoperatively were fully recovered after surgical treatment at the last follow-up except for three patients. Conclusions:The ASOTLF classification is established and has high consistency and reliability. The classification-oriented treatment strategy has achieved a relatively satisfactory effect, indicating that the classification has a certain guiding significance for treatment of OTLF.
9.Comparison of curative efficacy of percutaneous vertebroplasty and non-surgical treatment of type I acute symptomatic osteoporotic thoracolumbar fracture
Qingda LI ; Junsong YANG ; Lin GAO ; Baorong HE ; Tuanjiang LIU ; Xuefang ZHANG ; Jianan ZHANG ; Xin TIAN ; Changjun HE ; Mingyi YANG ; Yuan TUO ; Dingjun HAO
Chinese Journal of Trauma 2021;37(6):541-548
Objective:To compare the clinical efficacy of percutaneous vertebroplasty (PVP) and non-surgical treatment of patients with type I fracture according to the acute symptomatic osteoporotic thoracolumbar fracture (ASOTLF) classification.Methods:A retrospective case-control study was used to analyze the clinical data of 115 patients with ASOTLF admitted to Honghui Hospital of Xi'an Jiaotong University from January 2015 to December 2018. There were 48 males and 67 females, aged 65-92 years [(75.3±8.5)years]. According to clinical symptoms and imaging characteristics, all patients were identified with type I fracture according to the ASOTLF classification. Injury segments were at T 6 to T 10 in 10 patients, at T 11 in 15, at T 12 in 26, at L 1 in 34, ay L 2 in 18, at L 3 in 7, and at L 4 in 5. A total of 73 patients received PVP combined with anti-osteoporosis treatment (surgery group), and 42 patients received non-surgery combined anti-osteoporosis treatment (non-surgery group). Before treatment, at 1 day, 1 month, 3 months, 6 months after treatment, and at the last follow-up, the visual analogue scale (VAS) was used to assess the pain, the Roland Morris Disability (RMD) score to assess the spinal function, and the Quality of Life Questionnaire of the European Foundation for Osteoporosis (QUALEFFO) score to evaluate the quality of life. The bone mineral density was compared between groups before treatment and at 1 year after treatment. The complications were observed as well. Results:All patients were followed up for 12-18 months [(13.2±4.6)months]. At 1 day, 1 month, and 3 months after treatment, the VAS in surgery group [(3.9±0.6)points, (3.3±0.6)points, (2.9±0.3)points] was significantly lower than that in non-surgery group [(6.0±0.7)points, (5.0±0.8)points, (4.2±1.0)points, respectively] (all P<0.05); the RMD score in surgery group [(15.2±0.7)points, (12.6±0.7)points, (10.6±0.7)points] was significantly lower than that in non-surgery group [(16.4±0.8)points, (14.6±0.8)points, (12.7±0.6)points, respectively] (all P<0.05). At 1 day and 1 month after treatment, the QUALEFFO score in surgery group [(46.0±1.1)points, (41.4±0.8)points] was lower than that in non-surgery group [(50.3±0.8)points, (44.7±1.2)points] (all P<0.05). There was no statistically significant difference between the two groups at other time points of the above indicators ( P>0.05). At 1 year after treatment, the bone mineral density in surgery group was (-3.0±0.9)SD, and was (-2.8±1.1)SD in non-surgery group ( P>0.05). There was no significant difference in the incidence of complications between surgery group [37%(27/73)] and non-surgery group [33%(14/42)] ( P>0.05). Conclusion:For patients with ASOTLF type I fracture, PVP and non-surgical treatment has similar effects in anti-osteoporosis and occurrence of complications, but the PVP is superior to non-surgical treatment in early pain relief, spinal function improvement and quality of life.
10.Rush poppers use and risks of human papillomavirus infection among men who have sex with men in Urumqi: mediation effect through high?risk sexual behaviors
Xiaoqing TUO ; Hui WANG ; Mahan YELEDAN ; Zhanlin ZHANG ; Zheng GONG ; Tian TIAN ; Zhen CHEN ; Hailili GULISIYA ; Jianghong DAI
Chinese Journal of Preventive Medicine 2019;53(2):202-205
Objective To study the prevalence of rush poppers use among men who have sex with men (MSM) in Urumqi and to analyze the mediating effect of high-risk sexual behavior between the use of rush poppers and human papillomavirus (HPV) infection. Methods From January to June 2018, 651 MSM were recruited through network and publicity. Data was collected by using online questionnaire and anal swab were collected from them for HPV genotyping. According to Baron and Kenny's criterion, multivariate logistic regression models was used to analyze the mediation effect of high-risks sexual behaviors (multiple sexual partners, anal intercourse condom use) between rush poppers use and HPV infection. Results A total of 651 subjects were (32.0 ± 8.0) years old, and 174 subjects (26.7%)had ever used rush poppers in the past 6 months, while 350 subjects (46.9%) had more than 2 sexual partners and 188 subjects (28.9%) did not use anal condom. After adjusting age and marital status, rush poppers use was associated with HPV infection ( OR (95%CI ) was 2.34 (1.63-3.36), P<0.05), and sexual partners in the past 6 months (OR (95%CI) was 2.72 (1.89-3.93), P<0.05).After adjustment for age, marital status, sexual partners in the past 6 months, and anal condom use, rush poppers use was still associated with HPV infection (OR (95%CI) was 2.21 (1.53-3.19), P<0.05).After adjustment and adjustment of age, marital status, rush poppers use and anal sex condom use, the number of sexual partners at nearly 6 months was still associated with HPV infection ( OR (95%CI ) was 1.46 (1.05-2.04), P<0.05). Conclusion Sexual partners in the past 6 months have a mediation effect between rush poppers use and HPV infection in Urumqi. For the prevention of sexually transmitted diseases, we should focus on rush poppers use.

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