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.

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.

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.

BACKGROUND: Congenital heart disease (CHD) is a leading cause of birth defect-related mortality. However, more recent CHD mortality data for China are lacking. Additionally, limited studies have evaluated sex, rural-urban, and region-specific disparities of CHD mortality in China. METHODS: We designed a population-based study using data from the Dataset of National Mortality Surveillance in China between 2008 and 2021. We calculated age-adjusted CHD mortality using the sixth census data of China in 2010 as the standard population. We assessed the temporal trends in CHD mortality by age, sex, area, and region from 2008 to 2021 using the joinpoint regression model. RESULTS: From 2008 to 2021, 33,534 deaths were attributed to CHD. The period witnessed a two-fold decrease in the age-adjusted CHD mortality from 1.61 to 0.76 per 100,000 persons (average annual percent change [AAPC] = -5.90%). Females tended to have lower age-adjusted CHD mortality than males, but with a similar decline rate from 2008 to 2021 (females: AAPC = -6.15%; males: AAPC = -5.84%). Similar AAPC values were observed among people living in urban (AAPC = -6.64%) and rural (AAPC = -6.12%) areas. Eastern regions experienced a more pronounced decrease in the age-adjusted CHD mortality (AAPC = -7.86%) than central (AAPC = -5.83%) and western regions (AAPC = -3.71%) between 2008 and 2021. Approximately half of the deaths (46.19%) due to CHD occurred during infancy. The CHD mortality rates in 2021 were lower than those in 2008 for people aged 0-39 years, with the largest decrease observed among children aged 1-4 years (AAPC = -8.26%), followed by infants (AAPC = -7.01%). CONCLUSIONS CHD mortality in China has dramatically decreased from 2008 to 2021. The slower decrease in CHD mortality in the central and western regions than in the eastern regions suggested that public health policymakers should pay more attention to health resources and health education for central and western regions.
Humans ; Heart Defects, Congenital/mortality* ; Male ; Female ; China/epidemiology* ; Infant ; Child, Preschool ; Adult ; Child ; Adolescent ; Infant, Newborn ; Middle Aged ; Young Adult ; Aged ; Rural Population

OBJECTIVE: To establish a similarity measurement model for patients with dentofacial deformity based on 3D craniofacial features and to validate the similarity results with quantifying subjective expert scoring. METHODS: In the study, 52 cases of patients with skeletal Class Ⅲ malocclusions who underwent bimaxillary surgery and preoperative orthodontic treatment at Peking University School and Hospital of Stomatology from January 2020 to December 2022, including 26 males and 26 females, were selected and divided into 2 groups by sex. One patient in each group was randomly selected as a reference sample, and the others were set as test samples. Three senior surgeons rated the similarity scores between the test samples and the reference sample. Similarity scores ranged from 1 to 10, where 1 was completely different, and 10 was exactly the same. Scores larger than 7.5 was considered as clinically similar. Preoperative cone beam computed tomography (CBCT) and 3D facial images of the patients were collected. The three-dimensional hard and soft tissue features, including distances, angles and 3D point cloud features were extracted. The similarity measurement model was then established to fit with the experts' similarity scoring by feature selection algorithm and linear regression model. To verify the reliability of the model, 14 new patients were selected and input to similarity measurement model for finding similar cases. The similarity scoring of these similar cases were rated by experts, and used to evaluate the reliability of the model. RESULTS: The similarity metric models indicated that the features of the middle and lower craniofacial features were the main features to influence the craniofacial similarity. The main features that were related to the expert' s similarity scoring included distance of anterior nasal spine-menton (ANS-Me), distance of right upper canion point-Frankfurt horizontal plane (U3RH), distance of left superior point of the condyle-left gonion (CoL-GoL), distance of left gonion-menton (CoL-Me), distance of pogonion-midsagittal plane (Pog-MSP), distance of right alar base-left alar base (AlR-AlL), angle of pronasale-soft tissue pogonion-labrale inferius (Pn-Pog' -Li), distance of trichion-right tragus (Tri-TraR), distance of left exocanthion-left alar base (ExL-AlL), lower 1/3 of skeletal face, middle and lower 2/3 of skeletal face and upper lip region of soft tissue. Fourteen new patients were chosen to evaluate the model. The similar cases selected by the model had an average experts' similarity scoring of 7.627± 0.711, which was not significantly different with 7.5. CONCLUSION The similarity measurement model established by this model could find the similar cases which highly matched experts' subjective similarity scoring. The study could be further used for similar cases retrieval in skeletal Ⅲ malocclusion patients.
Humans ; Male ; Female ; Imaging, Three-Dimensional/methods* ; Cone-Beam Computed Tomography ; Malocclusion, Angle Class III/surgery* ; Orthognathic Surgical Procedures/methods* ; Face/anatomy & histology* ; Cephalometry/methods* ; Adult ; Adolescent ; Dentofacial Deformities/surgery* ; Young Adult

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)

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.

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.

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.