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.

Objective:We aimed to develop a novel visualized model based on nomogram to predict postoperative overall survival.Methods:This was a multicenter, retrospective, observational cohort study, including participants with histologically confirmed gastric and colorectal cancer who underwent radical surgery from 11 medical centers in China from August 1, 2015 to June 30, 2018. Baseline characteristics, histopathological data and nutritional status, as assessed using Nutrition Risk Screening 2002 (NRS 2002) score and the scored Patient-Generated Subjective Global Assessment, were collected. The least absolute shrinkage and selection operator regression and Cox regression were used to identify variables to be included in the predictive model. Internal and external validations were performed.Results:There were 681 and 127 patients in the training and validation cohorts, respectively. A total of 188 deaths were observed over a median follow-up period of 59 (range: 58 to 60) months. Two independent predictors of NRS 2002 and Tumor-Node-Metastasis (TNM) stage were identified and incorporated into the prediction nomogram model together with the factor of age. The model's concordance index for 1-, 3- and 5-year overall survival was 0.696, 0.724, and 0.738 in the training cohort and 0.801, 0.812, and 0.793 in the validation cohort, respectively.Conclusions:In this study, a new nomogram prediction model based on NRS 2002 score was developed and validated for predicting the overall postoperative survival of patients with gastric colorectal cancer. This model has good differentiation, calibration and clinical practicability in predicting the long-term survival rate of patients with gastrointestinal cancer after radical surgery.

Objective:To assess the predictive value of dosiomics in predicting the occurrence of bone marrow suppression (BMS) in patients with pelvic tumors during radiotherapy.Methods:A retrospective analysis was conducted on the clinical data and radiotherapy planning documents of 129 patients with pelvic region tumors who underwent radiotherapy at the First Affiliated Hospital of Nanjing Medical University from January 2019 to January 2023. The region of interest (ROI) was outlined for bone marrow in the pelvic region by Accu Contour software in planning CT, and the ROI was exported together with the dose distribution file. According to a stratified randomization grouping method, the patients were divided into the training set and test set in an 8 vs. 2 ratio. The dosiomic features were extracted from the ROI, and the two independent samples t-test and the least absolute shrinkage and selection operator (LASSO) algorithm was employed to identify the best predictive characteristics. Subsequently, the dosiomic scores were calculated. Clinical predictors were identified through both univariant and multivariate logistic regression analyses. Predictive models were constructed by using clinical predictors alone and combining clinical predictors and dosiomic scores. The efficacy of predictive model was assessed by plotting the receiver operating characteristic (ROC) curve and evaluating its performance through the area under the ROC curve (AUC), the calibration curve, and decision curve analysis (DCA). Results:Fourteen dosiomic features that showed a strong correlation with the occurrence of BMS were screened and utilized to calculate the dosiomic scores. Based on both univariant and multivariate logistic regression analyses, chemotherapy, planning target volume (PTV) and V 5 Gy were identified as clinical predictors. According to the combined model, the AUC values for the training set and test set were 0.911 and 0.868, surpassing those of the clinical model (AUC=0.878 and 0.824). Furthermore, the analysis of both the calibration curve and DCA suggested that the combined model had higher calibration and net clinical benefit. Conclusion:The combined model has a high diagnostic value for predicting BMS in patients with pelvic tumors during radiotherapy.

Portopulmonary hypertension(PoPH)represents one of complications occurred in patients with portal hypertension,which is characterized by high mortality rate and poor prognosis.The pathogenesis of PoPH remains unclear;it is believed to involve a complex interplay of factors including hyperdynamic circulation,imbalance of vasoactive substances,genetic factors and inflammatory responses.Up to the present,there is no specific treatment or medication for PoPH.However,medications such as endothelin receptor antagonists,prostacyclins and their ana-logues,phosphodiesterase-5 inhibitors and guanylate cyclase stimulants have been applied in the treatment of PoPH patients.The efficacy and safety of these treatment approaches still require further validation through large-scale,multicentered and randomized controlled trials.Liver transplantation may benefit a sub-group of patients but need a comprehensive assessment of individual cases.This article reviews the diagnosis,epidemiology,pathophysiology and current therapeutic performance of PoPH to further understand the pathogenesis of the disease and to improve diagnosis and treatment.Future research should focus on the development of new therapeutic drugs and evaluation of long-term effects of existing treatment methods,thereby providing more effective and safer treatment options to patients with PoPH.

The latest epidemiological data suggests that the situation of adult diabetes in China is severe, and metabolic diseases have become significant chronic illnesses that have a serious impact on public health and social development. After more than six years of practice, the National Metabolic Management Center(MMC) has developed distinctive approaches to manage metabolic patients and has achieved a series of positive outcomes, continuously advancing the standardized diagnosis and treatment model. In order to further improve the efficiency, based on the first edition, the second edition guideline was composed by incorporating experience of the past six years in conjunction with the latest international and domestic guidelines.

Objective:To understand the epidemiological characteristics of mpox epidemic in Guangzhou and provide scientific evidence for the prevention and control of the disease.Methods:Based on the mpox surveillance system in Guangzhou, suspected mpox cases with fever and rash were reported by local hospitals at all levels to centers for disease control and prevention in Guangzhou for sampling, investigation and diagnosis. Descriptive epidemiological analysis was conducted on the clinical characteristics and treatment of the mpox cases and positive detection rate reported in Guangzhou as of 24:00 on June 23. Whole genome sequencing of the virus isolates was performed using Illumina Miniseq high-throughput sequencing platform.Results:The first mpox case in Guangzhou was reported on June 10 in 2023. As of 24:00 on June 23, a total of 25 confirmed mpox cases were reported. All the mpox cases were men with a M( Q1, Q3) of 32 (26, 36) years, the majority of the cases were MSM (96.0%). The main clinical features were rash (100.0%, 25/25), lymphadenectasis (100.0%, 25/25) and fever (52.0%, 13/25). Rash usually occurred near the genitals (88.0%, 22/25). The close contacts, mainly family members (40.4%, 23/57), showed no similar symptoms, such as fever or rash. The positive rate of mpox virus in household environment samples was 30.5%. The analyses on 3 complete gene sequences of mpox virus indicated that the strains belonged to West African type Ⅱb clade, B.1.3 lineage. Conclusions:Hidden transmission of mpox virus had occurred in MSM in Guangzhou. However, the size of affected population is relatively limited, and the possibility of wide spread of the virus is low.

Objective:To investigate the efficacy and safety of prolonged dual antiplatelet therapy (DAPT) (aspirin + clopidogrel) after coronary artery bypass grafting (CABG) for more than 12 months.Methods:1 900 patients who received CABG treatment in Tianjin Chest Hospital from January 2019 to October 2020 were continuously included, and 1 528 patients were finally identified according to the inclusion and exclusion criteria. According to whether the patients continued to take DAPT treatment 12 months after discharge, they were divided into the extended DAPT group and the standard DAPT group. Cox multivariate regression and propensity score matching (PSM) analysis were performed on major cardiovascular and cerebrovascular adverse events (MACCE) and clinically related bleeding events in the two groups during 12-24 months after discharge to evaluate the efficacy and safety of extended DAPT treatment for more than 12 months. Results:Of the 1 528 patients, 624 (40.8%) continued to take DAPT 12 months after discharge. Compared with patients receiving standard DAPT, patients receiving extended DAPT had a lower incidence of MACCE within 12 to 24 months ( HR=0.597, 95% CI: 0.399-0.892, P=0.012); ( HR=0.519, 95% CI: 0.338-0.798, P=0.003), and there was no significant increase in clinically relevant bleeding risk ( HR=1.209, 95% CI: 0.522-2.798, P=0.658), ( HR=1.112, 95% CI: 0.452-2.737, P=0.817). At the same time, prolonged DAPT treatment also brought a good net benefit. Conclusion:Prolonged DAPT treatment after CABG for more than 12 months significantly reduced the risk of ischemia at 12-24 months after surgery, and did not significantly increase the risk of bleeding at 12-24 months after surgery. It may be beneficial for patients treated with CABG to continue DAPT (aspirin+ clopidogrel) on the basis of intensive DAPT therapy for 1 year.

Objective:To investigate the protective effect of liriodendrin on acute myocardial infarction in rats and to explore the related mechanisms.Methods:From January to December 2019, 30 SPF male Wistar rats with a body weight of(200±10)g were randomly divided into a sham operation group, a control group, and a liriodendringroupwith 10 rats in each group using the numerical sampling method.The liriodendron group was intragastrically administered with a liriodendrinsolution(10 ml/kg)once a day from 5 days before myocardial infarction model construction to 3 days after surgery.The control group and the sham surgery group were intragastrically administered with 10 ml/kg normal saline.After surgery, high-sensitivity troponin T levels were measured in the three groups.Cardiac function of the rats was assessed using echocardiography on the 3rd day post-surgery.Then, the rats were sacrificed, followed by hematoxylin-eosin(HE)staining and TdT-mediated dUTP nick-end labeling(TUNEL)staining of cardiac tissues and measurement of interleukin(IL)-1β and tumor necrosis factor(TNF-α)levels.Western blot and real-time polymerase chain reaction(PCR)were used to detect the expression of apoptosis-related proteins and transcriptional activity.Results:High-sensitivity troponin T levels in the liriodendrin group[(1.74±0.63)μg/L]were lower than in the myocardial infarction group[(3.54±1.60)μg/L]at 2 hours after surgery( t=2.69, P<0.05). Echocardiography showed that, compared with the myocardial infarction group, the ejection fraction was higher in the liriodendrin group, and the left ventricular end-diastolic diameter, left ventricular end-systolic diameter, left ventricular end-diastolic volume and left ventricular end-systolic volume were lower in the liriodendrin group( P<0.05). Histological staining showed that the myocardial tissue of the control group was severely damaged, with infiltration of a large number of in flammatory cells.The number of TUNEL-positive cells in the liriodendrin group(56.66±2.414)was statistically significantly reduced, compared with in the myocardial infarction group(76.55±1.843)( t=6.55, P<0.05). The levels of IL-1β and TNF-α in the myocardial infarction group were higher than those in the liriodendrin group( P<0.05). The expression of apoptosis-related proteins in the liriodendrin group was lower( P<0.05)and the transcriptional activity of mRNA was also lower( P<0.05)than in the myocardial infarction group. Conclusions:Liriodendrin may protect cardiomyocytes after myocardial infarction in rats by inhibiting local inflammation and cell apoptosis.