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:To explore the clinical manifestations, pathology, and prognosis of hepatic mesenchymal hamartoma (MHL).Methods:Clinical data of 10 MHL patients treated at the First Medical Center of Chinese PLA General Hospital from December 2009 to July 2024 were retrospectively analyzed, including seven males and three females, aged (48±23) years. Patients’ age, gender, clinical manifestations, treatment methods, prognosis, and other clinical data were collected.Results:Among them, four cases presented with upper abdominal distension and pain, while the other six showed no abnormal symptoms. All patients had palpable round masses of varying sizes in the upper abdomen. Nine patients had single lesion, among which five were located in the right hepatic lobe, three in the left hepatic lobe, and one in the caudate lobe. One patient had multiple lesions located in both the left and right anterior lobe. The maximum diameter of lesions ranged from 1.5 to 20.0 cm. Seven cases presented with unilocular cystic-solid masses, and three with multilocular cystic-solid masses, with varying sizes of cystic cavities. Microscopically, the tumors exhibited myxoid stroma with spindle or stellate cells, irregular branching bile ducts, residual hepatocyte islands, and variably sized cystic spaces. Four cases with malignant transformation additionally showed undifferentiated mesenchymal cells with atypia, mitotic figures, tumor giant cells, and eosinophilic cytoplasmic inclusions. Immunohistochemistry indicated tumor tissue exhibited positive expression of hepatocyte marker Hepacyte and negative expression of alpha-fetoprotein. The proliferative bile duct epithelium showed positive expression of CK7, CK19, and CK8/18. The spindle cell area expressed vimentin and SMA, with focal expression of desmin, and a Ki67 proliferation index of 5%. In the region of MHL complicated by undifferentiated embryonal sarcoma, there was positive expression of desmin, myogenin, and myoglobin, with a Ki67 proliferation index as high as 30%, and focal expression of S-100, α1-antitrypsin, and CK. A total of seven patients were followed up. Among them, two patients with MHL accompanied by undifferentiated embryonal sarcoma formation experienced tumor recurrence and metastasis after surgery, one patient died after the operation, and the remaining four patients showed no signs of recurrence or metastasis as of the last follow-up.Conclusion:MHL is a rare benign mesenchymal tumor of the liver, which is clinically and radiologically difficult to distinguish from other hepatic tumors. Definitive diagnosis requires percutaneous biopsy or postoperative pathological examination of the tumor. Patients with non-malignant MHL who undergo surgical treatment generally have a favorable prognosis.

Schizophrenia (SZ) stands as a severe psychiatric disorder. This study applied diffusion tensor imaging (DTI) data in conjunction with graph neural networks to distinguish SZ patients from normal controls (NCs) and showcases the superior performance of a graph neural network integrating combined fractional anisotropy and fiber number brain network features, achieving an accuracy of 73.79% in distinguishing SZ patients from NCs. Beyond mere discrimination, our study delved deeper into the advantages of utilizing white matter brain network features for identifying SZ patients through interpretable model analysis and gene expression analysis. These analyses uncovered intricate interrelationships between brain imaging markers and genetic biomarkers, providing novel insights into the neuropathological basis of SZ. In summary, our findings underscore the potential of graph neural networks applied to multimodal DTI data for enhancing SZ detection through an integrated analysis of neuroimaging and genetic features.
Humans ; Schizophrenia/pathology* ; Diffusion Tensor Imaging/methods* ; Male ; Female ; Adult ; Brain/metabolism* ; Young Adult ; Middle Aged ; White Matter/pathology* ; Gene Expression ; Nerve Net/diagnostic imaging* ; Graph Neural Networks

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:To explore the clinical manifestations, pathology, and prognosis of hepatic mesenchymal hamartoma (MHL).Methods:Clinical data of 10 MHL patients treated at the First Medical Center of Chinese PLA General Hospital from December 2009 to July 2024 were retrospectively analyzed, including seven males and three females, aged (48±23) years. Patients’ age, gender, clinical manifestations, treatment methods, prognosis, and other clinical data were collected.Results:Among them, four cases presented with upper abdominal distension and pain, while the other six showed no abnormal symptoms. All patients had palpable round masses of varying sizes in the upper abdomen. Nine patients had single lesion, among which five were located in the right hepatic lobe, three in the left hepatic lobe, and one in the caudate lobe. One patient had multiple lesions located in both the left and right anterior lobe. The maximum diameter of lesions ranged from 1.5 to 20.0 cm. Seven cases presented with unilocular cystic-solid masses, and three with multilocular cystic-solid masses, with varying sizes of cystic cavities. Microscopically, the tumors exhibited myxoid stroma with spindle or stellate cells, irregular branching bile ducts, residual hepatocyte islands, and variably sized cystic spaces. Four cases with malignant transformation additionally showed undifferentiated mesenchymal cells with atypia, mitotic figures, tumor giant cells, and eosinophilic cytoplasmic inclusions. Immunohistochemistry indicated tumor tissue exhibited positive expression of hepatocyte marker Hepacyte and negative expression of alpha-fetoprotein. The proliferative bile duct epithelium showed positive expression of CK7, CK19, and CK8/18. The spindle cell area expressed vimentin and SMA, with focal expression of desmin, and a Ki67 proliferation index of 5%. In the region of MHL complicated by undifferentiated embryonal sarcoma, there was positive expression of desmin, myogenin, and myoglobin, with a Ki67 proliferation index as high as 30%, and focal expression of S-100, α1-antitrypsin, and CK. A total of seven patients were followed up. Among them, two patients with MHL accompanied by undifferentiated embryonal sarcoma formation experienced tumor recurrence and metastasis after surgery, one patient died after the operation, and the remaining four patients showed no signs of recurrence or metastasis as of the last follow-up.Conclusion:MHL is a rare benign mesenchymal tumor of the liver, which is clinically and radiologically difficult to distinguish from other hepatic tumors. Definitive diagnosis requires percutaneous biopsy or postoperative pathological examination of the tumor. Patients with non-malignant MHL who undergo surgical treatment generally have a favorable prognosis.

Objective Our previous studies established that microRNA (miR)-451 from human umbilical cord mesenchymal stem cell-derived exosomes (hUC-MSC-Exos) alleviates acute lung injury (ALI). This study aims to elucidate the mechanisms by which miR-451 in hUC-MSC-Exos reduces ALI by modulating macrophage autophagy. Methods Exosomes were isolated from hUC-MSCs. Severe burn-induced ALI rat models were treated with hUC-MSC-Exos carrying the miR-451 inhibitor. Hematoxylin-eosin staining evaluated inflammatory injury. Enzyme-linked immunosorbnent assay measured lipopolysaccharide (LPS),tumor necrosis factor-α,and interleukin-1β levels. qRT-PCR detected miR-451 and tuberous sclerosis complex 1 (TSC1) expressions. The regulatory role of miR-451 on TSC1 was determined using a dual-luciferase reporter system. Western blotting determined TSC1 and proteins related to the mammalian target of rapamycin (mTOR) pathway and autophagy. Immunofluorescence analysis was conducted to examine exosomes phagocytosis in alveolar macrophages and autophagy level. Results hUC-MSC-Exos with miR-451 inhibitor reduced burn-induced ALI and promoted macrophage autophagy. MiR-451 could be transferred from hUC-MSCs to alveolar macrophages via exosomes and directly targeted TSC1. Inhibiting miR-451 in hUC-MSC-Exos elevated TSC1 expression and inactivated the mTOR pathway in alveolar macrophages. Silencing TSC1 activated mTOR signaling and inhibited autophagy,while TSC1 knockdown reversed the autophagy from the miR-451 inhibitor-induced. Conclusion miR-451 from hUC-MSC exosomes improves ALI by suppressing alveolar macrophage autophagy through modulation of the TSC1/mTOR pathway,providing a potential therapeutic strategy for ALI.

Objective To study the application value of CAD/CAM technology in the teaching of inlay manufacturing.Methods A total of 60 undergraduates interned in the Department of Stomatology,Yan'an Hospital,Kunming Medical University were randomly divided into an experimental group(n=30)and a control group(n=30).We selected appropriate clinical cases for students to prepare for mandibular molar's proximal occlusal inlays.The instructor guided the results of the first preparation in different ways,and the students made the second modification and preparation,and the assessment team scored and evaluated the five aspects of the final preparation,the shape of the preparation,the shape of the occlusal surface,the dovetail retention,and the adjacent surface.Results The scores of all detection indexes in the experimental group were higher than those in the control group(P<0.05).Conclusion The application of CAD/CAM technology in inlay manufacturing teaching can effectively improve students'clinical hands-on ability and achieve better teaching effects than traditional teaching methods.

Objective:To evaluate the effect of sevoflurane on Ca 2+ transporter expression in cardiomyocytes during right ventricular remodeling in rats with pulmonary arterial hypertension. Methods:Twenty-four clean-grade healthy male Sprague-Dawley rats, aged 8-10 weeks, weighing 200-250 g, were divided into 4 groups ( n=6 each) by the random number table method: control group (CM group), sevoflurane group (CS group), monocrotaline group (M group) and sevoflurane + monocrotaline group (S group). Monocrotaline 60 mg/kg was intraperitoneally injected in group M and group S, and monocrotaline lysate was intraperitoneally injected in group CM. The rats in S and CS groups inhaled 2.5% sevoflurane for 1 h, twice a week, at an interval of 3 days starting from the first day after injection of monocrotaline. Pulmonary artery acceleration time and pulmonary artery ejection time were measured by transthoracic echocardiography at 6 weeks after monocrotaline injection. The chest was exposed under 3% sevoflurane anesthesia, the heart was perfused, and the pulmonary artery branch and right ventricular myocardial tissues were retained. The wall thickness of pulmonary arterioles and cross-section area of right ventricular cardiomyocytes were observed by HE staining. The expression of Ca 2+ transporter in right ventricular cardiomyocytes was detected by Western blot. Results:Compared with CM group, the ratio of pulmonary artery acceleration time to pulmonary artery ejection time was significantly decreased, the cross-section area of right ventricular cardiomyocytes was increased, the wall thickness of pulmonary arteriole was increased, the expression of type 1 sodium-calcium exchange and inositol triphosphate receptor was up-regulated, and the expression of voltage-dependent L-type calcium channel α1C subunit, type 2 ryanodine receptor, sarcoplasmic reticulum calcium pump 2α and proteinphilin-2 was down-regulated in M group ( P<0.01). Compared with group M, the ratio of pulmonary artery acceleration time to pulmonary artery ejection time was significantly increased, the cross-section area of right ventricular cardiomyocytes was decreased, the wall thickness of pulmonary arteriole was decreased, the expression of type 1 sodium-calcium exchange and inositol triphosphate receptor was down-regulated, and the expression of voltage-dependent L-type calcium channel α1C subunit, type 2 ryanodine receptor, sarcoplasmic reticulum calcium pump 2α and proteinphilin-2 was up-regulated in group S ( P<0.01). Conclusions:The mechanism by which sevoflurane improves right ventricular remodeling is related to regulating the expression of Ca 2+ transporter in cardiomyocytes of rats with pulmonary arterial hypertension.

Diabetic gastroparesis （DGP） is a common diabetic neuropathy that affects the normal function of gastric motility and emptying. Clinically， it often manifests as abdominal distension， nausea and vomiting， early satiety， dyspepsia， etc. The pathogenesis of DGP is multifactorial， closely related to many factors， such as chronic hyperglycemia， neuropathy， autonomic nervous system disorders， inflammation， and oxidative stress. These factors can interact with each other， leading to delayed gastric emptying and the occurrence of related symptoms. Traditional Chinese medicine （TCM） has significant advantages in the prevention and treatment of DGP， including a long history， remarkable efficacy， individualized treatment， diverse therapeutic formulations， and improvement in the quality of life. Additionally， TCM is known for its low adverse reactions， good tolerance， and multi-targeted effects， making it an important approach in the management of DGP. Previous research has found that the main mechanisms of Chinese medicine in the prevention and treatment of DGP include the regulation of gastrointestinal hormones， inhibition of inflammatory responses， reduction of oxidative stress， enhancement of interstitial cells of Cajal activity， inhibition of pyroptosis， and modulation of related signaling pathways such as stem cell factor （SCF）/cellular growth factor receptor （c-Kit）， adenosine monophosphate-activated protein kinase （AMPK）， Ras homologous genome member A （RhoA）/Rho-associated coiled-coil forming kinase （ROCK）. This article primarily summarized the research progress on Chinese medicine in preventing and treating DGP through the inhibition of inflammatory responses， reduction of oxidative stress， enhancement of interstitial cells of Cajal activity， inhibition of pyroptosis， and regulation of related signaling pathways， aiming to provide a reference and basis for further research on the application value of Chinese medicine in the prevention and treatment of DGP.