Objective: To define the mechanism by which swine TRIM25 restricts vesicular stomatitis virus replication. Methods: Porcine 3D4/21 cells with TRIM25 overexpression or knockdown were infected with vesicular stomatitis virus. Viral replication was quantified by immunoblotting, quantitative reverse transcription polymerase chain reaction, and 50% tissue culture infectious dose assays. Type I interferon signaling was assessed by transcript quantification, interferon-beta and interferon-stimulated response element reporter assays, and co-immunoprecipitation.Viral RNA binding was tested by RNA immunoprecipitation. Results: TRIM25 overexpression reduced viral RNA and infectious titers, whereas TRIM25 knockdown increased replication (p < 0.01). TRIM25 increased interferon-beta and interferon-stimulated gene expression and enhanced interferon-beta and interferonstimulated response element promoter activity (p < 0.01). Mechanistically, TRIM25 promoted Lys63-linked ubiquitination of RIG-I and increased phosphorylation of TANK-binding kinase 1 and interferon regulatory factor 3. TRIM25 also bound vesicular stomatitis virus genomic RNA, and binding required the C-terminal region. Conclusions and Relevance: Porcine TRIM25 restricts vesicular stomatitis virus replication by amplifying type I interferon signaling and directly binding viral RNA.

Background/Aims: Liver transplantation (LT) following total hepatectomy is a life-saving treatment for hepatocellular carcinoma (HCC). The HCC recurrence after LT hinders the effectiveness of the procedure. The objective of this study is to develop a pre-operative risk stratification model based on a liquid biopsy. Methods: We conducted a comprehensive multi-omics study of 260 HCC patients from three centers, including clinical data, low-coverage whole-genome sequencing of cell-free DNA (cfDNA) from plasma, as well as whole-exome, single-nucleus RNA, and spatial transcriptomics from matched tumor and non-tumor tissues. Results: We identified cfDNA-derived copy number alteration (CNA) signatures associated with post-transplant recurrence. By integrating cfDNA-derived CNA profiles with single-cell transcriptomic data, we traced recurrence-associated cfDNA to a distinct subpopulation of malignant cells within the primary tumor. These cells were embedded in a pro-metastatic microenvironment of specialized endothelial subtypes and cancer-associated fibroblasts. Notably, most recurrence-associated lesions were detectable in cfDNA prior to liver transplantation (LT). Building on these insights, we developed the ZJU Criteria based on CNA fragments and tumor markers, a pre-LT risk prediction tool that integrates conventional clinical factors with cfDNA-derived CNA signatures, and validated it using internal and independent external cohorts. Conclusion Our findings suggest that post-transplant recurrence commonly originates from advanced subclones that emerge late during tumor evolution. The ZJU Criteria provides an accurate, non-invasive strategy that significantly improves pre-LT risk stratification and clinical decision-making for patients with HCC.

Radiation-induced lung injury is a prevalent side effect of radiotherapy for chest cancer. The "three phases and three methods "is an innovative theory based on the evolution of the core pathogenesis of radiation-induced lung injury. Its formation also considers the understanding of radiation-induced lung injury by ancient and modern medical practitioners, pathological characteristics, clinical manifestations, and the development patterns of radiation-induced lung injury. The "three phases and three methods" refers to the three phases of the course and the three treatment methods. The core pathogenesis of radiation-induced lung injury from the beginning, middle and late stages is heat toxicity, yin deficiency, and blood stasis. Therefore, the course of radiation-induced lung injury is divided into three phases: blazing heat toxin, yin deficiency and heat accumulation, and static blood obstruction. The method of clearing the lung and resolving toxins, enriching yin and venting heat, invigorating blood and dissolving stasis are used respectively. Traditional Chinese medicines commonly used in each phase include Flos Lonicerae, Atrina Glass, heartleaf houttuynia herb, Radix Ophiopogonis, American Ginseng, Forsythiae Fructus, Radix Salviae Miltiorrhizae, Rhizoma Ligustici chuanxiong, Scorpio, etc. This article presents the theoretical origins of the "three phases and three methods" concept by reviewing of ancient literature, inheriting experience, and summarizing disease pathogenesis, as well as elaborating on the academic connotations of the "three phases and three methods". The scientific validity of the "three phases and three methods" is verified by literature, clinical, and basic research. The "three phases and three methods" interprets the core characteristics of each stage of radiation-induced lung injury, improves the traditional Chinese medicine prevention and treatment system for radiation-induced lung injury, and provides theoretical basis for achieving complete process management.

Under the current situation of "low prevalence and low infection" of schistosomiasis in China, and to provide a basis for achieving the goal of eliminating schistosomiasis by 2030 proposed by the Healthy China Action (2019 - 2030) as scheduled, the Hunan Provincial Corps Hospital of the Chinese People's Armed Police Force established a schistosomiasis monitoring and early warning index system based on the previous studies on schistosomiasis early warning index system and the recent literature analysis, combined with the current potential risk factors affecting the transmission and prevalence of schistosomiasis, and organized two rounds of expert consultation and carried out project promotion meetings. The experts reached a consensus on the comprehensiveness and practicability of the index system, aiming to lay a solid foundation for construction of China's schistosomiasis prevention and control early warning system.

Objective To investigate the inhibitory effect of running combined with chitosan on high-fat diet(HFD)induced obesity in rats through the expression of fatty acid transporter 4(FATP4)and Toll like receptor 4(TLR4)and its mechanism.Methods 50 male Wistar rats were randomly divided into normal control(NC)group,HFD group,chitosan(Chi)group,running exercise(Run)and chitosan+running exercise(Chi+Run)group,with 10 rats in each group.The levels of serum total cholesterol(TC),triglyceride(TG),high-density lipoprotein cholesterol(HDL-C),low-density lipoprotein cholesterol(LDL-C),very low density lipoprotein cholesterol(VLDL-C),alanine aminotransferase(ALT)and aspartate aminotransferase(AST)were detected.ELISA was used to detect serum TNF-α,IL-6,APN,Ghrelin,Leptin(LP),and Ins levels.Western blot was used to test the expression of FATP4 and TLR4 proteins in liver and adipose tissue,and HE staining was used to evaluate liver and adipose tissue pathology.Results Compared with the HFD group,the Chi,Run,and Chi+Run groups showed an increase in HDL-C,serum APN,and Ghrelin(P<0.05),as well as an decreased in body weight,fat mass,obesity index,TC,TG,LDL-C,VLDL-C,ALT,AST,TNF-α,IL-6,LP,Ins,FATP4 protein expression,TLR4 protein expression,adipocyte size and quantity in liver and adipose tissue(P<0.05).The HDL-C was higher in Chi+Run group than in Chi and Run groups(P<0.05),and the final weight,LDL-C,TG,AST,IL-6,the expression of FATP4 protein,TLR4 protein,and adipocyte size in the liver and adipose tissue were lower in Chi+Run group than in Chi and Run groups(P<0.05).Conclusions The inhibitory effect of running combined with Chi on HFD induced obesity was superior to that of running or Chi alone,and its mechanism may be related to the downregulation of FATP4 and TLR4.

BACKGROUND:The abnormal aggregation of proteins and the loss of neurons are typical pathological changes observed in neurodegenerative diseases.Changes in the levels of O-linked N-acetylglucosamine glycosylation are closely related to relevant pathological changes and are promising potential therapeutic targets.OBJECTIVE:To review the role of O-linked N-acetylglucosamine glycosylation in neurodegenerative diseases and the current advancements in its clinical applications,aiming to provide new insights for the treatment of neurodegenerative disorders.METHODS:The first author conducted a literature search in the CNKI,VIP,WanFang Database,ChiCTR,Web of Science,PubMed,Cochrane Library,Clinical Trials and Alzforum,using the search terms"O-GIcNAcylation,Neurodegenerative diseases,Alzheimer's disease,Parkinson's disease,Amyotrophic lateral sclerosis,Huntington's disease,OGA inhibitors,Clinical trial"in Chinese and English.A total of 66 relevant articles were included for review.RESULTS AND CONCLUSION:O-linked N-acetylglucosamine glycosylation is involved in the development and functional regulation of neurons,and its levels gradually decrease as neuronal development matures.In neurodegenerative diseases,the pathological proteins involved are regulated by O-linked N-acetylglucosamine glycosylation.Most evidence suggests that using O-GIcNAcase inhibitors to enhance O-linked N-acetylglucosamine glycosylation levels can significantly alleviate related pathological changes,making it a potential therapeutic strategy for neurodegenerative diseases.Some O-GIcNAcase inhibitors have completed Phase I clinical trials,demonstrating good safety and tolerability.

Objective To investigate the inhibitory effect of running combined with chitosan on high-fat diet(HFD)induced obesity in rats through the expression of fatty acid transporter 4(FATP4)and Toll like receptor 4(TLR4)and its mechanism.Methods 50 male Wistar rats were randomly divided into normal control(NC)group,HFD group,chitosan(Chi)group,running exercise(Run)and chitosan+running exercise(Chi+Run)group,with 10 rats in each group.The levels of serum total cholesterol(TC),triglyceride(TG),high-density lipoprotein cholesterol(HDL-C),low-density lipoprotein cholesterol(LDL-C),very low density lipoprotein cholesterol(VLDL-C),alanine aminotransferase(ALT)and aspartate aminotransferase(AST)were detected.ELISA was used to detect serum TNF-α,IL-6,APN,Ghrelin,Leptin(LP),and Ins levels.Western blot was used to test the expression of FATP4 and TLR4 proteins in liver and adipose tissue,and HE staining was used to evaluate liver and adipose tissue pathology.Results Compared with the HFD group,the Chi,Run,and Chi+Run groups showed an increase in HDL-C,serum APN,and Ghrelin(P<0.05),as well as an decreased in body weight,fat mass,obesity index,TC,TG,LDL-C,VLDL-C,ALT,AST,TNF-α,IL-6,LP,Ins,FATP4 protein expression,TLR4 protein expression,adipocyte size and quantity in liver and adipose tissue(P<0.05).The HDL-C was higher in Chi+Run group than in Chi and Run groups(P<0.05),and the final weight,LDL-C,TG,AST,IL-6,the expression of FATP4 protein,TLR4 protein,and adipocyte size in the liver and adipose tissue were lower in Chi+Run group than in Chi and Run groups(P<0.05).Conclusions The inhibitory effect of running combined with Chi on HFD induced obesity was superior to that of running or Chi alone,and its mechanism may be related to the downregulation of FATP4 and TLR4.

Objective To construt and validate a risk prediction model for hepatocellular carcinoma(HCC)in patients with chronic liver disease based on age-male-ALBI-platelets(aMAP)score combined with RAR and PIV.Methods A total of 143 patients with chronic liver disease were divided into the HCC group(32 cases)and the non-HCC group(111 cases)according to whether HCC occurred.General clinical data,aMAP score and peripheral blood indicator level were compared between two groups.Multivariate Logistic regression was used to analyze influencing factors of HCC in inpatients with chronic liver disease.A nomogram risk prediction model was constructed and validated.Results Compared with the non-HCC group,there were higher age,higher proportion of males,higher levels of total bilirubin(TBIL),red blood cell distribution width(RDW),neutrophil count(NEU)and monocyte count(MON),lower levels of albumin(ALB)and lymphocyte count(LYM),higher levels of aMAP score,RDW to ALB(RAR)and pan-immune inflammation value(PIV)in the HCC group(P＜0.05).Multivariate Logistic regression showed that higher levels of aMAP score,RAR and PIV were independent risk factors for HCC in inpatients with chronic liver disease(P＜0.05).The area under receiver operator characteristic(ROC)curve(AUC)of the nomogram risk prediction model constructed based on above factors was 0.823(95%CI:0.747-0.899).The calibration curve showed that the predicted value was basically consistent with the actual observed value,and the Brier score was 0.125.The decision curve showed that the model had a clear positive net benefit.The AUC of internal validation of the prediction model by Bootstrap method was 0.823(95%CI:0.820-0.825),indicating that the model had a good degree of differentiation.Conclusion The nomogram risk prediction model based on aMAP score,RAR and PIV showed a good predictive performance of HCC in patients with chronic liver disease,which could benefits the individualized treatment and follow-up.

Objective To investigate the mechanisms by which miR-23 regulates the PI3K/AKT/mTOR signaling pathway to influence myocardial remodeling,fibrosis,and angiogenesis in hypertensive heart failure(HF)rats.Methods Forty rats were randomly divided into four groups(n=10 per group):a control group,a model group,an antagomir-NC group,and an antagomir-23 group.The HF model was established using a high-salt diet,and intervention was performed via tail vein injection of antagomir-23.Cardiac function parameters,the degree of myocardial fibrosis,cell apoptosis levels,and the expression of angiogenesis-related proteins including CD31,VEGF,and bFGF were measured in each group.Concurrently,the activity of the PI3K/AKT/mTOR signaling pathway was assessed.A dual-luciferase reporter assay was conducted to confirm that miR-23 targets PI3K.Results Inhibition of miR-23 significantly improved cardiac function in hypertensive HF rats,reduced myocardial fibrosis and apoptosis,and enhanced the expression of CD31,VEGF,bFGF,and activated the PI3K/AKT/mTOR signaling pathway in hypertensive HF rats(all P<0.05).The dual-luciferase assay confirmed that miR-23 negatively regulates PI3K expression.Conclusion Inhibition of miR-23 can activate the PI3K/AKT/mTOR signaling pathway,promote angiogenesis,reduce myocardial damage,thereby delaying the progression of hypertensive heart failure.

Cemental tear is a rare and indetectable condition unless obvious clinical signs present with the involvement of surrounding periodontal and periapical tissues. Due to its clinical manifestations similar to common dental issues, such as vertical root fracture, primary endodontic diseases, and periodontal diseases, as well as the low awareness of cemental tear for clinicians, misdiagnosis often occurs. The critical principle for cemental tear treatment is to remove torn fragments, and overlooking fragments leads to futile therapy, which could deteriorate the conditions of the affected teeth. Therefore, accurate diagnosis and subsequent appropriate interventions are vital for managing cemental tear. Novel diagnostic tools, including cone-beam computed tomography (CBCT), microscopes, and enamel matrix derivatives, have improved early detection and management, enhancing tooth retention. The implementation of standardized diagnostic criteria and treatment protocols, combined with improved clinical awareness among dental professionals, serves to mitigate risks of diagnostic errors and suboptimal therapeutic interventions. This expert consensus reviewed the epidemiology, pathogenesis, potential predisposing factors, clinical manifestations, diagnosis, differential diagnosis, treatment, and prognosis of cemental tear, aiming to provide a clinical guideline and facilitate clinicians to have a better understanding of cemental tear.
Humans ; Dental Cementum/injuries* ; Consensus ; Diagnosis, Differential ; Cone-Beam Computed Tomography ; Tooth Fractures/therapy*