Evading host immunity killing is a critical step for virus survival. Inhibiting viral immune escape is crucial for the treatment of viral diseases. Serine/threonine kinase 39 (STK39) was reported to play an essential role in ion homeostasis. However, its potential role and mechanism in viral infection remain unknown. In this study, we found that viral infection promoted STK39 expression. Consequently, overexpressed STK39 inhibited the phosphorylation of interferon regulatory factor 3 (IRF3) and the production of type I interferon, which led to viral replication and immune escape. Genetic ablation or pharmacological inhibition of STK39 significantly protected mice from viral infection. Mechanistically, mass spectrometry and immunoprecipitation assays identified that STK39 interacted with PPP2R1A (a scaffold subunit of protein phosphatase 2A (PP2A)) in a kinase activity-dependent manner. This interaction inhibited DDB1 and CUL4 associated factor 1 (DCAF1)-mediated PPP2R1A degradation, maintained the stabilization and phosphatase activity of PP2A, which, in turn, suppressed the phosphorylation of IRF3, decreased the production of type I interferon, and then strengthened viral replication. Thus, our study provides a novel theoretical basis for viral immune escape, and STK39 may be a potential therapeutic target for viral infectious diseases.

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*

Ankylosing spondylitis (AS) is linked to an increased prevalence of myocardial infarction (MI). However, research dedicated to elucidating the pathogenesis of AS-MI is lacking. In this study, we explored the biomarkers for enhancing the diagnostic and therapeutic efficiency of AS-MI. Datasets were obtained from the Gene Expression Omnibus database. We employed weighted gene co-expression network analysis and machine learning models to screen hub genes. A receiver operating characteristic curve and a nomogram were designed to assess diagnostic accuracy. Gene set enrichment analysis was conducted to reveal the potential function of hub genes. Immune infiltration analysis indicated the correlation between hub genes and the immune landscape. Subsequently, we performed single-cell analysis to identify the expression and subcellular localization of hub genes. We further constructed a transcription factor (TF)-microRNA (miRNA) regulatory network. Finally, drug prediction and molecular docking were performed. S100A12 and MCEMP1 were identified as hub genes, which were correlated with immune-related biological processes. They exhibited high diagnostic value and were predominantly expressed in myeloid cells. Furthermore, 24 TFs and 9 miRNA were associated with these hub genes. Enzastaurin, meglitinide, and nifedipine were predicted as potential therapeutic agents. Our study indicates that S100A12 and MCEMP1 exhibit significant potential as biomarkers and therapeutic targets for AS-MI, offering novel insights into the underlying etiology of this condition.
Humans ; Spondylitis, Ankylosing/complications* ; Systems Biology/methods* ; Myocardial Infarction/diagnosis* ; Biomarkers/metabolism* ; MicroRNAs/genetics* ; Gene Regulatory Networks ; Gene Expression Profiling ; Machine Learning

Functional dyspepsia(FD)is a common functional gastrointestinal disease in clinical practice,which has the characteristics of high incidence,difficult to cure,and recurrence.FD belongs to the categories of"ruffian"and"stomach pain"in TCM,and the disease is located in the stomach,which is closely related to the liver and spleen,and the syndrome of liver depression and spleen deficiency is the most common.This article summarized the literature related to the TCM treatment for FD with liver depression and spleen deficiency syndrome,and concluded the clinical application,efficacy characteristics and mechanism,so as to provide reference for clinical treatment and basic research.The analysis found that the clinical efficacy of TCM in the treatment of FD is significant,which can not only improve the digestive symptoms of patients,but also improve their anxiety and depression state and daily life quality,and has the characteristics of overall regulation,syndrome differentiation and treatment,and improvement of physical fitness.Its mechanism may involve multiple pathways and levels such as abnormal gastric motility,abnormal brain-intestinal interaction and immune inflammatory response.

Objective:To explore the clinical efficacy of the splenic vessel-oriented anatomical plane priority strategy in Da Vinci robotic Kimura distal pancreatectomy.Methods:A retrospective analysis was conducted on 26 patients who underwent robotic-assisted distal pancreatectomy at Zhejiang Provincial People’s Hospital from January 2019 to September 2024. The cohort included 7 male and 19 female patients, aged (49.3±16.7) years. Surgical outcomes, including operative time, intraoperative blood loss, postoperative complications, and hospital stay, were analyzed, and surgical techniques were summarized.Results:All 26 patients successfully completed the surgery. Pathological diagnoses included 5 cases of intraductal papillary mucinous neoplasm, 5 serous cystadenomas, 1 pancreatic neuroendocrine tumor, 6 solid pseudopapillary neoplasms, 4 mucinous cystic neoplasms, and 5 neuroendocrine tumors. The maximum tumor diameter was (2.3±1.1) cm, and the operative time was (183.2±77.4) min. The spleen preservation rate was 100% (26/26). Intraoperative blood loss was 50.0 (17.5, 125) ml, and postoperative hospital stay was (10.1±3.7) d. No Clavien-Dindo grade III or higher complications occurred. The post-operative pancreatic fistula (POPF) rate was 53.8% (14/26), including 38.5% (10/26) biochemical leak and 15.3% (4/26) grade B POPF, with no grade C POPF.Conclusion:The splenic vessel-oriented anatomical plane priority strategy in robotic-assisted spleen-preserving distal pancreatectomy (Kimura technique) is safe and feasible, significantly improving the spleen preservation rate.

In the tumor microenvironment,tumor-associated macrophages construct complex interaction networks through highly plasticity,promoting the dynamic evolution of the cancer ecosystem.With the innovation of single-cell sequencing technology,the heterogeneity,functional diversity,and interaction mechanisms of tumor-associated macrophages with tumor microenvironment have been revealed.This suggests that tumor-associated macrophages may become a new target for tumor targeted therapy,driving the development of precision anti-cancer strategies.This review summarizes the relevant research progress,explores the interaction mechanisms,describes the classification and clinical therapeutic potential,aiming to provide new perspectives and guidance for tumor research and clinical practice.

Objective:To investigate the effects of dictyophora polysaccharides(DIP)on cognitive dysfunction induced by chronic alco-hol exposure in rats.Methods:Sixty male Sprague-Dawley(SD)rats were randomly divided into five groups(n=12):control group(normal saline),DIP group[DIPH,DIP administered by gavage at 300 mg/(kg·d)for 28 consecutive days],alcohol group[EtOH,60%alcohol administered by gavage at 10 mg/(kg·d)for 28 consecutive days],low-dose DIP treatment group[EtOH+DIPL,60%alcohol administered at 10 mg/(kg·d)and DIP administered at 100 mg/(kg·d)by gavage,with an interval of 6 hours between doses,for 28 consecutive days],and high-dose DIP treatment group[EtOH+DIPH,60%alcohol administered at 10 mg/(kg·d)and DIP administered at 300 mg/(kg·d)by gavage,with an interval of 6 hours between doses,for 28 consecutive days].On day 25 of gavage,water maze training was provided for the rats for 4 days.On day 29,a water maze test was performed to determine the memory and learning functions of the rats;HE staining was used to evaluate the edema and inflammation of the liver and brain tissues;presence of inflammatory cells and the expression of myelin basic protein(MBP)in brain tissue were measured using immunohistochemical staining;Western blot was used to measure the expression of 2,2-cyclic nucleotide-3-phosphodiesterase(CNP)in the hippocampal tissue;the structural integrity of the myelin sheath was evaluated using LuxoL fast blue(LFB)staining and transmission electron microscopy.Results:Compared with the control group,the EtOH group showed a significantly increased escape latency,reduced expression of MBP,and decreased density of the myelin sheath.DIP intervention significantly improved cognitive dysfunction in rats,increased the expression of MBP and CNP,and reduced myelin damage.Conclusion:At a dose of 300 mg/kg,DIP may ameliorate cognitive dysfunction induced by chronic alcohol exposure by pro-tecting the structural and functional integrity of myelin sheaths.

Objective:To observe the pathological changes of myocardial tissue under differentdegrees of coronary atherosclerotic le-sions,to measure the expression levels of proteins associated with the cyclic GMP-AMP synthase(cGAS)-stimulator of interferon genes(STING)signaling pathway in coronary arteries,and to investigate the role of cGAS-STING in the development and progression of coronary heart disease.Methods:Eligible cases of coronary heart disease and control cases were selected and divided into control group with normal coronary arteries and grade Ⅰ,Ⅱ,Ⅲ,and Ⅳ coronary artery stenosis groups.HE staining was used to observe and evaluate the pathological conditions of coronary arteries,Western blotting was used to measure the expression levels of downstream pro-teins of the cGAS-STING pathway in coronary tissue,and ELISA was used to measure the levels of inflammatory factors in coronary tis-sue.A correlation analysis was performed to investigate the correlation of the expression levels of downstream proteins of the cGAS-STING signaling pathway and related inflammatory factors with the development and progression of coronary heart disease.Results:Mi-croscopic examination showed that compared with the control group,the other four groups had varying degrees of pathological changes such as vascular wall thickening and luminal stenosis,with a gradual increase in the degree of stenosis from grade Ⅰ to grade Ⅳ coronary lesions.Compared with the control group,the grade Ⅰ,Ⅱ,Ⅲ,and Ⅳ coronary artery stenosis groups had significant increases in the expression levels of downstream proteins of the cGAS-STING signaling pathway and related inflammatory factors in coronary tis-sue,with a trend of increase from grade Ⅰ to grade Ⅳ coronary le-sions.The expression levels of downstream proteins of the cGAS-STING signaling pathway in coronary tissue were positively correlated with the development and progression of coronary heart disease(cGAS:r=0.927,P<0.001;p-Sting:r=0.889,P<0.001;p-TBK1:r=0.910,P<0.001;p-IRF3:r=0.936,P<0.001;IFN-1:r=0.936,P<0.001;TNF-α:r=0.945,P<0.001;IL-1β:r=0.962,P<0.001;IL-6:r=0.933,P<0.001).Conclusion:There are significant differences in the expression levels of downstream proteins of the cGAS-STING signaling pathway and related inflammatory factors,and this signaling pathway may be a potential target for the treatment of coronary heart disease.

Objective To systematically evaluate the performance and methodological quality of the risk prediction models for urinary incontinence after radical prostatectomy,so as to provide a reference for selecting the appropriate risk prediction tool.Methods A systematic search was conducted in PubMed,Web of Science,Cochrane Library,CINAHL,EMBASE,CNKI,Wanfang,VIP,and Chinese biomedical literature database from inception to Jan.23,2024.Two researchers independently conducted literature screening and data extraction,and the prediction model risk of bias assessment tool(PROBAST)was applied to assess the risk of bias and applicability of the included studies.MedCalc software was used to perform a meta-analysis of the area under curve(AUC)of the validation groups using the random effect model,and the publication bias and sensitivity analysis were also performed.Results A total of 8 studies were included,with a combined sample size of 7 216 cases.Six models reported the AUC values,and 7 models reported calibration.The applicability of 2 studies was acceptable,while 6 were poor.The most commonly used type of prediction model was logistic regression.After excluding models with extreme AUC values,the random-effects meta-analysis result was 0.840(95%confidence interval 0.786 to 0.895),with no heterogeneity(I2=0%,P=0.737).The bias risk was high in all 8 studies,mainly due to retrospective cohort data,transformation of continuous variables into binary variables,unaddressed missing data,selection of predictors based on univariate analysis,incomplete report of the model discrimination and calibration,and lack of external validation.Egger test result indicated no significant publication bias.Conclusion The development and validation process of the existing risk prediction models for urinary incontinence after radical prostatectomy is still imperfect.Future research should construct prediction models based on multicenter and large-sample data,strengthen the clinical applicability assessment of the models,and strictly follow the reporting standards and procedures,so as to establish high-quality risk prediction models for clinical practice.