BackgroundThe violent aggressive behaviors of patients with schizophrenia usually have the characteristics of suddenness， unpredictability， high severity， and great difficulty in prevention. Early identification and accurate assessment of their risk of violent aggression have significant clinical significance. ObjectiveTo construct a predictive model for the violence risk in hospitalized patients with schizophrenia， to identify the key factors influencing the occurrence of violent behavior in these patients， so as to provide references for clinical precise quantitative assessment and early intervention. MethodsA total of 200 patients with schizophrenia who were hospitalized at Taiyuan Psychiatric Hospital from March 2022 to September 2024 and met the diagnostic criteria of the International Classification of Diseases， eleventh edition （ICD-11） were collected to form the modeling cohort. They were randomly divided into a training set （n=140） and a test set （n=60） at a ratio of 7∶3. Based on the least absolute shrinkage and selection operator （LASSO） regression algorithm， the feature variables were screened and dimension-reduced. The support vector machine （SVM） from machine learning was selected for model training and prediction. The discrimination efficacy of the model was evaluated by the area under the receiver operating characteristic （ROC） curve （AUC）， accuracy， precision， sensitivity， specificity， F1 value， and Brier value. ResultsLASSO regression screening identified 16 feature variables. Pearson correlation analysis revealed a positive correlation between prior violent behavior frequency and clinical psychiatric symptom scores （r=0.580， P<0.01）， a positive correlation between hospitalization compliance and current disease status （r=0.550， P=0.003）， and a positive correlation between educational level and family per capita monthly income （r=0.367， P<0.01）. The SVM model achieved an AUC of 0.853， accuracy of 0.800， precision of 0.810， sensitivity of 0.895， specificity of 0.636， F1 value of 0.850， and Brier value of 0.168. ConclusionThe SVM model has a relatively high level of applicability and overall predictive performance in the assessment of violent risk in schizophrenia patients， which is helpful for the early identification of violent risks in such patients. ［Funded by Specialized Research Project for Enhancing the Competence of Health Professionals in Taiyuan City （number， Y2023006）］

Aim Mouse model of myocardial hypertro-phy was established via intraperitoneal injection of iso-proterenol(ISO)in mice.This approach allows for an in-depth investigation into the pharmacological effects and mechanisms of action of emodin,offering novel in-sights and directions for the improvement of myocardial hypertrophy.Methods The mice were randomly di-vided into the following groups:control group(CON),emodin group(EMO),MAPK activator control group(EMO+Ani),model group(ISO),treatment group(ISO+EMO),and activator intervention group(ISO+EMO+Ani).After treatment with emodin and inter-vention with MAPK activator,the heart weight ratio and cardiac size of each group were observed.Hematoxy-lin-eosin(HE)staining was used to observe the patho-logical changes in cardiac tissue,and kits were utilized to measure the levels of GSH,LDH,and MDA in the serum.Western blot was employed to detect the protein expression levels of inflammatory and oxidative factors,as well as p-p38,p-ERK,p38,and ERK in cardiac tis-sue.Results Emodin can significantly inhibit the production of myocardial inflammatory and oxidative factors induced by ISO,thereby effectively alleviating the degree of myocardial hypertrophy and fibrosis.Af-ter the p38/ERK signaling pathway was specifically ac-tivated by farnesol,the improvement effect of emodin on myocardial hypertrophy was weakened.Further comparison revealed that,compared with the myocardi-al hypertrophy pathological model group,the pathologi-cal protein expression levels in the farnesol-treated group showed no significant difference,and were even higher in some indicators.Conclusion Emodin can effectively inhibit the release of inflammatory factors and improve the state of oxidative stress by modulating the p38/ERK signaling pathway,thereby exerting an ameliorative effect on myocardial hypertrophy.

BACKGROUND:In previous studies,the equivalent structure of three-dimensional cell reconstruction of tissue engineering oral mucosa is similar to normal oral mucosa,including epithelial-like structure,lamina propria-like structure,and vascular lumen-like structure,and has initially achieved the establishment of vascular equivalent,but its vascularization characteristics are not very clear.OBJECTIVE:Vascular-like structures of vascularized oral mucosa equivalent were obtained by targeting vascular endothelial cells specific marker expression profiles correlated with laser capture microdissection system,and their vascularization ability was evaluated to reveal their vascularization characteristics.METHODS:Human gingival epithelial cells were cultured from human gingival epithelium and human gingival fibroblasts,human gingival mesenchymal stem cells were cultured from human gingival lamina propria.Human gingival mesenchymal stem cells were induced to differentiate into vascular endothelial-like cells after monoclonal expansion culture.Human gingival epithelial cells,human gingival fibroblasts,and vascular endothelial-like cells were loaded with acellular vascular matrix-0.25%human-like collagen type Ⅰ scaffold to construct the vascularized oral mucosa equivalent.The layered structure of oral mucosa equivalent(experimental group)and the acellular vascular matrix-0.25%human-like collagen type Ⅰ scaffold(control group)were implanted subcutaneously into the back of nude mice,respectively.14 days later,the incision surface of the two groups was coated with biogel.The biogel surface of the experimental group was inoculated with human gingival epithelial cells,while the control group was not inoculated with cells.The samples were collected after 14 days of feeding.The layered structure of oral mucosa equivalent was observed by morphology.The neovascular-like structures in oral mucosa equivalents were labeled by immunohistochemistry and immunofluorescence with a more comprehensive expression profile of vascular endothelial cells,and the vascularization characteristics were analyzed.A laser capture microdissection system was used to capture the neovascularization structures in the oral mucosa equivalents specifically labeled by immunohistochemistry and analyze their vascularization characteristics.RESULTS AND CONCLUSION:(1)The morphology showed that the cell level of oral mucosa equivalent was clear,and the structure was similar to that of normal oral mucosa,that is,there were epithelioid structures,lamina-like structures,and vascular cavelike structures,and there were scattered erythrocytes in the vascular cavelike structures.(2)The results of EdU Apollo tracer seed cells in the oral mucosa equivalent group showed that human gingival epithelial cells labeled with EdU Apollo 488 showed green fluorescence expression.DAPI labeled human gingival fibroblasts showed blue fluorescence expression and formed lamina-like structures in vivo.EdU Apollo 567 labeled vascular endothelial-like cells showed red fluorescence expression and formed a vascular-like structure in vivo.(3)Vascular endothelial cell specific marker expression profile immunofluorescence labeling of vascular structure showed that compared with normal oral mucosa,the expressions of CD31,CD51,CD54,CD105,Tie-2,VWF,vascular endothelial growth factor receptor 1,and vascular endothelial growth factor receptor 2 in oral mucosa equivalents were increased(P<0.000 1).There were no significant changes in CD34 expression(P>0.05).(4)Compared with the specifically labeled oral mucosal vascular structures,the expression levels of CD51,CD54,CD105,Tie-2,VWF,vascular endothelial growth factor receptor 1,and vascular endothelial growth factor receptor 2 of the oral mucosa equivalents targeted by the laser capture microdissection system were increased(P<0.000 1).There were no significant changes in expression of CD31 and CD34(P>0.05).(5)The results showed that the oral mucosa equivalent reconstructed by three-dimensional cell stratification could achieve good vascularization,and its vascularization characteristics were consistent with the immunological function and characteristics of neovascularization.Vascularization helps three-dimensional cell layer reconstruction of oral mucosa equivalent regeneration.

This study aims to investigate the anti-inflammatory and anti-apoptotic effects of total flavonoids of hawthorn leaves(TFHL)on lipopolysaccharide(LPS)-induced inflammatory injury in rat intestinal epithelial(IEC-6)cells,as well as the underlying mechanisms.An in vitro inflam-mation model was first established by treating IEC-6 cells with lipopolysaccharide(LPS).IEC-6 cells were then incubated with three concentrations of TFHL for 24 h prior to a further 24 h LPS treatment.RT-qPCR was used to quantify mRNA levels of the inflammatory genes COX-2 and iN-OS,while Western blotting was used to assess protein levels of the apoptotic markers Bax,cleaved Caspase-3,Bcl-2,and the JNK/p-JNK signaling pathway.Finally,cells were pretreated with TFHL and/or the JNK inhibitor SP600125 for 24 h before LPS exposure for 24 h,in order to evaluate the combined effects of TFHL and SP600125 on LPS-induced inflammatory cytokine expression and apoptotic protein levels in IEC-6 cells.The results showed that,compared with the LPS group,the mRNA level of COX-2 and iNOS in the 2.5,5.0,10.0 mg/L TFHL group and the Bax and Caspase-3 protein levels decreased significantly(P＜0.01),and the Bcl-2 protein level was significantly higher(P＜0.01),p-JNK protein level and p-JNK/JNK ratio decreased significantly(P＜0.01);compared with the LPS group,the COX-2 and iNOS mRNA levels of the TFHL+LPS group de-creased significantly(P＜0.01),Bax,and Caspase-3 protein levels decreased significantly(P＜0.01),and the level of Bcl-2 protein increased significantly(P＜0.05);compared with the LPS group,the COX-2 and iNOS mRNA levels of the TFHL+SP600125 group decreased significantly(P＜0.01),Bax and Caspase-3 protein levels decreased significantly(P＜0.01),and Bcl-2 protein level increased significantly(P＜0.01).These findings indicate that TFHL exerts anti-inflammato-ry and anti-apoptotic effects in LPS-challenged IEC-6 cells by inhibiting the JNK signaling path-way.

Objective To analyze the association between lifestyle and the risk of type 2 diabetes(T2D)among adult residents.Methods The data was sourced from the Shanghai Suburban Adult Cohort and Biobank.A total of 42 096 adult residents who had not developed T2D were recruited from four districts of Shanghai(Songjiang,Jiading,Minhang,and Xuhui)between 2016 and 2019.The follow-up ended on Feb 28,2023.A structured questionnaire was used to collect information on six lifestyle-related items,including smoking,alcohol consumption,BMI,waist circumference(WC),physical activity,and diet.The unhealthy lifestyle scores(UHLS)were calculated by counting the number of all the unhealthy lifestyle items,with a range of 0-6.New-onset T2D events diagnosed by physicians were obtained through the medical information system.Cox proportional hazards regression model and restricted cubic spline model were utilized to evaluate the association between unhealthy lifestyles and the risk of T2D incidence.Results About 28.1%of the participants led 4-6 unhealthy lifestyles.A total of 1 752 new T2D cases were identified during 218 513.4 person-years of follow-up.Analysis of single unhealthy lifestyle showed that abnormal WC(HR=1.5,95%CI:1.4-1.7)and abnormal BMI(HR=1.3,95%CI:1.2-1.5)were associated with an increased risk of T2D.Compared with individuals with a UHLS of 0-1,those with a UHLS of 3 and 4-6 had 30%(95%CI:1.1-1.6)and 50%(95%CI:1.2-1.8)higher risks of T2D,respectively.Each additional unhealthy lifestyle was associated with a 10%increase in T2D incidence risk(HR=1.1,95%CI:1.1-1.2).Conclusion The risk of T2D in adult residents increases with the cumulative number of unhealthy lifestyles.Adult residents with abnormal WC or BMI,or have three or more unhealthy lifestyles accumulated,will increase the risk of new-onset T2D.

AIM To investigate the improvement effects of Poria cocos polysaccharides(PCPs)on mouse nonalcoholic fatty liver disease(NAFLD).METHODS Forty-eight C57BL/6 mice were randomly divided into the blank group,the model group,the simvastatin group(4 mg/kg)and the high,medium and low dose PCPs groups(200,100 and 50 mg/kg),with 8 mice in each group.The NAFLD model was reproduced by 16 weeks feeding of high-fat and high-cholesterol diet,followed by 8 weeks administration of corresponding drug by gavage.The mice had their body mass and liver coefficient assessed;their levels of hepatic free fatty acid(FFA),and serum total cholesterol(TC),triglyceride(TG),high density lipoprotein cholesterol(HDL-C),low density lipoprotein cholesterol(LDL-C),aspartate aminotransferase(AST),alanine aminotransferase(ALT),γ-glutamyltransferase(γ-GT)and malondialdehyde(MDA)detected;their hepatic pathological changes and lipid deposition observed using HE staining,NAFLD activity score(NAS)and oil red O staining;and their hepatic protein expressions of Akt,mTOR,p-Akt,p-mTOR and SREBP-1c detected by Western blot.RESULTS Compared with the blank group,the model group demonstrated all increased body weight,liver coefficient,hepatic FFA level,and serum TC,TG,LDL-C,AST,ALT,γ-GT,MDA,IL-1β and TNF-α.levels(P＜0.05,P＜0.01);decreased HDL-C level and activities of SOD and GSH-Px(P＜0.05,P＜0.01);more obvious hepatic pathological damage as revealed by increased NAS score(P＜0.01)and increased lipid deposition area(P＜0.01).Compared with the model group,the groups intervened with high or medium dose PCPs,or simvastatin displayed decreased body weight,liver coefficient,hepatic FFA level,and serum TC,TG,LDL-C,AST,ALT,γ-GT,MDA,IL-1β and TNF-α levels(P＜0.05,P＜0.01);increased HDL-C level and SOD,GSH-Px activities(P＜0.05,P＜0.01);decreased hepatic pathological damage as revealed by the decreased NAS score and lipid deposition area(P＜0.05,P＜0.01);and decreased hepatic protein expressions of p-Akt,p-mTOR and SREBP-1c protein(P＜0.05)as well.CONCLUSION PCPs can improve mouse NAFLD,and its mechanism may lie in their function in reversing abnormal lipid metabolism via Akt/mTOR/SREBP-1c signaling pathway.

Increasing evidence showed that histone deacetylase 6(HDAC6)dysfunction is directly associated with the onset and progression of various diseases,especially cancers,making the development of HDAC6-targeted anti-tumor agents a research hotspot.In this study,artificial intelligence(AI)technology and molecular simulation strategies were fully integrated to construct an efficient and precise drug screening pipeline,which combined Voting strategy based on compound-protein interaction(CPI)prediction models,cascade molecular docking,and molecular dynamic(MD)simulations.The biological potential of the screened compounds was further evaluated through enzymatic and cellular activity assays.Among the identified compounds,Cmpd.18 exhibited more potent HDAC6 enzyme inhibitory activity(IC50=5.41 nM)than that of tubastatin A(TubA)(IC50=15.11 nM),along with a favorable subtype selectivity profile(selectivity index ≈ 117.23 for HDAC1),which was further verified by the Western blot analysis.Additionally,Cmpd.18 induced G2/M phase arrest and promoted apoptosis in HCT-116 cells,exerting desirable antiproliferative activity(IC50=2.59 μM).Furthermore,based on long-term MD simulation trajectory,the key residues facilitating Cmpd.18's binding were identified by decomposition free energy analysis,thereby elucidating its binding mechanism.Moreover,the representative conformation analysis also indicated that Cmpd.18 could stably bind to the active pocket in an effective conformation,thus demonstrating the potential for in-depth research of the 2-(2-phenoxyethyl)pyridazin-3(2H)-one scaffold.

AIM To investigate the improvement effects of Poria cocos polysaccharides(PCPs)on mouse nonalcoholic fatty liver disease(NAFLD).METHODS Forty-eight C57BL/6 mice were randomly divided into the blank group,the model group,the simvastatin group(4 mg/kg)and the high,medium and low dose PCPs groups(200,100 and 50 mg/kg),with 8 mice in each group.The NAFLD model was reproduced by 16 weeks feeding of high-fat and high-cholesterol diet,followed by 8 weeks administration of corresponding drug by gavage.The mice had their body mass and liver coefficient assessed;their levels of hepatic free fatty acid(FFA),and serum total cholesterol(TC),triglyceride(TG),high density lipoprotein cholesterol(HDL-C),low density lipoprotein cholesterol(LDL-C),aspartate aminotransferase(AST),alanine aminotransferase(ALT),γ-glutamyltransferase(γ-GT)and malondialdehyde(MDA)detected;their hepatic pathological changes and lipid deposition observed using HE staining,NAFLD activity score(NAS)and oil red O staining;and their hepatic protein expressions of Akt,mTOR,p-Akt,p-mTOR and SREBP-1c detected by Western blot.RESULTS Compared with the blank group,the model group demonstrated all increased body weight,liver coefficient,hepatic FFA level,and serum TC,TG,LDL-C,AST,ALT,γ-GT,MDA,IL-1β and TNF-α.levels(P＜0.05,P＜0.01);decreased HDL-C level and activities of SOD and GSH-Px(P＜0.05,P＜0.01);more obvious hepatic pathological damage as revealed by increased NAS score(P＜0.01)and increased lipid deposition area(P＜0.01).Compared with the model group,the groups intervened with high or medium dose PCPs,or simvastatin displayed decreased body weight,liver coefficient,hepatic FFA level,and serum TC,TG,LDL-C,AST,ALT,γ-GT,MDA,IL-1β and TNF-α levels(P＜0.05,P＜0.01);increased HDL-C level and SOD,GSH-Px activities(P＜0.05,P＜0.01);decreased hepatic pathological damage as revealed by the decreased NAS score and lipid deposition area(P＜0.05,P＜0.01);and decreased hepatic protein expressions of p-Akt,p-mTOR and SREBP-1c protein(P＜0.05)as well.CONCLUSION PCPs can improve mouse NAFLD,and its mechanism may lie in their function in reversing abnormal lipid metabolism via Akt/mTOR/SREBP-1c signaling pathway.

OBJECTIVE To investigate and control a cluster outbreak of human adenovirus(HAdV)in the intensive care unit(ICU)of a general hospital,and to provide reference for the prevention and control of HAdV infection.METHODS From Mar.to May 2024,the bronchoalveolar lavage fluids from suspected patients in Dazu Hospital affiliated to Chongqing Medical University were tested by targeted next-generation sequencing technology(tNGS),and the field epidemiological investigation method was used for case definitions,individual case investi-gations and description of the distribution.The causes were analyzed,and corresponding prevention and con-trol measures were taken.RESULTS From Mar.to May 2024,a total of 7 patients in the ICU of a general hospi-tal met the case definition,all of which were hospital-acquired infections,with the incidence rate of 4.24％(7/165).The main clinical manifestations of the patients were persistent fever,cough and expectoration,increased heart rate,accompanied by respiratory failure and/or diarrhea.The seven patients exhibited a concentrated trend in time,space and population characteristics.The bronchoalveolar lavage fluid specimens were all detected as HAdV type 21 by tNGS testing.After taking targeted prevention and control measures based on the biological characteris-tics of adenovirus,no new adenovirus infection cases were reported until early Jun.2024.CONCLUSIONS This outbreak of HAI is caused by the non-prevalent type of HAdV21 in China.Strengthening the monitoring of adeno-virus,isolating patients and close contacts,and taking strict disinfection and appropridate protective measures can effectively control the spread and prevalence.

Objective To observe the complication incidences after percutaneous lung biopsy and sealed the tract with different sealants.Methods A total of 129 patients with solitary pulmonary nodule who underwent CT-guided percutaneous lung biopsy were retrospectively included and divided into group A(n=37),B(n=47)and C(n=45).The biopsy tract was sealed with sealant A(1 g gelatin sponge particles mixed with 10 ml 50％glucose solution)in group A,with sealant B(1 g gelatin sponge particles mixed with 10 ml normal saline)in group B,while with sealant C(1 g gelatin sponge particles mixed with the coagulant enzyme from Bothrops atrox venom and 10 ml normal saline)in group C.The incidence rate of complications such as pneumothorax and hemoptysis were comparatively observed among groups.Binary logistic regression was performed to screen the independent influencing factors associated with complications of percutaneous lung biopsy.Results No significant difference of gender,age,proportion of smoking history nor emphysema,diameter of pulmonary nodules,depth of puncture into lung parenchyma nor times of puncture was found among groups(all P＞0.05).Complications occurred in 43 cases(43/129,33.33％),i.e.27 cases in group B(27/47,57.45％),11 cases in group A(11/37,29.73％)and 5 cases in group C(5/45,11.11％),and the complication rates decreased order of group B,A and C(all P＜0.05).Compared with sealant A,sealant B was associated with increased risk(OR[95％CI]=3.190[1.183,8.598],P=0.022),whereas sealant C was associated with reduced risk(OR[95％CI]=0.266[0.079,0.889],P=0.031)of complications.Conclusion After percutaneous lung biopsy,the complication incidences decreased sequentially when the needle tract was sealed with saline B,A and C.