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.

Objective To investigate and elucidate the effect of trigonelline(TRG)on the ARPE-19 ferroptosis sig-naling pathway under hypoxia conditions.Methods ARPE-19 cells were routinely cultured and intervened with different concentrations of TRG.According to the optimal concentration(40 mg·L-1)of TRG determined for ARPE-19 interven-tion,the cells were divided into an NC group(routinely cultured for 24 h),a CoCl2 group(treated with 150 mmol·L-1 CoCl2 for 24 h),a Fer-1 group(treated at first with 1 μmol·L-1 Fer-1 for 12 h and then with 150 mumol·L-1 CoCl2 for 12 h),and a TRG group(treated at first with 40 mg·L-1 TRG for 24 h and then with 150 mmol·L-1 CoCl2 for 24 h).The levels of glutathione(GSH),malondialdehyde(MDA)and Fe2+ions in each group of cells were evaluated by detectionkits.The levels of reactive oxygen species(ROS)in each group of cells were detected by flow cytometry.Western blot was used to analyze the expression levels of hypoxia-induced factor-1α(HIF-1α),vascular endothelial growth factor(VEGF),glutathione peroxidase 4(GPX4)and acyl-CoA synthetase long-chain family member 4(ACSL4)in each group of cells.The expression levels of VEGF and ACSL4 proteins in each group of cells were measured by immunofluorescence staining.Results The ROS levels in TRG and Fer-1 groups were significantly lower than those in the CoCl2 group(t=27.91,31.61;both P＜0.01).The change trend of MDA and Fe2+levels was the same with that of ROS levels in each group.Com-pared with those in the CoCl2 group,the GSH levels were increased significantly(t=15.95,12.76;both P＜0.01)and the relative expression levels of HIF-1α and VEGF proteins were decreased significantly in Fer-1 and TRG groups(all P＜0.01).The CoCl2 group had higher ACSL4 levels and lower GPX4 levels than the NC group(t=31.05,13.18;both P＜0.01).Fer-1 and TRG groups had lower ACSL4 expression levels and higher GPX4 expression levels than the CoCl2 group(all P＜0.01).The results of immunofluorescence staining showed that the expression levels of VEGF and ACSL4 proteins in the CoCl2 group were higher than those in the NC group.The expression levels of VEGF and ACSL4 proteins in Fer-1 and TRG groups were lower than those in the CoCl2 group.Conclusion TRG protects ARPE-19 cells from hypoxia-induced oxidative stress damage by inhibiting ferroptosis.

Objective:To explore the characteristics of social skills and problem behaviors of children and adolescents with autism spectrum disorder (ASD) and attention deficit hyperactivity disorder (ADHD), as well as the association with core symptoms.Methods:A total of 409 patients aged 5-18 years old with ASD or ADHD in the outpatient department of Nanjing Brain Hospital from 2023 to 2024, and 344 children and adolescents with typical development(TD) were recruited.All participants were matched in a ratio of 1∶1∶1 (ASD∶ADHD∶TD) according to gender and age, and 97 participants were included in each group for analysis.The Chinese version of the social skills improvement system rating scales(SSIS-RS-C) was used to evaluate social skills and problem behaviors, and autistic child behavior checklist(ABC), childhood autism rating scale(CARS), the Chinese version of the social communication questionnaire(SCQ) and the Chinese version of Swanson, Nolan, and Pelham, version Ⅳ scale-parent form(SNAP-Ⅳ) were used to evaluate the core symptoms of ASD and ADHD, respectively. SPSS 26.0 software was used to perform variance, Chi-square test, Spearman correlation analysis and multivariate Logistic regression analysis.Results:The social skills score of ASD group was lower than ADHD group ((61.53±24.26) vs (80.89±15.19), P<0.05), while the problem behavior score of ASD group was higher than ADHD group ((38.82±11.92) vs (34.00±12.45), P<0.05). In ASD group, the scores of ABC, CARS and SCQ were negatively correlated with the score of social skills ( r=-0.26--0.55, P<0.05). In ADHD group, the total score and each subscale of SNAP-Ⅳ were positively correlated with the score of problem behavior ( r=0.25-0.65, P<0.05). Multivariate Logistic regression analysis showed that empathy was a negative influencing factor of ASD ( B=-0.246, OR=0.782, P<0.05), and hyperactivity/inattention was a positive influencing factor of ASD ( B=0.589, OR=1.802, P<0.01), while only hyperactivity/inattention was a positive influencing factor of ADHD( B=0.779, OR=2.180, P<0.01). Conclusion:Children and adolescents with ASD and ADHD both have defects in social skills and problem behaviors, and these defects are associated with the core characteristics of their respective diseases.

Objective To investigate and elucidate the effect of trigonelline(TRG)on the ARPE-19 ferroptosis sig-naling pathway under hypoxia conditions.Methods ARPE-19 cells were routinely cultured and intervened with different concentrations of TRG.According to the optimal concentration(40 mg·L-1)of TRG determined for ARPE-19 interven-tion,the cells were divided into an NC group(routinely cultured for 24 h),a CoCl2 group(treated with 150 mmol·L-1 CoCl2 for 24 h),a Fer-1 group(treated at first with 1 μmol·L-1 Fer-1 for 12 h and then with 150 mumol·L-1 CoCl2 for 12 h),and a TRG group(treated at first with 40 mg·L-1 TRG for 24 h and then with 150 mmol·L-1 CoCl2 for 24 h).The levels of glutathione(GSH),malondialdehyde(MDA)and Fe2+ions in each group of cells were evaluated by detectionkits.The levels of reactive oxygen species(ROS)in each group of cells were detected by flow cytometry.Western blot was used to analyze the expression levels of hypoxia-induced factor-1α(HIF-1α),vascular endothelial growth factor(VEGF),glutathione peroxidase 4(GPX4)and acyl-CoA synthetase long-chain family member 4(ACSL4)in each group of cells.The expression levels of VEGF and ACSL4 proteins in each group of cells were measured by immunofluorescence staining.Results The ROS levels in TRG and Fer-1 groups were significantly lower than those in the CoCl2 group(t=27.91,31.61;both P＜0.01).The change trend of MDA and Fe2+levels was the same with that of ROS levels in each group.Com-pared with those in the CoCl2 group,the GSH levels were increased significantly(t=15.95,12.76;both P＜0.01)and the relative expression levels of HIF-1α and VEGF proteins were decreased significantly in Fer-1 and TRG groups(all P＜0.01).The CoCl2 group had higher ACSL4 levels and lower GPX4 levels than the NC group(t=31.05,13.18;both P＜0.01).Fer-1 and TRG groups had lower ACSL4 expression levels and higher GPX4 expression levels than the CoCl2 group(all P＜0.01).The results of immunofluorescence staining showed that the expression levels of VEGF and ACSL4 proteins in the CoCl2 group were higher than those in the NC group.The expression levels of VEGF and ACSL4 proteins in Fer-1 and TRG groups were lower than those in the CoCl2 group.Conclusion TRG protects ARPE-19 cells from hypoxia-induced oxidative stress damage by inhibiting ferroptosis.

Objective:To analyze the attributable burden of active smoking on the deaths of cancer in inhabitants aged 30 years and above in Zhejiang Province.Methods:Comparative risk assessment approach in the Global Burden of Disease Study was used with the data from Zhejiang Adult Tobacco Surveillance System and Death Monitoring Surveillance System in 2020, and population attributable fraction (PAF), years of life lost (YLL), work of potential years of life lost (WPYLL) attributed to smoking on the deaths of cancer in inhabitants aged 30 years and above in Zhejiang Province were calculated with a linear regression model.Results:In 2020, there were 81 536 cancer deaths aged 30 years and above in the surveillance areas of Zhejiang Province, of which 24 518 were attributed to active smoking (PAF: 30.07%, attributable mortality rate: 55.04/100 000). The YLL was 553 078 person-years, with a standardized YLL rate of 12.40‰, and the WPYLL was 56 606 person-years. Among various cancer types, laryngeal cancer had the highest smoking-attributable PAF (44.75%), while lung cancer accounted for the most significant number of attributable deaths and life loss, with an age-standardized YLL rate of 4.65‰.Conclusions:Active smoking is a significant risk factor for cancer mortality in Zhejiang Province, with lung cancer posing the most significant disease burden. It is urgent to advance tobacco control legislation, strengthen targeted interventions, and promote early cancer screening to reduce the disease burden associated with smoking-related cancers effectively.

[Summary]Diabetic peripheral neuropathy(DPN)is one of the most common complications of diabetes.The blood nerve barrier(BNB)is a barrier structure located in peripheral nerve tissue,protecting nerve tissue from toxic substances in the blood and maintaining material exchange and information transmission between nerves and blood.Studies have shown that changes in BNB may be the initial event leading to the occurrence of DPN.After BNB is destroyed,blood-borne pathogens can directly damage peripheral nerves and cause DPN.This article will review the physiological and pathological characteristics of BNB,the relationship between BNB and DPN,and the research progress in targeting BNB for the treatment of DPN.

Objective To construct a model combining with traditional Chinese medicine(TCM)syndrome for predicting the risk of disease progression in patients with idiopathic membranous nephropathy(IMN)by machine learning methods,thus to quantitatively evaluating the value of TCM syndrome in the prediction of the risk of disease progression in IMN.Methods Monofactor analysis,recursive feature elimination(RFE)and multivariate binary Logistic regression analysis were used to screen the independent related factors affecting the risk of disease progression of IMN,and then a risk prediction model was constructed.A total of 102 patients with IMN were randomly assigned to the training set and the test set in a ratio of 65∶35,and then the comparison was conducted in the performance indicators of accuracy,sensitivity,specificity,F1 value,and area under the receiver operating characteristic(ROC)area under the curve(AUC)of the risk prediction model with or without the inclusion of the TCM syndrome information.Results Before the inclusion of TCM syndrome information,12 clinical characteristic variables for patients with MN were obtained after monofactor analysis combined with RFE screening,and they were age,hemoglobin quantification,urinary occult blood,24-hour urine protein quantification,urine protein-creatinine ratio,estimated glomerular filtration rate(eGFR),creatinine,uric acid,alanine transaminase,anti-phospholipase A2 receptor antibody(PLA2R-Ab),total cholesterol,and low-density lipoprotein cholesterd.A risk cholesterol prediction model containing the above variables was constructed.The multivariate binary Logistic regression analysis showed that the differences of the clinical variables mentioned above between the training-set group and test-set group were statistically significant,and the risk prediction model presented good sensitivity and predictability.Monofactor analysis combined with RFE screening was performed again after the inclusion of TCM syndrome information,and then 14 variables were obtained,which included blood stasis syndrome and dampness obstruction syndrome.The sensitivity and specificity of the model with the inclusion of the TCM syndrome information were significantly improved when compared with those without the inclusion of TCM syndrome information.Conclusion The results of the study initially indicate that TCM syndrome can be used as an important supplementary variable for predicting the risk of disease progression in IMN,and will provide a reference for intelligent diagnosis through the integration of traditional Chinese and western medicine information,and will supply the guidance for the treatment of IMN with TCM.

Objective With the continuous development of human-machine interaction,human movement monitoring technology and health management level,ionic conductive hydrogels with excellent elasticity and biocompatibility have been increasingly used in the fields of wearable devices and aerospace medicine.In order to solve the problems of poor mechanical properties and unstable sensing signals of traditional ion-conductive hydrogels,it is of great significance to develop hydrogel materials with excellent performance.Methods The polyacrylamide/gelatin(PAM/Gelatin)dual-network ionic conductive hydrogels were prepared by a two-step method,and a systematic study of the chemical structure,mechanical properties and strain sensing response characteristics was carried out.Results The prepared hydrogels have high transparency and good tensile properties,and exhibit high sensitivity(GF=9.40),fast response and excellent response stability in the 0-800％strain range,which can realize the real-time monitoring of complex human motion and physiological signals.Conclusion The prepared hydrogel possesses excellent mechanical and sensing properties,and has potential applications in the wearable medical monitoring,especially in human physiological signal detection in aerospace medicine.

AIM: To investigate and clarify the intervention mechanism of trigonelline(TRG)in preventing ferroptosis in ARPE-19 cells based on the Nrf2/HO-1/GPX4 pathway.METHODS: The ARPE-19 cells were cultured and subsequently treated with varying concentrations of trigonelline to ascertain the most effective concentration for modulating the cells. Then the cells were categorized into distinct groups, including normal control(NC)group, high glucose(HG)group, Fer-1 group, TRG group based on the determined concentration. Samples from each group were then gathered to assess relevant indicators. The intracellular levels of glutathione(GSH), malondialdehyde(MDA), and Ferrion were quantified in accordance with the protocols provided by the GSH, MDA, and Ferrion detection kits. Flow cytometry was employed to measure the ROS levels within each group. Additionally, Western blot analysis was conducted to examine the expression of nuclear factor erythroid 2-related factor 2(Nrf2), heme oxygenase-1(HO-1), glutathione peroxidase(GPX4), and acyl-CoA synthetase long-chain family member 4(ACSL4)across the different groups.RESULTS: The preconditioning intervention with 40 μg/mL TRG effectively mitigated the decline in cell activity induced by high glucose levels. The levels of reactive oxygen species(ROS)and MDA in the HG group were markedly elevated compared to the NC group; and the TRG group exhibited significantly reduced levels of ROS and MDA compared to those of the HG group, with the antioxidant stress index GSH showing opposite trends to those of ROS and MDA across all the groups. Whereas the Fer-1 and TRG groups showed decreased expression levels of ACSL4 protein and iron ions, and the expression levels of Nrf2, HO-1 and GPX4 in the Fer-1 and TRG groups were increased.CONCLUSION: TRG protects ARPE-19 cells from the detrimental effects of high glucose by targeting the Nrf2/HO-1/GPX4 signaling pathway to counter ferroptosis.

Objective To retrieve,evaluate and summarise the best evidence on screening and management of psychological distress in patients who had ostomy for colorectal cancer.Methods Literatures on psychological distress screening and management in patients undergoing colorectal cancer ostomy were systematically searched across various websites and databases of home and abroad from inception to 20th June,2024 including Cochrane Library,PubMed,Embase,CINAHL,Web of Science,CNKI,Wangfang,VIP,UpToDate,National Guideline Clearing-house,National Comprehensive Cancer Network,the National Institute for Health and Care Excellence,Scottish Intercollegiate Guidelines Network,the International Guideline Collaboration Network,Wound,Ostomy and Continence Nurses Society,World Council of Enterostomal Therapists,Medlive,Chinese Nursing Association.The search aimed to identify evidence on psychological distress screening and management in patients with colorectal cancer and stomas,including guidelines,evidence summaries,expert consensuses,systematic reviews,and Meta-analyses.The search was limited to articles published from the inception of each database to 20th June,2024.The searched literature included guidelines,evidence summary,expert consensus,systematic review,meta-analysis,etc..Two researchers independently evaluated the quality of literature and extracted evidences,as well as checked and integrated the evidences together with a panel of evidence-based research experts.Results A total of 14 articles were included,comprising four guidelines,one expert consensus,two evidence summaries,four meta-analyses and three systematic reviews.The articles encompassed 7 dimensions with a total of 18 pieces of evidence,including one in screening timing,one in screening tools,3 in screening content,3 in drug intervention,3 in self-management,5 in psychological support and 2 in health education.Conclusion The evidence summarised in this study on the screening and management of psychological distress in patients who had ostomy for colorectal cancer is scientifically comprehensive.It provides an evidence-based basis for medical staff in prevention and management of psychological distress in patients.It is necessary to formulate a scientific management plan in clinical practice,according to the specific requirements of departments,the patients and their family members.