Inflammatory bowel disease (IBD) is a chronic inflammatory disorder of the gastrointestinal tract, which increases the incidence of colorectal cancer (CRC). In the pathophysiology of IBD, ubiquitination/deubiquitination plays a critical regulatory function. Josephin domain containing 2 (JOSD2), a deubiquitinating enzyme, controls cell proliferation and carcinogenesis. However, its role in IBD remains unknown. Colitis mice model developed by dextran sodium sulfate (DSS) or colon tissues from individuals with ulcerative colitis and Crohn's disease showed a significant upregulation of JOSD2 expression in the macrophages. JOSD2 deficiency exacerbated the phenotypes of DSS-induced colitis by enhancing colon inflammation. DSS-challenged mice with myeloid-specific JOSD2 deletion developed severe colitis after bone marrow transplantation. Mechanistically, JOSD2 binds to the C-terminal of inosine-5'-monophosphate dehydrogenase 2 (IMPDH2) and preferentially cleaves K63-linked polyubiquitin chains at the K134 site, suppressing IMPDH2 activity and preventing activation of nuclear factor kappa B (NF-κB) and inflammation in macrophages. It was also shown that JOSD2 knockout significantly exacerbated increased azoxymethane (AOM)/DSS-induced CRC, and AAV6-mediated JOSD2 overexpression in macrophages prevented the development of colitis in mice. These outcomes reveal a novel role for JOSD2 in colitis through deubiquitinating IMPDH2, suggesting that targeting JOSD2 is a potential strategy for treating IBD.

Objective: To investigate cardiovascular disease (CVD) prevention status among residents with intra-urban migration in Central China, so as to provide insights into targeted prevention and control of CVD. Methods: Basic data of residents aged 35 to 75 years who participated in Early Screening and Comprehensive Intervention Project for CVD high-risk populations in Central China from September 2015 to August 2020 were collected. According to birth place, type of registered residence and current residence, residents were divided into four groups: local residents in old urban area, local residents in new urban area, other urban migrants and other rural migrants. The status of CVD primary and secondary prevention, were analysed by using a robust Poisson regression model. Results: A total of 76 513 residents were recruited, including 29 420 males (38.45%) and 47 093 females (61.55%), and had a mean age of (56.36±9.84) years. There were 45 087 (58.93%) local residents in old urban area, 23 868 (31.19%) local residents in new urban area, 5 668 (7.41%) other urban migrants and 1 890 (2.47%) other rural migrants. After adjusting for variables such as age, gender and educational level, the results of robust Poisson regression analysis showed that compared with local residents in old urban area, local residents in new urban area had lower compliance rates of non- or moderate-drinking (RR=0.987, 95%CI: 0.975-1.000) and healthy diet (RR=0.535, 95%CI: 0.365-0.782), lower proportion of using aspirin as primary prevention in CVD high-risk population (RR=0.616, 95%CI: 0.511-0.741), lower awareness (RR=0.873, 95%CI: 0.782-0.974) and control rates (RR=0.730, 95%CI: 0.627-0.849) of hypertension; other urban migrants had higher compliance rate of non-smoking (RR=1.045, 95%CI: 1.017-1.075); other rural migrants had lower proportion of using aspirin as primary prevention in CVD high-risk population (RR=0.826, 95%CI: 0.707-0.966). Conclusion The CVD primaryprevention among local residents in new urban area is relatively poor among four groups of residents in Central China, and key interventions are needed.

Objectives:To evaluate the cost-effectiveness of typical pharmaceutical smoking cessation intervention strategies in China in the context of primary cancer prevention.Methods:Markov cohort simulation models were established to simulate the burden of 12 smoking caused cancer, including lung cancer, oral cancer, nasopharyngeal cancer, laryngeal cancer, esophageal cancer, gastric cancer, pancreatic cancer, liver cancer, kidney cancer, bladder cancer, cervical cancer, and acute myeloid leukemia. Taking incremental cost effectiveness ratio (ICER) as the main indicator, the model sets one year as the cycling period for 50 periods and simulates the cohort of 10 000 thirty-five-year-old current smokers with various smoking cessation strategies. To ensure the robustness of conclusion, univariate sensitivity analysis, probability sensitivity analysis, and age-group sensitivity analysis were conducted.Results:The results showed that varenicline intervention was the most cost-effective intervention. Compared to the next most effective option, incremental cost of each additional quality-adjusted life year is 11 140.28 yuan, which is below the threshold of willingness to pay (1 year GDP per capita). The value of ICER increased as the increasing age group of adopting intervention, but neither exceeded the threshold of willingness to pay. One-way sensitivity analysis showed that the value of discount rate, the hazard ratio and cost of intervention strategy had a greater impact on the result of ICER.Conclusion:In China, the use of varenicline to quit smoking is highly cost effective in the context of cancer primary prevention, especially for younger smokers.

Objective To investigate the association between metabolic associated fatty liver disease(MAFLD)and carotid atherosclerotic plaque.Methods A total of 1 107 patients who were hospitalized in The Second Affiliated Hospital of Kunming Medical University from July,2014 to December,2022 were enrolled,and all patients underwent abdominal ultrasound and CT angiography of the head and neck arteries.Baseline data and clinical diagnosis were collected,and the patients were divided into MAFLD group with 499 patients and non-MAFLD group with 608 patients based on medical history,clinical tests,and imaging findings.According to the CT value,carotid plaques were classified into calcified plaques,non-calcified plaques,and mixed plaques.According to the NASCET criteria,carotid stenosis was categorized as normal vessel,slight stenosis,mild stenosis,moderate stenosis,and severe stenosis/occlusion.The independent-samples t test was used for comparison of normally distributed continuous data between two groups,and the Mann-Whitney U rank sum test was used for comparison of non-normally distributed continuous data between two groups;the chi-square test was used for comparison of categorical data between two groups.Univariate and multivariate Logistic regression analyses were used to investigate the influencing factors for carotid atherosclerosis.Results Compared with the non-MAFLD group,the MAFLD group had a significantly higher proportion of patients with calcified plaques(74.3%vs 63.3%,P<0.05),non-calcified plaques(27.1%vs 17.1%,P<0.05),or mixed plaques(27.3%vs 20.7%,P<0.05),as well as a significantly higher proportion of patients with mild stenosis(50.9%vs 44.9%,P<0.05),moderate stenosis(14.6%vs 8.4%,P<0.05),or severe stenosis/occlusion(6.6%vs 3.5%,P<0.05).The univariate logistic regression analysis showed that MAFLD was a risk factor for calcified carotid plaques,non-calcified plaques,and mixed plaques,and it was also a risk factor for mild stenosis,moderate stenosis,and severe stenosis/occlusion of the carotid artery(all P<0.05).After adjustment for confounding factors,the multivariate Logistic regression analysis showed that MAFLD was an independent risk factor for calcified plaque,non-calcified plaque,mixed plaque,and moderate stenosis of the carotid arteries(all P<0.05).Conclusion MAFLD is an independent risk factor for moderate stenosis,calcified plaques,non-calcified plaques,and mixed plaques of the carotid arteries.

Objective:To screen the main characteristic variables affecting the incidence of cardiovascular and cerebrovascular diseases,and to construct the Bayesian network model of cardiovascular and cerebrovascular disease incidence risk based on the top 10 characteristic variables,and to provide the reference for predicting the risk of cardiovascular and cerebrovascular disease incidence.Methods:From the UK Biobank Database,315 896 participants and related variables were included.The feature selection was performed by categorical boosting(CatBoost)algorithm,and the participants were randomly divided into training set and test set in the ratio of 7∶3.A Bayesian network model was constructed based on the max-min hill-climbing(MMHC)algorithm.Results:The prevalence of cardiovascular and cerebrovascular diseases in this study was 28.8％.The top 10 variables selected by the CatBoost algorithm were age,body mass index(BMI),low-density lipoprotein cholesterol(LDL-C),total cholesterol(TC),the triglyceride-glucose(TyG)index,family history,apolipoprotein A/B ratio,high-density lipoprotein cholesterol(HDL-C),smoking status,and gender.The area under the receiver operating characteristic(ROC)curve(AUC)for the CatBoost training set model was 0.770,and the model accuracy was 0.764;the AUC of validation set model was 0.759 and the model accuracy was 0.763.The clinical efficacy analysis results showed that the threshold range for the training set was 0.06-0.85 and the threshold range for the validation set was 0.09-0.81.The Bayesian network model analysis results indicated that age,gender,smoking status,family history,BMI,and apolipoprotein A/B ratio were directly related to the incidence of cardiovascular and cerebrovascular diseases and they were the significant risk factors.TyG index,HDL-C,LDL-C,and TC indirectly affect the risk of cardiovascular and cerebrovascular diseases through their impact on BMI and apolipoprotein A/B ratio.Conclusion:Controlling BMI,apolipoprotein A/B ratio,and smoking behavior can reduce the incidence risk of cardiovascular and cerebrovascular diseases.The Bayesian network model can be used to predict the risk of cardiovascular and cerebrovascular disease incidence.

African swine fever(ASF),caused by the African swine fever virus(ASFV),is a highly contagious infectious disease of pigs.This disease has been spread rapidly in China since 2018,po-sing a huge threat to China's pig farming industry.To rapid detect the ASFV,a loop-mediated iso-thermal amplification(LAMP)combined with the disposable nucleic acid visualization test strip was established for visual detection of the nucleic acid of ASFV B646L gene.The method was easy to operate without special instruments and equipment,while it effectively avoided the disadvantage of false positives caused by aerosol contamination.The method was able to detect 1.16 copies/μL of the recombinant plasmid in 50 min at 65 ℃.In addition,the method was specific with no cross-re-action with classical swine fever virus,porcine reproductive and respiratory syndrome virus,por-cine parvovirus,transmissible gastroenteritis virus.The results in this study provides a rapid,con-venient,sensitive and reliable method for early diagnosis and screening for ASFV suspected infec-tion cases.

To establish a simple,convenient,sensitive,and specific method for rapid detection of Zi-ka virus(ZIKV),the whole genome sequences of ZIKV isolated from different times and regions were analyzed.The specific primers and probes were designed based on the screened target se-quences located in the conserved region of the ZIKV NS5 gene.By combining RT-LAMP isother-mal amplification technology and immunochromatography technology,a reverse transcription loop mediated isothermal amplification nucleic acid and flow visualization strip(RT-LAMP-VF)detec-tion method for ZIKV was established.The results showed that the method had good specificity and sensitivity.When the ratio of inner,outer,and ring primers(FIP∶LF∶F3)was 4∶2∶1,the detection method can specifically detect 102 copies/pL RNA transcripts or 2.15 pfu ZIKV at 61 ℃for 45 minutes,with no cross reaction with other flaviviruses such as Japanese encephalitis virus and classical swine fever virus.Other RNAs in blood tissue samples did not affect the sensitivity and specificity of RT-LAMP-VF,indicating that the method can be applied to clinical practice.The ZIKV RT-LAMP-VF detection method established in this study is easy to perform and does not require special instruments and equipment.It is particularly suitable for the rapid detection of ZIKV in grassroots units,providing technical support and material support for the establishment of on-site rapid detection and early warning and prediction systems for ZIKV disease.

The PCR-amplified severe fever with thrombocytopenia syndrome virus(SFTSV)Gn-DⅢ-Ⅲ gene was inserted into the pET-30a(+)prokaryotic expression vector to generate the re-combinant plasmid pET-SFTSV-Gn-D Ⅲ-Ⅲ.The plasmid was transformed into E.coli BL21(DE3)for Gn-DⅢ-m protein expression and the expression conditions were optimized.The Gn-DⅢ-Ⅲ protein purified with Ni-NTA column affinity chromatography was applied as the captured antigen to establish an indirect ELISA method for the detection of SFTSV antibody.The results demonstrated that the recombinant plasmid pET-SFTSV-Gn-D Ⅲ-Ⅲ was successfully constructed as identified by PCR and sequencing.The recombinant protein SFTSV Gn-D m-Ⅲ was soluble ex-pression in E.coli under the optimal induction conditions of 0.4 mmol/L IPTG at 25 ℃ for 4 h,and the protein purity was 91.77％after purification by Ni-NTA column.The optimal reaction con-ditions for the indirect ELISA of SFTSV antibody were as follows:coating antigen concentration(5 μg/mL),primary antibody(incubation at 37 ℃ for 1.5 h),and secondary antibody(diluted 1:10 000 and incubated at 37 ℃ for 1 h).The established method had no cross-reactivity with Rift Valley fever virus(RVFV),Ebola virus(EBOV),and tick-borne encephalitis virus(TBEV)posi-tive sera.The method had a high sensitivity,with P/N＞2.1 for SFTSV-positive sera diluted to 81920.Coefficients of variation for intra-and inter-batch reactions were less than 10％.Detection of four SFTSV-infected human clinical serum samples showed the serum samples from patients in re-mission were tested as positive(P/N＞2.1),while serum samples from patients with multiple or-gan failure were detected as negative(P/N＜2.1).The results indicated that the SFTSV Gn-D Ⅲ-Ⅲ protein was successfully expressed and purified,and it was used as the coating protein to estab-lish an indirect ELISA assay for SFTSV antibody,which possesses good specificity,sensitivity and reproducibility.This method might be applied to detect human SFTSV clinical serum samples.

Steatotic liver diseases (SLD) are the principal worldwide cause of cirrhosis and end-stage liver cancer, affecting nearly a quarter of the global population. SLD includes metabolic dysfunction-associated alcoholic liver disease (MetALD) and metabolic dysfunction-associated steatotic liver disease (MASLD), resulting in asymptomatic liver steatosis, fibrosis, cirrhosis and associated complications. The immune processes include gut dysbiosis, adiposeliver organ crosstalk, hepatocyte death and immune cell-mediated inflammatory processes. Notably, various immune cells such as B cells, plasma cells, dendritic cells, conventional CD4+ and CD8+ T cells, innate-like T cells, platelets, neutrophils and macrophages play vital roles in the development of MetALD and MASLD. Immunological modulations targeting hepatocyte death, inflammatory reactions and gut microbiome include N-acetylcysteine, selonsertib, F-652, prednisone, pentoxifylline, anakinra, JKB-121, HA35, obeticholic acid, probiotics, prebiotics, antibiotics and fecal microbiota transplantation. Understanding the immunological mechanisms underlying SLD is crucial for advancing clinical therapeutic strategies.

ObjectiveTo investigate the influence of different diagnostic criteria on the short-term prognosis of patients with acute-on-chronic liver failure （ACLF）. MethodsA total of 115 ACLF patients who were hospitalized in Department of Gastroenterology， The Second Affiliated Hospital of Kunming Medical University， from January 2018 to January 2022 were enrolled， and all patients received internal medical treatment combined with artificial liver therapy. According to the guidelines， the patients were divided into CMA guideline group （Diagnostic and treatment guidelines for liver failure by Chinese Medical Association）（n=100）， APASL guideline group （Consensus statements of Asian Pacific Association for the Study of the Liver）（n=94）， and EASL guideline group （Criteria proposed by European Association for the Study of the Liver）（n=36）. The above three guidelines were compared in terms of 90-day mortality rate. A one-way analysis of variance was used for comprision of continuous date between groups； the chi-square test was used for comprision of categorical date between groups. The receiver operating characteristic （ROC） curve of related variables. ResultsThe 90-day mortality rate was 50.0% in the CMA guideline group， 51.1% in the APASL guideline group， and 77.8% in the EASL guideline group， and the EASL guideline group had a significantly higher 90-day mortality rate than the CMA guideline group （χ²=8.351， P=0.004） and the APASL guideline group （χ²=7.650， P=0.006）. EASL guideline had a sensitivity of 22.2% and a specificity of 92.3% in predicting the risk of short-term mortality， with an area under the ROC curve was 0.576. ConclusionACLF patients who meet EASL guideline tend to have a worse short-term prognosis， and this guideline may help to identify patients at a relatively high risk of short-term death.