Objective:To explore the causal association between insulin-like growth factor-1(IGF-1)and colorectal cancer(CRC)based on two sample Mendelian randomization(MR)analysis.Methods:A bidirectional two sample MR analysis was conducted based on publicly aggregated data from the IEU OpenGWAS project.The inverse variance weighted(IVW)method was used as the main analysis model to assess the causal relationship between IGF-1 and CRC.Additional analyses were performed using weighted median(WM),MR-Egger regression,weighted mode estimator(WME),and simple mode(SM)methods.Sensitivity analysis was performed to assess the robustness of the results.Results:A total of 386 single nucleotide polymorphisms(SNPs)were selected as instrumental variables(IVs)with IGF-1 as the exposure factor.The MR analysis results revealed a positive causal association between IGF-1 and the risk of CRC[odds ratio(OR)=1.178,95％confidence interval(CI):1.092-1.272)](P＜0.001),and the association remained significant after adjusting for height[OR(95％CI)=1.214(1.111,1.327)](P＜0.001).Cochran's Q-test showed heterogeneity among the IVs(P＜0.05),while the horizontal pleiotropy of IV was not detected by the MR-Egger regression(P＞0.05).The leave-one-out analysis showed that the MR results were robust.Reverse MR analysis indicated no reverse causal relationship between IGF-1 and CRC[OR(95％CI):1.017(0.997,1.037)](P=0.103).Conclusion:There is a causal relationship between IGF-1 level and CRC,and elevated IGF-1 level could be a risk factor for CRC.

Objective:To discuss the influencing factors of angina pectoris in the patients with diabetes mellitus(DM),to construct a Bayesian network model to explore the network relationships among the influencing factors,and to predict the risk of angina pectoris in the patients with DM.Methods:Based on the UK Biobank(UKB)database,the Logistic regression aralysis model was used to screen the influencing factors of angina pectoris in the patients with DM.The taboo search algorithm was used for structure learning,and the Bayesian parameter estimation method was used for parameter learning to construct the Bayesian network model.Results:A total of 22 712 DM patients were included.The influencing factors of angina pectoris in the patients with DM included 14 variables:gender,age,body mass index(BMI),triglycerides(TG),total cholesterol(TC),glycated hemoglobin(HbA1c),hypertension,maternal smoking around delivery,smoking status,alcohol consumption,regular exercise,insomnia,sleep duration,and childhood relative body size(P<0.05).A Bayesian network model was constructed with 15 nodes and 22 directed edges.Among them,age,HbA1c,hypertension,regular exercise,BMI,and sleep duration were directly associated with the occurrence of angina pectoris in the patients with DM,while gender,smoking status,alcohol consumption,TC,TG,insomnia,childhood relative body size,and maternal smoking around delivery were indirectly associated with the occurrence of angina pectoris in the patients with DM.Conclusion:Age,HbA1c,hypertension,regular exercise,BMI,and sleep duration are direct influencing factors of angina pectoris in the patients with DM.Controlling HbA1c,blood pressure,and BMI levels,engaging in regular exercise,and maintaining appropriate sleep duration are beneficial for reducing the risk of angina pectoris in the patients with DM.

Objective:To screen the Alzheimer's disease(AD)-related genes and construct its diagnostic model using bioinformatics technology and machine learning(ML)algorithms,to discuss the immunological characteristics of AD patients,and to provide novel biomarkers for AD diagnosis.Methods:The AD-related gene expression dataset GSE125583 was downloaded from the Gene Expression Omnibus(GEO)database.Differentially expressed genes(DEGs)were identified through differential analysis.Gene Ontology(GO)functional enrichment and Kyoto Encyclopedia of Genes and Genomes(KEGG)signaling pathway enrichment analyses were performed to explore the biological functions and signaling pathways of DEGs.A protein-protein interaction(PPI)network was constructed,and hub genes were screened using Cytoscape software combined with three ML algorithms:Least Absolute Shrinkage and Selection Operator(LASSO),eXtreme Gradient Boosting(XGBoost),and Random Forest(RF).The screened hub genes were utilized to build an AD diagnostic model via RF,followed by feature importance ranking.The model's efficacy and key genes were evaluated using a test set.Single-sample gene set enrichment analysis(ssGSEA)was used for immune cell infiltration analysis between AD group and control group.Results:Differential analysis identified 1 287 DEGs.The GO functional enrichment analysis results revealed that DEGs were primarily involved in biological functions related to neural signaling,synapses,and vesicles.KEGG signaling pathway enrichment analysis indicated significant enrichment of DEGs in ion transport,neurotransmitter,and ligand-gated channel pathways.Nine overlapping hub genes were screened by the three ML algorithms.In the AD diagnostic model,the top four key genes with highest diagnostic performance were adenylate cyclase-activating polypeptide 1(ADCYAP1),brain-derived neurotrophic factor(BDNF),platelet-derived growth factor receptor β(PDGFRB),and C-X-C motif chemokine receptor 4(CXCR4),with corresponding area under the curve(AUC)values of 0.852,0.795,0.820,and 0.756,respectively.The model achieved an AUC of 0.828,accuracy of 81.25%,sensitivity of 84.40%,and specificity of 71.43%.The immune cell infiltration analysis results demonstrated higher infiltration of macrophages,monocytes,natural killer(NK)cells,and lymphocytes in AD tissue.Among these,NK/natural killer T(NKT)cells and plasmacytoid dendritic cells showed significant correlations with the four key genes(P<0.05).Conclusion:The feature genes screened based on bioinformatics and ML exhibit diagnostic potential for AD.Genes such as ADCYAP1 may serve as potential biomarkers for AD diagnosis,offering significant implications for early prevention and treatment.

Objective:To investigate the differences in prognosis between different surgical approaches in elderly patients with advanced ovarian cancer.Methods:Based on the Surveillance, Epidemiology and End Results (SEER) database, a cohort of elderly patients with advanced ovarian cancer from 2000 to 2020 was established. Through propensity score matching, 2 094 patients were selected from those who underwent two different surgical approaches to form a matched cohort (SEER database cohort), including 1 039 patients who received cytoreductive surgery and 1 055 patients who underwent local resection. Meanwhile, 148 elderly patients with advanced ovarian cancer who were treated at the First Affiliated Hospital of Shandong First Medical University from January 2012 to January 2024 were selected (hospital cohort), among whom 85 underwent cytoreductive surgery and 63 underwent local resection. The prognostic differences among patients who underwent cytoreductive surgery and local resection in two cohorts and stratified by the International Federation of Gynecology and Obstetrics (FIGO) staging were evaluated, respectively. The relationship between the causes of death and surgical approaches in elderly patients with advanced ovarian cancer was analyzed.Results:In the SEER database cohort, the median overall survival (OS) for patients who underwent cytoreductive surgery and local resection was 37 and 40 months, respectively, with 5-year OS rates of 31.47% and 33.74%, with no statistically significant difference ( χ2=0.78, P=0.378). After stratification by FIGO staging, the median OS for patients with stage ⅢB-ⅢC who underwent cytoreductive surgery ( n=998) and local resection ( n=962) was 38 and 40 months, respectively, with no statistically significant difference ( χ2=0.20, P=0.659). For patients with stage Ⅳ, the median OS for those who underwent cytoreductive surgery ( n=41) and local resection ( n=93) was 17 and 36 months, respectively, with a statistically significant difference ( χ2=9.37, P=0.002). Among 2 094 elderly patients with advanced ovarian cancer, 1 581 had clearly identified causes of death. In patients who underwent cytoreductive surgery, the proportions of deaths due to ovarian cancer and non-ovarian cancer were 94.52% (742/785) and 5.48% (43/785), respectively. In patients who underwent local resection, the proportions of deaths due to ovarian cancer and non-ovarian cancer were 91.46% (728/796) and 8.54% (68/796), respectively. There was a statistically significant difference in the distribution of causes of death between the two surgical approaches ( χ2=5.69, P=0.017). In the hospital cohort, the median OS for patients undergoing cytoreductive surgery and local resection was 39 and 51 months, respectively, with 5-year OS rates of 22.85% and 23.81%, with a statistically significant difference ( χ2=6.71, P=0.010). After stratification by FIGO staging, the median OS for patients with stage ⅢB-ⅢC undergoing cytoreductive surgery ( n=29) and local resection ( n=26) was 50 and 51 months, respectively, with no statistically significant difference ( χ2=0.15, P=0.699) ; for patients with stage Ⅳ undergoing cytoreductive surgery ( n=56) and local resection ( n=37), the median OS was 35 and 47 months, respectively, with a statistically significant difference ( χ2=6.55, P=0.011) . Conclusions:The survival outcomes of local resection in elderly patients with advanced ovarian cancer are not inferior to those of cytoreductive surgery. For FIGO stage Ⅳ patients, the survival period following local resection is superior to that of cytoreductive surgery.

OBJECTIVE To investigate the regulatory effects of salvianolic acid C(SAC)on the level of cuproptosis and inflammatory injury in cardiomyocytes after myocardial infarction(MI).METHODS①C57BL/6 mice were divided into a sham group,an MI model group,and SAC(5,10 and 20 mg·kg-1)groups,with 10 mice in each group.Mice in the SAC groups were pretreated with oral gavage of SAC for 1 week,while those in the sham and model groups received an equal volume of saline.One week later,an MI model was established in the model and SAC groups by ligating the left anterior descending coronary artery,while the sham group underwent thoracotomy without ligation.MI size was assessed using triphenyltetrazolium chloride(TTC)staining.Cardiomyocyte apoptosis was evaluated by TUNEL staining.The ultrastructure of cardiomyocyte mitochondria was observed under a transmission electron microscope.② Mouse cardiomyocytes HL-1 were divided into a control group,an oxygen-glucose deprivation(OGD)model group,OGD+SAC 1,5 and 10 μmol·L-1 groups,and a OGD+SAC(5 μmol·L-1)+nuclear factor erythroid 2-related factor 2(Nrf2)inhibitor ML385(2 μmol·L-1)group.Cells in the OGD+SAC groups were pretreated with SAC for 24 h while those in the OGD+SAC+ML385 group were pretreated with both SAC 5 μmol·L-1 and ML385 2 μmol·L-1 for 24 h.Except for the control group,an OGD model was established in HL-1 cells.ELISA was used to detect the levels of tumor necrosis factor-α(TNF-α),interleukin-6(IL-6)and IL-1β in mouse serum and HL-1 cell culture supernatants.The Cu+detection kit was used to measure Cu+levels in myocardial tissue and HL-1 cells.Cell viability was assessed using the CCK-8 kit.Apoptosis rates of HL-1 cells were detected by flow cytometry.Reactive oxygen species(ROS)levels in HL-1 cells were measured using a ROS detection kit.Western blotting analysis was performed to detect the expression levels of Nrf2,heme oxygenase-1(HO-1),and cupro-ptosis markers,ferredoxin 1(FDX1)and solute carrier family 31 member 1(SLC31A1)in myocardial tissue and HL-1 cells.RESLUTS ① Compared with the sham group,the MI model group exhibited increased myocardial infarction size,elevated cardiomyocyte apoptosis rates,mitochondrial swelling,vacuolation,and cristae rupture in cardiomyocytes,increased serum levels of TNF-α,IL-6,and IL-1β,elevated Cu+levels and expressions of FDX1 and SLC31A1 in myocardial tissue,and decreased expressions of Nrf2 and HO-1(P<0.01).Compared with the model group,the SAC 5,10 and 20 mg·kg-1 groups showed reduced MI size,decreased cardiomyocyte apoptosis rates,alleviated mitochondrial swelling,vacuola-tion,and cristae rupture,lower serum levels of TNF-α,IL-6 and IL-1β,decreased Cu+levels and expres-sions of FDX1 and SLC31A1 in myocardial tissue,and increased expressions of Nrf2 and HO-1(P<0.05,P<0.01).② Compared with the cell control group,the OGD model group demonstrated signifi-cantly decreased HL-1 cell viability,increased cell apoptosis rates,Cu+and ROS levels,expressions of FDX1 and SLC31A1,elevated levels of TNF-α,IL-6 and IL-1β in cell culture supernatants,and decreased expressions of Nrf2 and HO-1(P<0.01).Compared with the OGD model group,the SAC 1,5 and 10 μmol·L-1 groups showed increased HL-1 cell viability,decreased cell apoptosis rates,Cu+and ROS levels,expressions of FDX1 and SLC31A1,reduced levels of TNF-α,IL-6 and IL-1β in cell culture supernatants,and increased expressions of Nrf2 and HO-1(P<0.05,P<0.01).Compared with the SAC 5 μmol·L-1 group,the SAC 5 μmol·L-1+ML385 2 μmol·L-1 group exhibited decreased cell viability,increased cell apoptosis rates,Cu+and ROS levels,expressions of FDX1 and SLC31A1,elevated levels of TNF-α,IL-6,and IL-1β in cell culture supernatants,and decreased expressions of Nrf2 and HO-1(P<0.01).CONSLUSION SAC can activate the Nrf2/HO-1 signaling pathway,alleviate cuproptosis in cardiomyocytes after MI,and reduces inflammatory damage.

OBJECTIVE To explore the effect and underlying mechanism of leucine(Leu)on meta-bolic dysfunction-associated fatty liver disease induced by high fat diet(HFD)in mice.METHODS C57BL/6J male mice were randomly divided into chow diet(normal),chow diet+Leu(normal+Leu),HFD and HFD+Leu groups,with 10 mice in each group.The mice in the normal and normal+Leu groups received chow diet while those in the HFD and HFD+Leu groups received HFD.Drinking water for mice in the normal+Leu and HFD+Leu groups was supplemented with 1.5%Leu.The experiment lasted 24 weeks,total food and water intake of mice were recorded weekly to calculate energy and Leu intake respectively.Energy metabolism of mice was detected at week 20 by the Oxymas/CLAMS Animal Metabolic System heat production,CO2 exhalation,O2 consumption and respiratory exchange rate(RER).At the end of week 24,the mice were sacrificed and the livers were harvested,followed by the oil red O staining to reveal the fat content.Western blotting was performed to analyze the changes in the activity of the liver branched-chain α-keto acid dehydrogenase E1α(BCKDE1A),the activation of AMP-activated protein kinase alpha subunit(AMPKα),and the protein expressions of downstream effector molecules including silent information regulator 1(SIRT1)and peroxisome proliferator-activated receptor coactivator-1α(PGC-1α),fatty acid synthetase(FAS)and fatty acid binding protein 4(FABP4)in the liver of mice.RESULTS Total Leu intake of mice was significantly reduced in the HFD+Leu group,compared with the normal+Leu group.The mice fed with HFD significantly increased the energy intake body mass gain and liver mass,accompanied by fat accumulation in the liver,compared to the mice in the normal group.Simultaneously,the mice in the HFD group showed a decrease in CO2 exha-lation both by day and by night,and in the respiratory exchange ratio by day compared to the normal group.Compared with the HFD group,the body mass gain and liver mass obviously decreased in mice of the HFD+Leu group,and the liver fat accumulation was reduced.The mice in the HFD+Leu group exhib-ited higher heat production and O2 consumption,along with an increase in CO2 exhalation by day and by night.In addition,heat production,CO2 exhalation,and O2 consumption were significantly higher by night than by day(P<0.01).As for the respiratory exchange ratio,a night increase was seen in the mice from the normal group,normal+Leu group,and HFD group,but not in the HFD+Leu group.The results of Western blotting showed that compared with the normal group,the BCKDE1A phosphorylation inacti-vation was enhanced,AMPKα phosphorylation activation alleviated,the protein expressions of SIRT1 and PGC-1α downregulated(P<0.05),and the protein expressions of FAS and FABP4 increased in the livers of mice in the HFD group.Compared with the HFD group,the BCKDE1A phosphorylation inacti-vation was alleviated,AMPKα phosphorylation activation enhanced,the protein expressions of SIRT1 and PGC-1α increased,and the protein expressions of FAS and FABP4 downregulated in the livers of mice in the HFD+Leu group.CONCLUSION Leu can alleviate HFD-induced metabolic dysfunction-associated fatty liver disease in mice,which may be closely related to the promotion of energy metabo-lism and inhibition of fat synthesis.

Based on the Political Economic Social Technological(PEST)-Strengths Weakness Opportunity Threats(SWOT)model,by sorting out the macro-environmental factors such as politics,economy,society and technology,and combining the internal strengths and weaknesses of the hospital as well as the external opportunities and threats,it puts forward the strategies to optimize the comprehensive budget management.It is found that hospitals face problems in total budget management such as disconnection between budgeting and strategy,and low level of informatization,but they also have advantages such as resource optimization and support for decision-making.The external environment provides opportunities such as health insurance reform and financing channel expansion,while there are threats such as industry competition and data security.It is suggested to improve the budget management level and promote the high-quality development of hospitals by expanding funding sources,strengthening cost control,and promoting the integration of industry and finance.

Objective:Taking Inflammatory Bowel Disease(IBD)patients as an example,to explore the impact of disparities in regional outpatient security policies on medication reimbursement benefits for patients,and to provide insights for promoting the reform and development of equal outpatient security policy.Methods:39 cities from 9 provinces in China were selected as research samples to analyze the types,coverage,and benefits of their outpatient security policies.Indicators such as the individual out-of-pocket ratio,deductible,and specified reimbursement rate were used to simulate the actual reimbursement ratio for IBD patients using negotiated drugs.Results:Under the general outpatient coordination policy,the average actual reimbursement rate for medications in IBD patients was 26.36%for residents and 36.47%for employees.Under the outpatient chronic and special disease policy,the average actual reimbursement rate was 42.49%for residents and 50.94%for employees,while patients receiving drug treatment under the outpatient special drug policy have an average actual reimbursement rate of 51.62%(for residents)and 64.92%(for employees).Conclusion:Under China's outpatient security policies,there are significant disparities in reimbursement benefits for IBD patients across different regions.Therefore,it is recommended to strengthen the coordination of outpatient security policies across regions,optimize policy design,and provide patients with more equitable and accessible medical coverage.

Objective To introduce the fundamental principles of the multivariate functional mixed model(MFMM)and provide a methodological basis for interpreting the principal components derived from dimension reduction of multivariate functional data.Methods The MFMM models the mean function,auto-covariance function,and cross-covariance function within functions non-parametrically,clearly separating the shared latent processes common to all indicators from the specific latent processes unique to each indicator.In the case study,data from colorectal cancer patients at the Yunnan Cancer Hospital are used to extract the common and specific principal components of longitudinal carcinoembryonic antigen(CEA)and carbohydrate antigen 125(CA125)within 12 months post-surgery using MFMM,coupled with interpretation through a random survival forest prediction model.Results The MFMM identified 2 shared principal components for CEA and CA125,5 specific components for CEA,and 5 specific components for CA125.The random survival forest prediction model constructed based on these extracted components showed higher prediction accuracy than the baseline model.Furthermore,variable importance analysis revealed that the first specific component of CEA was the most important predictive variable after clinical baseline variables,while the importance of CA125 specific components was lower than that of CEA,consistent with the current consensus on colorectal cancer.Conclusion MFMM effectively manages the correlations among multiple longitudinal indicators and their changes over time,capturing the shared and specific processes of multiple longitudinal measurement indicators as they evolve.This enhances the model's interpretability and offers theoretical and practical advantages.

Objective:To review the Minimal Clinically Important Difference(MCID)of EQ-5D-3L calculated by anchor-based method,evaluate the reliability of existing MCID,and provide reference thresholds for the interpretation of clinical research results.Methods:CNKI,PubMed,Embase and others were searched from inception to June 30,2023.The nonparametric tests were used to analyze the impact of statistical methods and sample size on MCID.Results:A total of 51 studies were eventually included.Studies were primarily prospective in design,32 studies focused on musculoskeletal disorders,37 studies used a single anchor,45 studies adopted patient-perspective anchor,and the Receiver Operating Characteristic(ROC)curve was the main statistical analysis method.A total of 160 MCID were obtained from 51 studies,ranging from 0.003 to 0.540,and only 3 MCID from 2 studies were rated as"high reliability"across all core items of the evaluation instrument.It is found that statistical analysis methods,sample size,and measurement time interval all significantly affect MCID.Conclusion:The disease type in EQ-5D-3L MCID studies were not abundant and unbalanced,and the heterogeneity of MCID measured in the included studies was high.The reliability evaluation results showed that the existing MCID has poor reliability in all items except the first and second items of the evaluation instrument.