AIM:To evaluate the application effec-tiveness of a Bayesian mixture model based on the principal stratum strategy for estimating the com-plier average causal effect(CACE)in clinical trials with non-compliance.METHODS:Using a non-infe-riority randomized controlled trial investigating a novel drug for primary type 2 diabetes mellitus(non-inferiority margin:-0.4)as a case study,the primary analysis applied a Bayesian mixture model under the monotonicity assumption to estimate CACE of between-group differences in glycated he-moglobin(HbA1c)changes within the compliant stratum,followed by non-inferiority testing.Sensi-tivity analyses included a Bayesian mixture model relaxing the monotonicity assumption and compar-ing results with per-protocol set(PPS)analysis.RE-SULTS:In the primary analysis,the posterior mean of CACE for HbA1c change in the compliant stratum was 0.081％,with a one-sided 97.5％credible inter-val lower bound of-0.124,exceeding the non-infe-riority margin(-0.4％),supporting the non-inferiori-ty efficacy of the novel drug in the compliant stra-tum(P(H1|Data)=1).Consistent findings were ob-served in PPS analyses(estimated effect:0.136％;one-sided 97.5％credible interval lower bound:-0.069％),further validating methodological robust-ness.CONCLUSION:In clinical trials with noncom-pliance as an intercurrent event,the Bayesian mix-ture model under the principal stratum strategy ef-fectively adjusts for compliance-related bias and yields conservative,robust estimates of causal ef-fects,supporting its value in efficacy evaluation un-der complex compliance scenarios.

AIM:To develop a SAS macro tool for calculating pharmacokinetic(PK)parameters using non-compartmental analysis(NCA)that is applica-ble to various routes and frequencies of drug ad-ministration.METHODS:By incorporating the prin-ciples of NCA PK parameter calculations,the struc-ture of the SAS macro program is designed and pro-grammed.The usage of the macro program is dem-onstrated through simulated examples.RESULTS:Based on NCA,this study programmed a SAS macro using SAS macro language to calculate both single-dose and steady-state complete PK parameters.It supports three modes of drug administration:ex-travascular,intravenous infusion,and intravenous bolus injection,as well as four algorithms for calcu-lating area under the curve(AUC).By comparing with authoritative calculation software,the results were found to be highly consistent across various calculation scenarios,with more accurate calcula-tions for the time of first measurable concentration(Tlag).CONCLUSION:The％M_CREATE_PK_PARAM-ETERS macro is a SAS macro that supports compre-hensive PK parameter calculations in NCA,provid-ing an accurate,efficient,and flexible solution for PK parameter estimation with broad application prospects.

Objective:To systematically assess the operating dynamics and sustainability of the employees'basic medical insurance pooling fund and provide evidence for policy optimization.Methods:Using Province A as a case study,a dynamic actuarial model grounded in the revenue-expenditure balance framework was constructed.Seven policy simulation scenarios were designed to forecast and compare fund trajectories from 2024 to 2050.Results:Without further policy intervention,the pooling fund faces a high risk of medium-to long-term imbalance.Fertility incentives and relaxed migration policies have limited short-term effects,serving primarily to slightly delay the emergence of deficits.Financing-sharing reforms significantly improve revenue quality,while provider-payment reforms effectively curb non-demographic cost growth.Gradual postponement of retirement strengthens fund sustainability by extending contribution periods and delaying benefit outflows.Cross-provincial instant settlement exerts the greatest pressure on fund expenditure.A comprehensive reform package delivers the most favorable and sustainable balance across revenue,expenditure,and accumulation.Conclusion:Future reforms should center on delayed retirement and provider-payment restructuring,coordinated with contribution-base expansion,demographic optimization,and strengthened oversight of cross-regional medical services,thereby forming a multi-policy collaborative governance framework to ensure the long-term sustainability of the pooling fund.

Purpose The study aimed to analyze the relationship between MET gene variants and clinicopathologi-cal features in patients with non-small cell lung cancer(NSCLC).Methods Next-generation sequencing technology was used to detect MET gene variants in NSCLC specimens.The association between MET gene variant status and clini-copathological features was then analyzed.Results Among 1 633 cases of NSCLC,the overall MET mutation rate was 4.53％(74/1 633).Variants were mainly observed in male patients,never-smokers,those older than 60 years,ade-nocarcinoma histology,and patients with TNM stage Ⅲ+Ⅳ disease(P＜0.05).MET gene variant status showed no significant assocication with patient age,sex,smoking history,or pathological subtype(P＞0.05),but was statistical-ly correlated with clinical stage and presence of distant metastasis(P＜0.05).The two major variant types were MET exon 14 skipping and MET amplification,which together accounted for 71.62％of all variants.In addition,MET am-plification was positively correlated with EGFR(P=0.003,rs=0.340)and TP53 mutations(P=0.002,rs=0.362),but showed no correlation with KRAS or ALK gene mutations.In contrast,MET exon 14 skipping was nega-tively correlated with EGFR gene mutations(P＜0.001,rs=-0.409),and showed no significant correlation with KRAS,ALK,or TP53 mutations.Conclusion Different types of MET gene variants(amplification,exon 14 skip-ping,fusion,and others)are significantly associated with clinical advanced clinical stage and distant metastasis in NSCLC,but are independent of patient age,sex,smoking history,and pathological subtype.MET amplification fre-quently co-occur with EGFR and TP53 co-mutations.

Purpose The study aimed to analyze the relationship between MET gene variants and clinicopathologi-cal features in patients with non-small cell lung cancer(NSCLC).Methods Next-generation sequencing technology was used to detect MET gene variants in NSCLC specimens.The association between MET gene variant status and clini-copathological features was then analyzed.Results Among 1 633 cases of NSCLC,the overall MET mutation rate was 4.53％(74/1 633).Variants were mainly observed in male patients,never-smokers,those older than 60 years,ade-nocarcinoma histology,and patients with TNM stage Ⅲ+Ⅳ disease(P＜0.05).MET gene variant status showed no significant assocication with patient age,sex,smoking history,or pathological subtype(P＞0.05),but was statistical-ly correlated with clinical stage and presence of distant metastasis(P＜0.05).The two major variant types were MET exon 14 skipping and MET amplification,which together accounted for 71.62％of all variants.In addition,MET am-plification was positively correlated with EGFR(P=0.003,rs=0.340)and TP53 mutations(P=0.002,rs=0.362),but showed no correlation with KRAS or ALK gene mutations.In contrast,MET exon 14 skipping was nega-tively correlated with EGFR gene mutations(P＜0.001,rs=-0.409),and showed no significant correlation with KRAS,ALK,or TP53 mutations.Conclusion Different types of MET gene variants(amplification,exon 14 skip-ping,fusion,and others)are significantly associated with clinical advanced clinical stage and distant metastasis in NSCLC,but are independent of patient age,sex,smoking history,and pathological subtype.MET amplification fre-quently co-occur with EGFR and TP53 co-mutations.

Objective To analyze the innovative model and effectiveness of the four-level prevention of stroke in Nantong Medical and Prevention Collaborative Center for Cardiovascular and Cerebrovascular Disease,so as to provide new practical experience for the prevention and treatment of cerebrovascular disease.Methods In practice,Nantong city has explored the"53343"mode of collaborative treatment and prevention of cardiovascular and cerebrovascular diseases,and innovatively integrated this mode into four-level prevention to form a practice mode of zero-level guidance,first-level monitoring,second-level coordination and three-level leading.Data from the China Health Statistics Yearbook from 2011 to 2022 and the monitoring data of cardiovascular and cerebrovascular events in Nantong City on the Jiangsu Provincial Chronic Disease Management Information Platform from 2017 to 2023 were collected and processed by using Excel and SPSS 24.0,to analyze the changes of stroke surveillance data and effectiveness in Nantong City after applying the model.Results According to the monitoring data of cardiovascular and cerebrovascular events in Nantong City from the Jiangsu Provincial Chronic Disease Management Information Platform,despite the continuous increase in the number of monitored individuals over five years,the monitoring data for stroke from the Nantong Medical and Prevention Collaborative Center for Cardiovascular and Cerebrovascular Disease witnessed a decline in the number of monitored individuals for the first time in 2022.The stroke monitoring data from the same monitoring agency showed a more stable fluctuation trend compared to the number of national stroke patients discharged from 2017 to 2021.We established a coherent health service operation mechanism,cultivated 14 interdisciplinary talents,held a special continuing education class on stroke,strengthened the in-depth collaboration between clinical and public health,and provided a practical and innovative model for effective prevention and treatment of stroke.Conclusions The four-level prevention based on the medical and preventive collaboration center for cardiovascular and cerebrovascular diseases can achieve process and cycle health management,effectively slow down the upward trend of stroke,and improve the ability and level of scientific research and teaching.

Objective:To systematically assess the operating dynamics and sustainability of the employees'basic medical insurance pooling fund and provide evidence for policy optimization.Methods:Using Province A as a case study,a dynamic actuarial model grounded in the revenue-expenditure balance framework was constructed.Seven policy simulation scenarios were designed to forecast and compare fund trajectories from 2024 to 2050.Results:Without further policy intervention,the pooling fund faces a high risk of medium-to long-term imbalance.Fertility incentives and relaxed migration policies have limited short-term effects,serving primarily to slightly delay the emergence of deficits.Financing-sharing reforms significantly improve revenue quality,while provider-payment reforms effectively curb non-demographic cost growth.Gradual postponement of retirement strengthens fund sustainability by extending contribution periods and delaying benefit outflows.Cross-provincial instant settlement exerts the greatest pressure on fund expenditure.A comprehensive reform package delivers the most favorable and sustainable balance across revenue,expenditure,and accumulation.Conclusion:Future reforms should center on delayed retirement and provider-payment restructuring,coordinated with contribution-base expansion,demographic optimization,and strengthened oversight of cross-regional medical services,thereby forming a multi-policy collaborative governance framework to ensure the long-term sustainability of the pooling fund.

Objective To explore the mechanism of action of mitochondrial DNA(mtDNA)of alveolar epithelial type Ⅱ cells(AECⅡ)in silicotic fibrosis.Methods This study was divided into the animal experiment and cell experiment.Animal experiment:twenty-eight C57BL/6 mice were randomly divided into the saline group(n=14)and the silicosis model group(n=14),which were given 50 μL of sterile saline and 50 μL of 50 mg/mL of SiO2 suspension by tracheal perfusion respectively.HE staining and Masson staining were performed to observe the histopathological changes of mouse lung tissues after sampling with the exposure of 28 days and 56 days,and Western blot was used to detect the expression levels of functional proteins of pulmonary surfactant protein-D(SP-D),and Krebs von den Lungen-6(KL-6),and fibrotic protein of transforming growth factor-β1(TGF-β1)in mouse lung tissues.Cell experiment:AECⅡ cell line of A549 was exposed to different concentrations of SiO2 suspension.CCK-8 was used to detect cell viability,DAPI staining was used to observe cell apoptosis,Western blot was used to detect related protein expression,JC-1 was used to detect the changes of mitochondrial membrane potential,and RT-qPCR was used to detect mtDNA levels in whole cells,mitochondria,cytoplasm and supernatant.The expression levels of related proteins in AECⅡ were detected by Western blot after cleared mtDNA by DnaseⅠ.Results Histopathological examination of lung tissues showed that SiO2 exposure led to damage in mice lung tissues,with infiltration of inflammatory cell,silica nodules,and a significant increase of collagen fibers.After SiO2 exposure,the protein expressions of SP-D,KL-6 and TGF-β1 in lung tissues were up-regulated(P<0.05).DAPI staining and CCK-8 results showed a reduced activity and impaired apoptosis of AECⅡ after treated with 400 and 800 μg/mL SiO2.JC-1 assay results demonstrated that exposure to 800 μg/mL SiO2 caused a decrease of mitochondrial membrane potential in AECⅡ(P<0.05).RT-qPCR results showed that 800 μg/mL SiO2 exposure led to increased mtDNA levels in the cytoplasm and supernatant of AECⅡ(P<0.05).Western blot results showed that 800 μg/mL SiO2 exposure caused an increase in the levels of SP-D,KL-6,and TGF-β1 proteins,while which were ameliorated by Dnase Ⅰ treatment.Conclusion SiO2 exposure results in the escape and release of AECⅡ mtDNA and dysfunction of AECⅡ,thereby leading to the development of pulmonary fibrosis.

Objective:To analyze the trend of colorectal cancer incidence and age changes in cancer registration areas of Jiangsu Province from 2009 to 2019.Methods:Based on the continuous and complete data of 16 cancer registries with qualified quality control in Jiangsu Province from 2009 to 2019, the crude incidence rate, age-standardized incidence rate by Segi World Standard Population (ASIRW), age-specific incidence rate, mean age at onset, standardized mean age at onset, standardized age-specific incidence proportion, and incidence proportion of the population over 60 years old of colorectal cancer were calculated. Joinpoint software was used to calculate the average annual percentage change (AAPC) of crude incidence rate, ASIRW, age-specific incidence rate, and incidence proportion of the population over 60 years, respectively. Birth cohort models were constructed to analyze the incidence of colorectal cancer and its trends in the population born from 1929 to 2019. Linear regression models were used to analyze the correlation between mean age at onset, standardized mean age at onset and the year of onset.Results:From 2009 to 2019, a total of 48 036 new cases of colorectal cancer were collected from 16 cancer registries in Jiangsu Province, including 27 508 males and 20 528 females. The crude incidence rate and ASIRW of colorectal cancer in Jiangsu Province increased from 19.00/100 000 and 12.32/100 000 in 2009 to 33.49/100 000 and 16.75/100 000 in 2019, respectively, showing a significant upward trend (CR: AAPC=5.99%, ASIRW: AAPC=3.54%, P<0.001). The increase of ASIRW was greater in males than that observed in females (males: AAPC=4.31%, females: AAPC=2.34%, P<0.001), and greater in rural areas than in urban areas (rural areas: AAPC=4.03%, urban areas: AAPC=3.13%, P<0.001). The incidence of people over 50 years old increased significantly by year, with the 60~69 age group exhibiting a more rapid increase ( AAPC=4.97%, P<0.05). In the birth cohort, the incidence increased rapidly in the population over 50 years with the passage of birth year, with AAPCs ranging from 1.76% to 7.05% ( P<0.05). From 2009 to 2019, the standardized mean age at onset of colorectal cancer increased by 0.10 years annually. The proportion of standardized age-specific incidence exhibited a trend of increase in older age groups, and the incidence proportion of the population over 60 years old showed a significant yearly increase ( AAPC=0.86%, P<0.001). Conclusion:From 2009 to 2019, the incidence, mean age at onset and the incidence proportion of the population over 60 years old of colorectal cancer in Jiangsu Province could exhibit a rapid upward trend. The increase is particularly pronounced in males and rural areas. Additionally, the age-specific incidence distribution reveals a trend of increase in older age groups. Therefore, targeted adjustments and comprehensive prevention measures should be strengthened.

Objective Disability weight(DW)is a fundamental parameter for accurately estimating the disease burden of a population.Comparing the DW differences between provinces and respondent characteristics can provide a basis for accurately obtaining the disease burden.Methods Probit regression analysis was conducted on the paired comparison data obtained from the Chinese Disability Weight Measurement Study during 2020 to 2021.Pearson's correlation r was used to investigate the relation of probit regression coefficients between respondent's characteristics,as well as provinces.Results Based on the probit regression coefficients of paired comparison data,stratified analysis was conducted on these factors including province,age,gender,education level,income level,medical background,occupation,and disease experience status.All Pearson's correlations(r)of probit coefficients between sub-groups based on respondent's characteristics and provinces were above 0.9(P＜0.001).However,the comparison of health states valuation across different provinces showed regional differences in DW estimates of cardiovascular and circulatory disease,diabetes,neurological disorders,mental,behavioral and substance use disorders,hearing and vision loss,and musculoskeletal disorders.The DW estimates for the health states of"epilepsy,less severe(seizures 1～11 per year)"showed the greatest difference between Xinjiang(DW=0.575)and Henan(DW=0.343)provinces.Conclusion There is a high correlation between respondent's characteristics for probit regression coefficients of health states.The comparison of DW estimates between different provinces indicates some differences in health state preferences among these populations.