Purpose To evaluate the value of tumors invasion in the central airway(TICA)in predicting the severe immune checkpoint inhibitor-related pneumonitis(S-CIP)in lung cancer patients using propensity score matching(PSM).Materials and Methods The intact data of 162 consecutive lung cancer patients who received treatment with immune checkpoint inhibitors in Xi'an International Medical Center Hospital from September 2019 to March 2022 were retrospectively collected.Patients were divided into S-CIP group(23 cases)and non-S-CIP group(139 cases)according to the presence of S-CIP.The demographic information of the patients,including gender,age,history of smoking,thoracic radiotherapy histology,baseline lung diseases,classification,TNM stage,tumor location as well as TICA were collected.A binary Logistic regression was used to analyze the confounding factors and independent risk factors of S-CIP and to predict the development of S-CIP.A 1:1 matching was performed by the nearest neighbor method for PSM.The PSM was used to pair the two groups,and the value of TICA in predicting S-CIP before and after PSM was compared.The receiver operating characteristic curve and the area under the curve were used for model performance based on TICA.Results Before PSM,the proportion of baseline lung diseases(78.3%vs.32.4%,OR=6.802,P=0.001),thoracic radiotherapy history(69.6%vs.30.2%,OR=5.300,P=0.002)and TICA(65.2%vs.27.3%,OR=5.882,P=0.001)in the S-CIP group was higher than those in the non-S-CIP group,and were independent risk factor for predicting S-CIP.After PSM,20 patients were included in each group.The presence of TICA was higher in S-CIP group than that in the non-S-CIP group(60.0%vs.20.0%,OR=6.000,P=0.013).The area under the curves of Logistic regression model based on TICA was 0.700(95%CI 0.534-0.866).Conclusion TICA is an independent risk factor for development of S-CIP,which has moderate degree of accuracy in predicting S-CIP,can be used for risk prediction and early intervention to reduce the poor prognosis of S-CIP patients.

Objective Summarize and analyze the core issues in the process of the"three medics"linkage reform in China,and provide optimized paths and countermeasure suggestions for the coordinated development and governance of the"three medics".Methods The problem list of the"three medics"linkage reform in China was summarized through literature analysis and boundary analysis method.The problem system was constructed based on the macro model of the health system,and the prob-lem evaluation was conducted by using the social network analysis method and the entropy weight Topsis method.Results The problem list can be summarized into 4 major categories,with a total of 45 problem topics.Among them,there are 5 items in the external submodule category,18 items in the structure category,17 items in the process category,and 5 items in the result cate-gory.The total frequency proportions are 16.22％,27.15％,43.68％,and 12.95％ respectively.Among the process-related problem themes,"excessive medical treatment"has the highest attention,the entropy weight Topsis comprehensive evaluation value of"lagging information system construction"is the highest,and"insufficient cross-departmental collaboration"is closest to the centrality value and has the greatest correlation.Conclusion Guided by the framework of the theory of holistic governance,it is urgently necessary to construct an information system for the coordinated development of the"three medics",reshape the mechanisms of leadership decision-making,data linkage and information collaboration,and enhance the synergy among depart-ments.Taking the reform of medical service prices as the starting point,by improving the value-oriented medical insurance pay-ment mechanism,the compensation mechanism of public hospitals,the salary system,etc.,we promote the compatibility of in-centives among multiple subjects and form a closed loop of coordinated development of the"three medics"sectors.

County medical community serves as pivotal instruments for the hierarchical diagnostic and treatment system. Since their nationwide implementation in December 2023, there has been a pressing demand for governance theories to direct practical applications. Based on polycentric-collaborative governance theory, this study articulated a framework that modeled county medical community as accountable care organizations, anchored by a foundation of primary health care and a polycentric-collaborative governance structure. The framework encompassed critical dimensions, including problem orientation, diverse governance actors, multi-dimensional governance mechanisms, governance objectives, and evaluative metrics. This research also introduced 17 governance instruments, delineated 13 priority action fields, and pinpointed 5 potential reform areas, with a pronounced focus on bolstering governance capacity through value-based payment reforms and technological underpinnings of digital innovation. The framework′s viability and efficacy have been substantiated through a case study in Zhejiang Province. The framework presented herein could offer a comprehensive and systematic guide for county medical community practice, capturing the essence of the reform through a problem-oriented lens, fostering multi-actor involvement, and ensuring the harmonization of multi-dimensional governance mechanisms, thereby fortifying the reform′s systematic, integrative, and collaborative attributes.

Chemotherapy is currently the mainstay of systemic management for triple-negative breast cancer (TNBC), but chemoresistance significantly impacts patient outcomes. Our research indicates that Doxorubicin (Dox)-resistant TNBC cells exhibit increased glycolysis and ATP generation compared to their parental cells, with this metabolic shift contributing to chemoresistance. We discovered that ALKBH3, an m¹A demethylase enzyme, is crucial in regulating the enhanced glycolysis in Dox-resistant TNBC cells. Knocking down ALKBH3 reduced ATP generation, glucose consumption, and lactate production, implicating its involvement in mediating glycolysis. Further investigation revealed that aldolase A (ALDOA), a key enzyme in glycolysis, is a downstream target of ALKBH3. ALKBH3 regulates ALDOA mRNA stability through m¹A demethylation at the 3'-untranslated region (3'UTR). This methylation negatively affects ALDOA mRNA stability by recruiting the YTHDF2/PAN2-PAN3 complex, leading to mRNA degradation. The ALKBH3/ALDOA axis promotes Dox resistance both in vitro and in vivo. Clinical analysis demonstrated that ALKBH3 and ALDOA are upregulated in breast cancer tissues, and higher expression of these proteins is associated with reduced overall survival in TNBC patients. Our study highlights the role of the ALKBH3/ALDOA axis in contributing to Dox resistance in TNBC cells through regulation of ALDOA mRNA stability and glycolysis.

Objective To investigate the anti-tumor mechanism of natural compound toosendanin(TSN)combined with olaparib in triple-negative breast cancer(TNBC).Methods Human TNBC cell line MDA-MB-231 was cultured in vitro.Effects of TSN combined with olaparib on autophagy levels and cell viability in MDA-MB-231 cells were evaluated using 0.5,1.0,and 5.0 μmol/L olaparib alone or in combination.Surgical specimens from four TNBC patients who had residual tumors after neoadjuvant chemotherapy were selected to establish patient-derived organoid(PDO)models.The drug sensitivity of TSN combined with olaparib in TNBC patients was detected.Whether TSN combined with olaparib can exert autophagy inhibitory effects and tumor-killing effects in organoid model was verified.Results Olaparib induced autophagy in MDA-MB-231 cell line,and the combination of TSN and olaparib inhibited the proliferation of MDA-MB-231 cells(P＜0.01).In the TNBC PDOs model,the therapeutic effect of olaparib combined with TSN can significantly reduce the proliferation ability of tumor cells compared with olaparib alone.Conclusion The tumor-killing effect of TSN combined with olaparib is superior to that of olaparib alone,and the mechanism may be related to autophagy inhibition.

Objective To analyze the incidence of biliary complications in patients with cholecystolithiasis and calculus of common bile duct after laparoscopic common bile duct exploration(LCBDE)with one-stage suture,and explore the high-risk factors of its occurrence,and then put forward targeted prevention strategies.Methods The clinical data of 201 patients with cholecystolithiasis and calculus of common bile duct after LCBDE with one-stage suture in our hospital from January 2020 to April 2024 were retrospectively analyzed.After 3 months of follow-up,the incidence of postoperative biliary complications was observed,and the clinical data of patients in the biliary complications group and the non-biliary complications group were analyzed.The factors with statistically significant differences were included in the multivariate Logistic regression model to analyze the independent risk factors affecting the occurrence of patients with cholecystolithiasis and calculus of common bile duct after LCBDE with one-stage suture.Results Among the 201 patients,12 had biliary tract infection,5 had common bile duct stenosis,and 13 had bile leakage.The total incidence of biliary complications was 14.93%(30/201).Multivariate Logistic regression analysis showed that diabetes mellitus((OR)=1.092,95%CI:1.040～1.147),common bile duct diameter<1 cm((OR)=1.097,95%CI:1.053～1.144),stone incarceration at the lower end of common bile duct((OR)=1.120,95%CI:1.062～1.180),Calot triangle adhesion((OR)=1.099,95%CI:1.042～1.158),bile turbidity((OR)=1.082,95%CI:1.043～1.123)and operation time≥2 h((OR)=1.090,95%CI:1.044～1.138)were independent risk factors for patients with cholecystolithiasis and calculus of common bile duct after LCBDE with one-stage suture(P<0.05).Conclusion The risk of patients with cholecystolithiasis and calculus of common bile duct after LCBDE with one-stage suture is high.The occurrence of complications is related to diabetes mellitus,common bile duct diameter<1 cm,stone incarceration at the lower end of the common bile duct,Calot triangle adhesion,bile turbidity and operation time≥2 h.Targeted prevention strategies can be formulated clinically to prevent the occurrence of biliary complications.

Objective To analyze the incidence of biliary complications in patients with cholecystolithiasis and calculus of common bile duct after laparoscopic common bile duct exploration(LCBDE)with one-stage suture,and explore the high-risk factors of its occurrence,and then put forward targeted prevention strategies.Methods The clinical data of 201 patients with cholecystolithiasis and calculus of common bile duct after LCBDE with one-stage suture in our hospital from January 2020 to April 2024 were retrospectively analyzed.After 3 months of follow-up,the incidence of postoperative biliary complications was observed,and the clinical data of patients in the biliary complications group and the non-biliary complications group were analyzed.The factors with statistically significant differences were included in the multivariate Logistic regression model to analyze the independent risk factors affecting the occurrence of patients with cholecystolithiasis and calculus of common bile duct after LCBDE with one-stage suture.Results Among the 201 patients,12 had biliary tract infection,5 had common bile duct stenosis,and 13 had bile leakage.The total incidence of biliary complications was 14.93%(30/201).Multivariate Logistic regression analysis showed that diabetes mellitus((OR)=1.092,95%CI:1.040～1.147),common bile duct diameter<1 cm((OR)=1.097,95%CI:1.053～1.144),stone incarceration at the lower end of common bile duct((OR)=1.120,95%CI:1.062～1.180),Calot triangle adhesion((OR)=1.099,95%CI:1.042～1.158),bile turbidity((OR)=1.082,95%CI:1.043～1.123)and operation time≥2 h((OR)=1.090,95%CI:1.044～1.138)were independent risk factors for patients with cholecystolithiasis and calculus of common bile duct after LCBDE with one-stage suture(P<0.05).Conclusion The risk of patients with cholecystolithiasis and calculus of common bile duct after LCBDE with one-stage suture is high.The occurrence of complications is related to diabetes mellitus,common bile duct diameter<1 cm,stone incarceration at the lower end of the common bile duct,Calot triangle adhesion,bile turbidity and operation time≥2 h.Targeted prevention strategies can be formulated clinically to prevent the occurrence of biliary complications.

Objective To investigate the anti-tumor mechanism of natural compound toosendanin(TSN)combined with olaparib in triple-negative breast cancer(TNBC).Methods Human TNBC cell line MDA-MB-231 was cultured in vitro.Effects of TSN combined with olaparib on autophagy levels and cell viability in MDA-MB-231 cells were evaluated using 0.5,1.0,and 5.0 μmol/L olaparib alone or in combination.Surgical specimens from four TNBC patients who had residual tumors after neoadjuvant chemotherapy were selected to establish patient-derived organoid(PDO)models.The drug sensitivity of TSN combined with olaparib in TNBC patients was detected.Whether TSN combined with olaparib can exert autophagy inhibitory effects and tumor-killing effects in organoid model was verified.Results Olaparib induced autophagy in MDA-MB-231 cell line,and the combination of TSN and olaparib inhibited the proliferation of MDA-MB-231 cells(P＜0.01).In the TNBC PDOs model,the therapeutic effect of olaparib combined with TSN can significantly reduce the proliferation ability of tumor cells compared with olaparib alone.Conclusion The tumor-killing effect of TSN combined with olaparib is superior to that of olaparib alone,and the mechanism may be related to autophagy inhibition.

Purpose To evaluate the value of tumors invasion in the central airway(TICA)in predicting the severe immune checkpoint inhibitor-related pneumonitis(S-CIP)in lung cancer patients using propensity score matching(PSM).Materials and Methods The intact data of 162 consecutive lung cancer patients who received treatment with immune checkpoint inhibitors in Xi'an International Medical Center Hospital from September 2019 to March 2022 were retrospectively collected.Patients were divided into S-CIP group(23 cases)and non-S-CIP group(139 cases)according to the presence of S-CIP.The demographic information of the patients,including gender,age,history of smoking,thoracic radiotherapy histology,baseline lung diseases,classification,TNM stage,tumor location as well as TICA were collected.A binary Logistic regression was used to analyze the confounding factors and independent risk factors of S-CIP and to predict the development of S-CIP.A 1:1 matching was performed by the nearest neighbor method for PSM.The PSM was used to pair the two groups,and the value of TICA in predicting S-CIP before and after PSM was compared.The receiver operating characteristic curve and the area under the curve were used for model performance based on TICA.Results Before PSM,the proportion of baseline lung diseases(78.3%vs.32.4%,OR=6.802,P=0.001),thoracic radiotherapy history(69.6%vs.30.2%,OR=5.300,P=0.002)and TICA(65.2%vs.27.3%,OR=5.882,P=0.001)in the S-CIP group was higher than those in the non-S-CIP group,and were independent risk factor for predicting S-CIP.After PSM,20 patients were included in each group.The presence of TICA was higher in S-CIP group than that in the non-S-CIP group(60.0%vs.20.0%,OR=6.000,P=0.013).The area under the curves of Logistic regression model based on TICA was 0.700(95%CI 0.534-0.866).Conclusion TICA is an independent risk factor for development of S-CIP,which has moderate degree of accuracy in predicting S-CIP,can be used for risk prediction and early intervention to reduce the poor prognosis of S-CIP patients.

Objective Summarize and analyze the core issues in the process of the"three medics"linkage reform in China,and provide optimized paths and countermeasure suggestions for the coordinated development and governance of the"three medics".Methods The problem list of the"three medics"linkage reform in China was summarized through literature analysis and boundary analysis method.The problem system was constructed based on the macro model of the health system,and the prob-lem evaluation was conducted by using the social network analysis method and the entropy weight Topsis method.Results The problem list can be summarized into 4 major categories,with a total of 45 problem topics.Among them,there are 5 items in the external submodule category,18 items in the structure category,17 items in the process category,and 5 items in the result cate-gory.The total frequency proportions are 16.22％,27.15％,43.68％,and 12.95％ respectively.Among the process-related problem themes,"excessive medical treatment"has the highest attention,the entropy weight Topsis comprehensive evaluation value of"lagging information system construction"is the highest,and"insufficient cross-departmental collaboration"is closest to the centrality value and has the greatest correlation.Conclusion Guided by the framework of the theory of holistic governance,it is urgently necessary to construct an information system for the coordinated development of the"three medics",reshape the mechanisms of leadership decision-making,data linkage and information collaboration,and enhance the synergy among depart-ments.Taking the reform of medical service prices as the starting point,by improving the value-oriented medical insurance pay-ment mechanism,the compensation mechanism of public hospitals,the salary system,etc.,we promote the compatibility of in-centives among multiple subjects and form a closed loop of coordinated development of the"three medics"sectors.