Objective:To clarify the effect of the reform of Sichuan medical association on the coordinated development of medical re-sources supply and regional economy,and provide a basis for continuing to promote the coordinated development.Methods:Based on the panel data of 18 prefecture-level cities and 3 autonomous prefectures in Sichuan Province from 2009 to 2021,the medical resources invest-ment and economic development level of each city(state)in Sichuan Province were calculated by entropy weight method.Through the cou-pled coordination model,the degree of coordinated development was measured.The discontinuous time series model is used to measure the impact of the implementation of the medical association policy on the degree of coordinated development.Results:From 2009 to 2021,the supply of medical resources in Sichuan Province showed an overall upward trend,but the characteristics of the first concentration were ob-vious.In 2021,the coupling degree between medical resources investment and economic development in Sichuan Province is high(0.808),but the coupling coordination degree was still in a barely coordinated stage(0.540).The implementation of the reform of medical associa-tion effectively promoted the coordinated development of medical resource supply and regional economy.Conclusion:Local governments need to further strengthen the building of medical associations.By making long-term medical resources planning and exploring the role of digital technology in the medical field,it will further promote the expansion and balanced distribution of high-quality medical resources.

Objective:To clarify the effect of the reform of Sichuan medical association on the coordinated development of medical re-sources supply and regional economy,and provide a basis for continuing to promote the coordinated development.Methods:Based on the panel data of 18 prefecture-level cities and 3 autonomous prefectures in Sichuan Province from 2009 to 2021,the medical resources invest-ment and economic development level of each city(state)in Sichuan Province were calculated by entropy weight method.Through the cou-pled coordination model,the degree of coordinated development was measured.The discontinuous time series model is used to measure the impact of the implementation of the medical association policy on the degree of coordinated development.Results:From 2009 to 2021,the supply of medical resources in Sichuan Province showed an overall upward trend,but the characteristics of the first concentration were ob-vious.In 2021,the coupling degree between medical resources investment and economic development in Sichuan Province is high(0.808),but the coupling coordination degree was still in a barely coordinated stage(0.540).The implementation of the reform of medical associa-tion effectively promoted the coordinated development of medical resource supply and regional economy.Conclusion:Local governments need to further strengthen the building of medical associations.By making long-term medical resources planning and exploring the role of digital technology in the medical field,it will further promote the expansion and balanced distribution of high-quality medical resources.

Objective:To clarify the effect of the reform of Sichuan medical association on the coordinated development of medical re-sources supply and regional economy,and provide a basis for continuing to promote the coordinated development.Methods:Based on the panel data of 18 prefecture-level cities and 3 autonomous prefectures in Sichuan Province from 2009 to 2021,the medical resources invest-ment and economic development level of each city(state)in Sichuan Province were calculated by entropy weight method.Through the cou-pled coordination model,the degree of coordinated development was measured.The discontinuous time series model is used to measure the impact of the implementation of the medical association policy on the degree of coordinated development.Results:From 2009 to 2021,the supply of medical resources in Sichuan Province showed an overall upward trend,but the characteristics of the first concentration were ob-vious.In 2021,the coupling degree between medical resources investment and economic development in Sichuan Province is high(0.808),but the coupling coordination degree was still in a barely coordinated stage(0.540).The implementation of the reform of medical associa-tion effectively promoted the coordinated development of medical resource supply and regional economy.Conclusion:Local governments need to further strengthen the building of medical associations.By making long-term medical resources planning and exploring the role of digital technology in the medical field,it will further promote the expansion and balanced distribution of high-quality medical resources.

Objective:To clarify the effect of the reform of Sichuan medical association on the coordinated development of medical re-sources supply and regional economy,and provide a basis for continuing to promote the coordinated development.Methods:Based on the panel data of 18 prefecture-level cities and 3 autonomous prefectures in Sichuan Province from 2009 to 2021,the medical resources invest-ment and economic development level of each city(state)in Sichuan Province were calculated by entropy weight method.Through the cou-pled coordination model,the degree of coordinated development was measured.The discontinuous time series model is used to measure the impact of the implementation of the medical association policy on the degree of coordinated development.Results:From 2009 to 2021,the supply of medical resources in Sichuan Province showed an overall upward trend,but the characteristics of the first concentration were ob-vious.In 2021,the coupling degree between medical resources investment and economic development in Sichuan Province is high(0.808),but the coupling coordination degree was still in a barely coordinated stage(0.540).The implementation of the reform of medical associa-tion effectively promoted the coordinated development of medical resource supply and regional economy.Conclusion:Local governments need to further strengthen the building of medical associations.By making long-term medical resources planning and exploring the role of digital technology in the medical field,it will further promote the expansion and balanced distribution of high-quality medical resources.

Objective:To clarify the effect of the reform of Sichuan medical association on the coordinated development of medical re-sources supply and regional economy,and provide a basis for continuing to promote the coordinated development.Methods:Based on the panel data of 18 prefecture-level cities and 3 autonomous prefectures in Sichuan Province from 2009 to 2021,the medical resources invest-ment and economic development level of each city(state)in Sichuan Province were calculated by entropy weight method.Through the cou-pled coordination model,the degree of coordinated development was measured.The discontinuous time series model is used to measure the impact of the implementation of the medical association policy on the degree of coordinated development.Results:From 2009 to 2021,the supply of medical resources in Sichuan Province showed an overall upward trend,but the characteristics of the first concentration were ob-vious.In 2021,the coupling degree between medical resources investment and economic development in Sichuan Province is high(0.808),but the coupling coordination degree was still in a barely coordinated stage(0.540).The implementation of the reform of medical associa-tion effectively promoted the coordinated development of medical resource supply and regional economy.Conclusion:Local governments need to further strengthen the building of medical associations.By making long-term medical resources planning and exploring the role of digital technology in the medical field,it will further promote the expansion and balanced distribution of high-quality medical resources.

Objective:To clarify the effect of the reform of Sichuan medical association on the coordinated development of medical re-sources supply and regional economy,and provide a basis for continuing to promote the coordinated development.Methods:Based on the panel data of 18 prefecture-level cities and 3 autonomous prefectures in Sichuan Province from 2009 to 2021,the medical resources invest-ment and economic development level of each city(state)in Sichuan Province were calculated by entropy weight method.Through the cou-pled coordination model,the degree of coordinated development was measured.The discontinuous time series model is used to measure the impact of the implementation of the medical association policy on the degree of coordinated development.Results:From 2009 to 2021,the supply of medical resources in Sichuan Province showed an overall upward trend,but the characteristics of the first concentration were ob-vious.In 2021,the coupling degree between medical resources investment and economic development in Sichuan Province is high(0.808),but the coupling coordination degree was still in a barely coordinated stage(0.540).The implementation of the reform of medical associa-tion effectively promoted the coordinated development of medical resource supply and regional economy.Conclusion:Local governments need to further strengthen the building of medical associations.By making long-term medical resources planning and exploring the role of digital technology in the medical field,it will further promote the expansion and balanced distribution of high-quality medical resources.

Objective:To clarify the effect of the reform of Sichuan medical association on the coordinated development of medical re-sources supply and regional economy,and provide a basis for continuing to promote the coordinated development.Methods:Based on the panel data of 18 prefecture-level cities and 3 autonomous prefectures in Sichuan Province from 2009 to 2021,the medical resources invest-ment and economic development level of each city(state)in Sichuan Province were calculated by entropy weight method.Through the cou-pled coordination model,the degree of coordinated development was measured.The discontinuous time series model is used to measure the impact of the implementation of the medical association policy on the degree of coordinated development.Results:From 2009 to 2021,the supply of medical resources in Sichuan Province showed an overall upward trend,but the characteristics of the first concentration were ob-vious.In 2021,the coupling degree between medical resources investment and economic development in Sichuan Province is high(0.808),but the coupling coordination degree was still in a barely coordinated stage(0.540).The implementation of the reform of medical associa-tion effectively promoted the coordinated development of medical resource supply and regional economy.Conclusion:Local governments need to further strengthen the building of medical associations.By making long-term medical resources planning and exploring the role of digital technology in the medical field,it will further promote the expansion and balanced distribution of high-quality medical resources.

Objective:To clarify the effect of the reform of Sichuan medical association on the coordinated development of medical re-sources supply and regional economy,and provide a basis for continuing to promote the coordinated development.Methods:Based on the panel data of 18 prefecture-level cities and 3 autonomous prefectures in Sichuan Province from 2009 to 2021,the medical resources invest-ment and economic development level of each city(state)in Sichuan Province were calculated by entropy weight method.Through the cou-pled coordination model,the degree of coordinated development was measured.The discontinuous time series model is used to measure the impact of the implementation of the medical association policy on the degree of coordinated development.Results:From 2009 to 2021,the supply of medical resources in Sichuan Province showed an overall upward trend,but the characteristics of the first concentration were ob-vious.In 2021,the coupling degree between medical resources investment and economic development in Sichuan Province is high(0.808),but the coupling coordination degree was still in a barely coordinated stage(0.540).The implementation of the reform of medical associa-tion effectively promoted the coordinated development of medical resource supply and regional economy.Conclusion:Local governments need to further strengthen the building of medical associations.By making long-term medical resources planning and exploring the role of digital technology in the medical field,it will further promote the expansion and balanced distribution of high-quality medical resources.

The main lysosomal protease cathepsin D (cathD) is essential for maintaining tissue homeostasis via its degradative function, and its loss leads to ceroid accumulation in the mammalian nervous system, which results in progressive neurodegeneration. Increasing evidence implies non-proteolytic roles of cathD in regulating various biological processes such as apoptosis, cell proliferation, and migration. Along these lines, we here showed that cathD is required for modulating dendritic architecture in the nervous system independent of its traditional degradative function. Upon cathD depletion, class I and class III arborization (da) neurons in Drosophila larvae exhibited aberrant dendritic morphology, including over-branching, aberrant turning, and elongation defects. Re-introduction of wild-type cathD or its proteolytically-inactive mutant dramatically abolished these morphological defects. Moreover, cathD knockdown also led to dendritic defects in the adult mushroom bodies, suggesting that cathD-mediated processes are required in both the peripheral and central nervous systems. Taken together, our results demonstrate a critical role of cathD in shaping dendritic architecture independent of its proteolytic function.

OBJECTIVE: To investigate the effect of down-regulation of miR-205-5p on 3-bromopyruvate-induced apoptosis in human nasopharyngeal carcinoma CNE2Z cells. METHODS: Nasopharyngeal carcinoma CNE2Z cells were transfected with miR- 205-5p-mimic or miR-205-5p-inhibitor, treated with 80 μmol/L 3-bromopyruvate alone, or exposed to both of the treatments. The proliferation of the treated cells was examined with MTT assay, and early apoptosis of the cells was detected using a mitochondrial membrane potential detection kit (JC-1). DAPI fluorescence staining was used to detect morphological changes of the cell nuclei and late cell apoptosis; Annexin V-FITC/PI double staining was employed to detect the cell apoptosis rate. Western blotting was used to detect the expressions of Bcl-2, Bax, Mcl-1 and Bak proteins. RESULTS: Exposure to 3-bromopyruvate significantly inhibited the proliferation of CNE2Z cells, and increasing the drug concentration and extending the treatment time produced stronger inhibitory effects. Treatment with 80 μmol/L 3-bromopyruvate for 24, 48 and 72 h resulted in inhibition rates of (45.7±1.21)%, (64.4±2.02)% and (78.3±1.55)% in non-transfected CNE2Z cells, respectively; the inhibition rates were (27.7±1.04)%, (34.8±2.10)% and (44.3±1.57)% in the cells transfected with miR-205-5p-mimic, and were (80.5 ± 0.94)%, (87.9 ± 0.50)% and (93.8 ± 1.16)% in cells transfected with miR-205-5p-inhibitor, respectively. The results of mitochondrial membrane potential detection showed that the relative proportion of red and green fluorescence decreased significantly in miR-205-5p-inhibitor-transfected cells with 3-bromopyruvate treatment. Combined treatment of the cells with 3-bromopyruvate and miR-205-5p-inhibitor transfection obviously increased nuclear fragmentation and nuclear pyknosis and significantly increased cell apoptotic rate as compared with the two treatments alone ( < 0.01), causing also decreased expressions of Bcl-2 and Mcl-1 proteins and increased expressions of Bax and Bak proteins. CONCLUSIONS Inhibition of miR-205-5p enhances the proapototic effect of 3-bromopyruvate in CNE2Z cells possibly in relation to the down-regulation of Mcl-1 and Bcl-2 and the up-regulation of Bak and Bax proteins.