Objective To investigate the therapeutic effects of the newly developed phosphodiesterase 5 inhibitor,CPD1,on pathological myocardial hypertrophy induced by abdominal aortic constriction(AAC)in rats,and its impact on activation of the autophagy signaling pathway in myocardial tissue.Methods Male Sprague Dawley rats weighing 180～200 g were divided randomly into five groups:Control,Sham,model(AAC),CPD1 treatment(AAC-CPD1,5 mg/kg),and sildenafil treatment(AAC-Sif,20 mg/kg)groups.Rats in all groups except the Control group underwent blunt dissection of the abdominal aorta at the branch point of the left renal artery.Rats in the AAC and treatment groups also underwent constriction and ligation surgery,while rats in the Sham group underwent dissection without ligation.After 3 days of modeling,rats in the treatment groups received either CPD1 or sildenafil via gavage,while rats in the Control,Sham,and AAC groups received an equal volume of physiological saline by gavage,once daily for 8 weeks.Small-animal ultra-high-resolution echocardiography and left ventricular catheterization were employed to assess left heart function and the heart mass index,and expression levels of the hypertrophy indicator,atrial natriuretic peptide(ANP),the key autophagy pathway factor,p62,and LC3A/B in rat left heart tissue were evaluated by Western blot and reverse transcription-polymerase chain reaction.Results Abdominal aortic stenosis affected left heart function in rats,characterized by an increased cardiac mass index and significant enlargement of myocardial cell cross-sectional area.ANP expression levels in left heart tissue were significantly elevated(P＜0.05),while autophagy signaling activity was reduced,with notable accumulation of LC3Ⅰprotein and reduced conversion to LC3Ⅱ.Expression levels of p62 protein were significantly increased.CPD1 and sildenafil significantly improved left ventricular function in AAC rats,reduced cardiac hypertrophy,inhibited expression levels of ANP and p62 proteins(P＜0.05),activated autophagy signaling,and promoted the conversion of LC3Ⅰ to LC3Ⅱ.Notably,low-dose CPD1 treatment was equivalent to high-dose sildenafil.Conclusions CPD1 promotes the activation of the autophagy signaling pathway in left heart tissue,inhibits the expression of p62 and ANP,reduces the cross-sectional area of myocardial cells,and improves pathological myocardial hypertrophy and left heart function impairment caused by AAC.CPD1 also has the advantage of a lower effective dose compared with sildenafil,offering a new treatment option for pathological myocardial hypertrophy.

Objective:To understand the development status of maternal and child health care institutions in China from 2012 to 2022, identify the challenges they face, and provide references for further promoting the high-quality development of these institutions.Methods:Data from the China Health Statistics Yearbook (2013—2015), China Health and Family Planning Statistics Yearbook (2016—2017), and China Health and Wellness Statistics Yearbook (2018—2023) were used. Descriptive analysis was conducted on the data related to resource allocation and utilization efficiency, service provision, income and expenditure structure, and operational status of maternal and child health care institutions in China from 2012 to 2022, using methods such as fixed-base growth rate, year-on-year growth rate, and average annual growth rate. Results:From 2012 to 2022, the number of maternal and child health care institutions in China decreased from 3 044 to 3 031. In terms of resource allocation, the average annual growth rates of bed numbers and business-use floor area were 5.404% and 10.923%, respectively, while the average annual growth rate of health professionals was 7.183%. Regarding service provision, the average annual growth rates of outpatient visits and inpatient admissions were 3.954% and 1.572%, respectively. In terms of service efficiency, the bed occupancy rate decreased from 76.9% to 53.9%, and the average number of patients seen per physician per day decreased from 8.85 to 7.30. In terms of income and expenditure and operations, the income-expenditure surplus rate decreased from 9.16% to 5.41%, and the debt-to-asset ratio increased from 27.88% to 33.60%. During the same period, the average annual growth rates of bed numbers and business-use floor area in grassroots maternal and child health care institutions were 4.545% and 10.091%, respectively, lower than the national average. The number of outpatient visits increased from 89.03 million to 126.93 million, with an average annual growth rate of 3.610%, while the number of inpatient admissions decreased from 4.19 million to 3.91 million, with an average annual decline of 0.689%. The income-expenditure surplus rate of grassroots institutions decreased from 7.76% to 4.05%, 1.36 percentage points lower than the national level, and the debt-to-asset ratio increased from 27.53% to 36.37%, higher than the overall level.Conclusions:From 2012 to 2022, maternal and child health care institutions in China achieved certain developments in resource allocation and service scale. However, several challenges remain, including unbalanced resource allocation, decreased utilization efficiency, slowed growth in medical service volume, imbalanced income and expenditure structure, increased asset operation risks, and restricted development of grassroots institutions. It is recommended that relevant management departments and maternal and child health care institutions optimize resource allocation, plan for service transformation and upgrading, expand income sources, strengthen internal financial control, and reinforce the construction of high-quality and efficient maternal and child health care systems to promote the high-quality development of maternal and child health care institutions in China.

BACKGROUND:Degeneration of nucleus pulposus cells is a key component of intervertebral disc degeneration.Ferroptosis,a novel form of programmed cell death,is closely associated with the onset and progression of intervertebral disc degeneration;however,its precise mechanisms remain unclear.OBJECTIVE:To establish an oxidative stress model in vitro by inducing ferroptosis in nucleus pulposus cells using tert-butyl hydroperoxide and to investigate the mechanisms of tert-butyl hydroperoxide-induced ferroptosis in nucleus pulposus cells,thereby elucidating the role of ferroptosis in the pathogenesis of intervertebral disc degeneration.METHODS:Nucleus pulposus cells were treated with varying concentrations of tert-butyl hydroperoxide(0,25,50,100,and 200 μmol/L),and cell morphology and viability were assessed using fluorescence microscopy and the cell counting kit-8 assay.Interventions with 100 μmol/L tert-butyl hydroperoxide,10 μmol/L RSL3,or dimethylsulfoxide were applied to nucleus pulposus cells,and cell proliferation was evaluated using the EdU assay.The expression levels of ferroptosis-related proteins(glutathione peroxidase 4,ferritin heavy chain 1,PTGS2,and ACSL4)and intervertebral disc degeneration marker proteins(matrix metalloproteinase 13 and Col2A)were analyzed via western blot and immunofluorescence.Additionally,reactive oxygen species and lipid peroxidation levels were quantified using the reactive oxygen species detection kit and C11-BODIPY probe.Mitochondrial morphological changes were observed under transmission electron microscopy.RESULTS AND CONCLUSION:(1)tert-Butyl hydroperoxide treatment significantly reduced the viability and proliferation of nucleus pulposus cells.(2)tert-Butyl hydroperoxide induced typical ferroptosis-related morphological changes in nucleus pulposus cells.(3)tert-Butyl hydroperoxide exposure led to a decrease in the expression of ferroptosis-suppressing proteins glutathione peroxidase 4 and ferritin heavy chain 1,while increasing the expression of ferroptosis-promoting factors ACSL4 and PTGS2.(4)tert-Butyl hydroperoxide elevated intracellular reactive oxygen species production and lipid peroxidation levels in nucleus pulposus cells.(5)Transmission electron microscopy revealed ferroptosis-specific mitochondrial changes in nucleus pulposus cells treated with tert-butyl hydroperoxide,including contraction,reduced cristae,and increased membrane density.(6)tert-Butyl hydroperoxide treatment also resulted in the increased expression of matrix metalloproteinase 13 and decreased expression of Col2A in nucleus pulposus cells.In conclusion,tert-butyl hydroperoxide induces ferroptosis in nucleus pulposus cells,contributing to the development of intervertebral disc degeneration.This process may represent a key pathological mechanism in intervertebral disc degeneration and offers potential targets for developing novel therapeutic strategies.

Objective:To understand the development status of maternal and child health care institutions in China from 2012 to 2022, identify the challenges they face, and provide references for further promoting the high-quality development of these institutions.Methods:Data from the China Health Statistics Yearbook (2013—2015), China Health and Family Planning Statistics Yearbook (2016—2017), and China Health and Wellness Statistics Yearbook (2018—2023) were used. Descriptive analysis was conducted on the data related to resource allocation and utilization efficiency, service provision, income and expenditure structure, and operational status of maternal and child health care institutions in China from 2012 to 2022, using methods such as fixed-base growth rate, year-on-year growth rate, and average annual growth rate. Results:From 2012 to 2022, the number of maternal and child health care institutions in China decreased from 3 044 to 3 031. In terms of resource allocation, the average annual growth rates of bed numbers and business-use floor area were 5.404% and 10.923%, respectively, while the average annual growth rate of health professionals was 7.183%. Regarding service provision, the average annual growth rates of outpatient visits and inpatient admissions were 3.954% and 1.572%, respectively. In terms of service efficiency, the bed occupancy rate decreased from 76.9% to 53.9%, and the average number of patients seen per physician per day decreased from 8.85 to 7.30. In terms of income and expenditure and operations, the income-expenditure surplus rate decreased from 9.16% to 5.41%, and the debt-to-asset ratio increased from 27.88% to 33.60%. During the same period, the average annual growth rates of bed numbers and business-use floor area in grassroots maternal and child health care institutions were 4.545% and 10.091%, respectively, lower than the national average. The number of outpatient visits increased from 89.03 million to 126.93 million, with an average annual growth rate of 3.610%, while the number of inpatient admissions decreased from 4.19 million to 3.91 million, with an average annual decline of 0.689%. The income-expenditure surplus rate of grassroots institutions decreased from 7.76% to 4.05%, 1.36 percentage points lower than the national level, and the debt-to-asset ratio increased from 27.53% to 36.37%, higher than the overall level.Conclusions:From 2012 to 2022, maternal and child health care institutions in China achieved certain developments in resource allocation and service scale. However, several challenges remain, including unbalanced resource allocation, decreased utilization efficiency, slowed growth in medical service volume, imbalanced income and expenditure structure, increased asset operation risks, and restricted development of grassroots institutions. It is recommended that relevant management departments and maternal and child health care institutions optimize resource allocation, plan for service transformation and upgrading, expand income sources, strengthen internal financial control, and reinforce the construction of high-quality and efficient maternal and child health care systems to promote the high-quality development of maternal and child health care institutions in China.

Objective To investigate the therapeutic effects of the newly developed phosphodiesterase 5 inhibitor,CPD1,on pathological myocardial hypertrophy induced by abdominal aortic constriction(AAC)in rats,and its impact on activation of the autophagy signaling pathway in myocardial tissue.Methods Male Sprague Dawley rats weighing 180～200 g were divided randomly into five groups:Control,Sham,model(AAC),CPD1 treatment(AAC-CPD1,5 mg/kg),and sildenafil treatment(AAC-Sif,20 mg/kg)groups.Rats in all groups except the Control group underwent blunt dissection of the abdominal aorta at the branch point of the left renal artery.Rats in the AAC and treatment groups also underwent constriction and ligation surgery,while rats in the Sham group underwent dissection without ligation.After 3 days of modeling,rats in the treatment groups received either CPD1 or sildenafil via gavage,while rats in the Control,Sham,and AAC groups received an equal volume of physiological saline by gavage,once daily for 8 weeks.Small-animal ultra-high-resolution echocardiography and left ventricular catheterization were employed to assess left heart function and the heart mass index,and expression levels of the hypertrophy indicator,atrial natriuretic peptide(ANP),the key autophagy pathway factor,p62,and LC3A/B in rat left heart tissue were evaluated by Western blot and reverse transcription-polymerase chain reaction.Results Abdominal aortic stenosis affected left heart function in rats,characterized by an increased cardiac mass index and significant enlargement of myocardial cell cross-sectional area.ANP expression levels in left heart tissue were significantly elevated(P＜0.05),while autophagy signaling activity was reduced,with notable accumulation of LC3Ⅰprotein and reduced conversion to LC3Ⅱ.Expression levels of p62 protein were significantly increased.CPD1 and sildenafil significantly improved left ventricular function in AAC rats,reduced cardiac hypertrophy,inhibited expression levels of ANP and p62 proteins(P＜0.05),activated autophagy signaling,and promoted the conversion of LC3Ⅰ to LC3Ⅱ.Notably,low-dose CPD1 treatment was equivalent to high-dose sildenafil.Conclusions CPD1 promotes the activation of the autophagy signaling pathway in left heart tissue,inhibits the expression of p62 and ANP,reduces the cross-sectional area of myocardial cells,and improves pathological myocardial hypertrophy and left heart function impairment caused by AAC.CPD1 also has the advantage of a lower effective dose compared with sildenafil,offering a new treatment option for pathological myocardial hypertrophy.

BACKGROUND:Degeneration of nucleus pulposus cells is a key component of intervertebral disc degeneration.Ferroptosis,a novel form of programmed cell death,is closely associated with the onset and progression of intervertebral disc degeneration;however,its precise mechanisms remain unclear.OBJECTIVE:To establish an oxidative stress model in vitro by inducing ferroptosis in nucleus pulposus cells using tert-butyl hydroperoxide and to investigate the mechanisms of tert-butyl hydroperoxide-induced ferroptosis in nucleus pulposus cells,thereby elucidating the role of ferroptosis in the pathogenesis of intervertebral disc degeneration.METHODS:Nucleus pulposus cells were treated with varying concentrations of tert-butyl hydroperoxide(0,25,50,100,and 200 μmol/L),and cell morphology and viability were assessed using fluorescence microscopy and the cell counting kit-8 assay.Interventions with 100 μmol/L tert-butyl hydroperoxide,10 μmol/L RSL3,or dimethylsulfoxide were applied to nucleus pulposus cells,and cell proliferation was evaluated using the EdU assay.The expression levels of ferroptosis-related proteins(glutathione peroxidase 4,ferritin heavy chain 1,PTGS2,and ACSL4)and intervertebral disc degeneration marker proteins(matrix metalloproteinase 13 and Col2A)were analyzed via western blot and immunofluorescence.Additionally,reactive oxygen species and lipid peroxidation levels were quantified using the reactive oxygen species detection kit and C11-BODIPY probe.Mitochondrial morphological changes were observed under transmission electron microscopy.RESULTS AND CONCLUSION:(1)tert-Butyl hydroperoxide treatment significantly reduced the viability and proliferation of nucleus pulposus cells.(2)tert-Butyl hydroperoxide induced typical ferroptosis-related morphological changes in nucleus pulposus cells.(3)tert-Butyl hydroperoxide exposure led to a decrease in the expression of ferroptosis-suppressing proteins glutathione peroxidase 4 and ferritin heavy chain 1,while increasing the expression of ferroptosis-promoting factors ACSL4 and PTGS2.(4)tert-Butyl hydroperoxide elevated intracellular reactive oxygen species production and lipid peroxidation levels in nucleus pulposus cells.(5)Transmission electron microscopy revealed ferroptosis-specific mitochondrial changes in nucleus pulposus cells treated with tert-butyl hydroperoxide,including contraction,reduced cristae,and increased membrane density.(6)tert-Butyl hydroperoxide treatment also resulted in the increased expression of matrix metalloproteinase 13 and decreased expression of Col2A in nucleus pulposus cells.In conclusion,tert-butyl hydroperoxide induces ferroptosis in nucleus pulposus cells,contributing to the development of intervertebral disc degeneration.This process may represent a key pathological mechanism in intervertebral disc degeneration and offers potential targets for developing novel therapeutic strategies.

Evidence indicates that metabolic reprogramming characterized by the changes in cellular metabolic patterns contributes to the pathogenesis of pulmonary fibrosis(PF).It is considered as a promising ther-apeutic target anti-PF.The well-documented against PF properties of Tanshinone ⅡA(Tan ⅡA)have been primarily attributed to its antioxidant and anti-inflammatory potency.Emerging evidence suggests that TanⅡA may target energy metabolism pathways,including glycolysis and tricarboxylic acid(TCA)cycle.However,the detailed and advanced mechanisms underlying the anti-PF activities remain obscure.In this study,we applied[U-13C]-glucose metabolic flux analysis(MFA)to examine metabolism flux disruption and modulation nodes of Tan ⅡA in PF.We identified that Tan ⅡA inhibited the glycolysis and TCA flux,thereby suppressing the production of transforming growth factor-β1(TGF-β1)-dependent extracellular matrix and the differentiation and proliferation of myofibroblasts in vitro.We further revealed that Tan ⅡA inhibited the expression of key metabolic enzyme hexokinase 2(HK2)by inhibiting phosphoinositide 3-kinase(PI3K)/protein kinase B(Akt)/mammalian target of rapamycin(mTOR)/hypoxia-inducible factor 1α(HIF-1α)pathway activities,which decreased the accumulation of abnormal metabolites.Notably,we demonstrated that Tan ⅡA inhibited ATP citrate lyase(ACLY)activity,which reduced the collagen synthesis pathway caused by cytosol citrate consumption.Further,these results were validated in a mouse model of bleomycin-induced PF.This study was novel in exploring the mechanism of the occurrence and develop-ment of Tan ⅡA in treating PF using 13C-MFA technology.It provided a novel understanding of the mechanism of Tan ⅡA against PF from the perspective of metabolic reprogramming.

Objective:To analyze the allocation of general practitioners per 10 000 population in China and its influencing factors, so as to provide reference for optimizing the allocation of general practitioners resources in China.Methods:The number of general practitioners per 10 000 population and other relevant data of 31 provinces (except Hong Kong, Macao and Taiwan) in China from 2012 to 2021 were collected from China Statistical Yearbook, China Health Statistics Yearbook, China Health and Family Planning Statistical Yearbook. The geographical area data of 31 provinces (except Hong Kong, Macao and Taiwan) from 2012 to 2021 were retrieved from the website of the Central People ′s Government. The influencing factors of the number of general practitioners per 10 000 population were preset by literature analysis and unstructured interview. Taking the number of general practitioners per 10 000 population as the dependent variable, the correlation between it and the preset influencing factors was analyzed by panel data regression. Results:From 2012 to 2021, the average annual growth rate of the number of general practitioners per 10 000 population in each province of China was greater than 0. The factors affecting the number of general practitioners per 10 000 population included the number of people per square kilometer ( r=3.818, P<0.01), the number of beds in medical and health institutions per capita ( r=2.135, P<0.01), the proportion of the elderly population aged 65 and above ( r=0.180, P<0.01), and the proportion of total expenditure in medical and health institutions to gross domestic product ( r=0.080, P<0.01). Conclusions:The development trend of general practitioners resources allocation in China is good, but the government needs to integrate the population agglomeration and aging trend, the allocation of medical and health resources, the investment support for the development of general practitioners and other influencing factors, optimize the allocation of general practitioners resources according to local conditions, and strengthen policy support for areas and links where the allocation of general practitioners resources is relatively weak.

Objective:To analyze the allocation of general practitioners per 10 000 population in China and its influencing factors, so as to provide reference for optimizing the allocation of general practitioners resources in China.Methods:The number of general practitioners per 10 000 population and other relevant data of 31 provinces (except Hong Kong, Macao and Taiwan) in China from 2012 to 2021 were collected from China Statistical Yearbook, China Health Statistics Yearbook, China Health and Family Planning Statistical Yearbook. The geographical area data of 31 provinces (except Hong Kong, Macao and Taiwan) from 2012 to 2021 were retrieved from the website of the Central People ′s Government. The influencing factors of the number of general practitioners per 10 000 population were preset by literature analysis and unstructured interview. Taking the number of general practitioners per 10 000 population as the dependent variable, the correlation between it and the preset influencing factors was analyzed by panel data regression. Results:From 2012 to 2021, the average annual growth rate of the number of general practitioners per 10 000 population in each province of China was greater than 0. The factors affecting the number of general practitioners per 10 000 population included the number of people per square kilometer ( r=3.818, P<0.01), the number of beds in medical and health institutions per capita ( r=2.135, P<0.01), the proportion of the elderly population aged 65 and above ( r=0.180, P<0.01), and the proportion of total expenditure in medical and health institutions to gross domestic product ( r=0.080, P<0.01). Conclusions:The development trend of general practitioners resources allocation in China is good, but the government needs to integrate the population agglomeration and aging trend, the allocation of medical and health resources, the investment support for the development of general practitioners and other influencing factors, optimize the allocation of general practitioners resources according to local conditions, and strengthen policy support for areas and links where the allocation of general practitioners resources is relatively weak.

OBJECTIVE To provide reference for chronic disease management in grass-root institution . METHODS System structure design and audit class setting of the regional pretrial center in Changning district of Shanghai were introduced. The number of prescriptions/medical orders from the start of application to February 28，2022 were counted. The prescriptions/medical orders intercepted by the system ，prescriptions/medical orders intervened by physicians ，chronic disease types and drug use of regional multiple chronic diseases were counted and analyzed. RESULTS Compared with the data when the center was on line in September 2021，total qualified rate of prescriptions/medical orders （97.67％ vs. 86.42％）significantly increased ，the number of prescriptions/ medical orders intercepted by the system and intervened by physicians decreased by 55.39％ and 72.67％ in February 2022， respectively. The top five diseases were hypertension （26.52％），coronary heart disease （20.53％），sleep disorders （16.71％），diabetes（15.24％）and bone diseases （14.09％）. Among them ， there were many problematic prescriptions involving coronary heart disease ，sleep disorder and bone disease. CONCLUSIONS The incidence of chronic diseases among community residents remains high. In addition to common chronic diseases such as coronary heart disease ，hypertension and diabetes ，the incidence of sleep disorders and bone diseases is also increasing. With the help of the regional pretrial center ，the focus of chronic disease management can be adjusted timely ，drug supervision can be carried out in real time so as to improve the level of rational drug use in grass-root institution.