This study explored the effect of the Mycobacterium tuberculosis(Mtb)PE/PPE family protein PE_PGRS37 on the growth of Mycobacterium smegmatis(Ms)and macrophage autophagy during Mtb infection.The pe_pgrs37 gene was amplified from Mtb genome through PCR,and the recombinant vector pAIN-PE_PGRS37 was successfully constructed through homologous recombi-nation.pAIN-PE_PGRS37 and pAIN were integrated into Ms through electroshock to construct pAIN-PGRS37/Ms and pAIN/Ms re-combinant bacteria.Western blotting indicated that the PE_PGRS37 protein was correctly expressed in pAIN-PE_PGRS37/Ms.The re-combinant bacteria were inoculated in 7H9/7H10 medium,and their colony morphology and growth curves were observed.No signifi-cant difference in colony morphology was observed between pAIN-PE_PGRS37/Ms and pAIN/Ms.The growth rate significantly in-creased between 10 and 16 h,and a plateau was reached at 26 h.After infection of U937 cells with pAIN-PE_PGRS37/Ms and pAIN/Ms,macrophage autophagy flow was detected with western blotting and immunofluorescence.In the pAIN-PE_PGRS37/Ms-infected group,compared with the pAIN/Ms-infected group,macrophage LC3-II and p62 protein expression was significantly up-regulated(P<0.001)and inhibited autophagosome and lysosome fusion.The intracellular survival of the recombinant bacteria was detected through colony counting,and pAIN-PE_PGRS37/Ms showed significantly greater survival in macrophages at 12 h,24 h,and 48 h than pAIN/Ms(P<0.05).Our results suggested that PE_PGRS37 protein promotes Mycobacterium survival in macrophages by blocking macro-phage autophagy flow,thus inhibiting macrophage autophagy.

This study explored the effect of the Mycobacterium tuberculosis(Mtb)PE/PPE family protein PE_PGRS37 on the growth of Mycobacterium smegmatis(Ms)and macrophage autophagy during Mtb infection.The pe_pgrs37 gene was amplified from Mtb genome through PCR,and the recombinant vector pAIN-PE_PGRS37 was successfully constructed through homologous recombi-nation.pAIN-PE_PGRS37 and pAIN were integrated into Ms through electroshock to construct pAIN-PGRS37/Ms and pAIN/Ms re-combinant bacteria.Western blotting indicated that the PE_PGRS37 protein was correctly expressed in pAIN-PE_PGRS37/Ms.The re-combinant bacteria were inoculated in 7H9/7H10 medium,and their colony morphology and growth curves were observed.No signifi-cant difference in colony morphology was observed between pAIN-PE_PGRS37/Ms and pAIN/Ms.The growth rate significantly in-creased between 10 and 16 h,and a plateau was reached at 26 h.After infection of U937 cells with pAIN-PE_PGRS37/Ms and pAIN/Ms,macrophage autophagy flow was detected with western blotting and immunofluorescence.In the pAIN-PE_PGRS37/Ms-infected group,compared with the pAIN/Ms-infected group,macrophage LC3-II and p62 protein expression was significantly up-regulated(P<0.001)and inhibited autophagosome and lysosome fusion.The intracellular survival of the recombinant bacteria was detected through colony counting,and pAIN-PE_PGRS37/Ms showed significantly greater survival in macrophages at 12 h,24 h,and 48 h than pAIN/Ms(P<0.05).Our results suggested that PE_PGRS37 protein promotes Mycobacterium survival in macrophages by blocking macro-phage autophagy flow,thus inhibiting macrophage autophagy.

Pontine autosomal dominant microangiopathy and leukoencephalopathy (PADMAL) is an extremely rare autosomal dominant cerebral small vessel disease. Since the discovery of the pathogenic gene COL4A1, several PADMAL pedigrees have been reported in recent years. The pathogenesis of PADMAL is due to the increased formation of type Ⅳ collagen caused by mutation of the 3′ untranslated region of COL4A1. Abnormal accumulation of collagen in the extracellular matrix leads to thickening of the basement membrane and narrowing of the lumen. Patients present with recurrent lacunar infarction at early stage, and cognitive impairment may occur as the disease progresses. The main imaging changes of PADMAL are multiple lacunar infarcts and bilateral hemispherical white matter lesions. Under electron microscope, the lumen of small blood vessels in the skin is obviously narrowed and the basement membrane is thickened. Currently, there are no effective treatments or interventions for PADMAL.

Health insurance fund regulation (HIFR) is a vital issue in the modernization of healthcare security governance, with its importance as a primary task of the healthcare security department continually reinforced in policy practice. This study focused on the 22 specialized policies issued by the National Healthcare Security Administration from its establishment in 2018 to March 2024, deeply analyzed their issue characteristics, and summarized the evolutionary trends of policy changes, as well as the knowledge production patterns that existed in the series of policy formulation, implementation, and feedback processes. Our analysis revealed that the diverse issue characteristics had led to heterogeneous directions in HIFR policies. The policy development process presented distinct composite evolutionary trends, mainly manifested in four aspects: the integration of regulatory system and content, the convergence of professional and societal forces, the parallelism of special governance and regular supervision, and the complementarity of conventional and emerging methods. Additionally, the study demonstrated that the knowledge production embedded in policy evolution encompassed four different dimensions: problem rectification, norm setting, pilot experience, and technical absorption. Together with issue characteristics and policy evolution, they formed an integrated, dynamic, and open system of knowledge production, continuously promoting the renewal and iteration of regulation policies.

Objective: To explore the relationship between premenarchal dietary carbohydrate and dietary fiber intakes and age at menarche in Chinese girls. Methods: Based on dietary and menarcheal information on 750 girls from the Chinese Health and Nutrition Survey, multivariate linear regression models and logistic models were used to analyze the influence of dietary carbohydrate and dietary fiber intakes before menarche onset and age at menarche. Carbohydrate intake was replaced by engergg ratio carbohydrate for a sensitivity analysis. Results: Adjusting for residence, per capita household income, body mass index standard deviation score, and energy intake, higher intake and higher energy ratio of carbohydrate were associated with later age at menarche(P<0.01). Compared to girls at the lowest tertile of carbohydrate intake level, those at the highest tertile had a 0.35 years(2.8%) delay in age at menarche, while 55% decreased[OR(95%CI)=0.45(0.30-0.69)]. Dietary fiber intake was not associated with age at menarche in any model(P>0.2). Conclusion Girls with higher premenarcheal carbohydrate intake experienced menarche later, while dietary fiber intake was not associated with age at menarche.

Objective: To investigate the prospective effects of the consumption of protein and animal foods before menarche on the age at menarche among Chinese girls. Methods: This paper was based on the data collected in the China Health and Nutrition Survey(CHNS) from 1997 to 2015. A total of 683 girls aged 6 and over who had completed information on age at menarche, height, weight, per capita annual household income, maternal education level and participated in at least one complete dietary survey within 1 to 4 years before menarche were included. Urban-rural stratified multivariable linear regression model was used to examine the effects of protein and animal foods intake before menarche on Chinese girls age at menarche in urban and rural areas. Results: After adjusted for total energy intake, body mass index standard deviation score and per capita annual household income, the consumption of meat before menarche was negatively associated with the age at menarche among rural Chinese girls(B=-0.003, P=0.00), but not among urban Chinese girls(B=0.002, P>0.05). Total protein, dairy, eggs and aquatic products intake before menarche were not associated with Chinese girls age at menarche in urban and rural areas(B=0.002, -0.001, 0.003, 0.000; 0.001, 0.001, -0.001, -0.003, P>0.05). Conclusion Higher intake of meat before menarche might lead to earlier menarche onset in rural Chinese girls. The consumption of total protein, dairy, eggs, and aquatic products before menarche did not affect the age at menarche in Chinese girls.

Objective: To examine the prospective association between peripubertal diet quality and pubertal timing. Methods: Multivariate regression analyses were performed using data obtained from 1 588 SCCNG (Southwest China Childhood Nutrition and Growth) study participants, which included dietary data, anthropometric parameters, and information about potential confounders during peri puberty, two and four years before the onset of menarche or voice break. Dietary intake in peri puberty was assessed using a validated food frequency questionnaire. Diet quality was determined using the Chinese Children Dietary Index (CCDI), which measures adherence to current dietary recommendations. Age at menarche or voice break (M/VB) were used as pubertal markers. Results: The CCDI score ranged from 58.0 to 132.5 for girls and from 48.3 to 129.9 for boys. The pubertal markers consistently indicated that girls and boys with a higher peripubertal diet quality entered puberty later than their counterparts with lower CCDI scores (higher vs. lower CCDI tertiles: age at M was 13.1 years (11.2-13.3) and 12.5 years (12.0-13.9)(P<0.01); VB was 13.8 years (12.1-14.8) and 13.4 years (12.5-15.1)（P=0.03), after adjusting for paternal education level, energy intake, and pre pubertal body fat. Conclusion Children with a higher diet quality during peri puberty entered puberty at a later age. Dietary guidance and intervention are needed for better dietary quality among children during pubertal transition.

Based on the data from China Health and Nutrition Survey (CHNS), 840 girls aged 6-15 years who had information about menarche and participated in dietary survey at least once within 1-5 years before onset of menarche between 1989 and 2015 were included in the study. The median age at baseline of the 840 participants was 10 (9, 11) years. The median age at menarche of the participants was 13 (12, 14) years. After adjusting for the age of birth, place of residence, body mass index Z-score, physical activity level and annual household income per capita, the average age of menarche was advanced by 0.036 (95% CI: -0.068, -0.004) years for every 10 g increase in daily fat intake before menarche. The average age at menarche was 0.008 (95% CI: -0.014, -0.001) years earlier for every 1% increase in the daily energy supply ratio of fat before menarche.

Objective: To explore the prospective effect of dietary intake of total fat and fatty acids on menarcheal timing among girls,and to provide a theoretical basis for preventing the early puberty development of Chinese children. Methods: Using the data from 1997-2015 China Health and Nutrition Survey (CHNS), 1 240 girls aged 6-13 with menarche information, baseline dietary survey data and at least one follow up assessment were selected. Cox regression analysis was performed to examine the prospective effect of dietary intake of total fat and fatty acids before menarche on age at menarche. Results: The mean baseline age of the participants was (8.3±1.8). After adjustment for year of birth, residence, household income, dietary energy intake and body mass index Z score at baseline, girls in the highest quartile of intake of total fat and polyunsaturated fatty acid (PUFA) had a 30% and 34% higher probability of experiencing menarche at an earlier age than those in the lowest quartile [ HR(HR 95%CI )=1.30 (1.01~1.68)，1.34(1.05~1.70)]. After adjusting for the confounders, there were no correlations between the intake of saturated fatty acid (SFA) and monounsaturated fatty acid (MUFA) and the onset of menarche [ HR(HR 95%CI )=1.24(0.98~1.58),1.25(0.97~ 1.62 )]( P >0.05). Conclusion Higher dietary intake of total fat and PUFA before menarche may lead to earlier age at menarche and no correlation between intake of SFA and MUFA before menarche with age at menarche is found among Chinese girls.

Ferroptosis is a non-apoptotic regulated cell death caused by iron accumulation and subsequent lipid peroxidation. Currently, the therapeutic role of ferroptosis on cancer is gaining increasing interest. Baicalin an active component in