Zigui-Yichong-Fang protects against cyclophosphamide-induced premature ovarian insufficiency via the SIRT1/Foxo3a pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Zigui-Yichong-Fang (ZGYCF) is a traditional Chinese medicine prescription for the treatment of infertility and premature ovarian insufficiency (POI). It is clinically used to regulate hormone levels, improve ovarian reserve and increase pregnancy rate. However, the exact mechanism of action is not yet clear. AIMS OF THE STUDY: This study aimed to explore the potential impact and mechanism of ZGYCF on POI, and provide a scientific basis for its clinical application. MATERIALS AND METHODS: UHPLC‒MS/MS was used to identify the main compounds of ZGYCF. Female 8-week-old C57BL/6N mice were randomized into four group containing the vehicle control (Veh) group, the cyclophosphamide (CTX) model group, the low-dose ZGYCF (CTX-ZG-L) group and the high-dose ZGYCF (CTX-ZG-H) group. A mouse POI model was induced with a single intraperitoneal injection of CTX, and the therapeutic effects of different doses of ZGYCF on POI were evaluated according to the ovarian weight coefficient, serum AMH, serum E2, ovarian histomorphology and follicle counts. After the dose screening experiment, the CTX-ZG-L group was renamed the CTX-ZG group and subjected to follow-up experiments. RNA-seq was used to explore the mechanism of POI and the therapeutic mechanism of ZGYCF on POI in Veh group, CTX group and CTX-ZG group. The mechanism of action of ZGYCF on POI were determined by measuring serum hormone level, histomorphology, follicle counts, protein expression and acetylation modification in groups of Veh, CTX, CTX-ZG and CTX-ZG-Nam (SIRT1 inhibitor). RESULTS: A total of 37 compounds in ZGYCF were identified. ZGYCF attenuated the morphological changes in ovarian tissue in POI model mice, increased serum AMH and E2 levels, reduced the damage to primordial follicles and other follicles at all stages, and protected ovarian reserve. RNA-seq results suggested that the genes expression of the PI3K signaling and apoptosis signaling pathways was increased in POI mice, while ZGYCF upregulated SIRT1 gene and the expression of estradiol, apoptosis inhibition and other signaling pathway genes. Immunohistochemical staining, TUNEL staining, Western blot analysis and immunoprecipitation results showed that in CTX group, SIRT1 expression and Foxo3a nuclei localization were decreased, while Ac-Foxo3a, p-AKT, p-Foxo3a and apoptotic markers were upregulated. After administration of ZGYCF, these conditions were reversed, however, after treatment with the SIRT1 inhibitor, the results were opposite to those of ZGYCF. CONCLUSIONS: Acetylated Foxo3a plays an important role in the occurrence of POI. ZGYCF improves the ovarian reserve of CTX-induced POI mice by activating SIRT1-mediated deacetylation of Foxo3a, and played a role in the treatment of POI. SIRT1 may be a novel target for ZGYCF to ameliorate POI.

Assessing Spatial Accessibility of Community Hospitals for the Elderly in Beijing, China.

Accessibility of health services signifies the quality and equitability of universal health provision. The hierarchical medical system recently implemented in China offers the policy instruments to improve medical services to the elderly in an aging society. As the critical primary care gateway, accessibility to community hospitals has significant impacts on people's health. However, current research has paid little attention to spatial accessibility within walking distance of community hospitals, especially for the elderly. This study selected four districts with different urbanization levels in the rapidly developing Beijing metropolis. The spatial interaction model was applied to measure the accessibility of community hospitals for the elderly at the community level. An attractiveness index was computed based on key hospital traits. The results showed that: (1) community hospitals could cover 82.66% of elderly residents, and 77.63% of the communities were within walking distance. The served elderly proportion was relatively high in central urban areas and low in the suburbs. (2) The attractiveness indices of hospitals varied notably between districts, with higher values in more urbanized areas. (3) The spatial accessibility for the elderly of hospitals differed significantly between the four districts, with a descending gradient from central to suburban and rural areas, as indicated by the Gini coefficients and Lorenz curves. (4) The accessibility index was strongly related to the served elderly population and the hospital-residence distance. The findings provide policy directions to the government, including providing more primary-care resources to suburban and rural areas, building new community hospitals in identified provision gaps, upgrading some clinics to hospitals in rural areas, and planning hospitals according to the projected trend of the elderly population in terms of quantity and distribution. The considerable provision disparity between core urban, suburban and rural areas can be addressed by refined spatial health planning informed by research.

Effects of Self-Rated Health Status on Residents' Social-Benefit Perceptions of Urban Green Space.

Urban green spaces (UGS) provide many social benefits and improves residents' wellbeing. Studying residents' perceptions of UGS's social benefits and driving factors could promote public health and environmental justice. A questionnaire survey of 432 Beijing residents and statistical tests assessed the impacts of residents' living environments and self-rated health status on UGS perceptions. The results showed: (1) perceptions of UGS' physical health benefits were subdued, with an inclination towards other social benefits. Respondents more highly perceived accelerating patient recovery and reducing morbidity and mortality rates. Perceptions of bearing larger-head babies with higher weight were relatively low. For other social benefits, perceptions of improving the environment and life quality were higher, but reducing anger outbursts and resolving conflicts were lower. (2) Childhood living environments did not affect perceptions of social benefits, but current living environments did. Suburb residents understood reducing pain-relief medication demands and bearing larger-head babies better than city residents. City residents understood UGS' investments considerable and sustained returns better than village residents. City residents agreed with accelerating patient recovery higher than village ones. (3) Respondents with "poor" self-rated health status had better perceptions of other social benefits. Those with "excellent" ratings did not fully understand UGS' physical health benefits. "Poor" ratings understood improving a city's image and making cities livable and sustainable better than "good" or "fair" ratings. "Excellent" ratings had less understanding of larger-head babies than "good" or "fair" ratings. The study could enhance appreciation of UGS' social benefits to facilitate planning and management to meet residents' expectations.