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ObjectiveTo identify the possible health impact of the 14th five⁃year plan for the development of employment and social security in Deqing County and propose improvement measures through health impact assessment.MethodsBased on the data of Deqing County， stakeholder interviews and Delphi Consultation Method， this study described the current status of employment and social security and analyzed the potential health impacts of implementing the 14th five⁃year plan for the development of employment and social security in Deqing County.ResultsThrough a quick assessment process， the results showed that the implementation of the plan would bring mixed health impacts. Positive impacts included enhanced social security capacity， improved health levels of low-income populations and families， increased convenience of medical treatment， and improved efficiency of health services. Negative impacts included reduced accessibility of digital services for the elderly， increased gap in benefits for retirees， increased risk of discrimination against disabled individuals， increased risks of layoffs and unemployment for vulnerable groups， and increased employment instability for middle-aged and elderly populations.ConclusionThe 14th five⁃year plan for the development of employment and social security in Deqing County will bring a series of positive health impacts， but negative health impacts also warrant attention.

Objective To investigate the effect of sildenafil (Sil) on the expression of NLRP3/caspase-1 pathway in the aorta vascular tissue of erectile dysfunction (ED) rat models. Methods ED rat model was established and randomly divided into ED group and Sil group. Another 10 rats were selected as control group. After intragastric administration of Sil(20 mg /kg, once a day for 2 weeks), HE staining was used to observe the morphological change of aorta. Aortic fibrosis was detected by Masson staining. The content and distribution of interleukin-1β (IL-1β) and endothelial nitric oxide synthase (eNOS) in aorta were determined by immunohistochemistry. RT-qPCR and Western blot were used to detect the expression of NLRP3, caspase-1, GSDMD, IL-1β and eNOS in the aorta. Results In ED group, there were pathological changes in aortic morphology, more local exfoliation of endothelial cells and obvious fibrosis. The mRNA and protein expressions of NLRP3, caspase-1, GSDMD and IL-1β were increased, and the mRNA and protein expressions of eNOS were decreased in the aorta of the rats in the experimental group(P＜0.05). Compared with the ED group, the aortic morphological changes of the Sil group were improved, the local endothelial cell shedding was reduced, and the fibrosis was alleviated. The mRNA and protein expression of NLRP3, caspase-1, GSDMD and IL-1β decreased, while the mRNA and protein expression of eNOS increased in aorta(P＜0.05). Conclusions The expression of NLRP3/caspase-1 pathway protems in the aorta vescular tissue of rats with ED is up-regulated by Sil, which may improve the inflammatory response, vascular fibrosis and endothelial dysfunction by inhibiting the NLRP3/caspase-1 pathway in the aorta vascular tissue of rats with ED.

Dachshund homolog 1 (DACH1), a key cell-fate determinant, regulates transcription by DNA sequence-specific binding. We identified diminished Dach1 expression in a large-scale screen for mutations that convert injury-resistant podocytes into injury-susceptible podocytes. In diabetic kidney disease (DKD) patients, podocyte DACH1 expression levels are diminished, a condition that strongly correlates with poor clinical outcomes. Global Dach1 KO mice manifest renal hypoplasia and die perinatally. Podocyte-specific Dach1 KO mice, however, maintain normal glomerular architecture at baseline, but rapidly exhibit podocyte injury after diabetes onset. Furthermore, podocyte-specific augmentation of DACH1 expression in mice protects from DKD. Combined RNA sequencing and in silico promoter analysis reveal conversely overlapping glomerular transcriptomic signatures between podocyte-specific Dach1 and Pax transactivation-domain interacting protein (Ptip) KO mice, with upregulated genes possessing higher-than-expected numbers of promoter Dach7-binding sites. PTIP, an essential component of the activating histone H3 lysine 4 trimethylation (H3K4Me3) complex, interacts with DACH1 and is recruited by DACH1 to its promoter-binding sites. DACH1-PTIP recruitment represses transcription and reduces promoter H3K4Me3 levels. DACH1 knockdown in podocytes combined with hyperglycemia triggers target gene upregulation and increases promoter H3K4Me3. These findings reveal that in DKD, diminished DACH1 expression enhances podocyte injury vulnerability via epigenetic derepression of its target genes., Introduction Dachshund homolog 1 (DACH1) was originally identified as an essential member of the retinal determination gene network (RDGN), a fundamental signal that governs cell fate during development. That DACH1 [...]

Inflammation is a key contributor to diabetic kidney disease pathogenesis, including reactive oxidation stress (ROS)‐mediated nuclear factor‐κB (NF‐κB) signaling pathway. In this study, we examined the effect of Astragaloside IV (AS‐IV) on anti‐inflammatory and anti‐oxidative properties under high glucose (HG) condition and the potential mechanism in glomerular mesangial cells (GMCs). We showed that AS‐IV concentration‐dependently reduced GMCs proliferation, restrained ROS release and hydrogen peroxide content, and suppressed pro‐inflammatory cytokines as well as pro‐fibrotic factors expression, which were associated with the inhibition of NF‐κB and nuclear factor‐erythroid 2‐related factor 2 (Nrf2) signaling activation. Accordingly, both NF‐κB overexpression by using RNA plasmid and Nrf2 gene silencing by using RNA interference weakened the ability of AS‐IV to ameliorate HG‐induced oxidative stress, inflammation, and cell proliferation. Furthermore, phosphatidylinositide 3‐kinases (PI3K)/serine/threonine protein kinase (Akt) and extracellular regulated protein kinases (ERK) signaling pathway regulated the process of AS‐IV‐induced Nrf2 activation and antioxidant capacity, which evidenced by using PI3K inhibitor LY294002 or ERK inhibitor PD98059 that largely abolished the AS‐IV efficacy. Taken together, these results indicated that AS‐IV protected against HG‐induced GMCs damage by inhibiting ROS/NF‐kB‐induced increases of inflammatory cytokines, fibrosis biomarkers, and cell proliferation via up‐regulation of Nrf2‐dependent antioxidant enzyme expression, which were mediated by PI3K/Akt and ERK signaling pathway activation. [ABSTRACT FROM AUTHOR]