Trends in the mobility of primary healthcare human resources in underdeveloped regions of western China from 2000 to 2021: Evidence from Nanning.

OBJECTIVE: This research aimed to identify the fundamental and geographic characteristics of the primary healthcare personnel mobility in Nanning from 2000 to 2021 and clarify the determinants that affect their transition to non-primary healthcare institutions. METHODS: Through utilizing the Primary Healthcare Personnel Database (PHPD) for 2000-2021, the study conducts descriptive statistical analysis on demographic, economic, and professional aspects of healthcare personnel mobility across healthcare reform phases. Geographic Information Systems (QGIS) were used to map mobility patterns, and R software was employed to calculate spatial autocorrelation (Moran's I). Logistic regression identified factors that influenced the transition to non-primary institutions. RESULTS: Primary healthcare personnel mobility is divided into four phases: initial (2000-2008), turning point (2009-2011), rapid development (2012-2020), and decline (2021). The rapid development stage saw increased mobility with no spatial clustering in inflow and outflow. From 2016 to 2020, primary healthcare worker mobility reached its peak, in which the most significant movement occurred between township health centers and other institutions. Aside from their transition to primary medical institutions, the primary movement of grassroots health personnel predominantly directs towards secondary general hospitals, tertiary general hospitals, and secondary specialized hospitals. Since 2012, the number and mobility distance of primary healthcare workers have become noticeably larger and remained at a higher level from 2016 to 2020. The main migration of primary healthcare personnel occurred in their districts (counties). Key transition factors include gender, education, ethnicity, professional category, general practice registration, and administrative division. CONCLUSIONS: This study provides evidence of the features of primary healthcare personnel mobility in the less developed western regions of China, in which Nanning was taken as a case study. It uncovers the factors that impact the flow of primary healthcare personnel to non-primary healthcare institutions. These findings are helpful to policy refinement and support the retention of primary healthcare workers.

Circ-USP9X interacts with EIF4A3 to promote endothelial cell pyroptosis by regulating GSDMD stability in atherosclerosis.

Endothelial pyroptosis is a pathological mechanism of atherosclerosis (AS). Circular RNAs (circRNAs) are vital in AS progression by regulating endothelial cell functions. The study aimed to explore whether circ-USP9× regulated pyroptosis of endothelial cell to involve in AS development and the molecular mechanism. Pyroptosis was determined using lactate dehydrogenase (LDH) assay, enzyme linked immunosorbent assay (ELISA), flow cytometry, propidium iodide (PI) staining assay, and western blot. The mechanism of circ-USP9× was determined using RNA pull-down and RNA binding protein immunoprecipitation (RIP) assays. Results showed that circ-USP9× was upregulated in AS and oxidized low-density lipoprotein (ox-LDL)-treated human umbilical vein endothelial cells (HUVECs). Knockdown of circ-USP9× suppressed ox-LDL induced pyroptosis of HUVECs. Mechanically, circ-USP9× could bind to EIF4A3 in the cytoplasm. Moreover, EIF4A3 was bound to GSDMD and further affects GSDMD stability. Overexpression of EIF4A3 rescued cell pyroptosis induced by circ-USP9× depletion. In short, circ-USP9× interacted with EIF4A3 to enhance GSDMD stability, thus further promoting ox-LDL-induced pyroptosis of HUVECs. These findings suggested that circ-USP9× participates in AS progression and may be a potential therapeutic target for AS.

Circular RNA circ_0090231 promotes atherosclerosis in vitro by enhancing NLR family pyrin domain containing 3-mediated pyroptosis of endothelial cells.

Atherosclerosis (AS) is an inflammatory disease caused by multiple factors. Multiple circRNAs are involved in the development of AS. The present study focusses on delineating the role of circ_0090231 in AS. Human aortic endothelial cells (HAECs) were treated with oxidized low-density lipoprotein (ox-LDL) to construct an in vitro AS model. Real-time quantitative polymerase-chain reaction (RT-qPCR) was used to detect the levels of circ_0090231, IL-1ß, and IL-18 transcripts. CircRNA/target gene interactions were predicted using StarBase and TargetScan and confirmed using an RNA pull-down assay and dual-luciferase reporter assay. Further, 3-(4,5)-dimethylthiahiazo(-2)-3,5-diphenytetrazoliumromide (MTT) and lactate dehydrogenase (LDH) release assays were performed to evaluate cell viability and damage in the AS model, respectively. Cell pyroptosis and protein expression were determined using flow cytometry and western blotting respectively. The treatment of HAECs with ox-LDL not only led to significant increase in the levels of circ_0090231 but also resulted in improved cell viability as well as reduced cell injury and pyroptosis as compared to that in non-treated cells. The circ_0090231 was also identified to function as a sponge for miR-635, knockdown of which reverses the effects of circ_0090231 inhibition. Furthermore, our results revealed that levels of NLRP3, a miR-635 target, are not only augmented in the AS model but its overexpression also weakens the miR-635 regulatory effects in the AS development. Taken together, the circ_0090231/miR-635/NLRP3 axis affects the development of AS by regulating cell pyroptosis, thus providing new insights into the mechanism of AS development.

MicroRNA-150 restores endothelial cell function and attenuates vascular remodeling by targeting PTX3 through the NF-κB signaling pathway in mice with acute coronary syndrome.

MicroRNAs (miRNAs) have been known to function as important regulators in the vascular system, with various physiopathological effects such as vascular remodeling and hypertension modulation. We aimed to explore whether microRNA-150 (miR-150) regulates endothelial cell function and vascular remodeling in acute coronary syndrome (ACS), and the involvement of PTX3 and NF-κB signaling pathway. Ten normal mice and sixty ApoE-/- mice were chosen, and their coronary artery tissues and endothelial cells were extracted. ApoE-/- mice were injected with a series of inhibitor or mimic for miR-150, or siRNA against PTX3. The miR-150 expression, NF-κB1, RELA, and PTX3 mRNA expression were assessed by reverse transcription quantitative polymerase chain reaction, and pentraxin-3, p-P50, and p-P65 protein expression by Western blot analysis. Cell viability and migration were assessed by MTT assay and scratch test. Matrigel tube formation assay was employed to determine vascular remodeling of endothelial cells. The dual-luciferase reporter assay verified that PTX3 was a target of miR-150. Mice with ACS presented with decreased miR-150 but increased PTX3. It was observed that the miR-150 mimic and siRNA against PTX3 reduced levels of PTX3, NF-κB1, and RELA in mice, and the miR-150 inhibitor reversed the tendency. The in vitro cell experimentation proved that miR-150 might facilitate endothelial cell proliferation, migration, and restrain vascular remodeling via inhibiting PTX3 expression. On the basis of the results of this study, it was hypothesized that miR-150 could possibly maintain endothelial cell function and suppress vascular remodeling by inhibiting PTX3 through the NF-κB signaling pathway in mice with ACS.