Objective To investigate the changes in osteoprotegerin (OPG) / receptor activator of nuclear factor-κB ligand (RANKL) ratio in sepsis-associated acute lung injury (SA-ALI) and the role of regulation of this ratio on the inflammatory response in SA-ALI. Methods Eighteen C57BL/6 male mice were randomly divided into sham operation group, cecal ligation and perforation (CLP) group and RANKL group, with 6 mice in each group. Before the experiment, the RANKL group was intraperitoneally injected with 5 μg (0.2 mL) of recombinant RANKL antibody, whereas both the sham operation group and the CLP group were intraperitoneally injected with a volume-matched normal saline. One hour later, the sham operation group underwent only abdominal exploration and repositioning, while the other groups underwent the CLP surgery to induce the SA-ALI model. After 24 h of modelling, all mice were sacrificed and samples were collected. Pathological evaluation of lung tissues was performed by haematoxylin-eosin staining; enzyme-linked immunosorbent assay was used to detect serum concentrations of interleukin (IL)-6, tumor necrosis factor (TNF)-α, and IL-1β; while the mRNA and protein expression of OPG and RANKL, along with their ratio values, were detected by real-time polymerase chain reaction for quantitative analysis and protein immunoblotting. Results The SA-ALI mouse model was successfully established. Compared with the sham operation group, mice in the CLP group showed disturbed alveolar structure, obvious alveolar and interstitial haemorrhage and inflammatory cell infiltration, elevated serum levels of IL-6, TNF-α and IL-1β (P<0.05), significantly increased mRNA and protein expression of OPG and elevated OPG/RANKL ratio in lung tissue (P<0.05), whereas RANKL mRNA and protein expression was significantly decreased (P<0.05). Compared with the CLP group, the pathological damage of lung tissue in the RANKL group was reduced, the infiltration of alveolar and interstitial inflammatory cells was significantly improved, and the alveolar structure and morphology were more regular, with lower serum levels of IL-6, TNF-α and IL-1β (P<0.05), significantly lower mRNA and protein expression of OPG and OPG/RANKL ratio in lung tissue (P<0.05), and significantly higher mRNA and protein expression of RANKL in lung tissue (P<0.05). Conclusion The alteration of OPG/RANKL ratio may be related to the pathophysiological process of SA-ALI, and the decrease in its level may reflect the attenuation of the inflammatory response in SA-ALI.
ObjectiveTo systematically review and compare global pharmaceutical regional pooled procurement mechanisms, with the aim of generating evidence to inform decision-making in optimization of medicines regional pooled procurement. MethodsComprehensively search published literature about pharmaceutical regional pooled procurement mechanisms from the inception of each database to the end of 2025 from CNKI, Web of Science, PubMed, Embase and Scopus. Characteristics of the targeted mechanisms were extracted from the included literature. Supplementary information was obtained from official websites of the referenced pharmaceutical regional pooled procurement mechanisms, related international organizations and major media platforms. The compiled information was then categorized for comparative analysis. ResultsA total of 74 literature were included in the analysis, which identified 15 pharmaceutical regional pooled procurement mechanisms. Geographically, the literature predominantly focused on Europe (n=39) and the Americas (n=31). Among these, the Joint Procurement Agreement of the European Union (n=30) and the Revolving Fund of the Pan American Health Organization (n=26) were studied the most. All continents established pharmaceutical regional pooled procurement mechanisms. The majority of these mechanisms (n=10, 66.7%) remain operational. The scope of procured medical products ranged from essential medicines and vaccines to expensive novel medicines, which closely aligns with the regional economic development. To secure operation and management, most of these mechanisms levy an administrative fee on the member states. ConclusionTo ensure the sustainability of the pharmaceutical regional pooled procurement, it is essential to foster stronger regional identity and solidarity, leverage economies of scale, ensure greater transparency, establish stable funding mechanisms, and strengthen technological capacity for accurate forecasting, monitoring and evaluation of the supply and demand.