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Background: The aim is to investigate the clinical efficacy of Alprostadil in diabetes mellitus (DM) combined with peripheral atherosclerosis and to investigate the molecular mechanisms. Methods: Patients included 154 cases with DM combined with peripheral atherosclerosis and were divided into the conventional group (77 cases) and the Alprostadil group (77 cases). Both groups of patients were given conventional treatment, and the Alprostadil group was given Alprostadil treatment on the basis of the conventional group. The therapeutic efficacy and clinical symptom improvement were compared, and the adverse reactions were observed. An in vitro cell model was constructed using high glucose (HG) (50 mM) and oxidized low-density lipoprotein (50 μg/mL) treatment. Results: The total effective rate of treatment in the Alprostadil group was higher than that in the conventional group. The biochemical indices of whole blood viscosity, plasma viscosity, erythrocyte pressure volume, and fibrinogen, as well as the level of inflammatory factors in the Alprostadil group were lower than those in the conventional group. The incidence rate of adverse reactions of Alprostadil administration was lower than that in the conventional group (P = .030). Alprostadil inhibited platelet aggregation and promoted platelet spreading. Alprostadil had an ameliorative effect on HG- and oxidized low-density lipoprotein cholesterol (ox-LDL)-induced human umbilical vascular endothelial cells (HUVECs), and promoted apoptosis and inflammatory response of HUVECs. Conclusion: Clinically, the use of Alprostadil as an adjunct to conventional therapy for the treatment of DM combined with peripheral atherosclerosis has high clinical efficacy. In addition, Alprostadil has a significant ameliorative effect on high glucose- and ox-LDLinduced HUVECs. [ABSTRACT FROM AUTHOR]

Programmed death-ligand 1 (PD-L1) blockade has revolutionized the prognosis of several cancers, but shows a weak effect on pancreatic cancer (PC) due to poor effective immune infiltration. Chemokine C-C motif ligand 21 (CCL21), a chemokine promoting T cell immunity by recruiting and colocalizing dendritic cells (DCs) and T cells, serves as a potential antitumor agent in many cancers. However, its antitumor response and mechanism combined with PD-L1 blockade in PC remain unclear. In our study, we found CCL21 played an important role in leukocyte chemotaxis, inflammatory response, and positive regulation of PI3K-AKT signaling in PC using Metascape and gene set enrichment analysis. The CCL21 level was verified to be positively correlated with infiltration of CD8+ T cells by the CIBERSORT algorithm, but no significant difference in survival was observed in either The Cancer Genome Atlas or the International Cancer Genome Consortium cohort when stratified by CCL21 expression. Additionally, we found the growth rate of allograft tumors was reduced and T cell infiltration was increased, but tumor PD-L1 abundance elevated simultaneously in the CCL21-overexpressed tumors. Then, CCL21 was further verified to increase tumor PD-L1 level through the AKT-glycogen synthase kinase-3β axis in human PC cells, which partly impaired the antitumor T cell immunity. Finally, the combination of CCL21 and PD-L1 blockade showed superior synergistic tumor suppression in vitro and in vivo. Together, our findings suggested that CCL21 in combination with PD-L1 blockade might be an efficient and promising option for the treatment of PC. [ABSTRACT FROM AUTHOR]