Objective:To investigate the role of monocyte chemoattractant protein-1 in the progress that isometric exercise training improves arteriogenesis.Method:Twenty-four male Sprague-Dawley rats were used,weighing (200±20)g.The rats were randomized into control group (CG),myocardial ischemia group (MI),exercise training group (ET),MCP-1 inhibitor group (LG).There were 6 rats in each group.Rats were continuously administered 10mg/kg subcutaneously isoproterenol for successive 2 weeks to establish the myocardial ischemia model.Successfully modeled rats were in groups MI,ET and LG.Isometric exercise training were performed in group ET and LG.The rats in group LG were given MCP-1 inhibitor leflunomide by gavage.After 8 weeks of training,the left ventricular myocardium was extracted and relative collateral blood flow (RCBF) was measured by microspheres.Artery density (AD) and monocytes were measured by immunohistochemistry analysis.Western blot analysis and real-time quantitative PCR were performed to assay protein and mRNA of MCP-1.Result:RCBF and AD increased significantly in group ET as compared to the rest groups.RCBF and AD in group LG showed higher than that in group MI but not significant.The number of monocytes,MCP-1 mRNA and MCP-1 expression were significantly elevated in ischemic myocardium of group ET.Interestingly,the number of monocytes,MCP-1 mRNA and MCP-1 expression showed lower than that in group MI but also not significant.Conclusion:Eight weeks of isometric exercise training can increase the expression of MCP-1 in ischemic myocardium and promote the arteriogenesis.

Objective To investigate the effect of fibroblast growth factor-2 (FGF-2) on the formation of collateral arteries in the remote myocardium promoted by the isometric exercise (IE).Methods Twenty-four male Sprague-Dawley rats weighing (200±20)g were randomized into a sham operation group (SO),a myocardial ischemia group (MI),an isometric exercise group (IE) and an FGF inhibitor group (Inhi-FGF),each of 6.Rats in the SO group were injected with saline subcutaneously for 2 weeks while those of the MI group were being injected with 10 mg/(kg · d) of isoproterenol subcutaneously to induce myocardial ischemia.Rats in group IE accepted isometric exercise and the same injections as group MI,while those in group Inhi-FGF were also given 100 mg/(kg · d) of formononetin intragastrically in addition to the group IE treatment.After 8 weeks of IE the myocardium of the rats' left ventricles was resected.The relative collateral blood flow (RCBF) was measured using the microsphere method.The artery density and the number of smooth muscle cells were evaluated using immunohistochemical analysis.Western blotting was performed to assay the levels of FGF-2 protein and its receptor FGFR-1.Results Compared to the SO,MI and InhiFGF groups,significant increases in the RCBF,artery density,the number of smooth muscle cells and the relative levels of FGF-2 protein and FGFR-1 were observed in group IE.In the Inhi-FGF group the artery density,the number of smooth muscle cells and the relative protein level of FGF-2 were significantly lower than those of the MI group,but there were no significant differences in the RCBF or FGFR-1 levels between the two groups.The artery density had a positive linear correlation with the number of smooth muscle cells.The RCBF correlated with the artery density,the number of smooth muscle cells and the FGF-2 protein levels.Conclusion IE can promote the expression of FGF-2 and its acceptor,resulting in the formation of collateral arteries and better blood perfusion of an ischemic myocardium.

Heavy ion radiation has significant radiological and biological advantages over conventional radiation. While directly killing tumor cells, heavy ion beam can reduce immune escape and promote the initiation and activation of effector T cells by inducing immunogenic death of tumor cells, regulating tumor phenotype, enhancing antigen formulation, and changing tumor microenvironment to regulate the immune response. This article will review the immunomodulatory effect of heavy ion beam and the molecular mechanisms associated with immune checkpoint inhibitor therapy.

Objective:To explore the alteration of JAK2/STAT3 pathway after carbon ion ( 12C 6+) irradiation and the difference in the infiltration of CD8 + T cells in lung cancer regulated by downstream protein FOXP3. Methods:Significantly altered JAK2/STAT3 pathway and related differentially-expressed genes and proteins such as FOXP3 in lung cancer after carbon ion irradiation were screened based on RNA sequencing analysis in the Lewis tumor model of C57BL/6 mice. The correlation between FOXP3 and major immune cell infiltration in the immune microenvironment of lung cancer was analyzed using the ssGSEA immune infiltration algorithm in the R software "GSVA" and CD8 + T cell infiltration in the immune microenvironment of lung cancer was evaluated based on the carbon ion combined with STAT3 inhibition pathway (niclosamide). Results:The JAK2/STAT3 pathway was inhibited and the expression of related genes and proteins was downregulated in lung cancer after carbon ion irradiation. Immune scoring based on the ssGSEA algorithm showed that FOXP3 expression was significantly negatively correlated with CD8 + T cell infiltration in the immune microenvironment of lung cancer. The role of targeting the JAK2/STAT3 pathway in increasing CD8 + T cell infiltration in lung cancer was further clarified by carbon ion irradiation combined with STAT3 inhibition (niclosamide). Conclusion:Carbon ion irradiation ( 12C 6+) can play a synergistic role with immunotherapy by targeting the JAK2/STAT3 pathway.