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This review comprehensively summarizes the changes in fibroblasts, endothelial cells, mast cells, monocytes\/macrophages, neutrophils, dendritic cells, natural killer cells, and lymphocytes within the myocardial microenvironment during coxsackievirus B3 infection, highlighting their critical roles in disease development. Additionally, it provides an overview of recent findings on potential therapeutic approaches targeting the myocardial microenvironment. 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