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For treatment, metformin (MET) (HY-B0627, MedChemExpress LLC, China) and empagliflozin (EMPA) (HY-15409, MedChemExpress LLC, China) were administrated by gavage at doses of 200 mg/kg/d ( 2.2 Two-hit-induced hFpEF mouse model The mouse HFpEF model established in this study is based on the double-hit hypothesis proposed by Schiattarella GG et al., which combines metabolic stress and mechanical stress to simulate the pathophysiological conditions of HFpEF ( 2.3 Pathological morphological staining The harvested hearts were fixed in 4% buffered formaldehyde for 24 h, embedded in paraffin, and sectioned into 5 m thick slices