ObjectiveTo investigate the effect and mechanism of Bukan Yilidan on perimenopausal psycho-cardiac disease by mitochondrial autophagy mediated by dynamin-related protein 1（Drp1）/phosphatase and tensin homolog（PTEN） induced putative kinase 1（PINK1）/Parkin pathway. MethodsSixty rats were randomly divided into the blank group， model group， western medicine group（isosorbide mononitrate 7.2 mg·kg^-1+sertraline hydrochloride tablets 18 mg·kg^-1）， Bukan Yilidan low， medium and high dose groups（2.59， 5.18， 10.35 g·kg^-1）， with 10 rats in each group. Except for the blank group， the rat model of perimenopausal psycho-cardiac disease was prepared by ovariectomy（OVX） combined with high-fat feeding， chronic unpredictable mild stress（CUMS） and subcutaneous multi-point injection of isoproterenol hydrochloride. After successful modeling， the general state and tongue image of rats were observed. The depression status of rats in vivo was evaluated by open field test， sucrose preference test， forced swimming immobility time and grip strength value， and the cardiac function of rats was evaluated by electrocardiogram and echocardiography. The levels of serum norepinephrine（NE）， dopamine（DA） and 5-hydroxytryptamine（5-HT） were detected by enzyme-linked immunosorbent assay（ELISA）， and biochemical detection was used to assess myocardial injury by measuring serum levels of high-density lipoprotein cholesterol（HDL-C）， low-density lipoprotein cholesterol（LDL-C）， triglyceride（TG）， total cholesterol（TC）， aspartate aminotransferase（AST）， alanine aminotransferase（ALT）， lactate dehydrogenase（LDH） and creatine kinase isoenzyme（CK-MB）. Hematoxylin-eosin（HE） and Nissl staining were used to observe the pathological status of hippocampus and myocardial tissue in rats， the status of mitophagosomes in hippocampus and myocardium was observed by transmission electron microscope（TEM）， and Western blot was used to detect the contents of Drp1， mitochondrial fusion protein 2（Mfn2）， optic atrophy protein 1（OPA1）， PINK1， Parkin， p62 and microtubule-associated protein light chain 3B（LC3B） in hippocampus and myocardium. ResultsCompared with the blank group， the food intake and water intake of rats in the model group decreased， the hair was dark yellow， the gloss and smoothness decreased， the spirit was depressed， the tongue was light purple or dark purple， accompanied by petechiae or ecchymosis， the sublingual collaterals were purple and black， and the tongue coating was white and smooth. The indexes of open field test， grip strength and sucrose preference of rats decreased significantly， and the immobility time of forced swimming increased significantly（P<0.01）. Electrocardiogram and echocardiography showed that ST segment was significantly depressed， and left ventricular fractional shortening（LVFS） and left ventricular ejection fraction（LVEF） were significantly decreased（P<0.05， P<0.01）. Pathological observation showed that the number of hippocampal neurons and myocardial cells decreased， and the structural damage was obvious. The levels of serum TC， TG， LDL-C， CK-MB， LDH， AST and ALT increased， while the levels of HDL-C， 5-HT， DA and NE decreased（P<0.05， P<0.01）. TEM showed obvious mitochondrial damage in hippocampus and myocardial tissue. The protein expressions of Drp1， PINK1， Parkin and p62 in hippocampus and myocardium were increased， while the protein expressions of OPA1， Mfn2 and LC3BⅡ/Ⅰ were decreased（P<0.05， P<0.01）. Compared with the model group， the mental state， body curling up， fear of cold and other symptoms of rats in each administration group were improved， and the degree of pale purple or dark purple tongue was reduced. The scores of open field test， grip strength， sucrose preference， LVFS and LVEF were increased， and the immobility time of forced swimming was shortened（P<0.05， P<0.01）. The ST segment of electrocardiogram had a significant recovery（P<0.01）， pathological observation showed that the damage of nerve cells and myocardial tissue was improved. The levels of serum TC， TG， LDL-C， CK-MB， LDH， AST and ALT decreased， while the levels of HDL-C， 5-HT， DA and NE increased（P<0.05， P<0.01）. TEM showed that mitochondrial damage was reduced in hippocampal neurons and cardiomyocytes with visible mitochondrial autophagosomes. The protein expressions of Drp1， PINK1， Parkin and p62 in hippocampus and myocardium were decreased， while the protein expressions of OPA1， Mfn2 and LC3BⅡ/Ⅰ were increased（P<0.05， P<0.01）. ConclusionBukan Yilidan can alleviate depression， lipid metabolism disorder and myocardial ischemia injury in rats with perimenopausal psycho-cardiac disease， and its mechanism may be related to inhibiting Drp1/PINK1/Parkin signaling pathway and enhancing mitochondrial autophagy.

Hepatocellular carcinoma (HCC) is one of the most common malignancies and is a major cause of cancer-related mortalities worldwide (Forner et al., 2018; He et al., 2023). Sarcopenia is a syndrome characterized by an accelerated loss of skeletal muscle (SM) mass that may be age-related or the result of malnutrition in cancer patients (Cruz-Jentoft and Sayer, 2019). Preoperative sarcopenia in HCC patients treated with hepatectomy or liver transplantation is an independent risk factor for poor survival (Voron et al., 2015; van Vugt et al., 2016). Previous studies have used various criteria to define sarcopenia, including muscle area and density. However, the lack of standardized diagnostic methods for sarcopenia limits their clinical use. In 2018, the European Working Group on Sarcopenia in Older People (EWGSOP) renewed a consensus on the definition of sarcopenia: low muscle strength, loss of muscle quantity, and poor physical performance (Cruz-Jentoft et al., 2019). Radiological imaging-based measurement of muscle quantity or mass is most commonly used to evaluate the degree of sarcopenia. The gold standard is to measure the SM and/or psoas muscle (PM) area using abdominal computed tomography (CT) at the third lumbar vertebra (L3), as it is linearly correlated to whole-body SM mass (van Vugt et al., 2016). According to a "North American Expert Opinion Statement on Sarcopenia," SM index (SMI) is the preferred measure of sarcopenia (Carey et al., 2019). The variability between morphometric muscle indexes revealed that they have different clinical relevance and are generally not applicable to broader populations (Esser et al., 2019).
Humans ; Aged ; Sarcopenia/diagnostic imaging* ; Carcinoma, Hepatocellular/diagnostic imaging* ; Muscle, Skeletal/diagnostic imaging* ; Deep Learning ; Prognosis ; Radiomics ; Liver Neoplasms/diagnostic imaging* ; Retrospective Studies