Chronic heart failure （CHF） is a complex clinical syndrome caused by ventricular dysfunction， with mitochondrial energy metabolism disorder being a critical factor in disease progression. Heart-Yang deficiency syndrome， as the core pathogenesis of CHF， persists throughout the disease course. Insufficiency of heart-Yang leads to weakened warming and propelling functions， resulting in the accumulation of phlegm-fluid， blood stasis， and dampness. This eventually causes Qi stagnation with phlegm obstruction and blood stasis with water retention， forming a vicious cycle that exacerbates disease progression. According to the theory of reinforcing Yang， the clinical experience of the traditional Chinese medicine （TCM） master Tang Zuxuan in treating CHF with heart-Yang deficiency syndrome， and achievements from molecular biological studies， this study innovatively proposes an integrated research framework of "TCM syndrome differentiation and staging-mitochondrial metabolism mechanisms-intervention with Yang-reinforcing prescriptions" which is characterized by the integration of traditional Chinese and Western medicine. Heart-Yang deficiency syndrome is classified into mild （Stage Ⅰ-Ⅱ）， severe （Stage Ⅲ）， and critical （Stage Ⅳ） stages. The study elucidates the precise correlations between the pathogenesis of each stage and mitochondrial metabolism disorders from theoretical， pathophysiological， and therapeutic perspectives. The mild stage is characterized by impaired biogenesis and substrate-utilization imbalance， corresponding to heart-Yang deficiency and phlegm-fluid aggregation. Linggui Zhugantang and similar prescriptions can significantly improve the expression of peroxisome proliferator-activated receptor gamma co-activator-1α（PGC-1α）/silent information regulator 2 homolog 1 （SIRT1） and ATPase activity. The severe stage centers on oxidative stress and structural damage， reflecting Yang deficiency with water overflow and phlegm-blood stasis intermingling. At this stage， Zhenwu Tang and Qiangxin Tang can effectively mitigate oxidative stress damage， increase adenosine triphosphate （ATP） content， and repair mitochondrial structure. The critical stage arises from calcium overload and mitochondrial disintegration， leading to the collapse of Yin-Yang equilibrium. At this stage， Yang-restoring and crisis-resolving prescriptions such as Fuling Sini Tang and Qili Qiangxin capsules can inhibit abnormal opening of the mitochondrial permeability transition pore （MPTP）， reduce cardiomyocyte apoptosis rate， and protect mitochondrial function. By summarizing the characteristics of mitochondrial energy metabolism disorders at different stages of CHF， this study explores the application of the theory of reinforcing Yang in treating heart-Yang deficiency syndrome and provides new insights for the clinical diagnosis and treatment of CHF.

Chronic heart failure （CHF） is a group of complex clinical syndromes caused by abnormal changes in the structure and/or function of the heart due to various reasons， resulting in disorders of ventricular contraction and/or diastole. CHF is a condition where primary diseases such as coronary heart disease， hypertension and pulmonary heart disease recur frequently and persist for a long time， presenting blood stasis in meridians and collaterals， stagnation of water and dampness， and accumulation of Qi in collaterals. Its pathogenesis is complex and may involve myocardial energy metabolism disorders， oxidative stress responses， myocardial cell apoptosis， autophagy， inflammatory responses， etc. According to the theory of restraining hyperactivity to acquire harmony， we believe that under normal circumstances， the adenosine monophosphate-activated protein kinase （AMPK） signaling pathway functions normally， maintaining human physiological activities and energy metabolism. Under pathological conditions， the AMPK signaling pathway is abnormal， causing energy metabolism disorders， inflammatory responses， and myocardial fibrosis. Traditional Chinese medicine （TCM） can regulate the AMPK signaling pathway through multiple mechanisms， targets， and effects， effectively curbing the occurrence and development of CHF. It has gradually become a research hotspot in the prevention and treatment of this disease. Guided by the theory of TCM， our research group， through literature review， summarized the relationship between the AMPK pathway and CHF and reviewed the research progress in the prevention and control of CHF with TCM active ingredients， TCM compound prescriptions， and Chinese patent medicines via regulating the AMPK pathway. The review aims to clarify the mechanism and targets of TCM in the treatment of CHF by regulating the AMPK pathway and guide the clinical treatment and drug development for CHF.

ObjectiveTo examine the influences of Shenfu injection on the endogenous metabolic byproducts in the myocardium of the rat model exhibiting chronic heart failure， thus deciphering the therapeutic mechanism of the Qi-reinforcing and Yang-warming method. MethodsSD rats were randomly allocated into a control group and a modeling group. Chronic heart failure with heart-Yang deficiency syndrome in rats was modeled by multi-point subcutaneous injection of isoproterenol， and the rats were fed for 14 days after modeling. The successfully modeled rats were randomized into model， Shenfu injection （6.0 mL·kg^-1）， and trimetazidine （10 mg·kg^-1） groups and treated with corresponding agents for 15 days. The control group and the model group were injected with equal doses of normal saline， and the samples were collected after the intervention was completed. Cardiac color ultrasound was performed. Hematoxylin-eosin （HE） staining was used to observe histopathological morphology， and the serum level of N-terminal pro-brain natriuretic peptide （NT-proBNP） was assessed by enzyme-linked immunosorbent assay （ELISA）. The mitochondrial morphological and structural changes of cardiomyocytes were observed by transmission electron microscopy， and the metabolic profiling was carried out by ultra high performance liquid chromatography-quantitative exactive-mass spectrometry （UHPLC-QE-MS）. Differential metabolites were screened and identified by orthogonal partial least squares-discriminant analysis （OPLS-DA） and other methods， and then the MetaboAnalyst database was used for further screening. The relevant biological pathways were obtained through pathway enrichment analysis. The receiver operating characteristic （ROC） curve was established to evaluate the diagnostic value of each potential biomarker for myocardial injury and the evaluation value for drug efficacy. ResultsThe results of color ultrasound showed that Shenfu Injection improved the cardiac function indexes of model rats （P<0.05）. The results of HE staining showed that Shenfu injection effectively alleviated the pathological phenomena such as myocardial tissue structure disorder and inflammatory cell infiltration in model rats. The results of ELISA showed that Shenfu injection effectively regulated the serum NT-proBNP level in the model rats. Transmission electron microscopy （TEM） showed that Shenfu injection effectively restored the mitochondrial morphological structure. The results of metabolomics showed that the metabolic phenotypes of myocardial samples presented markedly differences between groups. Nine differential metabolites could be significantly reversed in the Shenfu injection group， involving three metabolic pathways： pyruvate metabolism， histidine metabolism， and citric acid cycle （TCA cycle）. The results of ROC analysis showed that the area under the curve （AUC） values of all metabolites were between 0.75 and 1.0， indicating that the differential metabolites had high diagnostic accuracy for myocardial injury， and the changes in their expression levels could be used as potential markers for efficacy evaluation. ConclusionShenfu injection significantly alleviated the damage of cardiac function， myocardium， and mitochondrial structure in the rat model of chronic heart failure with heart-Yang deficiency syndrome by ameliorating energy metabolism remodeling. Reinforcing Qi and warming Yang is a key method for treating chronic heart failure with heart-Yang deficiency syndrome.

Chronic heart failure is the terminal stage of various cardiovascular diseases， and cardiomyocyte apoptosis is the turning point of decompensation. Studies have shown that traditional Chinese medicine （TCM） could regulate apoptosis-related signaling pathways and factors and inhibit or up-regulate the expression of apoptosis-related proteins. Thus， TCM can reduce cardiomyocyte apoptosis， protect the myocardial tissue and improve the cardiac function， demonstrating remarkable clinical effects. In recent years， the research on the treatment of chronic heart failure based on the inhibition of cardiomyocyte apoptosis is increasing and becomes the current research hotspot. On the basis of literature review， this paper discovers that TCM regulates apoptosis factors and multiple signaling pathways to inhibit apoptosis and inflammation and delay the progression of chronic heart failure through classical pathways such as the death receptor pathway， the mitochondrial pathway， and the endoplasmic reticulum pathway. At the same time， the studies in this field have the following problems： Repeated studies with shallow， simple， and fragmented contents， treating animal models with TCM prescriptions without syndrome differentiation， treating diseases with drugs at only one concentration which is insufficient to indicate efficacy， and lacking comprehensive， holistic， and systematic studies on the relationships of apoptosis with inflammatory responses， pyroptosis， ferroptosis， and autophagy. In the future， more scientific， reasonable， comprehensive， and feasible experimental schemes should be designed on the basis of comprehensively mastering the research progress in this field， and the communication and cooperation between researchers in different disciplines should be strengthened. The specific pathological mechanism of cardiomyocyte apoptosis in chronic heart failure and the signaling pathways， active components， and action targets of TCM in inhibiting cardiomyocyte apoptosis in chronic heart failure should be elucidated. Such efforts are expected to provide sufficient reference for the clinical treatment of chronic heart failure.

Hepatic stellate cells (HSCs) are the primary fibrogenic cells in the liver, and their activation plays a crucial role in the development and progression of hepatic fibrosis. Here, we report that retinoid X receptor-alpha (RXRα), a unique member of the nuclear receptor superfamily, is a key modulator of HSC activation and liver fibrosis. RXRα exerts its effects by modulating calcium/calmodulin-dependent protein kinase kinase β (CaMKKβ)-mediated activation of AMP-activated protein kinase-alpha (AMPKα). In addition, we demonstrate that K-80003, which binds RXRα by a unique mechanism, effectively suppresses HSC activation, proliferation, and migration, thereby inhibiting liver fibrosis in the CCl₄ and amylin liver NASH (AMLN) diet animal models. The effect is mediated by AMPKα activation, promoting mitophagy in HSCs. Mechanistically, K-80003 activates AMPKα by inducing RXRα to form condensates with CaMKKβ and AMPKα via a two-phase process. The formation of RXRα condensates is driven by its N-terminal intrinsic disorder region and requires phosphorylation by CaMKKβ. Our results reveal a crucial role of RXRα in liver fibrosis regulation through modulating mitochondrial activities in HSCs. Furthermore, they suggest that K-80003 and related RXRα modulators hold promise as therapeutic agents for fibrosis-related diseases.

Ursodeoxycholic acid (UDCA) is a naturally occurring, low-toxicity, and hydrophilic bile acid (BA) in the human body that is converted by intestinal flora using primary BA. Solute carrier family 7 member 11 (SLC7A11) functions to uptake extracellular cystine in exchange for glutamate, and is highly expressed in a variety of human cancers. Retroperitoneal liposarcoma (RLPS) refers to liposarcoma originating from the retroperitoneal area. Lipidomics analysis revealed that UDCA was one of the most significantly downregulated metabolites in sera of RLPS patients compared with healthy subjects. The augmentation of UDCA concentration (≥25 μg/mL) demonstrated a suppressive effect on the proliferation of liposarcoma cells. [¹⁵N₂]-cystine and [¹³C₅]-glutamine isotope tracing revealed that UDCA impairs cystine uptake and glutathione (GSH) synthesis. Mechanistically, UDCA binds to the cystine transporter SLC7A11 to inhibit cystine uptake and impair GSH de novo synthesis, leading to reactive oxygen species (ROS) accumulation and mitochondrial oxidative damage. Furthermore, UDCA can promote the anti-cancer effects of ferroptosis inducers (Erastin, RSL3), the murine double minute 2 (MDM2) inhibitors (Nutlin 3a, RG7112), cyclin dependent kinase 4 (CDK4) inhibitor (Abemaciclib), and glutaminase inhibitor (CB839). Together, UDCA functions as a cystine exchange factor that binds to SLC7A11 for antitumor activity, and SLC7A11 is not only a new transporter for BA but also a clinically applicable target for UDCA. More importantly, in combination with other antitumor chemotherapy or physiotherapy treatments, UDCA may provide effective and promising treatment strategies for RLPS or other types of tumors in a ROS-dependent manner.

Objective To investigate the postoperative efficacy of laparoscopic hiatal hernia repair(LHHR)combined with Toupet or Dor fundoplication for the treatment of esophageal hiatal hernia(HH).Methods A retrospective analysis was conducted on the case data of HH patients who underwent LHHR combined with Toupet(Toupet group,n=53)and Dor(Dor group,n=53)fundoplication between December 2018 and December 2022 in Department of General Surgery of Gansu Provincial Hospital.Intraoperative and postoperative recovery outcomes of both groups were observed.We analyzed and compared the incidence of dysphagia and gastroesophageal reflux disease questionnaire(GERD-Q)scores at preoperative and postoperative intervals of 1 month,6 months,and 1 year.The incidence of postoperative complications and the 1-year recurrence rate were compared between the two groups.Additionally,factors influencing postoperative dysphagia within the first month were examined.Results The differences between the two groups in operation time,intraoperative bleeding,postoperative ventilation time,postoperative extubation time and hospitalization time were not statistically significant(P>0.05).There was no significant difference in the incidence of immediate postoperative dysphagia in two groups(P>0.05).Furthermore,the differences between the two groups in the incidence of postoperative complications,such as bloating,abdominal pain and diarrhea,were not statistically significant(P>0.05).The incidence of dysphagia in Toupet group was higher than that in Dor group at 1 month postoperatively,and the difference was statistically significant(P=0.017);but the difference in the incidence of dysphagia between the two groups at 6 months and 1 year postoperatively was not statistically significant(P=0.767,1.000).The results of binary logistic regression analysis showed that both surgical procedure(OR=2.613,95%CI 1.141-5.983,P=0.023)and esophageal contractile reserve function(OR=2.921,95%CI 1.203-7.095,P=0.018)were independent risk factors for the incidence of dysphagia in patients with HH at 1 month after surgery.Compared with the preoperative period,the GERD-Q symptom scores were lower in both groups at 1 month,6 months,and 1 year postoperatively,and the difference was statistically significant(P<0.05);but there was no statistically significant difference between the groups at the same time point(Fintergroup=0.334,P=0.565).The difference between the two groups in 1-year postoperative recurrence rates was not statistically significant(P>0.05).Conclusions LHHR combined with Toupet or Dor fundoplication are both safe and effective surgical procedures for the treatment of HH,with excellent reflux control,fewer complications and lower recurrence rates,but Toupet fundoplication is more likely to have postoperative short-term dysphagia than Dor fundoplication.

Objective To utilize single-cell and peripheral blood transcriptomic data from 3D brain organoids,combined with machine learning,to analyze the role of mitochondrial autophagy genes in schizophrenia(SCZ).Methods By integrating two machine learning algorithms,we identified differentially expressed mitochondrial autophagy-related genes between schizophrenia patients and healthy controls using peripheral blood RNA sequencing data.The relationship between mitophagy gene,immune cells and inflammatory factors was further explored.Comprehensive single-cell analysis was used to explore the signaling pathways and specific transcription factors based on mitophagy genes.Results Using machine learning,seven key mitophagy genes expressed in schizophrenia patients were identified.Based on Mitoscore analysis,at the single-cell level,neurons with high mitochondrial autophagy activity(Mitohigh_Neuron)formed new interactions with endothelial cells via the SPP1 signaling pathway.Conclusion This study identified two subtypes of mitophagy and seven key mitophagy genes in schizophrenia,providing new insights into the pathogenesis of the disease.

Perimenopausal syndrome （MPS）， a common endocrine system disease， is one of the diseases responding specifically to traditional Chinese medicine （TCM）. The China Association of Chinese Medicine organized experts in endocrinology， gynecology， and interdisciplinary fields of both Western and Chinese medicine to discuss the advantages and challenges of diagnosing and treating MPS with Western medicine， TCM， and integrative medicine. Experts at the conference believe that MPS is initiated by estrogen decline and rooted in deficiency， with the pathogenesis being imbalance between Yin and Yang in the kidney. The hormone replacement therapy in Western medicine for menopause can rapidly alleviate related symptoms by quickly restoring the estrogen level and timely detect and delay complications of menopause， whereas such a therapy has certain risks， necessitating close monitoring of adverse reactions. Moreover， the various contraindications and precautions limit the clinical application of the hormone replacement therapy. TCM has advantages in synergistically alleviating symptoms such as hot flashes， sweating， sleep disorders， and emotional abnormalities of MPS without causing obvious adverse reactions. However， its efficacy is slower than the hormone replacement therapy， and the TCM evidence for preventing and treating complications of menopause remains unclear. Three suggestions were proposed for the future development of both Western and TCM for ameliorating MPS. First， an integrated diagnosis and treatment system for MPS with both Western and Chinese medicine should be established. Second， high-quality evidence-based interventions for MPS should be developed with TCM alone or in combination with Western medicine. Third， efforts should be made to promote the new TCM drug development and the interdisciplinary cooperation for treating MPS.

Objective We aimed to compare the efficacy and prognosis of percutaneous coronary intervention(PCI)in complex and high-risk patients with coronary heart disease(CHD)treated with extracorporeal membrane oxygenation(ECMO)combined with intra-aortic balloon pump(IABP)assistance,and explore the application value of combined use of mechanical circulatory support(MCS)devices in complex PCI.Methods A total of patients who met the inclusion criteria and underwent selective PCI supported by MCS at the Department of Cardiology,the First Affiliated Hospital of the Air Force Medical University from January 2018 to December 2022 were continuously enrolled.According to the mechanical circulatory support method,the patients were divided into ECMO+IABP group and IABP group.Clinical characteristics,angiographic features,in-hospital outcomes,and complications were collected.The intra-hospital outcomes and major adverse cardiovascular events(MACE)at one month and one year after the procedure were observed.The differences and independent risk factors between the two groups in the above indicators were analyzed.Results A total of 218 patients undergoing elective PCI were included,of which 66 patients were in the ECMO+IABP group and 152 patients were in the IABP group.The baseline characteristics of the two groups of patients were generally comparable,but the ECMO+IABP group had more complex lesion characteristics.The proportion of patients with atrial fibrillation(6.1％vs.0.7％,P=0.030),left main disease(43.9％vs.27.0％,P=0.018),triple vessel disease(90.9％vs.75.5％,P=0.009),and RCA chronic total occlusion disease(60.6％vs.35.5％,P＜0.001)was higher in the ECMO+IABP group compared to the IABP group.The proportion of patients with previous PCI history was higher in the IABP group(32.9％vs.16.7％,P=0.014).There was no statistically significant difference in the incidence of in-hospital complications between the two groups(P=0.176),but the incidence of hypotension after PCI was higher in the ECMO+IABP group(19.7％vs.9.2％,P=0.031).The rates of 1-month MACE(4.5％vs.2.6％,P=0.435)and 1-year MACE(7.6％vs.7.9％,P=0.936)were comparable between the two groups.Multivariate analysis showed that in-hospital cardiac arrest(OR 7.17,95％CI 1.27-40.38,P=0.025)and after procedure hypotension(OR 3.60,95％CI 1.10-11.83,P=0.035)were independent risk factors for the occurrence of 1-year MACE.Conclusions Combination use of ECMO+IABP support can provide complex and high-risk coronary heart disease patients with an opportunity to achieve coronary artery revascularization through PCI,and achieve satisfactory long-term prognosis.