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.

Chronic heart failure （CHF） refers to a clinical syndrome in which the function or structure of the heart is changed due to damage to the original myocardium， resulting in reduced pumping and/or filling functions of the heart. In recent years， the mechanisms， pathways， and targets of traditional Chinese medicine （TCM） in the treatment of CHF have been continuously confirmed， and the application of TCM theories in guiding the syndrome differentiation and precise treatment of CHF is currently a research hotspot. On the basis of the syndrome differentiation and treatment in TCM， Professor LI Candong innovatively proposed the thinking of five differentiation： Disease differentiation， syndrome differentiation， pathogenesis differentiation， symptom differentiation， and individual differentiation. This article explores the clinical diagnosis and treatment of CHF from this thinking， emphasizing comprehensive syndrome differentiation， objective analysis， dynamic assessment， and individualized treatment. In terms of diagnosis， the first is to identify the disease name， cause， location， severity， and type of CHF， determine the type and its evolution， and clarify the process of transmission and transformation between deficiency and excess. Secondly， it is necessary to distinguish the authenticity， severity， primary and secondary， urgency and complexity of CHF syndromes， providing scientific guidance for syndrome differentiation and treatment. Thirdly， according to the symptoms and the principles of deficiency and excess， the physician should identify the core pathogenesis of CHF from the perspectives of Qi， blood， Yin， Yang， deficiency， stasis， phlegm， water， and toxins. Fourthly， from the macro， meso and micro levels， the physician should carefully distinguish the presence or absence， severity， authenticity， and completeness of the symptoms to guide the diagnosis and treatment process of CHF. Finally， personalized medication for CHF should be promoted based on the patient's gender， age， constitution， and living habits. In terms of treatment， based on the thinking of five differentiation， we propose that the treatment of CHF should integrate the disease and syndrome， clarify the pathogenesis， and apply precise treatment. The treatment should be people-oriented， staged， and typed， and the medication should be adjusted according to symptoms. This diagnostic and therapeutic approach is based on the holistic concept and syndrome differentiation and treatment， and combines the three causes for appropriate treatment， providing new ideas and insights for the diagnosis and treatment of 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.

Traditional Chinese medicine （TCM） diagnostics is a discipline that studies the basic theories and fundamental skills of diagnostic methods， disease diagnosis， and differentiation in accordance with the theories of TCM. The artificial intelligence （AI） technology has gained remarkable achievements in the intelligentization of the four diagnostic methods in TCM and the standardization of differentiation and diagnosis. However， it still faces many challenges. The standardization of clinical data collection is difficult， and the data quality is uneven， which affects the usability of the data. The integration of the four diagnostic information is insufficient. Most instruments can only collect data from a single diagnostic method， lacking overall integrity. The scientific nature of the diagnostic model needs to be improved. The existing models lack dynamics and the reasoning logic of TCM differentiation. The accuracy of intelligent methods needs to be improved， and the existing evaluation indicators cannot fully reflect the practical application effect of the model. Furthermore， the relevant laws and regulations are still not perfect， and data security and patient privacy lack guarantees. The cultivation of compound talents is insufficient， and there is a lack of interdisciplinary talents who are proficient in both TCM and AI. On this basis， this paper expounded on the current development status， difficulties， and bottlenecks of AI in TCM diagnosis and then explored the development trend of AI in the field of TCM diagnosis. It proposed solutions such as optimizing the data collection process， constructing multimodal diagnostic models， facilitating multi-disciplinary exchanges and cooperation， improving laws and regulations， and cultivating compound talents. It is hoped that modern， standardized， normalized， and intelligent TCM diagnosis can be further promoted， thereby providing new impetus and methods for the inheritance and innovation of TCM.

Chronic heart failure （CHF）， as the terminal stage of various cardiovascular diseases， is characterized by a prolonged course and a high mortality rate， posing a serious threat to human health and life. According to physician Sun Yikui's theory of "Mingmen Dongqi" （dynamic Qi of life gate） in the Ming Dynasty and the modern medicine concept of mitochondrial quality control （MQC）， this paper systematically explores the pathogenic mechanisms and evolutionary patterns of CHF， as well as its intrinsic connection with microstructural homeostasis， and further proposes potential traditional Chinese medicine （TCM） intervention strategies. CHF is often caused by damage to the heart Qi at the early stage. As the disease progresses， prolonged illness affects the kidneys， leading to the dynamic Qi decline of life gate. Further， it results in the failure of the functions of sustaining and consolidating， causing the disintegration of the physical form， which corresponds to mitochondrial kinetic disorders. The deficiency in primary driving force results in impaired Qi transformation， corresponding to mitochondrial autophagy dysfunction， forming a pathological transmission chain of "life gate-mitochondrion" that ultimately leads to myocardial structural disintegration and energy metabolism failure. Modern research indicates that patients with CHF exhibit significant MQC imbalance. Disrupted mitochondrial dynamics lead to network fragmentation， and impaired autophagy causes metabolic blockage， constituting the key microscopic mechanisms underlying ventricular remodeling and pump failure. Chinese herbal medicines， such as those with the effects of warming and tonifying kidney Yang or reinforcing healthy Qi， can intervene in multiple signaling pathways-including PTEN-inducible kinase 1 （PINK1）/Parkin and AMP-activated protein kinase/dynamin-related protein 1 （AMPK/Drp1）-to regulate mitochondrial dynamics and autophagy activity. This repairs damaged MQC networks and improves the microenvironment of myocardial energy metabolism. These intervention strategies align closely with the TCM therapeutic principles of warming and tonifying life gate， replenishing Qi， and activating blood， demonstrating the advantages of holistic regulation based on kidney-centered treatment and mitochondrial-targeted approaches. By integrating the "Mingmen Dongqi" theory with the MQC mechanism， this paper establishes a theoretical framework for the integrated prevention and treatment of CHF， offering new perspectives and insights for clinical practice and future research.

Chronic heart failure （CHF）， as the terminal stage of various cardiovascular diseases， is characterized by a prolonged course and a high mortality rate， posing a serious threat to human health and life. According to physician Sun Yikui's theory of "Mingmen Dongqi" （dynamic Qi of life gate） in the Ming Dynasty and the modern medicine concept of mitochondrial quality control （MQC）， this paper systematically explores the pathogenic mechanisms and evolutionary patterns of CHF， as well as its intrinsic connection with microstructural homeostasis， and further proposes potential traditional Chinese medicine （TCM） intervention strategies. CHF is often caused by damage to the heart Qi at the early stage. As the disease progresses， prolonged illness affects the kidneys， leading to the dynamic Qi decline of life gate. Further， it results in the failure of the functions of sustaining and consolidating， causing the disintegration of the physical form， which corresponds to mitochondrial kinetic disorders. The deficiency in primary driving force results in impaired Qi transformation， corresponding to mitochondrial autophagy dysfunction， forming a pathological transmission chain of "life gate-mitochondrion" that ultimately leads to myocardial structural disintegration and energy metabolism failure. Modern research indicates that patients with CHF exhibit significant MQC imbalance. Disrupted mitochondrial dynamics lead to network fragmentation， and impaired autophagy causes metabolic blockage， constituting the key microscopic mechanisms underlying ventricular remodeling and pump failure. Chinese herbal medicines， such as those with the effects of warming and tonifying kidney Yang or reinforcing healthy Qi， can intervene in multiple signaling pathways-including PTEN-inducible kinase 1 （PINK1）/Parkin and AMP-activated protein kinase/dynamin-related protein 1 （AMPK/Drp1）-to regulate mitochondrial dynamics and autophagy activity. This repairs damaged MQC networks and improves the microenvironment of myocardial energy metabolism. These intervention strategies align closely with the TCM therapeutic principles of warming and tonifying life gate， replenishing Qi， and activating blood， demonstrating the advantages of holistic regulation based on kidney-centered treatment and mitochondrial-targeted approaches. By integrating the "Mingmen Dongqi" theory with the MQC mechanism， this paper establishes a theoretical framework for the integrated prevention and treatment of CHF， offering new perspectives and insights for clinical practice and future research.

ObjectiveThis study aims to explore the mechanism and targets of Shenfu Injection in regulating glycolysis to intervene in myocardial fibrosis in chronic heart failure based on the hypoxia-inducible factor-1α （HIF-1α）/ 6-phosphofructo-2-kinase/fructose-2，6-bisphosphatase 3 （PFKFB3） signaling pathway. MethodsA rat model of chronic heart failure was established by subcutaneous injection of isoproterenol （ISO）. After successful modeling， the rats were randomly divided into the Sham group， Model group， Shenfu injection （SFI， 6 mL·kg^-1） group， and inhibitor （3PO， 35 mg·kg^-1） group， according to a random number table， and they were treated for 15 days. Cardiac function was evaluated by echocardiography， and serum N-terminal pro-brain natriuretic peptide （NT-proBNP） levels were detected by enzyme-linked immunosorbent assay （ELISA）. Fasting body weight and heart weight were measured， and the heart index （HI） was calculated. Pathological changes in myocardial tissue were observed by hematoxylin-eosin （HE） and Masson staining， and the fibrosis rate was calculated. Biochemical assays were used to determine serum levels of glucose （GLU）， lactic acid （LA）， and pyruvic acid （PA）. Western blot was used to analyze the expression of proteins related to the HIF-1α/PFKFB3 signaling pathway （HIF-1α and PFKFB3）， glycolysis-related proteins （HK1， HK2， PKM2， and LDHA）， and fibrosis-related proteins ［transforming growth factor （TGF）-β₁， α-smooth muscle actin （α-SMA）， and Collagen type Ⅰ α1 （ColⅠA1）］. Real-time PCR was used to detect the mRNA expression of HIF-1α and PFKFB3 in myocardial tissue. ResultsCompared with the Sham group， the Model group showed significantly decreased left ventricular ejection fraction （LVEF）， left ventricular shortening fraction （LVFS）， interventricular septal thickness （IVSd）， and interventricular septal strain （IVSs） （P<0.05）， while left ventricular internal dimension at end-diastole （LVDd） and end-systole （LVIDs） were increased （P<0.05）. Serum NT-proBNP levels were significantly increased （P<0.01）， and body weight was decreased. Heart weight was increased， and the HIT index was increased （P<0.05）. Myocardial tissue exhibited inflammatory cell infiltration and collagen fiber deposition， and the fibrosis rate was significantly increased （P<0.05）. Serum GLU was decreased （P<0.05）， while LA and PA levels were increased （P<0.05）. Protein expressions of HIF-1α， PFKFB3， HK1， HK2， PKM2， LDHA， TGF-β₁， α-SMA， and ColⅠA1， as well as the mRNA expression of HIF-1α and PFKFB3 were increased （P<0.05）. Compared with the Model group， both the SFI group and 3PO groups showed significant improvements in LVEF， LVFS， IVSd， and IVSs （P<0.05） and decreases in LVDd， LVIDs， and NT-proBNP levels （P<0.05）. Body weight was significantly increased. Heart weight was significantly decreased， and the HIT index was significantly decreased （P<0.05）. Inflammatory cell infiltration， collagen fiber deposition， and the fibrosis rate were significantly decreased （P<0.05）. Serum GLU levels were significantly increased （P<0.05）， while LA and PA levels were decreased （P<0.05）. Expressions of glycolysis-related proteins， fibrosis-related proteins， and HIF-1α/PFKFB3 pathway-related proteins and mRNAs were significantly suppressed （P<0.05）. ConclusionSFI improves cardiac function in chronic heart failure by downregulating the expression of HIF-1α/PFKFB3 signaling pathway-related proteins， regulating glycolysis， and inhibiting myocardial fibrosis.

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.

Chronic heart failure(CHF)is the end-stage of a variety of heart diseases with complex pathogenesis,which may involve myocardial fibrosis,inflammation reaction and oxidative stress.Chinese materia medica has the characteristics of multiple pathways,levels,and targets in the treatment of CHF,with significant therapeutic effects.Based on the TCM theories,this article described the research progress of TCM and its effective components,TCM compounds and Chinese patent medicines in regulating TGF-β signaling pathway in the treatment of CHF,and summarized the mechanism and target of TCM regulating TGF-β pathway in the treatment of CHF,including inhibiting myocardial fibrosis,reducing inflammatory reaction and apoptosis,so as to provide a reference for the related research of Chinese materia medica in the treatment of CHF.