1.Shenfu Injection Improve Chronic Heart Failure by Regulates Glycolytic Pathway Mediated by HIF-1α/PFKFB3 Pathway
Ji OUYANG ; Kun LIAN ; Xiaoqian LIAO ; Lichong MENG ; Lin LI ; Zhenyu ZHAO ; Zhixi HU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(16):136-145
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.
2.Cardiomyocyte Apoptosis in Chronic Heart Failure and Traditional Chinese Medicine Intervention
Kun LIAN ; Peiyao LI ; Zhiguang SONG ; Jianhang ZHANG ; Junxian LEI ; Lin LI ; Zhixi HU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(16):165-172
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.
3.Comparison of different regimens in isoprenaline-induced chronic heart failure models
Yuquan TAN ; Junyu ZHANG ; Meng YANG ; Fei WANG ; Senjie ZHONG ; Lin LI ; Zhixi HU
Acta Laboratorium Animalis Scientia Sinica 2024;32(2):161-167
Objective To compare animal models of chronic heart failure(CHF)prepared by three different protocols,to establish a stable,reliable,and reproducible mouse model of CHF.Methods Twenty-five male C57BL/6J mice were divided randomly into four groups:a blank group,model A group(MA group),model B group(MB group),and model C group(MC group).The model groups adopted different preparation protocols for continuous injection of isoprenaline.The MA group and MB group were dose-decreasing models:MA group:subcutaneous injection of 10 mg/kg on day 1,5 mg/kg on day 2,2.5 mg/(kg·d)on days 3~30,total 30 days;and MB group:subcutaneous injection of 20 mg/kg on day 1,10 mg/kg on day 2,5 mg/(kg·d)on days 3~14,total 14 days.The MC group used a constant dose of intraperitoneal injection of 7.5 mg/(kg·d)for 28 days.The day after the final injection,the survival and model-formation rates for each group of mice were calculated.Cardiac function was measured by cardiac ultrasound and serum levels of N-terminal pro B-type natriuretic peptide,interleukin-6,and tumor necrosis factor-α were measured.Results CHF was successfully induced in all the model groups after all injections at the end of the fourth week.However,comprehensive test result showed that the MC model was the most stable.Conclusions An isoprenaline-induced mouse model of CHF using constant intraperitoneal injection of 7.5 mg/(kg·d)for 28 days may be the most suitable model for subsequent research on traditional Chinese medicine.
4.Discussion on the Scientific Connotation of"Reinforcing Yang from Yin"Method in the Treatment of Chronic Heart Failure Based on Mitochondrial Energy Metabolism
Fei WANG ; Senjie ZHONG ; Xinchun LI ; Kun LIAN ; Lin LI ; Zhixi HU
Chinese Journal of Information on Traditional Chinese Medicine 2024;31(1):6-10
Chronic heart failure is the final stage of various cardiovascular diseases,and mitochondrial energy metabolism disorders have been proved to play an important role in the development of chronic heart failure.TCM believes that heart yin is the material basis of heart yang(qi),and deficiency of heart yang(qi)is the core pathogenesis of chronic heart failure.Based on mitochondrial energy metabolism,this article expounded the scientific connotation of"reinforcing yang from yin"in the treatment of chronic heart failure from the aspects of theoretical connotation,pathogenesis,pathophysiological relationship and modern research.In-depth study at the microscopic level demonstrated that the application of"reinforcing yang from yin"method can effectively improve the reconstruction of heart energy substrate(yin),enhance mitochondrial function,and finally provide energy support(yang),which could offer ideas for theoretical research and clinical prevention and treatment of chronic heart failure.
5.Visual Analysis of Research Trends and Hotspots in Animal Models of Chronic Heart Failure
Kun LIAN ; Xin LI ; Siyuan HU ; Yuehang XU ; Ji OUYANG ; Zhixi HU
Traditional Chinese Drug Research & Clinical Pharmacology 2024;35(3):394-401
Objective To understand the research situation of animal model of chronic heart failure(CHF)based on visualization software and bibliometrics methods,and to explore the research hotspots of animal models of CHF and guide the design of animal experiments and scientific research.Methods Literature related to animal model of CHF included in Web of Science core collection from January 1,2001 to October 10,2022 were retrieved.After reading the full text and obtaining the final included literature,VOSviewer and CiteSpace software were used to analyze the contents of institutions,journals and co-cited journals,authors and co-cited authors,keywords.Results A total of 961 papers were included,and the number of published papers increased steadily.The United States and China are the main research countries.Johns Hopkins University and Harvard University are major research institutions.The most frequently published and cited journals are AM J PHYSIOL-HEART C and CIRCULATION,etc..Schultz Harold D and Sabbah Hani N are more influential in author selection."Myocardial infarction","cardiac hypertrophy",and"rat"are the most frequent keywords,10 clusters and 18 emergent words were formed.Conclusion The research in this field is numerous,high quality but scattered.Commonly used animal models are rodents and dogs.The main modeling methods are surgery and drugs.The main pathological mechanisms are mainly myocardial hypertrophy,oxidative stress,and myocardial fibrosis.
6.Traditional Chinese Medicine Intervenes in Chronic Heart Failure Progression by Regulating NF-κB Signaling Pathway: A Review
Kun LIAN ; Ying DENG ; Siqin TANG ; Lin LI ; Ting WANG ; Zhixi HU
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(21):243-251
Chronic heart failure (CHF) is a clinical syndrome resulting from damage to the myocardium, leading to changes in the function or structure of the heart and causing reduced pumping and/or filling capacity. Its pathogenesis is complex, potentially involving myocardial fibrosis, apoptosis and autophagy of cardiomyocytes, inflammatory responses, oxidative stress, and myocardial remodeling. Our team believes that the fundamental pathogenesis of CHF is heart-Qi deficiency, with the disease location in the heart, which is closely related to other organs. Due to heart-Qi deficiency, blood circulation weakens, leading to blood stasis, which in turn generates water-dampness and phlegm turbidity that accumulate over time and become toxic. The interaction between water stasis, Qi stagnation, blood stasis, and phlegm toxicity further weakens the body, creating a vicious cycle (deficiency, stasis, water retention, and toxicity) that is difficult to resolve. Under physiological conditions, the nuclear factor-κB (NF-κB) signaling pathway functions normally, maintaining vital activities and immune responses. However, in pathological states, the NF-κB signaling pathway becomes imbalanced, triggering inflammatory responses and other issues. Research has shown that traditional Chinese medicine (TCM) can regulate the NF-κB signaling pathway through multiple pathways, targets, and effects, effectively improving the progression of CHF. As a result, this has become a research hotspot for the prevention and treatment of the disease. Guided by TCM theory, this research group reviewed the literature to summarize the activation pathways of the NF-κB pathway and its interactions with other pathways. Additionally, the group summarized the research progress on the regulation of the NF-κB pathway in the treatment of CHF using Chinese medicines, their active ingredients, Chinese medicine compounds, and Chinese patent medicines. This study is expected to clarify the mechanisms and targets by which TCM treats CHF by regulating the NF-κB pathway, thereby guiding clinical treatment and drug development for CHF.
7.Selection and Weight Determination of Diagnostic Items for Qi Stagnation Syndrome Based on Delphi Method and Analytic Hierarchy Process
Xuan ZHOU ; Ge FANG ; Qingyu MA ; Xiaojuan LI ; Yongxin LI ; Zhixi HU ; Xiantao LI ; Jiaxu CHEN
Journal of Traditional Chinese Medicine 2024;65(21):2211-2216
ObjectiveUsing the Delphi method and analytic hierarchy process (AHP) to screen diagnostic items for qi stagnation syndrome and determine their weights, providing a reference for the development of a diagnostic scale of qi stagnation syndrome. MethodsLiterature related to qi stagnation syndrome were screened from databases including CNKI, Wanfang, VIP, SinoMed (from inception to October 31, 2020). Through systematic review of literature and expert discussions, the information on the four examinations of traditional Chinese medicine were organized and an item pool was constructed. The Delphi method was used to screen the item indicators, while the AHP was employed to determine their weights. Statistical methods such as mean value, full score ratio, rank sum, unimportant percentage, and coefficient of variation were used for item screening, with the weights calculated by AHP serving as the item weights. ResultsA total of 235 articles and books were included for analysis, resulting in an item pool of 16 items. After three rounds of expert consultation, a total of 84 valid questionnaires were collected, with a total expert enthusiasm coefficient of 99% and authority coefficient of 0.86, 0.84, 0.83, respectively, and the coordination coefficients were 0.45, 0.49, and 0.29, respectively. Through the statistics analysis, 8 diagnosis items were screened out, including distension (stuffi-ness) or distending pain or scurrying pain, wiry pulse, depressed emotions, frequent sighing, deep and wiry pulse, irritability, pale red tongue, and thin white coating. The AHP showed that the order of weights of the first-level indicators from high to low was clinical symptoms, pulse manifestation, and tongue manifestation; the order of weights of the second-level indicators from high to low was distension (stuffiness) or distending pain or scurrying pain, wiry pulse, depressed emotions, frequent sighing, deep and wiry pulse, irritability, pale red tongue, and thin white coating. ConclusionBy applying the Delphi method and AHP to analyze and evaluate the diagnostic items for qi stagnation syndrome, key diagnostic items were screened and their weights determined, laying the foundation for the development of a diagnostic scale for qi stagnation syndrome.
8.Research on optimization technology of ventilation system in an industrial X-ray inspection workshop
Yi GUAN ; Zhixi GUO ; Xiaojing ZHANG ; Chao WANG ; Xiuping LI ; Qingdong WU ; Song WANG ; Dongliang CHAI
Chinese Journal of Industrial Hygiene and Occupational Diseases 2024;42(11):862-868
Objective:To investigate the reasonable airflow organization and exhaust system facilities during the operation of the inspection workshop, and solve the problem of the accumulation of harmful gases such as ozone and nitrogen oxides in the workshop.Methods:In May 2023, computational fluid dynamics (CFD) technology was used to numerically simulate the diffusion of ozone and nitrogen oxides generated by industrial radiographic inspection operations, and the comparative detection method was used to analyze the ozone and nitrogen oxides concentrations before and after the renovation of the ventilation system of the inspection workshop.Results:After the renovation of ventilation system, the average concentration of ozone in the inspection workshop decreased from 0.81 mg/m 3 to 0.03 mg/m 3, and the average concentration of nitrogen oxides decreased from 0.42 mg/m 3 to 0.01 mg/m 3, and the differences were statistically significant ( t=20.51, 10.38, P<0.001) . Conclusion:The ventilation facilities of the inspection workshop are set up in the airflow organization mode of sending up and down the exhaust, and the ventilation pipes are scientifically designed through the calculation of ventilation hydraulic balance, which can effectively control the concentration of harmful gases in the inspection workshop.
9.Syndrome Treatment of Chronic Heart Failure and Diabetes Mellitus omorbidity Based on "Syndrome-based Treatment of Disease"
Lichong MENG ; Kun LIAN ; Xinchun LI ; Cong LU ; Zhixi HU
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(24):233-242
Chronic heart failure (CHF) and diabetes mellitus (DM) comorbidity presents a myriad of symptoms and a complex pathogenesis, making the traditional diagnostic and treatment model of "using disease to treat syndrome" often inadequate in clinical practice. The concept of "syndrome-based treatment of disease" is rooted in the core thinking of traditional Chinese medicine (TCM) syndrome differentiation and treatment, emphasizing the importance of syndrome as the guiding principle. This approach categorizes various diseases according to their corresponding syndrome categories for exploration, adhering to the principle of starting from the syndrome and addressing the disease thereafter, which highlights the advantages of TCM holistic view and syndrome differentiation and treatment. The pathogenesis of CHF is characterized by deficiency of both Qi and Yin, along with blood stasis, affecting organs such as the lung, spleen, and kidney, which in turn impacts the distribution and metabolism of body fluids. Dysfunction in body fluid regulation leads to stagnation, resulting in pathological products like phlegm and turbidity, which exacerbates syndromes of Yin deficiency and excessive heat. As the conditions of Yin deficiency and dryness-heat intensify, and as body fluid depletion continues, the patient's DM symptoms worsen, contributing to or aggravating the comorbidity. Following the diagnostic approach of "syndrome-based treatment of disease", TCM diagnosis and treatment of CHF and DM comorbidity should focus on the core pathogenesis of "deficient Qi retention". This study categorized CHF and DM comorbidity into four stages: A (comorbid risk period), B (precomorbid period), C (intermediate stage of comorbidity), and D (advanced comorbidity), proposing corresponding TCM syndrome types for each stage. In terms of treatment, adhering to the principle of "tonifying deficiency and relieving stagnation", the specific methods included invigorating Qi and strengthening the body, nourishing Yin and generating body fluids, activating blood circulation and Qi, and promoting diuresis and removing toxins. This study reviewed recent research progress on Chinese medicine compound prescriptions for CHF combined with DM, aiming to achieve precise treatment for both diseases and provide a scientific basis for the application of TCM in the prevention and treatment of CHF and DM comorbidity.
10.Clinical Research Progress in TCM Intervention in "Psycho-cardiological Disease"
Kun LIAN ; Lin LI ; Bo NING ; Siyuan HU ; Yanjie LU ; Zhixi HU
Chinese Journal of Information on Traditional Chinese Medicine 2024;31(7):188-192
In recent years,with the increase of social pressure,the incidence of"psycho-cardiological disease"increases.Western medicine mainly uses conventional cardiovascular drugs combined with antidepressant or anxiety drugs.TCM has the characteristics of multi-pathway,multi-target,multi-mechanism,integration and low toxicity.It has unique advantages in the intervention of"psycho-cardiological disease"and has significant clinical efficacy.However,the pathogenesis,clinical diagnosis,syndrome differentiation and treatment of this disease are not the same.This article summarized relevant literature and reviewed the etiology,pathogenesis,experience in syndrome differentiation and treatment,and clinical research of this disease from the perspective of TCM,in order to provide reference for diagnosis of disease,precision treatment and improvement of curative efficacy of"psycho-cardiological disease".

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