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.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.
4.Status Analysis of Unplanned Reoperation in Cardiac Surgery Department of a Provincial Grade A Tertiary General Hospital
Mingjuan XIA ; Kun LI ; Ying LIAN ; Rucai ZHAN ; Yanfei SU ; Lingchen KONG ; Min XU
Chinese Hospital Management 2024;44(2):67-71
Objective To analyze the current situation of unplanned reoperation in cardiac surgery and to discuss the management measures of unplanned reoperation.Methods The information of patients undergoing cardiac surgery in a class A tertiary comprehensive hospital during 2018-2022 was collected to analyze the incidence of unplanned reoperation,major ca uses,disease types,surgica l moda lities and Complications.Results A tota l of 3902 patients underwent surgery,of whom 73(1.87%)underwent unplanned reoperation.The main cause of unplanned reoperation was bleeding(50%).The disease types with the highest unplanned reoperation composition ratio were coronary heart disease(38.4%),and the disease types with the highest incidence were dilated cardiomyopathy(11.1%).The average hospitalization cost,the average length of hospitalization,mortality rate and medical dispute rate of patients who had unplanned reoperation were significantly higher than those who did not have unplanned reoperation,the difference was statistically significant(P=0.001).Conclusion The hospital should strengthen the perioperative management of cardiac surgery,focus on supervising disease types and surgical modalities with high incidence of unplanned reoperation,and strictly implement the system of operation classification and the system of reporting unplanned reoperation to ensure the quality of patient surgery.
5.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.
6.Expert Consensus on Clinical Diseases Responding Specifically to Traditional Chinese Medicine: Perimenopausal Syndrome
Shiwan HU ; Haiyan LIANG ; Kun MA ; Xiaona MA ; Zihan FANG ; Wenpei BAI ; Xinmin LIU ; Hongtian LI ; Fengmei LIAN ; Wei ZHANG ; Lihua QIN ; Min SHANG ; Ailuan LAI ; Xiuxiang TENG ; Mei MO ; Xiaoxiao ZHANG ; Linhua ZHAO
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(21):234-242
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.
7.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.
8.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.
9.Long-term therapeutic efficacy and prognosis analysis of complex high-risk coronary heart disease patients undergoing elective percutaneous coronary intervention with extracorporeal membrane oxygenation combined with intra-aortic balloon pump
Tian-Tong YU ; Shuai ZHAO ; Yan CHEN ; You-Hu CHEN ; Gen-Rui CHEN ; Huan WANG ; Bo-Hui ZHANG ; Xi ZHANG ; Bo-Da ZHU ; Peng HAN ; Hao-Kao GAO ; Kun LIAN ; Cheng-Xiang LI
Chinese Journal of Interventional Cardiology 2024;32(9):501-508
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.
10.Analysis of In-Hospital and One-year After Procedure Outcomes in Patients With Coronary Chronic Total Occlusion Recanalized With Dissection and Re-entry Operation Pattern
Jin LI ; Tiantong YU ; Haokao GAO ; Huan WANG ; Bo WANG ; Yue CAI ; Genrui CHEN ; Kun LIAN ; Yamin ZHANG ; Li YANG ; Hua YANG ; Ling TAO ; Chengxiang LI
Chinese Circulation Journal 2024;39(7):661-668
Objectives:We aimed to compare the impact of dissection and re-entry(DR)recanalizing pattern with non-DR on the in-hospital results and prognostic outcomes of patients treated successfully by percutaneous coronary intervention(PCI)of chronic total occlusion(CTO)and examine the benefit of DR in CTO PCI. Methods:A total of 815 consecutive patients with CTO meeting the inclusion criteria in the Department of Cardiology of the First Affiliated Hospital of PLA Air Force Military Medical University from January 2018 to December 2020 were enrolled and divided into DR group(n=239)and non-DR group(n=576)according to whether DR recanalizing pattern was used in the procedure.The clinical characteristics,coronary angiographic characteristics,procedure results,and complications were collected,and the prognostic outcomes within one year after the procedure were observed.Propensity score matching by the clinical and coronary angiographic characteristics was performed and results were compared with 208 matched patients in each group.The endpoints were the major adverse cardiovascular events(MACE)consisting of all-cause death and myocardial infarction,clinically driven target vessel revascularization(TVR)one year after the procedure,and in-hospital outcomes. Results:The mean age of all patients was(60.9±10.9)years old,and 87.4%were male.As compared with the non-DR group,the proportion of blunt cap,ambiguous,calcification,angle>45°,and diseased landing zone,as well as mean J-CTO score was higher in the DR group(all P<0.05).The mean stent length and median procedure time were longer in the DR group,median guidewires and consumed contrast volume was also higher in the DR group(all P<0.001).Incidence of in-hospital death,myocardial infarction,perforation,side branch loss,bleeding of BARC 3rd grade and above,and contrast-related impairment of renal function were similar between the two groups(all P>0.05).However,peripheral vascular complications occurred more frequently in the DR group(P=0.007).One year after the procedure,the incidence of MACE(2.9%vs.2.4%,log-rank P=0.750)and clinically driven TVR(5.8%vs.3.9%,log-rank P=0.365)as well as all-cause death(2.9%vs.1.0%,log-rank P=0.154)and myocardial infarction(0.5%vs.1.9%,log-rank P=0.184)were similar between the two matched groups.Multivariate Cox regression analysis showed no significant association between DR and MACE(HR=1.129,95%CI:0.427-2.979,P=0.807)and TVR(HR=0.606,95%CI:0.213-1.722,P=0.347).LVEF≤40%(HR=2.775,95%CI:1.137-6.774,P=0.025)and elevated residual SYNTAX score(HR=1.089,95%CI:1.032-1.150,P=0.002)were risk factors for MACE,and diseased landing zone(HR=2.144,95%CI:1.019-4.513,P=0.045),rescued ADR(HR=3.479,95%CI:1.109-10.919,P=0.033),and prolonged procedure time(HR=1.007,95%CI:1.002-1.013,P=0.007)were risk factors for TVR. Conclusions:CTO lesion recanalized with PCI utilizing DR operation pattern was associated with more complex characteristics,more devices and time consumed,and longer stent length,while no significant association was observed between DR operation pattern and MACE and TVR one year after the procedure,as well as in-hospital complication..

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