1.Development and validation of a quality appraisal tool for case reports in traditional Chinese medicine using the Delphi method
Duoting TAN ; Hao LIANG ; Yipin YU ; Jin GUO ; Liqin ZHONG ; Zhixi HU
Digital Chinese Medicine 2025;8(2):137-146
Objective:
To develop a quality appraisal tool for case reports in traditional Chinese medicine (TCM) based on their characteristics.
[Methods]:
An extensive literature search was conducted in Chinese Biomedical Literature Database (CBM), China National Knowledge Infrastructure (CNKI), and China Science and Technology Journal Database (CSTJ), focusing on expert consensus statements and checklists for TCM case reports. Relevant items were extracted, and a Delphi method involving 34 experts was used in two rounds to rate each item on a 5-point Likert scale. Items were screened based on measures of central tendency and coordination (including total score, mean score, percentage of items rated as unimportant, and coefficient of variation). The weighted average method was used to determine item weights and construct the appraisal tool. Internal consistency was assessed using Cronbach’s α coefficient. The finalized tool was pilot-tested by two reviewers independently appraising 20 case reports, with an additional four reviewers evaluating 5 of these cases to compare inter-rater consistency.
Results:
A total of 9 513 articles were retrieved, and 96 items from 25 articles were extracted. After two rounds of the Delphi method, 27 items across 10 domains were retained. The Cronbach’s α coefficient was 0.72 in the first round (acceptable range), and 0.96 in the second round, indicating strong internal consistency. The tool was piloted by six reviewers, achieving a kappa value of 0.663 and a Kendall’s coefficient of concordance of 0.845, demonstrating high consistency among reviewers.
Conclusion
The developed TCM case report quality appraisal tool, consisting of 27 items in 10 domains, offers a scientific and reliable means of assessing the quality of TCM case reports. The tool showed high consistency and practical utility, and its application is expected to enhance the standardization, scientific rigor, and evidence quality of TCM case reports, facilitating the integration of traditional medical knowledge with modern evidence-based standards.
2.Danhong Injection Regulates Mitochondrial Dynamics in Rat Model of Chronic Heart Failure via AMPK/Drp1 Pathway
Jiahao YE ; Zizheng WU ; Yao ZHANG ; Lichong MENG ; Zhixi HU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(16):126-135
ObjectiveTo investigate the effects of Danhong injection on mitochondrial dynamics, morphology, and function in the rat model of chronic heart failure by mediating the adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK)/dynamin-related protein 1 (Drp1) pathway. MethodsFrom 75 SD rats, 15 rats were randomly selected as the sham group, and the remaining 60 rats were used to prepare a rat model of chronic heart failure by abdominal aortic constriction (AAC). The modeled rats were randomly allocated into model, Danhong Injection (6 mL·kg-1), and captopril (8.8 mg·kg-1) groups and administrated with corresponding agents for 15 consecutive days. The levels of N-terminal pro-brain natriuretic peptide (NT-pro BNP), adenosine diphosphate (ADP), adenosine triphosphate (ATP), interleukin (IL)-6, IL-1β, and tumor necrosis factor (TNF)-α and the activities of mitochondrial respiratory chain complexes Ⅰ-Ⅳ were determined by enzyme-linked immunosorbent assay. The changes in cardiac function were detected by echocardiography. The ultrastructural changes of myocardial mitochondria were observed by transmission electron microscopy. Western blot was employed to assess the protein levels of AMPK, p-AMPK, Drp1, p-Drp1, optic atrophy 1 (Opa1), mitofusin (Mfn2), and fission l (Fis1) in the myocardial tissue. Real-time PCR was performed to determine the mRNA levels of Opa1, Mfn2, and Fis1, and immunohistochemistry to detect the expression of p-AMPK. ResultsCompared with the sham group, the model group showed elevated levels of NT-pro BNP, ADP, TNF-α, IL-6, and IL-1β (P<0.01), declined ATP level (P<0.01), weakened activities of mitochondrial respiratory chain complexes Ⅰ-Ⅳ (P<0.01), decreased left ventricular ejection fraction (LVEF) and left ventricular fraction shortening (LVFS) (P<0.01), and increased left ventricular internal diameter at end-diastole (LVDd) and leaf ventricular internal diameter at end-systole (LVIDs) (P<0.01). Electron microscopy results showed that the model group presented heavily abnormal myocardial structure, with large areas of myofilament structure destroyed and dissolved, significantly enlarged residual structural gaps, and fragmented mitochondria. Western blot results showed that the model group demonstrated down-regulated protein levels of p-AMPK, Mfn2, and Opa1 (P<0.01) and up-regulated protein levels of p-Drp1 and Fis1 (P<0.01) in the myocardial tissue. Real-time PCR results showed that the model group presented up-regulated mRNA level of Fis1 (P<0.01) and down-regulated mRNA levels of Mfn2 and Opa1 (P<0.01). Immunohistochemistry results showed reduced expression of p-AMPK in the model group compared with sham group (P<0.01). Compared with the model group, Danhong injection lowered the levels of NT-pro BNP, ADP, TNF-α, IL-6, and IL-1β (P<0.01), raised the level of ATP (P<0.01), increased the activities of mitochondrial respiratory chain complexes Ⅰ-Ⅳ (P<0.05, P<0.01), increased the LVEF and LVFS (P<0.01), decreased the LVDd and LVIDs (P<0.05, P<0.01), alleviated mitochondrial damage, up-regulated the protein levels of p-AMPK, Mfn2, and Opa1 (P<0.05, P<0.01), down-regulated the protein levels of p-Drp1 and Fis1 (P<0.01), reduced the mRNA level of Fis1 (P<0.01), elevated the mRNA levels of Mfn2 and Opa1 (P<0.05, P<0.01), and promoted the expression of p-AMPK (P<0.05). ConclusionDanhong injection repairs the imbalance of mitochondrial dynamics, restores the mitochondrial function, improves the myocardial energy metabolism, and reduces the inflammatory response by regulating the AMPK/Drp1 pathway, thus improving the cardiac function.
3.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.
4.Mechanism of Qili Qiangxin Capsules in Treating Chronic Heart Failure Based on Theory of Collateral Diseases
Kun LIAN ; Kexin LIU ; Xueqin WANG ; Fengting LIU ; Liyan LIAO ; Zhixi HU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(16):146-155
Chronic heart failure (CHF) is the terminal stage of various heart diseases, with high morbidity, mortality, and hospitalization rate. According to the theory of collateral diseases, the core pathogenesis of CHF is blood stasis of collaterals, water retention and stagnation, and pathogen accumulation in collaterals. Accordingly, the treatment should focus on reinforcing healthy Qi to warm Yang, activating blood to dredge collaterals, and excreting water to alleviate edema. On this basis, Qili Qiangxin capsules (QLQX) are created. This prescription can effectively treat chronic heart failure. Modern studies have shown that QLQX contains a variety of pharmacological components such as flavonoids, alkaloids, terpenoids, phenylpropanoids, phenolic acids, and cardiac glycosides. QLQX can improve the cardiac function, inhibit myocardial fibrosis, improve hemodynamics, mitigate inflammation, reduce cardiomyocyte apoptosis, and regulate the nervous system, with mild adverse reactions. This study analyzed the etiology and pathogenesis of CHF based on the theory of collateral diseases, explored the relationship between the prescription and syndrome, and delved into the material basis and mechanism of QLQX in the treatment of CHF, aiming to provide reference for the clinical application and scientific research of QLQX.
5.Pathogenesis of Chronic Heart Failure with Anxiety and Depression and Therapeutic Mechanisms of Bupleuri Radix-based Formulas from Theory of Shaoyang Pivot
Duoting TAN ; Kun LIAN ; Hao LIANG ; Lichong MENG ; Zhixi HU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(16):156-164
Chronic heart failure (CHF), as the terminal stage of various cardiovascular diseases, is characterized by a prolonged clinical course and recurrent exacerbations. The coexistence of CHF with anxiety and depression falls under the category of psycho-cardiological diseases. Studies have demonstrated that anxiety and depression are closely associated with adverse outcomes including elevated risks of cardiovascular events and increased mortality in CHF patients. The complex pathogenesis poses challenges to modern medical treatments, which often face limited efficacy and concurrent side effects. According to the theory of Shaoyang Pivot in traditional Chinese medicine (TCM), this paper elucidates that obstructed Shaoyang Pivot—manifested as Qi transformation disorder, dysregulated fluid metabolism, and abnormal distribution of ministerial fire-serves as a critical pathological basis for CHF with anxiety and depression. Bupleuri Radix-based Formulas, such as Xiao Chaihu Tang, Chaihu Guizhi Tang, and Chaihu Jia Longgu Muli Tang, aim to harmonize lesser Yang to restore the Qi transformation, activate Yang to promote water excretion, and redistribute ministerial fire, thus effectively alleviating pathological states such as Qi stagnation, blood stasis, water retention, and phlegm-fire disturbing the heart in CHF patients with anxiety and depression. Consequently, they mitigate symptoms of this psycho-cardiological disease. Mechanism studies have revealed that Bupleuri Radix-based formulas exhibit multi-target effects, including modulation of neurotransmitters, suppression of inflammatory responses, regulation of lipid metabolism, protection of cardiomyocytes, and improvement of the endothelial function. By interpreting the TCM pathogenesis of CHF with anxiety and depression from the theory of Shaoyang Pivot, this paper delves into the therapeutic principles and mechanisms of Bupleuri Radix-based formulas, providing a theoretical foundation for optimizing TCM diagnosis and treatment strategies for psycho-cardiological diseases.
6.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.
7.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".
8.Exploration on the Role of Macrophage Polarization in Pulmonary Fibrosis and TCM Intervention Based on the Theory of Healthy Qi and Pathogenic Factors
Chinese Journal of Information on Traditional Chinese Medicine 2024;31(8):17-22
Healthy qi-pathogenic factors struggle exists in the whole process of formation and development of pulmonary fibrosis(PF).Macrophage polarization is an important mechanism in the development of PF and participates in the process of PF by releasing relevant cytokines.This article explored the association between macrophage polarization and PF from the aspects of the theory of healthy qi and pathogenic factors and PF,the role of macrophage polarization in PF,and the correlation between the theory of healthy qi and pathogenic factors and macrophage polarization,and further explored the mechanism of Chinese materia medica,so as to provide theoretical guidance for the clinical diagnosis and treatment of PF.
9.Regulatory Mechanism of Mitochondrial Autophagy in Myocardial Ischemia/Reperfusion Injury Based on the Theory of"Deficiency Qi Retention"
Meng YANG ; Siyuan HU ; Lin LI ; Zhixi HU
Chinese Journal of Information on Traditional Chinese Medicine 2024;31(10):8-13
Mitochondrial autophagy is the main regulator of cardiac homeostasis and function,and its dysfunction can lead to calcium overload,excessive opening of mitochondrial permeability transition pore,abnormal material metabolism,and other damaging changes,reducing myocardial cell activity,which is a key pathological mechanism of myocardial ischemia/reperfusion injury(MIRI)."Deficiency qi retention"is the core mechanism of MIRI,and mitochondrial autophagy is an important mechanism of MIRI,which runs through the every stage of its occurrence and development.This article took"deficiency qi retention"as the entry point to explore the association between mitochondrial autophagy and MIRI,explained the scientific connotation of"deficiency qi retention",and summarized the progress of research on the method of supplementing deficiency and promoting stagnation for prevention and treatment of MIRI,with a view to providing theoretical reference for clinical diagnosis and treatment of MIRI.
10.Study on Medication Law of National Patented Chinese Herbal Prescriptions for the Treatment of Benign Prostatic Hyperplasia Based on Data Mining
Lichong MENG ; Kun LIAN ; Jin GUO ; Ziyi WANG ; Zhixi HU
Chinese Journal of Information on Traditional Chinese Medicine 2024;31(11):60-66
Objective To explore the prescribing law of TCM in national patents for the treatment of benign prostatic hyperplasia(BPH);To provide a reference for clinical medication.Methods Data on TCM compound prescriptions for the treatment of BPH were retrieved from the China National Intellectual Property Administration(CNIPA)patent retrieval and analysis system,covering the period from January 1,2000,to October 31,2023.The frequency,efficacy category,properties and tastes,meridian tropism,core complex co-occurrence network,and potential TCM clusters mentioned in the patents were analyzed using Excel 2016,SPSS Modeler 18.0,SPSS Statistics 27,and Cytoscape 3.10.0 software.Results A total of 182 patents were included,involving 404 kinds of Chinese materia medica,with a total frequency of 2054 times.Among them,22 kinds of Chinese materia medica had a frequency of≥20,with the most frequently used Chinese materia medica being Astragali Radix,Glycyrrhizae Radix et Rhizoma,Phellodendri Chinensis Cortex,Epimedii Folium,Salviea Miltiorrhizae Radix et Rhizoma,Plantaginis Semen,Poria,Vaccariae Semen,Alismatis Rhizoma and Paeoniae Radix Rubra.The high-frequency herbs primarily consisted of tonifying herbs(267 times,13.00%),blood circulation-activating and stasis-resolving herbs(216 times,10.52%),and diuretic and dampness-percolating herbs(147 times,7.16%).The properties of the herbs were mainly sweet and cold,and they were mainly attributed to the liver and kidney meridians.Association rule analysis yielded 10 common drug pairs,including Cornus Officinalis-Rehmannize Radix et Praeparata,Curcumae Rhizoma-Sparganii Rhizoma,and Astragali Radix-Codonopsis Radix.The drug combination with the highest confidence was Angelicae Sinensis Radix-Phellodendri Chinensis Cortex-Glycyrrhizae Radix et Rhizoma.Clustering analysis revealed five drug combinations,while potential TCM clustering analysis identified five groups,among which the"Zingiberis Rhizoma-Os Draconis-Angelicae Pubescentis Radix-Scallion-Rice Bran-Speranskiae Herba"network demonstrated the highest degree of interconnection(Score=6).Conclusion The high-frequency herbs in national patents for the treatment of BPH with TCM compound prescriptions mainly focus on tonifying the spleen and kidney,activating blood circulation to remove stasis,and clearing heat and draining dampness,providing a reference for clinical practice.

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