1.Mechanism of Fibrinogen Overexpression in Influencing Coronary Heart Disease with Syndrome of Blood Stasis in Rats Based on Mitochondrial Quality Control System
Manli ZHOU ; Liping WANG ; Weixiong JIAN
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(10):149-158
ObjectiveTo study the effect and mechanism of fibrinogen (Fib) overexpression on mitochondrial quality control system in the rat model of coronary heart disease with the syndrome of blood stasis. MethodsForty male SD rats were randomly assigned into normal, model, Fib, and empty vector (AAV) groups, with 10 rats in each group. The model, Fib, and AAV groups were fed with a high-fat diet adaptively and administrated with 3×106 U·kg-1 vitamin D3 powder by gavage after 7 days and 2×106 U·kg-1 vitamin D3 solution after 14 days. After being fed with a high-fat diet for 7 weeks, rats in each group received subcutaneous injection of isoproterenol (5 mg·kg-1) for 3 days. During the modeling period, rats in the normal group were fed with ordinary feed without any special treatment. The changes in blood lipid and hemorheological indexes of rats in each group were measured. The aorta tissue was stained with hematoxylin-eosin (HE), and the standard lead Ⅱ electrocardiograms (ECGs) of rats in each group were recorded. Enzyme-linked immunosorbent assay (ELISA) and real-time PCR were employed to verify the overexpression levels of Fib in the liver and plasma. Western blotting was employed to determine the protein levels of mitofusin 2 (Mfn2), optic atrophy protein 1 (OPA1), dynamin-related protein 1 (Drp1), phosphorylated adenosine monophosphate-activated protein kinase (p-AMPK)/adenosine monophosphate-activated protein kinase (AMPK), peroxisome proliferator-activated receptor γ-coactivator-1α (PGC-1α), PTEN-induced putative kinase 1, and Parkin. Real-time PCR was employed to determine the mRNA levels of AMPK and PGC-1α in the myocardial tissue. The changes in levels of adenosine triphosphate (ATP) and adenosine monophosphate (AMP) in the myocardial tissue were determined by ELISA. ResultsCompared with the normal group, the other three groups showed elevated levels of total cholesterol and low-density lipoprotein cholesterol (P<0.01) and no significant changes in levels of triglyceride and high-density lipoprotein cholesterol. Compared with the model group, the Fib and AAV groups showed risen levels of total cholesterol (P<0.05, P<0.01). Compared with the normal group, the model and Fib groups presented increases in low shear viscosity and middle shear viscosity (P<0.05, P<0.01), and the Fib group showcased an increase in high shear viscosity (P<0.01). Compared with the model group, the Fib group showed increases in low shear viscosity, middle shear viscosity, and high shear viscosity (P<0.05, P<0.01). Compared with the Fib group, the AAV group demonstrated decreases in low shear viscosity, middle shear viscosity, and high shear viscosity (P<0.05, P<0.01). The normal group had an complete aortic structure with well arrangement of elastic fibers. In the model group, the vascular wall became thickened and the intima was rough with inflammatory infiltration. In the Fib group, the intima calcification formed a cavity structure and the intima was abnormally proliferated, while in the AAV group, the intima smooth muscle was slightly proliferated with local calcification. The ECG of the normal group indicated sinus rhythm, and that of the model group presented ST segment oblique elevation (>0.1 mV). The ECG of the Fib group presented characteristic ST segment arch back elevation with T-wave towering, and that of the AAV group presented ST segment oblique elevation. Compared with the normal group, the model and Fib groups showed elevations in levels of liver Fib, plasma Fib, and liver Fibα mRNA (P<0.01), and the AAV group had risen levels of Fib and Fibα mRNA (P<0.01). Compared with the model group, the Fib group presented risen levels of liver Fib and Fibα mRNA (P<0.01). Compared with the Fib group, the AAV group presented decreases in levels of liver Fib, plasma Fib, and liver Fibα mRNA (P<0.01). Compared with the normal group, the other three groups had down-regulated protein and mRNA levels of Mfn2, OPA1, PINK1, Parkin, p-AMPK/AMPK, and PGC-1α (P<0.05, P<0.01) and up-regulated protein levels of Drp1 (P<0.01). Compared with those in the model group, the mRNA and protein levels of Mfn2, OPA1, PINK1, Parkin, p-AMPK/AMPK, and PGC-1α were all down-regulated (P<0.05, P<0.01) and the protein level of Drp1 was up-regulated (P<0.01) in the Fib group. Compared with the Fib group, the AAV group showed differences in protein levels of OPA1, PGC-1α, Parkin, and Drp1 (P<0.05, P<0.01) and an increasing trend in the mRNA levels of AMPK and PGC-1α with no significant difference. Compared with the normal group, the other three groups had elevated levels of ATP in the myocardial tissue (P<0.01). Compared with the model group, the Fib group showed elevated levels of ATP and AMP (P<0.01). Compared with the Fib group, the AAV group exhibited lowered levels of ATP and AMP (P<0.01). ConclusionFib can achieve the overexpression effect in the rat model of coronary heart disease with the syndrome of blood stasis. At the same time, the overexpression of Fib can induce the damage of the mitochondrial quality control system in the myocardial tissue, inhibit mitochondrial dynamics and mitochondrial biosynthesis, and down-regulate mitochondrial autophagy, thereby aggravating myocardial injury in the rat model.
2.Platelet Metabolomics Analysis in Rats of Coronary Heart Disease with Blood Stasis Syndrome by Overexpression of Fibrinogen
Manli ZHOU ; Jiale ZHU ; Liping WANG ; Weixiong JIAN
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(6):230-237
ObjectiveTo analyze the metabolomic characteristics of platelets in fibrinogen(FIB) overexpression rats of coronary heart disease with blood stasis syndrome(CHD-BSS), explore potential biomarkers, and investigate the mechanism of FIB overexpression on CHD-BSS. MethodsSD rats were randomly divided into BSS group and BSS+FIB overexpression group(BSS+FIB group), with 10 rats in each group. Both the BSS+FIB group and the BSS group were fed a high-fat diet combined with oral administration of vitamin D3 and subcutaneous injection of isoproterenol, but rats in the BSS+FIB group were overexpressed with FIB during the initial modeling stage by transfection with adeno-associated virus(AAV). The overexpression level of FIB in rat liver and plasma samples was detected by enzyme-linked immunosorbent assay(ELISA) and real-time fluorescence quantitative polymerase chain reaction(Real time PCR), as well as the expression level of liver FIB A(FGA) mRNA. The characteristics of metabolites in rat platelet samples were analyzed by ultra-high performance liquid chromatography-quadrupole-electrostatic field orbital trap high-resolution mass spectrometry(UPLC-Q-Exactive Orbitrap-MS), and the differential metabolites between groups were screened by principal component analysis(PCA) and orthogonal partial least squares-discriminant analysis(OPLS-DA), and the enriched pathways were analyzed. The accuracy of potential biomarkers in the diagnosis of CHD-BSS was evaluated by receiver operating characteristic(ROC) curve. The expression of autophagy related proteins phosphorylated adenosine monophosphate(AMP) activated protein kinase(p-AMPK)/AMPK, phosphorylated mammalian target of rapamycin(p-mTOR)/mTOR, microtubule-associated protein 1 light chain 3(LC3) Ⅱ/Ⅰ and p62 in platelets were detected by Western blot. ResultsCompared with the BSS group, the expression levels of FIB in liver and plasma samples of the BSS+FIB group were significantly increased(P<0.05, P<0.01), and the expression level of FIB mRNA in the liver was remarkably increased(P<0.01), indicating successful overexpression of FIB. Platelet metabolomics results showed significant differences in metabolic profiles between the BSS+FIB group and the BSS group, and a total of 25 significantly enriched metabolic pathways and 8 metabolites involved in these metabolic pathways, among which uric acid, guanosine and ribose 1-phosphate levels were up-regulated, while adenosine diphosphate(ADP), AMP, guanosine diphosphate(GDP), adenylosuccinate and norepinephrine levels were down-regulated. The diagnostic ability analysis of differential metabolites showed that all 8 differential metabolites had good diagnostic ability, with an area under the curve(AUC)>0.85. Western blot results showed that compared with the BSS group, the expression levels of p-mTOR/mTOR and p62 proteins in platelets of the BSS+FIB group was significantly reduced(P<0.01), while the expression levels of p-AMPK/AMPK and LC3Ⅱ/Ⅰ proteins were increased, but the difference was not statistically significant. ConclusionOverexpression of FIB can change the metabolic characteristics of CHD-BSS rat model, involving multiple aspects such as vascular endothelial injury, platelet activation and myocardial function damage. Among them, overexpression of FIB may enhance the occurrence of platelet autophagy, thereby inducing platelet activation and promoting thrombus formation.
3.Research Paradigms and Methods in Integrated Imaging of Traditional Chinese and Western Medicine
Yingjie WU ; Nuan CUI ; Guojiang XIN ; Wanghua LIU ; Weixiong JIAN ; Hao LIANG
Chinese Journal of Information on Traditional Chinese Medicine 2025;32(5):7-12
The integration of TCM and Western medicine in imaging aims to enrich the sources of diagnostic information by utilizing medical imaging technologies,focusing on key elements such as TCM imaging,Western medical imaging,diseases and TCM syndrome types,thereby facilitating the complementary strengths of both systems.With the advancement of digital imaging and artificial intelligence technologies,various research models and methodologies have emerged.This article discussed the development and application of integrated imaging of traditional Chinese and Western medicine,and proposed three primary research paradigms in this field:Analyzing TCM images(e.g.,tongue and face)through manual or image processing techniques to assist in the diagnosis of Western medical diagnosis;Mapping Western medical imaging signs(e.g.,computed tomography,magnetic resonance imaging and ultrasound imaging)to TCM syndrome patterns for objective evidence in TCM diagnosis and treatment;Applying imaging omics to extract and integrate features from both TCM and Western medical images for comprehensive diagnosis.This study reviewed the three paradigms,explained relevant concepts and technologies,and proposed a specific research workflow of integrated imaging omics of traditional Chinese and Western medicine,aiming to provide a reference for innovative development in this field.
4.Exploration on the Biological Connotation of Treating Coronary Heart Disease from Kidney Based on Endothelial Cell Aging
Yilei HU ; Lei CAI ; Zhiyan MA ; Xiaoxin LUO ; Weixiong JIAN
Chinese Journal of Information on Traditional Chinese Medicine 2025;32(4):14-18
Coronary heart disease has a significant age correlation,and cell aging is the basic factor of aging of the body.Aging endothelial cells can interfere with the development of coronary heart disease through oxidative stress,mitochondrial dysfunction and other ways.This article focused on the mechanism of endothelial cell aging promoting coronary heart disease,which is related to"kidney"in TCM.Kidney has physiological characteristics such as participating in the growth and aging,the interaction of essence and blood,water and liquid metabolism,etc.Deficiency of kidney essence can slow down the generation of kidney turbidity,which can also be followed by blood stasis,phlegm and other pathogenic factors eroding arteries,which is consistent with the role of endothelial cell aging in promoting plaque development and accelerating thrombosis.The article also discussed the biological connotation of treating coronary heart disease from kidney from the perspective of endothelial cell aging,and put forward that the basic principle of treating coronary heart disease from kidney should be tonifying kidney and expelling turbidity,and then treat it according to different syndromes such as heart-kidney disharmony,qi stagnation in the heart and chest,phlegm obstruction in collaterals and blood stasis obstruction in collaterals,providing new ideas for the biological research and clinical application of TCM in the treatment of coronary heart disease.
5.Research Paradigms and Methods in Integrated Imaging of Traditional Chinese and Western Medicine
Yingjie WU ; Nuan CUI ; Guojiang XIN ; Wanghua LIU ; Weixiong JIAN ; Hao LIANG
Chinese Journal of Information on Traditional Chinese Medicine 2025;32(5):7-12
The integration of TCM and Western medicine in imaging aims to enrich the sources of diagnostic information by utilizing medical imaging technologies,focusing on key elements such as TCM imaging,Western medical imaging,diseases and TCM syndrome types,thereby facilitating the complementary strengths of both systems.With the advancement of digital imaging and artificial intelligence technologies,various research models and methodologies have emerged.This article discussed the development and application of integrated imaging of traditional Chinese and Western medicine,and proposed three primary research paradigms in this field:Analyzing TCM images(e.g.,tongue and face)through manual or image processing techniques to assist in the diagnosis of Western medical diagnosis;Mapping Western medical imaging signs(e.g.,computed tomography,magnetic resonance imaging and ultrasound imaging)to TCM syndrome patterns for objective evidence in TCM diagnosis and treatment;Applying imaging omics to extract and integrate features from both TCM and Western medical images for comprehensive diagnosis.This study reviewed the three paradigms,explained relevant concepts and technologies,and proposed a specific research workflow of integrated imaging omics of traditional Chinese and Western medicine,aiming to provide a reference for innovative development in this field.
6.Exploration on the Biological Connotation of Treating Coronary Heart Disease from Kidney Based on Endothelial Cell Aging
Yilei HU ; Lei CAI ; Zhiyan MA ; Xiaoxin LUO ; Weixiong JIAN
Chinese Journal of Information on Traditional Chinese Medicine 2025;32(4):14-18
Coronary heart disease has a significant age correlation,and cell aging is the basic factor of aging of the body.Aging endothelial cells can interfere with the development of coronary heart disease through oxidative stress,mitochondrial dysfunction and other ways.This article focused on the mechanism of endothelial cell aging promoting coronary heart disease,which is related to"kidney"in TCM.Kidney has physiological characteristics such as participating in the growth and aging,the interaction of essence and blood,water and liquid metabolism,etc.Deficiency of kidney essence can slow down the generation of kidney turbidity,which can also be followed by blood stasis,phlegm and other pathogenic factors eroding arteries,which is consistent with the role of endothelial cell aging in promoting plaque development and accelerating thrombosis.The article also discussed the biological connotation of treating coronary heart disease from kidney from the perspective of endothelial cell aging,and put forward that the basic principle of treating coronary heart disease from kidney should be tonifying kidney and expelling turbidity,and then treat it according to different syndromes such as heart-kidney disharmony,qi stagnation in the heart and chest,phlegm obstruction in collaterals and blood stasis obstruction in collaterals,providing new ideas for the biological research and clinical application of TCM in the treatment of coronary heart disease.
7.Application of three artificial kidney hydronephrosis methods in percutaneous nephrolithotripsy
Weixiong TAO ; Yuan SHI ; Jian LI ; Mi LU ; Junjun WANG ; Hui ZHANG
China Modern Doctor 2024;62(12):57-59
Objective To compare the effects of three kinds of artificial hydronephrosis in percutaneous nephrolithotomy.Methods A total of 120 patients who underwent single-tract percutaneous nephrolithotomy in the Eighth Hospital of Wuhan from May 2020 to April 2022 were selected and divided equally into three groups according to different methods of artificial hydronephrosis.Patients in group A were received preoperative indwelling ureteral catheter and injection of normal saline through ureteral catheter to dilate renal pelvis and form artificial hydronephrosis.Patients in Group B were placed with double J catheters before surgery,and the bladder was filled with physiological saline through the catheter.The renal pelvis was dilated through the double J catheters,resulting in artificial hydronephrosis.Patients in Group C were received intravenous injection of furosemide and stimulated diuretic method to actively dilate renal pelvis to form hydronephrosis.The one-time puncture success rate,channel establishment time,overall operation time,stone clearance rate and incidence of surgical complications of percutaneous nephrolithotomy after hydronephrosis were compared among the three groups.Results The operation was successfully completed in the three groups.There was no significant difference in the one-time puncture success rate and channel establishment time between group A and group B(P>0.05),which were all higher than group C(P<0.05).The overall operation time of group B was shorter than that of group A and group C(P<0.05).There were no significant differences in stone clearance rate and surgical complications among the three groups(P>0.05).Conclusion Preoperative indwelling of double J tubes to create artificial kidney hydronephrosis has advantages such as high success rate of one-time puncture,short channel establishment time,and surgical time.
8.Syndrome Differentiation from Micro to"Near-micro":Origins,Controversies and Prospects
Liqin ZHONG ; Dan SHENG ; Wanghua LIU ; Zhixi HU ; Qinghua PENG ; Weixiong JIAN ; Yingjie WU ; Yanjie WANG ; Shuyue FU ; Hao LIANG
Chinese Journal of Information on Traditional Chinese Medicine 2024;31(3):8-12
As an emerging discipline that combines traditional diagnostic methods with modern scientific technology,micro syndrome differentiation has good prospects for development,but there are some controversies in the research process.Based on ancient and modern literature,this article reviewed the origin and flow of research on micro syndrome differentiation,and summarized the problems to be improved in the process of research on micro syndrome differentiation from three aspects:application of disease type,guiding ideology and micro indicators.Based on this,the article further expounded the new thinking on"near-micro"syndrome differentiation from three aspects:connotation,scope of application,and links to traditional identification and micro-identification,and pointed out that the modern medical detection basis should be incorporated into the field of TCM syndrome differentiation,and at the same time,it should be based on the overall thinking mode of TCM,which would provide a new idea for the development of modern TCM diagnosis technology.
9.Chinese Medicine Intervention on Autophagy in Lung Cancer from Theory of Healthy Qi Deficiency and Pathogenic Qi Stagnation: A Review
Yunfeng YU ; Pei TANG ; Manli ZHOU ; Xiaoxin LUO ; Weixiong JIAN
Chinese Journal of Experimental Traditional Medical Formulae 2023;29(18):190-197
Autophagy, a mechanism of cell self-protection and self-renewal, is associated with the occurrence and development of lung cancer. Favorable autophagy can slow down the progression of lung cancer, while unfavorable autophagy can promote the progression. Therefore, regulating the level of autophagy is of great significance in the treatment of lung cancer. Healthy Qi deficiency and pathogenic Qi stagnation is an extension of the theory of deficiency and Qi stagnation proposed by the Academician WANG Yongyan. It refers to the pathological process that the abnormal body fluid metabolism caused by Qi deficiency of lung, spleen, and kidney results in phlegm and blood stasis. Lung cancer has the root cause of Qi deficiency of lung, spleen, and kidney and the syndrome of phlegm and blood stasis. The autophagy in lung cancer is interconnected with healthy Qi deficiency and pathogenic Qi stagnation. The Qi deficiency of lung, spleen, and kidney is the key factor for the weakening of favorable autophagy in lung cancer, which inhibits the apoptosis of tumor cells and leads to the accumulation of harmful substances. Phlegm and blood stasis is a direct factor enhancing the unfavorable autophagy in lung cancer, which promotes the autophagic death of normal cells, weakens the immunosuppressive effect of immune cells on tumor cells, and leads to the proliferation and migration of tumor cells. The combination of healthy Qi deficiency and pathogenic Qi stagnation results in the development of autophagy in an unfavorable direction and finally leads to the continuous progression of lung cancer. Therefore, the traditional Chinese medicine (TCM) treatment of lung cancer should follow the principle of reinforcing healthy Qi and expelling pathogenic Qi, removing phlegm and resolving stasis, so as to enhance favorable autophagy while inhibiting unfavorable autophagy. Such therapy can inhibit the proliferation and migration of tumor cells and promote the remission of lung cancer. According to the existing literature, Chinese medicine monomers are mainly used to treat lung cancer by regulating autophagy. The Chinese medicine intervention of autophagy in lung cancer mainly aims to promote the activation of autophagy. This may be because the favorable autophagy weakening caused by the Qi deficiency of lung, spleen, and kidney is the fundamental reason for the development of lung cancer.
10.Inflammatory Mechanism of Coronary Heart Disease and Intervention Strategies of Chinese Medicine Based on ''Phlegm,Stasis,Toxin'' Theory
Pei LIU ; Yunfeng YU ; Xinyu YANG ; Manli ZHOU ; Yanzhen ZHAO ; Weixiong JIAN
Chinese Journal of Experimental Traditional Medical Formulae 2023;29(12):185-191
More and more evidence shows that there is a close relationship between the inflammatory state and coronary heart disease. Inflammatory state triggers the damage of vascular endothelium in the early stage of coronary heart disease and ultimately mediates the formation of atherosclerotic plaque. The mechanism of occurrence and development of heart disease is of great significance. Phlegm is a pathological product formed by the subtle imbalance of the spleen and stomach in the transportation and transformation of water and grain. It is the general summary of a series of abnormally accumulated inflammatory substances, such as low density lipoprotein, inflammatory cells, and inflammatory factors. The nature of Phlegm determines the invasiveness and turbidity of Phlegm. Phlegm invades the meridians, causing damage to the meridians and gradually accumulating, which eventually causes the local meridian damage to aggravate. This process is similar to the persistent damage of the vascular endothelium caused by inflammation. Phlegm blocks the meridians, affects the operation of Qi and blood, causes Qi stagnation and blood stasis, and finally forms the outcome of heart and blood stasis. This process is similar to the mechanism of atherosclerotic plaques formed by continuous inflammatory damage. Heart blood stasis, depression and heat, heat toxin endogenous, forming the syndrome of heat toxin stasis, which is similar to the process of atherosclerotic plaque rupture and thrombosis causing acute cardiovascular events.The formation of Phlegm is rooted in the deficiency of spleen. Based on the ''phlegm,stasis,toxin'' theory, spleen deficiency is the intrinsic pathogenesis of the inflammatory state of coronary heart disease, and the invasion of phlegm, blood stasis of heart, heat and blood stasis are the evolution of inflammatory damage of coronary heart disease. Traditional Chinese medicine differentiation and treatment is based on strengthening the spleen and nourishing Qi to treat the root and removing phlegm and blood stasis, and clearing heat and detoxifying to treat symptoms. The related Chinese medicine compounds, Chinese patent medicines, and single Chinese medicines can reduce the inflammatory indicators of coronary heart disease, thereby improving the prognosis of coronary heart disease.

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