1.Exploring Pathogenesis and Treatment Principles of Chronic Obstructive Pulmonary Disease Based on Spleen-mitochondria Correlation
Shiyi WANG ; Miao YU ; Xinyao HE ; Zi WANG ; Haijun LUAN ; Yibo SUN ; Haotong WANG ; Linlin WANG ; Lijian PANG
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(3):258-264
According to the Qi-blood-body fluid theory and the association between the spleen in visceral manifestation theory of traditional Chinese medicine (TCM) and mitochondria in modern cellular biology, it is proposed that the role of the spleen in generating and transforming Qi and blood is analogous to the energy-producing function of mitochondria—both serving as fundamental power sources for vital activities of the human body. The spleen governs transportation and transformation, playing a critical role in energy metabolism and the digestion and absorption of nutrients. Similarly, mitochondria are vital for maintaining physiological functions such as cellular energy supply, cell survival, and overall human metabolism. Furthermore, spleen deficiency is closely linked to mitochondrial dysfunction. Accordingly, mitochondrial energy conversion and substance metabolism are regarded as the microscopic essence of the spleen's function in transportation and transformation. Spleen deficiency and mitochondrial dysfunction contribute to the formation of pathological products such as phlegm-turbidity and blood stasis. This aligns with the pathogenesis of chronic obstructive pulmonary disease (COPD), with Qi deficiency as the root cause and phlegm-turbidity and blood stasis as the manifestations. Therefore, the integrative treatment of COPD should follow the therapeutic principle of invigorating the spleen and reinforcing healthy Qi, while also resolving phlegm and removing blood stasis to address both root cause and manifestations. This approach can improve the mitochondrial function, regulate energy metabolism, and reduce oxidative stress levels to alleviate COPD symptoms, slow down disease progression, and improve prognosis. By integrating the holistic concept of TCM with molecular mechanisms of modern medicine, this paper explores the pathogenesis and therapeutic principles of COPD from the spleen-mitochondria correlation. It not only provides a new direction for the modern development of TCM and the integration of Chinese and Western medicine but also offers a theoretical foundation for the integrated treatment of chronic, complex age-related diseases.
2.Exploring Pathogenesis and Treatment Principles of Chronic Obstructive Pulmonary Disease Based on Spleen-mitochondria Correlation
Shiyi WANG ; Miao YU ; Xinyao HE ; Zi WANG ; Haijun LUAN ; Yibo SUN ; Haotong WANG ; Linlin WANG ; Lijian PANG
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(3):258-264
According to the Qi-blood-body fluid theory and the association between the spleen in visceral manifestation theory of traditional Chinese medicine (TCM) and mitochondria in modern cellular biology, it is proposed that the role of the spleen in generating and transforming Qi and blood is analogous to the energy-producing function of mitochondria—both serving as fundamental power sources for vital activities of the human body. The spleen governs transportation and transformation, playing a critical role in energy metabolism and the digestion and absorption of nutrients. Similarly, mitochondria are vital for maintaining physiological functions such as cellular energy supply, cell survival, and overall human metabolism. Furthermore, spleen deficiency is closely linked to mitochondrial dysfunction. Accordingly, mitochondrial energy conversion and substance metabolism are regarded as the microscopic essence of the spleen's function in transportation and transformation. Spleen deficiency and mitochondrial dysfunction contribute to the formation of pathological products such as phlegm-turbidity and blood stasis. This aligns with the pathogenesis of chronic obstructive pulmonary disease (COPD), with Qi deficiency as the root cause and phlegm-turbidity and blood stasis as the manifestations. Therefore, the integrative treatment of COPD should follow the therapeutic principle of invigorating the spleen and reinforcing healthy Qi, while also resolving phlegm and removing blood stasis to address both root cause and manifestations. This approach can improve the mitochondrial function, regulate energy metabolism, and reduce oxidative stress levels to alleviate COPD symptoms, slow down disease progression, and improve prognosis. By integrating the holistic concept of TCM with molecular mechanisms of modern medicine, this paper explores the pathogenesis and therapeutic principles of COPD from the spleen-mitochondria correlation. It not only provides a new direction for the modern development of TCM and the integration of Chinese and Western medicine but also offers a theoretical foundation for the integrated treatment of chronic, complex age-related diseases.
3.Treatment of Liver Cancer by Intervening TGF-β Signaling Pathway with Traditional Chinese Medicine: A Review
Hao CHENG ; Haohao GUO ; Jun SUN ; Juan XUE ; Chunyan JI ; Shiyi LI ; Yuxue DING ; Huaqiang YUE
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(8):318-326
Liver cancer is one of the most common malignant tumors in the digestive system and ranks sixth among newly diagnosed malignant tumors worldwide. Transforming growth factor-β (TGF-β) regulates cell differentiation, proliferation, apoptosis, and other physiological and pathological mechanisms and exerts cancer-suppressive and pro-cancerous dual effects in the process of tumor development. In recent years, with the continuous exploration of the mechanism of liver cancer, it has been found that the conversion of the cancer-suppressive effect into a pro-cancerous effect of this pathway plays a key role in the development of liver cancer. Traditional Chinese medicine (TCM) provides a unique perspective for the classification, diagnosis, and treatment of liver cancer with its comprehensive regulatory effects of multi-components, multi-targets, and multi-pathways. This paper summarized that the cancer-suppressive mechanisms of the TGF-β signaling pathway included promoting cancer cell cycle arrest, apoptosis, autophagy, et al, while the pro-cancerous mechanisms included promoting cancer cell proliferation, invasion and metastasis, immunosuppression, angiogenesis, et al. The TCM compounds intervening this pathway were sorted out, including Jianpi Huayu compound, Fuyang Baoyuan compound, Yipi Yanggan compound, Fuzheng Jiedu compound, compound Astragalus and Salvia, Biejia Jianwan, Dahuang Zhechong pill, and Qingxiang powder. The single TCMs mainly included Schizocapsa plantaginea, Dendrobii Caulis, Gleditsia sinensis, and Dracaena cochinchinensis. The active ingredients of TCM are mainly concentrated on flavonoids, alkaloids, glycosides, phenolics, terpenoids, polysaccharides, and other kinds of compounds. At the same time, it summarized that the liver cancer inhibition mechanism of TCM by regulating this pathway mainly included promoting apoptosis of liver cancer cells, blocking the cell cycle, and inhibiting liver cancer cell proliferation, migration, invasion, angiogenesis, immune escape, etc. The mechanism aims to give full play to the advantages of TCM and precisely regulate the TGF-β signal, thereby exerting positive anti-tumor effects, opening up a new direction for the precise targeted treatment of liver cancer, and providing a scientific basis and a new strategy for the application of TCM in the treatment of liver cancer.
4.Treatment of Liver Cancer by Intervening TGF-β Signaling Pathway with Traditional Chinese Medicine: A Review
Hao CHENG ; Haohao GUO ; Jun SUN ; Juan XUE ; Chunyan JI ; Shiyi LI ; Yuxue DING ; Huaqiang YUE
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(8):318-326
Liver cancer is one of the most common malignant tumors in the digestive system and ranks sixth among newly diagnosed malignant tumors worldwide. Transforming growth factor-β (TGF-β) regulates cell differentiation, proliferation, apoptosis, and other physiological and pathological mechanisms and exerts cancer-suppressive and pro-cancerous dual effects in the process of tumor development. In recent years, with the continuous exploration of the mechanism of liver cancer, it has been found that the conversion of the cancer-suppressive effect into a pro-cancerous effect of this pathway plays a key role in the development of liver cancer. Traditional Chinese medicine (TCM) provides a unique perspective for the classification, diagnosis, and treatment of liver cancer with its comprehensive regulatory effects of multi-components, multi-targets, and multi-pathways. This paper summarized that the cancer-suppressive mechanisms of the TGF-β signaling pathway included promoting cancer cell cycle arrest, apoptosis, autophagy, et al, while the pro-cancerous mechanisms included promoting cancer cell proliferation, invasion and metastasis, immunosuppression, angiogenesis, et al. The TCM compounds intervening this pathway were sorted out, including Jianpi Huayu compound, Fuyang Baoyuan compound, Yipi Yanggan compound, Fuzheng Jiedu compound, compound Astragalus and Salvia, Biejia Jianwan, Dahuang Zhechong pill, and Qingxiang powder. The single TCMs mainly included Schizocapsa plantaginea, Dendrobii Caulis, Gleditsia sinensis, and Dracaena cochinchinensis. The active ingredients of TCM are mainly concentrated on flavonoids, alkaloids, glycosides, phenolics, terpenoids, polysaccharides, and other kinds of compounds. At the same time, it summarized that the liver cancer inhibition mechanism of TCM by regulating this pathway mainly included promoting apoptosis of liver cancer cells, blocking the cell cycle, and inhibiting liver cancer cell proliferation, migration, invasion, angiogenesis, immune escape, etc. The mechanism aims to give full play to the advantages of TCM and precisely regulate the TGF-β signal, thereby exerting positive anti-tumor effects, opening up a new direction for the precise targeted treatment of liver cancer, and providing a scientific basis and a new strategy for the application of TCM in the treatment of liver cancer.
6.Association of Estimated Glucose Disposal Rate With the Stenosis Severity of Coronary Artery Disease: A Cross-sectional Study
Yubin WU ; Zhiteng CHEN ; Maoxiong WU ; Wenhao LIU ; Qian CHEN ; Shiyi ZHOU ; Yan-xin CHEN ; Min XIA
Journal of Sun Yat-sen University(Medical Sciences) 2024;45(1):136-145
ObjectiveTo investigate the association between estimated glucose disposal rate (eGDR) and the severity of coronary heart disease. MethodsWe conducted a hospital-based cross-sectional study that included 1258 patients (mean age: 62(53-68) years) who underwent coronary angiography for suspected coronary artery disease (53.9% were male). Insulin resistance level (IR) was calculated according to eGDR formula: eGDR = 21.158 - (0.09 × WC) - (3.407 × hypertension) - (0.551 × HbA1c) [hypertension (yes = 1 / no = 0), HbA1c = HbA1c (%)]. Subjects were grouped according to the eGDR quantile. CAD severity was determined by the number of narrowed vessels: no-obstructive CAD group (all coronary stenosis were<50%, n=704), Single-vessel CAD group (only one involved major coronary artery stenosis≥50%, n=205), Multi-vessel CAD group (two or more involved major coronary arteries stenosis≥50%, n=349); Multivariate logistic regression model was used to analyze the association between eGDR and CAD severity. The linear relationship between eGDR and CAD in the whole range of eGDR was analyzed using restricted cubic spline. Subgroup analyses were used to assess the association between eGDR and CAD severity in different diabetic states. Receiver operating characteristic (ROC) curve analysis were used to evaluate the value of eGDR in improving CAD recognition. ResultsA decrease in the eGDR index was significantly associated with an increased risk of CAD severity (OR: 2.79; 95%CI: 1.72~4.55; P<0.001). In multivariate logistic regression models, individuals with the lowest quantile of eGDR (T1) were 2.79 times more likely to develop multi-vessel CAD than those with the highest quantile of eGDR (T3) (OR: 2.79; 95%CI: 1.72~4.55; P<0.001). Multivariate restricted cubic spline analysis showed that eGDR was negatively associated with CAD and multi-vessel CAD (P-nonlinear>0.05). In non-diabetic patients, compared with the reference group (T3), the T1 group had a significantly increased risk of CAD (OR: 1.42; 95% CI: 1.00~2.01; P<0.05) and multi-vessel CAD (OR: 1.86; 95%CI: 1.21~2.86; P<0.05). No statistical association was found between eGDR and CAD in diabetic patients. In ROC curve analysis, when eGDR was added to traditional model for CAD, significant improvements were observed in the model's recognition of CAD and multi-vessel CAD. ConclusionOur study shows eGDR levels are inversely associated with CAD and CAD severity. eGDR, as a non-insulin measure to assess IR, could be a valuable indicator of CAD severity for population.
7.Relationship between blood indicators and course of nontraumatic osteonecrosis of femoral head in different stages:multiple logistic regression analysis
Zixuan WU ; Shiyi SUN ; Cheng ZHANG ; Guangyi ZHANG ; Tongjie YANG ; Haijun HE
Chinese Journal of Tissue Engineering Research 2024;28(36):5865-5871
BACKGROUND:Up to now,there is no literature on the relationship between blood laboratory tests and the course of nontraumatic osteonecrosis of femoral head in different stages.It is necessary to further explore and analyze so as to better clarify the influencing factors of nontraumatic osteonecrosis of femoral head. OBJECTIVE:To analyze the relationship between blood laboratory indicators and the course of nontraumatic osteonecrosis of the femoral head by the Association Research Circulation Osseous(ARCO),thus exploring the influencing factors of blood laboratory indicators on the course of nontraumatic osteonecrosis of the femoral head. METHODS:This study used a retrospective study design.A total of 2 103 patients with osteonecrosis of the femoral head were retrieved from Wangjing Hospital of China Academy of Chinese Medical Sciences database,and 1 075 patients with nontraumatic osteonecrosis of the femoral head were ultimately included based on inclusion and exclusion criteria.Patient age,gender,body mass index,and blood laboratory test results were collected.Blood laboratory tests included low-density lipoprotein,total cholesterol,triglycerides,high-density lipoprotein,apolipoprotein β,apolipoprotein α1,uric acid,total protein quantitative,alkaline phosphatase,activated partial thromboplastin time,prothrombin time,prothrombin time International Normalized Ratio,prothrombin time activity,fibrinogen quantitative,coagulation time of thrombin,D-dimer,total iron binding capacity,and platelet count.The indicators of patients with different age groups and different ARCO stages were compared,and multiple Logistic regression analysis was applied to explore the influencing factors of ARCO stages in osteonecrosis of the femoral head. RESULTS AND CONCLUSION:(1)There were statistical differences in total cholesterol,uric acid,prothrombin time,prothrombin time International Normalized Ratio,and D-dimer among ARCO stages in the young group(P<0.05).Among young patients in ARCO stage II,total cholesterol levels were higher than those in ARCO stage III(P<0.05).Uric acid levels in ARCO stage IV were higher than those in ARCO stage II and III(P<0.05).Prothrombin time and prothrombin time International Normalized Ratio were shorter in ARCO stage IV and II than in ARCO stage III(P<0.05).D-dimer levels were higher in ARCO stage III and IV than in ARCO stage II(P<0.05).(2)There were statistically significant differences in high-density lipoprotein,coagulation time of thrombin,and D-dimer among ARCO stages in the middle-aged group(P<0.05).Among middle-aged patients in ARCO stage IV,high-density lipoprotein levels were higher than those in ARCO stages II and III(P<0.05).Coagulation time of thrombin was shorter in ARCO stage IV than in ARCO stage III(P<0.05).D-dimer levels were higher in ARCO stages IV than in ARCO stages II and III(P<0.05).(3)The uric acid,activated partial thromboplastin time,D-dimer,and platelet count in the elderly group showed statistically significant differences(P<0.05).The uric acid level in ARCO stage IV was higher than that in ARCO stage II and III patients in the elderly group(P<0.05),while the activated prothrombin time in ARCO stage II patients was shorter than that in ARCO stage III patients in the elderly group(P<0.05).The D-dimer level in ARCO stage III and IV patients was higher than that in ARCO stage II patients in the elderly group(P<0.05).The platelet count in ARCO stage IV was lower than that in ARCO stage III patients in the elderly group(P<0.05).(4)Multiple logistic regression analysis showed that total cholesterol and platelet count may be protective factors for course of nontraumatic osteonecrosis of the femoral head,while D-dimer,uric acid,overweight,and young and middle age may be risk factors for course of nontraumatic osteonecrosis of the femoral head.(5)It is indicated that total cholesterol,high-density lipoprotein,uric acid,prothrombin time,prothrombin time International Normalized Ratio,and D-dimer are statistically significant among patients with different ARCO stages.Total cholesterol and platelet count may be protective factors for the course of nontraumatic osteonecrosis of the femoral head,while D-dimer,uric acid,overweight,and middle-aged and young age groups may be hazard factors for the course of nontraumatic osteonecrosis of the femoral head.
8.Exploration on the Main Factors Affecting the Prognosis of Osteonecrosis of Femoral Head Based on the Delphi Method
Shiyi SUN ; Guangyi ZHANG ; Haijun HE ; Zixuan WU ; Cheng ZHANG
Chinese Journal of Information on Traditional Chinese Medicine 2024;31(11):147-152
Objective To discuss the entries of prognostic factors affecting osteonecrosis of the femoral head(ONFH);To determine optimized and uniform prognostic influences.Methods Through literature pre-search and clinical research,the questionnaire was designed.Experts were selected based on the Delphi method and the questionnaire was distributed to the experts online,and after the questionnaire was recovered,Excel 2016 and SPSS 26.0 software were applied to process the data.The positive coefficients of experts,the degree of authority of experts,the degree of coordination of experts'opinions,the degree of concentration of experts'opinions,and the weight coefficients of the entries were calculated for the evaluation of the importance.Results Totally 116 articles were included.A list of prognostic factors indicators based on original literature was extracted.The first and second rounds of consultation had 30 and 40 experts respectively,and the collected questionnaires were all valid.Finally,10 major prognostic factors affecting ONFH were identified,including whether strictly on crutches,whether in pain(duration of pain),hip mobility,time to confirmation of osteonecrosis,ARCO staging,JIC staging,whether the anterolateral column is preserved,necrotic area,CT supracondylar subchondral fracture zone,and oral administration of traditional Chinese medicine.Conclusion This article summarizes the relevant factors that affect the progression of ONFH,which can further enhance clinical physicians'understanding of the prognosis of ONFH,and can delay the progression of ONFH by effectively intervening in important factors.
9.Macrophage LMO7 deficiency facilitates inflammatory injury via metabolic-epigenetic reprogramming.
Shixin DUAN ; Xinyi LOU ; Shiyi CHEN ; Hongchao JIANG ; Dongxin CHEN ; Rui YIN ; Mengkai LI ; Yuseng GOU ; Wenjuan ZHAO ; Lei SUN ; Feng QIAN
Acta Pharmaceutica Sinica B 2023;13(12):4785-4800
Inflammatory bowel disease (IBD) is a formidable disease due to its complex pathogenesis. Macrophages, as a major immune cell population in IBD, are crucial for gut homeostasis. However, it is still unveiled how macrophages modulate IBD. Here, we found that LIM domain only 7 (LMO7) was downregulated in pro-inflammatory macrophages, and that LMO7 directly degraded 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3 (PFKFB3) through K48-mediated ubiquitination in macrophages. As an enzyme that regulates glycolysis, PFKFB3 degradation led to the glycolytic process inhibition in macrophages, which in turn inhibited macrophage activation and ultimately attenuated murine colitis. Moreover, we demonstrated that PFKFB3 was required for histone demethylase Jumonji domain-containing protein 3 (JMJD3) expression, thereby inhibiting the protein level of trimethylation of histone H3 on lysine 27 (H3K27me3). Overall, our results indicated the LMO7/PFKFB3/JMJD3 axis is essential for modulating macrophage function and IBD pathogenesis. Targeting LMO7 or macrophage metabolism could potentially be an effective strategy for treating inflammatory diseases.
10.Association between lesion location and depressive symptoms in acute ischemic stroke patients using voxel-based lesion-symptom mapping
Jinjing WANG ; Mengmeng GU ; Shiyi JIANG ; Dawei YIN ; Peng WANG ; Wen SUN ; Xinfeng LIU
Chinese Journal of Internal Medicine 2023;62(1):70-75
Objective:The study aimed to investigate the association between lesion location and post-stroke depression (PSD) in acute ischemic stroke patients.Methods:In this case-control study, acute ischemic stroke patients were recruited from the Department of Neurology, First Affiliated Hospital of the University of Science and Technology of China (USTC), between September 2020 and June 2021. According to the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) criteria, the patients were divided into the PSD and non-PSD groups. The 24-item Hamilton Rating Scale (HAMD) was used to evaluate the severity of depression. The Student′s t-test, Mann-Whitney test, and Chi-square test were used to compare the clinical baseline characteristics of PSD and non-PSD groups. Voxel-based lesion-symptom mapping (VLSM) was applied to investigate the association between lesion location and depression occurrence and severity. Results:A total of 70 and 173 patients were admitted to the PSD and non-PSD groups, respectively. The mean age of patients was 59 years (23-86). There were 153 males and 90 females. Univariate analysis showed a significant difference only in Hamilton Anxiety ( P=0.025) and Depression ( P<0.001) scores between the PSD and non-PSD groups. VLSM analysis identified clusters within the anterior cingulate gyrus ( Z=-3.05, P<0.001), left hippocampus ( Z=-3.15, P<0.001), and left lingual lobe ( Z=-3.08, P<0.001) where lesions were significantly associated with PSD. Additionally, the severity of PSD was associated with damage in the anterior cingulate gyrus ( Z=-3.64, P<0.001), left hippocampus ( Z=-3.51, P<0.001), left lingual lobe ( Z=-4.18, P<0.001), and pericalcarine cortex ( Z=-3.65, P<0.001). Conclusion:VLSM demonstrated that lesion location could be used to predict the occurrence of PSD in patients with acute ischemic stroke.

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