1.Mechanism of Tangbikang Dry Paste in Prevention and Treatment of Type 2 Diabetic Peripheral Neuropathy Based on GLO-1/AGE/RAGE Pathway
Lijia WU ; Chengfei ZHANG ; Xiaolei JIA ; Lingling QIN ; Haiyan WANG ; Yukun HUANG ; You WANG ; Xincui BAO ; Jing YANG ; Cuiyan LYU ; Tonghua LIU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(11):60-69
ObjectiveTo investigate the mechanism of Tangbikang dry paste in the prevention and treatment of type 2 diabetic peripheral neuropathy (DPN) based on the glyoxalase-1 (GLO-1)/advanced glycation end products (AGE)/receptor for advanced glycation end products (RAGE) pathway. MethodsA total of 56 Sprague-Dawley rats were randomly divided, with eight assigned to the normal group. The remaining 48 rats were fed a high-fat diet combined with intraperitoneal injection of streptozotocin (STZ) to induce a type 2 diabetes mellitus (T2DM) model. Based on blood glucose levels, the rats were randomly assigned to the model group, Tanglin group (13.5 mg·kg-1), metformin group (135 mg·kg-1), and Tangbikang dry paste low-, medium-, and high-dose groups (3, 6, 12 g·kg-1). Successful modeling of DPN was confirmed by a decrease in mechanical pain threshold in the model group at week 4. Fasting blood glucose, body weight, and mechanical pain threshold were measured every 4 weeks. After 16 weeks of intervention, the pathological morphology of the sciatic nerve was observed using hematoxylin-eosin (HE) staining. The expression of RAGE, AGE, protein kinase C (PKC), and collagen (COL) in the sciatic nerve was assessed by immunohistochemistry. The mRNA expression of RAGE, PKC, Toll-like receptor (TLR), COL, and GLO-1 was detected using real-time quantitative PCR (Real-time PCR). Serum levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), creatinine (CREA), urea (UREA), interleukin-6 (IL-6), and tumor necrosis factor (TNF)-α were measured by enzyme-linked immunosorbent assay (ELISA). ResultsCompared with the normal group, the model group showed significantly increased fasting blood glucose (P<0.01), decreased body weight and mechanical pain threshold (P<0.01), and elevated serum AST, ALT, CREA, UREA, IL-6, and TNF-α levels (P<0.01). The expression of RAGE, AGE, and PKC in the sciatic nerve was significantly increased (P<0.01), while COL expression was decreased (P<0.01). The mRNA expression of TLR, RAGE, and PKC was upregulated (P<0.01), whereas COL and GLO-1 mRNA levels were downregulated (P<0.01). Histological examination showed irregular nerve morphology, axonal alterations, and myelin degeneration. Compared with the model group, fasting blood glucose levels in the Tangbikang dry paste high-dose group at all time points and in the medium-dose group at weeks 4 and 16 were significantly reduced (P<0.05, P<0.01). No significant changes in body weight were observed across all Tangbikang dose groups. The mechanical pain threshold was elevated at different time points after administration in all Tangbikang groups (P<0.05, P<0.01). Serum IL-6 and TNF-α levels were decreased in all dose groups (P<0.05, P<0.01). The expression of RAGE, AGE, and PKC in the sciatic nerve was reduced (P<0.01), while COL expression was increased (P<0.01). The mRNA expression of TLR, RAGE, and PKC was downregulated (P<0.01), whereas GLO-1 mRNA expression was upregulated (P<0.05, P<0.01). Additionally, COL mRNA expression was significantly increased in the low- and high-dose groups (P<0.01). Pathological changes in the sciatic nerve were milder in all Tangbikang groups compared to the model group. ConclusionTangbikang dry paste significantly improves DPN, and its mechanism may be associated with the regulation of the GLO-1/AGE/RAGE signaling pathway.
2.Effect of Gynostemma pentaphyllum Alcohol Extract on Glucose and Lipid Metabolism Disorders in db/db Mice Based on Transcriptomics and Gut Microbiota
Yifei ZHU ; Lei DING ; Wei LIU ; Yahui SUN ; Lingling QIN ; Lili WU ; Tonghua LIU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(11):80-89
ObjectiveTo investigate the efficacy and underlying mechanisms of Gynostemma pentaphyllum alcohol extract in improving glucose and lipid metabolism disorders in db/db mice through transcriptomics and gut microbiota analysis. MethodsEighteen db/db mice were randomly assigned to the model(DM) group, metformin(MET) group, and G. pentaphyllum alcohol extract(GP) group, with six mice in each group, based on stratification of fasting blood glucose and body weight. An additional six db/m mice were selected as the normal control(NC) group. Mice in the NC and DM groups were administered deionized water (10 mL·kg-1) daily. The MET group received metformin (0.195 g·kg-1) by gavage. The GP group was treated with G. pentaphyllum alcohol extract (3.9 g·kg-1) by gavage for six weeks. Fasting blood glucose was measured every two weeks. After six weeks of intervention, serum levels of total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), aspartate aminotransferase (AST), alanine aminotransferase (ALT), creatinine (CREA), and blood urea nitrogen (BUN) were assessed. Enzyme-linked immunosorbent assay (ELISA) was used to measure insulin (FINS), adiponectin (ADP), and tumor necrosis factor-α (TNF-α). Hematoxylin-eosin (HE) staining was used to observe liver histomorphology, periodic acid-Schiff (PAS) staining was employed to assess hepatic glycogen synthesis, and Oil Red O staining was used to detect hepatic lipid deposition. Liver transcriptomic data were used to identify differentially expressed genes in the liver and conduct enrichment analysis. Real-time PCR was employed to verify the expression levels of adiponectin gene (Adipoq), peroxisome proliferator-activated receptor gamma coactivator-1α (PGC-1α), AMP-activated protein kinase (AMPK), peroxisome proliferator-activated receptor α (PPARα), glucokinase (GCK), forkhead box (Fox)O1, FoxO3, phosphoenolpyruvate carboxykinase (PEPCK), and glucose-6-phosphatase (G6PC). Metagenomic sequencing was conducted to analyze changes in gut microbiota composition. ResultsCompared with the NC group, the DM group exhibited significantly elevated fasting blood glucose (P<0.01), serum AST, ALT, TC, TG, LDL-C, and HDL-C (P<0.01). FINS, homeostatic model assessment for insulin resistance (HOMA-IR), and the inflammatory cytokine TNF-α were significantly increased (P<0.01), while ADP was significantly decreased (P<0.05). Histological analysis confirmed severe hepatic steatosis and excessive lipid accumulation in the DM group, along with markedly reduced glycogen synthesis. Compared with the DM group, the GP group showed significantly decreased fasting blood glucose (P<0.01), reduced serum TC, LDL-C, and HDL-C levels (P<0.05), significantly decreased serum TG and AST levels (P<0.01), significantly reduced FINS, HOMA-IR, and TNF-α levels (P<0.01), and significantly increased ADP (P<0.01). Hepatic steatosis and lipid deposition were significantly alleviated, while glycogen synthesis was markedly enhanced. Transcriptomic differential and enrichment analyses suggested that the mechanisms by which G. pentaphyllum alcohol extract improved hepatic glucose and lipid metabolism in db/db mice may involve regulation of the AMPK and FoxO signaling pathways. Real-time PCR results confirmed that expression of PGC-1α, PEPCK, G6PC, FoxO1, and FoxO3 was significantly downregulated following treatment with G. pentaphyllum alcohol extract (P<0.05, P<0.01), whereas mRNA expression of Adipoq, PPARα, GCK, and AMPK was significantly upregulated (P<0.05, P<0.01). Metagenomic analysis showed that the relative abundance of Lactobacillus, Alistipes, and Akkermansia species was higher in the GP group than in the DM group. ConclusionG. pentaphyllum alcohol extract may improve glucose and lipid metabolism disorders in db/db mice by regulating the hepatic AMPK/PPARα pathway to suppress lipid deposition and alleviate hepatic steatosis, by inhibiting gluconeogenesis through the AMPK/PGC-1α and FoxO pathways to lower fasting blood glucose, and by increasing the abundance of beneficial gut bacteria such as Lactobacillus, Alistipes, and Akkermansia to restore gut microbiota balance.
3.Mechanism of Tangbikang Dry Paste in Prevention and Treatment of Type 2 Diabetic Peripheral Neuropathy Based on GLO-1/AGE/RAGE Pathway
Lijia WU ; Chengfei ZHANG ; Xiaolei JIA ; Lingling QIN ; Haiyan WANG ; Yukun HUANG ; You WANG ; Xincui BAO ; Jing YANG ; Cuiyan LYU ; Tonghua LIU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(11):60-69
ObjectiveTo investigate the mechanism of Tangbikang dry paste in the prevention and treatment of type 2 diabetic peripheral neuropathy (DPN) based on the glyoxalase-1 (GLO-1)/advanced glycation end products (AGE)/receptor for advanced glycation end products (RAGE) pathway. MethodsA total of 56 Sprague-Dawley rats were randomly divided, with eight assigned to the normal group. The remaining 48 rats were fed a high-fat diet combined with intraperitoneal injection of streptozotocin (STZ) to induce a type 2 diabetes mellitus (T2DM) model. Based on blood glucose levels, the rats were randomly assigned to the model group, Tanglin group (13.5 mg·kg-1), metformin group (135 mg·kg-1), and Tangbikang dry paste low-, medium-, and high-dose groups (3, 6, 12 g·kg-1). Successful modeling of DPN was confirmed by a decrease in mechanical pain threshold in the model group at week 4. Fasting blood glucose, body weight, and mechanical pain threshold were measured every 4 weeks. After 16 weeks of intervention, the pathological morphology of the sciatic nerve was observed using hematoxylin-eosin (HE) staining. The expression of RAGE, AGE, protein kinase C (PKC), and collagen (COL) in the sciatic nerve was assessed by immunohistochemistry. The mRNA expression of RAGE, PKC, Toll-like receptor (TLR), COL, and GLO-1 was detected using real-time quantitative PCR (Real-time PCR). Serum levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), creatinine (CREA), urea (UREA), interleukin-6 (IL-6), and tumor necrosis factor (TNF)-α were measured by enzyme-linked immunosorbent assay (ELISA). ResultsCompared with the normal group, the model group showed significantly increased fasting blood glucose (P<0.01), decreased body weight and mechanical pain threshold (P<0.01), and elevated serum AST, ALT, CREA, UREA, IL-6, and TNF-α levels (P<0.01). The expression of RAGE, AGE, and PKC in the sciatic nerve was significantly increased (P<0.01), while COL expression was decreased (P<0.01). The mRNA expression of TLR, RAGE, and PKC was upregulated (P<0.01), whereas COL and GLO-1 mRNA levels were downregulated (P<0.01). Histological examination showed irregular nerve morphology, axonal alterations, and myelin degeneration. Compared with the model group, fasting blood glucose levels in the Tangbikang dry paste high-dose group at all time points and in the medium-dose group at weeks 4 and 16 were significantly reduced (P<0.05, P<0.01). No significant changes in body weight were observed across all Tangbikang dose groups. The mechanical pain threshold was elevated at different time points after administration in all Tangbikang groups (P<0.05, P<0.01). Serum IL-6 and TNF-α levels were decreased in all dose groups (P<0.05, P<0.01). The expression of RAGE, AGE, and PKC in the sciatic nerve was reduced (P<0.01), while COL expression was increased (P<0.01). The mRNA expression of TLR, RAGE, and PKC was downregulated (P<0.01), whereas GLO-1 mRNA expression was upregulated (P<0.05, P<0.01). Additionally, COL mRNA expression was significantly increased in the low- and high-dose groups (P<0.01). Pathological changes in the sciatic nerve were milder in all Tangbikang groups compared to the model group. ConclusionTangbikang dry paste significantly improves DPN, and its mechanism may be associated with the regulation of the GLO-1/AGE/RAGE signaling pathway.
4.Effect of Gynostemma pentaphyllum Alcohol Extract on Glucose and Lipid Metabolism Disorders in db/db Mice Based on Transcriptomics and Gut Microbiota
Yifei ZHU ; Lei DING ; Wei LIU ; Yahui SUN ; Lingling QIN ; Lili WU ; Tonghua LIU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(11):80-89
ObjectiveTo investigate the efficacy and underlying mechanisms of Gynostemma pentaphyllum alcohol extract in improving glucose and lipid metabolism disorders in db/db mice through transcriptomics and gut microbiota analysis. MethodsEighteen db/db mice were randomly assigned to the model(DM) group, metformin(MET) group, and G. pentaphyllum alcohol extract(GP) group, with six mice in each group, based on stratification of fasting blood glucose and body weight. An additional six db/m mice were selected as the normal control(NC) group. Mice in the NC and DM groups were administered deionized water (10 mL·kg-1) daily. The MET group received metformin (0.195 g·kg-1) by gavage. The GP group was treated with G. pentaphyllum alcohol extract (3.9 g·kg-1) by gavage for six weeks. Fasting blood glucose was measured every two weeks. After six weeks of intervention, serum levels of total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), aspartate aminotransferase (AST), alanine aminotransferase (ALT), creatinine (CREA), and blood urea nitrogen (BUN) were assessed. Enzyme-linked immunosorbent assay (ELISA) was used to measure insulin (FINS), adiponectin (ADP), and tumor necrosis factor-α (TNF-α). Hematoxylin-eosin (HE) staining was used to observe liver histomorphology, periodic acid-Schiff (PAS) staining was employed to assess hepatic glycogen synthesis, and Oil Red O staining was used to detect hepatic lipid deposition. Liver transcriptomic data were used to identify differentially expressed genes in the liver and conduct enrichment analysis. Real-time PCR was employed to verify the expression levels of adiponectin gene (Adipoq), peroxisome proliferator-activated receptor gamma coactivator-1α (PGC-1α), AMP-activated protein kinase (AMPK), peroxisome proliferator-activated receptor α (PPARα), glucokinase (GCK), forkhead box (Fox)O1, FoxO3, phosphoenolpyruvate carboxykinase (PEPCK), and glucose-6-phosphatase (G6PC). Metagenomic sequencing was conducted to analyze changes in gut microbiota composition. ResultsCompared with the NC group, the DM group exhibited significantly elevated fasting blood glucose (P<0.01), serum AST, ALT, TC, TG, LDL-C, and HDL-C (P<0.01). FINS, homeostatic model assessment for insulin resistance (HOMA-IR), and the inflammatory cytokine TNF-α were significantly increased (P<0.01), while ADP was significantly decreased (P<0.05). Histological analysis confirmed severe hepatic steatosis and excessive lipid accumulation in the DM group, along with markedly reduced glycogen synthesis. Compared with the DM group, the GP group showed significantly decreased fasting blood glucose (P<0.01), reduced serum TC, LDL-C, and HDL-C levels (P<0.05), significantly decreased serum TG and AST levels (P<0.01), significantly reduced FINS, HOMA-IR, and TNF-α levels (P<0.01), and significantly increased ADP (P<0.01). Hepatic steatosis and lipid deposition were significantly alleviated, while glycogen synthesis was markedly enhanced. Transcriptomic differential and enrichment analyses suggested that the mechanisms by which G. pentaphyllum alcohol extract improved hepatic glucose and lipid metabolism in db/db mice may involve regulation of the AMPK and FoxO signaling pathways. Real-time PCR results confirmed that expression of PGC-1α, PEPCK, G6PC, FoxO1, and FoxO3 was significantly downregulated following treatment with G. pentaphyllum alcohol extract (P<0.05, P<0.01), whereas mRNA expression of Adipoq, PPARα, GCK, and AMPK was significantly upregulated (P<0.05, P<0.01). Metagenomic analysis showed that the relative abundance of Lactobacillus, Alistipes, and Akkermansia species was higher in the GP group than in the DM group. ConclusionG. pentaphyllum alcohol extract may improve glucose and lipid metabolism disorders in db/db mice by regulating the hepatic AMPK/PPARα pathway to suppress lipid deposition and alleviate hepatic steatosis, by inhibiting gluconeogenesis through the AMPK/PGC-1α and FoxO pathways to lower fasting blood glucose, and by increasing the abundance of beneficial gut bacteria such as Lactobacillus, Alistipes, and Akkermansia to restore gut microbiota balance.
5.Modified Buwangsan Ameliorates Cognitive Dysfunction in Rat Model of Type 2 Diabetes Mellitus by Regulating Autophagy in Hippocampus via PI3K/Akt/mTOR Pathway
Jie YANG ; Tonghua LIU ; Wei LIU ; Lili WU ; Lingling QIN
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(13):104-113
ObjectiveTo evaluate the therapeutic effects of modified Buwangsan on cognitive dysfunction in the rat model of type 2 diabetes mellitus with mild cognitive impairment (T2DM-MCI) and explore the underlying mechanism. MethodsThirty-six 5-week-old SPF-grade SD rats were randomly assigned into 6 groups: Normal (Con, fed with a normal diet), model (DM, fed with a high-sugar and high-fat diet), low-dose modified Buwangsan (L-BWS, 1.86 g·kg-1), medium-dose modified Buwangsan (M-BWS, 3.72 g·kg-1), high-dose modified Buwangsan (H-BWS,7.44 g·kg-1), and huperzine A (SSJJ, 0.018 mg·kg-1). The rats were treated by gavage once a day for 12 weeks. The body weight and blood glucose level were monitored dynamically. Morris water maze was employed to test the cognitive function of rats. Hematoxylin-eosin and Nissl staining were employed to observe the pathological changes of the hippocampus. The levels of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6) in the serum and hippocampus were assessed by enzyme-linked immunosorbent assay. Western blotting was employed to determine the expression levels of key autophagy-related proteins including microtubule-associated protein 1 light chain 3 (LC3), type Ⅲ phosphatidylinositol 3-kinase complex regulatory subunit (Beclin1), and phosphorylated UNC-51-like kinase (p-ULK) 1/2 in the hippocampus. Immunofluorescence staining was employed to observe the regulation of p-PI3K/PI3K, p-mTOR/mTOR, and p-Akt/Akt ratios. ResultsCompared with the DM group, the L-BWS, M-BWS, H-BWS, and SSJJ groups showed increases in body weight at the end of the experiment (P<0.05), and the M-BWS, H-BWS and SSJJ groups showed declines in fasting blood glucose level (P<0.05). In the water maze test, compared with the DM group, the M-BWS, H-BWS, and SSJJ groups presented shortened escape latency (P<0.001). The L-BWS, M-BWS, H-BWS, and SSJJ group showcased regularly arranged cells in the hippocampus and cortex, markedly increased number of neurons, and significantly recovered Nissl bodies. Compared with the DM group, the L-BWS, M-BWS, H-BWS, and SSJJ groups had reductions in the levels of IL-1β and IL-6 in the serum and hippocampus (P<0.05), increases in the LC3-II/LC3-I ratio and expression level of beclin1 in the hippocampus (P<0.05) and the p-ULK level (P<0.05). The p-PI3K/PI3K, p-Akt/Akt, and p-mTOR/mTOR ratios in the hippocampus decreased in the M-BWS, H-BWS, and SSJJ groups (P<0.01). ConclusionModified Buwangsan significantly ameliorates cognitive dysfunction and neurological damage in the rat model of T2DM through multiple mechanisms. It regulates metabolic disorders, lowers the blood glucose level, improves lipid metabolism, and alleviates oxidative stress. It promotes the protection and repair of neurons by inhibiting inflammatory responses and activating the autophagy pathway in the hippocampus. At the same time, modified Buwangsan relieves autophagy inhibition by regulating the PI3K/Akt/mTOR signaling pathway to alleviate the brain tissue injury.
6.Modified Buwangsan Ameliorates Cognitive Dysfunction in Rat Model of Type 2 Diabetes Mellitus by Regulating Autophagy in Hippocampus via PI3K/Akt/mTOR Pathway
Jie YANG ; Tonghua LIU ; Wei LIU ; Lili WU ; Lingling QIN
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(13):104-113
ObjectiveTo evaluate the therapeutic effects of modified Buwangsan on cognitive dysfunction in the rat model of type 2 diabetes mellitus with mild cognitive impairment (T2DM-MCI) and explore the underlying mechanism. MethodsThirty-six 5-week-old SPF-grade SD rats were randomly assigned into 6 groups: Normal (Con, fed with a normal diet), model (DM, fed with a high-sugar and high-fat diet), low-dose modified Buwangsan (L-BWS, 1.86 g·kg-1), medium-dose modified Buwangsan (M-BWS, 3.72 g·kg-1), high-dose modified Buwangsan (H-BWS,7.44 g·kg-1), and huperzine A (SSJJ, 0.018 mg·kg-1). The rats were treated by gavage once a day for 12 weeks. The body weight and blood glucose level were monitored dynamically. Morris water maze was employed to test the cognitive function of rats. Hematoxylin-eosin and Nissl staining were employed to observe the pathological changes of the hippocampus. The levels of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6) in the serum and hippocampus were assessed by enzyme-linked immunosorbent assay. Western blotting was employed to determine the expression levels of key autophagy-related proteins including microtubule-associated protein 1 light chain 3 (LC3), type Ⅲ phosphatidylinositol 3-kinase complex regulatory subunit (Beclin1), and phosphorylated UNC-51-like kinase (p-ULK) 1/2 in the hippocampus. Immunofluorescence staining was employed to observe the regulation of p-PI3K/PI3K, p-mTOR/mTOR, and p-Akt/Akt ratios. ResultsCompared with the DM group, the L-BWS, M-BWS, H-BWS, and SSJJ groups showed increases in body weight at the end of the experiment (P<0.05), and the M-BWS, H-BWS and SSJJ groups showed declines in fasting blood glucose level (P<0.05). In the water maze test, compared with the DM group, the M-BWS, H-BWS, and SSJJ groups presented shortened escape latency (P<0.001). The L-BWS, M-BWS, H-BWS, and SSJJ group showcased regularly arranged cells in the hippocampus and cortex, markedly increased number of neurons, and significantly recovered Nissl bodies. Compared with the DM group, the L-BWS, M-BWS, H-BWS, and SSJJ groups had reductions in the levels of IL-1β and IL-6 in the serum and hippocampus (P<0.05), increases in the LC3-II/LC3-I ratio and expression level of beclin1 in the hippocampus (P<0.05) and the p-ULK level (P<0.05). The p-PI3K/PI3K, p-Akt/Akt, and p-mTOR/mTOR ratios in the hippocampus decreased in the M-BWS, H-BWS, and SSJJ groups (P<0.01). ConclusionModified Buwangsan significantly ameliorates cognitive dysfunction and neurological damage in the rat model of T2DM through multiple mechanisms. It regulates metabolic disorders, lowers the blood glucose level, improves lipid metabolism, and alleviates oxidative stress. It promotes the protection and repair of neurons by inhibiting inflammatory responses and activating the autophagy pathway in the hippocampus. At the same time, modified Buwangsan relieves autophagy inhibition by regulating the PI3K/Akt/mTOR signaling pathway to alleviate the brain tissue injury.
7.Construction of a Diagnostic Model for Traditional Chinese Medicine Syndromes of Chronic Cough Based on the Voting Ensemble Machine Learning Algorithm
Yichen BAI ; Suyang QIN ; Chongyun ZHOU ; Liqing SHI ; Kun JI ; Chuchu ZHANG ; Panfei LI ; Tangming CUI ; Haiyan LI
Journal of Traditional Chinese Medicine 2025;66(11):1119-1127
ObjectiveTo explore the construction of a machine learning model for the diagnosis of traditional Chinese medicine (TCM) syndromes in chronic cough and the optimization of this model using the Voting ensemble algorithm. MethodsA retrospective analysis was conducted using clinical data from 921 patients with chronic cough treated at the Respiratory Department of Dongfang Hospital, Beijing University of Chinese Medicine. After standardized processing, 84 clinical features were extracted to determine TCM syndrome types. A specialized dataset for TCM syndrome diagnosis in chronic cough was formed by selecting syndrome types with more than 50 cases. The synthetic minority over-sampling technique (SMOTE) was employed to balance the dataset. Four base models, logistic regression (LR), decision tree (dt), multilayer perceptron (MLP), and Bagging, were constructed and integrated using a hard voting strategy to form a Voting ensemble model. Model performance was evaluated using accuracy, recall, precision, F1-score, receiver operating characteristic (ROC) curve, area under the curve (AUC), and confusion matrix. ResultsAmong the 921 cases, six syndrome types had over 50 cases each, phlegm-heat obstructing the lung (294 cases), wind pathogen latent in the lung (103 cases), cold-phlegm obstructing the lung (102 cases), damp-heat stagnating in the lung (64 cases), lung yang deficiency (54 cases), and phlegm-damp obstructing the lung (53 cases), yielding a total of 670 cases in the specialized dataset. High-frequency symptoms among these patients included cough, expectoration, odor-induced cough, throat itchiness, itch-induced cough, and cough triggered by cold wind. Among the four base models, the MLP model showed the best diagnostic performance (test accuracy: 0.9104; AUC: 0.9828). Compared with the base models, the Voting ensemble model achieved superior performance with an accuracy of 0.9289 on the training set and 0.9253 on the test set, showing a minimal overfitting gap of 0.0036. It also achieved the highest AUC (0.9836) in the test set, outperforming all base models. The model exhi-bited especially strong diagnostic performance for damp-heat stagnating in the lung (AUC: 0.9984) and wind pathogen latent in the lung (AUC: 0.9970). ConclusionThe Voting ensemble algorithm effectively integrates the strengths of multiple machine learning models, resulting in an optimized diagnostic model for TCM syndromes in chronic cough with high accuracy and enhanced generalization ability.
8.Effect of South African Herb Hoodia gordonii on Liver Glucolipid Metabolism and PI3K/Akt/FoxO1 Signalling Pathway in db/db Mice
Chengfei ZHANG ; Qiue ZHANG ; Linging QIN ; Wei LIU ; Guangyuan XU ; Xuesheng MA ; Lili WU ; Tonghua LIU
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(5):57-64
ObjectiveTo observe the effects of the South African herb Hoodia gordonii (HG) on glucolipid metabolism in diabetic db/db mice and explore the possible mechanisms of HG on the liver of db/db mice based on the phosphoinositide-3 kinase (PI3K)/protein kinase B (Akt)/factor forkhead protein O1 (FoxO1) signaling pathway. MethodA total of 30 db/db mice were randomly divided into five groups according to fasting blood glucose: model group, metformin group (0.195 g·kg-1), and low dose (0.39 g·kg-1), medium dose (0.78 g·kg-1), and high dose (1.56 g·kg-1) HG groups, with six m/m mice in each group, and another six m/m mice were set as normal group. The mice in the normal and model groups were given saline of 9 mL·kg-1 by gavage. Body weight, water intake, and fasting blood glucose of the mice in each group were measured weekly. After six weeks of continuous administration, serum insulin (FINS), low-density lipoprotein cholesterol (LDL), total cholesterol (TC), triglyceride (TG), alanine aminotransferase (ALT), aspartate aminotransferase (AST), urea, and creatinine (CREA) were measured, and liver sections were embedded and stained with hematoxylin-eosin (HE), periodic acid-Schiff (PAS), and oil red O. Protein expression of PI3K p85, p-Akt, and p-FoxO1 in liver was detected by immunohistochemistry. The mRNA expression of PI3K, Akt, and FoxO1 in liver tissue was detected by real-time polymerase chain reaction (Real-time PCR). ResultAfter six weeks of administration intervention, it was found that fasting blood glucose was significantly downregulated in mice in the three HG groups (P<0.05). The level of islet resistance index was significantly reduced in both the low and medium dose HG groups (P<0.05). The expression levels of TC, TG, and LDL were reduced in all HG groups (P<0.05, P<0.01). Pathologically, HG could alleviate hepatocyte steatosis, reduce the volume and content of lipid droplets in liver, and increase the distribution of glycogen granules in liver to some extent in mice. Immunohistochemical assays revealed that PI3K p85 protein expression was significantly increased in the low, medium, and high dose HG groups compared with the model group (P<0.01). p-Akt protein expression was significantly increased in the medium and high dose HG groups (P<0.05, P<0.01). p-FoxO1 protein expression was significantly increased in the low, medium, and high dose HG groups (P<0.05, P<0.01). Compared with the model group, PI3K mRNA was increased in low dose, medium dose, and high dose HG groups (P<0.05), and Akt mRNA was increased in high dose HG group (P<0.05). FoxO1 mRNA was decreased in low dose, medium dose, and high dose HG groups (P<0.05). ConclusionHG can ameliorate the disorder of glucolipid metabolism in db/db mice, which may be related to its activation of the hepatic PI3K/Akt/FoxO1 signaling pathway.
9.Expert Consensus on Clinical Diseases Responding Specifically to Traditional Chinese Medicine: Threatened Abortion
Xinchun YANG ; Shuyu WANG ; Huilan DU ; Songping LUO ; Zhe JIN ; Rong LI ; Xiangyan RUAN ; Qin ZHANG ; Xiaoling FENG ; Shicai CHEN ; Fengjie HE ; Shaobin WEI ; Qun LU ; Yanqin WANG ; Yang LIU ; Qingwei MENG ; Zengping HAO ; Ying LI ; Mei MO ; Xiaoxiao ZHANG ; Ruihua ZHAO
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(7):241-246
Threatened abortion is a common disease of obstetrics and gynecology and one of the diseases responding specifically to traditional Chinese medicine (TCM). The China Association of Chinese Medicine organized experts in TCM obstetrics and gynecology, Western medicine obstetrics and gynecology, and pharmacology to deeply discuss the advantages of TCM and integrated Chinese and Western medicine treatment as well as the medication plans for threatened abortion. After discussion, the experts concluded that chromosome, endocrine, and immune abnormalities were the key factors for the occurrence of threatened abortion, and the Qi and blood disorders in thoroughfare and conception vessels were the core pathogenesis. In the treatment of threatened abortion, TCM has advantages in preventing miscarriages, alleviating clinical symptoms and TCM syndromes, relieving anxiety, regulating reproductive endocrine and immune abnormalities, personalized and diversified treatment, enhancing efficiency and reducing toxicity, and preventing the disease before occurrence. The difficulty in diagnosis and treatment of threatened abortion with traditional Chinese and Western medicine lies in identifying the predictors of abortion caused by maternal factors and the treatment of thrombophilia. Recurrent abortion is the breakthrough point of treatment with integrated traditional Chinese and Western medicine. It is urgent to carry out high-quality evidence-based medicine research in the future to improve the modern diagnosis and treatment of threatened abortion with TCM.
10.Expert Consensus on Clinical Diseases Responding Specifically to Traditional Chinese Medicine:Fibromyalgia Syndrome
Juan JIAO ; Jinyang TANG ; Xiujuan HOU ; Mengtao LI ; Dongfeng LIANG ; Yuhua WANG ; Weixia JING ; Guangtao LI ; Qin ZHANG ; Yongfeng ZHANG ; Guangyu LI ; Qian WANG ; Yang YANG ; Jin HUO ; Mei MO ; Jihua GUO ; Xiaoxiao ZHANG ; Quan JIANG
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(1):216-222
Fibromyalgia syndrome (FMS) is a refractory, chronic non-articular rheumatic disease characterized by widespread pain throughout the body, for which there are no satisfactory therapeutic drugs or options. There are rich Chinese medical therapies, and some non-drug therapies, such as acupuncture, Tai Chi, and Ba-Duan-Jin, have shown satisfactory efficacy and safety and definite advantages of simultaneously adjusting mind and body. FMS is taken as a disease responding specifically to traditional Chinese medicine (TCM) by the National Administration of Traditional Chinese Medicine in 2018. In order to clarify the research progress in FMS and the clinical advantages of TCM/integrated Chinese and Western medicine, the China Academy of Chinese Medicine organized a seminar for nearly 20 experts in Chinese and Western medicine, including rheumatology, psychology, acupuncture and moxibustion, and encephalopathy, with the topic of difficulties in clinical diagnosis and treatment of FMS and advantages of TCM and Western medicine. The recommendations were reached on the difficulties in early diagnosis and solutions of FMS, mitigation of common non-specific symptoms, preferential analgesic therapy, TCM pathogenesis and treatment advantages, and direction of treatment with integrated Chinese and Western medicine. FMS is currently facing the triple dilemma of low early correct diagnosis, poor patient participation, and unsatisfactory benefit from pure Western medicine treatment. To solve the above problems, this paper suggests that rheumatologists should serve as the main diagnostic force of this disease, and they should improve patient participation in treatment decision-making, implement exercise therapy, and fully utilize the holistic and multidimensional features of TCM, which is effective in alleviating pain, improving mood, and decreasing adverse events. In addition, it is suggested that FMS treatment should rely on both TCM and Western medicine and adopt multidisciplinary joint treatment, which is expected to improve the standard of diagnosis and treatment of FMS in China.

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