1.Ameliorative Effect of Wendantang Combined with Danshenyin and Dushentang on Ischemic Heart Disease with Phlegm-stasis Syndrome in Mice Based on Circulating Monocytes
Fenghe YANG ; Ziqi TIAN ; Zhiqian SONG ; Shitao PENG ; Wenjie LU ; Tao LIN ; Chun WANG ; Zhangchi NING
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(3):22-32
ObjectiveTo investigate the ameliorative effect of Wendantang combined with Danshenyin and Dushentang (WDD) on mice with ischemic heart disease (IHD) presenting phlegm-stasis syndrome based on the inflammatory phenotype and differentiation of circulating monocytes. MethodsA model of IHD with phlegm-stasis syndrome was established using left anterior descending coronary artery ligation supplemented with a high-fat diet. Eighty model mice were randomly assigned to the model group, WDD low-dose group (WDD-L), WDD medium-dose group (WDD-M), WDD high-dose group (WDD-H), and atorvastatin calcium tablet group, with 16 mice in each group. An additional 16 C57BL/6J mice were designated as the sham-operation group. The WDD groups received intragastric administration at doses of 8.91, 17.81, 35.62 g·kg-1, and the atorvastatin calcium tablet group received the corresponding drug at 1.3 mg·kg-1, twice daily. The sham-operation and model groups were given the same volume of pure water by gavage each day. After 5 consecutive weeks of administration, the cardiac index was calculated. Cardiac function was assessed by echocardiography. Myocardial histopathology was examined by hematoxylin-eosin (HE) staining. Serum N-terminal pro-B-type natriuretic peptide (pro-BNP) content was measured by enzyme-linked immunosorbent assay (ELISA). Hemorheological parameters were analyzed using an automated hemorheology analyzer. Serum levels of total cholesterol (TC), triglycerides (TG), low-density lipoprotein (LDL), and high-density lipoprotein (HDL) were determined using an automated biochemical analyzer. Changes in circulating monocytes were detected by flow cytometry. Mouse bone marrow mononuclear cells were isolated in vitro and divided into blank group, model serum group, WDD-L drug-containing serum group, WDD-M drug-containing serum group, and WDD-H drug-containing serum group. CD36 expression and macrophage differentiation in each group were assessed by flow cytometry. The mechanism by which WDD mediates circulating monocyte differentiation was further explored using CD36 knockdown/overexpression RAW264.7 cell lines. ResultsCompared with the sham-operation group, the model group showed a significantly increased cardiac index (P0.01), significantly decreased fractional shortening (FS) (P0.01), and significantly increased left ventricular end-diastolic internal diameter (LVDD) and left ventricular end-systolic internal diameter (LVDS) (P0.01). Cardiomyocytes exhibited marked deformation and necrosis with inflammatory cell infiltration. Serum pro-BNP levels were significantly elevated (P0.01), and whole-blood viscosity (BV) at high, medium, and low shear rates was significantly increased (P0.01). Compared with the model group, the WDD groups showed significantly reduced cardiac index (P0.05, P0.01), significantly increased FS (P0.05, P0.01), significantly decreased LVDD and LVDS (P0.01), markedly improved cardiomyocyte morphology, significantly reduced inflammatory infiltration, significantly decreased serum pro-BNP levels (P0.01), and significantly decreased BV at high, medium, and low shear rates (P0.01), with the most pronounced improvement observed in the WDD-M group. Compared with the sham-operation group, TC, TG, and LDL levels were significantly increased in the model group (P0.05, P0.01), while HDL levels were significantly decreased (P0.05). After WDD-H treatment, TC, TG, and LDL levels were significantly reduced and HDL levels were significantly increased in mice (P0.05, P0.01). Compared with the sham-operation group, classical monocytes in blood and bone marrow and intermediate monocytes in blood were significantly increased in the model group (P0.01), whereas intermediate monocytes in bone marrow and non-classical monocytes in blood were significantly decreased (P0.01). After WDD administration, all circulating monocyte subsets in blood and bone marrow were significantly alleviated (P0.05, P0.01), with the WDD-M group showing the optimal effect. In vitro, compared with the blank group, CD36 expression on bone marrow monocytes and the proportion of differentiated macrophages were significantly increased in the model serum group (P0.01), and CD36 expression was significantly upregulated on RAW264.7 cells (P0.01). Compared with the model serum group, all drug-containing serum groups exhibited significantly reduced CD36 expression on bone marrow monocytes and significantly reduced macrophage differentiation (P0.01). WDD downregulated CD36 expression in both CD36 knockdown and overexpression RAW264.7 cell lines (P0.05, P0.01), with the strongest regulatory effect observed in the WDD-M drug-containing serum group. ConclusionWDD can significantly improve the manifestations of phlegm-stasis syndrome in IHD mice and reduce the proportion of classical circulating monocytes. Its mechanism may be related to the inhibition of CD36 expression on classical circulating monocytes.
2.Ameliorative Effect of Wendantang Combined with Danshenyin and Dushentang on Ischemic Heart Disease with Phlegm-stasis Syndrome in Mice Based on Circulating Monocytes
Fenghe YANG ; Ziqi TIAN ; Zhiqian SONG ; Shitao PENG ; Wenjie LU ; Tao LIN ; Chun WANG ; Zhangchi NING
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(3):22-32
ObjectiveTo investigate the ameliorative effect of Wendantang combined with Danshenyin and Dushentang (WDD) on mice with ischemic heart disease (IHD) presenting phlegm-stasis syndrome based on the inflammatory phenotype and differentiation of circulating monocytes. MethodsA model of IHD with phlegm-stasis syndrome was established using left anterior descending coronary artery ligation supplemented with a high-fat diet. Eighty model mice were randomly assigned to the model group, WDD low-dose group (WDD-L), WDD medium-dose group (WDD-M), WDD high-dose group (WDD-H), and atorvastatin calcium tablet group, with 16 mice in each group. An additional 16 C57BL/6J mice were designated as the sham-operation group. The WDD groups received intragastric administration at doses of 8.91, 17.81, 35.62 g·kg-1, and the atorvastatin calcium tablet group received the corresponding drug at 1.3 mg·kg-1, twice daily. The sham-operation and model groups were given the same volume of pure water by gavage each day. After 5 consecutive weeks of administration, the cardiac index was calculated. Cardiac function was assessed by echocardiography. Myocardial histopathology was examined by hematoxylin-eosin (HE) staining. Serum N-terminal pro-B-type natriuretic peptide (pro-BNP) content was measured by enzyme-linked immunosorbent assay (ELISA). Hemorheological parameters were analyzed using an automated hemorheology analyzer. Serum levels of total cholesterol (TC), triglycerides (TG), low-density lipoprotein (LDL), and high-density lipoprotein (HDL) were determined using an automated biochemical analyzer. Changes in circulating monocytes were detected by flow cytometry. Mouse bone marrow mononuclear cells were isolated in vitro and divided into blank group, model serum group, WDD-L drug-containing serum group, WDD-M drug-containing serum group, and WDD-H drug-containing serum group. CD36 expression and macrophage differentiation in each group were assessed by flow cytometry. The mechanism by which WDD mediates circulating monocyte differentiation was further explored using CD36 knockdown/overexpression RAW264.7 cell lines. ResultsCompared with the sham-operation group, the model group showed a significantly increased cardiac index (P<0.01), significantly decreased fractional shortening (FS) (P<0.01), and significantly increased left ventricular end-diastolic internal diameter (LVDD) and left ventricular end-systolic internal diameter (LVDS) (P<0.01). Cardiomyocytes exhibited marked deformation and necrosis with inflammatory cell infiltration. Serum pro-BNP levels were significantly elevated (P<0.01), and whole-blood viscosity (BV) at high, medium, and low shear rates was significantly increased (P<0.01). Compared with the model group, the WDD groups showed significantly reduced cardiac index (P<0.05, P<0.01), significantly increased FS (P<0.05, P<0.01), significantly decreased LVDD and LVDS (P<0.01), markedly improved cardiomyocyte morphology, significantly reduced inflammatory infiltration, significantly decreased serum pro-BNP levels (P<0.01), and significantly decreased BV at high, medium, and low shear rates (P<0.01), with the most pronounced improvement observed in the WDD-M group. Compared with the sham-operation group, TC, TG, and LDL levels were significantly increased in the model group (P<0.05, P<0.01), while HDL levels were significantly decreased (P<0.05). After WDD-H treatment, TC, TG, and LDL levels were significantly reduced and HDL levels were significantly increased in mice (P<0.05, P<0.01). Compared with the sham-operation group, classical monocytes in blood and bone marrow and intermediate monocytes in blood were significantly increased in the model group (P<0.01), whereas intermediate monocytes in bone marrow and non-classical monocytes in blood were significantly decreased (P<0.01). After WDD administration, all circulating monocyte subsets in blood and bone marrow were significantly alleviated (P<0.05, P<0.01), with the WDD-M group showing the optimal effect. In vitro, compared with the blank group, CD36 expression on bone marrow monocytes and the proportion of differentiated macrophages were significantly increased in the model serum group (P<0.01), and CD36 expression was significantly upregulated on RAW264.7 cells (P<0.01). Compared with the model serum group, all drug-containing serum groups exhibited significantly reduced CD36 expression on bone marrow monocytes and significantly reduced macrophage differentiation (P<0.01). WDD downregulated CD36 expression in both CD36 knockdown and overexpression RAW264.7 cell lines (P<0.05, P<0.01), with the strongest regulatory effect observed in the WDD-M drug-containing serum group. ConclusionWDD can significantly improve the manifestations of phlegm-stasis syndrome in IHD mice and reduce the proportion of classical circulating monocytes. Its mechanism may be related to the inhibition of CD36 expression on classical circulating monocytes.
3.Clinical observation and insights on pathological changes during "deep cervical lymphaticovenous anastomosis+" in elderly patients with cognitive impairment
Xiaoju ZHENG ; Haijun LI ; Jinming ZHANG ; Fang LI ; Baoshan WANG ; Yuqi ZHENG ; Wenbin SONG ; Yan WANG ; Xinhong WANG ; Qian LIN ; Shuang DU ; Dengwen ZHANG ; Rongguo YANG ; Peng HE ; Zhe CHANG ; Yujiao LI ; Linjuan WU
Chinese Journal of Microsurgery 2025;48(3):268-276
Objective:To investigate intraoperative pathological findings and the interventional effects of "deep cervical lymphaticovenous anastomosis+" (dcLVA+) on deep cervical lymphatic drainage as well as the blood flow of carotid artery and jugular vein in elderly patients with cognitive impairment, and to put forward the thoughts based on the findings from the surgery.Methods:Between May 2024 and December 2024, retrospective analysis of Microsurgery Hospital, Fengcheng Hospital, Xi'an Medical College performed dcLVA+ between the deep cervical lymphatics or lymph nodes and jugular veins in 50 elderly patients with cognitive impairment (19 males and 31 females, aged 55-88 years with 69.94 years in average). Nine patients were found with Clinical Dementia Rating (CDR) score at 1 (mild), 7 with CDR score at 2 (moderate) and 34 with CDR score at 3 (severe). Intraoperative observations based on literature reviews had identified anatomical relationships between the lymphatic sacs containing cervical lymphatic chain and the carotid sheath. The lymph node count, size, distribution, thickness of fat tissue and conditions of lymphatic vessels were documented. Ultrasound was used to compare the blood flow of carotid artery and jugular vein as well as the cross-sectional areas at the planes of hyoid and cricoid cartilage before and after the closure of incisions under anaesthesia in 39 patients. Correlation analyses for Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCa), Activities of Daily Living (ADL) and Agitation behavior score before and 1 week after surgery were performed using Spearman's correlation and Wilcoxon paired tests. P<0.05 was considered statistically significant. Postoperative follow-ups were conducted via the visit of outpatient clinic and WeChat and telephone interviews. Results:In surgery, the cervical lymphatic chain was found running within an almost enclosed sac surrounding the carotid sheath. There were enlarged lymph nodes, increased fat deposition, lymphatic dilation or fibrosis in the sac. The preoperative blood flow in the carotid artery at the planes of hyoid and cricoid cartilage in the 39 patients was recorded at 150.52 ml/min±40.33 ml/min and 358.29 ml/min±129.30 ml/min, while that in the jugular vein was at 172.50 ml/min±63.94 ml/min and 317.00 ml/min±105.21 ml/min, respectively, both were far lower than the normal blood flow. There were statistically significant differences in the blood flow of carotid artery and jugular vein before and after surgery ( P<0.01). It was found that the preoperative blood flow of the internal carotid artery at the plane of hyoid was positively correlated with the preoperative scores of MMSE ( P<0.01), MoCa ( P<0.05) and ADL ( P<0.01). The blood flow of the common carotid artery at the plane of cricoid cartilage was found significantly and positively correlated with the preoperative scores of MMSE ( P<0.05). It was also noted that the blood flow of the internal carotid artery at the plane of hyoid was significantly and positively correlated with the postoperative ADL ( P<0.01) but negatively correlated with the Agitation behavior score ( P<0.05). The blood flow of the common carotid artery at the plane of cricoid cartilage was significantly and positively correlated with the postoperative scores of MMSE and MoCa ( P<0.05). The blood flow of the internal jugular vein at the plane of hyoid was negatively correlated with the Agitation behavior score ( P<0.01). The cross-sectional area of carotid artery at the plane of left hyoid was significantly and positively correlated with the MMSE score ( P<0.05). Statistically significant differences were observed in MMSE, MoCa, ADL and Agitation behavior score before and after surgery ( P<0.01). Conclusion:dcLVA+ shows a certain therapeutic benefit to the elderly patients with cognitive impairment. The intraoperatively observed pathological changes in cervical lymphatic sacs affect deep cervical lymphatic drainage and the blood flow of carotid artery and jugular vein. Further studies are necessary to find out whether the findings from this study would be the specific pathological changes and the morbidity mechanisms among the elderly patients with cognitive impairment.
4.Effect of silicate bioactive glass fiber on properties of calcium phosphate bone cement
Yuzheng LU ; Yingjie XIONG ; Yanbo SHAN ; Jianting YE ; Yanbin WU ; Jipeng SONG ; Yao ZHANG ; Wancheng LIN ; Qirui WENG ; Xuan CHENG ; Haoye MENG ; Wenjing XU ; Jiang PENG ; Lixiang DING
Chinese Journal of Tissue Engineering Research 2025;29(28):5994-6002
BACKGROUND:The development of calcium phosphate bone cement is limited due to its poor mechanical properties and weak osteogenic ability.Silicate bioactive glass is highly favored due to its excellent biological activity and osteogenic ability.Simultaneously,fiber structures can enhance the mechanical strength of materials.OBJECTIVE:To investigate the mechanical properties,biocompatibility,and osteogenic effect of silicate bioactive glass fiber composite calcium phosphate bone cement.METHODS:Different mass percentages(0%,10%,and 20%)of silicate bioactive glass fiber were added to the solid phase of calcium phosphate bone cement,mixed with the liquid phase and cured for 48 hours to obtain silicate bioactive glass fiber composite calcium phosphate bone cement.The mechanical properties,setting time,and ion precipitation of the cement were characterized.The three groups of bone cement extracts were co-cultured with MC3T3-E1 cells.The cell compatibility of the materials was evaluated by CCK-8 assay,live/dead staining,and phalloidin staining.After osteogenic induction,the osteogenic induction ability of the materials was evaluated by alkaline phosphatase staining,alizarin red staining,RUNX2 immunofluorescence staining,and RT-PCR.RESULTS AND CONCLUSION:(1)With the increase of silicate bioactive glass fiber content,the compressive strength and flexural strength of bone cement increased,and the setting time was prolonged.When bone cement was immersed in simulated body fluid,the precipitation of silicon ions,calcium ions,and phosphorus ions could be detected.Moreover,with the increase of silicate bioactive glass fiber content,the mass concentration of silicon ions and phosphorus ions released by bone cement increased,and the mass concentration of calcium ions decreased.(2)Live/dead staining and phalloidin staining results exhibited that silicate bioactive glass fiber composite calcium phosphate bone cement had no toxic effect on MC3T3-E1 cells.CCK-8 assay results showed that silicate bioactive glass fiber composite calcium phosphate bone cement could promote the proliferation of MC3T3-E1 cells.(3)With the increase of silicate bioactive glass fiber content in bone cement,the alkaline phosphatase activity and extracellular calcium deposition of MC3T3-E1 cells increased,the expression of RUNX2 protein increased,and the expression of alkaline phosphatase,osteocalcin,osteopontin,and RUNX2 mRNA expression increased.(4)The results indicate that silicate bioactive glass fibers can enhance the mechanical properties and osteogenic induction ability of calcium phosphate bone cement,among which 20%silicate bioactive glass fibers have a more obvious effect.
5.The regulatory effect and mechanism of PGC-1α on mitochondrial function.
Song-Hua NAN ; Chao-Jie PENG ; Ying-Lin CUI
Acta Physiologica Sinica 2025;77(2):300-308
Peroxisome proliferator-activated receptor γ coactivator 1 α (PGC-1α) is a core member of the PGC-1 family and serves as a transcriptional coactivator, playing a crucial regulatory role in various diseases. Mitochondria, the main site of cellular energy metabolism, are essential for maintaining cell growth and function. Their function is regulated by various transcription factors and coactivators. PGC-1α regulates the biogenesis, dynamics, energy metabolism, calcium homeostasis, and autophagy processes of mitochondria by interacting with multiple nuclear transcription factors, thereby exerting significant effects on mitochondrial function. This review explores the biological functions of PGC-1α and its regulatory effects and related mechanisms on mitochondria, providing important information for our in-depth understanding of the role of PGC-1α in cellular metabolism. The potential role of PGC-1α in metabolic diseases, cardiovascular diseases, and neurodegenerative diseases was also discussed, providing a theoretical basis for the development of new treatment strategies.
Humans
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Mitochondria/metabolism*
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Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha/physiology*
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Animals
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Energy Metabolism/physiology*
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Neurodegenerative Diseases/physiopathology*
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Autophagy/physiology*
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Transcription Factors/physiology*
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Metabolic Diseases/physiopathology*
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Cardiovascular Diseases/physiopathology*
6.Effect of Duhuo Jisheng Decoction on knee osteoarthritis model rabbits through regulation of cell pyroptosis mediated by PI3K/Akt/mTOR signaling pathway.
Lin-Qin HE ; Peng-Fei LI ; Xiao-Dong LI ; Qi-Peng CHEN ; Zong-Han TANG ; Yu-Xin SONG ; Han-Bing SONG
China Journal of Chinese Materia Medica 2025;50(1):187-197
This study aimed to investigate the underlying mechanisms of Duhuo Jisheng Decoction(DJD) in the prevention and treatment of knee osteoarthritis(KOA). Forty SPF New Zealand rabbits were randomly divided using SPSS 26.0 software into five groups: blank group, model group, low-dose DJD group, high-dose DJD group, and high-dose DJD+phosphatidylinositol 3-kinase(PI3K)/protein kinase B(Akt)/mammalian target of rapamycin(mTOR) signaling pathway activator group(high-dose DJD+740Y-P group), with eight rabbits in each group. Except for the blank group, the KOA model was established in the other groups using papain injection into the knee joint cavity combined with forced flexion of the knee joint. The day after modeling, the blank group and model group were given normal saline at 10 mL·kg~(-1) by gavage, the low-dose DJD group received DJD at 8.8 g·kg~(-1) by gavage, the high-dose DJD group received DJD at 35.2 g·kg~(-1) by gavage, and the high-dose DJD+740Y-P group received DJD at 35.2 g·kg~(-1) by gavage along with 740Y-P at 0.15 μmoL·kg~(-1) injected via the auricular vein. All groups received treatment continuously for four weeks. After modeling and intervention, behavioral observations were performed for all groups, and after the intervention, imaging assessments of the knee joints were conducted. Cartilage from the knee joints was collected, and gross morphological changes were observed. Pathological changes in cartilage tissue were examined using hematoxylin-eosin(HE) staining. The results of these observations were quantitatively evaluated using the Lequesne MG score, Kellgren-Lawrence(K-L) grading, Pelletier score, and Mankin score. ELISA was used to measure the levels of interleukin-1β(IL-1β), interleukin-18(IL-18), and matrix metalloproteinase 13(MMP13) in cartilage tissue. Real-time RT-PCR was used to detect the mRNA expression levels of PI3K, Akt, mTOR, Nod-like receptor protein 3(NLRP3), cysteine protease 1(caspase-1), and gasdermin D(GSDMD) in cartilage tissue. Western blot was employed to measure the protein expression levels of PI3K, Akt, mTOR, NLRP3, caspase-1, and GSDMD. The results showed that compared with the blank group, the model group exhibited significant knee joint degeneration, increased Lequesne MG score, K-L grading, Pelletier score, and Mankin score, elevated levels of IL-1β, IL-18, and MMP13 in cartilage tissue, activation of PI3K, Akt, and mTOR phosphorylation along with increased mRNA expression levels, and elevated protein and mRNA expression levels of NLRP3, caspase-1, and GSDMD. Compared with the model group, these indicators were reversed in both the low-dose and high-dose DJD groups, with the high-dose group showing greater decline degree than the low-dose DJD group. However, compared with the high-dose DJD group, the improvements in knee joint degeneration were less pronounced in the high-dose DJD+740Y-P group, with increased Lequesne MG score, K-L grading, Pelletier score, Mankin score, elevated levels of IL-1β, IL-18, and MMP13, activation of PI3K, Akt, and mTOR phosphorylation along with increased mRNA expression, and increased protein and mRNA expression levels of NLRP3, caspase-1, and GSDMD. In conclusion, DJD is effective and safe in the treatment of KOA, and its mechanism may be related to the inhibition of PI3K/Akt/mTOR signaling pathway-mediated pyroptosis in cartilage tissue, thereby improving knee joint bone structure, reducing the inflammatory response, and preventing cartilage matrix degradation.
Animals
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Drugs, Chinese Herbal/administration & dosage*
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Rabbits
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TOR Serine-Threonine Kinases/genetics*
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Osteoarthritis, Knee/genetics*
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Proto-Oncogene Proteins c-akt/genetics*
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Signal Transduction/drug effects*
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Male
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Disease Models, Animal
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Pyroptosis/drug effects*
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Phosphatidylinositol 3-Kinases/genetics*
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Humans
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Female
7.Alpiniae Oxyphyllae Fructus-Saposhnikoviae Radix regulates NLRP3 inflammasome to ameliorate inflammatory response in diabetic kidney disease mice through PI3K/Akt/mTOR signaling pathway.
Zi-Jie YAN ; Lin ZHANG ; Xin-Yao HAN ; Tian-Peng MA ; Song-Jing ZHOU
China Journal of Chinese Materia Medica 2025;50(10):2798-2809
This study aims to evaluate the therapeutic effect of Alpiniae Oxyphyllae Fructus-Saposhnikoviae Radix(AOF-SR) in a diabetic kidney disease(DKD) mouse model, explore its potential mechanism in regulating the NOD-like receptor protein 3(NLRP3) inflammasome via phosphoinositide 3-kinase(PI3K)/protein kinase B(Akt)/mammalian target of rapamycin(mTOR) signaling pathway, and provide new theoretical support for traditional Chinese medicine(TCM) intervention in DKD. Using the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP), the active ingredients and potential targets of AOF-SR were screened and its molecular mechanisms were investigated through molecular docking, molecular dynamics simulations, and experimental validation. The db/db mice were randomly divided into four groups: model group, low-dose AOF-SR group, high-dose AOF-SR group, and canagliflozin group. The db/m mice served as normal group. After one week of acclimatization, the mice underwent drug intervention. Starting from one week after treatment, body weight, blood glucose levels, and 24-hour urinary protein(24hUP) were measured every two weeks. After 13 weeks of administration, tissue collection and indicator detection were performed. Blood glucose, 24hUP, urinary microalbumin(mAlb), serum creatinine(Scr), and blood urea nitrogen(BUN) levels were determined. Pathological changes in kidney tissue were observed using hematoxylin-eosin(HE) staining. Enzyme-linked immunosorbent assay(ELISA) was used to detect the levels of serum IL-1β, IL-18, and caspase-1, while RT-qPCR was employed to measure the mRNA expression levels of IL-1β, IL-18, caspase-1, and NLRP3. Western blot was used to assess the protein expression levels of NLRP3, PI3K, p-Akt, Akt, p-mTOR, and mTOR. Network pharmacology analysis indicated that wogonin, pinocembrin, hancinol, and kaempferol were the core compounds for drug treatment of the disease. Molecular docking and molecular dynamics simulations showed that core compounds, particularly wogonin, could specifically bind to PIK3R1, thereby regulating the PI3K/Akt/mTOR pathway. The experimental results indicated that both low and high doses of AOF-SR and canagliflozin significantly reduced blood glucose, 24hUP, mAlb, Scr, and BUN levels in db/db mice, while improving kidney pathological damage and inflammatory cell infiltration. Moreover, the treatments reduced the mRNA expression levels of caspase-1, IL-1β, and IL-18 in the kidneys of db/db mice, as well as the secretion of these factors in the serum. The drugs also inhibited the mRNA and protein expression levels of NLRP3 in the kidneys of db/db mice and decreased the protein levels of PI3K, p-Akt/Akt, and p-mTOR/mTOR. In conclusion, AOF-SR may improve kidney inflammation in DKD mice by regulating the PI3K/Akt/mTOR signaling pathway and inhibiting NLRP3 inflammasome activation.
Animals
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Mice
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NLR Family, Pyrin Domain-Containing 3 Protein/metabolism*
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Signal Transduction/drug effects*
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Phosphatidylinositol 3-Kinases/metabolism*
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Proto-Oncogene Proteins c-akt/metabolism*
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TOR Serine-Threonine Kinases/metabolism*
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Diabetic Nephropathies/metabolism*
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Inflammasomes/drug effects*
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Male
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Drugs, Chinese Herbal/chemistry*
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Humans
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Mice, Inbred C57BL
8.Multicenter randomized controlled trial of Yiqi Huoxue formula() for the treatment of ruptured lumbar disc herniation.
Yu ZHU ; Zhi-Qiang WANG ; Shun LIN ; Ying-Ying YAO ; Xue-Qiang SHEN ; Xiao-Chun LI ; Feng YU ; Xiao-Yang XIONG ; Yi SONG ; Meng-Fei CHEN ; Peng-Fei YU ; Hong JIANG ; Jin-Tao LIU
China Journal of Orthopaedics and Traumatology 2025;38(11):1112-1118
OBJECTIVE:
To observe the clinical symptoms and MRI outcomes of patients with ruptured lumbar disc herniation(LDH) through a multicenter randomized controlled study, and to evaluate the clinical efficacy and safety of Yiqi Huoxue formula() in the treatment of this disease.
METHODS:
A total of 160 outpatients and inpatients with ruptured LDH admitted to 4 medical centers from January 2023 to June 2023 were selected and randomly divided into the Yiqi Huoxue formula group and the control group, with 80 patients in each group. In the Yiqi Huoxue formula group, there were 43 males and 37 females, with an age of (41.03±9.56) years and a disease duration of (10.45±25.37) days, and the patients were treated with Yiqi Huoxue formula. In the control group, there were 34 males and 46 females, with an age of (42.14±8.73) years and a disease duration of (11.31±21.14) days;during the acute phase, patients in this group could take celecoxib capsules orally, and methylcobalamin orally at the same time. The Japanese Orthopaedic Association (JOA) score, Oswestry disability index (ODI), changes in the volume of herniated disc tissue on MRI, herniation rate, and absorption rate were recorded at the time of enrollment and during follow-ups at the 3rd, 6th, and 12th month after treatment.
RESULTS:
A total of 156 patients completed the clinical follow-up, and 4 patients withdrew midway. The clinical symptoms of all patients who completed the study were relieved to varying degrees, and reabsorption of herniated disc tissue was observed in all patients in the Yiqi Huoxue formula group after treatment. For the JOA score:in the Yiqi Huoxue formula group, it was (10.73±2.76) points before treatment and (24.65±2.19) points at the 12th month after treatment;in the control group, it was (11.01±1.20) points before treatment and (17.07±3.26) points at the 12th month after treatment. For the ODI score:in the Yiqi Huoxue formula group, it was (26.21±3.55) points before treatment and (5.65±2.19) points at the 12th month after treatment;in the control group, it was (27.92±2.51) points before treatment and (9.09±2.15) points at the 12th month after treatment. At the 12th month after treatment, the JOA and ODI scores of both groups were better than those before treatment, and the scores of the Yiqi Huoxue formula group were better than those of the control group, with statistically significant differences (P<0.05). In terms of the herniated disc volume and herniation rate on MRI, the Yiqi Huoxue formula group was superior to the control group, with statistically significant differences(P<0.05). Reabsorption occurred in 56.96%(45/79) of patients in the Yiqi Huoxue formula group, which was significantly higher than the 37.66%(29/77) in the control group.
CONCLUSION
After treatment with Yiqi Huoxue formula, patients with ruptured LDH show significant improvement in clinical symptoms and a marked reduction in the volume of herniated discs. During the follow-up period, no obvious adverse drug reactions are observed in patients, and no recurrence of symptoms is found at the last follow-up, indicating that the formula has safe and reliable efficacy.
Humans
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Male
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Female
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Intervertebral Disc Displacement/drug therapy*
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Adult
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Drugs, Chinese Herbal/adverse effects*
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Middle Aged
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Lumbar Vertebrae
9.Explainable machine learning model for predicting septic shock in critically sepsis patients based on coagulation indexes: A multicenter cohort study.
Qing-Bo ZENG ; En-Lan PENG ; Ye ZHOU ; Qing-Wei LIN ; Lin-Cui ZHONG ; Long-Ping HE ; Nian-Qing ZHANG ; Jing-Chun SONG
Chinese Journal of Traumatology 2025;28(6):404-411
PURPOSE:
Septic shock is associated with high mortality and poor outcomes among sepsis patients with coagulopathy. Although traditional statistical methods or machine learning (ML) algorithms have been proposed to predict septic shock, these potential approaches have never been systematically compared. The present work aimed to develop and compare models to predict septic shock among patients with sepsis.
METHODS:
It is a retrospective cohort study based on 484 patients with sepsis who were admitted to our intensive care units between May 2018 and November 2022. Patients from the 908th Hospital of Chinese PLA Logistical Support Force and Nanchang Hongdu Hospital of Traditional Chinese Medicine were respectively allocated to training (n=311) and validation (n=173) sets. All clinical and laboratory data of sepsis patients characterized by comprehensive coagulation indexes were collected. We developed 5 models based on ML algorithms and 1 model based on a traditional statistical method to predict septic shock in the training cohort. The performance of all models was assessed using the area under the receiver operating characteristic curve and calibration plots. Decision curve analysis was used to evaluate the net benefit of the models. The validation set was applied to verify the predictive accuracy of the models. This study also used Shapley additive explanations method to assess variable importance and explain the prediction made by a ML algorithm.
RESULTS:
Among all patients, 37.2% experienced septic shock. The characteristic curves of the 6 models ranged from 0.833 to 0.962 and 0.630 to 0.744 in the training and validation sets, respectively. The model with the best prediction performance was based on the support vector machine (SVM) algorithm, which was constructed by age, tissue plasminogen activator-inhibitor complex, prothrombin time, international normalized ratio, white blood cells, and platelet counts. The SVM model showed good calibration and discrimination and a greater net benefit in decision curve analysis.
CONCLUSION
The SVM algorithm may be superior to other ML and traditional statistical algorithms for predicting septic shock. Physicians can better understand the reliability of the predictive model by Shapley additive explanations value analysis.
Humans
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Shock, Septic/blood*
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Machine Learning
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Male
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Female
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Retrospective Studies
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Middle Aged
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Aged
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Sepsis/complications*
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ROC Curve
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Cohort Studies
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Adult
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Intensive Care Units
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Algorithms
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Blood Coagulation
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Critical Illness
10.Graph Neural Networks and Multimodal DTI Features for Schizophrenia Classification: Insights from Brain Network Analysis and Gene Expression.
Jingjing GAO ; Heping TANG ; Zhengning WANG ; Yanling LI ; Na LUO ; Ming SONG ; Sangma XIE ; Weiyang SHI ; Hao YAN ; Lin LU ; Jun YAN ; Peng LI ; Yuqing SONG ; Jun CHEN ; Yunchun CHEN ; Huaning WANG ; Wenming LIU ; Zhigang LI ; Hua GUO ; Ping WAN ; Luxian LV ; Yongfeng YANG ; Huiling WANG ; Hongxing ZHANG ; Huawang WU ; Yuping NING ; Dai ZHANG ; Tianzi JIANG
Neuroscience Bulletin 2025;41(6):933-950
Schizophrenia (SZ) stands as a severe psychiatric disorder. This study applied diffusion tensor imaging (DTI) data in conjunction with graph neural networks to distinguish SZ patients from normal controls (NCs) and showcases the superior performance of a graph neural network integrating combined fractional anisotropy and fiber number brain network features, achieving an accuracy of 73.79% in distinguishing SZ patients from NCs. Beyond mere discrimination, our study delved deeper into the advantages of utilizing white matter brain network features for identifying SZ patients through interpretable model analysis and gene expression analysis. These analyses uncovered intricate interrelationships between brain imaging markers and genetic biomarkers, providing novel insights into the neuropathological basis of SZ. In summary, our findings underscore the potential of graph neural networks applied to multimodal DTI data for enhancing SZ detection through an integrated analysis of neuroimaging and genetic features.
Humans
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Schizophrenia/pathology*
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Diffusion Tensor Imaging/methods*
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Male
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Female
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Adult
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Brain/metabolism*
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Young Adult
;
Middle Aged
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White Matter/pathology*
;
Gene Expression
;
Nerve Net/diagnostic imaging*
;
Graph Neural Networks

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