This paper outlines the development of artificial intelligence （AI） and its applications in traditional Chinese medicine （TCM） research， and elucidates the roles and advantages of large language models， knowledge graphs， and natural language processing in advancing syndrome identification， prescription generation， and mechanism exploration. Using spleen-stomach diseases as an example， it demonstrates the empowering effects of AI in classical literature mining， precise clinical syndrome differentiation， efficacy and safety prediction， and intelligent education， highlighting an upgraded research paradigm that evolves from data-driven and knowledge-driven approaches to intelligence-driven models. To address challenges related to privacy protection and regulatory compliance in cross-institutional data collaboration， a "trusted federated evidence-based analysis platform for TCM spleen-stomach diseases" is proposed， integrating blockchain-based smart contracts， federated learning， and secure multi-party computation. The deep integration of AI with privacy-preserving computing is reshaping research and clinical practice in TCM spleen-stomach diseases， providing feasible pathways and a technical framework for building a high-quality， trustworthy TCM big-data ecosystem and achieving precision syndrome differentiation.

Cyclin-dependent kinase 9 (CDK9) is a member of the transcription CDK subfamily and plays a role in transcriptional regulation. Selective CDK9 degraders possess potent clinical advantages over reversible CDK9 inhibitors. Herein, we report the first ATG101-recruiting selective CDK9 degrader, AZ-9, based on the hydrophobic tag kinesin degradation technology. AZ-9 showed significant degradation effects and selectivity toward other homologous cell cycle CDKs in vitro and in vivo, which could also affect downstream related phenotypes. Mechanism research revealed that AZ-9 recruits ATG101 to initiate the autophagy-lysosome pathway, and forms autophagosomes through the recruitment of LC3, which then fuses with lysosomes to degrade CDK9 and the partner protein Cyclin T1. These dates validated the existence of non-proteasomal degradation pathway of hydrophobic driven protein degradation strategy for the first time, which might provide research ideas for chemical induction intervention on other types of pathogenic proteins.

Objective To determine the effect of baicalein on high glucose-induced cardiac fibro-blast pyroptosis based on the nucleotide-binding oligomerization domain-like receptor protein 3(NLRP3)/cysteinyl aspartate-specific proteinase-1(Caspase-1)/gasdermin D(GSDMD)pathway.Methods Rat cardiac fibroblasts were grouped into control,high glucose group,low-,medium-and high-dose baicalein(H-,M-and L-baicalein)groups,and H-baicalein+NLRP3 agonist(BMS-986299)group.Except for the control group,all other groups were cultured in DMEM medium containing 40 mmol/L glucose,then 12.5,25 and 50 μmol/L baicalein was added into the medium correspondingly,and 1 μmol/L BMS-986299 was used to treat the H-baicalein+NLRP3 agonist group.Lactate dehydrogenase(LDH)cytotoxicity assay were employed to detect cell cytotoxicity.qRT-PCR and Western blotting were performed to determine the expression of NLRP3,Caspase-1,and GSDMD at mRNA and protein levels.Results High glucose treatment induced more EdU positive cells,higher pyroptotic rate,stronger cytotoxicity,higher Col-Ⅰ and Col-Ⅲ contents,and enhanced mRNA and protein levels of NLRP3,Caspase-1 and GSDMD in comparison to the control group(P＜0.05).The H-baicalein+NLRP3 agonist group had more EdU positive cells(26.85±2.95 cells vs 15.43±1.82 cells,P＜0.05),higher pyroptotic rate[(33.45±4.02)％vs(17.34±2.15)％,P＜0.05],stronger cytotoxicity[(27.94±2.93)％vs(14.13±1.87)％,P＜0.05],and increased contents of Col-Ⅰ(107.58±13.39 ng/ml vs 58.73±8.36 ng/ml,P＜0.05)and Col-Ⅲ(118.43±13.95 ng/ml vs 68.74±8.57 ng/ml,P＜0.05),and enhanced expression of NLRP3,Caspase-1 and GSDMD at both mRNA and protein levels(P＜0.05)when compared with the H-baicalein group.Conclusion Baicalein inhibits high glucose-induced cardiac fibroblast pyroptosis by suppressing NLRP3/Caspase-1/GSDMD pathway.

Objective:To analyze the correlation between caregiver characteristics and clinical manifestations of patients with Alzheimer′s disease (AD) dementia.Methods:It was a cross-sectional study. A total of 167 patients with AD dementia and 167 matched caregivers from Chinese Imaging, Biomarkers, and Lifestyle study of Alzheimer′s Disease (CIBL) study between January 1 and December 31, 2023 were consecutively selected as the study subjects. The data such as gender, age, body max index (BMI), waist to hip ratio, educational years, combined chronic diseases, disease course and the Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA), Neuropsychiatric Inventory (NPI), Activities of Daily Living (ADL), Mini-Nutritional Assessment (MNA), and Dietary Diversity Score (DDS) of the patients were collected. The data such as gender, educational years, the relationship with patients, and the Caregiver Burden Inventory (CBI) score in the caregivers were also evaluated. According to the gender of caregivers, the patients were divided into female caregiver group (108 cases) and male caregiver group (59 cases). The Spearman correlation and multiple linear regression analyses were used to assess the impact of the caregiver characteristics on the cognitive function, NPS, activities of daily living, and nutritional status of the patients with AD dementia.Results:Among the 167 patients with AD dementia, 80 cases were men, and 87 cases were women, with a mean age of (68.43±7.51) years. Among the 167 matched caregivers, 59 were spouse, 98 were offspring, and 10 were others (nanny or other relatives). The AD patients in the male caregiver group had lower BMI and MNA scores than those in female caregivers′ group [(23.35±3.70) vs (24.80±3.33) kg/m 2, 22.00 (20.00, 24.50) vs 24.00 (21.00, 26.00) points] (both P<0.05). The educational years of the caregivers was negatively related to the ADL score ( r=-0.196), and was positively related to the MNA score of the patients ( r=0.180) (both P<0.05); while the CBI score of the caregiver was positively related to the age ( r=0.180), NPI score ( r=0.568) and ADL scores ( r=0.702) in the patients, and it was negatively related to the BMI ( r=-0.163), MMSE score ( r=-0.499), MoCA score ( r=-0.491) and MNA scores ( r=-0.387) in the patients (all P<0.05). The shorter educational years and elevated CBI score were independent risk factors for the decline in the MMSE score ( β=0.310, 95% CI: 0.021-0.598; β=-0.225, 95% CI:-0.297--0.154) and MNA score ( β=0.204, 95% CI: 0.067-0.340; β=-0.082, 95% CI:-0.116--0.049), as well as the increase in the NPI score ( β=-0.628, 95% CI:-1.208--0.047; β=0.575, 95% CI: 0.431-0.718) and ADL score ( β=-0.519, 95% CI:-0.860--0.179; β=0.361, 95% CI: 0.277-0.445) in the patients with AD dementia (all P<0.001). Conclusions:A low educational level of caregivers and a heavy caregiver burden are associated with decreased cognitive function, worsening NPS, reduced ADL, and declining nutritional status in patients with AD dementia.

Objective:To investigate the local hemodynamic spatial distribution of internal carotid artery stenosis and its correlation with plaque characteristics using high-resolution vessel wall imaging (HR-VWI) combined with computational fluid dynamics.Methods:This was a cross-sectional study. A retrospective analysis was conducted on the clinical and imaging data of 70 patients with moderate to severe stenosis at the initiation of the internal carotid artery in First Teaching Hospital of Tianjin University of Traditional Chinese Medicine and Tianjin First Central Hospital from March 2018 to June 2020. All patients underwent HR-VWI and CT angiography examinations. The parameters related to plaque characteristics, such as plaque length, maximum wall thickness, plaque volume, wall volume percentage and intraplaque hemorrhage (IPH) were measured and evaluated on HR-VWI images. CT angiography images were used to construct a local hemodynamic vascular model to measure various wall shear stress (WSS) derived parameters, such as time-averaged wall shear stress (TAWSS), oscillatory shear index (OSI), relative residence time (RRT), and transverse wall shear stress (transWSS), at the narrowest, proximal, and distal parts of the lesion. The Friedman test was used to analyze the difference of hemodynamic parameters in different parts of the lesion. Spearman correlation analysis was performed to assess the correlation between plaque burden and local hemodynamic parameters. Univariate and multivariate logistic regression analyses were used to explore the independent risk factors for predicting IPH.Results:Among the 70 patients, 25 patients with IPH and 45 patients without IPH. The overall differences in TAWSS, OSI, RRT and transWSS at the narrowest, proximal, and distal parts of the lesion in 70 patients were statistically significant ( P<0.05). The TAWSS and transWSS at the narrowest parts were significantly higher than those at the proximal and distal parts ( P<0.05). The OSI at the distal part was significantly higher than that at the narrowest and the proximal parts ( P<0.05). The RRT at the proximal part was significantly lower than that at the narrowest and the distal parts ( P<0.05). Spearman correlation analysis showed RRT at the distal part was correlated with plaque volume ( r s=0.249, P=0.044) and wall volume percentage ( r s=0.286, P=0.016), respectively. In a multivariate logistic regression showed plaque length ( OR=1.315, 95% CI 1.073-1.612, P=0.008) and TAWSS at the narrowest part ( OR=1.631, 95% CI 1.308-1.854, P=0.008) were independent risk factors for predicting IPH. Conclusions:The spatial distribution of local hemodynamics of moderate to severe stenosis at the initiation of the internal carotid artery is different, and the WSS parameters in different parts of the lesion have different effects on plaque volume, wall volume percentage and IPH.

Objective To investigate the effect of circRNA-homeodomain-interacting protein kinase 2(circHIPK2)on angiotensinⅡ(AngⅡ)-induced apoptosis of vascular endothelial cells through the regulation of the miR-7-5p/transcription factor 4(TCF4)axis.Methods Human umbilical vein endothelial cells(HUVECs)were randomly divided into the control,model,negative control cotrans-fection,circHIPK2 knockdown,miR-7-5p overexpression,and circHIPK2 knockdown+miR-7-5p knockdown groups.Except for the control group,all other groups were administered 10 nmol/L Ang Ⅱ to establish a hypertensive injury model.The circHIPK2,miR-7-5p,and TCF4 mRNA expression levels were detected after transfection.Apoptosis,proliferation,mitochondrial membrane potential,reactive oxygen species(ROS),antioxidant enzymes,pro-inflammatory factors,and TCF4 protein expression were assessed.Results Compared with the control group,the expressions of circHIPK2 and TCF4 mRNA,cell apoptosis rate,relative expression of ROS,levels of IL-6,IL-1β,and IL-18,and expressions of Bax and TCF4 protein increased,and cell viability,miR-7-5p mRNA expression,mitochondrial mem-brane potential,activities of superoxide dismutase(SOD)and catalase(CAT),and Bcl-2 protein expression decreased in the model group(P＜0.05).Both circHIPK2 knockdown and miR-7-5p overexpression reversed Ang Ⅱ-induced pathological changes in vascular endothelial cells.miR-7-5p knockdown reduced the effect of circHIPK2 knockdown on pathological cellular changes in the model group.Conclusion circHIPK2 knockdown can weaken TCF4 expression by upregulating miR-7-5p,thereby reducing Ang Ⅱ-induced inflam-mation and oxidative stress in vascular endothelial cells and ultimately inhibiting cell apoptosis.

Objective To analyze effects of caragliflozin and empagliflozin on inflammatory markers,glucose and lipid metabolism and miR-144 expression in obese patients with type 2 diabetes mellitus(T2DM).Methods A total of 148 obese T2DM patients admitted to our hospital from June 2021 to May 2024 were selected and divided into the caragliflozin group and the empagliflozin group by random number table method.The two groups were treated with canagliflozin and empagliflozin on the basis of conventional treatment for 6 months.The inflammatory indicators,glucose metabolism indicators,lipid metabolism indicators,microRNA-144(miR-144)expression,body mass index(BMI),clinical efficacy and incidence of adverse reactions were compared between the two groups.Results After a total of 7 cases were excluded during the treatment period,there were 71 cases in the caragliflozin group and 70 cases in the empagliflozin group.After treatment,the levels of tumor necrosis factor-α,interleukin-6,C-reactive protein,fasting blood glucose(FBG),2 h postprandial blood glucose(2 h-PPG),glycosylated hemoglobin(HbA1c),triglyceride(TG),total cholesterol,low density lipoprotein cholesterol,BMI and miR-144 expression were lower than those before treatment in two groups of patients(P＜0.05),and the levels of FBG,2 h-PPG,HbA1c,TG and miR-144 expression were lower in the caragliflozin group than those of the empagliflozin group(P＜0.05).After treatment,high density lipoprotein cholesterol was higher than that before treatment in the two groups(P＜0.05),and that in the canagliflozin group was higher than the empagliflozin group(P＜0.05).There were no significant differences in the clinical efficacy and incidence of adverse reactions between the two groups after treatment(P＞0.05).Conclusion Both caragliflozin and empagliflozin have certain therapeutic efficacy and good safety for obese T2DM patients,and caragliflozin is more effective in improving glucose and lipid metabolism.

Objective:To investigate the local hemodynamic spatial distribution of internal carotid artery stenosis and its correlation with plaque characteristics using high-resolution vessel wall imaging (HR-VWI) combined with computational fluid dynamics.Methods:This was a cross-sectional study. A retrospective analysis was conducted on the clinical and imaging data of 70 patients with moderate to severe stenosis at the initiation of the internal carotid artery in First Teaching Hospital of Tianjin University of Traditional Chinese Medicine and Tianjin First Central Hospital from March 2018 to June 2020. All patients underwent HR-VWI and CT angiography examinations. The parameters related to plaque characteristics, such as plaque length, maximum wall thickness, plaque volume, wall volume percentage and intraplaque hemorrhage (IPH) were measured and evaluated on HR-VWI images. CT angiography images were used to construct a local hemodynamic vascular model to measure various wall shear stress (WSS) derived parameters, such as time-averaged wall shear stress (TAWSS), oscillatory shear index (OSI), relative residence time (RRT), and transverse wall shear stress (transWSS), at the narrowest, proximal, and distal parts of the lesion. The Friedman test was used to analyze the difference of hemodynamic parameters in different parts of the lesion. Spearman correlation analysis was performed to assess the correlation between plaque burden and local hemodynamic parameters. Univariate and multivariate logistic regression analyses were used to explore the independent risk factors for predicting IPH.Results:Among the 70 patients, 25 patients with IPH and 45 patients without IPH. The overall differences in TAWSS, OSI, RRT and transWSS at the narrowest, proximal, and distal parts of the lesion in 70 patients were statistically significant ( P<0.05). The TAWSS and transWSS at the narrowest parts were significantly higher than those at the proximal and distal parts ( P<0.05). The OSI at the distal part was significantly higher than that at the narrowest and the proximal parts ( P<0.05). The RRT at the proximal part was significantly lower than that at the narrowest and the distal parts ( P<0.05). Spearman correlation analysis showed RRT at the distal part was correlated with plaque volume ( r s=0.249, P=0.044) and wall volume percentage ( r s=0.286, P=0.016), respectively. In a multivariate logistic regression showed plaque length ( OR=1.315, 95% CI 1.073-1.612, P=0.008) and TAWSS at the narrowest part ( OR=1.631, 95% CI 1.308-1.854, P=0.008) were independent risk factors for predicting IPH. Conclusions:The spatial distribution of local hemodynamics of moderate to severe stenosis at the initiation of the internal carotid artery is different, and the WSS parameters in different parts of the lesion have different effects on plaque volume, wall volume percentage and IPH.

Objective To analyze effects of caragliflozin and empagliflozin on inflammatory markers,glucose and lipid metabolism and miR-144 expression in obese patients with type 2 diabetes mellitus(T2DM).Methods A total of 148 obese T2DM patients admitted to our hospital from June 2021 to May 2024 were selected and divided into the caragliflozin group and the empagliflozin group by random number table method.The two groups were treated with canagliflozin and empagliflozin on the basis of conventional treatment for 6 months.The inflammatory indicators,glucose metabolism indicators,lipid metabolism indicators,microRNA-144(miR-144)expression,body mass index(BMI),clinical efficacy and incidence of adverse reactions were compared between the two groups.Results After a total of 7 cases were excluded during the treatment period,there were 71 cases in the caragliflozin group and 70 cases in the empagliflozin group.After treatment,the levels of tumor necrosis factor-α,interleukin-6,C-reactive protein,fasting blood glucose(FBG),2 h postprandial blood glucose(2 h-PPG),glycosylated hemoglobin(HbA1c),triglyceride(TG),total cholesterol,low density lipoprotein cholesterol,BMI and miR-144 expression were lower than those before treatment in two groups of patients(P＜0.05),and the levels of FBG,2 h-PPG,HbA1c,TG and miR-144 expression were lower in the caragliflozin group than those of the empagliflozin group(P＜0.05).After treatment,high density lipoprotein cholesterol was higher than that before treatment in the two groups(P＜0.05),and that in the canagliflozin group was higher than the empagliflozin group(P＜0.05).There were no significant differences in the clinical efficacy and incidence of adverse reactions between the two groups after treatment(P＞0.05).Conclusion Both caragliflozin and empagliflozin have certain therapeutic efficacy and good safety for obese T2DM patients,and caragliflozin is more effective in improving glucose and lipid metabolism.

Objective To determine the effect of baicalein on high glucose-induced cardiac fibro-blast pyroptosis based on the nucleotide-binding oligomerization domain-like receptor protein 3(NLRP3)/cysteinyl aspartate-specific proteinase-1(Caspase-1)/gasdermin D(GSDMD)pathway.Methods Rat cardiac fibroblasts were grouped into control,high glucose group,low-,medium-and high-dose baicalein(H-,M-and L-baicalein)groups,and H-baicalein+NLRP3 agonist(BMS-986299)group.Except for the control group,all other groups were cultured in DMEM medium containing 40 mmol/L glucose,then 12.5,25 and 50 μmol/L baicalein was added into the medium correspondingly,and 1 μmol/L BMS-986299 was used to treat the H-baicalein+NLRP3 agonist group.Lactate dehydrogenase(LDH)cytotoxicity assay were employed to detect cell cytotoxicity.qRT-PCR and Western blotting were performed to determine the expression of NLRP3,Caspase-1,and GSDMD at mRNA and protein levels.Results High glucose treatment induced more EdU positive cells,higher pyroptotic rate,stronger cytotoxicity,higher Col-Ⅰ and Col-Ⅲ contents,and enhanced mRNA and protein levels of NLRP3,Caspase-1 and GSDMD in comparison to the control group(P＜0.05).The H-baicalein+NLRP3 agonist group had more EdU positive cells(26.85±2.95 cells vs 15.43±1.82 cells,P＜0.05),higher pyroptotic rate[(33.45±4.02)％vs(17.34±2.15)％,P＜0.05],stronger cytotoxicity[(27.94±2.93)％vs(14.13±1.87)％,P＜0.05],and increased contents of Col-Ⅰ(107.58±13.39 ng/ml vs 58.73±8.36 ng/ml,P＜0.05)and Col-Ⅲ(118.43±13.95 ng/ml vs 68.74±8.57 ng/ml,P＜0.05),and enhanced expression of NLRP3,Caspase-1 and GSDMD at both mRNA and protein levels(P＜0.05)when compared with the H-baicalein group.Conclusion Baicalein inhibits high glucose-induced cardiac fibroblast pyroptosis by suppressing NLRP3/Caspase-1/GSDMD pathway.