1.Indobufen attenuates cerebral ischemia–reperfusion injury by inhibiting the NF-κB/Caspase-1/GSDMD pathway
Yiyin XU ; Dan XU ; Xue GOU ; Weirong FANG ; Yunman LI ; Hua SHAO ; Yongqing WANG
Journal of China Pharmaceutical University 2026;57(2):246-255
Indobufen is a new generation of antiplatelet agents and has been shown to have antithrombotic effects in animal models. However, its therapeutic potential and mechanisms against cerebral ischemia/reperfusion (I/R) injury remain unclear. In this study, we evaluated the in vivo neuroprotective effects of indobufen through both pretreatment and posttreatment regimens in a rat model of middle cerebral artery occlusion/reperfusion (MCAO/R). In vitro, human umbilical vein endothelial cells (HUVECs) subjected to oxygen-glucose deprivation/reoxygenation (OGD/R) were employed to investigate the relationship between indobufen and the pyroptosis-associated NF-κB/Caspase-1/GSDMD pathway. The pharmacodynamic tests revealed that indobufen ameliorated I/R injury by decreasing the level of thromboxane B2 (TXB2), infarct size, brain edema and neurological impairment in rats and rescuing cell pyroptosis in HUVECs. The underlying mechanisms were probably related to pyroptosis suppression by regulating the NF-κB/Caspase-1/GSDMD pathway. Overall, these studies indicate that indobufen exerts protective and therapeutic effects against I/R injury by pyroptosis suppression via downregulating NF-κB/Caspase-1/GSDMD pathway.
2.Mechanism of Different Dosage Forms of Kaixinsan in Improving Mitochondrial Function for Prevention and Treatment of Cognitive Disorder Based on AMPK/PGC-1α/SIRT3 Pathway
Shuyue KANG ; Yanzi YU ; Jiaqun SUN ; Wenxuan CHEN ; Yaqin YANG ; Qi WANG ; Weirong LI ; Limei YAO
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(7):15-24
ObjectiveTo explore the effects of different dosage forms of Kaixinsan (KXS) on the morphology and function of mitochondria in rat models of Alzheimer's disease (AD) and potential mechanisms of action. MethodsMale SD rats were randomly assigned to a sham group, model group, treatment groups receiving KXS decoction, powders, and granules (3.08 g·kg-1), as well as donepezil group (0.51×10-3 g·kg-1), with 10 rats in each group. AD model was created using intracerebroventricular injection of streptozocin (STZ). After 30 days of administration, behavioral assessments were conducted, and mitochondrial morphology was observed using transmission electron microscopy. Mitochondrial respiratory chain complex content was measured via enzyme-linked immunosorbent assay (ELISA). Changes in mitochondrial membrane potential were measured via JC-1 staining, and superoxide dismutase (SOD) activity and reactive oxygen species (ROS) levels were measured via biochemical assays. The mRNA expression of adenosine 5'-monophosphate-activated protein kinase (AMPK), peroxisome proliferator-activated receptor gamma coactivator-1α (PGC-1α), and silent information regulator 3 (SIRT3) was detected by real-time fluorescent quantitative polymerase chain reaction (Real-time PCR), and Western blot was used to examine the protein expression levels of optic atrophy protein1 (OPA1), mitochondrial fission protein 1 (FIS1), AMPK, p-AMPK, PGC-1α, and SIRT3. ResultsCompared with the sham group, rats in the model group had significantly lower recognition index, spontaneous alternation rate, escape latency, number of platform crossings, time spent in the target quadrant, and percentage of distance traveled in the target quadrant distance (P<0.05, P<0.01). Significant mitochondrial damage was observed in the hippocampal tissue, with a marked decrease in mitochondrial respiratory chain complex content (P<0.01) and reduced mitochondrial membrane potential (P<0.05). Additionally, the SOD activity was reduced, while ROS levels were elevated (P<0.01). The mRNA expression of PGC-1α and SIRT3 was significantly downregulated (P<0.01), along with decreased protein expression levels of OPA1, p-AMPK/AMPK, PGC-1α, and SIRT3, whereas FIS1 protein expression was significantly upregulated (P<0.05, P<0.01). Compared with the model group, rats in KXS-treated groups (various dosage forms) showed significant improvement in behavioral indexes (P<0.05, P<0.01), reduced hippocampal mitochondrial damage, and more organized mitochondrial cristae. Mitochondrial respiratory chain complex content was significantly increased (P<0.05, P<0.01), and mitochondrial membrane potentials were elevated (P<0.05). SOD activity was elevated, and ROS levels were significantly reduced (P<0.05, P<0.01). Furthermore, the mRNA expression of PGC-1α and SIRT3 was upregulated, with increased protein levels of OPA1, p-AMPK/AMPK, PGC-1α, and SIRT3, while FIS1 protein expression levels were significantly reduced (P<0.05, P<0.01). Across the KXS-treated groups, the granule group showed a higher spontaneous alternation rate than the decoction and powder groups (P<0.05). ConclusionKXS decoction, powders, and granules can improve the learning and memory ability of rats, with granules being the most effective. The mechanism of action may involve activation of the AMPK/PGC-1α/SIRT3 signaling pathway, improvement of the mitochondrial function, and subsequent amelioration of the brain energy metabolism disorders.
3.Mechanism of Different Dosage Forms of Kaixinsan in Improving Mitochondrial Function for Prevention and Treatment of Cognitive Disorder Based on AMPK/PGC-1α/SIRT3 Pathway
Shuyue KANG ; Yanzi YU ; Jiaqun SUN ; Wenxuan CHEN ; Yaqin YANG ; Qi WANG ; Weirong LI ; Limei YAO
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(7):15-24
ObjectiveTo explore the effects of different dosage forms of Kaixinsan (KXS) on the morphology and function of mitochondria in rat models of Alzheimer's disease (AD) and potential mechanisms of action. MethodsMale SD rats were randomly assigned to a sham group, model group, treatment groups receiving KXS decoction, powders, and granules (3.08 g·kg-1), as well as donepezil group (0.51×10-3 g·kg-1), with 10 rats in each group. AD model was created using intracerebroventricular injection of streptozocin (STZ). After 30 days of administration, behavioral assessments were conducted, and mitochondrial morphology was observed using transmission electron microscopy. Mitochondrial respiratory chain complex content was measured via enzyme-linked immunosorbent assay (ELISA). Changes in mitochondrial membrane potential were measured via JC-1 staining, and superoxide dismutase (SOD) activity and reactive oxygen species (ROS) levels were measured via biochemical assays. The mRNA expression of adenosine 5'-monophosphate-activated protein kinase (AMPK), peroxisome proliferator-activated receptor gamma coactivator-1α (PGC-1α), and silent information regulator 3 (SIRT3) was detected by real-time fluorescent quantitative polymerase chain reaction (Real-time PCR), and Western blot was used to examine the protein expression levels of optic atrophy protein1 (OPA1), mitochondrial fission protein 1 (FIS1), AMPK, p-AMPK, PGC-1α, and SIRT3. ResultsCompared with the sham group, rats in the model group had significantly lower recognition index, spontaneous alternation rate, escape latency, number of platform crossings, time spent in the target quadrant, and percentage of distance traveled in the target quadrant distance (P<0.05, P<0.01). Significant mitochondrial damage was observed in the hippocampal tissue, with a marked decrease in mitochondrial respiratory chain complex content (P<0.01) and reduced mitochondrial membrane potential (P<0.05). Additionally, the SOD activity was reduced, while ROS levels were elevated (P<0.01). The mRNA expression of PGC-1α and SIRT3 was significantly downregulated (P<0.01), along with decreased protein expression levels of OPA1, p-AMPK/AMPK, PGC-1α, and SIRT3, whereas FIS1 protein expression was significantly upregulated (P<0.05, P<0.01). Compared with the model group, rats in KXS-treated groups (various dosage forms) showed significant improvement in behavioral indexes (P<0.05, P<0.01), reduced hippocampal mitochondrial damage, and more organized mitochondrial cristae. Mitochondrial respiratory chain complex content was significantly increased (P<0.05, P<0.01), and mitochondrial membrane potentials were elevated (P<0.05). SOD activity was elevated, and ROS levels were significantly reduced (P<0.05, P<0.01). Furthermore, the mRNA expression of PGC-1α and SIRT3 was upregulated, with increased protein levels of OPA1, p-AMPK/AMPK, PGC-1α, and SIRT3, while FIS1 protein expression levels were significantly reduced (P<0.05, P<0.01). Across the KXS-treated groups, the granule group showed a higher spontaneous alternation rate than the decoction and powder groups (P<0.05). ConclusionKXS decoction, powders, and granules can improve the learning and memory ability of rats, with granules being the most effective. The mechanism of action may involve activation of the AMPK/PGC-1α/SIRT3 signaling pathway, improvement of the mitochondrial function, and subsequent amelioration of the brain energy metabolism disorders.
4.Development and application on a full process disease diagnosis and treatment assistance system based on generative artificial intelligence.
Wanjie YANG ; Hao FU ; Xiangfei MENG ; Changsong LI ; Ce YU ; Xinting ZHAO ; Weifeng LI ; Wei ZHAO ; Qi WU ; Zheng CHEN ; Chao CUI ; Song GAO ; Zhen WAN ; Jing HAN ; Weikang ZHAO ; Dong HAN ; Zhongzhuo JIANG ; Weirong XING ; Mou YANG ; Xuan MIAO ; Haibai SUN ; Zhiheng XING ; Junquan ZHANG ; Lixia SHI ; Li ZHANG
Chinese Critical Care Medicine 2025;37(5):477-483
The rapid development of artificial intelligence (AI), especially generative AI (GenAI), has already brought, and will continue to bring, revolutionary changes to our daily production and life, as well as create new opportunities and challenges for diagnostic and therapeutic practices in the medical field. Haihe Hospital of Tianjin University collaborates with the National Supercomputer Center in Tianjin, Tianjin University, and other institutions to carry out research in areas such as smart healthcare, smart services, and smart management. We have conducted research and development of a full-process disease diagnosis and treatment assistance system based on GenAI in the field of smart healthcare. The development of this project is of great significance. The first goal is to upgrade and transform the hospital's information center, organically integrate it with existing information systems, and provide the necessary computing power storage support for intelligent services within the hospital. We have implemented the localized deployment of three models: Tianhe "Tianyuan", WiNGPT, and DeepSeek. The second is to create a digital avatar of the chief physician/chief physician's voice and image by integrating multimodal intelligent interaction technology. With generative intelligence as the core, this solution provides patients with a visual medical interaction solution. The third is to achieve deep adaptation between generative intelligence and the entire process of patient medical treatment. In this project, we have developed assistant tools such as intelligent inquiry, intelligent diagnosis and recognition, intelligent treatment plan generation, and intelligent assisted medical record generation to improve the safety, quality, and efficiency of the diagnosis and treatment process. This study introduces the content of a full-process disease diagnosis and treatment assistance system, aiming to provide references and insights for the digital transformation of the healthcare industry.
Artificial Intelligence
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Humans
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Delivery of Health Care
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Generative Artificial Intelligence
5.Research progress on the mechanism of the kynurenine pathway in Alzheimer's disease
Qini CHEN ; Yujie MA ; Yaona LAI ; Minghuang GAO ; Ziqiao XU ; Hongying YANG ; Weirong LI ; Qi WANG
Chinese Journal of Comparative Medicine 2025;35(9):99-112
Alzheimer's disease(AD)is a typical progressive neurodegenerative disease,mainly manifesting as severe cognitive dysfunction,and involving memory,thought processes,and emotion.The kynurenine pathway(KP)is one of the main metabolic pathways of tryptophan,which can be divided into neurotoxicity and neuroprotective branches.Increasing evidence has suggested that KP is involved in the pathogenesis of AD.This review considers the role of KP in the pathogenesis of AD,with reference to the relevant literature on KP interventions in AD in the PubMed database.The result will provide an important reference for the use of KP as a target for AD drug development.
6.Research progress on the mechanism of the kynurenine pathway in Alzheimer's disease
Qini CHEN ; Yujie MA ; Yaona LAI ; Minghuang GAO ; Ziqiao XU ; Hongying YANG ; Weirong LI ; Qi WANG
Chinese Journal of Comparative Medicine 2025;35(9):99-112
Alzheimer's disease(AD)is a typical progressive neurodegenerative disease,mainly manifesting as severe cognitive dysfunction,and involving memory,thought processes,and emotion.The kynurenine pathway(KP)is one of the main metabolic pathways of tryptophan,which can be divided into neurotoxicity and neuroprotective branches.Increasing evidence has suggested that KP is involved in the pathogenesis of AD.This review considers the role of KP in the pathogenesis of AD,with reference to the relevant literature on KP interventions in AD in the PubMed database.The result will provide an important reference for the use of KP as a target for AD drug development.
7.Effect observation of Callicarpa nudiflora combined with dexamethasone retention enema in the treatment of acute radiation proctitis
Li LIU ; Weirong YAO ; Xiaoli WANG ; Huaigen ZHANG
Tumor 2025;45(1):47-54
Objective:To compare the efficacy differences between the combination therapy of Callicarpa nudiflora and dexamethasone versus dexamethasone monotherapy via retention enema in the treatment of acute radiation proctitis.Methods:A total of 100 patients with pelvic malignancies who developed acute radiation proctitis during radiotherapy at Jiangxi Provincial People's Hospital from November 2021 to June 2023 were enrolled,and randomly divided into two groups:a control group(50 cases)vs a treatment group(50 cases).Based on the acute radiation injury scoring criteria established by the Radiation Therapy Oncology Group(RTOG),patients with injury severity scores≤1 were excluded.Subsequently,the remaining patients received the following interventions:the control group(45 cases)underwent single-agent dexamethasone retention enema,while the treatment group(47 cases)received a combined regimen of Callicarpa nudiflora combined with dexamethasone retention enema.Clinical symptoms,defecation frequency,and routine fecal parameters(leukocyte and erythrocyte counts)were recorded before and at 2 weeks of retention enema,to compare the efficacy differences between the two regimens.Results:A statistically significant difference in therapeutic efficacy was observed between the treatment and control groups(χ2=11.37,P=0.003,P<0.05),with the regimen of Callicarpa nudiflora combined with dexamethasone retention enema in the treatment group demonstrating a markedly higher efficacy rate compared to the regimen of single-agent dexamethasone retention enema in the control group(82.2%vs 62.2%).Conclusion:Callicarpa nudiflora combined with dexamethasone retention enema in the treatment of acute radiation proctitis,can significantly alleviates clinical symptoms and improves life quality of patients with acute radiation proctitis.This approach provides novel insights for optimizing clinical treatment strategies for acute radiation proctitis.
8.Effect observation of Callicarpa nudiflora combined with dexamethasone retention enema in the treatment of acute radiation proctitis
Li LIU ; Weirong YAO ; Xiaoli WANG ; Huaigen ZHANG
Tumor 2025;45(1):47-54
Objective:To compare the efficacy differences between the combination therapy of Callicarpa nudiflora and dexamethasone versus dexamethasone monotherapy via retention enema in the treatment of acute radiation proctitis.Methods:A total of 100 patients with pelvic malignancies who developed acute radiation proctitis during radiotherapy at Jiangxi Provincial People's Hospital from November 2021 to June 2023 were enrolled,and randomly divided into two groups:a control group(50 cases)vs a treatment group(50 cases).Based on the acute radiation injury scoring criteria established by the Radiation Therapy Oncology Group(RTOG),patients with injury severity scores≤1 were excluded.Subsequently,the remaining patients received the following interventions:the control group(45 cases)underwent single-agent dexamethasone retention enema,while the treatment group(47 cases)received a combined regimen of Callicarpa nudiflora combined with dexamethasone retention enema.Clinical symptoms,defecation frequency,and routine fecal parameters(leukocyte and erythrocyte counts)were recorded before and at 2 weeks of retention enema,to compare the efficacy differences between the two regimens.Results:A statistically significant difference in therapeutic efficacy was observed between the treatment and control groups(χ2=11.37,P=0.003,P<0.05),with the regimen of Callicarpa nudiflora combined with dexamethasone retention enema in the treatment group demonstrating a markedly higher efficacy rate compared to the regimen of single-agent dexamethasone retention enema in the control group(82.2%vs 62.2%).Conclusion:Callicarpa nudiflora combined with dexamethasone retention enema in the treatment of acute radiation proctitis,can significantly alleviates clinical symptoms and improves life quality of patients with acute radiation proctitis.This approach provides novel insights for optimizing clinical treatment strategies for acute radiation proctitis.
9.Characteristics of Oral Breath Odor Map of Chronic Atrophic Gastritis Patients with Dampness-Heat Syndrome: A Cross-Sectional Study
Xuejuan LIN ; Yanyu HUANG ; Long ZHU ; Donglin CAO ; Shanshan DING ; Xinghui LI ; Yingying HU ; Meng LAN ; Weirong HUANG
Journal of Traditional Chinese Medicine 2024;65(16):1687-1694
ObjectiveTo explore the recognition of oral breath odor map of chronic atrophic gastritis (CAG) patients with dampness-heat syndrome by electronic nose technique. MethodsPatients with chronic gastritis were recruited, including 60 cases in CAG group of dampness-heat syndrome, 50 cases in CAG group of non-dampness-heat syndrome, 60 cases in chronic non-atrophic gastritis (CNAG) group of dampness-heat syndrome, 50 cases in CNAG group of non-dampness-heat syndrome, and 30 cases of healthy volunteers were selected to set up the health control group. Ten cases in the CAG dampness-heat group and 50 cases in the CAG non-dampness-heat group were selected to form the CAG group, and 10 cases in CNAG dampness-heat group and 50 cases in CNAG non-dampness-heat group were selected to form the CNAG group. In addition to the health control group, the remaining patients were tested for Helicobacter pylori (Hp); the electronic nose (GISXM-MQWA01) was used to collect the oral breath odor of all the participants to draw the mapping, and amplitudes and slopes of each curve (including curves A, B, C, D, E, F, G, H, I, J) of the oral odor mapping of health control group, CAG group, CNAG group, CAG dampness-heat group, CAG non-dampness-heat group, and CNAG dampness-heat group was compared. The modified transformer model was used to classify the odor mapping characteristics, and the confusion matrix method was used to evaluate the classification model, with metrics including accuracy and area under ROC curve (AUC). ResultsThe Hp positivity rate in CAG dampness-heat group was 80.00% (48/60), CAG non-dampness-heat group was 62.00% (31/50), CNAG dampness-heat group was 46.67% (28/60), and CNAG non-dampness-heat group was 42.00% (21/50); the difference in Hp positivity rate between CAG dampness-heat group and CAG non-dampness-heat group was statistically significant (P<0.05). The amplitudes of response curves A, B, C, D, F, G, and I, and slopes of A and F in the odor mapping of the CAG group were lower than those in health control group, while the amplitude and slope of curve E were higher than those in the health control group and CNAG group (P<0.05 or P<0.01); The amplitude of the response curves A, B, C, D, F, G, and I, and slopes of A, D, and F in the CNAG group were lower than those in the health control group (P<0.05 or P<0.01). The amplitude of response curve D and slope of response curve J in the odor mapping of the CAG dampness-heat group were higher than those in CNAG dampness-heat group, the amplitude of curve F was lower than that in CAG non-dampness-heat group, and the amplitude of curve H and slopes of curve A, H, and J were higher than those in CAG non-dampness-heat group (P<0.05). The recognition accuracy of CAG group and health control group reached 77.78%, AUC = 0.88; the recognition accuracy of CAG group and CNAG group was 69.44%, AUC = 0.61; the recognition accuracy of CAG dampness-heat group and CAG non-dampness-heat group reached 75.8%, AUC=0.70. ConclusionElectronic nose technology can make a more accurate identification of the oral breath odor in CAG patients with dampness-heat syndrome, with a decrease in the amplitude of the curve F and an increase in the amplitude of the curve H and in the slopes of the curves A, H, and J may as the characteristics of their odor mapping.
10.Research Progress of Potential Regulatory Effects on Osteoporosis by BMP-mediated Smad Dependent and Smad Independent Pathways
Yujie WANG ; Fangyu AN ; Chunlu YAN ; Jiayi SONG ; Weirong CHANG ; Jie ZHANG ; Zhipan XIAO ; Peng GAO ; Zhonghong LI
Chinese Journal of Modern Applied Pharmacy 2024;41(2):277-286
Osteoporosis can be induced by various factors including prolonged glucocorticoid usage, diminished estrogen levels, secondary hyperparathyroidism, and alterations in the microenvironment of bone tissue. The bone metabolism imbalance(osteogenic-lipogenic imbalance) plays a crucial role in the development of osteoporosis. This imbalance is primarily driven by an increase in the differentiation of bone marrow mesenchymal stem cells into adipocytes and a decrease in their differentiation into osteoblasts, thus forming the core of the osteogenic-lipogenic imbalance observed in osteoporosis. The bone morphogenesis protein(BMP) plays a crucial role in the regulation of the osteogenic-lipid balance in osteoporosis. This regulatory function is accomplished through both the Smad-dependent and Smad-independent pathways. This review centers on the Smad-dependent and Smad-independent pathways facilitated by BMP, offering a comprehensive overview of the potential mechanisms through which BMP-2, 4, 6, 7, and 9 contribute to the regulation of osteogenesis and lipid metabolism in osteoporosis via these pathways. In order to present novel insights for the identification of efficacious targets for clinical anti-osteoporosis medications.


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