1.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.
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.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
4.Discussion on the Treatment of Bronchiectasis Based on the Theory of Incubative Pathogenic Factors
An'an WANG ; Zherui WANG ; Weiling HUANG ; Weirong PAN ; Chengyong MA ; Yanlan LI ; Tiansong ZHANG
Chinese Journal of Information on Traditional Chinese Medicine 2024;31(2):173-176
Bronchiectasis has the characteristics of long course,gradual aggravation,easy recurrence and difficult to treat.The characteristics are similar to those arouse by incubative pathogenic factors.Based on the theory of incubative pathogenic factors,this disease is often related to the incubative pathogenic factors in the body's areas with deficient healthy qi,which occur at regular times.The etiology can be external,congenital,or internal.Treatment should focus on different characteristics of incubative pathogenic factors.Attention should be paid to clearing and dispersing in external pathogenic factors,while attention should be paid to supporting and promoting healthy qi in congenital pathogenic factors,and do not forget to remove internal pathogenic factors.
5.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.
6.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.
7.Effect of modified Dingke Decoction in patient with post infectious cough: a retrospective real-world study
An'an WANG ; Yanlan LI ; Chengyong MA ; Jing SUN ; Weirong PAN ; Zherui WANG ; Tiansong ZHANG
International Journal of Traditional Chinese Medicine 2024;46(8):980-985
Objective:To explore the curative efficacy of Dingke Decoction in the treatment of post infectious cough based on the the real-world clinical data.Methods:Retrospective cohort study was conducted. 245 patients with cough after infection in the hospital of Jingan Chinese Medical Hospital from July 2021 to July 2022 were set as study objects. The fact that whether the patients with Dingke Decoction or not were divided into control group (90 cases, without Dingke Decoction) and treatment group (155 cases, with Dingke Decoction). By using propensity nearest neighbor 1:1 matching to balance the confounding factors before treatment, 56 cases were successfully matched in both groups. The control group was treated symptomatically according to the actual clinical situation, while the treatment group was treated with modified Dingke Decoction on the basis of symptomatic treatment in the control group. The treatment for both groups lasted for 2 weeks. TCM symptom scores and cough severity score were evaluated using the Leicester Cough Quality of Life Questionnaire (LCQ) before and after treatment. Levels of tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) were detected through ELISA; adverse reactions during the treatment were recorded, and the clinical efficacy was evaluated.Results:The total effective rate of the treatment group was 91.07% (51/56), while that of the control group was 76.79% (43/56), with a statistically significant difference between the two groups ( χ2=4.24, P=0.040). The daytime cough symptom score (1.03 ± 0.67 vs. 1.20 ± 0.66, t=7.40) and nighttime cough symptom score (0.74 ± 0.62 vs. 1.26 ± 0.54, t=6.27) in the treatment group were lower than those in the control group after treatment ( P<0.001). After treatment, the LCQ physiological (5.30 ± 0.79 vs. 4.78 ± 1.09, t=-2.44), psychological (5.33 ± 0.92 vs. 4.70 ± 1.12, t=-2.39), and social (5.23 ± 0.94 vs. 4.60 ± 0.81, t=-2.86) scores in the treatment group were higher than those in the control group ( P<0.05). After treatment, he treatment group serum IL-6 [(14.29 ± 3.94) ng/L vs. (19.99 ± 5.17) ng/L, t=4.80] and TNF-α [(36.23 ± 7.83) ng/L vs. (42.44 ± 7.63) ng/L, t=3.11] were lower than those in the control group ( P<0.01). The incidence of adverse reactions in the control group was 8.92% (5/56) and 5.36% (3/56), respectively, without statistical significance ( χ2=0.54, P=0.716). Conclusion:Based on the real-world research method, medicine Dingke Decoction can improve the clinical efficacy and the quality life of post infectious cough patients, and the mechanism may be related to reducing airway inflammation response.
8.Etiological characteristics of Brucella melitensis in Henan Province, 2013-2022
Jiayong ZHAO ; Weirong SONG ; Baifan ZHANG ; Yingxin HU ; Yafei LI ; Jingjing PAN ; Haifeng WANG ; Wanshen GUO ; Xueyong HUANG ; Ying YE
Chinese Journal of Epidemiology 2024;45(11):1559-1565
Objective:To analyze the genus, drug resistance/virulence and phylogenetic characteristics of Brucella strains isolated from brucellosis surveillance sentinels in Henan Province from 2013 to 2022, and provide baseline data for the surveillance, early warning and outbreak tracing of brucellosis. Methods:Blood samples were collected from patients with Brucella infection for strain isolation, culture and species identification, drug susceptibility test, whole genome sequencing, splicing and assembly, functional/virulence/resistance gene prediction analysis and phylogenetic tree drawing based on single nucleotide polymorphism (SNP). Results:In 36 brucellosis patients, the majority were men (86.11%, 31/36), young adults aged 18-50 (88.89%, 32/36) and farmers/herdsmen (72.22%, 26/36). A total of 36 strains of Brucella melitensis were isolated, and average 1 305 functional proteins of 21 categories were predicted by strain genome; all the strains carried four main virulence factors (pmm, VirB group, BtpA/BtpB, BvrS/BvrR). The drug sensitivity rate was 100.00% to six types of antibiotics including levofloxacin, rifampicin, doxycycline, streptomycin, tetracycline and gentamicin, they showed different resistances to three antibiotics including compound trimethoprim-sulfamethoxazole, ciprofloxacin and ampicillin. The strains carried four types of resistance genes and two clusters of resistance genes, with four combinations of genotypes, the resistance mechanisms included antibiotic degradation/modification enzymes, resistant nodular cell differentiation (RND) efflux pumps, 16S/23S ribosomal rRNA binding site mutations, etc. The number of SNP differed in the genomes of 36 Brucellamelitensis strains ranged from 0 to 454 and phylogenetic tree was divided into three major branches, with relative branch distances between 0.000 0 and 0.498 6 for each strain. Conclusions:Human Brucellamelitensis strains isolated from surveillance sentinels in Henan from 2013 to 2022 carried multiple virulence and antibiotic resistance genes and had different drug resistance phenotypes. Single nucleotide polymorphism analysis and phylogenetic tree analysis showed significant differences in phylogenetic relationships among different strains.
9.HDAC3:a new target for atherosclerosis therapy
Zihan XIA ; He ZHANG ; Ziqiong ZHANG ; Xingyi LI ; Yining WANG ; Weirong WANG
Chinese Journal of Arteriosclerosis 2024;32(7):621-626,640
Histone deacetylase 3(HDAC3)is an epigenetic modification enzyme,which participates in the occur-rence and development of atherosclerosis(As).It is significant to search for effective HDAC3 inhibitors for the treatment of atherosclerosis.This article reviews the relationship between HDAC3 and atherosclerosis,the latest research progress of HDAC3 inhibitors,and the therapeutic effects of some traditional Chinese medicine on cardiovascular diseases by inhibi-ting HDAC3.It aims to provide new ideas for developing anti-atherosclerotic drugs targeting HDAC3.
10.Research Progress on the Mechanism of Regulating Glycolysis of Hepatic Stellate Cells Against Liver Fibrosis and the Prevention and Treatment of Traditional Chinese Medicine
Mengmeng HAO ; Lu LIU ; Langping YI ; Shuangwei LI ; Xin CHEN ; Hongying YANG ; Minghuang GAO ; Yousheng MO ; Weirong LI ; Qi WANG
Traditional Chinese Drug Research & Clinical Pharmacology 2024;35(7):1101-1106
Hepatic stellate cell(HSC)activation is a key link in the development of liver fibrosis.The metabolic reprogramming of activated HSC has become a hot topic in current research,especially the change of glycolysis is an important factor in regulating HSC activation.Based on the metabolic reprogramming in the process of HSC activation,this paper expounds the mechanism of regulating HSC activation and liver fibrosis through glycolysis,and reviews the research progress of traditional Chinese medicine and its active ingredients in regulating HSC glycolysis to prevent and treat liver fibrosis.Liver fibrosis is a complex pathological process involving multiple factors and pathways.From the perspective of regulating the glycolysis of activated HSC,it can provide a new idea for the development of anti-liver fibrosis drugs.


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