1.Arginine Metabolic Disorder in Heart Failure Rats: Analysis Based on Targeted Metabolomics and Bioinformatics
Zeyu LI ; Xiaoqing WANG ; Zhengyu FANG ; Yurou ZHAO ; He XIAO ; Penghaobang LIU ; Haiming ZHANG ; Chunyan LIU ; Yanhong HU
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(10):229-237
ObjectiveThis study systematically analyzed the arginine metabolic dysregulation in the rat model of heart failure (HF), providing a modern scientific basis for elucidating the pathogenesis of HF and offering new insights for the prevention and treatment of HF with traditional Chinese medicine (TCM). MethodsA thoracotomy was performed to ligate the left anterior descending coronary artery of rats, which induced acute myocardial ischemia and thus led to the development of post-myocardial infarction heart failure. The rats were divided into a sham surgery group and a model group, with eight rats in each group. Serum targeted metabolomics analysis was performed using ultra-performance liquid chromatography-triple quadrupole mass spectrometry (UPLC-TQ-S), and the spatial distribution of metabolites in cardiac tissue was observed using airflow-assisted desorption electrospray ionizationmass spectrometry imaging (AFADESI-MSI). Targets associated with HF and arginine metabolism were screened from databases including GeneCards and the Gene Expression Omnibus (GEO), a protein-protein interaction (PPI) network was constructed, and enrichment analysis of the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and Gene Ontology (GO) was performed. Finally, molecular docking was conducted to verify the binding between core metabolic components and key targets, and potential TCMs were predicted based on the core pathways and targets. ResultsCompared with the sham surgery group, the levels of arginine and citrulline in the serum of model rats were significantly decreased (P<0.01), while those of proline, ornithine, creatine, creatinine and glutamate were significantly increased (P<0.05, P<0.01). Cardiac mass spectrometry imaging showed a decreased abundance of arginine in the local myocardial tissue. Bioinformatics analysis identified 24 core functional targets, such as the angiotensin-converting enzyme (ACE), neuronal nitric oxide synthase (NOS1), 5-hydroxytryptamine receptor 2A (HTR2A), and epidermal growth factor receptor (EGFR), and enrichment analysis indicated that these targets were significantly involved in the calcium signaling pathway, neuroactive ligand-receptor interactions, and phosphatidylinositol signaling pathway. Molecular docking confirmed strong binding activities between arginine, citrulline and HTR2A, as well as between creatine, creatinine and EGFR. Based on pathway-target prediction, potential TCM interventions, such as ginseng and magnolia, were identified. ConclusionThis study revealed characteristic arginine metabolic disorder in HF, and the core targets of HF were closely associated with the phosphatidylinositol signaling pathway. It provides a modern biological interpretation of the pathogenesis of HF in TCM from the perspectives of metabolites and signaling pathways, and offers valuable insights for targeted therapy of HF and the development of TCM.
2.Arginine Metabolic Disorder in Heart Failure Rats: Analysis Based on Targeted Metabolomics and Bioinformatics
Zeyu LI ; Xiaoqing WANG ; Zhengyu FANG ; Yurou ZHAO ; He XIAO ; Penghaobang LIU ; Haiming ZHANG ; Chunyan LIU ; Yanhong HU
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(10):229-237
ObjectiveThis study systematically analyzed the arginine metabolic dysregulation in the rat model of heart failure (HF), providing a modern scientific basis for elucidating the pathogenesis of HF and offering new insights for the prevention and treatment of HF with traditional Chinese medicine (TCM). MethodsA thoracotomy was performed to ligate the left anterior descending coronary artery of rats, which induced acute myocardial ischemia and thus led to the development of post-myocardial infarction heart failure. The rats were divided into a sham surgery group and a model group, with eight rats in each group. Serum targeted metabolomics analysis was performed using ultra-performance liquid chromatography-triple quadrupole mass spectrometry (UPLC-TQ-S), and the spatial distribution of metabolites in cardiac tissue was observed using airflow-assisted desorption electrospray ionizationmass spectrometry imaging (AFADESI-MSI). Targets associated with HF and arginine metabolism were screened from databases including GeneCards and the Gene Expression Omnibus (GEO), a protein-protein interaction (PPI) network was constructed, and enrichment analysis of the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and Gene Ontology (GO) was performed. Finally, molecular docking was conducted to verify the binding between core metabolic components and key targets, and potential TCMs were predicted based on the core pathways and targets. ResultsCompared with the sham surgery group, the levels of arginine and citrulline in the serum of model rats were significantly decreased (P<0.01), while those of proline, ornithine, creatine, creatinine and glutamate were significantly increased (P<0.05, P<0.01). Cardiac mass spectrometry imaging showed a decreased abundance of arginine in the local myocardial tissue. Bioinformatics analysis identified 24 core functional targets, such as the angiotensin-converting enzyme (ACE), neuronal nitric oxide synthase (NOS1), 5-hydroxytryptamine receptor 2A (HTR2A), and epidermal growth factor receptor (EGFR), and enrichment analysis indicated that these targets were significantly involved in the calcium signaling pathway, neuroactive ligand-receptor interactions, and phosphatidylinositol signaling pathway. Molecular docking confirmed strong binding activities between arginine, citrulline and HTR2A, as well as between creatine, creatinine and EGFR. Based on pathway-target prediction, potential TCM interventions, such as ginseng and magnolia, were identified. ConclusionThis study revealed characteristic arginine metabolic disorder in HF, and the core targets of HF were closely associated with the phosphatidylinositol signaling pathway. It provides a modern biological interpretation of the pathogenesis of HF in TCM from the perspectives of metabolites and signaling pathways, and offers valuable insights for targeted therapy of HF and the development of TCM.
3.Role of PI3K/Akt Pathway in Epirubicin Resistance in Triple-Negative Breast Cancer Explored Through Transcriptomic Analysis
Lingshan NAN ; Xiaomin WANG ; Xi ZUO ; Haiming LI ; Dong CHEN ; Xiaohui YIN ; Ganlin ZHANG
Cancer Research on Prevention and Treatment 2026;53(5):339-348
Objective To establish an epirubicin (EPI)-resistant murine triple-negative breast cancer (TNBC) (4T1/EPI) cell line and evaluate its biological characteristics and drug resistance. Methods The EPI-resistant cell line 4T1/EPI was developed through intermittent induction with gradually increasing EPI concentrations in vitro. Morphological changes were observed under an inverted microscope. Drug resistance index (MTT assay), cell doubling time (CCK-8 assay), and migration ability (wound healing assay) were evaluated. Western blot was used to detect the expression of drug resistance-related proteins. Transcriptome sequencing and KEGG pathway enrichment analysis were performed to identify the pathways and targets involved in EPI resistance, followed by experimental validation. Results The 4T1 cells eventually grew normally in a medium containing 100 ng/mL EPI, confirming the establishment of the 4T1/EPI resistant cell line. After stable resistance was acquired, morphological alterations were observed. Compared with their parental 4T1 cells, 4T1/EPI cells showed significantly prolonged doubling time (P<0.01) and enhanced migration ability (P<0.05). Expression levels of drug resistance-related proteins MDR1, MRP1 (P<0.01), and ABCG2 (P<0.05) were elevated in 4T1/EPI cells. In vivo models also demonstrated significant EPI resistance in 4T1/EPI tumors in terms of tumor weight and volume. Transcriptome sequencing highlighted the involvement of the PI3K/Akt signaling pathway and ABC transporter pathway. Validation experiments showed the upregulation of Erbb3, Egfr, PI3K, and Akt (P<0.05) and significant downregulation of Fgfr1 (P<0.01) in 4T1/EPI cells. Conclusion The EPI-resistant TNBC cell line 4T1/EPI was successfully established, exhibiting significant resistance in vitro and in vivo. The mechanism may involve the EPI-induced upregulation of Egfr and Erbb3, activating the PI3K/Akt pathway and subsequently enhancing ABC transporter expression.
4.Study on the material basis of efficacy of Zhenyang jiuxin decoction for the treatment of chronic heart failure ZHAO Zhongkai,WANG Xu,YANG Jia,ZHAO Dantong,WU Yanqiu,CAO Peizhen,RONG Rong,SUN Qihui (1679) Study on the improvement mechanism of Bushen anzhi decoction on anxiety and insomnia in rats with kidney failing to store spirit
Zhenhui LI ; Xingping ZHANG ; Xu CHEN ; Haiming LI ; Guangke ZUO ; Hailong ZHU ; Ruining LIANG ; Miao WANG
China Pharmacy 2026;37(13):1685-1690
OBJECTIVE To explore the intervention mechanism of Bushen anzhi decoction (BSAZD) in rats with insomnia induced by kidney failing to store spirit. METHODS A total of 36 SD rats were randomly divided into normal group (normal saline), model group (normal saline), eszopiclone group (positive control group, 0.27 mg/kg), and low-, medium- and high-dose BSAZD groups (5.85, 11.70, 23.40 g/kg), with 6 rats in each group. Except for the normal group, rats in the remaining groups were subjected to combined administration of D-galactose and DL-4-chlorophenylalanine to establish the rat model of insomnia due to kidney failing to store spirit. After successful modeling, corresponding liquid medicine or normal saline was intragastrically administered once daily for 14 consecutive days. After the last administration, behavioral indicators and hippocampal histopathological morphology of rats were detected. Untargeted metabolomics was adopted to screen serum differential metabolites and enrich relevant signaling pathways. RESULTS Compared with the model group, the high-dose BSAZD group exhibited significantly increased open arm entries , open arm time and sleep time ( P <0.05), accompanied by markedly decreased closed arm entries, closed arm time and sleep latency ( P <0.05). Hippocampal neurons in the high-dose BSAZD group were arranged regularly, and the size, morphology and location of cell nuclei were nearly normal. Untargeted metabolomics analysis identified oxidized glutathione, glutamate and other differential metabolites in serum of rats in the high-dose BSAZD group; these differential metabolites were mainly enriched in GABAergic synapse, glutamatergic synapse, cAMP signaling pathway and 2-oxocarboxylic acid metabolism pathway. CONCLUSIONS BSAZD can improve sleep quality, relieve anxiety-like behaviors in rats with insomnia due to kidney failing to store spirit. Its therapeutic mechanism may be associated with regulating GABAergic and glutamatergic synaptic pathways to restore neurotransmitter balance and further alleviate oxidative stress injury, modulating the cAMP signaling pathway to facilitate neural repair, and intervening the 2-oxocarboxylic acid metabolism pathway to optimize energy supply.
5.Study on the material basis of efficacy of Zhenyang jiuxin decoction for the treatment of chronic heart failure ZHAO Zhongkai,WANG Xu,YANG Jia,ZHAO Dantong,WU Yanqiu,CAO Peizhen,RONG Rong,SUN Qihui (1679) Study on the improvement mechanism of Bushen anzhi decoction on anxiety and insomnia in rats with kidney failing to store spirit
Zhenhui LI ; Xingping ZHANG ; Xu CHEN ; Haiming LI ; Guangke ZUO ; Hailong ZHU ; Ruining LIANG ; Miao WANG
China Pharmacy 2026;37(13):1685-1690
OBJECTIVE To explore the intervention mechanism of Bushen anzhi decoction (BSAZD) in rats with insomnia induced by kidney failing to store spirit. METHODS A total of 36 SD rats were randomly divided into normal group (normal saline), model group (normal saline), eszopiclone group (positive control group, 0.27 mg/kg), and low-, medium- and high-dose BSAZD groups (5.85, 11.70, 23.40 g/kg), with 6 rats in each group. Except for the normal group, rats in the remaining groups were subjected to combined administration of D-galactose and DL-4-chlorophenylalanine to establish the rat model of insomnia due to kidney failing to store spirit. After successful modeling, corresponding liquid medicine or normal saline was intragastrically administered once daily for 14 consecutive days. After the last administration, behavioral indicators and hippocampal histopathological morphology of rats were detected. Untargeted metabolomics was adopted to screen serum differential metabolites and enrich relevant signaling pathways. RESULTS Compared with the model group, the high-dose BSAZD group exhibited significantly increased open arm entries , open arm time and sleep time ( P <0.05), accompanied by markedly decreased closed arm entries, closed arm time and sleep latency ( P <0.05). Hippocampal neurons in the high-dose BSAZD group were arranged regularly, and the size, morphology and location of cell nuclei were nearly normal. Untargeted metabolomics analysis identified oxidized glutathione, glutamate and other differential metabolites in serum of rats in the high-dose BSAZD group; these differential metabolites were mainly enriched in GABAergic synapse, glutamatergic synapse, cAMP signaling pathway and 2-oxocarboxylic acid metabolism pathway. CONCLUSIONS BSAZD can improve sleep quality, relieve anxiety-like behaviors in rats with insomnia due to kidney failing to store spirit. Its therapeutic mechanism may be associated with regulating GABAergic and glutamatergic synaptic pathways to restore neurotransmitter balance and further alleviate oxidative stress injury, modulating the cAMP signaling pathway to facilitate neural repair, and intervening the 2-oxocarboxylic acid metabolism pathway to optimize energy supply.
6.Safety and efficacy of hepatic arterial infusion chemotherapy using second-line lenvatinib plus immune checkpoint inhibitors in the treatment of progressive advanced hepatocellular carcinoma
Qiming WEI ; Sheng ZHONG ; Haiming ZHANG ; Hong ZHANG ; Fengtao ZHANG
Journal of Interventional Radiology 2025;34(3):261-267
Objective To investigate the safety and efficacy of hepatic arterial infusion chemotherapy(HAIC)using lenvatinib plus immune checkpoint inhibitors(ICI)in the treatment of progressive advanced hepatocellular carcinoma(HCC).Methods The clinical data of 67 patients with HCC of BCLC stage C,who received HAIC treatment at the Guangdong Provincial Hospital of Traditional Chinese Medicine of China from May 2018 to March 2022 and were assessed as in disease progression(PD)status after HAIC treatment,then had to further receive second-line treatment with lenvatinib plus ICI regimen.According to modified Response Evaluation Criteria in Solid Tumors(mRECIST),the tumor responses,including overall survival(OS),progression free survival(PFS),objective response rate(ORR),and disease control rate(DCR),were evaluated.Univariate analysis and multivariate analysis based on the COX proportional hazards regression model were used to determine the prognosis-related risk factors.According to the Common Terminology Criteria for Adverse Events version 5.0(CTCAE 5.0),the treatment-related adverse effects were recorded and evaluated.Results The median OS and median PFS in the 67 patients with HCC of BCLC stage C receiving second-line treatment with lenvatinib plus ICI regimen,who were evaluated as in PD status after first-line HAIC treatment,were 18.4 months and 7.2 months respectively.The ORR and DCR were 22.4%(15/67)and 67.4%(45/67)respectively.Univariate analysis and multivariate analysis showed that Eastern Cooperative oncology Group(ECOG)score and hepatitis B virus(HBV)infection were the independent risk factors affecting OS,while AFP level was an independent risk factor affecting PFS.The main treatment-related adverse reactions included elevation of transaminase level,hypertension,and hyperbilirubinemia.No death occurred during the therapeutic course.Conclusion For patients with HCC of BCLC stage C,who become in PD status after first-line HAIC treatment,second-line treatment with lenvatinib plus ICI regimen carries satisfactory efficacy and its adverse reaction is tolerable.
7.Fecal microbiota transplantation regulates the composition of intestinal-derived estrogens and their metabolites : a study on the correlation with non-alcoholic fatty liver disease
Wanli Li ; Xueping Qi ; Shuqi Cong ; Wanting Zhang ; Tingting Zhang ; Sheng Wang ; Haiming Fang ; Jiyue Wen ; Jiajia Wang
Acta Universitatis Medicinalis Anhui 2025;60(8):1423-1431
Objective :
To investigate the impact of fecal microbiota transplantation (FMT) on the composition of 15 intestinal-derived estrogens and their metabolites (EMs) and its correlation with non-alcoholic fatty liver disease (NAFLD) .
Methods:
Thirty male C57BL/6J mice were divided into a normal control group (Control) , a high- sugar high-fat diet combined with low-dose CCl4 -induced NAFLD model group ( Model) , and a group of model mice treated with fecal microbiota from normal female mice (FMT) . After 17 weeks of modeling , liver pathology in each group was observed using HE staining , biochemical methods were used to measure serum alanine aminotrans- ferase (ALT) and aspartate aminotransferase (AST) levels , as well as hepatic triglyceride (TG) and total choles- terol (TC) levels. and the content of 15 EMs in portal vein serum was detected using ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS) . The correlation between disease phenotype and intesti- nal EMs was analyzed using Pearson ′s method.
Results:
The NAFLD model was successfully established , and the FMT group showed improved liver structure and morphology , with significant decreases in liver function and hepatic lipids compared to the Model group. In NAFLD mice , the contents of E1 , E2 , and their 2- and 4-position metabo- lites in portal vein blood serum was reduced compared to normal mice , while the content of most 16- and 17-posi- tion metabolites ( except 16α-OHE1) increased compared to normal mice. Correlation analysis showed that ALT was strongly positively correlated with E3 and 17-epiE3 , and strongly negatively correlated with E1 , E2 , 4- MeOE1 , and 16α-OHE1 . The TC was strongly positively correlated with 17-epiE3 and strongly negatively correla- ted with E1 , 4-MeOE1 , and 16α-OHE1 .
Conclusion
FMT restores the disrupted composition of intestinal EMs and improves NAFLD.
8.Automatic acquisition and analytic procedure of acupuncture manipulation based on optical navigation.
Changshuai ZHANG ; Zihao FENG ; Weichao CHANG ; Weigang MA ; Yongjian WU ; Haiming LI ; Xingfang PAN ; Haiyan REN ; Yangyang LIU ; Zhaoshui HE ; Wenjun TAN
Chinese Acupuncture & Moxibustion 2025;45(10):1383-1390
This paper presents an automatic acquisition and analytic procedure of acupuncture manipulation based on optical navigation, aiming at solving the shortcomings of existing acquisition methods of acupuncture manipulation. An acquisition holder installed at the handle tail of filiform needle was designed to display the movement trajectory of the needle during acupuncture delivery by collecting the movement trajectory of holder. The 3-month old male Bama miniature pig was selected as the experimental subject, and 6 points, "Bojian" "Qiangfeng" "Housanli" "Xiaokua" "Huiyang" (BL35) and "Baihui" (GV20), were selected during acupuncture manipulation. The optical navigation system was used to collect the real-time data, and these data were per-processed and analyzed using mean filtering and Fourier transform. The acupuncture procedure was divided into 3 stages, inserting, lifting-thrusting, and twisting. The results showed that the accuracy was 96.3% at lifting-thrusting stage, and that was 100.0% at twisting stage. The decomposition effect of the entire procedure was satisfactory. This study provides a new approach to the quantitative analysis of acupuncture manipulation. In the future, it needs to further optimize the algorithm and expand the sample size so as to improve the accuracy of this analytic technique.
Acupuncture Therapy/methods*
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Male
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Animals
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Swine
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Acupuncture Points
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Humans
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Swine, Miniature
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Needles
9.Intestinal fibrosis associated with inflammatory bowel disease: Known and unknown.
Yao ZHANG ; Haiming ZHUANG ; Kai CHEN ; Yizhou ZHAO ; Danshu WANG ; Taojing RAN ; Duowu ZOU
Chinese Medical Journal 2025;138(8):883-893
Intestinal fibrosis is a major complication of inflammatory bowel disease (IBD), leading to a high incidence of surgical interventions and significant disability. Despite its clinical relevance, no targeted pharmacological therapies are currently available. This review aims to explore the underlying mechanisms driving intestinal fibrosis and address unresolved scientific questions, offering insights into potential future therapeutic strategies. We conducted a literature review using data from PubMed up to October 2024, focusing on studies related to IBD and fibrosis. Intestinal fibrosis results from a complex network involving stromal cells, immune cells, epithelial cells, and the gut microbiota. Chronic inflammation, driven by factors such as dysbiosis, epithelial injury, and immune activation, leads to the production of cytokines like interleukin (IL)-1β, IL-17, and transforming growth factor (TGF)-β. These mediators activate various stromal cell populations, including fibroblasts, pericytes, and smooth muscle cells. The activated stromal cells secrete excessive extracellular matrix components, thereby promoting fibrosis. Additionally, stromal cells influence the immune microenvironment through cytokine production. Future research would focus on elucidating the temporal and spatial relationships between immune cell-driven inflammation and stromal cell-mediated fibrosis. Additionally, investigations are needed to clarify the differentiation origins of excessive extracellular matrix-producing cells, particularly fibroblast activation protein (FAP) + fibroblasts, in the context of intestinal fibrosis. In conclusion, aberrant stromal cell activation, triggered by upstream immune signals, is a key mechanism underlying intestinal fibrosis. Further investigations into immune-stromal cell interactions and stromal cell activation are essential for the development of therapeutic strategies to prevent, alleviate, and potentially reverse fibrosis.
Humans
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Fibrosis/metabolism*
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Inflammatory Bowel Diseases/pathology*
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Animals
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Transforming Growth Factor beta/metabolism*
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Intestines/pathology*
10.Effect of interferon induced transmembrane protein 1 ( IFITM1 ) upregulation to cytokine release syndrome in CAR-T-treated B-cell acute lymphoblastic leukemia.
Mengyi DU ; Yinqiang ZHANG ; Chenggong LI ; Fen ZHOU ; Wenjing LUO ; Lu TANG ; Jianghua WU ; Huiwen JIANG ; Qiuzhe WEI ; Cong LU ; Haiming KOU ; Yu HU ; Heng MEI
Chinese Medical Journal 2025;138(10):1242-1244


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