1.In Vitro and in vivo Component Analysis of Total Phenolic Acids from Gei Herba and Its Effect on Promoting Acute Wound Healing and Inhibiting Scar Formation
Xixian KONG ; Guanghuan TIAN ; Tong WU ; Shaowei HU ; Jie ZHAO ; Fuzhu PAN ; Jingtong LIU ; Yong DENG ; Yi OUYANG ; Hongwei WU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(3):156-167
ObjectiveBased on ultra performance liquid chromatography-quadrupole-electrostatic field orbital trap high-resolution mass spectrometry(UPLC-Q-Orbitrap-MS), to identify the in vivo and in vitro chemical components of total phenolic acids in Gei Herba(TPAGH), and to clarify the pharmacological effects and potential mechanisms of the effective part in promoting acute wound healing and inhibiting scar formation. MethodsUPLC-Q-Orbitrap-MS was used to identify the chemical components of TPAGH and ingredients absorbed in vivo after topical administration. A total of 120 ICR mice were randomly divided into the model group, recombinant human epidermal growth factor(rhEGF) group(4 mg·kg-1), and low, medium, and high dose groups of TPAGH(3.5, 7, 14 mg·kg-1), with 24 mice in each group. A full-thickness skin excision model was constructed, and each administration group was coated with the drug at the wound site, and the model group was treated with an equal volume of normal saline, the treatment was continued for 30 days, during which 8 mice from each group were sacrificed on days 6, 12, and 30. The healing of the wounds in the mice was observed, and histopathological changes in the skin tissues were dynamically observed by hematoxylin-eosin(HE), Masson, and Sirius red staining, and enzyme-linked immunosorbent assay(ELISA) was used to dynamically measure the contents of interleukin-6(IL-6), tumor necrosis factor-α(TNF-α), vascular endothelial growth factor A(VEGFA), matrix metalloproteinase(MMP)-3 and MMP-9 in skin tissues. Network pharmacology was used to predict the targets related to the promotion of acute wound healing and the inhibition of scar formation by TPAGH, and molecular docking of key components and targets was performed. Gene Ontology(GO) biological process analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analysis were carried out for the related targets, so as to construct a network diagram of herbal material-compound-target-pathway-pharmacological effect-disease for further exploring its potential mechanisms. ResultsA total of 146 compounds were identified in TPAGH, including 28 phenylpropanoids, 31 tannins, 23 triterpenes, 49 flavonoids, and 15 others, and 16 prototype components were found in the serum of mice. Pharmacodynamic results showed that, compared with the model group, the TPAGH groups showed a significant increase in relative wound healing rate and relative scar inhibition rate(P<0.05), and the number of new capillaries, number of fibroblasts, number of new skin appendages, epidermal regeneration rate, collagen deposition ratio, and Ⅲ/Ⅰ collagen ratio in the tissue were significantly improved(P<0.05, 0.01), the levels of IL-6, TNF-α, MMP-3 and MMP-9 in the skin tissues were reduced to different degrees, while the level of VEGFA was increased. Network pharmacology analysis screened 10 core targets, including tumor protein 53(TP53), sarcoma receptor coactivator(SRC), protein kinase B(Akt)1, signal transducer and activator of transcription 3(STAT3), epidermal growth factor receptor(EGFR) and so on, participating in 75 signaling pathways such as advanced glycation end-products(AGE)-receptor for AGE(AGE/RAGE) signaling pathway, phosphatidylinositol 3-kinase(PI3K)/Akt signaling pathway, mitogen-activated protein kinase(MAPK) signaling pathway. Molecular docking confirmed that the key components genistein, geraniin, and casuariin had good binding ability to TP53, SRC, Akt1, STAT3 and EGFR. ConclusionThis study comprehensively reflects the chemical composition of TPAGH and the absorbed components after topical administration through UPLC-Q-Orbitrap-MS. TPAGH significantly regulates key indicators of skin healing and tissue reconstruction, thereby clarifying its role in promoting acute wound healing and inhibiting scar formation. By combining in vitro and in vivo component identification with network pharmacology, the study explores how key components may bind to targets such as TP53, Akt1 and EGFR, exerting therapeutic effects through related pathways such as immune inflammation and vascular regeneration.
2.Effect modification of amino acid levels in association between polycyclic aromatic hydrocarbon exposure and metabolic syndrome: A nested case-control study among coking workers
Jinyu WU ; Jiajun WEI ; Shugang GUO ; Huixia XIONG ; Yong WANG ; Hongyue KONG ; Liuquan JIANG ; Baolong PAN ; Gaisheng LIU ; Fan YANG ; Jisheng NIE ; Jin YANG
Journal of Environmental and Occupational Medicine 2025;42(3):325-333
Background Exposure to polycyclic aromatic hydrocarbons (PAHs) is associated with the development of metabolic syndrome (MS). However, the role of amino acids in PAH-induced MS remains unclear. Objective To explore the impact of PAHs exposure on the incidence of MS among coking workers, and to determine potential modifying effect of amino acid on this relationship. Methods Unmatched nested case-control design was adopted and the baseline surveys of coking workers were conducted in two plants in Taiyuan in 2017 and 2019, followed by a 4-year follow-up. The cohort comprised 667 coking workers. A total of 362 participants were included in the study, with 84 newly diagnosed cases of MS identified as the case group and 278 as the control group. Urinary levels of 11 PAH metabolites and plasma levels of 17 amino acids were measured by ultrasensitive performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). Logistic regression was used to estimate the association between individual PAH metabolites and MS. Stratified by the median concentration of amino acids, Bayesian kernel machine regression (BKMR) model was employed to assess the mixed effects of PAHs on MS. Due to the skewed data distribution, all PAH metabolites and amino acids in the analysis were converted by natural logarithm ln (expressed as lnv). Results The median age of the 362 participants was 37 years, and 83.2% were male. Compared to the control group, the case group exhibited higher concentrations of urinary 2-hydroxyphenanthrene (2-OHPhe), 9-hydroxyphenanthrene (9-OHPhe), and hydroxyphenanthrene (OHPhe) (P=0.005, P=0.049, and P=0.004, respectively), as well as elevated levels of plasma branched chain amino acid (BCAA) and aromatic amino acid (AAA) (P<0.05). After being adjusted for confounding factors, for every unit increase in lnv2-OHPhe in urine, the OR (95%CI) of MS was 1.57 (1.11, 2.26), and for every unit increase in lnvOHPhe, the OR (95%CI) of MS was 1.82 (1.16, 2.90). Tyrosine, leucine, and AAA all presented a significant nonlinear correlation with MS. At low levels, tyrosine, leucine, and AAA did not significantly increase the risk of MS, but at high levels, they increased the risk of MS. In the low amino acid concentration group, as well as in the low BCAA and low AAA concentration groups, it was found that compared to the PAH metabolite levels at the 50th percentile (P50), the log-odds of MS when the PAH metabolite levels was at the 75th percentile (P75) were 0.158 (95%CI: 0.150, 0.166), 0.218 (95%CI: 0.209, 0.227), and 0.262 (95% CI: 0.241, 0.282), respectively, However, no correlation between PAHs and MS was found in the high amino acid concentration group. Conclusion Amino acids modify the effect of PAHs exposure on the incidence of MS. In individuals with low plasma amino acid levels, the risk of developing MS increases with higher concentrations of mixed PAH exposure. This effect is partly due to the low concentrations of BCAA and AAA.
3.Integrated Optical and Magnetic Navigation for Simplified Percutaneous Transforaminal Endoscopic Lumbar Discectomy: A Novel Approach
Xing-Chen YAO ; Jun-Peng LIU ; Xin-Ru DU ; Li GUAN ; Yong HAI ; Jincai YANG ; Aixing PAN
Neurospine 2025;22(1):297-307
Objective:
This study aims to evaluate the clinical benefits of the integrated optical and magnetic surgical navigation system in assisting transforaminal endoscopic lumbar discectomy (TELD) for the treatment of lumbar disc herniation (LDH).
Methods:
A retrospective analysis was conducted on patients who underwent TELD for LDH at Beijing Chaoyang Hospital, Capital Medical University from November 2022 to December 2023. Patients treated with the integrated optical and magnetic surgical navigation system were defined as the navigation-guided TELD (Ng-TELD) group (30 cases), while those treated with the conventional x-ray fluoroscopy method were defined as the control group (31 cases). Record and compare baseline characteristics, surgical parameters, efficacy indicators, and adverse events between the 2 patient groups.
Results:
The average follow-up duration for the 61 patients was 11.8 months. Postoperatively, both groups exhibited significant relief from back and leg pain, which continued to improve over time. At the final follow-up, patients’ lumbar function and quality of life had significantly improved compared to preoperative levels (p < 0.05). The Ng-TELD group had significantly shorter total operation time (58.43 ± 12.37 minutes vs. 83.23 ± 25.90 minutes), catheter placement time (5.83 ± 1.09 minutes vs. 15.94 ± 3.00 minutes), decompression time (47.17 ± 11.98 minutes vs. 67.29 ± 24.23 minutes), and fewer intraoperative fluoroscopies (3.20 ± 1.45 vs. 16.58 ± 4.25) compared to the control group (p < 0.05). There were no significant differences between the groups in terms of efficacy evaluation indicators and hospital stay. At the final follow-up, the excellent and good rate of surgical outcomes assessed by the MacNab criteria was 98.4%, and the overall adverse event rate was 8.2%, with no statistically significant differences between the groups (p > 0.05).
Conclusion
This study demonstrates that the integrated optical and magnetic surgical navigation system can reduce the complexity of TELD, shorten operation time, and minimize radiation exposure for the surgeon, highlighting its promising clinical potential.
4.Integrated Optical and Magnetic Navigation for Simplified Percutaneous Transforaminal Endoscopic Lumbar Discectomy: A Novel Approach
Xing-Chen YAO ; Jun-Peng LIU ; Xin-Ru DU ; Li GUAN ; Yong HAI ; Jincai YANG ; Aixing PAN
Neurospine 2025;22(1):297-307
Objective:
This study aims to evaluate the clinical benefits of the integrated optical and magnetic surgical navigation system in assisting transforaminal endoscopic lumbar discectomy (TELD) for the treatment of lumbar disc herniation (LDH).
Methods:
A retrospective analysis was conducted on patients who underwent TELD for LDH at Beijing Chaoyang Hospital, Capital Medical University from November 2022 to December 2023. Patients treated with the integrated optical and magnetic surgical navigation system were defined as the navigation-guided TELD (Ng-TELD) group (30 cases), while those treated with the conventional x-ray fluoroscopy method were defined as the control group (31 cases). Record and compare baseline characteristics, surgical parameters, efficacy indicators, and adverse events between the 2 patient groups.
Results:
The average follow-up duration for the 61 patients was 11.8 months. Postoperatively, both groups exhibited significant relief from back and leg pain, which continued to improve over time. At the final follow-up, patients’ lumbar function and quality of life had significantly improved compared to preoperative levels (p < 0.05). The Ng-TELD group had significantly shorter total operation time (58.43 ± 12.37 minutes vs. 83.23 ± 25.90 minutes), catheter placement time (5.83 ± 1.09 minutes vs. 15.94 ± 3.00 minutes), decompression time (47.17 ± 11.98 minutes vs. 67.29 ± 24.23 minutes), and fewer intraoperative fluoroscopies (3.20 ± 1.45 vs. 16.58 ± 4.25) compared to the control group (p < 0.05). There were no significant differences between the groups in terms of efficacy evaluation indicators and hospital stay. At the final follow-up, the excellent and good rate of surgical outcomes assessed by the MacNab criteria was 98.4%, and the overall adverse event rate was 8.2%, with no statistically significant differences between the groups (p > 0.05).
Conclusion
This study demonstrates that the integrated optical and magnetic surgical navigation system can reduce the complexity of TELD, shorten operation time, and minimize radiation exposure for the surgeon, highlighting its promising clinical potential.
5.Integrated Optical and Magnetic Navigation for Simplified Percutaneous Transforaminal Endoscopic Lumbar Discectomy: A Novel Approach
Xing-Chen YAO ; Jun-Peng LIU ; Xin-Ru DU ; Li GUAN ; Yong HAI ; Jincai YANG ; Aixing PAN
Neurospine 2025;22(1):297-307
Objective:
This study aims to evaluate the clinical benefits of the integrated optical and magnetic surgical navigation system in assisting transforaminal endoscopic lumbar discectomy (TELD) for the treatment of lumbar disc herniation (LDH).
Methods:
A retrospective analysis was conducted on patients who underwent TELD for LDH at Beijing Chaoyang Hospital, Capital Medical University from November 2022 to December 2023. Patients treated with the integrated optical and magnetic surgical navigation system were defined as the navigation-guided TELD (Ng-TELD) group (30 cases), while those treated with the conventional x-ray fluoroscopy method were defined as the control group (31 cases). Record and compare baseline characteristics, surgical parameters, efficacy indicators, and adverse events between the 2 patient groups.
Results:
The average follow-up duration for the 61 patients was 11.8 months. Postoperatively, both groups exhibited significant relief from back and leg pain, which continued to improve over time. At the final follow-up, patients’ lumbar function and quality of life had significantly improved compared to preoperative levels (p < 0.05). The Ng-TELD group had significantly shorter total operation time (58.43 ± 12.37 minutes vs. 83.23 ± 25.90 minutes), catheter placement time (5.83 ± 1.09 minutes vs. 15.94 ± 3.00 minutes), decompression time (47.17 ± 11.98 minutes vs. 67.29 ± 24.23 minutes), and fewer intraoperative fluoroscopies (3.20 ± 1.45 vs. 16.58 ± 4.25) compared to the control group (p < 0.05). There were no significant differences between the groups in terms of efficacy evaluation indicators and hospital stay. At the final follow-up, the excellent and good rate of surgical outcomes assessed by the MacNab criteria was 98.4%, and the overall adverse event rate was 8.2%, with no statistically significant differences between the groups (p > 0.05).
Conclusion
This study demonstrates that the integrated optical and magnetic surgical navigation system can reduce the complexity of TELD, shorten operation time, and minimize radiation exposure for the surgeon, highlighting its promising clinical potential.
6.Integrated Optical and Magnetic Navigation for Simplified Percutaneous Transforaminal Endoscopic Lumbar Discectomy: A Novel Approach
Xing-Chen YAO ; Jun-Peng LIU ; Xin-Ru DU ; Li GUAN ; Yong HAI ; Jincai YANG ; Aixing PAN
Neurospine 2025;22(1):297-307
Objective:
This study aims to evaluate the clinical benefits of the integrated optical and magnetic surgical navigation system in assisting transforaminal endoscopic lumbar discectomy (TELD) for the treatment of lumbar disc herniation (LDH).
Methods:
A retrospective analysis was conducted on patients who underwent TELD for LDH at Beijing Chaoyang Hospital, Capital Medical University from November 2022 to December 2023. Patients treated with the integrated optical and magnetic surgical navigation system were defined as the navigation-guided TELD (Ng-TELD) group (30 cases), while those treated with the conventional x-ray fluoroscopy method were defined as the control group (31 cases). Record and compare baseline characteristics, surgical parameters, efficacy indicators, and adverse events between the 2 patient groups.
Results:
The average follow-up duration for the 61 patients was 11.8 months. Postoperatively, both groups exhibited significant relief from back and leg pain, which continued to improve over time. At the final follow-up, patients’ lumbar function and quality of life had significantly improved compared to preoperative levels (p < 0.05). The Ng-TELD group had significantly shorter total operation time (58.43 ± 12.37 minutes vs. 83.23 ± 25.90 minutes), catheter placement time (5.83 ± 1.09 minutes vs. 15.94 ± 3.00 minutes), decompression time (47.17 ± 11.98 minutes vs. 67.29 ± 24.23 minutes), and fewer intraoperative fluoroscopies (3.20 ± 1.45 vs. 16.58 ± 4.25) compared to the control group (p < 0.05). There were no significant differences between the groups in terms of efficacy evaluation indicators and hospital stay. At the final follow-up, the excellent and good rate of surgical outcomes assessed by the MacNab criteria was 98.4%, and the overall adverse event rate was 8.2%, with no statistically significant differences between the groups (p > 0.05).
Conclusion
This study demonstrates that the integrated optical and magnetic surgical navigation system can reduce the complexity of TELD, shorten operation time, and minimize radiation exposure for the surgeon, highlighting its promising clinical potential.
7.Integrated Optical and Magnetic Navigation for Simplified Percutaneous Transforaminal Endoscopic Lumbar Discectomy: A Novel Approach
Xing-Chen YAO ; Jun-Peng LIU ; Xin-Ru DU ; Li GUAN ; Yong HAI ; Jincai YANG ; Aixing PAN
Neurospine 2025;22(1):297-307
Objective:
This study aims to evaluate the clinical benefits of the integrated optical and magnetic surgical navigation system in assisting transforaminal endoscopic lumbar discectomy (TELD) for the treatment of lumbar disc herniation (LDH).
Methods:
A retrospective analysis was conducted on patients who underwent TELD for LDH at Beijing Chaoyang Hospital, Capital Medical University from November 2022 to December 2023. Patients treated with the integrated optical and magnetic surgical navigation system were defined as the navigation-guided TELD (Ng-TELD) group (30 cases), while those treated with the conventional x-ray fluoroscopy method were defined as the control group (31 cases). Record and compare baseline characteristics, surgical parameters, efficacy indicators, and adverse events between the 2 patient groups.
Results:
The average follow-up duration for the 61 patients was 11.8 months. Postoperatively, both groups exhibited significant relief from back and leg pain, which continued to improve over time. At the final follow-up, patients’ lumbar function and quality of life had significantly improved compared to preoperative levels (p < 0.05). The Ng-TELD group had significantly shorter total operation time (58.43 ± 12.37 minutes vs. 83.23 ± 25.90 minutes), catheter placement time (5.83 ± 1.09 minutes vs. 15.94 ± 3.00 minutes), decompression time (47.17 ± 11.98 minutes vs. 67.29 ± 24.23 minutes), and fewer intraoperative fluoroscopies (3.20 ± 1.45 vs. 16.58 ± 4.25) compared to the control group (p < 0.05). There were no significant differences between the groups in terms of efficacy evaluation indicators and hospital stay. At the final follow-up, the excellent and good rate of surgical outcomes assessed by the MacNab criteria was 98.4%, and the overall adverse event rate was 8.2%, with no statistically significant differences between the groups (p > 0.05).
Conclusion
This study demonstrates that the integrated optical and magnetic surgical navigation system can reduce the complexity of TELD, shorten operation time, and minimize radiation exposure for the surgeon, highlighting its promising clinical potential.
8.rTMS Improves Cognitive Function and Brain Network Connectivity in Patients With Alzheimer’s Disease
Gui-Zhi XU ; Lin LIU ; Miao-Miao GUO ; Tian WANG ; Jiao-Jiao GAO ; Yong JI ; Pan WANG
Progress in Biochemistry and Biophysics 2025;52(8):2131-2145
ObjectiveRepetitive transcranial magnetic stimulation (rTMS) has demonstrated efficacy in enhancing neurocognitive performance in Alzheimer’s disease (AD), but the neurobiological mechanisms linking synaptic pathology, neural oscillatory dynamics, and brain network reorganization remain unclear. This investigation seeks to systematically evaluate the therapeutic potential of rTMS as a non-invasive neuromodulatory intervention through a multimodal framework integrating clinical assessments, molecular profiling, and neurophysiological monitoring. MethodsIn this prospective double-blind trial, 12 AD patients underwent a 14-day protocol of 20 Hz rTMS, with comprehensive multimodal assessments performed pre- and post-intervention. Cognitive functioning was quantified using the mini-mental state examination (MMSE) and Montreal cognitive assessment (MOCA), while daily living capacities and neuropsychiatric profiles were respectively evaluated through the activities of daily living (ADL) scale and combined neuropsychiatric inventory (NPI)-Hamilton depression rating scale (HAMD). Peripheral blood biomarkers, specifically Aβ1-40 and phosphorylated tau (p-tau181), were analyzed to investigate the effects of rTMS on molecular metabolism. Spectral power analysis was employed to investigate rTMS-induced modulations of neural rhythms in AD patients, while brain network analyses incorporating topological properties were conducted to examine stimulus-driven network reorganization. Furthermore, systematic assessment of correlations between cognitive scale scores, blood biomarkers, and network characteristics was performed to elucidate cross-modal therapeutic associations. ResultsClinically, MMSE and MOCA scores improved significantly (P<0.05). Biomarker showed that Aβ1-40 level increased (P<0.05), contrasting with p-tau181 reduction. Moreover, the levels of Aβ1-40 were positively correlated with MMSE and MOCA scores. Post-intervention analyses revealed significant modulations in oscillatory power, characterized by pronounced reductions in delta (P<0.05) and theta bands (P<0.05), while concurrent enhancements were observed in alpha, beta, and gamma band activities (all P<0.05). Network analysis revealed frequency-specific reorganization: clustering coefficients were significantly decreased in delta, theta, and alpha bands (P<0.05), while global efficiency improvement was exclusively detected in the delta band (P<0.05). The alpha band demonstrated concurrent increases in average nodal degree (P<0.05) and characteristic path length reduction (P<0.05). Further research findings indicate that the changes in the clinical scale HAMD scores before and after rTMS stimulation are negatively correlated with the changes in the blood biomarkers Aβ1-40 and p-tau181. Additionally, the changes in the clinical scales MMSE and MoCA scores were negatively correlated with the changes in the node degree of the alpha frequency band and negatively correlated with the clustering coefficient of the delta frequency band. However, the changes in MMSE scores are positively correlated with the changes in global efficiency of both the delta and alpha frequency bands. Conclusion20 Hz rTMS targeting dorsolateral prefrontal cortex (DLPFC) significantly improves cognitive function and enhances the metabolic clearance of β-amyloid and tau proteins in AD patients. This neurotherapeutic effect is mechanistically associated with rTMS-mediated frequency-selective neuromodulation, which enhances the connectivity of oscillatory networks through improved neuronal synchronization and optimized topological organization of functional brain networks. These findings not only support the efficacy of rTMS as an adjunctive therapy for AD but also underscore the importance of employing multiple assessment methods—including clinical scales, blood biomarkers, and EEG——in understanding and monitoring the progression of AD. This research provides a significant theoretical foundation and empirical evidence for further exploration of rTMS applications in AD treatment.
9.Application of large language models in disease diagnosis and treatment.
Xintian YANG ; Tongxin LI ; Qin SU ; Yaling LIU ; Chenxi KANG ; Yong LYU ; Lina ZHAO ; Yongzhan NIE ; Yanglin PAN
Chinese Medical Journal 2025;138(2):130-142
Large language models (LLMs) such as ChatGPT, Claude, Llama, and Qwen are emerging as transformative technologies for the diagnosis and treatment of various diseases. With their exceptional long-context reasoning capabilities, LLMs are proficient in clinically relevant tasks, particularly in medical text analysis and interactive dialogue. They can enhance diagnostic accuracy by processing vast amounts of patient data and medical literature and have demonstrated their utility in diagnosing common diseases and facilitating the identification of rare diseases by recognizing subtle patterns in symptoms and test results. Building on their image-recognition abilities, multimodal LLMs (MLLMs) show promising potential for diagnosis based on radiography, chest computed tomography (CT), electrocardiography (ECG), and common pathological images. These models can also assist in treatment planning by suggesting evidence-based interventions and improving clinical decision support systems through integrated analysis of patient records. Despite these promising developments, significant challenges persist regarding the use of LLMs in medicine, including concerns regarding algorithmic bias, the potential for hallucinations, and the need for rigorous clinical validation. Ethical considerations also underscore the importance of maintaining the function of supervision in clinical practice. This paper highlights the rapid advancements in research on the diagnostic and therapeutic applications of LLMs across different medical disciplines and emphasizes the importance of policymaking, ethical supervision, and multidisciplinary collaboration in promoting more effective and safer clinical applications of LLMs. Future directions include the integration of proprietary clinical knowledge, the investigation of open-source and customized models, and the evaluation of real-time effects in clinical diagnosis and treatment practices.
Humans
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Large Language Models
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Tomography, X-Ray Computed
10.Integrated multiomics reveal mechanism of Aidi Injection in attenuating doxorubicin-induced cardiotoxicity.
Yan-Li WANG ; Yu-Jie TU ; Jian-Hua ZHU ; Lin ZHENG ; Yong HUANG ; Jia SUN ; Yong-Jun LI ; Jie PAN ; Chun-Hua LIU ; Yuan LU
China Journal of Chinese Materia Medica 2025;50(8):2245-2259
The combination of Aidi Injection(ADI) and doxorubicin(DOX) is a common strategy in the treatment of cancer, which can achieve synergistic anti-tumor effects while attenuating the cardiotoxicity caused by DOX. This study aims to investigate the mechanism of ADI in attenuating DOX-induced cardiotoxicity by multi-omics. DOX was used to induce cardiotoxicity in mice, and the cardioprotective effects of ADI were evaluated based on biochemical indicators and pathological changes. Based on the results, transcriptomics, proteomics, and metabolomics were employed to analyze the changes of endogenous substances in different physiological states. Furthermore, data from multiple omics were integrated to screen key regulatory pathways by which ADI attenuated DOX-induced cardiotoxicity, and important target proteins were selected for measurement by ELISA kits and immunohistochemical analysis. The results showed that ADI significantly reduced the levels of cardiac troponin T(cTnT) and N-terminal pro-B-type natriuretic peptide(NT-proBNP) and effectively ameliorated myocardial fibrosis and intracellular vacuolization, indicating that ADI showed therapeutic effect on DOX-induced cardiotoxicity. The transcriptomics analysis screened out a total of 400 differentially expressed genes(DEGs), which were mainly enriched in inflammatory response, oxidative stress, and myocardial fibrosis. After proteomics analysis, 70 differentially expressed proteins were selected, which were mainly enriched in the inflammatory response, cardiac function, and energy metabolism. A total of 51 differentially expressed metabolites were screened by the metabolomics analysis, and they were mainly enriched in multiple signaling pathways, including the inflammatory response, lipid metabolism, and energy metabolism. The integrated data of multiple omics showed that linoleic acid metabolism, arachidonic acid metabolism, and glycerophosphate metabolism pathways played an important role in DOX-induced cardiotoxicity, and ADI may exert therapeutic effects by modulating these pathways. Target validation experiments suggested that ADI significantly regulated abnormal protein levels of cyclooxygenase-1(COX-1), cyclooxygenase-2(COX-2), prostaglandin H2(PGH2), and prostaglandin D2(PGD2) in the model group. In conclusion, ADI may attenuate DOX-induced cardiotoxicity by regulating linoleic acid metabolism, arachidonic acid metabolism, and glycerophosphate metabolism, thus alleviating inflammation of the body.
Doxorubicin/toxicity*
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Animals
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Mice
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Cardiotoxicity/genetics*
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Drugs, Chinese Herbal/administration & dosage*
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Male
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Proteomics
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Metabolomics
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Injections
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Humans
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Multiomics

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