1.Baicalein mitigates ferroptosis of neurons after subarachnoid hemorrhage
Ting ZHU ; Tingting YUE ; Yue CUI ; Yue LU ; Wei LI ; Chunhua HANG
Chinese Journal of Tissue Engineering Research 2025;29(1):52-57
BACKGROUND:Ferroptosis is a mode of programmed cell death distinct from apoptosis,necrosis,and other novel cellular deaths,which occurs mainly due to accumulated lipid peroxidation.Ferroptosis has been shown to be involved in the pathological process following subarachnoid hemorrhage.Baicalein,serving as an adept sequestered of iron,evinces its prowess by quelling lipid peroxidative cascades.Nonetheless,the enigma lingers as to whether baicalein possesses the capacity to ameliorate neuronal ferroptosis,elicited in the wake of early brain injury after subarachnoid hemorrhage. OBJECTIVE:To investigate the effect and mechanism of baicalein on neuronal ferroptosis after subarachnoid hemorrhage. METHODS:Primary neuronal cells were extracted from C57BL/6L fetal mice at 16-17 days of gestation.Hemoglobin was used to stimulate primary neuronal cells to simulate an in vitro subarachnoid hemorrhage model.The viability of primary neuronal cells treated with baicalein at concentrations of 5,15,25,50,and 100 μmol/L for 24 hours was detected by CCK-8 assay to determine the optimal concentration of baicalein.Primary neuronal cells were divided into control group,hemoglobin group,and hemoglobin+baicalein group.The levels of reactive oxygen species and malondialdehyde in cells were detected by kits.The mRNA expressions of ferroptosis-related markers PTGS2,SLC7A11,and glutathione peroxidase 4 were detected by RT-PCR.The primary neuronal cells were further divided into control group,SLC7A11 inhibitor Erastin group,hemoglobin group,hemoglobin+baicalein group,and hemoglobin+baicalein+Erastin group.The expression of the ferroptosis related markers SLC7A11 and glutathione peroxidase 4 was detected by western blot assay. RESULTS AND CONCLUSION:(1)Baicalein(25 μmol/L)was selected as the following experimental concentration.(2)Compared with the hemoglobin group,the level of malondialdehyde and the level of reactive oxygen species were significantly decreased(P<0.05)in the hemoglobin+baicalein group.(3)Compared with the hemoglobin group,the mRNA expression of PTGS2 significantly decreased,and the mRNA expression of SLC7A11 and glutathione peroxidase 4 significantly increased(P<0.000 1)in the hemoglobin+baicalein group.(4)SLC7A11 inhibitor Erastin could reverse the baicalin-improved ferroptosis effect to a certain extent(P<0.05).(5)The results showed that baicalein could alleviate the ferroptosis of neuronal cells after subarachnoid hemorrhage through the SLC7A11/GPX4 pathway.
2.Impact factor selection for non-fatal occupational injuries among manufacturing workers by LASSO regression
Yingheng XIAO ; Chunhua LU ; Juan QIAN ; Ying CHEN ; Yishuo GU ; Zeyun YANG ; Daozheng DING ; Liping LI ; Xiaojun ZHU
Journal of Environmental and Occupational Medicine 2025;42(2):133-139
Background As a pillar industry in China, the manufacturing sector has a high incidence of non-fatal occupational injuries. The factors influencing non-fatal occupational injuries in this industry are closely related at various levels, including individual, equipment, environment, and management, making the analysis of these influencing factors complex. Objective To identify influencing factors of non-fatal occupational injuries among manufacturing workers, providing a basis for targeted interventions and surveillance. Methods A total of
3.Distribution characteristics of self-reported diseases and occupational injuries among workers in manufacturing enterprises
Lin ZHANG ; Zhi’an LI ; Yishuo GU ; Juan QIAN ; Chunhua LU ; Jianjian QIAO ; Yong QIAN ; Zeyun YANG ; Xiaojun ZHU
Journal of Environmental and Occupational Medicine 2025;42(2):165-170
Background Diseases severely affect the efficiency of workers. Comorbidity refers to the coexistence of two or more chronic diseases or health problems in the same individual. Previous studies have primarily focused on occupational injuries caused by environmental exposures, while the analysis of the epidemiological characteristics of self-reported diseases and occupational injuries among manufacturing workers has been insufficient. Objective To analyze the distribution of self-reported diseases and occupational injuries among manufacturing workers, the strength of correlation between different diseases, and common disease combinations, and to preliminarily explore the relationship between self-reported diseases and occupational injuries. Methods A cross-sectional survey was conducted to investigate the occupational injuries of
4.Percutaneous coronary intervention vs . medical therapy in patients on dialysis with coronary artery disease in China.
Enmin XIE ; Yaxin WU ; Zixiang YE ; Yong HE ; Hesong ZENG ; Jianfang LUO ; Mulei CHEN ; Wenyue PANG ; Yanmin XU ; Chuanyu GAO ; Xiaogang GUO ; Lin CAI ; Qingwei JI ; Yining YANG ; Di WU ; Yiqiang YUAN ; Jing WAN ; Yuliang MA ; Jun ZHANG ; Zhimin DU ; Qing YANG ; Jinsong CHENG ; Chunhua DING ; Xiang MA ; Chunlin YIN ; Zeyuan FAN ; Qiang TANG ; Yue LI ; Lihua SUN ; Chengzhi LU ; Jufang CHI ; Zhuhua YAO ; Yanxiang GAO ; Changan YU ; Jingyi REN ; Jingang ZHENG
Chinese Medical Journal 2025;138(3):301-310
BACKGROUND:
The available evidence regarding the benefits of percutaneous coronary intervention (PCI) on patients receiving dialysis with coronary artery disease (CAD) is limited and inconsistent. This study aimed to evaluate the association between PCI and clinical outcomes as compared with medical therapy alone in patients undergoing dialysis with CAD in China.
METHODS:
This multicenter, retrospective study was conducted in 30 tertiary medical centers across 12 provinces in China from January 2015 to June 2021 to include patients on dialysis with CAD. The primary outcome was major adverse cardiovascular events (MACE), defined as a composite of cardiovascular death, non-fatal myocardial infarction, and non-fatal stroke. Secondary outcomes included all-cause death, the individual components of MACE, and Bleeding Academic Research Consortium criteria types 2, 3, or 5 bleeding. Multivariable Cox proportional hazard models were used to assess the association between PCI and outcomes. Inverse probability of treatment weighting (IPTW) and propensity score matching (PSM) were performed to account for potential between-group differences.
RESULTS:
Of the 1146 patients on dialysis with significant CAD, 821 (71.6%) underwent PCI. After a median follow-up of 23.0 months, PCI was associated with a 43.0% significantly lower risk for MACE (33.9% [ n = 278] vs . 43.7% [ n = 142]; adjusted hazards ratio 0.57, 95% confidence interval 0.45-0.71), along with a slightly increased risk for bleeding outcomes that did not reach statistical significance (11.1% vs . 8.3%; adjusted hazards ratio 1.31, 95% confidence interval, 0.82-2.11). Furthermore, PCI was associated with a significant reduction in all-cause and cardiovascular mortalities. Subgroup analysis did not modify the association of PCI with patient outcomes. These primary findings were consistent across IPTW, PSM, and competing risk analyses.
CONCLUSION
This study indicated that PCI in patients on dialysis with CAD was significantly associated with lower MACE and mortality when comparing with those with medical therapy alone, albeit with a slightly increased risk for bleeding events that did not reach statistical significance.
Humans
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Percutaneous Coronary Intervention/methods*
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Male
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Female
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Coronary Artery Disease/drug therapy*
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Retrospective Studies
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Renal Dialysis/methods*
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Middle Aged
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Aged
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China
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Proportional Hazards Models
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Treatment Outcome
5.Expert consensus on perioperative basic prevention for lower extremity deep venous thrombosis in elderly patients with hip fracture (version 2024)
Yun HAN ; Feifei JIA ; Qing LU ; Xingling XIAO ; Hua LIN ; Ying YING ; Junqin DING ; Min GUI ; Xiaojing SU ; Yaping CHEN ; Ping ZHANG ; Yun XU ; Tianwen HUANG ; Jiali CHEN ; Yi WANG ; Luo FAN ; Fanghui DONG ; Wenjuan ZHOU ; Wanxia LUO ; Xiaoyan XU ; Chunhua DENG ; Xiaohua CHEN ; Yuliu ZHENG ; Dekun YI ; Lin ZHANG ; Hanli PAN ; Jie CHEN ; Kaipeng ZHUANG ; Yang ZHOU ; Sui WENJIE ; Ning NING ; Songmei WU ; Jinli GUO ; Sanlian HU ; Lunlan LI ; Xiangyan KONG ; Hui YU ; Yifei ZHU ; Xifen YU ; Chen CHEN ; Shuixia LI ; Yuan GAO ; Xiuting LI ; Leling FENG
Chinese Journal of Trauma 2024;40(9):769-780
Hip fracture in the elderly is characterized by high incidence, high disability rate, and high mortality and has been recognized as a public health issue threatening their health. Surgery is the preferred choice for the treatment of elderly patients with hip fracture. However, lower extremity deep venous thrombosis (DVT) has an extremely high incidence rate during the perioperative period, and may significantly increase the risk of patients′ death once it progresses to pulmonary embolism. In response to this issue, the clinical guidelines and expert consensuses all emphasize active application of comprehensive preventive measures, including basic prevention, physical prevention, and pharmacological prevention. In this prevention system, basic prevention is the basis of physical and pharmacological prevention. However,there is a lack of unified and definite recommendations for basic preventive measures in clinical practice. To this end, the Orthopedic Nursing Professional Committee of the Chinese Nursing Association and Nursing Department of the Orthopedic Branch of the China International Exchange and Promotive Association for Medical and Health Care organized relevant nursing experts to formulate Expert consensus on perioperative basic prevention for lower extremity deep venous thrombosis in elderly patients with hip fracture ( version 2024) . A total of 10 recommendations were proposed, aiming to standardize the basic preventive measures for lower extremity DVT in elderly patients with hip fractures during the perioperative period and promote their subsequent rehabilitation.
6.Short-term outcomes of the TRIANGLE operation after neoadjuvant chemotherapy in locally advanced pancreatic cancer
Dong XU ; Min TU ; Kai ZHANG ; Pengfei WU ; Nan LYU ; Qianqian WANG ; Jie YIN ; Yang WU ; Zipeng LU ; Jianmin CHEN ; Chunhua XI ; Jishu WEI ; Feng GUO ; Yi MIAO ; Kuirong JIANG
Chinese Journal of Surgery 2024;62(2):147-154
Objective:To investigate the safety and efficacy of the TRIANGLE operation after neoadjuvant chemotherapy in locally advanced pancreatic cancer(LAPC).Methods:This study is a retrospective case series analysis. Between January 2020 and December 2022, a total of 103 patients were diagnosed as LAPC who underwent neoadjuvant chemotherapy at the Pancreas Center, the First Affiliated Hospital of Nanjing Medical University. Among them, 26 patients (25.2%) underwent the TRIANGLE operation. There were 15 males and 11 females,with a age of (59±7) years (range: 49 to 74 years). The pre-treatment serum CA19-9( M(IQR)) was 248.8(391.6)U/ml (range: 0 to 1 428 U/ml),and the serum carcinoembryonic antigen was 4.1(3.8)μg/L(range: 1.4 to 13.4 μg/L). The neoadjuvant chemotherapy regimens included: mFOLFIRINOX regimen in 6 cases(23.1%), GnP regimen in 14 cases(53.8%), and mFOLFIRINOX+GnP regimen in 6 cases(23.1%). The follow-up duration extended until June 2023 or until the occurrence of the patient′s death or loss to follow-up. The Kaplan-Meier method was employed to estimate the 1-year and 3-year overall survival rates. Results:After neoadjuvant chemotherapy,CA19-9 levels decreased by 92.3(40.1)%(range:2.1% to 97.7%). Evaluation of the response to treatment revealed 13 cases(50.0%) of stable disease,11 cases(42.3%) of partial response,and 2 cases(7.7%) of complete response. The surgical operation consisted of 12 cases(46.2%) of pancreaticoduodenectomy,12 cases(46.2%) of distal pancreatectomy,and 2 cases(7.7%) of total pancreatectomy. Margin determination was based on the “standardised pathology protocol” and the “1 mm” principle. No R2 and R1(direct) resections were observed,while the R0 resection rate was 61.5%(16/26), and the R1(1 mm) resection rate was 38.5%(10/26).The R1(1 mm) resection rates for the anterior margin,posterior margin,transected margin,portal vein groove margin,and uncinate margin were 23.1%(6/26),19.2%(5/26),12.5%(3/24),2/14, and 1/12, respectively. The overall postoperative complication rate was 57.8%(15/26),with major complications including grade B/C pancreatic fistula 25.0%(6/24,excluding 2 cases of total pancreatectomy),delayed gastric emptying in 23.1%(6/26),wound complications 11.5%(3/26),postoperative hemorrhage 7.7%(2/26), chylous fistula 7.7%(2/26) and bile fistula 3.8%(1/26). No reoperation was performed during the perioperative period(<90 days). One patient died on the 32 nd day postoperatively due to a ruptured pseudoaneurysm. A total of 25 patients were followed up,with a follow-up time of 21(24)months(range: 8 to 42 months). During the follow-up period,8 cases(32.0%) died due to tumor recurrence and metastasis,while 17 patients(68.0%) remained alive,including 11 cases of disease-free survival,5 cases of distant metastasis,and 1 case of local recurrence. The overall survival rates at 1- and 3-year after the initiation of neoadjuvant chemotherapy were 95.8% and 58.9%, respectively. The overall survival rates at 1- and 3-year after surgery were 77.7% and 57.8%, respectively. Conclusion:Performing pancreatoduodenectomy according to the Heidelberg triangle protocol in LAPC patients after neoadjuvant chemotherapy might increase the R0 resection rate without increasing perioperative mortality or the incidence of major postoperative complications.
7.Inhibitory effect and mechanism of alkaloids derived from Gelsemium elegans Benth on lung cancer
Mingjing JIN ; Yanping LI ; Huansi ZHOU ; Binrui WANG ; Zhuoling WU ; Chunhua LU
Journal of Army Medical University 2024;46(23):2629-2641
Objective To determine the anti-lung cancer effect of koumine(KOU)and total alkaloids of Gelsemium elegans Benth(TAG)and investigate the underlying mechanism.Methods After low,medium and high concentrations(100,150,200 μg/mL)of KOU were used to treat human lung adenocarcinoma cell lines A549 and SPCA1,Live Cell Imaging and Analysis by Sartorius colony formation assay was employed to detect the cell proliferation.The transplanted tumor model of lung cancer cells in mice was constructed and divided into model group(model group),cyclophosphamide group(CTX group,20 mg/kg),KOU group(2 mg/kg)and TAG group(0.5 mg/kg).After the mice of the CTX,KOU and TAG groups were intraperitoneally injected with 0.1 mL/10 g corresponding agents every other day for 10 d,the growth of lung cancer solid tumors was observed grossly and with HE staining,immunohistochemical(IHC)assay and TUNEL staining to and calculate the tumor size and growth inhibitory rate.RNA sequencing analysis was performed on A549 cells treated with TAG for 48 h to screen the differentially expressed genes(DEGs)between the treatment group and the control group,and the obtained DEGs were further analyzed with Kyoto Encyclopedia of Genes and Genomes(KEGG)and Gene Ontology(GO)functional enrichment analyses.RT-qPCR was applied to further analyze and verify the expression of related genes.Results Live Cell Imaging and Analysis fitted that the confluence of A549 and SPCA1 cells was decreased and the number of cells in the treated groups was observed to decrease,with poor growth.The results of colony formation assay confirmed that KOU reduced the number of cell clones,especially at a dose of 200 μg/mL(P<0.01).Animal experiments showed that KOU and TAG treatment inhibited the tumor growth by 24.55%and 36.08%,respectively.TAG treatment resulted in significantly decreased tumor size when compared with the model group(P<0.05).RNA sequencing analysis revealed that there were totally 2 793 DEGs,including 1 433 up-regulated genes and 1 360 down-regulated ones.Enrichment analysis displayed that the DEGs were mainly enriched in IL-17 signaling pathway,tumor necrosis factor signaling pathway and P53 signaling pathway.The results of RT-qPCR were consistent with the results of RNA sequencing analysis.The expression levels of GADD34,ZFP36,GADD45 A,GADD45 B and TP53INP2 genes were significantly increased in the TAG group(P<0.01).Conclusion Alkaloids of Gelsemium elegans Benth inhibits the proliferation of lung cancer in vivo and in vitro.Transcriptomics find that KOU and TAG inhibit multiple DEGs and pathways of lung cancer.
8.Short-term outcomes of the TRIANGLE operation after neoadjuvant chemotherapy in locally advanced pancreatic cancer
Dong XU ; Min TU ; Kai ZHANG ; Pengfei WU ; Nan LYU ; Qianqian WANG ; Jie YIN ; Yang WU ; Zipeng LU ; Jianmin CHEN ; Chunhua XI ; Jishu WEI ; Feng GUO ; Yi MIAO ; Kuirong JIANG
Chinese Journal of Surgery 2024;62(2):147-154
Objective:To investigate the safety and efficacy of the TRIANGLE operation after neoadjuvant chemotherapy in locally advanced pancreatic cancer(LAPC).Methods:This study is a retrospective case series analysis. Between January 2020 and December 2022, a total of 103 patients were diagnosed as LAPC who underwent neoadjuvant chemotherapy at the Pancreas Center, the First Affiliated Hospital of Nanjing Medical University. Among them, 26 patients (25.2%) underwent the TRIANGLE operation. There were 15 males and 11 females,with a age of (59±7) years (range: 49 to 74 years). The pre-treatment serum CA19-9( M(IQR)) was 248.8(391.6)U/ml (range: 0 to 1 428 U/ml),and the serum carcinoembryonic antigen was 4.1(3.8)μg/L(range: 1.4 to 13.4 μg/L). The neoadjuvant chemotherapy regimens included: mFOLFIRINOX regimen in 6 cases(23.1%), GnP regimen in 14 cases(53.8%), and mFOLFIRINOX+GnP regimen in 6 cases(23.1%). The follow-up duration extended until June 2023 or until the occurrence of the patient′s death or loss to follow-up. The Kaplan-Meier method was employed to estimate the 1-year and 3-year overall survival rates. Results:After neoadjuvant chemotherapy,CA19-9 levels decreased by 92.3(40.1)%(range:2.1% to 97.7%). Evaluation of the response to treatment revealed 13 cases(50.0%) of stable disease,11 cases(42.3%) of partial response,and 2 cases(7.7%) of complete response. The surgical operation consisted of 12 cases(46.2%) of pancreaticoduodenectomy,12 cases(46.2%) of distal pancreatectomy,and 2 cases(7.7%) of total pancreatectomy. Margin determination was based on the “standardised pathology protocol” and the “1 mm” principle. No R2 and R1(direct) resections were observed,while the R0 resection rate was 61.5%(16/26), and the R1(1 mm) resection rate was 38.5%(10/26).The R1(1 mm) resection rates for the anterior margin,posterior margin,transected margin,portal vein groove margin,and uncinate margin were 23.1%(6/26),19.2%(5/26),12.5%(3/24),2/14, and 1/12, respectively. The overall postoperative complication rate was 57.8%(15/26),with major complications including grade B/C pancreatic fistula 25.0%(6/24,excluding 2 cases of total pancreatectomy),delayed gastric emptying in 23.1%(6/26),wound complications 11.5%(3/26),postoperative hemorrhage 7.7%(2/26), chylous fistula 7.7%(2/26) and bile fistula 3.8%(1/26). No reoperation was performed during the perioperative period(<90 days). One patient died on the 32 nd day postoperatively due to a ruptured pseudoaneurysm. A total of 25 patients were followed up,with a follow-up time of 21(24)months(range: 8 to 42 months). During the follow-up period,8 cases(32.0%) died due to tumor recurrence and metastasis,while 17 patients(68.0%) remained alive,including 11 cases of disease-free survival,5 cases of distant metastasis,and 1 case of local recurrence. The overall survival rates at 1- and 3-year after the initiation of neoadjuvant chemotherapy were 95.8% and 58.9%, respectively. The overall survival rates at 1- and 3-year after surgery were 77.7% and 57.8%, respectively. Conclusion:Performing pancreatoduodenectomy according to the Heidelberg triangle protocol in LAPC patients after neoadjuvant chemotherapy might increase the R0 resection rate without increasing perioperative mortality or the incidence of major postoperative complications.
9.The relationship between the expression of serum GP3 and CHI3L1 and the degree of liver fibrosis and pathological changes in patients with hepatitis
Jin LU ; Ming WEN ; Qingrong TANG ; Chunhua XU ; Chunling ZHAN ; Yizhou XU ; Lihui YANG
The Journal of Practical Medicine 2024;40(11):1586-1591
Objective Exploring the relationship between changes in serum Golgi apparatus transmem-brane glycoprotein 73(GP73)and chitosanase 3-like protein 1(CHI3L1)levels and liver fibrosis and lesion sever-ity in patients with hepatitis B(CHB).Methods Using a case-control study,80 patients diagnosed with CHB infection and developing liver fibrosis in the Infectious Disease Department of Changsha First Hospital from June 2020 to June 2023 were selected as the liver fibrosis group,while 120 patients diagnosed with CHB infection but not developing liver fibrosis in the Infectious Disease Department of our hospital were selected as the control group.The serum GP3,CHI3L1,liver function,and fibrosis indicators of the two groups of patients were compared,and the liver fibrosis group was divided into mild according to Scheuer system standards Perform stratified analysis on patients with significant liver fibrosis.Results The serum GP3 and CHI3L1 levels in the liver fibrosis group were significantly higher than those in the control group,with statistical significance(P<0.05);The ROC curves were plotted using serum GP3,CHI3L1,and GP3+CHI3L1,respectively.The sensitivity for diagnosing liver fibrosis in CHB patients was 62.81%,60.94%,and 96.33%,with specificity of 80.66%,80.05%,and 75.30%.The AUC values under the curves were 0.792,0.756,and 0.908,respectively;The levels of ALT,AST,HA,LN,PC III NP,C IV,and CG in the liver fibrosis group were higher than those in the control group,and the PLT measurement values were lower than those in the control group,with statistical significance(P<0.05);49 patients with moderate to severe liver fibrosis(33 in S2 phase and 16 in S3 phase)and 31 patients with mild liver fibrosis(all in S1 phase)had significantly higher serum GP3 and CHI3L1 levels than mild patients,with statistical significance(P<0.05);The levels of DBIL,ALT,AST,HA,LN,PC III NP,C IV,and CG in patients with moderate to severe liver fibrosis were higher than those in the mild group,and the PLT measurement values were lower than those in the mild group,with statistical significance(P<0.05).Conclusion The serum GP3 and CHI3L1 levels in CHB patients with liver fibrosis are significantly elevated,and there is a certain correlation with the degree of liver fibro-sis.The combination of these two indicators is beneficial for diagnosing liver fibrosis in CHB patients.
10.Mechanism of Ginkgo flavone aglycone in alleviating doxorubicin-induced cardiotoxicity based on transcriptomics and proteomics
Yujie TU ; Ying CAI ; Xueyi CHENG ; Jia SUN ; Jie PAN ; Chunhua LIU ; Yongjun LI ; Yong HUANG ; Lin ZHENG ; Yuan LU
China Pharmacy 2024;35(21):2596-2602
OBJECTIVE To investigate the mechanism by which Ginkgo flavone aglycone (GA) reduces the cardiotoxicity of doxorubicin (DOX) based on transcriptomics and proteomics. METHODS Thirty-six mice were randomly assigned to control group (CON group, tail vein injection of equal volume of physiological saline every other day+daily intragastric administration of an equal volume of physiological saline), DOX group (tail vein injection of 3 mg/kg DOX every other day), and GDOX group (daily intragastric administration of 100 mg/kg GA+tail vein injection of 3 mg/kg DOX every other day), with 12 mice in each group. The administration of drugs/physiological saline was continued for 15 days. Mouse heart tissues were collected for RNA-Seq transcriptomic sequencing and 4D-Label-free quantitative proteomic analysis to screen differentially expressed genes and proteins, which were then subjected to Kyoto encyclopedia of genes and genomes (KEGG) enrichment analysis. The expression levels of Apelin peptide (Apelin), phosphatidylinositol 3-kinase (PI3K), and protein kinase B (Akt) mRNA and protein in mouse heart tissues, as well as the phosphorylation levels of PI3K and Akt proteins, were verified. H9c2 cardiomyocytes were divided into control group (CON group), DOX group (2 μmol/L), and GDOX group (2 μg/mL GA+2 μmol/L DOX) to determine cell viability and the levels of key glycolytic substances in the cells. RESULTS Six common pathways were identified from transcriptomics and proteomics, including the Apelin signaling pathway, the PI3K-Akt signaling pathway, and insulin resistance. Among them, the Apelin and PI3K-Akt signaling pathways were the most enriched in terms of gene numbers. Target validation experiments showed that compared to the CON group, the relative expression of Apelin, PI3K and Akt mRNA and protein levels, as well as the phosphorylation levels of PI3K and Akt proteins, were significantly decreased in the DOX group (P<0.05 or P<0.01). The relative expression of Apelin, PI3K and Akt mRNA and the phosphorylation levels of PI3K and Akt proteins were significantly increased in the GDOX group as compared with the DOX group (P<0.05 or P<0.01). Cellular experiments indicated that compared to the CON group, cell viability in the DOX group was significantly decreased (P<0.05), the relative uptake of glucose and the relative production of pyruvate and lactate were significantly increased (P<0.05), and the relative production of ATP was significantly reduced (P<0.05). Compared to the DOX group, cell viability in the GDOX group was significantly increased (P< 0.05), and the relative production of pyruvate and lactate was significantly reduced (P<0.05). CONCLUSIONS GA may alleviate DOX-induced cardiotoxicity by upregulating the mRNA and protein expression of Apelin, PI3K, and Akt in heart tissues, and regulating glycolytic processes.

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