1.Analysis of Potential Active Components and Molecular Mechanism of Baoxin Granules Regulating Ferroptosis in Treatment of Heart Failure
Yu CHEN ; Maolin WANG ; Yun WANG ; Yifan ZHAO ; Jing XU ; Hongwei WU ; Fang WANG ; Xiaoang ZHAO ; Youming LI ; Jixiang TIAN
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(12):202-209
ObjectiveBased on ultra performance liquid chromatography-quadrupole-time-of-flight mass spectrometry(UPLC-Q-TOF-MS), network pharmacology, molecular docking and cell experiments, the active ingredients, possible targets and molecular mechanisms of Baoxin granules(BXG) regulating ferroptosis in the treatment of heart failure(HF) were explored. MethodsBXG intestinal absorption fluid was prepared by everted gut sac and the chemical composition contained therein were identified by UPLC-Q-TOF-MS. According to the obtained components, the potential targets of BXG were predicted, and the HF-related targets and related genes of ferroptosis were retrieved at the same time, and the intersecting targets were obtained by Venn diagram. In addition, the protein-protein interaction(PPI) network and the component-target network were constructed, and the core components and core targets were obtained by topological analysis. Then Gene Ontology(GO) function and Kyoto Encyclopedia of Genes and Genomes(KEGG) enrichment analysis were performed on the core targets, and molecular docking validation of the key targets and main components was carried out by AutoDockTools 1.5.7. H9c2 cells were used to establish a oxygen-glucose deprivation model, and the protective effect of BXG on cells was investigated by detecting cell viability, cell survival rate and reactive oxygen species(ROS) level. The protein expression levels of signal transducer and activator of transcription 3(STAT3), phosphorylation(p)-STAT3 and glutathione peroxidase 4(GPX4) were detected by Western blot to clarify the regulatory effect of BXG on ferroptosis. ResultsA total of 61 chemical components in BXG intestinal absorption fluid were identified, and network pharmacology obtained 27 potential targets of BXG for the treatment of HF, as well as 139 signaling pathways. BXG may act on core targets such as STAT3, tumor protein p53(TP53), epidermal growth factor receptor(EGFR), JUN and prostaglandin-endoperoxide synthase 2(PTGS2) through core components such as glabrolide and limonin, which in turn intervene in lipid and atherosclerosis, phosphatidylinositol 3-kinase/protein kinase B(PI3K/Akt), endocrine resistance and other signaling pathways to exert therapeutic effects on HF. Molecular docking showed that the docking results of multiple groups of targets and compounds were good. In vitro cell experiments showed that compared with the blank group, the cell viability and survival rate of the model group were significantly decreased, the level of ROS was significantly increased(P<0.01), the expression levels of STAT3, p-STAT3, p-STAT3/STAT3 and GPX4 proteins were significantly decreased(P<0.05, P<0.01). Compared with the model group, the cell viability and survival rate of the BXG group were significantly increased, the ROS level was significantly decreased(P<0.01), the STAT3, p-STAT3, p-STAT3/STAT3 and GPX4 protein levels were significantly increased(P<0.05, P<0.01). ConclusionBXG may inhibit the occurrence of ferroptosis by up-regulating the expression of STAT3 and GPX4, thus exerting a therapeutic effect on HF, and flavonoids may be the key components of this role.
2.Analysis of Potential Active Components and Molecular Mechanism of Baoxin Granules Regulating Ferroptosis in Treatment of Heart Failure
Yu CHEN ; Maolin WANG ; Yun WANG ; Yifan ZHAO ; Jing XU ; Hongwei WU ; Fang WANG ; Xiaoang ZHAO ; Youming LI ; Jixiang TIAN
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(12):202-209
ObjectiveBased on ultra performance liquid chromatography-quadrupole-time-of-flight mass spectrometry(UPLC-Q-TOF-MS), network pharmacology, molecular docking and cell experiments, the active ingredients, possible targets and molecular mechanisms of Baoxin granules(BXG) regulating ferroptosis in the treatment of heart failure(HF) were explored. MethodsBXG intestinal absorption fluid was prepared by everted gut sac and the chemical composition contained therein were identified by UPLC-Q-TOF-MS. According to the obtained components, the potential targets of BXG were predicted, and the HF-related targets and related genes of ferroptosis were retrieved at the same time, and the intersecting targets were obtained by Venn diagram. In addition, the protein-protein interaction(PPI) network and the component-target network were constructed, and the core components and core targets were obtained by topological analysis. Then Gene Ontology(GO) function and Kyoto Encyclopedia of Genes and Genomes(KEGG) enrichment analysis were performed on the core targets, and molecular docking validation of the key targets and main components was carried out by AutoDockTools 1.5.7. H9c2 cells were used to establish a oxygen-glucose deprivation model, and the protective effect of BXG on cells was investigated by detecting cell viability, cell survival rate and reactive oxygen species(ROS) level. The protein expression levels of signal transducer and activator of transcription 3(STAT3), phosphorylation(p)-STAT3 and glutathione peroxidase 4(GPX4) were detected by Western blot to clarify the regulatory effect of BXG on ferroptosis. ResultsA total of 61 chemical components in BXG intestinal absorption fluid were identified, and network pharmacology obtained 27 potential targets of BXG for the treatment of HF, as well as 139 signaling pathways. BXG may act on core targets such as STAT3, tumor protein p53(TP53), epidermal growth factor receptor(EGFR), JUN and prostaglandin-endoperoxide synthase 2(PTGS2) through core components such as glabrolide and limonin, which in turn intervene in lipid and atherosclerosis, phosphatidylinositol 3-kinase/protein kinase B(PI3K/Akt), endocrine resistance and other signaling pathways to exert therapeutic effects on HF. Molecular docking showed that the docking results of multiple groups of targets and compounds were good. In vitro cell experiments showed that compared with the blank group, the cell viability and survival rate of the model group were significantly decreased, the level of ROS was significantly increased(P<0.01), the expression levels of STAT3, p-STAT3, p-STAT3/STAT3 and GPX4 proteins were significantly decreased(P<0.05, P<0.01). Compared with the model group, the cell viability and survival rate of the BXG group were significantly increased, the ROS level was significantly decreased(P<0.01), the STAT3, p-STAT3, p-STAT3/STAT3 and GPX4 protein levels were significantly increased(P<0.05, P<0.01). ConclusionBXG may inhibit the occurrence of ferroptosis by up-regulating the expression of STAT3 and GPX4, thus exerting a therapeutic effect on HF, and flavonoids may be the key components of this role.
3.Short-term efficacy of improved Bentall operation with "pericardial lining" for aortic root aneurysm
Xianzhi WANG ; Jixiang LIANG ; Huan WANG ; Gen ZHANG ; Zhigang DENG ; Dongquan HE ; Cunfu MU ; Wenlin ZHANG ; Chunzhu XUE ; Yang HE ; Dianyuan LI
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2025;32(11):1615-1620
Objective To investigate the feasibility of a "pericardial lining" modified Bentall procedure for the treatment of patients with aortic root aneurysm. Methods This was a retrospective study that consecutively enrolled patients treated at the Affiliated Suzhou Hospital of Nanjing Medical University, The Affiliated Traditional Chinese Medicine Hospital of Southwest Medical University, and the First People's Hospital of Guangyuan from January 2023 to February 2024. Preoperative clinical data, imaging findings (including echocardiography and CT scans of the aortic root and the entire aorta), details of coronary artery management, surgical outcomes, and postoperative follow-up results were collected. All patients underwent the "pericardial lining" modified Bentall procedure: the aortic valve was replaced, and an autologous pericardial patch was divided into three equal leaflets based on the circumference of the aortic annulus measured by a valve sizer. These leaflets were then sutured to the aortic annulus. Fenestrations were created in two of the pericardial leaflets for anastomosis with the left and right coronary ostia. The pericardial leaflets were sutured to the wall of the aortic sinuses to form an integrated structure, thereby narrowing the sinus portion. A prosthetic vascular graft was anastomosed to the proximal and distal aorta, and no aortic root-to-right atrium shunt was created. Results A total of 5 patients, aged 37 to 68 years, were included. The preoperative Society of Thoracic Surgeons (STS) risk scores ranged from 2.8% to 3.9%. The diameter of the ascending aorta was 40-73 mm, the left ventricular end-diastolic diameter (LVEDD) was 45-71 mm, and the left ventricular ejection fraction (LVEF) was 47%-64%. Intraoperatively, the aortic cross-clamp time ranged from 85 to 180 min, and the cardiopulmonary bypass time ranged from 110 to 302 min. Postoperative follow-up echocardiography revealed that the ascending aortic diameter was 27-35 mm, LVEDD was 39-57 mm, and LVEF was 43%-61%. All surgeries were completed successfully with satisfactory immediate outcomes and no intraoperative complications. During the follow-up period, there was no mortality or reoperation. Conclusion For patients with aortic root aneurysm, the "pericardial lining" modified Bentall procedure yields satisfactory preliminary results, and the technique is demonstrated to be feasible.
4.A case report on multidisciplinary team collaborative diagnosis and treatment of severe immune checkpoint inhibitor-related myocarditis
Zhu JIXIANG ; He YIZI ; Guan QINGPEI ; Liu PANPAN ; Wang DONGHAO ; Li ZHIMING ; Zhou HUI
Chinese Journal of Clinical Oncology 2025;52(18):950-956
With the widespread useof immune checkpoint inhibitors(ICIs)in the treatment of various solid tumors,immune-related adverse events have attracted increasing clinical attention.Although ICI-associated myocarditis is rare,it typically has an insidious onset,progresses rapidly,and carries a high mortality rate,making it one of the most severe complications of ICI therapy.Early recognition and management remain challenging due to the absence of standardized diagnostic and therapeutic guidelines.ICI-associated myocarditis is characterized by the following features,with symptom onset commonly occurring within weeks of initiating ICI therapy.Its clinical manifestations are often non-specific and can be misdiagnosed as coronary artery disease or viral myocarditis.Prompt administration of high-dose corticosteroids combined with immunosuppressants,cardiac rhythm and functional support,is crucial for effective management.Although numerous stud-ies highlight the importance of early detection and multidisciplinary collaboration,there is still no consensus on standardized treatment pro-tocols.This report describes a case of acute ICI-associated myocarditis with ovarian cancer who developed symptoms after receiving com-bined apalutamide and toripalimab therapy.The patient responded well to corticosteroid pulse therapy,second-line immunosuppressants,and intensive care support.Due to recurrent ventricular arrhythmias,an implantable cardioverter defibrillator was placed,and cardiac func-tion remained stable during follow-up.Through this case and a review of the relevant literature,we discuss the clinical features,compre-hensive treatment strategies,and long-term management approaches for ICI-associated myocarditis,aiming to raise clinical awareness,pro-mote standardized multidisciplinary team collaboration,and ultimately improve patient outcomes.
5.Advances in conversion therapy for unresectable hepatocellular carcinoma
Ke YU ; Jiajia JIA ; Ying SHA ; Yufan TANG ; Baiquan ZHOU ; Bingbing WEN ; Luyao LI ; Jixiang LIU ; Ruifang FAN
Chinese Journal of Hepatobiliary Surgery 2025;31(9):706-711
Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide. Surgical resection remains the preferred treatment modality, offering the potential for cure. However, over half of HCC patients present as intermediate to advanced stages at diagnosis, with multiple factors precluding surgical resection. Conversion therapy represents an important treatment strategy by enabling tumor downstaging, offering future resectability for patients with intermediate-to-advanced HCC who are initially unresectable. This article reviews the relevant concepts and research progress in conversion therapy for HCC.
6.Study on the molecular mechanism of miR-886-5p targeting BAX to inhibit proliferation, migration and invasion of liver cancer cells
Shaopeng LIU ; Haichao LIU ; Hongxian YAN ; Minghui BAI ; Jixiang ZHANG ; Yingbo LI ; Chuang WANG ; Xiang ZOU
Chinese Journal of Hepatobiliary Surgery 2025;31(8):621-627
Objective:To investigate the molecular mechanism of miR-886-5p targeting BCL-2-associated X protein (BAX) to inhibit the proliferation, migration, and invasion of liver cancer cells.Methods:mRNA expression data of HCC patients were obtained from the Starbase database, including 370 liver cancer samples and 50 normal liver tissue samples adjacent to the cancer. Analyze the expression of miR-886-5p in the previously obtained data and investigate the relationship between miR-886-5p and BAX in liver cancer samples. After transfection of the corresponding plasmids into Huh7 and HepG2 cells, the following groups were established. Analyze the interaction between miR-886-5p and BAX in vitro, detect the protein expression by Western blotting, and verify the targeting relationship between the two by dual luciferase reporter gene assay.Results:Starbase database analysis found that the standardized expression level of miR-886-5p in 370 liver cancer samples was lower than that in normal liver tissue samples (0.12±0.07 vs. 0.73±0.27, t=-15.71, P<0.001), and the expression level of miR-886-5p was positively correlated with the expression level of BAX ( r=0.152, P=0.003). qRT-PCR analysis showed that the expression level of miR-886-5p in HL-7702 cells was higher than that in Huh7 (4.57±0.06 vs. 1.61±0.40, t=32.48) and HepG2 (4.57±0.06 vs. 1.03±0.13, t=143.9), and the expression level of BAX in HL-7702 cells was higher than that in Huh7 (4.01±0.12 vs. 1.28±0.09, t=82.20) and HepG2 (4.01±0.12 vs. 1.30±0.11, t=80.76), the differences were statistically significant (all P<0.001). The proliferation, migration, and invasion abilities of Huh7 and HepG2 cells decreased after transfection with miR-886-5p mimics, while the expression levels of BAX at the mRNA and protein levels increased. However, after inhibiting the expression of miR-886-5p, the above indicators of cells were the opposite, and the dif-ferences were statistically significant (all P<0.05). The viability, EdU positivity rate, cell migration rate, and number of transmembrane cells in the miR-886-5p+ BAX group were lower than those in the BAX group, and the relative expression levels of miR-886-5p, BAX mRNA, and BAX protein were higher than those in the BAX group. However, the above indicators in the Sponge+ BAX group showed opposite trends, and all differences were statistically significant (all P<0.05). There was a targeted binding site between miR-886-5p and BAX. Conclusion:Both miR-886-5p and BAX are downregulated in liver cancer, and miR-886-5p inhibits the proliferation, migration, and invasion of liver cancer cells by targeting BAX.
7.Acceptance and commissioning testing of multiparametric imaging using the big bore dual-source CT simulator for radiotherapy
Meijiao WANG ; Yi DU ; Kaining YAO ; Zhongsu FENG ; Jixiang CHEN ; Hao WU ; Kaixuan LI ; Haizhen YUE
Chinese Journal of Radiological Health 2025;34(5):764-769
Objective To evaluate the accuracy of multiparametric imaging on the dual-source CT through acceptance and commissioning testing, and to provide a reference for standardized clinical application. Methods Both the adult and pediatric dual-source CT scanning modes were used to scan the electron density phantom, and identical multiparametric image reconstruction tasks were performed, including the conventional CT images, the mixed CT images, the virtual monoenergetic images, the iodine images, the electron density images, and the effective atomic number images. Results In the adult scanning mode, the virtual monoenergetic CT numbers showed the greatest difference for the cortical bone (
8.Advances in conversion therapy for unresectable hepatocellular carcinoma
Ke YU ; Jiajia JIA ; Ying SHA ; Yufan TANG ; Baiquan ZHOU ; Bingbing WEN ; Luyao LI ; Jixiang LIU ; Ruifang FAN
Chinese Journal of Hepatobiliary Surgery 2025;31(9):706-711
Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide. Surgical resection remains the preferred treatment modality, offering the potential for cure. However, over half of HCC patients present as intermediate to advanced stages at diagnosis, with multiple factors precluding surgical resection. Conversion therapy represents an important treatment strategy by enabling tumor downstaging, offering future resectability for patients with intermediate-to-advanced HCC who are initially unresectable. This article reviews the relevant concepts and research progress in conversion therapy for HCC.
9.Study on the molecular mechanism of miR-886-5p targeting BAX to inhibit proliferation, migration and invasion of liver cancer cells
Shaopeng LIU ; Haichao LIU ; Hongxian YAN ; Minghui BAI ; Jixiang ZHANG ; Yingbo LI ; Chuang WANG ; Xiang ZOU
Chinese Journal of Hepatobiliary Surgery 2025;31(8):621-627
Objective:To investigate the molecular mechanism of miR-886-5p targeting BCL-2-associated X protein (BAX) to inhibit the proliferation, migration, and invasion of liver cancer cells.Methods:mRNA expression data of HCC patients were obtained from the Starbase database, including 370 liver cancer samples and 50 normal liver tissue samples adjacent to the cancer. Analyze the expression of miR-886-5p in the previously obtained data and investigate the relationship between miR-886-5p and BAX in liver cancer samples. After transfection of the corresponding plasmids into Huh7 and HepG2 cells, the following groups were established. Analyze the interaction between miR-886-5p and BAX in vitro, detect the protein expression by Western blotting, and verify the targeting relationship between the two by dual luciferase reporter gene assay.Results:Starbase database analysis found that the standardized expression level of miR-886-5p in 370 liver cancer samples was lower than that in normal liver tissue samples (0.12±0.07 vs. 0.73±0.27, t=-15.71, P<0.001), and the expression level of miR-886-5p was positively correlated with the expression level of BAX ( r=0.152, P=0.003). qRT-PCR analysis showed that the expression level of miR-886-5p in HL-7702 cells was higher than that in Huh7 (4.57±0.06 vs. 1.61±0.40, t=32.48) and HepG2 (4.57±0.06 vs. 1.03±0.13, t=143.9), and the expression level of BAX in HL-7702 cells was higher than that in Huh7 (4.01±0.12 vs. 1.28±0.09, t=82.20) and HepG2 (4.01±0.12 vs. 1.30±0.11, t=80.76), the differences were statistically significant (all P<0.001). The proliferation, migration, and invasion abilities of Huh7 and HepG2 cells decreased after transfection with miR-886-5p mimics, while the expression levels of BAX at the mRNA and protein levels increased. However, after inhibiting the expression of miR-886-5p, the above indicators of cells were the opposite, and the dif-ferences were statistically significant (all P<0.05). The viability, EdU positivity rate, cell migration rate, and number of transmembrane cells in the miR-886-5p+ BAX group were lower than those in the BAX group, and the relative expression levels of miR-886-5p, BAX mRNA, and BAX protein were higher than those in the BAX group. However, the above indicators in the Sponge+ BAX group showed opposite trends, and all differences were statistically significant (all P<0.05). There was a targeted binding site between miR-886-5p and BAX. Conclusion:Both miR-886-5p and BAX are downregulated in liver cancer, and miR-886-5p inhibits the proliferation, migration, and invasion of liver cancer cells by targeting BAX.
10.Advances of neoadjuvant and conversion therapy with PD-1 inhibitors in gastric cancer
Yufan TANG ; Baiquan ZHOU ; Simeng DAI ; Bingbing WEN ; Jixiang LIU ; Luyao LI ; Ruifang FAN
Chinese Journal of Gastrointestinal Surgery 2025;28(2):217-224
Gastric cancer (GC) is one of the most common malignant tumors of the digestive system in China. With the progress of immunotherapy research, programmed death receptor-1 (PD-1) inhibitor-based combinatory therapy offers new ideas for the treatment of advanced gastric cancer. In recent years, with the increasing status of immunotherapy in the treatment of advanced gastric cancer, a growing number of domestic and international clinical studies shown that immunotherapy could achieve better efficacy in the neoadjuvant therapy and conversion therapy for patients with advanced gastric cancer. This paper reviews the current research progress on the application of PD-1 inhibitors in the neoadjuvant therapy and conversion therapy of gastric cancer.

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