1.Endothelial cell-specific bone morphogenetic protein 2 affects angiogenesis:bioinformatics analysis and experimental validation
Ru YAN ; Kairu WANG ; Feiyan ZHANG ; Shaobin JIA ; Guangzhi CONG
Chinese Journal of Tissue Engineering Research 2025;29(1):103-110
BACKGROUND:Angiogenesis is the main treatment target of cardiovascular diseases.Bone morphogenetic protein 2 can modulate angiogenesis,but the regulatory effect of endothelial cell-specific bone morphogenetic protein 2 on angiogenesis is unclear. OBJECTIVE:To investigate the effect of endothelial-specific bone morphogenetic protein 2 on angiogenesis. METHODS:(1)Bioinformatics analysis:Cellular expression specificity and abundance of bone morphogenetic protein 2 were meta-analyzed by the PanglaoDB single-cell transcriptome database.The endothelial cell transcriptome sequencing dataset of the mouse hindlimb model and endocardial transcriptome dataset of mice overexpressing bone morphogenetic protein 2 were reanalyzed to evaluate the effect of endothelial cell bone morphogenetic protein 2 on the angiogenesis pathway.(2)Validation in vivo:After establishing the mouse hindlimb model,we compared the blood perfusion between the affected and sham limb at 7,14,and 21 days.The expression of the colocation of bone morphogenetic protein 2 and CD31 was explored by immunofluorescence and immunohistochemical staining.(3)Validation in vitro:The cultured human umbilical vein endothelial cells in vitro were divided into a control group,a hypoxia group,and a bone morphogenetic protein 2 inhibitor Noggin intervention group.After being cultured for 24 hours,the angiogenesis of endothelial cells in each group was observed. RESULTS AND CONCLUSION:(1)Endothelial cells are an important cell subgroup expressing bone morphogenetic protein 2.Both in the mouse hindlimb ischemia model and endocardial cells overexpressing bone morphogenetic protein 2,bone morphogenetic protein 2 was significantly up-regulated,and the angiogenesis pathway was significantly activated.(2)In the mouse hindlimb model,bone morphogenetic protein 2-positive blood vessels around neoangiogenesis increased significantly at 7 days of ischemia(P<0.05),and decreased significantly after 2 weeks of ischemia(P<0.001).(3)In umbilical vein endothelial cells cultured in vitro,after hypoxic intervention,the migration and sprouting of endothelial cells increased significantly,and the expression of angiogenesis factors vascular endothelial growth factor and platelet-derived growth factor was significantly increased.Noggin significantly reduced hypoxia-induced endothelial cell angiogenesis(P<0.001)and down-regulated the expression of vascular endothelial growth factor and platelet-derived growth factor(P<0.01).(4)These findings verify that endothelial cell-specific bone morphogenetic protein 2 can regulate angiogenesis,and targeting endothelial cell bone morphogenetic protein 2 is a promising way to improve angiogenesis.
2.Establishment of Content Determination Method of Zhihuoding Granules Based on Anti-inflammatory Activity and Fingerprint
Xin ZENG ; Guangzhi SHAN ; Wenling SU ; YIDERESI·MOLA ; Yue WANG ; Jianguo XING
Herald of Medicine 2025;44(7):1028-1034
Objective To establish the content determination method of Zhihuoding granules(ZHDG)by the anti-inflammatory active ingredients and fingerprint.Methods The inflammatory model of BEAS-2B cells was established by LPS(10 μg·mL-1)stimulation for 24 h,and the level of TNF-α in the supernatant was detected by enzyme-linked immunosorbent assay(ELISA).Using the reverse high-performance liquid chromatography(RP-HPLC)of 7 batch ZHDG fingerprint;HPLC was used to determine the content of geniposide and baicalin in granules.Results Compared with LPS Group,ZHDG,prim-O-glucosylcimifugin,5-O-methylvisammioside,baicalin,geniposide,and total polysaccharide extract all significantly decreased TNF-αlevels in BEAS-2B cells induced by LPS(P<0.05).Fingerprint spectra of 7 batches of ZHDG were established,with a similarity of 1.000 to the reference.A total of 15 peaks were calibrated,and 7 chromatographic peaks were identified.Gardenin and baicalin were selected as the index components of ZHDG for evaluation.The established method was rapid and accurate.Conclusion The method for the determination of baicalin and geniposide in ZHDG are exclusive,accurate,and effective,providing reference for the quality control and clinical application of ZHDG.
3.Spermidine/spermine N1-acetyltransferase 1 participates in vascular smooth muscle cell calcification
Kairu WANG ; Shizhe FU ; Jiahui LI ; Ru YAN ; Yuru MA ; Bo SHI ; Congyan YE ; Rui YAN ; Guangzhi CONG ; Shaobin JIA
Chinese Journal of Tissue Engineering Research 2025;29(32):6836-6842
BACKGROUND:Polyamines play a crucial role in tissue calcification.Spermidine/spermine N1-acetyltransferase 1(SAT1),as a key rate-limiting enzyme regulating intracellular polyamine metabolism,has been associated with various pathological processes.However,its role in vascular calcification remains unclear.OBJECTIVE:To investigate the role of SAT1 in rat vascular smooth muscle cell calcification.METHODS:(1)Bioinformatics analysis:Differential expression of SAT1 in human carotid atherosclerotic plaques and their surrounding healthy carotid artery tissues were using GEO datasets.PanglaoDB database was used to analyze SAT1 expression abundance and localization across different cell types through single-cell sequencing.(2)Rat vascular smooth muscle cells were divided into three groups:a control group cultured in DMEM medium,a calcification group induced by DMEM medium containing 10 mmol/L β-glycerophosphate sodium and 3 mmol/L calcium chloride,and the 50,100 μmol/L diacetylaminotriazamidine groups treated with the SAT1 inhibitor,diacetylaminotriazamidine,in addition to the calcification medium.After 7-10 days of culture,alizarin red S staining was performed,and cellular calcium content and alkaline phosphatase activity were assessed.Western blot was used to detect the protein expression of Runt-related transcription factor 2,bone morphogenetic protein 2,alpha-smooth muscle actin,and SAT1.Immunofluorescence staining was conducted to examine the expression of Runt-related transcription factor 2 and SAT1.RESULTS AND CONCLUSION:(1)Bioinformatics analysis revealed significantly upregulated expression of SAT1 and Runt-related transcription factor 2(P<0.05)in carotid atherosclerotic plaques compared with healthy carotid tissues(P<0.05).Single-cell sequencing database analysis confirmed SAT1 expression in vascular smooth muscle cells.(2)Compared with the control group,the calcification group showed significantly increased Runt-related transcription factor 2,bone morphogenetic protein 2,SAT1,calcium content,and alkaline phosphatase activity,while alpha-smooth muscle actin expression was significantly decreased(all P<0.05).Compared with the calcification group,the 50 and 100 μmol/L diacetylaminotriazamidine groups showed significantly decreased Runt-related transcription factor 2,bone morphogenetic protein 2,calcium content,and alkaline phosphatase activity,while alpha-smooth muscle actin expression was significantly increased(all P<0.05).(3)Immunofluorescence experiments demonstrated that compared with the calcification group,the expression intensity of Runt-related transcription factor 2 was significantly reduced in the 50 and 100 μmol/L diacetylaminotriazamidine groups.Overall,SAT1 may promote vascular smooth muscle cell calcification by upregulating Runt-related transcription factor 2 expression.
4.Transcatheter closure of atrial septal defect using fully biodegradable occluder under ultrasound guidance: A case report
Ying' ; ao ZHAO ; Yiming YAN ; Ziping LI ; Hang LI ; Fengwen ZHANG ; Fang FANG ; Guangzhi ZHAO ; Jing DONG ; Chuangshi WANG ; Jiande WANG ; Wenbin OUYANG ; Xiangbin PAN
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2025;32(12):1796-1799
Currently, transcatheter intervention is the preferred treatment for patients with anatomically suitable atrial septal defects. However, the use of nickel-titanium alloy occluders in interventional procedures results in lifelong presence of the implant in the body, leading to complications such as metal allergies and arrhythmias in some patients. To overcome the short-term and long-term complications associated with the presence of metal, and to avoid radiation exposure and metal toxicity, this paper reports a case of successful transcatheter closure of atrial septal defect in a pediatric patient with metal allergies using fully biodegradable occluder under ultrasound guidance, achieving excellent results by interventional therapy.
5.Clinical efficacy of transcatheter edge-to-edge repair in patients with non-central degenerative mitral regurgitation
Peijian WEI ; Junke CHANG ; Jianrui MA ; Guangzhi ZHAO ; Jing DONG ; Cheng WANG ; Fengwen ZHANG ; Shiguo LI ; Fujian DUAN ; Wenbin OUYANG ; Shouzheng WANG ; Fang FANG ; Xiangbin PAN
Chinese Journal of Cardiology 2025;53(4):373-381
Objective:To evaluate the clinical efficacy of mitral valve transcatheter edge-to-edge repair (TEER) in patients with non-central degenerative mitral regurgitation (DMR).Methods:This retrospective study included patients with non-central DMR who underwent TEER at Fuwai Hospital between January 2021 and February 2024. Patients were categorized into two groups: the commissure-involved group and the non-commissure group, based on whether the mitral valve commissures were involved. Clinical data, surgical outcomes, and echocardiographic findings at 3 months postoperatively were collected and compared, and patients were followed up. The primary endpoint was the procedural success rate at discharge.Results:A total of 59 patients were included, aged (68.6±9.3) years, including 23 females (39%). In the overall study population, 78% (46/59) of patients had severe mitral regurgitation. Forty-two cases were in the non-commissure group, and 17 cases were in the commissure-involved group. Patients in the non-commissure group mainly had lesions in the A1/P1 region, while patients in the commissure-involved group mainly had lesions in the A3/P3 region. There was no significant difference in the procedural success rate at discharge (93% vs. 88%, P=0.95) and the incidence of postoperative complications (5% vs. 6%, P=1.00) between the two groups. Two patients in the commissure-involved group experienced single leaflet device attachment, with one of them requiring conversion to surgical mitral valve surgery; In the non-commissure group, two patients experienced single-valve clamping, and one of them was converted to surgical mitral valve surgery. The follow-up time of the entire cohort was (15.5±10.3) months. In the non-commissure group, 2 patients died and 2 were readmitted. While in the commissure-involved group, no patients died and only 1 patient was readmitted. Conclusion:TEER is an effective treatment for patients with non-central DMR involving the commissures, without increasing the incidence of postoperative complications.
6.Expert consensus on clinical practice of image-guided multimodal thermal ablation for pulmonary tumors
Guangzhi WANG ; Fangfang XIE ; Rong LUO ; Jijin YANG ; Jiayuan SUN ; Yueyong XIAO
Chinese Journal of Interventional Imaging and Therapy 2025;22(6):369-374
Multimodal tumor therapy system is an integrated treatment system that combined deep cryoablation and radiofrequency ablation(RFA),with key benefit of remodeling tissue properties through cryoablation process,reduce local impedance,blood perfusion and thermal insulation effects of gases,thereby considerably boosting the efficiency and reach of subsequent RFA.Interventional Physician Branch of Shanghai Medical Doctor Association,the Solid Tumor Theranostics Committee of the Shanghai Anti-Cancer Association,Chinese Anti-Cancer Association Committee of Tumor Minimally Invasive Therapy and the Innovative and Translational Consortium for Tumor Multi-Modal Minimally Invasive Diagnosis and Treatment of Chinese Society of Biomedical Engineering organized relevanted experts in the field of tumor treatment in China to discuss and formulated this expert consensus,in order to standardize the procedures of multimodal ablation therapy for pulmonary tumors and enhance therapeutic effectiveness.
7.Echocardiography-guided Transcatheter Aortic Valve Replacement After Aortic Bioprosthetic Failure:a Case Report
Guangzhi ZHAO ; Shouzheng WANG ; Xiangbin PAN
Chinese Circulation Journal 2025;40(3):290-292
This article reports a case of transcatheter aortic valve replacement guided by echocardiography only for the treatment of aortic valve bioprosthesis failure.The patient developed bioprosthesis stenosis eight years after surgical bioprosthetic aortic valve replacement and underwent successful transcatheter aortic valve-in-valve replacement under echocardiography guidance.This offers a new treatment option for valve replacement after bioprosthetic valve failure under echocardiography guidance,and demonstrates the feasibility of echocardiography-guided interventional transcatheter valve-in-valve replacement.Also,this report discusses the technique details in valve positioning,reducing the risk of complications and improving prognosis.
8.Two Cases of Transcatheter Aortic Valve Replacement Guided by Echocardiography Alone for Severe Aortic Stenosis
Shouzheng WANG ; Guangzhi ZHAO ; Xiaopeng HU ; Hao SHI ; Bo PENG ; Xu WANG ; Xiangbin PAN
Chinese Circulation Journal 2025;40(3):284-289
Transcatheter aortic valve replacement(TAVR)has become an important therapeutic approach for severe aortic stenosis.However,complications associated with TAVR cannot be overlooked,among which contrast agents induced acute kidney injury(AKI)is a common complication.To explore methods to reduce the occurrence of AKI,this article reports two cases of successful treatment of severe aortic stenosis by TAVR under pure echocardiographic guidance,both of whom were elderly women aged 75 and 69,respectively,and both were implanted with a Evolute Pro 26 mm valve.Postoperative echocardiography showed good valve positioning and function.
9.Exploration on the mechanism of curcumin in intervening leukemia based on transcriptomics and network pharmacology
Guangzhi YU ; Na LI ; Zongxuan HUANG ; Sen WANG ; Fengyun DONG
Journal of Chinese Physician 2025;27(8):1162-1166
Objective:To explore the mechanism of curcumin (Cur) in intervening leukemia based on transcriptomics and network pharmacology.Methods:(1) Cell proliferation experiment: Leukemia MV-4-11 cells were cultured in vitro and divided into the control group (DMSO), 15 μmol/L curcumin group (Cur 15 μmol/L), and 20 μmol/L curcumin group (Cur 20 μmol/L). The CFSE method by flow cytometry was used to determine the inhibitory effect of curcumin on the growth of leukemia MV-4-11 cells at 0, 24, and 48 hours. (2) Network pharmacology analysis: the Smiles number of curcumin was obtained using the PubChem database. The targets of curcumin were retrieved from SwissTargetPrediction, SEA, TTD, and CTD platforms. Leukemia-related targets were screened using Genecards, OMIM, TTD, and CTD databases, and the intersection targets of curcumin-leukemia were further collected. (3) Transcriptomics and network pharmacology analysis: RNA from MV-4-11 cells in the control group and Cur group was collected, transcriptome sequencing was performed, and the common targets of differential genes in network pharmacology and transcriptomics were collected. The STRING website and Cytoscape software were used to construct a protein-protein interaction (PPI) network for the intersection targets. The David database and micro-bioinformatics were used for enrichment analysis based on gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases. Finally, the core targets and main pathways of curcumin in anti-leukemia were screened out.Results:(1) Compared with the control group, 15 μmol/L and 20 μmol/L curcumin significantly inhibited the proliferation of MV-4-11 cells (all P<0.05). (2) Network pharmacology analysis showed 1 209 curcumin drug targets and 7 702 leukemia-related targets, with 901 intersection targets for curcumin′s anti-leukemia effect. (3) Transcriptome sequencing showed 14 714 genes expressed in the curcumin group and 13 689 genes in the control group, with a total of 3 064 differentially expressed genes, including 2 189 up-regulated genes and 875 down-regulated genes. There were 182 intersection targets between network pharmacology and transcriptomics. KEGG enrichment results indicated that the anti-leukemia targets of curcumin were mainly related to cancer signaling pathways, phosphatidylinositol-3-kinase signaling pathway (PI3K-Akt) signaling pathway, and mitogen-activated protein kinase (MAPK) signaling pathway. Conclusions:This study obtained the gene expression profile of curcumin acting on leukemia and elaborated the molecular mechanism of inhibiting leukemia cell proliferation, which is mainly involved in cancer signaling pathways, PI3K-Akt signaling pathway, MAPK signaling pathway, etc., indicating that the inhibitory effect of curcumin on leukemia is multi-faceted and multi-level.
10.Relationship of concomitant anxiety and depression with serum inflammatory indicators in acute coronary syndrome patients
Mingrui WANG ; Yunzhi ZHANG ; Guangzhi LI ; Jing ZHANG ; Tingting YUN
Chinese Journal of Geriatric Heart Brain and Vessel Diseases 2025;27(8):1016-1020
Objective To analyze the influence of anxiety and depression on postoperative recovery of patients with acute coronary syndrome(ACS),and to analyze the relationship with neutrophil to lymphocyte ratio(NLR),lymphocyte to monocyte ratio(LMR)and platelet-to-lymphocyte ratio(PLR).Methods A total of 108 ACS patients undergoing surgical treatment in Hainan Provincial Anning Hospital from March 2022 to March 2024 were retrospectively recruited.According to their scores of Hamilton anxiety scale and Hamilton depression scale,they were divided into an anxiety and depression group(34 cases)and a non-anxiety and depression group(74 cases).The quality of life at 1 month after surgery and serum levels of NLR,LMR and PLR at 3 d after surgery were compared between groups.Spearman correlation analysis was performed to analyze the correlation between serum NLR,LMR and PLR and anxiety as well as depression in the ACS patients.Binary logistic regression analysis was used to construct an evaluation model with NLR,LMR and PLR as variables.Receiver operating characteristic(ROC)curve was plotted to analyze the value of serum NLR,LMR and PLR in evaluating anxiety and depression.Results At 1 month after surgery,the scores of dimensions of Short-Form 36 Questionnaire(SF-36)were significantly lower in the anxiety and depression group than the non-anxiety and depression group(P<0.01).The levels of serum NLR and PLR at 3 d post-operatively were obviously higher while that of LMR was notably lower in the anxiety and depression group than the non-anxiety and depression group(P<0.01).Spearman correlation analysis indicated that serum NLR and PLR levels(r=0.500,P=0.000;r=0.215,P=0.026)were positively correlated,and LMR level(r=-0.474,P=0.000)was negatively correlated with co-occurrence of anxiety and depression in the ACS patients.Binary logistic regression analysis suggested that NLR,LMR and PLR were high risk factors for anxiety and depression in ACS patients(OR=6.867,95%CI:2.792-16.887,P=0.000;OR=0.180,95%CI:0.078-0.419,P=0.000;OR=1.285,95%CI:1.038-1.591,P=0.032).ROC curve analysis showed that the AUC value of the three indicators combined together in evaluating anxiety and depression in the ACS patients was 0.900(95%CI:0.827-0.949,P=0.000),with a sensitivity of 73.53%and a specificity of 95.95%.The efficiency of combined evalu-ation was superior to that of each indicator.Conclusion Anxiety and depression can affect the postoperative recovery and serum NLR,LMR and PLR in ACS patients.Early combined detection of the three indicators can provide certain value for whether ACS patients are complicated with anxiety and depression.

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