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.

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.

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.

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.

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.

OBJECTIVE T o explore the clinical characteristics and risk factors for plastic bronchitis(PB)in the chil-dren with Mycoplasma pneumoniae pneumonia(MPP).METHODS A retrospective case-control study was con-ducted for the medical data of the children with MPP who hospitalized in pediatrics department of Affiliated Hos-pital of Jining Medical College and underwent bronchoscopy and bronchoalveolar lavage from Jan.2023 to Dec.2024.The enrolled children were divided into the PB group and the non-PB group according to the status of complication with PB.The baseline data,clinical characteristics,laboratory test indexes,imaging features,bron-choscopy findings and treatment outcomes were observed and compared between the two groups of children.RESULTS A total of 734 children with MPP were included in the study,131 of whom were assigned as the PB group,and 603 were assigned as the non-PB group.The children were younger[4.83(1.88,7.00)years],the du-ration of fever was longer,the peak temperature was higher[39.50(39.20,39.80)℃],the percentage of compli-cation with pleural effusion was higher(33.59％),the percentage of extrapulmonary organs involved was higher(27.48％),the levels of white blood cells,neutrophils percentage,C-reactive protein(CRP),lactic dehydrogen-ase(LDH),D-dimer(DD)and alanine aminotransferase(ALT)were higher in the PB group than in the non-PB group,and there were significant differences(P＜0.05).There were significant differences in the percentage of mucosal necrosis under bronchoscopy,number of times of treatments assisted by bronchoscopy and length of hospital stay between the two groups(P＜0.05).CONCLUSIONS The MPP children with PB are characterized by younger rage,longer duration of fever,higher peak temperature,higher percentage of complication with pleural effusion,extrapulmonary organs more likely to be involved,more intensive inflammatory reactions and higher percentage of mucosal necrosis under bronchoscopy.Some of the children need to be treated repeatedly with assis-tance of bronchoscopy,and the length of hospital stay is long.

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.

OBJECTIVE T o explore the clinical characteristics and risk factors for plastic bronchitis(PB)in the chil-dren with Mycoplasma pneumoniae pneumonia(MPP).METHODS A retrospective case-control study was con-ducted for the medical data of the children with MPP who hospitalized in pediatrics department of Affiliated Hos-pital of Jining Medical College and underwent bronchoscopy and bronchoalveolar lavage from Jan.2023 to Dec.2024.The enrolled children were divided into the PB group and the non-PB group according to the status of complication with PB.The baseline data,clinical characteristics,laboratory test indexes,imaging features,bron-choscopy findings and treatment outcomes were observed and compared between the two groups of children.RESULTS A total of 734 children with MPP were included in the study,131 of whom were assigned as the PB group,and 603 were assigned as the non-PB group.The children were younger[4.83(1.88,7.00)years],the du-ration of fever was longer,the peak temperature was higher[39.50(39.20,39.80)℃],the percentage of compli-cation with pleural effusion was higher(33.59％),the percentage of extrapulmonary organs involved was higher(27.48％),the levels of white blood cells,neutrophils percentage,C-reactive protein(CRP),lactic dehydrogen-ase(LDH),D-dimer(DD)and alanine aminotransferase(ALT)were higher in the PB group than in the non-PB group,and there were significant differences(P＜0.05).There were significant differences in the percentage of mucosal necrosis under bronchoscopy,number of times of treatments assisted by bronchoscopy and length of hospital stay between the two groups(P＜0.05).CONCLUSIONS The MPP children with PB are characterized by younger rage,longer duration of fever,higher peak temperature,higher percentage of complication with pleural effusion,extrapulmonary organs more likely to be involved,more intensive inflammatory reactions and higher percentage of mucosal necrosis under bronchoscopy.Some of the children need to be treated repeatedly with assis-tance of bronchoscopy,and the length of hospital stay is long.

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.

Objectives:To explore the feasibility of zero-ray radiofrequency catheter ablation for paroxymal atrial fibrillation under the guidance of transthoracic echocardiography combined with three-dimensional mapping system.Methods:This is a single-center prospective observational study.A total of 12 patients with paroxysmal atrial fibrillation who underwent radiofrequency catheter ablation in Fuwai Hospital,Chinese Academy of Medical Sciences from June 1,2024 to September 30,2024 were included.All patients underwent successful percutaneous puncture,atrial septal puncture under the guidance of transthoracic echocardiography,and all patients underwent left atrial modeling and discharge ablation under the guidance of transthoracic echocardiography combined with three-dimensional mapping system.The disappearance of pulmonary vein potential was confirmed after the ablation operation and as the ablation endpoint and successful ablation marker.The operation results and 1-month and 3-month follow-up results of the patients were observed.Results:There were 12 patients with paroxysmal atrial fibrillation,9 males and 3 females,aged(56.8±11.2)years,with a history of paroxysmal atrial fibrillation(4.2±2.3)years.The mean left atrial diameter was(36.5±2.5)mm,the left ventricular end-diastolic diameter was(47.8±4.1)mm,and the left ventricular ejection fraction was 55%-65%.The mean overall operation time was(102.25±14.51)min,the ultrasound operation time was(29.58±6.23)min,and the catheter operation time was(33.08±4.10)min.All patients completed circumferential pulmonary vein isolation without intraoperative complications.The hospitalization time was 2-6 days.At the 1-month follow-up after ablation,all patients showed sinus rhythm on 24-hour ambulatory electrocardiogram,and 2 patients had occasional atrial premature contractions without recurrence of atrial fibrillation.At the 3-month follow-up,two patients had occasional premature atrial contractions,and no recurrence of atrial fibrillation was recorded on the electrocardiogram of all patients.Conclusions:It is feasible to complete radiofrequency catheter ablation of paroxysmal atrial fibrillation under the guidance of transthoracic echocardiography combined with three-dimensional mapping system.