Activation of the p62-Keap1-Nrf2 pathway improves pulmonary arterial hypertension in MCT-induced rats by inhibiting autophagy.

Autophagy is implicated in the pathogenesis of pulmonary arterial hypertension (PAH). We aimed to investigate whether the p62-Keap1-Nrf2 pathway affects the development of PAH by mediating autophagy. A PAH rat model was established using monocrotaline (MCT). Pulmonary artery smooth muscle cells (PASMCs) were extracted, and the changes in proliferation, migration, autophagy, and oxidative stress were analyzed following overexpression or knockdown of p62. The impact of p62 on the symptoms of PAH rats was assessed by the injection of an adenovirus overexpressing p62. We found that the knockdown of p62 increased the proliferation and migration of PASMCs, elevating the oxidative stress of PASMCs and upregulating gene expression of NADPH oxidases. Co-IP assay results demonstrated that p62 interacted with Keap1. p62 knockdown enhanced Keap1 protein stability and Nrf2 ubiquitination. LC3II/I and ATG5 were expressed more often when p62 was knocked down. Treating with an inhibitor of autophagy reversed the impact of p62 knockdown on PASMCs. Nrf2 inhibitor treatment reduced the expression of Nrf2 and p62, while increasing the expression of Keap1, LC3II/I, and ATG5 in PASMCs. However, overexpressing p62 diminished mRVP, SPAP, and Fulton index in PAH rats and attenuated pulmonary vascular wall thickening. Overexpression of p62 also decreased the expression of Keap1, LC3II/I, and ATG5 and increased the nuclear expression of Nrf2 in PAH rats. Importantly, overexpression of p62 reduced oxidative stress and the NADPH oxidase expression in PAH rats. Overall, activation of the p62-Keap1-Nrf2 positive feedback signaling axis reduces the proliferation and migration of PASMCs and alleviates PAH by inhibiting autophagy and oxidative stress.

Platelet-derived growth factor subunit-B mediating the effect of dickkopf-1 on acute myocardial infarction risk: a two-step Mendelian randomization study.

Previous studies have indicated a potential connection between plasma levels of Dickkopf-1 (DKK1) and platelet-derived growth factor subunit-B (PDGF-B) with the development of atherosclerosis. However, the causal relationship between DKK1, PDGF-B, and the risk of acute myocardial infarction (AMI) is yet to be established. To address this research gap, we conducted Mendelian randomization (MR) and mediation analyses to investigate the potential mediating role of PDGF-B in the association between DKK1 and AMI risk. Summary statistics for DKK1 (n = 3,301) and PDGF-B (n = 21,758) were obtained from the GWAS meta-analyses conducted by Sun et al. and Folkersen et al., respectively. Data on AMI cases (n = 3,927) and controls (n = 333,272) were retrieved from the UK Biobank study. Our findings revealed that genetic predisposition to DKK1 (odds ratio [OR]: 1.00208; 95% confidence interval [CI]: 1.00056-1.00361; P = 0.0072) and PDGF-B (OR: 1.00358; 95% CI: 1.00136-1.00581; P = 0.0015) was associated with an increased risk of AMI. Additionally, genetic predisposition to DKK1 (OR: 1.38389; 95% CI: 1.07066-1.78875; P = 0.0131) was linked to higher PDGF-B levels. Furthermore, our MR mediation analysis revealed that PDGF-B partially mediated the association between DKK1 and AMI risk, with 55.8% of the effect of genetically predicted DKK1 being mediated through genetically predicted PDGF-B. These findings suggest that genetic predisposition to DKK1 is positively correlated with the risk of AMI, and that PDGF-B partially mediates this association. Therefore, DKK1 and PDGF-B may serve as promising targets for the prevention and treatment of AMI.

Investigating the causal effect of Dickkopf-1 on coronary artery disease and ischemic stroke: a Mendelian randomization study.

Epidemiological investigations have indicated a correlation between elevated plasma levels of Dickkopf-related protein 1 (DKK1) and the presence of atherosclerosis. However, the exact causal relationship of DKK1 with the development of coronary artery disease (CAD) and ischemic stroke (IS) remains unclear. To address this gap, our study aimed to explore their causal association using a two-sample Mendelian randomization (MR) approach. We obtained summary statistics from genome-wide association studies (GWAS) meta-analyses conducted by Folkersen et al. and Nikpay et al., which included data from 21,758 individuals for DKK1 and 42,096 cases of CAD. Additionally, we obtained data from the FinnGen biobank analysis round 5, which included 10,551 cases of IS. Eight MR methods were employed to estimate causal effects and detect directional pleiotropy. Our findings demonstrated that genetic liability to DKK1 was associated with increased risks of CAD (odds ratio [OR]: 1.087; 95% confidence interval [CI]: 1.024-1.154; P = 0.006) and IS (OR: 1.096; 95% CI: 1.004-1.195; P = 0.039). These results establish a causal link between genetic liability to DKK1 and elevated risks of CAD and IS. Consequently, DKK1 may represent a promising therapeutic target for the prevention and treatment of CAD and IS.

Case report: A novel mutation of RecQ-like helicase 5 in a Chinese family with early myocardial infarction, coronary artery disease, and stroke hemiplegia.

Background: Myocardial infarction (MI) is a type of severe coronary artery disease (CAD) that can lead to heart failure and sudden cardiac death. The prevalence of heart failure globally is estimated at 1%-2%, of which ∼60% of cases are the consequence of MI as the primary cause. At present, several disease-causing genes have been identified that may be responsible for MI, such as autophagy-related 16-like 1 (ATG16L1) and RecQ-like helicase 5 (RECQL5). Methods: In this study, we enrolled a Chinese family with MI, CAD, and stroke hemiplegia. Whole-exome sequencing was applied to analyze the genetic lesion of the proband. Sanger sequencing was used to validate the candidate mutation in five family members and 200 local control cohorts. Results: After data filtering, we detected a novel mutation (NM_004259: c.1247T>C/p.I416T) of RECQL5 in the proband. Sanger sequencing further validated that the novel mutation was existent in the affected individuals, including the proband's younger sister and her mother, and absent in the other healthy family members and 200 local control cohorts. Furthermore, bioinformatics analysis confirmed that the novel mutation, located in a highly evolutionarily conserved site, was predicted to be deleterious and may change the hydrophobic surface area and aliphatic index of RECQL5. Conclusion: Here, we report the second mutation (NM_004259: c.1247T>C/p.I416T) of RECQL5 underlying MI and CAD by whole-exome sequencing. Our study expanded the spectrum of RECQL5 mutations and contributed to genetic diagnosis and counseling of MI and CAD.

m6A regulator-mediated RNA methylation modification patterns are involved in the regulation of the immune microenvironment in ischaemic cardiomyopathy.

The role of RNA N6-methyladenosine (m6A) modification in the regulation of the immune microenvironment in ischaemic cardiomyopathy (ICM) remains largely unclear. This study first identified differential m6A regulators between ICM and healthy samples, and then systematically evaluated the effects of m6A modification on the characteristics of the immune microenvironment in ICM, including the infiltration of immune cells, the human leukocyte antigen (HLA) gene, and HALLMARKS pathways. A total of seven key m6A regulators, including WTAP, ZCH3H13, YTHDC1, FMR1, FTO, RBM15 and YTHDF3, were identified using a random forest classifier. A diagnostic nomogram based on these seven key m6A regulators could effectively distinguish patients with ICM from healthy subjects. We further identified two distinct m6A modification patterns (m6A cluster-A and m6A cluster-B) that are mediated by these seven regulators. Meanwhile, we also noted that one m6A regulator, WTAP, was gradually upregulated, while the others were gradually downregulated in the m6A cluster-A vs. m6A cluster-B vs. healthy subjects. In addition, we observed that the degree of infiltration of the activated dendritic cells, macrophages, natural killer (NK) T cells, and type-17 T helper (Th17) cells gradually increased in m6A cluster-A vs. m6A cluster-B vs. healthy subjects. Furthermore, m6A regulators, including FTO, YTHDC1, YTHDF3, FMR1, ZC3H13, and RBM15 were significantly negatively correlated with the above-mentioned immune cells. Additionally, several differential HLA genes and HALLMARKS signalling pathways between the m6A cluster-A and m6A cluster-B groups were also identified. These results suggest that m6A modification plays a key role in the complexity and diversity of the immune microenvironment in ICM, and seven key m6A regulators, including WTAP, ZCH3H13, YTHDC1, FMR1, FTO, RBM15, and YTHDF3, may be novel biomarkers for the accurate diagnosis of ICM. Immunotyping of patients with ICM will help to develop immunotherapy strategies with a higher level of accuracy for patients with a significant immune response.

Identification MNS1, FRZB, OGN, LUM, SERP1NA3 and FCN3 as the potential immune-related key genes involved in ischaemic cardiomyopathy by random forest and nomogram.

The immune molecular mechanisms involved in ischaemic cardiomyopathy (ICM) have not been fully elucidated. The current study aimed to elucidate the immune cell infiltration pattern of the ICM and identify key immune-related genes that participate in the pathologic process of the ICM. The differentially expressed genes (DEGs) were identified from two datasets (GSE42955 combined with GSE57338) and the top 8 key DEGs related to ICM were screened using random forest and used to construct the nomogram model. Moreover, the "CIBERSORT" software package was used to determine the proportion of infiltrating immune cells in the ICM. A total of 39 DEGs (18 upregulated and 21 downregulated) were identified in the current study. Four upregulated DEGs, including MNS1, FRZB, OGN, and LUM, and four downregulated DEGs, SERP1NA3, RNASE2, FCN3 and SLCO4A1, were identified by the random forest model. The nomogram constructed based on the above 8 key genes suggested a diagnostic value of up to 99% to distinguish the ICM from healthy participants. Meanwhile, most of the key DEGs presented prominent interactions with immune cell infiltrates. The RT-qPCR results suggested that the expression levels of MNS1, FRZB, OGN, LUM, SERP1NA3 and FCN3 between the ICM and control groups were consistent with the bioinformatic analysis results. These results suggested that immune cell infiltration plays a critical role in the occurrence and progression of ICM. Several key immune-related genes, including the MNS1, FRZB, OGN, LUM, SERP1NA3 and FCN3 genes, are expected to be reliable serum markers for the diagnosis of ICM and potential molecular targets for ICM immunotherapy.

Identification of m6A regulator-mediated RNA methylation modification patterns and key immune-related genes involved in atrial fibrillation.

The role of m6A in the regulation of the immune microenvironment in atrial fibrillation (AF) remains unclear. This study systematically evaluated the RNA modification patterns mediated by differential m6A regulators in 62 AF samples, identified the pattern of immune cell infiltration in AF and identified several immune-related genes associated with AF. A total of six key differential m6A regulators between healthy subjects and AF patients were identified by the random forest classifier. Three distinct RNA modification patterns (m6A cluster-A, -B and -C) among AF samples were identified based on the expression of 6 key m6A regulators. Differential infiltrating immune cells and HALLMARKS signaling pathways between normal and AF samples as well as among samples with three distinct m6A modification patterns were identified. A total of 16 overlapping key genes were identified by weighted gene coexpression network analysis (WGCNA) combined with two machine learning methods. The expression levels of the NCF2 and HCST genes were different between controls and AF patient samples as well as among samples with the distinct m6A modification patterns. RT-qPCR also proved that the expression of NCF2 and HCST was significantly increased in AF patients compared with control participants. These results suggested that m6A modification plays a key role in the complexity and diversity of the immune microenvironment of AF. Immunotyping of patients with AF will help to develop more accurate immunotherapy strategies for those with a significant immune response. The NCF2 and HCST genes may be novel biomarkers for the accurate diagnosis and immunotherapy of AF.

Effects of USF1 SNPs and SNP-Environment Interactions on Serum Lipid Profiles and the Risk of Early-Onset Coronary Artery Disease in the Chinese Population.

Background: Upstream transcription factor 1 (USF1) single-nucleotide polymorphisms (SNPs) are significantly associated with serum lipid levels in several different ethnic groups or populations, but their association with lipid levels and the risk of early-onset coronary artery disease (EOCAD) has not been reported in Han populations of southern China. Methods: Six USF1 SNPs (rs3737787, rs2774276, rs2516839, rs2516838, rs1556259, and rs2516837) were genotyped by next-generation sequencing (NGS) techniques in 686 control subjects and 728 patients with EOCAD. Results: The genotypic and allelic frequencies of the USF1 rs3737787 SNP were significantly different between the control and EOCAD groups. The subgroup analysis identified that the rs3737787T allele was related to a decreased risk of EOCAD, whereas the rs3737787C-rs2774276G-rs2516839A and rs3737787C-rs2774276G-rs2516839G haplotypes were related to an increased risk of EOCAD in men, and the rs3737787C-rs2774276G-rs2516839A and rs3737787T-rs2774276C-rs2516839A haplotypes were correlated with an increased risk of EOCAD in women (p < 0.05-0.01). Male rs3737787T allele carriers had lower low-density lipoprotein cholesterol (LDL-C), total cholesterol (TC), and triglyceride (TG) concentrations than the rs3737787T allele non-carriers (p < 0.01). The interactions of rs3737787 with alcohol consumption and rs2516839 with smoking affected serum TC and LDL-C levels in men, whereas the interaction of rs3737787 with alcohol consumption affected serum high-density lipoprotein cholesterol (HDL-C) levels and the rs2516839-smoking interaction affected serum TC levels in women (p I < 0.001). The expression levels of the USF1 mRNA, interleukin 1ß (IL-1ß), tumor necrosis factor-α (TNF-α), and interleukin 6 (IL-6) were significantly lower in controls than in patients with EOCAD, and rs3737787T allele carriers displayed lower IL-1ß, TNF-α, IL-6, and USF1 mRNA expression levels than the rs3737787T allele non-carriers. In addition, IL-1ß, TNF-α, and IL-6 expression levels were significantly positively correlated with USF1 mRNA levels (p < 0.01). Conclusion: Sex-specific correlations were identified between the USF1 rs3737787T allele with blood lipid levels and the risk of EOCAD. The USF1 rs3737787T allele affects the risk of EOCAD by modulating serum lipid levels and the expression of inflammatory factors, including IL-1ß, TNF-α, and IL-6.

Impact of the COVID-19 Pandemic on ST-Elevation Myocardial Infarction Management in Hunan Province, China: A Multi-Center Observational Study.

Background: This study aimed to investigate the impact of the COVID-19 pandemic on ST-segment elevation myocardial infarction (STEMI) care in China. Methods: We conducted a multicenter, retrospective cohort study in Hunan province (adjacent to the epidemic center), China. Consecutive patients presenting with STEMI within 12 h of symptom onset and receiving primary percutaneous coronary intervention, pharmaco-invasive strategy and only thrombolytic treatment, were enrolled from January 23, 2020 to April 8, 2020 (COVID-19 era group). The same data were also collected for the equivalent period of 2019 (pre-COVID-19 era group). Results: A total of 610 patients with STEMI (COVID-19 era group n = 286, pre-COVID-19 era group n = 324) were included. There was a decline in the number of STEMI admissions by 10.5% and STEMI-related PCI procedures by 12.7% in 2020 compared with the equivalent period of 2019. The key time intervals including time from symptom onset to first medical contact, symptom onset to door, door-to-balloon, symptom onset to balloon and symptom onset to thrombolysis showed no significant difference between these two groups. There were no significant differences for in-hospital death and major adverse cardiovascular events between these two groups. Conclusion: During the COVID-19 pandemic outbreak in China, we observed a decline in the number of STEMI admissions and STEMI-related PCI procedures. However, the key quality indicators of STEMI care were not significantly affected. Restructuring health services during the COVID-19 pandemic has not significantly adversely influenced the in-hospital outcomes.

The first case report of CODAS syndrome in Chinese population caused by two LONP1 pathogenic mutations.

Background: CODAS syndrome (MIM 600373) is a multi-system developmental disorder characterized by cerebral, ocular, dental, auricular, and skeletal anomalies. CODAS syndrome is rare in the world and no cases have been reported in Chinese population so far. Mutations in the LONP1 gene can contribute to CODAS syndrome, while the underlying molecular mechanisms requires further investigation. Method: We described a Chinese boy who has suffered from cognition impairment, cataracts, caries, abnormal auricle and skeletal anomalies since birth. The patient's parents are non-consanguineous and healthy. Whole-exome sequencing (WES) was employed to explore the genetic entity of this family. Results: A compound heterozygous missense mutation (NM_004793: c.2009C>T/p.A670V and c.2014C>T/p.R672C) of LONP1 was identified in the patient. Considering the clinical phenotypes and genetic results, the patient was diagnosed as CODAS syndrome. Conclusion: Here we reported the first case with CODAS syndrome in Chinese population. WES identified a compound heterozygous missense mutation of LONP1 gene in the patients. Our study not only provided data for genetic counseling and clinical diagnosis to this family, but also expanded the clinical spectrum of LONP1-related CODAS syndrome.

CXCR4 protects bone marrow-derived endothelial progenitor cells against hypoxia through the PI3K/Akt signaling pathway.

The present study aimed to investigate the regulatory mechanism of chemokine (C-X-C motif) receptor 4 (CXCR4) on endothelial progenitor cells (EPCs) through the phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) signaling pathway under hypoxic conditions. Mononuclear cells were isolated from the bone marrow (BM) of young Sprague-Dawley (SD) rats. Bone marrow-derived endothelial progenitor cells (BM-EPCs) were characterized by using Dil-labeled acetylated low-density lipoprotein (Dil-ac-LDL) and fluorescein isothiocyanate-labeled UEA (FITC-UEA-1). Phenotype identification of BM-EPCs was based on red cytoplasm and green cytomembrane. Flow cytometry was employed to examine the markers CD14, CD34, and KDR. Expression level of the EPC-specific surface marker CD14 was found to be negative, while the expression level of CD34 and KDR was positive. In addition, CXCR4 was stably overexpressed in BM-EPCs after transfection with adenovirus-CXCR4. Cell proliferation, migration and apoptosis abilities were measured through the application of CCK-8, followed by Transwell and flow cytometry assays. The expression level of CXCR4, PI3K and Akt was determined by reverse transcription-quantitative PCR and western blotting assays. Functional experiments demonstrated that hypoxia inhibited BM-EPC proliferation and migration, while accelerating BM-EPC apoptosis. Additionally, CXCR4 was found to promote proliferation and migration, and suppress apoptosis in BM-EPCs with or without hypoxia treatment. Evidence also demonstrated that CXCR4 markedly upregulated the expression levels of PI3K and Akt. Furthermore, PI3K inhibitor (LY294002) and CXCR4 inhibitor (AMD3100) effectively inhibited the proliferation, migration and resistance to apoptosis of CXCR4-mediated BM-EPCs under hypoxic conditions.

Zero contrast optical coherence tomography-guided percutaneous coronary intervention in patients with non-ST segment elevation myocardial infarction and chronic kidney disease.

OBJECTIVES: To investigate a strategy for ultra-low volume contrast percutaneous coronary intervention (PCI) with the aims of preserving renal function and observing the 90-day clinical endpoint in patients with non-ST-elevated myocardial infarction (non-STEMI) and chronic kidney disease (CKD). BACKGROUND: The feasibility, safety, and clinical utility of PCI with ultra-low radio-contrast medium in patients with non-STEMI and CKD are unknown. METHODS: A total of 29 patients with non-STEMI and CKD (estimated glomerular filtration rate [eGFR] of ≤60 ml/min/1.73 m2 ) were included. Ultra-low volume contrast PCI was performed after minimal contrast coronary angiography using zero contrast optical coherence tomography (OCT) guidance. Pre- and post-PCI angiographic measurements were performed using quantitative flow ratio (QFR) for pre-perfusion assessment and verifying improvement. RESULTS: The median creatinine level was 2.1 (inter-quartile range 1.8-3.3), and mean eGFR was 48 ± 8 ml/min/1.73 m2 pre-PCI. During the PCI procedure, OCT revealed 15 (52%) cases of abnormalities post-dilation. There was no significant change in the creatinine level and eGFR in the short- or long-term, and no major adverse events were observed. CONCLUSION: In non-STEMI patients with high-risk CKD who require revascularization, QFR and no contrast OCT-guided ultra-low contrast PCI may be performed safely without major adverse events.

Downregulated microRNA-330 suppresses left ventricular remodeling via the TGF-ß1/Smad3 signaling pathway by targeting SRY in mice with myocardial ischemia-reperfusion injury.

microRNAs (miRs) are essential in the development of heart failure. The aim of this study is to investigate the effect of microRNA-330 (miR-330) on left ventricular remodeling via the TGF-ß1/Smad3 signaling pathway by targeting the sex-determining region Y (SRY) in mice with myocardial ischemia-reperfusion injury (MIRI). Differentially expressed gene (DEG) in myocardial ischemia-reperfusion (IR) was screened out and the miR that targeted the DEG was also predicted and verified. A model of MIRI was established to detect the expression of miR-330, SRY, transforming growth factor-ß (TGF-ß1), and Sekelsky mothers against dpp3 (Smad3). To further investigate the role of miR-330 in MIRI with the involvement of SRY and TGF-ß1/Smad3 signaling pathway, the modeled mice were treated with different mimic, inhibitor, or small interfering RNA (siRNA) to observe the changes of the related gene expression, as well as the myocardial infarction size and volume of myocardial collagen. SRY was screened out and verified as a target gene of miR-330. The MIRI mice showed enlarged myocardial infarction size, increased volume of myocardial collagen, increased expression of miR-330, TGF-ß1 and Smad3, while decreased the expression of SRY. The MIRI mice treated with miR-330 inhibitor showed decreased myocardial infarction size, the volume of myocardial collagen, and expression of TGF-ß1 and Smad3 but promoted expression of SRY. Our findings demonstrated that downregulated miR-330 could suppress left ventricular remodeling to inhibit the activation of the TGF-ß1/Smad3 signaling pathway via negatively targeting of SRY in mice with MIRI. This can be a potential target in the strategy to attenuate patient suffering.

[Transthoracic echocardiography in transcatheter closure of atrial septal aneurysm combined with secoundum-type atrial septal defect].

OBJECTIVE: To explore the value of transthoracic echocardiography (TTE) in transcatheter closure of atrial septal aneurysm (ASA) combined with secoundum-type atrial septal defect (ASD). METHODS: Fourteen patients (3 males and 11 females) who had ASA combined with secoundum-type ASD were diagnosed by TTE or transesophageal echocardiography. The ASA projected to the right atrium in all patients. The width of basilar part was 13 approximately 24 (18.5+/-3.9) mm, and the vertical extent was 7 approximately 11(9.7+/-1.8) mm. Ten patients combined with single hole ASD and 4 patients with multiple hole ASD. Blood shifting from the left atrium to the right atrium was displayed in color Doppler in all patients. All patients were treated by transcatheter closure under the guiding of X fluoroscopy and TTE, and examined with TTE during the follow-up. RESULTS: Transcatheter closure was successfully performed by 14 occluders in all patients. No residual shunt was detected immediately by TTE after the procedure in all patients. During the 6 approximately 12 month follow-up, no residual shunt or occluder shifting was found, the dimensions of the heart became normal in 11 patients (79%) and were significantly decreased in 4. CONCLUSION: Transcatheter closure is feasible in patients with ASA combined with secoundum-type ASD, and extra attention must be paid to the specialty. TTE is very important in case selection before transcatheter closure, and it may be used to monitor and guide the procedure during transcatheter closure.

[Short and mid-term effects of percutaneous transcatheter closure of ventricular septal defects on the cardiac remodeling].

OBJECTIVE: To evaluate the short and mid-term changes of the cardiac morphology after percutaneous transcatheter closure of ventricular septal defects (VSD) with transthoracic echocardiography (TTE). METHODS: The left ventricular end-diastolic diameter (LVEDD), left ventricular end-diastolic volume (LVEDV), left atrial diameter (LAd), and right ventricular diameter (RVd) in 30 VSD patients were measured before the VSD closure,and on the 3rd day, 3rd month, and 6th month after the VSD closure by TTE. RESULTS: LVEDD and LVEDV significantly decreased on the 3rd day after the VSD closure compared with pre-VSD closure. LVEDD and LVEDV continuously decreased on the 3rd month and 6th month after the VSD closure. LAd was smaller on the 3rd month and 6th month after the VSD closure, but there was not significant difference between the 3rd and 6th month. RVd increased on the 3rd day after the VSD closure, while no significant difference was found among the 3rd month and 6th month before and after VSD closure. CONCLUSION: Percutaneous transcatheter VSD closure may effectively improve the cardiac remodeling in VSD patients in the short and mid-term follow-up.

[Simultaneous transcatheter therapy for ventricular septal defect combined with atrial septal defect].

OBJECTIVE: To access the possibility, methods and efficacy of simultaneous transcatheter therapy for ventricular septal defect ( VSD ) combined with atrial septal defect (ASD). METHODS: In 68 patients with VSD, four patients ranging from 3 to 24 years old were combined with ASD. The diameters of perimembranous VSD were 2 approximately 10.5 mm, and the diameters of secundum ASD were 4.6 approximately 7 mm under the echocardiography before the operation. Another 4 patients with VSD occluded by left ventriculography: 3 patients were occluded by VSD occluder first, and then occluded by ASD occuder. The other was only occluded by VSD occluder. RESULTS: All VSD was treated successfully at one time in 4 patients. The diameters of VSD occluder were 4, 8, 10, and 16 mm. ASD was occluded successfully at one time in 3 patients. The diameters of ASD occluder were 8, 10, and 10 mm. The successful rate of the operation was 100%. No complication occurred in the operation and follow-up. CONCLUSION: Simultaneous transcatheter closure for VSD combined with ASD is a safe, feasible and effective therapy.

[Effects of intracoronary diltiazem on no-reflow phenomenon after emergent percutaneous coronary intervention in patients with acute myocardial infarction].

OBJECTIVE: To assess the effects of intracoronary diltiazem on no-reflow phenomenon of infarct-related artery (IRA) after emergent percutaneous transluminal coronary angioplasty or/and intracoronary stenting (PTCA/Stenting) in the patients with acute myocardial infarction (AMI). METHODS: We studied 34 AMI patients with no-reflow phenomenon of IRA after emergent PTCA/Stenting between January 1999 and August 2005. Urokinase-treated group (n=16) was given intracoronary urokinase 30,0000 - 50,0000 units within 15 - 30 minutes between January 1999 and April 2002 while diltiazem-treated group (n=18) was given intracoronary diltiazem 0.5 - 2 mg within 10 - 30 minutes between May 2002 and August 2005. Fifteen minutes later, coronary arteriography (CAG) was performed and the thrombolysis in myocardial infarction (TIMI) flow grade was measured. RESULTS: No apparent change of TIMI flow grade was found between pre-administration and post-administration of intracoronary urokinase, but TIMI flow grade was significantly improved after intracoronary diltiazem (P<0.01). TIMI flow grade of diltiazem-treated group was significantly higher than that of urokinase-treated group after the administration (P<0.05). The percentage of the patients who reached TIMI flow grade 3 after the intracoronary administration was higher in the diltiazem-treated group than that in the urokinase-treated group (P<0.01). CONCLUSION: The intracoronary administration of diltiazem 0.5~2mg can effectively improve the no-reflow phenomenon after emergent PTCA/Stenting in patients with AMI.

[Therapeutic effect and safety of transcatheter occlusion of ventricular septal defects in 50 patients].

OBJECTIVE: To determine the therapeutic effect and safety of transcatheter closure of ventricular septal defects (VSD) in 50 patients. METHODS: Fifty patients were diagnosed by transthoracic echocardiography. To perform the operation, transthoracic echocardiography and X ray were used continuously to monitor the procedure. Transthoracic echocardiography and ECG were performed at 1, 3, and 6 months after the operation to evaluate the therapeutic effect. RESULTS: The VSD diameter ranged from 1.8 to 13.4 (5.54 +/- 2. 75) mm. The successful rate of the operation was 96.0%, and the complication rate of the operation was 16.7%. A 3 month follow-up was completed in 20 patients, and the median left ventricle end-diastolic dimension significantly decreased from (40.20 +/- 8.80) mm to (32.90 +/- 8.36) mm (P < 0.001). CONCLUSION: Transcatheter closure of ventricular septal defects is a good method with a high success rate of placement, fewer complications, and a good occlusion effect.

[Formation and function of coronary collateral circulation and their influencing factors].

OBJECTIVE: To clarify the formation and function of coronary collateral circulation (CCC) in coronary artery disease (CAD) patients with severe coronary artery stenosis and their influencing factors. METHODS: Coronary angiography was performed on 266 CAD patients with severe coronary stenosis. CCC formation was evaluated by Rentrop rating on those 266 patients and 401 severe stenosis arteries; while in CCC formed patients, CCC function was evaluated by Werner collateral collection (CC) rating. The formation, function of CCC and their influencing factors were analyzed and compared. RESULTS: CCC formation in those severe stenosis coronary arteries was related to the severity of coronary stenosis: the forming rate of CCC was 42.6% in vessels with 90%-94% stenosis (Group A), 56.9% with 95%-99% stenosis (Group B) and 93.0% with 100% stenosis (Group C) (p <0 .01). Between CCC forming and non-forming groups, there was no significant difference in age, gender, incidence of MI, hypertension and diabetes, history of smoking and serum levels of HDL-C and LDL-C (P > 0.05). In the CCC formation group, serum HDL-C level was the highest in the CC Grade 2 group (according to Werner function rating) and the lowest in the CC Grade 0 group (P < 0.05). Whereas, LDL-C level was the lowest in the CC Grade 2 group and the highest in the CC Grade 0 group (P < 0.05). CONCLUSION: Severity of coronary stenosis was the major influencing factor in CCC formation and function, and the rate of CCC formation increased with the exacerbation of coronary stenosis. Serum HDL-C and LDL-C level had no relationship with CCC formation, but related to CCC function. Better CCC function was found in patients with high level of HDL-C whereas the patients with high level of LDL-C had spoiled CCC function.