Identification and subtype analysis of biomarkers associated with the solute carrier family in acute myocardial infarction.

The dysregulation of some solute carrier (SLC) proteins has been linked to a variety of diseases, including diabetes and chronic kidney disease. However, SLC-related genes (SLCs) has not been extensively studied in acute myocardial infarction (AMI). The GSE66360 and GSE60993 datasets, and SLCs geneset were enrolled in this study. Differentially expressed SLCs (DE-SLCs) were screened by overlapping DEGs between the AMI and control groups and SLCs. Next, functional enrichment analysis was carried out to research the function of DE-SLCs. Consistent clustering of samples from the GSE66360 dataset was accomplished based on DE-SLCs selected. Next, the gene set enrichment analysis (GSEA) was performed on the DEGs-cluster (cluster 1 vs cluster 2). Three machine learning models were performed to obtain key genes. Subsequently, biomarkers were obtained through receiver operating characteristic (ROC) curves and expression analysis. Then, the immune infiltration analysis was performed. Afterwards, single-gene GSEA was carried out, and the biomarker-drug network was established. Finally, quantitative real-time fluorescence PCR (qRT-PCR) was performed to verify the expression levels of biomarkers. In this study, 13 DE-SLCs were filtered by overlapping 366 SLCs and 448 DEGs. The functional enrichment results indicated that the genes were implicated with amino acid transport and TNF signaling pathway. After the consistency clustering analysis, the samples were classified into cluster 1 and cluster 2 subtypes. The functional enrichment results showed that DEGs-cluster were implicated with chemokine signaling pathway and so on. Further, SLC11A1 and SLC2A3 were identified as SLC-related biomarkers, which had the strongest negative relationship with resting memory CD4 T cells and the strongest positive association with activated mast cells. In addition, the single-gene GSEA results showed that cytosolic ribosome was enriched by the biomarkers. Five drugs targeting SLC2A3 were predicted as well. Lastly, the experimental results showed that the biomarkers expression trends were consistent with public database. In this study, 2 SLC-related biomarkers (SLC11A1 and SLC2A3) were screened and drug predictions were carried out to explore the prediction and treatment of AMI.

Simplified stepwise anatomical ablation strategy for mitral isthmus: efficacy, efficiency, safety, and outcome.

AIMS: Bidirectional and durable block of mitral isthmus (MI) is essential for catheter ablation of persistent atrial fibrillation (PeAF) and perimitral flutter (PMF), but it remains a challenge. The aim of this study was to create a simple anatomical ablation strategy with minimal fluoroscopy that would yield a high success rate for MI block. METHODS AND RESULTS: Patients with PeAF or PMF were included. Mitral isthmus was ablated in a stepwise strategy. In Step 1, endocardial MI linear ablation was performed; in Step 2, ablation was targeted to the posterolateral portion of the left atrium along the MI line; in Step 3, epicardial ablation within the coronary sinus (CS) was performed across the MI line to the ostium of the vein of Marshall (VOM) or performed within the VOM if available; in Step 4, the catheter was rotated and ablated in the CS to isolate the CS; and in Step 5, the early activation site with complex component potential above the MI line during distal CS pacing was considered as the ablation target. All patients were followed up. A total of 178 (17 patients with mechanical prosthetic mitral valve) were included. One hundred and sixty-six patients achieved a confirmed MI bidirectional conduction block (93%). One patient had cardiac tamponade. Four patients showed re-conduction across the MI line during a repeated ablation. In the latest follow-up [12 (7, 16) months], 161 of 178 (90%) patients maintained their sinus rhythm. CONCLUSION: A simple stepwise anatomical ablation strategy for MI shows a high success rate with low fluoroscopy exposure.

Contribution of intracranial artery stenosis to white matter hyperintensities progression in elderly Chinese patients: A 3-year retrospective longitudinal study.

Background and purpose: There have been controversial results in previous studies for the association between intracranial artery stenosis (ICAS) and white matter hyperintensities (WMHs), and the correlation of ICAS with the progression of WMHs is uncertain. The aim of this study was to investigate the association between ICAS and the progression of WMHs. Methods: In this retrospective longitudinal study, we enrolled 302 patients aged 60 years and older who had received two brain MRI scans with a 3-year interval and was examined by CTA in the first MRI scan. We measured the stenosis of major intracranial arteries by CTA and assessed the progression of WMHs using the modified Rotterdam Progression scale (mRPS). We performed binary logistic regression analyses and established linear regression model to determine the relationship between the degree of ICAS and the progression of WMHs. Results: A total of 302 patients were enrolled, of which 48.3% experienced WMHs progression. After adjustment for confounding factors, the patients with Grade 2 ICAS had an OR of 2.8 (95% CI 1.4-5.5), and those with Grade 3 ICAS had an OR of 3.0 (95% CI 1.2-7.3) for the progression of WMHs. The ICAS degree remained associated with PVWMHs but had an attenuated relation to SCWMHs. ICAS severity was significantly associated with WMHs progression scores, higher for Grade 3 ICAS [ß (SE) = 0.18 (0.18)] followed by Grade 2 ICAS [ß (SE) = 0.10 (0.15)] compared with Grade 1 ICAS. Conclusions: Patients with more severe ICAS are more likely to have WMHs progression and have distinct relevancy to PVWMHs and SCWMHs, which may provide clues for understanding mechanisms of WMHs progression.

Fabrication of Rechargeable Photoactive Silk Fibroin/Polyvinyl Alcohol Blend Nanofibrous Membranes for Killing Bacteria.

Antibacterial materials that prevent bacterial infections and mitigate bacterial virulence have attracted great scientific interest. In recent decades, bactericidal polymers have been presented as promising candidates to combat bacterial pathogens. However, the preparation of such materials has proven to be extremely challenging. Herein, photoactive silk fibroin/polyvinyl alcohol blended nanofibrous membranes grafted with 3,3',4,4'-benzophenone tetracarboxylic dianhydride (G-SF/PVA BNM) were fabricated by an electrospinning technique. The premise of this work is that the G-SF/PVA BNM can store photoactive activity under light irradiation and release reactive oxygen species for killing bacteria under dark conditions. The results showed that the resultant G-SF/PVA BNM exhibited the integrated properties of an ultrathin fiber diameter (298 nm), good mechanical properties, robust photoactive activity and photo-store capacity, and great photoinduced antibacterial activity against E. coli and S. aureus (99.999% bacterial reduction with 120 min). The successful construction of blended nanofibrous membranes gives a new possibility to the design of highly efficient antibacterial materials for public health protection.

Impact of COVID-19 Pandemic on Mechanical Reperfusion in ST-Segment-Elevation Myocardial Infarction Undergoing Primary Percutaneous Coronary Intervention: A Multicenter Retrospective Study From a Non-epicenter Region.

Objective: The COVID-19 pandemic placed heavy burdens on emergency care and posed severe challenges to ST-segment-elevation myocardial infarction (STEMI) treatment. This study aimed to investigate the impact of COVID-19 pandemic on mechanical reperfusion characteristics in STEMI undergoing primary percutaneous coronary intervention (PPCI) in a non-epicenter region. Methods: STEMI cases undergoing PPCI from January 23 to March 29 between 2019 and 2020 were retrospectively compared. PPCI parameters mainly included total ischemic time (TIT), the period from symptom onset to first medical contact (S-to-FMC), the period from FMC to wire (FMC-to-W) and the period from door to wire (D-to-W). Furthermore, the association of COVID-19 pandemic with delayed PPCI risk was further analyzed. Results: A total of 14 PPCI centers were included, with 100 and 220 STEMI cases undergoing PPCI in 2020 and 2019, respectively. As compared to 2019, significant prolongations occurred in reperfusion procedures (P < 0.001) including TIT (420 vs. 264 min), S-to-FMC (5 vs. 3 h), FMC-to-W (113 vs. 95 min) and D-to-W (83 vs. 65 min). Consistently, delayed reperfusion surged including TIT ≥ 12 h (22.0 vs.3.6%), FMC-to-W ≥ 120 min (34.0 vs. 6.8%) and D-to-W ≥ 90 min (19.0 vs. 4.1%). During the pandemic, the patients with FMC-to-W ≥ 120 min had longer durations in FMC to ECG completed (6 vs. 5 min, P = 0.007), FMC to DAPT (24 vs. 21 min, P = 0.001), catheter arrival to wire (54 vs. 43 min, P < 0.001) and D-to-W (91 vs. 78 min, P < 0.001). The pandemic was significantly associated with high risk of delayed PPCI (OR = 7.040, 95% CI 3.610-13.729, P < 0.001). Conclusions: Even in a non-epicenter region, the risk of delayed STEMI reperfusion significantly increased due to cumulative impact of multiple procedures prolongation.

Prophylactic pulmonary vein isolation in typical atrial flutter patients without atrial fibrillation: a systematic review and meta-analysis of randomized trials.

BACKGROUND: New-onset atrial fibrillation (AF) is common after cavotricuspid isthmus (CTI)-dependent atrial flutter (AFL) ablation. The meta-analysis was conducted to evaluate the benefit of prophylactic pulmonary vein isolation (PVI) in typical AFL patients. METHODS: Randomized controlled trials (RCT) comparing prophylactic PVI to CTI ablation alone in typical AFL patients without prior documentation of AF were identified in the MEDLINE, EMBASE, and Cochrane databases. RESULTS: Four RCTs met the inclusion criteria. A total of 357 patients with follow-up of 20 ± 9 months were included. More patients in prophylactic PVI group were free from atrial arrhythmias (AA) compared with those in CTI group (69% versus 50%, OR = 2.36, 95% CI: 1.51 to 3.68; P = 0.0001). In the subgroup of age > 55, prophylactic PVI showed even higher incidence of freedom from AA. There is a lower occurrence of AF in prophylactic PVI group (27% versus 46%, OR = 0.45, 95% CI: 0.28 to 0.73; P = 0.001) and no difference of complications between prophylactic PVI group and CTI group (4% versus 2%; P = 0.33). CONCLUSION: Our study indicated the efficacy and safety of prophylactic PVI during CTI ablation in typical AFL patients without AF history, especially for elder patients. Large prospective RCTs are warranted to confirm the benefit of prophylactic PVI in typical AFL.

Everolimus (RAD001) inhibits the proliferation of rat vascular smooth muscle cells by up-regulating the activity of the p27/kip1 gene promoter.

OBJECTIVE: We investigated whether the inhibitory effect of the immunosuppressant everolimus (RAD001) on vascular smooth muscle cell (VSMC) proliferation is mediated by p27/kip1 gene promoter activity. METHODS: In this experimental study, cultured rat VSMCs were transiently transfected with a recombinant plasmid (pXp27) containing p27/kip1 gene promoter sequence and a chloramphenicol acetyltransferase (CAT) reporter gene. After stimulation with the mitogen platelet-derived growth factor (PDGF-BB, 10 ng/mL) in the presence or absence of RAD001 (10 nM), the promoter activity, mRNA expression, and protein expression of p27/kip1 were examined by CAT assay, RT-PCR, and immunoblotting, respectively. Cell cycle-related changes were detected by flow cytometry. DNA synthesis was determined using 3H-TdR incorporation. RESULTS: Compared with the non-stimulation group, PDGF-BB stimulation induced a significant proliferative response in the VSMCs as indicated by decreased p27/kip1 gene promoter activity, decreased p27/kip1 mRNA and protein expression, increased S-phase and G2/M-phase cells, and increased DNA synthesis. RAD001 intervention increased p27/kip1 gene promoter activity 3.5-fold, promoted p27/kip1 mRNA and protein expression, increased G0-phase cells, reduced DNA synthesis, and, overall, inhibited PDGF-BB-stimulated cell proliferation. CONCLUSION: RAD001 inhibits PDGF-BB-stimulated proliferation of cultured VSMCs by upregulating p27/kip1 gene promoter activity and increasing p27/kip1 mRNA and protein expression.

Exploring the substructural space of indole-3-carboxamide derivatives binding to renin: a novel active-site spatial partitioning approach.

Renin has recently attracted much attention in the antihypertensive community, since this enzyme starts the angiotensin-converting cascade and forms the rate-limiting step in this cascade. In the present study, we describe a new method called active-site spatial partitioning (ASSP) for quantitatively characterizing the nonbonding interaction profile between renin and the substructures of indole-3-carboxamide derivatives-a novel class of achiral renin inhibitors that exhibit both high affinity and strong specificity for renin, thus blocking its active state-on the basis of structural models of protein-ligand complexes. It is shown that the ASSP-derived potential parameters are highly correlated with the experimentally measured activities of indole-3-carboxamides; the statistical models linking the parameters and activities using a sophisticated partial least squares regression technique show much promise as an effective and powerful tool for generalizing and predicting the pharmaceutical potencies and the physicochemical properties of other modified derivatives. Furthermore, by visually examining substructure-color plots generated by the ASSP procedure, it is found that the relative importance of nonbonding contributions to the recognition and binding of a ligand by renin is as follows: steric < hydrophobic < electrostatic. The polar and charged moieties that float on the surface of the ligand molecule play a critical role in conferring electrostatic stability and specificity to renin-ligand complexes, whereas the aromatic rings embedded in the core region of the ligand are the main source of hydrophobic and steric potentials that lead to substantial stabilization of the complex architecture.

siRNA directed against Livin inhibits tumor growth and induces apoptosis in human glioma cells.

Livin, a novel member of the human inhibitors of apoptosis protein family, plays an important role in tumor progression and occurrence by inhibiting cell apoptosis. It is selectively expressed in the most common human neoplasms and appears to be involved in tumor cell resistance to chemotherapeutic agents. The present study was designed to investigate the potential of using RNA interference (RNAi) technique to downregulate Livin expression, and the subsequent effect on human glioma cells. The results showed that knockdown of Livin expression by short interfering RNA (siRNA) significantly inhibited glioma cell proliferation and increased cell apoptosis through cell arrest in the G(1)/G(0) phase of cell cycle in vitro. Furthermore, Livin siRNA significantly suppressed tumor growth in nude mice. Together, these findings suggest that RNAi-mediated downregulation of Livin expression could lead to potent antitumor activity in glioma cells and might serve as a novel therapeutic strategy in clinic.

Detection of C677T mutation of MTHFR in subject with coronary heart disease by hairpin probe with enzymatic color on microarray.

Molecular beacon (MB) is especially suited for detection of single nucleotide polymorphism (SNP), and the type of MB immobilized on the surface of microarray in particular, may detect multi-sample and multi-locus. However, the majority of MB needs to be labeled with fluorescence and quenching molecules on the two ends of the probe, and observed the reaction of fluorescence or complicated electrochemical signal produced hybridization of MB and target sequence by complex and expensive instruments. The "molecular beacon" and microarray designed appropriately in our study can produce visible light response signal induced by amplification effect of enzymatic color, and are avoided with the marker of fluorescence and quenching molecules and expensive instruments. The "molecular beacon" without fluorescence and quenching molecules is entitled as "hairpin DNA probe" by us for only the "hairpin" structure of traditional molecular beacon is adopted. The merits of two techniques, molecular beacon and amplification effect of enzymatic color, are successfully combined, and the technique is simple, sensitive and specific, to detect and compare the methylenetetrahydrofolate reductase (MTHFR) Gene C677T mutation of subjects between coronary heart disease (CHD) and control group. The results showed that MTHFR Gene C677T polymorphism is an independent risk factor for CHD.

Dendritic cells transfected with PD-L1 recombinant adenovirus induces T cell suppression and long-term acceptance of allograft transplantation.

The purpose of this study is to assess the potential of dendritic cells transfected with PD-L1 recombinant adenovirus induces CD8+ T cell suppression and kidney allograft tolerance. To prove it, DCs transfected with PD-L1 recombinant adenovirus (DC/Ad-PD-L1) were transferred into the MHC-mismatched rat kidney transplants. After kidney transplantation, the mixed lymphocyte reaction (MLR) assay and kidney function were analyzed. The results demonstrated that after administration of DC/Ad-PD-L1, the proliferation, cytokines secretion and activation marker expression of CD8+ T cells were suppressed. In addition, DC/Ad-PD-L1 could improve kidney function and survival of transplants. The findings suggested that DC/Ad-PD-L1 could induce CD8+ T cell tolerance and lead to kidney allograft tolerance, which provided a promising finding for clinical application.

Clinical efficiency and safety analysis of transcatheter closure of multiple atrial septal defects in adults.

BACKGROUND: Transcatheter closure of atrial septal defects (ASDs) is currently a reliable alternative to surgery, even though challenging in patients with multiple ASDs. HYPOTHESIS: The aim of this study was to evaluate the clinical efficiency and safety of transcatheter closure in multiple ASDs. METHODS: Multiple ASDs were diagnosed by transthoracic echocardiography (TTE) or transesophageal echocardiography (TEE). The occlusive condition and distance between 2 adjacent ASDs were measured by TTE examination. Then, the number and size of the occluder(s) was determined. TTE examinations were performed after transcatheter closure as follow-up. RESULTS: The transcatheter procedure was successful in 15 patients with multiple ASDs, using a single occluder in 9 patients and 2 occluders in the remaining 6 patients. Overall, 21 ASD occluders were implanted. During a follow-up period of 6 mo to 5 y, a slight residual shunt was found in 1 patient without any symptoms; a moderate residual shunt was identified at the inferior vena cava and the occluder was removed by surgery 1 mo after procedure. Other complications, including endocarditis, arrhythmia, thromboembolism, and atrioventricular valve damage were not recorded in any of the 15 patients during the follow-up period. CONCLUSION: Transcatheter closure of multiple ASDs is safe and efficient. Two occluders are necessary for the distance of 2 ASDs more than 7 mm, and a single occluder is sufficient for those 7 mm or less.

[Prognostic impact of heart block during transcatheter closure of ventricular septal defect].

OBJECTIVE: To investigate the prognostic impact of heart block during the transcatheter closure of ventricular septal defect (VSD). METHODS: Forty three patients developed complete left or right bundle branch block (CLBBB, CRBBB), incomplete left or right bundle branch block (ILBBB, IRBBB), and atrioventricular block (AVB) during and within 1 week post procedure were followuped at 1, 6, 12, 24, 36, 48 and 60 months post procedure. Electrocardiogram, dynamic electrocardiogram and transthoracic echocardiography were made. RESULTS: Bundle branch block and atrioventricular block were detected in 26 patients (CLBBB n = 4, CRBBB n = 5, ILBBB n = 2, IRBBB n = 10 and third-degree AVB n = 5) during the transcatheter closure of VSD, and in 17 patients (CLBBB n = 5, CRBBB n = 2, first-degree AVB n = 3, second-degree I-type AVB n = 1 and third-degree AVB n = 6) within 1 week post procedure. Heart block disappeared in 33 patients (76.7%) before discharge, in 37 patients (86.1%) at 1 month and in 41 patients (95.4%) at 6 months post procedure. CLBBB or CRBBB was seen in two cases at 24 months after closure. There was no heart failure and serious cardiac dilatation during follow up. CONCLUSION: The heart block occurred during the periprocedure period of transcatheter closure of VSD was a benign phenomenon without prognostic importance.

Clinical efficiency and safety analysis of transcatheter interventional therapy for compound congenital cardiovascular abnormalities.

OBJECTIVE: To investigate the efficiency and safety of transcatheter interventional therapy for compound congenital cardiovascular abnormalities. METHODS: From Nov 2001 to Jun 2006, a total of 36 patients (17 male, 19 female), aged 17.20 +/- 10.52, with compound congenital cardiovascular abnormalities underwent transcatheter interventional procedure. These patients included 11 with perimembranous ventricular septal defect (PVSD) and patent ductus arteriosus (PDA), 8 patients with PVSD and atrial septal defect (ASD), 8 patients with ASD and PDA, 7 patients with ASD and pulmonary stenosis (PS), 1 patient with ASD and mitral stenosis(MS), 1 patient with coarctation of aorta (COA) and PDA. According to the principle of "easy first, hard second," balloon valvuloplasties of PS or MS were performed before the closure of PVSD, and of PDA and ASD. Electrocardiogram and transthoracic echocardiogram were examined at 4 days, 1, 2, 6 and 12 months, respectively, after each procedure. RESULTS: Transcatheter interventional therapy for compound congenital cardiovascular abnormalities was successful in all patients. Among these, 2 occluders were planted in each of 27 patients, 7 patients with ASD combined with PS and 1 patient with ASD combined with MS underwent successfully performed balloon valvuloplasty and ASD closure, 1 patient with COA combined with PDA underwent successfully performed balloon valvuloplasty and subsequent covered stent implantation. No patient encountered serious adverse events during the (30.5 +/- 14.6) months of follow-up. CONCLUSIONS: Transcatheter interventional therapy for compound congenital cardiovascular abnormalities could obtain satisfactory results with technical feasibility.