Directional atherectomy and drug-coated balloon angioplasty vs. bare nitinol stent angioplasty for femoropopliteal artery lesions.

Background: The present study evaluated the prognosis of directional atherectomy (DA)+drug-coated balloon (DCB) angioplasty for femoropopliteal artery lesions compared with bare nitinol stent (BNS). Patients and methods: This retrospective cohort study included patients with femoropopliteal artery lesions who underwent percutaneous endovascular surgery between January 2016 and June 2019. The primary outcome was the primary patency rate after 12, 24, and 36 months; the secondary outcomes comprised incidence of flow-limiting dissections, technical success, limb salvage, and all-cause death. Results: During the study period, 110 (44%) patients underwent DA+DCB, and 140 (56%) patients underwent bare nitinol stent (BNS). There were no differences in the 12- and 24-month patency rates of the two groups (98.2% vs. 93.6% and 68.2% vs. 60.0%, both p>.05). The 36-month primary patency rate in the DA+DCB group was significantly higher than that of the BNS group (27.3% vs. 15.7%, p=.003). The technical success rate and all-cause death were similar between groups (p>.05). Flow-limiting dissections occurred more frequently in the BNS group than in the DA+DCB group (27.9% vs. 10.9%, p=.033). After adjustment for potential confounders, such as sex, smoking, hypertension, hyperlipidemia, ABI after surgery, TASC II B, lesion length ≥15 cm, two-vessel runoff, and three-vessel runoff, the HR for primary patency rate comparing BNS to DA+DCB was 2.61 (95%CI: 1.61-4.25). Conclusions: In this retrospective cohort study, DA+DCB was associated with a higher 30-month primary patency rate and a lower flow-limiting dissection incidence than BNS.

Identification of genes, pathways and transcription factor-miRNA-target gene networks and experimental verification in venous thromboembolism.

Venous thromboembolism (VTE) is a complex, multifactorial life-threatening disease that involves vascular endothelial cell (VEC) dysfunction. However, the exact pathogenesis and underlying mechanisms of VTE are not completely clear. The aim of this study was to identify the core genes and pathways in VECs that are involved in the development and progression of unprovoked VTE (uVTE). The microarray dataset GSE118259 was downloaded from the Gene Expression Omnibus database, and 341 up-regulated and 8 down-regulated genes were identified in the VTE patients relative to the healthy controls, including CREB1, HIF1α, CBL, ILK, ESM1 and the ribosomal protein family genes. The protein-protein interaction (PPI) network and the transcription factor (TF)-miRNA-target gene network were constructed with these differentially expressed genes (DEGs), and visualized using Cytoscape software 3.6.1. Eighty-nine miRNAs were predicted as the targeting miRNAs of the DEGs, and 197 TFs were predicted as regulators of these miRNAs. In addition, 237 node genes and 4 modules were identified in the PPI network. The significantly enriched pathways included metabolic, cell adhesion, cell proliferation and cellular response to growth factor stimulus pathways. CREB1 was a differentially expressed TF in the TF-miRNA-target gene network, which regulated six miRNA-target gene pairs. The up-regulation of ESM1, HIF1α and CREB1 was confirmed at the mRNA and protein level in the plasma of uVTE patients. Taken together, ESM1, HIF1α and the CREB1-miRNA-target genes axis play potential mechanistic roles in uVTE development.

Analysis of crucial genes, pathways and construction of the molecular regulatory networks in vascular smooth muscle cell calcification.

Vascular calcification (VC) accompanies the trans-differentiation of vascular smooth muscle cells (VSMCs) into osteo/chondrocyte-like cells and resembles physiological bone mineralization. However, the molecular mechanisms underlying VC initiation and progression have remained largely elusive. The aim of the present study was to identify the genes and pathways common to VSMC and osteoblast calcification and construct a regulatory network of non-coding RNAs and transcription factors (TFs). To this end, the Gene Expression Omnibus dataset GSE37558 including mRNA microarray data of calcifying VSMCs (CVSMCs) and calcifying osteoblasts (COs) was analyzed. The differentially expressed genes (DEGs) were screened and functionally annotated and the microRNA (miRNA/mRNA)-mRNA, TF-miRNA and long non-coding RNA (lncRNA)-TF regulatory networks were constructed. A total of 318 DEGs were identified in the CVSMCs relative to the non-calcified VSMCs, of which 43 were shared with the COs. The CVSMC-related DEGs were mainly enriched in the functional terms cell cycle, extracellular matrix (ECM), inflammation and chemotaxis-mediated signaling pathways, of which ECM was enriched by the DEGs for the COs as well. The protein-protein interaction network of CVSMCs consisted of 281 genes and 3,650 edges. There were 30 hub genes in this network, including maternal embryonic leucine zipper kinase (MELK), which potentially regulates the differentially expressed TF (DETF) forkhead box (FOX)M1 and is a potential target gene of Homo sapiens miR-485-3p and miR-181d. The TF-miRNA network included 251 TFs and 60 miRNAs, including 10 DETFs such as FOXO1 and snail family transcriptional repressor 2 (SNAI2). Furthermore, the lncRNAs H19 imprinted maternally expressed transcript (H19) and differentiation antagonizing non-protein coding RNA (DANCR) were predicted as the upstream regulators of FOXO1 and SNAI2 in the lncRNA-TF regulatory network. DANCR, MELK and FOXM1 were downregulated, and H19, FOXO1 and SNAI2 were upregulated in the CVSMCs. Taken together, the CVSMCs and COs exhibited similar molecular changes in the ECM. In addition, the MELK-FOXM1, H19/DANCR-FOXO1 and SNAI2 regulatory pathways likely mediate VSMC calcification.

Esophageal Histological Precursor Lesions and Subsequent 8.5-Year Cancer Risk in a Population-Based Prospective Study in China.

INTRODUCTION: Data on the associations between esophageal histological lesions and risk of esophageal squamous cell carcinoma (ESCC) in general populations are limited. We aimed to investigate these associations in a large Chinese general population to inform future Chinese ESCC screening guidelines. METHODS: We performed endoscopic screening of 21,111 participants aged 40-69 years from 3 high-risk areas of China in 2005-2009, and followed the cohort through 2016. Cumulative incidence and mortality rates of ESCC were calculated by baseline histological diagnosis, and hazard ratios of ESCC, overall and by age and sex, were assessed using the Cox proportional hazards models. RESULTS: We identified 143 new ESCC cases (0.68%) and 62 ESCC deaths (0.29%) during a median follow-up of 8.5 years. Increasing grades of squamous dysplasia were associated with the increasing risk of ESCC incidence and mortality. The cumulative ESCC incidence rates for severe dysplasia/carcinoma in situ, moderate dysplasia (MD), and mild dysplasia were 15.5%, 4.5%, and 1.4%, respectively. Older individuals (50-69 years) had 3.1 times higher ESCC incidence than younger individuals (40-49 years), and men had 2.4 times higher ESCC incidence than women. DISCUSSION: This study confirmed that increasing grades of squamous dysplasia are associated with increasing risk of ESCC and that severe dysplasia and carcinoma in situ require clinical treatment. This study suggests that in high-risk areas of China, patients with endoscopically worrisome MD should also receive therapy, the first screening can be postponed to 50 years, and endoscopic surveillance intervals for unremarkable MD and mild dysplasia can be lengthened to 3 and 5 years, respectively.

Sac Embolization and Side Branch Embolization for Preventing Type II Endoleaks After Endovascular Aneurysm Repair: A Meta-analysis.

Purpose:To investigate the efficacy and safety of preoperative side branch embolization or intraoperative sac embolization for preventing type II endoleaks after endovascular aneurysm repair (EVAR). Materials and Methods: A systematic literature search of MEDLINE and EMBASE was performed to identify studies that evaluated the outcomes of sac embolization vs no embolization or side branch embolization vs no embolization in patients who received EVAR. Among the 904 studies screened, 17 studies with 2084 participants were included in this review. Outcome measures included the type II endoleak rate, the reintervention rate for type II endoleaks, the incidence of types I/III endoleaks, and the rate of complications. Fixed (no heterogeneity) or random effects models were constructed for each outcome; the results are presented as the odds ratio (OR) with 95% confidence interval (CI). Results: The sac embolization group had significantly lower type II endoleak (OR 0.21, 95% CI 0.13 to 0.34, p<0.001) and reintervention (OR 0.15, 95% CI 0.07 to 0.33, p<0.001) rates than the no embolization group. No significant differences between the 2 groups were found for the type I/III endoleak rate (OR 0.57, 95% CI 0.23 to 1.37, p=0.21) or complication rate (OR 1.22, 95% CI 0.32 to 4.70, p=0.77). Compared with no embolization, side branch embolization was also associated with a decrease in type II endoleak (OR 0.35, 95% CI 0.21 to 0.60, p<0.001) and reinterventions (OR 0.10, 95% CI 0.04 to 0.27, p<0.001). One severe procedure-related complication (fatal colon ischemia) was reported in the side branch embolization group. Conclusion: Sac embolization and side branch embolization are safe and effective in preventing type II endoleaks. Further randomized trials are needed to directly compare the clinical outcomes of these procedures.

Integrative bioinformatics analysis of miRNA and mRNA expression profiles and identification of associated miRNA-mRNA network in aortic dissection.

BACKGROUND: Aortic dissection (AD) is one of the most lethal cardiovascular diseases. The aim of this study was to identify core genes and pathways revealing pathogenesis in AD. METHODS: We screened differentially expressed mRNAs and miRNAs using mRNA and miRNA expression profile data of AD from Gene Expression Omnibus. Then functional and pathway enrichment analyses of differential expression genes (DEGs) was performed utilizing the database for annotation, visualization, and integrated discovery (DAVID). Target genes with differential expression miRNAs (DEMIs) were predicted using the miRWalk database, and the intersection between these predictions and DEGs was selected as differentially expressed miRNA-target genes. In addition, a protein-protein interaction (PPI) network and miRNA-mRNA regulatory network were constructed. RESULTS: In total, 130 DEGs and 47 DEMIs were identified from mRNA and miRNA microarray, respectively, and 45 DEGs were DEMI-target genes. The PPI and miRNA-mRNA network included 79 node genes and 74 node genes, respectively, while 23 hub genes and 2 hub miRNAs were identified. The DEGs, PPI and modules differential expression miRNA-target genes were all mainly enriched in cell cycle, cell proliferation and cell apoptosis signaling pathways. CONCLUSION: Taken above, the study reveals some candidate genes and pathways potentially involving molecular mechanisms of AD. These findings provide a new insight for research and treatment of AD.

Dynamic imaging of allogeneic adipose-derived regenerative cells transplanted in ischemic hind limb of apolipoprotein E mouse model.

BACKGROUND: Transplantation of allogeneic adipose-derived regenerative cells (ADRCs) is a promising treatment modality for severe ischemic diseases. However, minimal information is available on the in vivo effects, fate, and migration of ADRCs, as well as the mechanisms of their therapeutic angiogenesis. MATERIALS AND METHODS: In this study, green fluorescent protein-expressing ADRCs (GFP-ADRCs) were obtained, labeled with acetylated 3-aminopropyltrimethoxysilane (APTS)-coated iron oxide nanoparticles (APTS NPs), and injected into an old apolipoprotein E knockout (ApoE-KO) mouse model with hind limb ischemia. Then, 3.0 T magnetic resonance imaging (MRI) was performed to dynamically trace the role of ADRCs targeting hind limb ischemia in the ApoE-KO mice model. RESULTS: Labeled cells were visualized as large hypointense spots in ischemic muscles by serial 3.0 T MRI scans during a 4-week follow-up. The presence of labeled GFP-ADRCs was confirmed by Prussian blue staining and fluorescence microscopy on postmortem specimens. CONCLUSION: This study showed that allogeneic ADRCs offer great potential application for therapeutic angiogenesis in severe ischemic disease based on the efficacy and feasibility of ADRC transplantation and on the available amounts of tissue.