A nomoscore of four genes for predicting the rupture risk in abdominal aortic aneurysm patients with osteoarthritis.

BACKGROUND: Abdominal aortic aneurysm (AAA) represents one of the most life-threatening cardiovascular diseases and is increasingly becoming a significant global public health concern. The aneurysms-osteoarthritis syndrome (AOS) has gained recognition, as patients with this syndrome often exhibit early-stage osteoarthritis (OA) and have a substantially increased risk of rupture, even with mild dilation of the aneurysm. The aim of this study was to discover potential biomarkers that can predict the occurrence of AAA rupture in patients with OA. METHODS: Two gene expression profile datasets (GSE98278, GSE51588) and two single-cell RNA-seq datasets (GSE164678, GSE152583) were obtained from the GEO database. Functional enrichment analysis, PPI network construction, and machine learning algorithms, including LASSO, Random Forest, and SVM-RFE, were utilized to identify hub genes. In addition, a nomogram and ROC curves were generated to predict the risk of rupture in patients with AAA. Moreover, we analyzed the immune cell infiltration in the AAA tissue microenvironment by CIBERSORT and validated key gene expression in different macrophage subtypes through single-cell analysis. RESULTS: A total of 105 intersecting DEGs that showed consistent changes between rAAA and OA dataset were identified. From these DEGs, four hub genes (PAK1, FCGR1B, LOX and PDPN) were selected by machine learning. High predictive performance was observed for the nomogram based on these hub genes, with an AUC of 0.975 (95 % CI: 0.942-1.000). Abnormal immune cell infiltration was detected in rAAA and correlated significantly with the hub genes. Ruptured AAA cases exhibited higher nomoscore values and lower M2 macrophage infiltration compared to stable AAA. Validation in animal models (PPE+BAPN-induced rAAA) confirmed the significant role of these biomarkers in AAA pathology. CONCLUSION: The present study successfully identified four potential hub genes (PAK1, FCGR1B, LOX and PDPN) and developed a robust predictive nomogram to assess the risk of AAA rupture. The findings also shed light on the connection between hub genes and immune cell components in the microenvironment of rAAA. These findings support future research on key genes in AAA patients with OA, providing insights for novel management strategies for AAA.

Perioperative Evaluation and Follow-Up Analysis of Carotid Body Tumor by Color Doppler Ultrasound.

BACKGROUND: The value of color doppler ultrasound (CDU) for perioperative evaluation and follow-up outcomes of carotid body tumor (CBT) remains elusive. This study aimed to investigate the role of CDU in CBT in our center. METHODS: From January 2015 to December 2020, 75, patients with CBT were included in the study. Computed tomography angiography (CTA) and CDU data of patients were collected and analyzed. The postoperative recovery and follow-up outcomes were summarized. RESULTS: A total of 91 CBTs in 75 patients were included in the study. 73.3% of the patients had unilateral lesions, while 26.7% had bilateral lesions. Lesions were categorized as Shamblin I (4.4%), Shamblin II (52.7%), and Shamblin III (42.9%). 79.5% lesions were treated by surgical resection, 12.3% were treated by surgical resection with internal carotid artery reconstructed by artificial vessel, while 8.2% were treated by surgical resection with internal carotid artery reconstructed by autogenous great saphenous vein. Compared with CTA, the sensitivity of CDU for the detection of CBT was 96.7%, the sensitivity and specificity of CDU for the detection of Shamblin I lesions were both 100%, the sensitivity and specificity for Shamblin II were 100% and 72.1%, respectively, while the sensitivity and specificity for Shamblin III were 69.2% and 100%, respectively. There were no statistically significant differences between CTA and CDU for the detection of the maximal diameter, volume of CBT, distance between the end of the tumor, and the mastoid process. 79.7% of the patients were followed up with CDU. The eecurrence of CBT occurred in 1 patient. CDU showed that stenosis and occlusion of artificial vessel occurred in 1 and 6 patients, respectively. The occlusion of autogenous great saphenous vein was found in 2 cases. CONCLUSIONS: CDU can accurately diagnose Shamblin I CBT, have high sensitivity for Shamblin II, and high specificity for Shamblin III CBT. It plays an important role in diagnosis, perioperative evaluation, and follow-up analysis of CBT.

Detection of Endoleak after Endovascular Aortic Repair through Deep Learning Based on Non-contrast CT.

OBJECTIVES: To develop and validate a deep learning model for detecting post-endovascular aortic repair (EVAR) endoleak from non-contrast CT. METHODS: This retrospective study involved 245 patients who underwent EVAR between September 2016 and December 2022. All patients underwent both non-enhanced and enhanced follow-up CT. The presence of endoleak was evaluated based on computed tomography angiography (CTA) and radiology reports. First, the aneurysm sac was segmented, and radiomic features were extracted on non-contrast CT. Statistical analysis was conducted to investigate differences in shape and density characteristics between aneurysm sacs with and without endoleak. Subsequently, a deep learning model was trained to generate predicted segmentation of the endoleak. A binary decision was made based on whether the model produced a segmentation to detect the presence of endoleak. The absence of a predicted segmentation indicated no endoleak, while the presence of a predicted segmentation indicated endoleak. Finally, the performance of the model was evaluated by comparing the predicted segmentation with the reference segmentation obtained from CTA. Model performance was assessed using metrics such as dice similarity coefficient, sensitivity, specificity, and the area under the curve (AUC). RESULTS: This study finally included 85 patients with endoleak and 82 patients without endoleak. Compared to patients without endoleak, patients with endoleak had higher CT values and greater dispersion. The AUC in validation group was 0.951, dice similarity coefficient was 0.814, sensitivity was 0.877, and specificity was 0.884. CONCLUSION: This deep learning model based on non-contrast CT can detect endoleak after EVAR with high sensitivity.

LncRNA H19/miR-107 regulates endothelial progenitor cell pyroptosis and promotes flow recovery of lower extremity ischemia through targeting FADD.

BACKGROUND: Peripheral artery disease (PAD) is an ischemic disease with a rising incidence worldwide. The lncRNA H19 (H19) is enriched in endothelial progenitor cells (EPCs), and transplantation of pyroptosis-resistant H19-overexpressed EPCs (oe-H19-EPCs) may promote vasculogenesis and blood flow recovery in PAD, especially with critical limb ischemia (CLI). METHODS: EPCs isolated from human peripheral blood was characterized using immunofluorescence and flow cytometry. Cell proliferation was determined with CCK8 and EdU assays. Cell migration was assessed by Transwell and wound healing assays. The angiogenic potential was evaluated using tube formation assay. The pyroptosis pathway-related protein in EPCs was detected by western blot. The binding sites of H19 and FADD on miR-107 were analyzed using Luciferase assays. In vivo, oe-H19-EPCs were transplanted into a mouse ischemic limb model, and blood flow was detected by laser Doppler imaging. The transcriptional landscape behind the therapeutic effects of oe-H19-EPCs on ischemic limbs were examined with whole transcriptome sequencing. RESULTS: Overexpression of H19 in EPCs led to an increase in proliferation, migration, and tube formation abilities. These effects were mediated through pyroptosis pathway, which is regulated by the H19/miR-107/FADD axis. Transplantation of oe-H19-EPCs in a mouse ischemic limb model promoted vasculogenesis and blood flow recovery. Whole transcriptome sequencing indicated significant activation of vasculogenesis pathway in the ischemic limbs following treatment with oe-H19-EPCs. CONCLUSIONS: Overexpression of H19 increases FADD level by competitively binding to miR-107, leading to enhanced proliferation, migration, vasculogenesis, and inhibition of pyroptosis in EPCs. These effects ultimately promote the recovery of blood flow in CLI.

Deciphering smooth muscle cell heterogeneity in atherosclerotic plaques and constructing model: a multi-omics approach with focus on KLF15/IGFBP4 axis.

BACKGROUND: Ruptured atherosclerotic plaques often precipitate severe ischemic events, such as stroke and myocardial infarction. Unraveling the intricate molecular mechanisms governing vascular smooth muscle cell (VSMC) behavior in plaque stabilization remains a formidable challenge. METHODS: In this study, we leveraged single-cell and transcriptomic datasets from atherosclerotic plaques retrieved from the gene expression omnibus (GEO) database. Employing a combination of single-cell population differential analysis, weighted gene co-expression network analysis (WGCNA), and transcriptome differential analysis techniques, we identified specific genes steering the transformation of VSMCs in atherosclerotic plaques. Diagnostic models were developed and validated through gene intersection, utilizing the least absolute shrinkage and selection operator (LASSO) and random forest (RF) methods. Nomograms for plaque assessment were constructed. Tissue localization and expression validation were performed on specimens from animal models, utilizing immunofluorescence co-localization, western blot, and reverse-transcription quantitative-polymerase chain reaction (RT-qPCR). Various online databases were harnessed to predict transcription factors (TFs) and their interacting compounds, with determination of the cell-specific localization of TF expression using single-cell data. RESULTS: Following rigorous quality control procedures, we obtained a total of 40,953 cells, with 6,261 representing VSMCs. The VSMC population was subsequently clustered into 5 distinct subpopulations. Analyzing inter-subpopulation cellular communication, we focused on the SMC2 and SMC5 subpopulations. Single-cell subpopulation and WGCNA analyses revealed significant module enrichments, notably in collagen-containing extracellular matrix and cell-substrate junctions. Insulin-like growth factor binding protein 4 (IGFBP4), apolipoprotein E (APOE), and cathepsin C (CTSC) were identified as potential diagnostic markers for early and advanced plaques. Notably, gene expression pattern analysis suggested that IGFBP4 might serve as a protective gene, a hypothesis validated through tissue localization and expression analysis. Finally, we predicted TFs capable of binding to IGFBP4, with Krüppel-like family 15 (KLF15) emerging as a prominent candidate showing relative specificity within smooth muscle cells. Predictions about compounds associated with affecting KLF15 expression were also made. CONCLUSION: Our study established a plaque diagnostic and assessment model and analyzed the molecular interaction mechanisms of smooth muscle cells within plaques. Further analysis revealed that the transcription factor KLF15 may regulate the biological behaviors of smooth muscle cells through the KLF15/IGFBP4 axis, thereby influencing the stability of advanced plaques via modulation of the PI3K-AKT signaling pathway. This could potentially serve as a target for plaque stability assessment and therapy, thus driving advancements in the management and treatment of atherosclerotic plaques.

Revealing PPP1R12B and COL1A1 as piRNA pathway genes contributing to abdominal aortic aneurysm through integrated analysis and experimental validation.

BACKGROUND: Abdominal aortic aneurysm (AAA) is a permanent dilation of the abdominal aorta, with a high mortality rate when rupturing. Although lots of piRNA pathway genes (piRPGs) have recently been linked to both neoplastic and non-neoplastic illnesses, their role in AAA is still unknown. Utilizing integrative bioinformatics methods, this research discovered piRPGs as biomarkers for AAA and explore possible molecular mechanisms. METHODS: The datasets were obtained from the Gene Expression Omnibus and piRPGs were identified from the Genecards database. The "limma" and "clusterProfiler" R-packages were used to discover differentially expressed genes and perform enrichment analysis, respectively. Hub piRPGs were further filtered using least absolute shrinkage and selection operator regression, random forests, as well as receiver operating characteristic curve. Additionally, multi-factor logistic regression (MLR), extreme gradient boosting (XGboost), and artificial neural network (ANN) were employed to construct prediction models. The relationship between hub piRPGs and immune infiltrating cells and sgGSEA were further studied. The expression of hub piRPGs was verified by qRT-PCR, immunohistochemistry, and western blotting in AAA and normal vascular tissues and analyzed by scRNA-seq in mouse AAA model. SRAMP and cMAP database were utilized for the prediction of N6-methyladenosine (m6A) targets therapeutic drug. RESULTS: 34 differentially expressed piRPGs were identified in AAA and enriched in pathways of immune regulation and gene silence. Three piRPGs (PPP1R12B, LRP10, and COL1A1) were further screened as diagnostic genes and used to construct prediction model. Compared with MLR and ANN, Xgboost showed better predictive ability, and PPP1R12B might have the ability to distinguish small and large AAA. Furthermore, the expression levels of PPP1R12B and COL1A1 were consistent with the results of bioinformatics analysis, and PPP1R12B showed a downward trend that may be related to m6A. CONCLUSION: The results suggest that piRPGs might serve a significant role in AAA. PPP1R12B, COL1A1, and LRP10 had potential as diagnostic-specific biomarkers for AAA and performed better in XGboost model. The expression and localization of PPP1R12B and COL1A1 were experimentally verified. Besides, downregulation of PPP1R12B caused by m6A might contribute to the formation of AAA.

Clinical characteristics and therapeutic strategy for patients with spontaneous isolated abdominal aortic dissection.

Objective: Spontaneous isolated abdominal aortic dissection (SIAAD) is a rare aortic emergency and not yet fully understood. This study aims to report the characteristics and treatments of 31 patients with SIAAD in the past 12 years. Methods: A total of 31 consecutive patients with SIAAD between 2010 and 2022 were included. The clinical manifestations, treatment strategies, and outcomes were reviewed. Following the SVS/STS reporting standard, we compared the clinical characteristics with different locations of primary entry, or different numbers of dissected zones. Furthermore, we compared the effects of surgical and conservative therapies on the outcome during the follow-up. Results: Among the 31 patients with SIAAD, 16 (51.6%) were in the acute phase on admission. The primary entry of SIAAD was mainly located in Zone 9 (67.7%). Most patient presented with dissection involving 1 or 2 aortic zones (61.3%). In addition, 35.5% and 64.5% of SIAADs involved the visceral and iliac arteries, respectively. Compared with asymptomatic SIAADs, the symptomatic ones had longer dissection lengths (P = 0.008) and tended to involve iliac artery more frequently (P = 0.098). There were differences in the number of dissected aortic zones (P = 0.005) among patients with primary entry located in Zone 5 (Supraceliac aorta), Zone 6-8 (Paravisceral aorta) and Zone 9 (Infrarenal aorta). The involvement of visceral artery (P = 0.039) and iliac artery (P = 0.006) was significantly different between the subgroups of SIAAD involving one, two, and three or more aortic zones. The cumulative incidence of adverse false lumen progression events was significantly lower (P = 0.000) and the rate of false lumen thrombogenesis or disappearance was higher in patients receiving surgery (P = 0.001). The cumulative all-cause mortality was 9.7% at 1-year, and 19.7% at 5-year, with no significant difference between surgical and conservative therapies. Conclusions: Clinical features of SIAAD vary depending on the location of the primary entry and the number of dissected aortic zones. Although surgery was not associated with a lower all-cause mortality compared with conservative therapy, it was associated with a lower incidence of adverse false lumen progression and a higher rate of aortic remodeling.

Identification of necroptosis-related gene TRAF5 as potential target of diagnosing atherosclerosis and assessing its stability.

BACKGROUND: Atherosclerosis (AS) is a leading cause of morbidity and mortality in older patients and features progressive formation of plaques in vascular tissues. With the progression of atherosclerosis, plaque rupture may occur and cause stroke, myocardial infarction, etc. Different forms of cell death promote the formation of a necrotic core of the plaque, leading to rupture. Necroptosis is a type of programmed cell death that contributes to the development of cardiovascular disease. However, the role of necroptosis in AS has not yet been investigated. METHODS: The Gene Expression Omnibus (GEO) database was used to obtain gene expression profiles. Differentially expressed genes (DEGs) and necroptosis gene sets were used to identify necroptosis-related differentially expressed genes (NRDEGs). The NRDEGs were used to construct a diagnostic model and were further screened using least absolute shrinkage selection operator (LASSO) regression and random forest (RF) analysis. The discriminatory capacity of the NRDEGs was evaluated using receiver operating characteristic (ROC) curves. Immune infiltration levels were estimated based on CIBERSORTx analysis. The GSE21545 dataset, containing survival information, was used to determine prognosis-associated genes. Univariate and multivariate Cox regression analyses combined with survival analysis determined gene prognostic values. RNA and protein levels were detected by RT-qPCR and western blotting in arteriosclerosis obliterans(ASO) and normal vascular tissues. Vascular smooth muscle cells (VSMCs) were treated with oxidized low-density lipoprotein (ox-LDL) to develop cell models of advanced AS. The effects of protein knockdown on necroptosis were assessed by western blotting and flow cytometry. EdU and Cell Counting Kit-8 assays were used to examine cell proliferation. RESULTS: TNF Receptor Associated Factor 5 (TRAF5) was identified as a diagnostic marker for AS based on the AUC value in both the GSE20129 and GSE43292 datasets. According to differential expression analysis, LASSO regression analysis, RF analysis, univariate analysis, multivariate analysis, and gene-level survival analysis, TRAF5 was markedly associated with necroptosis in AS. Silencing TRAF5 promotes necroptosis and attenuates the proliferation of ox-LDL-induced cell models of advanced AS. CONCLUSIONS: This study identified a diagnostic marker of necroptosis-related atherosclerosis, TRAF5, which can also be used to diagnose and assess atherosclerotic plaque stability. This novel finding has important implications in the diagnosis and assessment of plaque stability in atherosclerosis.

IL-13RA2 downregulation in fibroblasts promotes keloid fibrosis via JAK/STAT6 activation.

Keloids are considered the manifestation of a fibroproliferative disease characterized by chronic inflammation that is induced following skin injury. Deciphering the underlying mechanism of keloid formation is essential for improving treatment outcomes. Here, we found that more macrophages were activated toward the M2 subtype in keloid dermis when compared with normal dermis. Western blotting revealed that the level of phosphorylated STAT6 (p-STAT6), a known inducer of M2 polarization, was higher in keloid fibroblasts as opposed to fibroblasts from normal dermis. Moreover, keloid fibrosis was shown to be positively correlated with the level of p-STAT6. Further, we identified downregulation of IL-13RA2, a decoy receptor for IL-13, in keloid fibroblasts compared with fibroblasts from normal dermis. Ectopic expression of IL-13RA2 in keloid fibroblasts resulted in inhibition of STAT6 phosphorylation, cell proliferation, migration, invasion, extracellular matrix secretion, and myofibroblast marker expression, as well as an increase in apoptosis. Consistently, knockdown of IL-13RA2 in normal fibroblasts induced a keloidal status. Furthermore, both in vitro application and intratumoral injection of p-STAT6 inhibitor AS1517499 in a patient-derived xenograft keloid-implantation mouse model resulted in proliferation inhibition and tissue necrosis, apoptosis, and myofibroblast marker reduction. Collectively, this study elucidates the key role of IL-13RA2 in keloid pathology and inspires further translational research of keloid treatment concerning JAK/STAT6 inhibition.

Endovascular Treatment of Ruptured or Symptomatic Thoracoabdominal and Pararenal Aortic Aneurysms Using Octopus Endograft Technique: Mid-Term Clinical Outcomes.

OBJECTIVE: To evaluate the effectiveness and safety of using off-the-shelf "Octopus" technique to treat ruptured or symptomatic thoracoabdominal aortic aneurysm (TAAA) and pararenal abdominal aortic aneurysm (PRAAA). METHODS AND RESULTS: All cases who underwent "Octopus" technique from May 2016 to May 2019 at our center were retrospectively analyzed. A total of 10 cases (8 males) were included. The mean age was 54.5±14.2 years (range: 31-80 years). Eight cases presented as aneurysm rupture or impending rupture accepted emergency repair. Technical success, defined by placement of all endografts as planned, was achieved in all cases. A total of 30 target visceral branches were successfully cannulated, 9 celiac arteries were covered intentionally. Intraoperative endoleak was observed in 6 patients, all of them were gutter leak. During hospital stay, there was no death, no side branch occlusion or spinal cord ischemia. Median follow-up was 30 months (range: 12-50 months). One patient died of lung cancer at 14-month follow-up. There was no secondary endoleak. The primary endoleak were found spontaneously resolved in 3 cases at 7 days, 3-month, and 1-year imaging. One persistent endoleak totally resolved after sealing of gutter spaces at 4-month follow-up. The other 2 persistent endoleak decreased during follow-up, which are still under observation. The branch patency rate was 90.3% (28/31). All the 3 occluded branches were renal arteries. Branch occlusion occurred in 2 cases at 1-month follow-up and 1 case at 2-year follow-up, but renal insufficiency was not observed in these cases. Obvious aneurysm sac shrinkage (≥5 mm) was observed in all cases. The aneurysm size shrunk from 7.6±1.9 to 5.5±1.4 cm. No spinal cord ischemia occurred during follow-up. CONCLUSION: Treatment of ruptured TAAA and PRAAA with "Octopus" technique is feasible and safe for high surgical risk patients in the absence of fenestrated and branched devices. The long-term clinical outcomes needed to be investigated.

Novel insight of N6-methyladenosine modified subtypes in abdominal aortic aneurysm.

Background: N6-methyladenosine (m6A) is the most prevalent non-cap reversible modification present in messenger RNAs and long non-coding RNAs, and its dysregulation has been linked to multiple cardiovascular diseases, including cardiac hypertrophy and atherosclerosis. Although limited studies have suggested that m6A modification contributes to abdominal aortic aneurysm (AAA) development, the full landscape of m6A regulators that mediate modification patterns has not been revealed. Methods: To distinguish the m6A methylation subtypes in AAA patients, an unsupervised clustering method was carried out, based on the mRNA levels of 17 m6A methylation regulators. Differentially expressed genes were identified by comparing clusters. An m6Ascore model was calculated using principal component analysis and structured to assess the m6A methylation patterns of single samples. Subsequently, the relationship between the m6Ascore and immune cells and the hallmark gene set was analyzed. Finally, pairs of circRNA-m6A regulators and m6A regulators-m6A related genes were used to establish a network. Results: We identified three m6A methylation subtypes in the AAA samples. The m6Acluster A and C were characterized as more immunologically activated because of the higher abundance of immune cells than that in m6Acluster B. The m6Acluster B was less enriched in inflammatory pathways and more prevalent in pathways related to extracellular matrix stability. Subsequently, we divided the individual samples into two groups according to the m6Ascore, which suggested that a high m6Ascore predicted more active inflammatory pathways and higher inflammatory cell infiltration. A network consisting of 9 m6A regulators and 37 circRNAs was constructed. Conclusion: This work highlighted that m6A methylation modification was highly correlated with immune infiltration of AAA, which may promote the progression of AAA. We constructed an individualized m6Ascore model to provide evidence for individualized treatments in the future.

The Long Non-coding RNA AC148477.2 Is a Novel Therapeutic Target Associated With Vascular Smooth Muscle Cells Proliferation of Femoral Atherosclerosis.

Arteriosclerosis obliterans (ASO) is a limb manifestation of large vessel atherosclerosis. Phenotype switching of vascular smooth muscle cells (VSMCs) occurs in the course of the pathological process. The underlying mechanism of SMCs proliferation remains unclear. Several studies have demonstrated that the dysregulation of long non-coding RNA (lncRNAs) plays a pivotal part in the progression of ASO by exacerbating the proliferation of VSMCs. Based on the endogenous competitive RNA (ceRNA) hypothesis, the mechanism of lncRNAs involved in the pathology of VSMCs was exposed, while the entire map of the regulatory network remains to be elucidated. In the current study, genes and the lncRNAs modules that are relevant to the clinical trait were confirmed through weighted gene co-expression network analysis (WGCNA). In this study, we comprehensively constructed a specific lncRNAs-mediated ceRNA and RBP network. The three lncRNAs, HMGA1P4, C5orf66, and AC148477.2, influenced the proliferation of VSMCs and were found to be associated with the immune landscape, thus they were ultimately screened out. Further verification revealed that AC147488.2 was significantly down-regulated in both ASO arteries and all stages of proliferative VSMCs, which implied that AC147488.2 might have a significant impact on ASO. This finding would improve our understanding of the epigenetic regulation of ASO and unravel novel diagnostic and therapeutic targets.

Human umbilical cord mesenchymal stem cell-derived exosomal microRNA-148a-3p inhibits neointimal hyperplasia by targeting Serpine1.

BACKGROUND: Restenosis is inevitable when patients undergo percutaneous transluminal angioplasty due to neointimal hyperplasia (NIH). Human umbilical cord mesenchymal stem cell-derived exosomes (hucMSC-Exos) have been studied in the field of cardiovascular diseases. However, the effects and mechanisms of hucMSC-Exos on NIH are unclear. We aimed to investigate whether MSC-Exos regulate vascular smooth muscle cell (VSMC) functions to inhibit NIH and explore the underlying mechanisms. METHODS: HucMSCs and mouse VSMCs were isolated and characterized by flow cytometry and immunofluorescence. HucMSC-Exos were identified by transmission electron microscopy, nanoparticle tracking analysis and western blots. Exosomes (Exos) were intravenously injected into mice with left common carotid artery ligation, and their effects on NIH were assessed by haematoxylin and eosin (H&E) and immunohistochemistry staining. The effects of hucMSC-Exos on VSMCs were evaluated by Cell Counting Kit-8, scratch wound, Transwell and Western blot assays. MicroRNA sequencing data in the Gene Expression Omnibus and mRNA sequencing results were used to identify potential molecules in hucMSC-Exos and target genes in VSMCs, respectively. We tested the regulatory effect of microRNAs in Exos and target genes in VSMCs using overexpression and knockdown experiments. RESULTS: Primary hucMSCs, VSMCs and hucMSC-Exos were isolated and characterized. Administration of hucMSC-Exos suppressed NIH after artery ligation. H&E and immunohistochemistry results showed that hucMSC-Exos decreased the intima and media area and intima/media ratio, increased the contractile phenotype protein SM22a in the media layer and downregulated Serpine1 expression in the carotid artery. Exos were ingested by VSMCs, which inhibited migration and upregulated SM22a expression by suppressing Serpine1 expression in vitro. MiR-148a-3p was enriched in hucMSC-Exos and repressed Serpine1 by targeting its 3' untranslated region. Moreover, exosomal miR-148a-3p suppressed VSMC phenotypic switching and migration by targeting Serpine1. CONCLUSIONS: We found that hucMSC-Exos inhibited NIH in a mouse carotid artery ligation model and that the inhibitory effects on VSMC phenotypic switching and migration were mediated by delivery of miR-148a-3p to VSMCs to target Serpine1.

Characteristics and Prognosis of Abdominal or Thoracic Aortic Aneurysm Patients Admitted to Intensive Care Units After Surgical Treatment: A Multicenter Retrospective Observational Study.

OBJECTIVE: To investigate the characteristics and prognosis of abdominal or thoracic aortic aneurysm (AAA or TAA) patients admitted to intensive care unit (ICU) postoperatively. METHODS: Patients admitted to ICU postoperatively with a primary diagnosis of AAA or TAA were screened in the eICU Collaborative Research Database, which contained data from multiple ICUs throughout the continental United States in 2014 and 2015. Baseline characteristics and comorbidities and were investigated and factors associated with ICU mortality were explored using univariable logistic regression. Receiver operating characteristic (ROC) curve analysis was performed to evaluate the prognosis predictive performance of the widely used severity scoring system APACHE IVa. RESULTS: A total of 974 patients including 677 AAA and 297 TAA patients admitted to ICU postoperatively were included. Compared with TAA, AAA patients had a significantly higher median age (72 versus 64 years, P<0.001). 89.07% AAA and 84.51% TAA patients underwent elective surgery (P=0.046), 8.71% AAA and 31.99% TAA patients were with aortic dissection (P<0.001), and 10.19% AAA and 2.36% TAA patients suffered from rupture of aortic aneurysm (P<0.001). Hypertension requiring treatment was the most common comorbidity (57.31% for AAA and 61.95% for TAA). TAA patients had significantly higher ICU mortality (9.43% versus 2.36%, P<0.001) than AAA. Several factors were found to be significantly associated with ICU mortality, including urgent surgery, with aortic dissection, rupture of aortic aneurysm, TAA, and a higher APACHE IVa score on ICU admission. APACHE IVa showed a good predictive performance for ICU mortality with an area under the ROC curve of 0.9176 (95% CI 0.8789-0.9390). CONCLUSION: The prognosis of aortic aneurysm patients admitted to ICU postoperatively is yet to improve, and factors associated with prognosis are mainly related to the condition itself. APACHE IVa can be used for prognosis prediction.

Comparative Analysis of Patch Angioplasty Versus Selective Primary Closure during Carotid Endarterectomy Performed at a Single Vascular Center in China.

BACKGROUND: One of the ongoing debates about carotid endarterectomy (CEA) is the closure technique of arterial wall in the operation. Current guidelines recommend routine patch closure (PAC); this recommendation is based on the evidence reported 10-20 years ago. Therefore, the exact role of PAC and primary closure (PRC) remains uncertain. The objectives of this study were to compare the perioperative and long-term outcomes of patients who underwent CEA with different closure techniques. METHODS: From January 2013 and December 2018, one senior vascular surgeon performed CEA for 126 patients in the First Affiliated Hospital, Sun Yat-sen University. The closure technique (PAC or PRC) was determined on the characteristics (diameter and level) of carotid arteries. Patient demographics and clinical data were retrospectively collected by two research fellows by reviewing the hospital medical records and relevant radiologic studies, as were carotid duplex reports, indications, intraoperative data, closure technique, and perioperative complications. Data of long-term outcomes were gathered by reviewing outpatient clinic visits and associated supplementary examinations. RESULTS: PRC was performed in 78 operations (61.9%), and PAC was performed in 48 operations (38.1%). There were no statistical differences in demographic and clinical data between the two groups. Carotid clamp time (P < 0.001) and operating time (P < 0.001) were significantly longer when performing PAC (P < 0.001), and intraoperative blood loss was significantly more when performing PAC than that of PRC (P < 0.001). The postoperative outcome and the follow-up results showed that there was no significant difference in the short-term and middle-term overall survival rate and restenosis-free survival rate between the two groups. CONCLUSIONS: There are no differences in postoperative and middle-term outcomes between PAC and selective PRC, whereas PRC technique can save operation time and shorten the intraoperative carotid clamp time. PRC can be safely applied in patients with a greater than 5 mm internal carotid artery (ICA).

Association Between Blood Glucose Within 24 Hours After Intensive Care Unit Admission and Prognosis: A Retrospective Cohort Study.

PURPOSE: The aim of this study was to evaluate the association between blood glucose within 24 hours after intensive care unit (ICU) admission and prognosis. PATIENTS AND METHODS: A retrospective cohort study was conducted using data from a large critical care database. Patients who had a length of ICU stay ≥24 hours and at least two blood glucose records within 24 hours after ICU admission were included and hospital mortality was chosen as the primary outcome. The average, minimum, and maximum blood glucose within 24 hours after ICU admission were a priori selected as exposures and associations between each exposure and outcomes were assessed after adjusted for potential confounders. RESULTS: A total of 14,237 patients were included finally with an average age of 62.9±17.7 years and a mean SAPS II on admission of 34 (26-44). Among the study population, 20.2% (2872/14,237) had uncomplicated diabetes, and 6.7% (953/14,237) had complicated diabetes. Lowest hospital mortality rate was observed in the stratum with an average blood glucose ranged 110-140 mg/dL, a minimum blood glucose ranged 80-110 mg/dL, and a maximum blood glucose ranged 110-140 mg/dL. After adjusted for confounders including age, sex, disease severity scores and comorbidities, an average blood glucose ranged 110-140 mg/dL, a minimum blood glucose ranged 80-110 mg/dL, and a maximum blood glucose ranged 110-140 mg/dL were associated with the lowest risk of hospital mortality. Consistent results were found among patients without diabetes in the subgroup analyses stratified by diabetes. CONCLUSION: A range of 110-140 mg/dL for average and maximum blood glucose and a range of 80-110 mg/dL for minimum blood glucose within 24 hours after ICU admission predicted better prognosis especially among patients without diabetes.

Prognostic value of clinical and morphologic findings in patients with type B aortic intramural hematoma.

BACKGROUND: Aortic intramural hematoma (IMH) is a subset of acute aortic syndrome, and its prognosis may differ between races. This study aimed to study the prognosis of Chinese type B IMH patients and to find out risk factors. METHODS: A total of 71 type B IMH patients with or without penetrating atherosclerosis ulcer (PAU) administrated in our center between September 2013 and October 2017 were retrospectively studied. Both clinical and imaging data were collected and analyzed. The primary end point was aorta-related death, and the secondary end point was progression, which was defined as enlargement of aorta, increased aortic wall thickness, and aortic dissection or aneurysm formation. Kaplan-Meier survival analysis and Cox regression analysis were used for prognostic analysis. RESULTS: Among these 71 patients, 21 had simple type B IMH, when 50 had type B IMH in association with PAU. Twenty-five patients received optimal medical therapy (OMT) alone, while 46 patients received surgery and OMT. The mean follow-up time was 27.5 ± 13.5 months. For type B IMH patients, association with PAU indicated poor prognosis and required more intensive management (HR = 16.68, 1.96~141.87), while maximum aortic diameter (MAD) was an independent risk factor (HR = 1.096, 1.016~1.182). For patients with PAU-IMH, MAD was an independent risk factor (HR = 1.04, 1.021~1.194), while surgical treatment was independent protective factor (HR = 0.172, 0.042~0.696). CONCLUSION: Association with PAU and MAD were independent risk factors for type B IMH patients. Surgery may improve the outcomes for type B IMH in association with PAU.

Parallel Covered Stents Technique in the Treatment of Abdominal Aortic Diseases.

PURPOSE: To investigate the safety and efficacy of the parallel covered stents technique in the treatment of anatomically challenging aortic aneurysms, pseudoaneurysms, and dissections. MATERIALS AND METHODS: Data were retrospectively collected from 16 patients with abdominal aortic diseases who were treated with parallel covered stents (Gore Excluder, n = 14; Medtronic Endurant, n = 2) between January 2016 and July 2018. Patients were treated with this technique if they were unsuitable for either open repair or standard endovascular aortic repair with bifurcated stents. Such unfavorable anatomy included narrow aortic necks (≤18 mm), small vascular access (occluded or ≤6.0 mm), or compressed aortic lumens (≤18 mm). All patients were male, with a mean age of 64.7 ± 13.3 years. For true aneurysms (n = 4) and pseudoaneurysms (n = 4), the mean diameter and length of the proximal necks were 17.5 ± 2.6 mm (range, 14-21 mm) and 51.0 ± 12.5 mm (range, 39-75 mm), respectively. The minimal diameter of true lumen in cases with aortic dissection and penetrating ulcers (n = 8) was 14.8 ± 3.1 mm. Small or occluded femoral access was found in 3 patients. RESULTS: Technical success was 100%. Minor type I endoleaks, which were seen on completion angiography in 5 patients, had all resolved within 3 months. There were no perioperative deaths. Postoperative complications included supraventricular tachycardia in 1 patient and pneumonia combined with heart failure in 1 patient. Patency of all stents was observed at a mean follow-up of 21.8 ± 10.1 months. CONCLUSIONS: The parallel covered stents technique appears to offer a feasible solution for abdominal aortic diseases with unfavorable anatomy. Long-term follow-up is needed to further evaluate the safety and efficacy of this technique.

Waist circumference increases risk of coronary heart disease: Evidence from a Mendelian randomization study.

BACKGROUND: This study investigated whether expanding waist circumference (WC) is causally associated with an elevated risk of coronary heart disease (CHD), using a two-sample Mendelian randomization (MR) study through integrating summarized data from genome-wide association study. METHODS: The data included in this analysis were mainly from the Genetic Investigation of ANthropometric Traits (GIANT), Consortium and Coronary Artery Disease Genome wide Replication, and Meta-analysis plus the Coronary Artery Disease (C4D) Genetics (CARDIoGRAMplusC4D) Consortium. Three statistical approaches, inverse-variance weighted (IVW), weighted median, and MR-Egger regression method were conducted to assess the casual relationship. The exposure was WC, measured by 46 single-nucleotide polymorphisms from GIANT and the outcome was the risk of CHD. Then, we used the genetic data from Neale Lab and TAG to infer whether WC causally affected the established risk factors of CHD. RESULTS: The IVW method presented that genetically predicted WC was positively casually associated with CHD (odds ratio [OR]: 1.57, 95% CI = 1.33-1.84; p = 4.81e-08), which was consistent with the result of weighted median and MR-Egger regression. MR-Egger regression indicated that there was no directional horizontal pleiotropy to violate the MR assumption. Additionally, expanded WC was also associated with higher risk of hypertension and diabetes, higher cholesterol, more smoking intensity, and decreased frequency of physical activity. CONCLUSION: Our analysis provided strong evidence to indicate a causal relationship between WC and increased risk of CHD.

Endovascular Repair for Kommerell Diverticulum With Type A Aortic Dissection.

Total endovascular repair remains challenging for Kommerell diverticulum with chronic type A aortic dissection. We reported the first total endovascular repair for a Kommerell diverticulum with chronic retrograde type A aortic dissection. We conducted total endovascular repair with a unibody, single-branched, stent-graft combined with the chimney technique for reconstruction of both subclavian arteries. Completion angiography showed complete exclusion of the primary entry tear without endoleak and patency of all stent-grafts, and computed tomographic angiography at follow-up showed significant remodeling of the false lumen. In this case we show that total endovascular repair is feasible and safe in selective patients of this kind.