A non-canonical role for a small nucleolar RNA in ribosome biogenesis and senescence.

Cellular senescence is an irreversible state of cell-cycle arrest induced by various stresses, including aberrant oncogene activation, telomere shortening, and DNA damage. Through a genome-wide screen, we discovered a conserved small nucleolar RNA (snoRNA), SNORA13, that is required for multiple forms of senescence in human cells and mice. Although SNORA13 guides the pseudouridylation of a conserved nucleotide in the ribosomal decoding center, loss of this snoRNA minimally impacts translation. Instead, we found that SNORA13 negatively regulates ribosome biogenesis. Senescence-inducing stress perturbs ribosome biogenesis, resulting in the accumulation of free ribosomal proteins (RPs) that trigger p53 activation. SNORA13 interacts directly with RPL23, decreasing its incorporation into maturing 60S subunits and, consequently, increasing the pool of free RPs, thereby promoting p53-mediated senescence. Thus, SNORA13 regulates ribosome biogenesis and the p53 pathway through a non-canonical mechanism distinct from its role in guiding RNA modification. These findings expand our understanding of snoRNA functions and their roles in cellular signaling.

Pterostilbene alleviates abdominal aortic aneurysm via inhibiting macrophage pyroptosis by activating the miR-146a-5p/TRAF6 axis.

Pterostilbene (PTE), a natural stilbene found in blueberries and several varieties of grapes, has several pharmacological activities, including anti-inflammatory and antioxidative activities. However, its role in abdominal aortic aneurysm (AAA), which is a severe inflammatory vascular disease, remains incompletely understood. In this study, we investigated the protective effects of natural stilbene PTE on AAA formation and the underlying mechanism. Two AAA mouse models (Ang II-induced model and PPE-induced model) were used to examine the effect of PTE on AAA formation. We showed that PTE administration attenuated AAA formation in mice. Furthermore, we found that PTE significantly inhibited inflammatory responses in mouse aortas, as PTE suppressed macrophage pyroptosis and prevented macrophage infiltration in aortas, resulting in reduced expression of pro-inflammatory cytokines in aortas. We also observed similar results in LPS + ATP-treated Raw 264.7 cells (a macrophage cell line) and primary peritoneal macrophages in vitro. We showed that pretreatment with PTE restrained inflammatory responses in macrophages by inhibiting macrophage pyroptosis. Mechanistically, miR-146a-5p and TRAF6 interventions in vivo and in vitro were used to investigate the role of the miR-146a-5p/TRAF6 axis in the beneficial effect of PTE on macrophage pyroptosis and AAA. We found that PTE inhibited macrophage pyroptosis by miR-146a-5p-mediated suppression of downstream TRAF6 expression. Moreover, miR-146a-5p knockout or TRAF6 overexpression abrogated the protective effect of PTE on macrophage pyroptosis and AAA formation. These findings suggest that miR-146a-5p/TRAF6 axis activation by PTE protects against macrophage pyroptosis and AAA formation. PTE might be a promising agent for preventing inflammatory vascular diseases, including AAA.

SMYD2 regulates vascular smooth muscle cell phenotypic switching and intimal hyperplasia via interaction with myocardin.

The SET and MYND domain-containing protein 2 (SMYD2) is a histone lysine methyltransferase that has been reported to regulate carcinogenesis and inflammation. However, its role in vascular smooth muscle cell (VSMC) homeostasis and vascular diseases has not been determined. Here, we investigated the role of SMYD2 in VSMC phenotypic modulation and vascular intimal hyperplasia and elucidated the underlying mechanism. We observed that SMYD2 expression was downregulated in injured carotid arteries in mice and phenotypically modulated VSMCs in vitro. Using an SMC-specific SMYD2 knockout mouse model, we found that SMYD2 ablation in VSMCs exacerbated neointima formation after vascular injury in vivo. Conversely, SMYD2 overexpression inhibited VSMC proliferation and migration in vitro and attenuated arterial narrowing in injured vessels in mice. SMYD2 downregulation promoted VSMC phenotypic switching accompanied with enhanced proliferation and migration. Mechanistically, genome-wide transcriptome analysis and loss/gain-of-function studies revealed that SMYD2 up-regulated VSMC contractile gene expression and suppressed VSMC proliferation and migration, in part, by promoting expression and transactivation of the master transcription cofactor myocardin. In addition, myocardin directly interacted with SMYD2, thereby facilitating SMYD2 recruitment to the CArG regions of SMC contractile gene promoters and leading to an open chromatin status around SMC contractile gene promoters via SMYD2-mediated H3K4 methylation. Hence, we conclude that SMYD2 is a novel regulator of VSMC contractile phenotype and intimal hyperplasia via a myocardin-dependent epigenetic regulatory mechanism.

The Efficacy of Low-Kilovoltage X-Rays Intraoperative Radiation as Boost for Breast Cancer: A Systematic Review and Meta-Analysis.

Background: Intraoperative radiotherapy (IORT) is a novel promising technology that may replace external beam radiation therapy (EBRT) as boost for patients receiving breast-conserving surgery. To better evaluate the efficacy of IORT using low-kilovoltage (low-kV) X-rays as boost, we presented this meta-analysis according to the PRISMA checklist. Methods: Studies reported survival outcomes of intraoperative radiation using low-kilovoltage X-rays system (Intrabeam®, Carl Zeiss Meditec, Dublin, CA, USA) as boost were identified through electronic bibliographic database: PUBMED. The meta-analysis module in Stata (16.0) is used to pool the studies. A Poisson regression model is used to predict a 5-year local recurrence rate. Results: Twelve studies including 3006 cases were included in the final analysis, with a median follow-up of 55 months weighted by sample size. The pooled local recurrence rate is 0.39% per person-year (95% CI: 0.15%-0.71%), with a low degree of heterogeneity (I2 = 0%). The predicted 5-year local recurrence rate was 3.45%. No difference in pooled local recurrence rate was found between non-neoadjuvant patients studies and neoadjuvant patients studies (0.41% per person-year vs. 0.58% per person-year, P = 0.580). Conclusions: This study shows that low-kV IORT is an effective method as boost in breast cancer patients, with a low pooled local recurrence rate and low predicted 5-year local recurrence rate. Besides, no difference in the local recurrence rate was found between non-neoadjuvant patients studies and neoadjuvant patients studies. Low-kV IORT boost may be a promising alternative to EBRT boost in the future, which is being tested in the ongoing TARGIT-B trial.

The application of contrast-enhanced ultrasound for sentinel lymph node evaluation and mapping in breast cancer patients.

Background: To retrospectively investigate the application of contrast-enhanced ultrasound on sentinel lymph node (SLN-CEUS) for SLN evaluation and mapping in breast cancer patients. Methods: Patients diagnosed with breast cancer at the First Affiliated Hospital of Sun Yat-sen University from June 2019 to March 2021 were conveniently evaluated by SLN-CEUS. The results of SLN-CEUS and B mode-ultrasound (BUS) were collected and compared. For patients who only underwent SLN-CEUS, we conducted a 1:1 propensity score matching (PSM). The diagnostic parameters, including sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), false negative rate (FNR), false positive rate (FPR), and proportion of undetermined diagnoses were compared between the SLN-CEUS and BUS cohorts. The identification rate and FNR of sentinel lymph node biopsy (SLNB) were also assessed. Results: There were 327 patients in each of the SLN-CEUS and BUS cohorts. Among the entire cohort, both NPV [90.2% (95% CI, 85.4-93.5%) vs. 83.5% (95% CI, 77.8-88.0%), P=0.048] and accuracy [80.7% (95% CI, 76.5-85.0%) vs. 73.7% (95% CI, 68.9-78.5%), P<0.001] of SLN-CEUS were significantly higher than those of BUS. In non-neoadjuvant treatment (NAT) patients, the NPV [94.7% (95% CI, 89.9-97.4%) vs. 85.5% (95% CI, 79.1-90.2%), P=0.007] and accuracy [87.6% (95% CI, 83.2-92.0%) vs. 76.0% (95% CI, 70.4-81.5%), P<0.001] of SLN-CEUS were significantly higher than those of BUS. In NAT patients, no difference in diagnostic efficacy was found. The proportion of undetermined diagnoses of SLN-CEUS was significantly lower than that of BUS (5.8% vs. 15.3%, P<0.001). The identification rate of SLN-CEUS in overall patients, non-NAT patients, and NAT patients was 94.2%, 96.3%, and 89.9%, respectively. The FNR of SLNB with the blue-dye tracer in combination with SLN-CEUS in overall patients, non-NAT patients, and NAT patients was 7.3%, 4.0%, and 12.5%, respectively. Conclusions: Compared to BUS, SLN-CEUS is a better technique for diagnosing SLNs in early breast cancer patients, showing superiority in multiple diagnostic parameters. However, the diagnostic value of SLN-CEUS in NAT patients is still undetermined. SLN-CEUS is a promising mapping method in SLNB, with a high identification rate and a low FNR when used in combination with a blue-dye tracer.

Ultrasound-guided intraoperative inferior vena cava stent implantation for treatment of acute hypotension during orthotopic liver transplantation.

Severe obstruction of inferior vena cava (IVC) outflow after orthotopic liver transplantation can result in persistent hypotension, leading to transplantation failure and intraoperative circulatory instability and can even threaten the patient's life. IVC stent implantation is a therapeutic approach to relieve the obstruction of IVC outflow. In the present report, we describe two cases of IVC stent implantation assisted by color Doppler ultrasound during orthotopic liver transplantation to manage the persistent hypotension caused by acute obstruction of IVC outflow. At 1 and 3 months of follow-up, the stent position was optimal, and the stent and IVC patency were satisfactory without thrombosis.

SMYD2 Regulates Vascular Smooth Muscle Cell Phenotypic Switching and Intimal Hyperplasia via Interaction with Myocardin.

The SET and MYND domain-containing protein 2 (SMYD2) is a histone lysine methyltransferase that has been reported to regulate carcinogenesis and inflammation. However, its role in vascular smooth muscle cell (VSMC) homeostasis and vascular diseases has not been determined. Here, we investigated the role of SMYD2 in VSMC phenotypic modulation and vascular intimal hyperplasia and elucidated the underlying mechanism. We observed that SMYD2 expression was downregulated in injured carotid arteries in mice and phenotypically modulated VSMCs in vitro. Using a SMC-specific Smyd2 knockout mouse model, we found that Smyd2 ablation in VSMCs exacerbates neointima formation after vascular injury in vivo. Conversely, Smyd2 overexpression inhibits VSMC proliferation and migration in vitro and attenuates arterial narrowing in injured vessels in mice. Smyd2 downregulation promotes VSMC phenotypic switching accompanied with enhanced proliferation and migration. Mechanistically, genome-wide transcriptome analysis and loss/gain-of-function studies revealed that SMYD2 up-regulates VSMC contractile gene expression and suppresses VSMC proliferation and migration, in part, by promoting expression and transactivation of the master transcription cofactor myocardin. In addition, myocardin directly interacts with SMYD2, thereby facilitating SMYD2 recruitment to the CArG regions of SMC contractile gene promoters and leading to an open chromatin status around SMC contractile gene promoters via SMYD2-mediated H3K4 methylation. Hence, we conclude that SMYD2 is a novel regulator of VSMC contractile phenotype and intimal hyperplasia via a myocardin-dependent epigenetic regulatory mechanism and may be a potential therapeutic target for occlusive vascular diseases.

Retrospective Analysis of Carotid Body Tumor Surgical Management: Roles of Preoperative Image Investigation and Preoperative Embolization.

BACKGROUND: Carotid body tumors (CBT) surgery is a challenging procedure, and the role of embolization (EMB) in CBT surgery has remained unclear. This study is performed to analyze the management of CBTs, particularly the use of preoperative EMB and image features in minimizing surgical complications. METHODS: A total of 200 CBTs were identified among 184 medical records involving CBT surgery. Regression analysis was used to explore the prognostic predictors of cranial nerve deficit (CND), including image features. In addition, blood loss, operation times, and complication rates were compared between patients who had surgery only versus patients who had surgery along with preoperative EMB. RESULTS: Overall, 96 males and 88 females were identified for inclusion in the study, with a median age of 37.0 years. Computed tomography angiography (CTA) showed the presence of a tiny gap adjacent to the encasement of carotid vessels, which could help minimize carotid arterial injury. High-lying tumors that encased the cranial nerve were usually managed with synchronous cranial nerve resection. Regression analysis revealed that the incidence of CND was positively associated with Shamblin Ⅲ, high-lying, and a maximal CBT diameter of ≥ 5 cm. Among 146 EMB cases, 2 cases of intracranial arterial EMB occurred. No statistical difference was found between the EBM and non-EBM groups in terms of bleeding volume, operation time, blood loss, blood transfusion requirement, stroke, and permanent CND. Subgroup analysis revealed that EMB decreased CND in Shamblin III and low-lying tumors. CONCLUSIONS: CBT surgery should be performed with preoperative CTA to identify favorable factors for minimizing surgical complications. Shamblin Ⅲ or high-lying tumors, as well as CBT diameter, are predictors of permanent CND. EBM does not reduce blood loss or shorten operation time.

The Influencing Factors and Prognostic Evaluation in the Treatment Decisions for Acute and Subacute Nondissection-Related Superior Mesenteric Artery Thromboembolism.

BACKGROUND: The unclarified treatment strategy for acute and subacute ndSMA-TE limits the therapeutic efficacy and worsens the prognosis. This study aimed to determine the predictive factors impacting the treatment strategy for acute and subacute ndSMA-TE. METHOD: A database of 116 patients with nonchronic ndSMA-TE admitted between January 2001 and December 2021 was retrospectively analyzed. Univariate/multivariate logistic regression and the predictive models constructed by stepwise backward regression were used to explore the influencing factors of the treatment decisions and the risk factors for failed conservative treatment. The EuroQol-5 Dimension questionnaire was used to evaluate the long-term quality of life. RESULTS: Only the white blood cell (WBC) levels were significantly different between the conservative group and the surgical group (P = 0.013 < 0 .05, odds ratio (OR) = 1.153, 95% confidence interval (CI) [1.038, 1.306]). The WBC levels (P < 0.001, OR = 1.169, 95% CI [1.080, 1.286]) and heart diseases (except atrial fibrillation) (P = 0.011 < 0 .05, OR = 5.116, 95% CI [1.541, 20.452]) were included in the predictive model of the treatment decision. The hemoglobin levels (P = 0.005 < 0 .05, OR = 1.095, 95% CI [1.040, 1.187]) and no flatus or stool (P = 0.007 < 0 .05, OR = 0.031, 95% CI [0.002, 0.296]) were significant risk factors for the conservative treatment outcome. The EuroQol-5 Dimension evaluation demonstrated a fairly high long-term quality of life in both treatment strategies. CONCLUSIONS: Elevated WBC levels, decreased hemoglobin levels, and no flatus or stool can be used as predictive indicators for the surgical treatment of nonchronic ndSMA-TE to avoid a misdiagnosis and an inappropriate treatment.

Current Perspective and Strategy on Management of Spontaneous Jugular Venous Ectasia: A Systematic Review.

BACKGROUND: Spontaneous jugular venous ectasia (SJVE) is characterized by dilation of the internal jugular vein (IJV) and external jugular vein. It is generally considered a benign anomaly. There is no accepted categorization for this disorder. METHODS: We conducted a case series study and a systematic review of available articles on SJVE to understand the main characteristics, clinicopathologic classifications, and therapeutic approaches. RESULTS: From January 2001 to December 2021, 14 patients in our hospital were analyzed. A total of 110 original articles (295 cases/311 lesions) were included in the systematic review. We proposed a classification and categorized SJVE into 4 main types (type I-IV) plus one (type V) in which the specific ectasia was located around the jugular bulb at the IJV. CONCLUSIONS: Conservative treatment is preferred for patients with type I (without thrombus) SJVE and asymptomatic patients who can be treated without anticoagulants. The therapeutic efficiency of surgery was high, and the best surgical modalities were chosen according to the type of SJVE.

Comparisons of outcomes of open surgery versus endovascular intervention for thrombotic popliteal artery aneurysm with acute lower limb ischemia: a systematic review.

BACKGROUND: Thrombotic popliteal artery aneurysm (PAA) with acute lower limb ischemia (ALI) is a serious disease leading to amputation. The choice of emergency procedures is not clearly defined, and the difference in therapeutic efficiency between open surgery and endovascular intervention is still unclear. METHOD: We conducted a comprehensive search through PubMed, Wiley Online Library and ScienceDirect. According to the predefined inclusion and exclusion criteria, eligible articles were screened out, and all relevant data were extracted for further analysis. Our study was designed and developed based on Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) Guideline. We critically assessed all included articles by Joanna Briggs Institute (JBI) Critical Appraisal Checklists and the Methodological Index for Non-Randomized Studies (MINORS). RESULT: A total of 29 articles (1338 patients/1387 limbs) were included in the study. After a 1-year follow-up, the primary patency rate of the open surgery group was significantly lower than that of the endovascular intervention group (72.65 vs. 81.46%, P = 0.004), but without significant difference in the secondary patency rate (86.19 vs. 86.86%, P = 0.825). The limb salvage rate of the open surgery group was also significantly lower (83.07 vs. 98.25%, P < 0.001). After the 2-year follow-up, the primary patency rate of the open surgery group was still significantly lower (48.57 vs. 59.90%, P = 0.021). CONCLUSION: The outcome of endovascular intervention was better than that of open surgery especially in the 1-year limb salvage rate and primary patency rate at the 1-year and 2-year follow-ups.

CircCRIM1 Ameliorates Endothelial Cell Angiogenesis in Aging through the miR-455-3p/Twist1/VEGFR2 Signaling Axis.

Background: Aging leads to vascular endothelial cell senescence. Decreased expression of VEGFA and VEGFR2 plays a crucial role in impairing angiogenesis in senescent endothelial cells. Noncoding RNAs, including circular RNAs (circRNAs) and microRNAs (miRNAs), regulate endothelial cell proliferation, differentiation, apoptosis, and migration and participate in the occurrence and development of vascular diseases. However, the mechanism of noncoding RNAs in age-related vascular endothelial dysfunction remains unclear. Here, we aimed to identify the circRNA that is associated with VEGF/VEGFR2 signaling pathway activation in angiogenesis. Methods: Immunoblotting, quantitative reverse transcription-polymerase chain reaction (qRT-PCR), in vitro and in vivo experiments, luciferase assays, and chromatin immunoprecipitation followed by qRT-PCR (ChIP-qPCR) assays were performed to clarify the roles played by circCRIM1 in mouse aortic endothelial cell (MAEC) angiogenesis. Results: CircCRIM1 expression was downregulated in both an aging mouse model of lower limb ischemia in vivo and aging MAECs in vitro. Overexpressing circCRIM1 mediated through a plasmid or adeno-associated virus (AAV) reversed the downregulation of angiogenesis-related phenotype acquisition during aging. MiR-455-3p was confirmed to be a potential target of circCRIM1 through luciferase assays followed by RNA fluorescence in situ hybridization (FISH), which revealed the colocalization of circCRIM1 and miR-455-3p. CircCRIM1 was found to be a competitive endogenous RNA that sponged miR-455-3p and regulated angiogenesis-related phenotypes in MAECs. Furthermore, Twist1 was found to be downstream of miR-455-3p. A ChIP-qPCR assay showed that Twist1 promoted VEGFR2 expression by binding to the promoter region, playing a vital role in angiogenesis. Conclusions: Decreased expression of circCRIM1 impaired angiogenesis in aging via the miR-455-3p/Twist1/VEGFR2 axis. Our findings suggest that overexpression of circCRIM1 may be an effective therapeutic strategy for promoting ischemic lower limb blood flow recovery.

Stent patency rates and prognostic factors of endovascular intervention for iliofemoral vein occlusion in post-thrombotic syndrome.

OBJECTIVE: Post-thrombotic syndrome (PTS), an important complication of deep venous thrombosis (DVT), adversely affects patients' quality of life. Endovascular intervention in PTS can relieve symptoms rapidly with high therapeutic value. This study mainly focuses on how to improve postoperative stent patency rates and aims to find prognostic factors impacting patency. METHODS: According to the specific inclusion and exclusion criteria, PTS patients who underwent endovascular intervention at the First Affiliated Hospital of Sun Yat-sen University from December 1, 2014, to December 31, 2019, were included in this single-center prospective study. Follow-up data were collected and analyzed regularly over 2 years. RESULTS: Overall, 31 PTS patients were enrolled in the study. The mean age of these patients was 55.39 ± 11.81, including 19 male patients. Stent implantation was successful in 22 PTS patients, with a technical success rate of 70.97%. The average Villalta scores of the stent-implanted group and the non-stent-implanted group were 5.95 ± 2.57 and 5.78 ± 2.95, respectively, with no significant difference observed. In the stent-implanted group, the perioperative patency rate was 81.81% (18/22), and the follow-up patency rates were 68.18% (15/22) within 3 months, 59.09% (13/22) within 6 months, 45.45% (10/22) within 1 year, and 36.36% (8/22) within 2 years. Based on the stent placement segments, the 22 PTS patients were divided into two subgroups: the iliofemoral vein balloon dilation + iliofemoral vein stent implantation (FV-S) subgroup and the iliofemoral vein balloon dilation + iliac vein stent implantation (FV-B) subgroup. In the FV-S subgroup, the perioperative patency rate was 100.00% (14/14), and the follow-up patency rates were 85.71% (12/14), 71.43% (10/14), 57.14% (8/14) and 50.00% (7/14), which were higher than those for overall stent patency of all patients. The postoperative patency rates in the FV-B subgroup were 50.00% (4/8), 37.50% (3/8), 37.50% (3/8), 25.00% (2/8), and 12.50% (1/8). The secondary postoperative patency rates in the FV-B subgroup were 100.00% (8/8), 87.50% (7/8), 75.00% (6/8), 62.50% (5/8) and 50.00% (4/8). CONCLUSIONS: For PTS patients with iliofemoral vein occlusion but patent inflow, iliofemoral vein stent implantation is a more efficient therapeutic option than iliofemoral vein balloon dilation with iliac vein stent implantation for PTS patients.

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.

Integrative analysis prioritizes the relevant genes and risk factors for chronic venous disease.

OBJECTIVE: Chronic venous disease (CVD) refers to a range of symptoms resulting from long-term morphological and functional abnormalities of the venous system. However, the mechanism of CVD development remains largely unknown. Here, we aim to provide more information on CVD pathogenesis, prevention strategies, and therapy development through the integrative analysis of large-scale genetic data. METHODS: Genetic data were obtained from publicly accessible databases. We used different approaches, including Functional Mapping and Annotation, DEPICT, Sherlock, SMR/HEIDIS, DEPICT, and NetWAS to identify possible causal genes for CVD. Candidate genes were prioritized to further literature-based review. The differential expression of prioritized genes was validated by microarray from the Gene Expression Omnibus, a public genomics data repository and real-time quantitative polymerase chain reaction of varicose vein specimens. The causal relationships between risk factors and CVD were assessed using the two-sample Mendelian randomization approach. RESULTS: We identified 46 lead single-nucleotide polymorphisms and 26 plausible causal genes for CVD. Microarray data indicated differential expression of possible causal genes in CVD when compared with controls. The expression levels of WDR92, RSPO3, LIMA, ABCB10, DNAJC7, C1S, and CXCL1 were significantly downregulated (P < .05). PHLDA1 and SERPINE1 were significantly upregulated (P < .05). Dysregulated expression of WDR92, RSPO3, and CASZ1 was also found in varicose vein specimens by quantitative polymerase chain reaction. Two-sample Mendelian randomization suggested causative effects of body mass index (odds ratio [OR], 1.008; 95% confidence interval [CI], 1.005-1.010), standing height (OR, 1.009; 95% CI, 1.007-1.011), college degree (OR, 0.983; 95% CI, 0.991-0.976), insulin (OR, 0.858; 95% CI, 0.794-0.928), and metformin (OR, 0.944; 95% CI, 0.904-0.985) on CVD. CONCLUSIONS: Our study integrates genetic and gene expression data to make an effective risk gene prediction and etiological inferences for CVD. Prioritized candidate genes provide more insights into CVD pathogenesis, and the causative effects of risk factors on CVD that deserve further investigation.

Managing Emergent Surgery for Ruptured Abdominal Aortic Aneurysm during the COVID-19 Pandemic.

BACKGROUND: Coronavirus disease 2019 (COVID-19) has become a global pandemic which may compromise the management of vascular emergencies. An uncompromised treatment for ruptured abdominal aortic aneurysm (rAAA) during such a health crisis represents a challenge. This study aimed to demonstrate the treatment outcomes of rAAA and the perioperative prevention of cross-infection under the COVID-19 pandemic. METHODS: In cases of rAAA during the pandemic, a perioperative workflow was applied to expedite coronavirus testing and avoid pre-operative delay, combined with a strategy for preventing cross-infection. Data of rAAA treated in 11 vascular centers between January-March 2020 collected retrospectively were compared to the corresponding period in 2018 and 2019. RESULTS: Eight, 12, and 14 rAAA patients were treated in 11 centers in January-March 2018, 2019, and 2020, respectively. An increased portion were treated at local hospitals with a comparable outcome compared with large centers in Guangzhou. With EVAR-first strategy, 85.7% patients with rAAA in 2020 underwent endovascular repair, similar to that in 2018 and 2019. The surgical outcomes during the pandemic were not inferior to that in 2018 and 2019. The average length of ICU stay was 1.8 ± 3.4 days in 2020, tending to be shorter than that in 2018 and 2019, whereas the length of hospital stay was similar among 3 years. The in-hospital mortality of 2018, 2019, and 2020 was 37.5%, 25.0%, and 14.3%, respectively. Three patients undergoing emergent surgeries were suspected of COVID-19, though turned out to be negative after surgery. CONCLUSIONS: Our experience for emergency management of rAAA and infection prevention for healthcare providers is effective in optimizing emergent surgical outcomes during the COVID-19 pandemic.

Drug-Coated Balloon Angioplasty Versus Standard Uncoated Balloon Angioplasty for Long Femoropopliteal Lesions: Post Hoc Analysis of the 24-Month Results of the AcoArt I Study.

OBJECTIVE: Restenosis is a common complication after endovascular treatment of peripheral artery disease. Drug-coated balloon (DCB) treatment has been proven safe and effective in reducing the rate of restenosis for simple and short lesions. However, the clinical results of DCBs for long lesions are still very limited. This study aimed to evaluate the efficacy and safety of DCBs in the treatment of long femoropopliteal artery disease. And the results of this study will also complement the existing evidence of DCB treatment of long lesions. METHODS: Patients with lesion length ≥ 15cm according to computed tomography angiography (CTA) or angiography in the AcoArt I Study were included into this study. Based on the balloon catheter used in treatment, patients were divided into the DCB group and the percutaneous transluminal angioplasty (PTA) group. The demographic, lesion, and procedural characteristics and 24-month follow-up results were compared between the 2 groups. The primary efficacy endpoints were angiographic late lumen loss (LLL) at 6 months or at the time of clinically driven target lesion revascularization (CD-TLR), primary patency (PP), freedom from CD-TLR, and changes in the ankle-brachial index (ABI) and Rutherford class during 24 months of follow-up. The safety endpoint was the occurrence of major adverse events. RESULTS: The total number of patients was 87, including 42 in the DCB group and 45 in the PTA group. There were no significant differences between the 2 groups in demographic, lesion,and procedural characteristics. The 6-month follow-up angiography showed that the LLL was significantly smaller in the DCB group than the PTA group (0.27 ± 0.90 mm vs 1.32 ± 0.91 mm; P < 0.001). At 24 months, compared with the PTA group, the DCB group had a significantly higher rate of freedom from CD-TLR (81.58% vs 43.18%; P < 0.001) and a significantly higher PP rate (46.88% vs 15.00%; P = 0.003). The DCB group had a significantly higher ABI than the PTA group at 6, 12, and 24 months (P < 0.001, P = 0.004 and P = 0.018, respectively). The DCB group had a better Rutherford class than the PTA group at 6 and 12 months (P = 0.033 and P = 0.012, respectively); the Rutherford class did not significantly differ between the 2 groups at 24 months (P = 0.127). The incidence of major adverse events did not significantly differ between the 2 groups. CONCLUSION: The effectiveness of the DCB is superior to a standard uncoated balloon in treating long lesions during 24 months of follow-up. Furthermore, the safety of the DCB is equivalent to that of PTA.

Comparison of the Bifurcated Graft Reconstruction and Aortic Stump Closure in Open Surgical Conversion After Endovascular Aneurysm Repair.

BACKGROUND: The optimal management of the aortic stump in open surgical conversion (OSC) after Abdominal aortic aneurysm (AAA) endovascular aneurysm repair (EVAR) is debated. Therefore, we aimed to compare the efficacies and safety between the bifurcated prosthetic vascular graft in situ stump reconstruction (p-graft ISSR) and aortic stump closure (ASC) in OSC. METHODS: We analyzed 973 elective AAA patients admitted from January 01, 2001 to December 31, 2020, at the First Affiliated Hospital of Sun Yat-sen University. We conducted a statistical analysis of the clinical characteristics, procedural data, as well as outcomes and technique considerations of aortic stump management in OSC patients. RESULTS: A total of 24 male patients had OSC after EVAR. The rate of stent graft infection was 54.17% before OSC. Eleven patients underwent ASC, and 13 patients were treated with p-graft ISSR. The major complication after OSC was aortic stump bleeding (total incidence was 37.50%) (1 patient with a periaortic hematoma and 8 patients with a stump blowout). The total incidences of stump blowout between the patients with ASC and those with p-graft ISSR were significantly different (45.45% vs. 23.08%, P < 0.05). The total perioperative mortality was 25.00% (6 patients with stump blowouts). The perioperative survival rates between these 2 aortic stump management approaches were 72.72% and 76.92% (ASC vs. p-graft ISSR, P < 0.05). In total, 18 patients were followed up (3-180 months). There were 3 aorta-related deaths during the late follow-up period (including both of the 2 stump-blowout-related deaths just treated with ASC). CONCLUSIONS: If the condition of the aorta and peri-aortic tissue are suitable for a prosthetic graft bypass, the p-graft ISSR is highly recommended for OSC patients after EVAR.

AHNAK2 promotes thyroid carcinoma progression by activating the NF-κB pathway.

Thyroid carcinoma metastasis is the main reason for treatment failure; therefore, understanding the regulatory mechanisms of thyroid carcinoma metastasis is critical to treat patients with thyroid carcinoma. The present study aimed to investigate the role of AHNAK Nucleoprotein 2 (AHNAK2) in thyroid carcinoma metastasis. AHNAK2 was found to be upregulated in thyroid carcinoma tissues, especially in metastatic thyroid carcinoma tissues. Patients with high AHNAK2 expression had poor prognosis. AHNAK2 knockdown inhibited thyroid carcinoma migration, invasion, and metastasis. Mechanistic analysis showed that AHNAK2 knockdown reduced thyroid carcinoma progression by inhibiting nuclear factor kappa B (NF-κB) pathway activity. The results identified a novel target to treat metastatic thyroid carcinoma.

Tripartite motif-containing 3 (TRIM3) enhances ER signaling and confers tamoxifen resistance in breast cancer.

Tamoxifen resistance remains a clinical problem in estrogen receptor (ER)-positive breast cancer. SUMOylation of ERα enhances ERα-induced transcription activity. Tripartite motif-containing (TRIM) proteins are a new class of SUMO E3 ligases, which regulate the SUMOylation of proteins. However, the precise molecular mechanism and function of TRIM3 in SUMOylation and the response to tamoxifen remain unclear. In the present study, we observed that TRIM3 was dramatically overexpressed in breast cancer, which correlated with tamoxifen resistance. Furthermore, TRIM3 overexpression significantly correlated with poor survival of patients with ER+ breast cancer treated with tamoxifen. TRIM3 overexpression conferred cell survival and tumorigenesis, whereas knocking down of TRIM3 reduced these capabilities. Moreover, TRIM3, as a ubiquitin carrier protein 9 (UBC9) binding protein, promoted SUMO modification of estrogen receptor 1 (ESR1) and activated the ER pathway. Silencing UBC9 abolished the function of TRIM3 in regulating tamoxifen resistance. These results suggest TRIM3 as a novel biomarker for breast cancer therapy, indicating that inhibiting TRIM3 combined with tamoxifen might provide a potential treatment for breast cancer.