Long-term Outcomes of Endovascular Repair for Blunt Thoracic Aortic Injury: A 10 Year Multi-center Experience.

OBJECTIVE: This study aimed to assess the long-term outcomes in patients treated by thoracic endovascular aortic repair (TEVAR) for blunt thoracic aortic injuries (BTAI). MATERIALS AND METHODS: From January 2010 to December 2019, this retrospective observational study was conducted at 3 centers, involving 62 consecutive BTAI patients who underwent TEVAR. Computed tomography angiography scans were planned to be conducted at 6 months post-procedure, and annually thereafter. RESULTS: Technical success was achieved in all 62 procedures (100%), which included cases of dissection (n=35, 56.45%), pseudoaneurysm (n=20, 32.26%), and rupture (n=7, 11.29%). Mean injury severity score was 31.66±8.30. A total of 21 supra-arch branches were revascularized by chimney technique, with 12 cases involving the left subclavian artery (LSA) and 9 cases involving the left common carotid artery. In addition, 11 LSAs were covered during the procedure. The in-hospital mortality rate was 1.61% (n=1). The mean follow-up time was 86.82±30.58 months. The all-cause follow-up mortality rate was 3.28% (n=2). Stenosis or occlusion of 3 supra-arch branches (4.92%) was identified at follow-up, with 2 cases (3.28%) requiring re-intervention. No spinal cord ischemia, endoleak, or migration was observed. CONCLUSIONS: Despite only including patients with long-term follow-up, this study confirms the long-term safety and effectiveness of TEVAR for BTAI. For young BTAI patients, as the thoracic aorta increases with age, longer follow-up is needed to observe the potential mismatch between the endograft and the aorta. CLINICAL IMPACT: This study confirms the long-term safety and effectiveness of endovascular treatment for blunt thoracic aortic injury (BTAI). For young BTAI patients, as the thoracic aorta increases with age, longer follow-up is needed to observe the potential mismatch between the endograft and the aorta. Through a remarkably extended follow-up period (86.82±30.58 months) conducted at multiple centers in China, this study confirms the long-term safety and effectiveness of endovascular treatment for BTAI.

Coaxial electrospun Ag-NPs-loaded endograft membrane with long-term antibacterial function treating mycotic aortic aneurysm.

The use of endovascular stent-graft has become an important option in the treatment of aortic pathologies. However, the currently used endograft membranes have limited ability to prevent bacterial colonization. This makes them unsuitable for the treatment of mycotic aneurysms, as the infection is prone to progress after endograft implantation. Moreover, even in non-mycotic aortic pathologies, endograft infections can occur in the short or long term, especially for patients with diabetes mellitus or in immune insufficiency conditions. So, this study aimed to develop a kind of Ag-NPs-loaded endograft membrane by coaxial electrospinning technique, and a series of physical and chemical properties and biological properties of the Ag-NPs-loaded membrane were characterized. Animal experiments conducted in pigs confirmed that the Ag-NPs-loaded membrane was basically non-toxic, exhibited good biocompatibility, and effectively prevented bacterial growth in a mycotic aortic aneurysm model. In conclusion, the Ag-NPs-loaded membrane exhibited good biocompatibility, good anti-infection function and slow-release of Ag-NPs for long-term bacteriostasis. Thus, the Ag-NPs-loaded membrane might hold potential for preventing infection progression and treating mycotic aortic aneurysms in an endovascular way.

Selenium Deficiency Promotes Dilatation of the Aorta by Increasing Expression and Activity of Vascular Smooth Muscle Cell Derived Matrix Metalloproteinase-2.

OBJECTIVE: Selenium (Se) is a key part of the body's oxidation defence system. However, it is unclear whether Se affects the development of aortic aneurysm (AA). An animal experiment was conducted to clarify the role of Se in AA development. METHODS: C57BL/6N male mice were fed with a Se deficient (Se-D, < 0.05 mg/kg), Se adequate (Se-A, 0.2 mg/kg), or Se supplemented (Se-S, 1 mg/kg) diet for 8 weeks. Subsequently, an AA murine model (Se-D, n = 11; Se-A, n = 12; Se-S, n = 15) was established using angiotensin II (Ang II, 1 mg/kg/min) for four weeks plus ß-aminopropionitrile (BAPN, 1 mg/mL) for the first two weeks. Saline replaced Ang II, and BAPN was removed during the modelling process for sham mice (Se-A, n = 9). To determine whether Se deficiency promoted aortic dilation via matrix metalloproteinase-2 (MMP-2), the non-specific MMP inhibitor doxycycline (Dox, 100 mg/kg/day) was given to Se-D AA mice (n = 7) for two weeks. RESULTS: The maximum aortic diameter in Se-D AA model mice was significantly increased compared with Se-A AA model mice. MMP-2 expression and activity in the aortic media of Se-D AA model mice was significantly increased compared with Se-A AA model mice. A large number of vascular smooth muscle cells (VSMCs) were found aggregating in the media of the non-dilated aorta of Se-D AA model mice, which was completely inhibited by Dox. The percentage of VSMCs in aortic media of Se-D AA model mice was significantly higher than in Se-A AA model mice. The maximum aortic diameter and occurrence rate of AA in Se-D AA model mice with Dox were significantly reduced compared with Se-D AA model mice. CONCLUSION: Se deficiency promoted dilatation of the aorta in AA model mice by increasing expression and activity of VSMC derived MMP-2, causing abnormal aggregation and proliferation of VSMCs in aortic media.

TEVAR for aortic arch lesions combining physician-modified endograft and in-situ fenestration.

BACKGROUND: The aim of this retrospective study was to investigate the outcomes of combining physician-modified endograft (PMEG) and in-situ fenestration (ISF) for aortic arch repair. METHODS: A retrospective analysis was performed in 12 patients with aortic arch pathologies who underwent thoracic endovascular aortic repair with PMEG and ISF between June 2019 and February 2020. RESULTS: Revascularizations of supra-aortic arteries were successfully performed in 91.7% patients (11/12). One patient with aberrant right subclavian artery was unsuccessful because of tortuosity and sharp angle. One patient received endovascular exclusion by Viabahn due to artery injury of the femoral access. During the follow-up (mean 22.7 months), one patient underwent Bentall surgery because of retrograde type A aortic dissection, and one patient received coils embolization due to occurrence of a type I endoleak. In addition, one patient died of myocardial infarction 13 months after surgery. Results obtained after computed tomography angiography confirmed patency of all the supra-aortic arteries. CONCLUSIONS: Combining PMEG and ISF could be a feasible option for aortic arch lesions in selected patients. Long-term durability concerns require further evaluation.

Nanopore long-read RNA sequencing reveals functional alternative splicing variants in human vascular smooth muscle cells.

Vascular smooth muscle cells (VSMCs) are the major contributor to vascular repair and remodeling, which showed high level of phenotypic plasticity. Abnormalities in VSMC plasticity can lead to multiple cardiovascular diseases, wherein alternative splicing plays important roles. However, alternative splicing variants in VSMC plasticity are not fully understood. Here we systematically characterized the long-read transcriptome and their dysregulation in  human aortic smooth muscle cells (HASMCs) by employing the Oxford Nanopore Technologies long-read RNA sequencing in HASMCs that are separately treated with platelet-derived growth factor, transforming growth factor, and hsa-miR-221-3P transfection. Our analysis reveals frequent alternative splicing events and thousands of unannotated transcripts generated from alternative splicing. HASMCs treated with different factors exhibit distinct transcriptional reprogramming modulated by alternative splicing. We also found that unannotated transcripts produce different open reading frames compared to the annotated transcripts. Finally, we experimentally validated the unannotated transcript derived from gene CISD1, namely CISD1-u, which plays a role in the phenotypic switch of HASMCs. Our study characterizes the phenotypic modulation of HASMCs from an insight of long-read transcriptome, which would promote the understanding and the manipulation of HASMC plasticity in cardiovascular diseases.

Minimally Invasive Endovascular Repair for Nondissected Ascending Aortic Disease: A Systematic Review.

Objective: The aim of this study is to evaluate the efficacy of endovascular treatment for nondissected diseases of the ascending aorta. Data Sources. PubMed, Embase, and SciELO. Review Methods. In this study, we conducted a search on the PubMed, Embase, and SciELO databases for all cases of ascending aortic endovascular repair included in the literature published between January 2007 and July 2023, excluding type A aortic dissection. We reviewed 56 case reports and 7 observational studies included in this study, assessing the techniques, equipment, procedural steps, and results. We summarized the age, complications, follow-up time, and access route. Results: This study includes 63 articles reporting 105 patients (mean age: 64.96 ± 17.08 years) who received endovascular repair for nondissected ascending aortic disease. The types of disease include aneurysm (N = 16), pseudoaneurysm (N = 71), penetrating aortic ulcer (N = 10), intramural hematoma (N = 2), thrombosis (N = 2), iatrogenic coarctation (N = 1), and rupture of the aorta (N = 3). The success rate of surgery is 99.05% (104/105). Complications include endoleak (10.48%, 11/105), stroke (5.71%, 6/105), postoperative infection (1.91%, 2/105), acute renal failure (0.95%, 1/105), aortic rupture (0.95%, 1/105), thrombosis (0.95%, 1/105), and splenic infarction (0.95%, 1/105). Five patients required conversion to open surgery, two patients underwent endovascular reintervention, and four of these five patients underwent surgery due to endoleak. Early mortality was 2.86% (3/105). Conclusion: While the viability and results of endovascular repair for the treatment of ascending aortic disease are acknowledged in some circumstances, further research is needed to determine the safety and effectiveness of endovascular treatment for ascending aortic disease.

Pristimerin protects against pathological cardiac hypertrophy through improvement of PPARα pathway.

Pristimerin (PM), serving as a biological component mainly obtained from Celastraceae and Hippocrateaceae families, has been extensively explored for its numerous pharmacological activities, especially anti-cancer activity. However, the function of PM on pathological cardiac hypertrophy is poorly understood. This work was intended to investigate the effects of PM on pressure-overload induced myocardial hypertrophy and its potential pathways. Mouse model of pathological cardiac hypertrophy was generated by transverse aortic constriction (TAC) or minipump administration of the ß-adrenergic agonist ISO for 4 weeks, and PM (0.5 mg/Kg/d, i.p.) was treated for 2 weeks. PPARα-/- mice received TAC surgery were used for mechanism exploration. Moreover, neonatal rat cardiomyocytes (NRCMs) were utilized to explore the effect of PM following Angiotensin II (Ang II, 1.0 µM) administration. We found that PM attenuated pressure-overload induced cardiac dysfunction, myocardial hypertrophy and fibrosis in mice. Likewise, PM incubation dramatically reversed Ang II-mediated cardiomyocytes hypertrophy in NRCMs. RNA-Sequence showed that PM selectively contributed to improvement of PPARα/PGC1 signaling, while silencing PPARα abrogated the beneficial effects of PM on Ang II-treated NRCMs. Importantly, PM ameliorated Ang II-induced mitochondrial dysfunction and decrease in metabolic genes, whereas knockdown of PPARα eliminated these alterations in NRCMs. Similarly, PM presented limited protective effects on pressure-overload induced systolic dysfunction and myocardial hypertrophy in PPARα deficient mice. Overall, this study revealed that PM exerted protective activity against pathological cardiac hypertrophy through improvement of PPARα/PGC1 pathway.

Identification of blurred terahertz images by improved cross-layer convolutional neural network.

Terahertz imaging technology has been gradually used in space communication, radar detection, aerospace and biomedical fields. Nevertheless, there are still some limits in terahertz image, such as single tone, fuzzy texture features, poor image resolution and less data, which seriously affect the application and popularization of Terahertz image technology in many fields. Traditional convolutional neural network (CNN) is an effective method for image recognition, but it is limited in highly blurred terahertz image recognition due to the great difference between terahertz image and traditional optical image. This paper presents a proven method for higher recognition rate of blurred terahertz images by using an improved Cross-Layer CNN model with different definition terahertz image dataset. Compared to employing clear image dataset, the accuracy of blurred image recognition can be improved from about 32% to 90% with different definition dataset. Meanwhile, the recognition accuracy of high blurred image can be improved by approximately 5% in contrast to the traditional CNN, which makes the higher recognition ability of neural network. It can be demonstrated that various types of blurred terahertz imaging data can be effectively identified by constructing different definition dataset combined with Cross-Layer CNN. A new method is proved to improve the recognition accuracy of terahertz imaging and application robustness in real scenarios.

Angioplasty for Supra-Aortic Arterial Lesions from Takayasu Arteritis: Efficacy of Cutting Balloon Angioplasty Versus Conventional Balloon Angioplasty.

BACKGROUND: This retrospective study aimed to evaluate the safety and efficacy of cutting balloon angioplasty and conventional balloon angioplasty in supra-aortic arterial lesions caused by Takayasu arteritis. METHODS: A total of 46 patients with supra-aortic arterial lesions between January 2011 and December 2018 were included. Cutting balloon angioplasty was applied for 17 patients with 24 supra-aortic arterial lesions (group A), while 29 patients with 36 supra-aortic arterial lesions received conventional balloon angioplasty (group B). The preoperative clinical manifestation, operation result, and postoperative outcomes were recorded and compared in the 2 groups. RESULTS: Dizziness, visual disturbance, and unequal/absent pulses were the most common manifestations. The technical success of revascularization was 93.5% (43/46) in patients and 93.3% (56/60) in lesions. The stent implantation rate in group A was significantly lower than that in group B (4.2% vs. 50% in lesions, P < 0.05). Restenosis was the most common complication in both groups. Although the early (≤30 days) and late (>30 days) complications in group A were less than those in group B, there was no significant difference between the 2 groups (P > 0.05). Moreover, the primary-assisted patency of cutting balloon angioplasty and conventional balloon angioplasty at 1, 2, and 5 years were 66.7%, 62.5%, and 62.5% and 61.1%, 58.2%, and 49.8%, there was no significant difference between the 2 groups (P > 0.05), respectively. CONCLUSIONS: Compared with conventional balloon angioplasty, cutting balloon angioplasty could be considered a safe and effective alternative for supra-aortic arterial lesions caused by Takayasu arteritis, demonstrating better patency and clinical benefit.

Management of an Isolated Left Vertebral Artery on the Arch During Zone 2 Landing Thoracic Endovascular Aortic Repair: A Multicentre Retrospective Study.

OBJECTIVE: To compare the early and midterm outcomes of three different strategies for an isolated left vertebral artery on the arch (LVoA) revascularisation during thoracic endovascular aortic repair (TEVAR) with a proximal zone 2 landing. METHODS: Between January 2016 and December 2021, 67 patients with LVoA and aortic arch pathologies who underwent zone 2 landing TEVAR at four medical centres were enrolled. These patients were divided into three groups for comparison: the novel chimney (group A, n = 28) with the right brachial-left brachial through and through (RLT) procedure; in vitro fenestration (group B, n = 24); and transposition (group C, n = 15). The flow direction and velocity of the LVoA was examined by Doppler ultrasound in the pre-, intra-, and post-operative periods. Primary outcomes were all cause mortality and new neurological symptoms. RESULTS: No deaths or new neurological symptoms occurred within 30 days. Early type Ia endoleak rates were 18% (n = 5), 17% (n = 4), and 0% in groups A, B, and C, respectively (p = .22). All patients had antegrade flow of the LVoA. The mean ± standard deviation duration of follow up was 63.6 ± 4.0 months. No deaths were observed during follow up. The rates of new neurological symptoms were 0%, 8%, and 33% in groups A, B, and C, respectively. The rates of midterm type Ia endoleak were 7%, 12%, and 0% in groups A, B, and C, respectively (p = .35). Bidirectional flow rates in the LVoA were 0%, 21%, and 27% in groups A, B, and C, respectively (p = .021). Two (8%) and three (20%) patients in groups B and C underwent a secondary procedure because of mild dizziness, but this was not necessary in group A (p = .058). CONCLUSION: The novel chimney technique of the RLT procedure may be feasible for patients with a LVoA requiring zone 2 anchoring. Accurate determination of the safety and feasibility of this novel technique requires larger sample sizes and longer follow up.

Single-branched stent-graft with on-table fenestration for endovascular repair of primary retrograde type A aortic dissection: A multicenter retrospective study.

Objective: This study aims to evaluate the feasibility, efficacy, and safety of a single-branched stent-graft with on-table fenestration for primary retrograde type A aortic dissection (RTAD) during thoracic endovascular aortic repair (TEVAR). Materials and methods: From January 2019 to December 2021, 36 patients with primary RTAD from five tertiary hospitals received medical management in the acute phase. They underwent TEVAR with a proximal zone 1 landing for aortic arch reconstruction in the subacute phase, using a fenestration technique on a single-branched stent-graft. Nearly 2 weeks after admission, computed tomography angiography (CTA) was re-examined to evaluate the thrombosis status of retrograde false lumen (FL). The primary outcomes were technical success, patency of the target branch arteries, and absence of type Ia endoleaks. The second outcomes were stent-graft-related complications and all-cause mortality. Results: The mean age was 56.2 ± 11.3 years, and 29 (80.6%) were male. After a median interval of 18.0 [interquartile range (IQR), 17.0-20.3] days of medical treatment, the partial and complete thrombosis of proximal FL rates increased to 52.8% and 47.2%, respectively. One patient (2.8%) experienced postoperative type Ia endoleaks, and was successfully re-treated using coli and Onyx glue. The median hospital stay was 20.5 (IQR, 18.0-23.0) days. The overall technical success rate was 100%. The median follow-up time was 31.5 (IQR, 29.8-34.0) months. There was one death (2.8%) due to gastrointestinal bleeding. Distal aortic segmental enlargement (DASE) occurred in two (5.6%) patients. No major complications or recurrent dissections in the proximal landing zone were recorded during follow up. Conclusion: The retrograde FL in primary RTAD could realize partial or complete thrombosis after medical management in the acute phase, and it might be regarded as a valid proximal landing zone for endovascular repair. The single-branched stent graft with on-table fenestration performed in the subacute phase may be feasible strategy in selective primary RTAD patients.

Alpha-ketoglutarate ameliorates abdominal aortic aneurysm via inhibiting PXDN/HOCL/ERK signaling pathways.

Abdominal aortic aneurysm (AAA) represents the serious vascular degenerative disorder, which causes high incidence and mortality. Alpha-ketoglutarate (AKG), a crucial metabolite in the tricarboxylic acid (TCA) cycle, has been reported to exert significant actions on the oxidative stress and inflammation. However, its role in AAA still remains elusive. Herein, we examined the effects of AKG on the formation of AAA. The study established an elastase-induced mouse abdominal aortic aneurysms model as well as a TNF-α-mediated vascular smooth muscle cells (VSMCs) model, respectively. We displayed that AKG pre-treatment remarkably prevented aneurysmal dilation assessed by diameter and volume and reduced aortic rupture. In addition, it was also observed that AKG treatment suppressed the development of AAA by attenuating the macrophage infiltration, elastin degradation and collagen fibers remodeling. In vitro, AKG potently decreased TNF-α-induced inflammatory cytokines overproduction, more apoptotic cells and excessive superoxide. Mechanistically, we discovered that upregulation of vpo1 in AAA was significantly suppressed by AKG treatment. By exploring the RNA-seq data, we found that AKG ameliorates AAA mostly though inhibiting oxidative stress and the inflammatory response. PXDN overexpression neutralized the inhibitory effects of AKG on ROS generation and inflammatory reaction in MOVAS. Furthermore, AKG treatment suppressed the expression of p-ERK1/2, 3-Cl Tyr in vivo and in vitro. ERK activator disrupted the protective of AKG on TNF-α-induced VSMCs phenotypic switch. Conclusively, AKG can serve as a beneficial therapy for AAA through regulating PXDN/HOCL/ERK signaling pathways.

TCF7 is highly expressed in immune cells on the atherosclerotic plaques, and regulating inflammatory signaling via NFκB/AKT/STAT1 signaling.

Atherosclerosis, which is the fundamental basis for cardiovascular diseases in the global world, is driven by multiple roles of the immune system in the circulation and vascular plaque. Recent studies demonstrated that T-cell infiltrates into aorta plaque and plays an important role in recruiting macrophages to the vascular wall. Here, using single-cell sequencing, we found T cells in patients' plaques and differentially expressed genes (DEGs) of T cells in atherosclerosis mice. T cells and macrophages were continuously activated in atherosclerotic plaque in patients. Besides, other immune cells also take part in atherogenesis, such as natural killer (NK) cells, granulocytes. Interferon (IFN)/NFκB signaling, the AKT signaling pathway was highly activated in mouse (in vivo) and cell line (in vitro). TCF7 and XCL1 were regulated by AKT and NFκB, respectively through protein-protein network analysis. Therefore, we attempt to clarify and discover potential genes and new mechanisms associated with atherosclerosis for drug development.

Mid-term Comparison of One-Piece Branched Stent-Graft and Chimney Technique Treating Aortic Arch Pathologies.

PURPOSE: We compared the mid-term outcomes of a one-piece branched stent-graft with the chimney technique in the treatment of aortic arch pathologies. METHODS: Between August 2012 and December 2017, a retrospective analysis of 279 patients with thoracic aortic dissection (TAD) or aneurysm (TAA) who underwent thoracic endovascular aortic repair with b-TEVAR (n = 69, 58 TAD and 11 TAA) or c-TEVAR (n = 210, 151 TAD and 59 TAA) was performed. RESULTS: Forty-five double-chimney for the left subclavian artery (LSA) and left common carotid artery LCCA and 165 single-chimney for the LSA were performed in chimney-TEVAR (c-TEVAR) and 69 branched-TEVAR (b-TEVAR) with 36 single-branched stent-grafts and 33 branched stent-grafts combined with fenestration technique. The c-TEVAR group experienced more in-hospital complications than the b-TEVAR group (19.5 vs. 7.2%, p = 0.017), primarily because the c-TEVAR group experienced more in-hospital cerebral ischemia events (6.2 vs. 0%, p = 0.043) and intra-operative type I endoleaks (31.9 vs. 5.8%, p < 0.01). There were significantly more follow-up type I endoleaks (21.9 vs. 4.3%, p = 0.002), cerebral ischemia events (11.0 vs. 2.9%, p = 0.042), and re-interventions (12.9 vs. 4.3%, p = 0.048) in the c-TEVAR group than in the b-TEVAR group. However, follow-up mortality was not significantly different between the c-TEVAR and b-TEVAR groups (5.2 vs. 2.9%, p = 0.638). CONCLUSION: In patients with aortic pathologies involving the arch branches, customized b-TEVAR may result in fewer cerebral ischemia events and endoleaks than c-TEVAR. However, c-TEVAR should be considered an off-the-shelf treatment option for patients in need of emergency treatment. LEVEL OF EVIDENCE: Level 4, Case Series.

A Novel Solution for Distal Dilation of Chronic Dissection After Repair Involving Visceral Branches: The Road Block Strategy.

Aim: Notwithstanding that unprecedented endovascular progress has been achieved in recent years, it remains unclear what is the best strategy to preserve the blood perfusion of abdominal visceral arteries and promote positive aortic remodeling in patients with distal dilatation of chronic aortic dissection in abdominal visceral part (CADAV) after aortic repair. The present study developed a Road Block Strategy (RBS) to solve this conundrum. Methods and Results: This prospective single-center clinical study included patients suffering from symptomatic distal dilatation of CADAV after aortic repair treated with RBS from January 2015 to December 2019 and followed up regularly for at least 2 years. Stent grafts were implanted first to cover distal tears and expand the true lumen. Device embolization was performed to induce proximal and distal segmental false lumen thrombosis (FLT) apart from the level of the ostia of vital branches. Successful RBS was performed in 13 patients. Significant differences were found in maximum true lumen diameter (p < 0.05), blood flow area in false lumen (FL) (p < 0.001), and the ratio of blood lumen to FL area (p < 0.05) between the pre-procedure and the latest follow-up results. No aortic rupture, vital branches occlusion, thoracic and abdominal pain, or death occurred during hospitalization and follow-up. Conclusions: Our findings suggest that RBS is feasible in treating distal dilatation of chronic aortic dissection after prior proximal repair, inducing false lumen thrombosis, preventing deterioration of aortic dissection, and maintaining the patency of abdominal visceral arteries.

Quercetin Reduces the Virulence of S. aureus by Targeting ClpP to Protect Mice from MRSA-Induced Lethal Pneumonia.

The dramatic increase of methicillin-resistant Staphylococcus aureus (MRSA) poses a great challenge to the treatment of Staphylococcus aureus (S. aureus) infections. Therefore, there is an urgent need to identify novel anti-infective agents to attack new targets to overcome antibiotic resistance. Casein hydrolase P (ClpP) is a key virulence factor in S. aureus to maintain cellular homeostasis. We screened from flavonoids and finally determined that quercetin could effectively attenuate the virulence of MRSA. The results of the thermal shift assay showed that quercetin could bind to ClpP and reduce the thermal stability of ClpP, and the KD value between quercetin and ClpP was 197 nM as determined by localized surface plasmon resonance. We found that quercetin exhibited a protective role of a mouse model of MRSA-induced lethal infection in a murine model. Based on the above facts, quercetin, as a ClpP inhibitor, could be further developed as a potential candidate for antivirulence agents to combat S. aureus infections. IMPORTANCE The resistance of Staphylococcus aureus (S. aureus) to various antibiotics has increased dramatically, and thus the development of new anti-infective drugs with new targets is urgently needed to combat resistance. Caseinolytic peptidase P (ClpP) is a casein hydrolase that has been shown to regulate a variety of important virulence factors in S. aureus. Here, we found that quercetin, a small-molecule compound from traditional Chinese herbal flavonoids, effectively inhibits ClpP activity. Quercetin attenuates the expression of multiple virulence factors in S. aureus and effectively protects mice from lethal pneumonia caused by MRSA. In conclusion, we determined that quercetin is a ClpP inhibitor and an effective lead compound for the development of a virulence factor-based treatment for S. aureus infection.

Biochanin A as an α-hemolysin inhibitor for combating methicillin-resistant Staphylococcus aureus infection.

Methicillin-resistant Staphylococcus aureus (MRSA) is a multidrug-resistant pathogen that poses a significant risk to global health today. In S. aureus, α-hemolysin is an important virulence factor as it contributes to the capacity of the bacteria to infect the host. Here, we showed that biochanin A (bioA), an isoflavone present in red clover, cabbage and alfalfa, effectively inhibited hemolytic activity at a dose as low as 32 µg/mL. Further, western blot and RT-qPCR data showed that bioA reduced the production and expression of MRSA hemolysin in a dose-dependent manner. In addition, when different concentrations of bioA were added to a coculture system of A549 cells and S. aureus, it could significantly decrease cell injury. Importantly, the in vivo study showed that bioA could protect mice from pneumonia caused by a lethal dose of MRSA, as evidenced by improving their survival and reducing the number of bacterial colonies in lung tissues, the secretion of hemolysin into alveolar lavage fluid and the degree of pulmonary edema. In conclusion, biochanin A protected the host from MRSA infection by inhibiting the expression of the hemolysin of MRSA, which may provide experimental evidence for its development to a potential anti-MRSA drug.

Dataset of the vascular e-Learning during the COVID-19 pandemic (EL-COVID) survey.

This dataset supports the findings of the vascular e-Learning during the COVID-19 pandemic survey (the EL-COVID survey). The General Data Protection Regulation (GDPR) of the European Union was taken into consideration in all steps of data handling. The survey was approved by the institutional ethics committee of the Primary Investigator and an online English survey consisting of 18 questions was developed ad-hoc. A bilingual English-Mandarin version of the questionnaire was developed according to the instructions of the Chinese Medical Association in order to be used in mainland People's Republic of China. Differences between the two questionnaires were minor and did affect the process of data collection. Both questionnaires were hosted online. The EL-COVID survey was advertised through major social media. All national and regional contributors contacted their respective colleagues through direct messaging on social media or by email. Eight national societies or groups supported the dissemination of the EL-COVID survey. The data provided demographics information of the EL-COVID participants and an insight on the level of difficulty in accessing or citing previously attended online activities and whether participants were keen on citing these activities in their Curricula Vitae. A categorization of additional comments made by the participants are also based on the data. The survey responses were filtered, anonymized and submitted to descriptive analysis of percentage.

Chimney Graft Technique Combined With Embolization for Treating Ruptured Aortic Arch Lesions.

Background: This study aimed to share the experience in applying the chimney graft technique combined with embolization for treating aortic arch rupture under emergency conditions and evaluating early-term results in these patients. Methods: This study retrospectively included patients with ruptured aortic arch lesions who received the chimney graft technique combined with embolization between March 2016 and March 2021. The primary endpoint was a technical success, deemed as successful stent graft deployment to the planned location, patency of the target branch vessel, and absence of significant type I endoleak. The secondary endpoint was clinical success defined with the size of false lumen in follow-up remaining unchanged or decreasing over time, 30-day mortality, complication, and primary patency of chimney graft. Results: This study included 12 patients (age, 61 ± 12 years; male, 83%). Five patients (42%) received single chimney, one patient (8%) received double chimney, and six patients (50%) received triple chimney. Intraoperative type I endoleak occurred in six patients (50%) who underwent endovascular embolization in the primary operation. Post-operative type I endoleak, evaluated by computed tomography angiography examination following the primary operation, occurred in seven patients (58%), including one patient who received endovascular embolization two times. All patients with post-operative type I endoleak were successfully re-treated using coil and Onyx glue within 1 week, and the median length of stay was 22 ± 11 days (range: 7-44 days). Overall technical success was 100%. Eleven patients had completed their follow-up (median, 12 months, range: 1-34 months), and one patient was out of contact. The 30-day mortality was 9% (1/11, post-operative death of a patient with cerebral hemorrhage). No major complications and no chimney compression, migration, occlusion, or stenosis were recorded during follow-up. Seven patients (58%) have ≥6 months of clinical follow-up time with appropriate imaging. In four (57%) of these patients, diameter stabilization was detected, whereas three (43%) experienced significant reduction (≥5 mm). Conclusion: The patients in this study had satisfactory early-term outcomes. The chimney graft technique combined with coil and Onyx glue embolization may be a safe and effective treatment for ruptured aortic arch lesions under emergency conditions.

Vascular e-Learning During the COVID-19 Pandemic: The EL-COVID Survey.

BACKGROUND: The corona virus disease (COVID-19) pandemic has radically changed the possibilities for vascular surgeons and trainees to exchange knowledge and experience. The aim of the present survey is to inventorize the e-learning needs of vascular surgeons and trainees as well as the strengths and weaknesses of vascular e-Learning. METHODS: An online survey consisting of 18 questions was created in English, with a separate bilingual English-Mandarin version. The survey was dispersed to vascular surgeons and trainees worldwide through social media and via direct messaging from June 15, 2020 to October 15, 2020. RESULTS: Eight hundred and fifty-six records from 84 different countries could be included. Most participants attended several online activities (>4: n = 461, 54%; 2-4: n = 300, 35%; 1: n = 95, 11%) and evaluated online activities as positive or very positive (84.7%). In deciding upon participation, the topic of the activity was most important (n = 440, 51.4%), followed by the reputation of the presenter or the panel (n = 178, 20.8%), but not necessarily receiving accreditation or certification (n = 52, 6.1%). The survey identified several shortcomings in vascular e-Learning during the pandemic: limited possibility to attend due to lack of time and increased workload (n = 432, 50.5%), no protected/allocated time (n = 488, 57%) and no accreditation or certification, while technical shortcomings were only a minor problem (n = 25, 2.9%). CONCLUSIONS: During the COVID-19 pandemic vascular e-Learning has been used frequently and was appreciated by vascular professionals from around the globe. The survey identified strengths and weaknesses in current e-Learning that can be used to further improve online learning in vascular surgery.