Vascular smooth muscle cell (VSMC) migration is the key event in the pathogenesis of atherosclerosis (AS) and plaque instability. Trimethylamine-N-oxide (TMAO) induces VSMC migration to promote the progression of AS. However, the effects of the N6-methyladenosine (m6A) modification on this process remain unclear. Here, TMAO increased total m6A levels in human aortic smooth muscle cells (HASMCs) and decreased fat mass and obesity-associated protein (FTO) and YTH domain-containing family protein 2 (YTHDF2) protein expression. FTO or YTHDF2 overexpression significantly inhibited HASMC migration induced by TMAO. Mechanistically, the COL3A1 gene was shown to be critical for the regulation of HASMC migration by FTO or YTHDF2. Furthermore, methylated RNA immunoprecipitation and RNA stability assays demonstrated that FTO bound to the COL3A1 mRNA and altered its m6A modification, resulting in its decay. In vivo, VSMC-specific FTO or YTHDF2 deletion aggravated AS and plaque instability, whereas adeno-associated virus serotype 9 (AAV9)-mediated VSMC-specific YTHDF2 overexpression or COL3A1 knockdown exerted protective effects on AS and/or plaque instability. Notably, VSMC-specific FTO deletion promoted VSMC migration in atherosclerotic lesions in ApoE−/− AS model mice, whereas VSMC-specific YTHDF2 overexpression had the opposite effect. Overall, the in vitro and in vivo evidence highlights the critical role of the FTO/YTHDF2/COL3A1 axis in VSMC migration, AS, and plaque instability, suggesting that targeting the FTO/YTHDF2/COL3A1 axis in VSMCs may be a novel and promising therapeutic strategy for the treatment and prevention of AS and plaque instability.

Background Patients with severe asymptomatic carotid stenosis exhibit inferior baseline cognition. Whether cognition improves after carotid endarterectomy (CEA) remains inconclusive. This study investigated the relationship between regional cerebral perfusion and cognitive function following CEA in patients with asymptomatic carotid stenosis. Methods In this prospective observational cohort study, patients with unilateral severe asymptomatic carotid stenosis (70%–99%) undergoing CEA were recruited. Computed tomographic perfusion, a cognitive battery, and quantitative electroencephalogram were assessed preoperatively and 6 months after CEA. Perfusion impairment was defined using regions of interest computed tomographic perfusion parameters based on the anterior, middle, and posterior cerebral artery territories. Results A total of 52 individuals were included in the analysis. Preoperatively, perfusion impairment was most prevalent in anterior cerebral artery territory regions of interest (61.2%), followed by middle (55.8%) and posterior cerebral artery (PCA; 32.4%) territories. Perfusion‐impaired regions of interest associated with worse baseline cognition were primarily located in PCA territory. These patients with PCA perfusion impairment also exhibited reduced ipsilateral occipital γ‐band power on quantitative electroencephalogram (P=0.024). A majority of initially impaired regions of interest showed perfusion improvement, while no significant cognitive improvement was observed at the overall cohort level. However, patients with PCA‐territory perfusion improvement had better baseline‐adjusted 6‐month global cognitive, executive‐function, and memory scores, together with restored occipital γ‐band symmetry. Multivariate analysis identified concomitant vertebrobasilar stenosis and preoperative perfusion impairment in the cuneus region at the lateral ventricular plane as predictors of global cognitive improvement after CEA. Conclusions This exploratory study suggested that patients with asymptomatic carotid stenosis with PCA territory perfusion impairment may represent a potential subgroup for cognitive improvement after CEA.

BACKGROUND:Vascular smooth muscle cell (VSMC) phenotype switching plays a significant role in the pathogenesis of atherosclerosis (AS). However, the subtypes of VSMC transdifferentiation and their impact on AS progression and atherosclerotic plaque instability remains unclear. METHODS:We reanalysed scRNA-seq datasets of GSE155513 and GSE253903 and performed single-sample gene set enrichment analysis (ssGSEA) in three transcriptome datasets from unstable plaques to determine the major subtypes contributing the most to plaque instability. Using high-dimensional weighted gene co-expression network analysis (hdWGCNA), we identified hub genes in macrophage (MP)-like smooth muscle cells (SMCs) of unstable plaques. We conducted cell communication analysis according to tensin1 (TNS1) gene levels in VSMCs. TNS1 expression was analysed in human AS plaques. Finally, an AS model was established in VSMC-specific Tns1 knockout ApoE-/- mice to validate the causative role of TNS1 on atherosclerotic lesions. RESULTS:MP-like SMC was identified as the key subtype for plaque instability. hdWGCNA analysis for MP-like SMC identified blue module as the key gene module involved in unstable plaques. Decreased TNS1 expression in VSMCs was positively correlated with the down-regulation of contractile VSMC marker genes, SRF and MYCOD genes, negatively correlated with the up-regulation of CD68 and KLF4 genes, and activated VCAM, PDGF, THBS and CXCL signalling pathways. TNS1 mRNA expression levels were lower in human atherosclerotic arteries than in healthy arteries, and even lower in unstable plaques than in early and stable plaques. TNS1 protein levels in VSMCs were lower in human atherosclerotic plaques than in healthy arteries, and even lower in advanced plaques than in early plaques. VSMC-specific Tns1 gene deficiency aggravated AS progression and enhanced plaque instability with increased MP-like SMC transdifferentiation. CONCLUSION:The reduction of TNS1 gene in VSMCs might drive contractile VSMC transdifferentiation into MP-like SMC, the major subtype contributing to plaque instability. In vivo experimental results confirmed the role of Tns1 gene in contractile VSMC transdifferentiation into MP-like SMC and plaque instability.

Abdominal aortic aneurysm (AAA) is a progressive, age-associated vascular disorder characterized by dilation of the abdominal aorta and a high risk of rupture. RNA-binding motif protein 10 (RBM10), a key regulator of mRNA alternative splicing involved in cell cycle control and apoptosis, has not previously been investigated in AAA. This study aimed to characterize the expression and functional role of RBM10 in AAA pathogenesis. RBM10 expression in human AAA tissues was assessed by immunofluorescence. To explore its functional relevance, genome-wide transcriptomic profiling was performed in human aortic smooth muscle cells (HASMCs) transfected with RBM10 adenovirus or negative control for 24 h. The effects of RBM10 on HASMC proliferation and migration were evaluated using MTT and transwell assays, respectively. Apoptosis was quantified by flow cytometry. RBM10 expression was significantly elevated in human AAA tissues and in an established animal model. RBM10 overexpression markedly suppressed HASMC proliferation and migration while promoting apoptosis. Flow cytometry confirmed enhanced apoptotic rates, consistent with transcriptomic analysis demonstrating activation of the p53 pathway. Upregulation and activation of p53 were validated at the protein level. These findings indicate that RBM10 contributes to AAA progression by promoting smooth muscle cell apoptosis, likely through a p53-dependent mechanism. RBM10 may represent a promising therapeutic target for preventing or slowing AAA development.

Neointimal hyperplasia (NIH) is a complicated inflammatory process contributing to vascular restenosis. The present study aimed to explore whether chemokine‐like factor 1 (CKLF1) aggravates NIH via the nuclear factor‐kappa B (NF‐κB)/vascular cell adhesion molecule‐1 (VCAM‐1) pathway. We found the expression of CKLF1 and VCAM‐1 significantly increased in human carotid plaques compared to the control. In vivo, CKLF1 overexpression induced a thicker neointimal formation and VCAM‐1 expression was correspondingly upregulated. In vitro, CKLF1 activated NF‐κB and induced VCAM‐1 upregulation in human aortic smooth muscle cells (HASMCs). Functional experiments demonstrated that CKLF1 promoted monocyte adhesion and HASMC migration via VCAM‐1. These results suggest CKLF1 accelerates NIH by promoting monocyte adhesion and HASMC migration via the NF‐κB/VCAM‐1 pathway. Our findings contribute to a better understanding of the mechanisms underlying the causality of CKLF1 on NIH and could prove beneficial in designing therapeutic modalities with a focus on CKLF1.

Objective To summarize our experiences of endovascular treatment for abdominal aortic aneurysm (AAA) with common iliac artery aneurysm (CIAA) by using bell-bottom technique (BBT).Methods From February 2009 to June 2014,endovascular aortic repair (EVAR) was performed on 17patients with AAA with CIAA using BBT,including 16 patients with bilateral and 1 patient with unilateral CIAA.Among them,patients with common iliac artery (CIA) of less than 25 mm in diameter without involvement of the internal iliac artery and external iliac artery aneurvsm were treated with BBT.Results All procedures were successfully completed.There were 3 bilateral and 14 unilateral BBT.Type Ⅰa endoleak was noticed intraoperatively in 3 cases and balloon dilation were applied,the endoleak disappeared after dilation in 2 cases and in 1 case the diminished endoleak disappeared during the follow-up period.The median follow-up of the 17 cases was 28 months (ranging,4-68 months).During follow-up no AAA or CIAA rupture and no endoleak occurred,and no dilation of the CIAA was observed.None of them had BBT graft occlusion or buttock claudication.Conclusion AAA with CIAA can be successfully treated with EVAR and BBT,which can preserve internal iliac artery patency.

Objective A preliminary exploration of the application and effects of three-dimensional (3D) printing model teaching in clinical teaching of complex vascular disease for vascular surgical residents.Methods 28 medical residents were randomized into two teaching module groups.13 residents in the control group were received traditional anatomical altos combined with two-dimensional computed tomography images (CT)and 15 residents in the experimental group were received traditional teaching methods and 3D imaging model and real stent delivery system teaching.They were asked to answer anatomical characteristic,technical parameters and evaluative questions.Results Residents in the 3D experimental group were performed significantly better than those in the traditional group in EVAR rule,parameter measurement,total scores and satisfactory value,especially for the complex disease.There are no significantly different in aortic anatomical feature and disease type.Conclusions This randomized study revealed that the 3D model markedly improved the identification of AAA anatomy and EVAR feature by vascular surgical residents,especially for complex case.Therefore,the lifelike,visual and operative AAA model made by 3D technology should be used as a means of new medical education.

Atherosclerotic occlusive disease of the lower extremities (ASO-LE) has the third highest rate among systematic atherosclerosis obliterans, ranking after coronary heart disease and stoke, and the disease burden of ASO-LE has been continuously increasing. Invasive revascularizations, which is presented by endovascular therapy technique, has undergone a dramatic development in the past couples of decades. However, controversy concerned about the surgical management and operative indications has heated up in the meanwhile. Thus Society for Vascular Surgery (SVS) published the practice guidelines for ASO-LE with asymptomatic disease and claudication in March, 2015. At the first time the guideline definitely opposed the aggressive invasive revascularization for ASO-LE patients with asymptomatic disease or claudication under satisfied tolerance. Instead, it posed the extreme emphasis on the pharmacotherapy with risk reduction of atherosclerosis at the core and the exercise therapy with supervised or home-based exercise program at the core for ASO-LE patients with asymptomatic disease and claudication.

趋化因子超家族（ CKLFSF）在人类有九个成员，即：趋化素样因子（ CKLF）和CKLFSF1～8。该基因家族的基因编码的产物特点为其结构介于经典的趋化因子和四次跨膜蛋白之间。CKLF1具有CC家族趋化因子的结构特征和基本功能，即连续两个半胱氨酸的特征性结构和趋化功能〔1〕。本研究选择CK-LF1 C端的两段多肽--C19、C27多肽，体外观察二者对人主动脉平滑肌细胞的趋化活性。

Objective To evaluate the endovascular treatment of CSMAO.Methods This is a retrospective study on the clinical data of 11 cases with CSMAO managed from June 2009 to May 2014.Results There were 3 males,8 females,mean age 65 ±9 years.SMA stenosis in 3 cases (95％ stenosis in 2 and 90％ stenosis in 1).Total SMA occlusion at its origin in 5 cases.Stenosis involving both SMA and celiac artery in 2 cases.SMA stenosis and inferior mesenteric artery occlusion in 1 case.All CSMAO patients received endovascular treatment.The overall success rate was 90.9％.In 5 cases one self-expandable stent was implanted.In 1 case one self-expandable stent and one balloon-expandable stent was implanted.In 1 case a balloon-expandable stent was implanted.In 1 case a Viabahn stent graft was implanted,2 cases received a self-expandable stent respectively after CDT.Follow-up rate was 90.9％ from 12 months to 48 months.Stent patency rates were 100％ in 1 year and 80％ in 2 years.In-stent restenosis after the intervention in 1 case at 26 months,and then balloon expanded.Stenosis occurred under the stent in 1 case at 36 months,and managed by a stent.Motality was 9.1％.Conclusions Endovascular therapy for CSMAO is less traumatic and with rapid recovery.The short term result is satisfactory,especially suitable for elderly patients with a variety comorbidities.

OBJECTIVE:To study the treatment strategy and survival of patients with primary leiomyosarcoma of inferior vena cava (PIVCLMS).METHODS:Clinical data of 12 cases with PIVCLMS admitted in Peking University People's Hospital from January 2006 to September 2014 were reviewed retrospectively. All cases were confirmed by pathology examination. Among them, there were 4 male and 8 female patients with a mean age of (54 ± 9) years old. Tumors arose from the inferior vena cava (IVC) upper segment in 5 patients, from the middle in other 7 patients. Cardiac extension was observed in 4 cases. Tumor resection was undertaken in 8 patients, the other 4 patients were inoperable. The series was analyzed to identify clinical outcome of surgical strategy and protective factors for patient survival.RESULTS:In tumor resection group, 6 patients had radical resection and 2 underwent palliative resection. As for IVC reconstruction, caval wall resection with a direct suture was carried out in 6 patients or with prosthetic patch in 1 patient. The other 1 patient underwent a segment caval resection and prosthetic graft replacement in situ. In 4 cases of suprahepatic PIVCLMS cardiopulmonary bypass or perfusion by right atrial intubation was performed to assist bleeding control and maintain circulation stabilization, among them 1 patient survived for more than 101 months with no tumor recurrence or metastasis. Among the patients submitted to tumor resection 2 early postoperative deaths occurred, and another 2 patients had complications. All 4 patients submitted to non-resective operation (only neoplasm biopsy) died of PIVCLMS within 8 months. Except for 2 cases of early death, mean survival after tumor resection was (54 ± 40) months. Two patients presented local recurrence and hepatic metastasis at follow-up of 16 months and 68 months.CONCLUSIONS:Tumor resection is the only therapy for PIVCLMS with an expectation for long-term survival. The applicant of cardiopulmonary bypass makes some inoperable indicated to tumor resection.

This study evaluated the effectiveness of open surgery and endovascular repair (EVAR) for abdominal aortic pseudoaneurysm (pseudo-AAA) in patients with Behçet disease (BD) and investigated the optimal surgical management. Between January 2003 and April 2014, 11 consecutive patients (all men) with pseudo-AAA with BD were treated in Peking University People's Hospital. All patients were required to accept immunosuppressive medication once the diagnosis of BD was confirmed. Five open surgical procedures and 11 EVARs were performed for de novo and recurrent lesions. The de novo arterial lesions comprised 8 infrarenal, 1 juxtarenal, 1 suprarenal, and 1 with multiple thoracoabdominal aortic pseudoaneurysms. In the open surgery group, three of five procedures were performed as remedial measures for recurrence of pseudo-AAA. No early operative deaths were observed. In EVAR group, 9 tubular, 1 aortouniiliac tapered, 2 aortobiiliac stents grafts, and 2 uncovered stents were used. One patient undergoing chimney technique suffered type Ia endoleak. In a median of 28 months of follow-up, the overall survival was 72.7%, and the relapse-free survival was 45.5%. Nine recurrent pseudo-AAAs were recorded in five patients, with four after open surgery (66.7%) and five after EVAR (55%). Three aneurysm-associated death were linked with recurrent pseudo-AAA after open surgery (n = 2) and challenging anatomy after EVAR (n = 1). Our initial experience suggests that EVAR is a reasonably safe and effective alternative to surgical repair for most patients and that open surgery procedures remain the effective treatment for BD patients with complicated anatomy and recurrent pseudo-AAA.

Objective To evaluate the feasibility and effectiveness of EVT for TASC Ⅱ type D lesions in the PAD.Methods Clinical data were retrospectively reviewed on 148 PAD cases(173 limbs) managed from May 2009 to July 2014.There were 108 limbs with aorto-iliac occlusive lesions.55 limbs with femoral-popliteal artery occlusive lesions.10 limbs with both aorto-iliac and femoral-popliteal artery occlusive lesions.All the patients received EVT.Results There were 60 males,88 females,mean age 75 ± 9.The overall success rate was 93.6％.Preoperative ABI and after one week postoperative were significantly different (0.26 ±0.11 vs 0.73 ±0.20,P ＜0.05).3 cases developed intraoperative complications(1.7％),5 cases with postoperative complications (2.9％).There was no perioperative mortality.Primary patency rate was 85.5％ at 1 year,81.9％ at 2 years.Secondary patency rate was 98.8％ at 1 year,92.2％ at 2 years.139 patients (93.9％) were followed up from 4 months to 50 months.Four received below the knee amputation and two above the knee amputation during the follow-up period.Amputation rate was 3.5％.Mortality was 4.1％.Conclusions EVT is safe,effective,feasible for patients with TASC Ⅱ type D lesions of PAD,especially for elderly patients with a variety of concurrent diseases.

Vascular remodeling in response to hemodynamic alterations is a physiological process that requires coordinated signaling between endothelial, inflammatory and vascular smooth muscle cells (VSMCs). Extensive experimental and clinical studies have indicated the critical role of the Ras homolog gene family, member A/Rho-associated kinase (ROCK) signaling pathway in the pathogenesis of cardiovascular disease, where ROCK activation has been demonstrated to promote inflammation and remodeling through inducing the expression of proinflammatory cytokines and adhesion molecules in endothelial cells and VSMCs. However, the role of ROCK in flow-induced vascular remodeling has not been fully defined. The current study aimed to investigate the effect of the ROCK signaling pathway in flow-induced vascular remodeling by comparing the responses to partial carotid artery ligation in mice treated with fasudil (a ROCK inhibitor) and untreated mice. Intima-media thickness and neointima formation were evaluated by morphology. VSMC proliferation and inflammation of the vessel wall were assessed by immunohistochemistry. In addition, the expression levels of ROCK and the downstream effectors of ROCK, myosin light chain (MLC) and phosphorylated-MLC (p-MLC), were quantified by western blot analysis. Following a reduction in blood flow, ROCK1 and p-MLC expression increased in the untreated left common carotid arteries (LCA). Fasudil-treated mice developed a significantly smaller intima-media thickness compared with the untreated mice. Quantitative immunohistochemistry of the fasudil-treated LCA indicated that there was a reduction in proliferation when compared with untreated vessels. There were fewer CD45(+) cells observed in the fasudil-treated LCA compared with the untreated LCA. In conclusion, the expression of ROCK was enhanced in flow-induced carotid artery remodeling and ROCK inhibition as a result of fasudil treatment may attenuate flow-induced carotid artery remodeling.

Objective To investigate mid-term efficacy after stenting for TASC C and D femoropopliteal arterial lesions.Methods From September 2009 to December 2012,59 patients (68 limbs; TASC C ∶ TASC D =47 ∶ 21) after stenting for de novo TASC C/D femoropopliteal arterial lesions were retrospectively enrolled.Baseline clinical characteristics and procedural data were collected from hospital medical records,post-procedural runoff score was identified according to Society for Vascular Surgery (SVS) criteria.Patients were on routine follow-up to assess clinical results and vessel patency.Primary patency,secondary patency rates and clinical improvement rates were estimated by Kaplan-Meier survival analysis,and predictors of vessel patency were verified by Cox proportional hazards model.Results After stent placement ABI,was increased from 0.52 ±0.19 to 0.91 ±0.16 (P =0.008),Mean follow-up time was 24 months(12-48 months).Primary patency and secondary patency rates at 1,2,3 years were 54.0％,41.4％,41.4％ and 72.1％,56.3％,56.3％,respectively,clinical improvement rates at 1,2,3 years were 77.9％,65.8％,65.8％.Identified predictors of restenosis/occlusion included diabetes (HR 1.930,P =0.049,95％ CI 1.003-3.715),critical limb ischemia(HR 2.314,P =0.029,95％ CI 1.090-4.915) and runoff score ＞ 7 (HR 2.135,P=0.037,95％ CI 1.047-4.354).Conclusions Stent implantation for TASC C and D femoropopliteal arterial lesions is safe and effective with high clinical improvement rates.Diabetes,critical limb ischemia or poor runoff score imply poor primary patency rate.

Computational fluid dynamics (CFD) technology has the potential to simulate normal or pathologic aortic blood flow changes of mechanical properties and flow field, thereby helping researchers understand and reveal the occurrence, development and prognosis of aortic disease. In aortic diseases research, the initial conditions of CFD numerical simulation has experienced a developed process from idealization (forward engineering), rigid vessel wall, uniform cross-sections, laminar flow and stable blood flow towards personalization (reverse engineering), elastic vessel wall (fluid-solid coupling technique), cone-shaped diminishing cross-sections, turbulent flow, pulsatile blood flow. In this review, the research status, the technical superiority and application prospect of CFD technology were discussed with examples in following three major application areas: (1) dynamics characteristic and mechanical properties in normal thoracic aorta; (2) occurrence, advance and disruptive risk predicting in thoracic aortic aneurysm; (3) therapeutic effect and aneurysmal dilatation simulation in thoracic aortic dissection. For the future, the CFD technology may profoundly put an influence on the awareness to aortic diseases and treatment strategies.

Objective To summarize our experience on aortic dissection with distal true lumen occlusion.Methods Nineteen aortic dissection cases with aortic true lumen occlusion treated at our Hospital from February 2001 to January 2015 were reviewed.Three (3/19) were Stanford type A dissections,16 (16/19)were type B dissections.16 patients were treated with TEVAR (thoracic endovascular aortic repair),one with femoral artery thrombectomy,and 2 abandoned treatment.Depending on the malperfusion consequences,we applied branch vessel conservative therapy/stenting/bypass/intimal membrane fixation/CVVHDF (continuous venovenous hemodiafihration) for individual patients.Results There were 16 patients treated with TEVAR,including 20 stent grafts in thoracic aorta and 2 bare stents in abdominal aorta.The locations of adjunctive stenting included the iliac artery in 5 cases,the mesenteric artery in 2.3 chimney stents in carotid artery and 2 in left subclavian were used to secure enough proximal landing zone for TEVAR.2 axillary-axillary artery bypasses and 1 femoral-femoral bypass were performed.One patient with Stanford A dissection underwent femoral artery thrombectomy,and 2 cases with conservative therapy died in 24 hours.5 of 17 patients (29.4％) experienced renal failure,4 of which with coexistent osteofascial compartment syndrome.The 30-day in-hospital mortality rate was 17.6％ (3/17).Conclusions Early endovascular intervention is effective for aortic dissection with distal true lumen occlusion.

Objective To investigate the clinical features of spontaneous isolated superior mesenteric artery dissection (SISMAD), and to discuss its interventional therapy. Methods The clinical data of 10 patients with SISMAD, who were admitted to authors' hospital to receive interventional treatment during the period from January 2006 to June 2014, were retrospectively analyzed. All the 10 patients were males, aged 44-66 years with a mean of (53±8) years. Clinically, all patients presented with acute-onset abdominal pain or pain around umbilicus, as the effect of conservative treatment was poor, implantation of self-expandable bare stent was carried out. Results Successful implantation of self-expandable bare stent was accomplished in all 10 patients;only one stent was used in 7 patients and 2 stents were used in 3 patients. The blood in the true lumen of superior mesenteric artery (SMA) restored and the residual stenosis extent was less than 15%. The technical success rate was 100%. The abdominal pain was relieved in 8 patients on the operative day after treatment, and in 2 patients the abdominal pain was relieved in 2 days after treatment. All the patients were followed up for 7-71 months (mean of 36 months) and the follow-up rate was 100%. After the treatment patients had no symptoms of abdominal discomfort. Contrast-enhanced CT scan performed at 6, 12 and 24 months after the treatment showed that SMA and stent was patent and no aneurysmal dilatation was observed. Conclusion For the treatment of SISMAD endovascular implantation of self-expandable bare stent is clinically safe and feasible, and its long-term effect is satisfactory.

目的:研究情景式教学对医学研究生住院医师医患沟通能力培养的应用效果.方法:对我院研究生住院医师以标准化病人家属模拟急诊病例病情告知和术前谈话,使用利物浦医生沟通能力评价量表中文修订版进行沟通能力评价,根据评价结果开展医患沟通课堂培训以达到短期改善沟通能力目的.结果:培训前学生沟通能力普遍较低,与担任住院医师年资呈正相关,培训后学生对急诊术前手术谈话的沟通能力显著提高(P＜0.05).结论:情景式在医院教学与传统课堂教学有效结合有助于提高医学研究生住院医师的医患沟通能力,减少医疗纠纷风险.