BACKGROUND:This study provides an umbrella review to assess the methodological quality, biases and reliability of evidence regarding the factors influencing mortality in individuals with peripheral artery disease (PAD). It also offers a consolidated overview of the identified risk factors. METHODS:The review protocol was registered in PROSPERO (CRD42024615105). PubMed, Web of Science, the Cochrane Database of Systematic Reviews and Embase were used to search, covering the period from inception until September 2024. AMSTAR and GRADE were used to independently evaluate the methodological rigour and quality of the evidence. RESULTS:The review identified a total of 29 risk factors, of which 17 were significantly associated with higher mortality risk, while 12 did not show a notable association. The majority of the evidence was rated as low or very low quality, with only three risk factors being classified as having moderate-quality evidence. Key findings indicated that comorbidities such as chronic kidney disease, diabetes, underweight status, atrial fibrillation and depression were major contributors to higher mortality risk. In contrast, obesity and statin use were identified as being linked to a reduced risk of mortality. Additionally, blood biomarkers, including N-terminal pro-B-type natriuretic peptide, high-sensitivity C-reactive protein (CRP) and high-sensitivity cardiac troponin T, were identified as important predictors of mortality. CONCLUSION:Comorbid conditions are key factors contributing to elevated mortality among individuals with PAD, whereas obesity and statin use are linked to reduced mortality risk. Additionally, blood biomarkers offer valuable insights into assessing mortality risk within this patient group.

BACKGROUND:Sevoflurane (Sevo) preconditioning and postconditioning play a protective role against injury induced by hepatic ischemia/reperfusion (I/R). At the same time, the involvement of macrophage infiltration in this process and the precise mechanisms are unclear. Here, we designed this research to elucidate the protective effects of Sevo against hepatic I/R injury and the molecules involved. METHODS:The alleviating effect of Sevo on the liver injury was analyzed by liver function analysis, hematoxylin and eosin staining, Masson trichrome staining, terminal deoxynucleotidyl transferase-mediated 2'-deoxyuridine 5'-triphosphate nick end labeling, western blot analysis and an enzyme-linked immunosorbent assay. An in vitro cell model was developed using alpha mouse liver 12 (AML12) cells, and the cell model was treated with oxygen-glucose deprivation and reoxygenation and Sevo. Multiple bioinformatics databases were used to screen transcriptional regulators related to hepatic I/R injury and the targets of Krueppel-like factor 5 (KLF5). KLF5 expression was artificially upregulated alone or with integrin beta-2 (ITGB2) knockdown to substantiate their involvement in Sevo-mediated hepatoprotection. RESULTS:Sevo protected the liver against I/R injury by reducing cell apoptosis and inflammatory response. KLF5 was upregulated in liver tissues following I/R injury, whereas KLF5 overexpression aggravated macrophage infiltration and liver injury induced by I/R injury. KLF5 bound to the promoter of ITGB2 to enhance ITGB2 transcription. Knockdown of ITGB2 reversed the aggravation of injury caused by KLF5 overexpression in mice and AML12 cells. CONCLUSIONS:Sevo blocked KLF5-mediated transcriptional activation of ITGB2, thereby inhibiting macrophage infiltration in hepatic I/R injury.

Cerebral ischemia/reperfusion (I/R) injury is the main cause of death following trauma. The neuroprotective effect of sevoflurane (Sev) has been implicated in cerebral I/R injury. However, the mechanisms remain elusive. In this study, we aimed to explore its function in PC12 exposed to oxygen–glucose deprivation/reoxygenation (OGD/R) and in rats challenged with I/R. Sev pretreatment reduced the damage of PC12 cells after OGD/R treatment. Moreover, Sev pretreatment ameliorated neurobehavioral deficits induced by I/R treatment, reduced brain infarct volume, and decreased apoptosis of neurons in hippocampal tissues. Sev pretreatment reduced the surface expression of glutamate receptor 1 (GRIA1) in neurons, while GRIA1 reduced the neuroprotective effects of Sev pretreatment in vitro and in vivo. There was no difference in the surface expression of GRIA2 in rats with I/R and PC12 cells exposed to OGD/R. The ratio of GRIA1/GRIA2 surface expression was reduced, and calcium permeable-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (CP-AMPAR) was blocked by Sev. Together, Sev might exert beneficial effects on cerebral I/R-induced neuronal injury through inhibiting the surface expression of GRIA1 and blocking CP-AMPAR.

目的 探究miR-29b过表达对动脉硬化模型大鼠的干预作用及机制.方法 选取40只SD健康雄性大鼠,其中10只不进行任何处理为正常组,其余30只建立动脉硬化大鼠模型(其中10只为疾病模型组,10只进行沉默miR-29b表达干预为miR-29b沉默组,10只进行过表达miR-29b表达干预为miR-29b过表达组).选择使用反转录(RT)-聚合酶链反应(PCR)对miR-29b表达进行检测,并以免疫组化法检测内皮生长因子(VEGF)、转化生长因子(TGF)-β1及单核细胞趋化蛋白(MCP)-1水平,酶联免疫吸附试验检测一氧化氮(NO)、内皮素(ET)-1水平,以黄嘌呤氧化酶法检测活性氧(ROS)、丙二醛(MDA)及超氧化物歧化酶(SOD)水平.结果 与正常组相比,疾病模型组、miR-29b沉默组及miR-29b过表达组miR-29b表达明显低,VEGF水平明显高(P<0.05);与疾病模型组相比,miR-29b沉默组miR-29b表达明显低,VEGF水平明显高(P<0.05),miR-29b过表达组miR-29b表达明显高,VEGF水平明显低(P<0.05).与正常组相比,疾病模型组、miR-29b沉默组及miR-29b过表达组NO水平较明显低、ET-1水平明显高(P<0.05);与疾病模型组相比,miR-29b沉默组NO水平明显低,ET-1水平明显高,miR-29b过表达组NO水平明显高,ET-1水平明显低(P<0.05).与正常组相比,疾病模型组、miR-29b沉默组及miR-29b过表达组ROS、MDA水平明显高,SOD水平明显低(P<0.05);与疾病模型组相比,miR-29b沉默组ROS、MDA水平均明显高,SOD水平明显低,miR-29b过表达组ROS、MDA水平明显低,SOD水平明显高(P<0.05).与正常组相比,疾病模型组、miR-29b沉默组及miR-29b过表达组TGF-β1、MCP-1及IL-8水平均明显高(P<0.05);与疾病模型组相比,miR-29b沉默组TGF-β1、MCP-1及IL-8水平均明显高,miR-29b过表达组TGF-β1、MCP-1及IL-8水平均明显低(P<0.05).结论 在动脉硬化模型大鼠中,miR-29b明显参与其中,通过进行过表达miR-29b干预,能够抑制动脉硬化病情进展,能够减轻炎症反应及氧化应激损伤,改善内皮功能,且能够抑制动脉硬化的形成.

Background:Stanford type B aortic dissection (TBAD) is a rare cardiovascular emergency with rapid onset and great harm. Currently, no relevant studies have analyzed the difference in clinical benefits of endovascular repair in patients with TBAD in acute and non-acute stages. To investigate the clinical characteristics and prognosis of endovascular repair in patients with TBAD at different surgical timing. Methods:The medical records of 110 patients with TBAD from June 2014 to June 2022 were retrospectively selected as the study subjects. The patients were divided into an acute group (onset time ≤14 days) and a non-acute group (onset time >14 days) according to the time to surgery, and the two groups were compared in terms of surgery and hospitalization, aortic remodeling, and follow-up results. Univariate and multivariate logistic regression were used to analyze the factors affecting the prognosis of TBAD treated with endoluminal repair. Results:The proportion of pleural effusion, heart rate, the rate of complete thrombosis of the false lumen and the difference in the maximum diameter of the false lumen in the acute group were higher than those in the non-acute group (P=0.015, <0.001, 0.029, <0.001). The length of hospital stay and the maximum postoperative diameter of the false lumen was lower than in the non-acute group (P=0.001, 0.004). There was no statistically significant difference between the two groups in the technical success rate, overlapping stent length, overlapping stent diameter, immediate postoperative contrast type I endoleak, incidence of renal failure, ischemic disease, endoleaks, aortic dilatation, retrograde type A aortic coarctation, and death (P=0.386, 0.551, 0.093, 0.176, 0.223, 0.739, 0.085, 0.098, 0.395, 0.386); coronary artery disease [odds ratio (OR) =6.630, P=0.012], pleural effusion (OR =5.026, P=0.009), non-acute surgery (OR =2.899, P=0.037), and involvement of the abdominal aorta (OR =11.362, P=0.001) were all independent risk factors affecting the prognosis of TBAD treated with endoluminal repair. Conclusions:Acute phase endoluminal repair of TBAD may contribute to aortic remodeling, and the prognosis of TBAD patients can be assessed clinically in combination with coronary artery disease, pleural effusion, and involvement of the abdominal aorta for early intervention to reduce the associated mortality.

Background. Limb ischemia/reperfusion (I/R) injury, as a life-threatening syndrome, is commonly caused by skeletal muscle damage resulting from oxidative stress. Additionally, inflammation-induced pyroptosis and dysregulated autophagy are vital factors contributing to the aggravation of I/R injury. Of note, sulforaphane (SFN) is a natural antioxidant, but whether it worked in limb I/R injury and the possible mechanism behind its protection for skeletal muscle has not been clearly established. Methods. Effects of SFN on limb I/R-injured skeletal muscle were assessed by HE staining, followed by assessment of wet weight/dry weight (W/D) ratio of muscle tissues. Next, ELISA and biochemical tests were used to measure the inflammatory cytokine production and oxidative stress. Immunofluorescent analysis and Western blot were adopted to examine the level of pyroptosis- and autophagy-related proteins in vivo. Moreover, protein levels of Nrf2-ARE pathway-related factors were also examined using Western blot. Results. SFN treatment could protect skeletal muscle against limb I/R injury, as evidenced by diminished inflammation, pyroptosis, autophagy, and oxidative stress in skeletal muscles of mice. Further mechanistic exploration confirmed that antioxidative protection of SFN was associated with the Nrf2-ARE pathway activation. Conclusions. SFN activates the Nrf2-ARE pathway, and thereby inhibits pyroptosis and autophagy and provides a novel therapeutic strategy for the limb I/R-induced muscle tissue damage.

Objective Limb ischemia/reperfusion (I/R) injury is a clinical syndrome associated with severe damages to skeletal muscles and other fatal outcomes. Oxidative stress and inflammatory response play vital roles in the development of limb I/R injury. Existing evidence further indicates that Dl-3-n-butylphthalide (NBP) has anti-inflammatory and antioxidative properties. However, whether NBP can protect skeletal muscles from limb I/R injury and the mechanism in mediating the action of NBP treatment still remain to be investigated, which are the focuses of the current study. Methods The model of limb I/R injury was established and H&E staining was adopted to assess the pathological changes in skeletal muscles following limb I/R injury. Additionally, the W/D ratio of muscle tissue was also measured. ELISA and biochemical tests were carried out to measure the levels of inflammatory cytokines and oxidative stress in mouse models of limb I/R injury. Moreover, the levels of the HMGB1/TLR4/NF-κB pathway-related proteins were also determined using immunohistochemistry and immunoblotting. Results It was established that NBP treatment alleviated I/R-induced pathological changes in muscular tissue of mice, accompanied by lower W/D ratio of skeletal muscular tissue. Meanwhile, the limb I/R-induced inflammation and oxidative stress in skeletal muscles of mice were also inhibited by NBP. Mechanistic study indicated that the alleviatory effect of NBP was ascribed to inactivation of the HMGB1/TLR4/NF-κB pathway. Conclusions Our findings highlighted the potential of NBP as a novel strategy for limb I/R-driven muscle tissue damages by suppressing inflammatory response and oxidative stress via the HMGB1/TLR4/NF-κB pathway.

目的 探讨应用双导丝球囊预处理病变,是否会对药物涂层球囊(drug coated balloon,DCB)治疗股腘动脉硬化闭塞症的疗效产生影响.方法 回顾性分析于本中心诊疗的股腘动脉硬化闭塞症患者40例的临床资料,其中20例接受普通球囊(plain-balloon-angioplasty,PBA)结合DCB(对照组)治疗,20例接受双导丝球囊结合DCB(观察组)治疗,根据TASC分级标准将所有患者进行分级,并记录围手术期不良事件的发生,监测患者术前及术后3个月、6个月及1年踝肱指数(ankle brachial index,ABI),1年随访时需对其进行Rutherford分级.结果 2组病例均顺行真腔开通病变,完成手术治疗,2组病例靶血管病变长度及狭窄程度差异无统计学意义(P>0.05),预处理后残余狭窄率均低于30％,术中远端栓塞2例,观察组1例;对照组1例,最终截肢.对照组球扩后有1例患者出现限流性夹层,应用补救支架1枚.40例患者均获得随访,2组病例ABI均较术前升高,术后3、6、12个月呈逐渐降低的趋势,2组在组间、时点间、组间·时点间交互作用差异均有统计学意义(P<0.05).结论 对于股腘动脉硬化闭塞症,相比PBA结合DCB,双导丝球囊结合DCB可有效降低再干预率,且并未增加并发症发生率,但该结论尚需大样本、长期随访数据支持.

颅外段颈动脉硬化狭窄或闭塞是缺血性脑卒中发生的主要病因之一,通过早期的外科积极干预可以有效降低缺血性脑卒中发生率.DeBakey[1]在世界上成功地完成了首例颈动脉内膜剥脱术(carotid endarterectomy,CEA),随后各种高质量临床研究均证实CEA对降低脑卒中发生率的积极意义[2-5],CEA已成为一种安全有效的标准术式,用于治疗颅外段颈动脉狭窄或闭塞.近年来,随着腔内血管治疗技术的飞速发展,颈动脉支架置入术(carotid artery stenting,CAS)逐渐开始应用于临床并取得了良好效果.因CAS操作相对简单,手术创伤较小,目前应用广泛,在一定范围内可逐渐取代CEA[6].目前,临床上,关于CEA与CAS的选择及其远期疗效仍存在争议,本文通过文献回顾从以下几方面对颈动脉狭窄的外科治疗选择和疗效分析进行阐述.

目的 探讨AngioJet机械血栓抽吸技术腔内治疗慢性股腘动脉长段闭塞病变的有效性及安全性.方法 收集2019年5月至2020年5月河北医科大学第二医院收治的15例慢性股腘动脉长段闭塞病变患者的临床资料.观察全部患者的术中机械血栓抽吸时间、尿激酶使用剂量、腔内介入治疗成功率及围手术期相关并发症的发生情况.比较抽吸前后的病变段长度.观察术后肌红蛋白尿的发生情况、血色素降低程度、术后即刻效应.比较术前、术后1周、术后6个月的踝肱指数(ABI),术前与术后6个月的Rutherford分级.观察术后6个月管腔丢失率和再干预率.结果 15例慢性股腘动脉长段闭塞病变患者的腔内介入治疗成功率为100％(15/15).围手术期,无死亡、心脑血管疾病、远端动脉栓塞或出血事件发生.术中机械血栓抽吸时间为(361.87±57.44)s,尿激酶使用剂量为(25.67±4.03)万U.抽吸后的平均病变段长度明显短于抽吸前,差异有统计学意义(P<0.01).术后,有13例患者出现肌红蛋白尿,平均持续时间为(1.47±0.88)d.术后血色素较术前降低了(8.87±1.86)g/L.术后1例患者出现下肢肿胀,经硫酸镁持续湿敷后缓解.术后1周、术后6个月的ABI均高于术前,差异均有统计学意义(P<0.01).术后6个月,管腔丢失患者2例,再干预患者1例.术后6个月,患者的Rutherford分级优于术前(P<0.05).术后,造影检查结果显示,1例患者出现限流性夹层,植入一枚补救性支架.结论 AngioJet机械血栓抽吸技术不仅能够有效去除慢性股腘动脉长段闭塞病变的血栓,缩短病变长度,降低病变狭窄率,还可有效降低远端栓塞风险,提高远期通畅率,并可减少留置溶栓导管所致的出血等不良事件的发生.

Carboxypeptidase A4 (CPA4) is a member of the metallocarboxypeptidase family. Current studies have identified the roles of CPA4 in cancer biology and insulin sensitivity. However, the roles of CPA4 in other diseases are not known. In the present study, we investigated the roles of CPA4 in cardiac hypertrophy. The expression of CPA4 was significantly increased in the hypertrophic heart tissues of human patients and isoproterenol (ISO)-induced hypertrophic heart tissues of mice. We next knocked down Cpa4 with shRNA or overexpressed Cpa4 using adenovirus in neonatal rat cardiomyocytes and induced cardiomyocyte hypertrophy with ISO. We observed that Cpa4 overexpression promoted whereas Cpa4 knockdown reduced ISO-induced growth of cardiomyocyte size and overexpression of hypertrophy marker genes, such as myosin heavy chain β (β-Mhc), atrial natriuretic peptide (Anp), and brain natriuretic peptide (Bnp). Our further mechanism study revealed that the mammalian target of rapamycin (mTOR) signaling was activated by Cpa4 in cardiomyocytes, which depended on the phosphoinositide 3-kinase (PI3K)-AKT signaling. Besides, we showed that the PI3K-AKT-mTOR signaling was critically involved in the roles of Cpa4 during cardiomyocyte hypertrophy. Collectively, these results demonstrated that CPA4 is a regulator of cardiac hypertrophy by activating the PI3K-AKT-mTOR signaling, and CPA4 may serve as a promising target for the treatment of hypertrophic cardiac diseases.

F-box and WD repeat domain-containing 7 (FBXW7) is an E3-ubiquitin ligase, which serves as one of the components of the SKP1, CUL1, and F-box protein type ubiquitin ligase (SCF) complex. Previous studies reveal that FBXW7 participates in cancer, inflammation and Parkinson's disease. FBXW7 also contributes to angiogenesis of endothelial cells. However, the function of FBXW7 in cardiac homeostasis remains to elucidate. Here we identified the critical role of FBXW7 during cardiac hypertrophy in humans and rodents. Quantitative real-time PCR (qRT-PCR) and Western blot revealed that the mRNA and protein levels of FBXW7 were upregulated significantly in hypertrophic hearts in human and mouse as well as Angiotensin II (Ang II)-induced hypertrophic neonatal rat cardiomyocytes (NRCM). Gain-of-function (adenovirus) and loss-of-function (siRNA) experiments provided evidence that FBXW7 promoted Ang II-induced cardiomyocyte hypertrophy as demonstrated by the increase in the size of cardiomyocytes and overexpression of hypertrophic fetal genes myosin heavy chain 7 (Myh7) natriuretic peptide a (Nppa), brain natriuretic peptide (Nppb). Further mechanism study revealed that FBXW7 promoted the expression of sine oculis homeobox homolog 1 (SIX1) in cardiomyocytes, which relied on regulation of the stability of the histone methyltransferase EZH2 (Enhancer of zeste homolog 2). Previous work revealed the pro-hypertrophic role of the EZH2-SIX1 axis in rodents. Indeed, our genetic and pharmacological evidence showed that the EZH2-SIX1 signaling was critically involved in FBXW7 functions in Ang II-induced cardiomyocyte hypertrophy. Therefore, we identified FBWX7 as an important regulator of cardiac hypertrophy via modulating the EZH2-SIX1 axis.

目的 探讨非神经型糖尿病足患者靶向腔内介入治疗的有效性.方法 选取2019年5月至2020年5月河北医科大学第二医院诊治的44例非神经型糖尿病足患者的临床资料,患肢47条,其中43条患肢存在溃疡43处,所有患者均接受靶向腔内介入治疗.统计并比较术前及术后1个月患者Wagner分级及Fontaine分期、溃疡愈合情况、踝肱指数(ankle brachial index,ABI).结果 44例患者接受靶向腔内介入治疗,成功率95.5％;47条患肢成功率95.7％;43处溃疡成功率97.7％.术后1个月ABI较术前好转;Wagner分级及Fontaine分期较术前明显改善,差异有统计学意义(P<0.001);14处溃疡完全愈合,剩余溃疡28处,中位面积为1.00(0.48,2.00)cm2,较术前2.13(1.13,4.00)cm2降低,差异有统计学意义(P<0.05).结论 靶向腔内介入治疗非神经型糖尿病足可有效缓解下肢缺血症状,促进创面愈合,值得临床推广.

5-Hydroxytryptamine receptor 2A (HTR2A) is a central regulator of fetal brain development and cognitive function in adults. However, the roles of HTR2A in the cardiovascular system are not fully understood. Here in this study, we explored the function of HTR2A in cardiac hypertrophy. Significantly, the expression levels of HTR2A mRNA and protein levels were upregulated in hypertrophic hearts of human patients. Besides, the expression of HTR2A was also upregulated in isoproterenol (ISO)-induced cardiac hypertrophy in the mouse. Next, the expression of HTR2A was knocked down with shRNA or overexpressed with adenovirus in neonatal rat cardiomyocytes, and ISO was used to induce cardiomyocyte hypertrophy. We showed that HTR2A knockdown repressed ISO-induced cardiomyocyte hypertrophy, which was demonstrated by decreased cardiomyocyte size and repressed expression of hypertrophic fetal genes (e.g., myosin heavy chain beta (β-Mhc), atrial natriuretic peptide (Anp), and brain natriuretic peptide (Bnp)). By contrast, HTR2A overexpression promoted cardiomyocyte hypertrophy. Of note, we observed that HTR2A promoted the activation (phosphorylation) of AKT-mTOR (mammalian target of rapamycin) signaling in cardiomyocytes, and repression of AKT-mTOR with perifosine or rapamycin blocked the effects of HTR2A on cardiomyocyte hypertrophy. Finally, we showed that HTR2A regulated AKT-mTOR signaling through activating the PI3K-PDK1 pathway, and inhibition of either PI3K or PDK1 blocked the roles of HTR2A in regulating AKT-mTOR signaling and cardiomyocyte hypertrophy. Altogether, these findings demonstrated that HTR2A activated PI3K-PDK1-AKT-mTOR signaling and promoted cardiac hypertrophy.

Objective: Vascular smooth muscle cells (VSMCs) undergo the phenotypic changes from contractile to synthetic state during vascular remodeling after ischemia. SIRT1 protects against stress-induced vascular remodeling via maintaining VSMC differentiated phenotype. However, the effect of smooth muscle SIRT1 on the functions of endothelial cells (ECs) has not been well clarified. Here, we explored the role of smooth muscle SIRT1 in endothelial angiogenesis after ischemia and the underlying mechanisms. Methods: We performed a femoral artery ligation model using VSMC specific human SIRT1 transgenic (SIRT1-Tg) and knockout (KO) mice. Angiogenesis was assessed in in vivo by quantification of the total number of capillaries, wound healing and matrigel plug assays, and in vitro ECs by tube formation, proliferation and migration assays. The interaction of HIF1α with circRNA was examined by using RNA immunoprecipitation, RNA pull-down and in situ hybridization assays. Results: The blood flow recovery was significantly attenuated in SIRT1-Tg mice, and markedly improved in SIRT1-Tg mice treated with SIRT1 inhibitor EX527 and in SIRT1-KO mice. The density of capillaries significantly decreased in the ischemic gastrocnemius of SIRT1-Tg mice compared with SIRT1-KO and WT mice, with reduced expression of VEGFA, which resulted in decreased number of arterioles. We identified that the phenotypic switching of SIRT1-Tg VSMCs was attenuated in response to hypoxia, with high levels of contractile proteins and reduced expression of the synthetic markers and NG2, compared with SIRT1-KO and WT VSMCs. Mechanistically, SIRT1-Tg VSMCs inhibited endothelial angiogenic activity induced by hypoxia via the exosome cZFP609. The cZFP609 was delivered into ECs, and detained HIF1α in the cytoplasm via its interaction with HIF1α, thereby inhibiting VEGFA expression and endothelial angiogenic functions. Meantime, the high cZFP609 expression was observed in the plasma of the patients with atherosclerotic or diabetic lower extremity peripheral artery disease, associated with reduced ankle-brachial index. Knockdown of cZFP609 improved blood flow recovery after hindlimb ischemia in SIRT1-Tg mice. Conclusions: Our findings demonstrate that SIRT1 may impair the plasticity of VSMCs. cZFP609 mediates VSMCs to reprogram endothelial functions, and serves as a valuable indicator to assess the prognosis and clinical outcomes of ischemic diseases.

BACKGROUND:Atherosclerosis can lead to multiple cardiovascular diseases, especially myocardial infarction. Long noncoding RNAs (lncRNAs) are involved in multiple diseases, including atherosclerosis. LncRNA HOXA-AS3 was found to be notably upregulated in atherosclerosis. However, the biological function of HOXA-AS3 during the occurrence and development of atherosclerosis remains unclear. MATERIALS AND METHODS:Human vascular endothelial cells (HUVECs) were treated with oxidized low-density lipoprotein (oxLDL) to mimic atherosclerosis in vitro. Gene and protein expressions in HUVECs were detected by RT-qPCR and Western blot, respectively. Cell proliferation was tested by CCK-8 and Ki67 staining. Cell apoptosis and cycle were measured by flow cytometry. Additionally, the correlation between HOXA-AS3 and miR-455-5p was confirmed by dual luciferase report assay and RNA pull-down. Finally, in vivo model of atherosclerosis was established to confirm the function of HOXA-AS3 during the development of atherosclerosis in vivo. RESULTS:LncRNA HOXA-AS3 was upregulated in oxLDL-treated HUVECs. In addition, oxLDL-induced growth inhibition of HUVECs was significantly reversed by knockdown of HOXA-AS3. Consistently, oxLDL notably induced G1 arrest in HUVECs, while this phenomenon was greatly reversed by HOXA-AS3 siRNA. Furthermore, downregulation of HOXA-AS3 notably inhibited the progression of atherosclerosis through mediation of miR-455-5p/p27 Kip1 axis. Besides, silencing of HOXA-AS3 notably relieved the symptom of atherosclerosis in vivo. CONCLUSION:Downregulation of HOXA-AS3 significantly suppressed the progression of atherosclerosis via regulating miR-455-5p/p27 Kip1 axis. Thus, HOXA-AS3 might serve as a potential target for the treatment of atherosclerosis.

Objective To explore the phenolic tetrahydro-β-carboline-arginine-glycine-aspartic acid (THBCB-RGD) peptidomimetic conjugates' role in myocardial ischemia-reperfusion injury.Methods Using high performance liquid chromatography (HPLC) method to detect the stability of THBCB-RGD peptidomimetic conjugates.The oxyradical scavenging ability of THBCB-RGD peptidomimetic conjugates was assessed by PC12 cells survive experiment and acetylcholine induced vasodilatation experiment assessment.The antiplatelet aggregation activity of THBCB-RGD peptidomimetic conjugates was evaluated by platelet aggregation exprement.Through the in vivo experiment,we evaluated the antithrombotic activity of THBCB-RGD peptidomimetic conjugates.Next,we constructed the cardiac ischemia reperfusion model and observe the effects of phenolic THBCB-RGD peptidomimetic conjugates on myocardial oxidative stress and myocardial infarction.Results HPLC results show that THBCB-RGD peptidomimetic conjugates has a strong ability of scavenging (exhaustion time:240 min,180 min,240 min;RHBCB:30 min;P =0.005).NO,H2O2 and · OH as well as inhibiting platelet aggregation and thrombus formation (P =0.004 or P =0.000).It can also inhibit the aggregation of platelets and the formation of thrombus (P =0.003 or P =0.000).In addition,treatment with phenolic tetrahydro-β-carboline-RGD peptidomimetic conjugates before the heart ischemia-reperfusion injury can decrease the MDA content in myocardium and reduce the myocardial infarction area.Conclusion THBCB-RGD peptidomimetic conjugates showed a strong ability of scavenging oxyradical and anti-thrombosis.Addition,THBCB-RGD peptidomimetic conjugates play a protective role in cardiac ischemia-reperfusion injury by inhibiting oxidative stress and reducing the myocardial infarction area.

临床资料患者女,55岁。主因间歇胸闷,胸痛,呼吸困难,向右后背放射1年,加重2个月,伴剑突下憋胀而就诊,门诊查CTA示左肺上静脉异位引流至左侧无名静脉,右心增大;部分型肺静脉异位引流症（图1）。入院后检查:心界略大,各瓣膜听诊区未闻及杂音。彩超示:左室舒张功能减低（Ⅲ度）,二尖瓣中度反流,无房间隔缺损。DSA造影（图2）,经右股静脉穿刺,猪尾导管配合超滑导丝经下腔静脉、上腔静脉至左无名

目的 探讨抑郁症(DD)与下肢深静脉血栓形成(DVT)的相关性和不同治疗方案的有效性、安全性.方法 回顾性分析2015年3月5日至2015年12月5日河北医科大学第二医院血管外科收治的11例DD合并DVT的患者,记录既往口服抗抑郁药物的情况和患者入院、出院时患、健侧大小腿的周径差.根据Villalta评分标准,评估血栓形成后综合征(PTS)的发生率和严重程度.记录发生大出血、复发和肺栓塞等并发症的情况.结果 11例DD合并DVT的患者均有服用抗抑郁药的病史,其中5例患者置入下腔静脉滤器,4例患者接受导管接触溶栓(CDT)治疗,7例患者接受外周系统溶栓治疗.出院时所有患者的症状均得到改善.6个月随访时,5例患者发展为PTS,其中轻度病变3例,中度病变2例;1年随访时,1例患者复发,6例发展为PTS,其中轻度病变4例,中度病变2例.结论 DD体质和抗抑郁药物均易诱发下肢DVT;住院期间不同治疗方案均可以有效减轻患者的患肢症状;CDT可以有效减少PTS的发生率或减轻其发病程度.