Systemic vascular impairment is the most common complication of diabetes. Advanced glycation end products (AGEs) can exacerbate diabetes-related vascular damage by affecting the intima and media through a variety of mechanisms. In the study, we demonstrated that AGEs and their membrane receptor RAGE could induce the differentiation of EPCs into osteoblasts under certain circumstances, thereby promoting accelerated atherosclerosis. Differentiation into osteoblasts was confirmed by positive staining for DiI-acetylated fluorescently labeled low-density lipoprotein and FITC-conjugated Ulex europaeus agglutinin. During differentiation, expression of receptor for AGE (RAGE) was significantly upregulated. This upregulation was attenuated by transfection with RAGE-targeting small interfering (si)RNA. siRNA-mediated knockdown of RAGE expression significantly inhibited the upregulation of AGE-induced calcification-related proteins, such as runt-related transcription factor 2 (RUNX2) and osteoprotegerin (OPG). Additional experiments showed that AGE induction of EPCs significantly induced ERK, p38MAPK, and JNK activation. The AGE-induced upregulation of osteoblast proteins (RUNX2 and OPG) was suppressed by treatment with a p38MAPK inhibitor (SB203580) or JNK inhibitor (SP600125), but not by treatment with an ERK inhibitor (PD98059), which indicated that AGE-induced osteoblast differentiation from EPCs may be mediated by p38MAPK and JNK signaling, but not by ERK signaling. These data suggested that AGEs may bind to RAGE on the EPC membrane to trigger differentiation into osteoblasts. The underlying mechanism appears to involve the p38MAPK and JNK1/2 pathways, but not the ERK1/2 pathway.

This study aimed to investigate the effects of advanced glycation end products (AGEs) on the calcification of human arterial smooth muscle cells (HASMCs) and to explore whether AGEs can promote the calcification of HASMCs by activating the phosphoinositide 3-kinase (PI3K)/AKT-glycogen synthase kinase 3 beta (GSK3-β) axis. Cultured HASMCs were divided into five groups: blank control group, dimethyl sulfoxide (vehicle) group, AGEs group, LY294002 (AKT inhibitor) group, and TWS119 (GSK3-β inhibitor) group. Cells were pretreated with either vehicle, LY294002, or TWS119 for 2 hours followed by incubation with AGEs (25 μg/mL) for 5 days, and the expression levels of proteins in each group were analyzed by western blotting. AGE treatment promoted HASMC calcification, which coincided with increased expression of p-AKT and p-GSK3-β (serine 9). Also, AGEs upregulated the expression of osteoprotegerin and bone morphogenetic protein, and these effects were suppressed by LY294002 but enhanced by TWS119. In conclusion, AGEs promote calcification of HASMCs, and this effect is ameliorated by inhibition of AKT activity but potentiated by inhibition of GSK3-β activity. Hence, AGEs trigger HASMC calcification by regulating PI3K/AKT-GSK3-β signaling.

随着老龄化社会的到来，下肢动脉硬化闭塞症的患者也在逐年增多。介入治疗虽然能够复通血流，改善症状，但血管再狭窄/闭塞仍不能完全避免，从而导致症状复发甚至加重，出现下肢溃疡及坏疽。本文报道一例支架后再狭窄/闭塞的患者，成功地运用了支架下开通技术，使患者得以避免大截肢，随访6个月新支架血流通畅，足部溃疡愈合良好。

Advanced glycation end products (AGEs) have been widely regarded as an important inducing factor in the pathogenesis of diabetic arteriosclerosis, and the proliferation and migration of vascular smooth muscle cells (VSMCs) are also involved in this process. However, it is not clear whether AGEs promote atherosclerosis by inducing the proliferation and migration of VSMCs. To figure out this question, this study investigated the effects of AGEs on the proliferation and migration of human aorta vascular smooth muscle cells (HASMCs) and the underlying mechanisms. This study evaluated the effects of different concentrations of AGEs on cell proliferation and migration. CCK8, transwell, and western blotting assays demonstrated that AGEs significantly increased cell proliferation and migration in a concentration-dependent manner and that the optimal proproliferative and promigratory concentrations of AGEs were 10 mg/L and 20 mg/L, respectively. AGE-induced cell proliferation, migration, and expression of filament actin (F-actin) were markedly attenuated by a PI3K inhibitor (LY2940002). Additionally, the phosphorylation of AKT was reduced when the receptor of advanced glycation end product (RAGE) gene was silenced by lentivirus transfection, which led to a concomitant reduction of the expression of proliferation and migration-related proteins. These data indicate that AGEs may activate the PI3K/AKT pathway through RAGE and thus facilitate the proliferation and migration of HASMCs.

目的 探讨糖原合成酶激酶3β(GSK3β)选择性抑制剂TWS119对晚期糖基化终末产物(AGEs)诱导的人主动脉血管平滑肌细胞(HAVSMCs)迁移的作用及其可能机制.方法 通过细胞划痕和Transwell实验筛选出最适促HAVSMCs迁移的AGEs浓度后,将HAVSMCs随机分为对照组、AGEs组、AGEs+TWS119组和AGEs+DMSO组.采用Transwell实验检测各组细胞迁移能力,细胞骨架染色激光共聚焦显微镜下观察纤维肌动蛋白表达,Western blot检测GSK3β、磷酸化GSK3β和MMP-2蛋白表达.结果 AGEs组HAVSMCs迁移能力较对照组增强(P＜0.01);与AGEs组相比,AGEs+ TWS119组HAVSMCs迁移能力受到抑制,纤维肌动蛋白表达减弱,磷酸化GSK3β蛋白表达增加,MMP-2蛋白表达减少(P＜0.01).结论 TWS119可能通过降低GSK3β活性和下调MMP-2蛋白表达,进而抑制AGEs诱导的HAVSMCs迁移.

Objective To investigate the effect of protein kinase B on calcifition of human aorta vascular smooth muscle cells(HASMCs) stimulated by advanced glycation end products (AGEs). Methods HASMCs were cultured in vitro and randomly divided into control group,DMSO group,AGEs group and AGEs+LY294002 group. The calcification of each group was examined by von Kusaa;the expression of protein was detected by west-ern blot and ALP levels in each group by Elisa. Results The expression of bone morphogenetic protein-2(BMP-2)and osteoprotegerin(OPG)in AGEs group was significantly higher than that in control group(P < 0.05). The expression of phosphorylated AKT in AGEs group was significantly higher than that in control group (P < 0.05), and it was time and concentration dependent. Compared with that in AGEs group ,the expression of BMP and OPG in AGEs + LY294002 group was significantly decreased (P < 0.01). Conclusion AKT signaling pathway may play an important role on calcifition of HASMCs caused by AGEs.

Objective To investigate the effect of ERK1/2 phosphorylation on the proliferation of human aorta vascular smooth muscle cells (HAVSMCs) stimulated by advanced glycation end products (AGEs) Methods CCK8 was used to test the effect of AGEs with different concentration on the proliferation of HAVSMCs, and the effect of PD98059, a specific inhibitor of ERK1/2, on HAVSMCs proliferation stimulated by AGEs was also detected. Flow Cytometer (FCM) was used to detect the cell cycle transformation induced by AGEs. Western Blot was used to detect the expression of relative proteins. Results 10 mg/L AGEs observably facilitated the proliferation and the DNA synthesis of HAVSMCs and PD98059 (40 umol/L) markedly inhibited the proliferation and cell cycle evolution of HAVSMCs induced by AGEs. Furthermore, ERK1/2 phosphorylation, and PCNA were regulated by AGEs and thus it showed time and dose dependent. Conclusion AGEs participates in the proliferation of HAVSMCs by activating ERK1/2 signal path.

目的：探讨腔内介入治疗髂静脉受压综合征的安全性及疗效。方法对2011年8月至2015年3月该科收治的52例髂静脉受压综合征患者进行腔内介入治疗，其中2例患者行单纯球囊扩张，46例患者在球囊扩张后行支架植入术，4例合并下肢深静脉血栓形成患者予以置管溶栓术后行球囊扩张和支架植入术。术后予以抗凝、口服华法林治疗。观察手术技术成功率、围术期并发症及远期通畅率等指标。结果所有患者手术均顺利完成，手术技术成功率为100.00%。术后肢体肿胀、浅静脉曲张等症状改善明显。所有患者在术中及术后均无严重并发症发生。52例门诊随访12个月，1例支架内形成血栓，其余患者在随访期间髂静脉均通畅，通畅率为98.08%（51/52）。结论血管腔内介入治疗髂静脉受压综合征是一种疗效好、安全性高的方法。

Objective: Re-evaluation of the protective effect of carotid shunt tube for the brain in Carotid endarterectomy (CEA). Methods: This is a retrospective study of 59 patients with carotid stenosis undergone carotid endarterectomy. Thirty-five patients (A group) were used the conventional carotid shunt tube in CEA, while 24 patients (group B) were not given the carotid shunt tube. The new onset of stroke, TIA, other complications, and mortality in 30 days after CEA were compared between the two groups. The brain protection of the carotid shunt tube in Carotid endarterectomy (CEA) in extracranial carotid stenosis treatment was also evaluated. Results: In group A, 1 patient (2.86%) suffered small area of cerebral infarction, 3 patients (8.57%) suffered cerebral hyperperfusion syndrome. In group B, 1 patients (4.17%) suffered small area of cerebral infarction, 1 patient (4.17%) suffered myocardial infarction and died later, 1 patient (4.17%) showed cerebral hyperperfusion syndrome. There is of no statistical significance (P > 0.05) in terms of the occurrence rate of adverse events between groups. Conclusion: The conventional use of the carotid shunt tube in Carotid endarterectomy (CEA) on extracranial carotid stenosis treatment does not reduce the risk of perioperative complications.

Objective To evaluate the clinical effect of inferior vena cava filter placement combined with antegrade cathe-ter thrombolysis for acute lower extremity deep venous thrombosis( LEDVT) . Methods 87 cases of hospitalized patients with their clinical data(87 limbs)in the department of vascular surgery of affiliated hospital of Southwest China Medical University between April 2013 to November 2015 were retrospectively summarized. Limb detumescence rate,thrombolysis,venous patency improvement index and other indicators of patients in non-operative treatment group ( peripheral anticoagulant thrombolytic group ) and operative treatment group( antegrade catheter thrombolytic group) were analyzed. Results As for 53 cases in non-operative treatment group, perimeter difference(cm)of thigh before versus after thrombolytic therapy was(7. 82 ± 1. 96)vs. (3. 02 ± 1. 05)and perimeter differ-ence(cm)of calf before versus after thrombolytic therapy was(4. 25 ± 0. 87)vs. (2. 13 ± 0. 95). As for 34 cases in surgery treatment group,perimeter difference(cm)of thigh before versus after thrombolytic therapy was(7. 96 ± 2. 03)vs. (1. 85 ± 0. 71)and perimeter difference of calf before versus after thrombolytic therapy was(4. 37 ± 0. 65)vs. (1. 43 ± 0. 32). Limb detumescence rate,thromboly-sis and venous patency improvement index in perioperative period of operative treatment group was superior to non-operative treat-ment group,the difference being statistically significant(P<0. 05). Conclusion Inferior vena cava filter placement combined with antegrade catheter thrombolysis for acute lower extremity deep venous thrombosis has obvious short-term curative effect. However,its long-term effect needs to be further confirmed.