TNFα activation and TGFß blockage act synergistically for smooth muscle cell calcification in patients with venous thrombosis via TGFß/ERK pathway.

Venous calcification has been observed in post-thrombotic syndrome (PTS) patients; yet, the cell types and possible mechanisms regulating this process are still unclear. We evaluated the calcium deposition within the venous wall, the cell type involved in the calcified remodelling of the venous wall after thrombosis and explored possible mechanisms in vitro. Calcium deposition was found in human specimens of superficial thrombotic veins and was co-localized with VSMCs markers αSMA and TAGLN (also known as SM22α). Besides, the expression of osteogenesis-related genes was dramatically changed in superficial thrombotic veins. Moreover, the inhibition of the TGFß signalling pathway after TNFα treatment effectively induced the expression of osteogenic phenotype markers, the calcium salt deposits and the obvious phosphorylation of ERK1/2 and JNK2 in the VSMCs calcification model. Supplementing TGFß2 or blocking the activation of the ERK/MAPK signalling pathway prevented the transformation of VSMCs into osteoblast-like cells in vitro. Taken together, VSMCs have an important role in venous calcification after thrombosis. Supplementing TGFß2 or inhibiting the ERK/MAPK signalling pathway can reduce the appearance of VSMCs osteogenic phenotype. Our findings may present a novel therapeutic approach to prevent of vascular calcification after venous thrombosis.

Exosomes from Adipose Mesenchymal Stem Cells Overexpressing Stanniocalcin-1 Promote Reendothelialization After Carotid Endarterium Mechanical Injury.

OBJECTIVE: Stanniocalcin-1 (STC-1) is a secreted glycoprotein that participates in the regulation of inflammation, apoptosis, and necrosis. We investigated the reendothelialization effect of exosomes from adipose stem cells (ADSC) overexpressing STC-1 on injured carotid endarterium. METHODS: ADSCs were transfected with lentivirus vectors containing pre-STC-1. PHK-26 as molecular probe was used to track the exosomes engulfed by mice arterial endothelial cells (MAEC). The role of STC-1-ADSC-Exosome (S-ADSC-Exo) in MAECs was verified through scratch test and tube forming. Expressions of STC-1 and NLRP3 inflammasome were detected by western blot and quantitative reverse transcription polymerase chain reaction. Reendothelialization effect was inhibited by the antagonist of siRNA targeting STC-1. Carotid endarterium mechanical injury was induced by insertion with a guidewire into the common carotid artery lumen. Carotid arteries were harvested for histological examination, immunofluorescence staining, and Evan's blue staining. RESULTS: Transfection of STC-1 significantly enhanced STC-1 levels in ADSCs, their exosomes, and MAECs. Compared with the control group and the ADSC-Exo group, STC-1 enriched exosomes markedly inhibited the expressions of NLRP3, Caspase-1, and IL-1ß in MAECs, exhibited good lateral migration capacity, and promoted angiogenesis. Administration of siRNA targeting STC-1 completely abolished down-regulation of NLRP3, Caspase-1, and IL-1ß by STC-1 and inhibited effects of S-ADSC-Exo on lateral migration and angiogenesis. In vivo administration of S-ADSC-Exo had reendothelialization effect on post-injury carotid endarterium as evidenced by thinner arterial wall, low-expressed NLRP3 inflammasome, and more living endothelial cells. CONCLUSIONS: The reendothelialization effect of exosomes from ADSCs on post-injury carotid endarterium could be enhanced by genetic modification of the exosomes to contain elevated STC-1, possibly through suppression of NLRP3 inflammasome-mediated inflammation.

Three-dimensional computed tomography venography reconstruction facilitates identification of atypical radiologic features of May-Thurner syndrome.

OBJECTIVE: May-Thurner syndrome (MTS) is typically characterized by compression of the left common iliac vein by the overlying right common iliac artery. The present study evaluated the occurrence of atypical imaging features of MTS using three-dimensional computed tomography venography reconstruction (3D-CTV) and analyzed their correlation with clinical features. METHODS: We analyzed the data from 268 patients with left lower extremity chronic venous disease (CVD) using 3D-CTV at a single institution from January to June 2019. An area stenosis percentage >50% was defined as significant venous compression. Of the 268 patients, 92 had at least one significant iliac and/or vena cava compression confirmed by 3D-CTV. Of the 92 patients, 89 underwent digital subtraction venography via the left common femoral vein, and the outcomes were compared with their 3D-CTV findings. Different types of venous compression were evaluated using 3D-CTV. The relationship among compression type, sex, age, and CVD symptoms was evaluated. RESULTS: A total of 106 venous compression sites were found in 92 patients. Atypical compression included inferior vena cava (IVC) compression and partial IVC compression (8.5% and 55.7%, respectively). Multiple compression sites were present in 13 patients (14.1%). The compression sites correlated significantly with clinical symptoms (P = .017) and were related to sex (P = .001). The number of patients with IVC and partial IVC compression but false-negative venography findings was four (33.3%) and six (50%), respectively. CONCLUSIONS: 3D-CTV facilitates the detection of atypical venous compression in patients with MTS with notable chronic symptoms. Patients with multiple compression sites had more severe clinical symptoms and greater false-negative rates with venography. IVC compression was more likely to occur in female patients with MTS.

In Situ Laser Stent Graft Fenestration of the Left Subclavian Artery during Thoracic Endovascular Repair of Type B Aortic Dissection with Limited Proximal Landing Zones: 5-Year Outcomes.

PURPOSE: To assess safety and feasibility of in situ laser stent graft fenestration to revascularize the left subclavian artery (LSA) during thoracic endovascular repair (TEVAR) of type B aortic dissection (TBAD) with limited proximal landing zones with 5 years of follow-up. MATERIALS AND METHODS: In a single-center retrospective study, 130 patients with TBAD with limited proximal landing zones (≤ 1.5 cm) underwent in situ laser stent graft fenestration revascularizing the LSA during TEVAR from April 2014 to April 2019. Outcomes were assessed by CT angiography and clinic visits, including technical success rate, operative time, LSA patency, ischemic events, and late aorta-related complications during follow-up. RESULTS: Mean age of patients was 53 y (range, 33-73 y). Primary technical success rate was 96.9% (126/130). Three chimney stents were placed instead of fenestration, and 1 LSA fenestration was combined with a left common carotid artery (LCCA) chimney stent. Mean operative time was 53 min ± 28 with fluoroscopy time of 40 min ± 15. There were no neurologic complications and no deaths, with a mean duration of hospital stay of 9 d (range, 5-21 d). At a mean follow-up of 42 mo (range, 5-60 mo), there was a 97% primary LSA patency. Four patients had a type I endoleak, which disappeared during follow-up. One LCCA became occluded after 6 months. No type II or III endoleaks were found. Retrograde type A aortic dissection and stent graft-induced new distal entry were not found during follow-up. CONCLUSIONS: In situ laser fenestration to revascularize the LSA during TEVAR of TBAD with limited proximal landing zones was efficient, safe, and feasible based on 5-year follow-up.

Outcomes of emergency in situ laser fenestration-assisted thoracic endovascular aortic repair in patients with acute Stanford type A aortic dissection unfit for open surgery.

OBJECTIVE: This study investigated the outcomes of emergency in situ laser fenestration (ISLF)-assisted thoracic endovascular aortic repair (TEVAR) for patients with acute Stanford type A aortic dissection unfit for open surgery. METHODS: Twenty patients with acute Stanford type A aortic dissection who were found to be unfit for open surgery, underwent emergency ISLF-assisted TEVAR in our center between March 2016 and December 2018. Anatomic criteria for endovascular repair: coronary artery and aortic valve was not involved, proximal landing zone diameter of 45 mm or less, and proximal landing zone length of 20 mm or greater. Their clinical outcomes were reviewed retrospectively. RESULTS: Twenty patients achieved a procedural success of 100.0%. The 30-day mortality was 10%; two patients died, one of severe pneumonia and the other from cerebral hemorrhage after the operation. Rate of stroke at 30 days was 5%. The average follow-up time was 16 months (range, 3-26 months). One death owing to heart failure occurred at 23 months postoperatively. Kaplan-Meier curve analysis revealed that the 24-month survival rate was 77.1%. Two patients had type Ia endoleaks and one had a type II endoleak. There was no stent graft migration or fenestration-related endoleak and all patients had a thrombosed false lumen in the covered section of the stent grafts. No reintervention, myocardial infarction, transient ischemic attacks, cerebral infarction, or other complications occurred during the follow-up period. CONCLUSIONS: Emergency ISLF-assisted TEVAR is a safe and effective alternative method for treating acute Stanford type A aortic dissection unfit for open surgery.

Unclassified unilateral persistent sciatic artery in a patient with chronic intermittent claudication.

Patients with persistent sciatic artery are at high risk for development of limb ischemia, aneurysm formation, and embolism. In this report, we identify a nonclassified left leg persistent sciatic artery in a patient with chronic limb ischemia. Vascular reconstruction was carried out by common iliac-deep femoral artery bypass to restore adequate arterial flow. Our approach to placement of the distal anastomosis on the deep femoral artery instead of on the popliteal artery, which is used in routine practice, may potentially increase treatment efficacy and decrease surgical complications. At 2-year follow-up, the patient remained asymptomatic and in good health.

Identification of Key lncRNAs Associated With Atherosclerosis Progression Based on Public Datasets.

Atherosclerosis is one of the most common type of cardiovascular disease and the prime cause of mortality in the aging population worldwide. However, the detail mechanisms and special biomarkers of atherosclerosis remain to be further investigated. Lately, long non-coding RNAs (lncRNAs) has attracted much more attention than other types of ncRNAs. In our work, we found and confirmed differently expressed lncRNAs and mRNAs in atherosclerosis by analyzing GSE28829. We performed the weighted gene co-expression network analysis (WGCNA) by analyzing GSE40231 to confirm highly correlated genes. Gene Ontology (GO) analysis were utilized to assess the potential functions of differential expressed lncRNAs in atherosclerosis. Co-expression networks were also constructed to confirm hub lncRNAs in atherosclerosis. A total of 5784 mRNAs and 654 lncRNAs were found to be dysregulated in the progression of atherosclerosis. A total of 15 lncRNA-mRNA co-expression modules were identified in this study based on WGCNA analysis. Moreover, a few lncRNAs, such as ZFAS1, LOC100506730, LOC100506691, DOCK9-AS2, RP11-6I2.3, LOC100130219, were confirmed as important lncRNAs in atherosclerosis. Taken together, bioinformatics analysis revealed these lncRNAs were involved in regulating the leukotriene biosynthetic process, gene expression, actin filament organization, t-circle formation, antigen processing, and presentation, interferon-gamma-mediated signaling pathway, and activation of GTPase activity. We believed that this study would provide potential novel therapeutic and prognostic targets for atherosclerosis.

In situ diode laser fenestration of aortic arch stent grafts during thoracic endovascular aortic repair of Stanford type A aortic dissection.

AIMS: The aim of the study was to evaluate the feasibility, safety, and effectiveness of in situ diode laser fenestration of thoracic endovascular aortic repair (TEVAR) stent grafts to treat Stanford type A aortic dissection. METHODS AND RESULTS: Fifty-eight patients with acute or subacute Stanford type A aortic dissection treated with in situ diode laser fenestration during TEVAR under cerebral circulation protection with an extracorporeal bypass were reviewed retrospectively. Routine postoperative outcomes were recorded and assessed. Computed tomography angiography (CTA) was performed during the follow-up after 3, 6 and 12 months. Procedural success was achieved in 53 patients (91.4%). The average procedure time was 162±36 minutes. One patient died of pericardial tamponade during intervention, and one died of severe pneumonia after the intervention. Except for two minor strokes, no more fenestration-related complications occurred at 30 days and 12 months after the intervention. CTA imaging demonstrated 100% primary patency for the left subclavian artery and carotid arteries with favourable aortic remodelling after TEVAR during the follow-up. Two patients had a type Ia endoleak and one other a type II endoleak. CONCLUSIONS: In situ diode laser fenestration during TEVAR for type A aortic dissection was found to be feasible, safe, and effective, and may be beneficial as a less invasive approach.

Endovascular repair of aortic arch intramural hematoma and penetrating ulcers with 810 nm in situ laser-assisted fenestration: Preliminary results of a single-center.

PURPOSE: The aim of the present study was to report the clinical outcomes of the use of 810 nm in situ laser-generated fenestration (ISLF) for the treatment of aortic aneurysms (AAs) and intramural hematomas (IMHs) located in the aortic arch. STUDY DESIGN AND METHODS: Between April 2014 and September 2017, 23 patients (15 men, mean age 66.0 years) with AAs (n = 12) or IMHs (n = 11) underwent thoracic endovascular aortic repair (TEVAR) with 810 nm ISLF of the arch. The primary outcomes of the safety assessment were the presence of endoleaks, mortality and morbidity, including adverse in situ fenestration-related, cardiovascular, and cerebral events. RESULTS: Technical success was achieved in all cases. Urgent intervention was performed in 15 (65.2%) cases. Left subclavian artery (LSA) ISLF was applied in six patients, LSA and left common carotid artery (LCCA) ISLF in three patients, and total aortic arch vessel ISLF in two patients. One patient suffered minimal stroke after the procedure and recovered without permanent disability to the extremities in 2 weeks. There were no fenestration-related complications except in one patient with brachial artery access who suffered a hematoma and underwent incision repair at the puncture site. All fenestrations remained patent, and there were no endoleaks during a mean follow-up of 10.5 ± 5.7 (range: 2-21) months. CONCLUSIONS: Complete or incomplete endovascular arch reconstruction by ISLF in arch diseases (AAs and IMHs) is feasible and reproducible with safe, effective, and favorable primary results and no need for customized endografts. Lasers Surg. Med. 50:837-843, 2018. © 2018 Wiley Periodicals, Inc.

Treatment of Femoral Vein Obstruction Concomitant with Iliofemoral Stenting in Patients with Severe Post-thrombotic Syndrome.

BACKGROUND: The aim was to assess the clinical and anatomical outcomes of iliofemoral stenting, with concomitant femoral stenting or balloon angioplasty alone, in patients with severe post-thrombotic syndrome (PTS) and compromised inflow. METHODS: A database of patients with severe PTS who successfully underwent endovascular iliofemoral stenting was reviewed retrospectively. Patients with impaired inflow with chronic post-thrombotic obstructive lesions in the femoral vein (FV), but patent profunda vein, were selected and divided into two groups: the FV stenting (FV-S) group and the FV angioplasty (FV-A) group. Patients in the FV-S group were treated with concomitant iliofemoral and FV stenting, and patients in the FV-A group were treated with iliofemoral stenting and balloon angioplasty alone of the obstructed femoral vein. The clinical and stent outcomes were recorded and compared in the two groups. RESULTS: There were 45 patients in the FV-S group and 69 patients in the FV-A group. The groups were well matched for age, gender, and diseased limbs. The pre-procedural symptoms, CEAP classifications, VCSS scores, Villalta scores, and prevalence of active ulcers were also similar between the two groups. Immediate failure (<30 days post-procedure) in the femoral segment occurred more frequently in the FV-A group (70% in FV-A group vs. 24% in FV-S group, p < .001); however, all treated femoral vein segments had occluded at 12 months. There was no significant difference between the FV-S and FV-A groups in cumulative primary and secondary patency rates of the iliofemoral stent at 3 years (55% vs. 52%, p = .71, and 77% vs. 85%, p = .32, respectively). Complete pain relief, swelling relief, VCSS score, Villalta score, and freedom from ulcers at a median of 22 months (1-48 months) following the procedure were similar in the two groups. CONCLUSIONS: Stent placement to treat post-thrombotic iliofemoral obstruction with concomitant obstructed femoral vein but patent profunda vein shows cumulative patency rates and clinical outcomes similar to previous reports. Adjunctive femoral stenting or angioplasty of the obstructed femoral vein does not appear to improve clinical or stent outcomes in patients with severe PTS.

Staged endovascular repair of critical limb ischemia in high risk patients: the procedural and clinical outcomes.

BACKGROUND: The aim of this paper was to retrospectively evaluate the procedural and clinical outcomes after staged angioplasty in high-risk, chronic, critical limb ischemia (CLI) patients. METHODS: Between 2013 and 2015, 29 patients (29 limbs) (mean age 77 years) were treated by staged revascularization procedures in 1) the iliac artery-DFA alone or with the femoropopliteal artery followed by 2) the femoropopliteal artery and a below-the-knee artery. All patients had long-segment iliofemoral artery and below-the-knee artery (TASCII D) occlusions with abnormal serum myoglobin and ischemic lesions. Clinical outcome was assessed at 1, 3, 6, and 12 months. Clinical treatment efficacy was defined as patient survival with resolved CLI without major amputations after the last revascularization procedure. RESULTS: Angioplasty was performed in all limbs with a technical success rate of 100%. All the patients received 2 stage endovascular interventions. The interval time between the two stages was 19.56±6.56 days. In the second stage, the peroneal artery (PA) in 11 patients, the anterior tibial artery (ATA) in 7 patients, both the PA and ATA in 6 patients, and the posterior tibial artery (PTA) in 6 patients were recanalized. Rest pain and lesions were resolved in all patients after the second-stage revascularization. An upward shift of limb status and EQ-5D scores after the first or second revascularization indicated a significant change. No major amputations occurred, although minor amputations were required in 5 patients within 3 months after the second endovascular revascularization. The primary patency was 82.76%. Repeat TLR was necessary for 5 patients after endovascular BTK revascularization. Clinical treatment efficacy was 71% at 12 months; the cumulative rate of repeat target limb revascularization was 45.6%. CONCLUSIONS: Staged endovascular treatment in high-risk CLI patients can effectively relieve rest pain and symptoms of necrosis, which greatly improves the survival and quality of life of patients less suited for conventional repair.

Functional blocking of Ninjurin1 as a strategy for protecting endothelial cells in diabetes mellitus.

Ongoing efforts to remove pathological inflammatory stimuli are crucial for the protection of endothelial cells in diabetes. Nerve injury-induced protein 1 (Ninj1) is an adhesion molecule that not only contributes to inflammation but also regulates the apoptosis of endothelial cells. In the present study, Ninj1 was found highly expressed in endothelial cells in Type 2 diabetic mice and increased in high-glucose (HG) cultured HUVECs. Furthermore, we found that Ninj1 levels are up-regulated in endothelial cells in clinical specimens of diabetic patients when compared with nondiabetic tissues, indicating a biological correlation between Ninj1 and endothelial pathophysiology in diabetic condition. Functional blocking of Ninj1 promoted endothelial tube formation and eNOS phosphorylation in the HG condition. Additionally, blocking Ninj1 inhibited the activation of caspase-3 and increased the Bcl-2/Bax ratio, thus inhibiting HUVECs apoptosis induced by HG. HG-induced ROS overproduction, p38 MAPK and NF-κB activation, and the overexpression of VCAM-1, ICAM-1, MCP-1, and IL-6 genes were ameliorated after Ninj1 was blocked. Using the signaling pathway inhibitor LY294002, we found that Bcl-2 expression and eNOS phosphorylation after Ninj1 blockade were regulated via PI3K/Akt signaling pathway. The in vivo endothelial contents, α-SMA+PECAM-1+ vascular numbers, and blood perfusion in the hindlimb were markedly up-regulated after Ninj1 was blocked. According to our findings, functional blocking of Ninj1 shows protective effects on diabetic endothelial cells both in vitro and in vivo Thus, we consider Ninj1 to be a potential therapeutic target for preventing endothelial dysfunction in diabetes mellitus.

Comparison of Direct Iliofemoral Stenting Following AngioJet Rheolytic Thrombectomy vs Staged Stenting After AngioJet Rheolytic Thrombectomy Plus Catheter-Directed Thrombolysis in Patients With Acute Deep Vein Thrombosis.

PURPOSE: To compare the treatment outcomes in patients with acute proximal deep vein thrombosis (DVT) and iliofemoral stenosis who underwent either direct stenting after AngioJet rheolytic thrombectomy or staged stenting after AngioJet thrombectomy plus catheter-directed thrombolysis with urokinase. METHODS: From June 2014 to February 2016, 91 DVT patients underwent 2 treatments for duplex-verified iliofemoral stenosis: direct stenting (n = 46; mean age 54.8 years; 32 men) or staged stenting (n = 45; mean age 56.5 years; 27 men). The degree of patency after thrombectomy or thrombolysis was evaluated using the Venous Registry Index (VRI), while the risk of postthrombotic syndrome (PTS) was evaluated according to the Villalta scale. Patients were followed with periodic duplex ultrasound scans up to 1 year. RESULTS: The technical success rates were 100% in both groups; there was no 30-day mortality. Immediate (24-hour) clinical improvement was achieved in 42 (91%) of 46 direct group patients vs 33 (73%) of 45 staged group patients (p<0.001). A significant reduction (p<0.001) in the length of hospital stay was noted in the direct group (4.59±0.91) compared with that in the staged group (5.8±1.6). The stents used in the direct group were longer but with similar diameter compared with the staged group. The thrombolysis rates were 81.50%±5.76% in the direct group and 85.67%±3.84% in the staged group (p<0.001). The VRIs declined (improved) significantly in both groups (11.68±1.92 to 3.21±1.44 in the direct group and 12.17±2.29 to 2.36±1.19 in the staged group, both p<0.001). The Villalta scores were significantly better in the staged group (p<0.001). Recurrent DVT occurred in 2 patients in the direct group. The primary patency rates at 1 year were 93.5% in the direct group and 97.8% in the staged group (p=0.323). CONCLUSION: Both direct and staged stenting are effective treatment modalities for patients with acute proximal DVT. Compared with staged stenting, direct stenting provides similar treatment success and a significant reduction in the length of hospital stay; however, it has lower thrombolysis efficacy, and the risk of PTS at 1 year is greater with direct stenting.

Outcomes of endovascular recanalization versus autogenous venous bypass for thromboangiitis obliterans patients with critical limb ischemia due to tibioperoneal arterial occlusion.

OBJECTIVE: This study sought to compare the outcomes of endovascular recanalization (ER) vs autogenous venous bypass (AVB) for tibioperoneal arterial occlusion in thromboangiitis obliterans patients with critical lower limb ischemia. METHODS: A total of 90 limbs in 75 patients, successfully treated with ER (ER group, 35 patients, 43 limbs) and AVB (AVB group, 40 patients, 47 limbs) for tibioperoneal arterial occlusions from January 2009 to December 2015 in a single institution, were retrospectively analyzed. The characteristics and outcomes were compared between the two groups. The primary outcome was the amputation-free survival rate during follow-up; the secondary outcomes were patency rates, immediate failure, periprocedural complications, and rates of reintervention. Univariate and multivariate analysis to identify potentially significant predictors of amputation-free survival and primary patency in the whole study group was performed. RESULTS: Not all patients in the ER group were bypass candidates because of unavailable runoff arteries or adequate conduit for bypass. Other baseline characteristics were similar between groups. Patients in the ER group had a much higher incidence of immediate failure (36.36% in femoropopliteal segment and 65.52% in tibioperoneal segment vs 14.89% in AVB bypass; P = .03 and < .001). Although patients in the ER group had a significantly higher rate of reintervention (62.79% vs 27.66%; P < .001) associated with a significantly lower primary patency rate (18.96% in femoropopliteal segment and 14.37% in tibioperoneal segment vs 60.41% in AVB bypass; P = .008 and < .001) and secondary patency rate (33.85% in femoropopliteal segment and 21.29% in tibioperoneal segment vs 68.78% in AVB bypass; P = .04 and .002) at 3 years, the amputation-free survival in the ER group and AVB group was similar at 1 year (92.9% vs 93.2%; P = .81) and 3 years (87.8% and 90.6%; P = .66). Univariate and multivariate analysis showed that the presence of gangrene was independently associated with major amputation (hazard ratio, 2.24; 95% confidence interval, 1.33-4.3; P = .02); however, the presence of active ulcer was the only risk factor for poorer primary patency during follow-up (hazard ratio, 1.86; 95% confidence interval, 0.55-5.6; P = .04). CONCLUSIONS: ER is a valid strategy for limb salvage in thromboangiitis obliterans patients who are unsuitable for bypass, contributing an acceptable amputation-free survival as high as with AVB, even though it is associated with lower patency rates and a higher rate of reintervention.

In Situ Laser Fenestration Is a Feasible Method for Revascularization of Aortic Arch During Thoracic Endovascular Aortic Repair.

BACKGROUND: Reconstruction of the aortic major branches during thoracic endovascular aortic repair is complicated because of the complex anatomic configuration and variation of the aortic arch. In situ laser fenestration has shown great potential for the revascularization of aortic branches. This study aims to evaluate the feasibility, effectiveness, and safety of in situ laser fenestration on the three branches of the aortic arch during thoracic endovascular aortic repair. METHODS AND RESULTS: Before clinical application, the polytetrafluoroethylene and Dacron grafts were fenestrated by an 810-nm laser system ex vivo, which did not damage the bare metal portion of the endografts and created a clean fenestration while maintaining the integrity of the endografts. In vivo, 6 anesthetized female swine survived after this operation, including stent-graft implantation in the aortic arches, laser fenestration, and conduit implantation through the innominate arteries and the left carotid arteries. Based on the animal experiments, in situ laser fenestration during thoracic endovascular aortic repair was successively performed on 24 patients (aged 33-86 years) with aortic artery diseases (dissection type A: n=4, type B: n=7, aneurysm: n=2, mural thrombus: n=7). Fenestration of 3 aortic branches was performed in 2 (8.3%) patients. Both the left carotid artery and the left subclavian artery were fenestrated in 6 (25%) patients. Only left subclavian artery fenestration surgery was done in 16 (66.7%) patients. Among these patients, 1 fenestration was abandoned secondary to an acute takeoff of the innominate artery in a type III aortic arch. The average operative time was 137±15 minutes. The technical success rate was 95.8% (n=23). No fenestration-related complications or neurological morbidity occurred after this operation. During a mean postoperative 10-month follow-up (range: 2-17 months), 1 patient died of severe pneumonia, and all the left subclavian artery and carotid artery stents were patent with no fenestration-related endoleaks upon computed tomography angiography images. CONCLUSIONS: In situ laser fenestration is a feasible, effective, rapid, repeatable, and safe option for the reconstruction of aortic arch during thoracic endovascular aortic repair, which might be available to revascularize the 3 branches. However, follow-up periods should be extended to evaluate the robustness of this technique.

Glyoxalase-1 Overexpression Reverses Defective Proangiogenic Function of Diabetic Adipose-Derived Stem Cells in Streptozotocin-Induced Diabetic Mice Model of Critical Limb Ischemia.

Adipose-derived stem cell (ADSC)-based therapy is promising for critical limb ischemia (CLI) treatment, especially in patients with diabetes. However, the therapeutic effects of diabetic ADSCs (D-ADSCs) are impaired by the diabetes, possibly through intracellular reactive oxygen species (ROS) accumulation. The objective of the present study was to detect whether overexpression of methylglyoxal-metabolizing enzyme glyoxalase-1 (GLO1), which reduces ROS in D-ADSCs, can restore their proangiogenic function in a streptozotocin-induced diabetic mice model of CLI. GLO1 overexpression in D-ADSCs (G-D-ADSCs) was achieved using the lentivirus method. G-D-ADSCs showed a significant decrease in intracellular ROS accumulation, increase in cell viability, and resistance to apoptosis under high-glucose conditions compared with D-ADSCs. G-D-ADSCs also performed better in terms of migration, differentiation, and proangiogenic capacity than D-ADSCs in a high-glucose environment. Notably, these properties were restored to the same level as that of nondiabetic ADSCs under high-glucose conditions. G-D-ADSC transplantation induced improved reperfusion and an increased limb salvage rate compared D-ADSCs in a diabetic mice model of CLI. Histological analysis revealed higher microvessel densities and more G-D-ADSC-incorporated microvessels in the G-D-ADSC group than in the D-ADSC group, which was comparable to the nondiabetic ADSC group. Higher expression of vascular endothelial growth factor A and stromal cell-derived factor-1α and lower expression of hypoxia-induced factor-1α were also detected in the ischemic muscles from the G-D-ADSC group than that of the D-ADSC group. The results of the present study have demonstrated that protection from ROS accumulation by GLO1 overexpression is effective in reversing the impaired biological function of D-ADSCs in promoting neovascularization of diabetic CLI mice model and warrants the future clinical application of D-ADSC-based therapy in diabetic patients. Stem Cells Translational Medicine 2017;6:261-271.

Use of a stent-graft and vascular occlude to treat primary and re-entry tears in a patient with a Stanford type B aortic dissection / O uso de endoprótese e oclusor vascular para tratar ruptura primária e de re-entrada em paciente com dissecção aórtica tipo B de Stanford

Thoracic endovascular aortic repair for aortic dissections is recognized as an effective treatment. We herein report the case of a 72-year-old male with a Stanford type B aortic dissection. A stent-graft and double-disk vascular occluder was used to repair the primary and re-entry tears, respectively. At 3 month postoperatively, computed tomographic angiography revealed no endoleaks, the stent-graft and vascular occluder to be in optimal positions, the false lumen was almost completely thrombosed, and the visceral arteries were patent. This case illustrates that it is feasible to treat re-entry tears with a vascular occluder after primary proximal stent-graft repairs.

Reparação endovascular de aorta torácica para dissecção aórtica é reconhecida como um tratamento eficaz. Relatamos o caso de um homem de 72 anos de idade, com dissecção aórtica tipo B de Stanford. A endoprótese e oclusor duplo disco vascular foi usado para reparar as rupturas primária e de re-entrada, respectivamente. Aos três meses de pós-operatório, angiotomografia computadorizada não revelou vazamentos, o oclusor e a endoprótese vascular estavam em posições melhores, a falsa luz foi quase completamente trombosada, e as artérias viscerais estavam patentes. Esse caso demonstra que o tratamento de rupturas na re-entrada com endoprótese vascular após reparos proximais primários é viável.

Baicalin attenuates acute myocardial infarction of rats via mediating the mitogen-activated protein kinase pathway.

Baicalin is a bioactive ingredient from the herb and has possessed various pharmacological actions. The present study was performed to evaluate the cardioprotective potential of baicalin against myocardial infarction and explore the potential mechanism. Baicalin was intraperitoneally injected into the rats by the doses of 50, 100 and 200 mg/kg, respectively, once a day for 7 d and, 30 min after the last administration, the left coronary artery was ligated. Infarct size was measured to analyze the myocardial damage. Myocardial specific enzymes, including creatine kinase (CK), the MB isoenzyme of creatine kinase (CK-MB), lactate dehydrogenase (LDH) and cardiac troponin T (cTnT) were determined with the colorimetric method. Evidence for myocardial apoptosis was detected by caspase-3 activity measurement and Western blot analysis. We also examined the protein levels of three major subgroups of mitogen-activated protein kinases (MAPKs), namely, extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK) and p38 by immuoblotting. Our results indicated that baicalin significantly reduced the infarct size and myocardial enzymes (CK, CK-MB, LDH and cTnT). Administration of baicalin also suppressed the activity and protein expression of caspase-3. Moreover, the protein level of phosphorylated ERK (p-ERK) was found to be evidently augmented while the phosphorylated JNK (p-JNK) and phosphorylated p38 (p-p38) were strikingly diminished in infarcted rats with baicalin treatment. These findings suggest that the baicalin's cardioprotection associates with mediation of MAPK cascades in acute myocardial infarction of rats.

Use of a stent-graft and vascular occlude to treat primary and re-entry tears in a patient with a Stanford type B aortic dissection.

Thoracic endovascular aortic repair for aortic dissections is recognized as an effective treatment. We herein report the case of a 72-year-old male with a Stanford type B aortic dissection. A stent-graft and double-disk vascular occluder was used to repair the primary and re-entry tears, respectively. At 3 month postoperatively, computed tomographic angiography revealed no endoleaks, the stent-graft and vascular occluder to be in optimal positions, the false lumen was almost completely thrombosed, and the visceral arteries were patent. This case illustrates that it is feasible to treat re-entry tears with a vascular occluder after primary proximal stent-graft repairs.

Percutaneous endovenous treatment of congenital extratruncular venous malformations with an ultrasound-guided and 810-nm diode laser.

BACKGROUND: Venous malformations (VMs) are the commonest vascular anomalies. Treatment of extratruncular venous malformations (EVMs) is difficult. Surgery has been the mainstay therapy for EVMs but can be hazardous, leading to major blood loss and incomplete resection. Recurrence and cosmetic problems are also common after resection. Endovenous laser ablation (EVLA) has been found to be safe and effective for endovenous ablation of incompetent saphenous veins. We report our experience of diode laser ablation in percutaneous ultrasound (US)-guided treatment of congenital EVMs with respect to effectiveness and safety. METHODS: A consecutive series of patients (16 males and 22 females; age, 13-46 years) were treated by US-guided EVLA for EVMs at our institution. A questionnaire was used to assess preoperative and postoperative symptoms. Effectiveness was assessed by procedural success and clinical success. Subjective improvement of symptoms was further assessed simultaneously with objective evidence of improved clinical signs. This included reduction of lesion size, general swelling, or improved range of motion of the joint. Duplex US imaging was used to assess blood flow within lesions. Safety was assessed by morbidity and mortality, including laser-related adverse events, postoperative deep vein thrombosis, pulmonary embolism, and hematoma. RESULTS: All patients tolerated the procedure and recovered uneventfully. Fifty-six procedures were undertaken in 38 patients. All procedures were successful. Thirty-three patients had resolution of presenting pain symptoms after laser treatment; the remaining patients were able to significantly reduce the number of pain medications from that used before treatment. For complaints related to swelling and cosmetic effect, clinical success was 70% and 67%, respectively. No patients returned with recurrent symptoms after initial successful treatment at a mean follow-up of 12.7 months. Thirty-six (64%) treated lesions areas were classified as "excellent," 18 (32%) were "good," and 2 (4%) were "fair" using duplex US imaging at final follow-up. Better results were obtained with localized types of VMs, in which palliation was achieved after only one treatment. Complications were minor and improved quickly. CONCLUSIONS: Treatment of congenital EVMs with endovenous laser ablation under US guidance achieved palliation in most symptomatic patients; it was safe, with minimal morbidity during short-term follow-up.