Exo70 Promotes the Invasion of Pancreatic Cancer Cells via the Regulation of Exosomes.

Pancreatic cancer (PC) is an aggressive and fatal malignant tumor, and exosomes have been reported to be closely related to PC invasion and metastasis. Here we found that Exo70, a key subunit of the exocyst complex, promoted PC metastasis by regulating the secretion of tumor exosomes. Clinical sample studies showed that Exo70 was highly expressed in PC and negatively correlated with patients' survival. Exo70 promoted PC cell lines' invasion and migration. Interestingly, knockdown of Exo70, or using an Exo70 inhibitor (ES2) inhibited the secretion of tumor exosomes and increased the accumulation of cellular vesicles. Furthermore, Exo70 was found to accumulate in the exosomes, which then fused with neighboring PC cells and promoted their invasion. Moreover, Exo70 increased the expression of exosomal PD-L1, leading to the immune escape of PC cells. In vivo, knockdown of Exo70 or treatment with ES2 both decreased the tumor metastasis of PC cells in mice. This study provides new insight into the mechanism of invasion and metastasis in PC and identifies Exo70 as a potential prognostic factor and therapeutic target for PC.

Impacts, causes and biofortification strategy of rice selenium deficiency based on publication collection.

Selenium (Se) deficiency in rice will result in a Se hidden hunger threat to the general public's human health, particularly in areas where rice consumption is high. Nevertheless, the impact scope and coping strategies have not been given sufficient focus on a worldwide scale. In order to evaluate the impacts, causes and biofortification strategies of Se-deficient rice, this study collected data from the publications on three themes: market survey, field sampling and controlled experiments. According to the market survey, global rice Se concentrations were 0.079 mg/kg on mean and 0.062 mg/kg on median. East Asia has a human Se intake gap due to the region's high rice consumption and the lowest rice Se concentration in markets globally. Total Se concentrations in East Asian paddy soils were found to be adequate based on the field sampling. However, over 70 % of East Asian paddy fields were inadequate to yield rice that met the global mean for rice Se concentration. The Se-deficient rice was probably caused by widespread low Se bioavailability in East Asian paddy fields. There were two important factors influencing rice Se enrichment including root Se uptake and iron oxide in soils. Concentrating on these processes is beneficial to rice Se biofortification. Since Se is adequate in the paddy soils of East Asia. Rather of adding Se exogenously, activating the native Se in paddy soil is probably a more appropriate strategy for rice Se biofortification in East Asia. Meta-analysis revealed water management had the greatest impact on rice Se biofortification. The risks and solutions for rice Se deficiency were discussed in our farmland-to-table survey, which will be a valuable information in addressing the global challenge of Se hidden hunger. This study also provided new perspectives and their justifications, critically analyzing both present and future strategies to address Se hidden hunger.

Enhanced Soluble Expression of Linoleic Acid Isomerase by Coordinated Regulation of Promoter and Fusion Tag in Escherichia coli.

PAI is a linoleic acid isomerase from Propionibacterium acnes and is the key enzyme in the synthesis of trans10, cis12-conjugated linoleic acid. However, the majority of the expressed PAI in Escherichia coli occurs in its nonfunctional form in inclusion bodies, limiting the biosynthesis of conjugated linoleic acid. In an attempt to improve the solubility of recombinant PAI in Escherichia coli, three promoters representing different transcriptional strengths (T7, CspA, and Trc), paired with three fusion tags, (His6, MBP, and Fh8), respectively, were investigated in this study. Among the nine recombinant strains, Escherichia coli BL21 (DE3) (pET24a-Mpai), containing the T7 promoter and MBP fusion tag, led to a considerable increase in PAI solubility to 86.2%. MBP-PAI was purified 41-fold using affinity column chromatography. The optimum catalytical conditions of MBP-PAI were 37 °C and pH 7.5 with the addition of 1 mmol/L Tween-20. Most of the tested metal ions inhibited MBP-PAI activity. The apparent kinetic parameters (Km and Vmax) were measured with linoleic acid concentrations ranging from 71 µM to 1428 µM. The substrate linoleic acid did not exert any inhibitory effect on MBP-PAI. The Km of MBP-PAI was 253.9 µmol/L, and the Vmax was 2253 nmol/min/mg. This study provided a new method for improving the solubility of the recombinant linoleic acid isomerase in Escherichia coli.

Endovascular management of extensive lower extremity acute deep vein thrombosis with AngioJet rheolytic thrombectomy plus catheter-directed thrombolysis from contralateral femoral access.

PURPOSE: The aim of the present study was to report the clinical outcomes of endovascular treatment for extensive lower limb deep vein thrombosis with AngioJet rheolytic thrombectomy (ART) plus catheter-directed thrombolysis (CDT) using a contralateral femoral approach. METHODS: A retrospective analysis of consecutive ART+CDT treatments in 38 deep vein thrombosis patients (LET I-III, from September 2014 to March 2016) was performed. RESULTS: The technical success rate was 100%. Complete lysis was achieved in 82% of LET III segments (calf veins), 87% of LET II segments (popliteal-femoral veins), and 90% of LET III segments (iliac veins). The best results were obtained in patients treated within seven days of symptom onset. During follow-up, well-preserved, competent femoral valves were observed in 86% of the patients, and recanalization of LET III, LET II, and LET I segments was achieved in 100%, 94%, and 91% of the patients, respectively. The post-thrombotic syndrome rate was 17% during a mean 20-month follow-up.

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.

A liquid crystalline precursor incorporating chlorhexidine acetate and silver nanoparticles for root canal disinfection.

Lyotropic liquid crystals (LLC) have received increasing attention as a drug delivery system. In this study, a novel intra-canal disinfectant based on the glycerol monooleate (GMO) LLC precursor incorporation with chlorhexidine (CHX) and silver nanoparticles (Ag-NPs) was designed and evaluated. The LLC precursor with excellent fluidity was able to penetrate deeply into the complex tiny collateral branch root canals. The transformation of cubic LLC in root canals upon coming into contact with water provided long-lasting disinfection against multidrug-resistant bacteria to avoid the endodontic reinfection and follow-up visits. The GMO-ethanol-water (48% : 12% : 40%, w/w) formulation containing 0.5% CHX and 0.02% Ag-NPs was selected for further studies. The low viscosity of the precursor presented excellent injectability and flowabilities. From the in vitro release test, the release behaviours were found to be influenced by CHX and Ag-NP contents, allowing the optimized precursor to obtain a 28-day release profile. The CHX-Ag-NP containing LLC precursor exhibited an excellent and sustained sterilization effect on Enterococcus faecalis for more than one month with a bacterial inactivation rate of ≥98.5%, which was far more than the minimum clinical requirement (7 days). Furthermore, no in vitro toxicity was observed in the cytotoxicity evaluation. The CHX-Ag-NP containing LLC precursor was proved to be a promising intra-canal disinfectant in our study.

Catheter-Directed Thrombolysis of Acute Entire Limb Deep Vein Thrombosis From below the Knee Access: A Retrospective Analysis of a Single-Center Experience.

PURPOSE: To evaluate the safety and efficacy of below the knee (BTK) approach in the treatment of entire limb deep vein thrombosis (DVT). MATERIALS AND METHODS: Retrospective analysis of consecutive CDT treatment of acute entire limb DVT using a BTK approach (September 2010-February 2016) was performed. The patients included 51 men and 28 women with a mean age of 54 years. RESULTS: CDT was performed by accessing the ipsilateral the small saphenous vein (SSV) and posterior tibial vein (PTV; 24 via incision and 64 via puncture). Thirty-four patients underwent CDT within 3 days of symptom onset and lysis was successful in all cases (i.e., grade III).In contrast, only 22 (68.6%, 22/32) of those treated within 4-10 days and 0 (0%) of those treated after 10 days achieved grade III lysis. A total of 16 bleeding complications occurred, none of which were classified as major, and 11 of which were related to numbness at the site of incision. Poor wound healing was observed in one patient. Three patients treated using an SSV approach exhibited partial occlusion. One patient treated using a PTV approach experienced occlusion. During the 24-month follow-up period, the patency and PTS rates were 80.4% (37/46) and 30.4% (14/46), respectively. The overall patency rate was 87.1% (54/62) during a mean follow-up duration of 3.5 years. CONCLUSIONS: The use of a BTK approach in entire-limb DVT via SSV and PTV puncture is feasible and safe and may be considered an alternative to traditional CDT approach. © 2017 Wiley Periodicals, Inc.

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.

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.

An injectable in situ gel with cubic and hexagonal nanostructures for local treatment of chronic periodontitis.

Periodontitis is a chronic bacterial infection, and its effective treatment is dependent on the retention of antibiotics of effective concentrations at the periodontal pockets. In this study, a solution-gel based inverse lyotropic liquid crystalline (LLC) system was explored to deliver metronidazole to the periodontal pockets for local treatment of periodontitis. It was found that the metronidazole-loaded LLC precursor spontaneously transformed into gel in the presence of water in the oral cavity. The low viscosity of the precursor would allow its penetration to the rather difficult to reach infection sites, while the adhesiveness and crystalline nanostructures (inverse bicontinuous cubic Pn3m phase and inverse hexagonal phase) of the formed gel would permit its firm adhesion to the periodontal pockets. The LLC system provided sustained drug release over one week in vitro. Results from in vivo study using a rabbit periodontitis model showed that the LLC system was able to maintain the metronidazole concentrations in the periodontal pockets above the minimum inhibition concentration for over 10 days without detectable drug concentration in the blood. Owing to the spontaneous solution-gel transition in the periodontal pockets and unique liquid crystalline nanostructures, the LLC in situ gel provided effective treatment of periodontitis for a prolonged period of time with reduced systematic side effects, compared to metronidazole suspension which was effective for 24 h with detectable metronidazole concentrations in the blood after 6 h.

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.

Endovascular treatment of atherosclerotic popliteal artery disease based on dynamic angiography findings.

OBJECTIVE: To evaluate efficacy, safety, and midterm patency of endovascular treatment of obstructive popliteal artery (PA) disease. METHODS: A retrospective evaluation of patients with atherosclerotic PA disease who underwent percutaneous transluminal balloon angioplasty and provisional stent, based on both conventional and dynamic angiographies, was conducted from June 2011 to June 2014. Forty-three patients were included in the study, and most patients had limited surgical revascularization options. Demographic characteristics, angiographic findings, interventional data, complications, vessel patency, limb salvage rates, and survival rates were analyzed. RESULTS: The median lesion length was 5 cm with 72.1% having total occlusions. The second popliteal segment (P2) was involved most frequently (60.5%, n = 26). Critical limb ischemia was present in 69.8%. The technical success rate was 92.9% (42/43 limbs), with 29 cases requiring adjunctive nitinol stents after balloon angioplasty (47.6% based on conventional angiography, 21.4% based on dynamic angiography, and 4.8% additional stents based on dynamic angiography). Complications included thromboembolism (2.3%), perforation (2.3%), pseudoaneurysm (2.3%), and myocardial infarction (2.3%). Stent fracture was present in three cases (7.1%) during the mean follow-up period of 18.3 months. The baseline ankle-brachial index significantly improved after the intervention, from 0.49 ± 0.11 to 0.92 ± 0.14 (P < .01). The Rutherford-Becker class decreased from 3.95 ± 0.76 to 1.76 ± 0.95 (P < .01) at 12 months. The 1-year primary, primary-assisted, and secondary patency rates were 75.2% ± 6.8%, 82.4% ± 6.0%, and 89.9% ± 4.8%, respectively. The limb salvage and amputation-free survival rates at 12 months were 91.6% and 87.0%, respectively. CONCLUSIONS: Balloon angioplasty with a provisional stent based on dynamic angiography is a feasible, safe, and effective therapy for patients with obstructive PA disease. Although the occurrence of stent fracture is still inevitable, patients with critical limb ischemia who have limited surgical options may get more benefits from the endovascular treatment of PA obstructive diseases.

Endovascular Recanalization of Chronically Occluded Native Arteries After Failed Bypass Surgery in Patients with Critical Ischemia.

OBJECTIVE: The study aimed to evaluate the feasibility, safety, and outcome of endovascular recanalization of native chronic total occlusions (CTO) in patients with critical limb ischemia (CLI) and lower extremities bypass graft failure. METHODS: A retrospective review of CLI patients with failed lower limb grafts (>30 days after surgery) that underwent recanalization of native CTO was conducted in two institutions from January 2010 to June 2014. Twenty-eight patients (28 limbs) were included in the study, and all had limited surgical revascularization options. Demographics, procedural data, technical success, complications, vessel patency, limb salvage rates, and survival rates were analyzed. RESULTS: The mean follow-up period was 12.8 months. The technical success rate was 92.9% (26/28 limbs). The combined ipsilateral antegrade-retrograde approach was performed in nine limbs (32.1%). Major periprocedural (<30 days) complications included two myocardial infarctions (7.1%) and two stent thromboses (7.1%), resulting in one amputation. The ankle brachial index before discharge was significantly improved after recanalization (0.78 ± 0.08 vs. 0.31 ± 0.10, p < 0.01). The primary, assisted primary, and secondary patency rates at 12 months were 52.2, 65.8, and 82.2%, respectively. The limb salvage rate and amputation-free survival rate at 12 months were 91.6 and 87.0%, respectively. CONCLUSIONS: Endovascular recanalization of native CTO in patients with graft failure-related CLI is a feasible, safe, and effective procedure, with reasonable technical success, vessel patency, and limb salvage rates. The technique should be attempted before amputation in patients with limited surgical revascularization options.

The effect of stent placement for May-Thurner syndrome combined with symptomatic superficial venous reflux disease.

OBJECTIVE: The current study aimed to determine whether it is necessary to correct May-Thurner syndrome (MTS) simultaneously with superficial venous reflux disease (S-VRD) in limbs of combined symptomatic MTS/S-VRD. METHODS: A retrospective analysis of patients with S-VRD combined with MTS was conducted in a single institution from January 2001 to December 2010. Doppler ultrasound and phlebography were performed in patients with VRD. Computed tomography angiography or transfemoral venography was selectively performed in patients with severe symptoms or findings on phlebography suggestive of MTS. MTS was found in 207 patients. Among these, 121 patients were successfully treated with stent placement combined with endovenous laser ablation (EVLA); the remaining 86 patients, who were treated with EVLA for S-VRD alone, served as a control group. Clinical results, venous reflux, and quality of life were evaluated before and after treatment. Stent patency was followed up with Doppler ultrasound. RESULTS: There was no significant difference in age, female to male ratio, clinical symptoms, comorbidities, or percentage with S-VRD between the two groups. A total of 125 stents were placed in 121 patients in the EVLA + stent group. The rate of technical success was 100%. Follow-up periods ranged from 1 to 91 months (mean, 70.4 ± 21.3 months). The 4-year primary patency rate was 93.3%. The incidence of pain, edema, and ulceration was decreased significantly in the stent + EVLA group. However, there was a high rate of S-VRD recurrence in the EVLA-alone group. Quality of life improved significantly in the EVLA + stent group; improvements included relief of pain, edema, and fatigue and increased physical activity. For deep venous reflux, there was no significant improvement after stent placement for MTS. CONCLUSIONS: Stent placement is an effective and durable treatment of MTS combined with symptomatic S-VRD; it results in a high level of long-term patency and a significant relief of pain, edema, and ulceration. Furthermore, correction of MTS plays an important role in decreasing the recurrence rate of S-VRD after EVLA.

Technical details and clinical outcomes of transpopliteal venous stent placement for postthrombotic chronic total occlusion of the iliofemoral vein.

PURPOSE: To evaluate the technical aspects and early clinical results of stent placement for managing postthrombotic chronic total occlusion (CTO) of the iliofemoral vein through ipsilateral popliteal access. MATERIALS AND METHODS: A retrospective analysis of 110 patients (44 men; mean age, 51 y; 118 limbs; 102 left limbs) with postthrombotic CTO of the iliofemoral vein treated with stent placement in a single institution from January 2007-December 2011 was conducted. All occlusions were initially accessed via ipsilateral popliteal veins under the guidance of venography or ultrasonography. Technical aspects, quality of life, stent patency, and Villalta scores were recorded at follow-up evaluation. Risk factors of in-stent restenosis and early in-stent thrombosis were evaluated using Cox proportional hazards regression model. RESULTS: Percutaneous recanalization was successful in 112 of 118 limbs (95%). The mean duration of the procedure was 43 minutes (range, 10-120 min). The quality of life and Villalta scores were significantly improved (P < .01). The 3-year primary, assisted primary, and secondary cumulative stent patency rates were 70%, 90%, and 94%. During a median follow-up period of 25 months (range, 1-52 mo), the relief rates of severe leg pain (visual analog scale > 5) and severe leg swelling (grade 3) were 72% (49 of 68) and 70% (64 of 91), respectively, and the healing of ulcers was successful in 78% (36 of 46) of the cases. After stent placement, the limbs with visible remaining collateral circulation had a higher rate of early in-stent thrombosis (22.5% vs 6.1%; P = .007). The patients with long stents extending below the inguinal ligament had a higher rate of in-stent restenosis (hazard ratio = 1.77-6.5; P = .0146). CONCLUSIONS: Transpopliteal venous stent placement is an effective, safe, and feasible method of managing postthrombotic CTO of the iliofemoral vein. The stent extending below the inguinal ligament is the major risk factor of in-stent restenosis. The visible remaining collateral circulation after stent placement may indicate persistent hemodynamically significant stenosis.

Endovascular treatment for symptomatic stent failures in long-segment chronic total occlusion of femoropopliteal arteries.

OBJECTIVE: The objective of this study was to evaluate the outcomes of the secondary endovascular treatment (SEVT) for symptomatic recurrences in long-segment chronic total occlusion (CTO) of femoropopliteal arteries (FPAs) and to investigate the factors affecting the outcomes. METHODS: Data of patients undergoing FPA stent implantation for primary, long-segment (>10 cm) CTO lesions and receiving endovascular intervention for symptomatic recurrences more than once in our institution from July 1, 2008, to September 1, 2012, were reviewed. Follow-up results referring to SEVT procedures were analyzed, including primary patency, limb salvage (LS) rate, technical success rate, and prevalence of procedure-related complications. Primary patency and LS were analyzed with Kaplan-Meier curves. Univariate and multivariable analyses were performed to identify factors associated with recurrent restenosis with a Cox proportional hazards model. RESULTS: Ninety-one patients (mean age, 75.1 years) were included. The indications for SEVT were claudication (38.5%) and critical limb ischemia (61.5%). Preprocedural ankle-brachial index was 0.37 ± 0.16. The median time between initial endovascular treatment and SEVT was 6.5 months (range, 1.0-24.4 months). The arteries in 63 limbs were totally occluded. Fractures were found in 30 (18.8%) of the initially placed stents. Successful recanalization was achieved in 82 limbs (90.1%). The mean postprocedural ankle-brachial index was 0.84 ± 0.15 in those limbs that were successfully recanalized. The complication rate was 9.9%. One patient died of cerebral hemorrhage during catheter-directed thrombolysis. Other complications included the development of a groin hematoma (n = 5), distal embolization (n = 1), formation of a femoral pseudoaneurysm (n = 1), and development of acute heart failure (n = 1). The mean follow-up period was 11.0 ± 5.6 months. The cumulative primary patency rate after SEVT was 66.9% and 52.0% at 12 and 24 months. The LS rate since SEVT was 91.2% and 81.1% at 12 and 24 months. The multivariate analysis showed that stent fracture and stent overlap were independent predictors of recurrent restenosis (hazard ratio, 3.07; 95% confidence interval, 1.40-6.74; P = .005; hazard ratio, 4.75; 95% confidence interval, 1.77-12.75; P = .002). CONCLUSIONS: Endovascular treatment is feasible for FPA stent failure in long-segment CTO. However, SEVT does not achieve durable patency. Stent fracture and overlap are related to recurrent restenosis.

Role and mechanism of tissue plasminogen activator in venous wall fibrosis remodeling after deep venous thrombosis via the glycogen synthase kinase-3 beta signaling pathway.

BACKGROUND: Deep venous thrombosis (DVT) confers vein wall injury associated with fibrosis and extracellular matrix turnover. The activation of vascular smooth muscle cells (VSMCs) and phenotypic switching are postulated to be the significant contributing factors in the evolution of the pathogenic processes. This study investigated the effect of tissue plasminogen activator (tPA) on the phenotypic switching and collagen deposition of VSMCs, as well as related signaling pathway that leads to this activation. MATERIALS AND METHODS: The model of stasis-induced DVT was established by ligation of the femoral vein. VSMCs transfected with the plasmid vector carrying a rat recombinant tPA gene with an enhanced green fluorescent protein (EGFP) tag (AdtPA-EGFP). Fibrotic change, expression of collagen type I, the cell number of media, and intimal thickness score were evaluated; the comparisons were made among the AdtPA-EGFP-transfected group, an empty vector (AdNull-EGFP) transfected group, and a phosphate-buffered saline perfused group in vivo. tPA induced VSMCs phenotypic switching and collagen deposition in vitro. The related signaling pathway molecules and the cell cycle progression were also investigated by western blot and flow cytometry. RESULTS: In the AdtPA-EGFP stasis DVT model, early vein wall collagenolysis and deposition occurred more remarkable. Histological studies showed that the expression of vein wall collagen type I protein, cell number of media, and intimal thickness score was significantly increased (P < 0.05). In primary culture VSMCs, sustained stimulation with tPA induced collagen type I upregulation and triggered sequential signaling events involving Akt, extracellular signal-regulated kinases 1/2 (ERK1/2), glycogen synthase kinase-3 (GSK3)-ß phosphorylation, and cyclin D1 induction. Blockade of phosphatidylinositol 3-kinase-Akt and ERK1/2 activation suppressed tPA-induced GSK3ß phosphorylation, cyclin D1 expression, and the deposition of collagen type I. CONCLUSIONS: tPA was a profibrotic factor that potentiated the phenotypic switching and the deposition of collagen in VSMC. The effect of tPA on VSMCs involved activation of Akt and ERK1/2 pathways and inhibition of GSK3ß activity, which could promote a switch of the synthetic phenotype in VSMCs and lead to the remodeling of vascular injury.

Midterm outcomes of stent placement for long-segment iliac artery chronic total occlusions: a retrospective evaluation in a single institution.

PURPOSE: To assess the clinical and patency results of stent placement for long-segment iliac artery chronic total occlusions (CTOs). MATERIALS AND METHODS: A retrospective analysis of 217 patients (141 men and 76 women; mean age, 76.6 y; 256 limbs) with long-segment (>5 cm) iliac artery CTOs treated with stent placement was conducted in a single institution from January 2005 to July 2011. Demographics, clinical presentation, classification, comorbidity, ankle-brachial index (ABI) before and after treatment, technical success, patency, and complications were recorded at follow-up. The approach was initial access from the left brachial artery or the contralateral femoral artery. RESULTS: According to the TransAtlantic Inter-Society Consensus for the Management of Peripheral Arterial Disease (TASC II) classification, 27 patients were type B, 143 were type C, and 47 were type D. Clinical presentation was recorded according to the Rutherford-Becker classification: 35 patients presented with stage 3; 108, with stage 4; 53, with stage 5; and 21, with stage 6. Technical success was 96.5% (247 of 256). Periprocedural in-stent thrombosis occurred in nine patients and was treated successfully with catheter-directed thrombolysis. ABI increased from 0.36±0.16 (range, 0-0.57) before the procedure to 0.79±0.24 (range, 0.56-1.12) after the procedure. The mean duration of follow-up was 25.4 months (range, 1-72 months). The primary, primary assisted, and secondary patency of the iliac artery was 95.1%, 98.4%, and 99.2% at 1 year and 91.9%, 95.6%, and 97.5% at 2 years, respectively. Major complications were encountered in 17 (6.6%) patients, and minor complications occurred in 12 (4.7%) patients. CONCLUSIONS: These data suggest that stent placement is an effective, safe, and feasible method for treating long-segment iliac artery CTOs.

Nanostructured cubosomes as advanced drug delivery system.

Some kinds of amphiphilic lipids can spontaneously self-assemble with a proper ratio of water to form liquid crystalline, also known as cubic phase. With a curved bi-continuous lipid bilayer and two congruent networks of water channels, cubic phases can enclose hydrophilic, amphiphilic and hydrophobic drugs for delivery. Nanostructured cubosomes, prepared by fragmentation of bulk cubic phase gels or lyotropic methods, retain the same inner structure of cubic phase and possess much larger specific surface area and lower viscosity. These unique properties make cubosomes excellent delivery systems applicable for oral, mucosal, transdermal and parenteral drug delivery. This article gave an overview of the accelerated development and current status of cubosomes research, with respect to their preparation, characteristics and applications in pharmaceutics.

Cubic phase nanoparticles for sustained release of ibuprofen: formulation, characterization, and enhanced bioavailability study.

In order to improve the oral bioavailability of ibuprofen, ibuprofen-loaded cubic nanoparticles were prepared as a delivery system for aqueous formulations. The cubic inner structure was verified by cryogenic transmission electron microscopy. With an encapsulation efficiency greater than 85%, the ibuprofen-loaded cubic nanoparticles had a narrow size distribution around a mean size of 238 nm. Differential scanning calorimetry and X-ray diffraction determined that ibuprofen was in an amorphous and molecular form within the lipid matrix. The in vitro release of ibuprofen from cubic nanoparticles was greater than 80% at 24 hours, showing sustained characteristics. The pharmacokinetic study in beagle dogs showed improved absorption of ibuprofen from cubic nanoparticles compared to that of pure ibuprofen, with evidence of a longer half-life and a relative oral bioavailability of 222% (P < 0.05). The ibuprofen-loaded cubic nanoparticles provide a promising carrier candidate with an efficient drug delivery for therapeutic treatment.