Kaichuang Ye

Photothermal Theragnosis Synergistic Therapy Based on Bimetal Sulphide Nanocrystals Rather Than Nanocomposites

A new generation of photothermal theranostic agents is developed based on Cu3BiS3 nanocrystals. A computed tomography imaging response and photothermal effect, as well as near-infrared fluorescence emission, can be simultaneously achieved through Cu3BiS3 nanocrystals rather than frequently used nanocomposites. These results provide some insight into the synergistic effect from bimetal sulphide semiconductor compounds for photothermal theragnosis therapy.

Long-Term Outcomes of Stent Placement for Symptomatic Nonthrombotic Iliac Vein Compression Lesions in Chronic Venous Disease

PURPOSE To assess the clinical and patency results of stent placement for the management of symptomatic nonthrombotic iliac vein compression lesions (NIVCLs) in chronic venous disease (CVD). MATERIALS AND METHODS A retrospective analysis of patients with CVD was conducted at a single institution from January 2000 to May 2010. In 2,093 patients with CVD, venous computed tomography (CT) angiography or transfemoral venography was selectively performed in patients with severe symptoms and in patients with symptom recurrence after endovenous laser ablation (EVLA) for superficial venous insufficiency in the left lower extremity. NIVCLs were found in 297 patients (41 NIVCLs were found in 74 patients whose symptoms recurred after EVLA for superficial venous insufficiency). In 205 patients, NIVCLs were successfully treated with stent placement. Among these 205 patients, 117 patients (132 limbs) with associated superficial reflux were treated by EVLA for superficial venous insufficiency. Quality of life and the severity of venous disorders were evaluated by questionnaire and clinical examination before and after treatment. Patency was evaluated by duplex Doppler ultrasound. RESULTS A total of 227 stents were placed in 205 patients (224 limbs; median age, 50.53 years). The rate of technical success was 100%. Three limbs were treated with two stents because of proximal migration of the incipient stent. Follow-up periods ranged from 1-117 months (mean 50 months ± 36). The primary and assisted-primary cumulative patency rates at a mean of 4 years were 98.7% and 100%. The cumulative edema relief rate was 89.1% (156 of 175), and the healing rate for active ulcers was 82.3% (51 of 62). The pain level (using a visual analogue scale from 0-10) declined from a median level of 4.3 before the procedure to 0.4 after the procedure. Quality of life improved significantly after intervention. Complications were minor and improved quickly. CONCLUSIONS Venous stent placement is an effective and durable treatment for NIVCL, with long-term high patency and results in significant relief of the major symptoms of CVD. NIVCL is an important reason for symptom recurrence after left lower extremity varicose vein surgery.

Systematic review and meta-analysis of balloon angioplasty versus primary stenting in the infrapopliteal disease.

Objectives: We performed a systematic review and meta-analysis of comparing balloon angioplasty and primary stenting for symptomatic infrapopliteal disease to evaluate the clinical value of primary stenting in treating infrapopliteal diseases. Methods: Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines were followed. PubMed (1984-present), ScienceDirect (1980-present), Embase (1990-present), and CBM (1988-present) databases were searched for relevant articles. Finally, 16 studies (published between 2001 and 2013) satisfying the inclusion criteria were identified. The outcome parameters were immediate technical success, 1-year primary patency rate, 1-year limb salvage rate, and 1-year target vessel revascularization (TVR)-free rate. Comparisons were made with balloon angioplasty and primary stenting, and based on the different types of stents, we divided the primary stent group into the bare metal stent (BMS) group and drug-eluting stent (DES) group. Results: A total of 3789 patients and 4339 limbs constituted our final study population. The technical success rate of balloon angioplasty was 92.29% (95% confidence interval [CI] 88.75%-94.78%). Only 2 study reported the technical failure rates as 4% and 5.2% in the primary stent group. The pooled estimates of 1-year primary patency and TVR-free rate were similarly low in the balloon angioplasty group and BMS group (primary patency: 57.65%, 95% CI 53.54%-61.67% vs 60.95%, 95% CI 48.31%-72.28%, P = .38; TVR-free rate: 73.41%, 95% CI 66.51%-80.08% vs 73.66%, 95% CI 63.58%-81.75%, P = .91). The pooled estimates of 1-year primary patency and TVR-free rate in DES group were 81.10% (95% CI 75.48%-85.67%) and 90.30% (95% CI 85.30%-93.73%), respectively, which were better than those of the BMS and balloon angioplasty groups (P < .001 for both). The pooled estimate of 1-year limb salvage in the balloon angioplasty, BMS, and DES groups was 88.61% (95% CI 85.01%-91.43%), 94.41% (95% CI 89.52%-97.1%), and 95.20% (95% CI 86.97%-98.33%), respectively (P < .001). The BMS and DES groups had higher limb salvage rates than the balloon angioplasty group (P < .001 for both comparisons). The rates of severe complications were low both in the balloon angioplasty and in the primary stent groups. Conclusion: Primary BMS implantation had no advantage over balloon angioplasty in reducing restenosis or revascularization for infrapopliteal disease. Primary DES implantation seems to be a promising treatment for focal infrapopliteal lesions. Publication bias could not be ruled out, and the results should be treated with caution.

Long-term MRI tracking of dual-labeled adipose-derived stem cells homing into mouse carotid artery injury

Background Stem cell therapy has shown great promise for regenerative repair of injured or diseased tissues. Adipose-derived stem cells (ADSCs) have become increasingly attractive candidates for cellular therapy. Magnetic resonance imaging has been proven to be effective in tracking magnetic-labeled cells and evaluating their clinical relevance after cell transplantation. This study investigated the feasibility of imaging green fluorescent protein-expressing ADSCs (GFP-ADSCs) labeled with superparamagnetic iron oxide particles, and tracked them in vivo with noninvasive magnetic resonance imaging after cell transplantation in a model of mouse carotid artery injury. Methods GFP-ADSCs were isolated from the adipose tissues of GFP mice and labeled with superparamagnetic iron oxide particles. Intracellular stability, proliferation, and viability of the labeled cells were evaluated in vitro. Next, the cells were transplanted into a mouse carotid artery injury model. Clinical 3 T magnetic resonance imaging was performed immediately before and 1, 3, 7, 14, 21, and 30 days after cell transplantation. Prussian blue staining and histological analysis were performed 7 and 30 days after transplantation. Results GFP-ADSCs were found to be efficiently labeled with superparamagnetic iron oxide particles, with no effect on viability and proliferation. Homing of the labeled cells into the injured carotid artery tissue could be monitored by magnetic resonance imaging. Conclusion Magnetically labeled ADSCs with expression of GFP can home into sites of vascular injury, and may provide new insights into understanding of cell-based therapy for cardiovascular lesions.

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.

Noninvasive detection of macrophages in atherosclerotic lesions by computed tomography enhanced with PEGylated gold nanoparticles

Macrophages are becoming increasingly significant in the progression of atherosclerosis (AS). Molecular imaging of macrophages may improve the detection and characterization of AS. In this study, dendrimer-entrapped gold nanoparticles (Au DENPs) with polyethylene glycol (PEG) and fluorescein isothiocyanate (FI) coatings were designed, tested, and applied as contrast agents for the enhanced computed tomography (CT) imaging of macrophages in atherosclerotic lesions. Cell counting kit-8 assay, fluorescence microscopy, silver staining, and transmission electron microscopy revealed that the FI-functionalized Au DENPs are noncytotoxic at high concentrations (3.0 μM) and can be efficiently taken up by murine macrophages in vitro. These nanoparticles were administered to apolipoprotein E knockout mice as AS models, which demonstrated that the macrophage burden in atherosclerotic areas can be tracked noninvasively and dynamically three-dimensionally in live animals using micro-CT. Our findings suggest that the designed PEGylated gold nanoparticles are promising biocompatible nanoprobes for the CT imaging of macrophages in atherosclerotic lesions and will provide new insights into the pathophysiology of AS and other concerned inflammatory diseases.

Endovenous ablation with laser for great saphenous vein insufficiency and tributary varices : A retrospective evaluation

BACKGROUND Endovenous laser ablation (EVLA) is a minimally invasive technique for treating great saphenous vein (GSV) reflux for several years. We report our experience with EVLA and evaluate its effectiveness. METHODS A consecutive series of patients (639 women [60%] and 421 men [40%], age 23 to 79 years) were treated by EVLA for GSV reflux and tributary varices at our institution. A questionnaire was used to assess preoperative and postoperative symptoms. The primary outcomes for assessing safety were mortality and morbidity, including laser-related adverse events, postoperative infection, thrombotic events, etc. Effectiveness was assessed by the obliteration of the vein, disappearance of varicosities, and so on. RESULTS All patients tolerated the procedure well, recovered uneventfully, and returned to daily activities and work 3 days and 10 to 14 days, respectively, after the operation. Treatment with EVLA plus ligation of the GSV resulted in occlusion in all cases at 2 weeks follow-up and in 1169 of 1186 (99%) at 6-month follow-up; the rate of retreatment was low (36/1186). Complications were minor and improved quickly. CONCLUSIONS EVLA can reduce and relieve symptoms associated with varicose veins and achieve cosmetic goals. Vein emptying before exposure to laser energy and compression treatment afterwards may improve results.

MRI of iron oxide nanoparticle-labeled ADSCs in a model of hindlimb ischemia.

Adipose-derived stem cells (ADSCs) exhibit tremendous potential for repair of ischemic diseases. However, studies on the fate, migration, differentiation, and body distribution of the labeled ADSCs are rarely reported. In this study, magnetic iron oxide nanoparticles were designed, synthesized, and coated with meso-2,3-dimercaptosuccinic acid (DMSA) to produce DMSA nanoparticles (DMSA-NPs). The properties, size distribution, and characterization of DMSA-NPs were evaluated. Green fluorescent protein expressing ADSCs (GFP-ADSCs) were obtained and labeled with DMSA-NPs. The viability, cytotoxicity and multi-differentiation capacity of labeled GFP-ADSCs were evaluated in vitro. Labeled and non-labeled GFP-ADSCs were injected into a mouse model of hindlimb ischemia, and 3T magnetic resonance imaging (MRI) was acquired. The synthesized DMSA-NPs efficiently labeled the GFP-ADSCs in vitro and in vivo without affecting cell viability, proliferation, cell cycle, and multi-differentiation capacity. The MRI showed hypointense spots in the labeled GFP-ADSCs that lasted up to 8 weeks. Prussian blue staining and immunofluorescence assay at 4 and 8 weeks indicated that the labeled GFP-ADSCs were in and around the ischemic sites and some differentiated into capillaries. This observation is identical to that seen for transplants of unlabeled cells. Labeled cells were also identified mainly in the liver and spleen, with significantly smaller amounts in the lungs, intestines, heart, and kidney. Developed DMSA-NPs were shown to exhibit a considerable potential for use as nanoprobes for MRI of stem cells, which will enhance our understanding of cell-based therapeutic strategies for ischemic diseases.

In vivo MRI tracking of iron oxide nanoparticle-labeled human mesenchymal stem cells in limb ischemia.

Background Stem cell transplantation has been investigated for repairing damaged tissues in various injury models. Monitoring the safety and fate of transplanted cells using noninvasive methods is important to advance this technique into clinical applications. Methods In this study, lower-limb ischemia models were generated in nude mice by femoral artery ligation. As negative-contrast agents, positively charged magnetic iron oxide nanoparticles (aminopropyltriethoxysilane-coated Fe2O3) were investigated in terms of in vitro labeling efficiency, effects on human mesenchymal stromal cell (hMSC) proliferation, and in vivo magnetic resonance imaging (MRI) visualization. Ultimately, the mice were sacrificed for histological analysis three weeks after transplantation. Results With efficient labeling, aminopropyltriethoxysilane-modified magnetic iron oxide nanoparticles (APTS-MNPs) did not significantly affect hMSC proliferation. In vivo, APTS-MNP-labeled hMSCs could be monitored by clinical 3 Tesla MRI for at least three weeks. Histological examination detected numerous migrated Prussian blue-positive cells, which was consistent with the magnetic resonance images. Some migrated Prussian blue-positive cells were positive for mature endothelial cell markers of von Willebrand factor and anti-human proliferating cell nuclear antigen. In the test groups, Prussian blue-positive nanoparticles, which could not be found in other organs, were detected in the spleen. Conclusion APTS-MNPs could efficiently label hMSCs, and clinical 3 Tesla MRI could monitor the labeled stem cells in vivo, which may provide a new approach for the in vivo monitoring of implanted cells.

Clinical Assessment of Endovascular Stenting Compared with Compression Therapy Alone in Post-thrombotic Patients with Iliofemoral Obstruction

OBJECTIVE The study aimed to evaluate the clinical results of stent placement in post-thrombotic patients with iliofemoral obstruction compared with results in those treated with elastic compression stockings (ECS). METHODS A retrospective analysis of post-thrombotic patients with iliofemoral obstruction was conducted in a single institution from January 2007 to December 2012. Duplex ultrasound and selective phlebography were performed in patients with chronic venous disease and previous deep venous thrombosis (DVT). Post-thrombotic syndrome (PTS) with iliofemoral vein obstruction (Villalta score ≥10) was diagnosed in 216 patients. Among these, 122 patients were treated by stent placement, and the remaining 94 patients were treated conservatively with 30-40 mmHg ECS therapy. Technical success, stent patency rates, and complications were recorded after the interventions. Results including Villalta score, pain, edema, ulcer, and popliteal vein reflux were assessed in both groups. RESULTS Percutaneous iliofemoral venous stenting was successful in 116 of 122 patients (95.1%) without major complications. Follow up periods ranged from 3 to 58 months (median 21 months). Cumulative primary, assisted primary, and secondary stent patency rates at 3 years were 68.9%, 79.0%, and 91.6%, respectively. Among patients with severe PTS, the Villalta score decreased significantly with endotreatment, compared to the score of those treated by ECS therapy (16.12 ± 4.91 vs. 10.98 ± 5.89, p < .01). However, there was no significant score improvement between the two therapies in patients with moderate PTS (6.59 ± 2.37 vs. 5.75 ± 3.03, p = .22). There was a significantly higher 24 month recurrence free ulcer healing rate in the endotreatment groups (86.6% vs. 70.6%, p < .01). Both edema and pain improved significantly in the two groups. The popliteal vein reflux rate showed no significant change after endotreatment. CONCLUSIONS Endovascular treatment is a safe, effective, and feasible method to correct the iliofemoral obstruction of PTS. Only post-thrombotic patients with severe PTS as assessed by the Villalta score appear to benefit from the endovascular treatment.