High UV damage and low repair, but not cytosine deamination, stimulate mutation hotspots at ETS binding sites in melanoma.

Noncoding mutation hotspots have been identified in melanoma and many of them occur at the binding sites of E26 transformation-specific (ETS) proteins; however, their formation mechanism and functional impacts are not fully understood. Here, we used UV (Ultraviolet) damage sequencing data and analyzed cyclobutane pyrimidine dimer (CPD) formation, DNA repair, and CPD deamination in human cells at single-nucleotide resolution. Our data show prominent CPD hotspots immediately after UV irradiation at ETS binding sites, particularly at sites with a conserved TTCCGG motif, which correlate with mutation hotspots identified in cutaneous melanoma. Additionally, CPDs are repaired slower at ETS binding sites than in flanking DNA. Cytosine deamination in CPDs to uracil is suggested as an important step for UV mutagenesis. However, we found that CPD deamination is significantly suppressed at ETS binding sites, particularly for the CPD hotspot on the 5' side of the ETS motif, arguing against a role for CPD deamination in promoting ETS-associated UV mutations. Finally, we analyzed a subset of frequently mutated promoters, including the ribosomal protein genes RPL13A and RPS20, and found that mutations in the ETS motif can significantly reduce the promoter activity. Thus, our data identify high UV damage and low repair, but not CPD deamination, as the main mechanism for ETS-associated mutations in melanoma and uncover important roles of often-overlooked mutation hotspots in perturbing gene transcription.

Chitin nanocrystal-assisted 3D bioprinting of gelatin methacrylate scaffolds.

In recent years, there has been an increasing focus on the application of hydrogels in tissue engineering. The integration of 3D bioprinting technology has expanded the potential applications of hydrogels. However, few commercially available hydrogels used for 3D biological printing exhibit both excellent biocompatibility and mechanical properties. Gelatin methacrylate (GelMA) has good biocompatibility and is widely used in 3D bioprinting. However, its low mechanical properties limit its use as a standalone bioink for 3D bioprinting. In this work, we designed a biomaterial ink composed of GelMA and chitin nanocrystal (ChiNC). We explored fundamental printing properties of composite bioinks, including rheological properties, porosity, equilibrium swelling rate, mechanical properties, biocompatibility, effects on the secretion of angiogenic factors and fidelity of 3D bioprinting. The results showed that adding 1% (w/v) ChiNC to 10% (w/v) GelMA improved the mechanical properties and printability of the GelMA hydrogels, promoted cell adhesion, proliferation and vascularization and enabled the printing of complex 3D scaffolds. This strategy of incorporating ChiNC to enhance the performance of GelMA biomaterials could potentially be applied to other biomaterials, thereby expanding the range of materials available for use. Furthermore, in combination with 3D bioprinting technology, this approach could be leveraged to bioprint scaffolds with complex structures, further broadening the potential applications in tissue engineering.

Investigating the Mechanical Properties and Flexibility of N-BAR Domains in PICK1 by Molecular Dynamics Simulations.

INTRODUCTION: The proteins of the Bin/Amphiphysin/Rvs167 (BAR) domain superfamily are believed to induce membrane curvature. PICK1 is a distinctive protein that consists of both a BAR and a PDZ domain, and it has been associated with numerous diseases. It is known to facilitate membrane curvature during receptor-mediated endocytosis. In addition to understanding how the BAR domain facilitates membrane curvature, it's particularly interesting to unravel the hidden links between the structural and mechanical properties of the PICK1 BAR domain. METHODS: This paper employs steered molecular dynamics (SMD) to investigate the mechanical properties associated with structural changes in the PICK1 BAR domains. RESULTS: Our findings suggest that not only do helix kinks assist in generating curvature of BAR domains, but they may also provide the additional flexibility required to initiate the binding between BAR domains and the membrane. CONCLUSION: We have observed a complex interaction network within the BAR monomer and at the binding interface of the two BAR monomers. This network is crucial for maintaining the mechanical properties of the BAR dimer. Owing to this interaction network, the PICK1 BAR dimer exhibits different responses to external forces applied in opposite directions.

Emulsion-induced polymersomes taming tetrodotoxin for prolonged duration local anesthesia.

Injectable local anesthetics that can provide a continuous nerve block approximating the duration of a pain state would be a life-changing solution for patients experiencing post-operative pain or chronic pain. Tetrodotoxin (TTX) is a site 1 sodium channel blocker that is extremely potent compared to clinically used local anesthetics. Challengingly, TTX doses are limited by its associated systemic toxicity, thus shortening the achievable duration of nerve blocks. Here, we explore emulsion-induced polymersomes (EIP) as a drug delivery system to safely use TTX for local anesthesia. By emulsifying hyperbranched polyglycerol-poly (propylene glycol)-hyperbranched polyglycerol (HPG-PPG-HPG) in TTX aqueous solution, HPG-PPG-HPG self-assembled into micrometer-sized polymersomes within seconds. The formed polymersomes have microscopically visible internal aqueous pockets that encapsulate TTX with an encapsulation efficiency of up to 94%. Moreover, the polymersomes are structurally stable, enabling sustained TTX release. In vivo, the freshly prepared EIP/TTX formulation can be directly injected and increased the tolerated dose of TTX in Sprague-Dawley rats to 11.5 µg without causing any TTX-related systemic toxicity. In the presence of the chemical penetration enhancer (CPE) sodium octyl sulfate (SOS), a single perineural injection of EIP/TTX/SOS formulation produced a reliable sciatic nerve block for 22 days with minimal local toxicity.

Recognizing the Binding Pattern and Dissociation Pathways of the p300 Taz2-p53 TAD2 Complex.

The dynamic association and dissociation between proteins are the basis of cellular signal transduction. This process becomes much more complicated if one or both interaction partners are intrinsically disordered because intrinsically disordered proteins can undergo disorder-to-order transitions upon binding to their partners. p53, a transcription factor with disordered regions, plays significant roles in many cellular signaling pathways. It is critical to understand the binding/unbinding mechanism involving these disordered regions of p53 at the residue level to reveal how p53 performs its biological functions. Here, we studied the dissociation process of the intrinsically disordered N-terminal transactivation domain 2 (TAD2) of p53 and the transcriptional adaptor zinc-binding 2 (Taz2) domain of transcriptional coactivator p300 using a combination of classical molecular dynamics, steered molecular dynamics, self-organizing maps, and time-resolved force distribution analysis (TRFDA). We observed two different dissociation pathways with different probabilities. One dissociation pathway starts from the TAD2 N-terminus and propagates to the α-helix and finally the C-terminus. The other dissociation pathway is in the opposite order. Subsequent TRFDA results reveal that key residues in TAD2 play critical roles. Besides the residues in agreement with previous experimental results, we also highlighted some other residues that play important roles in the disassociation process. In the dissociation process, non-native interactions were formed to partially compensate for the energy loss due to the breaking of surrounding native interactions. Moreover, our statistical analysis results of other experimentally determined complex structures involving either Taz2 or TAD2 suggest that the binding of the Taz2-TAD2 complex is mainly governed by the binding site of Taz2, which includes three main binding regions. Therefore, the complexes involving Taz2 may follow similar binding/unbinding behaviors, which could be studied together to generate common principles.

Intracranial In Situ Thermosensitive Hydrogel Delivery of Temozolomide Accomplished by PLGA-PEG-PLGA Triblock Copolymer Blending for GBM Treatment.

Glioblastoma (GBM) recurrence after surgical excision has grown to be a formidable obstacle to conquer. In this research, biodegradable thermosensitive triblock copolymer, poly(D, L-lactic acid-co-glycolic acid)-b-poly(ethylene glycol)-b-poly(D, L-lactic acid-co-glycolic acid (PLGA-PEG-PLGA) was utilized as the drug delivery system, loading with micronized temozolomide(micro-TMZ) to form an in situ drug-gel depot inside the resection cavity. The rheology studies revealed the viscoelastic profile of hydrogel under various conditions. To examine the molecular characteristics that affect gelation temperature, 1H-NMR, inverse gated decoupling 13C-NMR, and GPC were utilized. Cryo-SEM and XRD were intended to disclose the appearance of the hydrogel and the micro-TMZ existence state. We worked out how to blend polymers to modify the gelation point (Tgel) and fit the correlation between Tgel and other dependent variables using linear regression. To simulate hydrogel dissolution in cerebrospinal fluid, a membraneless dissolution approach was used. In vitro, micro-TMZ@PLGA-PEG-PLGA hydrogel exhibited Korsmeyer-Peppas and zero-order release kinetics in response to varying drug loading, and in vivo, it suppressed GBM recurrence at an astoundingly high rate. Micro-TMZ@PLGA-PEG-PLGA demonstrates a safer and more effective form of chemotherapy than intraperitoneal TMZ injection, resulting in a spectacular survival rate (40%, n = 10) that is much more than intraperitoneal TMZ injection (22%, n = 9). By proving the viability and efficacy of micro-TMZ@PLGA-PEG-PLGA hydrogel, our research established a novel chemotherapeutic strategy for treating GBM recurrence.

Thermosensitive Hydrogels and Advances in Their Application in Disease Therapy.

Thermosensitive hydrogels, having unique sol-gel transition properties, have recently received special research attention. These hydrogels exhibit a phase transition near body temperature. This feature is the key to their applications in human medicine. In addition, hydrogels can quickly gel at the application site with simple temperature stimulation and without additional organic solvents, cross-linking agents, or external equipment, and the loaded drugs can be retained locally to improve the local drug concentration and avoid unexpected toxicity or side effects caused by systemic administration. All of these features have led to thermosensitive hydrogels being some of the most promising and practical drug delivery systems. In this paper, we review thermosensitive hydrogel materials with biomedical application potential, including natural and synthetic materials. We describe their structural characteristics and gelation mechanism and briefly summarize the mechanism of drug release from thermosensitive hydrogels. Our focus in this review was to summarize the application of thermosensitive hydrogels in disease treatment, including the postoperative recurrence of tumors, the delivery of vaccines, the prevention of postoperative adhesions, the treatment of nervous system diseases via nasal brain targeting, wound healing, and osteoarthritis treatment.

Paclitaxel-nanocrystals-loaded network thermosensitive hydrogel for localised postsurgical recurrent of breast cancer after surgical resection.

The recurrence of cancer after local surgery has been a difficult problem in the clinic for a long time. In recent years, local treatment via drug-loaded thermosensitive hydrogels have become a promising strategy to prevent cancer recurrence. Thus, a thermosensitive hydrogel based on poloxamer 407, poloxamer 188 and the bioadhesive excipient carbomer 974P was designed to locally release paclitaxel and prevent local tumour recurrence after direct smearing of the hydrogel at the site of injury in the surgical cavity. To improve the local drug concentration, paclitaxel was prepared into nanocrystals via a wet mill process. A series of studies were performed on this paclitaxel nanocrystal thermosensitive hydrogel (PTX-NCS-gel), including examination of its rheological properties and in vitro release and dissolution studies. Moreover, a postoperative tumour recurrence mouse model was established to evaluate the antitumour effects of this thermosensitive hydrogel. The results showed that PTX-NCS-gel had a clear, regular network structure with excellent temperature sensitivity and could be gelated within minutes at 33.1 °C. Additionally, the rheological property investigation indicated that the hydrogel has proper viscoelasticity and self-recovery ability. In vivo imaging showed that PTX-NCS-gel inhibited both local tumour recurrence and distant metastasis. Moreover, PTX-NCS-gel has the following advantages: it is more convenient to administer, avoids strong allergic responses, and has fewer side effects on the liver and spleen. This hydrogel has the potential to serve as a powerful auxiliary medication to prevent postoperative local tumour recurrence.

The Evaluation of Meloxicam Nanocrystals by Oral Administration with Different Particle Sizes.

Meloxicam (MLX) is a non-steroidal anti-inflammatory drug used to treat rheumatoid arthritis and osteoarthritis. However, its poor water solubility limits the dissolution process and influences absorption. In order to solve this problem and improve its bioavailability, we prepared it in nanocrystals with three different particle sizes to improve solubility and compare the differences between various particle sizes. The nanocrystal particle sizes were studied through dynamic light scattering (DLS) and laser scattering (LS). Transmission electron microscopy (TEM) was used to characterize the morphology of nanocrystals. The sizes of meloxicam-nanocrystals-A (MLX-NCs-A), meloxicam-nanocrystals-B (MLX-NCs-B), and meloxicam-nanocrystals-C (MLX-NCs-C) were 3.262 ± 0.016 µm, 460.2 ± 9.5 nm, and 204.9 ± 2.8 nm, respectively. Molecular simulation was used to explore the distribution and interaction energy of MLX molecules and stabilizer molecules in water. The results of differential scanning calorimetry (DSC) and powder X-ray diffraction (PXRD) proved that the crystalline state did not change in the preparation process. Transport studies of the Caco-2 cell model indicated that the cumulative degree of transport would increase as the particle size decreased. Additionally, plasma concentration-time curves showed that the AUC0-∞ of MLX-NCs-C were 3.58- and 2.92-fold greater than those of MLX-NCs-A and MLX-NCs-B, respectively. These results indicate that preparing MLX in nanocrystals can effectively improve the bioavailability, and the particle size of nanocrystals is an important factor in transmission and absorption.

Orchid drug-coated balloon versus standard percutaneous transluminal angioplasty for the treatment of femoropopliteal artery disease: 12-month result of the randomized controlled trial.

PURPOSE: To assess the efficacy and safety of the Orchid drug-coated balloon (coated with paclitaxel) for the treatment of femoropopliteal artery disease versus percutaneous transluminal angioplasty in Chinese population. METHODS: This is a prospective, single center, single-blinded, randomized controlled trial that randomized (1:1) 60 patients (38 men; mean age 68.7 ± 8.8) to drug-coated balloon group (n = 30) or percutaneous transluminal angioplasty group (n = 30). The primary efficacy endpoint was primary patency of the target lesion and clinically driven target lesion revascularization (CD-TLR) at 12 months. The primary safety end point was freedom from perioperative death at 30 days and freedom from limb-related death and major amputation at 12 months. RESULTS: Baseline characteristics were similar between the two groups. Drug-coated balloon group resulted in higher primary patency (82.8% vs. 48.3%, p = 0.005) and lower CD-TLR rates (3.5% vs. 27.6%; p = 0.001) versus percutaneous transluminal angioplasty group at 12 months. The ABI was significantly higher in drug-coated balloon group than percutaneous transluminal angioplasty group (0.86 ± 0.13 vs. 0.72 ± 0.18, p = 0.025). There were no perioperative death at 30 days, no limb-related death and no major amputation at 12 months in either group. CONCLUSIONS: The randomized controlled trial showed superior treatment effect with drug-coated balloon versus percutaneous transluminal angioplasty, with remarkably higher patency and lower CD-TLR rates. The result is consistent with other study and demonstrates the safety and efficacy of the Orchid drug-coated balloon for the treatment of femoropopliteal artery disease.

Unraveling the Role of Neutral Units for Single-Ion Conducting Polymer Electrolytes.

With the cationic transference number close to unity, single-ion conducting polymer electrolytes (SICPEs) are recognized as an advanced electrolyte system with improved energy efficiency for battery application. The relatively low ionic conductivity for most of the SICPEs in comparison with liquid electrolytes remains the major "bottleneck" for their practical applications. Polyethylene oxide (PEO) has been recognized as a benchmark for solid polymer electrolytes due to its high salt solubility and reasonable ionic conductivity. PEO has two advantages: (i) the polar ether groups coordinate well with lithium ions (Li+) providing good dissociation from anions, and (ii) the low Tg provides fast segmental dynamics at ambient temperature and assists rapid charge transport. These properties lead to active use of PEO as neutral plasticizing units in SICPEs. Herein, we present a detailed comparison of new SICPEs copolymerized with PEO units vs SICPEs copolymerized with other types of neutral units possessing either flexible or polar structures. The presented analysis revealed that the polarity of side chains has a limited influence on ion dissociation for copolymer-type SICPEs. The Li+-ion dissociation seems to be controlled by the charge delocalization on the polymerized anion. With good miscibility between plasticizing neutral units and ionic conductive units, the ambient ionic conductivity of synthesized SICPEs is still mainly controlled by the Tg of the copolymer. This work sheds light on the dominating role of PEO in SICPE systems and provides helpful guidance for designing polymer electrolytes with new functionalities and structures. Furthermore, based on the presented results, we propose that designing polyanions with a highly delocalized charge may be another promising route for achieving sufficient lithium ionic conductivity in solvent-free SICPEs.

Nonnegligible causes of symptoms of acute lower extremities--3 cases of May-Thurner syndrome with deep vein thrombosis.

BACKGROUND: May-Thurner syndrome is a kind of disease caused by the compression of the left common iliac vein. It is one of the causes of incomplete venous valves and superficial varicose veins in lower limbs, and is also a potential factor of acute deep vein thrombosis (DVT). METHOD: Here 3 cases are diagnosed as May-Thurner syndrome at different ages. CASE PRESENTATIONS: 1. A 35-year-old female patient was hospitalized with swelling of the left lower limb for 1 week. Computed tomography (CT) showed compression of the left common iliac vein with thrombosis. May-Thurner syndrome was diagnosed and catheter-directed thrombolysis was performed. 2. A 37-year-old male patient came to our hospital due to sudden swelling of the right lower extremity and pain for 3 days. Computed tomography showed compression of the left common iliac vein and deep venous thrombosis (DVT) of the right iliac vein. May-Thurner syndrome was diagnosed. The patient was performed with inferior vena cava (IVC) filter implantation, catheter-directed thrombolysis and balloon angioplasty for right iliac vein. And the patient recovered well; 3. A 55-year-old female patient came to our hospital with swelling and discomfort in the left lower extremity for 3 days. Computed tomography showed stenosis of the left common iliac vein with deep vein thrombosis. May-Thurner syndrome was diagnosed, balloon dilation and stent implantation were performed. During 3 years of follow-up, there was no swelling or new thrombosis in her lower limbs. CONCLUSION: When encountering unexplained deep vein thrombosis, iliac vein compression syndrome should be considered and treated in time to prevent the recurrence of thrombosis. Catheter-directed thrombolysis can relieve symptoms and stenting placement is the optimal way to relieve stenosis, supplemented by long-term anticoagulation therapy and graduated compression stockings.

Randomized clinical trial of radiofrequency-induced thermotherapy combined with transilluminated powered phlebectomy versus high ligation and stripping for the treatment of lower limb varicose veins.

OBJECTIVE: The objective of this study was to evaluate the efficacy and safety of radiofrequency-induced thermotherapy (RFiTT) combined with transilluminated powered phlebectomy (TIPP) in the treatment of lower limb varicose veins (VVs) in comparison with high ligation and stripping (HLS) combined with TIPP. METHODS: The patients with lower limb VVs were randomly assigned to RFiTT combined with TIPP or HLS combined with TIPP. The primary end point was total closure rate of the great saphenous vein at 12 months. Secondary end points included Venous Clinical Severity Score and 14-item Chronic Venous Insufficiency Questionnaire score changes at 12 months and perioperative complications. RESULTS: The total closure rate of the great saphenous vein at 12 months was slightly lower in the RFiTT group (90.9% [90/99]) than in the HLS group (97.0% [98/101]) but not statistically significant (χ2 = 0.068; P = .08). Operation time, intraoperative blood loss, duration in hospital, duration in bed, and resumption of activities were statistically significantly better with RFiTT than with HLS. There were no significant differences between the groups in deep venous thrombosis, phlebitis, hematomas, pain, and infection. However, skin pigmentation and paresthesia were statistically significantly better with RFiTT than with HLS. At 12 months, both groups showed similar improvement from baseline in Venous Clinical Severity Score (1.28 ± 0.57 in the RFiTT group vs 1.33 ± 0.61 in the HLS group) and 14-item Chronic Venous Insufficiency Questionnaire score (67.32 ± 1.29 in the RFiTT group vs 67.45 ± 1.32 in the HLS group); however, neither group was superior to the other. CONCLUSIONS: RFiTT combined with TIPP is an effective treatment method for lower limb VVs and had a more satisfactory clinical outcome in surgical data, skin pigmentation, and paresthesia than HLS at the 12-month follow-up.

Luminescent Vesicles Self-assembled Directly from an Amphiphilic Europium Complex in an Ionic Liquid.

Novel luminescent vesicles with enhanced emission were successfully achieved for the first time by an amphiphilic europium complex through its spontaneously self-assembly in an ionic liquid, 1-butyl-3-methylimidazolium hexafluorophosphate ([Bmim]PF6). The complex was prepared by europium ions coordinated with terpyridine ligands, which were modified with the hydrophilic ethoxy chains. The enhanced absolute quantum yield and prolonged fluorescence lifetime of complex in vesicles were observed because of the effective shielding of the quench effects caused by both solvent and complex concentration. Compared to the aggregates formed in other solvents, the vesicles obtained in [Bmim]PF6 showed the best luminescence intensity with the quantum efficiency (37.74%) and luminescent emission lifetime (1.915 ms) both increased about 10 times more. Furthermore, this europium complex was designed to show unsaturated coordination, which made the vesicle luminescence easily quenched when contacting with water. The fluorescence sensing of water with this vesicle as probe was therefore possible, where several unique properties like high sensitivity, low detection limit (0.05 vol %), visible color change, and fast response had been observed. Such designed systems are expected to provide strategies to develop novel supramolecular aggregates in ionic liquids and offer guidance for luminescence detection with facile and wide applications.

Randomized controlled trial of orchid drug-coated balloon versus standard percutaneous transluminal angioplasty for treatment of femoropopliteal artery in-stent restenosis.

BACKGROUND: To assess the efficacy and safety of Orchid drug-coated balloon (DCB) for treatment of femoropopliteal (FP) artery in-stent restenosis (ISR) in Chinese patients. METHODS: The study is a prospective, single center, single-blinded, randomized controlled trial (RCT) that randomized (1:1) 74 patients to DCB group (N.=38) and PTA group (N.=36). The primary efficacy endpoint was primary patency of the target lesion at 12 months. Second efficacy endpoint included clinically-driven target-lesion revascularization (CD-TLR) and ABI change at 12 months. The primary safety endpoint included peri-operative death at 30 days, all-cause death, major amputation, and other major adverse events (MAEs) at 12 months. The primary functional endpoint included Walking Impairment Questionnaire (WIQ), quality-of-life measures (EQ-5D) and 6-minute walking test (6MWT). RESULTS: The DCB group had higher primary patency (87.9% vs. 51.6%; P=0.001) and lower rates of CD-TLR (6.1% vs. 35.5%; P=0.003) than the PTA group at 12 months. There were no peri-operative deaths, and no major amputations at 12 months in two groups. There were 1(2.6%) in the DCB group and 2 (5.6%) in the PTA group of all-cause deaths (P=0.524). CONCLUSIONS: Results from the study showed superior treatment effect with Orchid DCB versus PTA for the treatment of FP ISR, and without an apparent difference in safety.

Combination of Rotarex Thrombectomy and Drug-Coated Balloon for the Treatment of Femoropopliteal Artery In-Stent Restenosis.

BACKGROUND: The optimal treatment method for femoropopliteal (FP) artery in-stent restenosis (ISR) remains controversial. We assess the efficacy and safety of combination of Rotarex thrombectomy and drug-coated balloon (DCB) for the treatment of FP ISR. METHODS: From June 2016 to July 2017, 32 patients with FP ISR who underwent combination of Rotarex thrombectomy and DCB angioplasty were included in a prospective registry. The primary end point was primary patency of the target lesion defined as a peak systolic velocity ratio <2.4 documented by duplex ultrasound at 12 months without clinically driven target lesion revascularization (CD-TLR). The secondary outcome measure was the rate of major adverse limb events. The primary functional end point was assessed using the Walking Impairment Questionnaire (WIQ). RESULTS: Twenty-nine (90.6%) patients completed 12-month follow-up. Mean ankle-brachial index was 0.45 ± 0.14 at baseline and 0.84 ± 0.12 at 12 months (P < 0.05). The WIQ score was 30.45 ± 21.14 at baseline and 52.68 ± 29.75 at 12 months (P < 0.05). The Kaplan-Meier estimate of the primary patency rate at 12 months was 86.2% (25/29), and freedom from CD-TLR rate at 12 months was 89.7% (26/29). CONCLUSIONS: The data suggest that combination of Rotarex thrombectomy and DCB for treatment of FP ISR is safe and effective with satisfying primary patency rate and freedom from CD-TLR rate at 12-month follow-up.

WITHDRAWN: Drug Coated Balloon vs. Standard Percutaneous Transluminal Angioplasty for the Treatment of Femoropopliteal Artery Disease: 12 - Month Results of the LEGFLOW OTW China Randomised Controlled Trial.

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Expression of platelet-derived growth factor in the vascular walls of patients with lower extremity arterial occlusive disease.

The aim of the present study was to quantitatively analyze the expression of platelet-derived growth factor (PDGF)-A and PDGF-B in the vascular walls of patients with lower extremity arterial occlusive disease (LEAOD). The expression levels of PDGF-A and PDGF-B in the lower extremity arteries of 19 LEAOD patients (case group) and three healthy subjects (control group) was determined using quantitative polymerase chain reaction. Intergroup comparisons revealed that the relative mRNA expression levels were higher in the case group, as compared with the control group, for PDGF-A (34.38±5.80 vs. 21.94±1.05; P<0.05) and PDGF-B (33.95±5.92 vs. 24.15±3.12; P<0.05). In addition, the expression of PDGF-A revealed a positive linear correlation with the expression of PDGF-B (P<0.05). Therefore, the expression levels of PDGF-A and PDGF-B were found to be higher in the vascular walls of LEAOD patients, while the expression of PDGF-A was found to correlate with the expression of PDGF-B. A significant increase in the expression levlels of PDGF-A and PDGF-B were observed in the vascular walls of patients with LEAOD, and the expression of PDGF-A was associated with the expression of PDGF-B.

[Efficacy of short-term catheter-directed thrombolysis used with rt-PA combined with endovascular interventional therapy in patients with lower limb ischemia].

OBJECTIVES: To evaluate the performance effect of short-term catheter-directed thrombolysis with different dosage of rt-PA allied with endovascular interventional therapy for patients with acute lower limb ischemia. METHODS: To separate 84 consecutive patients suffered from acute lower limb ischemia into two groups at random, then adopt catheter-directed thrombolysis for each group of patients injected 20 mg (Group A) or 10 mg (Group B) rt-PA into the occlusive lesion correspondingly, and subsequently perform endovascular intervention on significant underlying lesions on the base of angiography results. Adopt statistical methods to assess treatment effectiveness, rates of complication and amputation rates within 30 days, 6 months or 12 months. The statistic analysis was performed under SPSS 16.0 format, and adopts t test and χ(2) test. RESULTS: There was no statistical difference on patient characteristics and lesions between both groups (P > 0.05). Procedural success rates as well clinical success rates were all 100%. Not incur any diversity on thrombolysis effectiveness between both groups injected different dosage of rt-PA (P > 0.05). Not found major differences on ratios of PTA or implant stent between both groups (P > 0.05). During the follow-up period of 30-day, 6-, 12- months, there were no statistical differences on the amputation-free survival rates and complication rates between both groups. CONCLUSIONS: Whereas short-term catheter-directed thrombolysis combined with endovascular interventional therapy won good operation effectiveness on patients with acute lower limb ischemia, moreover the dosage of rt-PA did not impact on thrombolysis, it is worthy to be applied in the clinical practice.

Long-term results of endovascular therapy for proximal subclavian arterial obstructive lesions.

BACKGROUND: Endovascular therapy is a treatment option for localized occlusion of the subclavian artery. In this report the long-term experience with 59 patients is presented. METHODS: Between June 1998 and September 2008, we used endovascular therapy to treat 61 subclavian arterial obstructive lesions in 59 patients (46 males and 13 females, 34 - 82 years of age with a mean age (61.9 + or - 11.0) years). Twenty patients (34%) had clinical symptoms due to vertebrobasilar insufficiency, 26 (44%) had disabling arm ischemia, and 13 (22%) had both symptoms. We performed all procedures under local anesthesia. The approaches were from the femoral artery (n = 47), brachial artery (n = 1, involving bilateral subclavian disease) or both (n = 11). Sixty stents were implanted. All patients were followed-up at 1, 3, 6, and 12 months post-procedure, and annually thereafter. RESULTS: We achieved technical success in 58 (95.1%) arteries, all of which were stented. There were three technical failures; two were due to the inability to cross over an occlusion, necessitating the switch to an axillo-axillary bypass, and the third was due to shock after digital subtraction angiography and prior to stenting. Arterial stenosis pre- and post-stenting was (83.6 + or - 10.8)% and (2.5 + or - 12.5)% (P < 0.01). Clinical success was achieved in 55 of the 59 patients (93.4%). Of the four clinical failures, three were technical and the remaining patient had a stent thrombosis. Systolic blood pressure difference between the two brachial arteries was (44.7 + or - 18.5) vs. (2.2 + or - 3.9) mmHg (P < 0.01). Primary patency was 98% at 12 months, 93% at 24 months, and 82% at 5 years. Five patients were lost to follow-up by 12 months post-stenting. Significant recurrent obstruction developed in five patients with resumption of clinical symptoms. The overall survival rate was 98.2% at 12 months, 89.5% at 24 months, and 84.5% at 5 years. CONCLUSIONS: Endovascular therapy for proximal subclavian arterial obstructive lesions is effective and successful. This minimally invasive treatment may be the first choice of treatment for proximal subclavical arterial obstructive lesions.