Three-Year Outcomes, Risk Factors for Restenosis After Stenting for DVT Combined with Iliac Vein Compression Syndrome.

This study aimed to evaluate the safety and efficacy of pharmacomechanical catheter-directed thrombolysis (PCDT) and stenting for treating acute iliofemoral deep venous thrombosis (DVT) combined with iliac vein compression syndrome (IVCS), and to identify the predictors of stent restenosis. Patients with acute proximal DVT combined with IVCS underwent PCDT and stenting from January 2017 to December 2022 were enrolled. Primary and secondary patency were assessed by duplex ultrasound (DUS). The morbidity of postthrombotic syndrome (PTS) was assessed by the Villalta score. Risk factors for stent restenosis were assessed using univariate and multivariate Cox regression models. Total of 254 patients were included. The mean follow-up time was 36.06 ± 17.66 months. The primary patency rates at 1 year, 3 years, and 5 years were 92.5%±1.7%, 85.4%±2.4%, and 82.4%±2.9%, respectively. The incidence of stent restenosis was 14.2%. Discontinuation of anticoagulants within one year [hazard ratio (HR) = 5.03; P = .048] was the factor associated with acute in-stent thrombosis. Previous DVT history (HR =2.29; P = .037) and stent placement across the inguinal ligament (HR =6.70; P < .001) were identified as independent risk factors significantly associated with stent restenosis. The overall PTS rate was 19.3%. PCDT with stenting is safe and effective for patients with iliofemoral DVT secondary to IVCS, leading to low rates of PTS. Previous DVT history and stents placed across the inguinal ligament may be predictors of stent restenosis. Furthermore, stent restenosis typically occurs within one year and is mainly caused by acute thrombosis due to discontinuation of anticoagulants.

The YTH domain-containing protein family: Emerging players in immunomodulation and tumour immunotherapy targets.

BACKGROUND: The modification of N6-methyladenosine (m6A) plays a pivotal role in tumor by altering both innate and adaptive immune systems through various pathways, including the regulation of messenger RNA. The YTH domain protein family, acting as "readers" of m6A modifications, affects RNA splicing, stability, and immunogenicity, thereby playing essential roles in immune regulation and antitumor immunity. Despite their significance, the impact of the YTH domain protein family on tumor initiation and progression, as well as their involvement in tumor immune regulation and therapy, remains underexplored and lacks comprehensive review. CONCLUSION: This review introduces the molecular characteristics of the YTH domain protein family and their physiological and pathological roles in biological behavior, emphasizing their mechanisms in regulating immune responses and antitumor immunity. Additionally, the review discusses the roles of the YTH domain protein family in immune-related diseases and tumor resistance, highlighting that abnormal expression or dysfunction of YTH proteins is closely linked to tumor resistance. KEY POINTS: This review provides an in-depth understanding of the YTH domain protein family in immune regulation and antitumor immunity, suggesting new strategies and directions for immunotherapy of related diseases. These insights not only deepen our comprehension of m6A modifications and YTH protein functions but also pave the way for future research and clinical applications.

The genetic effects of hormones modulated by the Pituitary-Thyroid/Adrenal/Gonadal axis on the risk of developing venous thromboembolism: a mendelian randomization study.

BACKGROUND: The aim of this study was to explore the genetic effects of hormones modulated through the pituitary-thyroid/adrenal/gonadal axis on the risk of developing venous thromboembolism (VTE) and to investigate the potentially causal relationships between them. METHODS: A two-sample Mendelian randomization (MR) design was used. The single-nucleotide polymorphisms (SNPs) used as instrumental variables for various hormones and hormone-mediated diseases were derived from published genome-wide association studies (GWASs). Summary statistics for the risk of developing VTE (including deep venous thrombosis [DVT] and pulmonary embolism [PE]) were obtained from the UK Biobank and the FinnGen consortium. Inverse-variance weighting (IVW) was applied as the primary method to analyse causal associations. Other MR methods were used for supplementary estimates and sensitivity analysis. RESULTS: A genetic predisposition to greater free thyroxine (FT4) concentrations was associated with a greater risk of developing DVT (OR = 1.0007, 95%CI [1.0001-1.0013], p = 0.0174) and VTE (OR = 1.0008, 95%CI [1.0002-1.0013], p = 0.0123). Genetically predicted hyperthyroidism was significantly associated with an increased risk of developing DVT (OR = 1.0685, 95%CI [1.0139-1.1261], p = 0.0134) and VTE (OR = 1.0740, 95%CI [1.0165-1.1348], p = 0.0110). According to the initial MR analysis, testosterone concentrations were positively associated with the risk of developing VTE (OR = 1.0038, 95%CI [1.004-1.0072], p = 0.0285). After sex stratification, estradiol concentrations were positively associated with the risk of developing DVT (OR = 1.0143, 95%CI [1.0020-1.0267], p = 0.0226) and VTE (OR = 1.0156, 95%CI [1.0029-1.0285], p = 0.0158) in females, while the significant relationship between testosterone and VTE did not persist. SHBG rs858518 was identified as the only SNP that was associated with an increased risk of developing VTE, mediated by estradiol, in females. CONCLUSIONS: Genetically predicted hyperthyroidism and increased FT4 concentrations were positively associated with the risk of developing VTE. The effects of genetically predicted sex hormones on the risk of developing VTE differed between males and females. Greater genetically predicted estradiol concentrations were associated with an increased risk of developing VTE in females, while the SHBG rs858518 variant may become a potential prevention and treatment target for female VTE.

Recanalization of superficial femoral artery chronic total occlusion through retrograde popliteal approach recanalization of superficial femoral artery chronic total occlusion.

Purpose: This retrospective study aims to evaluate the safety, practicality, and efficacy of the independent retrograde popliteal approach for recanalization superficial femoral artery (SFA) occlusions when the bilateral common femoral artery approach is unavailable, such as after endovascular aneurysm repair or common iliac artery stenting. Methods: This treatment was considered for patients with contralateral iliac artery occlusion, severe iliac tortuosity, or those who had previously undergone endovascular aneurysm repair or common iliac stenting. Patients with SFA lesions extending into the P1-P2 segment of the popliteal artery or with calcification in the P3 segment were excluded. Angioplasty and stenting were conducted via the popliteal artery approach, with hemostasis at the puncture site achieved using an EXOSEAL vascular closure device. Patients were routinely followed up at 3, 6, and 12 months, and annually thereafter. Results: Forty-eight consecutive patients with SFA occlusion who underwent endovascular treatment via the retrograde popliteal artery approach were included in this study. Retrograde puncture of the popliteal artery was successful in all cases. Six-French sheaths were utilized in all procedures. The EXOSEAL vascular closure device was successfully applied in all 48 cases. No instances of pseudoaneurysms, arteriovenous fistulas, major bleeding, or embolic complications were observed. The technical success rate for SFA recanalization was 100 %. All patients experienced clinical improvement. The ankle-brachial index significantly increased from an initial 0.33 ± 0.11 at admission to 0.81 ± 0.19 at discharge (P < 0.001). The mean follow-up period was 25.1 ± 11.7 months. Kaplan-Meier analysis revealed primary patency rates of 82.5 % at 12 months and 71.8 % at 24 months. No patients required major amputation during the follow-up period. Conclusion: The endovascular treatment of SFA occlusions via the independent retrograde popliteal approach is a viable alternative, demonstrating a low incidence of puncture-related complications and a high success rate of recanalization.

Precisely Activating cGAS-STING Pathway with a Novel Peptide-Based Nanoagonist to Potentiate Immune Checkpoint Blockade Cancer Immunotherapy.

As an essential intracellular immune activation pathway, the cGAS-STING pathway has attracted broad attention in cancer treatment. However, low bioavailability, nonspecificity, and adverse effects of small molecule STING agonists severely limit their therapeutic efficacy and in vivo application. In this study, a peptide-based STING agonist is first proposed, and KLA is screened out to activate the cGAS-STING pathway by promoting mitochondrial DNA (mtDNA) leakage. To precisely activate the cGAS-STING pathway and block the PD-1/PD-L1 pathway, a multi-stimuli activatable peptide nanodrug (MAPN) is developed for the effective delivery of KLA and PD-L1 antagonist peptide (CVR). With rational design, MAPN achieved the site-specific release of KLA and CVR in response to multiple endogenous stimuli, simultaneously activating the cGAS-STING pathway and blocking PD-1/PD-L1 pathway, ultimately initiating robust and durable T cell anti-tumor immunity with a tumor growth inhibition rate of 78% and extending the median survival time of B16F10 tumor-bearing mice to 40 days. Overall, antimicrobial peptides, which can promote mtDNA leakage through damaging mitochondrial membranes, may be potential alternatives for small molecule STING agonists and giving a new insight for the design of novel STING agonists. Furthermore, MAPN presents a universal delivery platform for the effective synergy of multiple peptides.

Outcomes of thoracic endovascular aortic repair with physician-manufactured partial micropore stent grafts for aortic arch pathologies.

OBJECTIVE: Thoracic endovascular aortic repair (TEVAR) has been used extensively in the management of thoracic aortic diseases. Numerous efforts have been made to enhance clinical outcomes through the use of stent grafts. This study aimed to investigate the effectiveness and safety of physician-manufactured partial micropore stent grafts (PSMGs) in TEVAR. METHODS: Between December 2017 and June 2022, data were collected from 56 patients who underwent TEVAR using physician-manufactured PSMGs. The evaluation encompassed technical success, perioperative and follow-up morbidity and mortality, stroke incidence, and branch artery patency. RESULTS: In this investigation, 56 patients received treatment with physician-manufactured PSMGs. Of these patients, 46 were male, with a mean age of 62.1 ± 11.2 years. Aortic pathologies comprised aortic dissection (n = 31 [55.4%]), aortic aneurysms (n = 10 [17.9%]), penetrating aortic ulcer (n = 8 [14.3%]), and intramural hematoma (n = 7 [12.5%]). During a median follow-up of 18 months (interquartile range, 13-25 months), the stroke rate, supra-aortic branch patency rate, and endoleak rate were 0%, 100%, and 7.1%, respectively. There were no occurrences of all-cause mortality, stroke, or the necessity for open conversion. CONCLUSIONS: TEVAR with physician-manufactured PSMGs is a viable alternative for addressing aortic arch pathologies in proficient medical centers. The approach demonstrates favorable branch patency, a low complication rate, and minimal postoperative mortality.

Effectiveness of iliac vein stenting combined with endovenous laser treatment of recurrent varicose veins associated with iliac vein compression.

Background: Iliac vein compression syndrome (IVCS) is an underlying cause of varicose vein (VV) recurrence after venous surgery. However, the management of recurrent varicose veins (RVVs) combined with IVCS has rarely been reported. This study aimed to investigate the outcomes of a one-stop procedure to correct outflow obstruction and superficial reflux for patients with RVVs and IVCS. Methods: A retrospective analysis was conducted of 102 consecutive patients diagnosed with RVVs. Computed tomography venography (CTV) was performed to confirm IVCS. The cases were divided into 2 groups: the IRVVs group, including patients with RVVs and IVCS (n=48), and the RVVs group, including patients with RVVs only (n=54). The characteristics, vein reflux, and clinical, etiological, anatomical, and pathophysiological (CEAP) distribution were investigated. Then, the IRVVs group patients who underwent endovenous laser ablation (EVLA) (n=39) were divided into a further 2 groups: the EVLA + S group (n=19), who received EVLA and stenting of iliac vein, and the EVLA group (n=20), who received EVLA treatment alone. The great/small saphenous vein (GSV/SSV) trunk occlusion, VV recurrence, visual analogue scale (VAS), and venous clinical severity score (VCSS) were investigated. Results: The prevalence rate of femoral vein reflux was 81.2% in IRVVs group and 50% in RVVs group (P<0.05). In the IRVVs group, 72.9% of patients manifested as CEAP clinical class >3, which was higher than that in RVVs group (48.1%) (P<0.05). The 12-month GSV/SSV occlusion rate in the EVLA + S and EVLA groups were 94.7% and 90.0%, respectively. Totals of 9 patients in EVLA + S group and 6 patients in EVLA group had active venous ulcers, and the ulcer healing time in EVLA + S group was significantly shorter (27.22±7.12 vs. 46.67±9.83 days, P<0.05). The reductions in the VAS and VCSS values between baseline, 1 month, and 12 months in the EVLA + S group were more obvious than those in EVLA group (P<0.05). Conclusions: The one-stop combination treatment of iliac venous stenting and EVLA in patients with RVVs and IVCS is safe and effective and provides prominent symptom relief, improved quality of life, and a more satisfactory ulcer healing than EVLA alone.

Central Venous Catheter as a Novel Approach to Postoperative Thrombolysis in Patients with Acute Iliofemoral Deep Venous Thrombosis.

BACKGROUND AND AIMS: Percutaneous mechanical thrombectomy (PMT) along with postoperative thrombolysis (POT) has been the standard treatment for acute iliofemoral deep venous thrombosis (IFDVT). However, commonly used catheter directed thrombolysis (CDT) approaches for POT carry certain disadvantages, including the need for a sheath, inferior comfortability, and catheter-related complications. Therefore, we propose a new simplified method of POT using a central venous catheter (CVC). METHODS: The retrospective study analyzed patients with IFDVT who underwent POT using CVC from January 2020 to August 2021. The treatment modalities included filter placement, thrombus removal, iliac vein obstruction release, postoperative CVC thrombolysis, filter retrieval, and adequate full course anticoagulation. RESULTS: A total of 39 patients were included in this retrospective study. All patients underwent PMT surgery with a procedure success rate of 100%. In the post-PMT CVC thrombolysis, the puncture sites were located in the below-knee vein, including 58.97% in the peroneal vein. The mean duration of CVC-directed thrombolysis was 3.69 ± 1.08 days, and the total urokinase dose was 2.27 ± 0.71 MIU. A total of 37 patients (94.87%) had successful thrombolysis with a length of hospital stay of 5.82 ± 2.21 days. During CVC-directed thrombolysis, only four minor bleeding complications occurred, two of which were indwelling catheter-related. During the 12-month follow-up period, the patency rate and post-thrombotic syndrome incidences were 97.44% and 2.56%, respectively. CONCLUSION: Thrombolysis through a CVC is a feasible, safe, and effective POT method, and could be an alternative to the conventional CDT approach for patients with IFDVT.

One year follow-up outcomes of endovascular treatment for aortic dissection with a partial micropore stent graft in which fixation of the stent is done in zone 0: A pivotal trial first in human.

OBJECTIVE: This study aimed to verify the efficacy and safety of the treatment for patients diagnosed with DeBakey type I and type III thoracic aortic dissections using a partial micropore stent graft. METHODS: We conducted a retrospective analysis of 32 patients who suffered from thoracic aortic dissection and underwent endovascular repair using a partial micropore stent graft at our center between December 2018 and January 2020. RESULTS: The technical success rate for 32 patients was 100 %, while no 30-day mortality was observed. In the 30 patients finished follow-ups, 30 (mean: 1 per patient) micropore stents were implanted, while the openings of 90 (mean: 3 per patient) aortic arch branches were covered by the stents. After more than 12 months follow-up, 26 (86.7 %) of the 30 patients presented with a complete thrombosis in the false lumen, and 4 (13.3 %) patients presented with a partial thrombosis in the false lumen. All 90 aortic arch branches were patent. No aortic arch branch artery stenosis or occlusion was observed. CONCLUSIONS: The outcomes obtained during 12 months of follow-up suggested that performing endovascular repair for thoracic aortic dissection patients with a partial micropore stent graft is safe and effective, maintaining the patency of aortic arch branch vessels.

WIfI Classification Based Analysis of Risk Factors for Outcomes in Patients with Chronic Limb Threatening Ischaemia after Endovascular Revascularisation Therapy.

OBJECTIVE: The evaluation of limb status with the Wound, Ischaemia, and foot Infection (WIfI) classification and the assessment of patient risks combined with systemic factors, are recommended in patients with chronic limb threatening ischaemia (CLTI). However, there is little evidence of the application of the WIfI classification in the Chinese population. This study aimed to verify the use of the WIfI classification in a Chinese patient population, and to further identify local and systemic independent predictors of adverse CLTI outcomes. METHODS: A total of 474 patients who underwent endovascular therapy (EVT) for CLTI in a tertiary hospital between July 2017 and September 2020 were included in this retrospective study. The outcomes included one year major adverse limb events (MALEs), one year all cause mortality, and one year amputation free survival (AFS). Cox regression was used to analyse the association between risk factors and adverse outcomes. RESULTS: In total, 104 (21.9%) all cause deaths were recorded. The rate of MALEs was 17.5%, while the AFS was 71.9%. Multivariable analysis revealed that a body mass index (BMI) < 18.5 kg/m2 (p = .002), a left ventricular ejection fraction (LVEF) < 50% (p < .001), and WIfI wound grade (p < .001) were independent risk factors for MALEs, while age ≥ 77 years (p = .031), BMI < 18.5 kg/m2 (p < .001), coronary heart disease (p = .040), and WIfI clinical stages (p = .021) were independent risk factors for death in patients with CLTI. Age ≥ 77 years (p = .003), BMI < 18.5 kg/m2 (p < .001), coronary heart disease (p = .012), LVEF < 50% (p < .001), WIfI wound grade (p = .004), and WIfI clinical stages (p = .044) were independently associated with a decreased AFS rate. CONCLUSIONS: This study has confirmed the predictive ability of the WIfI classification for Chinese patients with CLTI who underwent EVT. Wound grade was the most sensitive and important risk factor of the three components of WIfI. In addition, systemic factors should be considered to ensure a more accurate prognosis prediction and appropriate clinical decision making in patients with CLTI.

Radionuclide Reduction by Combinatorial Optimization of Microbial Extracellular Electron Transfer with a Physiologically Adapted Regulatory Platform.

Microbial extracellular electron transfer (EET) is the basis for many microbial processes involved in element geochemical recycling, bioenergy harvesting, and bioremediation, including the technique for remediating U(VI)-contaminated environments. However, the low EET rate hinders its full potential from being fulfilled. The main challenge for engineering microbial EET is the difficulty in optimizing cell resource allocation for EET investment and basic metabolism and the optimal coordination of the different EET pathways. Here, we report a novel combinatorial optimization strategy with a physiologically adapted regulatory platform. Through exploring the physiologically adapted regulatory elements, a 271.97-fold strength range, autonomous, and dynamic regulatory platform was established for Shewanella oneidensis, a prominent electrochemically active bacterium. Both direct and mediated EET pathways are modularly reconfigured and tuned at various intensities with the regulatory platform, which were further assembled combinatorically. The optimal combinations exhibit up to 16.12-, 4.51-, and 8.40-fold improvements over the control in the maximum current density (1009.2 mA/m2) of microbial electrolysis cells and the voltage output (413.8 mV) and power density (229.1 mW/m2) of microbial fuel cells. In addition, the optimal strains exhibited up to 6.53-fold improvement in the radionuclide U(VI) removal efficiency. This work provides an effective and feasible approach to boost microbial EET performance for environmental applications.

Epigallocatechin Gallate Attenuates Gentamicin-Induced Nephrotoxicity by Suppressing Apoptosis and Ferroptosis.

Gentamicin (GEN) is a kind of aminoglycoside antibiotic with the adverse effect of nephrotoxicity. Currently, no effective measures against the nephrotoxicity have been approved. In the present study, epigallocatechin gallate (EG), a useful ingredient in green tea, was used to attenuate its nephrotoxicity. EG was shown to largely attenuate the renal damage and the increase of malondialdehyde (MDA) and the decrease of glutathione (GSH) in GEN-injected rats. In NRK-52E cells, GEN increased the cellular ROS in the early treatment phase and ROS remained continuously high from 1.5 H to 24 H. Moreover, EG alleviated the increase of ROS and MDA and the decrease of GSH caused by GEN. Furthermore, EG activated the protein levels of nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1). After the treatment of GEN, the protein level of cleaved-caspase-3, the flow cytometry analysis and the JC-1 staining, the protein levels of glutathione peroxidase 4 (GPX4) and SLC7A11, were greatly changed, indicating the occurrence of both apoptosis and ferroptosis, whereas EG can reduce these changes. However, when Nrf2 was knocked down by siRNA, the above protective effects of EG were weakened. In summary, EG attenuated GEN-induced nephrotoxicity by suppressing apoptosis and ferroptosis.

Enhanced Bioreduction of Radionuclides by Driving Microbial Extracellular Electron Pumping with an Engineered CRISPR Platform.

Dissimilatory metal-reducing bacteria (DMRB) with extracellular electron transfer (EET) capability show great potential in bioremediating the subsurface environments contaminated by uranium through bioreduction and precipitation of hexavalent uranium [U(VI)]. However, the low EET efficiency of DMRB remains a bottleneck for their applications. Herein, we develop an engineered CRISPR platform to drive the extracellular electron pumping of Shewanella oneidensis, a representative DMRB species widely present in aquatic environments. The CRISPR platform allows for highly efficient and multiplex genome editing and rapid platform elimination post-editing in S. oneidensis. Enabled by such a platform, a genomic promoter engineering strategy (GPS) for genome-widely engineering the EET-encoding gene network was established. The production of electron conductive Mtr complex, synthesis of electron shuttle flavin, and generation of NADH as intracellular electron carrier are globally optimized and promoted, leading to a significantly enhanced EET ability. Applied to U(VI) bioreduction, the edited strains achieve up to 3.62-fold higher reduction capacity over the control. Our work endows DMRB with an enhanced ability to remediate the radionuclides-contaminated environments and provides a gene editing approach to handle the growing environmental challenges of radionuclide contaminations.

Peptide-Targeted High-Density Lipoprotein Nanoparticles for Combinatorial Treatment against Metastatic Breast Cancer.

The sonic hedgehog (SHH) signaling pathway exhibits aberrant activation in triple-negative breast cancer (TNBC), wherein it regulates several malignant phenotypes related to tumor metastasis. GANT61, an inhibitor of the SHH signaling pathway, may offer promise when administered in combination with conventional chemotherapy to treat metastatic TNBC. However, poor bioavailability and substantial off-target toxicity limit its clinical application. To address these limitations, we designed a peptide-functionalized dual-targeting delivery system encapsulating paclitaxel and GANT61 in tLyP-1 peptide-modified reconstituted high-density lipoprotein nanoparticle (tLyP-1-rHDL-PTX/GANT61 NP) for metastatic TNBC treatment. The apolipoprotein A-1 and tLyP-1 peptide modified on the surface of nanoparticles enable the delivery system to target tumor cells by binding to the overexpressed scavenger receptor B type I and neuropilin-1 receptor. Moreover, the tLyP-1 peptide also enables the deep tumor penetration of nanoparticles further facilitating paclitaxel and GANT61 delivery. Increased cellular uptake of the nanoparticles was observed in both MDA-MB-231, BT-549 tumor cells, and their 3D tumor spheroids. A series of in vitro experiments reveal that GANT61 was able to suppress key metastasis-related tumor cell activities including angiogenesis, migration, invasion, and stemness. Owing to more effective drug administration, the metastasis suppression efficiency of GANT61 was significantly enhanced by the dual-targeting tLyP-1-rHDL delivery system. Meanwhile, the codelivery of paclitaxel and GANT61 by dual-targeting tLyP-1-rHDL nanoparticles demonstrated superior efficiency of disrupting proliferation and inducing apoptosis in tumor cells compared with drug solutions. In a spontaneous metastasis breast cancer NCG mice model, the tLyP-1-rHDL-PTX/GANT61 nanoparticles exhibited highly tumor-specific distribution and result in significant inhibition of the primary tumor growth and dramatic reduction of lung metastasis without obvious side effects. The present work suggests that a combination of the SHH signaling pathway suppression and chemotherapy assisted by peptide-functionalized targeting tLyP-1-rHDL nanoparticles may provide a promising strategy for metastatic TNBC treatment.

The effect of stent compression on in-stent restenosis and clinical outcomes in iliac vein compression syndrome.

BACKGROUND: To evaluate the effect of stent compression on in-stent restenosis (ISR) and clinical outcomes in patients with iliac vein compression syndrome (IVCS) after iliac vein stenting. METHODS: Fifty patients with IVCS treated with iliac vein stenting (Smart Control, Cordis, USA) between March 2017 and October 2018 were consecutively enrolled in this study. Computed tomography venography (CTV) was performed to assess stent compression and ISR. Based on the degree of stent compression, patients were allocated to a significant stent compression (SSC) group and an insignificant stent compression (ISC) group. The incidence of ISR was analyzed between the SSC and ISC groups. Patients' venous clinical severity scores (VCSSs) and responses to the chronic venous insufficiency questionnaire (CIVIQ) one year after stenting were compared between the two groups to evaluate the clinical improvement of venous insufficiency. RESULTS: In total, 34% of patients had SSC. There were significant differences in the incidence of ISR (52.9% vs. 21.2%, P=0.023), and in each group, there was one case of stent occlusion (5.88% vs. 3.03%, P=0.999). Patients in the SSC group had a higher VCSS score (8.41±5.92 vs. 3.15±2.87, P=0.04) and a lower CIVIQ score (83.35±8.86 vs. 92.21±4.32, P=0.001). CONCLUSIONS: SSC has a significant effect on the incidence of ISR and the clinical outcomes of venous insufficiency. Thus, a dedicated iliac venous stent with sufficient radial resistive force, crush resistance, and outward radial force is needed to prevent the occurrence of stent compression.

Mechanisms of Trx2/ASK1-Mediated Mitochondrial Injury in Pemphigus Vulgaris.

OBJECTIVE: Apoptotic events mediated by mitochondrial injury play an important role on the onset of Pemphigus vulgaris (PV). The thioredoxin-2 (Trx2)/apoptosis signal-regulating kinase 1 (ASK1) signaling pathway is considered a key cascade involved on the regulation of mitochondrial injury. Hence, we have investigated the regulatory mechanism of the Trx2/ASK1 signaling in PV-induced mitochondrial injury. METHODS: Serum and tissue samples were collected from clinical PV patients to detect the oxidative stress factors, cell apoptosis, and expression of members from Trx2/ASK1 signaling. HaCaT cells were cultured with the serum of PV patients and transfected with Trx2 overexpression or silencing vector. Changes in the levels of reactive oxygen species (ROS), mitochondrial membrane potential (△ψm), and apoptosis were further evaluated. A PV mouse model was established and administered with Trx2-overexpressing plasmid. The effect of ectopic Trx2 expression towards acantholysis in PV mice was observed. RESULTS: A series of cellular and molecular effects, including (i) increased levels of oxidative stress products, (ii) destruction of epithelial cells in the skin tissues, (iii) induction of apoptosis in keratinocytes, (iv) reduction of Trx2 protein levels, and (v) enhanced phosphorylation of ASK1, were detected in PV patients. In vitro experiments confirmed that Trx2 can inhibit ASK1 phosphorylation, alleviate ROS release, decrease △ψm, and lower the apoptotic rate. Injection of Trx2-overexpressing vectors in vivo could also relieve acantholysis and blister formation in PV mice. CONCLUSION: The Trx2/ASK1 signaling pathway regulates the incidence of PV mediated by mitochondrial injury.

In-situ reactive heat breaking cell wall by SO3 hydration: innovative cell-wall breaking technique to enhance extraction of cinnamaldehyde from cinnamon.

Cinnamaldehyde (CA) is one of the major active pharmaceutical ingredient of cinnamon bark. Hydrodistillation (HD) is usually used in CA extraction, however, the extraction yield is lower. The cell wall is a key factor limiting the extraction of essential oils. In-situ reactive heat breaking cell wall (RHB) could destroy the cell wall, which was conducive to the diffusion of CA. The aim of this work was to examine the effect of RHB pretreatment to HD extraction. Response surface methodology (RSM) was used to optimize RHB pretreatment parameters, and Box-Behnken Design (BBD) method was performed to evaluate the effects of different operating parameters. The maximum yield was increased to 3.31 ± 0.11% (w/w) from 2.08 ± 0.042% (w/w) after RSM optimization. Scanning electron microscopic (SEM) analysis showed that RHB destroyed and disrupted the cell wall of cinnamon bark. The GC analysis demonstrated that the purity of cinnamaldehyde was improved and no new components were presented in the extraction product from the cinnamon via RHB pretreatment. In conclusion, RHB is an effective pretreatment method for the CA extraction, and also may be used in the other herbal medicine extraction.

Four-year outcomes following endovascular repair in patients with traumatic isolated popliteal artery injuries.

OBJECTIVE: The effectiveness of endovascular treatment for popliteal arterial injury has not been well-documented. This study was aimed to investigate the midterm outcomes of endovascular repair of traumatic isolated popliteal arterial injury. METHODS: Medical records of the patients who underwent endovascular repair for traumatic popliteal arterial injuries from January 2012 to February 2020 were reviewed retrospectively. Clinical data including patient demographics, Injury Severity Score, type of injury, classification of acute limb ischemia, concomitant extremity fracture, runoff vessel status, complications, time of endovascular procedure, time interval from injury to blood flow restoration, length of hospital stay, reintervention, and follow-up were collected and analyzed. RESULTS: Endovascular repair was performed in 46 patients with traumatic popliteal arterial injuries. The mean Injury Severity Score was 15.8 ± 6.2. The overall limb salvage rate was 89.1%. There were 10 penetrating and 36 blunt injuries (78.3%). The initial angiographic findings revealed occlusion in 34 patients (73.9%), pseudoaneurysm in 2 (4.4%), active extravasation in 9 (19.5%), and arteriovenous fistulas in 1 (2.2%). Technical success was achieved in all 46 patients, via antegrade access in 24 patients (52.2%) and concurrent retrograde access in 22 (47.8%). The mean time interval from popliteal artery injury to blood flow restoration was 10.6 ± 4.9 hours and mean operative time was of 54.9 ± 10.0 minutes. The mean follow-up was 36.1 ± 14.5 months. The primary patency rate was 75.3% at 12 months, 61.9% at 24 months, and 55.7% at 48 months. The secondary patency rate was 92.2% at 12 and 24 months and 85.2% at 48 months. A Cox multivariate analysis revealed that single vessel runoff was an independent risk factor for primary patency loss. CONCLUSIONS: Endovascular repair of an isolated popliteal artery injury may be a safe and effective alternative treatment in select patients, with acceptable midterm outcomes. Single vessel runoff was an independent risk factor for primary patency loss.