The Efficiency of Preoperative Embolization in the Management of Shamblin Type III Carotid Body Tumor: A Single-Center Retrospective Study.

BACKGROUND: This study aims to determine the efficacy and safety of preoperative embolization in the management of Shamblin type III carotid body tumors (CBT). METHOD: In this retrospective study, patients with Shamblin type III CBT were included between January 2005 and January 2017. A total of 48 Patients were divided into preoperative embolization (SRE, n = 25) and non-preoperative embolization group (SR, n = 23). RESULT: Mean surgical time (145.24 ± 19.86 min vs 186.91 ± 17.808 min, P < 0.05) and intraoperative blood loss (271.4 ± 73.001 mL vs 380.36 ± 39.822 mL, P < 0.05) were markedly reduced in the SRE group compared with SR group. The preoperative tumor volume in the SRE group was larger than that in the SR group, but the volume was similar between the two groups after surgery. The number of tumor residual cases was higher in the SR group. The incidence of complications and duration of hospitalization were comparable between the two groups. CONCLUSION: This study demonstrates the efficacy of preoperative embolization in reducing the duration of surgery and volume of blood loss during the process of CBT resection. More prospective, well-designed studies are urgently needed to validate the current findings.

NINJ1 Facilitates Abdominal Aortic Aneurysm Formation via Blocking TLR4-ANXA2 Interaction and Enhancing Macrophage Infiltration.

Abdominal aortic aneurysm (AAA) is a common and potentially life-threatening condition. Chronic aortic inflammation is closely associated with the pathogenesis of AAA. Nerve injury-induced protein 1 (NINJ1) is increasingly acknowledged as a significant regulator of the inflammatory process. However, the precise involvement of NINJ1 in AAA formation remains largely unexplored. The present study finds that the expression level of NINJ1 is elevated, along with the specific expression level in macrophages within human and angiotensin II (Ang II)-induced murine AAA lesions. Furthermore, Ninj1flox/flox and Ninj1flox/floxLyz2-Cre mice on an ApoE-/- background are generated, and macrophage NINJ1 deficiency inhibits AAA formation and reduces macrophage infiltration in mice infused with Ang II. Consistently, in vitro suppressing the expression level of NINJ1 in macrophages significantly restricts macrophage adhesion and migration, while attenuating macrophage pro-inflammatory responses. Bulk RNA-sequencing and pathway analysis uncover that NINJ1 can modulate macrophage infiltration through the TLR4/NF-κB/CCR2 signaling pathway. Protein-protein interaction analysis indicates that NINJ1 can activate TLR4 by competitively binding with ANXA2, an inhibitory interacting protein of TLR4. These findings reveal that NINJ1 can modulate AAA formation by promoting macrophage infiltration and pro-inflammatory responses, highlighting the potential of NINJ1 as a therapeutic target for AAA.

Development and validation of a nomogram for identifying venous thromboembolism following oral and maxillofacial oncological surgery with simultaneous reconstruction.

OBJECTIVES: This study aimed to establish and validate a novel predictive model for venous thromboembolism (VTE) in patients undergoing oral and maxillofacial oncological surgery with simultaneous reconstruction. MATERIAL AND METHODS: A total of 372 patients were selected, and their demographic data, comorbidities, medical history, laboratory variables, postoperative Caprini scores, perioperative indicators, and procedures were recorded and analyzed to build the model. The predictive model is displayed as a nomogram. RESULTS: The incidence of VTE was 20.7% (77/372). Several factors were found to be significantly associated with VTE, including age (67 vs. 56 years, P < 0.001), preoperative level of D-dimer (0.56 vs. 0.36 mg/L, P < 0.001), proportion of female patients (46.8% vs. 33.6%, P = 0.032), hypertension (33.8% vs. 21%, P = 0.019). The predictive model was composed of age, gender, and preoperative D-dimer level, with good discriminative ability, as reflected by an area under the curve (AUC) of 0.756, the 95% confidence interval (CI) was 0.696-0.816. Moreover, it showed favorable diagnostic performance compared with both the 2005 (AUC 0.646, 95% CI = 0.578-0.714) and 2010 (AUC 0.627, 95% CI = 0.559-0.694) versions of the Caprini risk assessment model. For patients with malignant tumor, neoadjuvant chemotherapy was also an independent risk factor. CONCLUSIONS: This novel predictive model consists of three readily available clinical variables that show good diagnostic performance in predicting postoperative VTE.

An H2 S-BMP6 Dual-Loading System with Regulating Yap/Taz and Jun Pathway for Synergistic Critical Limb Ischemia Salvaging Therapy.

Critical limb ischemia, the final course of peripheral artery disease, is characterized by an insufficient supply of blood flow and excessive oxidative stress. H2 S molecular therapy possesses huge potential for accelerating revascularization and scavenging intracellular reactive oxygen species (ROS). Moreover, it is found that BMP6 is the most significantly up-expressed secreted protein-related gene in HUVECs treated with GYY4137, a H2 S donor, based on the transcriptome analysis. Herein, a UIO-66-NH2 @GYY4137@BMP6 co-delivery nanoplatform to strengthen the therapeutic effects of limb ischemia is developed. The established UIO-66-NH2 @GYY4137@BMP6 nanoplatform exerts its proangiogenic and anti-oxidation functions by regulating key pathways. The underlying molecular mechanisms of UIO-66-NH2 @GYY4137@BMP6 dual-loading system lie in the upregulation of phosphorylated YAP/TAZ and Jun to promote HUVECs proliferation and downregulation of phosphorylated p53/p21 to scavenge excessive ROS. Meanwhile, laser-doppler perfusion imaging (LDPI), injury severity evaluation, and histological analysis confirm the excellent therapeutic effects of UIO-66-NH2 @GYY4137@BMP6 in vivo. This work may shed light on the treatment of critical limb ischemia by regulating YAP, Jun, and p53 signaling pathways based on gas-protein synergistic therapy.

Prediction of preoperative in-hospital mortality rate in patients with acute aortic dissection by machine learning: a two-centre, retrospective cohort study.

OBJECTIVES: To conduct a comprehensive analysis of demographic information, medical history, and blood pressure (BP) and heart rate (HR) variability during hospitalisation so as to establish a predictive model for preoperative in-hospital mortality of patients with acute aortic dissection (AD) by using machine learning techniques. DESIGN: Retrospective cohort study. SETTING: Data were collected from the electronic records and the databases of Shanghai Ninth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine and the First Affiliated Hospital of Anhui Medical University between 2004 and 2018. PARTICIPANTS: 380 inpatients diagnosed with acute AD were included in the study. PRIMARY OUTCOME: Preoperative in-hospital mortality rate. RESULTS: A total of 55 patients (14.47%) died in the hospital before surgery. The results of the areas under the receiver operating characteristic curves, decision curve analysis and calibration curves indicated that the eXtreme Gradient Boosting (XGBoost) model had the highest accuracy and robustness. According to the SHapley Additive exPlanations analysis of the XGBoost model, Stanford type A, maximum aortic diameter >5.5 cm, high variability in HR, high variability in diastolic BP and involvement of the aortic arch had the greatest impact on the occurrence of in-hospital deaths before surgery. Moreover, the predictive model can accurately predict the preoperative in-hospital mortality rate at the individual level. CONCLUSION: In the current study, we successfully constructed machine learning models to predict the preoperative in-hospital mortality of patients with acute AD, which can help identify high-risk patients and optimise the clinical decision-making. Further applications in clinical practice require the validation of these models using a large-sample, prospective database. TRIAL REGISTRATION NUMBER: ChiCTR1900025818.

Safety and Efficacy of the Passeo-18 Lux Drug-Coated Balloon Catheter in Atherosclerotic Femoropopliteal Lesions: The Multicenter BIOLUX P-IV China Study.

BACKGROUND: The purpose of this trial was to assess the safety and effectiveness of a paclitaxel-coated balloon catheter in Chinese patients with de novo or nonstented restenotic femoropopliteal atherosclerotic lesions. METHODS: BIOLUX P-IV China is a prospective, independently adjudicated, multicenter, single-arm trial conducted in China. Patients with Rutherford class 2-4 were eligible, excluded were patients in which predilation resulted in severe (≥ grade D) flow-limiting dissection or residual stenosis > 70%. Follow-up assessments were conducted at 1, 6, and 12 months. The primary safety end point was 30-day major adverse event rate and the primary effectiveness end point was primary patency at 12 months. RESULTS: We enrolled 158 patients with 158 lesions. Mean age was 67.6 ± 9.6 years, diabetes was present in 53.8% (n = 85), and previous peripheral intervention/surgeries in 17.1% (n = 27). Lesions were 4.1 ± 0.9 mm in diameter and 74 ± 50 mm long with a mean diameter stenosis of 91 ± 13%; 58.2% (n = 92) were occluded (core laboratory analysis). Device success was achieved in all patients. The rate of major adverse events was 0.6% (95% confidence interval: 0.0; 3.5) at 30 days, consisting of 1 target lesion revascularization. At 12 months, binary restenosis was present in 18.7% (n = 26) and target lesion revascularization was performed in 1.4% (n = 2, all clinically driven), resulting in a primary patency of 80.0% (95% confidence interval: 72.4, 85.8); no major target limb amputation occurred. Clinical improvement at 12 months, defined as improvement of at least 1 Rutherford class, was 95.3% (n = 130). The median walking distance per 6-minute walk test was 279 m at baseline and improved by 50 m at 30 days and by 60 m at 12 months; the visual analogue scale changed from 76.6 ± 15.6 at baseline to 80.0 ± 15.0 at 30 days and 78.6 ± 14.6 at 12 months. CONCLUSIONS: Our results confirmed the clinical effectiveness and safety of a paclitaxel-coated peripheral balloon dilatation catheter for the treatment of de novo and nonstented restenotic lesion of the superficial femoral and proximal popliteal artery in Chinese patients (NCT02912715).

Developing and optimizing a machine learning predictive model for post-thrombotic syndrome in a longitudinal cohort of patients with proximal deep venous thrombosis.

BACKGROUND: Post-thrombotic syndrome (PTS) is the most common chronic complication of deep venous thrombosis (DVT). Risk measurement and stratification of PTS are crucial for patients with DVT. This study aimed to develop predictive models of PTS using machine learning for patients with proximal DVT. METHODS: Herein, hospital inpatients from a DVT registry electronic health record database were randomly divided into a derivation and a validation set, and four predictive models were constructed using logistic regression, simple decision tree, eXtreme Gradient Boosting (XGBoost), and random forest (RF) algorithms. The presence of PTS was defined according to the Villalta scale. The areas under the receiver operating characteristic curves, decision-curve analysis, and calibration curves were applied to evaluate the performance of these models. The Shapley Additive exPlanations analysis was performed to explain the predictive models. RESULTS: Among the 300 patients, 126 developed a PTS at 6 months after DVT. The RF model exhibited the best performance among the four models, with an area under the receiver operating characteristic curves of 0.891. The RF model demonstrated that Villalta score at admission, age, body mass index, and pain on calf compression were significant predictors for PTS, with accurate prediction at the individual level. The Shapley Additive exPlanations analysis suggested a nonlinear correlation between age and PTS, with two peak ages of onset at 50 and 70 years. CONCLUSIONS: The current predictive model identified significant predictors and accurately predicted PTS for patients with proximal DVT. Moreover, the model demonstrated a nonlinear correlation between age and PTS, which might be valuable in risk measurement and stratification of PTS in patients with proximal DVT.

Internal iliac artery preservation during endovascular aortic repair using in situ laser fenestration.

OBJECTIVE: The purpose of the present study was to evaluate the technical and short-term clinical outcomes of internal iliac artery (IIA) reconstruction during endovascular aortic repair (EVAR) with in situ laser-assisted fenestration in cases of abdominal aortic aneurysm (AAA) in which the iliac artery is unfit for an internal branched device (IBD). METHODS: In the present single-institution retrospective study, we analyzed patients with AAAs who had undergone EVAR with in situ laser-assisted fenestration for IIA reconstruction between January 2018 and April 2021. The study included patients with iliac artery anatomy unfit for the use of commercial IBDs. The primary safety end point was freedom from major adverse events and unplanned reinterventions within 30 days. The primary efficacy end point was freedom from IIA restenosis, reintervention, and symptoms due to pelvic ischemia at 1 year after the procedure. RESULTS: A total of 20 patients requiring IIA reconstruction but with anatomy unfit for IBD placement were treated with in situ laser-assisted fenestration during EVAR for aortoiliac aneurysms during the study period. The mean age of our patients was 72 years, and 90% were men. The technical success rate was 100%. No patient had died within 30 days after the procedure. A suspicious IIA perforation had occurred in one patient, which was treated with an additional covered stent, for a primary safety end point of 95.0%. After a mean follow-up of 11 months, all except for one of the reconstructed IIAs were patent. Three patients reported symptoms of buttock claudication on the IIA occluded side at their 3-month follow-up after the procedure. However, these symptoms had subsided in two of these patients at 6 months. Type II endoleaks without sac expansion had occurred in two patients owing to retrograde blood flow from the inferior mesenteric artery and lumbar artery. Both patients were kept under close surveillance. The rate of freedom from major adverse events and unplanned reinterventions within 30 days (primary efficacy end point) was 86.3% at 1 year after procedure. CONCLUSIONS: In situ laser-assisted fenestration was found to be a safe and effective alternative method for IIA reconstruction during EVAR for aortoiliac aneurysms in patients with anatomy unfit for IBD.

MnO2 doped graphene nanosheets for carotid body tumor combination therapy.

Combination therapy is a cornerstone of tumor therapy, which can make up for the shortcomings of a single treatment and improve the cure rate of cancer. Near infrared induced therapy is widely applied owing to good accessibility, safety profile, and a wide range of effectiveness. Here, we use reduced nanographene oxide (rNGO) sheets with MnO2 nanoparticles as a photothermal agent to trigger further photodynamic therapy and chemotherapy. Doxorubicin (DOX, chemotherapeutic agent) and methyl blue (MB, photosensitizer) are loaded onto graphene oxide through a strong physical bond and rapidly released under high temperature. Besides, MnO2 nanoparticles can catalyze hydrogen peroxide inside of tumor and produce oxygen as a raw material for photodynamic therapy. In vitro experiments illustrated an effective ablation of PC-12 cells by rGO@MnO2/MB/Dox incubation combined with 808 nm near-infrared (NIR) laser radiation. For in vivo experiments in a model of carotid body tumor, rGO@MnO2/MB/Dox was locally injected, followed by 808 nm NIR laser irradiation. We found that the number of tumor cells was significantly reduced, the tumor volume was reduced, and there were no side effects. This may provide a new idea for the combination treatment of carotid body tumor.

Light-activated gold nanorods for effective therapy of venous malformation.

Gold nanorods have been studied extensively in the field of tumor therapy but have not been explored in the treatment of venous malformation (VM), which is a common vascular disease in clinic practice lacking an effective therapeutic approach. Herein we reported a nanoplatform of CD31 antibody-conjugated gold nanorods for the photothermal therapy of venous malformation. We immobilized CD31 antibodies on gold nanorods using standard 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDC)/N-hydroxysulfosuccinimide sodium (NHS) amine coupling strategies. Besides, a VM xenograft model suitable for testing therapeutic efficacy was established by isolating and culturing VM patient endothelial cells. In vitro experiments indicated that anti-CD31 gold nanorods (GNRs) combined with photothermal therapy (PTT) contributed to the suppression of proliferation and activation of the apoptosis pathway. For in vivo experiments, anti-CD31 GNRs were locally injected into VM xenograft models followed by near infrared (NIR) 808 â€‹nm laser irradiation. Notably, VM on the mice was destroyed and absorbed. The anti-CD31 GNRs nanoplatform may serve as a new strategy for the treatment of VM which is of good biosafety and high value of applications.

Exosomal miR-17-5p from adipose-derived mesenchymal stem cells inhibits abdominal aortic aneurysm by suppressing TXNIP-NLRP3 inflammasome.

BACKGROUND: Preclinical studies have suggested that adipose-derived mesenchymal stem cells (ADSCs) transplantation can suppress abdominal aortic inflammation and aneurysm expansion through paracrine factors. Yet, the mechanism of action is not fully understood. In the present study, we further examined the function and mechanism of ADSC-derived exosomes (ADSC-exos) and their microRNA-17-5p (miR-17-5p) on the abdominal aortic aneurysm (AAA) progression. METHODS: ADSC-exos were isolated and identified. DiR and PKH67 staining were used to trace ADSC-exo in vivo and in vitro. Raw264.7 cells were applied to perform in vitro experiments, while a murine AAA model induced using angiotensin II (Ang II) was used for in vivo testing. The expression level of miR-17-5p in macrophages and Ang II-treated macrophages after ADSC-exos treatment was determined using reverse transcription-quantitative polymerase chain reaction (RT-qPCR). The target relation between miR-17-5p and thioredoxin-interacting protein (TXNIP) was identified by a dual-luciferase reporter gene assay. Artificial activation and block of experiments of miR-17-5p and TXNIP were conducted to clarify their functions in inflammation during AAA progression. The severity of AAA between groups was assessed by maximal aorta diameter, AAA incidence, survival rate, and histological stainings. Besides, inflammasome-related proteins and macrophage pyroptosis were further evaluated using western blot, RT-qPCR, and enzyme-linked immunosorbent assay (ELISA). RESULTS: The ADSC-exos were isolated and identified. In vivo testing showed that ADSC-exos were mainly distributed in the liver. Meanwhile, in vitro experiments suggested that ADSC-derived exosomes were taken up by macrophages, while inside, ADSC-exos miR-17-5p decreased a TXNIP induced by Ang II by directly binding to its 3'-untranslated region (3'UTR). Furthermore, overexpression of miR-17-5p enhanced the therapeutic function of ADSC-exos on inflammation during AAA expansion in vivo, while its inhibition reversed this process. Finally, overexpressed TXNIP triggered macrophage pyroptosis and was alleviated by ADSC-derived exosomes in vitro. CONCLUSION: ADSC-exos miR-17-5p regulated AAA progression and inflammation via the TXNIP-NLRP3 signaling pathway, thus providing a novel insight in AAA treatment.

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

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

Percutaneous Mechanical Thrombectomy for Acute Limb Ischemia With Aorto-iliac Occlusion.

Background: To evaluate the outcomes of percutaneous mechanical thrombectomy (PMT) with Rotarex catheter in patients with acute lower limb ischemia (ALI) caused by aorto-iliac occlusion. Materials and Methods: Data of patients with ALI caused by aorto-iliac occlusion in our institutions from January 2010 and April 2020 were reviewed. The primary end point was limb salvage rate. The secondary end points included technical success rate, survival rate, complications after the operation and during the follow-up. Results: A total of 85 patients with ALI was diagnosed with aorto-iliac occlusion. Thirty-eight patients were treated by PMT with Rotarex catheter and enrolled in present study. Twenty-four were male (63.2%), and 14 were female (36.8%). The mean age was 66 years (range 28-83). All 38 patients were treated with PMT, with additional catheter directed thrombolysis (2/38, 5.3%), balloon angioplasty (8/38, 21.1%) and stent deployment (7/38, 18.4%). The mean procedure time was 123 ± 31 min. Seven patients (18.4%) underwent continuous renal replacement therapy. Two patients received major amputations (above the knee) and 2 patients died for renal insufficiency and heart failure during the hospital stay. Thirty-day survival rate was 94.7% and limb salvage was 94.4%. The mean follow-up time was 14.0 months (8-22 months). There was no major amputation and target artery occlusion occurred during the follow-up period. Conclusion: PMT with Rotarex catheter could be new option for acute aorto-iliac occlusion, leading to safe and effective results.

Efficacy and safety of preoperative embolization in carotid body tumor treatment: A propensity score matching retrospective cohort study.

BACKGROUND: To assess the efficacy and safety of preoperative embolization (PE) in patients with carotid body tumor (CBTs). METHODS: In a single-center retrospective cohort study, 127 patients underwent surgical resection of CBTs from January 2003 to December 2019. One-to-one propensity score matching was conducted between patients with or without PE. RESULTS: Thirty-two (25.2%) patients received PE. After propensity score matching, no statistically significant differences were found in the baseline characteristics of 28 patients in each group. Compared with NPE group, operative time and estimated blood loss (EBL) were significantly reduced in the PE group. The incidence of stroke, perioperative complications, intraoperative blood transfusion, vascular reconstruction, hospital stay, tumor recurrence, and all-cause mortality were not different between the PE and NPE group. CONCLUSIONS: Preoperative embolization was efficient and safe with a reduction of intraoperative blood loss and operative time during CBT resection.

Endovascular revascularisation versus surgical revascularisation in patients with lower limb atherosclerosis obliterans: a protocol for systematic review and meta-analysis with trial sequential analysis and meta-regression.

INTRODUCTION: The revascularisation strategy for lower limb atherosclerosis obliterans (ASO) remains controversial. In this meta-analysis, we will summarise existing evidence to compare the long-term and short-term outcomes between endovascular revascularisation and open revascularisation for patients with ASO. METHODS: Relevant randomised controlled trials (RCTs) and cohort studies are included from the following databases: MEDLINE/PubMed, Embase and the Cochrane Library. The last search time is 1 August 2022. Two reviewers will independently identify RCTs and cohort studies according to eligibility and exclusion criteria. The risk of bias of included cohort studies, and RCTs are assessed with the Newcastle-Ottawa Scale, Methodological Index of Non-randomized Studies and Cochrane Collaboration's tool, respectively. The primary outcomes include overall survival, amputation-free survival and 30-day mortality. TSA Beta Software V.0.9.5.10 is used to perform the trial sequential analysis for primary outcomes. The Grades of Recommendations, Assessment, Development and Evaluation (GRADE) tool will be used to assess the level of evidence for outcome from RCTs. Stata V.17.0 software is used to pool primary outcomes. ETHICS AND DISSEMINATION: This study will be disseminated through peer-reviewed journals or conference reports. No ethical approval requirements are required because the results presented in this study are conducted based on published data. PROSPERO REGISTRATION NUMBER: CRD42022359591.

Elastic compression stockings to prevent post-thrombotic syndrome in proximal deep venous thrombosis patients without thrombus removal.

OBJECTIVE: To evaluate the effectiveness of elastic compression stockings (ECS) in prevention of post-thrombotic syndrome (PTS) in patients suffering from proximal deep venous thrombosis (DVT) who did not undergo thrombus removal procedures. METHODS: In this randomized trial, patients with Iliofemoral venous thrombosis (IFDVT) and femoral-popliteal venous thrombosis who had not undergone thrombus removal procedures were screened at a single medical institution between December 2016 and June 2018. These patients were randomly assigned as an ECS group (wear ECS) and control group (not wear ECS). The primary end point was the incidence of PTS based on the Villalta scale at 24 months. The secondary end points included patient quality of life and symptom severity based on the VEINES-QoL/Sym questionnaire. Recurrent DVT in the same limb, compliance with ECS use, and other adverse events were also recorded. A logistic regression analysis was also performed to determine risk factors of PTS. RESULTS: Two hundred thirty-two patients were included in this study. One hundred thirteen patients were in the ECS group and 119 in the control group. The incidence of PTS was 42.0% in the ECS group and 57.8% in the control group at 24 months (risk ratio [RR], 0.726; 95% confidence interval [CI] 0.547-0.964; P = .024). The VEINES-QoL score was 63.7 ± 4.6 in the ECS group, which was higher than in the control group (60.6 ± 6.9; P < .001). Moreover, the VEINES-Sym scores revealed that patients in the ECS group reported better symptom relief than those in the control group (45.8 ± 5.1 vs 43.8 ± 6.1; P = .014). According to Logistic regression analysis of the entire cohort, IFDVT was a risk factor for PTS (RR, 2.253; 95% CI, 1.136-4.468) and high compliance with the use of ECS was protect factor (RR, 0.516; 95% CI, 0.277-0.961). CONCLUSIONS: These results suggest that ECS can prevent PTS in patients with IFDVT and femoral popliteal venous thrombosis who do not undergo thrombus removal procedures.

Meta-analysis suggests statins reduce mortality after abdominal aortic aneurysm repair.

OBJECTIVE: The necessity and efficacy of statin treatment for abdominal aortic aneurysm (AAA) remains controversial. This systematic review and meta-analysis was conducted to investigate the effects of statin therapy on the outcomes of patients with AAA. METHODS: The Cochrane library, Embase, and MedLine were searched comprehensively to identify relevant cohort studies and randomized controlled trials. The primary outcomes included short- and long-term mortality after AAA repair, and secondary outcomes included the incidence of perioperative cardiovascular complications, sac shrinkage after endovascular aneurysm repair, and the growth rate of the aneurysms. Short-term mortality was defined as all-cause 30-day or in-hospital postoperative mortality. Long-term mortality was defined as the all-cause mortality at the end of follow-up period (≥1 year). A random effects model was used to combine the results of included studies. Forest plots were created to show the pooled results of each outcome. RESULTS: One post hoc analysis of a randomized trial and 36 cohort studies (n = 134,290 patients) were included in this systematic review. The average score of included studies by Newcastle-Ottawa Scale was 7.76. Patients taking or not taking statin therapy were all diagnosed with unruptured AAA, and 59.9% of these patients were given statin therapy. Compared with statin nonusers, patients in statin therapy had significantly lower long-term mortality (odds ratio, 0.67; 95% confidence interval, 0.59-0.75; P < .001; I2 = 71.7%), and short-term mortality after aneurysmal repair (odds ratio, 0.51; 95% confidence interval, 0.36-0.73; P < .001; I2 = 81.4%). No significant difference was found between patients taking or not taking statin treatment on perioperative cardiovascular complications or sac shrinkage after endovascular aneurysm repair or growth rate of AAA under surveillance. CONCLUSIONS: These findings suggest that statin use is associated with a significant decrease in long- and short-term mortality in patients after AAA repair. Based on these results, statin therapy is worth being used in clinical practice for the management of AAA.

A meta-analysis of randomized controlled trials on therapeutic efficacy and safety of autologous cell therapy for atherosclerosis obliterans.

OBJECTIVE: Atherosclerosis obliterans (ASO) is a chronic occlusive arterial disease and the most common type of peripheral arterial disease. Current treatment options like medication and vascularization have limited effects for "no-option" patients, and stem cell therapy is considered a viable option, although its application and efficacy have not been standardized. The objective of this review was to assess the safety and efficacy of autologous stem cell therapy in patients with ASO. METHODS: We performed a literature search of published randomized controlled trials (RCTs) for patients with ASO receiving stem cell therapy without a revascularization option. PubMed, Embase, and the Cochrane Library were searched. This study was conducted by a pair of authors independently and audited by a third author. Data were synthesized with a random-effects model. RESULTS: A total of 630 patients in 12 RCTs were included. The results showed that cell therapy significantly improved total amputation (relative risk [RR], 0.64; 95% confidence interval [CI], 0.47-0.87; P = .004), major amputation (RR, 0.69; 95% CI, 0.50-0.94; P = .02), ankle-brachial index (mean difference [MD], 0.08; 95% CI, 0.02-0.13; P = .004), transcutaneous oxygen tension (MD, 11.52; 95% CI, 3.60-19.43; P = .004), and rest pain score (MD, -0.64; 95% CI, -1.10 to -0.17; P = .007) compared with placebo or standard care. However, current studies showed cell therapy was not superior to placebo or standard care in all-cause death (RR, 0.75; 95% CI, 0.41-1.36; P = .34) and ulcer size (MD, -8.85; 95% CI, -29.05 to 11.36; P = .39). The number of trials included was limited. Moreover, most trials were designed for "no-option" patients, and thus the results should be applied with caution to other patients with peripheral arterial disease. CONCLUSIONS: Patients with ASO can benefit from autologous cell therapy in limb salvage, limb blood perfusion, and rest pain alleviation.

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

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

Exosomes derived from adipose-derived stem cells overexpressing glyoxalase-1 protect endothelial cells and enhance angiogenesis in type 2 diabetic mice with limb ischemia.

BACKGROUND: Diabetic limb ischemia is a clinical syndrome and refractory to therapy. Our previous study demonstrated that adipose-derived stem cells (ADSCs) overexpressing glyoxalase-1 (GLO-1) promoted the regeneration of ischemic lower limbs in diabetic mice, but low survival rate, difficulty in differentiation, and tumorigenicity of the transplanted cells restricted its application. Recent studies have found that exosomes secreted by the ADSCs have the advantages of containing parental beneficial factors and exhibiting non-immunogenic, non-tumorigenic, and strong stable characteristics. METHODS: ADSCs overexpressing GLO-1 (G-ADSCs) were established using lentivirus transfection, and exosomes secreted from ADSCs (G-ADSC-Exos) were isolated and characterized to coculture with human umbilical vein endothelial cells (HUVECs). Proliferation, apoptosis, migration, and tube formation of the HUVECs were detected under high-glucose conditions. The G-ADSC-Exos were injected into ischemic hindlimb muscles of type 2 diabetes mellitus (T2DM) mice, and the laser Doppler perfusion index, Masson's staining, immunofluorescence, and immunohistochemistry assays were adopted to assess the treatment efficiency. Moreover, the underlying regulatory mechanisms of the G-ADSC-Exos on the proliferation, migration, angiogenesis, and apoptosis of the HUVECs were explored. RESULTS: The G-ADSC-Exos enhanced the proliferation, migration, tube formation, and anti-apoptosis of the HUVECs in vitro under high-glucose conditions. After in vivo transplantation, the G-ADSC-Exo group showed significantly higher laser Doppler perfusion index, better muscle structural integrity, and higher microvessel's density than the ADSC-Exo and control groups by Masson's staining and immunofluorescence assays. The underlying mechanisms by which the G-ADSC-Exos protected endothelial cells both in vitro and in vivo might be via the activation of eNOS/AKT/ERK/P-38 signaling pathways, inhibition of AP-1/ROS/NLRP3/ASC/Caspase-1/IL-1ß, as well as the increased secretion of VEGF, IGF-1, and FGF. CONCLUSION: Exosomes derived from adipose-derived stem cells overexpressing GLO-1 protected the endothelial cells and promoted the angiogenesis in type 2 diabetic mice with limb ischemia, which will be a promising clinical treatment in diabetic lower limb ischemia.