Diagnostic Value of Lower Extremity Venous Duplication via Digital Subtraction Angiography Guided Venography.

INTRODUCTION: Lower limb venous anomalies, including duplicated veins, are common and have significant impacts on the outcomes and efficacy of venous surgery. Digital subtraction angiography (DSA) guided venography, serving as the tertiary diagnostic option for venous disorders, offers valuable informations to clinical practitioners. PATIENTS AND METHODS: A retrospective study was conducted on 195 patients with suspected venous disease, evaluating 259 limbs with venography imaging. Two experienced interventional vascularists evaluated the images to determine the incidence and characteristics of variances in the femoral, popliteal, great saphenous, and small saphenous veins. Moreover, blood samples were collected to assess the safety of the venography procedure by monitoring changes in renal function. RESULT: Duplication variations were found in the lower limb veins, with the highest prevalence in the femoral vein (11.28%, 22/195), followed by the great saphenous vein (4.1%, 8/195), and the popliteal vein (1.54%, 3/195). No severe contrast agent allergies or postoperative complications were reported. No statistically significant differences were found in creatinine and urea levels pre- and post-operation for patients without duplication variations, those with duplication of the great saphenous, femoral, or popliteal vein (P < .05). CONCLUSION: DSA-guided venography is effective in identifying venous variations in lower limb disease. DFV is the most common recurrent vein, while DPV is the least. Adequate preparation ensures safety, high spatial resolution, dynamic imaging, and low tissue interference.

ADAMTS13 inhibits H2O2-induced human venous endothelial cell injury to attenuate deep-vein thrombosis by blocking the p38/ERK signaling pathway.

Deep vein thrombosis (DVT) is a common complication in hematologic malignancies and immunologic disorders. Endothelial cell injury and dysfunction comprise the critical contributor for the development of DVT. A disintegrin and metalloproteinase with thrombospondin motifs 13 (ADAMTS13), a plasma metalloprotease that cleaves von Willebrand factor, acts as a critical regulator in normal hemostasis. This study was aimed to explore the role of ADAMTS13 in endothelial cell injury during DVT and the possible mechanism. First, human umbilical vein endothelial cells (HUVECs) were exposed to hydrogen peroxide (H2O2). Then, the mRNA and protein expressions of ADAMTS13 were evaluated with the reverse transcription-quantitative polymerase chain reaction and western blot. After treatment with recombinant ADAMTS13 (rADAMTS13; rA13), the viability and apoptosis of H2O2-induced HUVECs were assessed by cell counting kit-8 assay and terminal-deoxynucleoitidyl transferase-mediated nick end labeling staining. In addition, the levels of prostaglandin F1-alpha, endothelin-1, and reactive oxygen species were detected using the enzyme-linked immunosorbent assay and dichloro-dihydro-fluorescein diacetate assay. The expressions of proteins related to p38/extracellular signal-regulated kinase (ERK) signaling pathway were estimated with the western blot. Then, p79350 (p38 agonist) was used to pretreat cells to analyze the regulatory effects of rA13 on p38/ERK signaling in H2O2-induced HUVEC injury. The results revealed that ADAMTS13 expression was significantly downregulated in H2O2-induced HUVECs. The reduced viability and increased apoptosis of HUVECs induced by H2O2 were revived by ADAMTS13. ADAMTS13 also suppressed the oxidative stress in HUVECs after H2O2 treatment. Besides, ADAMTS13 was found to block p38/ERK signaling pathway, and p79350 reversed the impacts of ADAMTS13 on the damage of HUVECs induced by H2O2. To sum up, ADAMTS13 could alleviate H2O2-induced HUVEC injury through the inhibition of p38/ERK signaling pathway.

Ambient RNAs removal of cortex-specific snRNA-seq reveals Apoe+ microglia/macrophage after deeper cerebral hypoperfusion in mice.

BACKGROUND: Ambient RNAs contamination in single-nuclei RNA sequencing (snRNA-seq) is a challenging problem, but the consequences of ambient RNAs contamination of damaged and/or diseased tissues are poorly understood. Cognitive impairments and white/gray matter injuries are characteristic of deeper cerebral hypoperfusion mouse models induced by bilateral carotid artery stenosis (BCAS), but the molecular mechanisms still need to be further explored. More importantly, the BCAS mice can also offer an excellent model to examine the signatures of ambient RNAs contamination in damaged tissues when performing snRNA-seq. METHODS: After the sham and BCAS mice were established, cortex-specific single-nuclei libraries were constructed. Single-nuclei transcriptomes were described informatically by the R package Seurat, and ambient RNA markers of were identified in each library. Then, after removing ambient RNAs in each sample using the in silico approaches, the combination of CellBender and subcluster cleaning, single-nuclei transcriptomes were reconstructed. Next, the comparison of ambient RNA contamination was performed using irGSEA analysis before and after the in silico approaches. Finally, further bioinformatic analyses were performed. RESULTS: The ambient RNAs are more predominant in the BCAS group than the sham group. The contamination mainly originated from damaged neuronal nuclei, but could be reduced largely using the in silico approaches. The integrative analysis of cortex-specific snRNA-seq data and the published bulk transcriptome revealed that microglia and other immune cells were the primary effectors. In the sequential microglia/immune subgroups analysis, the subgroup of Apoe+ MG/Mac (microglia/macrophages) was identified. Interestingly, this subgroup mainly participated in the pathways of lipid metabolism, associated with the phagocytosis of cell debris. CONCLUSIONS: Taken together, our current study unravels the features of ambient RNAs in snRNA-seq datasets under diseased conditions, and the in silico approaches can effectively eliminate the incorrected cell annotation and following misleading analysis. In the future, snRNA-seq data analysis should be carefully revisited, and ambient RNAs removal needs to be taken into consideration, especially for those diseased tissues. To our best knowledge, our study also offers the first cortex-specific snRNA-seq data of deeper cerebral hypoperfusion, which provides with novel therapeutic targets.

Retrospective Analysis of the Safety and Efficacy of AngioJet Rheolytic Thrombectomy for Acute Pulmonary Embolism: A Single-Center Study.

BACKGROUND: To investigate the efficacy, safety, and feasibility of AngioJet Rheolytic Thrombectomy (ART) in the treatment of acute pulmonary embolism (APE). METHODS: Twelve patients with intermediate- or high-risk APE received ART and were followed up for 6-32 months. The technical success rate, clinical success rate, mortality, complication, and ancillary and laboratory tests before and after operation were analyzed retrospectively. RESULTS: The technical and clinical success rates of ART were both 91.67% (11/12). Except for the patient who died of heart failure during the operation, the rest of patients had no serious complications. After operation, arterial oxygen partial pressure increased while hemoglobin and troponin decreased (P < 0.05). All patients were free of recurrence of APE after 6-32 months of follow-up. Pulmonary artery thrombosis significantly reduced or disappeared. CONCLUSIONS: ART is an effective treatment for intermediate- and high-risk APE. It quickly clears the main pulmonary artery thrombus, relieves pulmonary hypertension, and improves the long-term prognosis of patients.

Midterm Results of Drug-Coated Balloon Alone or Combined with Rotarex Thrombectomy Device for Treatment of Subacute Femoropopliteal Artery Thrombotic Occlusion.

BACKGROUND: This retrospective multicenter study aimed to compare the midterm results of the Rotarex rotational thrombectomy device combined with drug-coated balloon (DCB) and DCB-alone for the treatment of subacute femoropopliteal artery thrombotic occlusion. METHODS: All patients (74, aged 70.1 ± 9.3 years) were nonrandomized and divided into 2 groups based on treatment strategy between 2018 and 2020. Intraoperative technical success (defined as <30% residual stenosis), dissection types and bailout-stenting rates were assessed. Ankle-brachial index (ABI), primary patency (PP, restenosis <50%) and freedom from clinically driven target lesion reintervention (CD-TLR) were documented at follow-up. RESULTS: Among them, 35 patients were treated with the Rotarex catheter combined with DCB while 39 patients underwent DCB-alone. The-overall technical success rate was 100%. Patients in the Rotarex + DCB group showed lower rate of bailout stenting than those in the DCB alone group (22.9% vs. 59.0%; P = 0.01). ABI at discharge was significantly higher in both groups. Mean follow-up time was 18.5 ± 3.4 months; 62 patients completed Doppler ultrasound investigation while 12 patients were censored. According to Kaplan-Meier analysis, the estimated PP was 82.0 ± 6.7% in the Rotarex + DCB group, whereas a significantly lower rate in the DCB alone group (60.9 ± 8.3%, P = 0.04). In addition, the freedom from CD-TLR rate was 82.9 ± 6.4% in the Rotarex + DCB group and 61.5 ± 7.8% in the DCB-alone group (P = 0.04). CONCLUSIONS: These initial data indicate that the Rotarex thrombectomy device combined with DCB is an effective choice for the treatment of subacute femoropopliteal artery thrombotic occlusion compared to DCB-alone. The combined procedure had superior midterm results.

Berberine promotes the viability of random skin flaps via the PI3K/Akt/eNOS signaling pathway.

Random skin flaps are often used in reconstruction operations. However, flap necrosis is still a common postoperative complication. Here, we investigated whether berberine (C20 H19 NO5 , BBR), a drug with antioxidant activity, improves the survival rate of random flaps. Fifty-four rats were divided into three groups: control, BBR and BBR + L -NAME groups (L -NAME, L -NG -Nitro-arginine methyl ester). The survival condition and the percentage of survival area of the flaps were evaluated on the seventh day after surgery. After animals were sacrificed, angiogenesis, apoptosis, oxidative stress and inflammation levels were assessed by histological and protein analyses. Our findings suggest that berberine promotes flap survival. The level of angiogenesis increased; the levels of oxidative stress, inflammation and apoptosis decreased; the levels of phosphoinositide 3-kinase (PI3K), phospho-Akt (p-Akt) and phospho-endothelial nitric oxide synthase (p-eNOS) increased in the flap tissue; and L -NAME reversed the effects of berberine on random skin flaps. Statistical analysis showed that the BBR group results differed significantly from those of the control and the BBR + L -NAME groups (p < .05). Our results confirm that berberine is an effective drug for significantly improving the survival rate of random skin flaps by promoting angiogenesis, inhibiting inflammation, attenuating oxidative stress, and reducing apoptosis through the PI3K/Akt/eNOS signaling pathway.

Efficacy and Safety of Absorb Everolimus-Eluting Bioresorbable Vascular Scaffold in Peripheral Artery Disease: A Single-Arm Meta-Analysis.

PURPOSE: This study aimed to evaluate the benefits and risks of patients with peripheral artery disease (PAD) treated with Absorb everolimus-eluting bioresorbable vascular scaffold (BVS) by analyzing all the published studies on the clinical characteristics of patients with PAD. MATERIALS AND METHODS: PubMed, Embase, and the Cochrane Library were searched for relevant studies. Efficacy, safety, and basic characteristics were analyzed. RESULTS: Four studies were included in meta-analysis, including a total number of 155 patients with PAD. The pooled overall primary patency, freedom from target lesion revascularization (TLR), symptom resolution, and wound healing were 90%, 96%, 94%, and 86%, respectively. The pooled perioperative complication and all-cause mortality were 4% and 9%, respectively. Preoperative total occlusion was detected in 43 of 192 lesions (22%). The mean lesion length was 27.26 mm. In terms of comorbidities, the pooled percentage of hypertension, hyperlipidemia, diabetes mellitus, coronary artery disease, chronic kidney disease history, and smoking were 65%, 74%, 49%, 43%, 20%, and 57%, respectively. CONCLUSION: Among these studies, hypertension, hyperlipidemia, and diabetes mellitus were the most common comorbidities in patients with PAD. The Absorb everolimus-eluting BVS was safe and showed the favorable clinical outcomes in both patency and TLR, especially in infrapopliteal disease with heavy calcification. The conclusions of this meta-analysis still needed to be verified by more relevant studies with more careful design, more rigorous execution, and larger sample size.

Effect of memantine on the survival of an ischemic random skin flap and the underlying mechanism.

BACKGROUND: Skin flap transplantation is a common wound repair method in orthopedic surgery, but skin flap necrosis remains problematic. Memantine, an excitatory amino acid receptor antagonist, is currently used in the treatment of moderate to severe Alzheimer's disease, due to its ability to promote angiogenesis and reduce oxidative stress. This study investigated the effect of memantine on the survival of random skin flaps in Sprague-Dawley (SD) rats. MATERIALS AND METHODS: Thirty six male SD rats were divided into control, high-dose (20 mg/kg per day), and low-dose (10 mg/kg per day) groups and underwent a McFarland flap procedure. Seven days later, the survival of the flap was evaluated, The microvascular density and neutrophil density were measured by hematoxylin and eosin staining. Lead angiography was used to detect angiogenesis, and laser Doppler was used to detect blood perfusion. Expression levels of vascular endothelial growth factor (VEGF), interleukin (IL)-1ß, IL-6, tumor necrosis factor (TNF)-α, Toll-like receptor (TLR) 4, nuclear factor kappa B(NF-κB) and Mitogen-activated protein kinase（MAPK）were detected by immunohistochemistry. Oxidative stress was evaluated by measuring the levels of malondialdehyde (MDA) and superoxide dismutase (SOD). RESULTS: Compared with the control group, the flap survival area of memantine group, especially the high-dose group, was larger, VEGF expression, microvascular density, angiogenesis, blood perfusion, and superoxide dismutase in the flap were higher in the Memantine-H group than in the Memantine-L and control groups (P < 0.01). In addition, levels of neutrophil density, IL-1ß, IL-6, TNF-α, TLR4, NF-κB, MAPK and malondialdehyde decreased significantly in the Memantine-H group (P < 0.01). CONCLUSIONS: Memantine can promote the survival of skin flap in rats by improving the blood supply, promoting angiogenesis, inhibiting the inflammatory response, and reducing ischemia-reperfusion injury.

A Systematic Review of Total Thoracic Endovascular Aortic Repair in Treatment of Kommerell Diverticulum Combined with Right-Sided Aortic Arch.

Kommerell diverticulum (KD) combined with right-sided aortic arch (RAA) and aberrant left subclavian artery (ALSA) are rare and limited to a few case reports and small series. Thoracic endovascular aortic repair (TEVAR), which is mini-invasive, is widely utilized in complicated aortic disease. We performed a systematic review of the literature to identify all patients who underwent endovascular repair for KD in terms of technical feasibility and procedural outcomes. Published and accepted studies only in English as well as article reference lists were searched and extracted to assess case series reporting solely TEVAR in KD patients. There were 28 patients with KD/RAA identified from 19 studies. All of them underwent endovascular technique for KD exclusion and the median age was 69 years (range 39-83 years). Hypertension (n=17) was the most common comorbidity in this cohort, followed by diabetes mellitus (n=3), hyperlipidemia (n=3), and smoking (n=3). The presenting symptoms were dysphagia (n=8, 29%), intermittent back pain (n=4, 14%), and acute aortic dissection (n=6, 21%), while asymptomatic was found in 9 patients (n=9, 32%). A technical success rate of 100% was reported associated with various managements of ALSA, proximal embolization (n=19, 68%), in-situ revascularization (n=3, 11%), and left carotid-subclavian bypass (n=3, 11%). All patients survived without severe complications and were discharged home within less than 14 days. The mean follow-up time was 9.3 months, patency was found in all patients, thrombosis and distinct shrinkage of KD aneurysm as indicated by CT-scans were noted (n=20, 71%), and type II endoleak was found in only 4 patients (n=4, 14%). TEVAR appears to be safe and offers favorable results, but it still needs substantial evidence to support routine use in KD. TEVAR is an alternative to open repair in selected cases, but it needs further investigation in a large cohort.

Transvenous Embolization of Carotid Cavernous Fistula through Inferior Petrosal Sinus with Detachable Coils and Ethylene Vinyl Alcohol Copolymer.

Carotid cavernous fistula (CCF) is a rare disease caused by abnormal communications between the internal carotid artery (direct fistula) or meningeal branches of the external carotid artery (indirect fistula) and the cavernous sinus (CS). Trauma is the most common cause of CCF. The clinical presentation of CCF is closely related to the venous drainage pattern. Orbital and neuro-ophthalmological symptoms are the most common clinical presentation of CCF with drainage through the superior ophthalmic vein (SOV). Endovascular embolization by arterial or venous approaches is the most common management of CCF. Transvenous embolization using detachable coils and ethylene-vinyl alcohol copolymer (EVOH) is an alternative method for the treatment of CCF. Endovascular embolization offers different options to treat CCF by minimally invasive approach decreasing morbidity and residual fistulas. The purpose of this article is to report our treatment experiences via the inferior petrosal sinus (IPS), and immediate-term outcomes of endovascular embolization of CCF by using detachable coils and EVOH.

MiR-489 inhibits proliferation and apoptosis of glioblastoma multiforme cells via regulating TWIST1 expression.

PURPOSE: To investigate the influences of micro ribonucleic acid (miR)-489 on the proliferation and apoptosis of glioblastoma multiforme (GBM) and the relationship between miR-489 and twist-related protein 1 (TWIST1) expression. METHODS: The GBM cells were isolated and cultured in vitro, and then transfected with miR-489 inhibitor, miR-489 mimics and miR-negative control (NC) or TWIST1-small interfering RNA (siRNA) and TWIST1-NC. The expression levels of miR-489 and TWIST1 gene in the cells were measured via quantitative reverse transcription-polymerase chain reaction (qRT-PCR), and the proliferative capacity of cells in each group was detected by cell counting kit-8 (CCK-8) assay. Besides, the target gene TWIST1 of miR-489 was predicted to construct the luciferase reporter gene vectors of TWIST1 containing miR-489 target sites. RESULTS: The expression level of miR-489 in GBM tissues and GBM cells isolated and cultured in vitro was remarkably lower than that in normal tissues and cells (p<0.01). The proliferative capacity of GBM cells was enhanced notably after inhibiting the expression of miR-489 (p<0.01), while it was obviously weakened by overexpressed miR-489 or TWIST1-siRNA (p<0.01). Moreover, the apoptosis rate was increased from 2.3±0.4% to 19.6±1.2% following miR-489 overexpression. TWIST1-siRNA could markedly down-regulate the expression level of TWIST1 (p<0.01) but evidently up-regulate the protein expression levels of Caspase-3 and Caspase-8 (p<0.01). The results of luciferase reporter assay manifested that miR-489 mimics significantly repressed TWIST1 (p<0.01). CONCLUSIONS: MiR-489 can repress the proliferation and promote the apoptosis of glioma cells by targeting TWIST1.

microRNA-331-3p maintains the contractile type of vascular smooth muscle cells by regulating TNF-α and CD14 in intracranial aneurysm.

Dysfunction of vascular smooth muscle cells (VSMCs) may be linked to intracranial aneurysm (IA) formation. VSMCs possess a phenotypic plasticity, capable of changing from a mature, contractile to a less differentiated, synthetic phenotype. In this study, we identify a microRNA candidate miR-331-3p that participates in regulating differentiation properties of VSMCs. The expression of TNF-α and CD14 was quantified in IA wall tissues obtained from 96 IA patients and their associations with clinicopathological features of IA were assessed. Then the interactions between miR-331-3p, TNF-α and CD14 were evaluated by determination of luciferase activity. Differentiated properties of VSMCs were assessed from phenotypic markers of contractile VSMCs, a-SMA and E-cadherin, and of synthetic VSMCs, ICAM-1, MCP-1, IL-6, MMP-2 and MMP-9. Rat IA models by ligation of left carotid artery and left renal artery and histological analysis of induced IAs were performed. The TNF-α and CD14 was highly expressed in IA wall tissues and associated with the type and diameter of aneurysm. Depletion of TNF-α or CD14 retarded VSMC apoptosis and transformation to the synthetic type but facilitated cell proliferation. Elevations in miR-331-3p, a direct negative regulator of both TNF-α and CD14, also reduced VSMC apoptosis and prevented VSMCs from synthetic type and increase their proliferation. Furthermore, miR-331-3p was demonstrated to inhibit the formation of IA by down-regulating TNF-α and CD14 in vivo. In conclusion, miR-331-3p maintains the contractile type of VSMCs, thus possibly inhibiting the progression of IA. These findings provide potential new strategies for the clinical treatment of IA.

Thoracic endovascular aortic repair in penetrating aortic ulcer combined with isolated left vertebral artery: A case report.

RATIONALE: Penetrating aorta ulcer (PAU) with isolated left vertebral artery (ILVA) is a rare condition, accounting for no more than 1% of all kinds of aorta diseases. And traditional treatment was open surgery with total arch replacement by elephant trunk. Here, we report a case of PAU combined with ILVA managed by thoracic endovascular aortic repair (TEVAR) technique. PATIENT CONCERNS: A 65-year-old male with chronic hypertension and Nicotine abuse underwent intermittent back pain for 2 years and aggravated a bit for 1 week. DIAGNOSES: Preoperative computed tomography angiogram (CTA) indicated PAU combined with ILVA. INTERVENTIONS: TEVAR was performed for PAU following with retrograde in situ fenestration and chimney technique for revascularization of ILVA and left subclavian artery (LSA), respectively. OUTCOMES: The operation was successfully and the patient was discharged from hospital after 1 week of treatment. Postoperatively, the images of CTA illustrated the patency of aorta, ILVA, and LSA without obvious endoleak. Besides, no ischemia attack or other relative syndromes were detected at 6-months follow-up. LESSONS: This case demonstrates that TEVAR is an alternative to elephant trunk especially for PAU with ILVA. And it also showed the precise exposure of ILVA and necessity to reconstruct ILVA during TEVAR operation in order to reduce the occurrence of ischemia attack.

Detrimental Role of miRNA-144-3p in Intracerebral Hemorrhage Induced Secondary Brain Injury is Mediated by Formyl Peptide Receptor 2 Downregulation Both In Vivo and In Vitro.

Although microRNA-144-3p (miRNA-144-3p) has been shown to suppress tumor proliferation and invasion, its function in intracerebral hemorrhage (ICH)-induced secondary brain injury (SBI) remains unclear. Thus, this study was designed to investigate the role of miRNA-144-3p in ICH. To accomplish this, we used adult male Sprague-Dawley rats to establish an in vivo ICH model by injecting autologous blood, while cultured primary rat cortical neurons were exposed to oxyhemoglobin (OxyHb) to mimic ICH in vitro. To examine the role of miRNA-144-3p in ICH-induced SBI, we used an miRNA-144-3p mimic and inhibitor both in vivo and in vitro. Following ICH induction, we found miRNA-144-3p expression to increase. Additionally, we predicted the formyl peptide receptor 2 (FPR2) to be a potential miRNA-144-3p target, which we validated experimentally, with FPR2 expression downregulated when miRNA-144-3p was upregulated. Furthermore, elevated miRNA-144-3p levels aggravated brain edema and neurobehavioral disorders and induced neuronal apoptosis via the downregulation of FPR2 both in vivo and in vitro. We suspected that these beneficial effects provided by FPR2 were associated with the PI3K/AKT pathway. We validated this finding by overexpressing FPR2 while inhibiting PI3K/AKT in vitro and in vivo. In conclusion, miRNA-144-3p aggravated ICH-induced SBI by targeting and downregulating FPR2, thereby contributing to neurological dysfunction and neural apoptosis via PI3K/AKT pathway activation. These findings suggest that inhibiting miRNA-144-3p may offer an effective approach to attenuating brain damage incurred after ICH and a potential therapy to improve ICH-induced SBI.