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Background: Angiogenesis is a hallmark of cancer, which is regulated by diverse factors, including long non-coding RNAs (lncRNAS). Our previous study showed that the long non-coding RNA H22954 inhibits tumor growth, albeit whether it is involved in the angiogenesis of cancer re-mains unknown. Objectives: This study aimed to investigate the role of lncRNA H22954 in angiogenesis of acute myeloid leukemia (AML) and the underlying molecular mechanism. Methods: Bioinformatics analysis was conducted to screen the targeted molecule of H22954. Western blot and ELISA analysis detected PDGFA protein expression, and RT-qPCR detected H22954 and PDGFA expression in cell lines and AML samples. Dual-luciferase reporter gene assay and half-life assay were applied to validate the relationship between H22954 and PDGFA. The functional experi-ment was conducted to investigate the role of H22954 in tube formation. Results: Overexpression of H22954 inhibited angiogenesis in mouse xenograft tumors and cultured acute myeloid leukemia (AML) cells. Bioinformatics analysis and luciferase assay revealed that H22954 targeted the 3’ untranslated region (UTR) of the platelet-derived growth factor subunit A (PDGFA) gene. In transfected cells, H22954 overexpression reduced PDGFA expression and protein levels. Tube formation was rescued following the addition of exogenous human PDGFA to the con-ditioned medium from cells overexpressing H22954. The expression of H22954 in K562 cells re-duced the half-life of PDGFA mRNA. Furthermore, H22954 expression was inversely correlated with PDGFA expression in patient samples. Conclusion: These findings indicate that H22954 inhibits angiogenesis in AML through the down-regulation of PDGFA expression. Administering recombinant lncRNA H22954 may be a therapeutic approach for patients with AML.

Deep venous thrombosis is one of the most common venous thromboembolic diseases and has a low cure rate and a high postoperative recurrence rate. Furthermore, emerging evidence indicates that microRNAs are involved in deep venous thrombosis. miR-296-5p is an important microRNA that plays a critical role in various cellular functions, and S100A4 is closely related to vascular function. miR-296-5p is downregulated in deep venous thrombosis patients, and its predicted target S100A4 is upregulated in deep venous thrombosis patients. Therefore, it was hypothesized that miR-296-5p may play a vital role in the development of deep venous thrombosis by targeting S100A4. An Ox-LDL-stimulated HUVEC and deep venous thrombosis mouse model was employed to detect the biological functions of miR-296-5p and S100A4. Dual luciferase reporter assays and pull-down assays were used to authenticate the interaction between miR-296-5p and S100A4. ELISA and Western blotting were employed to detect the protein levels of thrombosis-related factors and the endothelial-to-mesenchymal transition (EndMT)-related factors. The miR-296-5p levels were reduced, while the S100A4 levels were enhanced in deep venous thrombosis patients, and the miR-296-5p levels were negatively correlated with the S100A4 levels in deep venous thrombosis patients. miR-296-5p suppressed S100A4 expression by targeting the 3ʹ UTR of S100A4. MiR-296-5p knockdown accelerated ox-LDL-induced HUVEC apoptosis, oxidative stress, thrombosis-related factor expression, and EndMT, while S100A4 knockdown antagonized these effects in ox-LDL-induced HUVECs. S100A4 knockdown reversed the effect induced by miR-296-5p knockdown. Moreover, the in vivo studies revealed that miR-296-5p knockdown in deep venous thrombosis mice exacerbated deep venous thrombosis formation, whereas S100A4 knockdown had the opposite effect. These results indicate that elevated miR-296-5p inhibits deep venous thrombosis formation by inhibiting S100A4 expression. Both miR-296-5p and S100A4 may be potential diagnostic markers and therapeutic targets for deep venous thrombosis.

Normally, ipsilateral hemodynamic compromise of patients with carotid stenosis (CS) is subjectively identified by collateral circulation through cerebral angiography in the clinical process. It is unclear whether collaterals would linearly determine cerebral perfusion in CS patients. This study aimed to investigate the independent role of collateral circulation on cerebral perfusion in CS patients and the underlying interrelations among them. From 2017 to 2020, 124 CS patients who underwent carotid endarterectomy (CEA) with both preoperative CTP and digital substruction angiography (DSA) images were enrolled. Division of subgroups was based on degree of CS (50–70%, 70–90%, and near-occlusion (NO)) and grades of collateral circulation by DSA. Differences in CTP parameters between CS patients with different collateral circulation were analyzed. Among 124 CS patients, grades 2 and 3 were highly associated with carotid NO (n = 22, 32.35% and n = 22, 32.35%) compared with others ( P < 0.0001 ). The collateral circulation was found to have poor relation with cerebral perfusion parameters in all enrolled patients but significantly improved ipsilateral cerebral perfusion in patients with carotid NO ( P < 0.05 ). Linear hemodynamic compromise was barely related to degree of CS in lobes supplied by middle cerebral artery (MCA) except the frontal lobe ( P < 0.05 ). The grades of collateral circulation are positively associated with degree of CS while having nonsignificant effect on cerebral perfusion. Overall, severity of CS is poorly related to hemodynamic status while the perfectibility of compensation defined by grades of collateral circulation effectively alleviates ipsilateral cerebral perfusion deficit in carotid NO.

Mitochondrial autophagy, the elimination of damaged mitochondria through autophagy, contributes to neuron survival in cerebral ischemia. Long non-coding RNAs (lncRNAs)/microRNAs (miRNAs)/mRNAs are important regulatory networks implicated in various biological processes, including cerebral ischemia-reperfusion (I/R) injury. Therefore, this work clarifies a novel RGD1564534-mediated regulatory network on mitochondrial autophagy in cerebral I/R injury.Differentially expressed lncRNAs in cerebral I/R injury were predicted by bioinformatics analysis. Expression of RGD1564534 was examined in the established middle cerebral artery occlusion (MCAO) rats and oxygen glucose deprivation/reoxygenation (OGD/R)-exposed neurons. We conducted luciferase activity, RNA pull-down and RIP assays to illustrate the interaction among RGD1564534, miR-101a-3p and Dusp1. Gain- or loss-of-function approaches were used to manipulate RGD1564534 and Dusp1 expression. The mechanism of RGD1564534 in cerebral I/R injury was evaluated both in vivo and in vitro.RGD1564534 was poorly expressed in the MCAO rats and OGD/R-treated cells, while its high expression attenuated nerve damage, cognitive dysfunction, brain white matter and small vessel damage in MCAO rats. In addition, RGD1564534 promoted mitochondrial autophagy and inhibited NLRP3 inflammasome activity. RGD1564534 competitively bound to miR-101a-3p and attenuated its binding to Dusp1, increasing the expression of Dusp1 in neurons. By this mechanism, RGD1564534 enhanced mitochondrial autophagy, reduced NLRP3 inflammasome activity and suppressed the neuron apoptosis induced by OGD/R.Altogether, RGD1564534 elevates the expression of Dusp1 by competitively binding to miR-101a-3p, which facilitates mitochondrial autophagy-mediated inactivation of NLRP3 inflammasome and thus retards cerebral I/R injury.

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.

To evaluate the efficacy and safety of hybrid revascularization by carotid endarterectomy and endovascular intervention in the treatment of chronic internal carotid artery occlusion (ICAO).We performed a retrospective analysis of patients who received hybrid treatment for symptomatic chronic ICAO between December 2016 and December 2018. Fifty-six patients with long-segment ICAO were enrolled and divided into the short duration (1-3 months) and long ICAO duration (3 months) groups, and their clinical and angiographic data were analyzed.The mean duration was 106.8 ± 36.1 days from the date of ICAO diagnosis to revascularization. Totally, 10 patients (17.8%, n = 56) in the short duration group while no patients in the long duration group failed recanalization (n = 7). Perioperative complications included intraoperative thromboembolism in 1 (1.8%) patient and subarachnoid hemorrhage in 2 (3.6%) patients. Early phase postoperative hypertension was noted in 11 (19.6%) patients and cervical hemorrhage in 1 (1.8%) patient. No severe neurological deficits occurred. Overall, the 6-month modified Rankin score, Mini-mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA) scores in patients with successful recanalization significantly improved versus the baseline (P 0.05). After successful recanalization, the long duration group demonstrated more stents for revascularization compared with the short duration group (P 0.05). Five (10.8%) patients had recurrent transient ischemic attack, and 1 (2.2%) patient developed stroke in the successful revascularization group during 6 months of follow-up. ICA restenosis occurred in 5 (8.9%) patients and re-occlusion was noted in 1 (1.8%) patient.Hybrid operation may be feasible and effective for patients with symptomatic chronic complete ICAO according to our limited data. The original occlusion site from the carotid bifurcation and the duration of ICAO should be considered as independent indicators for successful recanalization as well as perioperative outcomes.

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.

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.

To evaluate the efficacy and safety of catheter-directed thrombolysis (CDT) in treating with inferior vena cava (IVC) thrombosis after filter implantation.A retrospective analysis of 13 patients with IVC thrombosis after filter implantation was conducted at our institution from June 2009 to June 2012. A total of 26 lower extremities were involved.IVC filters were implanted via right internal jugular vein. Then CDT was performed through small saphenous vein, popliteal vein or femoral vein. The dosage of urokinase was 0.6-1 million/day. The occlusive segment in IVC was managed with percutaneous transluminal angioplasty (PTA) and stenting.The obstructed IVC was re-opened after CDT in 11 cases. The average CDT time was 8.3 (7-13) days. PTA (n = 2) and stenting (n = 1) were performed. A total of 4 retrievable filters were planted and retrieved later successfully.No severe complications occurred. During the follow-ups, no clinically detetable sighs of pulmonary embolism were observed.CDT is effective, safe and feasible in the treatment of IVC thrombosis after filter implantation.