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.

Human umbilical cord mesenchymal stem cell-derived exosomes promote microcirculation in aged diabetic mice by TGF-ß1 signaling pathway.

BACKGROUND: Microvascular dysfunction is one of the most common pathological characteristics in Type 2 diabetes. Human mesenchymal stem cell-derived exosomes (hUCMSCs-Exo) have diverse functions in improving microcirculation; however, the molecular mechanism of hUCMSCs-Exo in regulating burn-induced inflammation is not well understood. METHODS: hUCMSCs-Exo were extracted by hypervelocity centrifugation method, and exosome morphology was observed by transmission electron microscopy, exosome diameter distribution was detected by particle size analysis, and exosome specific proteins were identified by Western blot.2. DB/DB mice were randomly divided into exosomes group and PBS group. Exosomes and PBS were injected into the tail vein, respectively, and the calf muscle tissue was taken 28 days later. 0.5% Evans blue fluorescence assessment microvascular permeability. The expression of CD31 was detected by immunofluorescence.The morphology and function of microvessels in muscle tissue of lower limbs was evaluated by transmission electron microscopy.3. TMT proteomics was used to detect the changes of differential protein expression in lower limb muscle tissues of the PBS group and the exosome group, and data analysis was performed to screen key signal molecules and their involved biological pathways. Key signal molecules CD105 were verified by Western blot. The expression of TGF-ß1 in exosomes were evaluated by Western blot. RESULTS: Electron microscopy showed that hUCMSCs-Exo presented a uniform vesicle structure, and NTA showed that its diameter was about 160 nm. Western blot showed positive expression of specific proteins CD9, CD81 and TSG101 on exosomes.2. There is no significant change in blood glucose and body weight before and after the exosome treatment. The exosome group can significantly reduce the exudation of Evans blue. Compared with the PBS group. Meanwhile, CD31 immunofluorescence showed that the red fluorescence of exosome treatment was significantly increased, which was higher than that of PBS group. Transmission electron microscopy showed smooth capillary lumen and smooth and complete surface of endothelial cells in the exosome group, while narrow capillary lumen and fingerlike protrusion of endothelial cells in the PBS group.3.Quantitative analysis of TMT proteomics showed that there were 82 differential proteins, including 49 down-regulated proteins and 33 up-regulated proteins. Go enrichment analysis showed that the differential proteins were involved in molecular function, biological process, cell components,among which CD105 was one of the up-regulated proteins. Through literature search, CD105 was found to be related to endothelial cell proliferation. Therefore, this study verified the changes of CD105 in the exosome group, and it was used as the mechanism study of this study. 4. Western blot analysis showed that the expression of CD105 protein in lower limb muscle tissue of exosome group was significantly increased compared with that of PBS group. Based on the fact that CD105 is a component of the TGF-ß1 receptor complex and exosomes are rich in growth factors and cytokines, this study further examined the expression of TGF-ß1 in exosomes, and the results showed that exosomes had high expression of TGF-ß1. CONCLUSION: By improving the integrity of microvascular endothelial cells, hUCMSCs-Exo can improve the permeability of microvessels in diabetic lower muscle tissue, further promote the proliferation of lower limb muscle cells and inhibit the apoptosis of tissue cells. The mechanism may be associated with exosomes rich in TGF-ß1, which is likely to promote endothelial cell proliferation and improve permeability through binding to the endothelial CD105/TßR-II receptor complex, while promoting angiogenesis and protecting skeletal muscle cells from apoptosis.

Hydroxysafflor yellow A inhibits endothelial cell ferroptosis in diabetic atherosclerosis mice by regulating miR-429/SLC7A11.

CONTEXT: Ferroptosis may play an essential role in lipid peroxidation and endothelial dysfunction of aortic endothelial cells (ECs) in type 2 diabetes mellitus (T2DM) with atherosclerosis (AS). Hydroxysafflor yellow A (HSYA) has shown substantial antioxidant stress and anti-ferroptosis. OBJECTIVE: This study confirms whether HSYA improves symptoms in a mouse model of T2DM/AS and elucidates the underlying mechanisms. MATERIALS AND METHODS: ApoE-/- mice were fed with high fat combined with 30 mg/kg streptozotocin to establish a T2DM/AS model. Then mice were treated with intraperitoneal injections of 2.25 mg/kg HSYA for 12 weeks. Human Umbilical Vein Endothelial cells (HUVEC) induced by 33.3 mM d-glucose +100 µg/mL ox-LDL were used to construct a high lipid and high glucose cell model treated with 25 µM HSYA. The changes in oxidative stress- and ferroptosis-related markers were detected, and the regulatory effect of HSYA on the miR-429/SLC7A11 was also verified. Normal ApoE-/- mice or HUVEC cells were used as the control group. RESULTS: HSYA effectively reduced atherosclerotic plaque formation in the T2DM/AS mouse model and inhibited HUVEC ferroptosis, such as upregulating GSH-Px, SLC7A11 and GPX4, but inhibited ACSL4. Furthermore, HSYA also downregulated the expression of miR-429, which further regulated SLC7A11 expression. After miR-429 mimic or SLC7A11 siRNA transfection in the HUVEC, the antioxidative stress and anti-ferroptosis effects of HSYA were significantly abolished. CONCLUSIONS: HSYA is expected to become an important health drug to prevent the occurrence and development of T2DM/AS.

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.

GATA6 Inhibits Neuronal Autophagy and Ferroptosis in Cerebral ischemia-reperfusion Injury Through a miR-193b/ATG7 axis-dependent Mechanism.

Ferroptosis is a newly described form of regulated necrotic cell death, which is engaged in the pathological cell death related to stroke, contributing to cerebral ischemia-reperfusion (I/R) injury. Therefore, we performed this study to clarify the role of GATA6 in neuronal autophagy and ferroptosis in cerebral I/R injury. The cerebral I/R injury-related differentially expressed genes (DEGs) as well as the downstream factors of GATA6 were predicted bioinformatically. Moreover, the relations between GATA6 and miR-193b and that between miR-193b and ATG7 were evaluated by chromatin immunoprecipitation and dual-luciferase reporter assays. Besides, neurons were treated with oxygen-glucose deprivation (OGD), followed by overexpression of GATA6, miR-193b, and ATG7 alone or in combination to assess neuronal autophagy and ferroptosis. At last, in vivo experiments were performed to explore the impacts of GATA6/miR-193b/ATG7 on neuronal autophagy and ferroptosis in a rat model of middle cerebral artery occlusion (MCAO)-stimulated cerebral I/R injury. It was found that GATA6 and miR-193b were poorly expressed in cerebral I/R injury. GATA6 transcriptionally activated miR-193b to downregulate ATG7. Additionally, GATA6-mediated miR-193b activation suppressed neuronal autophagy and ferroptosis in OGD-treated neurons by inhibiting ATG7. Furthermore, GATA6/miR-193b relieved cerebral I/R injury by restraining neuronal autophagy and ferroptosis via downregulation of ATG7 in vivo. In summary, GATA6 might prevent neuronal autophagy and ferroptosis to alleviate cerebral I/R injury via the miR-193b/ATG7 axis.

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.

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.

Peri-procedural variables and outcomes of long-period hemodynamic instability after carotid artery angioplasty and stenting.

OBJECTIVES: The aim of this study is to identify the peri-procedural risk factors and outcomes of hemodynamic instability (HI) after carotid artery stenting (CAS). METHODS: A single-center, retrospective study was performed in 168 patients who underwent CAS procedure between September 2017 and September 2020. The presence of HI, as defined by hypertension (systolic blood pressure >160 mmHg), hypotension (systolic blood pressure <90 mmHg), and/or bradycardia (heart rate <60 bpm), was recorded. Long-period HI was defined as persistent HI lasting more than 24 h. Patient demographics, comorbidities, peri-procedural variables, and risk factors were recorded. Clinical outcomes including cerebral hyperperfusion syndrome, hemorrhage, transient ischemic attack (TIA), stroke, myocardial infarction, and mortality within 30 days of the procedure were evaluated. Logistic regression was used to analyze the independent risk factors of long-period HI following CAS. RESULTS: Among 168 patients (mean age, 68.2 ± 8.3 years; 81.5% male), the frequency of post-procedural long-period HI was noted in 42 patients (25.0%). Male was prone to experience HI (odds ratio, 9.156, p = 0.021). Aggressive inflation pressure (>7 atm) and 5 mm balloon for pre-dilatation were risk factors of long-period HI (OR, 7.372, p = 0.035; OR, 3.527, p = 0.023). Intraoperative peak blood pressure and larger-sized stents remained independent predictors for the development of HI (OR, 1.043, p = 0.027, and OR, 1.973, p = 0.015). Patients with prolonged HI were more likely to suffer TIA and stroke compared to other patients and significant difference was found in the occurrence of TIA (p < 0.05). Non-significance was found in mortality rate and other outcomes. CONCLUSIONS: CAS-induced HI occurs in a considerable percentage while several peri-procedural variables are determined as independent predictors to develop long-period HI. Patients with prolonged HI are associated with increased risk of neurologic events and thus standardized intervention as well as management of long-period HI are of critical importance during clinical process.

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.

RGD1564534 represses NLRP3 inflammasome activity in cerebral injury following ischemia-reperfusion by impairing miR-101a-3p-mediated Dusp1 inhibition.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

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.

Nomogram-Based Risk Model of Small (≤5 mm) Intracranial Aneurysm Rupture in an Eastern Asian Study.

Background and Purpose: Risk stratification of small unruptured intracranial aneurysms (IAs) (< =5 mm) is important for clinical decision-making and management. The aim of this study was to develop an individualized rupture risk model for small IAs in an eastern Asian population. Methods: This study retrospectively enrolled 343 patients with ruptured (n = 96) and unruptured (n = 285) small IAs. Clinical data and aneurysmal morphology were taken into consideration, regression analysis was performed to identify significant variables, and these variables were then incorporated into a predictive nomogram. The diagnostic performance of the nomogram was evaluated using the area under the receiver operating characteristic (ROC) curve (AUC) and calibration plot. Clinical effectiveness was validated by decision curve analysis (DCA). The PHASES score calculated for each case was used for comparison. Results: The nomogram achieved an AUC of 0.849 (95% CI: 0.805-0.893), with a sensitivity of 86.5%, a specificity of 70.9%, and accuracy of 74.7%, which was superior to PHASES score system (AUC = 0.693, sensitivity = 83.6%, specificity = 48.8%, and accuracy = 57.5%). A good agreement between predicted rupture risk and actual rupture status in the small aneurysms was observed, and DCA illustrated the benefit of using the nomogram when decisions needed to be made clinically. Conclusions: The nomogram based on clinical and morphological risk factors can be useful in assisting clinicians with individualized assessments and benefit-risk balancing in patients with small IAs (< =5 mm).

Different Grades of Collateral Circulation for Evaluating Cerebral Hemodynamic Status in Carotid Artery Stenosis.

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.

Independent role of circle of Willis for peri-procedural evaluation of carotid endarterectomy in patients with severe carotid stenosis.

OBJECTIVES: In patients with severe carotid stenosis (CS), collateral circulation via circle of Willis (CoW) is considered a compensatory response to maintain blood flow. The aim of this study was to evaluate the impact of CoW in patients with severe CS throughout carotid endarterectomy (CEA). METHODS: A database of patients (n = 124) undergoing CEA was sampled from 2013 to 2020. Severe CS was defined as 90-99% caliber stenosis and collateral circulation was identified by CoW opening. Baseline characteristics, Age-related white matter change (ARWMC) score, immediate neurologic events (INEs) and manifestations were recorded and compared. Correlation and regression analysis for CoW were further investigated. RESULTS: All patients enrolled were divided into two groups regarding to the visualized CoW opening and complete CoW was noticed in 57 patients. The prevalence of complete CoW was higher among asymptomatic patients (n = 39, 68.4%), while higher percentage of TIA or previous stroke were noticed in incomplete CoW (n = 45, 67.2%). Patients with incomplete CoW had a significantly higher median ARWMC score and remarkable cerebral perfusion deficit (P < 0.05*). Totally, 4 INEs (6.0%) were noted in patients with incomplete CoW after CEA. Cerebral hyperperfusion syndrome (CHS) was noticed in 10 patients and early-phase of postoperative hypertension (EPOH) in 15 ones with incomplete CoW versus patients with complete CoW (14.9% and 22.4% vs 3.5% and 7.0%, P < 0.05). Correlation analysis showed strong relationship between CoW opening and peri-operative factors like pre-operative symptoms, ARWMC, CHS and EPOH (P < 0.05*). Overall, CoW opening was an independent predictor of both CHS and EPOH (95% CI, 0.021-0.715 and 0.060-0.949, P < 0.05*) with logistic regression. CONCLUSIONS: Sufficient collateral circulation via CoW may promote ipsilateral cerebral perfusion and mitigate WMC in patients with severe CS. In addition, collaterals may improve the predictive power of the risk scale for post-procedural complications after CEA.

Analysis of the anatomic eligibility for transcarotid artery revascularization in Chinese patients who underwent carotid endarterectomy and transfemoral carotid artery stenting.

Objective: Transcarotid artery revascularization (TCAR) is thought to be a promising technique and instrument for treating carotid stenosis with favorable outcomes. Since there remain several differences in anatomic characteristics among races, this study was conducted to investigate the anatomic eligibility of TCAR in Chinese patients who underwent carotid revascularization. Methods: A retrospective review of patients with carotid stenosis from 2019 to 2021 was conducted. The anatomic eligibility of TCAR was based on the instruction of the ENROUTE Transcarotid Neuroprotection System. The carotid artery characteristics and configuration of the circle of Willis (CoW) were evaluated by CT angiography. The demographic and clinical characteristics and procedure-related complications were recorded. Logistic regression was used to analyze the independent factors for TCAR eligibility. Results: Of 289 consecutive patients [222 for carotid endarterectomy (CEA) and 67 for transfemoral carotid artery stenting (TF-CAS)] identified, a total of 215 patients (74.4%) met TCAR anatomic eligibility. Specifically, 83.7% had mild common carotid artery (CCA) puncture site plaque, 95.2% had 4-9 mm internal carotid artery diameters, 95.8% had >6 mm CCA diameter, and 98.3% had >5 cm clavicle to carotid bifurcation distance. Those who were female (OR, 5.967; 95% CI: 2.545-13.987; P < 0.001), were of an older age (OR, 1.226; 95% CI: 1.157-1.299; P < 0.001), and higher body mass index (OR, 1.462; 95% CI: 1.260-1.697; P < 0.001) were prone to be associated with TCAR ineligibility. In addition, 71 patients with TCAR eligibility (33.0%) were found to combine with incomplete CoW. A high risk for CEA was found in 29 patients (17.3%) with TCAR eligibility, and a high risk for TF-CAS was noted in nine patients (19.1%) with TCAR eligibility. Overall, cranial nerve injury (CNI) was found in 22 patients after CEA, while 19 of them (11.3%) met TCAR eligibility. Conclusion: A significant proportion of Chinese patients meet the anatomic criteria of TCAR, making TCAR a feasible treatment option in China. Anatomic and some demographic factors play key roles in TCAR eligibility. Further analysis indicates a potential reduction of procedure-related complications in patients with high-risk carotid stenosis under the TCAR procedure.

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.

MiR-296-5p ameliorates deep venous thrombosis by inactivating S100A4.

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 3' 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.

Recanalization of symptomatic chronic internal carotid artery occlusions by hybrid treatment.

OBJECTIVE: 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). METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.