Comparison of Outcomes between Stent Retriever Combined with Contact Aspiration and Contact Aspiration Alone in Patients without Hyperdense Artery Sign/Susceptibility Vessel Sign.

PURPOSE: To examine the relationship between hyperdense artery sign (HAS)/susceptibility vessel sign (SVS) and thrombus composition and evaluate the effect of HAS/SVS status on the association between first-line thrombectomy techniques and outcomes in patients with acute anterior circulation large vessel occlusion (LVO). MATERIALS AND METHODS: From January 2018 to June 2021, 103 consecutive patients with acute anterior circulation LVO (75 [63.1%] men; median age, 66 years) who underwent thrombectomy and for whom the removed clot was available for histological analyses were retrospectively reviewed. The presence of HAS and SVS was assessed on unenhanced computed tomography (CT) and susceptibility-weighted imaging, respectively. Association of first-line thrombectomy techniques (stent retriever [SR] combined with contact aspiration [CA] vs CA alone) with outcomes was assessed according to HAS/SVS status. RESULTS: Among the included patients, 55 (53.4%) were HAS/SVS-negative, and 69 (67.0%) underwent first-line SR + CA. Higher relative densities of fibrin/platelets (0.56 vs 0.51; P < .001) and lower relative densities of erythrocytes (0.32 vs 0.42; P < .001) were observed in HAS/SVS-negative patients compared with HAS/SVS-positive patients. First-line SR + CA was associated with reduced odds of distal embolization (adjusted odds ratio, 0.18; 95% CI, 0.04-0.83; P = .027) and a more favorable 90-day functional outcome (adjusted odds ratio, 5.29; 95% CI, 1.06-26.34; P = .042) in HAS/SVS-negative patients and a longer recanalization time (53 vs 25 minutes; P = .025) and higher risk of subarachnoid hemorrhage (24.2% vs 0%; P = .044) in HAS/SVS-positive patients. CONCLUSIONS: Absence of HAS/SVS may indicate a higher density of fibrin/platelets in the thrombus, and first-line SR + CA yielded superior functional outcomes than CA alone in patients with acute LVO without HAS/SVS.

CCDC58 is a potential biomarker for diagnosis, prognosis, immunity, and genomic heterogeneity in pan-cancer.

Coiled-coil domain-containing 58 (CCDC58) is a member of the CCDC protein family. Similar to other members, CCDC58 exhibits potential tumorigenic roles in a variety of malignancies. However, there is no systematic and comprehensive pan-cancer analysis to investigate the diagnosis, prognosis, immune infiltration, and other related functions of CCDC58. We used several online websites and databases, such as TCGA, GTEx, UALCAN, HPA, CancerSEA, BioGRID, GEPIA 2.0, TIMER 2.0, and TISIDB, to extract CCDC58 expression data and clinical data of patients in pan-cancer. Then, the relationship between CCDC58 expression and diagnosis, prognosis, genetic alterations, DNA methylation, genomic heterogeneity, and immune infiltration level were determined. In addition, the biological function of CCDC58 in liver hepatocellular carcinoma (LIHC) was investigated. Pan-cancer analysis results showed that CCDC58 was differentially expressed in most tumors and showed excellent performance in diagnosis and prediction of prognosis. The expression of CCDC58 was highly correlated with genetic alterations, DNA methylation, and genomic heterogeneity in some tumors. In addition, the correlation analysis of CCDC58 with the level of immune infiltration and immune checkpoint marker genes indicated that CCDC58 might affect the composition of the tumor immune microenvironment. Enrichment analysis showed that CCDC58-related genes were mainly linked to mitosis, chromosome, and cell cycle. Finally, biological function experiments demonstrated that CCDC58 plays an important role in tumor cell proliferation and migration. CCDC58 was first identified as a pan-cancer biomarker. It may be used as a potential therapeutic target to improve the prognosis of patients in the future.

Stress hyperglycemia increases short-term mortality in acute ischemic stroke patients after mechanical thrombectomy.

BACKGROUND AND PURPOSE: Glucose-to-glycated hemoglobin ratio (GAR) is considered a more reliable marker of stress hyperglycemia by correcting for basal blood glucose levels. This study aimed to investigate the extent to which GAR is associated with 3 month and 1 year all-cause mortalities in patients with acute ischemic stroke (AIS) undergoing mechanical thrombectomy (MT). METHODS: We retrospectively followed 553 AIS patients who underwent MT. The degree of stress hyperglycemia was quantified as the GAR, defined as fasting plasma glucose (mmol/L)/hemoglobin A1c (HbA1c) (%) on the second day after admission. According to the GAR quartiles, the patients were further categorized into four groups (group 1-group 4). We assessed the association between GAR and all-cause mortalities, clinical outcomes during hospitalization and function outcomes at 3 months. The associations between stress hyperglycemia and all-cause mortalities were analyzed using a Cox proportional-hazards model, while other outcomes were analyzed using multiple logistic regression analysis. RESULTS: The follow-up lasted a median of 18 months (range 0-66 months). The 3 month mortality rate was 9.58% (n = 53) and the 1 year mortality rate was 18.62% (n = 103). The Kaplan-Meier analysis revealed a significant inverse relationship between GAR and mortality (P < 0.001). In the Cox proportional-hazards model at 3 months, compared with group1, group 4 of GAR was associated with a significant increase in the risk of 3 month mortality (hazard ratio [HR] = 4.11, 95% confidence interval [CI] 1.41-12.0, P = 0.01) after adjusting for potential covariates. On multivariate logistic regression analysis, GAR was strongly associated with an increased risk of 3 month poor function outcome. CONCLUSIONS: Stress hyperglycemia, quantified by a higher GAR, is associated with all-cause mortality and poor functional outcomes in patients with AIS who undergo MT. Furthermore, GAR may contribute to improving the predictive efficiency of all-cause mortality in patients with AIS after MT, especially short-term all-cause mortality.

Thrombus migration in patients with acute ischaemic stroke undergoing endovascular thrombectomy.

OBJECTIVE: The impact of thrombus migration (TM) prior to endovascular thrombectomy (EVT) on clinical outcomes and revascularisation rates remains unknown. We aimed to examine whether preinterventional TM modifies the treatment effects of direct EVT versus bridging EVT in acute large vessel occlusion patients. METHODS: All patients undergoing catheter angiography in the Direct Intra-arterial thrombectomy in order to Revascularise acute ischaemic stroke patients with large vessel occlusion Efficiently in Chinese Tertiary hospitals: A Multicentre randomised clinical Trial were included. TM was determined by radiologists unaware of the study by analysing discrepancies between computed tomographic angiography at baseline and first-run digital subtraction angiography before EVT. The primary outcome was the score on the modified Rankin scale (mRS) assessed at 90 days. RESULTS: Of 627 included patients, the TM rate was 11.3% (71/627). In the multivariable logistic regression model, baseline National Institutes of Health Stroke Scale score (adjusted OR 0.956, 95% CI 0.916 to 0.999; p=0.043) and intravenous thrombolysis (adjusted OR 2.614, 95% CI 1.514 to 4.514; p<0.001) were independently associated with TM. The patients with TM were less likely to be completely recanalised than those without TM (21.27% vs 36.23%, p=0.040). The interaction of TM and the EVT treatment effect did not significantly affect mRS shift analysis (p=0.687) or mRS scores of 0 to 1 (p=0.436). CONCLUSION: Preinterventional TM does not modify the treatment effects of direct versus bridging EVT on functional outcomes in patients with acute ischaemic stroke with anterior large vessel occlusion. TM leads to a lower complete recanalisation rate.

Risk factors analysis of surgical complications of hepatic hemangioma: a modified Clavien-Dindo classification-based study.

PURPOSE: There are few studies on the risk factors of postoperative complications after surgical treatment of hepatic hemangioma (HH). This study aims to provide a more scientific reference for clinical treatment. METHODS: The clinical characteristics and operation data of HH patients undergoing surgical treatment in the First Affiliated Hospital of Air Force Medical University from January 2011 to December 2020 were retrospectively collected. All enrolled patients were divided into two groups based on the modified Clavien-Dindo classification: Major group (Grade II/III/IV/V) and Minor group (Grade I and no complications). Univariate and multivariate regression analysis was used to explore the risk factors for massive intraoperative blood loss (IBL) and postoperative Grade II and above complications. RESULTS: A total of 596 patients were enrolled, with a median age of 46.0 years (range, 22-75 years). Patients with Grade II/III/IV/V complications were included in the Major group (n = 119, 20%), and patients with Grade I and no complications were included in the Minor group (n = 477, 80%). The results of multivariate analysis of Grade II/III/IV/V complications showed that operative duration, IBL, and tumor size increased the risk of Grade II/III/IV/V complications. Conversely, serum creatinine (sCRE) decreased the risk. The results of multivariate analysis of IBL showed that tumor size, surgical method, and operative duration increased the risk of IBL. CONCLUSIONS: Operative duration, IBL, tumor size, and surgical method are independent risk factors that should be paid attention to in HH surgery. In addition, as an independent protective factor for HH surgery, sCRE should attract more attention from scholars.

An old thrombus may potentially identify patients at higher risk of poor outcome in anterior circulation stroke undergoing thrombectomy.

PURPOSE: To investigate thrombus age and its association with clinical and procedural parameters in patients with acute ischemic stroke (AIS) due to anterior circulation occlusions. METHODS: The thrombi of 107 consecutive AIS patients with occlusions in anterior circulation large-arteries were collected during mechanical recanalization. By hematoxylin-eosin staining analysis, thrombi were classified as fresh (< 3 days) or old (≥ 3 days) according to the hemosiderin positivity. Old thrombi were further classified as thrombi with focal hemosiderin or diffuse hemosiderin according to their predominant distribution. Neuro-interventional data and clinical outcomes were compared based on thrombus age. RESULTS: We identified fresh thrombi in 29 patients and old thrombi in 78 patients. Compared with patients with fresh thrombi, patients with old thrombi were associated with (i) a longer mechanical recanalization time (p = 0.027), (ii) a higher percentage of fibrin/platelets and leukocytes (all p = 0.02) and a lower percentage of erythrocytes (p = 0.001), and (iii) less favorable clinical outcomes at discharge (p = 0.019) and 90 days later (OR = 2.76, 95% CI = 1.09-6.99, p = 0.032). Furthermore, 18 (16.8%) of all patients had focal hemosiderin in old thrombi, which was independently linked to a poor clinical outcome 90 days later (adjusted OR = 5.37, 95% CI = 1.14-25.28, p = 0.034). CONCLUSION: The presence of old thrombi, particularly those with focal hemosiderin, may aid in identifying patients with acute ischemic anterior circulation stroke who are at a higher risk of poor clinical outcome at 3-month follow-up.

Quantitative Analysis of TP53-Related Lung Cancer Based on Radiomics.

Background: The role of TP53 mutations in the diagnosis and treatment of lung cancer has attracted increasing attention from experts worldwide. This study aimed to explore the expression of TP53 gene in lung cancer and its correlation with radiomics quantitative features. Methods: A total of 93 cases of lung cancer confirmed by pathology were selected, including 44 cases with TP53 mutations and 49 cases with TP53 wild-type. ITK-SNAP software was used to segment the pulmonary nodules, AK software was used to extract radiomic features, and a model was established to predict the type of TP53 gene mutation in lung cancer lesions. Results: A total of 852 features were extracted, and 10 features remained after feature selection. The accuracy, areas under the curve, specificity, sensitivity, positive predictive value, and negative predictive value of the logistic regression model were 0.80, 0.86, 0.89, 0.74, 0.90, and 0.71, respectively. Conclusion: TP53 gene mutations are correlated with radiomic features in lung cancer, which may have application value for TP53 therapy in the future.

A resource scheduling method for reliable and trusted distributed composite services in cloud environment based on deep reinforcement learning.

With the vigorous development of Internet technology, applications are increasingly migrating to the cloud. Cloud, a distributed network environment, has been widely extended to many fields such as digital finance, supply chain management, and biomedicine. In order to meet the needs of the rapid development of the modern biomedical industry, the biological cloud platform is an inevitable choice for the integration and analysis of medical information. It improves the work efficiency of the biological information system and also realizes reliable and credible intelligent processing of biological resources. Cloud services in bioinformatics are mainly for the processing of biological data, such as the analysis and processing of genes, the testing and detection of human tissues and organs, and the storage and transportation of vaccines. Biomedical companies form a data chain on the cloud, and they provide services and transfer data to each other to create composite services. Therefore, our motivation is to improve process efficiency of biological cloud services. Users' business requirements have become complicated and diversified, which puts forward higher requirements for service scheduling strategies in cloud computing platforms. In addition, deep reinforcement learning shows strong perception and continuous decision-making capabilities in automatic control problems, which provides a new idea and method for solving the service scheduling and resource allocation problems in the cloud computing field. Therefore, this paper designs a composite service scheduling model under the containers instance mode which hybrids reservation and on-demand. The containers in the cluster are divided into two instance modes: reservation and on-demand. A composite service is described as a three-level structure: a composite service consists of multiple services, and a service consists of multiple service instances, where the service instance is the minimum scheduling unit. In addition, an improved Deep Q-Network (DQN) algorithm is proposed and applied to the scheduling algorithm of composite services. The experimental results show that applying our improved DQN algorithm to the composite services scheduling problem in the container cloud environment can effectively reduce the completion time of the composite services. Meanwhile, the method improves Quality of Service (QoS) and resource utilization in the container cloud environment.

Bacterial Signatures of Cerebral Thrombi in Large Vessel Occlusion Stroke.

It is important to understand the microbial features of the cerebral thrombus and its clinical relevance in stroke patients, of which data were scarce. We aimed to investigate the microbial features of cerebral thrombi retrieved via thrombectomy in stroke patients with large vessel occlusion (LVO) and their correlations with 3-month mortality. In a prospective cohort study, thrombus samples were collected during mechanical thrombectomy in LVO stroke patients with successful revascularization at a tertiary hospital. Oral, fecal, and isolated plasma samples were collected within 12 h of admission. The microbial compositions of all samples were compared using 16S rRNA gene amplicon next-generation sequencing. Fluorescent in situ hybridization (FISH) was used to detect bacteria in thrombus samples. The primary outcome was 3-month mortality. Perioperative adverse events (AEs) within 48 h were also recorded. Bacterial DNA was detected in 96.2% of thrombus samples from 104 patients, and clusters of bacterial signals were seen in the thrombi with FISH. Compared with fecal and oral samples, the thrombus microbiota was mainly characterized by excessive enrichment of Proteobacteria, mainly originating from plasma. The bacterial concentrations, dominant bacteria, and distribution patterns differed in thrombi obtained from cardioembolic and large-artery atherosclerotic strokes. Higher abundances of Acinetobacter and Enterobacteriaceae were associated with a higher risk of perioperative AEs, and a higher abundance of Acinetobacter was independently associated with a higher risk of 90-day mortality. This study demonstrated the presence of bacteria in cerebral thrombi retrieved with thrombectomy in LVO strokes, with some bacteria associated with patients' prognoses. IMPORTANCE In this study, we (i) checked for the presence of bacteria in cerebral thrombi in over 95% of the LVO stroke patients using 16S rRNA sequencing, in contrast with periprocedural control samples that are bacteria negative; (ii) visualized clusters of bacterial signals in the thrombi using FISH; and (iii) cultivated Lactobacillus vaginalis, Bacillus cereus, and Kocuria marina in the bacterial culture of the tissue fragment solution of thrombus aspirates. We found excessive enrichment of Proteobacteria in the thrombi, mainly originating from plasma, as indicated with fast expectation-maximization microbial source tracking (FEAST). Different bacterial concentrations, dominant bacteria, and distribution patterns were found in thrombi obtained from cardioembolic and large-artery atherosclerotic LVO strokes. There was an association between higher abundances of Acinetobacter and Enterobacteriaceae in the thrombi and a higher risk of perioperative adverse events and an association between a higher abundance of Acinetobacter in the thrombi and a higher risk of 90-day mortality.

Comparing the efficacy and safety of the Skyflow device with those of the Solitaire FR stent in patients with acute ischemic stroke: a prospective, multicenter, randomized, non-inferiority clinical trial.

BACKGROUND: Mechanical thrombectomy is the standard treatment for acute ischemic stroke (AIS) with large vessel occlusion (LVO) in the anterior circulation. This trial aimed to indicate whether Skyflow, a new thrombectomy device, could achieve the same safety and efficacy as Solitaire FR in the treatment of AIS. METHODS: This study was a prospective, multicenter, randomized, single blind, parallel, positive controlled, non-inferiority clinical trial. Patients with intracranial anterior circulation LVO within 8 hours from onset were included to receive thrombectomy treatment with either the Skyflow or Solitaire FR stent retriever. The primary endpoint was the rate of successful reperfusion (modified Treatment In Cerebral Infarction (mTICI) ≥2b) after the operation. The safety endpoints were the rate of symptomatic intracranial hemorrhage (sICH) and subarachnoid hemorrhage (SAH) at 24 hours after operation. RESULTS: A total of 95 and 97 patients were involved in the Skyflow group and Solitaire FR group, respectively. A successful reperfusion (mTICI ≥2b) was finally achieved in 84 (88.4%) patients in the Skyflow group and 80 (82.5%) patients in the Solitaire FR group. Skyflow was non-inferior to Solitaire FR in regard to the primary outcome, with the criterion of a non-inferiority margin of 12.5% (p=0.0002) after being adjusted for the combined center effect and the National Institutes of Health Stroke Scale (NIHSS) score. The rate of periprocedural sICH and SAH did not differ significantly between the two groups. CONCLUSION: Endovascular thrombectomy with the Skyflow stent retriever was non-inferior to Solitaire FR with regard to successful reperfusion in AIS due to LVO (with a pre-specified non-inferiority margin of 12.5%).

The association between stress hyperglycemia and unfavorable outcomes in patients with anterior circulation stroke after mechanical thrombectomy.

Background and purpose: Stress hyperglycemia is common in critical and severe diseases. However, few studies have examined the association between stress hyperglycemia and the functional outcomes of patients with anterior circulation stroke, after mechanical thrombectomy (MT), in different diabetes status. This study therefore aimed to determine the relationship between stress hyperglycemia and the risk of adverse neurological functional outcomes in anterior circulation stroke patients with and without diabetes after MT. Methods: Data of 408 patients with acute anterior circulation stroke treated with MT through the green-channel treatment system for emergency stroke at the First Affiliated Hospital of Jinan University between January 2016 and December 2020 were reviewed retrospectively. The stress hyperglycemia ratio (SHR) was calculated as fasting plasma glucose (mmol/L) divided by glycosylated hemoglobin (%). The patients were stratified into four groups by quartiles of SHR (Q1-Q4). The primary outcome was an excellent (nondisabled) functional outcome at 3 months after admission (modified Rankin Scale score of 0-1). The relationship between stress hyperglycemia and neurological outcome after stroke was assessed using multivariate logistic regression. Results: After adjusting for potential confounders, compared with patients in Q1, those in Q4 were less likely to have an excellent outcome at 3 months (odds ratio [OR], 0.32, 95% confidence interval [CI], 0.14-0.66, p = 0.003), a good outcome at 3 months (OR, 0.41, 95% CI, 0.20-0.84, p = 0.020), and major neurological improvement (OR, 0.38, 95% CI, 0.19-0.73, p = 0.004). Severe stress hyperglycemia increased risks of 3-months all-cause mortality (OR, 2.82, 95% CI, 1.09-8.29, p = 0.041) and ICH (OR, 2.54, 95% CI, 1.21-5.50, p = 0.015). Conclusion: Stress hyperglycemia was associated with a reduced rate of excellent neurological outcomes, and increased mortality and ICH risks in patients with anterior circulation stroke after MT regardless of diabetes status.

High-Degree Middle Cerebral Artery Stenosis : Can Advanced 3D DSA-MRI Fusion Imaging Better Illustrate Plaques and Perforators?

PURPOSE: Endovascular treatment in severe middle cerebral artery (MCA) stenosis is controversial owing to high rates of periprocedural complications, especially occlusion of the lenticulostriate arteries (LSA). The characteristics of LSAs and the spatial relationships between MCA plaques and LSAs using the fusion of three-dimensional (3D) digital subtraction angiography (DSA) and magnetic resonance imaging (3D DSA-MRI fusion) were investigated. METHODS: We retrospectively analyzed data from 32 ischemic stroke or transient ischemic attack patients with severe MCA stenosis, who underwent MRI and DSA within 2 weeks after symptom onset. The patients were divided into culprit and non-culprit MCA stenosis groups. The 3D DSA-MRI fusion was performed on dedicated workstations, which allowed automated overlays of the target vessels. The characteristics of LSAs, plaque distribution and lesion patterns, and their relationships were evaluated. RESULTS: The 3D DSA-MRI fusion image was able to illustrate the spatial relationships between MCA plaques and LSA orifices. Of 42 LSA stems in 32 patients, 10 had MCA plaque over the LSA orifice and were all found in the culprit MCA stenosis group. Over half (51.9%) of the LSA stems in patients with culprit MCA stenosis originated from the stenotic MCA segment. The MCA plaque-LSA orifice spatial relationships were classified into four types, which were significantly different between the two groups (p = 0.016). CONCLUSION: The 3D DSA-MRI fusion technique enables visualization of the LSA orifice and MCA plaque and their spatial relationships. This classification of the type of spatial relationships can provide insights into the pathogenesis of MCA stroke and useful guides for treatment strategies.

Differences in Pathological Composition Among Large Artery Occlusion Cerebral Thrombi, Valvular Heart Disease Atrial Thrombi and Carotid Endarterectomy Plaques.

Background and Purpose: Acute ischemic stroke (AIS) with large artery occlusion (LAO) may lead to severe disability or death if not promptly treated. To determine the source of cerebral artery occlusion thrombosis, we studied the pathological components of cerebral artery thrombosis with different etiological classifications to guide clinical formulation of preventive treatment. Materials and Methods: Eighty-eight thrombi from AIS patients with LAO, 12 atrial thrombi from patients with valvular heart disease (VHD), and 11 plaques obtained by carotid endarterectomy (CEA) from patients with carotid artery stenosis were included in this retrospective study. The hematoxylin and eosin-stained specimens were quantitatively analyzed for erythrocytes, white blood cells (WBCs) and fibrin; platelets were shown by immunohistochemistry for CD31. Results: The thrombi of VHD showed the highest percentage of fibrin, followed by those of cardioembolism (CE) and stroke of undetermined etiology (SUE), and these values were higher than those of the other groups. Plaques obtained by CEA showed the highest erythrocyte number, followed by the large artery atherosclerosis (LAA) thrombi, and showed significantly noticeable differences between other stroke subtypes. The proportions of fibrin and erythrocytes in the thrombi of CE and SUE were most similar to those in the thrombi of VHD, and the LAA thrombi were the closest to those obtained by CEA. CE thrombi and CEA plaques had a higher percentage of WBCs than thrombi of other stroke thrombus subtypes and VHD. Conclusions: CE and most cryptogenic thrombi may originate from the heart, and the formation of carotid atherosclerotic plaques may be related to atherosclerotic cerebral embolism. Inflammation may be involved in their formation.

Optical/MRI dual-modality imaging of M1 macrophage polarization in atherosclerotic plaque with MARCO-targeted upconversion luminescence probe.

Pro-inflammatory M1 macrophage is identified as a prominent component initializing the progress of vulnerable atherosclerotic plaque. Here, we constructed anti-MARCO NaGdF4:Yb,Er@NaGdF4 upconversion nanoparticles (UCNPs) by conjugating polyclonal MARCO antibody to the surface of NaGdF4:Yb,Er@NaGdF4via condensation reaction. UCNPs displayed highly mono-dispersion with average sizes of 26.7 ±â€¯0.8 nm and favorable biocompatibility. In vivo upconversion optical imaging revealed that distinctive fluorescence signal could be observed in the regions of carotid artery 10 min post-injection, reached peak value at 1 h and decreased back to baseline at 24 h post-injection. The carotid artery wall demonstrated high signal intensity on T1-weighted MR images after anti-MARCO UCNPs injection, as determined by 7.0T MRI. Immunofluorescence staining of tissue section of carotid artery revealed that MARCO was highly abundant in shoulder regions of plaque. Anti-MARCO UCNPs is a promising optical/MRI dual-modality imaging probe which can non-invasively reflect M1 phenotype macrophages behavior in vivo.

Vertebral Artery Dissection Probably Caused by Massage: A Case Report.

MASSAGE has been recommended to more people as an adjunct to health care. We illustrate a case of vertebral artery dissection (VAD) probably caused by massage that almost resulted in the patient's death. The patient experienced sudden cardiac arrest and paralysis. After treatment with anticoagulation and antiplatelet, he finally discharged without any sequelae.

Acute ischemic stroke patients with diffusion-weighted imaging-Alberta Stroke Program Early Computed Tomography Score ≤ 5 can benefit from endovascular treatment: a single-center experience and literature review.

PURPOSE: The recommendation strength of the guidelines for mechanical thrombectomy among patients with large pre-treatment core infarct is weak. We evaluated the safety and outcome of endovascular treatment for acute ischemic stroke with diffusion-weighted imaging-Alberta Stroke Program Early Computed Tomography Score (DWI-ASPECTS) ≤ 5. METHODS: Data on acute ischemic stroke patients with DWI-ASPECTS ≤ 5 who underwent endovascular treatment within 6 h, or presented an arterial spin labeling-DWI (ASL-DWI) mismatch within 12 h, at our center were retrospectively collected. We report the clinical characteristics and outcome of every patient, and review the relevant literature. RESULTS: Among the 19 patients who were enrolled, all experienced successful reperfusion, and 10 achieved a favorable outcome (modified Rankin scale (mRS) ≤ 2). Two patients presented with symptomatic intracranial hemorrhage (sICH); both of them had a poor outcome (mRS > 2). CONCLUSION: Acute ischemic stroke patients with large DWI lesions caused by large vessel occlusion can achieve a favorable clinical outcome with endovascular treatment if recanalization is performed within 6 h, or after 6 h in case of an ASL-DWI mismatch.

Carotid DSA based CFD simulation in assessing the patient with asymptomatic carotid stenosis: a preliminary study.

BACKGROUND: Cerebrovascular events are frequently associated with hemodynamic disturbance caused by internal carotid artery (ICA) stenosis. It is challenging to determine the ischemia-related carotid stenosis during the intervention only using digital subtracted angiography (DSA). Inspired by the performance of well-established FFRct technique in hemodynamic assessment of significant coronary stenosis, we introduced a pressure-based carotid arterial functional assessment (CAFA) index generated from computational fluid dynamic (CFD) simulation in DSA data, and investigated its feasibility in the assessment of hemodynamic disturbance preliminarily using pressure-wired measurement and arterial spin labeling (ASL) MRI as references. METHODS: The cerebral multi-delay multi-parametric ASL-MRI and carotid DSA including trans-stenotic pressure-wired measurement were implemented on a 65-year-old man with asymptomatic unilateral (left) ICA stenosis. A CFD simulation using simplified boundary condition was performed in DSA data to calculate the CAFA index. The cerebral blood flow (CBF) and arterial transit time (ATT) of ICA territories were acquired. RESULTS: CFD simulation showed good correlation (r = 0.839, P = 0.001) with slight systematic overestimation (mean difference - 0.007, standard deviation 0.017) compared with pressure-wired measurement. No significant difference was observed between them (P = 0.09). Though the narrowing degree of in the involved ICA was about 70%, the simulated and measured CAFA (0.942/0.937) revealed a functionally nonsignificant stenosis which was also verified by a compensatory final CBF (fronto-temporal/fronto-parietal region: 51.58/45.62 ml/100 g/min) and slightly prolonged ATT (1.23/1.4 s) in the involved territories, together with a normal left-right percentage difference (2.1-8.85%). CONCLUSIONS: The DSA based CFD simulation showed good consistence with invasive approach and could be used as a cost-saving and efficient way to study the relationship between hemodynamic disorder caused by ICA stenosis and subsequent perfusion variations in brain. Further research should focus on the role of noninvasive pressure-based CAFA in screening asymptomatic ischemia-causing carotid stenosis.

Multimodality Imaging of Angiogenesis in a Rabbit Atherosclerotic Model by GEBP11 Peptide Targeted Nanoparticles.

Background and Aims: Angiogenesis is an important pathological process during progression of plaque formation, which can result in plaque hemorrhage and vulnerability. This study aims to explore non-invasive imaging of angiogenesis in atherosclerotic plaque through magnetic resonance imaging (MRI) and positron emission tomography (PET) by using GEBP11 peptide targeted magnetic iron oxide nanoparticles in a rabbit model of atherosclerosis. Methods: The dual-modality imaging probe was constructed by coupling 2, 3-dimercaptosuccinnic acid-coated paramagnetic nanoparticles (DMSA-MNPs) and the PET 68Ga chelator 1,4,7-triazacyclononane-N, N', N''-triacetic acid (NOTA) to GEBP11 peptide. The atherosclerosis model was induced in New Zealand white rabbits by abdominal aorta balloon de-endothelialization and atherogenic diet for 12 weeks. The plaque areas in abdominal artery were detected by ultrasound imaging and Oil Red O staining. Immunofluorescence staining and Prussian blue staining were applied respectively to investigate the affinity of GEBP11 peptide. MTT and flow cytometric analysis were performed to detect the effects of NGD-MNPs on cell proliferation, cell cycle and apoptosis in Human umbilical vein endothelial cells (HUVECs). In vivo MRI and PET imaging of atherosclerotic plaque were carried out at different time points after intravenous injection of nanoparticles. Results: The NGD-MNPs with hydrodynamic diameter of 130.8 nm ± 7.1 nm exhibited good imaging properties, high stability, low immunogenicity and little cytotoxicity. In vivo PET/MR imaging revealed that 68Ga-NGD-MNPs were successfully applied to visualize atherosclerotic plaque angiogenesis in the rabbit abdominal aorta. Prussian blue and CD31 immunohistochemical staining confirmed that NGD-MNPs were well co-localized within the blood vessels' plaques. Conclusion:68Ga-NGD-MNPs might be a promising MR and PET dual imaging probe for visualizing the vulnerable plaques.

Reduced silent information regulator 1 signaling exacerbates sepsis-induced myocardial injury and mitigates the protective effect of a liver X receptor agonist.

Myocardial injury and dysfunction are critical manifestations of sepsis. Previous studies have reported that liver X receptor (LXR) activation is protective during sepsis. However, whether LXR activation protects against septic heart injury and its underlying mechanisms remain elusive. This study was designed to determine the role of LXR activation in the septic heart with a focus on SIRT1 (silent information regulator 1) signaling. Male cardiac-specific SIRT1 knockout mice (SIRT1-/-) and their wild-type littermates were subjected to sepsis by cecal ligation and puncture (CLP) in the presence or absence of LXR agonist T0901317. The survival rate of mice was recorded during the 7-day period post CLP. Our results demonstrated that SIRT1-/- mice suffered from exacerbated mortality and myocardial injury in comparison with their wild-type littermates. Meanwhile, T0901317 treatment improved mice survival, accompanied by significant ameliorations of myocardial injury and dysfunction in wild-type mice but not in SIRT1-/- mice. Furthermore, the levels of myocardial inflammatory cytokines (TNF-α, IL-6, IL-1ß, MCP-1, MPO and HMGB1), oxidative stress (ROS generation, MDA), endoplasmic-reticulum (ER) stress (protein levels of CHOP, GRP78, GRP94, IRE1α, and ATF6), and cardiac apoptosis following CLP were inhibited by T0901317 treatment in wild-type mice but not in SIRT1-/- mice. Mechanistically, T0901317 enhanced SIRT1 signaling and the subsequent deacetylation and activation of antioxidative FoxO1 and anti-ER stress HSF1, as well as the deacetylation and inhibition of pro-inflammatory NF-ΚB and pro-apoptotic P53, thereby alleviating sepsis-induced myocardial injury and dysfunction. Our data support the promise of LXR activation as an effective strategy for relieving heart septic injury.

Moderate Autophagy Inhibits Vascular Smooth Muscle Cell Senescence to Stabilize Progressed Atherosclerotic Plaque via the mTORC1/ULK1/ATG13 Signal Pathway.

In order to investigate the effects of autophagy induced by rapamycin in the development of atherosclerosis plaque we established murine atherosclerosis model which was induced in ApoE-/- mice by high fat and cholesterol diet (HFD) for 16 weeks. Rapamycin and 3-Methyladenine (MA) were used as autophagy inducer and inhibitor respectively. The plaque areas in aortic artery were detected with HE and Oil Red O staining. Immunohistochemical staining were applied to investigate content of plaque respectively. In contrast to control and 3-MA groups, rapamycin could inhibit atherosclerosis progression. Rapamycin was able to increase collagen content and a-SMA distribution relatively, as well as decrease necrotic core area. Then we used MOVAS and culture with ox-LDL for 72 h to induce smooth muscle-derived foam cell model in vitro. Rapamycin and 3-MA were cultured together respectively. Flow cytometry assay and SA-ß-Gal staining experiments were performed to detect survival and senescence of VSMCs. Western blot analysis were utilized to analyze the levels of protein expression. We found that rapamycin could promote ox-LDL-induced VSMCs autophagy survival and alleviate cellular senescence, in comparison to control and 3-MA groups. Western blot analysis showed that rapamycin could upregulate ULK1, ATG13 and downregulate mTORC1 and p53 protein expression.