Exploring miR-21 as a key regulator in two distinct approaches of bone marrow stromal cells differentiation into Schwann-like cells.

The differentiation of bone marrow stromal cells (BMSCs) into Schwann-like cells (SCLCs) has the potential to promote the structural and functional restoration of injured axons. However, the optimal induction protocol and its underlying mechanisms remain unclear. This study aimed to compare the effectiveness of different induction protocols in promoting the differentiation of rat BMSCs into SCLCs and to explore their potential mechanisms. BMSCs were induced using two distinct methods: a composite factor induction approach (Protocol-1) and a conditioned culture medium induction approach (Protocol-2). The expression of Schwann cells (SCs) marker proteins and neurotrophic factors (NTFs) in the differentiated cells was assessed. Cell proliferation and apoptosis were also measured. During induction, changes in miR-21 and Sprouty RTK signaling antagonist 2 (SPRY2) mRNA were analyzed. Following the transfection of BMSCs with miR-21 agomir or miR-21 antagomir, induction was carried out using both protocols, and the expression of SPRY2, ERK1/2, and SCs marker proteins was examined. The results revealed that NTFs expression was higher in Protocol-1, whereas SCs marker proteins expression did not significantly differ between the two groups. Compared to Protocol-1, Protocol-2 exhibited enhanced cell proliferation and fewer apoptotic and necrotic cells. Both protocols showed a negative correlation between miR-21 and SPRY2 expression throughout the induction stages. After induction, the miR-21 agomir group exhibited reduced SPRY2 expression, increased ERK1/2 expression, and significantly elevated expression of SCs marker proteins. This study demonstrates that Protocol-1 yields higher NTFs expression, whereas Protocol-2 results in stronger SCLCs proliferation. Upregulating miR-21 suppresses SPRY2 expression, activates the ERK1/2 signaling pathway, and promotes BMSC differentiation into SCLCs.

Metformin treatment and acute ischemic stroke outcomes in patients with type 2 diabetes: a retrospective cohort study.

BACKGROUND AND PURPOSE: Preclinical studies have shown that metformin has neuroprotective actions in stroke. However, the optimal treatment timing and duration remain unknown. Herein, we examined the efficacy of metformin treatment on prognosis in acute ischemic stroke (AIS) patients, and assessed the optimal treatment timing and duration. METHODS: AIS patients with type 2 diabetes mellitus were retrospectively enrolled. Patients were grouped into those who never received metformin (MET - group), those who received metformin continuously before stroke and after admission (pre-stroke + /post-stroke + group), those who only received metformin before stroke onset (pre-stroke + /post-stroke - group), and those who only received metformin after admission (pre-stroke - /post-stroke + group). The all MET + group represents the sum of the three metformin treatment groups. The efficacy outcome was the 90-day modified Rankin Scale (mRS) score. RESULTS: In total, 309 eligible patients were included (MET - [N = 130], pre-stroke + /post-stroke + [N = 94], pre-stroke + /post-stroke - [N = 30], pre-stroke - /post-stroke + [N = 55]; all MET + [N = 179]). The all MET + group had a trend toward a lower 90-day mRS score compared with that in the MET - group (1 [0-2] vs 1 [0-3], unadjusted odds ratio [OR] = 0.652, P = 0.041; adjusted OR = 0.752, P = 0.218). In the three metformin treatment groups, only the pre-stroke + /post-stroke + group had a significantly lower 90-day mRS score (1 [0-1] vs 1 [0-3], adjusted OR = 0.497, 95%CI = 0.289-0.854; P = 0.011) and higher proportion of mRS score 0-1 (78.7% vs. 61.5%, adjusted OR = 2.278, 95%CI = 1.108-4.680; P = 0.025) than the MET - group. CONCLUSION: AIS patients with type 2 diabetes mellitus who receive continuous metformin treatment before stroke onset and after admission have improved functional outcome at 90 days.

Platelet Distribution Width: A Significant Predictor of Poor Outcome After Mechanical Thrombectomy.

OBJECTIVES: Elevated platelet distribution width (PDW) is a recognized marker of platelet activity. Herein, we investigated the association between admission PDW values and clinical outcome at 3 months in acute ischemic stroke (AIS) patients undergoing mechanical thrombectomy (MT). MATERIALS AND METHODS: We retrospectively collected consecutive patients diagnosed with AIS following MT from two stroke centers. PDW was measured on admission. Subjects were divided into two groups according to the clinical outcome using the modified Rankin Scale at 3 months. Multiple regression analyses and receiver operating characteristic (ROC) curves were performed to determine the associations between admission PDW values, clinical parameters, and functional outcome. RESULTS: A total of 162 subjects were enrolled. Patients in the poor outcome group had a significantly higher percentage of PDW >16.0 fL compared with the good outcome group (57.3% vs. 26.9%, P < 0.001). After adjusting for a range of confounding factors, multiple regression analysis showed that PDW >16.0 fL was an independent predictor of poor outcome at 3 months (odds ratio 4.572, 95% confidence interval 1.896-11.026, P = 0.001). ROC curve analysis revealed that PDW >16.0 fL predicted poor outcome with 57.3% sensitivity and 73.1% specificity (the area under the ROC curve 0.637, 95% confidence interval 0.558-0.711, P = 0.004). CONCLUSIONS: Elevated PDW is an independent predictor of poor functional outcome in patients with anterior circulation AIS undergoing MT at 3 months.

Piezoelectric Impact Energy Harvester Based on the Composite Spherical Particle Chain for Self-Powered Sensors.

In this study, a novel piezoelectric energy harvester (PEH) based on the array composite spherical particle chain was constructed and explored in detail through simulation and experimental verification. The power test of the PEH based on array composite particle chains in the self-powered system was realized. Firstly, the model of PEH based on the composite spherical particle chain was constructed to theoretically realize the collection, transformation, and storage of impact energy, and the advantages of a composite particle chain in the field of piezoelectric energy harvesting were verified. Secondly, an experimental system was established to test the performance of the PEH, including the stability of the system under a continuous impact load, the power adjustment under different resistances, and the influence of the number of particle chains on the energy harvesting efficiency. Finally, a self-powered supply system was established with the PEH composed of three composite particle chains to realize the power supply of the microelectronic components. This paper presents a method of collecting impact energy based on particle chain structure, and lays an experimental foundation for the application of a composite particle chain in the field of piezoelectric energy harvesting.

Novel anthranilic amide derivatives bearing the chiral thioether and trifluoromethylpyridine: Synthesis and bioactivity.

Ten anthranilic amides bearing skeletons of chiral thioether and trifluoromethylpyridine (5a-5j) were designed and synthesized. Bioassays indicated that some of compounds had excellent insecticidal activity. For example, compounds 5a, 5e and 5g had the median lethal concentrations (LC50) against Plutella xylostella of 7.3, 8.7 and 8.1 µg/mL respectively. The LC50 of 5a against Ostrinia nubilalis and Pseudaletia separata were 21.7 and 44.2 µg/mL respectively. Anti-TMV tests indicated that some compounds also showed good antiviral activity. For instance, the curative activities of compounds 5b and 5e were 57.2% and 63.6%, and with half maximal effective concentration (EC50) of 304.5 and 203.0 µg/mL, respectively, which were much higher than these of ribavirin (39.4%, EC50 = 819.8 µg/mL) and ningnanmycin (56.2%, EC50 = 361.4 µg/mL). The molecular docking between the most active compounds and ryanodine receptor of the Plutella xylostella were also discussed. Those results indicated that the novel anthranilic amide derivatives in present work were worthy of further research and development as novel pesticides.

A case report of thrombolysis resistance: thrombus ultrastructure in an ischemic stroke patient.

BACKGROUND: Following acute ischemic stroke (AIS), approximately half of patients do not achieve recanalization after intravenous administration of tissue plasminogen activator (rt-PA). Thrombolysis resistance is a possible reason for recanalization failure. Thrombolysis resistance is likely related to the ultrastructure and composition of the thrombus. However, there is a paucity of published information on the relationship between thrombus ultrastructure and thrombolysis resistance. CASE PRESENTATION: Two patients who underwent mechanical thrombectomy were observed within 4.5 h after stroke onset. One patient failed to respond to rt-PA (defined as thrombolysis resistant), and the other patient did not receive rt-PA treatment (non-rtPA). In each patient, the occluded artery was the internal carotid artery or middle cerebral artery. According to the Trial of ORG 10172 in Acute Stroke Treatment classification, both patients had large atherosclerotic cerebral infarction. By scanning electron microscopy (SEM) and transmission electron microscopy (TEM), we found that the thrombus structure was significantly different between the two patients. CONCLUSION: Grid-like dense fibrin, compressed polyhedral erythrocytes, and large accumulation of neutrophils may be characteristics of thrombolysis resistant thrombi.

Bilirubin: a novel predictor of hemorrhagic transformation and symptomatic intracranial hemorrhage after mechanical thrombectomy.

BACKGROUND AND PURPOSE: The role of bilirubin in patients treated with mechanical thrombectomy (MT) is unknown. We investigated the relationship between admission bilirubin levels and hemorrhagic complication in acute ischemic stroke (AIS) patients treated with MT and detailed the roles of direct bilirubin (DB), indirect bilirubin (IDB), and total bilirubin (TB). METHODS: Consecutive AIS patients treated with MT were enrolled from two stroke centers. Outcome measures included hemorrhagic transformation (HT) and symptomatic intracranial hemorrhage (sICH) within 48 h. An independent association of bilirubin with outcomes was identified by multivariate logistic regression analysis. The accuracies of bilirubin in predicting outcome were evaluated using receiver operating characteristic curve analysis. RESULTS: Of the 153 enrolled patients, 64 (41.8%) were diagnosed with HT, of which 28 (18.3%) had sICH. In univariate analyses, DB, IDB, and TB were higher in patients with HT and sICH than in patients without. After adjustment for potential confounders, DB (odds ratio [OR], 1.364; 95% confidence interval [CI], 1.133-1.641; p = 0.001), IDB (OR, 1.143; 95% CI, 1.052-1.242; p = 0.002), and TB (OR, 1.106; 95% CI, 1.041-1.175; p = 0.001) were independently associated with HT. IDB (OR, 1.177; 95% CI, 1.064-1.303; p = 0.002) and TB (OR, 1.102; 95% CI, 1.027-1.182; p = 0.007) were independently associated with sICH. Receiver operating characteristic curve analysis showed no significant difference between the three indicators of predicting HT and sICH. CONCLUSIONS: Elevated admission bilirubin is an independent predictor of HT and sICH in AIS patients treated with MT.

Causal association between particulate matter 2.5 and Alzheimer's disease: a Mendelian randomization study.

Background: Although epidemiological evidence implies a link between exposure to particulate matter (PM) and Alzheimer's disease (AD), establishing causality remains a complex endeavor. In the present study, we used Mendelian randomization (MR) as a robust analytical approach to explore the potential causal relationship between PM exposure and AD risk. We also explored the potential associations between PM exposure and other neurodegenerative diseases. Methods: Drawing on extensive genome-wide association studies related to PM exposure, we identified the instrumental variables linked to individual susceptibility to PM. Using summary statistics from five distinct neurodegenerative diseases, we conducted two-sample MR analyses to gauge the causal impact of PM on the risk of developing these diseases. Sensitivity analyses were undertaken to evaluate the robustness of our findings. Additionally, we executed multivariable MR (MVMR) to validate the significant causal associations identified in the two-sample MR analyses, by adjusting for potential confounding risk factors. Results: Our MR analysis identified a notable association between genetically predicted PM2.5 (PM with a diameter of 2.5 µm or less) exposure and an elevated risk of AD (odds ratio, 2.160; 95% confidence interval, 1.481 to 3.149; p < 0.001). A sensitivity analysis supported the robustness of the observed association, thus alleviating concerns related to pleiotropy. No discernible causal relationship was identified between PM and any other neurodegenerative diseases. MVMR analyses-adjusting for smoking, alcohol use, education, stroke, hearing loss, depression, and hypertension-confirmed a persistent causal relationship between PM2.5 and AD. Sensitivity analyses, including MR-Egger and weighted median analyses, also supported this causal association. Conclusion: The present MR study provides evidence to support a plausible causal connection between PM2.5 exposure and AD. The results emphasize the importance of contemplating air quality interventions as a public health strategy for reducing AD risk.

Efficacy and safety of oropharyngeal muscle strength training on poststroke oropharyngeal dysphagia: a systematic review and meta-analysis.

OBJECTIVES: To investigate how oropharyngeal muscle strength training affected the safety and performance of swallowing in patients with poststroke oropharyngeal dysphagia. DESIGN: Systematic review and meta-analysis. DATA SOURCES: Cochrane Central Register of Controlled of Trials, Web of Science, PubMed, Embase databases and ClinicalTrials.gov were systematically searched, for publications in English, from database inception to December 2022. ELIGIBILITY CRITERIA: Studies comparing the effect of oropharyngeal muscle strength training with conventional dysphagia therapy in patients with poststroke. Penetration-Aspiration Scale (PAS) and Functional Oral Intake Scale (FOIS) were assessed as the main outcomes. DATA EXTRACTION AND SYNTHESIS: Two researchers independently screened the literature, extracted data and evaluated the quality of the included studies, with disagreements resolved by another researcher. The Cochrane risk-of-bias tool was used to assess the risk of bias. Review Manager V.5.3 was employed for the meta-analysis. Random effect models were used for meta-analysis. RESULTS: Seven studies with 259 participants were included in this meta-analysis. The results showed that oropharyngeal muscle strength training could reduce PAS score compared with conventional dysphagia therapy (mean difference=-0.98, 95% CI -1.34 to -0.62, p<0.0001, I2=28%). The results also showed that oropharyngeal muscle strength training could increase FOIS score (mean difference=1.04, 95% CI 0.55 to 1.54, p<0.0001, I2=0%) and the vertical displacement of the hyoid bone (mean difference=0.20, 95% CI 0.01 to 0.38, p=0.04, I2=0%) compared with conventional dysphagia therapy. CONCLUSION: In patients with poststroke oropharyngeal dysphagia, oropharyngeal muscle strength training can improve swallowing safety and performance. PROSPERO REGISTRATION NUMBER: CRD42022302471.

Ioversol Induced Microglia Proinflammatory Activation and Oxidative Stress in Rats.

Contrast-induced encephalopathy (CIE) following angiography, though not often and reversible, can in some cases lead to permanent neurological dysfunction. To identify how neuroinflammation is involved in CIE, we investigated microglia responses to a bolus injection of ioversol in the internal carotid artery (ICA) in rats. MicroCT scanning indicated that the injected ioversol was cleared from the rat's brain within 25 min. However, proinflammatory activated and significantly increased microglia were found in the rat occipital cortex at 1 day, and the number of blood vessel-associated microglia was still significantly higher at 3-day post-injection, compared with sham- and PBS-treated rats. Moreover, significantly upregulated malondialdehyde (MDA), downregulated superoxide dismutase (SOD) levels, and elevated proinflammatory cytokines were observed in the brain of rats treated with ioversol. Ioversol administration decreased cell viability of primarily cultured microglia and induced significant proinflammatory activation. Furthermore, ioversol remarkably upregulated astrocytic aquaporin (AQP) 4 expression in the rats brain, and transwell cultures showed significantly enhanced microglia migrating to ioversol-treated endothelial cells. Immediate injection of edaravone dexborneol, a novel antioxidative drug, after ioversol injection effectively rescued ioversol-induced neuroinflammation. Together, these findings suggest that ioversol induced neuroinflammation and oxidative stress in the brain via microglia activation in a direct and indirect manner, which might contribute to the pathogenesis of CIE.

The fibrinogen-to-albumin ratio is associated with intracranial atherosclerosis plaque enhancement on contrast-enhanced high-resolution magnetic resonance imaging.

Background: Contrast-enhanced high-resolution magnetic resonance imaging (CE-HR-MRI) is a useful imaging modality to assess vulnerable plaques in intracranial atherosclerotic stenosis (ICAS) patients. We studied the relationship between the fibrinogen-to-albumin ratio (FAR) and plaque enhancement in patients with ICAS. Methods: We retrospectively enrolled consecutive ICAS patients who had undergone CE-HR-MRI. The degree of plaque enhancement on CE-HR-MRI was evaluated both qualitatively and quantitatively. Enrolled patients were classified into no enhancement, mild enhancement, and obvious enhancement groups. An independent association of the FAR with plaque enhancement was identified by multivariate logistic regression and receiver operating characteristic (ROC) curve analyses. Results: Of the 69 enrolled patients, 40 (58%) were classified into the no/mild enhancement group, and 29 (42%) into the obvious enhancement group. The obvious enhancement group had a significantly higher FAR than the no/mild enhancement group (7.36 vs. 6.05, p = 0.001). After adjusting for potential confounders, the FAR was still significantly independently associated with obvious plaque enhancement in multiple regression analysis (odds ratio: 1.399, 95% confidence interval [CI]: 1.080-1.813; p = 0.011). ROC curve analysis revealed that FAR >6.37 predicted obvious plaque enhancement with 75.86% sensitivity and 67.50% specificity (area under the ROC curve = 0.726, 95% CI: 0.606-0.827, p < 0.001). Conclusion: The FAR can serve as an independent predictor of the degree of plaque enhancement on CE-HR-MRI in patients with ICAS. Also, as an inflammatory marker, the FAR has potential as a serological biomarker of intracranial atherosclerotic plaque vulnerability.

PPM1K mediates metabolic disorder of branched-chain amino acid and regulates cerebral ischemia-reperfusion injury by activating ferroptosis in neurons.

Ischemic stroke is a neurological disorder caused by vascular stenosis or occlusion, accounting for approximately 87% of strokes. Clinically, the most effective therapy for ischemic stroke is vascular recanalization, which aims to rescue neurons undergoing ischemic insults. Although reperfusion therapy is the most effective treatment for ischemic stroke, it still has limited benefits for many patients, and ischemia-reperfusion (I/R) injury is a widely recognized cause of poor prognosis. Here, we aim to investigate the mechanism of protein phosphatase Mg2+/Mn2+ dependent 1 K (PPM1K) mediates metabolic disorder of branched-chain amino acids (BCAA) by promoting fatty acid oxidation led to ferroptosis after cerebral I/R injury. We established the I/R model in mice and used BT2, a highly specific BCAA dehydrogenase (BCKD) kinase inhibitor to promote BCAA metabolism. It was further verified by lentivirus knocking down PPM1K in neurons. We found that BCAA levels were elevated after I/R injury due to dysfunctional oxidative degradation caused by phosphorylated BCKD E1α subunit (BCKDHA). Additionally, the level of phosphorylated BCKDHA was determined by decreased PPM1K in neurons. We next demonstrated that BCAA could induce oxidative stress, lipid peroxidation, and ferroptosis in primary cultured cortical neurons in vitro. Our results further showed that BT2 could reduce neuronal ferroptosis by enhancing BCAA oxidation through inhibition of BCKDHA phosphorylation. We further found that defective BCAA catabolism could induce neuronal ferroptosis by PPM1K knockdown. Furthermore, BT2 was found to alleviate neurological behavior disorders after I/R injury in mice, and the effect was similar to ferroptosis inhibitor ferrostatin-1. Our findings reveal a novel role of BCAA in neuronal ferroptosis after cerebral ischemia and provide a new potential target for the treatment of ischemic stroke.

Safety and performance of oropharyngeal muscle strength training in the treatment of post-stroke dysphagia during oral feeding: protocol for a systematic review and meta-analysis.

INTRODUCTION: Dysphagia is a common functional disorder after stroke. Most patients post-stroke are incapable of oral feeding, which often leads to complications such as malnutrition, aspiration pneumonia and dehydration that seriously affect the quality of life of patients. Oropharyngeal muscle strength training is a major method of swallowing training, and recent studies have focused on healthy adults, elderly persons, and patients with head and neck cancer or neurodegenerative diseases; but there have been few studies on such training in patients with post-stroke dysphagia. Our study aims to systematically review the safety and performance of oropharyngeal muscle strength training in the treatment of post-stroke dysphagia during oral feeding. METHODS AND ANALYSIS: The Cochrane Library, Web of Science, PubMed, Embase and ClinicalTrials.gov databases will be systematically searched, and all relevant articles in English from the establishment of the databases to January 2022 will be reviewed. The study will be conducted in accordance with the recommendations of the Cochrane Handbook for Systematic Reviews of Interventions and will be reported in accordance with Preferred Reporting Items for Systematic Reviews and Meta Analyses guidelines. The primary outcome measures include the Penetration-Aspiration Scale and the Functional Oral Intake Scale. Two authors will independently screen the articles, extract the data and assess the study quality. Any disagreements during this process will be resolved by discussion or by consultation with a third author. Next, quantitative or qualitative, subgroup and sensitivity analyses of the included literature data will be performed as appropriate. ETHICS AND DISSEMINATION: Ethical approval is not required for this systematic review as no primary data collection will be required. The results of the present study will be published in a peer-reviewed journal in the field of deglutition disorders. PROSPERO REGISTRATION NUMBER: CRD42022302471.

Inter-subject registration-based one-shot segmentation with alternating union network for cardiac MRI images.

Medical image segmentation based on deep-learning networks makes great progress in assisting disease diagnosis. However, currently, the training of most networks still requires a large amount of data with labels. In reality, labeling a considerable number of medical images is challenging and time-consuming. In order to tackle this challenge, a new one-shot segmentation framework for cardiac MRI images based on an inter-subject registration model called Alternating Union Network (AUN) is proposed in this study. The label of the source image is warped with deformation fields discovered from AUN to segment target images directly. Initially, the volumes are pre-processed by aligning affinely and adjusting the global intensity to simplify subsequent deformation registration. AUN consists of two kinds of subnetworks trained alternately to optimize segmentation gradually. The first kind of subnetwork takes a pair of volumes as inputs and registers them using global intensity similarity. The second kind of subnetwork, which takes the predicted labels generated from the previous subnetwork and the labels refined using the information of intrinsic anatomical structures of interest as inputs, is intensity-independent and focuses attention on registering structures of interest. Specifically, the input of AUN is a pair of a labeled image with the texture in regions of interest removed and a target image. Additionally, a new similarity measurement more appropriate for registering such image pair is defined as Local Squared Error (LSE). The proposed registration-based one-shot segmentation pays attention to the problem of the lack of labeled medical images. In AUN, only one labeled volume is required and a large number of unlabeled ones can be leveraged to improve segmentation performance, which has great advantages in clinical application. In addition, the intensity-independent subnetwork and LSE proposed in this study empower the framework to segment medical images with complicated intensity distribution.

Association of methylenetetrahydrofolate reductase (MTHFR) rs1801133 (677C>T) gene polymorphism with ischemic stroke risk in different populations: An updated meta-analysis.

Background: Recently, increasing evidence has implicated methylenetetrahydrofolate reductase (MTHFR) gene mutation as a risk factor for ischemic stroke (IS) in the general population. However, studies have been inconclusive and lack evidence on specific populations. We aim to determine whether the rs1801133 (NC_000001.11 (MTHFR):g. 677C>T (p.Ala222Val) variant, we termed as MTHFR rs1801133 (677 C>T), is linked to an increased risk of IS in different age groups and ancestry groups. Methods: The literature relevant to our study was found by searching the PubMed, Cochrane Library, Web of Science, EMBASE, and CNKI databases. A random effect model analysis was used to calculate the pooled odds ratio (OR) and 95% confidence interval (CI) to evaluate any possible association. We conducted a subgroup analysis based on the age and ancestry groups of the included populations. Results: As of March 2022, 1,925 citations had been identified in electronic databases, of which 96 studies involving 34,814 subjects met our eligibility criteria. A strong link was found between IS and the MTHFR gene rs1801133 (677C>T) polymorphism in all genetic models [dominant genetic model (OR = 1.47; 95%CI = 1.33-1.61; p < 0.001), recessive genetic model (OR = 1.52; 95%CI = 1.36-1.71; p < 0.001), heterozygous model (OR = 1.36; 95%CI = 1.24-1.48; p < 0.001), homozygous model (OR = 1.82; 95%CI = 1.58-2.11; p < 0.001), and T allelic genetic model (OR = 1.37; 95%CI = 1.27-1.48; p < 0.001)]. Further subgroup analyses indicated that the MTHFR rs1801133 (677C>T) variant may increase the risk of IS in Asian, Hispanic, or Latin population, middle-aged, and elderly populations (p < 0.001). Conclusion: Our results implied that mutation of the T allele of MTHFR rs1801133 (677C>T) could be a risk factor for IS. A significant association was found among Asian, Hispanic, or Latin population, middle-aged, and elderly people.

Detection of acute ischemic stroke and backtracking stroke onset time via machine learning analysis of metabolomics.

The time window from stroke onset is critical for the treatment decision. However, in unknown onset stroke, it is often difficult to determine the exact onset time because of the lack of assessment methods, which can result in controversial and random treatment decisions. Previous studies have shown that serum biomarkers, in addition to imaging assessment, are useful for determining the stroke onset time. However, as yet there are no specific biomarkers or corresponding methodologies that are accurate and effective for determining the onset time of unknown onset stroke. Herein, we describe our novel advanced metabolites-based machine learning method (termed extreme gradient boost [XGBoost]) combined with recursive feature elimination, which accurately screened five metabolites from 1124 metabolites detected in serum. These metabolites were capable of both detecting acute ischemic stroke and backtracking the acute ischemic stroke onset time. To further investigate the pathological mechanisms of acute ischemic stroke, we also examined characteristic metabolites in different brain regions, and found two metabolites that could distinguish the core infarct area from the ischemic penumbra. Although this study is based on animal experiments, our machine learning framework and selected metabolites may provide a basis for clinical stroke evaluation and treatment.

Synthesis and inhibition of α-glucosidase of methyl glycyrrhetinate glycosides.

The synthesis of the methyl glycyrrhetinate glycosides and inhibition of α-glucosidase were studied. The carboxyl group of glycyrrhetinic acid was methylated, and glucose and galactose were introduced into the hydroxyl group to obtain compounds 7 and 12. Compound 1, 2, 7, 12 and glycyrrhizic acid (GL) were evaluated for their inhibitory activities against α-glucosidase. As a result, Compound 1, 2, 7, 12 and GL all showed significant α-glucosidase inhibitory activity and IC50 values were 0.465, 1.352, 0.759, 0.687 and 2.085 mM, respectively, and acted as non-competitive inhibitors. The activity of the compound 2, 7, 12 was lower than compound 1, but significantly higher than GL. Therefore, it was concluded that the change of structure in glycyrrhetinic acid by chemical modification had certain effect on bioactivity, and the change of carboxyl group, hydroxyl group and the type of monosaccharide introduced were the influencing factors.

The Safety and Efficiency of Tirofiban in Acute Ischemic Stroke Patients Treated with Mechanical Thrombectomy: A Multicenter Retrospective Cohort Study.

INTRODUCTION: Limited comparative studies have reported the safety and efficacy of tirofiban in acute ischemic stroke (AIS) patients after mechanical thrombectomy (MT). Additionally, the available studies are inconsistent with each other, which makes application of tirofiban unclear in neuro-intervention. Here, we performed a comparative retrospective study to investigate whether tirofiban combined with MT improves short- and long-term prognosis in AIS patients and whether its use is associated with complications. METHOD: Retrospective data were collected for AIS patients admitted between January 2013 and January 2019 at three stroke centers. According to whether tirofiban was used during the operation, patients were divided into tirofiban group and control group. Multivariate and COX regression analyses were performed to determine the association of tirofiban treatment with safety and efficiency in subjects treated with MT. RESULT: A total of 174 patients were analyzed, of whom 89 (51.1%) were treated with tirofiban. There were no differences in the incidence of symptomatic intracerebral hemorrhage (10.2% vs. 10.6%, p=0.918), parenchymal hemorrhage type 2 (18.0% vs. 16.5%, p=0.793), and reocclusion at 24 h (3.4% vs. 10.6%, p=0.060) between the tirofiban group and control group. Multivariate regression showed that tirofiban was not associated with intracerebral hemorrhage, early neurological deterioration, neurological improvement at 7 days, functional independence at 3-month and 9-month follow-up, or death at 9-month follow-up (adjusted p > 0.05 for all). However, AIS patients treated with MT + tirofiban showed a trend towards acquiring faster functional independence, with a median time to acquire functional independence of 4.0 months compared with 6.5 months in the control group (risk ratio = 1.49, 95% confidence interval 0.98-2.27; long rank p=0.066). CONCLUSION: Tirofiban may help AIS patients given MT to gain functional independence faster, without increasing the risk of complications.

Contrast-Induced Encephalopathy Resulting From Use of Ioversol and Iopromide.

BACKGROUND: Contrast-induced encephalopathy (CIE) is a rare disease, whose etiology and risk factors remain unclear and need investigation. METHODS: We collected 7 CIE cases from 2646 patients injected with ioversol and 5 CIE cases from 526 patients injected with iopromide, all of whom underwent neurointervention surgery in our regional centers. The incidence of CIE, its characteristics, and risks were analyzed in both groups. RESULTS: The overall incidence of CIE was 0.38%, specifically 0.95% and 0.26% in the iopromide and ioversol groups, respectively; the former incidence was significantly higher than the latter (P = 0.029). The risk of CIE with iopromide was 3.567 to 3.618 times higher than that with ioversol (single-factor analysis odds ratio [OR], 3.618; 95% confidence interval [CI], 1.144-11.443; P = 0.029; multifactor analysis OR, 3.567 (95% CI, 0.827-15.379); P = 0.088). Moreover, acute cerebral infarction was an independent risk factor for CIE (OR, 4.024; 95% CI, 1.137-14.236; P = 0.031). Contrast-induced encephalopathy could occur within 5 minutes after injecting contrast media. The CIE characteristics differed according to the medium. In the ioversol group, the most common characteristic was visual disorder (71.43%), whereas in the iopromide group, the most common characteristic was delirium (100%). CONCLUSIONS: Compared with ioversol, iopromide appeared more likely to lead to CIE. Acute cerebral infarction was an independent risk factor for CIE. The earliest CIE onset was within 5 minutes after injecting contrast. The characteristics of CIE varied significantly for different contrast media.

Basi-parallel anatomic scanning (BPAS-MRI) compared with high-resolution MRI for the diagnosis of vertebrobasilar artery abnormalities.

PURPOSE: To investigate the utility of basi-parallel anatomic scanning magnetic resonance imaging (BPAS-MRI) for the diagnosis of vertebrobasilar artery lesions. METHOD: From October 2017-November 2018, 105 consecutive patients with abnormal configuration of the vertebrobasilar artery on time-of-flight magnetic resonance angiography (TOF-MRA) were enrolled. Conventional high-resolution MRI combined with TOF-MRA were performed to diagnose lesions and were used as the standard for sensitivity and specificity determination. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of BPAS-MRI combined with TOF-MRA were calculated. The consistencies between the two methods were evaluated by kappa test. RESULTS: Of the 105 patients, 45 were diagnosed with arteriosclerosis, 46 with vertebral artery dysplasia, 11 with artery dissection or dissecting aneurysm, and 3 as simple dilatation. Results Compared with conventional high-resolution MRI combined with TOF-MRA, for vertebrobasilar arteriosclerosis, the sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of BPAS-MRI combined with TOF-MRA were 95.6 %, 95.0 %, 93.5 %, 96.6 % and 95.2 %, respectively and kappa value was 0.903. For vertebral artery dysplasia, they were 100 %, 96.6 %, 95.8 %, 100 %, and 98.1 %, respectively and kappa value was 0.961. For vertebrobasilar artery dissection or dissection aneurysm, they were 81.8 %, 96.8 %, 97.8 %, 75.0 % and 95.2 %, respectively and kappa value was 0.756. CONCLUSIONS: BPAS-MRI can show the outer contour of the vertebrobasilar artery system. Combined with TOF-MRA, it may be used to differentiate among vertebrobasilar artery abnormalities, and be used in hospitals where conventional high-resolution MRI is not feasible.