Thrombosis origin identification of cardioembolism and large artery atherosclerosis by distinct metabolites.

BACKGROUND: The diagnosis of cerebral thrombosis origin is challenging and remains unclear. This study aims to identify thrombosis due to cardioembolism (CE) and large artery atherosclerosis (LAA) from a new perspective of distinct metabolites. METHODS: Distinct metabolites between 26 CE and 22 LAA origin thrombi, which were extracted after successful mechanical thrombectomy in patients with acute ischemic stroke in the anterior circulation, were analyzed with a ultra performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-QTOF-MS) system. Enriched metabolic pathways related to the metabolites were identified. Least absolute shrinkage selection operator regression analyses and a filtering method were used to select potential predictors. Furthermore, four machine learning classifiers, including decision tree, logistic regression, random forest (RF), and k means unsupervised classification model, were used to evaluate the predictive ability of the selected metabolites. RESULTS: UPLC-QTOF-MS analysis revealed that levels of 88 and 55 metabolites were elevated in LAA and CE thrombi, respectively. Kyoto Encyclopedia of Genes and Genomes analysis revealed a significant difference between the pathways enriched in the two types of thrombi. Six metabolites (diglyceride (DG, 18:3/24:0), DG (22:0/24:0), phytosphingosine, galabiosylceramide (18:1/24:1), triglyceride (15:0/16:1/o-18:0), and glucosylceramide (18:1/24:0)) were finally selected to build a predictive model. The predictive RF model was confirmed to be the best, with a satisfactory stability and prediction capacity (area under the curve=0.889). CONCLUSIONS: Six metabolites as potential predictors for distinguishing between cerebral thrombi of CE and LAA origin were identified. The results are useful for understanding the pathogenesis and for secondary stroke prevention.

CRISPR Detection and Research on Screening Mutant Gene TTN of Moyamoya Disease Family Based on Whole Exome Sequencing.

Moyamoya disease (MMD) has a high incidence in Asian populations and demonstrates some degree of familial clustering. Whole-exome sequencing (WES) is useful in establishing key related genes in familial genetic diseases but is time-consuming and costly. Therefore, exploring a new method will be more effective for the diagnosis of MMD. We identified familial cohorts showing MMD susceptibility and performed WES on 5 affected individuals to identify susceptibility loci, which identified point mutation sites in the titin (TTN) gene (rs771533925, rs559712998 and rs72677250). Moreover, TTN mutations were not found in a cohort of 50 sporadic MMD cases. We also analyzed mutation frequencies and used bioinformatic predictions to reveal mutation harmfulness, functions and probabilities of disease correlation, the results showed that rs771533925 and rs72677250 were likely harmful mutations with GO analyses indicating the involvement of TTN in a variety of biological processes related to MMD etiology. CRISPR-Cas12a assays designed to detect TTN mutations provided results consistent with WES analysis, which was further confirmed by Sanger sequencing. This study recognized TTN as a new familial gene marker for moyamoya disease and moreover, demonstrated that CRISPR-Cas12a has the advantages of rapid detection, low cost and simple operation, and has broad prospects in the practical application of rapid detection of MMD mutation sites.

Identification of key pathways and genes in carotid atherosclerosis through bioinformatics analysis of RNA-seq data.

While acknowledging carotid atherosclerosis (CAS) as a risk factor for ischemic stroke, reports on its pathogenesis are scarce. This study aimed to explore the potential mechanism of CAS through RNA-seq data analysis. Carotid intima tissue samples from CAS patients and healthy subjects were subjected to RNA-seq analysis, which yielded, 1,427 differentially expressed genes (DEGs) related to CAS. Further, enrichment analysis (Gene Ontology, KEGG pathway, and MOCDE analysis) was performed on the DEGs. Hub genes identified via the protein-protein interaction network (PPI) were then analyzed using TRRUST, DisGeNET, PaGenBase, and CMAP databases. Results implicated inflammation and immunity in the pathogenesis of CAS. Also, lung disease was associated with CAS. Hub genes were expressed in multiple diseases, mainly regulated by RELA and NFKB1. Moreover, three small-molecule compounds were found via the CMAP database for management of CAS; hub genes served as potential targets. Collectively, inflammation and immunity are the potential pathological mechanisms of CAS. This study implicates CeForanide, Chenodeoxycholic acid, and 0317956-0000 as potential drug candidates for CAS treatment.

Beneficial consequences of Lupeol on middle cerebral artery-induced cerebral ischemia in the rat involves Nrf2 and P38 MAPK modulation.

Lupeol has been reported to exhibit anti-inflammatory and anti-tumor activities in many diseases, but its potential effects in cerebral ischemia injury have not been studied to date. In this work we present evidence for a beneficial effect of lupeol in a rat model of middle cerebral artery occlusion (MCAO) followed by reperfusion (MCAO/R) injury and provide some histological and biochemical evidence for its mechanism of action. A cerebral MCAO rat model was established by vascular occlusion for 2 h, followed by 24 h reperfusion period. The infarct volume, neurological deficits, and brain water content were compared with animals treated during reperfusion with different concentrations of lupeol. Macroscopic parameters, cell viability, pro-inflammatory factors generation, as well as oxidative stress parameters and associated apoptotic signaling cascades were evaluated. Treatment with lupeol significantly reduced the cerebral infarct volume and water content and recovered neuro behavioral functions in affected rats. Lupeol treatment down-regulated the expression of oxidative stress and inflammation factors. In addition, lupeol activated Nrf2, suppressed caspase-3 activity, reduced BAX/Bcl-2 ratio and inhibited phosphorylation of p38 MAPK. The data suggest that lupeol may exert protective effects against cerebral ischemia by suppressing oxidative stress and reduction of inflammation factors possible via activation of nuclear transcription factors and inhibition of cell death pathways.

Endovascular coiling versus surgical clipping for the treatment of unruptured cerebral aneurysms: Direct comparison of procedure-related complications.

BACKGROUND: Endovascular coiling and surgical clipping are routinely used to treat unruptured cerebral aneurysms (UCAs). However, the evidence to support the efficacy of these approaches is limited. We aimed to analyze the efficacy of endovascular coiling compared with surgical clipping in patients with UCAs. METHOD: A systematic search of 4 databases was conducted to identify comparative articles involving endovascular coiling and surgical clipping in patients with UCAs. We conducted a meta-analysis using the random-effects model when I> 50%. Otherwise, a meta-analysis using the fixed-effects model was performed. RESULTS: Our results showed that endovascular coiling was associated with a shorter length of stay (WMD: -4.14, 95% CI: (-5.75, -2.531), P < .001) and a lower incidence of short-term complications compared with surgical clipping (OR: 0.518; 95% CI (0.433, 0.621); P < .001), which seems to be a result of ischemia complications (OR: 0.423; 95% CI (0.317, 0.564); P < .001). However, surgical clipping showed a higher rate of complete occlusion after surgery, in both short-term (OR: 0.179, 95% CI (0.064, 0.499), P = .001) and 1-year follow-ups (OR: 0.307, 95% CI (0.146, 0.646), P = .002), and a lower rate of short-term retreatment (OR: 0.307, 95% CI (0.146, 0.646), P = .002). Meanwhile, there was no significant difference in postoperative death, bleeding, and modified Rankin Scale (mRS) > 2 between the 2 groups. CONCLUSIONS: The latest evidence illustrates that surgical clipping resulted in lower retreatment rates and was associated with a higher incidence of complete occlusion, while endovascular coiling was associated with shorter LOS and a lower rate of complications, especially ischemia.

Dual versus Single Antiplatelet Therapy in Carotid Artery Endarterectomy: Direct Comparison of Complications Related to Antiplatelet Therapy.

BACKGROUND: Dual and single antiplatelet therapies are routinely used in carotid artery endarterectomy (CEA). However, the efficacy and safety of these therapies are controversial. The present study aimed to comprehensively compare the clinical outcomes between dual and single antiplatelet therapies in CEA. METHODS: This study retrieved available academic studies evaluating the complications related to antiplatelet therapy between dual and single antiplatelet therapies in CEA from the databases of ScienceDirect, the Cochrane Library, EMBASE, and PubMed. References to previous reviews and related clinical trials were manually checked to retrieve potential literature that was not included in our electronic search results. RESULTS: A total of 10 articles (1 randomized controlled trial, 9 non-randomized controlled trials) were included in the study. The overall number of patients in the dual antiplatelet group was 14,280, and the number of patients in the single antiplatelet group was 125,850. The results revealed that the single antiplatelet group had a lower incidence of 30-day death (rate difference [RD] 0.002; 95% confidence interval [CI] 0.000-0.003; P = 0.014), neck hematoma (odds ratio [OR] 2.120; 95% CI 1.431-3.142; P < 0.001), myocardial infarction (RD 0.004; 95% CI 0.001-0.007; P = 0.003), and major bleeding (RD 0.005; 95% CI 0.002-0.008; P < 0.001). Meanwhile, the single antiplatelet group was associated with a shorter operation time (weighted mean difference 4.000; 95% CI= 2.564-5.436; P < 0.001). However, there was no significant difference in the rate of postoperative transient ischemic attack (P = 0.215), stroke (P = 0.130), or length of stay (P = 0.563). CONCLUSIONS: Based on current evidence, using single antiplatelet therapy in CEA may reduce operation time and the incidences of 30-day death, neck hematoma, major bleeding, and myocardial infarction without increasing the risks of transient ischemic attack, stroke, or a longer operation time.

Efficacy of Biomedical Glue Sling Technique Versus Traditional Technique for Microvascular Decompression for Hemifacial Spasm with Refractory Hypertension.

BACKGROUND: Microvascular decompression (MVD) is useful treatment for hemifacial spasm (HFS) with refractory hypertension (RHTN). The biomedical glue sling technique is a new method for MVD. In this study, we retrospectively compared the outcome of the biomedical glue sling technique with traditional technique in MVD for HFS with RHTN. METHODS: A retrospective study of HFS with RHTN treated by MVD was conducted between January 2010 and June 2016. Among 155 patients who underwent their first MVD at our institution, traditional technique was performed in 73 cases of patients and the biomedical glue sling technique was performed on 82 patients. RESULTS: At 3 days, 7 days, 1 month, 3 months, and 1 year after MVD surgery, in the traditional technique group the effective rates of MVD for HFS were 86.30%, 84.93%, 87.14%, 84.06%, and 83.33%. The effective rates for RHTN were 68.49%, 67.12%, 65.71%, 57.97%, and 57.58%. The incidence rates of complication were 5.48%, 5.48%, 4.29%, 2.90%, and 3.03%. In the biomedical glue sling technique group, the effective rates of MVD for HFS were 97.56%, 97.56%, 98.75%, 96.15%, and 94.59% (P < 0.05). The effective rates for RHTN were 85.37%, 82.93%, 81.25%, 79.49%, and 75.68% (P < 0.05). The incidence rates of complication were 6.10%, 6.10%, 5.00%, 3.85%, and 2.70% (P > 0.05). CONCLUSION: When HFS is associated with RHTN, the efficacy of the biomedical glue sling technique for MVD is higher than that of the traditional technique for both HFS and RHTN.