Serum biomarkers in patients with drug-resistant epilepsy: a proteomics-based analysis

ObjectiveTo investigate the serum biomarkers in patients with drug-resistant epilepsy (DRE).MethodsA total of 9 DRE patients and 9 controls were enrolled. Serum from DRE patients was prospectively collected and analyzed for potential serum biomarkers using TMT18-labeled proteomics. After fine quality control, bioinformatics analysis was conducted to find differentially expressed proteins. Pathway enrichment analysis identified some biological features shared by differential proteins. Protein–protein interaction (PPI) network analysis was further performed to discover the core proteins.ResultsA total of 117 serum differential proteins were found in our study, of which 44 were revised upwards and 73 downwards. The up-regulated proteins mainly include UGGT2, PDIA4, SEMG1, KIAA1191, CCT7 etc. and the down-regulated proteins mainly include ROR1, NIF3L1, ITIH4, CFP, COL11A2 etc. Pathway enrichment analysis identified that the upregulated proteins were mainly enriched in processes such as immune response, extracellular exosome, serine-type endopeptidase activity and complement and coagulation cascades, and the down-regulated proteins were enriched in signal transduction, extracellular exosome, zinc/calcium ion binding and metabolic pathways. PPI network analysis revealed that the core proteins nodes include PRDX6, CAT, PRDX2, SOD1, PARK7, GSR, TXN, ANXA1, HINT1, and S100A8 etc.ConclusionThe discovery of these differential proteins enriched our understanding of serum biomarkers in patients with DRE and potentially provides guidance for future targeted therapy

Functional MRI study of neurovascular coupling in patients with non-lesional epilepsy

ObjectiveThe diagnosis of patients with non-lesional epilepsy (NLE) is relatively challenging because of the absence of a clear focus on imaging, and the underlying pathological mechanism remains unclear. The neuronal activity and functional connectivity of NLE patients are significantly abnormal, and the neuronal activity of epilepsy patients is closely related to cerebral blood flow (CBF). Neurovascular coupling (NVC) offers insights into the relationship between neuronal activity and CBF. Hence, we intend to explore the alterations of NVC in NLE patients and their influences on cognitive function.MethodsClinical data of 24 patients with NLE (15 female; age range 19–40 years; median age 30.5 years) and 39 healthy controls (27 female; age range 19–40 years; median age 30 years) were collected, and resting-state functional magnetic resonance imaging (rs-fMRI) and 3D arterial spin labeling (ASL) were performed. The imaging indexes of amplitude of low-frequency fluctuation (ALFF) and CBF were calculated, respectively, by post-processing analysis. The differences in CBF, ALFF and CBF/ALFF ratio between the two groups were analyzed, along with correlation with clinical data of NLE patients.ResultsCompared with the healthy controls, the CBF of the right parahippocampal gyrus was significantly decreased, and the CBF/ALFF ratio of the right inferior parietal, but supramarginal and angular gyri was significantly increased in NLE patients (p < 0.001). Moreover, the CBF/ALFF ratio was positively correlated with epilepsy depression score (r = 0.546, p = 0.006).ConclusionNLE patients showed abnormal local NVC, which was associated with the severity of depression. The combined application of rs-fMRI and ASL can comprehensively evaluate the neuronal activity and cerebral blood perfusion in patients with NLE. The abnormal NVC is of great significance for us to explore the central mechanism of the occurrence and development of NLE

Study of brain network alternations in non-lesional epilepsy patients by BOLD-fMRI

ObjectiveTo investigate the changes of brain network in epilepsy patients without intracranial lesions under resting conditions.MethodsTwenty-six non-lesional epileptic patients and 42 normal controls were enrolled for BOLD-fMRI examination. The differences in brain network topological characteristics and functional network connectivity between the epilepsy group and the healthy controls were compared using graph theory analysis and independent component analysis.ResultsThe area under the curve for local efficiency was significantly lower in the epilepsy patients compared with healthy controls, while there were no differences in global indicators. Patients with epilepsy had higher functional connectivity in 4 connected components than healthy controls (orbital superior frontal gyrus and medial superior frontal gyrus, medial superior frontal gyrus and angular gyrus, superior parietal gyrus and paracentral lobule, lingual gyrus, and thalamus). In addition, functional connectivity was enhanced in the default mode network, frontoparietal network, dorsal attention network, sensorimotor network, and auditory network in the epilepsy group.ConclusionThe topological characteristics and functional connectivity of brain networks are changed in in non-lesional epilepsy patients. Abnormal functional connectivity may suggest reduced brain efficiency in epilepsy patients and also may be a compensatory response to brain function early at earlier stages of the disease

The Control Strategy Research of 4WID Vehicles Steering-by-Wire System

Abstract Once the traditional electric vehicle was refitted with distributed drive (4wid) system, the increasing of vehicle’s unsprung mass would significantly increase the steering resistance, as a result of that, the efficiency and accuracy of the original car’s steer-by-wire (SBW) system will be reduced. In order to solve this problem, taking BAIC-EV150 for example, this paper introduced a design of SBW control strategy for 4WID vehicles, and the corresponding refitting work of real vehicle were completed. The refitted vehicle adopted dual-motor, dual-controller to coordinate control the output torque, aiming at compensating the resistance moment. Simulation and experimental results show that the controller can meet the requirements of 4WID vehicle steering, and the dual-motor steering system based on fuzzy PID control is more responsive and more accurate than the single-motor steering system which under ordinary PID control.</jats:p

Dynamic Change of Eosinophil and Acute Ischemic Stroke

Abstract Background: Eosinopenia has been shown to be a predicative factor for the infection and mortality in ischemic stroke patients which mainly focused on static eosinophil count. This study aimed to explore the relationship between dynamic change of eosinophil count and short-term prognosis of acute ischemic stroke (AIS).Methods: A total of 174 patients with AIS were respectively enrolled. Blood samples for blood routine examination were obtained at admission before any treatments and the next day. Eosinopenia was defined as the continuous decrease of the count of eosinophil from the first day to the second. Infarct volume was measured by diffusion-weighted MR imaging volume. 90-day modified Rankin Scale scores were collected to assess the prognosis of patients with AIS.Results: Patients were divided into two groups according to whether they have eosinopenia. Patients with eosinopenia were more likely to have large infarct volume (3.2 [0.6-39.9] cm3 vs 1.1 [0.3-6.0] cm3, P =.004). Receiver operating characteristic analysis demonstrated that the eosinophil count on the second day was more accurate than the time of admission to identify the large cerebral infarction (LCI) (0.866 vs 0.603, P ＜.001). Logistic regression analysis revealed that eosinopenia was independently associated with LCI (P =.015) and poor outcome (P =.011), and patients with eosinopenia had a 4.05-fold greater risk for LCL (95% CI 1.31-12.51) and a 4.29-fold greater risk for worse clinical outcomes (95% CI 1.27-14.51) than patients without.Conclusion： Eosinophil is a dynamic variable, and its variation is associated with poor outcome in acute ischemic stroke patients.</jats:p

Efficacy and Safety of SPN-812 (Extended-Release Viloxazine) in Children and Adolescents with Attention-Deficit/Hyperactivity Disorder: A Systematic Review and Meta-Analysis

Background: SPN-812 has been approved for attention-deficit/hyperactivity disorder (ADHD) treatment in children and adolescents. Objective: We aimed to analyze the efficacy and safety of different doses of SPN-812 for ADHD pediatric patients of different ages, verify its clinical efficacy, and evaluate its safety. Methods: Up until 30 August 2023, randomized controlled trials (RCTs) were searched in EMBASE, MEDLINE, the Cochrane Library, and clinicaltrials.gov to evaluate different doses of SPN-812 and a placebo. Results: We pooled 1619 patients from five RCTs with a duration of 6&ndash;8 weeks. Patients (6&ndash;17 years old) in SPN-812 (100, 200, and 400 mg/d) groups were superior to the control group in all efficacy outcomes with lower attention-deficit/hyperactivity disorder rating scale-5 (ADHD-RS-5), Conners 3-parent short form composite T score (Conners 3-PS), Weiss functional impairment rating scale-parent (WFIRS-P), and increased clinical global impression-improvement (CGI-I) score (both p &lt; 0.05). At the same time, only SPN-812 300 mg/d did not show a significantly high risk of the adverse events (AEs) such as somnolence and decreased appetite (p = 0.09). There was no significant difference between placebo and SPN-812 groups (100, 200, and 400 mg/d) in serious adverse events (SAEs) such as syncope. The subgroup analyses showed that, both in children and adolescents subgroups, SPN-812 showed better efficacy than the placebo. The two age subgroups showed a significantly higher risk of AEs and an insignificant risk of SAEs than the placebo. Conclusion: At present, SPN-812 (100, 200, and 400 mg/d) is superior to the corresponding control in efficacy measures. However, the safety problem cannot be ignored

Table_1_Serum biomarkers in patients with drug-resistant epilepsy: a proteomics-based analysis.docx

ObjectiveTo investigate the serum biomarkers in patients with drug-resistant epilepsy (DRE).MethodsA total of 9 DRE patients and 9 controls were enrolled. Serum from DRE patients was prospectively collected and analyzed for potential serum biomarkers using TMT18-labeled proteomics. After fine quality control, bioinformatics analysis was conducted to find differentially expressed proteins. Pathway enrichment analysis identified some biological features shared by differential proteins. Protein–protein interaction (PPI) network analysis was further performed to discover the core proteins.ResultsA total of 117 serum differential proteins were found in our study, of which 44 were revised upwards and 73 downwards. The up-regulated proteins mainly include UGGT2, PDIA4, SEMG1, KIAA1191, CCT7 etc. and the down-regulated proteins mainly include ROR1, NIF3L1, ITIH4, CFP, COL11A2 etc. Pathway enrichment analysis identified that the upregulated proteins were mainly enriched in processes such as immune response, extracellular exosome, serine-type endopeptidase activity and complement and coagulation cascades, and the down-regulated proteins were enriched in signal transduction, extracellular exosome, zinc/calcium ion binding and metabolic pathways. PPI network analysis revealed that the core proteins nodes include PRDX6, CAT, PRDX2, SOD1, PARK7, GSR, TXN, ANXA1, HINT1, and S100A8 etc.ConclusionThe discovery of these differential proteins enriched our understanding of serum biomarkers in patients with DRE and potentially provides guidance for future targeted therapy.</p

Choriocapillaris Changes Are Correlated With Disease Duration and MoCA Score in Early-Onset Dementia

Purpose: Imaging of the choroid may detect the microvascular changes associated with early-onset dementia (EOD) and may represent an indicator for detection of the disease. We aimed to analyze the in vivo choriocapillaris (CC) flow density in EOD patients using optical coherence tomography angiography (OCTA) and evaluate the association with its clinical measures.Methods: This cross-sectional study used the OCTA to image and analyze the choriocapillaris (CC) of 25 EOD patients and 20 healthy controls. Choriocapillaris flow density in the 3 mm area and 6 mm area was measured by an inbuilt algorithm in the OCT tool. Brain volume using magnetic resonance imaging and cognitive assessment was done and recorded.Results: Significantly reduced capillary flow density of the choriocapillaris was seen in EOD patients when compared to healthy controls in the 3.0 mm (P = 0.001) and 6.0 mm (P &amp;lt; 0.001) area respectively. Montreal Cognitive Assessment (MoCA) scores in EOD patients positively correlated with choriocapillaris flow density in the 3 mm area (Rho = 0.466, P = 0.021). Disease duration of EOD patients also negatively correlated with choriocapillaris density in the 3 mm area (Rho = −0.497, P = 0.008).Discussion: Our report suggests that choriocapillaris damage may be a potential indicator of early-onset dementia. Microvascular impairment may be involved in the early phase of dementia without aging playing a role in its impairment.Clinical Trial Registration: www.ClinicalTrials.gov, ChiCTR2000041386.</jats:p