Causal link between oxidative stress and epilepsy: A two-sample Mendelian randomization study.

BACKGROUND: Although a growing body of research has indicated a strong link between oxidative stress and epilepsy, the exact nature of their interaction remains elusive. To elucidate this intricate relationship, we conducted a bidirectional Mendelian randomization (MR) analysis employing two independent datasets. METHODS: A two-sample MR analysis was performed using instrumental variables derived from genome-wide association study summary statistics of oxidative stress injury biomarkers (OSIB) and epilepsy. The OSIBs were selected from eight primary metabolic pathways associated with oxidative stress. Additionally, seven distinct epilepsy phenotypes were considered, which encompassed all epilepsy, generalized epilepsy, generalized tonic-clonic seizures, focal epilepsy, focal epilepsy with hippocampal sclerosis (focal HS), focal epilepsy with lesions other than HS (focal NHS), and lesion-negative focal epilepsy. Causal estimates were computed using the inverse-variance weighted method or the Wald ratio method, and the robustness of causality was assessed through sensitivity analyses. RESULTS: For OSIB and epilepsy, 520 and 23 genetic variants, respectively, were selectively extracted as instrumental variants. Genetically predicted higher kynurenine level was associated with a decreased risk of focal epilepsy (odds ratio [OR] 1.950, 95% CI 1.373-2.528, p = .023) and focal NHS (OR 1.276, 95% CI 1.100-1.453, p = .006). For reverse analysis, there was a suggestive effect of focal NHS on urate (OR 1.19 × 1015, 95% CI 11.19 × 1015 to 1.19 × 1015, p = .0000746) and total bilirubin (Tb) (OR 4.98, 95% CI 3.423-6.543, p = .044). In addition, genetic predisposition to focal HS was associated with higher Tb levels (OR 9.83, 95% CI 7.77-11.888, p = .034). CONCLUSION: This MR study provides compelling evidence of a robust association between oxidative stress and epilepsy, with a notable emphasis on a causal relationship between oxidative stress and focal epilepsy. Additional research is warranted to confirm the connection between oxidative stress and the risk of epilepsy and to unravel the underlying mechanisms.

Whole-cycle management of women with epilepsy of child-bearing age: ontology construction and application.

BACKGROUND: The effective management of epilepsy in women of child-bearing age necessitates a concerted effort from multidisciplinary teams. Nevertheless, there exists an inadequacy in the seamless exchange of knowledge among healthcare providers within this context. Consequently, it is imperative to enhance the availability of informatics resources and the development of decision support tools to address this issue comprehensively. MATERIALS AND METHODS: The development of the Women with Epilepsy of Child-Bearing Age Ontology (WWECA) adhered to established ontology construction principles. The ontology's scope and universal terminology were initially established by the development team and subsequently subjected to external evaluation through a rapid Delphi consensus exercise involving domain experts. Additional entities and attribute annotation data were sourced from authoritative guideline documents and specialized terminology databases within the respective field. Furthermore, the ontology has played a pivotal role in steering the creation of an online question-and-answer system, which is actively employed and assessed by a diverse group of multidisciplinary healthcare providers. RESULTS: WWECA successfully integrated a total of 609 entities encompassing various facets related to the diagnosis and medication for women of child-bearing age afflicted with epilepsy. The ontology exhibited a maximum depth of 8 within its hierarchical structure. Each of these entities featured three fundamental attributes, namely Chinese labels, definitions, and synonyms. The evaluation of WWECA involved 35 experts from 10 different hospitals across China, resulting in a favorable consensus among the experts. Furthermore, the ontology-driven online question and answer system underwent evaluation by a panel of 10 experts, including neurologists, obstetricians, and gynecologists. This evaluation yielded an average rating of 4.2, signifying a positive reception and endorsement of the system's utility and effectiveness. CONCLUSIONS: Our ontology and the associated online question and answer system hold the potential to serve as a scalable assistant for healthcare providers engaged in the management of women with epilepsy (WWE). In the future, this developmental framework has the potential for broader application in the context of long-term management of more intricate chronic health conditions.

Differentiation of epilepsy and psychogenic nonepileptic events based on body fluid characteristics.

OBJECTIVE: Differential diagnosis between epileptic seizures and psychogenic nonepileptic events (PNEEs) is a worldwide problem for neurologists. The present study aims to identify important characteristics from body fluid tests and develop diagnostic models based on them. METHODS: This is a register-based observational study in patients with a diagnosis of epilepsy or PNEEs at West China Hospital of Sichuan University. Data from body fluid tests between 2009 and 2019 were used as a training set. We constructed models with a random forest approach in eight training subsets divided by sex and categories of tests, including electrolyte, blood cell, metabolism, and urine tests. Then, we collected data prospectively from patients between 2020 and 2022 to validate our models and calculated the relative importance of characteristics in robust models. Selected characteristics were finally analyzed with multiple logistic regression to establish nomograms. RESULTS: A total of 388 patients, including 218 with epilepsy and 170 with PNEEs, were studied. The AUROCs of random forest models of electrolyte and urine tests in the validation phase achieved 80.0% and 79.0%, respectively. Carbon dioxide combining power, anion gap, potassium, calcium, and chlorine in electrolyte tests and specific gravity, pH, and conductivity in urine tests were selected for the logistic regression analysis. C (ROC) of the electrolyte and urine diagnostic nomograms achieved 0.79 and 0.85, respectively. SIGNIFICANCE: The application of routine indicators of serum and urine may help in the more accurate identification of epileptic and PNEEs.

Advances in Epilepsy: Mechanisms, Clinical Trials, and Drug Therapies.

Epilepsy is a common disease of the nervous system characterized by transient brain dysfunction caused by an abnormal electrical discharge from the brain neurons. The pathogenesis of epilepsy is complex and remains elusive. Nowadays, drug therapy is the mainstay method for the treatment of epilepsy. More than 30 antiseizure drugs (ASDs) were approved for clinical use. Unfortunately, about 30% of patients still display pharmacoresistance against ASDs. The long-term use of ASDs may cause adverse effects, raise tolerability concerns, bring unexpected drug interactions, generate withdrawal symptoms, and increase the economic burden. Thus, the research uncovering more effective ASDs that are safe is still a difficult and urgent task. In this Perspective, we describe the pathogenesis, clinical trials, and drug therapy progress of epilepsy, focusing on summarizing the current situation of small-molecule drug candidates progressing in epilepsy therapy, which provides future directions for the development of more promising ASDs.

Pharmacological modulation of autophagy for epilepsy therapy: Opportunities and obstacles.

Epilepsy (EP) is a long-term neurological disorder characterized by neuroinflammatory responses, neuronal apoptosis, imbalance between excitatory and inhibitory neurotransmitters, and oxidative stress in the brain. Autophagy is a process of cellular self-regulation to maintain normal physiological functions. Emerging evidence suggests that dysfunctional autophagy pathways in neurons are a potential mechanism underlying EP pathogenesis. In this review, we discuss current evidence and molecular mechanisms of autophagy dysregulation in EP and the probable function of autophagy in epileptogenesis. Moreover, we review the autophagy modulators reported for the treatment of EP models, and discuss the obstacles to, and opportunities for, the potential therapeutic applications of novel autophagy modulators as EP therapies.

Fas -670 A/G polymorphism predicts prognosis of hepatocellular carcinoma after curative resection in Chinese Han population.

BACKGROUND: Apoptosis, also called programmed cell death, is a genetically controlled process against hyperproliferation and malignancy. The Fas-Fas ligand (FasL) system is considered a major pathway for apoptosis in cells and tissues. Thus, this study aimed to investigate whether single nucleotide polymorphisms (SNPs) in Fas and FasL gene may have effects on the recurrence and survival of patients with hepatocellular carcinoma (HCC) after curative hepatectomy. METHODS: We investigated the relationship between Fas rs1800682, rs2234767 and FasL rs763110 polymorphisms and recurrence-free survival (RFS) as well as overall survival (OS) in 117 Chinese Han patients with HCC who underwent hepatectomy. RESULTS: In Kaplan-Meier survival analysis, only Fas rs1800682 (-670 A/G) was associated with RFS and OS. Compared with AA genotype, the AG/GG genotype was significantly associated with better RFS (P = 0.008) and OS (P = 0.020). Moreover, multivariate Cox regression analysis showed that Fas rs1800682 remained as a significant independent predictor of RFS for HCC patients with hepatectomy [AG/GG vs. AA: adjusted hazard ratio = 0.464, 95% confidence interval: 0.275-0.782, P = 0.004], but was not an independent predictor of OS (P = 0.395). CONCLUSIONS: This study demonstrated that Fas -670 G allele may play a protective role in the recurrence and survival of HCC patients with hepatectomy. Furthermore, Fas rs1800682 polymorphism might be a promising biomarker for HCC patients after hepatectomy.

Multi-centered clinical study on effects of nano-amomi paste in treating children's anorexia.

OBJECTIVE: To assess the effect and safety of nano-Amoni Paste (nmAP) in the treatment of children's anorexia (AR). METHODS: One hundred and eighty patients of AR were assigned according to the randomized, double-blinded, double-simulated and parallel controlled principle to three groups, the treated group (TG), the positive control group (PCG) and the negative control group (NCG), 60 in each group. The patients in TG were treated by sticking 1.5 ml of nmAP on the acupoint of Shenque (Ren 8) once a day and orally taking placebo liquid 10 ml twice a day; those in PCG and NCG treated with sticking paste of placebo on Ren 8, and oral taking of Shanmai Jianpi Oral Liquid and placebo liquid respectively, 10 ml each time twice per day. The course of treatment for all was 10 days, all patients were treated for 2 courses. RESULTS: The total effective rate and the effective rate on cardinal symptom in TG was 85.0% and 95.0% respectively, that in PCG 86.2% and 96.55% and in NCG 45.5% and 65.45%, respectively, showing significant difference between groups (P<0.05). Comparison of the clinical manifestation before and after treatment showed significant improvement in volume of food intake, appetite, complexion and reduction of restlessness symptom (P<0.05) in all three groups, and there was no adverse reaction found in them. CONCLUSION: nmAP is an effective and safe remedy for treatment of Children's anorexia.