Variants in 3p24.3 predicts the risk of early neurological deterioration in large artery atherosclerotic stroke.

The rate of early neurological deterioration (END) differs in different subtypes of ischaemic stroke. Previous studies showed PLCL2 gene is a novel susceptibility locus for the occurrence of atherosclerosis and thrombotic events. The objective of this research is to examine the efficacy that PLCL2 may have on the risk of END in large artery atherosclerotic (LAA) stroke. Tagged single nucleotide polymorphisms (SNPs) were identified by a strategy of fine-mapping. The genotyping of the selected SNPs was performed by SNPscan. The impact of PLCL2 on indicating the susceptibility of END in LAA patients was evaluated by binary logistic regression. The SNP-SNP interactions of PLCL2 for END was assessed by generalized multifactor dimensionality reduction (GMDR). A total of 1527 LAA stroke patients were recruited, 582 patients (38 %) experienced END. Compared to participants without END, participants experienced END were much older (P = 0.018), more likely to suffer pre-existing diabetes mellitus (P = 0.036), higher frequent in active tobacco users (P = 0.022) and had much higher median NIHSS on admission (P < 0.001). Rs4685423 was identified to be a predictor to the risk of END: the frequency of END in AA genotype patients is lower than that in AC or CC genotype patients (multivariate-adjusted, OR 0.63; 95 % CI 0.49-0.80; P < 0.001). The SNP-SNP interactions analysis indicates rs4685423 has the greatest impacton the risk of END for LAA patients. The time from admission diagnosis to END onset in AA genotype patients is much later than that in CA or CC genotype patients (log-rank, P = 0.005). In summary, the PLCL2 rs4685423 SNP is probably associated with the END risk in LAA stroke patients.

The E3 ligase TRIM7 suppresses the tumorigenesis of gastric cancer by targeting SLC7A11.

Tripartite motif-containing protein 7 (TRIM7), as an E3 ligase, plays an important regulatory role in various physiological and pathological processes. However, the role of TRIM7 in gastric cancer (GC) is still undefined. Our study detected the expression of TRIM7 in clinical specimens and investigated the regulatory effect and molecular mechanism of TRIM7 on GC progression through in vitro and in vivo experiments. Our finding showed that TRIM7 was significantly downregulated in GC, and patients with high expression of TRIM7 showed long overall survival. Both in vitro and in vivo experiments showed that TRIM7 dramatically suppressed the malignant progression of GC. Further investigation showed that ferroptosis was the major death type mediated by TRIM7. Mechanistically, TRIM7 interacted with SLC7A11 through its B30.2/SPRY domain and promoted Lys48-linked polyubiquitination of SLC7A11, which effectively suppressing SLC7A11/GPX4 axis and inducing ferroptosis in GC cells. In vivo experiments and correlation analysis based on clinical specimens further confirmed that TRIM7 inhibited tumor growth through suppressing SLC7A11/GPX4 axis. In conclusion, our investigation demonstrated for the first time that TRIM7, as a tumor suppressor, induced ferroptosis via targeting SLC7A11 in GC, which provided a new strategy for the molecular therapy of GC by upregulating TRIM7.

Gentiopicroside inhibits the progression of gastric cancer through modulating EGFR/PI3K/AKT signaling pathway.

BACKGROUND: This study was designed to clarify the function and potential mechanism of gentiopicroside (GPS) in regulating the malignant progression of gastric cancer (GC) through in vitro cellular experiments and in vivo animal models. METHODS: AGS and HGC27 cells were divided into control group and GPS treatment groups (50 µM and 100 µM). Then, the cellular proliferation, colony formation, migration, invasion, and apoptosis were detected, respectively. Transmission electron microscope (TEM) was used to observe the mitochondrial changes, and the mitochondrial membrane potential (MMP) was determined using the JC-1 commercial kit. Network pharmacology analysis was utilized to screen the potential molecule that may be related to the GPS activity on GC cells, followed by validation tests using Western blot in the presence of specific activator. In addition, xenografted tumor model was established using BALB/c nude mice via subcutaneous injection of HGC27 cells, along with pulmonary metastasis model. Then, the potential effects of GPS on the tumor growth and metastasis were detected by immunohistochemistry (IHC) and HE staining. RESULTS: GPS inhibited the proliferation, invasion and migration of GC cell lines in a dose-dependent manner. Besides, it could induce mitochondrial apoptosis. Epidermal growth factor receptor (EGFR) may be a potential target for GPS action in GC by network pharmacological analysis. GPS inhibits activation of the EGFR/PI3K/AKT axis by reducing EGFR expression. In vivo experiments indicated that GPS induced significant decrease in tumor volume, and it also inhibited the pulmonary metastasis. For the safety concerns, GPS caused no obvious toxicities to the heart, liver, spleen, lung and kidney tissues. IHC staining confirmed GPS downregulated the activity of EGFR/PI3K/AKT. CONCLUSIONS: Our investigation demonstrated for the first time that GPS could inhibit GC malignant progression by targeting the EGFR/PI3K/AKT signaling pathway. This study indicated that GPS may be serve as a safe anti-tumor drug for further treatment of GC.

External validation of the AntiEpileptic Drug Monitoring in PREgnancy (EMPiRE) model for predicting seizures in pregnant women with epilepsy.

BACKGROUND: The AntiEpileptic Drug Monitoring in PREgnancy (EMPiRE) model is the only available tool for predicting seizures in pregnant women with epilepsy (WWE) using anti-seizure medications (ASMs); however, its predictive performance requires validation. This study aimed to evaluate the predictive ability of this model in pregnant Chinese WWE and its potential usefulness in clinical practice. METHODS: Data of the EMPiRE model were derived from the EMPiRE study, a prospective multicenter cohort study that recruited women on ASM monotherapy (lamotrigine, carbamazepine, phenytoin or levetiracetam) or polytherapy (lamotrigine with either carbamazepine, phenytoin or levetiracetam). Based on the applicable population of the EMPiRE model, we evaluated 280 patients registered in the Wenzhou Epilepsy Follow-up Registry Database from January 1, 2010, to December 31, 2020. A total of 158 eligible patients were included in the validation cohort. We collected data on the baseline characteristics of patients, eight predictors of the EMPiRE model and outcome events. The outcome was the occurrence of tonic-clonic or non-tonic-clonic seizures at any time in pregnancy up to 6 weeks postpartum. We used the equation of the EMPiRE model to obtain the predicted probabilities of seizures. The predictive ability of the EMPiRE model was quantified by the C-statistic (scale 0-1, values > 0.5 show discrimination), GiViTI calibration test and decision curve analysis (DCA). RESULTS: Of 158 eligible patients, 96 patients (60.8%, 96/158) experienced one or more seizures at any time between pregnancy and 6 weeks postpartum. The EMPiRE model showed good discrimination with a C-statistic of 0.76 (95% confidence interval [CI] 0.70-0.84). The GiViTI calibration belt showed that the predicted probabilities, which ranged from 16 to 96% (95% CI), were lower than the actual probabilities. DCA indicated that the highest net proportional benefit was obtained for predicted probability thresholds of 15-18% and 54-96%. CONCLUSIONS: The EMPiRE model could discriminate well between WWE with and without seizures during pregnancy and 6 weeks postpartum, but the risk of seizures may be underestimated. The limitations of the model for specific medication regimens may limit its real-world application. If the model is further improved, it will be incredibly valuable.

Changes in seizure frequency and anti-seizure medication therapy during pregnancy and one year postpregnancy.

Seizure control in women with epilepsy (WWE) during pregnancy is a vital concern. The aim of this study was to compare changes in seizure frequency and anti-seizure medication (ASM ) therapy in WWE in a real-world setting over three epochs (prepregnancy, pregnancy, and postpregnancy). We screened WWE who were pregnant between 1 January 2010 and 31 December 2020 from the epilepsy follow-up registry database of a tertiary hospital in China. We reviewed and collected follow-up data for the following time periods: 12 months before pregnancy (epoch 1), throughout pregnancy and the first 6 weeks postpartum (epoch 2), and from 6 weeks to 12 months postpartum (epoch 3). Seizures were classified into two categories: tonic‒clonic/focal to bilateral tonic‒clonic seizures and non-tonic‒clonic seizures. The main indicator was the seizure-free rate over the three epochs. Using epoch 1 as a reference, we also compared the percentage of women with an increased seizure frequency, as well as changes in ASM treatment, in epochs 2 and 3. Ultimately, 271 eligible pregnancies in 249 women were included. The seizure-free rates in epoch 1, epoch 2, and epoch 3 were 38.4%, 34.7%, and 43.9%, respectively (P = 0.09). The top three ASMs used in the three epochs were lamotrigine, levetiracetam, and oxcarbazepine. Using epoch 1 as a reference, the percentages of women with increased frequencies of tonic‒clonic/focal to bilateral tonic‒clonic seizures in epoch 2 and epoch 3 were 17.0% and 14.8%, respectively, while the percentages of women with an increased frequency of non-tonic‒clonic seizures in epoch 2 and epoch 3 were 31.0% and 21.8% (P = 0.02). The percentage of women whose ASM dosages were increased in epoch 2 was higher than that in epoch 3 (35.8% vs. 27.3%, P = 0.03). The seizure frequency during pregnancy may not differ significantly from that during prepregnancy and postpregnancy if WWE are treated according to the guidelines.

Study on the Tribological Behavior and the Interaction between Friction and Oxidation of Graphite Reinforced by Impregnated Phosphate at High Temperatures.

The stability of the graphite seal device is a key factor for the normal operation of aero engines. However, conventional graphite exhibits poor comprehensive performance due to its porous structure, which limits its application at high temperatures. Therefore, in this paper, phosphate was used to impregnated graphite pores, and the interaction between the friction, wear, and oxidation of phosphate-impregnated graphite against superalloy at high temperatures was studied through pin-on-disk friction tests. The results revealed that the coefficient of friction (COF) of matrix graphite fluctuated greatly, from 0.07 to 0.17, in the range of 100 °C to 500 °C, while the COF of impregnated graphite was stable, at around 0.13, from 100 °C to 500 °C. The wear rates of the two types of graphite were close from 20 °C to 300 °C, while the wear rate of the impregnated graphite was significantly lower than that of the matrix graphite at higher temperatures, from 400 °C and 500 °C. The reason was that the impregnated phosphate reacted with graphite at a high temperature, forming the inert site which helped to inhibit the oxidation and maintain the mechanical properties of the impregnated graphite at high temperatures. In addition, the impregnated graphite could maintain better integrity of the contact surface and reduce the inclusion of large hard metal oxides, thus effectively reducing the abrasive wear of the disk. Therefore, the wear depth of the superalloy disk samples with impregnated graphite was significantly lower than that of the matrix graphite. The results promote the application of phosphate-impregnated graphite under the high temperature conditions of aero engines.

Effect of Particle Size and Morphology of Siliceous Supplementary Cementitious Material on the Hydration and Autogenous Shrinkage of Blended Cement.

Supplementary cementitious material (SCM) plays an important role in blended cement, and the effect of the particle size and morphology of siliceous supplementary cementitious material on hydration should not be ignored. In this study, 0.5 h and 1 h of wet grinding was applied to pretreat iron ore tailing powder (TP), and the divergence in pozzolanic behavior and morphology were investigated. Then, the treated TPs were used to replace the 30% cement contents in preparing blended cementitious paste, and the impact mechanism of morphology on performance was studied emphatically. M, the autogenous shrinkages of pastes were tested. Finally, hydration reaction kinetics was carried out to explore the hydration behavior, while X-ray diffraction (XRD) and thermogravimetric analysis (TGA) were used to characterize the hydration product properties, respectively. Meanwhile, microscopy intrusion porosimetry (MIP) was also carried out to characterize the pore structures of hardened specimens. Results indicated that wet grinding has a dramatic effect on particle size and morphology, but hardly affects the phase assemblages and pozzolanic reactivity of TP, while the particle shape of TP changes from sub-circular to clavate and, finally, back to sub-circular. The results of hydration reaction kinetics, representing the morphology of particles, had a significant effect on hydration rate and total heat, and compared with the sub-circle one, the clavated particle could inhibit the hydration procedure. With the increasing grinding time, the compressive strength of cementitious paste was increased from 17.37% to 55.73%, and the micro-pore structure became denser; however, the autogenous shrinkage increased.

Enumeration optimization of open pit production scheduling based on mobile capacity search domain.

The optimization of open pit mine production scheduling is not only a multistage decision-making problem but also involves space-time dynamic action among multiple factors, which makes it difficult to optimize production capacity, mining sequence, mining life, and other factors simultaneously in optimizing design. In addition, the production capacity is disorderly expanded, the calculation scale is large, and the optimization time is long. Therefore, this article designs a mobile capacity search domain method to improve computing efficiency without omitting the optimal production capacity. At the same time, taking the maximum net present value as the objective function, an enumeration method is used to optimize the possible paths in different capacity domains and calculate the infrastructure investment and facility idle cost required to meet the maximum production capacity on each possible path to control the disorderly expansion and violent fluctuation of production capacity. The research shows that the open pit mine production scheduling optimization algorithm proposed in this article can not only realize the simultaneous optimization of the three elements of production capacity, mining sequence, and mining life but also improve the computing efficiency by 200 times. Furthermore, the production capacity fluctuation is less than 1.4%. The mining life of the mine is extended by 13 years, and the overall economic benefit is increased by 18%.

Uric acid played a role in the association between gender and deep vein thrombosis in patients with stroke.

BACKGROUND AND AIMS: Gender-specific differences were found in serum uric acid (SUA) levels and the risk of isolated distal deep vein thrombosis (IDDVT). This study aimed to explore the association among gender, SUA, and IDDVT in stroke patients. METHODS AND RESULTS: Finally, 3404 patients were recruited and divided into two groups: IDDVT (n = 1233) and Non-IDDVT (n = 2171) groups. Propensity score matching (PSM) was conducted to match the patients. Binary logistic regression was adopted to explore the association between SUA and IDDVT, with the SUA divided into quartiles. After PSM, 975 patients were included in each group. Non-IDDVT group had a larger proportion of male than IDDVT group (64.9% vs. 52.7%, p < 0.001). Moreover, males showed higher SUA levels than females (316.7 ± 102.1 vs. 261.8 ± 94.0 µmol/L, t = 12.1, p < 0.001). The highest quartile of SUA (≥346 µmol/L) showed a lower risk of IDDVT (OR = 0.629, p = 0.001), while the lowest quartile (≤225 µmol/L) showed a higher risk of IDDVT (OR = 1.361, p = 0.022). CONCLUSION: In patients with stroke, SUA played a protective role in IDDVT. Females had a higher risk of IDDVT, which may be owing to the lower SUA levels than males. In clinical practice, more attention should be paid to the risk of IDDVT in females, especially those with lower SUA levels.

Validation of Predictive Models for Autoimmune Encephalitis-Related Antibodies to Cell-Surface Proteins Expressed in Neurons: A Retrospective Study Based in a Hospital.

Objective: Autoimmune encephalitis (AE) is a severe but treatable autoimmune disorder that is diagnosed by antibody (Ab) testing. However, it is unrealistic to obtain an early diagnosis in some areas since the Ab status cannot be immediately determined due to time and technology restrictions. In our study, we aimed to validate the Antibody Prevalence in Epilepsy and Encephalopathy (APE2) score among patients diagnosed with possible AE as a predictive model to screen AE patients with antibodies to cell-surface proteins expressed in neurons. Methods: A total of 180 inpatients were recruited, and antibodies were detected through serological and/or cerebrospinal fluid (CSF) evaluations. The APE2 score was used to validate the predictive models of AE with autoantibodies. Results: The mean APE2 score in the Ab-positive cases was 7.25, whereas the mean APE2 score in the Ab-negative cases was 3.18 (P < 0.001). The APE2 score had a receiver operating characteristic (ROC) area under the curve of 0.924 [P < 0.0001, 95% confidence interval (CI) = 0.875-0.973]. With a cutoff score of 5, the APE2 score had the best psychometric properties, with a sensitivity of 0.875 and a specificity of 0.791. Conclusion: The APE2 score is a predictive model for AE with autoantibodies to cell-surface proteins expressed in neurons and was validated and shown to have high sensitivity and specificity in our study. We suggest that such a model should be used in patients with a suspected diagnosis of AE, which could increase the detection rate of Abs, reduce testing costs, and help patients to benefit from treatment quickly.

Patient Preference for Antiepileptic Drugs Treatment in China: Evidence From the Discrete Choice Experiment.

Objective: Explore Chinese patients' risk-benefit preferences and willingness-to-pay (WTP) for antiepileptic drugs (AEDs) treatment through the discrete choice experiment (DCE). Method: Six attributes including the efficacy of AEDs, adverse reactions (digestive system, neuropsychic systems, and the effects on the fetus), dosing frequency and drug costs (to estimate patient WTP) were included in the DCE questionnaire based on results collected from literature reviews, expert consultation, and patient survey. The alternative-specific conditional logit model was used to analyze patient preference and WTP for each attribute and its level and to assess the sociodemographic impact and clinical characteristics. Results: A total of 151 valid questionnaires were collected. The result shows that five out of the six attributes are significant, except the dosing frequency. Among the six attributes, the efficacy of AEDs (10.0; 95% CI 8.9-11.1) is mostly concerned by patients, followed by the effects of AEDs on the fetus (8.9; 95% CI 7.7-10.1), duration of side effects in the neuropsychic system (4.9; 95% CI 3.7-6.0) and adverse reactions of the digestive system (3.2; 95% CI 1.5-4.2). The patients surveyed are willing to spend ¥ 1,246 (95% CI, ¥ 632- ¥ 1,861) per month to ensure 100% seizure control, and ¥ 1,112 (95% CI, ¥ 586-¥ 1,658) to reduce the risk of the drug affecting the fetus to 3%. Besides, it was found that personal characteristics including the intention for conception and AEDs treatment regimens have statistical significance. Conclusion: Improving the drug's efficacy and reducing its side effects are predominant considerations for patients with epilepsy in China, especially for those who are concerned about the seizure control and the drug effect on the fetus. This finding is useful to physicians and can encourage shared decision-making between the patients and their doctors in the clinic.

Comparison of the performance of suicide ideation scales in adult patients with epilepsy in China.

OBJECTIVE: The aims of this study were to evaluate and compare the performance of the Chinese version of the Suicide Ideation Scale-Current (SSI-C) and the Suicide Ideation Scale-Worst (SSI-W) as suicide ideation screening tools in patients with epilepsy (PWE). METHODS: A consecutive sample of Chinese adult PWE recruited from a tertiary hospital completed the SSI-C and SSI-W and the suicidality module of the Chinese version of the Mini International Neuropsychiatric Interview (MINI) Plus 5.0.0. RESULTS: A total of 260 consecutive PWE were recruited. The area under the curve (AUC) for the SSI-C was 0.831, and the optimal cutoff score was >1 (sensitivity 73%, specificity 91%); for the SSI-W, the AUC was 0.958, and the optimal cutoff score was >2 (sensitivity 94.6%, specificity 87.4%). The AUC for the SSI-W was larger than that for the SSI-C, and the two-factor structure was considered significant. CONCLUSION: Our results showed that the SSI-C and SSI-W had good validity as suicidal ideation screening tools in PWE in southern China and can be recommended for clinical suicidal ideation screening. The SSI-W is a better suicidal ideation screening tool than the SSI-C according to the results of our study.

Comparison of the performance of two depression rating scales in patients with epilepsy in southern China.

OBJECTIVE: The aim of this study was to evaluate and compare the performance of the Chinese version of the Neurological Disorder Depression Inventory for Epilepsy (CNDDI-E) with that of the depression subscale of the Hospital Anxiety and Depression Scale (C-HADS-D) as screening tools for depression in the same patients with epilepsy (PWE). METHODS: A total of 213 consecutive PWE were evaluated. Receiver operating characteristic (ROC) analysis was performed using the C-NDDI-E and C-HADS-D as predictors and the Chinese version of the Mini International Neuropsychiatric Interview (C-MINI) as the gold standard. RESULTS: The area under the curve (AUC) for the C-NDDI-E was 0.870, and the optimal cutoff score was >11 (sensitivity 85.71%, specificity 79.78%); for the C-HADS-D, the AUC was 0.804, and the optimal cutoff score was >5 (sensitivity 85.71%, specificity 62.36%). The AUC for the C-NDDI-E was larger than the AUC for the C-HADS-D, but the comparison of the AUCs revealed no significant differences (P = 0.1444). CONCLUSION: Our findings indicate that the C-NDDI-E and C-HADS-D have high validity and support the use of these screening tools for depression in PWE. Moreover, the C-NDDI-E is a better screening scale for diagnosing depression than the C-HADS-D according to the results of this study.

Two Novel SNPs in the PLCL2 Gene Associated with Large Artery Atherosclerotic Stroke Identified by Fine-Mapping.

A genome-wide association study (GWAS) reported that the single nucleotide polymorphism (SNP) rs4618210 in the PLCL2 gene is related to myocardial infarction (MI) in the Japanese population, but no study has examined the correlation of PLCL2 with ischemic stroke (IS). The present study was designed to investigate whether the genetic variation in PLCL2 is associated with large artery atherosclerotic (LAA) stroke in a Han Chinese population. Tagging SNPs (tSNPs) of the PLCL2 gene were determined by a fine-mapping strategy and were genotyped by improved multiplex ligation detection reaction (iMLDR) technology in 669 LAA stroke patients and 668 healthy controls. A logistic regression model was used to analyze the associations between genetic variation at PLCL2 and the risk of LAA stroke. Two SNPs were significantly associated with the risk of LAA stroke after adjusting for potential confounders: for rs4685423, the AA genotype and CA genotype decreased the risk of LAA stroke compared with the CC genotype (multivariate-adjusted, P = 0.001); for rs4618210, the AA genotype and GA genotype decreased the risk of LAA stroke compared with the GG genotype (multivariate-adjusted, P = 0.007). In addition, haplotype analysis indicated that compared with haplotype TTT, haplotype TAT decreased the risk of LAA stroke in block 2 (adjusted OR, 0.706; 95% CI, 0.550-0.907; P = 0.006). The analysis of SNP-SNP interactions showed that rs4685423 was the most influential contributor to LAA stroke risk. SNPs rs4685423 and rs4618210 in the PLCL2 gene may be related to the risk of LAA stroke in Han Chinese.

Polymorphism of IL6 receptor gene is associated with ischaemic stroke in patients with metabolic syndrome.

The interleukin 6 receptor (IL6R) gene has been shown to locate in the chromosome 1q21 associated with metabolic syndrome (MetS), a condition related to the augmented risk of ischaemic stroke (IS), cardiovascular diseases and all-cause mortality. The aim of this study was to assess the relationship between IL6R gene polymorphisms and IS in patients with MetS in the Chinese Han population. We designed a case-control study enrolling 447 patients with MetS plus IS and 438 patients with MetS alone. Tag single nucleotide polymorphisms (SNPs) of the IL6R gene were determined by a fine-mapping strategy and genotyped using SNPscan technology. A logistic regression model was used to analzse the associations between the genetic variations in IL6R and the risk of IS in MetS patients. The linkage disequilibrium (LD) analysis was performed and four gamete rules were used to define the block. The haplotypes was reconstructed by the SNPstats software. Two SNPs were significantly related to the risk of IS in MetS patients after adjusting for potential confounders as follows: regarding rs12083537, the GG genotype and the GA genotype decreased the risk of IS in the MetS patients compared with the IS risk in the patients with the AA genotype (multivariate-adjusted, P = 0.005); and regarding rs8192284, the CC genotype and the AC genotype decreased the risk of IS compared with the IS risk in the patients with the AA genotype (multivariate-adjusted, P = 0.004). Strong LD was existed in block 2 and the haplotype analysis showed that compared with the ACCG haplotype, the ATCT haplotype (adjusted OR 1.700; 95% CI 1.246-2.319; P = 0.001) increased the risk of IS in the MetS patients. The analysis of the SNP-SNP interactions showed that rs8192284 was the most influential contributor to the risk of IS in the MetS patients. Our results indicate that rs12083537 and rs8192284 in the IL6R gene might be related to the risk of IS in MetS patients.

External validation and comparison of two prediction models for seizure recurrence after the withdrawal of antiepileptic drugs in adult patients.

OBJECTIVE: The models currently available for predicting the risk of seizure recurrence after antiepileptic drug (AED) withdrawal in adult epilepsy patients include the prediction model developed by Lamberink et al (Lamberink model, 2017) and the Medical Research Council prediction model (MRC model, 1993). However, there was no external validation for the two models. The purpose of this study was to perform an independent external validation and a comparison of the Lamberink model and the MRC model in adult patients. METHODS: The study population was recruited from the Wenzhou Epilepsy Follow-up Registry Database (WEFURD). All the predictors of the Lamberink and MRC models and the occurrence of seizure recurrence in the participants were collected based on the WEFURD. Participants' predicted probabilities of seizure recurrence were obtained by a Web-based tool and the prognostic index formula. The external validation of the Lamberink model and the MRC model were quantified by discrimination, calibration, and decision curve analysis (DCA). RESULTS: Of 212 patients, 126 (59.4%) had seizure recurrence after AED withdrawal. The Lamberink 2-year model, the Lamberink 5-year model, the MRC 1-year model, and the MRC 2-year model had areas under the curve of 0.71 (95% confidence interval [CI] = 0.64-0.78), 0.68 (95% CI = 0.60-0.76), 0.60 (95% CI = 0.50-0.69), and 0.58 (95% CI = 0.50-0.66), respectively. Additionally, the Lamberink 2-year model had a significantly better integrated discrimination improvement than the MRC 2-year model (P < .001). Regarding calibration, the Lamberink 2-year model (P = .121) and the MRC 1-year model (P = .264) were well calibrated, but the Lamberink 5-year model (P = .022) and the MRC 2-year model (P = .008) were not. In the DCA, the Lamberink 2-year model performed well at threshold probabilities of 30%-65%. SIGNIFICANCE: This external validation shows that the Lamberink 2-year model might be more accurate and has greater clinical benefit than others for guiding drug withdrawal in adult epilepsy clinics.

Association between a functional interleukin 6 receptor genetic variant and the risk and functional outcome of large artery atherosclerotic stroke.

Purpose: To investigate whether the Asp358Ala of interleukin 6 receptor related to the risk and outcome of large artery atherosclerotic (LAA) stroke in Han Chinese.Materials and methods: A prospective cohort study was conducted on 768 patients with LAA stroke and 686 non-stroke controls. The genotypes of Asp358Ala polymorphism were determined using SNPscan technology. Associations between genotypes and the risk of LAA stroke were analyzed with logistic regression model.Results: CC genotype (P < 0.001) and AC genotype (P = 0.023) decreased the risk of LAA stroke compared with AA genotype. Multivariate logistic regression analysis revealed that CC genotype was significantly associated with the risk of LAA stroke (P = 0.002). In the subgroup analyses, polymorphisms of Asp358Ala were significantly associated with the risk of LAA stroke in additive model, dominant model and recessive model (P = 0.009, P = 0.017, P = 0.012, respectively) for male, but not for female. Further regression analysis showed that compared with participants with AA genotype and obesity, participants with CC genotype and non-obesity were less likely to suffer LAA stroke (P = 0.003). For male participants, these associations were still existed (additive model, P = 0.022). After 3-month follow-up, patients with C allele had good functional prognosis compared with patients with A allele (P = 0.009).Conclusion: The study demonstrated that the Asp358Ala polymorphism might be associated with susceptibility to the development and outcome of LAA stroke in Han Chines.

Relative Seizure Relapse Risks Associated with Antiepileptic Drug Withdrawal After Different Seizure-Free Periods in Adults with Focal Epilepsy: A Prospective, Controlled Follow-Up Study.

BACKGROUND: Approximately two-thirds of patients with newly diagnosed epilepsy become seizure-free after antiepileptic drug (AED) treatment. A crucial issue for these patients and their families, especially after a long period of seizure freedom, is when to stop their medications. OBJECTIVE: The aim of this study was to identify the optimal timing of AED withdrawal in adults with focal epilepsy who had been seizure-free for ≥ 2 years. METHODS: Adults with focal epilepsy who had been seizure-free for ≥ 2 years were recruited. Based on their decision to discontinue (withdrawal) or continue (non-withdrawal) AED treatment, patients were assigned to withdrawal or non-withdrawal subgroups according to the length of remission (2 to < 3 years, 3 to < 4 years, 4 to < 5 years and ≥ 5 years). The relapse risks of the withdrawal and corresponding non-withdrawal subgroups were compared, and the relative relapse risks were assessed in a Cox proportional hazard regression model. RESULTS: A total of 213 eligible patients began to withdraw from AED treatment; 70 had been seizure-free for 2 to < 3 years, 62 had been seizure-free for 3 to < 4 years, 37 had been seizure-free for 4 to < 5 years and 44 had been seizure-free for ≥ 5 years. The figures for the corresponding non-withdrawal subgroups were 463, 334, 251 and 182, respectively. There was a significantly higher risk of seizure relapse in patients withdrawing from AEDs after 2 to < 5 years of seizure freedom than in the corresponding non-withdrawal controls, and the relative relapse risk was 3.052 (95% confidence interval [CI] 2.126-4.381; p < 0.001) for the seizure-free period of 2 to < 3 years, 3.617 (95% CI 2.384-5.488; p < 0.001) for 3 to < 4 years and 2.644 (95% CI 1.456-4.799; p = 0.001) for 4 to < 5 years. However, for patients who were seizure-free for ≥ 5 years, AED withdrawal did not significantly increase the risk of seizure relapse compared with that of patients continuing treatment (hazard ratio [HR] 1.362, 95% CI 0.634-2.926, p = 0.428). Compared with a seizure-free period of 2 to < 3 years, the relative relapse risk after AED withdrawal was significantly reduced only after being seizure-free for ≥ 5 years (HR 0.441, 95% CI 0.233-0.834; p = 0.012). CONCLUSION: Overall, for adults with focal epilepsy, withdrawal from AEDs significantly increased the risk of seizure relapse after being seizure-free for 2 to < 5 years, but might not increase the risk if the seizure-free period was ≥ 5 years.

Validation of the Chinese version of the Scale for Suicide Ideation-Worst in adult patients with epilepsy.

OBJECTIVE: The aim of this study was to validate the Chinese version of the Scale for Suicide Ideation-Worst (SSI-W) for screening suicide ideation in Chinese adult patients with epilepsy (PWE). METHOD: A consecutive sample of Chinese adult PWE from a tertiary hospital completed the SSI-W and the suicidality module of the Chinese version of the Mini International Neuropsychiatric Interview (MINI) Plus 5.0.0. RESULTS: A total of 269 PWE completed the scales. According to the MINI, 59 patients (21.9%) had suicidal ideation. The Cronbach's α coefficient for the SSI-W was 0.96. Receiver operating characteristic (ROC) curve analysis showed that the area under the curve (AUC) for the SSI-W was 0.957 (95% confidence interval [CI] = 0.935-0.980). With a cutoff score of 2 points, the SSI-W demonstrated the best psychometric properties: a sensitivity of 95.8%, a specificity of 87.3%, a positive predictive value (PPV) of 56.7%, and a negative predictive value (NPV) of 99.0%. The scores for items 11 (Reason for attempt) and 18 (Final acts) were not significantly different (p > 0.05) in patients with suicidal ideation, while the scores for the other items were significantly different between these groups of patients. CONCLUSION: The Chinese version of the SSI-W proved to be a reliable and effective assessment tool for screening suicidal ideation in Chinese adult PWE.

Risk factors for suicidal tendency in adult patients with epilepsy in China.

OBJECTIVE: The major cause of premature mortality in people with epilepsy (PWE) is suicide. Actual data on the risk of suicidal tendency in adult PWE in China are scarce. In our study, associations between possible risk factors and suicidal tendency in adult PWE in China were investigated. METHODS: People with epilepsy (n = 251) were recruited, and their demographic and clinical characteristics were evaluated. Suicide risk was examined using the suicidality module (SM) of the Mini International Neuropsychiatric Interview (MINI) Plus Chinese Version 5.0.0. RESULTS: Suicidal tendency was present in 36 (14.3%) of the 251 PWE. On the basis of the results of univariate analyses, family relationship (P < 0.001), age at epilepsy onset (P = 0.037), seizure-free period (P = 0.041), seizures/month (P = 0.015), depressive disorders (P < 0.001), and number of antiepileptic drugs (AEDs) (P = 0.017) were associated with suicidal tendency. Multivariate analysis revealed that moderate or poor family relationships (odds ratio (OR): 6.468, 95% confidence interval (CI): 2.418-17.300) and depressive disorders (OR: 3.548, 95% CI: 1.575-7.995) were associated with high odds of suicidal tendency. CONCLUSION: Suicidal tendency is common among adult PWE. This study reveals that family relationships and depressive disorders are independent risk factors for suicidal tendency among adult PWE. Therefore, while maintaining treatment of epilepsy, more attention should be directed to the social support and mental state of PWE to prevent suicide.