Objective To investigate the efficacy and mechanism of topiramate combined with oxcarbazepine in children with epilepsy.Methods The targeted genes of topiramate and oxcarbazepine were analyzed by pharm GKB database;targeted genes of epilepsy in children were screened by GeneCards database;the drug-disease-target gene network map was constructed using Cytoscape 3.9.1 software.A total of 83 children with epilepsy were enrolled and treated for the first time,which were divided into topiramate group and combined drugs group according to the different drugs used.The level of serum mechanistic target of rapamycin(mTOR),epidermal growth factor receptor(EGFR),nitrogen permease regulator 3-like protein(NPRL3)of two groups were observed by ELISA,and the EEG and therapeutic effect were recorded.Results mTOR,EGFR,NPRL3 were the target genes of topiramate combined with oxcarbazepine in the treatment of epilepsy in children.There was no significant difference in seizure rate between the combined drugs group and topiramate group(x2=3.239,P=0.072).The efficacy of combined drug group was significantly better than that of the topiramate group(x2=5.817,P=0.049).The rate of standing wave ratio(SWR)≤2 in EEG spike in the combined drug group was significantly higher than that in the topiramate group(P=0.018).There was different in spike location between combined drug group and topiramate group(P=0.002),while not different statistically in spike region of two groups(P＞0.05).Compared with those in topiramate group,the number of sharp waves in the combination group was significantly reduced at 1 month,3 months and 6 months after treatment,and the sharp wave clearance rate was significantly increased at 1 month,3 months,5 months and 6 months after treatment(P＜0.05-0.01).There was no significant difference in levels of mTOR,EGFR,NPRL3 between the combination group and topiramate groups before treatment(all P＞0.05).Compared with those in topiramate group,the levels of mTOR,EGFR in combined drug group after treatment were significantly decreased(P=0.028,P=0.006),and the level of NPRL3 was significantly increased(P=0.007).Survival analysis showed the median duration of epilepsy work was 6(5,6)months,the seizure rate was 55.42％.Compared with patients with mTOR ≤9.93(16.7％),patients with mTOR＞9.93(93.1％)had a significantly higher probability of epilepsy(x2=11.430,P＜0.001).Conclusion Topiramate combined with oxcarbazepine may reduce the pike and wave rate of EEG,improve epileptic seizures,the mechanism maybe related to the levels of mTOR,NPRL3 and EGFR.

Objective To investigate the efficacy and mechanism of topiramate combined with oxcarbazepine in children with epilepsy.Methods The targeted genes of topiramate and oxcarbazepine were analyzed by pharm GKB database;targeted genes of epilepsy in children were screened by GeneCards database;the drug-disease-target gene network map was constructed using Cytoscape 3.9.1 software.A total of 83 children with epilepsy were enrolled and treated for the first time,which were divided into topiramate group and combined drugs group according to the different drugs used.The level of serum mechanistic target of rapamycin(mTOR),epidermal growth factor receptor(EGFR),nitrogen permease regulator 3-like protein(NPRL3)of two groups were observed by ELISA,and the EEG and therapeutic effect were recorded.Results mTOR,EGFR,NPRL3 were the target genes of topiramate combined with oxcarbazepine in the treatment of epilepsy in children.There was no significant difference in seizure rate between the combined drugs group and topiramate group(x2=3.239,P=0.072).The efficacy of combined drug group was significantly better than that of the topiramate group(x2=5.817,P=0.049).The rate of standing wave ratio(SWR)≤2 in EEG spike in the combined drug group was significantly higher than that in the topiramate group(P=0.018).There was different in spike location between combined drug group and topiramate group(P=0.002),while not different statistically in spike region of two groups(P＞0.05).Compared with those in topiramate group,the number of sharp waves in the combination group was significantly reduced at 1 month,3 months and 6 months after treatment,and the sharp wave clearance rate was significantly increased at 1 month,3 months,5 months and 6 months after treatment(P＜0.05-0.01).There was no significant difference in levels of mTOR,EGFR,NPRL3 between the combination group and topiramate groups before treatment(all P＞0.05).Compared with those in topiramate group,the levels of mTOR,EGFR in combined drug group after treatment were significantly decreased(P=0.028,P=0.006),and the level of NPRL3 was significantly increased(P=0.007).Survival analysis showed the median duration of epilepsy work was 6(5,6)months,the seizure rate was 55.42％.Compared with patients with mTOR ≤9.93(16.7％),patients with mTOR＞9.93(93.1％)had a significantly higher probability of epilepsy(x2=11.430,P＜0.001).Conclusion Topiramate combined with oxcarbazepine may reduce the pike and wave rate of EEG,improve epileptic seizures,the mechanism maybe related to the levels of mTOR,NPRL3 and EGFR.

Objective:To investigate the relation between rs2298771 genotype in voltage-gated sodium channels 1A ( SCN1A) polymorphism and antiepileptic drug (AED) response in children with epilepsy. Methods:Sixty-two children with epilepsy admitted to Department of Neurology, Zhangjiakou First Hospital from June 2022 to December 2023 were divided into AED response group and AED resistance group ( n=31) according to their response to AED. In addition, 31 children with pharyngitis or mild gastroenteritis admitted to Department of Pediatrics at the same period were selected as control group. Real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR) was used to analyze the rs2298771 genotype in SCN1A polymorphism, and differences in rs2298771 genotype and allele in SCN1A polymorphism were compared among the 3 groups. Relation between rs2298771 genotype in SCN1A polymorphism and AED response was analyzed. Multivariate Logistic regression was used to analyze the influencing factors for AED response in children with epilepsy. Results:(1) Significant differences in type of first seizure and AEDs were noted between AED response group and AED resistance group ( P<0.05); compared with the AED resistance group, the AED response group had significantly lower seizure frequency, significantly longer duration after last seizure, and statistically higher proportions of children with normal EEG or with one kind of AED ( P?0.05). (2) Compared with the control group and AED response group, the AED resistance group had significantly higher rs2298771 GC genotype and G allele, and statistically lower rs2298771 AA genotype and A allele in SCN1A polymorphism ( P?0.05). (3) In the AED response group, rs2298771 AA and AG genotype in SCN1A polymorphism were positively correlated with levetiracetam ( P?0.05); in AED resistance group, rs2298771 AG genotype in SCN1A polymorphism was positively correlated with topiramate and valproic acid ( P<0.05). (4) Multivariate Logistic regression analysis showed that duration after last seizure ( OR=3.249, 95% CI=1.097-9.621, P=0.033), rs2298771 genotype in SCN1A polymorphism ( OR=9.660, 95% CI=4.680-19.970, P=0.011) and seizure frequency ( OR=0.160, 95% CI=0.032-0.804, P=0.026) were independent influencing factors for AED response in children with epilepsy. Conclusion:Epilepsy children with shorter duration after last seizure, rs2298771 GG genotype in SCN1A polymorphism, and high seizure frequency are susceptible to AED resistance; especially, AG genotype is correlated with topiramate and valproic acid.

OBJECTIVETo evaluate whether atorvastatin inhibits oxidized low-density lipoproteins (Ox-LDL)-stimulated foam cell formation from THP-1 macrophages by regulating the activation of peroxisome proliferator-activated receptor γ (PPARγ) and nuclear factor-κB (NF-κB). Methods THP-1 macrophages were pretreated with 10, 20, or 40 µmol/L atorvastatin for 2 h, and after washing with PBS twice, the cells were incubated with 60 µg/ml of Ox-LDL for 48 h. The quantity of intracellular lipid of the cells was detected with Oil red O staining and enzymatic fluorometric method. The expression of the scavenger receptors of CD36 and SRA were analyzed with Western blotting. We also examined the effect of atorvastatin on adenosine triphosphate (ATP)-binding cassette transporter A1 (ABCA1) expression and the activation of PPARγ and p-iκB, and further assessed the capacity of the macrophages to bind to Dil-oxLDL.

RESULTSAtorvastatin potently inhibited ox-LDL-induced macrophage-derived foam cell formation, down-regulated the expression of CD36 and SRA, and up-regulated the expression of ABCA1. Atorvastatin markedly suppressed the activation of PPARγ and p-iκB in ox-LDL-stimulated THP-1 macrophages (P<0.05) and significantly decreased the Dil-oxLDL-binding capacity of the macrophages (P<0.05).

CONCLUSIONAtorvastatin as an effective anti-atherosclerosis agent can suppress the activation of PPARγ and p-iκB to reduce lipid accumulation in macrophages.

ATP Binding Cassette Transporter 1 ; metabolism ; Atorvastatin Calcium ; Cell Line ; Foam Cells ; cytology ; drug effects ; Heptanoic Acids ; pharmacology ; Humans ; I-kappa B Proteins ; metabolism ; Lipoproteins, LDL ; metabolism ; Macrophages ; cytology ; drug effects ; NF-kappa B ; metabolism ; PPAR gamma ; metabolism ; Pyrroles ; pharmacology ; Signal Transduction ; drug effects ; Transcriptional Activation ; Up-Regulation

Objective To evaluate whether atorvastatin inhibits oxidized low-density lipoproteins (Ox-LDL)-stimulated foam cell formation from THP-1 macrophages by regulating the activation of peroxisome proliferator-activated receptorγ(PPARγ) and nuclear factor-κB (NF-κB). Methods THP-1 macrophages were pretreated with 10, 20, or 40μmol/L atorvastatin for 2 h, and after washing with PBS twice, the cells were incubated with 60 μg/ml of Ox-LDL for 48 h. The quantity of intracellular lipid of the cells was detected with Oil red O staining and enzymatic fluorometric method. The expression of the scavenger receptors of CD36 and SRA were analyzed with Western blotting. We also examined the effect of atorvastatin on adenosine triphosphate (ATP)-binding cassette transporter A1 (ABCA1) expression and the activation of PPARγand p-iκB, and further assessed the capacity of the macrophages to bind to Dil-oxLDL. Results Atorvastatin potently inhibited ox-LDL-induced macrophage-derived foam cell formation, down-regulated the expression of CD36 and SRA, and up-regulated the expression of ABCA1. Atorvastatin markedly suppressed the activation of PPARγand p-iκB in ox-LDL-stimulated THP-1 macrophages (P<0.05) and significantly decreased the Dil-oxLDL-binding capacity of the macrophages (P<0.05). Conclusion Atorvastatin as an effective anti-atherosclerosis agent can suppress the activation of PPARγ and p-iκB to reduce lipid accumulation in macrophages.

Objective To evaluate whether atorvastatin inhibits oxidized low-density lipoproteins (Ox-LDL)-stimulated foam cell formation from THP-1 macrophages by regulating the activation of peroxisome proliferator-activated receptorγ(PPARγ) and nuclear factor-κB (NF-κB). Methods THP-1 macrophages were pretreated with 10, 20, or 40μmol/L atorvastatin for 2 h, and after washing with PBS twice, the cells were incubated with 60 μg/ml of Ox-LDL for 48 h. The quantity of intracellular lipid of the cells was detected with Oil red O staining and enzymatic fluorometric method. The expression of the scavenger receptors of CD36 and SRA were analyzed with Western blotting. We also examined the effect of atorvastatin on adenosine triphosphate (ATP)-binding cassette transporter A1 (ABCA1) expression and the activation of PPARγand p-iκB, and further assessed the capacity of the macrophages to bind to Dil-oxLDL. Results Atorvastatin potently inhibited ox-LDL-induced macrophage-derived foam cell formation, down-regulated the expression of CD36 and SRA, and up-regulated the expression of ABCA1. Atorvastatin markedly suppressed the activation of PPARγand p-iκB in ox-LDL-stimulated THP-1 macrophages (P<0.05) and significantly decreased the Dil-oxLDL-binding capacity of the macrophages (P<0.05). Conclusion Atorvastatin as an effective anti-atherosclerosis agent can suppress the activation of PPARγ and p-iκB to reduce lipid accumulation in macrophages.