BACKGROUND: Oxidative injury due to increased intracellular peroxides leads to more frequent onset of epileptic seizure, and the consumption of peroxides through oxidation-reduction played an important role in protection of the central nervous system neurons.OBJECTIVE: To analyze the changes of antioxidants in plasma and erythrocyte of patients with epilepsy.DESIGN: Nonrandomized, paralleled, concurrent controlled study.SETTING: Department of laboratory, psychology, and pharmacy in a university hospital.PARTICIPANTS: Totally 32 epileptic patients were diagnosed in the Department of Neurology, Xiangya Second Hospital, Central South University between March and December 2000 according to the diagnostic and classification criteria of International League Against Epilepsy. The patients consisted of 17 male and 15 female subjects aged from 27 to 59 years, all of whom denied previous anti-epileptic drug exposure(epileptic group) . Another 26concurrent epileptic patients, including 16 male and 10 female subjects aged from 24 to 58 years, confirmed according to the same criteria and treated at the Department of Neurology were also recruited in this study, who reported a history of anti-epileptic therapy with phenobarbiturals for more than one year without acute onset of epileptic seizures during this period(treatment group) .Totally 39 normal controls including 23 male and 16 female subjects were enrolled from those receiving routine health examinations with normal physical indexes. Informed consent was obtained from all these participants.METHODS: Fasting venous blood(2 mL) were collected from each subject at 8:00 - 9:00 am. Enzyme-coupled continuous monitoring was employed to determine the activity of erythrocyte glutathione reductase (EGR), glutathione peroxidase ( GSH-Px ), and catalase (CAT). Pyrogallol autoxidation colorimetry was used to determine the activity of erythrocyte superoxide dismutase(SOD) .The level of erythrocyte malonaldehyde(MDA) was examined with improved TBA colorimetry. Meanwhile hemoglobin(HB) concentration and osmotic fragility of incubated erythrocytes(expressed as the hemolytic percentage)were examined. Plasma vitamin A, C, and E were also determined with high-performance liquid chromatography. Plasna ceruloplasmin(CER) was examined with immunodiffusion assay.MAIN OUTCOME MEASURES: The activity of EGR, GSH-Px, SOD,CAT, content of MDA, erythrocyte hemolytic percentage and the levels of CER and vitamin A, C, E.RESULTS: Only one patient failed to complete the treatment. Erythrocyte MDA content, hemolytic percentage, activity of GSH-Px, and CAT, and CER in epileptic group [ ( 176. 5 ± 12.0) μmol/L, (3.32 ± 0.95 )%, ( 1 503.6±130.0) nkat/g, (75.3±14.6) K/g, (487.0±25.4) mg/L] and treatment group[(129.5±7.4) μmol/L, (1.52±0.20)%, (1 323.6± 95.0) nkat/g, (64.2 ± 10. 1) K/g, (345.0 ± 15.2) mg/L] were significantly higher than those in the control group( t = 2.46 -3.89, P ＜ 0.05 ], but the activity of erythrocyte GR and SOD and the content of plasma vitamin A, E,C[(101.7 ± 13.3) nkat/g, (20.2 ±0. 8) μkat/g, (1. 18 ±0. 83) μmol/L,(20.7 ±4. 5) μmol/L, (20. 6 ±3.6) μmol/L, and(213.4 ±45.0) nkat/g,(28.5 ±0. 9) μkat/g, (3. 14 ±0. 30) μmol/L, (40. 5 ±6.6) μmol/L,(38. 1 ±5.1) μmol/L] were significantly lower than those in the control group ( t = 2.46 - 2.97, P ＜ 0. 05). The activity of GR and SOD and plasma vitamin A, C content of normal control group were significantly higher than those in the epileptic group [(161.7±25.0) nkat/g, (26.7±0.9) μkat/g, (2.09±0. 35) μmol/L, (26.2 ±4. 1) μmol/L, t =2.46 -2.66, P ＜0.05].CONCLUSION: The decrement of intracellular GSH-Px and SOD, and plasma levels of vitamin A, C, E, and CER in epileptic patients can be indicative of the activity of the free radicals during the onset of epileptic seizures.

Purpose: Oligometastatic non–small cell lung cancer (NSCLC) patients have been increasingly regarded as a distinct group that could benefit from local treatment to achieve a better clinical outcome. However, current definitions of oligometastasis are solely numerical, which are imprecise because of ignoring the biological heterogeneity caused by genomic characteristics. Our study aimed to profile the molecular alterations of oligometastatic NSCLC and elucidate its potential difference from polymetastasis. Materials and Methods: We performed next-generation sequencing to analyze tumors and paired peripheral blood from 77 oligometastatic and 21 polymetastatic NSCLC patients to reveal their genomic characteristics and assess the genetic heterogeneity. Results: We found ERBB2, ALK, MLL4, PIK3CB, and TOP2A were mutated at a significantly lower frequency in oligometastasis compared with polymetastasis. EGFR and KEAP1 alterations were mutually exclusive in oligometastatic group. More importantly, oligometastasis has a unique significant enrichment of apoptosis signaling pathway. In contrast to polymetastasis, a highly enriched COSMIC signature 4 and a special mutational process, COSMIC signature 14, were observed in the oligometastatic cohort. According to OncoKB database, 74.03% of oligometastatic NSCLC patients harbored at least one actionable alteration. The median tumor mutation burden of oligometastasis was 5.00 mutations/Mb, which was significantly associated with smoking, DNA damage repair genes, TP53 mutation, SMARCA4 mutation, LRP1B mutation, ABL1 mutation. Conclusion Our results shall help redefine oligometastasis beyond simple lesion enumeration that will ultimately improve the selection of patients with real oligometastatic state and optimize personalized cancer therapy for oligometastatic NSCLC.