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Central and systemic inflammation play pivotal roles in epileptogenesis and proepileptogenesis in temporal lobe epilepsy (TLE). The interplay between peripheral CD4+ T cells and central microglia orchestrates the "systemic-central" immune response in TLE. However, the precise molecular mechanisms linking central and systemic inflammation in TLE remain unknown. This preliminary findings revealed an imbalance in Th1/Th2 subsets in the peripheryï¼accompanied by related cytokines release in TLE patients. they proposed that this peripheral Th1/Th2 imbalance may influence central inflammation by mediating microglial state dynamics within epileptic foci and distant brain regions. In Li-pilocarpine-induced TLE rats, a peripheral Th1/Th2 imbalance and observed corresponding central and systemic responses is confirmed. Notably, CD4+ T cells infiltrated through the compromised blood-brain barrierand are spatially close to microglia around epileptic foci. Intravenous depletion and reinfusion of CD4+ T cells modulated microglia state dynamics and altered neuroinflammatory cytokines secretion. Moreover, mRNA sequencing of the human hippocampus identified Notch1 as a key regulator of Th1/Th2 differentiation, CD4+ T cell recruitment to brain infiltration sites, and the regulation of microglial responses, seizure frequency, and cognition. This study underscores the significance of Th1/Th2 imbalance in modulating the "systemic-central" response in TLE, highlighting Notch1 as a potential therapeutic target.
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Neuroinflammation mediated by microglia made a significant contribution in the pathophysiology of epilepsy. Icariin (ICA), a bioactive ingredient isolated from Epimedium, has been shown to present both antioxidant and anti-inflammatory properties. This study was to explore the potential therapeutic effects of icariin on mouse pilocarpine model of epilepsy and its underlying mechanisms in vivo and in vitro. To this end, we firstly measured the serum concentrations of the proinflammatory cytokines IL-1ß and IL-6 from patients with temporal lobe epilepsy and found that patients with a higher seizure frequency showed correspondingly higher inflammatory reaction. Mouse pharmacokinetic study, transmembrane transportation assay, and cell viability assay collectively demonstrated that ICA was able to cross the blood-brain barrier and has good biocompatibility. The acute and chronic epilepsy models were next established in a pilocarpine mouse model of acquired epilepsy. Icariin has been identified that it could cross the blood-brain barrier and enter the hippocampus to exhibit therapeutic effects. ICA treatment dramatically promoted microglial polarization to the M2 phenotype in epilepsy mice both in the acute and chronic phases. Reduced release of M1-associated proinflammatory factors, such as IL-1ß and IL-6, corroborates the altered glial cell polarization. Furthermore, ICA alleviated seizure intensity and mortality in acute phase epileptic mice. Models in the chronic group also showed improved general condition, cognition ability, and memory function after ICA treatment. Taken together, our research strongly suggested that icariin has the potential to treat epilepsy via inhibiting neuroinflammation by promoting microglial polarization to the M2 phenotype.
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Epilepsia , Pilocarpina , Humanos , Ratones , Animales , Pilocarpina/farmacología , Interleucina-6 , Enfermedades Neuroinflamatorias , Epilepsia/inducido químicamente , Epilepsia/tratamiento farmacológico , Convulsiones/tratamiento farmacológico , Antiinflamatorios/farmacología , Antiinflamatorios/uso terapéutico , Microglía , Modelos Animales de EnfermedadRESUMEN
PURPOSE: The incidence of chromosomal polymorphisms (CP) is increased in infertile couples, but its impact on reproduction is uncertain, especially undergoing assisted reproductive technology treatment. The purpose of the present study was to investigate the effect of CP on the outcomes of in vitro fertilization/intracytoplasmic sperm injection-embryo transfer (IVF/ICSI-ET) treatment METHODS: A total of 1331 infertile couples undergoing IVF/ICSI treatment were involved in this retrospective case-control study. The participants were divided into 4 groups according to CP variations: (i) normal chromosomes (NC) group; (ii) CP group; (iii) both chromosomal polymorphisms (BCP) group; and (iv) double chromosomal polymorphisms (DCP) group. The CP group was further divided into five subgroups: qh+, D/G, inv(9), Yqh+ and Yqh-. The outcomes of IVF/ICSI-ET treatment were compared among the groups. RESULTS: There were no differences observed between the eight groups in terms of number of oocytes retrieved, MII rate, fertilization rate, cleaved embryo rate, and quality embryo rate for both females and males (p > 0.05). In both male and female, some of the CP subgroups experienced more oocyte retrieval operations and more embryo transfer operations to achieve pregnancy than the NC groups (p < 0.05). The rates of live births were significantly lower in some of the CP subgroups compared to the NC group (p < 0.05). CONCLUSION: In conclusion, the pregnancy outcomes of ET were affected by CP. It was speculated that this may be associated with the effect of chromosome polymorphism on embryo quality, although this could not be observed or determined by morphological evaluation.
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Infertilidad , Semen , Embarazo , Masculino , Femenino , Humanos , Estudios Retrospectivos , Estudios de Casos y Controles , Índice de Embarazo , Fertilización In Vitro , Transferencia de Embrión , Oocitos , CromosomasRESUMEN
OBJECTIVE: To investigate the effects of chromosome polymorphism on the clinical outcomes of in vitro fertilization/embryo transfer (IVF/ET)-assisted reproductive technology. METHODS: The case data of 2740 patients treated between January 2018 and January 2019 were retrospectively analyzed. The patients were organized into two groups: a case group and a control group. In the case group (n = 81), one or both parents were characterized by chromosomal polymorphism; in the control group (n = 2659), both parents had normal chromosome karyotyping. The primary outcomes included clinical pregnancy rate (clinical pregnancy rate of fresh transfer cycles = number of clinical pregnancy cycles/number of fresh embryo transfer cycles × 100%) and live birth rate (live birth rate per fresh transfer cycles = number of live births/numbers of fresh embryo transfer cycles × 100%). The propensity score matching (PSM) method was used for statistical analysis. RESULTS: After PSM 1:2 matching for the patients in the two groups, 72 patients were successfully matched. The clinical pregnancy rate and live birth rate in the case group were lower than in the control group before PSM (clinical pregnancy rate: 33.30% case group vs. 46.60% control group, p = .020; live birth rate: 30.90% case group vs. 47.90% control group, p = .03). The differences were statistically significant (p < .05). The live birth rate in the case group was also significantly lower than in the control group after PSM (34.98% case group vs. 74.52% control group; p = .028). The correlation coefficient between clinical pregnancy and grouping (i.e. if there was a characteristic chromosome polymorphism) was -.045 (p = .02), while the correlation coefficient between live birth and grouping was -.046. CONCLUSION: Chromosome polymorphism is weakly negatively correlated with live birth in IVF/ET-assisted reproduction and can significantly reduce the live birth rate of patients.
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Transferencia de Embrión , Fertilización In Vitro , Embarazo , Femenino , Humanos , Estudios Retrospectivos , Fertilización In Vitro/efectos adversos , Transferencia de Embrión/efectos adversos , Índice de Embarazo , Embarazo Múltiple , Nacimiento Vivo , CromosomasRESUMEN
PURPOSE: This study explores the effects of endometrial thickness (EMT) before embryo transfer on newborn birth weight after in vitro fertilization-frozen embryo transfer (IVF-FET). METHODS: We collected the medical records related to singleton live births after IVF-FET from June 2015 to February 2019. Pregnant women were aged ≤ 42 years at delivery. Afterward, analyses were performed on outcomes related to newborns (birth weight, gestational age, delivery mode, percentage of newborns with low birth weight, and incidence of macrosomia) and pregnant women (pregnancy-induced hypertension, gestational diabetes mellitus, premature rupture of membranes, and placenta previa). RESULTS: The birth weight was higher in singleton newborns delivered by patients with EMT > 12 mm before embryo transfer than those delivered by patients with a thinner endometrium. The mean birth weight was 85.107 g higher in the EMT ≥ 12 mm group and 25.942 g higher in the 8-12 mm EMT group than in the EMT < 8 mm group. Independent predictors of newborn birth weight included pregnancy-induced hypertension, premature rupture of membranes, placenta previa, newborn sex, gestational age, delivery mode, number of implanted embryos, follicle-stimulating hormone levels, estradiol levels, and pre-pregnancy body mass index. CONCLUSION: The weight of newborn singletons is associated with EMT before embryo transfer in patients undergoing the first FET cycle. Specifically, the birth weight is lower for newborns delivered by patients with a thinner endometrium. Accordingly, it is warranted to increase EMT before embryo transfer for improving neonatal outcomes after fertility treatment.
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Transferencia de Embrión , Endometrio , Fertilización In Vitro , Femenino , Humanos , Recién Nacido , Embarazo , Peso al Nacer , Estudios de Cohortes , Nacimiento Vivo , Complicaciones del Embarazo , Resultado del Embarazo , Estudios Retrospectivos , AdultoRESUMEN
INTRODUCTION: Approximately 50% of cases with recurrent spontaneous abortion (RSA) have unexplained etiology. Aberrant expression of transmembrane and ubiquitin-like domain containing 1 (TMUB1) is closely related to a series of diseases, including RSA. However, the function and underlying mechanism of TMUB1 in the occurrence of RSA has not been described. METHODS: TMUB1 expression was detected in the placental villous tissues of 30 women with normal miscarriages and 12 women with RSA. The pregnant mice were injected intraperitoneally with lipopolysaccharide (LPS) to induce abortion. Human chorionic trophoblast cells were treated with LPS. Pathological analysis of placental tissues was performed by hematoxylin and eosin staining. RESULTS: TMUB1 was highly expressed in the placental villous tissues of RSA patients compared to the patients who underwent induced abortions. After LPS administration, the mice exhibited high embryo absorption and pathological alterations, as well as presented an increase in inflammation and apoptosis (the etiology of RSA induction) in placental tissues. Moreover, the upregulated expression of TMUB1 was also found in placental tissues of LPS-induced mice, and further investigation showed that TMUB1 deficiency blocked embryo loss as well as inhibited apoptotic rate and inflammation after LPS activation. Furthermore, we found that the loss of TMUB1 suppressed the phosphorylation of IkappaB kinase (IKK) α/ß and attenuated cytoplasmic-nuclear translocation of nuclear factor-κB (NF-κB) p65 in LPS-induced cells. CONCLUSION: Our results indicate that TMUB1 may involve in the modulation of apoptosis and NF-κB pathway-mediated inflammation in RSA. Therefore, TMUB1 may develop as a potential biomarker for RSA treatment.
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Aborto Espontáneo , FN-kappa B , Humanos , Femenino , Ratones , Embarazo , Animales , FN-kappa B/metabolismo , Lipopolisacáridos/toxicidad , Placenta , Inflamación/metabolismo , Quinasa I-kappa B/metabolismo , ApoptosisRESUMEN
AIMS: Differentiating mesial temporal lobe epilepsy (MTLE) and neocortical temporal lobe epilepsy (NTLE) remains challenging. Our study characterized the metabolic profiles between MTLE and NTLE and their correlation with surgical prognosis using 18 F-FDG-PET. METHODS: A total of 137 patients with intractable temporal lobe epilepsy (TLE) and 40 age-matched healthy controls were recruited. Patients were divided into the MTLE group (N = 91) and the NTLE group (N = 46). 18 F-FDG-PET was used to measure the metabolism of regional cerebra, which was analyzed using statistical parametric mapping. The volume of abnormal metabolism in cerebral regions and their relationship with surgical prognosis were calculated for each surgical patient. RESULTS: The cerebral hypometabolism of MTLE was limited to the ipsilateral temporal and insular lobes (p < 0.001, uncorrected). The NTLE patients showed hypometabolism in the ipsilateral temporal, frontal, and parietal lobes (p < 0.001, uncorrected). The MTLE patients showed extensive hypermetabolism in cerebral regions (p < 0.001, uncorrected). Hypermetabolism in NTLE was limited to the contralateral temporal lobe and cerebellum, ipsilateral frontal lobe, occipital lobe, and bilateral thalamus (p < 0.001, uncorrected). Among patients who underwent resection of epileptic lesions, 51 (67.1%) patients in the MTLE group and 10 (43.5%) in the NTLE group achieved Engel class IA outcome (p = 0.041). The volumes of metabolic increase for the frontal lobe or thalamus in the MTLE group were larger in non-Engel class IA patients than Engel class IA patients (p < 0.05). CONCLUSIONS: The spatial metabolic profile discriminated NTLE from MTLE. Hypermetabolism of the thalamus and frontal lobe in MTLE may facilitate preoperative counseling and surgical planning.
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Epilepsia del Lóbulo Temporal , Neocórtex , Humanos , Epilepsia del Lóbulo Temporal/diagnóstico por imagen , Epilepsia del Lóbulo Temporal/cirugía , Epilepsia del Lóbulo Temporal/metabolismo , Neocórtex/diagnóstico por imagen , Neocórtex/cirugía , Fluorodesoxiglucosa F18 , Resultado del Tratamiento , Metaboloma , Tomografía de Emisión de Positrones , Hipocampo/metabolismoRESUMEN
PURPOSE: This study was carried out to test the validity and reliability of the Chinese version of the Stigma Scale of Epilepsy (SSE), with aim to better understand the public stigmatizing attitudes of epilepsy in China and help elucidate stigma determinants for interventions. METHODS: The SSE was translated into Simplified Chinese Mandarin. In this study, most of the participants were enrolled via convenience sampling by randomly distributing questionnaires on the streets and parts of the participants were recruited by an online platform named Wenjuanxing. We assessed the psychometric properties of the SSE in 310 Chinese native-speaker. Cronbach's alpha was tested for reliability. Index of Content Validity (CVI) was calculated. Exploratory and confirmatory analysis were used to explore the factor structure and verify the validity of SSE. RESULTS: The Cronbach's alpha is 0.936 for the overall scale, and the CVI value is greater than 0.78. The exploratory factor analysis (EFA) extracted SSE six factors: the fear of seizure attacks (factor 1), sympathy for patients with epilepsy (PWEs) (factor 2); difficulties faced by PWEs (factor 3); speculation on PWEs' feeling (factor 4); discrimination against PWEs (factor 5); and knowledge about epilepsy (factor 6). The item 13 was proven to be problematic and has been eliminated. The confirmatory factor analysis (CFA) ensured the great construct validity (χ2/SD = 1.725, goodness of fit index (GFI) = 0.916, and root mean square error of approximation (RMSEA) = 0.048), convergent validity (the factor loads of each item corresponding to each latent variable >0.6, average variance extracted (AVE) > 0.5, and composite reliability (CR) > 0.7), and discrimination validity (all of the absolute value of correlation coefficient are <0.5,and less than the square root of AVE) of the SSE. CONCLUSIONS: The Chinese version of the SSE scale was a valid and reliable tool to measure epilepsy-associated stigma in the Chinese society.
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OBJECTIVE: This study was conducted to test the validity and reliability of the Chinese version of the epilepsy stigma scale (ESS), which aims to better understand the stigma of patients with epilepsy (PWEs), lays the foundation for future investigation and explores appropriate strategies to mitigate PWEs' stigma in Chinese culture. METHODS: The scale was translated following standard procedures. For psychometric validation, the Chinese version of the ESS was administered to 214 PWEs above the age of 16 who were diagnosed with epilepsy by two trained epileptologists and were taking anti-seizure drugs for at least a month. All of the patients were recruited from Xiangya Hospital of Central South University of China from August 2021 to September 2021. RESULTS: The Cronbach's alpha coefficient was 0.893 for the entire scale, 0.903 for felt stigma, and 0.688 for enacted stigma. Exploratory and confirmatory factor analyses were conducted and showed that the scale was grouped under two dimensions, and the results of confirmatory factor analysis support the structure. CONCLUSION: The Chinese version of the ESS is a valid and reliable tool to assess epilepsy-related stigma in Chinese culture.
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Epilepsia , China , Epilepsia/diagnóstico , Humanos , Psicometría , Reproducibilidad de los Resultados , Encuestas y CuestionariosRESUMEN
Purpose: To evaluate the knowledge, anxiety, depression, and sleep quality toward COVID-19 among Chinese medical staff from tertiary and basic-level hospitals in central south areas of China. Method: A structured questionnaire was composed of Demographic and clinical characteristics of medical staff, Knowledge toward COVID-19 including epidemiology and clinical manifestations, The Self-rating anxiety scale (SAS), Center for Epidemiologic Studies Depression Scale (CES-D), and The Pittsburgh Sleep Quality Index (PSQI). It was administered to medical staff from tertiary hospitals (Group A) (n = 407) and basic-level hospitals (Group B) (n = 388) during February 2020 and May 2020. Results: Medical staff in group A had a stronger knowledge toward COVID-19 than group B (23.69 ± 5.83 & 18.15 ± 6.35, p < 0.001). Mild anxiety symptoms were found in both groups. The SAS scores (Mean ± SD) of group B were 58.87 ± 10.17, which was significantly higher than that of group A (52.59 ± 12.09, p < 0.001). There were no significant differences in CES-D scores between the two groups (p = 0.981). The mean score of total PSQI in group B (8.41 ± 3.03) was statistically higher than that of group A (7.31 ± 3.74, p < 0.001). Additionally, the scores of sub-components of group B, including subjective sleep quality, sleep latency, sleep disorder, sleeping medication use and daytime dysfunction, were significantly higher compared to Group A (p < 0.05). Conclusions: Our study showed greater anxiety, more severe depression and poorer sleep quality among medical staff in central south areas of China during the COVID-19 outbreak. Additionally, compared to the tertiary hospital group, medical staff from basic-level hospitals had poorer knowledge toward COVID-19 and worse mental health conditions. In addition, residence, specialty, title and education level may also be factors of knowledge of COVID-19 and psychiatry problems. In light of this information, more attention should be paid to early identification and intervention of symptoms of anxiety and depression in susceptible medical staff from the basic-level hospitals.
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This retrospective study aimed to evaluate pregnancy outcome and newborn health condition for a specific group of infertile patients with unicornuate uterus. A total of 34 patients were confirmed to have unicornuate uterus. These patients received 47 cycles of in vitro fertilisation-embryo transfer (IVF-ET) or intracytoplasmic sperm injection-embryo transfer (ICSI-ET), achieved 21 clinical pregnancies with a clinical pregnancy rate of 60.61%. Full-term delivery rate was 76.47%. Eleven patients gave birth to single neonates, while six patients gave birth to twins. Foetal growth restriction was detected in three foetuses in twins. Obstetric complications were reported in three patients with single foetus (27.27%, 3/11), and four out of six patients with twin pregnancies (66.67%, 4/6). This study demonstrated that Han Chinese women with unicornuate uterus have a good chance to conceive and deliver healthy neonates despite increased risk of complications. Impact statement What is already known on this subject: Unicornuate uterus is a rare form of malformation affecting about 1% of infertile patients. Patients with unicornuate uterus have a lower chance of conceiving. It has been reported that assisted reproduction such as in vitro fertilisation-embryo transfer (IVF-ET) was less likely to be successful in patients with unicornuate uterus. What do the results of this study add: Retrospective study of 34 cases of Han Chinese women with unicornuate uterus offered a new perspective. Half of these 34 patients conceived and delivered 23 neonates (11 singletons and 6 pairs of twins). Complications were more frequent but manageable. What are the implications of these findings for clinical practice and/or further research: Our data will serve as a valuable tool for counselling infertile patients with unicornuate uterus with regard to their expected pregnancy outcomes.
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Transferencia de Embrión , Fertilización In Vitro , Resultado del Embarazo/epidemiología , Inyecciones de Esperma Intracitoplasmáticas , Útero/anomalías , Adulto , China/epidemiología , Femenino , Humanos , Recién Nacido , Masculino , Embarazo , Índice de Embarazo , Embarazo Gemelar , Estudios RetrospectivosRESUMEN
PURPOSE: Polycystic ovary syndrome (PCOS) is a common endocrine disorder disease among women in reproductive-age. Since follicle stimulating hormone (FSH) exerts important biological functions, the association between PCOS and FSH receptor (FSHR) polymorphisms attracts wide attention. The aim of this study was to evaluate whether polymorphisms of FSHR at 307 and 680 codons are associated with PCOS patients in China. METHODS: Patients with PCOS (n = 215) and controls (n = 205) were recruited from Shanxi Province in north China. They are Han ethnics. Genomic DNA was isolated from the venous blood. The Ala307Thr and Ser680Asn polymorphisms of FSHR were analyzed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and direct DNA sequencing. RESULTS: The distributions of genotype and allele of Ala307Thr and Ser680Asn polymorphisms of FSHR were not statistically different between the PCOS patients and the controls. Analysis of the frequency of FSHR polymorphisms showed no statistical difference among the PCOS patients with different obesity standards. Although there were no statistical differences in the most of the endocrine parameters including LH, LH/FSH, E2, P and T as well as the clinical pregnancy rate, there were significant differences in the levels of FSH and PRL among PCOS patients carrying different genotypes of Ala307Thr and Ser680Asn polymorphisms. CONCLUSION: The Ala307Thr and Ser680Asn polymorphisms of FSHR are not associated with PCOS in Han ethnic Chinese women in north China. The FSHR polymorphisms was related to the levels of FSH and PRL but not other PCOS-associated endocrine hormones as well as clinical pregnancy rate in PCOS patients of Han Chinese ethnical population.