Self-limiting epilepsy syndrome（SeLES）can be classified into two types based on age of onset：one occurring in the neonatal to infant period and the other in the childhood period.These diseases can exhibit complete remission within a specific age range，or be completely controlled with anti-seizure drugs.Children with SeLES typically have normal cognition or only mild cognitive impairment.In recent years，advancements in genetic testing technology have led to a better understanding of the genetic etiologies of SeLES，offering more possibilities for precision treatment.This article aims to explore the role of genetic factors in SeLES，providing reference for the diagnosis，precise drug selection，and prognosis of this type of hereditary epilepsy syndrome，in order to provide theoretical support for the long-term management of patients，and improve their quality of life.

The tumor microenvironment (TME) is a critical determinant of tumor initiation, progression, and therapeutic response, and serves as the basis for designing precise delivery strategies. Its marked heterogeneity underscores the need for a more comprehensive understanding of its composition and function. In addition to the extensively studied classical TME, emerging evidence highlights the significant roles of the tumor mechanical microenvironment and the tumor microbial microenvironment in modulating treatment efficacy. These non-classical dimensions not only independently influence tumor behavior but also interact dynamically with classical TME components. Mechanical cues within the TME, including matrix stiffness and solid stress, significantly affect drug distribution and treatment efficacy, suggesting that mechanical remodeling represents a potential strategy to enhance therapeutic outcomes. Concurrently, tumor-associated microbiota and their metabolites participate in immune regulation and metabolic reprogramming, contributing to tumor development and offering novel therapeutic targets. Moreover, recent advances have broadened our understanding on the multilayered regulatory landscape of the TME through the investigation of previously underappreciated factors such as neural regulation, metabolic niche dynamics, spatiotemporal heterogeneity, and epigenetic modulation. This review systematically summarizes the characteristics of these diverse TME dimensions and highlights recent progress in targeted delivery strategies, to facilitate the development of more personalized and effective anticancer therapies.
Humans ; Tumor Microenvironment ; Neoplasms/pathology* ; Drug Delivery Systems ; Antineoplastic Agents/administration & dosage*

In 2023, new diagnostic criteria were proposed to distinguish myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) from other inflammatory diseases of the central nervous system.With typical clinical presentation and neuroimaging features, the seropositive status of anti-myelin oligodendrocyte glycoprotein-IgG (MOG-IgG) is essential for the diagnosis of MOGAD.Advances in cell transfection immunofluorescence assays have improved diagnostic accuracy in the last few years, but there are differences in the positive predictive value of serum MOG-IgG titers in the context of different MOGAD prevalence.Therefore, alternative diagnostic methods need to be further explored, and the clinical significance of low MOG-IgG titers should be carefully interpreted.In this review, the main clinical features, current understanding and challenges of MOGAD were discussed, including uncertainties about the specificity and pathogenicity of myelin oligodendrocyte glycoprotein autoantibodies and the need to identify immunopathological targets for future therapies.Moreover, it is necessary to search for and validate biomarkers that can help diagnose and detect disease activity, and it is important to identify MOGAD patients who need long-term immunotherapy.

In 2023, new diagnostic criteria were proposed to distinguish myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) from other inflammatory diseases of the central nervous system.With typical clinical presentation and neuroimaging features, the seropositive status of anti-myelin oligodendrocyte glycoprotein-IgG (MOG-IgG) is essential for the diagnosis of MOGAD.Advances in cell transfection immunofluorescence assays have improved diagnostic accuracy in the last few years, but there are differences in the positive predictive value of serum MOG-IgG titers in the context of different MOGAD prevalence.Therefore, alternative diagnostic methods need to be further explored, and the clinical significance of low MOG-IgG titers should be carefully interpreted.In this review, the main clinical features, current understanding and challenges of MOGAD were discussed, including uncertainties about the specificity and pathogenicity of myelin oligodendrocyte glycoprotein autoantibodies and the need to identify immunopathological targets for future therapies.Moreover, it is necessary to search for and validate biomarkers that can help diagnose and detect disease activity, and it is important to identify MOGAD patients who need long-term immunotherapy.

OBJECTIVE: To explore the genetic characteristics of a fetus with a high risk by maternal serum screening during the second trimester. METHODS: Genetic counseling was provided to the pregnant woman on March 22, 2020 at Henan Provincial People's Hospital. G-banded chromosomal karyotyping and array comparative genomic hybridization (aCGH) were carried out on the amniotic fluid sample and peripheral blood samples from the couple. RESULTS: The fetus and the pregnant woman were respectively found to have a 46,XX,der(6)t(6;14)(q27;q31.2) and 46,XX,t(6;14)(q27;q31.2) karyotype, whilst the husband was found to have a normal karyotype. aCGH analysis has identified a 6.64 Mb deletion at 6q26q27 and a 19.98 Mb duplication at 14q31.3q32.33 in the fetus, both of which were predicted to be pathogenic copy number variations. No copy number variation was found in the couple. CONCLUSION The unbalanced chromosome abnormalities in the fetus have probably derived from the balanced translocation carried by the pregnant woman. aCGH can help to determine the types of fetal chromosome abnormalities and site of chromosomal breakage, which may facilitate the prediction of fetal outcome and choice for subsequent pregnancies.
Pregnancy ; Female ; Humans ; Comparative Genomic Hybridization ; DNA Copy Number Variations ; Translocation, Genetic ; Chromosome Aberrations ; Fetus ; Prenatal Diagnosis

OBJECTIVE: To investigate the clinical phenotype and genetic characteristics of a Chinese pedigree affected with Cohen syndrome. METHODS: A proband who was admitted to Zhengzhou People's Hospital on June 2, 2021 due to intellectual disability and developmental delay, in addition with her younger sister and other family members, were selected as the study subjects. Clinical data of the proband and her younger sister were collected. Genomic DNA was extracted from peripheral venous blood and chorionic villi samples. Chromosomal abnormalities were detected with chromosomal microarray analysis (CMA). Whole exome sequencing (WES) and Sanger sequencing were carried out to detect candidate variants in the proband. With RNA extracted from the peripheral blood samples, VPS13B gene transcripts and expression were analyzed by PCR and real-time quantitative PCR. Prenatal diagnosis was carried out at 12 weeks' gestation. RESULTS: The proband was a 10-year-old female with clinical manifestations including development delay, obesity, severe myopia and peculiar facial features. Her sister was 3 years old with a similar phenotype. CMA revealed no chromosomal abnormality in the proband, while WES results revealed that the proband and her sister had both harbored compound heterozygous variants of the VPS13B gene, namely c.10076_10077delCA (p.T3359fs*29) and c.6940+1G>T, which were respectively inherited from their mother and father. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), both variants were classified as pathogenic (PVS1+PS4+PM4+PP1; PVS1+PM2_Supporting+PM3+PP1). In vivo splicing assay confirmed that the c.6940+1G>T variant has produced a frameshift transcript with skipping of exon 38. Compared with the control group, the expression of RNA in the peripheral blood of the proband's parents has decreased to 65% ~ 70% (P < 0.01), whilst that in the proband and her sister has decreased to 40% (P < 0.001). Prenatal diagnosis at 12 weeks of gestation has found that the fetus only harbored the heterozygous c.10076_ 10077delCA variant. CONCLUSION The c.10076_10077delCA (p.T3359fs*29) frameshift variant and c.6940+1G>T splicing variant probably underlay the Cohen syndrome in this pedigree. Genetic testing has facilitated the diagnosis of this disease.
Female ; Humans ; East Asian People ; Intellectual Disability/genetics* ; Mutation ; Myopia/genetics* ; Pedigree ; Vesicular Transport Proteins/genetics* ; Child, Preschool ; Child

OBJECTIVE: To analyze the genomic variation characteristics of fetal with abnormal serological screening, and to further explore the value of copy number variation (CNV) detection technology in prenatal diagnosis of fetal with abnormal serological screening. METHODS: 7617 singleton pregnant women who underwent amniocentesis for prenatal diagnosis solely due to abnormal Down's serological screening were selected. According to the results of serological screening, the patients were divided into high risk group, borderline risk group and single abnormal multiple of median (MOM) group. CMA and CNV-Seq were used to detect the copy number variation of amniotic fluid cell genomic DNA and combined with amniotic fluid cell karyotype analysis for prenatal diagnosis. Outpatient revisit combined with telephone inquiry was used for postnatal follow-up. RESULTS: Among 7617 amniotic fluid samples, aneuploidy was detected in 138cases (1.81%) by CMA and CNV-Seq, 9 cases of aneuploid chimerism were detected by amniotic fluid cell karyotype analysis, and 203 cases of fetus carrying pathogenic and likely pathogenic CNV (P/LP CNV) were detected, the variant of uncertain significance (VUS) was detected in 437 cases (5.7%), the overall abnormal detection rate was 10.33%. The detection rate of aneuploidy by CMA and CNV-Seq in three group were 123 cases (2.9%), 13 cases (1.3%) and 2 cases (0.4%), respectively,and showing no significant difference (χ ²=7.469, P=0.024). The detection rate of pathogenic and likely pathogenic CNV in three group were 163cases (2.6%); 24 cases (2.6%) and 16 cases (3.3%), respectively, and showing no significant difference (χ ²=0.764, P=0.682). The CMA reported 2.9% (108/3729)P/LP CNV, and CNV-seq reported 2.4% (95/3888)P/LP CNV, both tests showed similar detective capabilities (χ ²=1.504, P=0.22).The most popular P/LP CNV in this cohort were Xp22.31 microdeletion, 16p13.11 microduplication /microdeletion, 22q11.21 microduplication /microdeletion. In fetuses with P/LP CNV CNV, 59 fetuses were terminated pregnancy, and 32 of 112 fetuses born had abnormal clinical manifestations. Non-medically necessary termination of pregnancy occurred in 11 fetuses carrying VUS CNV, 322 fetuses carrying VUS CNV were born, 4 of them presented abnormal clinical manifestations. CONCLUSION Compared with the traditional chromosome karyotype, CMA and CNV-Seq can improve the detection rate of pathogenic and likely pathogenic CNV. CMA and CNV-seq can be used for first tier diagnosis of pregnant women in the general population with abnormal Down's serological screening.
Amniotic Fluid ; Aneuploidy ; Chromosome Aberrations ; DNA Copy Number Variations ; Female ; Genomics ; Humans ; Pregnancy ; Pregnancy Trimester, Second ; Pregnant Women ; Prenatal Diagnosis/methods* ; Technology

Objective:To explore the status quo of self-learning readiness of in-service nurses in self-taught examination and its correlation with general self-efficacy.Methods:Convenience sampling method was conducted with nurses who studied in the self-taught nursing examination of a university from a university in Sichuan Province from March to May 2020. General information questionnaire, Chinese version of Self-regulated Learning Readiness Scale for Nursing Education (SLDRS) and General Self-Efficacy Scale (GSES) were used to investigate the research. SPSS 24.0 was used to analyze the scores, multiple linear stepwise regression analysis was used to analyze the influencing factors, and Pearson correlation analysis was used to analyze the correlation between self-learning readiness and general self-efficacy. A total of 468 questionnaires were collected and 455 were valid.Results:The total scores of 455 nurses were (147.93±18.07) points, and the overall average scores were (3.70±0.45) points. Multiple linear stepwise regression analysis showed that the desire to continue to study for postgraduate students, the times of face-to-face classes in each subject, the preference for nursing major, aimlessness and satisfaction with the forms of assistance were the important influencing factors of autonomous learning readiness ( P<0.05). There is a positive correlation between self-learning readiness and general self-efficacy ( r=0.551, P<0.05). Conclusion:The self-learning readiness of nurses for self-taught examination is at a medium level. Their self-learning ability may be improved by encouraging them to carry out career planning, improving their professional identity and self-efficacy, and choosing teaching methods that are more suitable for in-service staff.

Objective:To investigate the association between prenatal genotype and phenotype of 16p13.11 microdeletion syndrome, aiming to provide a reference for prenatal diagnosis and genetic counseling.Methods:This retrospective study analyzed the results of comparative genomic hybridization microarray and low-coverage whole genome sequencing performed on 4 230 pregnant women in the Henan Provincial People's Hospital from July 2018 to July 2021. Indications for prenatal diagnosis, pedigree information and pregnancy outcomes of 17 fetuses with 16p13.11 microdeletion were described.Results:Prenatal diagnostic indications in the 17 fetuses were ultrasound abnormalities in five cases (increased nuchal translucency in four and cerebral ventriculomegaly with 10.7 mm in one), inter-twin weight discordance over 20% in one case, high risk in five cases and marginal risk in one in trisomy-21 serum screening, advanced maternal age in three cases (one with echogenic intracardiac focus in the left ventricle and two with normal ultrasound images) and adverse pregnancy history in two cases with normal ultrasound images. Pedigree verification that performed on 12 cases revealed that five were caused by de novo mutations and seven were inherited from their parents. The follow-up results showed that five cases were terminated, two lost to follow-up and 10 born alive (inheritance patterns were de novo mutations in three cases, parental inheritance in six and unknown pattern in one). These 10 infants were followed up from age 7 months to 3 years and 2 months and the results showed that one case was born with choroid plexus cyst of the left ventricle and presented instability of gait at 1 year and 3 months; one was a premature infant with 33 gestational weeks whose parents reported his language ability was not well at 2 years and 1 month old but without other abnormalities; one case had low muscle tone and was unable to keep head upright at 3 months who recovered at 5 months old after rehabilitation treatment according to the parents' report; all seven parents in the remaining seven cases reported no abnormalities. Conclusions:There was no specific prenatal diagnostic indication for 16p13.11 microdeletion syndrome. Genetic tracing, pregnancy outcome analysis and follow-up surveillance would provide reference for genetic counseling of 16p13.11 microdeletion syndrome.

Objective:To study the effect of baicalein on the expression of glutamate receptor related protein in PC12 cells injured by Aβ 25-35. Methods:PC12 cells were divided into control group, model group, estradiol group and baicalein group with different concentrations. The survival condition of PC12 cells in each group were detected by thiazole blue (MTT). PC12 cells were divided into control group, model group, estradiol group and baicalein group. The control group and model group were cultured with DMEM medium, and the estradiol group was added with 1×10 -3 μmol/L estradiol DMEM medium, baicalein group was added with 1 μmol/L baicalein DMEM medium. After 2 hours of intervention, 20 μmol/L Aβ 25-35 was added to the model group, estradiol group and baicalein group with induced PC12 cell injury. After 22 hours of intervention, flow cytometry was used to detect the apoptosis of PC12 cells. The expression of estrogen receptor β (ER β), phosphorylated c-Jun N-terminal kinase (p-JNK/JNK) and ionic receptor N-methyl-D-aspartate receptor 1 (NMDAR1), glutamate receptor 2 (GluR2) and calcium/calmodulin dependent protein kinase Ⅱ (CaMK Ⅱ) were detected by Western blot. Results:Compared with model group, 1 μmol/L baicalein significantly increased the proliferation rate [(95.80±2.47)% vs. (64.34±3.84)%]. The apoptosis rate of PC12 cells[(7.83±0.67)% vs. (12.84±0.91)%] was significantly decreased in baicalein group ( P<0.01). The expression of NMDAR1 (0.582±0.012 vs. 0.352±0.012), GluR2(0.538±0.017 vs. 0.355±0.006), ER β (0.362±0.015 vs. 0.262±0.018) in baicalein group were significantly increased ( P<0.01), the expression of p-JNK/JNK (0.476±0.013 vs. 0.752±0.014) and CaMK Ⅱ(0.499±0.019 vs. 0.670±0.016) in baicalein group were significantly decreased ( P<0.01). Conclusions:Baicalein has a protective effect on PC12 cells injured by Aβ 25-35. Its mechanism may be related to the inhibition of p-JNK/JNK activity by activating ERβ and regulating the expression of glutamate receptor related protein.