Objective:To investigate the steady-state mechanism of interconversion between the SMN1 and SMN2 genes in a normal population. Methods:Fluorescence PCR capillary electrophoresis was employed to assess gene conversion and copy number variation of SMN1 and SMN2 in a cohort of 1, 133 healthy individuals (including 256 males and 877 females) recruited between 2019 and 2023. This study was approved by the Ethics Committee of Henan Provincial People′s Hospital (Ethics No.: 2019-134). Results:No significant gender difference was observed in the single copy carrying rate of SMN1. The probability of conversion from SMN1 to SMN2 was determined to be 3.2% for females, 2.7% for males, and 3.1% for the overall population. The probability of conversion from SMN2 to SMN1 was found to be 5.5% for females, 6.3% for males, and 5.6% for the overall population. No statistically significant difference was found in the conversion probability between different genders ( P>0.05). Among the 99 cases of gene conversion, the SMN1 gene predominantly exhibited a copy number of 2 (97.0%), with the remainder having 3 copies (3%). The SMN2 gene primarily showed a copy number of 2 (72.7%), with the rest having 1 copy (27.3%). Conclusion:Gene conversion tends to normalize the copy numbers of both SMN1 and SMN2 genes towards 2. However, SMN1 exhibited a higher priority over SMN2, causing the copy numbers approaching two.

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.

OBJECTIVE: To investigate the steady-state mechanism of interconversion between the SMN1 and SMN2 genes in a normal population. METHODS: Fluorescence PCR capillary electrophoresis was employed to assess gene conversion and copy number variation of SMN1 and SMN2 in a cohort of 1,133 healthy individuals (including 256 males and 877 females) recruited between 2019 and 2023. This study was approved by the Ethics Committee of Henan Provincial People's Hospital (Ethics No.: 2019-134). RESULTS: No significant gender difference was observed in the single copy carrying rate of SMN1. The probability of conversion from SMN1 to SMN2 was determined to be 3.2% for females, 2.7% for males, and 3.1% for the overall population. The probability of conversion from SMN2 to SMN1 was found to be 5.5% for females, 6.3% for males, and 5.6% for the overall population. No statistically significant difference was found in the conversion probability between different genders (P > 0.05). Among the 99 cases of gene conversion, the SMN1 gene predominantly exhibited a copy number of 2 (97.0%), with the remainder having 3 copies (3%). The SMN2 gene primarily showed a copy number of 2 (72.7%), with the rest having 1 copy (27.3%). CONCLUSION Gene conversion tends to normalize the copy numbers of both SMN1 and SMN2 genes towards 2. However, SMN1 exhibited a higher priority over SMN2, causing the copy numbers approaching two.
Humans ; Male ; Female ; Survival of Motor Neuron 2 Protein/genetics* ; Survival of Motor Neuron 1 Protein/genetics* ; Gene Conversion ; DNA Copy Number Variations/genetics* ; Adult ; Middle Aged ; Gene 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 investigate the steady-state mechanism of interconversion between the SMN1 and SMN2 genes in a normal population. Methods:Fluorescence PCR capillary electrophoresis was employed to assess gene conversion and copy number variation of SMN1 and SMN2 in a cohort of 1, 133 healthy individuals (including 256 males and 877 females) recruited between 2019 and 2023. This study was approved by the Ethics Committee of Henan Provincial People′s Hospital (Ethics No.: 2019-134). Results:No significant gender difference was observed in the single copy carrying rate of SMN1. The probability of conversion from SMN1 to SMN2 was determined to be 3.2% for females, 2.7% for males, and 3.1% for the overall population. The probability of conversion from SMN2 to SMN1 was found to be 5.5% for females, 6.3% for males, and 5.6% for the overall population. No statistically significant difference was found in the conversion probability between different genders ( P>0.05). Among the 99 cases of gene conversion, the SMN1 gene predominantly exhibited a copy number of 2 (97.0%), with the remainder having 3 copies (3%). The SMN2 gene primarily showed a copy number of 2 (72.7%), with the rest having 1 copy (27.3%). Conclusion:Gene conversion tends to normalize the copy numbers of both SMN1 and SMN2 genes towards 2. However, SMN1 exhibited a higher priority over SMN2, causing the copy numbers approaching two.

[Objective]To explore the protective effect of glucocorticoid-induced transcription factor 1(GLCCI1)on cognitive dysfunction in diabetic mice and its mechanism.[Methods]Twenty-four C57BL/6J mice were randomly divided into 4 groups,namely Control,DM,DM+AAV-Glcci1,and DM+AAV-NC.The Control group was intraperitoneally injected with saline,while the other groups were all injected with streptozotocin(STZ).Two weeks after successful modeling,the DM+AAV-Glcci1 group was brain stereotactic injected with Glcci1 overexpressing adeno-associated virus,and the DM+AAV-NC group was stereoscopically injected with the control virus.After 12 weeks,the Morris water maze test was used to evaluate the learning and memory abilities of mice in each group.Subsequently,the localized expression of GLCCI1 in the hippocampus were determined by immunofluorescence and immunohistochemistry experiments.The myelin morphology in the hippocampus was observed by LFB staining,the neuronal morphology was observed by Nissl staining,and the myelin-related proteins MBP and CNPase were stained by immunohistochemistry.Molecular docking was used to predict the interaction between GLCCI1 and HSPA5.The expression of endoplasmic reticulum stress-related proteins was detected by Western blot.[Results]The results of the behavioral experiment showed that compared with the mice in the Control group,DM mice exhibited obvious cognitive dysfunction behaviors(P＜0.000 1),and the learning and memory abilities of mice improved after overexpression of Glcci1(P=0.000 7).The results of immunofluorescence and immunohistochemistry showed that GLCCI1 was expressed in hippocampal neuron cells.Compared with Control mice,the expression level of GLCCI1 in DM mice was significantly downregulated(P＜0.000 1).The molecular docking results revealed that GLCCI1 interacts with HSPA5.The Western blot results indicated that,compared with the Control group,the expression levels of endoplasmic reticulum stress-related proteins HSPA5(P＜0.000 1),ATF4(P＜0.000 1),ATF6(P=0.001 1),and p-ELF2α/elF2α(P=0.000 1)in the DM group were significantly increased;Compared with the DM group,the expression of the corresponding protein HSPA5(P＜0.000 1),ATF4(P＜0.000 1),ATF6(P=0.000 2),and p-ELF2α/elF2α(P=0.000 1)was significantly down-regulated after overexpression of Glcci1.LFB staining showed that compared with the Control group,the myelin integrity of DM mice decreased significantly(P=0.010 3),the expressions of myelin-related proteins MBP and CNPase decreased significantly(P=0.000 4,P=0.000 2),and Nissl staining observed disordered neuronal arrangement.Compared with the mice in the DM group,the myelin integrity in the hippocampal region significantly increased after overexpression of Glcci1(P=0.000 3),the expressions of myelin-related proteins MBP and CNPase significantly increased(P=0.001 4,P=0.000 1),and the ordered arrangement of neurons was observed by Nissl staining.[Conclusion]The down-regulation of GLCCI1 expression in hippocampal neurons promotes demyelination of hippocampal neurons and thereby induces diabetic cognitive dysfunction.The specific mechanism may be related to endoplasmic reticulum stress.

Objective To investigate the effect of sustained fatigue on the passive and active biomechanical characteristics of the knee.Methods Twenty-seven healthy university students were recruited to perform a fatigue experiment using an isokinetic dynamometer.The fatigue experiment included three fatigue cycles with more than 30 sustained quadriceps submaximal voluntary isometric contractions per cycle.The maximum passive torque,mean maximum voluntary contraction(MVC)torque,integrated electromyography of the vastus lateralis and biceps femoris,and co-contraction index(CI)during different fatigue cycles were compared.Results The maximum passive torque decreased significantly only after the 3rd fatigue cycle(P＜0.05).The mean MVC torque and integrated electromyography of the vastus lateralis and biceps femoris decreased significantly during the 1st,2nd,and 3rd fatigue cycles(P＜0.05).However,the Cl did not change significantly(P＞0.05).Conclusions Sustained fatigue intervention with 90-fold isometric contraction training of the quadriceps significantly affected the active and passive biomechanical properties of the knee.After fatigue intervention,the resistance of the knee joint to passive flexion and extension decreased.With fatigue intervention,the active contraction ability of the quadriceps decreased,and the activation of the quadriceps femoris and hamstring muscles also decreased;however,the co-contraction level of the two muscle groups remained unchanged.This mild muscle group co-contraction pattern is beneficial for maintaining a benign mechanical loading environment in the knee joints.These results help us understand the active and passive biomechanical properties of knee joints after fatigue.

Objective: To understand the current situation of academic burnout among primary and middle school students and to explore its associated factors, so as to provide a scientific guidance and preventing and amelioration academic burnout among primary and middle school students. Methods: Between September and October 2023, a total of 10 474 primary and middle school students residing in Wuxi City participated in a questionnaire survey and physical examination conducted through stratified cluster random sampling. Latent profile analysis was used to classify academic burnout among primary and middle school students. Furthermore, differences in the types of academic burnout among children and adolescents with varying characteristics were examined using the Chi square test. Additionally, multinomial Logistic regression analysis was utilized to identify the associated factors for academic burnout. Results: The academic burnout of primary and middle school students was divided into 4 categories:no/light academic burnout group(43.6%),physical and mental exhaustion group (32.9%), low achievement group(15.0%), high physical and mental exhaustion/high academic burnout group(8.5%). Middle and high school students, boys, not living with parents, smoking, daily screen time ≥2 hours, suffering from campus bullying, sometimes/often subjected to cyber attacks, abused by parents were more likely to have high physical and mental exhaustion/high academic alienation among primary and middle school students ( OR=1.70, 1.42, 1.56, 1.56, 2.31, 1.48, 2.94, 3.03, 5.94, 2.08, P <0.01). Conclusions The phenomenon of academic burnout among primary and middle school students is prominent. And targeted intervention measures shoould be actively taken to prevent and reduce the occurrence of academic burnout among primary and middle school students.

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