Objective·To explore the correlation between the genetic variations rs7305526 and rs11615756 of nitric oxide synthase 1(NOS1)and the human sleep traits,including insomnia,sleep duration,and clinical quantitative traits related to obstructive sleep apnea(OSA).Methods·The NOS1 gene expression pattern at the whole-brain level using the Allen Human Brain Atlas dataset was analyzed.Subsequently,we performed expression quantitative trait locus(eQTL)analysis to investigate the impact of rs7305526 and rs11615756 on NOS1 gene expression.Regression analysis was conducted to assess the associations between rs7305526 and rs11615756 with insomnia and sleep duration based on the United Kingdom Biobank(UKB)Genome-Wide Association Study(GWAS)dataset.Furthermore,we explored the relationships between rs7305526 and rs11615756 with clinical quantitative traits of OSA,such as respiratory events,oxygen levels,and sleep traits,using clinical monitoring data from the Shanghai Sleep Health Study Cohort(SSHS)based on standard polysomnography(PSG).Results·The NOS1 gene demonstrated elevated levels of expression in various brain regions crucial for regulating sleep,namely the amygdala,basal forebrain,striatum,and thalamus,as well as in the respiratory center,including the mesencephalon and pontine tegmentum.In contrast,the expression level of NOS1 gene was significantly reduced or absent in areas such as the cerebral cortex and cerebellum.Variants rs7305526 and rs11615756 were significantly negatively correlated with the expression levels of NOS1 in the cerebral cortex.Additionally,rs11615756 was also significantly negatively correlated with the expression level of NOS1 in the amygdala.Analysis of the UKB GWAS data revealed that the variant rs7305526 was not significantly associated with either insomnia or sleep duration,while rs11615756 demonstrated a noteworthy negative correlation specifically with sleep duration.Data obtained from the SSHS indicated a significant association between rs7305526 and alterations in clinical quantitative traits of OSA,including lowest pulse blood oxygen saturation(LSpO2),apnea-hypopnea index(AHI),and the ratio of non-rapid eye movement(NREM)stage 2 sleep duration.Although rs11615756 showed a notable negative correlation solely with the quantity of NREM stages 2 and 3,both rs11615756 and rs7305526 showed significant correlations with some respiratory events and oxygen traits after stratification according to the severity of OSA.Conclusion·Genetic variants of NOS1 gene are respectively associated with human sleep duration traits and OSA-related variables,suggesting that NOS1 gene plays a crucial regulatory role in human sleep and clinical quantitative traits of OSA.The regulation of sleep traits by rs7305526(C>A)is independent of its regulation of respiratory events and oxygen traits.

Objective·To explore the correlation between the genetic variations rs7305526 and rs11615756 of nitric oxide synthase 1(NOS1)and the human sleep traits,including insomnia,sleep duration,and clinical quantitative traits related to obstructive sleep apnea(OSA).Methods·The NOS1 gene expression pattern at the whole-brain level using the Allen Human Brain Atlas dataset was analyzed.Subsequently,we performed expression quantitative trait locus(eQTL)analysis to investigate the impact of rs7305526 and rs11615756 on NOS1 gene expression.Regression analysis was conducted to assess the associations between rs7305526 and rs11615756 with insomnia and sleep duration based on the United Kingdom Biobank(UKB)Genome-Wide Association Study(GWAS)dataset.Furthermore,we explored the relationships between rs7305526 and rs11615756 with clinical quantitative traits of OSA,such as respiratory events,oxygen levels,and sleep traits,using clinical monitoring data from the Shanghai Sleep Health Study Cohort(SSHS)based on standard polysomnography(PSG).Results·The NOS1 gene demonstrated elevated levels of expression in various brain regions crucial for regulating sleep,namely the amygdala,basal forebrain,striatum,and thalamus,as well as in the respiratory center,including the mesencephalon and pontine tegmentum.In contrast,the expression level of NOS1 gene was significantly reduced or absent in areas such as the cerebral cortex and cerebellum.Variants rs7305526 and rs11615756 were significantly negatively correlated with the expression levels of NOS1 in the cerebral cortex.Additionally,rs11615756 was also significantly negatively correlated with the expression level of NOS1 in the amygdala.Analysis of the UKB GWAS data revealed that the variant rs7305526 was not significantly associated with either insomnia or sleep duration,while rs11615756 demonstrated a noteworthy negative correlation specifically with sleep duration.Data obtained from the SSHS indicated a significant association between rs7305526 and alterations in clinical quantitative traits of OSA,including lowest pulse blood oxygen saturation(LSpO2),apnea-hypopnea index(AHI),and the ratio of non-rapid eye movement(NREM)stage 2 sleep duration.Although rs11615756 showed a notable negative correlation solely with the quantity of NREM stages 2 and 3,both rs11615756 and rs7305526 showed significant correlations with some respiratory events and oxygen traits after stratification according to the severity of OSA.Conclusion·Genetic variants of NOS1 gene are respectively associated with human sleep duration traits and OSA-related variables,suggesting that NOS1 gene plays a crucial regulatory role in human sleep and clinical quantitative traits of OSA.The regulation of sleep traits by rs7305526(C>A)is independent of its regulation of respiratory events and oxygen traits.

To investigate the effects of ventricular shunt placement in children with post-infective hydrocephalus.
 Methods: A total of 24 cases of post-infectious hydrocephalus, who received ventricular shunt, were enrolled. Age, gender, disease progression, clinical manifestation, laboratory data, treatment, prognosis, complication, and sequela for each patient were retrospectively reviewed.
 Results: Of the 24 cases, 8 had a full recovery, 11 had slight sequela, 2 had severe sequela, 1 was in vegetative state, and 2 died because of bacterial meningitis and tubercular meningitis. Epilepsy, mental impairment, visual and hearing damage were the main sequelae.
 Conclusion: Ventricular shunt is the preferred treatment in children with post-infective hydrocephalus, which shows positive clinical efficacy and can improve the long-term prognosis of such patients.
Child ; Humans ; Hydrocephalus ; Retrospective Studies ; Treatment Outcome ; Tuberculosis, Meningeal ; Ventriculoperitoneal Shunt

Objective: To summarize the clinical features and gene variation characteristics of a child with Okur-Chung syndrome caused by CSNK2A1 gene variation. Methods: The medical records of one patient who was diagnosed with Okur-Chung syndrome in Department of Pediatrics, Xiangya Hospital of Central South University in July 2018 were analyzed. Using "CSNK2A1" gene as the keyword, relevant information about CSNK2A1 gene was searched at CNKI, Wangfang Data, OMIM, PubMed, ClinVar, Decipher (until August 2018). The characteristics of CSNK2A1 gene variation and the clinical phenotype of children with Okur-Chung syndrome were summarized. Results: The boy, 1 year and 8 months old, was sent to hospital at the age of 1 year and 6 months because of delayed growth for more than 1 year. He was susceptible to cough while eating or drinking. He was also suffering from constipation and poor sleep. Physical examination showed that his body weight was 10.2 kg, microcephalus, broad nasal bridge, micrognathia and hypotonia were observed. Whole exome-sequencing test identified a de novo heterozygous variation c.524A>G (p.D175G) in CSNK2A1 gene. This was the first case report of CSNK2A1 gene variation in the mainland of China. So far, a total of 52 cases were reported worldwide (52 single nucleotide variants), including 35 cases in 7 articles, 9 cases in Decipher database and 14 cases in ClinVar database, 6 of which were also reported in PubMed. In previously reported 52 cases, there were 48 missense variants, whereas, splice and frameshift variations were found in 3 cases and 1 case, respectively. Among the variation sites, p.K198R was the most common sites (12 cases), followed by p.R47 (6 cases), p.R80H (4 cases) and p.S51 (4 cases). Among these 52 cases, only 27 cases have been elaborately described in other studies, so the clinical characteristics were summarized in 28 cases eventually (including 27 cases in the articles and this patient), 27 of whom presented severe intellectual disability or global development delay, 1 case with mild language development delay, and 19 had hypotonia; 8 had autism spectrum disorders, 5 had attention deficit hyperactivity disorder, and 9 had sleep problems. 20 had dysmorphic facial features, 10 of them had microcephalus. 16 had failure to thrive or short stature, 12 had gastrointestinal or oromotor problem, 5 had immunological problem, and 4 had skin abnormalities. Conclusions The main clinical feature of patients with CSNK2A1 gene variations is intellectual disability with multiple systems involved, such as microcephalus, abnormal facial shape and hypotonia. The variation of CSNK2A1 gene is the cause of Okur-Chung syndrome. Missense variation is the main cause, and P. K198R is the hotspot variation.

Objective: To explore the clinical features and genetic characteristics of myoclonic-atonic epilepsy (MAE) caused by SLC6A1 gene mutation. Methods: The clinical data of a patient with SLC6A1 gene mutation from Xiangya Hospital of Central South University was collected. The related literatures were reviewed from Wanfang Data, China National Knowledge Infrastructure, PubMed (until July 2019) by using keywords " SLC6A1" and " myoclonic-atonic epilepsy" . The characteristics of SLC6A1 gene mutation and the clinical phenotype of children with myoclonic-atonic epilepsy were summarized. Results: A 8 year and 8 months old girl was enrolled in the study. Her first attack happened at the age of 19 months, and multiple seizure types including myoclonic-atonic, atonic and absence were observed. The seizures were well controlled by valproate (VPA), but she has mild-moderate intellectual disability. Whole exome-sequencing study identified a de novo nonsense variant of c. 46G>T(p.Glu16*)in SLC6A1 gene. A total of 27 cases including the present case with SLC6A1 gene mutation were analyzed. 22 mutations were identified, including 11 missense mutations, 5 nonsense mutations, 3 frameshift mutations, 2 splicing mutation and 1 with chromosome microdeletion. Among them 26 patients had more one type of seizures, 20 cases had absence seizures, 17 cases had atonic seizures, 14 cases had myoclonic seizures, 11 cases had myoclonic-atonic seizures, 4 cases had generalized tonic-clonic seizures, 3 cases had eyelid myoclonias, 2 cases had nonconvulsive status epilepticus and 2 cases had tonic seizure. 24 patients had described intelligence assessment. Among them, 18 had developmental delay before epilepsy onset, 11 had developmental regression after onset. There were 9 cases with autistic features, 4 cases with attention deficit hyperactivity disorder and 3 cases with ataxia. The seizures of 17 cases were controlled, 4 cases had partial seizure control, 3 cases had no significant improvement, and other 3 cases were unclear. Conclusions The main clinical feature of MAE patients with SLC6A1 gene mutations is absence and atonic seizures, cognition before epilepsy onset can be impaired, and some patients had behavioral problems, such as autistic features or attention deficit hyperactivity disorders. VPA is recommend as first-line treatment.

Objective To summarize the clinical features of global developmental delay (GDD) children,and to explore the relationship between severity of GDD and social-culture factors.Methods Sign the informed consent before enrollment.Collect clinical data in detail about 100 GDD children (GDD group) and 95 children with normal development (healthy control group),and analyze their regular clinical data,physical examination,intellectual disability test,electroencephalography (EEG) and cranial imaging test.Spearman rank correlation was used to analyze the differences of social and cultural factors between GDD group and healthy control group,such as maternal reproductive age,parental education level and family economic status.At the same time,we compared the lag degree of total developmental quotient and the degree of developmental retardation of five energy areas with the above factors.Results Significant associations were found between GDD and maternal/paternal education,economic level of family,but no sgnificant association was found between maternal age and GDD.And analysis in the relationship between severity of delay in all domains of the child's developmental status about language and social-culture factors,we only obtained the severity of delay in abilities about language is related with maternal education.Spearman rank correlation statistics explains that if there are the lower level of education with mothers,the delay of language domain will more severe (rs =-0.505,P ＜ 0.05).Conclusions Significant associations were found between GDD and maternal/paternal education,economic level of family.The higher maternal education was an important protective factor against risk of GDD.Improving the cognition of parents in child health care,early be diagnosed,early be intervened,is the most important for children with language development.

Objective: To explore the feasibility of high-throughput texture analysis in the distinction of single brain metastases (SBM) from high-grade gliomas (HGG) and validate the established model. Methods: A total of 86 patients who were histologically diagnosed with SBM or HGG were retrospectively collected, including 43 patients with SBM and 43 with HGG. All of patients were performed preoperative conventional head magnetic resonance imaging (MRI) scans. A total of 236 fluid-attenuated inversion recovery (FLALR) images containing the information of tumors were selected from the MRI images and each image was considered as an object. The training set had 200 images, including 106 from SBM group and 94 from HGG group, whereas the validation set had 36 images, including 19 from SBM group and 17 from HGG. After images preprocessing, images segmentation, features extraction, and features selection, a radiomic diagnostic model was finally established using the training set. The diagnostic performance of the diagnostic model was evaluated using a receiver operating characteristic (ROC) curve. Hierarchical clustering analysis was used to evaluate the quality of the extracted feature data and the classification effect of the model. The model was further validated using the independent validation set. Results: A total of 629 features were extracted and quantified from each sample, and 41 features were selected to establish feature subsets and the diagnostic model. The classification decision function of the model is f(x)=sign and the kernel function of the model is K(x, x_i)=exp. In the training set, the diagnostic accuracy, sensitivity, specificity, positive predictive value and negative predictive value were 0.845, 0.849, 0.840, 0.857 and 0.832, respectively. The area under the ROC curve reached to 0.939. Similar results were obtained in the validation set. Conclusion The high-throughput texture analysis shows high accuracy in differentiating SBM from HGG.