Posterior reversible encephalopathy syndrome in children with acute lymphoblastic leukemia during remission induction chemotherapy: a single-center retrospective study.

BACKGROUND: This study investigated the clinical characteristics, cranial magnetic resonance imaging (MRI) features, MRI follow-up, and prognosis of children with acute lymphoblastic leukemia (ALL) who developed posterior reversible encephalopathy syndrome (PRES) during remission induction chemotherapy. METHODS: We analyzed the age, gender, PRES symptoms and signs, cranial MRI findings, therapeutic effect, and prognosis of children with ALL who developed PRES during chemotherapy from January 2010 to December 2013 at the Hematology Oncology Center of Beijing Children's Hospital. Changes in cranial MRI findings were analyzed, and intelligence (IQ) and cognitive function were evaluated using the Wechsler Scale and the Wisconsin Card Score Test after the children completed chemotherapy. RESULTS: There were 850 children with newly diagnosed ALL in this period; 13 (1.5%), 6 boys and 7 girls, developed PRES. All were diagnosed as B-cell ALL. The median age at PRES onset was 7 years (2-11 years). The median day of PRES onset was day 28 (day 17-34) of remission induction chemotherapy. Of the 13 children with PRES onset and seizures, 4 had visual disturbances and 2 had consciousness disturbances. Cranial MRI showed hyperintensity in the subcortical white matter on T2-weighted axial and fluid-attenuated inversion recovery (FLAIR) images. The lesion locations were as follows: occipital lobe, 12 (92.3%) patients; frontal lobe, 7 (53.8%) patients; temporal lobe, 5 (38.4%) patients; parietal lobe, 3 (23.1%) patients; and cerebellum, 1 (7.7%) patient. There were 8 (61.5%) patients with vasogenic edema and 5 (38.5%) with cytotoxic edema. After treatment, all children recovered within one month, when their PRES symptoms were relieved, they continued to receive chemotherapy. However, 1 child (1.07%) died of severe central nervous system infection one year after PRES treatment, and 3 (25%) had recurrent seizures and were diagnosed with epilepsy after three months of PRES treatment. Their cranial MRIs showed cytotoxic edema, which was acute stage on day 15, with aggravated lesions on cranial MRI. The cranial MRI lesions returned to normal at one month in 3 (23.1%) patients, at three months in 6 (46.1%) patients, at one year in 8 (61.5%) patients, and at two years in 12 (92.3%) patients. The 12 surviving children all returned to school, and their full-scale, verbal, and performance IQs were normal, with no significant differences in intelligence or cognitive function compared with children with ALL without PRES during the same period. CONCLUSIONS: PRES can occur during remission induction chemotherapy treatment of children with ALL, but the incidence is low. Cranial MRI can be used for diagnosis and to characterize lesions. The children recover about a month after treatment, and cranial MRI lesions return to normal within two years. The time for complete resolution of MRI lesions differs, and children with cytotoxic edema have worse prognosis with sequelae, such as epilepsy, which requires close monitoring. PRES does not affect intelligence or cognitive development.

Associations of essential element serum concentrations with autism spectrum disorder.

This case-control study explored the associations between autism spectrum disorder (ASD) and the serum concentration of nine chemical elements in children. The study recruited 92 Chinese children with ASD and 103 typically developing individuals. Serum concentrations of nine chemical elements (calcium, iodine, iron, lithium, magnesium, potassium, selenium, strontium, and zinc) were determined by inductively coupled plasma mass spectrometry (ICP-MS) and inductively coupled plasma atomic emission spectrometry (ICP-AES). An unconditional logistic regression model was used to analyze the associations between the serum concentrations of the elements and the risk of ASD. After adjusting for confounders, the multivariate analysis results showed that zinc ≤ 837.70 ng/mL, potassium > 170.06 µg/mL, and strontium ≤ 52.46 ng/mL were associated with an increased risk of ASD, while selenium > 159.80 ng/mL was associated with a decreased risk of ASD. Furthermore, the degree of lithium and zinc deficiency was associated with ASD severity. The results indicated that metallomic profiles of some specific elements might play important roles in the development of ASD, a finding of scientific significance for understanding the etiology, and providing dietary guidance for certain ASD types.

Urinary Metabolomic Study in a Healthy Children Population and Metabolic Biomarker Discovery of Attention-Deficit/Hyperactivity Disorder (ADHD).

Objectives: Knowledge of the urinary metabolomic profiles of healthy children and adolescents plays a promising role in the field of pediatrics. Metabolomics has also been used to diagnose disease, discover novel biomarkers, and elucidate pathophysiological pathways. Attention-deficit/hyperactivity disorder (ADHD) is one of the most common psychiatric disorders in childhood. However, large-sample urinary metabolomic studies in children with ADHD are relatively rare. In this study, we aimed to identify specific biomarkers for ADHD diagnosis in children and adolescents by urinary metabolomic profiling. Methods: We explored the urine metabolome in 363 healthy children aged 1-18 years and 76 patients with ADHD using high-resolution mass spectrometry. Results: Metabolic pathways, such as arachidonic acid metabolism, steroid hormone biosynthesis, and catecholamine biosynthesis, were found to be related to sex and age in healthy children. The urinary metabolites displaying the largest differences between patients with ADHD and healthy controls belonged to the tyrosine, leucine, and fatty acid metabolic pathways. A metabolite panel consisting of FAPy-adenine, 3-methylazelaic acid, and phenylacetylglutamine was discovered to have good predictive ability for ADHD, with a receiver operating characteristic area under the curve (ROC-AUC) of 0.918. A panel of FAPy-adenine, N-acetylaspartylglutamic acid, dopamine 4-sulfate, aminocaproic acid, and asparaginyl-leucine was used to establish a robust model for ADHD comorbid tic disorders and controls with an AUC of 0.918.

Gray Matter Alterations in Pediatric Schizophrenia and Obsessive-Compulsive Disorder: A Systematic Review and Meta-Analysis of Voxel-Based Morphometry Studies.

Objective: The aim of this study is comparing gray matter alterations in SCZ pediatric patients with those suffering from obsessive-compulsive disorder (OCD) based on a systematic review and an activation likelihood estimation (ALE) meta-analysis. Methods: A systematic literature search was performed in PubMed, Elsevier, and China National Knowledge Infrastructure (CNKI). A systematic review and an ALE meta-analysis were performed to quantitatively examine brain gray matter alterations. Results: Children and adolescents with schizophrenia had decreased gray matter volume (GMV) mainly in the prefrontal cortex (PFC), temporal cortex (such as the middle temporal gyrus and transverse temporal gyrus), and insula, while children and adolescents with OCD mainly had increased GMV in the PFC and the striatum (including the lentiform nucleus and caudate nucleus), and decreased GMV in the parietal cortex. Conclusions: Our results suggest that gray matter abnormalities in the PFC may indicate homogeneity between the two diseases. In children and adolescents, structural alterations in schizophrenia mainly involve the fronto-temporal and cortico-insula circuits, whereas those in OCD mainly involve the prefrontal-parietal and the prefrontal-striatal circuits.

Nucleoporin 37 promotes the cell proliferation, migration, and invasion of gastric cancer through activating the PI3K/AKT/mTOR signaling pathway.

Gastric cancer is a kind of malignant tumor in the world. Emerging studies have proved the regulatory role of nucleoporin 37 in the development of several malignant tumors. However, the potential effect of NUP37 in gastric cancer is still unclear. In this study, we searched for the Cancer Genome Atlas analysis to explore the potential correlation between NUP37 and gastric cancer. Then, we analyzed NUP37 expression in gastric cancer tissues and cell lines. After constructing a NUP37-silenced model in NCI-N87 cells and a NUP37-overexpressed model in MKN45 cells, we evaluated the role of NUP37 in cell proliferation, migration, and invasion as well as its underlying mechanism. TCGA analysis showed that NUP37 expression was highly expressed in stomach adenocarcinoma, which showed a lower survival rate than normal samples. Moreover, NUP37 was found to be highly expressed in gastric cancer tissues and cell lines. Functionally, NUP37 deficiency promoted gastric cancer cell apoptosis and inhibited cell proliferation, migration, and invasion, whereas NUP37 overexpression exhibited the opposite results. Mechanically, upregulation of NUP37 activated the PI3K/AKT/mTOR signaling pathway. Furthermore, the rescue assay exhibited that the mTOR inhibitor rapamycin significantly reversed the promoting effect of NUP37 in cell proliferation, migration, and invasion. In conclusion, our study identified that NUP37 promoted malignant behavior of gastric cancer cells including invasion, proliferation, and migration through activating the PI3K and its downregulated signaling pathway, indicating that NUP37 might become a novel prognostic target for further gastric cancer therapy.

Knockdown of Serum- and Glucocorticoid-Regulated Kinase 1 Enhances Cisplatin Sensitivity of Gastric Cancer Through Suppressing the Nuclear Factor Kappa-B Signaling Pathway.

BACKGROUND: Previous studies have published the promoting effect of serum and glucocorticoid-regulated kinase 1 (SGK1) in various malignant tumors. However, whether SGK1 promotes gastric cancer remains a mystery. AIMS: To clarify the function of SGK1 in gastric cancer and its potential regulatory mechanism. STUDY DESIGN: Cell culture study. METHODS: The SGK1-silenced model was generated in two gastric cancer cell lines and further evaluated their malignant behavior and susceptibility to cisplatin. The interaction between miR-15a-5p and SGK1 was evaluated by the luciferase reporter assay. The knockdown efficiency of SGK1 was confirmed by RT- qPCR and Western blot assays. Cell proliferation rate was assessed with CCK-8 assay, and flow cytometry was used to determine cell cycle progression and apoptosis. RESULTS: Western blot data displayed an elevated level of SGK1 in gastric cancer cell lines. Functionally, SGK1 deficiency suppressed gastric cancer cell proliferation (P < .01) by acting on cell-cycle progression. Moreover, SGK1 deficiency suppressed cell invasion and migration of gastric cancer cells (P < .01). Further, the silencing of SGK1 obviously suppressed cell proliferation and induced apoptosis of the cells after cisplatin treatment (P < .01), indicating that SGK1 deficiency facilitated the chemosensitivity of these 2 gastric cancer cell lines to cisplatin. Mechanically, downregulation of SGK1 repressed the cytoplasm- to-nucleus translocation of NF-κB p65. Interestingly, we found that miR-15a-5p binds to the 3'UTR of SGK1, which was confirmed using luciferase activity assay (P < .05). Moreover, the data suggested that SGK1 reversed the suppression effect of miR-15a-5p on gastric cancer cell migration (P < .01). CONCLUSION: Loss of SGK1 suppresses the malignant behavior of gastric cancer cells and increases cisplatin sensitivity by restraining the NF-κB signaling pathway. Moreover, SGK1 may exert an inhibitory effect in gastric cancer by being targeted by miR-15a-5p. Therefore, SGK1 may be a prospective target for future gastric cancer therapy.

The relationship between the simultaneity present of cagA and hopQI genes in Helicobacter pylori and the risk of gastric cancer.

Helicobacter pylori is a bacterium that causes infections in the gastrointestinal tract. This type of bacterium is very common and contagious at the same time. H. pylori enters the mouth and continues its course along the gastrointestinal tract. H. pylori infection induces an inflammatory response that leads to the activity of neutrophils, lymphocytes, plasma cells, and macrophages. In addition to the bacterial role in gastric mucosa, the host's inflammatory response may also play a role in disease outcome. In inflammation, the risk of carcinogenesis increases due to DNA damage increased proliferation and the creation of an environment rich in cytokines and growth factors. Genetic methods and diagnosis of H. pylori genes are used to identify healthy and healthy gastric cancer patients infected with H. pylori. In relation to the genes associated with H. pylori pathogenesis, the presence of genes such as cagA, hopQI, hopQII and so on is used, and PCR of a part of these genes amplified fragments of different lengths. One of the less-studied cases is the association of two or more pathogenic genes simultaneously with H. pylori. In this research, the frequency of disease and healthy individuals who are infected with H. pylori and have two genotypes cagA and hopQI at the same time, was examined. In order to diagnose H. pylori-infected individuals in healthy and gastric cancer patients, after PCR of glmM gene, PCR product electrophoresis on agarose gel was used. For this purpose, gastric tissue biopsy was used in patients and saliva was used in healthy individuals. For this purpose, 100 gastric biopsy samples were collected from patients with gastric cancer and 100 saliva samples from healthy individuals. According to the data, there is a significant relationship between the simultaneous presence of two genes cagA and hopQI and gastric cancer. In patients, 45.3% showed both genotypes, while in healthy individuals only 10.5% have this genotype and other healthy but infected with H. pylori (90.8%) do not have this genotype. To be. No report was observed on the simultaneous study of cagA and hopQI genes. No report was observed regarding the simultaneous study of cagA and hopQI genes.

LINC_00355 promotes gastric cancer progression by upregulating PHF19 expression through sponging miR-15a-5p.

BACKGROUND: Long non-coding RNAs exert vital roles in several types of cancer. The objective of this study was to explore the role of LINC_00355 in gastric cancer (GC) progression and its potential mechanism. METHODS: The expression levels of LINC_00355 in GC tissues and cells were detected by quantitative real-time PCR, followed by assessing the effects of LINC_00355 knockdown or overexpression on cell properties. Dual-luciferase reporter assay was utilized to identify the relationship between LINC_00355 and microRNA (miR)-15a-5p and miR-15a-5p and PHD finger protein 19 (PHF19), followed by the rescue experiments. RESULTS: The results showed that LINC_00355 was highly expressed in GC tissues and cells compared with the corresponding control. LINC_00355 knockdown decreased the viability, migration, and invasion and increased the accumulation of GC cells in G1 phase and apoptosis. Meanwhile, LINC_00355 downregulation markedly increased cleaved caspase 3 and cleaved poly (ADP-ribose) polymerase protein levels, whereas decreased cyclin D1, cyclin E, matrix metalloproteinase (MMP) 9, MMP2, and N-cadherin protein levels in GC cells. However, LINC_00355 overexpression had the opposite effects. It was verified that LINC_00355 upregulated the expression of PHF19 through sponging miR-15a-5p. Furthermore, PHF19 overexpression reversed the effect of LINC_00355 knockdown on GC cell properties, including cell viability, migration, invasion, and apoptosis. CONCLUSIONS: Collectively, these results suggest that LINC_00355 promotes GC progression by up-regulating PHF19 through sponging miR-15a-5p. Our findings may provide an important clinical basis for reversing the malignant phenotype of GC.

A proteomic analysis of urine biomarkers in autism spectrum disorder.

Autism spectrum disorder (ASD) is a neurodevelopmental condition characterized by early-onset social-communication challenges, restricted and repetitive behaviors, or unusual sensory-motor behaviors. A lack of specific biomarkers hinders the early diagnosis and treatment of this disease in many children. This study analyzes and validates potential urinary biomarkers using mass spectrometry proteomics. Global proteomics profiles of urine from 19 ASD patients and 19 healthy control subjects were compared to identify significantly changed proteins. These proteins were validated with targeted proteomics using parallel reaction monitoring (PRM) in an independent validation set consisting of samples from 40 ASD patients and 38 healthy controls. A total of 34 significantly changed proteins were found in the discovery set, among which seven proteins were identified as potential biomarkers for ASD through PRM assays in the validation set. Of these seven proteins, immunoglobulin kappa variable 4-1, immunoglobulin kappa variable 3-20, and immunoglobulin lambda variable 1-51 were up-regulated, while ATP synthase F1 subunit alpha, 10 kDa heat shock protein, apolipoprotein C-III, and arylsulfatase F were down-regulated. Six of these seven proteins support previous findings that ASD is accompanied by altered immune response and lipid metabolism, as well as mitochondrial dysfunction. This study lays the groundwork for additional research using biomarkers to clinically diagnose ASD. The proteomics and PRM raw data of this study have been deposited under the accession number IPX0002592000 at iProX. SIGNIFICANCE: This study identified 34 proteins in urine of ASD patients that were significantly changed from the urinary proteins of healthy subjects using LC-MS/MS-based proteomics in a discovery set. Seven of these proteins were validated by PRM analysis in an independent validation set. This report represents the first description of combined label-free quantitative proteomics and PRM analysis of targeted proteins for discovery of ASD urinary biomarkers. The results will be helpful for early diagnosis and can provide additional insight into the molecular mechanisms of ASD.

The clinical intervention choice for pediatric tic disorder patients from a tertiary children's hospital in China: a large-scale retrospective study based on electronic medical records.

Pharmacological intervention played an important role in the management of tic disorder. Large-scale prescription data for pediatric tic disorder patients in the real-world setting were scarce. The demographic and prescription data of tic disorder were extracted from the electronic medical records database of Beijing Children's Hospital from 2018 to 2020. The intervention choice for outpatient pediatric tic disorder patients was analyzed. A total of 20 417 patients were included, 28.1% (n = 5028) of them did not receive any pharmacological treatment. Over 70% were prescribed with anti-tic medication. For children less than 6 years of age, clonidine adhesive patches (CAPs) and traditional Chinese medicine (TCM) were the common choice. With the age growing, the use of antipsychotics was on the rise; 22% (n = 3389) were prescribed for at least two anti-tic medication, and the most common medication combination group was tiapride and TCM (33.7%), followed by CAP and TCM (22.1%). The clinical intervention choice for tic disorder is highly individualized. The pharmacological choice was influenced by severity, duration of symptom, age, the acceptance of parents and other factors.

Association Study of MTHFR C677T Polymorphism and Birth Body Mass With Risk of Autism in Chinese Han Population.

Objective: To explore the association of the methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism with birth body mass and risk of autism in Chinese Han population. Methods: A total 1,505 Chinese Han autism patients were recruited, using the Diagnostic and Statistical Manual of Mental Disorders, 4th revised version (DSM-IV-R) diagnostic criteria for autism, and 1,308 sex-matched healthy controls were also enrolled for the study. All the participants' birth body masses were counted according to the medical records. The MTHFR C677T genotypes were detected using the polymerase chain reaction-restrict fragment length polymorphism (PCR-RFLP) method. The association between C677T polymorphism, birth body mass, and risk of autism were analyzed using the chi-square tests. Results: The present study found that the MTHFR 677T was significantly associated with risk of autism [P = 0.004, odds ratio (OR) = 1.18, 95% CI = 1.02-1.29). The autism children more frequently showed low birth body mass (<2.5 kg) than healthy control subjects (8.6 vs. 5.3%, P = 0.001, OR = 1.67, 95% CI = 1.24-2.26). The interactive effects between MTHFR 677T and low birth body mass (P = 0.0001, OR = 2.18, 95% CI = 1.44-3.32) were also significantly associated with risk of autism. Conclusions: The MTHFR C677T polymorphism and low birth body mass may be associated with risk of autism in Chinese Han population.

The therapeutic effect of habit reversal training for Tourette syndrome: a meta-analysis of randomized control trials.

OBJECTIVES: Comprehensive behavioral intervention for tics (CBIT) and habit reversal training (HRT) are forms of cognitive behavioral therapy that can effectively reduce tic symptoms in patients with tic disorders, but their efficacies and potential moderators were needed to be clarified. METHODS: In the present study, a meta-analysis was performed to identify the efficacy of HRT and CBIT for individuals with tic disorders. The standard mean difference (SMD) was calculated to assess the effect size of the efficacy of HRT. Subgroup analysis and meta-regression analysis were performed to identify the potential heterogeneity of the SMD of HRT. RESULTS: A total of 10 randomized controlled trials (RCTs) including 586 patients with tic disorders were identified. The pooled SMD was -0.43 (95% CI: -0.71, -0.16). The effect size of HRT was moderated by different 'Comparison Conditions' (it means the different behavioral therapies in the control group). CONCLUSION: Overall, the authors found a small to medium effect size for the efficacy of HRT. As the most promising behavioral therapy, they conclude that HRT is effective for the treatment of patients with tic disorders. Further high-quality RCTs are needed to determine the efficacy of HRT compared with that of medications.

Altered structural cerebral cortex in children with Tourette syndrome.

PURPOSE: In this study, we used magnetic resonance imaging (MRI) to investigate the anatomical alterations of cerebral cortex in children with Tourette syndrome (TS) and explore whether such deficits were related with their clinical symptoms. METHODS: All subjects were scanned in a 3.0T MRI scanner with three-dimensional T1-weighted images (3DT1WI). Then, some surface-based features were extracted by using the FreeSurfer software. After that, the between-group differences of those features were assessed. RESULTS: Sixty TS patients and 52 age- and gender-matched healthy control were included in this study. Surface-based analyses revealed altered cortical thickness, cortical sulcus, cortical curvature and local gyrification index (LGI) in TS group compared with healthy controls. The brain regions with significant-group differences in cortical thickness included postcentral gyrus, superiorparietal gyrus, rostral anterior cingulate cortex in the left hemisphere and frontal pole, lateral occipital gyrus, inferior temporal gyrus in the right hemisphere. In addition, the superior temporal gyrus, medial orbitofrontal gyrus, supramarginal gyrus, medial orbitofrontal gyrus, superiorparietal gyrus and lateral occipital gyrus showed significant between-group differences for cortical sulcus. Moreover, the brain regions with significant between-group differences in cortical curvature were located in caudal anterior cingulate cortex, supramarginal gyrus, inferior parietal gyrus and lateral occipital gyrus. The alteration of LGI were most prominent in the inferior temporal gyrus and insula. Additionally, there was no statistical difference in brain surface area for TS children compared with controls. CONCLUSION: The results of this study revealed that cortical thickness, sulcus, cortical curvature and LGI were changed in multiple brain regions for children with TS.

Transcranial direct current stimulation reduces seizure frequency in patients with refractory focal epilepsy: A randomized, double-blind, sham-controlled, and three-arm parallel multicenter study.

BACKGROUND: Transcranial direct current stimulation (tDCS) has been explored in epilepsy with limited samples, varied parameters, and inconclusive results. We aimed to study the efficacy of tDCS for patients with refractory focal epilepsy. METHOD: We conducted a randomized, double-blind, sham-controlled, and three-arm (Group 1 (sham), Group 2 (20-min), and Group 3 (2 × 20-min)) tDCS parallel multicenter study. The primary outcome measurement was seizure frequencies (SFs). The study consisted of 28-days baseline, 14-days treatment, and 56-days follow-up. The cathode was placed over the epileptogenic focus, and the current intensity was 2 mA. The generalized estimating equations model, one-way analysis of variance, chi-square and Kruskal-Wallis test were used for analysis. RESULTS: Of the 82 enrolled patients, 70 patients were included for final analysis (Group 1, n = 21; Group 2, n = 24; and Group 3, n = 25). There was a significant reduction in SFs for both active tDCS groups compared with the sham group. Patients in Group 2 showed a significantly 50.73-21.91% greater reduction in SFs that lasted for 4 weeks (p = 0.008-0.060). Patients in Group 3 showed a significantly 63.19-49.79% greater reduction in SFs compared with the sham group that lasted for 5 weeks (p = 0.011-0.045). Patients in Group 3 had a 64.98-66.32% greater reduction in SFs at W9-W10, when compared with Group 2 (p = 0.021-0.022). CONCLUSION: Fourteen consecutive days tDCS significantly decreased SFs in patients with refractory focal epilepsy, with 2 × 20-min daily stimulation protocol being superior to 20-min daily stimulation protocol.

Characterization of Intestinal Microbiota and Probiotics Treatment in Children With Autism Spectrum Disorders in China.

Background: Most previous studies have found that human intestinal microbiota affect the symptoms of autism spectrum disorder (ASD), especially gastrointestinal (GI) symptoms, but regarding this, there is limited data of non-western ethnicity. Probiotics can reconstitute the host intestinal microbiota and strengthen gastrointestinal function, however, clinical data proving the effect of probiotics treatment on ASD is lacking. Methods: This study explored the significant differences between ASD and neurotypical (NT), and the improvement of applied behavior analysis (ABA) training in combination with probiotics, vs. ABA training only. Results: We found significant differences between the ASD group and the NT group in the evenness of the intestinal microbiota and the relative abundance of the bacterial phyla and genus. At the phylum level, relative abundance of Bacteroidetes in the ASD group was significantly lower than in the NT group. At the genus level, the relative abundance of Bacteroides, Bifidobacterium, Ruminococcus, Roseburia, and Blautia in the ASD group was significantly lower than that in the NT group. After a 4-week ABA training program in combination with probiotics treatment, the ATEC and GI scores decreased more than the control group with ABA training only. Conclusion: Our findings suggest that intestinal microbiota is different between the NT children and the ASD children with or without GI problems. In combination with ABA training, probiotics treatment can bring more benefit to ASD children. Clinical trials with a more rigorous design and larger sample size are indispensable for further validation.

Premonitory urges located in the tongue for tic disorder: Two case reports and review of literature.

BACKGROUND: Premonitory urges (PUs) was defined as the uncomfortable physical sensations of inner tension that can be relieved by producing movement responses. Nearly 70%-90% patients with Tourette syndrome reported experiences of PUs. CASE SUMMARY: In this paper, we present two cases of young patients with PUs located in their tongue, which is very rare and easily misdiagnosed in clinical work. Both two young patients complained of an itchy tongue and cannot help biting their tongue. These two cases were worth reporting because it was rare that PUs was the initial symptom and located in the tongue. The results indicated that PUs seem to play an important role in the generation of tics. CONCLUSION: Thus, PUs may be the first process, and an essential part, of the formation of tics.

The Correlation Between the Severity of Premonitory Urges and Tic Symptoms: A Meta-Analysis.

Objectives: Premonitory urges (PUs) are defined as sensory experiences of pre-tic inner tension. Evidence suggests that most patients with Tourette syndrome experience PUs, which are transiently relived by the expression of tics. However, recent studies have revealed inconsistent results regarding the correlation between the severity of PUs and the severity of tic symptoms. Methods: A meta-analysis was performed to confirm the correlation between the severity of the urge and the severity of the expression of the tic. In total, 10 studies involving 626 patients with tic disorders were included in this meta-analysis. Results: The correlation coefficient (r) was extracted from each selected study, and a pooled correlation coefficient (r) and its 95% confidence intervals (CIs) were calculated. Sensitivity and subgroup analyses were performed to identify the potential sources of heterogeneity. The pooled correlation coefficient (r) of the relationship between the severity of PUs and tic symptoms was 0.296 (95% CI: 0.215-0.376) with an I2 of 15.2% (95% CI: 0.00-56.5) based on a fixed effects model. The correlation was stronger in adults than in children (p = 0.03). Conclusion: A slight to moderate positive correlation was observed between the severity of PUs and tic symptoms. This correlation may be affected by the age of the patients. Further research should seek to elucidate the relationships among PUs, tic suppression, and tic expression to support the development of behavioral intervention therapies to reduce tic symptoms.

Association between CNTNAP2 polymorphisms and autism: A family-based study in the chinese han population and a meta-analysis combined with GWAS data of psychiatric genomics consortium.

Autism is a childhood neuropsychiatric disorder with evidence of a strong genetic component in the complex etiologies. Contactin-associated protein-like 2 (CNTNAP2), a member of the neurexin superfamily, plays an essential role in neural development. CNTNAP2 was considered as one of the most susceptible genes for autism spectrum disorder (ASD). Some studies indicated the association of CNTNAP2 with ASD, while others reported no association. Given the inconsistent results of the previous studies, we performed a family-based association study between 9 single-nucleotide polymorphisms (SNPs) of CNTNAP2 and autism in 640 autistic trios in the Chinese Han population. Then, an updated meta-analysis, combined with the data from Psychiatric Genomics Consortium (iPSYCH-PGC ASD, 2017) and available association studies, was conducted. No SNPs were significantly associated with autism in the Chinese Han population. In the meta-analysis, the two frequently reported SNPs (rs2710102 and rs7794745) showed no significant association with ASD. Therefore, CNTNAP2 polymorphisms might not be associated with autism. Autism Research 2019, 12: 553-561. © 2019 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: In present family-based association study, no single-nucleotide polymorphisms (SNPs) were significantly associated with autism in the Chinese Han population. In the updated meta-analysis, the association between the two frequently reported SNPs (rs2710102 and rs7794745) in CNTNAP2 and the risk of ASD was explored. However, the results showed no significant association. Therefore, our study suggested that CNTNAP2 polymorphisms might not be associated with autism.

Replication of previous GWAS hits suggests the association between rs4307059 near MSNP1AS and autism in a Chinese Han population.

Autism is a complex neurodevelopmental disorder with high heritability. Previous genome-wide association studies (GWAS) demonstrated that some single-nucleotide polymorphisms (SNPs) were significantly associated with autism, while other studies focusing on these GWAS hits showed inconsistent results. Besides, the association between these variants and autism in the Chinese Han population remains unclear. Therefore, this family-based association study was performed in 640 Chinese Han autism trios to investigate the association between autism and 7 SNPs with genome-wide significance in previous GWAS (rs4307059 near MSNP1AS, rs4141463 in MACROD2, rs2535629 in ITIH3, rs11191454 in AS3MT, rs1625579 in MIR137HG, rs11191580 in NT5C2, and rs1409313 in CUEDC2). The results showed a nominal association between the T allele of rs4307059 and autism under both additive model (T>C, Z = 2.250, P = .024) and recessive model (T>C, Z = 2.109, P = .035). The findings provided evidence that rs4307059 near MSNP1AS might be a susceptibility variant for autism in the Chinese Han population.

Association between mild or moderate obstructive sleep apnea-hypopnea syndrome and cognitive dysfunction in children.

BACKGROUND: Childhood obstructive sleep apnea-hypopnea syndrome (OSAHS), the most common sleep-related breathing disorder, may lead to cognitive impairment. This study aims to investigate the association between mild or moderate childhood OSAHS and cognitive dysfunction. METHODS: A total of 59 children (4-12 years of age) diagnosed with mild or moderate OSAHS by polysomnography and 60 age-  and sex-matched healthy children were included in the study. The China-Wechsler Younger Children Scale of Intelligence and China-Wechsler Intelligence Scale for Children were used to evaluate the cognition of the participating children aged <6 years and ≥6 years, respectively. RESULTS: In the <6-years-old subgroup, children with OSAHS had significantly lower scores of full-scale IQ (FIQ), verbal IQ (VIQ), comprehension test, and visual analysis than the healthy children (all p < 0.05). In the ≥6-years-old subgroup, VIQ and classification test scores were significantly lower in children with OSAHS than in the healthy controls (all p < 0.05). FIQ, VIQ, and performance IQ (PIQ) scores did not correlate with AHI, OAHI, and the lowest nocturnal SO2. Notably, in the <6-years-old subgroup of OSAHS, the accumulated time of SO2<90% (p = 0.046) and the percentage of the accumulated time of SO2<90% in the total sleep time (p = 0.034) correlated with PIQ negatively and significantly. CONCLUSIONS: Mild to moderate childhood OSAHS may adversely affect cognitive function, particularly in young children (<6 years of age). This study may increase the awareness of childhood OSAHS-associated cognitive dysfunction and advocate early interventions in childhood OSAHS.