Evaluating the relationship between the proportion of X-chromosome deletions and clinical manifestations in children with turner syndrome.

Purpose: Analyze the relationship between changes in the proportion of X-chromosome deletions and clinical manifestations in children with Turner syndrome (TS). Methods: X-chromosome number abnormalities in 8,635 children with growth retardation were identified using fluorescence in situ hybridization (FISH). Meanwhile, the relationship between the proportion of X-chromosome deletions and the clinical manifestations of TS, such as face and body phenotype, cardiovascular, renal, and other comorbidities in children with TS was analyzed. Results: A total of 389 children had X-chromosome number abnormalities, with an average age at diagnosis of 9.2 years. There was a significant increase in diagnoses around the ages of 3 and 7 years and highest number of diagnoses at 10 years of age. 130 with XO (complete loss of an X-chromosome), 205 with XO/XX, 8 with XO/XXX, 23 with XO/XX/XXX, 19 with XO/XY, and 4 with XO/XY/XYY. Body and facial phenotypes increased with higher mosaicism proportions, with a relatively high correlation shown with Pearson correlation analysis (r = 0.26, p = 1.7e-06). The incidence of congenital heart malformations was 25.56%, mainly involving a bicuspid aortic valve, and were more common in patients who had complete loss of an X-chromosome. However, this relationship was not present for renal disease (p = 0.26), central nervous system, thyroid, or liver disease. Conclusion: The mosaicism (XO/XX) is the most common karyotype of TS in screened cases. The phenotypes in children with TS may increase with the proportion of X-chromosome deletions, but the renal disease and comorbidities did not show the same characteristics.

Heterozygous CAPZA2 mutations cause global developmental delay, hypotonia with epilepsy: a case report and the literature review.

CAPZA2 encodes the α2 subunit of CAPZA, which is vital for actin polymerization and depolymerization in humans. However, understanding of diseases associated with CAPZA2 remains limited. To date, only three cases have been documented with neurodevelopmental abnormalities such as delayed motor development, speech delay, intellectual disability, hypotonia, and a history of seizures. In this study, we document a patient who exhibited seizures, mild intellectual disability, and impaired motor development yet did not demonstrate speech delay or hypotonia. The patient also suffered from recurrent instances of respiratory infections, gastrointestinal and allergic diseases. A novel de novo splicing variant c.219+1 G > A was detected in the CAPZA2 gene through whole-exome sequencing. This variant led to exon 4 skipping in mRNA splicing, confirmed by RT-PCR and Sanger sequencing. To our knowledge, this is the third study on human CAPZA2 defects, documenting the fourth unambiguously diagnosed case. Furthermore, this splicing mutation type is reported here for the first time. Our research offers additional support for the existence of a CAPZA2-related non-syndromic neurodevelopmental disorder. Our findings augment our understanding of the phenotypic range associated with CAPZA2 deficiency and enrich the knowledge of the mutational spectrum of the CAPZA2 gene.

Restoration of nNOS Expression Rescues Autistic-Like Phenotypes Through Normalization of AMPA Receptor-Mediated Neurotransmission.

Autism spectrum disorder (ASD) is associated with a range of abnormalities characterized by deficits in socialization, communication, repetitive behaviors, and restricted interests. We have recently shown that neuronal nitric oxide synthase (nNOS) expression was decreased in the basolateral amygdala (BLA) of mice after postnatal valproic acid exposure. Neuronal activity-regulated pentraxin (Narp) could contribute to the regulation of the GluA4 2-amino-3-(5-methyl-3-oxo-1,2-oxazol-4-yl) propanoic acid (AMPA) subunits which are predominantly expressed in interneurons. However, the specific role of nNOS re-expression on excitatory neurotransmitter with relevance to ASD core symptoms in VPA-treated animals remains to be elucidated. Herein, nNOS overexpression using a lentiviral vector and L-arginine-activating PI3K-Akt-mTOR signaling can restore nNOS expression in the BLA induced by VPA. Restoration of nNOS expression in these mice was sufficient to reduce the severity of ASD-like behavioral patterns such that animals exhibited decreases in abnormal social interactions and communication, stereotyped/repetitive behaviors, and anxiety-like traits. Most strikingly, re-expression of nNOS upregulated surface expression of Narp and GluA4 in nNOS-positive interneuron as shown by immunoprecipitation and Western blotting. Whole-cell patch-clamp recordings demonstrated that restoration of nNOS had a significant enhancing effect on AMPA receptor-mediated excitatory glutamatergic synaptic neurotransmission, which was inhibited by disturbing the interaction between Narp and GluA4 in acutely dissociated BLA slices. Overall, these data offer a scientific basis for the additional study of nNOS re-expression as a promising therapeutic target by correcting AMPA receptor-mediated synaptic function in ASD and related neurodevelopmental disorders.

Sagittal septum duplication of bladder and duplication of posterior urethra combined with congenital megacolon: a case report and literature review.

BACKGROUND: Duplication of the bladder with duplication of the posterior urethra is a relatively rare congenital malformation. Cases of sagittal septum duplication of the bladder with duplication of the posterior urethra have rarely been reported. Furthermore, the combination thereof with congenital megacolon is rare. CASE PRESENTATION: A 21-year-old male was admitted to our hospital because of frequent urination for two months. He presented to another hospital first with frequent urination and underwent computed tomography (CT) and testicular biopsy. Anti-inflammatory therapy was administered by the doctor to the patient. For further diagnosis and treatment, the patient went to the outpatient department in our hospital on June 6, 2022. After admission, the patient underwent ultrasound, CT, MRI, cystoscopy, and other related examinations and tests. The examination results suggested that the patient had duplication of the bladder with duplication of the posterior urethra. In addition, the patient's mother reported that he had suffered from long-term constipation with abdominal distension before the age of 5 years. At the time, he was admitted to the local hospital and was diagnosed with congenital megacolon based on the relevant examinations. After the patient was diagnosed with duplication of bladder and urethra, the doctor recommended surgical treatment to the patient. However, he considered that he only had frequent urination symptoms, and chose conservative treatment rather than to undergo surgical treatment. Thus, the doctor prescribed anti-inflammatory treatment. Four months later, the patient reported that frequent urination symptoms persisted, and was also considering fertility-related problems. The outpatient follow-up will be continued. CONCLUSIONS: In this article, we summarize the imaging findings of duplication of the bladder with duplication of the posterior urethra and propose the advantages and disadvantages of each type of imaging examination. We also review the relevant literature on cases of bladders with duplication of the posterior urethra. The related differential diagnosis is summarized, and the significance of guiding clinical treatment and diagnosis is discussed.

Neuroprotective Effects of CXCR2 Antagonist SB332235 on Traumatic Brain Injury Through Suppressing NLRP3 Inflammasome.

The inflammatory process mediated by nucleotide-binding oligomerization domain (NOD)-like receptor family pyrin domain comprising 3 (NLRP3) inflammasome plays a predominant role in the neurological dysfunction following traumatic brain injury (TBI). SB332235, a highly selective antagonist of chemokine receptor 2 (CXCR2), has been demonstrated to exhibit anti-inflammatory properties and improve neurological outcomes in the central nervous system. We aimed to determine the neuroprotective effects of SB332235 in the acute phase after TBI in mice and to elucidate its underlying mechanisms. Male C57BL/6J animals were exposed to a controlled cortical impact, then received 4 doses of SB332235, with the first dose administered at 30 min after TBI, followed by additional doses at 6, 24, and 30 h. Neurological defects were assessed by the modified neurological severity score, while the motor function was evaluated using the beam balance and open field tests. Cognitive performance was evaluated using the novel object recognition test. Brain tissues were collected for pathological, Western blot, and immunohistochemical analyses. The results showed that SB332235 significantly ameliorated TBI-induced deficits, including motor and cognitive impairments. SB332235 administration suppressed expression of both CXCL1 and CXCR2 in TBI. Moreover, SB332235 substantially mitigated the augmented expression levels and activation of the NLRP3 inflammasome within the peri-contusional cortex induced by TBI. This was accompanied by the blocking of subsequent production of pro-inflammatory cytokines. Additionally, SB332235 hindered microglial activity induced by TBI. These findings confirmed the neuroprotective effects of SB332235 against TBI, and the involved mechanisms were in part due to the suppression of NLRP3 inflammasome activity. This study suggests that SB332235 may act as an anti-inflammatory agent to improve functional outcomes in brain injury when applied clinically.

[Clinical characteristics and genetic analysis of two children with Tuberous sclerosis complex].

OBJECTIVE: To explore the clinical characteristics and genetic variants in two children with Tuberous sclerosis complex (TSC). METHODS: Two children who had presented at the Children's Hospital Affiliated to Zhengzhou University respectively in June 2020 and July 2021 were selected as the study subjects. Clinical data of the children were collected, and potential pathogenic variants were screened by whole exome sequencing (WES). Candidate variants were verified by Sanger sequencing of their family members. RESULTS: Child 1 was a 7-month-and-29-day-old male, and child 2 was a 2-year-and-6-month-old male. Both children had shown symptoms of epileptic seizures and multiple hypomelanotic macules. Genetic testing revealed that both children had harbored de novo variants of the TSC2 gene, namely c.3239_3240insA and c.3330delC, which were unreported previously. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), both variants were rated as pathogenic (PVS1+PS2+PM2_Supporting). CONCLUSION: This study has uncovered the genetic etiology for two children with TSC. Above findings have also enriched the phenotypic and mutational spectrum of TSC in the Chinese population.

[Analysis of CLCN4 gene variant in a child with Raynaud-Claes syndrome].

OBJECTIVE: To analyze the clinical phenotype and genetic variant in a child with Raynaud-Claes syndrome (RCS). METHODS: A child who was diagnosed with RCS at the Children's Hospital Affiliated to Zhengzhou University for delayed language and motor development in August 2022 was selected as the study subject. Clinical data of the child were collected, and potential genetic variant was detected by next-generation sequencing and Sanger sequencing. The pathogenicity of the candidate variant was analyzed. RESULTS: The child, a 4-year-and-4-month-old male, has manifested global developmental delay, speech disorders, special facial features and behavioral abnormalities. Genetic testing revealed that he has harbored a hemizygous c.1174C>T (p.Gln392Ter) variant of the CLCN4 gene, which was not detected in either of his parents. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the variant was rated as pathogenic (PVS1+PS2+PM2_Supporting). CONCLUSION: The c.1174C>T (p.Gln392Ter) variant of the CLCN4 gene probably underlay the PCS in this child. Above finding has expanded the mutational spectrum of the CLCN4 gene and enabled genetic counseling and prenatal diagnosis for his family.

[Analysis of clinical phenotypes and MMACHC gene variants in 65 children with Methylmalonic acidemia and homocysteinemia].

OBJECTIVE: To carry out Sanger sequencing for MMACHC gene variants among 65 Chinese pedigrees affected with combined methylmalonic aciduria and homocysteinemia, and summarize their genetic and clinical characteristics and prognosis. METHODS: Clinical characteristics of the 65 children identified with Methylmalonic acidemia and homocysteinemia at the Children's Hospital Affiliated to Zhengzhou University (Zhengzhou Children's Hospital) from April 2017 to April 2022 were selected as the study subjects. Potential variants of the MMACHC gene were detected by direct sequencing of the PCR products. RESULTS: The median age of the 65 children was 3 months (14 days to 17 years old). These included 28 cases (43.08%) from neonatal screening, 11 cases (16.92%) with a history of jaundice, and 9 cases (13.85%) with various degrees of anemia. The main clinical symptoms included development delay, slow growth, epilepsy, hydrocephalus, lethargy, feeding difficulty, regression or decline in motor ability, recurrent respiratory infections, anemia, jaundice, respiratory and heart failures, hydrocephalus, limb weakness, and hypertension. Blood and urine tandem mass spectrometry screening has revealed increase of methylmalonic acid, propionyl carnitine, propionyl carnitine/acetylcarnitine ratio, and propionyl carnitine/free carnitine ratio to various extents, and blood homocysteine was increased in all patients. The detection rate of genetic variants was 98.46% (128/130), and in total 22 types of MMACHC gene variants were detected. The most common ones have included c.609G>A (W203X) (58/128), c.658-660del (K220del) (19/128), and c.80A>G (Q27A) (16/128). Two novel variants have been identified, namely c.565C>T (p.R189C) and c.624_ 625delTG (p.A208Afs), which were respectively predicted as likely pathogenic (PM2_Supporting+PM3+PP2+PP3) and pathogenic (PVS1+PM2_Supporting+PM3+PP2) based on the guidelines from the American College of Medical Genetics and Genomics (ACMG). Exon 4 had the highest frequency for the detection. CONCLUSION: Identification of MMACHC gene variants has confirmed the diagnosis in the children, among which the c.609G>A variant has the highest frequency. Discovery of the new variants has enriched the mutational spectrum of the MMACHC gene.

Functional Evaluation of a Novel GRIN2B Missense Variant Associated with Epilepsy and Intellectual Disability.

Epilepsy, a neurological condition, is widely prevalent among individuals with intellectual disability (ID). It is well established that N-methyl-D-aspartate (NMDA) receptors play an important role in both epilepsy and ID. Autosomal dominant mutations in the GRIN2B gene, which encodes the GluN2B subunit of the NMDA receptor, have been reported to be associated with epilepsy and ID. However, the underlying mechanism of this association is not well-understood. In this study, we identified a novel GRIN2B mutation (c.3272A > C, p.K1091T) in a patient with epilepsy and ID. The proband was a one year and ten months old girl. GRIN2B variant was inherited from her mother. We further investigated the functional consequences of this mutation. Our findings revealed that the p.K1091T mutation created a Casein kinase 2 phosphorylation site. Using recombinant NMDA receptors containing the GluN2B-K1091T along with GluN1 in HEK 293T cells, we observed significant defects in its interactions with postsynaptic density 95. It is accompanied by reduced delivery of the receptors to the cell membrane and a decrease in glutamate affinity. Moreover, primary neurons expressing GluN2B-K1091T also exhibited impaired surface expression of NMDA receptors, a reduction in dendritic spine number and excitatory synaptic transmission. In summary, our study reports a novel GRIN2B mutation and provides functional characteristics of this mutation in vitro, thereby contributing to the understanding of GRIN2B variants in epilepsy and ID.

Radiomics and stacking regression model for measuring bone mineral density using abdominal computed tomography.

BACKGROUND: Measurement of bone mineral density (BMD) is the most important method to diagnose osteoporosis. However, current BMD measurement is always performed after a fracture has occurred. PURPOSE: To explore whether a radiomic model based on abdominal computed tomography (CT) can predict the BMD of lumbar vertebrae. MATERIAL AND METHODS: A total of 245 patients who underwent both dual-energy X-ray absorptiometry (DXA) and abdominal CT examination (training cohort, n = 196; validation cohort, n = 49) were included in our retrospective study. In total, 1218 image features were extracted from abdominal CT images for each patient. Combined with clinical information, three steps including least absolute shrinkage and selection operator (LASSO) regression were used to select key features. A two-tier stacking regression model with multi-algorithm fusion was used for BMD prediction, which can integrate the advantages of linear model and non-linear model. The prediction results of this model were compared with those using a single regressor. The degree-of-freedom adjusted coefficient of determination (Adjusted-R2), root mean square error (RMSE), and mean absolute error (MAE) were used to evaluate the regression performance. RESULTS: Compared with other regression methods, the two-tier stacking regression model has a higher regression performance, with Adjusted-R2, RMSE, and MAE of 0.830, 0.077, and 0.06, respectively. Pearson correlation analysis and Bland-Altman analysis showed that the BMD predicted by the model had a high correlation with the DXA results (r = 0.932, difference = -0.01 ± 0.1412 mg/cm2). CONCLUSION: Using radiomics, the BMD of lumbar vertebrae could be predicted from abdominal CT images.

Maternal and neonatal exposure to risk factors for neonates with moderate or severe hypoxic ischemic encephalopathy: a cross-sectional study.

BACKGROUND: To investigate the association between maternal and neonatal exposure to the relevant influencing factors and risk of moderate or severe hypoxic ischemic encephalopathy (HIE), and the possible interactions in the Chinese population. METHODS: A cross-sectional study comprising 228 neonates from Henan Children's Hospital during the five-year period 2015-2020 in China was conducted. All neonatal basic demographic information and clinical records were documented from the neonatal HIE database. Comparisons between mild HIE and moderate or severe HIE were conducted with the t-test or Wilcoxon rank-sum test for continuous variables and the Chi-square test for categorical variables. Unconditional multiple logistic regression models were used to generate the odds ratios(ORs) and 95% confidence intervals(CIs). In addition, we also used an additive model to test for possible biological interactions among the factors. RESULTS: Of the 228 neonates, the males had a statistically significantly higher frequency compared with the females between the two groups (P = 0.030). Trend analysis results found that with the decreased of the neonatal birth weight, the detection rates of moderate or severe HIE in males and females were gradually increased (Ptrend < 0.05). The detection of moderate or severe HIE in males and females increased with the decreased of neonatal gestational age at birth(Ptrend < 0.05). However, no interaction was detected between neonatal birth weight and gestational age at birth based on the additive model, the Relative Excess Risk of Interaction and 95% CI was 0.821(-0.046,1.687). The adjusted multiple logistic regression model showed that low birth weight(ORadj:1.965, 95%CI:1.086-4.127),premature infant(ORadj:1.557, 95%CI:1.589-4.862),1-min Apgar's score < 7(ORadj:5.618, 95%CI:3.724-7.353),intrauterine distress(ORadj:4.916, 95%CI:3.431-7.398),amniotic fluid contamination (ORadj:3.965, 95%CI:2.153-5.782) significantly increased the risk of neonatal moderate or severe HIE. CONCLUSION: Neonates with low birth weight, premature infant,1-min Apgar's score < 7, intrauterine distress, amniotic fluid contamination are risk factors for moderate or severe HIE. Notably, we found no biological interaction between risk factors based on the additive model, these findings may help to inform prevention strategies, as this may effectively reduce the incidence of neonatal moderate or severe HIE.

Association between overweight, obesity and sleep duration and related lifestyle behaviors is gender and educational stages dependent among children and adolescents aged 6-17 years: a cross-sectional study in Henan.

BACKGROUND: To investigate the associations between overweight, obesity and sleep duration and related lifestyle behaviors in children and adolescents at different gender and educational stages. METHODS: A cross-sectional study comprising 18723 children and adolescents with a stratified cluster sampling method of Henan Province was conducted in 2019. A self-reported questionnaire was used to collect the information about demographic characteristics as well as sleep and lifestyle behaviors. Anthropometric measurements (height and weight) were taken and body mass index was computered as an indicator of overweight and obesity. The Chi-square test, one-way analysis of variance and multiple logistic regression were used to data analysis. RESULTS: Among the respondents, 12657(67.6%) were with normal weight, 3711(19.8%) were overweight and 2355(12.6%) were obesity. The average age of the participants was 12.6 years old. The proportion of overweight and obesity in the 10191 boys was 18.7% and 14.2% respectively. The proportion of overweight and obesity in the 8532 girls was 21.2% and 10.6% respectively. In trend analyses, sleep duration at different gender found with the decreased of the sleep duration, the proportions of overweight/obesity in boys and girls were gradually increased (Ptrend<0.05). In the adjusted logistic regression models, the results showed stratified by gender, compared with the recommended sleep duration group, students with very short sleep duration and short sleep duration showed an increased ORadj of 2.56 and 2.13 in boys, 2.34 and 2.09 in girls respectively. According to different educational stages, those in very short sleep duration and short sleep duration showed an increased ORadj of 2.15 and 1.69 in primary school, 2.26 and 1.58 in middle school, 2.23 and 1.51 in high school respectively. CONCLUSIONS: Children and adolescents with very short sleep duration and short sleep duration may increase the risk of overweight/obesity, the association differed based on the gender-specific and educational stages-specific. Gender and educational stages should be regarded as specific characteristics for the effects on overweight/obesity in Henan Province.

Preoperative clinical-radiomics nomogram for microvascular invasion prediction in hepatocellular carcinoma using [Formula: see text]F-FDG PET/CT.

PURPOSE: To develop a clinical-radiomics nomogram by incorporating radiomics score and clinical predictors for preoperative prediction of microvascular invasion in hepatocellular carcinoma. METHODS: A total of 97 HCC patients were retrospectively enrolled from Shanghai Universal Medical Imaging Diagnostic Center and Changhai Hospital Affiliated to the Second Military Medical University. 909 CT and 909 PET slicers from 97 HCC patients were divided into a training cohort (N = 637) and a validation cohort (N = 272). Radiomics features were extracted from each CT or PET slicer, and features selection was performed with least absolute shrinkage and selection operator regression and radiomics score was also generated. The clinical-radiomics nomogram was established by integrating radiomics score and clinical predictors, and the performance of the models were evaluated from its discrimination ability, calibration ability, and clinical usefulness. RESULTS: The radiomics score consisted of 45 selected features, and age, the ratio of maximum to minimum tumor diameter, and [Formula: see text]F-FDG uptake status were independent predictors of microvascular invasion. The clinical-radiomics nomogram showed better performance for MVI detection (0.890 [0.854, 0.927]) than the clinical nomogram (0.849 [0.804, 0.893]) ([Formula: see text]). Both nomograms showed good calibration and the clinical-radiomics nomogram's clinical practicability outperformed the clinical nomogram. CONCLUSIONS: With the combination of radiomics score and clinical predictors, the clinical-radiomics nomogram can significantly improve the predictive efficacy of microvascular invasion in hepatocellular carcinoma ([Formula: see text]) compared with clinical nomogram.

The GluN2B-Trp373 NMDA Receptor Variant is Associated with Autism-, Epilepsy-Related Phenotypes and Reduces NMDA Receptor Currents in Rats.

Autism spectrum disorder (ASD) is a neurodevelopmental condition with core clinical features of abnormal communication, social interactions, atypical intelligence, and a higher risk of epilepsy. Prior work has suggested that de novo heterozygous mutations in the GRIN2B gene that encodes the GluN2B subunit of N-methyl-D-aspartic acid receptors are likely linked to ASD. However, whether GLuN2B-Trp373 mutation derived from autistic individuals causes ASD-like behavioral aberrations in rats remains to be determined. Here, through in utero electroporation and in vivo studies, we conducted a battery of tests to examine ASD-associated behaviors, cognitive impairments, and susceptibility to pentylenetetrazol-induced seizures. Whole-cell patch recording was utilized to determine whether the GluN2B-Trp373 mutation influences GluN2B-containing NMDA receptor currents in rats. Results show that, behaviorally, GLuN2B-Trp373 mutant rats exhibited core behavioral manifestations of ASD, such as social interaction deficits, increases in stereotyped behaviors and anxiety stereotyped/repetitive, impaired spatial memory, and enhanced risk of pentylenetetrazol-induced seizures, consistent with many of the hallmarks of low-functioning ASD in humans. Functionally, the GluN2B-Trp373 mutation results in reduced GluN2B surface protein expression together with decreased hippocampal NMDA receptor currents. Collectively, our findings highlight that GluN2B-Trp373 mutations can drive the manifestation of ASD-associated symptoms via the suppression of NMDA receptor currents.

A systematic review of Vaccine Breakthrough Infections by SARS-CoV-2 Delta Variant.

Vaccines are proving to be highly effective in controlling hospitalization and deaths associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, as shown by clinical trials and real-world evidence. However, a deadly second wave of coronavirus disease 2019 (COVID-19), infected by SARS-CoV-2 variants, especially the Delta (B.1.617.2) variant, with an increased number of post-vaccination breakthrough infections were reported in the world recently. Actually, Delta variant not only resulted in a severe surge of vaccine breakthrough infections which was accompanied with high viral load and transmissibility, but also challenged the development of effective vaccines. Therefore, the biological characteristics and epidemiological profile of Delta variant, the current status of Delta variant vaccine breakthrough infections and the mechanism of vaccine breakthrough infections were discussed in this article. In addition, the significant role of the Delta variant spike (S) protein in the mechanism of immune escape of SARS-CoV-2 was highlighted in this article. In particular, we further discussed key points on the future SARS-CoV-2 vaccine research and development, hoping to make a contribution to the early, accurate and rapid control of the COVID-19 epidemic.

Non-prescription antibiotic use for cough among Chinese children under 5 years of age: a community-based cross-sectional study.

OBJECTIVE: This study aimed to investigate the non-prescription use of antibiotics for cough among children under 5 years in China. DESIGN: A community-based cross-sectional survey. SETTING: A face-to-face interview based on a standard questionnaire in the community from October to December 2019. PARTICIPANTS: A total of 3102 children under 5 years of age were enrolled with probability proportionate to size sampling method. The children's caregivers provided the responses as their agents. OUTCOME MEASURES: Cough in the past month, non-prescription use of antibiotics after cough. RESULTS: 1211 of 3102 children were reported to have a cough in the past month. Of these, 40.2% (487/1211) were medicated with antibiotics, and 18.7% (91/487) of these were not prescribed. Cephalosporins were the most frequently used antibiotic (52.8%), and community pharmacies were the main source (53.7%). Children who coughed for 1-2 weeks (OR 1.73, 95% CI 1.03 to 2.90) or 3-4 weeks (OR 2.39, 95% CI 1.08 to 4.97), with runny nose (OR 1.86, 95% CI 1.13 to 3.19) or those whose family annual income between ¥50 000 and ¥100 000 (OR 4.44, 95% CI 1.52 to 18.95) had a higher risk of non-prescription use of antibiotics than those coughing for <1 week, without runny nose or with family annual income <¥50 000. CONCLUSIONS: Our findings indicated that a high proportion of infants and young children had been treated with antibiotics for cough, and nearly one in five of them were used without prescription. More public health campaigns and further education on the appropriate use of antibiotics are needed to ensure the rational treatment of cough in children.

Development of a nomograph integrating radiomics and deep features based on MRI to predict the prognosis of high grade Gliomas.

The purpose of this study was to assess the overall survival of patients with HGG using a nomogram which combines the optimized radiomics with deep signatures extracted from 3D Magnetic Resonance Images (MRI) as well as clinical predictors. One training cohort of 168 HGG patients and one validation cohort of 42 HGG patients were enrolled in this study. From each patient's 3D MRI, 1284 radiomics features were extracted, and 8192 deep features were extracted via transfer learning. By using Least Absolute Shrinkage and Selection Operator (LASSO) regression to select features, the radiomics signatures and deep signatures were generated. The radiomics and deep features were then analyzed synthetically to generate a combined signature. Finally, the nomogram was developed by integrating the combined signature and clinical predictors. The radiomics and deep signatures were significantly associated with HGG patients' survival time. The signature derived from the synthesized radiomics and deep features showed a better prognostic performance than those from radiomics or deep features alone. The nomogram we developed takes the advantages of both radiomics and deep signatures, and also integrates the predictive ability of clinical indicators. The calibration curve shows our predicted survival time by the nomogram was very close to the actual time.

Health seeking behavior and associated factors among individuals with cough in Yiwu, China: a population-based study.

BACKGROUND: Previous studies have shown that a certain proportion of the population did not seek medical treatment after coughing, and understanding the potential reasons is crucial for disease prevention and control. METHOD: A population-based study was conducted with the probability proportional to population size sampling in Yiwu, Zhejiang, China. A total of 5855 individuals aged ≥15 years lived in Yiwu for more than 6 months were included. All participants completed a laptop-based questionnaire to collect detailed information by a face-to-face interview. Characteristics of individuals were described by categories of health seeking behavior using frequency and percentage. Univariate and multivariate logistic regression analyses were performed to estimate the associations of social-demographic and cough characteristics with health seeking behavior. RESULTS: 19.3% (1129/5855) of participants had a cough in the past month, 40% (452/1129) had sought medical treatment. Of these, 26.5% (120/452) chose hospitals at county level or above. Individuals aged ≥65 years old (OR = 2.25, 95% CI: 1.23, 4.12), female (OR = 1.57, 95% CI: 1.21, 2.06), living in rural areas (OR = 1.30, 95% CI: 1.003, 1.69), persistent cough for 3-8 weeks (OR = 2.91, 95% CI: 1.72, 4.92) and with more accompanying symptoms (P trend < 0.001) were more likely to seek medical treatment, but those coughed for > 8 weeks were not (p > 0.5). Female (OR = 0.33, 95% CI: 0.21, 0.54) and people living in rural areas (OR = 0.57, 95% CI: 0.36, 0.92) were less likely to choose hospitals at county level or above while the higher educated were more likely to (OR = 3.29, 95% CI: 1.35, 8.02). Those who coughed for more than 2 weeks were more likely to choose hospitals at or above the county level. But the number of accompanying symptoms does not show any significant relationship with the choice of medical facility. CONCLUSION: The present study found that age, sex, living areas and features of cough were associated with health seeking behavior. It is worth noting that those who coughed for too long (e.g. > 8 weeks) were less likely to seek medical treatment. Targeted measures should be developed based on the key factors found in this study to guide persons to seek medical treatment more scientifically.

Epimutation of MMACHC compound to a genetic mutation in cblC cases.

BACKGROUND: Methylmalonic aciduria (MMA) combined with homocystinuria, cobalamin(cbl)C deficiency type (OMIM 277400), is the most common autosomal recessive inherited disorder of intracellular cobalamin metabolism caused by mutations in the MMACHC gene (OMIM 609831), of which more than 100 mutations have been identified to date. In this study, we only identified a coding mutation in one allele at the MMACHC gene locus, and no large fragments deletion or duplication were found. Up to now, only three epimutation cblC cases were reported. We hypothesized whether the MMACHC was hypermethylated. METHODS: To address this hypothesis, the entire coding region and adjacent splice sites of the panel genes involved in metabolic diseases were sequenced using the Illumina HiSeq X platform, followed by confirmation via Sanger sequencing in their parents and brothers. Methylation analysis of the MMACHC was performed using an EpiTect Bisulfite Kit and methylation-specific PCR (MSP) to investigate the role of epimutations in cblC disease. RESULTS: We identified a clearly pathogenic single heterozygous c.658_660del, p. (K220del) mutation, which was also identified in the mother. Analysis of the MMACHC indicated a heterozygous epimutation consisting of 34 hypermethylated CpG sites in a CpG island encompassing the promoter and first exon of the MMACHC, which was also identified in the father. Furthermore, we identified a single heterozygous c.*2C>T mutation in the sixth exon of the PRDX1 (OMIM 176763) in patients and their fathers, which was the only sequence variation that segregated with the MMACHC methylation. Neither c.658_660del and epimutation in MMACHC nor c.*2C>T in PRDX1 was discovered in her brother. CONCLUSION: We report compound heterozygotes in MMACHC for a genetic mutation and an epimutation in cblC cases. To our best knowledge, this is the first report of two cblC cases from China caused by compound heterozygous mutations with a coding mutation in one allele and an epimutation in the other at the MMACHC locus.