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Background Congenital anomalies of the kidney and urinary tract (CAKUT) are the leading cause of kidney failure in children with phenotypic and genotypic heterogeneity. Our objective was to describe the genetic spectrum and identify the risk factors for kidney failure in children with CAKUT. Methods Clinical and genetic data were derived from a multicentre network [Chinese Children Genetic Kidney Disease Database (CCGKDD)] and the Chigene database. A total of 925 children with CAKUT who underwent genetic testing from 2014 to 2020 across China were studied. Data for a total of 584 children were obtained from the CCGKDD, including longitudinal data regarding kidney function. The risk factors for kidney failure were determined by the Kaplan–Meier method and Cox proportional hazards models. Results A genetic diagnosis was established in 96 of 925 (10.3%) children, including 72 (8%) with monogenic variants, 20 (2%) with copy number variants (CNVs) and 4 (0.4%) with major chromosomal anomalies. Patients with skeletal abnormalities were more likely to have large CNVs or abnormal karyotypes than monogenic variants. Eighty-two patients from the CCGKDD progressed to kidney failure at a median age of 13.0 years (95% confidence interval 12.4–13.6) and 24 were genetically diagnosed with variants of PAX2, TNXB, EYA1, HNF1B and GATA3 or the 48,XXYY karyotype. The multivariate analysis indicated that solitary kidney, posterior urethral valves, bilateral hypodysplasia, the presence of certain variants and premature birth were independent prognostic factors. Conclusions The genetic spectrum of CAKUT varies among different subphenotypes. The identified factors indicate areas that require special attention. [ABSTRACT FROM AUTHOR]

Background: Primary vesicoureteral reflux (VUR) is a common congenital anomaly of the kidney and urinary tract (CAKUT) in childhood. The present study identified the possible genetic contributions to primary VUR in children. Methods: Patients with primary VUR were enrolled and analysed based on a national multi-center registration network (Chinese Children Genetic Kidney Disease Database, CCGKDD) that covered 23 different provinces/regions in China from 2014 to 2019. Genetic causes were sought using whole-exome sequencing (WES) or targeted-exome sequencing. Results: A total of 379 unrelated patients (male: female 219:160) with primary VUR were recruited. Sixty-four (16.9%) children had extrarenal manifestations, and 165 (43.5%) patients showed the coexistence of other CAKUT phenotypes. Eighty-eight patient (23.2%) exhibited impaired renal function at their last visit, and 18 of them (20.5%) developed ESRD at the median age of 7.0 (IQR 0.9–11.4) years. A monogenic cause was identified in 28 patients (7.39%). These genes included PAX2 (n = 4), TNXB (n = 3), GATA3 (n = 3), SLIT2 (n = 3), ROBO2 (n = 2), TBX18 (n = 2), and the other 11 genes (one gene for each patient). There was a significant difference in the rate of gene mutations between patients with or without extrarenal complications (14.1% vs. 6%, P = 0.035). The frequency of genetic abnormality was not statistically significant based on the coexistence of another CAKUT (9.6% vs. 5.6%, P = 0.139, Chi-square test) and the grade of reflux (9.4% vs. 6.7%, P = 0.429). Kaplan–Meier survival curve showed that the presence of genetic mutations did affect renal survival (Log-rank test, P = 0.01). PAX2 mutation carriers (HR 5.1, 95% CI 1.3–20.0; P = 0.02) and TNXB mutation carriers (HR 20.3, 95% CI 2.4–168.7; P = 0.01) were associated with increased risk of progression to ESRD. Conclusions: PAX2, TNXB, GATA3 and SLIT2 were the main underlying monogenic causes and accounted for up to 46.4% of monogenic VUR. Extrarenal complications and renal function were significantly related to the findings of genetic factors in children with primary VUR. Like other types of CAKUT, several genes may be responsible for isolated VUR. [ABSTRACT FROM AUTHOR]

Hematologic and neurological expression 1 (HN1) has been reported to involved in certain cancers, but its role in hepatocellular carcinoma (HCC) is largely unknown. The contribution of HN1 to HCC progression was investigated in the present study. We found that HN1 was significantly up‐regulated in HCC tissues, compared with normal tissues, by analyzing the Oncomine and Human Protein Atlas database; and found that high expression of HN1 was markedly associated with worse overall survival, relapse‐free survival, progression‐ free survival and disease‐specific survival in HCC patients via exploring the Kaplan‐Meier plotter database. Functional assays revealed that HN1 knockdown by siRNA induced G1 cell cycle arrest, and inhibited the growth and migration of HCC cells; accordingly, HN1 over‐expression promoted HCC cells proliferation and migration. Further studies indicated that HN1 knockdown reduced the expression of cyclin D1 and CDK4, while upregulated the cell cycle inhibitor p21WAF1/Cip1. Moreover, HN1 knockdown decreased c‐Met (receptor tyrosine kinase of hepatocyte growth factor) expression, and suppressed ERK activation, which is a common downstream signaling pathway triggered by c‐Met; consistently, HN1 over‐expression reversed these effects. Meanwhile, down‐regulation of c‐Met partly eliminated the effect of HN1 over‐expression in HCC cells. Thus, the present findings suggested that HN1 promotes the progression of HCC to some extent by up‐regulating the expression of c‐Met, and may act as a potential biomarker and therapeutic target for the treatment of HCC. [ABSTRACT FROM AUTHOR]

Objective: The effect of using standardized parent training history-taking on the quality of medical records and communication skills among pediatric interns was determined.Methods: Fifth-year interns who were undertaking a pediatric clinical practice rotation were randomized to intervention and control groups. All of the pediatric interns received history-taking training by lecture and bedside teaching. The pediatric interns in the intervention group also received standardized parent history-taking training. The following two outcome measures were used: the scores of medical records, which were written by the pediatric interns after history-taking from real parents of pediatric patients; and the communication assessment tool (CAT) assessed by real parents.Results: The general information, history of present illness (HPI), past medical history, personal history, family history, diagnosis, diagnostic analysis, and differential diagnosis scores in the intervention group were significantly higher than the control group (p < 0.05). Assessment of the CAT indicated that the real parents were more satisfied with the pediatric interns in the intervention group.Conclusions: Standardized parent training history-taking is effective in improving the quality of medical records by pediatric interns. Standardized parent training history-taking is a superior teaching tool for clinical reasoning ability, as well as communication skills in clinical pediatric practice. [ABSTRACT FROM AUTHOR]

Bayesian regularized BP neural network(BRBPNN) technique was applied in the chlorophyll-a prediction of Nanzui water area in Dongting Lake. Through BP network interpolation method, the input and output samples of the network were obtained. After the selection of input variables using stepwise/multiple linear regression method in SPSS 11.0 software, the BRBPNN model was established between chlorophyll-a and environmental parameters, biological parameters. The achieved optimal network structure was 3-11-1 with the correlation coefficients and the mean square errors for the training set and the test set as 0.999 and 0.00078426, 0.981 and 0.0216 respectively. The sum of square weights between each input neuron and the hidden layer of optimal BRBPNN models of different structures indicated that the effect of individual input parameter on chlorophyll-a declined in the order of alga amount > secchi disc depth (SD) > electrical conductivity (EC). Additionally, it also demonstrated that the contributions of these three factors were the maximal for the change of chlorophyll-a concentration, total phosphorus (TP) and total nitrogen (TN) were the minimal. All the results showed that BRBPNN model was capable of automated regularization parameter selection and thus it may ensure the excellent generation ability and robustness. Thus, this study laid the foundation for the application of BRBPNN model in the analysis of aquatic ecological data(chlorophyll-a prediction) and the explanation about the effective eutrophication treatment measures for Nanzui water area in Dongting Lake. [ABSTRACT FROM AUTHOR]