Advances in genetics and prevention of monogenic global developmental delay and intellectual disability / 中华围产医学杂志

Global developmental delay/intellectual disability (GDD/ID) is an enormous group of neurodevelopmental disorders with diverse clinical and genetic heterogeneity. The estimated prevalence of GDD/ID was 1%-3%, affecting about 150 million people. GDD/ID is one of the leading causes of disability in children worldwide. The causes of GDD/ID are complex, comprising genetic and environmental factors. It is often co-morbid with a variety of psychiatric behavioral disorders, such as autism spectrum disorder and attention deficit hyperactivity disorder. Owing to the improvement of genetic technology, monogenic GDD/ID has been one of the hot-spot research in genomic era, and the relevant preventive measures deserve extensive attention. In this review, we summarized the advances in genetics and prevention of monogenic GDD/ID.

Prenatal diagnosis of monogenic global developmental delay/intellectual disability in 43 pedigrees / 中华围产医学杂志

Objective:To summarize the prenatal diagnostic characteristics of monogenic global developmental delay/intellectual disability(GDD/ID) pedigrees.Methods:This study retrospectively collected the prenatal molecular diagnostic results of 43 pedigrees that were affected with monogenic GDD/ID in the genetic counseling clinic of Peking University First Hospital from January 2015 to June 2019. The results of prenatal molecular tests were validated after birth or pregnancy termination. Pregnancy outcomes and healthy condition of the offspring were followed up. All data were analyzed by descriptive statistical analysis.Results:Among the 43 pedigrees, 24 were affected with autosomal recessive inheritance (AR) GDD/ID, in which six (25%) fetuses were found to carry two pathogenic variants; 13 (55%) had only one pathogenic variant; five (20%) did not harbor any variant. GDD/ID inherited in an autosomal dominant inheritance (AD) pattern was found in 13 pedigrees, in which 11 fetuses carried no variants while the other two fetuses had the same variants as the proband had (in one pedigree, a low-level variant was detected in the peripheral blood sample of the father while absent in peripheral blood samples of parents in the other pedigree, so it was suspected that the variants of these two affected fetuses were inherited from parental mosaicism). In the other six pedigrees with X-linked inheritance (XL) of GDD/ID, one male fetus was found to harbor the pathogenic variant, while no variants were detected in the others. Maternal contamination was excluded in all prenatal samples using short tandem repeat for linkage analysis. Postnatal validations were consistent with the prenatal tests. All nine affected fetuses were terminated, and the other thirty-four children were delivered and in good health.Conclusions:Prenatal molecular diagnostic test is an effective method to detect pathogenic variants during the first and second trimesters for pedigrees affected by monogenic GDD/ID. For pedigrees affected with AD or XL patterns caused by de novo mutations, potential parental mosaicism should be noted and prenatal diagnostic tests are also recommended.

Problem exploration and measures on the investigator initiated trial from the perspective of scientific research supervision / 中华医学科研管理杂志

Objective By analyzing the problems existed in the Investigator Initiated Trial (IIT),this article put forward the corresponding countermeasures and therefore provides reference for the standardization of clinical research project management.Methods Four types of problems identified in the supervision of hospital IIT projects are analyzed according to literature review,data analysis of clinical research project,comparative study and summary.Identified problems are existed in the following aspects:scientific research supervision function,research method guidelines,technical specification of the diagnosis and treatment,scientific research design and project approval review,research funds,medical ethics committee,construction of Biobank and Regulation Conflicts.Results This article put forward 6 countermeasures for improvement:establishing and perfect IIT project scientific research supervision entity,bring in the IIT project steering group to strengthen the scientific review;Strengthen risk management to ensure medical safety,carry out IIT training,establish IIT management database information system,build a comprehensive integrated development multi-point application model of hospital BioBank.Conclusions The establishment of the hospital's IIT scientific research supervision system,management mode and technical standard system is of great importance to standardize clinical research,ensure research quality and guide the clinical research work of the hospital effectively.

Preliminary study of risk management mode for investigator-initiated clinical trials / 中华医学科研管理杂志

Objective To explore the risk management model of investigator-initiated clinical trials (IITs) from the prospective of clinical research management personnel,to provide further reference for its construction and implementation in China.Methods The risks in IITs and its current situation of risk management were analyzed.Risk management standards including ISO 31000 and related guidelines were adopted to explore the risk management mode for China-based IIT.Results This article proposed the new risk management mode for IITs and also introduced the specified frame and procedures of related risk management.Conclusions The risk management model proposed in this article provided reference for clinical research management.

Distributions and associations between duration of sleep, daytime naps and insomnia symptoms among Chinese adults / 中华流行病学杂志

Objective To investigate the distribution of sleep duration,daytime naps habits,and insomnia-related symptoms among participants from the China Kadoorie Biobank (CKB) study,and to examine the associations between the sleep-associated factors.Methods A self-designed computer-based questionnaire was adopted to collect social-demographic information and lifestyle-related factors of the participants.A total of 452 829 Chinese adults aged 30-79 years,without self-reported histories of coronary heart disease,stroke,chronic obstructive pulmonary diseases or cancer,were included in this study.General linear regression and multinomial logistic regression models were used to estimate the distributions on duration of sleep,daytime naps habits,and insomnia-related symptoms in different populations,after adjusted for gender,age,and residential regions.Gender-specific logistic regression model was adopted to examine the associations between the above mentioned sleep-related factors.Results The average sleep duration of the participants was 7.41 hours per day,with 20.3％ of them having daytime naps all year round,but 40.1％ only had daytime naps in summer,and 39.6％ had no habits of daytime naps.11.0％,10.0％,and 2.1％ of the participants reported having had symptoms as difficulty in falling asleep,waking up too early or with daytime dysfunction,respectively.There were significant differences on the distributions in sleep-related factors between participants with different gender,age,residential areas,education levels,household income,and marital status (P＜0.05).Results from the logistic regression showed that longer sleep duration was associated with lower risks of insomnia-related symptoms trend (P＜0.001).Factor as without habits of daytime naps seemed to be associated with higher risks of insomnia-related symptoms (P＜0.05).Participants with longer sleep duration were more likely to have the habit of taking daytime naps (P＜0.05).Conclusions The distributions of sleep duration,habits on daytime naps and insomnia-related symptoms varied according to the differences on social-demographic factors.There were associations existed between the sleeping-related factors,which would influence the promotion on optimal sleep duration and better quality of sleep.

Distributions and associations between duration of sleep, daytime naps and insomnia symptoms among Chinese adults / 中华流行病学杂志

Objective To investigate the distribution of sleep duration,daytime naps habits,and insomnia-related symptoms among participants from the China Kadoorie Biobank (CKB) study,and to examine the associations between the sleep-associated factors.Methods A self-designed computer-based questionnaire was adopted to collect social-demographic information and lifestyle-related factors of the participants.A total of 452 829 Chinese adults aged 30-79 years,without self-reported histories of coronary heart disease,stroke,chronic obstructive pulmonary diseases or cancer,were included in this study.General linear regression and multinomial logistic regression models were used to estimate the distributions on duration of sleep,daytime naps habits,and insomnia-related symptoms in different populations,after adjusted for gender,age,and residential regions.Gender-specific logistic regression model was adopted to examine the associations between the above mentioned sleep-related factors.Results The average sleep duration of the participants was 7.41 hours per day,with 20.3％ of them having daytime naps all year round,but 40.1％ only had daytime naps in summer,and 39.6％ had no habits of daytime naps.11.0％,10.0％,and 2.1％ of the participants reported having had symptoms as difficulty in falling asleep,waking up too early or with daytime dysfunction,respectively.There were significant differences on the distributions in sleep-related factors between participants with different gender,age,residential areas,education levels,household income,and marital status (P＜0.05).Results from the logistic regression showed that longer sleep duration was associated with lower risks of insomnia-related symptoms trend (P＜0.001).Factor as without habits of daytime naps seemed to be associated with higher risks of insomnia-related symptoms (P＜0.05).Participants with longer sleep duration were more likely to have the habit of taking daytime naps (P＜0.05).Conclusions The distributions of sleep duration,habits on daytime naps and insomnia-related symptoms varied according to the differences on social-demographic factors.There were associations existed between the sleeping-related factors,which would influence the promotion on optimal sleep duration and better quality of sleep.

NQO1 C609T gene polymorphism associated with an increased risk of post operative cognitive dysfunction / 中华行为医学与脑科学杂志

Objective To investigate the association between the C609T polymorphism of NAD (P)H:quinoneoxidoreductase (NQO1) gene and post operative cognitive dysfunction (POCD).Methods 90 ASA Ⅰ-Ⅱ patients of 59 to 78 years old, undergoing elective hip replacement with epidural anesthesia were enrolled.All patients were given a battery of 5 neuropsychological tests before operation and seven days after operation.Patients were divided into POCD group and control group according to test results (45 patients in each group).The single nucleotide polymorphism C609T of NQO1 gene was detected using real-time PCR by Taqman probes and subjected to odd ratio assessment.Results 5 samples in control group couldn' t be used in the real-time PCR analysis due to quality control.The frequency of C/C genotype in POCD control was lower than that of control group ( 30.0% vs 11.1% ) with statistical significance ( OR = 0.292,95 % CI 0.092 ～ 0.92 1, P ＜ 0.05 ).The C/T +T/T genotype frequency was significantly higher in group POCD than in the control group(88.8% vs 70% ).Patients presented with C/T + T/T genotype showed an evidently increased risk of POCD ( OR =3.42,95% CI 1.08 ～ 10.82,P ＜ 0.05 ).The frequency of C allele of NQO1 gene in group control was 56.2%, as compared with 40% in group POCD with significance ( OR = 0.519,95% CI 0.282 ～ 0.955, P ＜ 0.05 ).The frequency of T allele of NQOI gene in control group was 43.7% ,as compared with 60.0% in POCD group( OR = 1.93,95% CI 1.047 ～3.552,P＜O.05).Conclusion The NQO1 gene single nucleotide polymorphism C609T is evidently associated with the increased risk of POCD.