BackgroundMeiotic homologous recombination (HR) plays an essential role in gametogenesis. In most eukaryotes, meiotic HR is mediated by two recombinase systems: ubiquitous RAD51 and meiosis-specific DMC1. In the RAD51-mediated HR system, RAD51 and five RAD51 paralogues are essential for normal RAD51 function, but the role of RAD51 in human meiosis is unclear. The knockout of Rad51 or any Rad51 paralogue in mice exhibits embryonic lethality. We investigated a family with meiotic arrest, azoospermia and infertility but without other abnormalities.MethodsHomozygosity mapping and whole-exome sequencing were performed in a consanguineous family. An animal model carrying a related mutation was created by using a CRISPR/Cas9 system.ResultsWe identified a 1 bp homozygous substitution (c.41T>C/p.Leu14Pro) on a RAD51 paralogue, namely, XRCC2, in the consanguineous family. We did not detect any XRCC2 recessive mutation in a cohort of 127 males with non-obstructive-azoospermia. Knockin mice with Xrcc2-c.T41C/p.Leu14Pro mutation were generated successfully by the CRISPR/Cas9 method. The homozygotes survived and exhibited meiotic arrest, azoospermia, premature ovarian failure and infertility.ConclusionA XRCC2 recessive mutation causing meiotic arrest and infertility in humans was duplicated with knockin mice. Our results revealed a new Mendelian hereditary entity and provided an experimental model of RAD51-HR gene defect in mammalian meiosis.

Abstract. The aim of the present retrospective study was to investigate the diagnosis, treatment and prognosis of pediatric anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis. A total of 23 pediatric patients with anti-NMDAR encephalitis were included in the present study. The clinical data, laboratory test results, imaging examination, treatment outcomes, and follow-up records were reviewed and analyzed. A total of 8 patients exhibited prodromal symptoms, including fever, cough, and vomiting. Clinical symptoms included epilepsy, convulsions, ataxia, coma, dyskinesia, personal behavior change and hallucinations. A total of 20 cases had the initial neurologic symptoms of dyskinesia or seizure, whereas 3 cases exhibited psychiatric symptoms of personal behavior change and hallucinations. Furthermore, pediatric patients >6 years old had more psychiatric symptoms than those ≤6 years. A total of 20 cases exhibited abnormal electroencephalography records, with 1 case of extreme δ brush. A total of 10 cases exhibited abnormal brain magnetic resonance imaging detection. Furthermore, the CSF protein contents for pediatric patients ≤6 years old was significantly higher than those >6 years. For treatment, 18 pediatric patients received the first-line treatment of methylprednisone and intravenous injection of immunoglobulin, and 6 cases were subjected to the second-line treatment of rituximab. A total of 2 patients underwent plasma exchange and/or cyclophosphamide treatment. In follow-up, 12 cases reported no convulsion, whereas 11 cases had moderate or severe neurological and psychiatric sequelae. The recovery rate for pediatric patients ≤6 years old was significantly higher than those >6 years. Anti-NMDAR encephalitis is commonly seen in pediatric patients, mainly with initial neurological symptoms. These patients could respond to immunotherapy, and younger pediatric patients typically have a better prognosis.

ObjectiveSevere mental illness (SMI) represents major social and public health problem in China, especially in low- or middle-income regions. We aim to assess the prevalence and distribution of SMI in Hunan province in central China.MethodsMultistage stratified random sampling methods were used to select qualified subjects in 123 districts and counties in Hunan province. 89465 individuals were randomly identified, and 72999 (81.6%) completed the supplemental 12-Item General Health Questionnaire (GHQ-12) and Cue questionnaire of psychiatric abnormal behaviors. 6082 suspected individuals having high or moderate risk, or psychiatric cues, were administered the Structured Clinical Interview for DSM-IV Axis I disorders (SCID-I) by psychiatrists.Results720 respondents were definitely diagnosed as SMI. The 1-month and lifetime prevalence was 9.35‰ and 10.10‰, respectively. The most frequent SMI was schizophrenia, followed by bipolar disorder, intellectual disability, epileptic mental disorder, paranoid psychosis and schizoaffective disorders, with 1-month prevalence ranging from 0.11‰ to 6.50‰ and lifetime prevalence ranging from 0.24‰ to 6.86‰. Multivariate logistic regression analysis revealed that lower education, farmer occupation, retirees or jobless/unemployed, unmarried or divorced and age of 30–64 years old were major factors that associated with the increased risk of SMI. In addition, only 33.3% of 528 patients who completed questionnaire sought help in psychiatric institutions, and up to 51.7% of 720 patients were not referred to the SMI management system in Hunan province.ConclusionsThese findings provided a large-scale prevalence data of SMI in a provincial sample of China. The psychiatric disorders brought economical and psychological burden for family and society, which may shed light on the significance of scaling up province-wide mental health service and strengthening the SMI management.

Hand, foot, and mouth disease (HFMD) is endemic in the Pacific region, especially in mainland China. The case-fatality ratio of HFMD is increasing steadily. Knowledge of the changing epidemiology of HFMD in different regions is necessary for implementing appropriate intervention strategies. In this study, we describe the clinical and epidemiological characteristics of HFMD in Hunan Children’s Hospital between 2013 and 2017. A total of 7203 patients with HFMD were admitted, with complication and mortality rates of 35.62% and 0.78%, respectively. The total number of children with HFMD, proportion of severely ill children, and HFMD mortality rate were the highest in 2014. The number of cases caused by EV-A71 and CV-A16 decreased continuously, while the number of cases caused by ‘other enteroviruses’ increased yearly since 2014, suggesting that other enteric viruses will gradually replace EV-A71 and CV-A16 as the main pathogenic HFMD agents. Furthermore, EV-A71 and mixed infections accounted for the high case fatality rates in children with severe HFMD, among whom EV-A71 infection resulted in the highest complication and mortality rates; the mild form of the disease was dominated by ‘other enteroviruses’. In conclusion, the changing etiological pattern highlights the need to improve pathogen surveillance and vaccine strategies for HFMD control.