Accurate timing of myelination is crucial for the proper functioning of the central nervous system. Here, we identified a de novo heterozygous mutation in TMEM63A (c.1894G>A; p. Ala632Thr) in a 7-year-old boy exhibiting hypomyelination. A Ca²⁺ influx assay suggested that this is a loss-of-function mutation. To explore how TMEM63A deficiency causes hypomyelination, we generated Tmem63a knockout mice. Genetic deletion of TMEM63A resulted in hypomyelination at postnatal day 14 (P14) arising from impaired differentiation of oligodendrocyte precursor cells (OPCs). Notably, the myelin dysplasia was transient, returning to normal levels by P28. Primary cultures of Tmem63a^-/- OPCs presented delayed differentiation. Lentivirus-based expression of TMEM63A but not TMEM63A_A632T rescued the differentiation of Tmem63a^-/- OPCs in vitro and myelination in Tmem63a^-/- mice. These data thus support the conclusion that the mutation in TMEM63A is the pathogenesis of the hypomyelination in the patient. Our study further demonstrated that TMEM63A-mediated Ca²⁺ influx plays critical roles in the early development of myelin and oligodendrocyte differentiation.
Animals ; Cell Differentiation/physiology* ; Oligodendroglia/metabolism* ; Mice, Knockout ; Mice ; Male ; Myelin Sheath/metabolism* ; Humans ; Child ; Cells, Cultured ; Oligodendrocyte Precursor Cells/metabolism*

Cardiomyopathy, Dilated/metabolism* ; Humans ; Microfilament Proteins/metabolism* ; Models, Cardiovascular ; Mutation ; Myocytes, Cardiac ; Pluripotent Stem Cells/metabolism* ; Transcription Factors/metabolism* ; Troponin T/metabolism*

Objective To investigate the correlation between the location of ruptured intracranial vertebral artery dissecting aneurysm (VADA)and the outcome after endovascular treatment. Methods Thirty-six patients with ruptured intracranial VADA undergoing endovascular treatment were enrolled retrospectively. According to the relationship between VADA and the location of the opening of posterior inferior cerebellar artery(PICA),they were divided into 3 groups:proximal to PICA group (n=13), distal to PICA group (n=13),and PICA involvement group (n=10). The demographic data, vascular risk factors, clinical features, imaging features, endovascular treatment mode, postoperative complications, and differece of the good outcome rate(defined as the modified Rankin scale 0-2)after 6 months of treatment were compared.Results Seven patients in the proximal to PICA group received reconstructive endovascular treatment (RET), and 6 received endovascular internal trapping(EIT);the good outcome rate was 100%(13/13).Seven patients in the distal to PICA group received RET,6 were treated with EIT;the good outcome rate was 84.6%(11/13).Four patients in the PICA involvement group received RET,and 6 received EIT,and 2 of them received contralateral vertebral artery retrograde PICA stenting combined with VADA segment and proximal vertebral artery coil embolization;the good outcome rate was 60.0%(6/10). There were significant differences in the overall outcome good rate among the 3 groups (P<0.05). The good outcome rate in the PICA involvement group was significant lower than that in the proximal to PICA group,and significantly lower than that in the proximal to PICA combined with distal to PICA group(P<0.05).Multivariate logistic regression analysis showed that only Fisher grade 3-4 was the independent risk factor for poor outcome (odds ratio 28.0, 95% confidence interval 1.71-458.82; P=0.020). Conclusions The surgical options of endovascular treatment for ruptured intracranial VADA needs to evaluate the relationship between the location of dissecting aneurysms and the PICA origin. The risk of endovascular treatment in patients with intracranial VADA involving the origin of PICA is higher and it may affect the outcome.

OBJECTIVE To investigate the risk factors and to take some useful measures to prevent and reduce infection in order to enhance medical quality,to ensure medical security,to strengthen hospital infection manangement and to prevent hospital infection effectively. METHODS We investigated the prevalence rate of hospital infection among our hospitalized patients in 2001,2003 and 2005, respectively. RESULTS The hospital infection rate was 4.6-6.42% in these years.Risk factors and the abuse of antibiotic were decreasing. CONCLUSIONS In order to control hospital infection rate,mensures should be taken including intensively monitoring the departments with high infection rate,strengthening hospital operation,rationally using the antibiotics,and studying the management for hospital infection.