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*

Objective: To investigate the current status of myopia in children and adolescents in Qamdo, Tibet, and analyze related influencing factors, so as to provide a basis for the prevention and control of adolescents in plateau areas. Methods: A cross sectional study was conducted among 959 children and adolescents randomly selected from one district and two counties in Qamdo (from the fourth grade of elementary school to the second grade of high school) for visual acuity and refraction tests and filled out a vision related behavior questionnaire to analyze the incidence of myopia among adolescents in the region and its associated factors. Results: The myopia rate of adolescents in grades 4-11 was 54.43%, the rate of undercorrection of refractive errors was 85.25%, and the percentage of students wearing eyeglasses was 34.67%,fully vision correction rate was 42.54%. The myopia rate of students in grades 4-6 was 35.14%, 64.71% in grades 7-9, and 73.48% in grades 10-11. The myopia rate increased with grades( χ 2= 101.18 , P <0.01). The myopia rate (70.40%) of urban students (grades 4-9) was higher than that of county level(41.45%), and the myopia rate of students with myopia from either parent (68.24%) was higher than that of students without myopia (51.91%) , the myopia rate of girls (59.96%) was higher than that of boys (48.36%)( χ 2=53.19，13.46，12.98， P <0.01). Use electronic products for more than 2.5 hours per day, electronic devices usage after bedtime, the light low indoor brightness when studying on a sunny day, and only use one of the table lamps or roof lights when studying at night, preference for fried food, poor sleep quality, in the morning the students who still feel tired are at higher risk of myopia( χ 2=10.35, 10.91, 6.87, 4.25, 4.97, 5.71, 12.11, P < 0.05). Multivariate regression analysis showed that the occurrence of myopia was related to region, grade, gender, parental myopia, time spent on electronic products every day in the past 5 months, and sleep quality( P <0.05). Conclusion The high rate of myopia in children and adolescents in Qamdo may be related to the quality of sleep, the length of time electronic products are used, the eye environment, and the frequency of eating fried foods. Outdoor activities do not show significant differences.

Long noncoding RNA (lncRNA) comprises a group of RNAs that are longer than 200 nucleotides. The lncRNA does not contain functional open reading frames and cannot encode proteins. RNA accounts for a large proportion in the total noncoding RNAs. The number, type, and function of lncRNA are unclear, so they have been called the dark matter of the genome. With the applica-tion of a new generation of gene sequencing technology, lncRNA is found to be involved in the mechanisms mediating the signal trans-duction pathway, regulating the cell cycle, and inducing cell apoptosis. In this article, the authors summarized the up-to-date research progress on lncRNA in digestive system neoplasms in China and overseas to provide new insights into the genetic diagnosis and treat-ment of digestive system neoplasms in clinics.

Objective To study the impact of hepatitis B virus (HBV) infection on the activity of cord hematopoietic stem cells. Methods CD34+ cells were isolated from healthy human cord blood by miniMACS. Cells were cultured in IMDM complete culture medium containing stem cell factor (SCF),fms-like tyrosine kinase 3 ligand (FL), thrombopoietin (TPO), interleukin-3 (IL-3) and 10% fetal bovine serum. High copies HBV were added to the culture system. The proliferation of stem ceils and virus replication were observed. Following the proliferation, dendritic cells (DCs) were induced by adding granulocyte-macrophage colony-stimulating factor and IL-4. Morphous of stem cells and DCs were observed by microscope and the cell surface molecules were detected. Results The proliferation of stem cells infected with HBV was significantly lower than that of healthy stem cells (P＜0.01),and enhanced after adding cytokines (P＜0.01). At the same time, HBV replication was increased after adding cytokines in the culture system (P＜0.01), but the proliferation was still lower than that of healthy stem cells with cytokines in the culture medium (P＜0.05). Dane particles were found in the cytoplasma of stem cells infected with HBV by electron microscope. The expression of CD80,CD86 ,CD1a and HLA-DR on DCs derived from HBV infected stem cells were all lower than those on DCs from non-infected stem cells (P＜0.01). Conclusions HBV could infect CD34+ stem cell and the proliferation of the stem cell could enhance the virus replication. HBV could not only inhibit the proliferation of stem cells,but also down-regulate the immuno-phenotype expression of DCs derived from CD34+stem cells.