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 explore the correlation of traditional Chinese medicine(TCM)syndrome elements with language function and activities of daily living(ADL)in patients suffering post-stroke aphasia(PSA).Methods Ninety-eight PSA patients hospitalized at the College of Rehabilitation Medicine,Fujian University of Traditional Chinese Medicine from April 2023 to April 2024 were selected.The language function,TCM syndrome elements,and their correlations were analyzed.Results(1)Among PSA patients,males outnumbered females.PSA patients exhibited different performances on various aphasia-related scales,with language impairments mainly concentrated in naming and spontaneous speech.(2)The distribution of TCM syndrome elements varied in PSA patients with different age groups.In the age group＜50 years old,qi obstruction(100.00%),phlegm syndrome(100.00%),and dampness syndrome(100.00%)were predominant.In the age group of 50-59 years old,phlegm syndrome(100.00%)and yang hyperactivity syndrome(96.30%)were predominant.In the age group of 60-69 years old,phlegm syndrome(100.00%)and yang hyperactivity syndrome(96.15%)were also predominant.In the age group of 70-79 years old,qi deficiency syndrome(100.00%)was predominant.In the age group of 80-89 years old,syndromes such as qi insecurity,qi obstruction,qi deficiency,phlegm,yang hyperactivity,blood stasis,wind stirring,and blood cold were concentrated(all 100.00%).However,there were no statistically significant differences in the distribution of TCM syndrome elements among various age groups(P＞0.05).(3)The distribution of deficiency and excess syndrome elements varied in PSA patients with different genders.Among deficiency syndrome elements,yang hyperactivity,qi deficiency,and yin deficiency were predominant in males,while yang hyperactivity,qi deficiency,and blood deficiency were predominant in females.Among excess syndrome elements,phlegm syndrome,qi obstruction,and dampness syndrome were predominant in males,while phlegm syndrome,qi obstruction,and qi stagnation syndrome were predominant in females.However,there were no statistically significant differences in the distribution of deficiency and excess syndrome elements between genders(P＞0.05).(4)After controlling the factors of age group and gender,partial correlation analysis of syndrome elements and language function showed that among the disease-location syndrome elements,spontaneous naming(r=-0.588,P=0.027)and sematic cued naming(r=-0.558,P=0.038)in the Boston Naming Test(BNT)were negatively correlated with the large intestine;among the disease-nature syndrome elements,BNT sematic cued naming(r=0.821,P＜0.001)was positively correlated with qi sinking,while BNT spontaneous naming was negatively correlated with blood heat(r=-0.544,P=0.044)and was positively correlated with fluid depletion(r=0.860,P=0.028);BNT recognitive naming was positively correlated with external wind(r=0.966,P=0.034);errors in BNT sematic cued naming were negatively correlated with qi sinking(r=-0.540,P=0.005);the Modified Barthel Index(MBI)was positively correlated with essence deficiency(r=0.572,P=0.021).Conclusion The TCM syndrome elements of phlegm,qi block,yang hyperactivity,and qi deficiency are commonly seen in PSA patients.There is a certain correlation of language function and ADL with TCM syndrome elements in PSA patients.

Objective Based on the lanthanum bromide scintillator detector, the calculation method of G(E) function was developed to measure the air absorbed dose rate. Methods Firstly, the gamma energy spectrumof the lanthanum bromide detector were simulated and the response functions with different energies were determined with Monte Carlo simulation method. Then, the G(E) function was calculated by the least square method. Finally, the air absorbed dose rate measured by the lanthanum bromide detector using G(E) function conversion method was compared with the theoretical calculation value based on the point source experiments. Results The experimental verification results showed that the relative deviation between thecalculated value with G(E) function and the theoretical calculation value wasmostly controlled within ± 6%, which verified the accuracy of G(E) function. Conclusion The results showed that the method of G(E) function could be applied to calculate the gamma radiation dose rate based on the in-situ the gamma spectrum with LaBr₃ detector.

Objective To study the method of dose reconstruction in human body under the photon external radiation accident condition,and to verify the accuracy of the method for the local dose distribution.Methods Based on the open source Monte Carlo tool kit Geant 4 and using the human voxel phantom recommended by ICRP Publication 103,the dose reconstruction method under the condition of external radiation accident was studied to evaluate the average absorbed dose,organ absorbed dose and local dose distribution.To validate the code,several irradiation experiments were implemented in some standard radiation fields by putting TLDs in the tissue equivalent physical phantom ART.A voxel phantom was used to reconstruct the radiation doses,which was created based on the CT scan image of the ART phantom with resolution of 1.57 mm× 1.57 mm× 10.00 mm.The result of experiment were compared with those of dose reconstruction simulation.Results The relative uncertainty of the measured values was 10.9％.The relative uncertainty of the dose reconstruction simulation values was 7.10％ at the non-tissueinterface area and 16.6％ at the tissue-interface area.For 451 measuring points,the average of the simulated value divided by the measured value was 0.972,with the standard deviation of 0.083 8.In the range of 0.95-1.05,0.90-1.10 and 0.80-1.20,and the proportions were 49.2％,79.4％ and 96.4％,respectively.Conclusions The method of Monte Carlo dose reconstruction based on human voxel phantom meets the accuracy requirement of actual uses both at the whole body or organ level and at the local dose distribution level.It can be used as a powerful tool for dose assessment of the exposed people in an external radiation accidents and provide support for diagnosis and treatment.

Stroke is characterized by a group of acute cerebral vascular diseases which attack acutely with focal neurological deficits. Residual motor deficits often sojourn after stroke. Cortical stimulation, which is a technique developed many decades ago, has recently re-emerged as a promising method for researchers in their quest to causally probe cortical representations of sensorimotor and cognitive functions and to facilitate the treatment of various neuropsychiatric disorders. The article summarizes the research progress of cortical stimulation in the promotion of motor function recovery after stroke, the method of operation, the possible mechanisms and the prospect.