Objective: To evaluate the intervention effect of low-frequency repetitive transcranial magnetic stimulation (rTMS) among children with autism spectrum disorder (ASD), so as to provide the reference for the treatment scheme of ASD children. Methods: From May to September 2021, children with ASD aged 3 to 12 years were recruited from Elim Training and Ability Development Center as the research subjects and randomly assigned to the intervention group and the control group at ratio of a 1∶1 ratio. The control group only received behavioral training intervention. The intervention group received low-frequency rTMS treatment once a day (5 times/week) on the left dorsolateral prefrontal cortex for 1 month, a total of 20 times, as well as behavioral training. The Autism Behavior Scale (ABC), the Clancy Autism Behavior Scale (CABS), and the Social Responsiveness Scale (SRS) were used to evaluate the behavioral characteristics, symptoms, and social functioning of ASD before and after the intervention, respectively. Adverse events occurring during the intervention period in the intervention group were also collected. The generalized estimation equation was used to compare the differences in scores of each scale between the two groups of children before and after intervention, and to evaluate the intervention effect. Results: Sixty children with ASD were included, with 26 in the intervention group (4 dropouts) and 27 in the control group (3 dropouts). There were 20 and 22 male children in the intervention and control groups, respectively, accounting for 76.92% and 81.48%. The median ages were 5.00 (interquartile range, 1.13) years and 4.50 (interquartile range, 2.00) years, respectively. There were no statistically significant differences between the two groups of children in terms of gender, age, preschool special education time, and total raw scores of Autism Diagnostic Observation Schedule Second Edition (all P>0.05). After one month of intervention, the ABC, CABS, and SRS scores of the intervention group decreased by 16.70, 1.50, and 3.75 points compared to before intervention, respectively, while the control group decreased by 1.07, 0.50, and 1.70 points, respectively (all P<0.05). There was an interaction between the groups and time for ABC scores (P<0.05), while there was no interactions between the groups and time for CABS or SRS scores (both P>0.05). No serious adverse events occurred in the intervention group during the intervention period. Conclusions Low-frequency rTMS treatment has an improvement effect on the behavioral characteristics of children with ASD and shows good safety, and its effect is superior to that of behavioral training treatment. However, it has no obvious improvement effect on social functioning.

The maintenance of hematopoietic stem cells (HSCs) is a complex process involving numerous cell-extrinsic and -intrinsic regulators. The first member of the cyclin-dependent kinase family of inhibitors to be identified, p21, has been reported to perform a wide range of critical biological functions, including cell cycle regulation, transcription, differentiation, and so on. Given the previous inconsistent results regarding the functions of p21 in HSCs in a p21-knockout mouse model, we employed p21-tdTomato (tdT) mice to further elucidate its role in HSCs during homeostasis. The results showed that p21-tdT+ HSCs exhibited increased self-renewal capacity compared to p21-tdT- HSCs. Zbtb18, a transcriptional repressor, was upregulated in p21-tdT+ HSCs, and its knockdown significantly impaired the reconstitution capability of HSCs. Furthermore, p21 interacted with ZBTB18 to co-repress the expression of cKit in HSCs and thus regulated the self-renewal of HSCs. Our data provide novel insights into the physiological role and mechanisms of p21 in HSCs during homeostasis independent of its conventional role as a cell cycle inhibitor.
Animals ; Hematopoietic Stem Cells/cytology* ; Cyclin-Dependent Kinase Inhibitor p21/genetics* ; Mice ; Cell Self Renewal ; Repressor Proteins/genetics* ; Mice, Inbred C57BL ; Mice, Knockout ; Humans ; Gene Expression Regulation