Conversion of 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC) by ten-eleven translocation (TET) family proteins leads to the accumulation of 5hmC in the central nervous system; however, the role of 5hmC in the postnatal brain and how its levels and target genes are regulated by TETs remain elusive. We have generated mice that lack all three Tet genes specifically in postnatal excitatory neurons. These mice exhibit significantly reduced 5hmC levels, altered dendritic spine morphology within brain regions crucial for cognition, and substantially impaired spatial and associative memories. Transcriptome profiling combined with epigenetic mapping reveals that a subset of genes, which display changes in both 5hmC/5mC levels and expression patterns, are involved in synapse-related functions. Our findings provide insight into the role of postnatally accumulated 5hmC in the mouse brain and underscore the impact of 5hmC modification on the expression of genes essential for synapse development and function.
Animals ; Brain/growth & development* ; 5-Methylcytosine/metabolism* ; Mice ; Synapses/genetics* ; Proto-Oncogene Proteins/metabolism* ; DNA-Binding Proteins/metabolism* ; Dioxygenases/metabolism* ; Cognition/physiology* ; Gene Expression ; Mixed Function Oxygenases/metabolism* ; Epigenesis, Genetic ; Mice, Knockout ; Mice, Inbred C57BL

Objective:To retrospectively analyze the urodynamics quality in Southwest China, and find out the main issues of urodynamics quality in Southwest China and try to find out the improvement ways.Methods:In this study, a two-stage sampling method was used.In the first stage, 10 medical institutions in Southwest China were selected by cluster sampling from March to June, 2020.In the second stage, according to the development of UDS in Southwest China, the sample size estimation formula was adopted, and the loss of follow-up rate in reports extraction was considered, the initial sample size was 350. As the workload of UDS in the 10 medical institutions involved in the study was equivalent, 35 urodynamics traces from each medical institution were selected. The initial samples should also meet the inclusion criteria: ①patients with clear medical history and complete clinical data; ②UDS traces were clear; ③UDS system was water filled system; ④age>18, and 150 urodynamic traces were included in the final study. We evaluated the quality of enrolled urodynamics traces, and the quality evaluation standard according to the guidelines established by the International Continence Society (ICS). The evaluation conducted by two independent urologist with more than 10 years working experience. Artifacts were divided into non-technical artifacts: abnormal abdominal pressure changes, urine volume <150 ml when did the uroflow test, and technical artifacts: non-standard zero setting, fail to record all urodynamics parameters, baseline drift, catheter displacement, misjudgment of detrusor physiological contraction and detrusor overactive in voiding phase, misjudgment between detrusor overactive and bladder low compliance in filling phase.Results:non-technical artifacts: 32 cases were found abnormal abdominal pressure changes (21.3%), 21 cases (14.0%) were found when did the uroflow test the urine volume <150 ml, and technical artifacts: Non-standard zero setting in 28 cases (18.7%), fail to record all urodynamics parameters in 8 cases, baseline drift in 16 cases, catheter displacement in 9 cases and misjudgment of detrusor physiological contraction and detrusor overactive in voiding phase in 12 cases, misjudgment between detrusor overactive and bladder low compliance in filling phase in 24 cases (16.0%).Conclusions:At present, the urodynamics quality in Southwest China need to be improved. The main issues were that the operator didn’t obey the basic operation and quality control process, and the operator did not have enough basic knowledge of urodynamics. It can be improved by strictly carry out the operation standard of UDS, identifying and correcting artifacts in time, and promoting the standardized urodynamic training courses.

Objective: To investigate the expression levels of serum miR-638 in the patients with breast cancer and its clinical value. Methods: One hundred and fifty-two patients with breast cancer were selected as the disease group, and 102 healthy persons as the control group. The expression levels of miR-638 in their serum samples were detected by the quantitative reverse transcription-polymerase chain reaction (qRT-PCR), and the expression levels of serum miR-638 in the patients with different pathological stages, before and after operation, and before and after chemotherapy were compared. The diagnosis efficacy of serum miR-638 alone and in combination with CEA, CA125, CA15-3 for breast cancer was analyzed by the ROC curve and Z test. Results: The expression levels of serum miR-638 in the breast cancer group (3.6 [1.3～10.5]) were significantly lower than that in the control group (79.0 [52.5～120.8],P＜0.01). The linear regression analysis showed that chemotherapy and pathological staging were the main factors influencing the expression levels of serum miR-638. The area under the ROC curve (AUC ROC ) of serum miR-638 in the diagnosis of breast cancer was 0.954. When the cut-off value of serum miR-638 was 27.47, its sensitivity and specificity for the diagnosis of breast cancer were 94% and 86.2%, respectively. The area under the ROC curve (AUC ROC ) of serum miR-638 combined with CEA, CA125 and CA15-3 in the diagnosis of breast cancer was 0.978 8. When the combined cut-off value was 0.29, their sensitivity and specificity for the diagnosis of breast cancer were 95.4% and 89.5%, respectively. There was no significant difference in the AUC ROC between miR-638 alone and combined screening (Z=1.68,P=0.091). Conclusion Serum miR-638 may be a potential molecular marker for the screening of breast cancer.

Adult ; Anti-Inflammatory Agents ; therapeutic use ; Dexamethasone ; therapeutic use ; Facial Nerve Diseases ; surgery ; Female ; Hemifacial Spasm ; surgery ; Humans ; Male ; Microvascular Decompression Surgery ; adverse effects ; Middle Aged ; Postoperative Nausea and Vomiting ; prevention & control

Adult ; Anesthesia, General ; methods ; Anesthesia, Intravenous ; methods ; Cesarean Section ; methods ; Female ; Humans ; Muscular Atrophy, Spinal ; Pregnancy