Loss-of-function variants in CSDE1 have been strongly linked to neuropsychiatric disorders, yet the precise role of CSDE1 in neurogenesis remains elusive. In this study, we demonstrate that knockout of Csde1 during cortical development in mice results in impaired neural progenitor proliferation, leading to abnormal cortical lamination and embryonic lethality. Transcriptomic analysis revealed that Csde1 upregulates the transcription of genes involved in the cell cycle network. Applying a dual thymidine-labelling approach, we further revealed prolonged cell cycle durations of neuronal progenitors in Csde1-knockout mice, with a notable extension of the G1 phase. Intersection with CLIP-seq data demonstrated that Csde1 binds to the 3' untranslated region (UTR) of mRNA transcripts encoding cell cycle genes. Particularly, we uncovered that Csde1 directly binds to the 3' UTR of mRNA transcripts encoding Cdk6, a pivotal gene in regulating the transition from the G1 to S phases of the cell cycle, thereby maintaining its stability. Collectively, this study elucidates Csde1 as a novel regulator of Cdk6, sheds new light on its critical roles in orchestrating brain development, and underscores how mutations in Csde1 may contribute to the pathogenesis of neuropsychiatric disorders.
Animals ; Neurogenesis/genetics* ; Cell Cycle/genetics* ; Mice, Knockout ; Mice ; Neural Stem Cells/metabolism* ; DNA-Binding Proteins/metabolism* ; Cyclin-Dependent Kinase 6/genetics* ; Cell Proliferation ; 3' Untranslated Regions ; Cerebral Cortex/embryology* ; RNA-Binding Proteins ; Mice, Inbred C57BL

Objective To investigate the effects of selective cyclooxygease-2 inhibitor on pulmonary surfactant protein(SP-B) and transforming growth factor(TGF-β1) of hyperoxic lung injury in newborn rats.Methods One hundred and five SD rats were randomly divided into 3 groups (35 cases in each group):air group (group Ⅰ),in which the rats were exposed to room air;hyperoxia group(group Ⅱ),in which the rats were exposed to hyperoxia(850 mL/L oxy gen);Celecoxib group(group Ⅲ),in which the rats were exposed to heyperoxia(850 mL/L oxygen) and intraperitoneally injected with 5 mg/kg Celecoxib.The lungs of rats were removed on 3 d,7 d,14 d after birth and the following indices were measured:lung section from the lower right lung were stained with HE,and the histological changes was examined;the contents of SP-B and TGF-β1 in the bronchoalveolar lavage fluid of left lung was determinated by using enzyme-linked immunosorbent assay (ELISA);right upper lung was immunohistochemically stained to measure the contents of SP-B and TGF-β1,quantitative real-time PCR(RT-PCR) was used to detect the mRNA expression of SP-B and TGF-β1.Results There were no inflammatory cells and exudation in the lung in group Ⅰ;in group Ⅱ,the structure disorder,pulmonary edema,and inflammatory infiltrates were found;but the damage was obviously alleviated in group Ⅲ.Protein expression could be better detected by ELISA,at the time of 14 day,SP-B was expressed at different levels in3 groups:(29.93±6.40) ng/L in group Ⅰ,(18.20 ±3.70) ng/L in group Ⅱ and (19.63 ±10.20) ng/L in group Ⅲ,SP-B level in group Ⅱ was significantly lower than that in group Ⅰ (t =13.152,P ＜ 0.01),and the expres sion in group Ⅲ was significantly higher than that in group Ⅱ (t =5.190,P ＜ 0.01).TGF-β1 was expressed at different levels in 3 groups:(34.73 ±2.30) μg/L in group Ⅰ,(41.66 ± 1.80) μg/L in group Ⅱ and (38.03 ±0.20) μg/L in group Ⅲ,and the level of TGF-β1 was significantly higher in group Ⅱ than that in group Ⅰ (t =6.584,P ＜ 0.01),but the expression of group Ⅲ was significantly lower than that in group Ⅱ (t =5.609,P ＜ 0.01).The expression of mRNA was detected by RT-PCR,and at the time of 14 day,SP-B mRNA was expressed at different levels in 3 groups:3.14 ±0.10 in group Ⅰ,0.81 ±0.06 in group Ⅱ and 1.12 ±0.06 in group Ⅲ,and SP-B level in group Ⅱ was significantly lower than that in the group Ⅰ (t =55.050,P ＜0.01),and the expression in group Ⅲ was significantly higher than that in group Ⅱ (t =10.305,P ＜ 0.01).TGF-β1 mRNA was expressed at different levels in the 3 groups:1.94 ±0.03 in group Ⅰ,13.26 ±0.43 in group Ⅱ and 6.49 ±0.26 in group Ⅲ,the level of TGF-β1 was significantly higher in group Ⅱ than that in group Ⅰ (t =75.471,P ＜ 0.01),while the expression of group Ⅲ was significantly lower than that in group Ⅱ (t =38.470,P ＜ 0.01).Conclusions Cyclooxygenase-2 inhibitor can attenuate hyperoxic lung injury in rats,and the mechanism might be related to the reduction of prostaglandin.

OBJECTIVETo observe the change of myeloid-derived suppressor cells (MDSCs) percentage in peripheral blood after operation in rectal cancer patients and to examine its association with the prognosis.

METHODSBlood samples of pre-operation and postoperative 21-day from 64 stage I(-III( rectal cancer patients who underwent surgery in Department of General Surgery, The Affiliated Cancer Hospital, Zhengzhou University between January and December 2009 were collected. MDSCs percentage was detected by flow cytometry. Its association with the prognosis of patients was analyzed.

RESULTSMDSCs percentage of postoperative 21-day decreased significantly compared with pre-operation (P<0.01). When local recurrence or distant metastasis presented, MDSCs percentage increased again (all P<0.01) and reached the preoperative level(P>0.05). All the patients were further divided into two groups based on median MDSCs percentage. Patients with higher MDSCs percentage before operation (>3.78%) and after operation (>2.11%) had significantly lower 5-year overall survival(OS) (58.1% and 62.1%) and 5-year disease-free survival (DFS)(54.8% and 58.6%) as compared to those with lower MDSCs percentage(5-year OS 87.9% and 84.8%; 5-year DFS 82.8% and 80.0%, all P<0.05). Multivariate analysis showed that preoperative MDSCs percentage was an independent prognostic factor of rectal cancer(HR:4.065, 95% CI:1.026 to 16.108, P=0.04).

CONCLUSIONSPreoperative increased MDSCs percentage may be an important predictor of poor OS in rectal cancer patients. Dynamic change of MDSCs percentage can reflect the disease development.

Objective To summarize the experience of vagina reconstruction with six kinds of axial pattern skin flaps Methods Six kinds of axial pattern skin flaps have been used for vagina reconstruction in 126 cases,including of hypogastric skin flap,thoraco umblical skin flap,labia minora skin flap,scrotal skin flap,penis skin flap and pudendal femoral skin flap Results All flaps were survived,but one case of necrosis occurred in hypogastric skin flap Conclusion The pudendal femoral skin flap is the first choice of flap for vagina reconstruction The advantages of this method are (1) the reconstructed vagina has good sensation and flexibility;(2)the linear scars of donor site are hidden and inconspicuous;(3)the flap is close to recipient site the procedure is simple