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 analyze the cellular senescence pathways and their associated genes with bioinformatic analysis by screening differentially expressed genes(DEGs)during embryonic kidney development with aid of transcriptomics in order to explore the relationship between cellular senescence and embryonic kidney development.Methods After the kidney tissues from mice at embryonic age of 14.5 days(E14.5 group)and 18.5 days(E18.5 group)were collected,the kidney tissue structure was observed with periodic acid Schiff(PAS)staining,the expression profiles of the related genes during embryonic kidney development were analyzed by transcriptomics,and the changes in the genes related to cellular senescence were further analyzed with bioinformatics.The expression levels of target genes were verified by real-time quantitative fluorescence PCR and Western blotting.Results With the development of the embryonic kidney,the kidney structure gradually matured.The results of transcriptomic and bioinformatic analyses revealed that cellular senescence-related genes played an important role in the development of embryonic kidney.The mRNA and protein levels of Cdkn1a(P21),which was correlated with cellular senescence,were significantly higher(P＜0.05),while the mRNA levels of Skp2,Ccne1,Ccnd2,and Cdk4 were decreased in the E1 8.5 group than the E14.5 group(P＜0.05).Conclusion Obvious changes in the expression levels of cellular senescence-related genes are observed during embryonic kidney development,suggesting that cellular senescence plays an important role in the development.

Humans ; Melanoma/therapy* ; Skin Neoplasms/therapy* ; Methylation ; Prognosis ; Immunotherapy ; RNA ; Biomarkers, Tumor ; Melanoma, Cutaneous Malignant

Objective:To investigate the association between Onodera's prognostic nutritional index (OPNI) and postoperative adverse outcomes in elderly gastrointestinal surgery patients and assess the predictive value.Methods:A total of 230 elderly patients who received gastrointestinal surgery were prospectively enrolled. Clinical data, including age, sex, preoperative laboratory parameters, surgery process and clinical outcomes, were collected. The optimal cut-off value of OPNI was obtained using NRS 2002, a well-recognized nutritional risk screening tool, as the standard. The associations of OPNI, geriatric nutritional risk index (GNRI) and albumin with in-hospital mortality, complication incidence and duration of postoperative hospital stay were evaluated using Chi-square test or nonparametric test as appropriate. Confounders were identified through univariate analysis and logistic and linear regression models were developed to validate the correlation and assess the predictive value of OPNI for postoperative clinical outcomes.Results:The optimal cut-off value for the OPNI was 41.25, which yielded a sensitivity of 72.7% and a specificity of 59.9% with area under the curve (AUC) at 0.682. The incidence of OPNI-based malnutrition (defined as OPNI < 41.25) was 50% (115/230). Univariate analysis indicated that patients with OPNI < 41.25 had a significantly higher mortality (8.70% versus 2.61%, P = 0.046) and complication incidence (20.00% versus 9.57%, P = 0.026) and significantly longer postoperative hospital stay (11.17 d versus 8.49 d, P = 0.009) than patients with OPNI ≥ 41.25. Patients with GNRI < 98 had a longer postoperative hospital stay than those with GNRI ≥ 98 (10.71 d versus 7.55 d, P = 0.001) while there was no significant difference in mortality or complication incidence between the two groups ( P > 0.05). As for subgroups divided according to albumin levels (< 35 g/L or ≥35 g/L), no significant differences in mortality, postoperative complications incidence, or duration of postoperative hospital stay were observed ( P > 0.05). Multivariate analysis verified that OPNI < 41.25 was an independent risk factor for the development of postoperative complications ( OR: 2.660, 95% CI: 1.079-6.557, P = 0.034) and prolonged postoperative hospital stay ( R2 = 0.135, regression coefficient = 2.73, P = 0.047), where the AUC of the regression model for complications was 0.812 (95% CI: 0.741-0.882). GNRI < 98 was the independent risk factor for prolonged postoperative hospital stay ( R2 = 0.134, regression coefficient = 2.797, P = 0.049). Conclusion:OPNI is an independent risk factor for adverse clinical outcomes after gastrointestinal surgery in elderly patients and demonstrates good predictive value with the cut-off value of 41.25.

Background::The CHA 2DS 2–VASc score was initially applied to stratify stroke risk in patients with atrial fibrillation (AF) and was found to be effective in predicting all-cause mortality outcomes. To date, it is still unclear whether circulating long non-coding RNAs (lncRNAs) as emerging biomarkers, can improve the predictive power of the CHA 2DS 2–VASc score in stroke and all-cause mortality. Methods::Candidate lncRNAs were screened by searching the literature and analyzing previous RNA sequencing results. After preliminary verification in 29 patients with AF, the final selected lncRNAs were evaluated by Cox proportional hazards regression in 192 patients to determine whether their relative expression levels were associated with stroke and all-cause mortality. The c-statistic, net reclassification improvement (NRI), and integrated discrimination improvement of the patients were calculated to evaluate the discrimination and reclassification power for stroke and all-cause mortality when adding lncRNA expression levels to the CHA 2DS 2–VASc score model. Results::Five plasma lncRNAs associated with stroke and all-cause mortality in AF patients were selected in our screening process. Patients with elevated H19 levels were found to have a higher risk of stroke (hazard ratio [HR] 3.264, 95% confidence interval [CI]: 1.364–7.813, P = 0.008). Adding the H19 expression level to the CHA 2DS 2–VASc score significantly improved the discrimination and reclassification power of the CHA 2DS 2–VASc score for stroke in AF patients. In addition, the H19 level showed a marginally significant association with all-cause mortality (HR 2.263, 95% CI: 0.889–5.760, P = 0.087), although it appeared to have no significant improvement for the CHA 2DS 2–VASc model for predicting all-cause mortality. Conclusions::Plasma expression of H19 was associated with stroke risk in AF patients and improved the discriminatory power of the CHA 2DS 2–VASc score. Therefore, lncRNA H19 served as an emerging non-invasive biomarker for stroke risk prediction in patients with AF.

Objective:To explore the effects of mutual-aid training mode in nursing interns.Methods:From June 2017 to June 2019, this study selected 70 nursing interns as subjects in Department of Acupuncture and Rehabilitation of Jiangsu Provincial Hospital of Chinese Medicine by convenience sampling. Nursing interns from June 2017 to June 2018 were in control group ( n=35) , and those from July 2018 to June 2019 were in observation group ( n=35) . Nursing interns of control group received the traditional training mode, while observation group carried out the mutual-aid training mode. The study compared the theoretical achievement, operational performance, clinical thinking ability and teaching effect. Results:After training, the theoretical achievement and operational performance of nursing students in observation group were higher than those in control group with statistical differences ( P<0.05) ; the total score and dimension scores of clinical thinking ability of nursing students in observation group were higher than those in control group with statistical differences ( P<0.05) ; the teaching effect evaluation of nursing students in observation group was better than that in control group with a statistical difference ( P<0.05) . Conclusions:The mutual-aid training mode can improve nursing students' clinical nursing skills and nursing quality which is worthy of clinical popularization.

AIM To study the chemical constituents from Vigna umbellata Ohwi et Ohashi.METHODS The ethyl acetate fraction of 80％ ethanol extract from V.umbellata was isolated and purified by silica,Sephadex LH-20 and ODS column,then the structures of obtained compounds were identified by spectral data and physicochemical properties.RESULTS Twelve compounds were isolated and elucidated as (+) catechin (1),(-) epicatechin (2),3-furanmethanol-β-D-glucopyranoside (3),myricetin-3-O-β-D-glucopyranoside (4),quercetin7-O-β-D-glucopyranoside (5),(+) catechin-3-O-β-D-glucopyranoside (6),(+) catechin-5-O-β-D-glucopyranoside (7),quercetin-3 '-O-α-L-rhamnoside (8),(±) dihydroquercetin (9),quercetin (10),ethyl gallate (11),propanediol (12).CONCLUSION All the compounds are isolated from V.umbellata for the first time,and compounds 4,8,9,11,12 are first obtained from genus Vigna.

Objective To prevent unplanned extubation,reduce complications caused by restraint, improve satisfaction degree of patients′relatives,and to lower nurses′work stress.Methods Transparent restraint protection gloves were developed,within which fingers could move freely and with the help of which unplanned extubation could be prevented.A total of 1 00 ICU patients were selected and divided into intervention group and control group randomly,each with 50 cases.Patients in the intervention group used the new type restraint gloves,while patients in the control group used traditional ones.Restraint effects of the two groups were compared.Results Unplanned extubation happened to non patient in the intervention group,while it happened to 6 cases in the control group,Fisher′s exact test was used in comparison between the two groups (P <0.05). Scores of satisfaction degree in the intervention group were (3.1 4 ±0.639)points,while the scores in the control group were (2.20 ±0.756)points (t =6.71 4,P <0.01 );scores of nurses′work stress on accident extubation of patients in the intervention group were (2.1 2 ±0.761 )points,lower than that in the control group with (t =-8.696,P <0.01 ).Conclusions Transparent restraint protection gloves can effectively prevent unplanned extubation,reduce complications caused by restraint,improve satisfaction degree of patients′relatives,and lower nurses′work stress.

The UL49.5 gene of most herpesviruses is conserved and encodes glycoprotein N. However, the UL49.5 protein of duck enteritis virus (DEV) (pUL49.5) has not been reported. In the current study, the DEV pUL49.5 gene was first subjected to molecular characterization. To verify the predicted intracellular localization of gene expression, the recombinant plasmid pEGFP-C1/pUL49.5 was constructed and used to transfect duck embryo fibroblasts. Next, the recombinant plasmid pDsRed1-N1/glycoprotein M (gM) was produced and used for co-transfection with the pEGFP-C1/pUL49.5 plasmid to determine whether DEV pUL49.5 and gM (a conserved protein in herpesviruses) colocalize. DEV pUL49.5 was thought to be an envelope glycoprotein with a signal peptide and two transmembrane domains. This protein was also predicted to localize in the cytoplasm and endoplasmic reticulum with a probability of 66.7%. Images taken by a fluorescence microscope at different time points revealed that the DEV pUL49.5 and gM proteins were both expressed in the cytoplasm. Overlap of the two different fluorescence signals appeared 12 h after transfection and continued to persist until the end of the experiment. These data indicate a possible interaction between DEV pUL49.5 and gM.
Animals ; Ducks/virology ; Genes, Viral/genetics ; Mardivirus/*genetics ; Membrane Glycoproteins/*genetics ; Microscopy, Fluorescence ; Phylogeny ; Polymerase Chain Reaction/veterinary ; Viral Envelope Proteins/*genetics

Objective To evaluate the predictive accuracy of several risk-assessment strategies to predict the risk of significant neonatal hyperbilirubinemia, and to establish the best prediction model.Methods The transcutancous bilirubin (TcB) levels of 4907 term and near-team infants were measured.Trace blood bilirubin levels of the infants whose TcB levels ≥250 μmol/L were detected. Clinical data of newborns and their mothers were collected and were analyzed with Logistic regression model to investigate its correlation with signifrcant hyperbilirubinemia. Clinical high risk factors of significant neonatal hyperbilirubinemia were determined. Accuracy of three prediction methods for significant hyperbilirubinemia was compared by receiver operating characteristic (ROC) curve. The three methods included: whether predischarge bilirubin level (within 72 hours after birth) expressed in risk zone on an hour-specific bilirubin nomogram; clinical risk factors other than predischarge bilirubin level; and combination of the predischarge bilirubin risk zone and other clinical risk factors. Results Two hundred and eighty-six newborns (5.8%) were found with significant hyperbilirubinemia. The risk factors of significant neonatal hyperbilirubinemia were divided into three groups according to OR: (1) Major risk factors:predischarge (within 72 hours after birth) bilirubin level in the high risk-zone (OR=96. 39, 95% CI:53.32-174.27, P = 0. 000), large cephalohematoma (OR = 36.45, 95% CI: 10. 02-132.56,P=0. 0076), gestational age 35-36+6 weeks (OR= 30. 72, 95% CI 14.47-65.23, P=0. 0001) and exclusive breast feeding and weight loss was ＞9% of birth-weight (OR=22.44, 95% CI: 4.42-114. 03, P=0. 0016). (2) Minor risk factors: gestational age 37-37+6 weeks (OR=3.26, 95% CI:1.92-5. 55, P=0. 0232), predischarge bilirubin level in P76-P95(OR=13. 64, 95% CI: 8. 10-22.97,P=0. 0001) and bruising (OR = 2.32, 95% CI: 1.14-4.71, P = 0. 0497). (3)Protective factors (those factors associated with decreased risk of hyperbilirubinemia): predischarge bilirubin level in low-risk zone (≤P40) (OR=0. 00), gestational age ≥40 weeks (OR=0.21, 95% CI: 0.09-0.44,P=0. 0402) and mixed breeding (OR=0. 75, 95% CI: 0. 58-0.95, P=0.0059). The area under the ROC curve of predischarge bilirubin level was 0. 8687 and 0. 7375 for clinical risk factors other than predischarge bilirubin level. The area under the ROC curve of a combination of the predischarge bilirubin risk zone and additional clinical risk factors was 0. 9367. Conclusions The risk of significant neonatal hyperbilirubinemia could be simply and accurately predicted by infant's predischarge bilirubin level and the combination of predischarge bilirubin level, and clinical risk factors might improve the accuracy of prediction significantly.