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 establish a protocol for virus isolation using the mixed method, and evaluate the efficacy of the suspended method and the mixed method in isolating herpes simplex virus (HSV).Methods:Simulated HSV-infected clinical samples were prepared using HSV-1 F strain and CDC-P1 strain. Both the suspended method and the mixed method were used to isolate HSV-1 from these samples. The virus isolation efficiency of the mixed method under various conditions was assessed. These conditions included different multiplicity of infection (MOI), cell seeding densities, and virus adsorption times.The 50% tissue culture infective dose (TCID 50) assay was used for the assessment. The positive rates of virus detection under low viral load conditions were compared between the two methods. Results:Under the conditions of a MOI of 0.005, a virus adsorption time of 15 min, and a cell seeding density of 1×10 6 cell/ml, the mixed method achieved effective isolation of HSV-1. When the virus titer of the sample was 100 TCID 50/ml, the positivity rate of the mixed method reached 100.0%, while the positivity rates of the suspended method were 50.7% (38/75) and 52.0% (39/75) after cultured for 72 h and 96 h, respectively. When the virus titer of the sample was 10 TCID 50/ml, the positivity rate of the mixed method was 100.0%, while the positivity rate of the suspension method was 0. Conclusions:The mixed method exhibits significantly higher efficiency in HSV isolation compared with the suspended method. Under the conditions of high viral load, both the suspended method and the mixed method can be effective in isolating HSV-1. For clinical samples with low viral loads, the mixed method has greater applicability.

Objective To analyze the short-term clinical outcomes of emergency conversion to surgery during transcatheter aortic valve replacement (TAVR). Methods Clinical data of patients who underwent emergency surgical conversion from TAVR in the Department of Cardiovascular Surgery, the Second Hospital of Hebei Medical University, from 2018 to 2023 were collected. Postoperative follow-up results at 1 month were recorded. Results A total of 253 patients underwent TAVR, of whom 11 (4.3%) required emergency conversion to surgery. Among these 11 patients, 7 were male and 4 were female, with a mean age of (69.55±5.01) years. The primary cause for emergency surgical conversion was valve stent displacement (63.6%), followed by left ventricular perforation/rupture (18.2%) and significant perivalvular regurgitation persisting after a second valve implantation (18.2%). One (9.1%) patient died intraoperatively. Among the 10 surviving patients, postoperative complications included pulmonary infection in 8 patients, severe pneumonia in 7, pleural effusion in 3, liver dysfunction in 8, renal dysfunction in 3, upper gastrointestinal bleeding in 5, cerebrovascular complications in 1, atrial fibrillation in 1, ventricular premature contractions in 1, atrioventricular block in 1, and complete left bundle branch block in 3. At 1-month postoperative follow-up, one additional patient died, yielding a 30-day mortality rate of 18.2% after TAVR emergency surgical conversion. The quality of life improved significantly compared to preoperative status in 9 (81.8%) patients, and no patients were readmitted for cardiovascular diseases. Conclusion The incidence of emergency conversion to surgery during TAVR is low, but the rates of surgical complications and 30-day postoperative mortality are high. Nevertheless, when severe complications occur during TAVR, emergency conversion to surgery can still yield satisfactory short-term clinical outcomes for a majority of these patients.

Depressive disorders are common mental illnesses characterized by significant and persistent low mood, with features such as high prevalence, high disability rate, and high suicide rate. The microbiota-gut-brain axis may be one of the potential mechanisms underlying depressive disorders. Gut microbiota metabolites, as important mediators of MGBA signaling, play roles in depressive disorders through multiple pathways. These include short-chain fatty acids, which can regulate the transmission of the vagus nerve, inflammatory responses, and 5-hydroxytryptamine synthesis; secondary bile acids, which can activate farnesoid X receptor and Takeda G protein-compled receptor 5; and choline, which can regulate DNA methylation and trimethylamine N-oxide production. This article reviews the literature on the potential mechanisms of action of gut microbiota metabolites, such as short-chain fatty acids, secondary bile acids, and choline, in depressive disorders. The literature was retrieved from CNKI, PubMed, and Web of Science databases from 2010 to 2025. It aims to provide a theoretical basis for the prevention and treatment of depressive disorders.

To examine the evolution of surgical techniques and trends in overall inpatient burden for pediatric adenoidectomy in Beijing tertiary hospitals from 2013 to 2022. A retrospective observational study was conducted using the regional health information platform of Beijing. Data from children aged ≤14 years who underwent adenoidectomy between 2013 and 2022 were extracted, including total hospitalization cost, length of stay(LOS), surgical material cost, surgical fee, operative technique, perioperative antimicrobial drugs cost, coagulation factor cost, and blood transfusion cost. The Mann-Kendall trend test was used to assess temporal changes in total hospitalization expenses and the structure of cost components. The results showed that over the 10-year period from 2013 to 2022, a total of 25 989 children underwent adenoidectomy in tertiary hospitals. The proportion of children aged ≤6 years increased from 59.83% to 76.11%, showing a significant upward trend ( Z=2.15, P=0.032). Only one case required surgical hemostasis due to postoperative bleeding. During the ten-year period, the median hospitalization cost for adenoidectomy in tertiary hospitals was ￥12 425.82 (￥11 307.43, ￥14 955.42).Overall hospitalization cost demonstrated a fluctuating downward pattern, decreasing from ￥15 229.73 in 2013 to ￥13 927.52 in 2022, this declining trend was not statistically significant( Z=-0.54, P=0.592). In contrast, the surgical costs showed an upward trend over the decade increasing from ￥1 856.22 in 2013 to ￥3 726.45 in 2022, which was statistically significant ( Z=3.22, P=0.001), while the cost of surgical materials showed no significant increase ( Z=1.79, P=0.074).Concurrently, the average LOS decreased remarkably from 10.56 days in 2013 to 3.26 days in 2022 ( Z=-3.94, P<0.001). The cost of perioperative antimicrobial drugs decreased ( Z=-3.94, P<0.001), while the cost of coagulation factors and blood transfusion remained unchanged ( Z=0.54, P=0.592; Z=0.56, P=0.578). Comparison between 2013-2017 and 2018-2022 showed a significant increase in the use of coblation from 28.9% to 42.5% ( χ2=638.7, P<0.001).Furthermore, in the coblation group, total hospitalization cost decreased by 27.73%, surgical cost increased by 94.98%, surgical material cost decreased by 10.33%, LOS shortened by 56.24%, and antimicrobial drug cost increased by 43.03%. In contrast, the non-coblation group showed a 23.94% increase in total hospitalization cost, a 57.08% increase in surgical procedure cost, a 33.88% increase in material cost, and a 30.14% reduction in LOS and a 26.0% decrease in antimicrobial drugs cost. In conclusion,from 2013 to 2022, total hospitalization cost for pediatric adenoidectomy in Beijing tertiary hospitals remained stable. Compared to non-coblation techniques, coblation was associated with a shorter LOS, lower total costs, a higher proportion of surgical fees, and a decreased proportion of material costs, without a significant increase in overall healthcare costs.

Objective:To investigate the dynamic changes of cellular miRNA expression profiles in EBV latently infected Raji cells upon reactivation with Phorbol ester (TPA).Methods:Total RNA was extracted using TRIzol reagent from Raji cells treated with TPA at different time points (0 h, 24 h, 48 h). Small RNA libraries were constructed and sequenced on an Illumina SE50 platform. Differentially expressed miRNAs were identified, and their target genes were predicted and functionally annotated. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were carried out through online tools. Additionally, miRanda and RNAhybrid software were used to predict cellular miRNAs targeting the EBV genome. Real-time RT-qPCR was employed to validate the expression levels of differentially expressed novel miRNAs.Results:High-throughput sequencing identified 1 301 celluar miRNAs, comprising 1 189 known and 112 novel miRNAs. A total of 264 known differentially expressed cellular miRNAs and 13 novel miRNAs were identified through high-throughput miRNA sequencing. Secondary structure prediction revealed that the novel miRNAs exhibited typical pre-miRNA hairpin structures. Stem-loop quantitative real-time PCR (RT-qPCR) validation of Novel_miR_183 and Novel_miR_242 did not exhibit a statistically significant difference ( F=1.407, P=0.370 7 for Novel_miR_183; F=1.277, P=0.397 0 for Novel_miR_242) between the TPA-stimulated and untreated groups. Target gene prediction analysis revealed that the differentially expressed cellular miRNAs were involved in various important biological processes and signaling pathways. Furthermore, 1 189 known cellular miRNAs and 108 novel miRNAs were predicted to target the EBV genome. Conclusions:Treatment of Raji cells with TPA stimulation successfully reactivated Raji cells and significantly altered their miRNA expression patterns. Differentially expressed miRNAs were identified, suggesting that these miRNAs probably play crucial roles in regulating EBV infection and replication by directly targeting the EBV genome.

Objective:To investigate the effect of nuclear factor erythroid-2 related factor (Nrf2) overexpression on high-risk human papillomavirus type 16 (HPV16) E6 protein.Methods:The pRK5-FLAG-NFE2L2 plasmid was constructed, and pRK5-FLAG-NFE2L2 and pRK5-HA-HPV16E6 plasmids were co-transfected in HEK293T cells, and the expression of the two proteins was detected by Western blotting (WB). Next, pRK5-HA-HPV16E6 and pRK5-FLAG-Nrf2 plasmids were expressed using an in vitro transcription system to observe the expression of both. Finally, pEGFP-HPV16E6 and pLVX-mCherry-Nrf2 plasmids were co-transfected in HEK293T cells, and the cellular localization of the E6 protein and the Nrf2 protein was observed using fluorescence microscopy.Results:Nrf2 protein was successfully overexpressed in HEK293T cells, and the WB result showed that Nrf2 inhibited HPV16 E6 protein expression in a significant dose-dependent manner. The expression of HPV16 E6 protein in the TNT Quick Coupled Transcription/Translation Systems was affected by Nrf2, while the expression of HPV16 E6 in TnT SP6 High-Yield Wheat Germ Protein Expression System was no longer inhibited by Nrf2. Fluorescence imaging further showed no intracellular co-localization of Nrf2 and HPV16 E6.Conclusions:Overexpression of the nuclear transcription factor Nrf2 reduces HPV16 E6 protein expression, but there is no intracellular co-localization of them.

Objective:To establish a protocol for virus isolation using the mixed method, and evaluate the efficacy of the suspended method and the mixed method in isolating herpes simplex virus (HSV).Methods:Simulated HSV-infected clinical samples were prepared using HSV-1 F strain and CDC-P1 strain. Both the suspended method and the mixed method were used to isolate HSV-1 from these samples. The virus isolation efficiency of the mixed method under various conditions was assessed. These conditions included different multiplicity of infection (MOI), cell seeding densities, and virus adsorption times.The 50% tissue culture infective dose (TCID 50) assay was used for the assessment. The positive rates of virus detection under low viral load conditions were compared between the two methods. Results:Under the conditions of a MOI of 0.005, a virus adsorption time of 15 min, and a cell seeding density of 1×10 6 cell/ml, the mixed method achieved effective isolation of HSV-1. When the virus titer of the sample was 100 TCID 50/ml, the positivity rate of the mixed method reached 100.0%, while the positivity rates of the suspended method were 50.7% (38/75) and 52.0% (39/75) after cultured for 72 h and 96 h, respectively. When the virus titer of the sample was 10 TCID 50/ml, the positivity rate of the mixed method was 100.0%, while the positivity rate of the suspension method was 0. Conclusions:The mixed method exhibits significantly higher efficiency in HSV isolation compared with the suspended method. Under the conditions of high viral load, both the suspended method and the mixed method can be effective in isolating HSV-1. For clinical samples with low viral loads, the mixed method has greater applicability.

To examine the evolution of surgical techniques and trends in overall inpatient burden for pediatric adenoidectomy in Beijing tertiary hospitals from 2013 to 2022. A retrospective observational study was conducted using the regional health information platform of Beijing. Data from children aged ≤14 years who underwent adenoidectomy between 2013 and 2022 were extracted, including total hospitalization cost, length of stay(LOS), surgical material cost, surgical fee, operative technique, perioperative antimicrobial drugs cost, coagulation factor cost, and blood transfusion cost. The Mann-Kendall trend test was used to assess temporal changes in total hospitalization expenses and the structure of cost components. The results showed that over the 10-year period from 2013 to 2022, a total of 25 989 children underwent adenoidectomy in tertiary hospitals. The proportion of children aged ≤6 years increased from 59.83% to 76.11%, showing a significant upward trend ( Z=2.15, P=0.032). Only one case required surgical hemostasis due to postoperative bleeding. During the ten-year period, the median hospitalization cost for adenoidectomy in tertiary hospitals was ￥12 425.82 (￥11 307.43, ￥14 955.42).Overall hospitalization cost demonstrated a fluctuating downward pattern, decreasing from ￥15 229.73 in 2013 to ￥13 927.52 in 2022, this declining trend was not statistically significant( Z=-0.54, P=0.592). In contrast, the surgical costs showed an upward trend over the decade increasing from ￥1 856.22 in 2013 to ￥3 726.45 in 2022, which was statistically significant ( Z=3.22, P=0.001), while the cost of surgical materials showed no significant increase ( Z=1.79, P=0.074).Concurrently, the average LOS decreased remarkably from 10.56 days in 2013 to 3.26 days in 2022 ( Z=-3.94, P<0.001). The cost of perioperative antimicrobial drugs decreased ( Z=-3.94, P<0.001), while the cost of coagulation factors and blood transfusion remained unchanged ( Z=0.54, P=0.592; Z=0.56, P=0.578). Comparison between 2013-2017 and 2018-2022 showed a significant increase in the use of coblation from 28.9% to 42.5% ( χ2=638.7, P<0.001).Furthermore, in the coblation group, total hospitalization cost decreased by 27.73%, surgical cost increased by 94.98%, surgical material cost decreased by 10.33%, LOS shortened by 56.24%, and antimicrobial drug cost increased by 43.03%. In contrast, the non-coblation group showed a 23.94% increase in total hospitalization cost, a 57.08% increase in surgical procedure cost, a 33.88% increase in material cost, and a 30.14% reduction in LOS and a 26.0% decrease in antimicrobial drugs cost. In conclusion,from 2013 to 2022, total hospitalization cost for pediatric adenoidectomy in Beijing tertiary hospitals remained stable. Compared to non-coblation techniques, coblation was associated with a shorter LOS, lower total costs, a higher proportion of surgical fees, and a decreased proportion of material costs, without a significant increase in overall healthcare costs.