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 construct and evaluate the rat model of thyroid nodule liver-qi depression syndrome with the combination of disease and syndrome,so as to lay a foundation for the exploration of the mechanism and clinical research of traditional Chinese medicine in the treatment of thyroid nodule.Methods 36 rats were randomly divided into three groups.The model was induced by chronic unpredictable mild stress(CUMS)stimulation combined with propylthiouracil(PTU).The rats in the blank group were fed with saline at the dose of 1 mL·100 g-1·d-1,and the rats in the PTU group were fed with 0.1%PTU solution at the dose of 1 mL·100 g-1·d-1.The rats in the CUMS+PTU group were fed with CUMS stimulation in a single cage and intragastric administration of 0.1%PTU solution according to the dose of 1 mL·100 g-1·d-1,and the modeling time lasted for 6 weeks.After the establishment of the model,the model of combination of disease and syndrome was evaluated comprehensively by means of animal behavior detection,ultrasonic image,apparent morphology observation,pathological staining and serum hormone index detection.Results Compared with control group and PTU group,the total distance in the open field was significantly shortened,the sucrose preference rate was significantly decreased,and the swimming suspension time was significantly prolonged in the CUMS+PTU group,showing obvious symptoms of liver qi stagnation.In addition,compared with the other two groups,the thyroid gland of CUMS+PTU group showed obvious enlargement and nodule formation,thyroid index significantly increased,and thyroid follicular epithelial cells showed a high phase of proliferation.In terms of hormone levels,compared with control group,the serum levels of free triiodothyronine(FT3)and free thyroxine(FT4)in CUMS+PTU group were significantly lower,while the level of thyroid stimulating hormone(TSH)was significantly higher,which was in line with the current evaluation criteria of thyroid nodule model.Conclusion The method of CUMS stimulation combined with PTU drug induction can successfully prepare the rat model of thyroid nodule liver-qi depression syndrome,and the comprehensive evaluation method is stable and reliable,which is helpful to improve the scientific nature of the disease-syndrome combination model.

OBJECTIVES: This study evaluated the association between obesity and glaucoma in middle-aged and older people. A population-based retrospective cohort study was conducted using data from the China Health and Retirement Longitudinal Study. METHODS: Glaucoma was assessed via self-reports. Multivariate logistic regression analysis and a Cox proportional hazards model were used to assess the relationship between obesity and glaucoma risk. RESULTS: Older males living in urban areas who were single, smokers, and non-drinkers were found to have a significantly higher incidence of glaucoma (all p<0.05). Diabetes, hypertension, and kidney disease were also associated with higher glaucoma risk, while dyslipidemia was associated with lower risk (all p<0.05). After the model was adjusted for demographic, socioeconomic, and health-related variables, obesity was significantly associated with a 10.2% decrease in glaucoma risk according to the Cox proportional hazards model (hazard ratio, 0.90; 95% confidence interval [CI], 0.83 to 0.97) and an 11.8% risk reduction in the multivariate logistic regression analysis (odds ratio, 0.88; 95% CI, 0.80 to 0.97). A further subgroup analysis showed that obesity was associated with a reduced risk of glaucoma in people living in rural areas, in smokers, and in those with kidney disease (all p<0.05). Obesity also reduced glaucoma risk in people with diabetes, hypertension, or dyslipidemia more than in healthy controls (all p<0.05). CONCLUSIONS This cohort study suggests that obesity was associated with a reduced risk of glaucoma, especially in rural residents, smokers, and people with kidney disease. Obesity exerted a stronger protective effect in people with diabetes, hypertension, or dyslipidemia than in healthy people.

The application of gene therapy in ocular diseases is gradually expanding from mono-gene inherited diseases to multigene, multifactorial, common and chronic diseases. This emerging therapeutic approach is still in the early exploratory stage of treating diseases, and the expected benefits and risks remain highly uncertain. In the delivery process of gene therapy drugs, viral vector is currently one of the most mature and widely used vectors. The occurrence of vector-associated immunity will affect the short-term and long-term effects of gene therapy, and even cause permanent and serious damage to visual function. Therefore, gene therapy vector-associated immunity is the focus and challenge for the safety and long-term efficacy of gene therapy. During the perioperative and follow-up of gene therapy, attention should be paid to the monitoring of vector-associated immune inflammation, and appropriate measures should be taken to deal with the corresponding immune response, so as to achieve the best visual benefits for patients.

Most inherited retinal diseases (IRDs) severely impair vision and lack effective treatments.With the approval of Luxturna, the world's first gene therapy drug for IRDs in 2017 by the U. S.FDA, gene therapy has brought new hope for the treatment of the disease.With an early onset and a relatively small number of patients, the understanding of the natural course of IRDs is limited in the past.The research on gene therapy of IRDs is mainly based on the in-depth understanding of the pathogenesis and natural course of disease, and the selection of the optimal treatment window for the implementation of gene therapy is the premise of successful treatment.At the same time, the main vector for gene therapy is recombinant virus vector, and its tissue-immunogenicity, tumorigenicity, safety of its integration with host cells and effectiveness determine the outcome of therapy, so the evaluation technology of IRDs gene therapy needs to be established.Gene therapy for ophthalmic diseases also involves the consideration of laws and regulations, ethics, product process, races and regional environment, disease progression, gene mutation types, patient benefit and risk ratio, and other factors.Therefore, it is of great significance to take full account of the differences in IRDs population, especially the particularity of children patients, and actively carry out the study on the natural course of IRDs in China for the scientific and normative development of clinical trials of gene therapy, the effective establishment of endpoint and outcome indicators for clinical studies of gene therapy, and the compliance with international norms of ethics.

Objective? To explore the effects of new orthopedic high-waist shoes on preventing foot drop deformity among spinal cord injury patients with lower limb paralysis. Methods? From April 2016 to January 2018, we selected a total of 44 spinal cord injury patients with paralysis. All of the patients were divided into experimental group and control group according to the order of admission and random number sampling approaches. Patients of experimental group wore new orthopedic high-waist shoes from the first day after admission, while patients of control group used the square soft pillow in foot. We compared the incidence of foot drop deformity among patients two weeks after admission. Results? The incidences of foot drop deformity, pressure injury on foot as well as strephenopodia of patients in experimental group and control group were 18.2% vs. 40.9%, 4.5% vs. 18.2% as well as 27.3% vs. 59.1% respectively with statistical differences (P＜0.05). Conclusions? Early use of new orthopedic high-waist shoes can effectively prevent foot drop, protect function of ankle joint and promote the rehabilitation of neuromuscular function in limb among spinal cord injury patients with paralysis.

Objective To evaluate the value of polymerase chain reaction (PCR) combined with probe detection method in diagnosis of Mycoplasma pneumonia (MP) pneumonia (MPP) in children and to analyze the factors influencing the diagnostic accuracy,and to identify the rate of MP mutation for drug resistance and the involving factors.Methods Two hundred and twenty-five children with MPP hospitalized in the Department of Respiratory Medicine,Beijing Children's Hospital,Capital Medical University between June 2015 and March 2016 were enrolled in this study.Nasopharyngeal swab samples from the participants within 24 hours of admission were detected by using PCR combined with fluorescence probes for MP-DNA and macrolide-resistant mutations.The information of age,sex,clinical symptoms,course of disease,duration by admission,the history of macrolide treatment and the increase or decrease of quadruple or more serum MP antibody titer were extracted from medical records within 4 weeks of treatment,which received further correlation analysis with the detection rate of MP-DNA and the drug resistance mutation.Results The sensitivity of the MPP by using the method of PCR combined with fluorescence probes was 80.4％ (181/225 cases),while the specificity was 98.0％ (99/101 cases).The MP-DNA positive rate for patients with double MP antibody 4 times increased during treatment was 88.8％ (71/80 cases),which was significantly higher than that of patients with antibody titer ≥1 ∶ 160 [75.9％ (110/145 cases)],and the difference was sigmficant(x =5.443,P =0.020).The positive rate of MP-DNA of patients had no obvious association with gender,age,and disease duration and macrolide treatment history before admission.Macrolide-resistant mutation rate of MP-DNA was 85.1％ (154/181 cases),macrolide-resistant mutation rate of MP for patients finishing one course of macrolide treatment when admission(89.6％)was higher than that of the patients without using macrolide and the patients treated with macrolide but not finishing one course of treatment (71.9％ and 86.6％),and the significant difference among the three groups was observed(x2 =4.454,P =0.035).Conclusions PCR combined with fluorescence probe for MP-DNA detection has a high accuracy for the diagnosis of MPP,and the overall mutation rate is high,suggesting that the clinical treatment of MPP needs to be adjusted according to drug resistance in children.

BACKGROUND: At present, most of the literature on joint replacement focus on the causes and countermeasures of long-term complications, but seldom focuses on causes of postoperative short-term complications, such as wound exudation and delayed union. Whether the incidence of sustained exudation and delayed wound healing in patients with hypertension after hip replacement is higher than that in patients with normal blood pressure is not reported at present.OBJECTIVE: To identify the correlation of hypertension with persistent wound exudation and delayed wound healing in patients after femoral head replacement.METHODS: Data of 205 elderly patients with femoral neck fractures were retrospectively analyzed. All patients underwent femoral head replacement. In accordance with the hypertension diagnostic criteria of 2010 Chinese Guidelines for the Management of Hypertension, patients were divided into hypertension group and control group.Intraoperative blood loss, postoperative blood loss, the days of prolonged wound exudation, the wound dehiscence, and the prevalence of delayed wound healing were compared between the two groups. Then, we analyzed the relationship of hypertension with wound exudation and delayed wound healing.RESULTS AND CONCLUSION: (1) The average systolic blood pressures were 153.55 mmHg and 128.82 mmHg in the hypertension and control groups, respectively (P < 0.05). (2) No significant difference in age, gender, MNA-SF score, diabetes, body mass index, intraoperative blood loss, and postoperative blood loss was found between the two groups (P > 0.05). (3) The time of persistent wound exudation was 4.03 days and 2.08 days in the hypertension group and control group, respectively (P < 0.05). (4) The prevalence of delayed wound healing was significantly higher in the hypertension group than that in the control group (P < 0.05). (5) Hypertensive patients had a higher risk of prolonged wound exudation and delayed healing than their normotensive counterparts, and the hypertension is one of the important influence factors for delayed wound healing.

Objective To research the epithelial-mesenchymal transition (EMT) effects of cuprous oxide nanoparticles (CONPs) on melanoma.Methods Cuprous oxide nanoparticles were prepared hydrothermally.The B16 cells were cultured with cuprous oxide nanoparticlesat different concentrations (5,25,50 μg/ml).The changes of the morphology of the B16 cell were observed under the inverted microscope.The effects of CONPs on B16 cell migration ability were detected through the Wound healing assay and the Transwell assay.Then cell immunofluorescence and western blotting were used to test the EMT related molecular markers, including E-cadherin, N-cadherin, Cytokeratin, and Vimentin.Results The synthesized cuprous oxide nanoparticles distribute uniformly with a diameter of 40 nm.Our study indicated that CONPs inhibited the EMT of B16 cell.A conversion process was discovered in this study.In B16 cells, CONPs inhibited B16 cell migration, promoted the expression of E-cadherin, Cytokeratin and Desmoplakin, while the expression of N-cadherin and Vimentin was repressed in protein level.Conclusion Cuprous oxide nanoparticles can significantly restrain the invasion and metastasis of melanoma cells and inhabit the EMT of B16 cells.

Sjögren's syndrome is a kind of autoimmune disease, whose main clinical symptoms are dry mouth, dry eye and chronic parotid glandular inflammation. The conservative treatments include artificial tears or saliva,oral administration of corticosteroids,and immunosuppressantsl with limited effectiveness. Along with the development of molecular biology, vast attentions are being paid to researches on gene therapy for Sjögren's syndrome, hopefully to bring gospel to patients with Sjögren's syndrome. This article reviews the recent research progresses on transcatheter delivery of recombinant adenovirus vector with aquaporin gene in experimental treatment of Sjögren's syndrome.
Adenoviridae ; Aquaporins ; genetics ; Autoimmune Diseases ; therapy ; Catheters ; Genetic Therapy ; Genetic Vectors ; administration & dosage ; Humans ; Sjogren's Syndrome ; therapy