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

Purpose To investigate the clinicopathological features,molecular subtypes,and prognostic factors of diffuse midline glioma(DMG)with H3K27 alterations.Methods Clinical data from 19 patients from DMG were col-lected.The clinical manifestations,histopathological features,immunophenotypes,and molecular genetic characteris-tics were analyzed.Relevant literature was also reviewed.Results Among the 19 patients,12 cases had tumors loca-ted in the thalamus,while 7 cases had tumors in other midline regions(including 4 cases in the brainstem,1 case in the cerebellum,and 2 cases in the spinal cord).Clinical symptoms primarily included dizziness,gait instability,and blurred vision.Histological features were diverse,with 12 cases classified as high-grade gliomas and 7 cases as low-grade.Immunohistochemistry revealed a loss of H3K27me3 expression in all cases,with 18 cases showing diffuse H3K27M positivity and 1 case expressing EZHIP.Of the 16 cases that underwent next-generation sequencing(NGS),1 case showed EGFR mutation(1/16,6％),while the remaining 15 cases had H3F3A K27M mutations(15/16,94％).Among these,7 cases had ATRX mutations(7/15,46.6％),5 cases had MAPK pathway alterations(5/15,33.3％,including 2 cases FGFR1,2 cases NF1,1 case co-mutated with BRAF and NF1),5 cases had PDGFRA mis-sense mutations(5/15,33.3％),4 cases had p53 missense or frameshift deletions(4/15,26.6％).One case each had a DICER1 missense mutation and an IDH1-S202R frameshift deletion(1/15,6.6％).The prognosis was general-ly poor,with a median survival of 9.5 months.Conclusion DMG exhibits high tumor heterogeneity and an overall poor prognosis.The predominant molecular aleration was the H3F3A K27M mutation.Patients with co-altered MAPK pathway showed relatively better outcomes,providing new insights into the molecular genetic characteristics of DMG.

Purpose To investigate the clinicopathological features,molecular subtypes,and prognostic factors of diffuse midline glioma(DMG)with H3K27 alterations.Methods Clinical data from 19 patients from DMG were col-lected.The clinical manifestations,histopathological features,immunophenotypes,and molecular genetic characteris-tics were analyzed.Relevant literature was also reviewed.Results Among the 19 patients,12 cases had tumors loca-ted in the thalamus,while 7 cases had tumors in other midline regions(including 4 cases in the brainstem,1 case in the cerebellum,and 2 cases in the spinal cord).Clinical symptoms primarily included dizziness,gait instability,and blurred vision.Histological features were diverse,with 12 cases classified as high-grade gliomas and 7 cases as low-grade.Immunohistochemistry revealed a loss of H3K27me3 expression in all cases,with 18 cases showing diffuse H3K27M positivity and 1 case expressing EZHIP.Of the 16 cases that underwent next-generation sequencing(NGS),1 case showed EGFR mutation(1/16,6％),while the remaining 15 cases had H3F3A K27M mutations(15/16,94％).Among these,7 cases had ATRX mutations(7/15,46.6％),5 cases had MAPK pathway alterations(5/15,33.3％,including 2 cases FGFR1,2 cases NF1,1 case co-mutated with BRAF and NF1),5 cases had PDGFRA mis-sense mutations(5/15,33.3％),4 cases had p53 missense or frameshift deletions(4/15,26.6％).One case each had a DICER1 missense mutation and an IDH1-S202R frameshift deletion(1/15,6.6％).The prognosis was general-ly poor,with a median survival of 9.5 months.Conclusion DMG exhibits high tumor heterogeneity and an overall poor prognosis.The predominant molecular aleration was the H3F3A K27M mutation.Patients with co-altered MAPK pathway showed relatively better outcomes,providing new insights into the molecular genetic characteristics of DMG.

Objective:To compare the efficacy of double thread elastic locking intramedullary nail (ELIN) and threaded elastic intramedullary nail (TEIN) in the treatment of mid-shaft clavicular fracture.Methods:From August 2017 to September 2020, 33 patients with mid-shaft clavicular fractures were treated with ELIN (double threaded nail group), including 14 males and 19 females, age 52.09±16.32 years old; Robinson classification: 20 cases of type 2A2, 6 cases of type 2B1, and 7 cases of type 2B2. Thirty-two patients were selected as the control group with TEIN fixation (single threaded nail group) during the same period, including 13 males and 19 females; age 43.25±15.03 years old; Robinson classification: 19 cases of type 2A2 and 5 cases of type 2B1, 8 cases of 2B2 type. The operation time, intraoperative incision length, fracture healing time, internal fixation removal time, Constant-Murley shoulder joint score, disabilities of the arm, shoulder, and hand (DASH) score, fracture reduction and postoperative complications were compared between the two groups.Results:The patients in both groups were followed up after operation, the double-threaded screw group was followed up for 16-48 weeks (average, 23.7 weeks), and the single threaded nail group was followed up for 15-51 weeks (average, 22.9 weeks). The operation time of the double threaded nail group and the single threaded nail group were 19.45±6.74 min and 19.59±4.98 min, and the length of the incision was 1.70±0.79 cm and 1.73±0.84 cm. The fracture healing time were 12.12±1.29 weeks and 13.88±1.84 weeks. The internal fixation removal time was 13.09±1.31 weeks and 15.69±1.94 weeks. The Constant-Murley shoulder score was 93.18±3.78 points and 90.09±4.03 points, and the DASH scores were 1.49± 0.49 points and 3.85±1.13 points; There was no significant difference in operation time and incision length between the two groups ( t=0.01, 0.19; P>0.05), while fracture healing ( t=3.70, P<0.001), internal fixation removal time ( t=6.34, P<0.001), Constant-Murley shoulder score ( t=3.19, P<0.001), DASH score ( t=10.95, P<0.001) differences were statistically significant. The length of the clavicle on the healthy side was 16.38±1.09 cm in the double threaded nail group, and the length of the clavicle on the affected side after internal fixation removal was 16.33±1.12 cm. There was no obvious shortening deformity on the affected side, and there was no significant difference in the length of the clavicle between the two sides ( t=1.57, P=0.127). The clavicle lengths of the healthy side and the affected side after internal fixation removal in the single threaded nail group were 16.55±1.12 cm and 15.12±1.18 cm, and the difference was statistically significant ( t=8.02, P<0.001). The postoperative shortening values of the double-threaded screw group and the single-threaded screw group were 9.47±2.12 mm and 17.41±2.42 mm, and the difference was statistically significant ( t=14.07, P<0.001). Postoperatively, 5 cases of bursitis and 2 cases of skin irritation occurred in the double threaded nail group; While 6 cases of bursitis, 3 cases of skin irritation, 4 cases of shortening malunion, and 1 case of broken nail occurred in the single threaded nail group (fracture delayed union after replacement of internal fixation); the other patients did not experience screw retraction, wound infection, delayed fracture union or nonunion, neurovascular injury, and achieved osseous union. Conclusion:Both elastic intramedullary nails are effective surgical methods for the treatment of middle clavicle fractures, and the operation time is short and minimally invasive. However, compared with the TEIN, the fracture healing time of the double-threaded ELIN is shorter, the internal fixation removal time is earlier, the shoulder joint and upper limb function is better, and the shortening deformity is less likely to occur.

Objective:By comparing standard gonadotropin-releasing hormone antagonist regimen and gonadotropin-releasing hormone agonist-antagonist protocol (AAP regimen) in Patient-Oriented Strategies Encompassing Individualized Oocyte Number (POSEIDON) group 3 and group 4 patients with low prognosis, to study if AAP regimen could improve the clinical outcomes in low prognosis patients.Methods:A case-control study was performed, the clinical data of 646 cycles of prospective poor ovarian response (POR) patients (POSEIDON group 3 and 4) who received in vitro fertilization and embryo transfer (IVF-ET) in Peking University Third Hospital Department of Obstetrics and Gynecology, Reproductive Medical Center from January 2016 to May 2018 were retrospectively analyzed. The total number of AAP cycle was 323, and control group was selected from the database with 1∶1 matching of contemporaneous prospective POR patients (POSEIDON group 3 and group 4) with similar age and approaching date of oocyte retrieval. Patients' general information, ovarian stimulation indexes and clinical outcomes were compared. Results:AAP group had fewer antral follicle count (AFC) [3.00(2.00,4.00) vs. 4.00(2.00,5.00), P<0.001] and similar anti-Müllerian hormone (AMH) level [0.51(0.25,0.83) μg/L vs. 0.53(0.31,0.81) μg/L, P>0.05] compared with control group. AAP group had shorter duration of gonadotropin (Gn) used [10.00(8.00,11.00) d vs. 10.00(9.00,11.00) d, P=0.020] and lower dosage of Gn used [2 675.00(2 100.00,3 300.00) U vs. 3 075.00(2 550.00,3 750.00) U, P<0.001] than control group. AAP group had similar number of oocytes obtained [3.00(2.00,5.00) vs. 4.00(2.00,6.00), P>0.05] compared with control group. Under the same proportion of fertilization schemes (routine or intracytoplasmic sperm injection methods), AAP group had higher fertilization rate [74.15% (955/1288) vs. 69.13% (918/1328), P=0.004] and good-quality embryo rate [62.57% (585/935) vs. 56.94% (509/894), P=0.014], and ultimately had higher embryo implantation rate [22.31% (87/390) vs. 15.84% (64/404), P=0.020], cumulative clinical pregnancy rate [32.50% (78/240) vs. 22.86% (56/245), P=0.018] and cumulative live birth rate [25.83% (62/240) vs. 17.96% (44/245), P=0.036]. Conclusion:For POSEIDON patients with low prognosis and POR, controlled ovarian hyperstimulation with AAP regimen had better clinical outcomes compared with conventional antagonist regimen.

Objective:By comparing standard gonadotropin-releasing hormone antagonist regimen and gonadotropin-releasing hormone agonist-antagonist protocol (AAP regimen) in Patient-Oriented Strategies Encompassing Individualized Oocyte Number (POSEIDON) group 3 and group 4 patients with low prognosis, to study if AAP regimen could improve the clinical outcomes in low prognosis patients.Methods:A case-control study was performed, the clinical data of 646 cycles of prospective poor ovarian response (POR) patients (POSEIDON group 3 and 4) who received in vitro fertilization and embryo transfer (IVF-ET) in Peking University Third Hospital Department of Obstetrics and Gynecology, Reproductive Medical Center from January 2016 to May 2018 were retrospectively analyzed. The total number of AAP cycle was 323, and control group was selected from the database with 1∶1 matching of contemporaneous prospective POR patients (POSEIDON group 3 and group 4) with similar age and approaching date of oocyte retrieval. Patients' general information, ovarian stimulation indexes and clinical outcomes were compared. Results:AAP group had fewer antral follicle count (AFC) [3.00(2.00,4.00) vs. 4.00(2.00,5.00), P<0.001] and similar anti-Müllerian hormone (AMH) level [0.51(0.25,0.83) μg/L vs. 0.53(0.31,0.81) μg/L, P>0.05] compared with control group. AAP group had shorter duration of gonadotropin (Gn) used [10.00(8.00,11.00) d vs. 10.00(9.00,11.00) d, P=0.020] and lower dosage of Gn used [2 675.00(2 100.00,3 300.00) U vs. 3 075.00(2 550.00,3 750.00) U, P<0.001] than control group. AAP group had similar number of oocytes obtained [3.00(2.00,5.00) vs. 4.00(2.00,6.00), P>0.05] compared with control group. Under the same proportion of fertilization schemes (routine or intracytoplasmic sperm injection methods), AAP group had higher fertilization rate [74.15% (955/1288) vs. 69.13% (918/1328), P=0.004] and good-quality embryo rate [62.57% (585/935) vs. 56.94% (509/894), P=0.014], and ultimately had higher embryo implantation rate [22.31% (87/390) vs. 15.84% (64/404), P=0.020], cumulative clinical pregnancy rate [32.50% (78/240) vs. 22.86% (56/245), P=0.018] and cumulative live birth rate [25.83% (62/240) vs. 17.96% (44/245), P=0.036]. Conclusion:For POSEIDON patients with low prognosis and POR, controlled ovarian hyperstimulation with AAP regimen had better clinical outcomes compared with conventional antagonist regimen.

Objective To explore the control levels of blood glucose,blood lipid,blood pressure(BP),and body mass index(BMI)in the community-managed patients with type 2 diabetes in Jiangsu and to provide the basis for better management of type 2 diabetes in communities. Methods From December 2013 to January 2014,20 053 patients with type 2 diabetes and have received disease management according to the National Basic Public Health Service were recruited in Changshu County of Suzhou City, Huai'an and Qinghe Districts of Huai'an City. Questionnaire survey, anthropometric and laboratory measurements were conducted. According to the Chinese guidelines for type 2 diabetes prevention and treatment(2013),the control levels of blood glucose,blood lipid,BP, and BMI were assessed. Results Among 20 053 patients with type 2 diabetes,the proportions for controlled fasting plasma glucose(FPG) and HbA1Cwere 31.4% and 41.9% respectively,and 25.3% of the patients simultaneously achieved goals of FPG and HbA1Ccontrol. There were 23.9%,55.7%,75.5% and 24.2% of the patients met goals for total cholesterol (TC), triglyceride (TG), high-density lipoprotein-cholesterol (HDL-C), and low-density lipoprotein-cholesterol(LDL-C), respectively. Only 10. 3% of the patients achieved all the 4 targets of blood lipid. Furthermore,there were 25.4% and 35.9% patients achieved BP and BMI targets respectively,and the control rates for BP and BMI of females were higher than those of males(all P<0.05). Less than 1% of the patients had all eights indices controlled at target levels. Conclusions The achievement of comprehensive targets among community patients with type 2 diabetes remains poor in Jiangsu. Follow-up and management of type 2 diabetes should be strengthened in communities,health education and comprehensive intervention on disease complications should also be reinforced accordingly.

Objective To explore the problems of hospital elevator safety management.Methods Retrospective analysis of hospital management status of the elevator was done,and specific improvement measures were presented.Results In hospital elevator safety management,staff plays a very important role,and its technical level directly affects management effect.Conclusion Hospital elevator safety management quality directly affects the patients' visit.It needs to get attention from the hospital.

Objective To analyze the urine trace albumin(mALb)/creatinine(Cr) ratio and blood uric acid(UA),and other various metabolic index level in patients with diabetic nephropathy(DN),combined with clinical data such as patients' age,body mass index(BMI),course of diseases,to explore the related mechanism of occurrence and development of DN.Methods 76 DN patients were selected.The microalbuminuria group(urinary mALb/Cr<300μg/mg) had 46 cases,the clinical albuminuria group(urinary mALb/Cr≥300μg/mg) included 30 cases,another 49 diabetic patients without kidney damage were seleted as control group.The urinary mALb/Cr,blood UA,fasting blood glucose(FBG),triacylglycerol(TG),total cholesterol(TC),high-density lipoprotein(HDL),low density lipoprotein(LDL),glycosylated hemoglobin(HbA1c) levels were determined.The BMI and the length of the course of the disease calculate.Results The patients' age,course of the disease,urinary mALb/Cr,blood UA,FBG,TC,TG,LDL,HbA1c and BMI level in the clinical albuminuria group and microalbuminuria group were significantly higher than those in the control group,the differences were statistically significant (F=6.18,12.48,141.43,12.48,8.49,4.98,6.18,3.89,3.17,3.89,all P<0.05).The high uric acid hematic disease rates of the clinical albuminuria group and microalbuminuria group were 26.09% and 26.09%,which were significantly higher than 10.20% of the control group,the differences were statistically significant(x2=4.074,24.833,all P<0.05).Urinary mALb/Cr was positively correlated with age,duration,BMI,UA,TG,TC,LDL,FBG,HbA1c(r=0.120,0.299,0.148,0.340,0.157,0.149,0.103,0.487,0.103).Multiple linear stepwise regression analysis suggested that duration,blood UA,FBG were independent risk factors of urinary mALb/Cr;TG,BMI,urinary mALb/Cr were independent risk factors for blood UA.Conclusion Urinary mALb/Cr and blood UA are the independent risk factors,high uric acid hematic disease may participate in the development process of DN,and diabetes duration,UA,BMI,TG,TC,LDL,FBG,HbA1C associated with increased urinary mALb/Cr excretory DN patients,the effective monitoring can improve the symptoms of DN and quality of life.

Objective To understand the epidemiological characteristics of head injuries through data gathered from the Jiangsu Injury Surveillance System.Methods Data on head injury that occurred during 2006-2014 were collected from the Jiangsu injury surveillance system and analyzed by SPSS 19.0 software.Results From 2006 to 2014,data on 133 172 cases of head injuries were collected which accounting for 26.2％ (133 172/509 175) of all the injury cases.Among them,males were 2.18 times higher than the females.The top five leading causes of head injuries were falls 24.6％ (32 796/133 172),blunt force injuries 24.4％ (32 446/133 172),motor car accident injuries 20.3％ (26 993/133 172),knife or sharp force injuries 10.7％ (14 183/133 172) and non-motor car accident injuries 6.7％ (8 919/133 172).Main locations that head injuries occured would involve roads/ streets 32.5％ (43 262/133 172),working places 22.2％ (29 526/133 172),at home 20.5％ (27 925/ 133 172) and public residences 10.8％ (14 367/133 172).Recreation activates 37.9％ (50 479/133 172),driving 26.1％(34 749/133 172),paid jobs 24.8％ (33 034/133 172) were the three major activities related to head injuries.Severity of injuries would depend on the situations on site.As for minor injuries,bruise accounted for 63.5％ (67 929/106 912).Brain trauma 21.5％ (5 119/23 803) and fracture 14.9％ (3 554/23 803) appeared an increasing trend.Severe injuries would include brain trauma 74.6％ (1 833/2 457).78.8％ (104 940/133 172) of the patients with head injuries would go home after receiving treatment the hospital,with fetality only as 0.1％ (134/133 172).Conclusion Data from the Jiangsu surveillance program showed that Head injury appeared the highest proportion among all the body injuries that called for special attention.