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: This study aimed to explore the association between body mass index (BMI) and mortality based on the 10-year population-based multicenter prospective study. METHODS: A general population-based multicenter prospective study was conducted at four sites in rural China between 2013 and 2023. Multivariate Cox proportional hazards models and restricted cubic spline analyses were used to assess the association between BMI and mortality. Stratified analyses were performed based on the individual characteristics of the participants. RESULTS: Overall, 19,107 participants with a sum of 163,095 person-years were included and 1,910 participants died. The underweight (< 18.5 kg/m ²) presented an increase in all-cause mortality (adjusted hazards ratio [ aHR] = 2.00, 95% confidence interval [ CI]: 1.66-2.41), while overweight (≥ 24.0 to < 28.0 kg/m ²) and obesity (≥ 28.0 kg/m ²) presented a decrease with an aHR of 0.61 (95% CI: 0.52-0.73) and 0.51 (95% CI: 0.37-0.70), respectively. Overweight ( aHR = 0.76, 95% CI: 0.67-0.86) and mild obesity ( aHR = 0.72, 95% CI: 0.59-0.87) had a positive impact on mortality in people older than 60 years. All-cause mortality decreased rapidly until reaching a BMI of 25.7 kg/m ² ( aHR = 0.95, 95% CI: 0.92-0.98) and increased slightly above that value, indicating a U-shaped association. The beneficial impact of being overweight on mortality was robust in most subgroups and sensitivity analyses. CONCLUSION This study provides additional evidence that overweight and mild obesity may be inversely related to the risk of death in individuals older than 60 years. Therefore, it is essential to consider age differences when formulating health and weight management strategies.
Humans ; Body Mass Index ; China/epidemiology* ; Male ; Female ; Middle Aged ; Prospective Studies ; Rural Population/statistics & numerical data* ; Aged ; Follow-Up Studies ; Adult ; Mortality ; Cause of Death ; Obesity/mortality* ; Overweight/mortality*

Objective:To explore the effectiveness of interprofessional cooperative simulation in teaching emergency care for shock patients among intensive care unit (ICU) undergraduate nursing students.Methods:An interprofessional cooperative simulation-based teaching faculty team was established for ICU undergraduate nursing students, and a shock case library was developed. Using convenience sampling, 32 ICU undergraduate nursing students in 2022 were selected as the control group and received conventional simulation-based teaching, with students rotating through roles as nurses, standardized patients, doctors, and family members. In the experimental group, 34 ICU undergraduate nursing students in 2023 and 24 ICU clinical medicine interns were recruited to act as doctors for interprofessional cooperative simulation-based teaching. Each group was divided into subgroups, with each subgroup consisting of 4-5 nursing students. One group completed simulation-based training per month for a total of 8 sessions, with each session lasting 3 hours. The teaching adopted the on-site "tidal ward" in situ simulation, and the scenarios included patient history collection and health assessment, shock emergency care, nursing evaluation, and health education. The differences between the two groups of nursing students were compared in terms of ICU exit theoretical assessment score, objective structured clinical examination skill assessment score, and satisfaction with simulation-based teaching. SPSS 22.0 was used for independent samples t test and Mann-Whitney U test. Results:The experimental group achieved significantly higher scores in theoretical assessment (84.65±8.06), total score of satisfaction with simulation-based teaching (101.00±5.13), and clinical learning and multiprofessional team dimensions (47.32±3.35) compared to the control group ( P<0.001). The experimental group achieved higher scores in objective structured clinical examination skill assessment (81.40±7.22), guiding feedback and reflection (37.50±3.04), and judgmental thinking and clinical reasoning (16.00±2.03) compared to the control group, though the differences were not significant ( P=0.977, 0.668, and 0.636). Conclusions:Interprofessional cooperative simulation enhances the shock patient emergency care abilities and satisfaction with simulation-based teaching for undergraduate nursing students.

Objective:To explore the effectiveness of interprofessional cooperative simulation in teaching emergency care for shock patients among intensive care unit (ICU) undergraduate nursing students.Methods:An interprofessional cooperative simulation-based teaching faculty team was established for ICU undergraduate nursing students, and a shock case library was developed. Using convenience sampling, 32 ICU undergraduate nursing students in 2022 were selected as the control group and received conventional simulation-based teaching, with students rotating through roles as nurses, standardized patients, doctors, and family members. In the experimental group, 34 ICU undergraduate nursing students in 2023 and 24 ICU clinical medicine interns were recruited to act as doctors for interprofessional cooperative simulation-based teaching. Each group was divided into subgroups, with each subgroup consisting of 4-5 nursing students. One group completed simulation-based training per month for a total of 8 sessions, with each session lasting 3 hours. The teaching adopted the on-site "tidal ward" in situ simulation, and the scenarios included patient history collection and health assessment, shock emergency care, nursing evaluation, and health education. The differences between the two groups of nursing students were compared in terms of ICU exit theoretical assessment score, objective structured clinical examination skill assessment score, and satisfaction with simulation-based teaching. SPSS 22.0 was used for independent samples t test and Mann-Whitney U test. Results:The experimental group achieved significantly higher scores in theoretical assessment (84.65±8.06), total score of satisfaction with simulation-based teaching (101.00±5.13), and clinical learning and multiprofessional team dimensions (47.32±3.35) compared to the control group ( P<0.001). The experimental group achieved higher scores in objective structured clinical examination skill assessment (81.40±7.22), guiding feedback and reflection (37.50±3.04), and judgmental thinking and clinical reasoning (16.00±2.03) compared to the control group, though the differences were not significant ( P=0.977, 0.668, and 0.636). Conclusions:Interprofessional cooperative simulation enhances the shock patient emergency care abilities and satisfaction with simulation-based teaching for undergraduate nursing students.

Objective To investigate the clinical characteristics and prognosis of pneumococcal meningitis(PM),and drug sensitivity of Streptococcus pneumoniae(SP)isolates in Chinese children.Methods A retrospective analysis was conducted on clinical information,laboratory data,and microbiological data of 160 hospitalized children under 15 years old with PM from January 2019 to December 2020 in 33 tertiary hospitals across the country.Results Among the 160 children with PM,there were 103 males and 57 females.The age ranged from 15 days to 15 years,with 109 cases(68.1% )aged 3 months to under 3 years.SP strains were isolated from 95 cases(59.4% )in cerebrospinal fluid cultures and from 57 cases(35.6% )in blood cultures.The positive rates of SP detection by cerebrospinal fluid metagenomic next-generation sequencing and cerebrospinal fluid SP antigen testing were 40% (35/87)and 27% (21/78),respectively.Fifty-five cases(34.4% )had one or more risk factors for purulent meningitis,113 cases(70.6% )had one or more extra-cranial infectious foci,and 18 cases(11.3% )had underlying diseases.The most common clinical symptoms were fever(147 cases,91.9% ),followed by lethargy(98 cases,61.3% )and vomiting(61 cases,38.1% ).Sixty-nine cases(43.1% )experienced intracranial complications during hospitalization,with subdural effusion and/or empyema being the most common complication[43 cases(26.9% )],followed by hydrocephalus in 24 cases(15.0% ),brain abscess in 23 cases(14.4% ),and cerebral hemorrhage in 8 cases(5.0% ).Subdural effusion and/or empyema and hydrocephalus mainly occurred in children under 1 year old,with rates of 91% (39/43)and 83% (20/24),respectively.SP strains exhibited complete sensitivity to vancomycin(100% ,75/75),linezolid(100% ,56/56),and meropenem(100% ,6/6).High sensitivity rates were also observed for levofloxacin(81% ,22/27),moxifloxacin(82% ,14/17),rifampicin(96% ,25/26),and chloramphenicol(91% ,21/23).However,low sensitivity rates were found for penicillin(16% ,11/68)and clindamycin(6% ,1/17),and SP strains were completely resistant to erythromycin(100% ,31/31).The rates of discharge with cure and improvement were 22.5% (36/160)and 66.2% (106/160),respectively,while 18 cases(11.3% )had adverse outcomes.Conclusions Pediatric PM is more common in children aged 3 months to under 3 years.Intracranial complications are more frequently observed in children under 1 year old.Fever is the most common clinical manifestation of PM,and subdural effusion/emphysema and hydrocephalus are the most frequent complications.Non-culture detection methods for cerebrospinal fluid can improve pathogen detection rates.Adverse outcomes can be noted in more than 10% of PM cases.SP strains are high sensitivity to vancomycin,linezolid,meropenem,levofloxacin,moxifloxacin,rifampicin,and chloramphenicol.[Chinese Journal of Contemporary Pediatrics,2024,26(2):131-138]

OBJECTIVE: To investigate the effect of holmium laser ω-shaped pre-transection of the prostate apex (PTPA) with preservation of the bladder neck on the urinary continence and sexual function of the patients with BPH after transurethral holmium laser enucleation of the prostate (HoLEP). METHODS: This retrospective study included 165 cases of BPH undergoing holmium laser ω-shaped PTPA with preservation of the bladder neck following HoLEP from January 2018 to January 2023. We recorded and compared the baseline, perioperative and 12-month follow-up data on the patients, and evaluated their urination function using IPSS, maximum urinary flow rate (Qmax), postvoid residual urine volume (PVR), and quality of life (QOL) scores. For those who had had sexual activity and normal ejaculation before surgery, we further assessed their erectile and ejaculatory functions postoperatively. RESULTS: The mean surgical time was (70.35±12.27) min, the intraoperative blood loss (60.12±19.54) ml, and the weight of the excised gland (56.37±13.71) g. The hospital stay and postoperative catheter-indwelling time averaged (5.13±2.34) and (3.21±1.37) d, respectively. Significant improvements were observed in IPSS, QOL, PVR and Qmax at 3, 6 and 12 months after surgery compared with the baseline (P<0.05), which all remained stable throughout the follow-up period. At 3 months after surgery, stress urinary incontinence was found in 10.91% of the patients, and all but 1 case (0.6%) recovered within 12 months. There were no significant changes in the IIEF-5 and Erectile Hardness Scale (EHS) scores postoperatively (P>0.05). Retrograde ejaculation occurred in 19 (11.52%) of the patients, but none experienced painful ejaculation after surgery. CONCLUSION Holmium laser ω-shaped PTPA with preservation of the bladder neck is safe and effective for the treatment of BPH, which can effectively improve the urinary continence and protect the sexual function of the patient.
Humans ; Male ; Prostatic Hyperplasia/surgery* ; Lasers, Solid-State/therapeutic use* ; Retrospective Studies ; Quality of Life ; Urinary Bladder ; Urinary Incontinence ; Transurethral Resection of Prostate/methods* ; Prostate/surgery* ; Ejaculation ; Aged ; Middle Aged

COVID-19 has been prevalent for three years. The virulence of SARS-CoV-2 is weaken as it mutates continuously. However, elderly patients, especially those with underlying diseases, are still at high risk of developing severe infections. With the continuous study of the molecular structure and pathogenic mechanism of SARS-CoV-2, antiviral drugs for COVID-19 have been successively marketed, and these anti-SARS-CoV-2 drugs can effectively reduce the severe rate and mortality of elderly patients. This article reviews the mechanism, clinical medication regimens, drug interactions and adverse reactions of five small molecule antiviral drugs currently approved for marketing in China, so as to provide advice for the clinical rational use of anti-SARS-CoV-2 in the elderly.

Tbx18,Wt1,and Tcf21 have been identified as epicardial markers during the early embryonic stage.However,the gene markers of mature epicardial cells remain unclear.Single-cell transcriptomic analysis was performed with the Seurat,Monocle,and CellphoneDB packages in R software with standard pro-cedures.Spatial transcriptomics was performed on chilled Visium Tissue Optimization Slides(10x Genomics)and Visium Spatial Gene Expression Slides(10x Genomics).Spatial transcriptomics analysis was performed with Space Ranger software and R software.Immunofluorescence,whole-mount RNA in situ hybridization and X-gal staining were performed to validate the analysis results.Spatial transcriptomics analysis revealed distinct transcriptional profiles and functions between epicardial tissue and non-epicardial tissue.Several gene markers specific to postnatal epicardial tissue were identified,including Msln,C3,Efemp1,and Upk3b.Single-cell transcriptomic analysis revealed that cardiac cells from wildtype mouse hearts(from embryonic day 9.5 to postnatal day 9)could be categorized into six major cell types,which included epicardial cells.Throughout epicardial development,Wt1,Tbx18,and Upk3b were consistently expressed,whereas genes including Msln,C3,and Efemp1 exhibited increased expression during the mature stages of development.Pseudotime analysis further revealed two epicardial cell fates during maturation.Moreover,Upk3b,Msln,Efemp1,and C3 positive epicardial cells were enriched in extracellular matrix signaling.Our results suggested Upk3b,Efemp1,Msln,C3,and other genes were mature epicardium markers.Extracellular matrix signaling was found to play a critical role in the mature epicardium,thus suggesting potential therapeutic targets for heart regeneration in future clinical practice.

The coronavirus disease 2019 (COVID-19) has been a global epidemic for more than three years, causing more than 6.9 million deaths. COVID-19 has the clinical characteristics of strong infectivity and long incubation period, and can cause multi-system damage, mainly lung damage, clinical symptoms of acute respiratory distress syndrome (ARDS) and systemic multiple organ damage. The SARS-CoV-2 virus is still constantly mutating. At present, there is no global consensus on the pathological changes of COVID-19 associated deaths and even no consensus on the criteria for determining the cause of death. The investigation of the basic pathological changes and progression of the disease is helpful to guide the clinical treatment and the development of therapeutic drugs. This paper reviews the autopsy reports and related literature published worldwide from February 2020 to June 2023, with a clear number of autopsy cases and corresponding pathological changes of vital organs as the inclusion criteria. A total of 1 111 autopsy cases from 65 papers in 18 countries are included. Pathological manifestations and causes of death are classified and statistically analyzed, common pathological changes of COVID-19 are summarized, and analytical conclusions are drawn, suggesting that COVID-19 infection can cause life-threatening pathological changes in vital organs. On the basis of different health levels of infected groups, the direct cause of death is mainly severe lung damage and secondary systemic multiple organ failure.
Humans ; SARS-CoV-2 ; COVID-19/pathology* ; Cause of Death ; Lung/pathology* ; Autopsy

The traditional life concept of "body-mind holism" in Chinese medicine has drawn a special attention with the development of modern psychosomatic medicine. The "body-mind holism" is valuable in the guidance for clinical acupuncture practice, but, it is only remained on the theoretical significance by the medical masters in the past dynasties. In the paper, based on the understanding of Huangdi Neijing (Yellow Emperor's Internal Classic), the similarities and differences are compared between the body-mind theory and psychosomatic medicine. In association with clinical observation, from three aspects, i.e. body-mind pathogenesis, acupoint detection and observing the mind, and body-mind treatment, the guidance of "body-mind holism" is explored for the clinical diagnosis and treatment of acupuncture and moxibustion; the referents of "body" and "mind" are clarified in views of disease, diagnosis and treatment; and the treatment strategies of acupuncture and moxibustion are discussed in the perspective of "body-mind holism".
Moxibustion ; Psychosomatic Medicine ; Acupuncture Therapy ; Acupuncture ; Acupuncture Points ; Medicine, Chinese Traditional ; Meridians