Mutations in the cyclin-dependent kinase-like 5 gene (CDKL5) cause a severe neurodevelopmental disorder, yet the impact of truncating mutations remains unclear. Here, we introduce the Cdkl5^492stop mouse model, mimicking C-terminal truncating mutations in patients. 492stop/Y mice exhibit altered dendritic spine morphology and spontaneous seizure-like behaviors, alongside other behavioral deficits. After creating cell lines with various Cdkl5 truncating mutations, we found that these mutations are regulated by the nonsense-mediated RNA decay pathway. Most truncating mutations result in CDKL5 protein loss, leading to multiple disease phenotypes, and offering new insights into the pathogenesis of CDKL5 disorder.
Animals ; Disease Models, Animal ; Mice ; Protein Serine-Threonine Kinases/deficiency* ; Mutation/genetics* ; Epileptic Syndromes/genetics* ; Humans ; Dendritic Spines/pathology* ; Spasms, Infantile/genetics* ; Male ; Seizures/genetics* ; 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*

Public cell culture platform is an important facility in laboratory animal facilities, providing essential support for scientific research such as the development of animal tumor disease models and transgenic animals. By establishing a public cell culture experimental platform, laboratory animal centers can effectively integrate experimental animals and cell culture resources, optimizing the allocation of scientific research resources to facilitate better research outcomes. The majority of cells cultured in these platforms are used for animal experiments. Contamination or quality issues in these cells not only affect experimental results but also jeopardize the health of experimental animals, potentially leading to microbial infections and contamination of entire animal facilities. Therefore, public cell culture laboratories within experimental animal facilities impose stricter quality control measures than conventional cell culture rooms. This study takes the public cell culture platform at the Laboratory Animal Center of Shanghai Jiao Tong University as a case study to discuss management experiences, focusing on facility maintenance and management, personnel management and quality control of cell biological risk. The aim is to provide useful reference for the management of public cell culture laboratories in experimental animal facilities and other institutions.

Small for gestational age (SGA) infants are more likely to experience neurocognitive impairments compared to appropriate for gestational age (AGA) infants. This paper reviews recent research on the neurocognitive development of SGA children. SGA can lead to a "brain-sparing effect" due to growth restriction, which may affect cerebral blood flow and brain structure. However, this does not guarantee normal brain development. Restrictive blood flow can result in changes in brain structure, such as reduced total white matter and gray matter volume in various brain regions, including the cerebral cortex, hippocampus and cerebellum, ultimately leading to decreased head circumference. SGA children also exhibit lower scores in all neurocognitive domains, including intelligence, attention, memory, and executive function. This may result in poor academic performance and an increased risk of social, behavioral, and neurological problems, such as cerebral palsy, epilepsy, visual and hearing impairments, as well as comorbidities like attention deficit hyperactivity disorder(ADHD), autism spectrum disorder(ASD), anxiety, depression, and schizophrenia. Several risk factors for SGA-related neurocognitive impairments have been identified, including gestational hypertension, abnormal gestational weight, smoking, and catch-up growth. Studies have shown that the best interventions to improve cognitive dysplasia include nutrient supplementation, continued breastfeeding, high-quality education, and appropriate early intervention (responsive parenting) are effective in improving cognitive outcomes for SGA children.

Pyroptosis is the programmed death of cells accompanied by an inflammatory response and is widely involved in the development of a variety of diseases, such as infectious diseases, cardiovascular diseases, and neurodegeneration. It has been shown that cellular scorching is involved in the pathogenesis of pulmonary arterial hypertension ( PAH) in cardiovascular diseases. Patients with PAH have perivascular inflammatory infiltrates in lungs, pulmonary vasculopathy exists in an extremely inflam-matory microenvironment, and pro-inflammatory factors in cellular scorching drive pulmonary vascular remodelling in PAH patients. This article reviews the role of cellular scorch in the pathogenesis of PAH and the related research on drugs for the treatment of PAH, with the aim of providing new ideas for clinical treatment of PAH.

AIM: To analyze the abnormal refractive status of infants and young children aged 6 to 48 months, and to provide basis for the correction of ametropia and the early prevention and treatment of amblyopia.METHODS: Infants and young children aged 6 to 48 months were examined for refraction by Spot vision screener for natural optometry. Clinical data of infants and young children with refractive abnormalities were collected, Ciliary muscle paralysis agent was used for retinoscopy and optometry, and the results were statistically analyzed.RESULTS: A total of 168 cases(336 eyes)with abnormal Spot refractive outcomes were collected, with a high proportion of hyperopia and astigmatism abnormalities, 38.4% and 28.6%, respectively, while the proportion of myopia was low(12.2%). There were 90 cases of anisometropia(≥1.00 D), among which 41 cases(45.6%)were astigmatic anisometropia, 33 cases(36.7%)were hyperopic anisometropia, and 16 cases(17.8%)were myopic anisometropia, accounting for the least proportion. A total of 109 infants and young children with Spot refractive abnormalities completed ciliary muscle paralysis retinal optometry. The analysis of the difference and correlation between Spot diopter and post ciliary muscle paralysis optometry results showed that the difference in astigmatism was 0.34±0.64 D(P<0.001), the difference in hyperopia was -2.10±1.27 D(P<0.001), and the difference in myopia was -0.43±0.91 D(P=0.023). Although there was a statistical difference between the two results, astigmatism, hyperopia, and myopia were highly positively correlated, respectively(r=0.694, 0.762, 0.909).CONCLUSION: The main refractive abnormalities in infants and young children aged 6 to 48 months are astigmatism, hyperopia, and anisometropia, with fewer abnormalities in myopia. For screening abnormalities, further ciliary muscle paralysis agent retinoscopy and optometry should be performed, and glasses correction should be given to effectively prevent refractive amblyopia in infants and young children.

Objective:This study aimed to introduce droplet digital PCR (ddPCR) for monitoring Epstein-Barr virus (EBV) infection after allogeneic hematopoietic stem cell transplantation (alloHSCT) in children and assess its viability as a complementary detection method in clinical settings.Methods:A total of 290 blood samples from 47 children undergoing alloHSCT were collected. Both ddPCR and real-time quantitative PCR (qPCR) were employed to detect EBV DNA load in plasma, with a comparison of detection efficiencies between the two methods. Continuous monitoring of 39 children was conducted to observe dynamic changes in EBV DNA load in plasma and analyze the merits and drawbacks of both methods.Results:The EBV positive detection rate of ddPCR was significantly higher than that of qPCR ( χ2=20.25, P<0.001), particularly in samples with low viral loads. Among the children monitored continuously for EBV DNA, 14 out of 39 exhibited positive ddPCR result. Notably, in two cases where patients displayed rash and fever symptoms with positive ddPCR result but negative qPCR result, ddPCR demonstrated heightened sensitivity in early EBV infection detection. Conclusions:ddPCR holds certain advantages in monitoring EBV infection post-alloHSCT in children, especially for samples with low viral loads. However, as this method is still in the exploratory stage of clinical application, further research and practice are needed to validate its utility.

Objective:To explore the treatment methods and clinical efficacy of penetrating high-voltage electric burns to thoracoabdominal wall.Methods:This study was a retrospective observational study. From March 2020 to March 2023, six male patients with penetrating high-voltage electric burns to thoracoabdominal wall who met the inclusion criteria were hospitalized at West China Hospital of Sichuan University, aged 42 to 57 years. Among them, one patient had thoracoabdominal wall defects with perforation and necrosis of the gastric wall and diaphragm, two patients had thoracoabdominal wall defects with perforation and necrosis of the gastric wall alone, and three patients had abdominal wall defects with perforation and necrosis of the small intestine. In the emergency department, aesthetic plastic and burn surgery, general surgery, and/or thoracic surgery doctors jointly formulated an emergency surgery plan for the patients. Three patients with perforation and necrosis of the gastric wall underwent subtotal gastrectomy and anastomosis. One of them, who also had diaphragmatic perforation and necrosis, underwent resection of the necrotic diaphragm and repair. The other three patients with perforation and necrosis of the small intestine underwent resection and anastomosis of the necrotic intestinal segment. After debriding the thoracoabdominal wall wounds conservatively in stage Ⅰ and repairing the abdominal wall defects with greater omentum coverage, the thoracoabdominal wall wounds were treated with vacuum sealing drainage (VSD). Seven days later, a stage Ⅱ thorough debridement of the thoracoabdominal wall wounds was performed, and bovine acellular dermal matrix was transplanted onto the surface of the greater omentum and the surrounding skin wounds without skin coverage, and the VSD treatment of the thoracoabdominal wall wounds was continued. After 7 days, the VSD treatment was stopped, and after the fresh granulation tissue well developed in the wounds, a stage Ⅲ transplantation of meshed split-thickness skin graft from the lateral femur was performed to close the thoracoabdominal wall wounds, followed by continuing VSD treatment for another 7 days. Data were recorded including the status of patients' enteral nutrition recovery and occurrence of complications such as abdominal infection after stage Ⅰ surgery, the time from starting moist dressing change to the wound being ready for skin grafting after stage Ⅱ surgery, the microbiological culture of wound exudate samples and conditions of wound surrounding areas from starting moist dressing change to wound healing after stage Ⅱ surgery, skin graft survival, and wound healing time. Follow-up was carried out to observe the occurrence of gastrointestinal symptoms, abdominal wall hernia, scars, and functional disorders, etc.Results:All six patients resumed enteral nutrition on day 2 to 4 after stage Ⅰ surgery, with no occurrence of intestinal obstruction, anastomotic leakage, or abdominal infection. The time from starting moist dressing change to the wound being ready for skin grafting after stage Ⅱ surgery was 8 (6, 12) days. During the period from starting moist dressing change to wound healing after stage Ⅱ surgery, microbiological culture of wound exudate sample showed Enterobacter cloacae in one patient and Pseudomonas aeruginosa in another patient, while the remaining four patients had negative cultures; no patient developed wound edge inflammation. All grafted skin survived, and the wound healing time was 38 (30, 46) days. During follow-up from 12 to 36 months after stage Ⅲ surgery, patients had no intractable constipation or intestinal obstruction symptoms, no obvious local tissue herniation requiring surgical treatment, no scar ulceration, and no functional disorders. Conclusions:For penetrating high-voltage electric burns to thoracoabdominal wall, a sequential three-stage surgical treatment plan under a multidisciplinary team collaboration model can effectively protect organ function and control wound infection. Long-term follow-up shows good gastrointestinal function and thoracoabdominal wall appearance. This method is highly reproducible and effective, which is suitable for clinical promotion and use.

Objective To investigate the distribution and antimicrobial resistance profiles of the common pathogens isolated from urine from 2015 to 2021 in the CHINET Antimicrobial Resistance Surveillance Program.Methods The bacterial strains were isolated from urine and identified routinely in 51 hospitals across China in the CHINET Antimicrobial Resistance Surveillance Program from 2015 to 2021.Antimicrobial susceptibility was determined by Kirby-Bauer method,automatic microbiological analysis system and E-test according to the unified protocol.Results A total of 261 893 nonduplicate strains were isolated from urine specimen from 2015 to 2021,of which gram-positive bacteria accounted for 23.8％(62 219/261 893),and gram-negative bacteria 76.2％(199 674/261 893).The most common species were E.coli(46.7％),E.faecium(10.4％),K.pneumoniae(9.8％),E.faecalis(8.7％),P.mirabilis(3.5％),P.aeruginosa(3.4％),SS.agalactiae(2.6％),and E.cloacae(2.1％).The strains were more frequently isolated from inpatients versus outpatients and emergency patients,from females versus males,and from adults versus children.The prevalence of ESBLs-producing strains in E.coli,K.pneumoniae and P.mirabilis was 53.2％,52.8％and 37.0％,respectively.The prevalence of carbapenem-resistant strains in E.coli,K.pneumoniae,P.aeruginosa and A.baumannii was 1.7％,18.5％,16.4％,and 40.3％,respectively.Lower than 10％of the E.faecalis isolates were resistant to ampicillin,nitrofurantoin,linezolid,vancomycin,teicoplanin and fosfomycin.More than 90％of the E.faecium isolates were ressitant to ampicillin,levofloxacin and erythromycin.The percentage of strains resistant to vancomycin,linezolid or teicoplanin was＜2％.The E.coli,K.pneumoniae,P.aeruginosa and A.baumannii strains isolated from ICU inpatients showed significantly higher resistance rates than the corresponding strains isolated from outpatients and non-ICU inpatients.Conclusions E.coli,Enterococcus and K.pneumoniae are the most common pathogens in urinary tract infection.The bacterial species and antimicrobial resistance of urinary isolates vary with different populations.More attention should be paid to antimicrobial resistance surveillance and reduce the irrational use of antimicrobial agents.

Objective To understand the distribution and changing resistance profiles of clinical isolates of Enterococcus in hospitals across China from 2015 to 2021.Methods Antimicrobial susceptibility testing was conducted for the clinical isolates of Enterococcus according to the unified protocol of CHINET program by automated systems,Kirby-Bauer method,or E-test strip.The results were interpreted according to the Clinical & Laboratory Standards Institute(CLSI)breakpoints in 2021.WHONET 5.6 software was used for statistical analysis.Results A total of 124 565 strains of Enterococcus were isolated during the 7-year period,mainly including Enterococcus faecalis(50.7％)and Enterococcus faecalis(41.5％).The strains were mainly isolated from urinary tract specimens(46.9％±2.6％),and primarily from the patients in the department of internal medicine,surgery and ICU.E.faecium and E.faecalis strains showed low level resistance rate to vancomycin,teicoplanin and linezolid(≤3.6％).The prevalence of vancomycin-resistant E.faecalis and E.faecium was 0.1％and 1.3％,respectively.The prevalence of linezolid-resistant E.faecalis increased from 0.7％in 2015 to 3.4％in 2021,while the prevalence of linezolid-resistant E.faecium was 0.3％.Conclusions The clinical isolates of Enterococcus were still highly susceptible to vancomycin,teicoplanin,and linezolid,evidenced by a low resistance rate.However,the prevalence of linezolid-resistant E.faecalis was increasing during the 7-year period.It is necessary to strengthen antimicrobial resistance surveillance to effectively identify the emergence of antibiotic-resistant bacteria and curb the spread of resistant pathogens.