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*

Objective:To understand the characteristics of new infections in the newly reported HIV-1 infected population in Luzhou, to find out the characteristics of the high-risk population, which may provide a basis for developing precise prevention and control measures locally.Methods:HIV-1 LAg Avidity EIA test was applied for newly reported cases in Luzhou from 2018 to 2021. The chi-square test was used for univariate analysis, logistic regression model for multivariate analysis, and spatial autocorrelation and hotspot analysis were applied to explore the spatial distribution characteristics of new infections in Luzhou city.Results:A total of 4 494 cases reported in the odd-numbered months were selected for testing, with 673 newly infected cases and the proportion of newly infected cases was 14.98%. Newly infected cases were predominantly male (472/673, 70.13%), married (335/673, 49.78%), heterosexual transmission (621/673, 92.27%), age>50 years (520/673, 77.27%), and junior high school or lower education (599/673, 89.00%). The proportion of new infections in each year were 11.74% (129/1 099), 17.11% (247/1 444), 13.57% (154/1 134) and 17.50% (143/817), respectively, with a statistically significant difference ( χ2=20.024, P<0.001) and an upward trend ( χ2=5.997, P=0.014). There were statistically significant differences in different transmission routes, gender, education level, occupation, sample source and residence (all P<0.05). Logistic regression analysis showed that gender, marital status, transmission route, current address, and sample source were all influencing factors for new infections. There are spatial autocorrelation characteristics of new case incidence in 2018 and 2021, hotspot areas gradually shifted from dispersed to relatively concentrated, with the number fluctuating with reported year. Conclusions:The proportion of new HIV-1 infections in Luzhou is relatively low throughout the province, but it is on the rise. The proportion of new infections is higher among youth, students, homosexual transmission, and retired persons. Attention should be focused on hotspot areas and routine surveillance and testing of key populations in hotspot areas should be strengthened.

Objective To summarize the changing prevalence of carbapenem resistance in Enterobacterales based on the data of CHINET Antimicrobial Resistance Surveillance Program from 2015 to 2021 for improving antimicrobial treatment in clinical practice.Methods Antimicrobial susceptibility testing was performed using a commercial automated susceptibility testing system according to the unified CHINET protocol.The results were interpreted according to the breakpoints of the Clinical & Laboratory Standards Institute(CLSI)M100 31st ed in 2021.Results Over the seven-year period(2015-2021),the overall prevalence of carbapenem-resistant Enterobacterales(CRE)was 9.43％(62 342/661 235).The prevalence of CRE strains in Klebsiella pneumoniae,Citrobacter freundii,and Enterobacter cloacae was 22.38％,9.73％,and 8.47％,respectively.The prevalence of CRE strains in Escherichia coli was 1.99％.A few CRE strains were also identified in Salmonella and Shigella.The CRE strains were mainly isolated from respiratory specimens(44.23±2.80)％,followed by blood(20.88±3.40)％and urine(18.40±3.45)％.Intensive care units(ICUs)were the major source of the CRE strains(27.43±5.20)％.CRE strains were resistant to all the β-lactam antibiotics tested and most non-β-lactam antimicrobial agents.The CRE strains were relatively susceptible to tigecycline and polymyxins with low resistance rates.Conclusions The prevalence of CRE strains was increasing from 2015 to 2021.CRE strains were highly resistant to most of the antibacterial drugs used in clinical practice.Clinicians should prescribe antimicrobial agents rationally.Hospitals should strengthen antibiotic stewardship in key clinical settings such as ICUs,and take effective infection control measures to curb CRE outbreak and epidemic in hospitals.

Objective To characterize the changing species distribution and antibiotic resistance profiles of respiratory isolates in hospitals participating in the CHINET Antimicrobial Resistance Surveillance Program from 2015 to 2021.Methods Commercial automated antimicrobial susceptibility testing systems and disk diffusion method were used to test the susceptibility of respiratory bacterial isolates to antimicrobial agents following the standardized technical protocol established by the CHINET program.Results A total of 589 746 respiratory isolates were collected from 2015 to 2021.Overall,82.6％of the isolates were Gram-negative bacteria and 17.4％were Gram-positive bacteria.The bacterial isolates from outpatients and inpatients accounted for(6.0±0.9)％and(94.0±0.1)％,respectively.The top microorganisms were Klebsiella spp.,Acinetobacter spp.,Pseudomonas aeruginosa,Staphylococcus aureus,Haemophilus spp.,Stenotrophomonas maltophilia,Escherichia coli,and Streptococcus pneumoniae.Each microorganism was isolated from significantly more males than from females(P＜0.05).The overall prevalence of methicillin-resistant S.aureus(MRSA)was 39.9％.The prevalence of penicillin-resistant S.pneumoniae was 1.4％.The prevalence of extended-spectrum β-lactamase(ESBL)-producing E.coli and K.pneumoniae was 67.8％and 41.3％,respectively.The overall prevalence of carbapenem-resistant E.coli,K.pneumoniae,Enterobacter cloacae,Pseudomonas aeruginosa,and Acinetobacter baumannii was 3.7％,20.8％,9.4％,29.8％,and 73.3％,respectively.The prevalence of β-lactamase was 96.1％in Moraxella catarrhalis and 60.0％in Haemophilus influenzae.The H.influenzae isolates from children(＜18 years)showed significantly higher resistance rates to β-lactam antibiotics than the isolates from adults(P＜0.05).Conclusions Gram-negative bacteria are still predominant in respiratory isolates associated with serious antibiotic resistance.Antimicrobial resistance surveillance should be strengthened in clinical practice to support accurate etiological diagnosis and appropriate antimicrobial therapy based on antimicrobial susceptibility testing results.

Objective:To investigate the application of 18F-FDG PET/MR and its derived parameters in the diagnosis and staging of bladder cancer. Methods:Forty patients (32 males, 8 females; age (66.8±11.2) years) with suspected bladder cancer between December 2019 and March 2022 were retrospectively included and underwent 18F-FDG PET/MR in Nanjing First Hospital. Parameters including SUV max, SUV mean, maximum tumor diameter and mean of apparent diffusion coefficient (ADC mean) were obtained, and bladder cancer muscle invasiveness and lymph node involvement were determined. The efficacy of 18F-FDG PET/MR and its derived parameters for tumor diagnosis and staging was analyzed using transurethral resection of bladder tumor (TUR-BT) or radical cystectomy (RC) and extended pelvic lymph node dissection (ePLND) histopathology as the " gold standard". Independent-sample t test, Mann-Whitney U test or χ2 test was used to analyze the data, and Delong test was used to compare different AUCs. Results:Of 40 patients, 8 were non-muscle invasive bladder cancer (NMIBC), 32 were muscle invasive bladder cancer (MIBC), and 5 were pathologically confirmed to have lymph node metastasis. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy of 18F-FDG PET/MR for identifying MIBC were 96.9%(31/32), 7/8, 96.9%(31/32), 7/8, 95.0%(38/40), respectively, and those for lymph node metastasis were 4/5, 90.0%(18/20), 4/6, 18/19, 88.0%(22/25), respectively. For pathological tumor (pT) staging, significant differences were observed between pT2-3 and pT1 groups in maximum tumor diameter ( t=-2.37, P=0.024), SUV mean( Z=-2.11, P=0.035), and ADC mean( t=2.91, P=0.006). The AUCs of maximum tumor diameter, SUV mean and ADC mean in distinguishing MIBC were 0.781, 0.746, and 0.825, respectively. The sensitivity, specificity, PPV, NPV, and accuracy of MRI alone in identifying MIBC were 87.5%(28/32), 1/8, 80.0%(28/35), 1/5 and 72.5%(29/40), respectively, with the AUC of 0.500. The AUC of 18F-FDG PET/MR in identifying MIBC was 0.796, which was better than MRI alone ( Z=5.54, P<0.001), and the accuracy of PET/MR was also higher than MRI alone ( χ2=7.44, P=0.006). Conclusion:Compared with MRI alone, 18F-FDG PET/MR significantly improves the diagnostic efficacy of bladder cancer and the accuracy of pT staging.

Objective To summarize the changing prevalence of carbapenem resistance in Enterobacterales based on the data of CHINET Antimicrobial Resistance Surveillance Program from 2015 to 2021 for improving antimicrobial treatment in clinical practice.Methods Antimicrobial susceptibility testing was performed using a commercial automated susceptibility testing system according to the unified CHINET protocol.The results were interpreted according to the breakpoints of the Clinical & Laboratory Standards Institute(CLSI)M100 31st ed in 2021.Results Over the seven-year period(2015-2021),the overall prevalence of carbapenem-resistant Enterobacterales(CRE)was 9.43％(62 342/661 235).The prevalence of CRE strains in Klebsiella pneumoniae,Citrobacter freundii,and Enterobacter cloacae was 22.38％,9.73％,and 8.47％,respectively.The prevalence of CRE strains in Escherichia coli was 1.99％.A few CRE strains were also identified in Salmonella and Shigella.The CRE strains were mainly isolated from respiratory specimens(44.23±2.80)％,followed by blood(20.88±3.40)％and urine(18.40±3.45)％.Intensive care units(ICUs)were the major source of the CRE strains(27.43±5.20)％.CRE strains were resistant to all the β-lactam antibiotics tested and most non-β-lactam antimicrobial agents.The CRE strains were relatively susceptible to tigecycline and polymyxins with low resistance rates.Conclusions The prevalence of CRE strains was increasing from 2015 to 2021.CRE strains were highly resistant to most of the antibacterial drugs used in clinical practice.Clinicians should prescribe antimicrobial agents rationally.Hospitals should strengthen antibiotic stewardship in key clinical settings such as ICUs,and take effective infection control measures to curb CRE outbreak and epidemic in hospitals.

Objective To characterize the changing species distribution and antibiotic resistance profiles of respiratory isolates in hospitals participating in the CHINET Antimicrobial Resistance Surveillance Program from 2015 to 2021.Methods Commercial automated antimicrobial susceptibility testing systems and disk diffusion method were used to test the susceptibility of respiratory bacterial isolates to antimicrobial agents following the standardized technical protocol established by the CHINET program.Results A total of 589 746 respiratory isolates were collected from 2015 to 2021.Overall,82.6％of the isolates were Gram-negative bacteria and 17.4％were Gram-positive bacteria.The bacterial isolates from outpatients and inpatients accounted for(6.0±0.9)％and(94.0±0.1)％,respectively.The top microorganisms were Klebsiella spp.,Acinetobacter spp.,Pseudomonas aeruginosa,Staphylococcus aureus,Haemophilus spp.,Stenotrophomonas maltophilia,Escherichia coli,and Streptococcus pneumoniae.Each microorganism was isolated from significantly more males than from females(P＜0.05).The overall prevalence of methicillin-resistant S.aureus(MRSA)was 39.9％.The prevalence of penicillin-resistant S.pneumoniae was 1.4％.The prevalence of extended-spectrum β-lactamase(ESBL)-producing E.coli and K.pneumoniae was 67.8％and 41.3％,respectively.The overall prevalence of carbapenem-resistant E.coli,K.pneumoniae,Enterobacter cloacae,Pseudomonas aeruginosa,and Acinetobacter baumannii was 3.7％,20.8％,9.4％,29.8％,and 73.3％,respectively.The prevalence of β-lactamase was 96.1％in Moraxella catarrhalis and 60.0％in Haemophilus influenzae.The H.influenzae isolates from children(＜18 years)showed significantly higher resistance rates to β-lactam antibiotics than the isolates from adults(P＜0.05).Conclusions Gram-negative bacteria are still predominant in respiratory isolates associated with serious antibiotic resistance.Antimicrobial resistance surveillance should be strengthened in clinical practice to support accurate etiological diagnosis and appropriate antimicrobial therapy based on antimicrobial susceptibility testing results.

Objective:To understand the characteristics of new infections in the newly reported HIV-1 infected population in Luzhou, to find out the characteristics of the high-risk population, which may provide a basis for developing precise prevention and control measures locally.Methods:HIV-1 LAg Avidity EIA test was applied for newly reported cases in Luzhou from 2018 to 2021. The chi-square test was used for univariate analysis, logistic regression model for multivariate analysis, and spatial autocorrelation and hotspot analysis were applied to explore the spatial distribution characteristics of new infections in Luzhou city.Results:A total of 4 494 cases reported in the odd-numbered months were selected for testing, with 673 newly infected cases and the proportion of newly infected cases was 14.98%. Newly infected cases were predominantly male (472/673, 70.13%), married (335/673, 49.78%), heterosexual transmission (621/673, 92.27%), age>50 years (520/673, 77.27%), and junior high school or lower education (599/673, 89.00%). The proportion of new infections in each year were 11.74% (129/1 099), 17.11% (247/1 444), 13.57% (154/1 134) and 17.50% (143/817), respectively, with a statistically significant difference ( χ2=20.024, P<0.001) and an upward trend ( χ2=5.997, P=0.014). There were statistically significant differences in different transmission routes, gender, education level, occupation, sample source and residence (all P<0.05). Logistic regression analysis showed that gender, marital status, transmission route, current address, and sample source were all influencing factors for new infections. There are spatial autocorrelation characteristics of new case incidence in 2018 and 2021, hotspot areas gradually shifted from dispersed to relatively concentrated, with the number fluctuating with reported year. Conclusions:The proportion of new HIV-1 infections in Luzhou is relatively low throughout the province, but it is on the rise. The proportion of new infections is higher among youth, students, homosexual transmission, and retired persons. Attention should be focused on hotspot areas and routine surveillance and testing of key populations in hotspot areas should be strengthened.