Objective To establish the pharmacokinetic model of linezolid in neonates,and to optimize the administration regimen. Methods A prospective study was conducted among 64 neonates with sepsis who received linezolid as anti-infective therapy,and liquid chromatography-tandem mass spectrometry was used to measure the plasma concentration of the drug. Clinical data were collected,and nonlinear mixed effects modeling was used to establish a population pharmacokinetic (PPK) model. Monte Carlo simulation and evaluation was performed for the optimal administration regimen of children with different features. Results The pharmacokinetic properties of linezolid in neonates could be described by a single-compartment model with primary elimination,and the population typical values for apparent volume of distribution and clearance rate were 0.79 L and 0.34 L/h,respectively. The results of goodness of fit,visualization verification,and the Bootstrap method showed that the model was robust with reliable results of parameter estimation and prediction. Monte Carlo simulation results showed that the optimal administration regimen for linezolid in neonates was as follows:6 mg/kg,q8h,at 28 weeks of gestational age (GA);8 mg/kg,q8h,at 32 weeks of GA;9 mg/kg,q8h,at 34-37 weeks of GA;11 mg/kg,q8h,at 40 weeks of GA. Conclusions The PPK model established in this study can provide a reference for individual administration of linezolid in neonates. GA and body weight at the time of administration are significant influencing factors for the clearance rate of linezolid in neonates.

Objective To monitor the antifungal resistance of clinical isolates of Candida spp.in the East China region.Methods MALDI-TOF MS or molecular methods were used to re-identify the strains collected from January 2018 to December 2022.Antifungal susceptibility testing was performed using the broth microdilution method.The susceptibility test results were interpreted according to the breakpoints of 2022 Clinical and Laboratory Standards Institute(CLSI)documents M27 M44s-Ed3 and M57s-Ed4.Results A total of 3 026 strains of Candida were collected,65.33％of which were isolated from sterile body sites,mainly from blood(38.86％)and pleural effusion/ascites(10.21％).The predominant species of Candida were Candida albicans(44.51％),followed by Candida parapsilosis complex(19.46％),Candida tropicalis(13.98％),Candida glabrata(10.34％),and other Candida species(0.79％).Candida albicans showed overall high susceptibility rates to the 10 antifungal drugs tested(the lowest rate being 93.62％).Only 2.97％of the strains showed dose-dependent susceptibility(SDD)to fluconazole.Candida parapsilosis complex had a SDD rate of 2.61％and a resistance rate of 9.42％to fluconazole,and susceptibility rates above 90％to other drugs.Candida glabrata had a SDD rate of 92.01％and a resistance rate of 7.99％to fluconazole,resistance rates of 32.27％and 48.24％to posaconazole and voriconazole non-wild-type strains(NWT),respectively,and susceptibility rates above 90％to other drugs.Candida tropicalis had resistance rates of 29.55％and 26.24％to fluconazole and voriconazole,respectively,resistance rates of 76.60％and 21.99％to posaconazole and echinocandins non-wild-type strains(NWT),and a resistance rate of 2.36％to echinocandins.Conclusions The prevalence and species distribution of Candida spp.in the East China region are consistent with previous domestic and international reports.Candida glabrata exhibits certain degree of resistance to fluconazole,while Candida tropicalis demonstrates higher resistance to triazole drugs.Additionally,echinocandins resistance has emerged in Candida albicans,Candida glabrata,Candida tropicalis,and Candida parapsilosis.

Objective:To analyze the clinical characteristics and prognosis of patients with CD5+diffuse large B-cell lymphoma(DLBCL).Methods:The clinical data of 161 newly treated DLBCL patients in Gansu Provincial Hospital from January 2013 to January 2020 were retrospectively analyzed.According to CD5 expression,the patients were divided into CD5+group and CD5-group.The clinical characteristics and prognosis of the two groups were statistically analyzed.Results:The median age of patients in CD5+group was 62 years,which was higher than 56 years in CD5-group(P=0.048).The proportion of women in CD5+group was 62.96％,which was significantly higher than 41.79％in CD5-group(P=0.043).The proportion of patients with IPI score＞2 in CD5+group was 62.96％,which was higher than 40.30％in CD5-group(P=0.031).Survival analysis showed that the median overall survival and progression-free survival time of patients in CD5+group were 27(3-77)and 31(3-76)months,respectively,which were both shorter than 30(5-84)and 32.5(4-83)months in CD5-group(P=0.047,P=0.026).Univariate analysis showed that advanced age,positive CD5 expression,triple or double hit at initial diagnosis,high IPI score and no use of rituximab during chemotherapy were risk factors for the prognosis of DLBCL patients.Further Cox multivariate regression analysis showed that these factors were also independent risk factors except for advanced age.Conclusion:CD5+DLBCL patients have a worse prognosis than CD5-DLBCL patients.Such patients are more common in females,with advanced age and high IPI score,which is a special subtype of DLBCL.

OBJECTIVE: This study was aimed at investigating the carrier rate of, and molecular variation in, α- and β-globin gene mutations in Hunan Province. METHODS: We recruited 25,946 individuals attending premarital screening from 42 districts and counties in all 14 cities of Hunan Province. Hematological screening was performed, and molecular parameters were assessed. RESULTS: The overall carrier rate of thalassemia was 7.1%, including 4.83% for α-thalassemia, 2.15% for β-thalassemia, and 0.12% for both α- and β-thalassemia. The highest carrier rate of thalassemia was in Yongzhou (14.57%). The most abundant genotype of α-thalassemia and β-thalassemia was -α ^3.7/αα (50.23%) and β ^IVS-II-654/β ^N (28.23%), respectively. Four α-globin mutations [CD108 (ACC>AAC), CAP +29 (G>C), Hb Agrinio and Hb Cervantes] and six β-globin mutations [CAP +8 (C>T), IVS-II-848 (C>T), -56 (G>C), beta nt-77 (G>C), codon 20/21 (-TGGA) and Hb Knossos] had not previously been identified in China. Furthermore, this study provides the first report of the carrier rates of abnormal hemoglobin variants and α-globin triplication in Hunan Province, which were 0.49% and 1.99%, respectively. CONCLUSION Our study demonstrates the high complexity and diversity of thalassemia gene mutations in the Hunan population. The results should facilitate genetic counselling and the prevention of severe thalassemia in this region.
Humans ; beta-Thalassemia/genetics* ; alpha-Thalassemia/genetics* ; Hemoglobinopathies/genetics* ; China/epidemiology* ; High-Throughput Nucleotide Sequencing

Chronic heart failure(CHF) is a series of clinical syndromes in which various heart diseases progress to their end stage. Its morbidity and mortality are increasing year by year, which seriously threatens people's life and health. The diseases causing CHF are complex and varied, such as coronary heart disease, hypertension, diabetes, cardiomyopathy and so on. It is of great significance to establish animal models of CHF according to different etiologies to explore the pathogenesis of CHF and develop drugs to prevent and treat CHF induced by different diseases. Therefore, based on the classification of the etiology of CHF, this paper summarizes the animal models of CHF widely used in recent 10 years, and the application of these animal models in traditional Chinese medicine(TCM) research, in order to provide ideas and strategies for studying the pathogenesis and treatment of CHF, and provide ideas for TCM modernization research.
Animals ; Medicine, Chinese Traditional ; Heart Failure ; Heart Diseases ; Chronic Disease ; Models, Animal

Objective: To compare the effects of the China Children's Asthma Action Plan (CCAAP)-based remote joint management model with traditional management model on the control of childhood asthma. Methods: A retrospective cohort study was conducted to analyze the general data and asthma control assessment data of 219 children with asthma who attended the respiratory department of Guangzhou Women's and Children's Medical Center from April 2021 to October 2021 and were followed up for 1 year or more. According to the follow-up management model, the CCAAP-based remote joint management model was used in the observation group and the traditional management model was used in the control group, and the propensity score matching method was applied to match the data of children in the two management models for comparison. Paired-samples t-test, Wilcoxon signed-rank test, McNemar χ²-test or χ²-test or nonparametric tests were used to compare the general data and asthma control assessment data between the two matched groups of children. Results: Among 219 children with asthma, 145 were male and 74 were female, aged at consultation (7.2±2.4) years. There were 147 cases in the observation group and 72 cases in the control group, and 27 cases in each of the observation and control groups were successfully matched. The number of asthma exacerbation aura, acute exacerbations, and emergency room visits or hospitalizations for asthma exacerbations were lower in the observation group than in the control group after pairing (1 (0, 2) vs. 3 (1, 5) times, 0 (0,0) vs. 0 (0, 1) times, 0 (0,0) vs. 1 (0, 1) times, Z=-3.42, -2.58, -3.17, all P<0.05). The use of peak flowmeters was higher in children aged 5 years and older in the observation group than in the control group after pairing (100% (22/22) vs. 13% (3/23), χ²=54.00,P<0.001). The ratio of actual to predicted 1st second expiratory volume of force after follow-up in the observation group after pairing was higher than that before follow-up in the observation group and after follow-up in the control group ((95±11)% vs. (85±10)%, (95±11)% vs. (88±11)%, t=-3.40, 2.25, all P<0.05). The rate of complete asthma control after follow-up was higher in both the observation and control groups after pairing than before follow-up for 12 months in both groups (93% (25/27) vs. 41% (11/27), 52% (14/27) vs. 41% (11/27), H=56.19, 45.37, both P<0.001), and the rate of complete control of asthma in children in the observation group was higher than that in the control group at 3 and 12 months of follow-up management (56% (15/27) vs. 25% (5/20), 93% (25/27) vs. 52% (14/27), χ²=47.00, 54.00, both P<0.001). The number of offline follow-up visits, inhaled hormone medication adherence scores, and caregiver's asthma perception questionnaire scores were higher in the observation group than in the control group after pairing (6 (4, 8) vs. 4 (2,5), (4.8±0.3) vs. (4.0±0.6) score, (19.3±2.6) vs. (15.2±2.7) score, Z=6.58, t=6.57, 5.61, all P<0.05), and the children in the observation group had lower school absences, caregiver absences, asthma attack visit costs, and caregiver PTSD scores than the control group (0 (0,0) vs.3 (0, 15) d, 0 (0,0) vs. 3 (0, 10) d, 1 100 (0, 3 700) vs. 5 000 (1 000, 10 000) yuan, 1.3 (1.1, 1.9) vs. 2.0 (1.2, 2.7) score, Z=-2.89, -2.30, 2.74, 2.73, all P<0.05). Conclusion: The CCAAP-based joint management model of asthma control is superior to the traditional management model in the following aspects: it can effectively improve asthma control, self-monitoring, and lung function in children; it can improve treatment adherence and caregivers' asthma awareness; and it can reduce the duration of absenteeism from school, the cost of asthma exacerbation visits, and caregiver's negative psychology.
Humans ; Child ; Female ; Male ; Retrospective Studies ; Asthma/therapy* ; China ; Hospitalization ; Hospitals

Objective To investigate the Gram-positive coccus resistance in nationwide's tertiary hospitals and understand the trend of antimicrobial resistance.Methods All the clinical isolates were collected from 19 hospitals and the minimal inhibitory concentrations(MICs)were tested using agar/broth dilution method recommended.Results A total of 1 974 pathogenic Gram-positive coccus from 19 tertiary hospitals in 19 cities nationwide over the period from July 2021 to June 2022 were studied.Based on the MIC results,the prevalence of methicillin resistant Stapylococcus aureus(MRSA)and methicillin resistant Stapylococcus epidermidis(MRSE)were 36.4％and 79.9％respectively.No vancomycin insensitivity Staphylococcus was detected.Staphylococcus aureus were 100％susceptibility to linezolid and teicoplanin.Antibiotic resistance rate of Enterococcus faecalis and Enterococcus faecium to ampicillin were 3.1％and 92.9％.The detectation rate of vancomycin resistant Enterococcus(VRE)was 1.6％.Nonsusceptibility rate of Enterococcus faecalis to linezolid was 32.2％,two consecutive monitoring rises and nonsusceptibility rate of Enterococcus faecium(12.5％)was also significantly increased.The prevalence of penicillin non-susceptible Streptococcus pneumoniae(PNSSP)was 0.8％based on non-meningitis and parenteral administration criterion,decrease of nearly 30 percentage points from the previous surveillance.While for cases of oral penicillin,the rate was 71.8％,showing similar to last time.The results indicated that the number of strains with higher MIC value of penicillin(MIC ≥4 mg·L-1)decreased significantly.There were no significant differences of resistance rates of Stapylococcus aureus,Stapylococcus epidermidis,Enterococcus faecalis,Enterococcus faecium and Streptococcus pneumoniae among various groups such as different department,age,or specimen source.Conclusion VRE detection ratio stablized at a relatively low level.The number of Streptococcus pneumoniae with higher MIC value of penicillin decreased significantly compared with the previous monitoring.The increase of linezolidin-insensitive Enterococcus was noteworthy.

Objective To investigate the Gram-negative bacteria resistance in nationwide's tertiary hospitals and understand the trend of antimicrobial resistance.Method All the clinical isolates were collected from 19 hospitals and the minimal inhibitory concentrations(MICs)were tested using agar/broth dilution method recommended.Results A total of 4 066 pathogenic isolates from 19 tertiary hospitals in 19 cities nationwide over the period from July 2021 to June 2022 were studied.Based on the MIC results,Escherichia coli and Klebsiella pneumoniae showed extended spectrum β-lactamase(ESBLs)phenotype rates of 55.0％and 21.0％,respectively,ESBLs phenotype rate of Klebsiella pneumoniae keep going down.The ratios of carbapenems resistance Klebsiella pneumoniae increased by 5 percentage points compared with the previous monitoring.Carbapenems,moxalactam,sitafloxacin,β-lactam combination agents,fosfomycin trometamol,and amikacin displayed desirable antibacterial activity against Enterbacterales,susceptibal rates were above 75％.In addition,tigacycline,omacycline,colistin and fluoxefin maintained good antibacterial activity against their respective effective bacteria/species,and the bacterial sensitivity rates by more than 80％.Resistance rates of Pseudomonas aeruginosa and Acinetobacter baumannnii to imipenem were 26.3％and 72.1％and multidrug-resistant(MDR)detection rates were 41.1％and 77.3％,extensively drug-resistant(XDR)were 12.0％and 71.8％,respectively.Comparison of drug resistance rates from different wards,ages and specimen sources indicated that the proportion of resistance in Klebsiella pneumoniae and Acinetobacter baumannii isolated from intensive care unit(ICU)were significantly higher than non-ICU.Carbapenem resistance rates of Klebsiella pneumoniae isolated from ICU were more than 35％.Resistance rates of Haemophilus influenzae isolated in children to β-lactam,macrolide,clindamycin and ESBLs detection rate in Klebsiella pneumoniae isolated from children were more than those from adults and the old people,so bacterial resistance in children is an important problem in China.Conclusion ESBLs detection rate of Escherichia coli increased slightly after years of continuous decline.The proportion of carbapenem resistant Pseudomonas aeruginosa was stable,but the resistance rate of Klebsiella pneumoniae and Acinetobacter baumannii to carbapenems was still increased,which should be paid more attention.

Objective: To investigate the incidence and trend of short-term outcomes among preterm infants born <34 weeks' gestation. Methods: A secondary analysis of data from the standardized database established by a multicenter cluster-randomized controlled study "reduction of infection in neonatal intensive care units (NICU) using the evidence-based practice for improving quality (REIN-EPIQ) study". This study was conducted in 25 tertiary NICU. A total of 27 192 infants with gestational age <34 weeks at birth and admitted to NICU within the first 7 days of life from May 2015 to April 2018 were enrolled. Infants with severe congenital malformation were excluded. Descriptive analyses were used to describe the mortality and major morbidities of preterm infants by gestational age groups and different admission year groups. Cochran-Armitage test and Jonckheere-Terpstra test were used to analyze the trend of incidences of mortality and morbidities in 3 study-years. Multiple Logistic regression model was constructed to analyze the differences of outcomes in 3 study-years adjusting for confounders. Results: A total of 27 192 preterm infants were enrolled with gestational age of (31.3±2.0) weeks at birth and weight of (1 617±415) g at birth. Overall, 9.5% (2 594/27 192) of infants were discharged against medical advice, and the overall mortality rate was 10.7% (2 907/27 192). Mortality for infants who received complete care was 4.7% (1 147/24 598), and mortality or any major morbidity was 26.2% (6 452/24 598). The incidences of moderate to severe bronchopulmonary dysplasia, sepsis, severe intraventricular hemorrhage or periventricular leukomalacia, proven necrotizing enterocolitis, and severe retinopathy of prematurity were 16.0% (4 342/27 192), 11.9% (3 225/27 192), 6.8% (1 641/24 206), 3.6% (939/25 762) and 1.5% (214/13 868), respectively. There was a decreasing of the overall mortality (P<0.001) during the 3 years. Also, the incidences for sepsis and severe retinopathy of prematurity both decreased (both P<0.001). However, there were no significant differences in the major morbidity in preterm infants who received complete care during the 3-year study period (P=0.230). After adjusting for confounders, infants admitted during the third study year showed significantly lower risk of overall mortality (adjust OR=0.62, 95%CI 0.55-0.69, P<0.001), mortality or major morbidity, moderate to severe bronchopulmonary dysplasia, sepsis and severe retinopathy of prematurity, compared to those admitted in the first study year (all P<0.05). Conclusions: From 2015 to 2018, the mortality and major morbidities among preterm infants in Chinese NICU decreased, but there is still space for further efforts. Further targeted quality improvement is needed to improve the overall outcome of preterm infants.
Bronchopulmonary Dysplasia/epidemiology* ; Gestational Age ; Humans ; Infant ; Infant Mortality/trends* ; Infant, Newborn ; Infant, Premature ; Infant, Premature, Diseases/epidemiology* ; Patient Discharge ; Retinopathy of Prematurity/epidemiology* ; Sepsis/epidemiology*

Objective: To explore the heterogeneity and correlation of clinical phenotypes and genotypes in children with disorders of sex development (DSD). Methods: A retrospective study of 1 235 patients with clinically proposed DSD in 36 pediatric medical institutions across the country from January 2017 to May 2021. After capturing 277 DSD-related candidate genes, second-generation sequencing was performed to analyzed the heterogeneity and correlation combined with clinical phenotypes. Results: Among 1 235 children with clinically proposed DSD, 980 were males and 255 were females of social gender at the time of initial diagnosis with the age ranged from 1 day of age to 17.92 years. A total of 443 children with pathogenic variants were detected through molecular genetic studies, with a positive detection rate of 35.9%. The most common clinical phenotypes were micropenis (455 cases), hypospadias (321 cases), and cryptorchidism (172 cases) and common mutations detected were in SRD5A2 gene (80 cases), AR gene (53 cases) and CYP21A2 gene (44 cases). Among them, the SRD5A2 mutation is the most common in children with simple micropenis and simple hypospadias, while the AMH mutation is the most common in children with simple cryptorchidism. Conclusions: The SRD5A2 mutation is the most common genetic variant in Chinese children with DSD, and micropenis, cryptorchidism, and hypospadias are the most common clinical phenotypes. Molecular diagnosis can provide clues about the biological basis of DSD, and can also guide clinicians to perform specific clinical examinations. Target sequence capture probes and next-generation sequencing technology can provide effective and economical genetic diagnosis for children with DSD.
3-Oxo-5-alpha-Steroid 4-Dehydrogenase/genetics* ; Child ; China/epidemiology* ; Cryptorchidism/genetics* ; Disorders of Sex Development/genetics* ; Female ; Genital Diseases, Male ; Genotype ; Humans ; Hypospadias/genetics* ; Male ; Membrane Proteins/genetics* ; Penis/abnormalities* ; Phenotype ; Retrospective Studies ; Steroid 21-Hydroxylase/genetics*