Abstract Background Trends in growth and development of children and adolescents are considered to be a "biological standard of living conditions", reflecting a combination of genetic trajectories, environmental factors centered on nutrition and disease, and socio-economic circumstances. Differences in growth and developmental velocity exist between individuals. Objective To construct an equation for predicting maturity offsets from longitudinal data on height, sitting height, and weight to assess the physiological maturity level of individuals. Design Cohort study. Methods According to the Shanghai Longitudinal Growth and Development Study (SLGDS), data were collected from healthy children aged 6.0-14.0 years who had more than four measurements of height, sitting height, and weight with an interval of at least 11 months between each data acquisition. Boys had at least one measurement before 10 years of age and after 12 years of age, and girls had at least one measurement before 9 years of age and after 11 years of age. Fourteen variables of age, height, weight, sitting height and their interactions and ratios were selected for the construction of prediction equations. Correlation analysis and Lasso method were applied to select predictors by gender, and stepwise regression was used to construct the equations. The predictive performance of the equations were evaluated by R2, standard error of estimate (SEE), and Bland-Altman analysis. Main outcome measures Maturity offset［chronological age at the time of measurement-age at Peak Height Velocity (aPHV)］. Results In the SLGDS, 580 children met the inclusion and exclusion criteria. The modeling sample was 439 (180 boys and 259 girls) and the validation sample was 141 (56 boys and 85 girls). Differences in overall measurements between two samples of boys and girls were not significant. The difference was statistically significant in the shorter follow-up duration for boys' modeling sample and the longer duration for girls' modeling sample. Three of the 14 variables were included in the equations for both of boys (age, sitting height, and BMI) and girls (age, sitting height, and quetelet index).Conclusion The maturity offset equations in Shanghai children based on age, sitting height, and BMI for boys, and age, sitting height, and quetelet index for girls were better than the current internationally used maturity offset equations.

Background Sitting height/leg length ratio (SH/LL) and Sitting height/height ratio (SH/H) are the important indicators of body proportion assessment. Their scientific assessment will supply valuable information in clinical practices, but the detailed data on their growth reference standards have not been reported. Objective To construct the SH/LL and SH/H growth charts for Chinese children and adolescents from birth to 18 years. Design A cross-sectional survey. Methods Stature and sitting height of 92 494 healthy urban children aged 0-18 years were measured in two national surveys in 2005 in China, which named The National Survey on the Physical Growth and Development of Children in the Nine Cities of China and The Chinese National Survey on Student's Constitution and Health. Leg length was calculated by height minus sitting height and the SH/LL ratio and SH/H ratio were calculated. Growth reference standards of SH/LL and SH/H were constructed using the LMS method. Main outcome measures Reference values of SH/LL and SH/H. Results The Z-scores growth charts of SH/LL and SH/H (-3SD, -2SD, -1SD, Median, +1SD, +2SD, +3SD) were constructed. The median of SH/LL declined from birth (2.00) to 13 years in boys (111) and to 11 years in girls (1.13), then increased slightly to the age of 18 (1.16 in boys and 1.18 in girls). A similar growth pattern was found in the SH/H, that is, the median of SH/H was 0.67 at birth and declined to the lowest point (0.53) with age, then increased slightly to 0.54 at 18 years old. Conclusions The growth charts of SH/LL and SH/H are used in assessing body proportions for Chinese children and adolescent individuals, and they could be used in conjunction with the growth charts of height, weight for Chinese children aged 0-18 years.

Background：Constructing language development milestones and collecting milestone data are not only key steps in language development monitoring, but also the preliminary basis for the development of language screening and diagnostic tools. Objective：To construct language development milestones for Chinese-speaking children aged 0 to 5.5 years, providing a reference basis for language development screening and diagnostic tool development. Design：Cross-sectional survey. Methods：Based on existing developmental assessment tools and literature, a language development milestone item pool was established through expert consultation and cognitive interviews. From October 2022 to November 2022, 1,976 children aged 0 to 6 years were sampled from five provinces including Zhejiang, Sichuan, Liaoning, Jiangxi, and Hainan. Using stratification by urban and rural areas, gender, and age groups, developmental milestone data were collected through parent reports in both primary care settings (age <36 months) and kindergartens (age ≥36 months). The characteristics of language development milestones for children in different age groups were analysed descriptively using an item response theory model. Data comparisons were conducted between the data collected in the current study for Chinese-speaking children and data obtained from other published research on English-speaking children. Main outcome measures：Response rate, different item function, model fit, and estimated developmental age of each item when passing probabilities is 25%, 50%, and 75%. Results：A total of 63 language development milestone items were included in the item pool. After data cleaning, 1 659 children were included in the data analysis, including 827 boys and 832 girls, with an average age of (2.5±1.9) years. The response rate for all 63 language milestones was higher than 99%. Three items showed different item function based on maternal education, and 14 items showed poor model fit. Conclusions：The language development milestones for Chinese-speaking children aged 0 to 5.5 years established using the item response theory model provide a clear description of the language development trajectory of native Chinese-speaking children. This work offers valuable empirical data for the future development of language development evaluation tools for Chinese-speaking children, clinical monitoring of language development, and research into related neural mechanisms.

Background：The Swanson, Nolan, and Pelham, version scale (SNAP-Ⅳ) is the most widely used assessment tool for evaluating the core symptoms of attention-deficit/hyperactivity disorder (ADHD) in children. However, there is still a lack of systematic review of the measurement properties of the SNAP-Ⅳ scale, which may introduce bias and potentially affect the assessment validity of the measurement tool. Objective：To evaluate the measurement properties of the SNAP-Ⅳ based on the Consensus-based Standards for the selection of health Measurement Instruments (COSMIN), and to provide evidence-based measurement instrument recommendations for the screening, diagnosis and efficacy evaluation of children with ADHD. Design：Systematic review. Methods：Related literature was systematically searched in databases of China National Knowledge Infrastructure (CNKI), Wanfang Database, VIP Database, China Biomedical Literature Database (CBM), PubMed, Cochrane Library, EMBASE, and Web of Science from the inception to April 21, 2022. Two reviewers independently screened the literature, and the measurement properties of the SNAP-Ⅳ scale were objectively evaluated according to the COSMIN manual. Main outcome measures：Content validity and internal consistency of the SNAP-Ⅳ scale. Results：A total of 14 studies involving 6 language versions were included. The content validity of the SNAP-Ⅳ scale was rated as "sufficient" (moderate quality evidence) in terms of relevance, comprehensiveness, and comprehensibility. However, there was no reported content on the development of the SNAP-Ⅳ scale. The parent and teacher versions of the SNAP-Ⅳ scale showed "sufficient" internal consistency (high-quality evidence). There was no high-quality evidence indicating "insufficient" measurement properties. The overall recommendation was classified as level A. Conclusion：The SNAP-Ⅳ scale is recommended for the screening, diagnosis, and treatment evaluation of children with ADHD, and its results can be considered reliable.

Background：Implementation research refers to systematically integrating evidencebased practice into clinical scenarios to improve the quality and effectiveness of healthcare services and bridge the gap between evidence and clinical practice. However, this type of research has not received much attention. Objective：To develop implementation strategies of the recommendations for venous access devices (VADs) selection in hospitalized children from Clinical Practice Guideline on Infusion Therapy in Children, to evaluate the impact of evidence implementation on patient outcomes, the evidencebased practice behaviors of healthcare workers, and organization environment changes in the hospital, and to identify conflicts between recommendations and clinical practice in different clinical settings. Design：Implementation study. Methods：We developed strategies to promote evidence implementation at Children's Hospital of Fudan University from four perspectives: dissemination, implementation process, integration, and capacity building. These strategies, along with correspongding individualized action plans, were applied in the VAD selection for children's infusion therapy. The implementation process and outcomes were evaluated from four aspects: reach, effectiveness (or efficacy), adoption, and implementation according to the REAIM framework. Main outcome measures：VAD selection error rate, and compliance of VAD selection among nurses. Results：The implementation period was from May 30, 2022, to October 30, 2022. We enrolled 2,343 patients in the intervention group and 2,309 patients in the control group. （1）Reach: During the implementation period, 4, 652 pediatric patients met the inclusion criteria. Out of these, 2, 343 patients received the implementation strategy and individualized action plan. (2) Effectiveness: Among the hospitalized children in the 10 wards, there was no statistically significant gender difference between the two groups. However, there were significant differences in patient age, emergency admission status, surgical status, and department. After adjusting for age, emergency admission status, surgical status, and department, compared to the control group, the intervention group had a 25% reduction in VAD selection error rate (OR=0.745, 95%CI: 0.6120.906). There was no statistically significant difference in the incidence of extravasation/infiltration between the control and intervention groups (OR=1.070, 95%CI: 0.8221.393). The nurses' knowledge level in VAD selection was significantly higher in the intervention group (83.9±12.4) compared to that of the control group (56.0±13.1). Compliance rate of five audit indicators was 100% before, during, and after implementation, compliance rate of four indicators significantly improved before, during, and after implementation, compliance rate of seven indicators showed no statistically significant difference before, during, and after implementation. (3) Adoption: During the implementation period, all 10 wards selected by cluster random sampling (100%) fully participated in the strategy implementation and adopted all 17 pieces of evidence (100%). Multiple rounds of course training (4 hours each) and practical training (3 hours each) were conducted to help nurses understand the implementation strategies and action plans, and all 214 nurses (100%) completed the training courses. (4) Implementation: The study developed six implementation strategies, achieving an 83.3% completion rate. The costeffectiveness index of peripheral intravenous catheter (PIVC) infusion materials before and after the intervention was 2.1>0, indicating that the intervention led to cost savings. Conclusion：The process evaluation of the guideline recommendations indicated a positive result across the four domains of reach, effectiveness (or efficacy), adoption, and implementation based on the REAIM framework. However, a moderate result was indentified in the compliance evaluation of nurses' VAD selection behavior in the effectiveness domain.

Background：Matching health and health-related information with International Classification of Functioning, Disability and Health, known more commonly as ICF can be helpful to describe and compare quantitative data, qualitative research results and patient report results. However, there are few literature about children and adolescents in this field. Objective：To provide support and suggestions for Clinical Practice Guidelines for Children and Adolescents with Cerebral Palsy (CANDLEP) by identifying the location, link, code of health and health-related information about children and adolescents in ICF for children and youth (ICF-CY) . Design：Scoping review. Methods：Literature was searched by using the keywords of "ICF" and "relate" in English databases of PubMed, Embase(Ovid), Cochrane and Chinese databases of SinoMed, CNKI and WanFang. Literature features were extracted from those matching health and health-related information with ICF-CY by six people with Fleiss kappa of 0.80. Main outcome measures：The matched content, the quality control of matching, presentation of matched results, the ICF-CY code distribution of matched cerebral palsy-related literature. Results：A total of 136 articles were enrolled in this scoping review. Among 110 articles focusing on specific populations, 31 were related to cerebral palsy; 107 used matching rules to promote quality control; 84 adopted the matching rules proposed by Cieza et al., among which 73 used the 2005 edition; and 93 reported the matching reliability. The matched content involved evaluation, intervention objectives, intervention methods, and outcome assessment. In 71 articles evaluation tools were matched with ICF-CY code. Frequency, breadth and density were main indicators for matched results report. Matched codes for cerebral palsy were mainly activities and participation. Conclusion：Matching health and health-related information about children and adolescents with ICF-CY is an important means to promote the clinical implementation of ICF-CY. Cerebral palsy has received the most attention within included articles focusing on population, which provides valuable evidence for the elaboration of ICF-CY elements in CANDLEP development.

Background：Chinese Infectious Disease Surveillance of Pediatrics (ISPED) program collected and summarized the data of antibiotics resistance from 12 member hospitals every year to monitor the bacterial drug resistance and pathogen changes among Chinese children. Objective：To investigate the antimicrobial resistance profiles of pathogens and bacteria infection in Chinese children and guide the reasonable use of antibiotics. Design：A cross-sectional survey. MethodsFrom January 1st to December 31rd in 2022, clinical isolates were collected from children hospitals in China enrolled in ISPED program. Antimicrobial susceptibility testing was carried out according to a unified protocol using Kirby-Bauer method or automated systems. Penicillin susceptibility of streptococcus pneumonia was detected by E-test. All of the antimicrobial susceptibility testing results were interpreted according to the criteria set by Clinical and Laboratory Standards Institute (CLSI) in 2022. Main outcome measures：Distribution of bacteria strains in children, changes of bacteria drug resistance to isolated strains, and detection of multi-drug resistant organisms (MDROs). Results：A total of 50,399 isolates were collected, of which 38.8% was gram-positive organisms and 61.2% was gram-negative organisms. Top ten pathogens were as follows, Escherichia coli (14.3%), Haemophilus influenza (11.8%), Straphylococcus aureus (11.4%), Streptococcus pneumonia (11.3%), Moraxella catarrhalis (7.3%), Coagulase-negative staphylococci (6.8%), Klebsiella pneunoniae (5.3%), Pseudomonas aeruginosa (4.4%), Acinetobacter baumannii(2.3%) and Enterococcus faecalis (2.1%). E. coli was the most common pathogen in neonates and children over 5 years old. H. influenza was the major pathogen in children from the age of >28 days to 1 year. S. pneumoniae was the main pathogenic bacteria in children at the age of 1 to 5 years old. The proportion of penicillin-insensitive S. pneumoniae (PNSP) from cerebrospinal fluid and non-cerebrospinal fluid were 88.9% and 6.6%, respectively. The ratios of methicillin-resistant S. aureus (MRSA), carbapenem-resistant Enterobacteriaceae (CRE), carbapenem-resistant P. aeruginosa (CR-PA), carbapenem-resistant A. baumannii (CR-AB) were 32.8%, 4.5%, 7.6% and 24.3%, respectively. The detection rates of MRSA, CRE and CR-PA in the neonatal group were 33.2%, 6.4% and 11.3%, much higher than those in the non-neonatal group (32.6%、4.2% and 7.5%). CR-AB in the neonatal group accounted for 10.9%, which was lower than that in the non-neonatal group (26.3%). Conclusions：The detection rate of MDROs in 2022 shows the continuous decrease compared to the previous years. More attention should be paid to the colonization, infection and spread of MRSA, CRE and CR-PA in the neonatal population.

Background：Changes in diastolic function are usually the first to occur when there is abnormal cardiac function. Currently, although there are many studies on ventricular systolic function, there is limited research on the changes in left ventricular diastolic function in congenital heart disease (CHD). Objective：To assess left ventricular diastolic function indices of CHD with lefttoright shunt before and after interventional therapy using echocardiography. Design：Selfcontrolled beforeafter trial. Methods：The case group of this study included pediatric patients under 18 years old who were diagnosed with patent ductus arteriosus (PDA), ventricular septal defect (VSD), or atrial septal defect (ASD) and underwent interventional treatment at the Children's Hospital of Chongqing Medical University. Patients with complex CHD, congenital developmental abnormalities, or genetic metabolic diseases were excluded from the study. Healthy children were recruited as the control group. Multiplesectional echocardiographic scans were performed on the lower sternal border, parasternal area, and suprasternal area to collect left ventricular diastolic function parameters (including left ventricular structure, blood flow spectrum for mitral valve and pulmonary veins, and tissue Doppler motion spectrum for mitral annular) as well as general information (age, height, weight, body surface area) during the ultrasound examination. Left ventricular function parameters in the case group were compared within 1 week before intervention surgery, 1 day after the surgery, and 1 month after the surgery to analyze the changes by taking the parameters of healthy children as the reference. Main outcome measures：Recovery levels of left atrial volume index (LAVI), early diastolic mitral flow peak velocity(E)/late diastolic mitral flow peak velocity(A) ratio, E/early diastolic mitral annular peak velocity at ventricular septum(E') ratio, and E/early diastolic mitral annular peak velocity at lateral wall(e') ratio after interventional therapy. Results：A total of 163 cases of CHD patients were included. There were 60 cases in the PDA subgroup, 42 cases in the VSD subgroup, and 61 cases in the ASD subgroup. A total of 61 healthy children were recruited for the control group. The PDA and VSD subgroups had significantly lower age, height, weight, and BSA compared to the control group. In the PDA, VSD, and ASD subgroups, LAVI, E/A ratio, E/e' ratio and E/E' ratio for mitral annular by tissue Doppler motion spectrum were significantly higher than those in the control group before the procedure with statistical significance. These indices decreased 1 day after the procedure and returned to the level of the control group 1 month after the procedure. The pulmonary vein flow spectrum D showed a decreasing trend before the procedure, 1 day after the procedure, and 1 month after the procedure, with a lower level in the control group 1 month after the procedure. Conclusion：Echocardiography can be used as an assessment tool for left ventricular diastolic function in children with common left-to-right shunt type CHD. There are varying degrees of left ventricular diastolic dysfunction in PDA, VSD, and ASD, which can be improved by interventional treatment, and can recover to almost normal levels after 1 month.

Background：The severity of mycoplasma pneumoniae pneumonia (MPP) is related to the formation of mucus plugs (MUP) in the airway, but the current MUP detection mainly depends on bronchoscopy. Objective：To establish a nomogram predictive model based on clinical features and plasma cytokines for airway MUP formation in MPP children. Design：Case -control study. Methods：Children who were diagnosed as MPP and underwent bronchoscopy were classified into MUP and non -MUP groups. Clinical features, inflammatory markers and cytokines in both plasma and BALF were collected. Univariate analysis was performed to identify statistically significant clinical features, inflammatory markers, and cytokine risk factors between the two groups. Spearman correlation analysis was conducted to assess the correlation between inflammatory markers, plasma cytokines and BALF cytokines and to exclude collinearity issues. A receiver operating characteristic (ROC) curve was generated to assess the predictive performance of a multivariable logistic regressionbased predictive model using the R package of RMS. Main outcome measures：Predictive efficacy of the nomogram model for predicting the probability of airway mucus plug formation in children with MPP. Results：A total of 263 children with MPP were included in the analysis, including 134 males and 129 females, with an average age of (7.0 ± 0.2) years. There were 82 (31.2%) cases in the MUP group and 181 cases in the non -MUP group. Univariate analysis showed significant differences between the two groups in age, maximum temperature before bronchoscopy, decreased breath sounds upon auscultation at admission, chest CT showing pulmonary consolidation, imaging suggesting pleural effusion, extrapulmonary complications, proportion of severe pneumonia, neutrophil percentage, CRP, PCT, D -dimer, LDH, IgA, lymphocyte percentage, and ALT. Cytokine analysis revealed significant differences between the two groups in levels of IL -5, IL -6, IL -8, and IFN -γ in plasma, as well as in levels of IL -1β, IL -5, IL -8, IL -10, IFN -γ, and TNF -α in BALF. Spearman correlation analysis showed there was no collinearity in neutrophil percentage, CRP, PCT, LDH, D -dimer, IgA, plasma IFN -γ, plasma IL -6, plasma IL -5, and plasma IL -8; there was a certain correlation between blood inflammatory markers and BALF cytokines; plasma cytokines (IFN -γ, IL -6, IL -5, and IL -8) were positively correlated with their corresponding BALF cytokines. The nomogram predictive model for the formation of airway mucus plugs in MPP patients, based on age, pleural effusion, D -dimer, and plasma IFN -γ levels, had an AUC of 0.817 (95% CI: 0.747 -0.889) with the sensitivity of 79.0% and specificity of 69.1%. Conclusion：The nomogram predictive model based on age, pleural effusion, D -dimer, and plasma IFN -γ levels had a good predictive performance for the formation of airway mucus plugs in MPP patients.

Background：Transcutaneous carbon dioxide partial pressure (TcPCO2) and transcutaneous oxygen partial pressure (TcPO2) monitoring make it possible to continuously monitor neonatal PCO2/PO2 and reduce the number of blood collections. However, clinicians are very concerned about its safety and accuracy. Objective：To reflect the consistency of TcPCO2/TcPO2 monitoring values and PaCO2/PaO2 monitoring values through a systematic review and meta-analysis. Design：Systematic review and meta-analysis. Methods：A systematic literature retrieval was performed in English databases of Ovid MEDLINE, Ovid Embase and Chinese databases of SinoMed, Wanfang and CNKI. Search strategy was developed using key words of neotate, TcPCO2 and TcPO2. After deduplication, the literature was first screened by reading titles and abstracts by two leading authors independently who then finished the full-text screening. A self-made excel form was used to extract the year of publication, gestational age at birth, gestational age at monitoring, birth weight, weight at monitoring, sample size and the number of monitored pairs, the probe temperature, monitoring site, duration and equipment, blood gas values difference by TcPCO2/TcPO2and PaCO2/PaO2 , correlation coefficient and adverse events. Meta-analysis was performed by Stata 17. Main outcome measures：Difference in blood gas results between TcPCO2/TcPO2and PaCO2/PaO2. Results：A total of 875 articles were retrieved in both Chinese and English. After deduplication, preliminary screening, and full-text screening, 40 articles were included in the analysis, including 14 in Chinese and 26 in English. The summarized differences between TcPCO2 and PaCO2 in probe temperature subgroups of 44℃ vs 43℃, 42℃, 40℃ vs 41℃, and 38℃ vs 39℃ were 2.37(95%CI: 2.17 to 2.67), 2.48(95%CI: 1.17 to 3.79), 4.47(95%CI: 3.03 to 5.92), and 5.96(95%CI: 5.27 to 6.64) respectively, and the Pearson coefficient ranged from 0.78 to 0.89 among the four subgroups. For the deviation from PaCO2, it was 5% in the 43℃ vs 44℃ subgroup, 118% to 14.8% in the 40℃ vs 41℃ subgroups, and 17% in the 38℃ vs 39℃ subgroups. The summarized difference between TcPO2 and PaO2 in probe temperature subgroups of 44℃ vs 43℃, 42℃, 40℃ vs 41℃, and 38℃ vs 39℃ were -7.28(95%CI: -12.92 to -1.63), -5.61(95%CI: -6.61 to -4.62), -28.85(95%CI: -35.12 to -22.58) and -31.42(95%CI: -35.97 to -26.88) respectively, and the Pearson coefficient was 0.35~0.91 among the four subgroups. Eight studies described mild skin redness and no adverse events of skin burns were reported. Conclusion：Without controlling the monitoring site, duration, time point, equipment, and neonatal diseases and conditions, TcPCO2 values are strongly correlated with the PaCO2 values, which is about 7mmHg higher than PaCO2. Under standardized operations, TcPCO2 can replace PaCO2. Within 38℃ to 44℃, the commonly used clinical probe temperature, the higher the probe temperature, the more accurately TcPCO2 can reflect PaCO2, the less skin redness adverse events will occur. Since TcPO2 is weakly related to PaO2, it is not recommended to use TcPO2 to reflect PaO2.

Background：Preschoolers are experiencing a key period of shaping healthy dietary behaviors, for which daily monitoring and timely intervention is urgently required. However, there is a lack of efficient tools for quantifying this level in China so far. Objective：To introduce a scale questionnaire named Nutrition Quotient for Preschoolers from the South Korea (NQ-P), and evaluate its reliability and validity. Design：Crosssectional study. MethodsThe Chinese version of NQ-P was obtained after forward and backward translation, research group review and modification. Guardians of preschoolers in two kindergartens were crosssectionally investigated and the data was collected for reliability and validity analysis. Main outcome measures;NQ-P(Chinese version) scores. Results:The Chinese version of NQ-P used the same scoring and weighting method as the original version, which included 14 items and 3 dimensions (balance, moderation, environment). A total of 440 guardians of preschoolers aged 36.5 years completed the study (97.3%). Among 440, 51.8% were boys, and among those who filled the questionnaires, 317(72.0%) were mothers, 115(26.1%) were fathers, and 282 of them were primary meal planners. Confirmatory factor analysis showed CFI were 0.768 for NQ-P total score, 0.9050.909 for 3 dimensions, RMSEA were 0.063 for NQ-P total score and 0.0310.043 for 3 dimensions. Cronbach's α were 0.7060.774 for NQ-P scores. Retest Kappa were 0.790.98 for 14 items. Conclusions:The Chinese version of NQ-P has acceptable validity and reliability, and can be used to initially evaluate the dietary quality of preschoolers by investigating their guardians.

Background：The Chinese Infectious Disease Surveillance of Pediatrics （ISPED） program collects and analyzes the monitoring data of antibiotics resistance from its member units annually to understand changes in pediatric infectious pathogens and resistance patterns in China. Objective：To explore the status of bacterial infections and resistance in children in China for 2023, aiming to guide the rational use of antimicrobial agents in pediatrics. Design：Crosssectional survey. Methods：Clinical isolates were collected from children hospitals in China enrolled in the ISPED program from January 1st to December 31st, 2023. Antimicrobial susceptibility testing was carried out using a unified protocol using the KirbyBauer method or automated systems. Penicillin susceptibility of streptococcus pneumonia was detected by Etest, with results evaluated according to the 2022 standards of the Clinical and Laboratory Standards Institute (CLSI). Main outcome measures：The distribution characteristics of bacteria strains in children, changes in antimicrobial resistance of major isolated strains, and the detection of multidrugresistant organisms (MDROs) in the pediatric population. Results：A total of 58,335 isolates were collected, of which 40% were grampositive organisms and 60% were gramnegative. The top five pathogens were as follows, Escherichia coli (14.5%), Streptococcus pneumonia (12.4%), Staphylococcus aureus (11.8%), Haemophilus influenza (10.2%), and Moraxella catarrhalis (6.4%). The most common pathogens in neonates and nonneonates were S. aureus (17%) and E. coli (14.4%), respectively. The primary specimen was the lower respiratory tract (47.1%), and the most common pathogens were S. pneumonia (24.3%) and H. influenza (19.4%). The rates of βlactamase production in Haemophilus influenzae and Moraxella catarrhalis were high, at 74.7% and 98.6%, respectively. Both S. pneumoniae and S. pyogenes showed highresistance to erythromycin and clindamycin. The proportion of penicillininsensitive S. pneumoniae (PNSP) from cerebrospinal fluid and noncerebrospinal fluid was 93.2% and 9%, respectively. Methicillinresistant S. aureus (MRSA) and Coagulasenegative staphylococci (MRCNS) accounted for 31.2% and 77.2%, respectively. The carbapenemresistant Enterobacteriaceae (CRE), carbapenemresistant P. aeruginosa (CRPA), carbapenemresistant A. baumannii (CRAB) were 3.7%, 8.1% and 30.8%, respectively. The detection rate of CRPA in the neonatal group was higher than that in the nonneonatal group (19.7% vs 7.4%, P<0.01), whereas the detection rate of CRAB was lower than that in the nonneonatal group (23.2% vs 32.1%, P<0.05). CRAB isolated from neonates presented higher resistance to multiple antimicrobials than nonneonates（P<0.05）. The detection rates of MRSA, CRE, CRPA and CRAB in the ICU department were much higher than those in other departments (P<0.001), especially CRAB, which was as high as 62.9%, much higher than that in the hematology department (23.5%, P<0.01) and other departments (28.1%, P<0.001). In addition, the proportion of CRE in hematology patients was 12.8%, higher than the 3.5% in other departments (P<0.001). Conclusion：In 2023, the detection rates of CRE and MRSA in Chinese children showed a decrease compared to previous years, while the overall detection rates of CRAB and CRPA increased compared to the previous two years, with a notably higher detection rate of CRPA in the neonatal group and CRAB in the nonneonatal group. Proactive screening and continuous monitoring of MDROs in the ICU and hematology departments should be strengthened.

Background：Neck circumference is a new anthropometric measurement parameter in recent years. However, there is no published study on the reference standard values and the growth charts of neck circumference for children and adolescents in China. Objective：To establish the reference standard values of neck circumference of children and adolescents aged 3-16 years and then to explore the cut-off values of neck circumference in predicting abdominal obesity in children and adolescents so as to provide a new index and reference for the clinical application of physical assessment in children and adolescents. Design：A cross-sectional study. Methods：The subjects were children and adolescents aged 3-16 years who underwent physical examination in the Children's Health Clinic of the Children's Hospital Affiliated to Nanjing Medical University from July 2021 to September 2022. Children with diseases that may affect neck circumference, growth and development, or limb disability, abnormal posture, or deformity were excluded. The neck circumference, height, weight, waist circumference and body composition were measured by 3 surveyors strictly according to the operating manual which was made by ourselves. Ten percent of samples were randomly selected for repeated verification, and the coincidence rate before and after verification should be ≥99%. Double track entry and logical check were carried out for data entry and arrangement. The neck circumference reference standard values of children and adolescents aged 3-16 years were established according to gender and age groups, and the growth charts were constructed by Lambda-median-sigma (LMS) method. Abdominal obesity was defined as waist-to-height ratio (WHtR) >0.48 in boys aged 6-16 years and girls aged 6-9 years, and WHtR >0.46 in girls aged 10-16 years. The association of neck circumference with other physical measures and abdominal obesity was analyzed. The area under the receiver operating characteristic (ROC) curve was used to analyze the accuracy of neck circumference reference in predicting abdominal obesity. Main outcome measures：The reference standard values of neck circumference for children and adolescents aged 3-16 years and the cut-off values of neck circumference for assessing abdominal obesity for children and adolescents aged 6-16 years. Results：A total of 18 371 children and adolescents aged 3-16 years were included in the analysis, including 10 701 boys (58.2%) and 7 670 girls. There were 5 407 (29.4%) children with abdominal obesity. In addition to body fat mass, neck circumference, age, height, weight, BMI, waist circumference, WHtR, skeletal muscle and skeletal muscle percentage (PSM) of boys were significantly greater than those of girls, body fat percentage (PBF) of girls was greater than that of boys, and the differences were statistically significant (all P<0.05). The neck circumference of boys and girls aged 3-16 years increased with age, and the neck circumference of boys was always greater than that of girls at each age. The average growth rate was 0.85 cm/year for boys and 0.65 cm/year for girls, which was similar for boys and girls aged 7 to 8 years. The annual growth rate of boys was greater than that of girls before the age of 7 and after the age of 8, and it was more obvious after the age of 12. For boys and girls, neck circumference was positively correlated with abdominal obesity (r male=0.614, r female=0.541), BMI (r male=0.824, r female= 0.800), waist circumference (r male=0.827, r female=0.801), WHtR (r male=0.729, r female=0.683) and PBF (r male=0.669, r female=0.679), and was negatively correlated with PSM (r male=-0.497, r female=-0.470). The optimal cut-off values of neck circumference for assessing abdominal obesity were 27.15-37.05 cm for boys and 26.25-30.50 cm for girls aged 6-16 years, both of which were located in the P75 of all gender and age groups. The area under the curve(AUC) of neck circumference in assessing abdominal obesity were ≥0.83 in boys and ＞0.79 in girls of all ages. Conclusions：The neck circumference of boys was greater than that of girls in all age groups and it increased with age from 3 to 16 years old. The optimal cut-off values of neck circumference for assessing abdominal obesity were 27.15-37.05 cm for boys and 26.25-30.50 cm for girls aged 6-16 years, and the AUC was≥0.83 in boys and ＞0.79 in girls of all ages, with high accuracy.

Background：Retinopathy of prematurity (ROP) can cause irreversible visual impairment in severe cases, and there is a lack of appropriate risk prediction model for identifying severe ROP specifically tailored to the Chinese preterm population. Objective：To construct and validate an early risk prediction model for severe ROP in premature infants with gestational age ≤ 34 weeks based on the Chinese neonatal population. Design：Retrospective cohort study. Methods：From January 2020 to March 2022, premature infants admitted to the Neonatal Intensive Care Unit (NICU) with a gestational age of ≤ 34 weeks and who underwent a complete eye examination were included. The cohort was divided into training and validation sets using the June 2021 admission time as the cutoff point. Clinical information was collected at the time of the first postnatal eye examination, and regular screenings and followups were conducted according to the ROP screening guidelines. Severe ROP is defined as having stage 3 or higher lesions, positive for plus disease, or requiring laser and cryotherapy treatment. All other cases are categorized as mild ROP. In the training set, clinical variables with collinearity were excluded based on the Pearson correlation coefficient and the final predictive factors were determined through Lasso regression and logistic regression analysis, then the prediction model was constructed and presented as a nomogram. In the validation set, the area under the curve (AUC) of receiver operating characteristic (ROC) was used to evaluate the discrimination and determine the optimal cutoff value of the prediction model, in which the sensitivity and specificity of the model were calculated. Based on the total population, clinical efficacy of the model was finally assessed by decision curve analysis (DCA). Main outcome measures：The predictive performance of the model for identifying premature infants who will progress to severe ROP. Results：There were 1,380 cases in the training set (76 cases with severe ROP) and 592 cases in the validation set (36 cases with severe ROP). The differences in the distribution of baseline information between these two groups were not statistically significant. The nomogram prediction model established by including five predictors of gestational age, birth weight, prenatal corticosteroids, invasive mechanical ventilation, and lateonset sepsis had an AUC of 0.87 (95% CI: 0.83 to 0.90) and 0.88 (95% CI: 0.82 to 0.94) in the training and validation sets, respectively. When the predictive threshold was set at 0.04, the model had a sensitivity of 0.833 (95% CI: 0.7120.955) and a specificity of 0.786 (95% CI: 0.7520.820) in the validation set. The clinical decision curve demonstrates that the model has good clinical utility and provides higher net benefits when the threshold probability ranges from 5% to 40%. Conclusions：The severe ROP prediction model established has a certain reference value for evaluating the risk of severe ROP in neonates with gestational age ≤ 34 weeks.

Background The collective living environment during the preschool period is associated with a high incidence of acute upper respiratory tract infections (AURTIs). Objective To explore the effectiveness of physiological saline nasal irrigation (seawater) in preventing AURTIs in healthy preschool children entering childcare centers, providing a theoretical basis for improving hygiene and healthcare in childcare institutions. Design Singlecenter randomized controlled trial (RCT). Methods Healthy children in the middle class of kindergartens were selected as the study subjects, and cluster random sampling was conducted at the class level. The study was not blinded. The intervention group received nasal care with seawater nasal irrigation at room temperature, with one spray before entering and leaving the kindergarten each day, for a semester of kindergarten attendance (192 times over 96 days). The operation was performed according to the recommended methods in the Expert Consensus on Nasal Saline Irrigation in Children with Upper Respiratory Tract Infections (2023). The control group received organized interventions when entering and leaving the kindergarten each day. The kindergarten healthcare doctors recorded nasal irrigation twice daily and adverse reactions. Interrupted nasal irrigation time, the first report of AURTIs, onset time of nasal symptoms, relief time, disappearance time, and withdrawal time were also recorded. Those meeting the following criteria were excluded: children in the intervention group with nasal irrigation interruption ≥1 week (including Saturdays and Sundays); children with absenteeism exceeding 20% of the school days during the study period (19 days); children who withdrew from the study halfway (e.g., transferring schools); children who used antibiotics, antiviral drugs, or antichlamydial infection drugs based on medical records during the study period; children whose first occurrence of AURTI or nasal symptoms was not reported to the kindergarten within 24 hours according to the CRF table. Main outcome measures Incidence of AURTIs (the number of children who developed AURTI within 48 hours of enrollment divided by the number of enrollees). Results A total of 234 children in the middle class of kindergartens who met the inclusion and exclusion criteria were included in the analysis, with 120 in the intervention group and 114 in the control group. There were no statistically significant differences in gender, age, weight, and actual days in kindergarten between the two groups of children. The incidence of AURTIs during the study period ［55 (45.8%) vs. 81 (71.0%)］and the average number of AURTIs ［(0.7±1.0) vs. (1.4±1.3)］ in the intervention group were significantly lower than those in the control group (P<0.05). There were no statistically significant differences in the incidence of AURTIs between boys and girls in the intervention group. It is the same with the control group. However, there were statistically significant differences in the incidence of AURTIs between two groups in both boys and girls. The intervention group showed statistically significant differences in the relief time ［(2.3±1.0 days) vs. (2.8±0.9 days)］ and disappearance time ［(5.4±1.1 days) vs. (5.8±1.0 days)］ of nasal symptoms compared to the control group. Three cases of mild nasal bleeding occurred in the intervention group, but nasal irrigation intervention continued because of the children's tolerance, and no nasal irritation or ear pain was found. Conclusion Physiological seawater nasal irrigation can reduce the incidence and frequency of AURTIs in healthy preschool children entering childcare centers. It can also effectively relieve nasal symptoms associated with AURTIs and shorten the duration of symptoms. The clinical operation is simple and convenient with few adverse reactions.

Background: Executive functions (EFs) are crucial for the physical and psychological development of children, and exercise is a cost-effective method to enhance EFs in children. Studies have shown that exercise combined with cognitive training (ECT), which involves higher cognitive engagement, may have a more significant effect on children's EFs. However, existing research conclusions are inconsistent. Objective: To systematically analyzed the intervention effect of ECT on EFs in children. Design: Systematic review. Methods: A systematic search was conducted on PubMed, Web of Science, Cochrane, Embase, Google Scholar, and China National Knowledge Infrastructure (CNKI) databases from the inception to October 17, 2023. Inclusion criteria were: randomized controlled trials (RCT) or non-randomized controlled trials（NRCT）; healthy child participants; ECT intervention with both exercise and at least one explicit cognitive task component for the experimental group; any form of exercise other than cognitive engagement or traditional physical education (PE) for the control group; intervention duration longer than 6 weeks; at least one EF-related assessment outcome; articles in Chinese or English. Risk of bias was assessed using the 2010 Physiotherapy Evidence Database (PEDro) scale. The percentage change in each outcome measure before and after the intervention ［(post-test-pre-test) / pre-test × 100%］ was extracted or calculated, with a P-value < 0.05 indicating significant results. The overall effect size of the indicator was evaluated by the proportion of significant results in all included literature, with > 2/3 indicating a significant effect of the intervention strategy. Main outcome measures: Percentage change in EF indicators before and after the intervention. Results: Nine English articles were included. Four articles had aerobic exercise (AE) control groups, and 8 had PE control groups. The intervention lasted from 6 to 40 weeks with 1 to 10 times per week and 10 to 150 minutes for single exercise. PEDro scale scores were 5 in 3 articles, 6 in 5 articles and 7 in 1 article.The improvement in working memory in the ECT group was more significant than that in PE group, with an effectiveness of 71.4%. Improvement in cognitive flexibility were more significant in the ECT group compared to both AE and PE groups, with effectiveness of 100% and 75%, respectively. Conclusions: ECT significantly improves EFs in school-aged healthy children, with a greater enhancement in cognitive flexibility compared to AE and PE, an improvement in working memory superior to PE, and equivalent improvement in inhibitory control when compared to AE and PE.

Background：The disturbance coefficient(DC) is the main technical parameter of noninvasive brain edema dynamic monitoring instruments, and there is no normal reference value for children and adolescents at home abroad. Objective：To establish the reference intervals of DC for children and adolescents aged 116 years. Design：Multicenter prospective crosssectional survey. Methods：From March 2020 to March 2023, children and adolescents aged 116 years without craniocerebral injury were recruited from 6 hospitals 2 kindergarten and primary schools in Chongqing, Sichuan and Shenzhen. The noninvasive brain edema dynamic monitor was used for continuous monitoring for 15 minutes, and the monitoring average was taken as the final DC value of the subjects. Generalized Additive Models for Location, Scale, and Shape (GAMLSS) were used to draw P1, P5, P10, P25, P50, P75, P90, P95, P99 percentile values and percentile curves for disturbance coefficients of different ages. Independent sample ttest was used to analyze the difference of DC between boys and girls, and analysis of variance was used to calculate the DC mean value in different age groups and the difference of DC in different age groups. The changes of DC with age, weight and head circumference were explored by drawing scatter plots and Loess local weighted nonparametric regression curves. Main outcome measures：Disturbance coefficient. Results：A total of 1 247 children and adolescents with no cranial injuries were included in the study, including 787 males (63.1%) and 460 females. The observed fitted percentile curves of disturbance coefficients for children and adolescents of different ages showed that the level of disturbance coefficients gradually increased with age, and the growth of disturbance coefficient curves slowed down and eventually stopped after 5 years of age. In the overall population, there was no significant difference in DC levels between males and females (P>0.05), and there was no significant difference in DC among children and adolescents of different ages and genders. Correlation analysis showed that when age＜5 years old, body weight<18.0 kg and head circumference<51.0 cm, DC was significantly positively correlated with age, body weight and head circumference (r=0.663, 0.454 and 0.474, respectively). On the contrary, when age≥5 years old, body weight≥18.0 kg and head circumference≥51.0 cm, DC did not change significantly and gradually stabilized at 107. Conclusions：The study constructed the percentile curve of DC in children and adolescents aged 1 to 16 years old. When the age was ＜5 years old, the DC increased with age, and when the age was ≥5 years old, the DC gradually stabilized at 107.

Background：The clinical characteristics of neonatal vocal cord paralysis (VCP) and the factors influencing shortterm prognosis remain uncertain. Objective：To investigate the factors influencing the discharge outcomes of neonatal VCP. Design：Retrospective cohort study. Methods：The study included neonates diagnosed with VCP by medical history, clinical signs, and bronchoscopy results in the Neonatal Intensive Care Unit (NICU) of Jinan Children's Hospital between April 2013 and January 2022. The cases were divided into two groups: the improved discharge group (those who did not require invasive ventilation and were able to suckle independently at discharge) and the nonimproved discharge group. The data collected for univariate analysis included maternal data of age, gestational hypertension, gestational diabetes, mode of delivery, premature rupture of membranes, nuchal cord, umbilical cord torsion, and amniotic fluid conditions; neonatal data of gender, gestational age, birth weight, 1minute Apgar score, associated malformations, and laryngeal obstruction; VCP etiology of birth injury, neurogenic, iatrogenic, and idiopathic; unilateral VCP and bilateral VCP (complete paralysis and incomplete paralysis) by bronchoscopy; and prognosis at the time of discharge. Variables with a P-value <0.10 in the univariate analysis were included as independent variables in the multivariate logistic regression analysis. Main outcome measures：Factors influencing the improved discharge. Results：A total of 133 cases of neonatal VCP were included in the analysis. The age of the first bronchoscopy examination was 6 (4, 12) days, the admission age was 13.0 (3.0, 20.5) days, and the gestational age was 39.0 (38.0, 40.0) weeks. There were 71 cases (53.4%) with associated malformations, 43 cases (32.3%) with unilateral VCP and 90 cases with bilateral VCP including 57 cases of incomplete paralysis and 33 cases of complete paralysis. The improved discharge group consisted of 96 cases (72.2%), while the non-improved discharge group had 37 cases, including 28 cases with difficulty weaning, 8 cases with tracheostomy (7 cases of bilateral incomplete paralysis and 1 case of bilateral complete paralysis). All tracheostomized patients were successfully weaned from positive pressure ventilation and discharged. Among them, 4 cases had restored vocal cord mobility within 9 months, and the remaining 4 cases were lost to follow-up. Thirty-seven cases had feeding-swallowing-breathing coordination disorders. Multivariate logistic regression analysis was performed on variables with a P-value <0.10 in the univariate analysis, including cesarean section, polyhydramnios, birth weight, low Apgar score, neurogenic injury, laryngeal obstruction, and type of vocal cord paralysis. The results showed that bilateral incomplete paralysis was a negative factor for improved discharge in neonates with VCP (OR=6.785, 95% CI: 2.191-21.013, P=0.001). Conclusion：Neonates with bilateral VCP, especially for the incomplete ones have poorer discharge outcomes, and tracheostomy can be used as a palliative treatment option.

Background：The Food and Drug Administration(FDA) Adverse Event Reporting System (FAERS) is an open database. After the outbreak of COVID-19, it is important to further evaluate the potential safety signals associated with the use of ibuprofen and acetaminophen. This is crucial for improving safety and protecting public health. Objective：To provide references for the clinical discovery, prevention, and management of adverse events (AEs) in children by performing signal detection of AEs related to ibuprofen and acetaminophen in children using the FAERS database. Design：Data mining analysis. Methods：The OpenVigil 2.1 software was used to extract AE reports with ibuprofen or acetaminophen as primary or secondary suspect drugs in patients aged ≤17 years, without restriction on gender or country. The reporting odds ratio (ROR) and Bayesian confidence propagation neural network (BCPNN) were used for signal detection. The AE reports were analyzed based on gender, country, year, and age groups (≤3 years, -11 years, and -17 years). The detected potential risk signals were classified according to SystemOrgan Classes (SOC) based on the Preferred Terms in the Medical Dictionary for Regulatory Activities. The changes in strong and mediumstrong potential risk signals were analyzed before and after the COVID-19 pandemic. Main outcome measures：Strong and mediumstrong potential risk signals before and after COVID-19. Results：A total of 7,552 (53.5 percent) reports were related to ibuprofen and 6,562 reports were related to acetaminophen in the FAERS database from the first quarter of 2004 to the third quarter of 2022. The number of AE reports for acetaminophen was higher in females, while the number of AE reports for ibuprofen was higher in males, with statistically significant differences. The number of AE reports for ibuprofen was higher than that for acetaminophen in the ≤3 years and -11 years age groups, while the number of AE reports for acetaminophen was higher than that for ibuprofen in the -17 years age group, with statistically significant differences. The United States accounted for 42.8% of ibuprofen-related AE reports and 41.7% of acetaminophen-related AE reports. Among the top 10 countries reporting AE, except for the United States and China, all were European countries. There were 358 potential risk signals for ibuprofen, including 2 strong signals, 58 medium-strong signals, and 298 weak signals. For acetaminophen, there were 283 potential risk signals, including 6 strong signals, 48 medium-strong signals, and 229 weak signals. Ibuprofen had more signals detected in the gastrointestinal system, skin and subcutaneous tissue, infectious and parasitic diseases, renal and urinary system, respiratory system, thorax, and mediastinum, and eye disorders by SOC compared to acetaminophen. Acetaminophen had more signals detected in the hepatobiliary system, psychiatric disorders, investigations, general disorders and administration site conditions, and nervous system disorders by SOC compared to ibuprofen. Three strong signals for ibuprofen were detected before the COVID-19 pandemic, including angioedema, extra dose administered, and accidental exposure to product. No strong signals were detected after the pandemic. However, attention should be paid to the change from weak to medium-strong signals in renal interstitial nephritis, acute kidney injury, nephrotic syndrome, toxic nephropathy, and membranous glomerulonephritis in the renal and urinary system disorders by SOC. Four strong signals for acetaminophen were detected before COVID-19, including liver necrosis, liver injury, acute liver failure, and liver failure. No strong signals were detected after the pandemic. However, attention should be paid to the medium-strong signals of suicide attempt, drug dependence, and drug abuse in the psychiatric disorders by SOC. Conclusion：Physicians, pharmacists, and patients are encouraged to actively report potential safety signals associated with the use of ibuprofen and acetaminophen, as there is an increased risk of renal adverse events with ibuprofen and an increased risk of intentional poisoning and suicide events with acetaminophen.

Background：There are few reports about the outcomes of neonatal hyperthyrotropin (HT) in China. Objective：To investigate the outcome and influencing factors of HT in neonatal intensive care units (NICU). Design：Case-control study. Methods：Consecutive cases of HT infants were enrolled in the NICU of Xinjiang Uygur Autonomous Region People's Hospital from January 1, 2011, to December 31, 2021. The inclusion criteria were as follows: the concentration of thyroid-stimulating hormone (TSH) was 6-20 mU·L ^-1at the first test between 3 and 21 days after birth and the free thyroxine (FT4) was within the normal range. During the follow-up after discharge, TSH<6 mU·L ^-1 was considered as the normal level and TSH≥10 mU·L ^-1 was the indicator for levothyroxine (LT4) as needed. A dosage less than 3 μg·kg ^-1·d ^-1 could be an indicator for considering discontinuation of LT4 treatment. The administration could be stopped if TSH was tested normal in the re-examination 1 month later. Main outcome measures：The influencing factors of abnormal TSH levels at 3 months of age (90±15 days) and LT4 treatment discontinuation at the age of 3 years. Results：A total of 836 neonates were included in this study. At 3 months of age, 390 cases were lost to followup or unable to be assessed. Normal thyroid function was found in 304 cases ［TSH: 3.6 (2.7,4.5) mU·L-1, FT4:18.3 (15.6,20.4) pmol·L ^-1］, and thyroid dysfunction was found in 142 cases［TSH: 17.7 (9.6,22.1) mU·L ^-1, FT4 is 15.7 (13.3,19.4) pmol·L-1］. The influencing factors of thyroid dysfunction were female (OR=1.68, 95%CI: 1.07-2.64), cesarean section (OR=0.52, 95%CI: 0.32-0.83), maternal thyroid disease during pregnancy (OR=0.31, 95%CI: 0.15-0.67), comorbid congenital malformation or syndrome (OR=7.92, 95%CI: 2.22-28.25), infectious disease at admission (OR=0.56, 95%CI: 0.33-0.96). At the age of 3 years, among 142 children with thyroid dysfunction, 18 (12.6%) were lost to follow-up, 48 (33.8%) turned into normal TSH levels without taking LT4, and 45 out of 76 cases taking LT4 stopped the administration and 31 still continued the treatment. The risk of not being able to discontinue LT4 treatment before the age of 3 years was 4.89 times higher in infants with congenital malformations or syndromes compared to those without the comorbidity (OR=4.89, 95% CI: 1.06-22.57). Conclusion：Special attention should be paid to the follow-up of thyroid function in HT infants in the NICU, especially for female infants and those with comorbid congenital malformations or syndromes.

Background:Few studies have focused on the adherence to and implementation barriers of clinical practice guideline recommendations. Objective:To assess compliance with the Clinical Practice Guidelines for IntraHospital Transport of Pediatric Patients (2023) among medical staff in the emergency department and PICU and to identify the implementation barriers. Design:Field study Methods:The research was carried out in the emergency department, PICU, and general wards of Children's Hospital of Fudan University. Through participation in the practice of medical staff during intrahospital transport of critically ill children, field notes were used to describe the current situation of oneway transport from the emergency department or PICU to general wards, as well as to analyze the barriers to implementing recommendations in the guideline. Based on recommendations 15 of the guideline, the PICUtotargetdepartment process (Appendix 2G in the guideline), was divided into three phases (pretransport, during transport, and upon arrival at the receiving department) and 10 specific indicators. Descriptive observation, interviews, focus observation, and selective observation were employed to collect data. A template analysis method was used to extract baseline data from the field notes and analyze compliance with specific indicators and barriers. Main outcome measures:Barriers to adhering to recommendations of 15 in the guideline. Results:From January 1st to March 21st, 2024, 49 intrahospital transports of critically ill children involving 25 medical staff (7 emergency nurses, 7 PICU doctors, and 11 PICU nurses) were observed. Ten transports were from the emergency department to the PICU, and 18 and 21 were from the PICU to internal and surgical wards, respectively. The 25 participating medical staff had an average age of 31.3±5.0 years, and the children transported (49 cases) had an average age of 70.0±48.6 months. The average transport time was 16.1±6.0 minutes, with an average bedside handoff time of 6.8±3.5 minutes. Bedside handoffs were interrupted in 11 cases, and two adverse events were recorded during transport: forgetting to carry tube feeding and a child vomiting en route. The 10 indicators across the three phases of transport (pretransport, during transport, and upon arrival at the receiving department) showed partial compliance with the guideline recommendations. The transport decisionmaking, child placement, and inquiry indicators generally aligned with the guideline; the monitoring, telephone communication, and transport planning indicators partially complied, while transport personnel, equipment and medication preparation, evaluation and documentation, and handoff of the child's condition did not meet the guidelines The preparation for receiving the child was in line with the recommendations. Potential barriers to guideline implementation included low enthusiasm among medical staff for adopting new practices, lack of effective communication mechanisms between departments, gaps between recommended practice and clinical situations, poor adherence to specific guideline evidence, and insufficient innovation in the guideline recommendations. Conclusion:Adherence to the guideline recommendations for intrahospital transport of critically ill children is poor. Barriers include insufficient awareness among medical staff regarding the safety of intrahospital transport and a gap between the guideline recommendations and actual clinical transport scenarios.

Background Despite that numerous researches have investigated the pathogenesis of Kawasaki disease (KD), including epidemiology, genetics, infection, immunity, and inflammation. However, the causes of KD is still not well underlined. Objective We analyzed the blood samples of KD patients and control cases using modified highthroughput metagenomics sequencing to identify the bacterial and viral composition and relative abundances, aiming to demonstrate the potential pathogenic virus of KD. Design Casecontrol study. Methods We collected the blood samples from KD patients and controls, then purification, extraction and sequencing of viruslike particles had been completed. After quality control of raw data, macrogenome was assembled by MEGAHIT software and species annotating was performed on kraken2. Obtaining relative abundance of each sample at different taxonomic levels (phylum, order, family, genus, and species), we normalized taxon abundance with the online tool Wekemo Bioincloud. The top 20 taxa were displayed and analyzed comparatively using linear discriminant analysis. LDA>2 was set as the criteria of significant differences in abundance between groups for filtering potential pathogenic species. Main outcome measures Relative abundance of each sample at different taxonomic levels (phylum, order, family, genus, and species). Results We found that there was little difference between KDs and the controls in terms of overall microorganism. Only phylum Cossaviricota and species Bacillussp Y1 were significantly different. However, there was a great significant difference between viral population annotations. The relative abundances of Uroviricota, Nucleocytoviricota, and Taleaviricota were significantly higher in controls compared with KD patients. Various genera, such as Orthohepadnavirus, Pegunavirus, Montyvirus, Orthonairovirus, Toursvirus, showed significantly higher relative abundance in KDs. In KD patients, the relative abundance of Woodchuckhepatitis virus, Propionibacterium virus (PHL112N00, ATCC29399BT, Pirate, and P105), Diadromus pulchellus toursvirus, and so on were significantly more abundant than that in controls. Conclusion Summarily, we screened out several candidates KD pathogenic viruses, like WHV, Orthonairovirus, and DpTV1. These viruses may be responsible for acute febrile illness or liver damage in KD patients, or they may be able to disrupt patients' immune systems, but further investigations are required.

Background：Premature infants are prone to hemodynamically significant patent ductus arteriosus (hsPDA), which can lead to changes in cerebral blood flow parameters. However, there is limited research on the recovery of cerebral blood flow after ductus arteriosus ligation. Objective：To analyze the impact of hsPDA on cerebral blood flow in premature infants and the recovery of cerebral blood flow after ductus arteriosus ligation using bedside transcranial Doppler ultrasound measurements. Design：Case series report. Methods：Cases who were diagnosed with hsPDA, born at a gestational age of less than 37 weeks, and admitted to the NICU of Zhejiang University School of Medicine Children's Hospital from July 2022 to January 2023, were selected from the HIS system as the case group. The control group consisted of infants with gestational age<37 weeks at the same period in NICU who were confirmed to have no PDA by echocardiography after 72 hours of birth. Cases with concurrent cyanotic or complex congenital heart diseases, severe intracranial hemorrhage or hydrocephalus, and cases undergoing surgical treatment for intestinal infection, necrosis, and perforation were excluded from both groups. Cerebral blood flow parameters of the middle cerebral artery (MCA) and basilar artery (BA) were measured using echocardiography. Main outcome measures：Blood flow parameters of MCA and BA after ductus arteriosus ligation. Results：There were twenty-eight cases in the case group. Arterial duct closure was achieved through medical treatment in 7 cases and surgical intervention in 21 cases. Fourteen cases （50%）were male, and the internal diameter of the PDA was measured to be 2.77±0.53 mm. The control group consisted of 30 cases, and 14 cases (46.7%) were male. No statistically significant differences were found in gender, birth weight, and age between the two groups. The gestational age at birth in the case group was lower than that in the control group, and this difference was statistically significant. For the MCA and BA, the preoperative systolic peak flow velocity (Vs) between the case group and control group had no statistically significant differences; the enddiastolic velocity (Vd) in the case group were lower compared to that in the control group; the preoperative resistance index (RI) and the ratio of Vs to Vs (S/D) were both higher in the case group than that in the control group. These differences were statistically significant. The cerebral blood flow parameters (Vs, Vd, RI and S/D) of MCA and BA in case group after surgery (within 72 hours after PDA ligation surgery in 21 cases) have no statistically significant differences compared to that in the control group. Conclusion：hsPDA causes the abnormities of blood flow parameters in the anterior and posterior circulation of cerebral artery in premature infants. After ductus arteriosus ligation, cerebral blood flow can rapidly recover.

Background：In adult asthma studies, salmeterol/fluticasone propionate combination(FSC) has been shown to achieve better efficacy and comparable safety than fluticasone propionate alone(FP), but reliable clinical evidence is still lacking in children with asthma. Objective：To conduct a systematic review and meta-analysis on salmeterol/fluticasone propionate combination and fluticasone propionate alone in the step-up treatment of children with asthma, and to explore the efficacy and safety of the two groups. Design:Systematic review and meta-analysis. Methods:Randomized controlled trials(RCTs) of salmeterol/fluticasone propionate combination versus fluticasone propionate alone were systematically searched in Cochrane, MEDLINE (via PubMed), Embase, Web of Science, CBM, CNKI and Wanfang databases from the inception to September 2023. Two researchers independently finished literature screening, data extraction, risk of bias assessment, and evidence quality summary. Data analysis was completed through R Studio1.4.1717. Main outcome measures:Asthma exacerbations and adverse events related to inhaled corticosteroids (ICS) and FSC. Results:A total of 11 RCTs with 9 438 children with asthma were included. The comparison between fluticasone propionate/salmeterol combination and fluticasone propionate alone showed a statistical difference in the improvement in maximal expiratory flow at 50% vital capacity(MEF50) (MD=0.17, 95%CI: 0.16-0.18,P<0.000 1), mean morning peak expiratory flow(PEF) (MD=4.84, 95%CI: 4.53-5.15,P<0.000 1) before and after treatment, improved percentage of symptom-free days (MD=1.39, 95%CI: 1.36-1.41,P<0.05) and albuterol-free days (MD=1.09, 95%CI: 1.06-1.12, P<0.05) before and after treatment. But there was no statistically significant difference in the reduction in asthma exacerbations(RR=0.87, 95%CI: 0.70-1.09, P=0.22),the incidence of reduced ICS and FSC-related adverse events(RR=0.99, 95%CI: 0.61-1.60, P=0.95) and other adverse events(RR=0.98, 95%CI: 0.91-1.05, P=0.55). Conclusions:Compared with fluticasone propionate, salmeterol/Fluticasone propionate combined therapy significantly improved lung function (MEF50, mean morning PEF) and asthma symptoms, and reduced the use of salbutamol in treatment, but there was no difference in the reduction in asthma exacerbations. The safety was similar in both groups, with no additional drug-related adverse events or increased incidence of adverse events due to the addition of salmeterol.

Objective: To investigate the association between body composition and blood pressure in children. Design: Systematic review/Meta-analysis. Methods: We conducted computer searches in four Chinese databases (CNKI, Wanfang Data, VIP and CBM), as well as four international databases (PubMed, Web of Science, and EBSCO) from inception to August 8, 2023. We included longitudinal cohort studies examining the relationship between body composition and childhood blood pressure. Two reviewers independently screened the literature, extracted data, and assessed the risk of bias in the included studies. We summarized the results quantitatively and qualitatively. Main outcome measures: Association between body composition and childhood hypertension. Results: A total of 9 longitudinal cohort studies were included, investigating the longitudinal relationship between body composition and systolic and diastolic blood pressure in children. Seven of these studies reported the association of fat mass-related indicators with blood pressure in children, showing a positive correlation between childhood fat mass percentage and blood pressure. However, conclusions regarding other fat mass indicators were inconsistent. Two studies reported on the relationship between non-fat mass and childhood blood pressure with inconsistent findings. Three studies reported a positive correlation between fat mass and the occurrence of high systolic and diastolic blood pressure in childhood, although the risk of hypertension may be negatively correlated with neonatal fat mass. Conclusion: The percentage of body fat in children is positively correlated with both diastolic and systolic blood pressure. Body composition has a significant impact on blood pressure in children.

Background: The effectiveness of clinical practice and the improvement of care quality are evaluated based on the satisfaction and experience of parents whose infants have been admitted to the neonatal intensive care unit (NICU). Currently, there is a lack of a professional assessment tool in China for evaluating parental satisfaction in the NICU. Objective: To translate the Empowerment of Parents in The Intensive Care-Neonatology (EMPATHIC-N) into Chinese to make it a family-centered parent satisfaction assessment tool appropriate for NICUs in China. Design: Cross-sectional study. Methods: The original version of the EMPATHIC-N scale was translated into Chinese using ten steps of scale translation and cultural adaptation summarized by Wild. The sample size was estimated to facilitate sampling methods. The parents were included for infants admitted to the NICU at Children's Hospital of Fudan University between March 2021 and June 2022，with a gestational age＜37 weeks，the birth weight＜1,500 g, and the length of stay ＞72 hours. Infants who passed away during their hospitalization were excluded. A nurse who has received training explained the purpose of the study to the parents and guided them to complete the questionnaire. Each family received one copy. The parent, either the mother or the father, filled out the questionnaire on the spot, and the data were checked by the nurse. The internal consistency reliability and Spearman-Brown split-half reliability of the Chinese version of the EMPATHIC-N scale were tested using Cronbach's α coefficients and split-half reliability coefficients. The construct validity of the Chinese version of the EMPATHIC-N scale was evaluated through exploratory factor analysis and confirmatory factor analysis. Main outcome measuresReliability and validity of EMPATHIC-N scale in Chinese. Results: A total of 330 questionnaires were distributed and all were effectively collected. The Chinese version of the EMPATHIC-N scale comprises 57 items. During exploratory factor analysis, principal component analysis resulted in the extraction of five factors including information provision, care and treatment, parental involvement, unit environment, and professional attitude. These factors exhibited characteristic root values exceeding 1, contributing to a cumulative variance explanation rate of 87.4%. The factor loadings for each item ranged from 0.706 to 0.953. The validation factor analysis model's fitting results revealed a chi-square degree of freedom ratio of χ2/df=6.635, with an RMSEA of 0.131, a SRMR of 0.053, a CFI of 0.807, and load factor numbers ranging from 0.792 to 0.999. The evaluation of convergent validity revealed that the average variance extracted (AVE) of the scale ranged from 0.757 to 0.964, while the composite reliability value was between 0.974 and 0.996. The discriminant validity evaluation revealed that the square root of the AVE of the five factors in the scale ranged from 0.870 to 0.982. Furthermore, the square root of each factor's AVE was greater than the absolute value of its correlation coefficient with other factors. Internal consistency test showed that the coefficients for Cronbach's alpha of the five factors and the total scale α are 0.976, 0.996, 0.975, 0.995, 0.973, and 0.982, respectively. The Spearman-Brown split-half reliability results revealed that the split-half correlation coefficients for the five factors and the total scale were 0.988, 0.998, 0.980, 0.994, 0.984, and 0.771, respectively. Conclusion: The Chinese version of the EMPATHIC-N scale exhibits satisfactory reliability, convergent validity, and discriminant validity, however, the model fitting effect is not satisfactory. It is imperative to validate the evaluation tool for parental satisfaction in the full-time accompanying NICU setting.

Background Over the past two decades, implementing perioperative feeding protocols in infants with critical congenital heart disease (CCHD) has a certain effect on fostering their physical development and enhancing their clinical outcomes. Nevertheless, the existence of diverse feeding protocols and their appropriate application to different infant populations and feeding stages remains a pending issue. Objective To evaluate the effect of standardized perioperative feeding protocols on the physical development and clinical outcomes of critically ill infants with CCHD. Design Systematic review and meta-analysis. Methods Systematic retrieval was conducted across foreign language databases, including PubMed, Embase, The Cochrane Library, and Web of Science, as well as Chinese databases, such as SinoMed, China National Knowledge Infrastructure, and Wanfang Database. CCHD infants adhering to a standardized feeding protocol during the perioperative period were included. The outcomes evaluated included the incidence of necrotizing enterocolitis (NEC), physical development indicators, hospital length of stay (LOS), ICU LOS and mechanical ventilation duration. The study type consisted of randomized controlled trial (RCT), non-randomized trial, cohort study, case series report, and systematic review/meta-analysis. The literature was searched from the inception of the database up to December 11, 2022. Three individuals conducted literature screening and data extraction based on the predefined criteria. The risk of bias assessment for non-randomized studies and randomized clinical trials was performed using ROBINS-I and ROB 2, respectively. Meta-analysis was carried out using RevMan 5.4 and R version 4.2.2. Main outcome measures The incidence of NEC. Results A total of 11 studies conducted in the US from 2000 to 2020 were included. One article employed a non-randomized control trial, 9 used case before-after study design, and 1 used self-before-after study design. The standardized feeding protocol was implemented in 3 studies during the pre-operation period, 4 during the post-operation period, and 5 during the perioperative period. The gestational age of participants ranged from 35 to 41 weeks. Among the included articles, 8 reported the incidence of NEC as the primary outcome. Separate meta-analyses were conducted by different stages of intervention implementation. In a meta-analysis of two articles that implemented standardized protocols during the peri-operation period, the result revealed that there was no statistically significant difference in the incidence of NEC between the two groups［odds ratio (OR)=0.57 (95% CI: 0.19-1.76)］. The results of the other 2 meta-analyses were as follows: one for 3 articles implementing intervention during the pre-operation period showed no statistically significant difference［OR=0.95 (95% CI: 0.48-1.88)］ , and the other for 3 articles during the post-operation also showed no statistically significant difference［OR=0.69 (95% CI: 0.35-1.34)］. Among the 4 articles that reported the weight-for-age z-score at discharge, a meta-analysis of 3 of them found no statistically significant difference between the two groups, WMD=-0.10 (95% CI: -0.37- 0.17). Ten articles reported LOS. A meta-analysis of LOS for intervention during the pre-operation period revealed that LOS was significantly shorter in the study group, WMD=-6.83 (95% CI: -12.13--1.53). However, other meta-analyses of ICU LOS (2 articles) and mechanical ventilation duration (3 articles) all revealed no statistically significant differences between the two groups. The critical appraisal of the included articles indicated that 4 of them were at moderate risk of bias, 6 were at high risk, and 1 was at critical risk. Conclusions A standardized perioperative feeding protocol implemented in surgical infants with CCHD can not reduce the incidence of NEC, improve the weight-for-age z-score at discharge, and cut down the LOS, ICU LOS, and mechanical ventilation duration.

Background：The clinical manifestations of primary ciliary dyskinesia(PCD) are relatively diverse and often undiagnosed or delayed in diagnosis and treatment. Objective：To investigate the clinical characteristics and genetic spectrum of primary ciliary dyskinesia in children. Design：Case series study. Methods：The medical records system was used to collect clinical information on PCD gene-positive children admitted to Children's Hospital, Zhejiang University School of Medicine between June 1, 2017 and December 31, 2023. This information included gender, age of onset and diagnosis, clinical manifestations, auxiliary examinations, and genetic testing results. A search of Chinese and English databases was conducted to include case series reports of PCD with PCD-related gene positivity in China. The search period spanned from the establishment of the database until December 2023. This study summarises the clinical phenotypes and genotypes of PCD cases in China, as well as their distribution across various regions of the country. Main outcome measures：Clinical characteristics and genetic spectrum of children in China. Results：Thirteen children diagnosed with PCD were analysed, comprising of 7 boys (53.8%) and 6 girls. The median age of onset was 9.0 years (ranging from 3 days to 14.3 years), and the median age of diagnosis was 11.3 years (ranging from 24 days to 14.9 years). The study found that the most common clinical manifestations were cough and expectoration in 11 cases (84.6%), sinusitis in 10 cases (76.9%), fever in 7 cases (53.8%), bronchiectasis, visceral transposition, and atelectasis in 6 cases each (46.2%), nasal congestion, purulent nasal discharge, and Kartagener syndrome in 4 cases each (30.8%). Thirteen children were found to have eight gene mutations. Of the 23 double allelic gene mutation sites identified, 4 cases were related to DNAH11 gene mutation (28.6%), 3 cases to DNAH5 gene mutation (21.4%), and 1 case each to CCDC114, DNAH9, DNAAF3, ODAD1, CCNO, and RSPH1 gene mutations. ACMG classified 8 mutations as pathogenic, 7 as possibly pathogenic, and 8 as variants of uncertain significance (VUS). All 8 VUS sites were predicted to be deleterious by protein function software prediction. This analysis includes seventy-two case series reports or case reports including 391 PCD cases and 316 gene-positive cases. A total of 40 PCD-related genes were detected. The top five most frequent gene mutation sites were DNAH5 (21.2%), DNAH11 (17.7%), CCDC40 (7.9%), HYDIN (6.6%), and CCNO (6.0%). The most frequent clinical phenotypes of PCD cases were chronic cough and expectoration (91.3%), chronic sinusitis (87.0%), bronchiectasis (70.6%), and abnormal lung function (64.2%). In Beijing, Shanghai, and Zhejiang province, the main gene variations were DNAH11 and DNAH5. In Chongqing, the main variation was HYDIN (19.1%), while in Guangdong province, it was DNAH1 (22.2%). In Guangxi Zhuang Autonomous Region, the main variations were RSPH4A (13.3%)、HYDIN (10.0%)、DNAH11 (10.0%)、CCDC40 (10.0%), and ZMYND10 (10.0%). In Hunan province, the main variations were DNAH5 (18.2%) and DNAAF4 (13.6%). Conclusion：In China, the most commonly occurring genes related to PCD are DNAH11 and DNAH5. The main clinical symptoms include respiratory issues, such as persistent coughing, expectoration, and chronic sinusitis.

Background：It is still unknown on the etiology, pathogenicity and associated prognostic factors of kawasaki disease(KD). Currently, multiple exposures which are collaborating with genetic background would induce the immunological responses and trigger the onset of KD, even coronary artery injuries. Objective：To explore the significance of genetic susceptibility related to KD, IVIG resistance and coronary artery lesions. Design：Casecontrol study. Methods：Complete KD was diagnosed according to American Heart Association(AHA) guidelines, and coronary artery lesion was defined with echocardiography Zscore>2 according to the JCS/JSCS 2020 guidelines. From April 2020 to January 2022, we continuously recruited complete KD patients at West China Second University Hospital of Sichuan University. The children who were underwent physical examination and blood test from child health department in our hospital were enrolled in the controls. The whole exome sequencing of peripheral blood samples, quality control of raw data, enrichment analysis and site annotation were performed to screen for single nucleotide polymorphisms (SNPs) and associated genes related to KD, IVIG resistance and coronary artery lesions, which helped to compare the response to treatment and clinical outcomes of KD. Main outcome measures：Sites of SNPs and genes which had been associated with KD, IVIG resistance and coronary artery lesions. Results：In total, 171 complete KD patients were enrolled, including 32 cases (27%) of coronary artery lesions and 55 cases (31%) of IVIG resistance, and 139 cases were enrolled in control group. There were no statistical differences in the age between two groups. A total of 609,732 SNPS were screened through upstream analysis. The two groups were separated by the principal component analysis categorized by Han and other ethic minorities, and there was no substructure in the principal component categorized by gender classification. With P<0.000 1 as the threshold, fifteen candidate genes were associated with KD susceptibility, including MYT1L、CYP26B1、NECTIN3、TENM3、GFI1B、KNDC1、LOC100133315、RNF121、SYNE3、MAPKBP1、SLFN14、MYOM1、ABCA7、PIP5K1C、PTGER1(30 SNPs). While six candidate genes had been identified to be associated with coronary artery lesion, including DGKH、CCDC130、KLF7、METTL6、COLQ、PRKN(19 SNPs). Moreover, there were also six candidate genes had been recognized as risk factors with IVIG resistance, including MICALCL、NT5DC3、KRT75、LOC105370980、TXK、BRD2(8 SNPs). Conclusion：In this study,MYT1L（chr2, rs4381806）、NECTIN3（chr3, rs2399373）、MAPKBP1（chr15, rs2303517）have some significance in exploring the pathogenesis of KD. The SNP sites and genes asscociated with IVIG resistance and coronary artery lesions required further investigation.

Background：Overuse and misuse of empiric antibiotic use for early onset sepsis (EOS) in neonatal intensive care units (NICUs) is widespread, which is associated with adverse outcomes in preterm infants and increased risk of immunerelated diseases in children. The Antimicrobial Stewardship Program (ASP) targeting at EOS can effectively reduce the irrational use of antimicrobial drugs in premature infants. Objective：To carry out multidisciplinary collaborative ASP to shorten the course of empiric antimicrobial drug treatment for EOS, and to explore the effect of ASP in reducing the use of antimicrobial drugs in the early postnatal period in extremely premature infants. Design：Quality improvement research. Methods：Consecutive cases of premature infants who were admitted to the NICU at Children's Hospital of Fudan University within 24 hours after birth from November 1, 2020 to July 31, 2023 and had a gestational age of <32 weeks were included. Those with major congenital anomalies, death or discharge within 7 days, or definite indications for antibiotic prescription within 3 days after birth were excluded. The ASP program was implemented on October 31, 2022. Infants were divided into a control group (before the ASP) and an intervention group (after the ASP). Both two groups have the same subgroups of ruleout sepsis, clinical sepsis and confirmed sepsis. Multidisciplinary ASP team was established to evaluate whether to prescribe empirical antibiotics according to the risk factors of EOS (low, medium, high risk) and the illness severity. ASP team conducted weekly audit of antibiotics for each very premature infant, and provided recommendations and feedback under the supervision of the chief of NICU. Main outcome measures：Discontinuation rate of early antimicrobial drug (within 72 hours after birth). Results：From November 1, 2021 to October 31, 2022, 186 cases were retrospectively included in the control group with 102 ruleout sepsis cases and 80 clinical sepsis, and from November 1, 2022 to July 31, 2023, 135 cases were prospectively included in the intervention group with 58 ruleout sepsis cases and 70 clinical sepsis. There was no significant difference between the two groups and ruleout sepsis subgroups in the two groups in terms of infant and maternal characteristics and NICU treatment. Clinical sepsis neonates showed significant differences in gestational age, prenatal hormone use, prenatal intravenous antibiotic treatment, and mechanical ventilation within 7 days after birth. Among the ruleout sepsis infants, the proportion of infants who discontinued initial antibiotics within 72 hours in the preand postASP period showed a statistically significant difference (P=0.008). Ruleout sepsis neonates in the intervention subgroup had a 2.8 times higher early antibiotic discontinuation rate than those in the control subgroup (OR=2.76,95% CI: 1.285.94). The ASP program had no effect on antimicrobial drug use (length of treatment/1,000 patient days), the rate of early antimicrobial use, mortality, the incidence of late sepsis, and necrotizing enterocolitis. Conclusions：Among very preterm infants with ruleout sepsis, ASP increased the proportion of infants who discontinued empiric antibiotics within 72 hours after birth. Attention should be paid to the diagnosis of clinical sepsis and the time of empirical antibiotic discontinuation, which may increase the rate of early antibiotic discontinuation and reduce the length of treatment during hospitalization.

Background：6-mercaptopurine (6-MP) is one of the main drugs used in the maintenance therapy of acute lymphoblastic leukemia (ALL), and its metabolism enzyme gene polymorphism is associated with the degree of bone marrow suppression caused by the drug. Objective：To investigate the relationship between the dose of 6-MP use and TPMT and NUDT15 gene polymorphisms during maintenance therapy in children with ALL. Design：Retrospective cohort study. Methods：Children with a clear diagnosis of ALL at the First Affiliated Hospital of Zhengzhou University from January 2020 to December 2021 were included, who achieved complete remission after prior chemotherapy and entered the maintenance therapy stage with oral 6-mercaptopurine (6-MP) treatment. Before starting oral 6-MP, genetic testing for TPMT and NUDT15 genotypes was conducted to analyze the dosage and bone marrow suppression of 6-MP treatment in children with different TPMT and NUDT15 genotypes. Main outcome measures：6-MP dosage. Results：This study analyzed 61 pediatric ALL patients undergoing maintenance therapy. Among them, 48 patients were included in the statistical analysis of TPMT gene polymorphism (excluding 13 cases with NUDT15 gene mutations), with 45 wild-type cases and 3 mutant cases. Additionally, 58 patients were included in the statistical analysis of NUDT15 gene polymorphism (excluding 3 cases with TPMT gene mutations), with 45 CC genotype cases, 9 CT genotype cases, and 4 TT genotype cases. During the maintenance therapy with 6-MP, significant differences in WBC, Hb, and PLT counts were observed among patients with different TPMT and NUDT15 genotypes (all P< 0.05). Patients experienced varying degrees of neutropenia after medication, including 15 cases with wild-type TPMT and 3 mutant TPMT cases, as well as 15 CC genotype cases, 5 CT genotype cases, and 4 TT genotype cases of NUDT15 gene. The differences in bone marrow suppression among patients with different TPMT and NUDT15 genotypes were statistically significant (all P< 0.05). Furthermore, there were significant differences in the dosage of 6-MP among patients with different TPMT and NUDT15 genotypes (all P< 0.05). Specifically, the maintenance therapy dosage of 6-MP for patients with wild-type TPMT and mutant TPMT was (40.81 ± 6.02) and (16.25 ± 4.42) mg·m-2·d-1, respectively. For patients with CC genotype, CT genotype, and TT genotype of the NUDT15 gene, the 6-MP dosage was (40.81 ± 6.02), (34.28 ± 4.53), and (10.00 ± 1.28) mg·m-2·d-1, respectively. Conclusion：Patients with mutations in the TPMT and NUDT15 genes experience more severe bone marrow suppression compared to those with the wild-type genotype. The dosage of 6-MP used during maintenance therapy in pediatric ALL patients is associated with TPMT and NUDT15 gene polymorphisms.