Background: Sitting height and leg length are the useful indicators for the linear growth evaluation of children and adolescents, but the growth reference standards of the two indicators have not been reported. Objective: To study and formulate the growth reference of sitting height and leg length of Chinese children and adolescents aged 0-18 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—The National Survey on the Physical Growth and Development of Children in the Nine Cities of China (NSPGDC) and The Chinese National Survey on Students' Constitution and Health (CNSSCH). Leg length was calculated by height minus sitting height. Growth reference standards of sitting height and leg length were constructed using the LMS method. Main outcome measures: Reference values of sitting height and leg length. Results: The percentile and the Z-scores reference values of sitting height and leg length for Chinese boys and girls aged 0-18 years were shown and their growth charts were drawn. Sitting height increased about 14 cm, 6 cm and 4 cm during the first, second and third year after birth, respectively. After that, the annual increment of sitting height is nearly 2-3 cm. Then the increments became slightly higher at 11-13 years for boys and 9-11 years for girls and gradually became smaller and smaller. Sitting height nearly stopped increasing at the age of 17 years for boys and 15 years for girls. Leg length increased respectively about 11-12 cm and 6.5 cm during the first and second year after birth, then the annual increment was 4-5 cm during 2-5 years, and leg length stopped increasing nearly at 15 years for boys and 13 years for girls. Conclusion: The growth reference standards of sitting height and leg length were formulated, which provide more data and reference for perfecting the growth evaluation system of children and adolescents in China.

Background：The clinical spectrum of 16p11.2 microdeletion syndrome is highly heterogeneous, and most studies are case reports. Objective：To summarize the clinical features of 16p11.2 microdeletion syndrome with epilepsy as the main phenotype, so as to improve the clinical understanding of this disease. Design：Case series report. Methods：From July, 2017 to October, 2021, children with epilepsy diagnosed as 16p11.2 microdeletion syndrome in the Department of Neurology, Shenzhen Children's Hospital were included. The clinical manifestations, laboratory examination results, EEG and neuropsychological evaluation results, imaging examination reports, treatment and follow-up of children were intercepted from the medical record system. Peripheral venous blood was collected from patients and their parents for the genetic testing. Main outcome measures：Clinical phenotype and genetic abnormality analysis. Results：Totally 11 patients (age range: 336 months; median age: 7 months; male:6, female: 5), were enrolled. All 11 patients presented focal seizure as the early symptom. There are 8 cases of language retardation and 2 cases of motor retardation (including 1 case of paroxysmal motorinduced dyskinesia). By EGG, 8 patients were found having intermittent discharge while the other 3 patients had normal EGG backgrounds, and by brain MR imaging, 1 case of abnormal white matter signal was observed. The 11 cases of 16p11.2 microdeletion showed a deletion of 524908 kb and 8 of them were de novo mutations. The overlapping region chr16:2967499130199601 contains 27 proteincoding genes and 6 of them are diseaserelated OMIM genes. Only PRRT2 was well evidenced to be haploinsufficient, which causes benign infantile epilepsy. Epilepsy was easy to control in all these patients. Nine cases were treated with antiepileptic drugs, including monotherapy of oxcarbazepine, sodium valproate or topiramate (n=8) and combination therapy of phenobarbital and levetiracetam (n=1). Paroxysmal motorinduced dyskinesia occurred after the combination therapy cure the disease and was stopped, but it did not happen again after the oxcarbazepine treatment. Conclusion：16p11.2 microdeletion syndrome is one of the potential causes of epilepsy, which should be paid attention to in genetic evaluation. For children with 16p11. 2 microdeletion syndrome, dynamic neuropsychological evaluation is needed and attention should be paid to PKD symptoms so as to make timely diagnosis and treatment.

Objective: To compare the reliability and validity of the CRIES scale, PIPP scale and N-PASS scale for neonatal postoperative pain assessment and then find the most reliable and valid postoperative pain assessment scale for neonates. Methods: The convenience sampling method was adopted to select 67 newborns who had been operated in a third-grade A children's hospital in Chongqing from August 2019 to January 2020 as the research objects. Data were collected through general information questionnaire and bedside video recording. Three scales were used to evaluate the pain of each patient for a total of 2,412 times at 1, 2, 4, 8, 12 and 24 hours after surgery. The reliability and validity of three scales were evaluated by correlation analysis, reliability analysis, principal component analysis and exploratory factor analysis. Results: The Cronbach's alpha coefficients of CRIES, PIPP, and N-PASS were 0.906, 0.769, and 0.915 respectively. The test-retest reliability was 0.917, 0.753 and 0.919, respectively. Criterion validity was 0.887,0.874 and 0.920, respectively. Exploratory factor analysis extracted 1, 2 and 2 components, and the cumulative variance contribution rate was 72.717%, 71.133% and 87.252%, respectively. Conclusion: The reliability and validity of the N-PASS scale was higher than that of the CRIES scale and PIPP scale, which was more suitable for the assessment of neonatal postoperative pain.

Background: Large Bcell lymphoma in children with interferon regulatory factor 4(IRF4)gene rearrangement is defined as a unique subtype in the 2017 WTO lymphoma classification. Since it is clinically rare with special clinical features, it is necessary to distinguish it from other large Bcell lymphomas. Objective: To investigate the clinical manifestations, pathological features, treatment and prognosis of large Bcell lymphoma with IRF4 gene rearrangement in children. Design: Case series report. Methods: The clinical data of children with large Bcell lymphoma with IRF4 gene rearrangement diagnosed and treated in Beijing Children's Hospital affiliated to Capital Medical University from May 2018 to October 2021 were collected retrospectively. The clinical characteristics were summarized, and PubMed, Wanfang and CNKI were searched for literature review. Main outcome measures: Complete response rate of large Bcell lymphoma in children with IRF4 gene rearrangement. Results: Six cases were included in the analysis, accounting for 2.7% of the invasive mature Bcell lymphoma treated in our hospital in the same period. There were 5 males (83.3%) and 1 female. The age of onset was 7 (4 13) years old. The involved sites were the neck and head in 4 cases, the intestine in 1 case and both of the head and neck and intestine in 1 case. No metastasis was found from the onset to followup. Four cases were in stageⅡ and 2 cases were in stage Ⅲ. Among the 62 cases including 56 from literature review, 61.2% were male, the age of onset was 11.15 (3,18) years old, the main site of tumor was 79% in the head and neck, and 21% in the intestine and groin. Most of them were isolated lesions, and no metastasis was found from the onset to followup. Clinical stage ⅠⅡ accounted for 79%. Under light microscope, 2 of 6 cases showed complete nodular follicular structure featured by nodules of different sizes, lack of "starry sky phenomenon" formed by mantle area and phagocytic nuclear fragments and 4 cases showed completely diffuse like structure with medium or large tumor cells, scattered nuclear chromatin and small basophilic nucleoli. Immunohistochemistry showed the expression of CD20 and PAX5, the strong expression of BCL6 and MUM1, and the positive index of 90% to 95% for Ki67. Three cases were positive for CD10 and BCL2, six cases were positive for IRF4 rearrangement by fluorescence in situ hybridization (FISH), and BCL6, BCL2 and CMYC gene rearrangements were not detected. Sixtytwo cases showed complete diffuse like structure (43.5%), complete nodular follicular like structure (37.1%) and mixed like structure (19.4%) and 88.7% could detect rearrangement with IRF4 . Conclusion: Large Bcell lymphoma with with IRF4 rearrangement is clinically rare. The tumor is mainly involved in the head and neck. The clinical stage is mainly early lesions, which are more isolated and inert, slow progress, weak invasiveness and good prognosis. The pathological morphology showed complete diffuse like, follicular like and mixed like structures. Immunohistochemistry showed the expression of CD20 and PAX5, the strong expression of BCL6 and MUM1, and the high positive index of Ki67. IRF4 rearrangement could be detected by FISH combined with secondgeneration gene sequencing.

Background：SLC6A1 encodes the gammaaminobutyric acid (GABA) transporter protein 1 (GAT1), which is responsible for the reuptake of GABA from the synapse. It plays an important role in the pathogenesis of neurological disorders such as epilepsy, intellectual disability and autism. Objective：To summarize the clinical phenotypes and results of genetic testing in children with SLC6A1 mutations. Design：Case series report. Methods：Patients with SLC6A1 mutations treated in the Department of Neurology, Children's Hospital of Fudan University from December 2007 to October 2021 were enrolled. The clinical data of patients were collected to summarize the clinical manifestations, therapeutic effects and genetic results. The relationship between reported gene variants and clinical phenotypes was summarized through searching databases. Main outcome measures：Mutation sites of SLC6A1 gene and clinical phenotypes. Results：Five children were included in the study, including 4 males and 1 female. They experienced seizure onset from 1 to 3 years old. Among them, 4 had myoclonic seizures，3 cases had absence seizures, 2 cases had myoclonicatonic seizures, and 1 had generalized tonicclonic seizures. Developmental delay was present in all patients. Delayed language development was prominent. Four of the 5 patients became seizure free. Two patients received valproic acid monotherapy, and the other two received valproic acid in combination with levetiracetam. De novo heterozygous SLC6A1 gene mutations were identified in these patients, including 3 missense mutations, 1 splicing mutation and 1 nonsense mutation. Two mutations including c.1379T>G (p.L460R), and c.1485G>A (p.W495X) have not been previously reported in public. Alteration of amino acids of GAT1 caused by pathogenic or likely pathogenic missense variants are largely clustered around the extracellular domain of EC34 and the seventh transmembrane domain. Conclusion：Most of the patients associated with SLC6A1 gene mutations experienced seizure onset in early childhood. The patients presented with various types of seizures. Valproic acid was effective to control seizures. Most of the patients had developmental delays. The discovery of new variants has enriched the spectrum of SLC6A1 gene variants.

Background：Rehabilitation of children and adolescents with cerebral palsy（CP） needs highquality clinical practice guidelines to provide effective assessment and intervention to improve the health condition of children and adolescents with CP. Objective：To improve and perfect the topic structure of Clinical Practice Guidelines for Children and Adolescents with Cerebral Palsy (CANDLE). Design：A Scoping review Methods：We searched English literature in Google Scholar and Chinese literature in CNKI, WangFang and VIP from January 1, 2010 to May 2, 2022 to get literature about children and adolescents with CP including guidelines, expert consensus, systematic review, and scoping review. Grey literature was searched in Google and BAIDU. According to intelligent sorting of Google scholar, researchers preliminarily screened literature by reading titles and abstracts until consecutive 50 articles of failed to match the inclusion criteria. The included literature was rescreened by reading full texts. References of the included literature after the second screening were compared with the final list of the included studies to find differences. Those unduplicated ones were screened by reading titles and abstracts. Researchers extracted data about questions proposed by the scoping review to a selfmade Excel sheet. The sheet consists of items of the application condition of The International Classification of Functioning, Disability and Health for Children and Youth（ICFCY）, function assessment, development, intervention, and functional influencing factor of children and adolescents with CP. The consistency of extracted data by 6 researchers was requested to be over 80%. Qualitative and quantitative methods were used to analyze data, and the core member of the CANDLE team answered the questions proposed by the scoping review. Main outcome measures：Questions proposed by the scoping review. Results：A total of 372 articles were enrolled in this scoping review. There has been a gradual increase in the number of guidelines, expert consensus, systematic reviews and scoping reviews in the past years. We got 7 English scoping reviews from 2010 to 2018, and 42 from 2018 to 2022. The majority of English literature focuses on intervention techniques, assessment techniques, and function status. Intervention techniques in Chinese literature accounted for 66.7%. There were 37 kinds of intervention techniques in 181 English articles. Four articles adopted ICFCY or ICF concept, and 78 articles partially used ICF concept in their structure. A total of 47 guidelines and expert consensus were enrolled. Among them, 9 expert consensus and 7 guidelines used function as a starting point. In 6 comprehensive guidelines, contents about function related to posture and motor were shown by muscular tension, mobility, hand activity, secondary musculoskeletal, daily living and leisure activities. There were 104 articles (31%) discussing the assessment method separately within 20 articles using COSMIN. Nine articles (3%) independently elaborated the effect of development characteristics on function. A total of 41 articles (12.1%) analyzed the interaction between function and background factors through the methods of correlation and influencing factors. Conclusion：The overall structure of CANDLE was initially formed through this scoping review. Eight domains were established with function as the core, each of which is shown through five elements (ICFCY as the framework, assessment, development, interaction, and intervention). Questions of interest within the scope are built on the elements.

Background: It is unknown whether the pathogen spectrum of acute respiratory infection (ARTI) have changed significantly since the outbreak of COVID-19. Objective: To analyze the etiological characteristics of hospitalized children with ARTI before and after COVID-19 epidemic in Shenzhen, in order to provide reference for the clinical diagnosis, treatment and prevention of ARTI. Design: Cross-sectional survey. Methods: Pharyngeal swab samples submitted for the first time excluding those of neonates after hospitalization for clinical diagnosis of ARTI in Shenzhen Children's Hospital from September 2, 2019 to February 28, 2021 were included. Multiple PCR and capillary electrophoresis were used to detect 13 kinds of common pathogens in nasopharyngeal secretion samples. Based on the data from March 2020 to February 2021, the pathogen profiles of ARTI in different seasons were compared, from March to May in spring, from June to August in summer, from September to November in autumn, and from December to February of the next year in winter. Data from September 2,2019 to January 24,2020 were used as pre-COVID-19 data and from September 2, 2020 to January 24, 2021 as post-COVID-19 data for comparison. Main outcome measures: Mycoplasma, chlamydia and common virus spectrum of ARTI. Results: Among 12,022 cases of nasopharyngeal secretion, pathogens were detected in 7,589 cases with the detection rate of 63.13%. The highest detection rate was for human rhinovirus (HRV,24.83%), followed by respiratory syncytial virus (RSV,14.12%), human parainfluenza virus (HPIV,8.33%), human metapneumovirus (HMPV,7.01%), and mycoplasma pneumoniae (MP,5.37%).There were 1,329 cases of mixed infection with two or more pathogens was detected simultaneously, accounting for 11.05% (1,329/12,022). HRV and MP were the most common combination. The highest detection rate was 66.99% (1,924/2,874) in autumn, with RSV ranked first in the list (25.89%), followed by HRV (24.01%).The lowest detection rate was 16.20% (132/815) in spring, with HRV ranked first in the list (5.03%), followed by MP (3.80%).The detection rate of pathogens in children aged 6 months to 6 years was higher than the overall average.With the increase of age, the detection rate of RSV and HPIV decreased significantly, while the detection rate of MP increased. There was no significant difference in the detection rate between male and female patients (P>0.05). Before COVID-19 epidemic, the detection rate of pathogens was 78.57%（2,592/3,299）, with HRV(36.37%), MP (15.40%), RSV(10.03%), adenovirus (9.03%) as the main pathogens. A total of 764 mixed infection cases were found (23.16%). After COVID-19 epidemic, the detection rate of pathogens during the same period was 65.89%（3,500/5,312）, with HRV (23.78%), RSV (14.74%), HMPV(12.65%) and HPIV (12.12%) as the main pathogens, and there were 459 cases (8.64%) of mixed infections. Conclusion: The pathogen spectrum of ARTI had changed significantly after the outbreak of COVID-19. The detection rate of HMPV,HPIV,RSV,Bocavirus had increased significantly. However, the detection rate of MP, chlamydia, influenza A,H1N1, H3N2, influenza B, HRV, adenovirus, mixed infections decreased significantly.

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Background: There are few studies on the efficacy and safety of perampanel in children with drug-resistant epilepsy, and the efficacy and safety are not clear. Objective: To investigate the efficacy and safety of perampanel in the treatment of children with drug-resistant epilepsy. Design: Cohort study. Methods: Children aged 0-18 years who were diagnosed with drug-resistant epilepsy and treated with perampanel in Peking University First Hospital from January to December 2020 were included in the cohort study, and the end point was at least 6 months' treatment. Efficacy was the dependent variable, and the gender, etiology, epileptic syndrome, baseline frequency of seizures, age at onset, age at time of dosing, course of disease at dosing, dosage of drugs, number of treatments were independent variables. The univariate and multivariate logistic regression analysis were used to analyze the related factors of efficacy. The adverse reactions of perampanel in the treatment of children with drug-resistant epilepsy were also analyzed. Main outcome measures: The frequency of seizures decreased ≥50% from baseline at the last follow-up (within 1 month) . Results: A total of 50 patients were included (34 males and 16 females)，and all the patients were followed up at least 6 months. The epileptic syndromes included infantile spasms in 6 cases, Lennox-Gastaut syndrome in 2 cases, epileptic encephalopathy with electrical status epilepticus during sleep in 3 cases, and Rasmussen encephalitis in 2 cases. Specific causes of epilepsy were found in 66.0% (33/50) of the patients, including structural causes in 19 cases, genetic causes in 9 cases, immunological causes in 4 cases, and metabolic causes in 1 case. The baseline frequency of seizures ranged form once per 2 weeks to hundreds of times per day. Eighteen percent (9/50) of the patients had seizure less than once a day, 36.0% (18/50) of the patients with seizures of 1-10 times per day, 32.0% (16/50) with seizures of 1-10 times per day, 14.0% (7/50) with seizures of more than 100 times per day. Three types of treatments (range from 1 to 6 types) were used in combination with perampanel, and three types of treatments (range from 0-10 types) were previously used. The age at time of dosing was 64.5 months (4 months to 18 years), and course of disease at dosing was 22.0 months (2 months to 17.3 years). The duration of perampanel at the last follow-up was 8.0 (6.0-14.0) months. At the last follow-up, the maximum daily dose of perampanel was 0.175 (0.06-0.5) mg·kg-1·d-1 and 4 (0.5-2) mg·d-1.The rate of efficacy was 46.0%(23/50). At the last follow-up, 41 patients were treated with perampanel, and the retention rate was 82.0%. Nine patients stopped treatments because of poor efficacy. No correlation was found between the efficacy and gender, etiology, epileptic syndrome, baseline frequency of seizures, age at onset, age at time of dosing, course of disease at dosing, dosage of drugs, or number of treatments. Six patients (12.0%) were observed with irritability and drowsiness during the treatment, and no other serious adverse reactions were observed. Conclusion: The overall rate of efficacy of using perampanel to treat drug-resistant epilepsy was 46%. The safety and tolerability of perampanel in the treatment of children with drug-resistant epilepsy were relatively good, and no related factors with efficacy were found.

Background：The longterm survival of children with neuroblastoma (NB) associated with MYCN amplification is not promising, and few studies have been previously reported in China. Objective：To summarize the related factors of clinical characteristics, therapeutic effect and prognosis in NB children with MYCN amplification and to further improve the recognization of this group in NB. Design：Case series report. Methods：The clinical information of NB with MYCN amplification, diagnosed and treated from Feb 2007 to Jan 2020, were analyzed retrospectively, and the tumor location, size, metastasis, treatment, and risk factors affecting the prognosis were analyzed. Main outcome measures：Factors affecting the 3year survival of NB with MYCN amplification. Results：A total of 133 NB patients with MYCNAmp were included in this study, accounting for 12.02% of total NB patients in the same period in our center. The median age of onset was 35.7±9.8 months. There were 129 cases (97%) located in abdomen region and 4 cases (3%) in posterior mediastinal region. There were 81 cases (60.9%) with bone marrow metastasis, 80 cases (60.2%) with bone metastasis and 24 cases (18.1%) with central nerves system metastasis. Serum LDH ≥1 500 U·L-1was shown in 99 cases (74.4%). NES ≥100 ng·mL-1was found in 126 cases (94.7%). The largest tumor diameter (>10 cm) was in 89 cases (66.9%). The 3year OS and EFS were 19.7% and 19.0%. There were 78 cases of progressive recurrence, 8, 20, 46 and 4 cases of progressive recurrence happened at induction, consolidation, maintenance and withdrawal, respectively. Primary tumor, bone marrow, central nervous system and bone were the most common sites of progressive recurrence. The median time of first progression was 11.3 months. Bone marrow and bone metastasis, deletion of 1p36 were risk factors. Conclusion：A single center with large sample of MYCNAmp NB showed that the primary tumor was predominantly located in the retroperitoneal adrenal region, with a high rate of early distant metastasis, and more than 50% of the children developed tumor progression during maintenance therapy with 3year OS of 19.7%. These children urgently need targeted therapy and other new treatment to further improve the efficacy and the prognosis.

Background：Children's Hospital of Fudan University was the designated hospital for newborns in the SARSCoV2 omicron variant wave in Shanghai from March to May 2022. Facing the complexity of the current pandemic, it was a challenge for special populations such as newborns to coordinate pandemic control and medical treatment. Objective：To implement and improve the bubble strategy for newborns on the basis of the overall strategy in the hospital. Design：Observational study. Methods：Four small bubbles were developed in the bubble management of newborns in the hospital.The COVID19 ward in Shanghai Public Health Clinical Center, as a small red bubble, was used to admit the infants with nucleic acid or antigen positive results, in accordance with the protocol set by Children's Hospital of Fudan University. The isolation ward, as a small orange bubble, was set in a separate building in the hospital including negative pressure rooms. Infants with highrisk epidemic history were admitted. All infants in the small orange bubble were required to complete a 7day medical observation and perform nucleic acid test every day. The negative pressure rooms and the nonnegative pressure rooms had their own independent places for storing materials. The staff were protected by grade II and grade I (+4) standard protective equipment respectively. The transportation of stuff and specimens was carried out by special "ferrymen". The transition ward with single rooms and multiperson rooms, as a small yellow bubble, was set to admit lowrisk epidemic history infants. Nucleic acid testing was performed every 24 hours and medical observation would be ended if nucleic acid was negative for 3 consecutive days. The single rooms and the multiperson rooms had their own independent places for storing materials. The staff were protected by grade II and grade I (+4) standard protective equipment respectively. The transportation of stuff and specimens was carried out by special "ferrymen". The clean wards, as the small green bubbles, were the areas for routine hospitalized infants as usual. They admitted defined riskfree infants from orange and yellow bubbles. The transport of infants was uniformly taken by 120 emergency vehicles of the whole city. The infants were transported to the bubble by the transport team of the corresponding bubble. Infants came out of the the small red bubble according to the protocol of COVID19 ward in the other article of the whole hospital in this issue. Infants came out of small orange bubble according to the following protocols: a.The 7days medical observation was completed; b. There was no COVID19 patients in the building of the family where the infants lived after being discharged; c. The health code of the home caregivers and the coresidents was green, or the isolation had been removed; d. The health code of the family members who took the infants out of the hospital was green, and the nucleic acid within 48 hours was negative. Infants could come out of small yellow bubble after 72h medical observation. During the hospitalization of the infants, the medical staff conveyed humanistic care to the parents of the newborn through WeChat to relieve the doubts, anxieties and difficulties of parents at any time. Main outcome measures：No occupational exposure and nosocomial infections among medical staff. Results：A total of 677 infants were admitted, of which 158 (130 from Shanghai Public Health Clinical Center, 21 from other medical institutions, and 7 transported by small orange bubble team) were admitted into the small orange bubble for management. There were 10(6.4%) premature infants out of them. The remaining 519 infants (375 from the community, 144 transported by the small yellow bubble team) admitted into the yellow bubble for management. There were 173 (33.3%) preterm infants, 82 (15.8%) infants with intubation, 45(8.7%) with noninvasive ventilation, all of whom entered the small green bubbles after medical observation, including 137 in the NICU and 382 in the general ward. The average length of stay was 13.5 days. One infant was diagnosed as complex congenital heart disease in the small orange bubble and transported to CCU after medical observation. Two infants with positive nucleic acid test in the small orange bubble who had contact history with COVID19 mothers after birth were and transported to the red bubble for management. There were 324 medical staff participating in the work of the small red, orange, yellow and green bubbles, and no occupational exposure or hospital infection occurred. Conclusion：It is feasible to implement newborn bubble management in this pandemic wave, and the effect of preventing and controlling occupational exposure and hospital infection is good.

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Background：Primary microcephaly (MCPH) is a rare genetic disorder characterized by occipitofrontal circumference equal to or below -2 SDs at birth, facial deformity and intellectual disability. Objective：To summarize and analyze the clinical and genetic characteristics of patients with primary microcephaly caused by ASPM gene defects (ASPMMCPH) in both the China Neonatal Genome Project (CNGP) and HGMD database. Design：Case series report. Methods：The newborns with biallelic pathogenic/likely pathogenic (P/LP) variants in ASPM gene in the CNGP were included. The clinical and genetic features were summarized. We established the P/LP variant list of ASPM gene from CNGP, HGMD and ClinVar database, and calculated the frequency of carrying ASPM P/LP variants in the whole CNGP cohort. And finally, the genotypephenotype association of ASPMMCPH was summarized by analyzing the records from the HGMD database. Main outcome measures：The assessment of the frequency of carrying ASPM P/LP variants in the whole CNGP cohort. Results：Twelve P/LP variants in ASPM gene were identified in 6 patients, of which 6 variants were novel. Prenatal B-ultrasound showed microcephaly and primary microcephaly was diagnosed after birth for all of the 6 patients. But other typical clinical features were absent. The frequency of carrying P/LP variants in ASPM gene in the whole CNGP cohort was 0.001 206 043. In the previously reported cases, the incidence of microcephaly, facial deformity and mild to moderate developmental delay was more than 50%. Brain MRI showed abnormal gyri and ventricular dilation. Regarding the types of variants, the proportion of lossoffunction variants was 96.43%. There was no statistically significant difference between the effect of lossoffunction and missense variants on the degree of developmental delay. Conclusion：Six novel P/LP variants in ASPM gene were identified in this study. The frequency of carrying P/LP variants in ASPM gene was assessed. Genetic testing was recommended for fetuses with microcephaly.

Background: Primary mitochondrial diseases have high clinical and genetic heterogeneity, and peripheral nervous system is one of the most commonly involved organ. Objective: To investigate the clinical and genetic characteristics of hereditary peripheral neuropathy caused by COX20 gene variants. Design: Case series report. Methods: Four patients with hereditary peripheral neuropathy caused by COX20 gene variants treated in the Children's Hospital of Fudan University from May 2018 to May 2020 were enrolled, and their clinical manifestations, molecular tests, data of treatment and followups were retrospectively reviewed. Also, we searched published articles using keyword of "COX20", and "Complex Ⅳ deficiency" in Chinese and English databases from the inception to December 2021. The relationship between COX20 gene variantion and clinical phenotypes was summarized. Main outcome measures: COX20 gene variantion sites and clinical phenotypes. Results: Four patients including 2 males and 2 females were enrolled. Three patients had delayed motor mile stones. All 4 patients presented with walking instability onset at early childhood, and nerve conduction study revealed polyperipheral neuropathy especially with sensory axonal damaged. Whole exome sequencing of 4 patients revealed compound heterozygous variants of COX20 gene, including 2 reported missense variants, 1 reported nonsense variant and 1 novel variant—c.262delG(p.E88kfs*35) which has never been reported before. Literature review showed 22 patients from 18 families (including our cases) have been reported till now, with the median age of onset at 5 years old (1.017 years old). All patients presented with walking difficulty or unsteady gait at onset(22/22, 100%). Common clinical manifestations included developmental retardation(11/22, 50.0%), dysarthria(14/22, 63.6%), muscle weakness with or without foot deformity(14/22, 63.6%), ataxia(8/22, 36.4%), dystonia(6/22, 27.3%), and cognitive regression(5/22, 22.7%). Nerve conduction and electromyography tests revealed polyperipheral neuropathy in most patients (19/21, 90.5%). Magnetic resonance imaging revealed spinal cord atrophy in 4 patients (4/10, 40%) and cerebellum atrophy in 4 patients (4/18, 22.2%). Nine patients lost the ability of independent walking at a median age of 10(721) years. A total of 9 pathogenic variants in four types were reported, including five missense variants, two splice site mutations, one nonsense variant and one frameshift variant. Conclusion: COX20related patients always present with peripheral axonal neuropathy at an early childhood onset. The disease progresses gradually with a high disability rate. Some patients also have dysphagia, ataxia, dystonia, and cognitive regression. Among all the COX20 variants reported now, missense variants are the most common.

Background：Chinese Infectious Disease Surveillance of Pediatrics(ISPED)was established in 2015. The data of antibiotics resistance were collected from each hospital and summarized every year to monitor the infectious etiology changes and bacterial drug resistance among Chinese children. Objective：This study is aimed to investigate the bacterial infectious and antimicrobial resistance profiles of pathogens in Chinese children and guide the reasonable use of antibiotics. Design：A crosssectional survey. Methods：Clinical isolates were collected from 13 tertiary children hospitals in China from January 1st to December 31st in 2021. 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 of Clinical and Laboratory Standards Institute (CLSI) 2021. All members used the standard methods to perform bacterial culture,identification and antimicrobial susceptibility test and reported the isolated effective strains and bacterial resistance data in a structured format every year for data summary and statistical analysis. Main outcome measures：Detect the distribution of bacteria strains in children and the changes of bacteria drug resistance. Results：A total of 63 508 isolates were collected, of which 39.9% was grampositive organisms and 60.1% was gramnegative organisms. Top ten pathogens were as follows, Escherichia coli (12.7%), Streptococcus pneumonia (12.3%), Straphylococcus aureus (11.6%), Haemophilus influenza (11.4%), Moraxella catarrhalis (6.5%), Klebsiella pneunoniae (5.2%), Pseudomonas aeruginosa (4.0%), Staphylococcus epidermidis (3.7%), Acinetobacter baumannii (2.4%) and Streptococcus pyogenes (2.1%). The distribution of the primary pathogenic bacteria in different age groups was different. Among them, Saureus had the highest isolation rate in neonates (18.7%), and S.pneumoniae was the main pathogenic bacteria in children aged from >28 d to 5 years old, arranging from 13.6% to 20.8%. E.coli was the most common pathogen in children over 5 years old (22.4%). The proportion of penicillininsensitive S.pneumoniae (PNSP) decreased to 9.6%. Multidrugresistant bacteria (MDROs) showed high levels of resistance to a variety of clinical antibiotics, and the ratios of carbapenemresistant Enterobacteriaceae (CRE), K.pneumoniae (CRKP), P.aeruginosa (CRPA), A.baumannii (CRAB) were 4.6%, 14.8%, 6.7% and 30.7%, respectively. The proportions of CRPA and CRAB showed a decreasing trend in the past 6 years. The former had a higher detection rate in the neonatal group, while the latter had a higher detection rate in the nonneonatal group. Moreover, the resistance rates of CRPA and CRAB to multiple antibiotics were significantly higher in the nonneonatal group than in the neonatal group. Methicillinresistant Saureus(MRSA) was relatively stable, with a detection rate of 33.2% in 2021. Conclusion：The detection rate of MDROs in 2021 was lower than previous years, and the resistance ratio of MDROs also decreased in pediatric patients. We must pay attention to the infection and colonization of CRPA in the neonatal population.

Background: Chinese ISPED (Infectious Disease Surveillance of Pediatrics) was established in 2015. The data of antibiotics resistance were collected from each member hospital and summarized every year to monitor the bacterial drug resistance among Chinese children. Objective: This study aimed to investigate the antimicrobial resistance profiles of pathogens in Chinese children and guide the reasonable use of antibiotics. Design: This is a crosssectional survey. Every member hospital was required to perform the standard procedure of bacterial culture, identification and antimicrobial susceptibility test and to report the isolated strains and drugresistant bacteria. All data were analyzed to reflect the current bacterial infection and drug resistance among children in mainland China. Methods: Clinical isolates were collected from 11 tertiary children's hospitals in China from January 1st to December 31st in 2020. 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 of Clinical and Laboratory Standards Institute(2020). Main outcome measures: The distribution of bacteria strains and the changes of bacteria drug resistance in pediatrics, especially the multidrugresistant organisms(MDRO) among pediatric patients. Results: A total of 42,786 isolates were collected, of which 38.5% was grampositive organisms and 61.5% was gramnegative organisms. Top five pathogens were Escherichia coli (16.4%), Straphylococcus aureus(12.6%), Streptococcus pneumonia (9.8%), Coagulase negative staphylococci (7.3%) and Klebsiella pneunoniae (7.0%). Top three pathogens in the neonatal group were Staphylococcus aureus (19.3%), Escherichia coli (18.6%) and Klebsiella pneumoniae (13.2%) and top three pathogens in the nonneonatal group were Escherichia coli (16.2%), Staphylococcus aureus (11.7%) and Streptococcus pneumoniae (11.2%). The proportion of respiratory specimens decreased from 53.9% in 2019 to 45.2% in 2020. Most MDROs presented highlevel drug resistance to various antibiotics. The prevalence of Carbapenen Resistant Enterobacteriaceae (CRE) , Pseudomonas aeruginosa (CRPA) , and Acinetobacter baumannii (CRAB) was 4.9%, 9.5% and 33.5% respectively. The prevalence of CRPA was higher in the neonatal group than that in the nonneonatal group (19.4% vs 9.2%) and CRAB was just the opposite (14.8% vs 37.1%). The detection rates of MethicillinResistant Staphylococcus aureus (MRSA) and Coagulase negative staphylococci (MRCNS) were 31.5% and 75.9% respectively. Conclusion: Both the detection rates of MDROs and their antimicrobial resistance in children were decreased in 2020.

Background：Currently in clinical genetic diagnosis, both exome capture sequencing (ES) and whole genome sequencing (WGS) have a wide range of application scenarios. Each has its own advantages in terms of either better costeffective performance or a wider variant detection range. The establishment of an integrative genetic diagnosis process that supports two different library preparation and sequencing protocols is essential to further improve the sensitivity and efficiency of genetic testing. Objective：By integrating the analysis of various variant types fitting both ES and WGS scenarios, the normalization and structuring of complex clinical phenotypes of genetic diseases, and the phenotypeoriented genetic variation analysis system to establish an integrated process from the application of genetic test to the feedback of a diagnostic report. Design：Process development. Methods：An integrated fullprocess closedloop analysis system for highthroughput sequencing data (Fudan Process 3.0) was established including the modules of processing the medical history, extracting structured terms of phenotype, sequencing experiment, detecting variants, interpretating variants, checking quality control, and analyzing both genotypes and phenotypes. In terms of testretest analysis of representative cases, we selected representative cases with various type of conclusive pathogenic variants and diagnosis difficulties to present the analysis process from sequencing experiments and clinical history to the generation of a draft report. Main outcome measures：The structured phenotype terms of patients, the data quality control parameters, the status of variant detection and interpretation, and the final diagnosis during the analysis of representative cases. Results：During the reanalysis of 3 representative cases, the optimized trio genome sequencing, probandonly WGS and CES were carried out respectively. The structured phenotype was successfully extracted from the medical history. The data quality of FastQ and BAM files was well controlled. After interpretation, a combined genotype and phenotype analysis was performed to detect the complex inheritance pattern of three cases respectively. In example 1, detected point mutation NM_058172 (c. 1294C>T and 4q21.22 about 13 kb structural variant deletion on ANTXR2) matched the recessive inheritance model. In example 2, a pathogenic variant m. 14459G>A on mitochondrial gene MTND6 with heterogeneity>99.5% was detected. In example 3, a homozygous pathogenic variant NM_000344（c. 863G>T combined with a single-copy deletion of SMN1 gene）was detected. Conclusion：The Fudan Process 3.0 is well functioned in processing either ES or WGS data to analyze various variant types and draw genetic diagnosis conclusions, especially in handling cases with complex variant types.

Background：As Omicron variant is extremely infectious, the pandemic of Omicron variant in Shanghai from March to May this year is complex, dynamic and uncertain, therefore it is more challenging for hospitals. Objective：To summarize the experience of bubble management of preventing and controlling nosocomial infection and occupational exposure of COVID19. Design：Observational study. Methods：In this pandemic, our hospital is designed as a big bubble. Six key medical departments are designed as medium bubbles, including the outpatient of COVID19, fever clinic, emergency department, special ward of COVID19, neonatal isolation ward and transition ward. Several important departments of medium bubbles are designed as small bubbles. Those with a red code, positive results of coronavirus nucleic acid or antigen tests, or infection history of COVID19, and the close contacts of COVID19 were admitted to the outpatient of COVID19. According to the condition and epidemic history, they were arranged to different functional small bubbles. Those fever patients with a green code or a yellow code were admitted to fever clinic. Those with emergent conditions but without fever were admitted to the emergency department which was further divided into two small bubbles named as the buffer area and general area . The backup was also available. Patients with a positive PCR result were admitted to the special ward of COVID19 while those with severe critical illness were in the ICU, and the other with mild or common type were in the general ward. All newly admitted children except critical illness and neonates were in the transition ward. Neonates with negative primary screening nucleic acid from pregnant women with COVID19 were admitted to neonatal isolation ward while all neonates were arranged in the small bubble of negative pressure area first. After daily nucleic acid tests for 3 days, those with negative resulst were transferred to nonnegative pressure area and the other with positive results were transferred to special ward of COVID19. The flow of personnel and meterial with different risk rate was not allowed. The staff with the lower risk moving to the higher level risk should be reported to the department of medical affairs. Meanwhile the plan of the bubble burst is ready. Standard training contents and assessment requirements were formulated according to different posts of staff, and checked through voice and video monitoring system and onsite supervision. Main outcome measures：Nosocomial infection and occupational exposure of COVID19. Results：A total of 432 patients with COVID19 were admitted to our hospital, including 341 patients with mild type (78.9%), 88 patients with common type(20.4%), and 3 patients with critical illness. Each critical illness had invasive mechanical ventilation while one patient had additional CRRT and ECMO .None of them died from COVID19. Twentynine patients had underlying disease and 109 staff successively worked in outpatient and inpatient of COVID19 including 46 doctors, 49 nurses, 9 medical technicians and 5 auxiliary medical personnel, none of which had nosocomial infection and occupational exposure of COVID19. A total of 189 persons with a red code were intercepted at the entrance of the hospital. All patients with red codes were guided to the outpatient of COVID19, therefore, none of them was permitted into the general outpatient and emergency department. The total number of outpatient and emergency patients was 253 571, 12 114 of which was admitted to emergency. Six emergency patients were positive of primary nucleic acid test. Three patients with COVID19 entered the general area of emergency, resulting in the closed disinfection and sterilization for 3 times, activating the backup emergency area. A total of 8 328 patients were admitted to fever clinic, 50 of which were transferred to the outpatient of COVID19 after positive nucleic acid test. The total number of outpatient of COVID19 was 763. According to grade V triage,3 of 4 cases of grade I /II were critical illness. In total, 690 neonates were admitted to our hospital including 516 cases of lowrisk epidemic history and 174 cases of highrisk epidemic history, 2 cases of which were positive of nucleic acid test. Six hundred and ninetythree patients were admitted to the transition ward including 223 emergency cases and 470 selective cases, 1 of which was positive of nucleic acid test. All staff working in the isolation ward participated in theoretical training and special training on highrisk bubbles was carried out for 29 times for 291 people. Both theoretical training and operation training were qualified.Video monitoring and onsite supervision were performed for 304 people. Conclusion：There was neither nosocomial infection nor cupational exposure of COVID19 in this bubble management.

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Background: Offlabel drug use is common in neonates. Appropriate and effective administration of antibiotics for Carbapenemresistant Enterobacteriaceae （CRE） infection in neonates is challenging. Sulfamethoxazole compound (SMZco) can be taken orally with high bioavailability, however, it is not recommended to be used in infants under 2 months. Objective: To summarize the experience and therapeutic effect of oral SMZco for the CRE septicemia in newborns. Design: Case series report. Methods: Through the hospital drug management system, SMZco medical records that meet the following criteria were collected: a. Patients were hospitalized in NICU of Beijing Children's Hospital, Capital Medical University from January 2018 to June 2021; b. The age on admission was ≤ 28 d or the corrected age was ≤ 44 weeks; c. The CRE septicemia was confirmed by positive blood culture results and clinical manifestations. The oral SMZco as a combined use of medications was administered when the pros and cons were thoroughly discussed by neonatal physicians and clinical pharmacists, and formal written consents were signed by parents. The dose of SMZco was referred to that for children above 2 months old. Signs of allergy and manifestations of bilirubin encephalopathy had been closely watched during the treatment. Complete blood counting and renohepatofunction were monitored weekly. The following information was collected: demographic characteristics, history of surgical intervention or long line catheterization, ventilation time, time interval between blood drawing and culture positive, species of the positive culture results together with the drug sensitivity test, age of starting SMZco administration, dosage of SMZco, WBC, PLT and CRP before and after SMZco treatment, adverse reactions and clinical outcomes. Main outcome measures: Discharge after improvement. Results: A total of 9 newborns with CRE septicemia were enrolled, among which 5 were males, 6 received surgery intervention before CRE septicemia was confirmed, and 8 had history of long line catheterization. The average gestational age was (31.0 ± 4.4) weeks, ventilation time was (793±381）h . Specimens for the positive CRE cultures were blood (2 cases), tracheal bronchial secretion (3 cases), tip of PICC (1 case), surgical wound swab (1 case), blood and tracheal bronchial secretion (1 case) and blood+cerebrospinal fluid (1 case). Before the administration of SMZco, all cases were treated with broadspectrum antibiotics for more than 2 weeks. There were 2 cases of CRE meningitis. The medium time of positive CRE culture was 39 (23.5,49) d of hospitalization before or after being transferred to our center. Among the 9 cases, 8 were Klebsiella pneumoniae and 1 was Escherichia coli, all of which produced extendedspectrum βlactamases. Analysis of antimicrobial susceptibility assay revealed resistance to Amikacin (3 cases), Gentamicin (6 cases), Ciprofloxacin (7 cases), and Tetracycline (3 cases). All were sensitive to SMZco and Tegacyclin. SMZco treatment was initiated at 49(38,70.5) days of life for patients, and the dose of SMZ was 4060 mg·kg-1·d-1. There were 6 cases treated with oral SMZco in combination of intravenous carbapenems or thirdgeneration cephalosporins, while 3 cases were with oral SMZco only. Six out of nine patients completed the SMZco course of (24.3 ± 11.6) days, while three out of nine patients did not complete the required SMZco course due to their discharge against medical advice. Among the 6 patients with complete SMZco course, 1 was treated for 10 d (tracheal bronchial secretion positive), and the other 5 were treated for more than 2 weeks. All patients presented improved clinical symptoms and inflammatory markers after the starting of SMZco. All patients had normalization of WBC and PLT, 7 patients had normalization of CRP and other 2 patients had dramatically improved CRP before discharge against medical advice. No allergy was found, nor signs of bilirubin encephalopathy or hemolytic anemia or thrombocytopenia. There were 3 patients (33.3%) with an ALT elevation 2.23.5 times of normal value, which was normalized after symptomatic intervention. All patients had normal renal function during SMZco treatment. Conclusion: For neonates who had culture confirmed CRE septicemia, under the instruction of drug sensitivity results, a combined use of oral SMZco is a choice to treat the CRE infection when the treatment response of strong broad spectrum antibiotics is negative. However, it is necessary to strictly follow the procedures of offlabel drug use, parent consenting, and close monitoring of side effects.

Background：With an increasing number of very preterm infants (VPI, <32 weeks' gestation) treated in China, central vascular catheterization has become a common technique in Chinese neonatal intensive care units (NICUs). Inappropriate use of central vascular catheters(CVCs) may occur in the treatment, but there is still lack of relative data. Objective：To retrospectively analyze the firstyear data from the standardized database of the Chinese Neonatal Network (CHNN) and preform hospitallevel questionnaires, to reveal the current problem of central vascular catheterization among VPIs in Chinese NICUs and to provide baseline data for future quality improvement program. Design：Crosssectional study. Methods：The study described the current situation of central catheterization across gestational age (GA) weeks, including rate, duration and site variation, using the firstyear data of CHNN (from Jan. 1st 2019 to Dec. 31st 2019) from the participating NICUs. Questionnaires were collected on hospital level in terms of the regulation and management of CVC wards, indications of insertion and removal, and related complications of central catheterization. Infants with GA of 24+0~31+6 weeks, admitted into CHNN database from Jan. 1st 2019 to Dec. 31st 2019 within 24 hours after birth were included. Those infants with major congenital anomalies, transferred to other hospitals or discharge against medical advice were excluded. Incomplete and substandard data were also excluded. Subgroup analysis were done for infants with GA at 2428 weeks and 2931 weeks. Research sites were classified into children's specialized hospitals, maternal and children's healthcare centers and general hospitals. Questionnaires were designed to investigate the regulation, management, indications, maintenance and related complications of central catheterization, which were filled by department directors or senior neonatologists authorized by the director. Main outcome measures：The type, rate and duration of central catheterization. Results：A total of 6,532 VPIs from 57 CHNN participating sites were included in the analysis. A total of 69.9% (4,563/6,532) cases received central catheterization. Overall, 38.8% (2,532/6,532), 5.6% (368/6,532), 59.6% (3,895/6,532) and 0.8% (55/6,532)infants received umbilical venous catheters(UVC), umbilical artery catheters(UAC), peripherally inserted central catheters(PICC) and surgical central venous catheters(SCVC). Infants with central catheterization had smaller GA and lower birthweight, and were more likely to be smallforGA, multiple birth, outborn and with 5min Apgar score less than 7, compared to noncatheterized infants (P <0.01). The proportion of pregnancy hypertension, antenatal hormone use, and cesarean section was also higher in the mothers of catheterized infants. The mortality rate did not differ between catheterized and noncatheterized infants but catheterized infants had higher rate of each morbidity and longer hospitalization (P <0.01). Rate of any type of central catheterization generally decreased along with the increasing GA, and the rates were 87.8% and 63.1% for 2428 GA weeks and 2931 GA weeks respectively. Rates of UAC and UVC also decreased along with the increasing GA. Rate of PICC was the highest at 2528 GA weeks, and it was still as high as 52.8% for infants at 2931 GA weeks. The rate of using two or more catheters(UVC/PICC/SCVC) was 29% at 2528 GA weeks, which decreased to 21.8% at 2931 GA weeks. The median duration of UAC, UVC and PICC were 6.0 (IQR: 4.08.0) days, 7.0 (IQR: 4.09.0) days and 22 (IQR: 15.031.0)days, respectively. There were significant variations among NICUs with different hospital types on the catheterization rates and the duration. Response rate of the questionnaire was 91.2% (52/57). Only 50% (26/52) hospitals have hospital guidelines for central vascular catheterization. There were also significant variations on the indications of insertion and removal, and the longest duration as well. A total of 62% (32/52) hospitals had central linerelated leakage and 23% (12/52) had thrombosis within one year. Conclusion：Central vascular catheterization has been commonly used in Chinese NICUs. However, overuse and insufficiency are both existing. Other major problems are the exceeding length of PICC and significant site variation. Guidelines and regulations are on demand. National quality improvement efforts are needed to promote the rationale and standardized use of central catheters for VPIs in NICUs.

Background：The primary hyperoxalurias (PHs) is a rare hereditary nephrolithiasis and nephrocalcinosis caused by different gene mutations of enzymes that control the glyoxylate metabolism. PH1 and PH2 have already been paid more attention, while PH3 is the most recently identified type and there are only a few PH3 cases reported to date. Objective：To summarize the clinical phenotypes of PH3 patients and to explore the putative mutation hotspot regions in different ethnic groups. Design：Case series report. Methods：From January 2015 to December 2021, the PH3 patients diagnosed by genetic testing in Children's Hospital of Fudan University were enrolled. Clinical and molecular biological data were collected from inpatient medical history. The Chinese and English literature of PH3 cases was searched in PubMed, Embase, Wanfang database and CNKI database to collect case source (country), gender, number of cases, onset age, diagnosis age, clinical manifestations (urolithiasis, nephrocalcinosis, hypercalciuria, hyperoxaluria), followup time, kidney function (chronic kidney disease stage 2, chronic kidney disease stage 3, chronic kidney disease stage 45), followup, outcome of urinary tract stones (active stones, asymptomatic stones or disappearance of stones), and HOGA1 gene mutation type. Main outcome measures：Clinical phenotypes and hotspot variation in different ethnic groups. Results：Eight PH3 patients were enrolled (7 boys, 1 girl). The median age of onset was 10 months, and the median diagnosis age was 16 months. Initial symptoms showed urinary tract infection in 5 patients and gross hematuria in 3 patients. Imaging evaluation identified the diagnosis of nephrolithiasis in 8 cases, and none of them showed nephrocalcinosis. Three patients were tested for urinary excretion of oxalate, and 1 showed hyperoxaluria. Six patients conducted urinary calcium test and 5 of them showed hypercalciuria. One patient was loss to follow up and the other 7 cases were followed up for a median of 25 months. The glomerular filtration rate remained stable. Furthermore, 3 cases showed kidney stones disappearing during the followup. All the 8 cases had HOGA1 gene variant, including compound heterozygous variants in 5 cases and homozygous variants in the other 3 cases. According to ACMG classification, 6 variants were identified as likely pathogenic variants and the other 4 were identified as pathogenic variants. Among 82 articles related to PH3, 23 were case reports or case series reports which included 321 cases of PH3. Among these cases, 36 patients from China and 293 patients form Europe and America. The percentage of nephrolithiasis in Chinese group and EuropeanAmerican group were 83 percent(30/36) and 85 percent(195/230) respectively. The percentage of nephrocalcinosis in these two groups were 3 percent (1/29) and 8 percent (20/261). There was no difference in hyperoxaluria between the two groups ［90 percent (26/29) vs 96percent (66/69)］. There was significant difference in hypercalciuria between the two groups ［44 percent (11/25) vs 23 percent (34/150)］. In Chinese group, one patient progressed to endstage renal disease when he was 25 years old. In EuropeAmerica group, there were 2 patients progressed to endstage renal disease at the age of 8 and 33 respectively. The percentage of active stone in these two groups were 13 percent (3/23) and 37 percent (22/59), and the difference was significant. The hotspot variants of the Chinese group were c.834G>A (splice site), c.834_c.834+1GG>TT (splice site) and c.769T＞G (p.C257G), accounting for 28 percent(20/72), 21percent(15/72) and 11 percent(8/72), respectively. The hotspot variants of the EuropeanAmerican populations were c.700+5G>T (splice site) and c.944_946delAGG (p. E315del), accounting for 40 percent(236/586) and 12 percent(73/586), respectively. Conclusion：The age of onset and diagnosis of PH3 is quite earlier, and the overall prognosis is better than that of PH1 and PH2. Chinese and EuropeanAmerican PH3 patients may have different hotspot variants for HOGA1 gene.

Objective：To summarize the clinical features of Hashimoto's encephalopathy (HE) in children. Methods：Children diagnosed with HE hospitalized in the Department of Neurology at Hebei Children's Hospital from January 2017 to December 2020 were selected. The clinical characteristics, laboratory examination results, imaging results, treatment and prognosis of the disease were retrospectively analyzed. Results：Among the 7 HE patients, there were 5 males with onset age of 5 to 12 years. Three cases had fever at the onset of the disease. Before the onset of the disease, infection, viral encephalitis, hyperappetite and increased defecation, and epilepsy were found in 1 case, respectively. Three cases had depileptic seizure and 2 of them were epileptic status. Three cases had abnormal mental behavior and 3 had consciousness change. One patient had cranial nerve injury. One case had increased WBC and CRP. CSF cells increased in 3 cases, and CSF protein increased in one case. The oligoclonal bands were positive in 2 of 5 cases receiving the examination. Thyroid peroxidase (TPO) antibodies were normal in 4 patients at the onset of the disease, but increased when the disease was aggravated within two weeks. Three cases had increased TPO antibodies at the onset of the disease. There were 2 cases of hyperthyroidism, 2 cases of central hypothyroidism, 1 case of low T3 syndrome, and 1 case of reduced free T3 and T4. One patient had normal thyroid function at the time of admission and central hypothyroidism occurred later. Thyroid ultrasound showed polycystic nodules in two cases. Three cases had cranial MR abnormality. Seven cases were abnormal in video electroencephalogram, showing different degrees of slow wave release, and 1 case was epileptic. All 7 cases were treated with immunoglobulin shock combined with high-dose methylprednisolone sodium succinate. The symptoms of 6 cases were relieved after 3 to 8 days of treatment and 1 case remained unchanged after 1 month of shock treatment, whose symptoms were relieved after 7 days of the second round of hormone shock treatment. Seven cases had been followed up for 1 to 4 years. One case recurred twice, and the symptoms were relieved after hormone or immunoglobulin shock treatment. Three patients with abnormal cranial MR were followed up within 2 months, and the imaging returned to normal. TPO antibodies were reexamined in 4 cases, thyroid function was followed up in 3 cases, and the relevant indexes returned to normal within 1 year. Conclusion：The clinical manifestations, laboratory indicators and imaging characteristics of HE are not specific, so it is necessary to distinguish it from various diseases. For pediatric patients with unknown encephalopathy, the possibility of HE should be considered after excluding autoimmune encephalitis, inflammation and demyelination diseases , and TPO antibodies should be detected for many times to assist in the diagnosis.

Background: Juvenile idiopathic arthritis (JIA) associated uveitis is the most common extraarticular manifestation of JIA. Untimely treatment may lead to serious complications and the risk of blindness. Objective: To investigate the clinical features of JIA patients complicated with uveitis. Design: Case series report. Methods: Patients complicated with uveitis admitted to the department of rheumatology and immunology of the Children's Hospital Affiliated to the Capital Institute of Pediatrics from March 2018 to May 2020 were included. Demographic data, laboratory examination, subtype of JIA, ocular manifestations and complications, treatment, and followup were intercepted from the medical records. Main outcome measures: Uveitis and complications, treatment and outcome. Results: Of the 278 cases with JIA, fifteen cases were complicated with uveitis, including 4 males and 11 females. The onset age was within 8 years old. Among the 15 patients, there were 13 cases of oligoarticular type, 1 case of polyarticular type and 1 case of enthesitisrelated arthritis type; there were 2 patients with the onset of visual impairment and the other 13 cases with the onset of arthritis; eye lesions were found in 12 cases at the initial diagnosis, and in 3 patients at the course of 12.5 years. All of the 15 patients were diagnosed with anterior uveitis with 8 cases of bilateral lesions and 7 cases of unilateral lesions. Visual impairment was detected in 7 cases. There were 12 patients treated with biological agents, 13 with methotrexate, 1 with sulfasalazine and mycophenolate mofetil, and 3 with glucocorticoids. For local medication, 13 cases were treated with glucocorticoids, 11 cases with mydriasis drugs, 11 cases with nonsteroidal antiinflammatory drugs, and 3 cases with antibiotics. During the followup (1441 months), the arthritis of all patients was improved after treatment. Eye lesions recovered in 7 cases, improved in 1 case, and delayed and repeated in 2 cases, remained no changes in 5 cases. Conclusion: Uveitis is the main extraarticular manifestation of JIA, which is more common in oligoarticular type, occult onset, and highly disabling. Without treatment in time, serious complications may occur. Regular visual and fundus examination in children with JIA is very important for early detection and treatment of ocular lesions.

Background: Researches have demonstrated the correlation between geneotype and phenotype as well as decreased head circumference and intracranial volume in Rett Syndrome (RTT),but it is unclear how the phenotypes and neuroimaging parameters correlate. Objective: To investigate the correlations between the clinical severity and developmental level, sleep status and gray and white matter parameters in typical RTT to guide thte diagnosis and treatment. Design: Crosssectional correlation analysis. Methods: Children with typical RTT underwent MECP2 gene testing were included. The clinical severity was evaluated based on the Rett Syndrome Severity Scale (RSSS). Griffiths Development ScalesChinese (GDSC) was used to assess the developmental status. Children Sleep Habit Questionnaire (CSHQ) was used to assess the sleep status. Magnetic resonance imaging (MRI) was applied to obtain the brain white and gray matter index. Multiple linear regression analysis was applied. Main outcome measures: The correlations between RSSS, GDSC, CSHQ and neuroimaging parameters. Results: A total of 22 children with typical RTT administered at Children's Hospital of Fudan University from July 2014 to June 2021 were recruited. Twentytwo children were all females and aged 3.1±0.8 years old. All had been detected with pathogenic variants in the MECP2 gene. RSSS score was 5.91±1.38, the GDSC total DQ was 17.89±7.93 and the CSHQ score was 54.05±5.52. Multiple linear regression analysis revealed that RSSS was significantly correlated with BDQ(r=-0.518， P=0.007)，DDQ(r=-0.4， P=0.032) and total DQ(r=-0.429， P=0.023) of GDSC as well as GMV(r=-0.571， P=0.003)， WMV(r=-0.514， P=0.007)， FA(r=-0.472， P=0.013)， MD(r=0. 519， P=0.007)， RD(r=0.528， P=0.006) and AD(r=0.491， P=0.01) for MRI parameters. Conclusion: The RSSS score of typical RTT correlated with developmental level and gray and white matter parameters,and it has potential value in assessing the clinical severity in patients with RTT.

Background: Hypothermia treatment is now effective treatment for hypoxic ischemic encephalopathy (HIE). Currently, there is still no consensus on enteral nutrition to infants with HIE during therapeutic hypothermia at home and abroad. Objective: To study the safety of enteral nutrition during hypothermia treatment for HIE in neonates. Design: Retrospective non-randomized controlled study. Methods: Neonates with HIE undergoing hypothermia at the Department of neonatology, Children's Hospital of Chongqing Medical University between January 2019 to June 2020 were included in the study. According to whether patients received enteral nutrition during hypothermia treatment, they were divided into enteral nutrition (EN) group and unfed group. Data of general conditions, clinical manifestations, laboratory examinations, diagnosis, treatment, age of starting feeds, type, volume, and mode of enteral nutrition were collected. Main outcome measures: Incidence of neonatal necrotizing enterocolitis (NEC) during hospitalization. Results: A total of 95 patients with HIE were included in the analysis, including 51 patients in the EN group and 44 patients in the unfed group. Patients in the EN group had lower incidence of abdominal distension than the unfed group (P=0.047) and there were no significant differences in the incidence of vomiting, bloody stools, and convulsion between the two groups. No statistically significant differences were found in blood gas analysis measured within an hour of birth, first blood routine test after admission, intracranial hemorrhage in brain sonography, and abnormalities in cranial magnetic resonance between the two groups. Patients in the EN group had a shorter mean length of parenteral nutrition and hospital stay compared with the unfed group (P<0.001). There were no significant differences between the two groups regarding complications such as NEC and feeding intolerance. In the EN group, 60.8% received formula and 41.1% were fed on day 1 of life. The mean total volume was 19.1 mL·kg-1 over a 24 hour period and 68.6% did not increase feeds during hypothermia treatment. One patient developed NEC (I), and improved after conservative medical therapy. No deaths occurred. Conclusion: Early minimal enteral nutrition during hypothermia was associated with lower incidence of abdominal distension, a shorter mean length of parenteral nutrition and hospital stay, but did not increase incidence of NEC.

Background：At present, there are few reports about acute leukemia in children with peripheral facial paralysis as the initial symptom, and it is easy to be misdiagnosed clinically. Objective：To investigate the clinical characteristics，treatment and prognosis of children diagnosed with acute leukemia presented with peripheral facial paralysis as the initial symptom. Design：Case series report. Methods：The children diagnosed with acute leukemia presented with peripheral facial paralysis as the initial symptom admitted to the Department of Pediatrics of Peking University People's Hospital from January 2010 to September 2021 were included. The clinical characteristics, laboratory examinations, treatment and outcome were analyzed. Main outcome measures：The outcome of facial paralysis，5year eventfree survival（EFS），overall survival（OS）. Results：A total of 1 018 children with acute leukemia were admitted during the study period, including 728 patients with ALL and 290 patients with AML. Sixteen children(1.6%) presented with peripheral facial paralysis as the initial symptom, including 7 males and 9 females, with a median age of 5 years (214 years), and a median time from onset of facial paralysis to diagnosis of facial paralysis was 9.5 days(131 days).There were 2 cases （12.5%) of Bcell leukemia, 1 case(6.2%) of Tcell leukemia and 13 cases(81.3%) of M2 myeloid leukemia. All 16 patients had unilateral leukemia, 5（31.2%）were left and 11（68.8%）were right. 15 cases underwent head MR examination, 2 cases showed dural and leptomeningeal thickening and enhancement (including 1 case with suspicious facial nerve injury), 1 case showed leukemia infiltration of medial rectus muscle and orbital segment of optic nerve, and 3 cases showed mastoiditis.Cerebrospinal fluid(CSF) was examined in 15 cases, of which 1 case had CSF minimal residual positive and transient elevation of CSF protein occurred in 1 case. One patient gave up treatment after leukemia diagnosis, and the other 15 patients received chemotherapy. Eight patients remains continuous remission with regular chemotherapy，6 patients received hematopoietic stem cell transplantation, and 1 patient died after relapse due to multiple organ dysfunction during chemotherapy. The symptoms of facial paralysis disappeared in 13 cases within 1 month, and in 2 case within 3 months. The median followup time was 44.5(0.23111) months，the 5year eventfree survival(EFS) was(48.2±13.0)％，and 5year overall survival(OS) was (87.5±8.3)％．The 5year EFS and 5year OS of 13 AML children were (51.3±14.6) % and (84.6±10.0) %, respectively, with 5year OS 100% in the transplant patients and (87.5±11.7) % in the onlychemotherapy patients, showing no statistical difference (P=0.48). Conclusion：Peripheral facial paralysis as the initial symptom of childhood acute leukemia is likely to be misdiagnosed. For children with peripheral facial paralysis, comprehensive examination should be completed to exclude secondary causes before steroid therapy. Intensive central nervous system therapy should be considered in children with acute leukemia with facial paralysis. The overall survival rate of AML children with facial paralysis was not significantly affected, but they were more likely to relapse.

Background：The Omicron pandemic in Shanghai from March to May 2022 is very challenging for the emergency department to attach equal importance to emergency rescue and pandemic prevention and control. Objective：To explore the effect of bubble strategy on emergency rescue and pandemic prevention and control. Design：Observational study. Methods：During this pandemic period, the hospital is designed as a big bubble, and the emergency department is designed as a medium bubble. The buffer zone, resuscitation room, consulting room and observation room are designed as small bubbles. Based on "four zones, two channels and twice triage", the original layout and process of emergency department were modified. The four zones were as the following: a. the clean zone mainly included personnel living room and personal protective equipment (PPE) donning room; b. the potentially contaminated zone was set between the contaminated zone and clean zone, including PPE doffing room 1 and 2; c. the contaminated zone included the second triage area, waiting area, resuscitation room, consulting rooms and observation room; d. the highrisk contaminated zone included the first triage area and buffer zone. Two channels were clean and contamination channels. Twice triage referred to the initial screening at the entrance of the emergency department, and fivelevel triage after admission to the emergency department. The buffer zone was used for those who were diagnosed with critical illness but had a red health code and no negative nucleic acid test results within 48 hours. Level Ⅰ/Ⅱ patients with negative nucleic acid test results within 48 hours were admitted to the resuscitation room. Level ⅢⅤ patients with negative nucleic acid test results within 48 hours or negative onsite antigen test results were arranged to the consulting room. Patients who had negative nucleic acid test results on the day of entering the hospital and requirements for observation are admitted to the observation room. The second emergency room was set up as a backup emergency room when the major emergency department needed to be closed temporarily because of the presence of COVID19 infection patients. The bubble rupture plan was established. If a patient treated in the consulting room or resuscitation room was confirmed to be COVID19 infection, the first environmental sampling was performed at the exposure site to evaluate the degree of environmental contamination, and a second sampling was performed after terminal disinfection to evaluate the environmental safety. The second emergency room was activated if necessary. Main outcome measures：Nosocomial infection and occupational exposure of medical staff. Results：A total of 12 114 patients were admitted to the emergency department of our hospital, including 15 level Ⅰ patients, 310 level Ⅱ patients, 8 728 level Ⅲ patients, 2 564 level Ⅳ patients and 497 level Ⅴ patients. There were 7 major rescues, 32 medium rescues and 1 070 minor rescues. Fiftyeight patients were admitted to the PICU and 3 patients died in the emergency department. A total of 36 doctors, 38 nurses and 3 sanitation workers participated in the emergency department bubble, rotating every 5 days. Neither nosocomial infection nor occupational exposure occurred. Twentynine patients were admitted to the buffer zone, among which 3 patients were confirmed to be COVID19 infection and 3 patients were transferred to the PICU because of critical illness. In total, 652 patients were admitted to the observation room, among which 12 patients were transferred to PICU because of illness deterioration. Fiftyfive patients were guided to the COVID19 clinic by the initial screening, of which 4 patients were positive for nucleic acid test. A total of 6 patients with novel coronavirus infection were admitted to the emergency department. Among them, 3 children with positive nucleic acid test results were admitted to the consulting room, which caused environmental contamination. Terminal disinfection and environmental sampling were performed and the emergency department reopened when all environmental samples were tested negative. Conclusion：By adjusting the layout of emergency department and modifying the treatment process, it is possible to meet the needs of emergency care and pandemic prevention and controlat the same time, and to achieve the double zero of nosocomial infection and occupational exposure. The risk of bubble rupture existed, so it was necessary to make a plan.

Background: In clinical practice, food protein-induced proctocolitis (FPIPC) might still be misdiagnosed as neonatal necrotizing enterocolitis (NEC) for neonates with bloody stool and abdominal distension and positive portal vein gas (PVG) by abdominal ultrasound. Objective: To compare the clinical data and abdominal ultrasound examination results of NEC and FPIPC and to analyze the related factors of NEC. Design: Case-control study. Methods: Newborns with PVG positive by abdominal ultrasound were included from the inpatient settings of Children's Hospital of Chongqing Medical University from January 1, 2019 to December 31, 2019. According to the first diagnosis at discharge, they were divided into NEC group and FPIPC group. The general information, clinical manifestations and signs, the results of laboratory examination and abdominal ultrasound reports of the children were collected from the electronic medical records and the factors with statistical significance and clinical value were screened out for Logistic regression analysis. Main outcome measures: Factors associated with the diagnosis of NEC in neonates with positive PVG on abdominal ultrasound. Results: There were 68 cases in NEC group and 42 cases in FPIPC group. The gestational age, birth weight and the age and weight at the admission in the NEC group were lower than those in the FPIPC group. The percentage of abdominal distention, low reaction and reduced bowel tone, neutrophils proportion, and the percentage of elevated CRP and abnormal PCT in NEC group were higher than those in FPIPC group. The percentage of diarrhea in FPIPC group was higher than that in NEC group(P<0.05). Abdominal ultrasound examination showed the proportion of intestinal peristalsis and peritoneal effusion in NEC group was higher than that in FPIPC group (P<0.05).There was no significant difference in the age of PVG detection between the two groups. There was no significant difference in the proportion of PVG that did not disappear within 3 days after abdominal ultrasound re-examination (67 cases in NEC group and 37 cases in FPIPC group) between the two groups. Logistic regression showed that decreased abdominal bowel sounds (OR=14.7, 95%CI: 2.6~82.2, P=0.002), CRP>10 mg·L-1 (OR=24.7, 95%CI:1.4~431.7, P=0.028) and slower intestinal peristalsis(OR=26.9, 95%CI: 1.853~389.9, P=0.016) were associated with NEC. Conclusion: When abdominal ultrasound on neonates showed positive PVG, gestational age, birth weight, clinical manifestations, inflammation, abdominal ultrasound characteristics should be combined to make differentiate diagnosis. NEC should be paid attention when there were weakened abdominal bowel sounds, elevated CRP increases, and slower bowel movements by abdominal ultrasound.

Background: Infusion Therapy Standards of Practice published in 2021 did not provide a clear recommendation on how to choose between normal saline and heparin saline as the locking solution for neonates and children, however, Clinical Practice Guideline on Infusion Therapy in Children recommended using heparin solution. Objective: To compare the effects of heparin saline (HS) and 0.9% normal saline (NS) solution as the locking solution of a peripheral intravenous catheter (PIVC) on different pediatric populations. Design: Systematic review and metaanalysis of RCTs. Methods: Hospitalized pediatric patients who need PIVC were divided into the intervention group using HS and the control group using NS. Literature was searched in English databases of Ovid MEDLINE, PubMed, Cochrane Library, and Chinese database of SinoMed from April 1, 2014 to November 23, 2021 for there have been two articles of systematic review and metaanalysis on this topic published in 2005 and 2013. RoB 2 was used to evaluate the risk of bias in the included studies. Main outcome measures: PIVC duration and the related complications. Results: A total of 21 RCTs were included in the analysis. The duration of PIVC in HS group was 8.62 h longer than that in NS group (95%Cl: 2.9814.26, I2=91%, random effects model), and the difference was statistically significant. After removal of four literature about neonates because of greater heterogeneity, the metaanalysis of other eight literature showed that PIVC duration in neonates of HS group was increased by 6.04 h (95%Cl: 4.177.91, I2=56%, random effects model), and the difference was statistically significant. The pooled results of five studies for both neonates and children showed that the PIVC duration of HS group was prolonged by 6.22 h(95%Cl: 2.729.73, I2=20%, random effects model), and the difference was statistically significant. For the population of children, the pooled results of three studies indicated that the PIVC duration was prolonged by 6.94 h(95%Cl: -1.2715.15, I2=27%, fixed effects model ) in HS group, and there was no statistically significant difference. According to the pooled results of 18 studies, the incidence of complications decreased by 17% (RR=0.83, 95%Cl: 0.710.97, I2=19.5%, fixed effects model) in HS group compared with that of NS group, and the difference was statistically significant. The incidence of complications in neonates decreased by 25% in HS group(RR =0.75, 95%Cl: 0.620.91, I2=0%, fixed effects model) according to the pooled analysis of 9 studies, and the difference was statistically significant. There was no significant difference in reducing the incidence of complications between the two groups for children (4 studies) and the population of both newborns and children (5 studies). Conclusion: Locking PIVC by heparin saline is desirable for the neonatal population in terms of duration and complication incidence. Whether it is beneficial to the whole pediatric population still needs to be further explored.

Background：Mild neonatal hypoxic-ischemic encephalopathy (HIE) has been considered to have better long-term outcomes. In recent years, there was evidence that the long-term outcomes of mild HIE were worse than those of normal children. Objective：To explore whether mild neonatal HIE benefits from hypothermia therapy. Design：Systematic review and meta-analysis. Methods：Literature was searched in databases of PubMed, Embase, Cochrane, CINAHL from the establishment to Dec 6,2021, and in database of SinoMed from the establishment to Nov 12, 2021. Retrieved papers were first screened by titles and abstracts. A second phase of screening was subsequently undertaken to screen papers for exclusion criteria as follows either: a. the diagnosis of mild neonatal HIE failing to meet the modified Sarnat standard; b. neonates with congenital malformations; c. failure to extract the outcome data of neonatal mild HIE; d. the follow-up time <12 months. GRADE methodology was used to rate the quality of evidence body. Publication bias analysis was adopted for more than 10 articles in either evidence body, and extracted data were analyzed using Revman 5.4 and R. The I2 test was used for heterogeneity. If I2≤50%, the fixed effect model should be adopted; if I2>50%, the random effect model should be adopted. Main outcome measures：Rate of death and major neurodevelopmental disabilities at more than 12 months. Results：1,839 articles were identified through database searching. A total of 113 full-text articles were assessed for eligibility and 24 articles were included in this review. The review was conducted for 4 RCTs, 7 cohort studies, and 13 case series reports. A total of 21 literature reported nervous system disability by dichotomous variables, and three literature reported nervous system disability by continuous ones. Follow-up time in 16 articles was from 12 months to 3 years, and 9 articles over 3 years (1 article reported neurological disability at 24 months and 7 years old respectively). No deaths were reported in the 24 articles during the observation period. A total of 369 infants with mild neonatal HIE was reported in 21 articles with dichotomous variables and the results showed that the incidence of major neurodevelopmental disabilities in mild HIE survivors was 21% (95%CI: 0.14-0.29), I2=80%, and there was publication bias (Egger test, t=4.68, P<0.01). The incidence of major neurodevelopmental disabilities was 11% (95%CI: 0.00-0.23) on therapeutic hypothermia (6 articles) and 21 percent (95%CI: 0.13-0.29) on non-therapeutic hypothermia (19 articles). There was no difference (OR=0.78, 95%CI: 0.27-2.31, I2=0) in the incidence of major neurodevelopmental disabilities between mild HIE patients treated with therapeutic hypothermia and those not treated with therapeutic hypothermia (4 RCTs), and patients who received non-therapeutic hypothermia compared with normal children (4 cohort studies) had higher incidence of major neurodevelopmental disabilities (OR=19.06, 95%CI: 7.01-51.85, I2=42%). The incidence of neurological disability was 20 percent (95%CI: 11%-29%) in subgroups whose follow-up time was from 12 months to 3 years and 24 percent (95%CI: 11%-36%) in over 3 years. Conclusion：When patients diagnosed with mild HIE was followed up until the age of 3 years old, the potential incidence of major neurodevelopmental disabilities increased to 24%, and benefits of combining with support treatment of therapeutic hypothermia as auxiliary is greater than the disadvantages.

Background：Iatrogenic skin injury is a common problem in neonates admitted to NICU. Objective：To investigate the incidence of neonatal iatrogenic skin injury in NICUs in China. Design：Cross-sectional survey. Methods：Children's Hospital of Fudan University took the lead in establishing the NICU clinical data database of neonatal iatrogenic skin injury, which included 22 tertiary hospitals in 15 provinces, autonomous regions and municipalities directly under the central government. The causes of iatrogenic skin injury were related to diapers, viscose, pressure (including medical devices), surgery, vascular access, and physical or chemical factors. The continuous cases reported by NICUs of the cooperative hospitals were sent to the database, and the data were from the electronic medical record system or paper medical document records. The reported data included demographic data, medical devices use, iatrogenic skin injury events, the age, weight and length of hospital stay of the infant at the time of each iatrogenic skin injury, the location, size, type, color, treatment measures and prognosis of skin injury. The leading hospital trained the cooperating hospitals according to the indicators in the database and started data collection after passing the examination. The leading hospital was responsible for reviewing the data. Main outcome measures：Incidence of iatrogenic skin injury in NICU hospitalized neonates. Results：From December 1, 2019 to January 31, 2020, the data of NICU consecutive cases (n=8,126) collected by 22 cooperative hospitals were all qualified and included in this analysis. There were 521 cases of iatrogenic skin injury (6.4%), and the incidence of iatrogenic skin injury in NICU in children's specialized hospitals, general hospitals and maternal and child health hospitals were 7.4%(280/3,783), 6.4% (153/2,387) and 4.5%(88/1,956), respectively. There were 566 times of iatrogenic skin injury in 521 neonates, and 45 cases (8.6%) had two times of iatrogenic skin injury. The median age of neonates with iatrogenic skin injury was 6 (3, 17) days, those within 1 week after birth accounting for 57.4%(n=299). The median corrected gestational age of neonates with iatrogenic skin injury was 37.2% (32.7, 40.0) weeks, those with the corrected gestational age≥40 weeks accounting for 57.4%(n=294). The median weight of neonates with iatrogenic skin injury was 2,800 (1,9123,450) g, those with the weight≥2,500 g accounting for 59.1%(n=308). There were 250 cases of diaperrelated skin injury (48.0%), 81 cases of pressurerelated (including medical devicerelated) (15.5%), 69 cases of viscoserelated (13.2%), 70 cases of various physical and chemical factorsrelated (13.4%), 22 cases of vascular accessrelated (4.2%), 14 cases of surgeryrelated (2.7%), and 15 cases of other types (2.9%). The proportion of all kinds of iatrogenic skin injury in neonates aged 17 days was the highest. Except that pressurerelated skin injury was easy to occur in very low birth weight infants and iatrogenic viscoserelated skin injury was easy to occur in all body recombination, other types of skin injury mostly occurred in neonates weighing≥2,500 g. Pressure-related and viscose-related skin injuries mostly occurred in neonates with the corrected gestational age of 28-32 weeks. Vascular access-related skin injuries accounted for a relatively even proportion in each corrected gestational age group, and other skin injuries were more likely to occur in neonates with the corrected gestational age >32 weeks. Most iatrogenic skin injuries(78.9%) occurred within one-week hospitalization stay of <1 week. The incidence rate decreased week by week. Conclusion：The incidence of iatrogenic skin injury in NICU neonates in China was 6.4%. Diaper-related dermatitis, the application of medical devices, and the use of medical tape were the three main factors of iatrogenic skin injury in neonates. Iatrogenic skin injury was affected by many factors, such as gestational age, birth weight, and the use of various catheters.

Background: Great heterogeneity exists in studies on the relationship between adolescents' mental health and 24-h movement consisting of sleep, sedentary behavior, and physical activity. Therefore, it is difficult to obtain high-quality evidence synthesis sufficient to guide clinical practice. Objective: To summarize and evaluate the current status of research on the relationship between 24-hour movement (sleep, sedentary behavior, and physical activity) and mental health in children and adolescents, as well as the problems in research design, so as to provide a reference for future research. Design: Scoping review. Methods: PubMed, Embase, Web of Science, and CNKI databases were searched from the inception to September 28, 2022, with the keywords of sleep, sedentary behavior, physical activity, 24-h movement, mental health, and adolescents to identify research on the correlation or causal inference between 24-h movement and mental health in healthy children and adolescents. Data extraction forms for movement type, measurement methods, classification of measurement items, and specific item measurement were gradually refined in the process of data extraction and synthesis after reading the text title, abstract, and full text for screening. Main outcome measures: Study types and measurement instruments for the relationship between 24-h movement and mental health in adolescents. Results: A total of 927 articles were retrieved from the English and Chinese databases, and after de-duplication, initial screening and full-text screening, 55 articles were finally included with 45 (82%) cross-sectional studies and 10 prospective cohort studies; 47 (85%) subjective reports and 8 objective monitoring articles. For sleep, 54 described sleep duration and 4 assessed sleep quality, sleep latency, daytime sleepiness, and sleep disruption. For sedentary behavior, there were 50 subjective reports, 5 objective reports, and 46 studies about screen exposure. For physical activity, hours of moderate-to-vigorous physical activity were assessed in 47 subjective reports and 8 objective reports. A total of 32 studies focused on depression, 9 on anxiety, 5 on stress, and 35 on other mental health outcomes (positive mood, behavioral problems, life satisfaction or health-related quality of life, mental illness and symptoms, emotion regulation skills, and cell phone addiction). Forty-four papers explored the correlation between 24-h movement and mental health, 8 papers explored changes in the structure of 24-h movement using isochronous substitution models, and 3 explored mediators of 24-h movement affecting mental health. Conclusions: There are few studies on the association between 24-h movement and mental health in adolescents, and the measurement tools used need to be standardized. In the future, isochronous substitution models or real-world intervention studies are needed to find the recommended 24-h movement packages that can maximize the health effects of the movement and are easy to achieve at the same time.

Background：Coronavirus Disease 2019 (COVID19) vaccination plays an important role in controlling the pandemic and protecting population from developing into a severe type. The vaccination safety in children with a history of allergy has been a common concern. Objective：To provide the best immunization practice and recommendations for children with a history of allergy. Design：Case series report. Methods：Children and adolescents aged 3 to 17 who were consulted at the designated pediatric COVID19 vaccine advisory clinic in Children's Hospital of Fudan University between August 12nd, 2021 and December 3rd, 2021 were included. Based on individual's past medical history, current health status, and parental concerns, individualized assessments are made, and recommendations for deferring and recommending vaccinations are given. Telephone followup was conducted to collect adverse events following immunization (AEFI) within 72 h and 28 d after vaccination and any unsolicited adverse events reported by parents. The causal association between AEFI and vaccine was assessed. Main outcome measures：AEFI of COVID19 vaccine. Results：A total of 116 children consulted for COVID19 vaccination, including 67 boys (57.8%) and 49 girls, aged (10.1±3.1) years old. Seventyseven (66.4%) were recommended to start vaccination, and 39 were recommended to defer vaccination after individualized assessment in the immunization advisory clinic. The followings were recommended to defer the vaccination 25 cases in the acute phase of allergic disease among 70 cases (60.3%) with a history of allergy, 5 cases of severe allergic reactions among 11 cases (9.5%) with a history of other vaccine or drug allergy, 5 cases in the acute phase of the disease in 13 cases (11.2%) with a history of nondrug allergy, and 3 cases of acute illness (respiratory tract infection) among 21 cases (18.1%) with atopy, and 1 case（0.9%）with a history of allergic to the first dose of COVID19 vaccine. All patients in the deferring vaccination group completed the telephone followup 3 months after the consultation. Seventyseven children in the recommended starting vaccination group were followed up for 3 times, among which 54 cases were in the vaccinated subgroup (47 children receiving 2 doses of vaccine, 7 children receiving 1 dose of vaccine), and 23 cases were in the unvaccinated subgroup. There were no significant differences in gender, allergic disease history, other vaccine or drug allergy history, nondrug allergy history and atopy between the two subgroups. The age ［(10.4±3.0) years vs (9.0±3.1) years old, P=0.04］ between the two subgroups had statistically significant difference. No severe allergic reactions were collected during the telephone followup at 4 d and 28 d after vaccination. Within 72 hours after vaccination, 18 cases (17.8%) were solicited with 10 systemic adverse events, 5 cases (5.0%) of rash and cough respectfully, 4 cases (4.0%) of runny nose, 3 cases (3.0%) of anorexia and fever respectfully, 2 cases (2.0%) of sore throat, 1 case (1.0%) of fatigue, myalgia, nausea and vomiting respectively. There was a causal relationship with the AEFIs and COVID19 vaccine after preliminary judgement. No additional solicited adverse reactions were reported in the 28 d and 3month telephone followup. Within 28 days after vaccination, parents voluntarily reported 5 cases of unsolicited adverse events, 3 cases (3.0%) of idiopathic dermatitis or eczema, and 2 cases (2.0%) of allergic rhinitis. No causal relationship with COVID19 vaccine was found. The incidence of AEFIs of COVID19 vaccine within 28 days was 33.3% (18/54). Conclusion：It is safe for children whose allergic diseases are in remission status, those who had nonsevere allergic reactions to nonCOVID19 vaccines or other drugs, those who had nondrug allergy history, and those who had atopy to receive inactivated COVID19 vaccines. The systemic adverse reactions of AEFIs of COVID19 vaccine all occurred within 72 hours after vaccination, and were causally related to the COVID19 vaccination.