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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：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.

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: 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: 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：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：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.

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.

Background：Authoritative clinical practice guidelines and expert consensus have recommended the use of rituximab (RTX) in the treatment of children with frequent relapsing/steroid-dependent nephrotic syndrome (FRNS/SDNS) of steroid-sensitive nephrotic syndrome(SSNS). However, there is a discrepancy in terms of clinical indications, treatment, and follow-up protocols. Objective：To comprehensively examine relapse and steroid therapy during over one year follow-up in patients diagnosed with FRNS/SDNS who were administered the initial course of RTX while being in remission. Design：Systematic review and meta-analysis. Methods：Keywords of SSNS, FRNS, SDNS, and RTX were used to search China Biology Medicine Database, PubMed, Embase, Scopus, and Cochrane from the inception to June 26, 2022. The preliminary and full-text screening were conducted by two independent reviewers, who also extracted the relevant data. Unsure or controversial literature underwent a third-party review. At least one RTX intervention for children aged between 1 and 22 years with SSNS was included. Main outcome measures：The frequency of relapse, time to the first relapse, cumulative steroid dosage, and percentage of patients who withdrew from steroids in those who were followed-up for more than 1 year after receiving RTX intervention. Results：A total of 26 studies (1 in Chinese and 25 in English) were eligible including 8 randomized controlled trials (RCT), 1 non-randomized study of interventions (NRSI), 8 cohort studies, and 9 case series reports. Two subgroups were defined as FRNS/SDNS+ group in which immunosuppressants were used before RTX intervention and FRNS/SDNS- group in which no other immunosuppressants were used before RTX intervention. Meta-analysis of 9 studies on the relapse rate of FRNS/SDNS during at least 1-year follow-up showed a 78% reduction in the relapse rate of RTX compared to the control group (OR=0.22, 95%CI: 0.09 to 0.53). In FRNS/SDNS+ group， RTX reduced the relapse rate by 67 % compared to the control group (OR=0.33, 95%CI: 0.12 to 0.94). In FRNS/SDNS- group, RTX reduced the relapse rate by 85 % compared to the control group (OR=0.15, 95%CI: 0.03 to 0.68) in the absence of other immunosuppressants. Additionally, the meta-analysis of 20 studies indicated that the relapse rate after RTX was 42% (95% CI: 32 to 53). The meta-analysis of 9 studies on the time to the first relapse of FRNS/SDNS+ during at least 1-year follow-up indicated that the median time to the first relapse was 9.89 months (95%CI: 7.14 to 12.65). According to the meta-analysis of 3 studies on the median relapse free survival (RFS) from the initiation of FRNS/SDNS- to at least 1-year follow-up, RTX (1-2 doses) had a longer median RFS of 20 days compared to the control, with a median survival ratio (MSR) of 0.69 (95%CI: 0.52 to 0.87). The meta-analysis of four studies on the reduction of FRNS/SDNS cumulative steroid dose over a 1-year period found that RTX produced a significant decrease compared to the control group with a statistically significant difference (SMD=-1.12, 95%CI: -1.49 to -0.74). According to the meta-analysis of two studies on FRNS/SDNS steroid withdrawal rate within a three-month follow-up, the rate of RTX was 14.6 times higher compared to the control group (CNI or CTX) (OR=14.62, 95% CI: 5.43 to 39.39). The meta-analysis of three studies on the steroid withdrawal rate of FRNS/SDNS+ during a six-month follow-up after RTX showed a withdrawal rate of 68% (95% CI: 56 to 79). Conclusions：Compared with controls, RTX showed limited benefits in terms of relapse rate and first relapse time from the initiation of treatment to 1-year follow-up, and it could provide benefits in steroid reduction rather than steroid withdrawal. Addition of RTX in FRNS/SDNS patients, as compared with placebo or blank control, can reduce the 1-year follow-up relapse rate by at least 88%. The overall relapse rate for FRNS/SDNS patients who received RTX treatment at the 1-year follow-up was 43%. The addition of RTX treatment for FRNS/SDNS can provide 10 months of relapse-free survival time.

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

BackgroundSoon after the emergence of community transmission of COVID19, the Chinese government has introduced a series of nonpharmaceutical interventions (NPI) to eliminate COVID19 and these NPIS have already affected the prevalence of other common respiratory pathogens. 
 ObjectiveThis study aimed to analyze the epidemiological characteristics of mycoplasma pneumoniae (Mp) and chlamydia trachomatis (CT) of acute respiratory infections （ARTI） in children during the COVID19 pandemic. 
 DesignObservational study.
 MethodsRespiratory specimens for the detection of Mp, CT and other 9 common respiratory viruses were collected from children with ARTI at Children's Hospital of Fudan University from February 2019 to May 2021. The detection data were divided into the group of single pathogen infection (only Mp and CT were detected) and coinfection (Mp+CT, Mp or CT +any one or more of 9 common respiratory viruses and Mp+CT+ one or more of 9 common respiratory viruses). Respiratory specimens (nasopharyngeal aspirates/bronchoalveolar lavage fluid) were collected and tested in our hospital. a. Three satages were compared including "preCOVID19" period: from February 1, 2019 to January 31, 2020, without actively implemented nationwide NPI; b."COVID19"period, from February 1, 2020 to May 31, 2020, when strict nationwide NPI were implemented and schools were closed; c."postCOVID19"period, from June 1, 2020 to May 31, 2021, when nationwide NPI were relaxed, schools were reopened and social work was resumed. All the enrolled samples were divided into 5 age groups: ≤28 days, ~12 months, ~3 years, ~6 years and ≥7 years according to the age at the time of ARTI diagnosis.
 Main outcome measuresThe epidemiological changes of Mp and CT during the COVID19 pandemic.
 ResultsA total of 10 358 specimens tested for respiratory pathogens were enrolled in this analysis, including 6 080 in the preCOVID19 period, 754 in the COVID19 period and 3 524 in the postCOVID19 period. The total number decreased by 42.04% ［(6 080-3524)/6 080］during postCOVID19 when compared to preCOVID19. Among all the enrolled patients, 6 138 were male and 4 220 were female. The overall detection rate of Mp was 12.39%, the observed prevalence declined sharply and was decreased by 96.29% ( P<0.001) with a significant difference. The overall detection rate of CT was 1.45%. The detection rate showed an increasing trend and was increased by 65.49% (P=0.003). The detection rate of single Mp and CT infection was 10.84%. Compare to the pre-COVID-19 period, the detection rate of Mp was decreased by 96.05% and the detection rate of CT was increased by 119.70% in the post-COVID-19 period, with a significant difference. The overall coinfection rate was 2.89%. The coinfection rate of Mp was decreased by 97.32% (P<0.001), while no significant difference was observed in the coinfection rate of MP+CT and CT. Mp peaked in summer during the pre-COVID-19 period, whereas the annual peak was interrupted after the NPI were adopted. CT was detected throughout the whole study period. The examination rates were sharply decreased with the increase of age in the group of older than 12 months in both three periods, while the detection rate of Mp showed a great increase in the pre-COVID-19 period, an increase in the COVID-19 period and a slight increase in the post-COVID-19 period. The increase in the detection rate of CT was observed in the age of ≤28 days and -12 months in all three periods, while the examination rate and detection rate of CT showed a sharply decrease in children older than 12 months with the increase of age in the whole study period.
 ConclusionThe public health interventions aiming to eliminate COVID-19 have great impact on the prevalence of the atypical pathogens. The detection rate of Mp was significantly reduced, and the seasonality of Mp was disappeared, while the detection rate of CT was significantly increased.





Key wordsAcute respiratory tract infections;Mycoplasma pneumoniae;Chlamydia trachomatis;Epidemiology

Background：Sirolimus (SRL) is used in children for organ transplantation, autoimmune diseases, lymphatic malformation, vascular malformation, tuberous sclerosis and other diseases. However, it has great pharmacokinetic variability, which requires therapeutic drug monitoring (TDM). Objective：To reveal the causes of abnormal serum concentration of sirolimus. Design：Case report. Methods：We described the clinical data of 2 children with immunodeficiency treated with SRL for 6 months, analyzed the causes of abnormal drug concentration in children, and reviewed the literature. Main outcome measures：Whole blood trough concentration (Cmin) reached the target range of 510 ng·mL-1. Results：For child A, the drug interaction between SRL and voriconazole and CYP3A5 rs776746C/C genotype were the reasons for the slow drug metabolism and abnormal increase of Cmin. The dose decreased to 20% of the initial dose and gradually returned to the standard range. For child B, CYP3A5 rs776746 C/C genotype and ABCB1 gene rs1045642 T /T genotype were the reasons for the decrease of drug clearance rate and the abnormal increase of Cmin. After reducing the initial dose to 50%, the serum concentration of SRL gradually decreased to normal, and the treatment concentration was within the standard range. Conclusion：Systematic method will help to determine the cause of Cmin abnormal value of SRL. The sample factors, clinical factors and genetic factors should be considered before adjusting the treatment plan, and the comprehensive treatment management (CMM) of SRL should be optimized.

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.

Background Pineoblastoma are rare central nervous system tumors in children, and very few reports are available about this special cohort in China. Objective To investigate the clinical features, survival outcome and prognostic factors in pediatric pineoblastoma. Design Retrospective cohort study. Methods Children with pineoblastoma (confirmed by pathology) admitted to pediatric department of Beijing Shijitan Hospital from January 2017 to December 2021, were included for clinical analysis. The last follow-up was August 31, 2022 by clinic visit or telephone. The sex, age at diagnosis, clinical manifestations, imaging findings, surgical and pathological results, treatment and follow-up of the patients were included for analysis. Main outcome measures Overall survival (OS) and progression-free survival (PFS). Results Among 16 patients, 15 were males and 1 was female. The median age of onset was 67.6 (range, 20.7-129.4) months, with 4 cases less than 3 years old at the time of diagnosis. The main onset symptoms were intracranial hypertension, and there was no children with obvious endocrine dysfunction. MR images of the primary intracranial tumors showed space-occupying tumors in the pineal region and behind the third ventricle, and tumor spread to the fourth ventricle in one case. Supratentorial hydrocephalus was found in thirteen cases before operation. Five patients experienced metastases (M+) at the time of diagnosis, with spinal cord spread in 3 cases, brainstem and spinal cord spread in one case, and sacral spinal canal metastasis in one case. All the tumors of the sixteen patients were surgically removed with 12 cases under gross total resection and 4 cases near total resection. The surgeries were undertaken through transcallosal interforniceal approach in 15 cases, and Poppen approach in one case, with no obvious perioperative complications in these patients. Ki-67 index was less than 30% in 3 cases, 30%-60% in 5 cases and 61%-80% in 8 cases. All of the patients were treated with both radiotherapy and chemotherapy after surgery, including 9 cases receiving chemotherapy first followed by radiotherapy, and 7 cases receiving chemotherapy following radiotherapy. The median follow-up time was 47.6(36.8, 56.9)months. At last follow-up, nine patients experienced tumor recurrence or progression, and two of them died. The mean OS was 90.7±7.6 (range: 10.8-102.2) months, The 1, 3, 5-year OS were (93.8±6.1)%, (85.9±9.3)% and (85.9±9.3)%, respectively. The median PFS time was 29.5 (17.6, 50.0) months, and the 1, 3, 5-year PFS were (87.5±8.3)%, (41.5±13.8)% and (33.2%±13.3)%, respectively. Univariate analysis showed that boys had better overall survival than girls (χ2=5.405, P=0.02). The PFS of children with Ki-67 index of 30%-60% was shorter than that of <30% (χ2 =4.600, P=0.032). Multivariate COX regression analysis also showed that the risk of PFS in children with Ki-67 index of 30-60% was 3.2 times higher than that in children with Ki-67 index < 30%(HR=3.211, 95% CI: 1.027-10.037, P=0.045) Conclusion Pineoblastoma in children are rare. Ki-67 index is a prognostic factor affecting PFS.

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

Background It is difficult to dignose mycoplasma pneumoniae encephalitis (MPE) and the available medicine is limited. Objective To summarize the clinical features, diagnosis and treatment of children diagnosed with MPE. DesignCase series report. Methods The clinical manifestations, laboratory examination and imaging changes, treatment and outcomes in consecutively hospitalized patients diagnosed with MPE from January 2017 to December 2019 were retrospectively analyzed. Main outcome measures Recurrence or relapse. Results A total of 4 patients were all boys without any other underlying diseases. All of them mainly presented with fever and nervous system abnormality, 2 of whom had respiratory symptoms and 1 developed gastrointestinal symptoms. Serum mycoplasma pneumoniae (MP) IgM antibody detection was positive and other common pathogens were negative in all cases. As to cerebrospinal fluid test, 3 cases showed increased nucleated cell number, 1 case had weak positive protein and 1 case presented increased cerebrospinal fluid immunoglobulin. Multiple lesions in cranial magnetic resonance imaging (MRI) and abnormal electroencephalographic (EEG) were showed in all patients. Only one patient's condition was gradually worsened after 2 times of methylprednisolone and three times of intravenous immunoglobulin (IVIG) treatment, but the following condition was improved after three weeks of levofloxacin therapy combined with methylprednisolone pulse treatment and maintenance therapy. The other three patients' conditions were improved after receiving three weeks of levofloxacin therapy combined with IVIG pulse treatment and glucocorticoid. Follow-up after discharge showed that all patients' conditions continued to improve without recurrence or relapse. Conclusion The diagnosis of MPE can be established based on positive serological MP-IgM and the clinical manifestations and imaging features of encephalitis after other common pathogens were excluded. Levofloxacin combined with glucocorticoid and gamma globulin can achieve obvious efficacy and improve the prognosis of MPE.

Background：Though screening techniques for neonatal major congenital heart disease (mCHD) are becoming increasingly mature, their widespread acceptance and application still need to be built on economic factors. Currently, there are few studies related to the health economics of mCHD screening, and most of the data are from developed countries. Objective：To investigate the effectiveness and economics of mCHD screening. Design：Systematic review. Methods：The search strategy was established according to the rule of PIROS  participant for neonatal, index for pulse oximetry (POX), reference for echocardiography and surgery, outcome for neonatal mCHD, and study design for cost analysis, costeffectiveness analysis, costutility analysis, and costbenefit analysis. Web of Science, The Cochrane Library, MedLine, Embase, SinoMed, CNKI, and Wanfang Databases were searched from 2000 to April 28, 2022. By reading the title, abstract, and full text, relevant information was extracted including health economics indicators evaluation method, research perspective, cost collection range, sensitivity analysis type, discount rate, and health economics evaluation results such as the cost of saving one Life year (LYS), the cost of gaining a quality adjusted life year (QALY), the cost of avoiding a disability adjusted life year (DALY), the cost of an additional case diagnosed on time, and the incremental costeffectiveness/utility ratio(ICER). The quality of literature was evaluated by the Quality of Health Economic Studies (QHES) instrument. Main outcome measures:The cost and costeffectiveness of screening. Results：Eleven articles were included from 2007 to 2020, of which 7 were able to extract the data of POX screening, 4 were able to extract the data of clinical evaluation (CE) , and POX+CE screening, and 1 was able to extract the data of POX+MUR screening. There were 2 about social science, 9 about medical system, 4 about population, 7 about models, 1 with both direct cost and indirect cost, and 10 with only direct cost. Based on the exchange rate of USD in June 2022, the cost of POX screening is 224.5 USD, in which the labor cost is 2.537.4 USD, the cost of onetime probe is 13.422 USD, and the cost of reusable probe is 0.10.9 USD. CE screening costs 0.504.50 USD. MUR screening costs 1.302.0 USD. Echocardiography (ECHO) costs 301300 USD for screening positive cases. CEA/CUA (costeffectiveness/utility analysis) was used in 8 articles, among which 2 articles evaluated POX screening, 5 for POX+CE screening, and 1 for POX+MUR. The cost of using a probe and echocardiography was the main cost of screening without considering labor costs. POX, POX+MUR, and POX+CE have cost effectiveness. POX+MUR has cost effectiveness compared with ECHO. When ECHO+CE can detect other congenital defects, it has cost effectiveness compared with POX+CE. Conclusion：The cost of mCHD screening is mainly reflected in whether to use a onetime probe and echocardiography. POX, POX+MUR, and POX+CE have cost effectiveness. Neonatal mCHD screening is economically acceptable at different economic development levels.

Background：The 2019 international consensus on central precocious puberty (CPP) proposed that random serum luteinizing hormone (LH) has important reference value for the confirmation or exclusion of CPP, but there is no corresponding diagnostic criteria in China. Objective：By verifying the diagnostic value of the cutoff value of serum LH basal value proposed in the international consensus in 2019 for CPP, it is expected to reduce unnecessary GnRH stimulation tests and provide guidance for clinical practice. Design：Diagnostic accuracy study. Methods：According to the Chinese Expert Consensus on the Diagnosis and Treatment of Central Precocious Puberty (2022 edition) (referred to as the Chinese consensus), the recommended value of LH (chemiluminescence method) (peak LH ≥5 IU·L-1and peak LH /FSH ≥0.6 combined with clinical) was used as the gold standard for the diagnosis of CPP. According to the two cutoff values (0.83 and 0.20 IU·L-1) recommended by the international consensus, girls aged 49 years who met the diagnostic criteria of precocity, did not have menarche, had breast development Tanner stage Ⅲ or below, and underwent GnRH stimulation test were enrolled. Peripheral precocity was excluded. The clinical data of age, height, weight, body mass index (BMI), Tanner stage, gonadal axis hormones and sex hormones, bone age (TW3), pituitary MR and uterine and ovarian ultrasound were collected. Main outcome measures：Sensitivity and specificity of different basic luteinizing hormone cutoff values for diagnosing CPP. Results：A total of 352 girls with precocious puberty were included in the analysis. Among them, 203 cases were diagnosed as CPP and 149 cases were diagnosed as PT according to the gold standard. The average age of precocious puberty was (7.3±1.0) years, and the average height was (130.6±10.3) cm. The CPP girls had significantly higher mean age, height and bone age, and baseline serum LH, FSH, LH/FSH, and E2 levels than the PT girls. The differences were statistically significant. The specificity of baseline serum LH value ≥0.83 IU·L-1 (100%, 95%CI:97%100%) was better than that of baseline serum LH value <0.20 IU·L-1(45%, 95%CI:37%53%) and from 0.20 to 0.82 IU·L-1 (56%, 95%CI:47%63%). The CPP girls with a baseline LH level of ≥0.83 IU·L-1 had significantly higher breast Tanner stage, bone age, and bone agechronological age difference than those with a baseline LH level of <0.83 IU·L-1 (P<0.05), and a significantly lower pituitary height than those with a baseline LH level of < 0.83 IU·L-1 (P<0.05). Conclusions：When chemiluminescence method is used to detect gonadal hormone in children with precocious puberty, CPP can be diagnosed with serum LH base value ≥ 0.83 IU·L-1, and GnRH excitation test is not required LH <0.20 IU·L-1 cannot be used as the exclusion criteria for CPP, and sexual GnRH excitation test should be selected to assist diagnosis based on clinical characteristics.

Objective: To systematically analyze the survival rate and trajectory of motor function in the natural history of SMA patients so as to provide benchmark data for the intervention of SMA. Methods: PubMed, Embase, Cochrane, CNKI, CBM and Wanfang database were searched by using the keywords of spinal muscular atrophy and natural history, from the inception to November 27th 2022. Results: A total of 17 case series reports (n=1905) and 2 sham controls of Nusinersen in RCTs (n=83) for SMA were included in the analysis. The survival rates at the age of 6 months (4 studies), 12 months (5 studies) and 18 months (4 studies) were 86%, 52% and 32%, respectively. The meta-analysis of event-free survival rates from natural history case series reports of type 1 SMA showed that it was 76%,34% and 16% at the age of 6 months (3 studies), 12 months (4 studies) and 18 months (3 studies) respectively. Conclusion: Natural history of SMA patients varied in different types, of which type 1 SMA showed lower survival and event-free survival rates, while type 2-3 SMA patients present with slower regression of motor function.

Background There are many reports on the systematic review of the screening protocols for neonatal congenital heart disease, and the appropriate screening timing and locations for screening are also worthy of attention. Objective To evaluate the diagnostic accuracy and false positive rate of neonatal major congenital heart disease (mCHD) screening at different screening timing and locations. Design Meta-analysis of diagnostic accuracy studies. Methods The literature search and selection have been completed in the development of neonatal CHD screening (NCHDS) guideline. The positive infants in screening were diagnosed as mCHD by cardiac ultrasound (gold standard), or infants with symptoms and signs were confirmed as mCHD in the follow-up by cardiac ultrasound, surgery, or cardiac catheterization (gold standard). The risk of bias and clinical applicability of the included literature were evaluated with the QUADAS-2 scale. The data were extracted and the diagnostic accuracy parameters such as sensitivity, specificity and false positive rate were summarized with the random effect model. Main outcome measures Accuracy of neonatal mCHD screening at different timing and locations. Results Among the 16 studies on the screening timing, 9 were in the postnatal period of ≤ 24 h, 7 were in the period of -48 h, 3 were in the period of -72 h and 3 were in the period of 6-72 h. The sensitivity of neonatal mCHD screening at different timing were 0.788(95%CI:0.600-0.921), 0.579(95%CI:0.378-0.757), 0.586(95%CI:0.369-0.775)and 0.897(95%CI: 0.836-0.937), respectively. And the specificity were 0.985（95%CI: 0.946-0.996, 0.998(95%CI:0.994-0.999), 0.996(95%CI:0.987-0.999)and 0.994(95%CI: 0.983-0.998), respectively. The false positive rates were 0.015 (95%CI: 0.004-0.057), 0.002(95%CI: 0.001-0.006), 0.004(95%CI：0.001-0.016)and 0.006(95%CI：0.002-0.019), respectively. The AUC of neonatal mCHD screening at ≤ 24 h, -48 h, -72h and 6-72 h after birth was 0.916, 0.973, 0.939 and 0.973, respectively. Among the 20 literatures on screening locations, there were 15 in maternity hospitals, 2 in NICU, 2 in out of hospital settings, and 1 in maternity hospitals + NICU. The sensitivity of neonatal mCHD screening was 0.701(95%CI: 0.576-0.802), 0.797(95%CI: 0.675-0.881), 0.571(95%CI: 0.230-0.856) and 0.821(95%CI: 0.555-0.944), respectively. The specificity was 0.995 (95%CI: 0.990-0.998), 0.885 (95%CI: 0.778-0.944), 0.993 (95%CI: 0.988-0.996) and 0.916 (95%CI: 0.189-0.998), respectively. The false positive rates of the neonatal mCHD screening in maternity hospital and NICU were 0.006 (95%CI: 0.003-0.011) and 0.030 (95%CI: 0.001-0.636) respectively, and the AUC were 0.960 and 0.757 respectively. The sensitivity and specificity were 0.817 and 0.996 in the subgroup within 24 h after birth, and 0.680 and 0.996 in the subgroup >24 h after birth. Conclusion When pursuing high sensitivity of screening and accepting high false positive rate, screening within 24 hours after birth can be selected. For low false-positive rate, screening after 24 hours after birth can be selected. Neonatal mCHD screening should be implemented in the maternity hospital for its good accuracy and low false-positive rate.

Background: Childhood lymphoma with SH2D1A gene mutation is rare in clinical practice and has special clinical features and prognosis. Objective:To summarize the clinical manifestations, pathological features, treatment and prognosis of childhood lymphoma with SH2D1A gene mutation. Design:Case series report. Methods:Consecutive hospitalized patients who were newly diagnosed with lymphoma under the age of 18 and had SH2D1A gene mutation indicated by highthroughput whole exon gene sequence were enrolled from Beijing Children's Hospital affiliated to Capital Medical University between June 2017 and July 2022. The treatment plan was determined according to the pathological diagnosis. Invasive mature Bcell lymphoma was treated based on the modified LMB89 regimen. Mature Tcell lymphoma complicated with hemophagocytic syndrome(HLH) was first controlled by the HLH regimen, and chemotherapy was given after the diagnosis by the SMILE regimen. The efficacy was evaluated in the middle period after 2 to 3 months of chemotherapy. Ultrasound and PET/CT were performed at 3 months after chemotherapy. Tumor ultrasound, liver function, LDH and immune function were tested every 3 months within 1 and 2 years after chemotherapy. Main outcome measures:Clinical characteristics and prognosis of children lymphoma with SH2D1A gene mutation. Results:A total of six male patients of childhood lymphoma with SH2D1A gene mutation were summarized. The median age of onset was 5(412) years. The tumor lesions involved the gastrointestinal tract in 3 cases, central nervous system, head and neck, and multiple organs in 1 case each. In terms of clinical stages, there was 1 case of stage Ⅱ, 3 cases of stage Ⅲ, and 2 cases of stage Ⅳ. For pathological types, 3 cases were for diffuse large Bcell lymphoma, 1 case for highgrade mature Bcell lymphoma, 1 case for Burkittlike lymphoma with 11q abnormality, and 1 case for systemic EpsteinBarr virus positive Tcell lymphoma in children. Humoral immunity and/or cellular immunity decreased in 5 cases. Whole blood and plasma EBVDNA were negative in 5 cases at the beginning of the disease, and whole blood EBVDNA increased to ≥105 copy number /mL during the course of the disease in 2 of them. One patient had familial HLH at the beginning of the disease, with multiple whole blood EBVDNA of 106 copies/mL. Six cases showed SH2D1A gene mutation, among which 2 cases showed no abnormal SAP protein detection; 1 case had chromosomal abnormality; 3 cases completed chemotherapy; 2 cases died due to hemophagocytic syndrome, and 1 case received rituximab immunotherapy. Conclusion:Lymphoma in children with SH2D1A gene mutation is rare in clinical practice. The main pathological manifestation is nonHodgkin lymphoma (mature Bcell lymphoma), and the prognosis is poor. Allogeneic hematopoietic stem cell transplantation may improve the prognosis of the disease when there is a need.

Background：The prevalence of hyperuricemia (HUA) is increasing, which is not only related to gout, urate nephropathy and kidney stones, but also related to the occurrence and development of endocrine metabolism, cardiovascular and cerebrovascular diseases. Objective：To assess the association of maternal hyperuricemia with adverse pregnancy outcomes and neonatal disease. Design：Retrospective nested casecontrol study. Methods：Data were retrospectively collected from People's Hospital of Peking University between January 1st 2020 and December 31st 2020. According to the maternal uric acid value in the third trimester of pregnancy, the newborns were divided into the group of HUA and normal uric acid. The pregnancy outcomes and clinical outcomes of neonates in two groups were compared. According to the maternal uric acid value in the third trimester of pregnancy(μmol·L-1), pregnant women were divided into the group of low concentration (<360), medium concentration (~420) and high concentration (>420). Linear regression and logistic regression models were used to analyze the relationship between maternal uric acid value and preterm, low birth weight and smallforgestationalage infants. Spearman rank correlation analysis was used to analyze the correlation between maternal uric acid value in the third trimester of pregnancy and neonatal uric acid value at 24 hours after birth. Main outcome measures：The relationship between maternal uric acid value and preterm and low birth weight and smallforgestationalage infants. Results：A total of 2 397 pregnant women (2 581 newborns) were enrolled, of which 216 cases (9%) were in the HUA group. The birth weight of newborns in the HUA group was lower than that of the nonHUA group (2 925 g vs 3 260 g, P<0.001). The proportions of preterm birth (18.5% vs 8.9%), low birth weight (23.1% vs 7.1%), small for gestational age (29.2% vs 10.6%), and transfer to pediatrics (19.9% vs 11.1%) were higher in the HUA group (P<0.001). The birth weight of newborns in the high concentration group was lower than those in the low concentration group (-54g，95%CI: -106.48-1.63, P=0.043). The risk of newborns with preterm and smallforgestationalage infants delivery increased by 74% (OR=1.74，95%CI:1.082.8, P=0.023) and 85% (OR=1.85，95%CI：1.262.73，P=0.002), respectively. The uric acid value of the newborn at 24 hours after birth was moderately correlated with the uric acid value of the pregnant mother in the third trimester of pregnancy (r=0.613, P=0.000). There was no significant difference in neonatal complications between the two groups. Conclusion：Maternal hyperuricemia in the third trimester of pregnancy is associated with the occurrence of perterm, low birth weight and smallforgestationalage infants.

Background：The quantitative analysis focused on virus shedding duration of immunocompromised (IC) children infected with SARSCoV2 during the Omicron wave is rare. Objective：To investigate the differences in virus shedding duration between IC and nonIC patients infected with Omicron and to provide firstline information for public health policy making and precise epidemic prevention strategy. Design：Retrospective cohort study. Methods：The study population was Omicron infected inhospital pediatric patients. According to their immune condition, these patients were divided into IC and nonIC groups. The immunocompromised state was divided into complete immunocompromised condition, relative immunocompromised condition, and immunosuppressive therapy. The nonIC group was matched with gender, age, type of SARSCoV2 infection, and 1:3 ratio in the IC group. The SARSCoV2 genome PCR test detected nasal swab samples. Cycle threshold (Ct) value ≥35 was the endpoint. Main outcome measures：SARSCoV2 virus shedding time. Results：From April 12 to May 12, 2022, we enrolled 728 patients hospitalized in Renji Hospital, School of Medicine, Shanghai Jiao Tong University, the dedicated hospital in Shanghai. Among them, 33 patients were in the IC group, including 8 cases in complete immunocompromised state and 23 cases in a relative immunocompromised state. Two patients without complete or relative immunocompromised state received immunosuppressive therapy. Ninetynine patients were included in the nonIC group. No significant differences were detected in clinical phenotypes, treatment, and vaccination between the two groups. The virus shedding time between IC and nonIC groups had a significant difference (16.5±6.8 vs. 10.3±4.4 days). The virus shedding duration of mild type was (14.0±8.3) and (9.7±3.1) days, (18.3±4.9) and (11.2±5.9) days in moderate type. Significant differences were detected. The virus shedding duration of the two groups had significant differences during the 9th14th days (P=0.0050.039). The virus shedding duration of moderate type in two groups had significant differences during the 10th15th days. Three patients (9%) in the IC group had positive PCR test results again after two weeks. The disease type of these three patients were milder than the previous infection. All three patients were unvaccinated. Conclusion：Virus shedding duration of IC patients was significantly longer than that of nonIC patients in Omicron wave. The prolonged virus shedding duration in IC patients was mainly in the 9th14th days. The IC patients had a higher risk of recurrent positive PCR results, which indicated longer isolation time and a strict nucleic acid test strategy after negative PCR test results.

Background：Over the past 20 years, rituximab (RTX) has shown better efficacy than other immunosuppressants in the treatment of children with steroid-sensitive nephrotic syndrome (SSNS), but reports of adverse events still need to be accumulated. Objective：To understand the adverse events of rituximab for children with SSNS. Design：Systematic review and meta-analysis. Methods：PubMed, Embase, Cochrane, Scopus and Chinese Biology Medicine databases were searched from the inception to June 26, 2022, with the keywords of SSNS and RTX. The preliminary screening, full text screening and data extraction were all completed by the same two reviewers. Unsure or controversial literature was submitted to a third reviewer. At least one RTX intervention for children aged between 1 and 22 years with SSNS was included. Main outcome measures：The incidences of adverse events. Results：A total of 47 studies (5 in Chinese and 42 in English) were included in the analysis, including 7 doublearm intervention studies (5 randomized controlled trials, 2 nonrandomized study) and 40 case series reports. Comparing RTX with placebo or conventional immunosuppressants (control group) in SSNS children, there were no statistically significant differences in the incidences of adverse events (7 studies, 130/184 vs 107/177), serious adverse events (4 studies, 14/140 vs 9/122), infusion reaction (1 study, 19/24 vs 13/24) and infection (2 studies, 33/56 vs 23/38). In case series reports of SSNS children treated with RTX, the incidences of adverse events, serious adverse events, infusion reaction, infection and serum sickness were 59 percent (95%CI: 55 percent to 63percent), 7 percent (95%CI: 6 percent to 9 percent),31 percent (95%CI: 28 percent to 35 percent), 21 percent (95%CI: 18 percent to 24 percent) and 5 percent (95%CI: 2 percent to 10 percent), respectively. Studies reporting both neutropenia and agranulocytosis revealed the incidence of neutropenia was 9 percent (95%CI: 5 percent to 17 percent) and the incidence of agranulocytosis was 4 percent (95%CI: 2 percent to 10 percent). Studies focusing on hypogammaglobulinemia revealed the incidence of hypogammaglobulinemia was 51 percent (95%CI: 42 percent to 60 percent). Conclusions：RTX treatment of SSNS did not increase the incidences of adverse events, serious adverse events and infection, but hypogammaglobulinemia and serum sickness should be of concern.

Background：The use of dezocine, a new opioid agonistantagonist, for postoperative analgesia in children is poorly reported, and there is no accepted reference dose for its use in children. Objective：To investigate the efficacy and safety of dezocine in postoperative analgesia in children, and to provide a suitable reference dose for analgesia in postoperative children. Design：Singlecenter randomized controlled study. Methods：With the preoperative classification of ⅢⅣ by the American Society of Anesthesiologists (ASA), patients directly transferred to PICU after congenital heart disease (CHD) were enrolled from Children's Hospital of Chongqing Medical University at the age of >28 d at the time of surgery. A random number table was used and the grouping results were sealed in an envelope. The PICU physician on duty was responsible for the subject assignment, and the bedside nurse performed the intervention. All patients were randomized into 5 groups. Subjects in the experimental group were continuously injected with lowdose (group D1), mediumdose (group D2), or highdose (group D3) dezocine after the operation, and those in the control group were injected with sufentanil (group SF) or morphine (group M). The postoperative pain and sedation scores were observed. The outcome observers and data analysts were not blinded. Invasive ventilatorassisted ventilation, symptomatic management, and midazolam sedation were performed after admission to the PICU in both five groups. D1, D2, and D3 groups received dezocine 20, 30, 40 μg·kg-1·h-1 respectively, SF group received sufentanil 0.08 μg·kg-1·h-1, and M group received morphine 20 μg·kg-1·h-1. All intravenous injection was administrated through a syringe pump. Face Pain Scale (FPS) and Child Revised Impact of Events Scale (CRIES) were used to evaluate pain, and Ramsay and ComfortB were used to score sedation. All scales were completed by PICU specialist nurses. Main outcome measures：The percentage of satisfaction with analgesia/sedation at 1 h, 4 h, 8 h, 12 h, and 24 h after the operation. Results：A total of 152 children with congenital heart disease were enrolled, 30, 30, 31, 31, and 30 in groups D1, D2, D3, SF, and M, respectively, all of whom completed the designed intervention and observation. There were no significant differences in age, weight, sex, extracorporeal circulation time, pediatric critical illness score (PCIS) and preoperative ASA grading among the 5 groups. Compared with group M, the FPS scores were higher in the D2 group at 24h and the D3 group at 4 h and 24 h; the CRIES scores were higher in the D1 and D2 groups at 1 h and 4 h and in the D3 group at 4 h and 24 h ; the Ramsay scores were higher in the D2 and D3 groups at 1 h and 4 h; the ComfortB scores were higher in the D1 group at 4 h and 12 h, in the D2 group at 1h and 4 h and in the D3 group at 1 h, 4 h, and 12 h. All the differences were statistically significant. There was no statistically significant difference in analgesia/sedation satisfaction between the D group(D1, D2, D3) and the SF group in terms of the four scales. The differences in vital signs and related indexes were not statistically significant among the 5 groups at each postoperative time point. The proportion of additional sedative/analgesic drugs was lower in groups D1 and D2 than in groups M and SF, and the differences were statistically significant. Two cases of hypotension and one case of respiratory depression were observed in group M. Conclusions：The analgesic effect of dezocine in postoperative children with congenital heart disease is better than that of morphine and comparable to that of sufentanil. Dezocine has fewer adverse reactions.

Background：Fetal lung development is later than other organs, and the maturity of lung development is closely related to pregnancy outcome. Objective：To investigate the relationship between the ratio of systolic acceleration time/ejection time (AT/ET) of fullterm fetal main pulmonary artery ultrasound and neonatal lung maturity and its predictive value. Design：Casecontrol study. Methods：Pregnant women who underwent ultrasound examination of fetal main pulmonary arteries in Xinxiang Central Hospital of Henan Province from October 2019 to October 2020 were taken as the research objects. According to fetal amniotic fluid or tracheal aspiration liquid lamellar bodies (LB)≥50×109·L-1 after delivery, they were divided into mature and immature groups. The clinical data and AT/ET ratio of fetal main pulmonary artery were compared between the two groups. Multivariate logistic regression analysis was used to analyze the factors affecting neonatal lung maturity. Spearman correlation analysis to explore the correlation between AT/ET ratio and neonatal lung maturity. ROC curve was drawn to analyze the predictive value of AT/ET ratio on neonatal lung maturity. Main outcome measures：The relationship between AT/ET ratio of fetal main pulmonary artery and neonatal lung maturity. Results：Ultrasound images of 102 pregnant women and their pulmonary aorta and LB data of newborns were analyzed in this paper, aged from 23 to 36 (29.4±1.0) years, with 37+138+6 (38.3±0.1) weeks of ultrasonic examination of main pulmonary artery. There were 76 cases in mature lung group and 26 cases in immature lung group. There were significant differences in nutritional status, fetal respiratory motor score, PSV and AT/ET in the middle of fetal main pulmonary artery between the two groups (P<0.05). Multivariate logistic regression analysis showed that AT/ET in the middle segment of fetal main pulmonary artery was an independent factor affecting neonatal lung maturity (OR=0.881, 95%CI:0.6780.983). Spearman correlation analysis showed that AT/ET ratio in the middle of fetal main pulmonary artery was positively correlated with neonatal lung maturity (r=0.678, P=0.003). ROC curve showed that the best cutoff value of AT/ET in the middle of fetal main pulmonary artery for predicting neonatal lung maturity was 0.22. At this time, the sensitivity was 92.1% (95%CI：84.1%97.4%), the specificity was 84.6% (95%CI:70.9%93.4%), and the AUC was 0.818 (95%CI:71.5%92.7%). The kappa value of lung maturity predicted by AT/ET ratio was 0.812 (P<0.05). Conclusion：AT/ET in the main pulmonary artery of fullterm fetus is closely related to the lung maturity of newborns, and has certain predictive value for the lung maturity of newborns.

Background: The high prevalence of hearing loss in China is associated with a high carrier rate of pathogenic variants in genes for hearing loss. At present, there is a lack of screening data on carriers of pathogenic genes for hearing loss among newborns in neonatal intensive care units (NICU). Objective: To investigate the carrier rate of GJB2 and SLC26A4, pathogenic genes for hearing loss, in NICU newborns. Design: Cross-sectional survey. Methods: Newborns were enrolled in the NICU at Children's Hospital of Fudan University from January 2016 to December 2021, with admission days≤28 d and high-throughput sequencing completed before discharge. Those with positive hearing-loss-associated genetic findings after birth were excluded. The sex, gestational age and birth weight were collected from electronic medical records. The number of cases identified with pathogenic variants in GJB2 and SLC26A4 and the standard terminology of the human phenotype of the children were extracted from the sequencing database. Carrier rate(%)=the number of heterozygous pathogenic or likely pathogenic (P/LP) variants/total number of study subjects. PubMed, Embase, and Wanfang databases were searched. Literature that previously reported the carrier status of the GJB2 gene and/or SLC26A4 gene P/LP mutations in NICU patients, newborns and pregnant women in China were included and reviewed. Main outcome measures: Carrier rate of P/LP variants in the GJB2 gene and SLC26A4 gene. Results: A total of 14 924 neonates were included, including 8 587 males (57.5%) and 6 337 females, with a gestational age of (35.6±3.7) weeks and a birth weight of (2 711.7±887.1) g. A total of 18 heterozygous P/LP mutations were detected in 2 009 children (13.462%) carrying P/LP mutations of the GJB2 gene, among which c.109G>A was the most common (10.902%), followed by c.235del (1.749 %), c.299_300del (0.409%), c.176_191del (0.154%), c.508_511dup (0.074%) and c.257C>G. There were 305 children (2.044%) carrying P/LP mutations of the SLC26A4 gene. A total of 31 heterozygous P/LP mutations were detected, and the six highest carrier rates were for c.919-2A>G (1.139%), c. .2168A>G (0.181%), c.1226G>A (0.100%), c.1229C>T (0.094%), c.1174A>T (0.080%) and c.1003T>C, respectively. Conclusions: It is suggested that c.109G>A, c.508_511dup and c.257C>G on the GJB2 gene and c.1003T>C on the SLC26A4 gene should be included in the carrier screening for pathogenic genes for hearing loss among newborns in NICU.

Background：Based on consensusbased standards for the selection of health measurement instruments（COSMIN）, we evaluated the psychometric properties of the evaluation tools for topics in different domains of the clinical practice guideline for children and adolescents with cerebral palsy (CANDLE) and established the inclusion and exclusion criteria of evaluation tools in CANDLE. Objective：To systematically evaluate Gross Motor Function Measure88 and 66 (GMFM88 and GMFM66) based on COSMIN methods, clarify the evidence level of each psychometric property, provide evidence for its clinical practice, and explore the value of COSMIN methods in assessing field observation evaluation tools. Design：A systematic review. Methods：MEDLINE, Embase and SinoMed databases were searched for relevant research literature on GMFM88 and GMFM66 measurement properties. The updated COSMIN Risk of Bias checklist was used to evaluate the methodological quality of all measurement properties, and updated criteria for good measurement properties were used to score each measurement property study. The GRADE method of COSMIN revision was adopted to assess the evidence quality. Main outcome measures：The content validity of GMFM88 and GMFM66. Results：GMFM88 had better evidence for content validity than GMFM66, and both of them have highquality reliability research. GMFM88 had more evidence to support its internal consistency and measurement errors than GMFM66, but it lacked structural validity research. GMFM88/66 had highquality evidence in concurrent validity and concurrent responsiveness, and low or very lowquality evidence in discrimination validity and discrimination responsiveness. GMFM66 showed better criterion responsiveness than GMFM88. Conclusion：GMFM88/66 has highquality evidence in reliability, internal consistency, and construct validity. COSMIN methods could be useful for the assessment of field observation evaluation tools.