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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：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：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 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：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.

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 few clinical studies on newborn screening for Duchenne Muscular Dystrophy（DMD） with creatine kinase（CK） or creatine kinase isoenzymeMM（CKMM）, and the diagnostic accuracy is not clear. Objective：To systematically evaluate the accuracy of creatine kinase or creatine kinaseMM in newborn screening for DMD. Design：Systematic review and metaanalysis． Methods：Literature was searched in databases of Embase, Cochrane Library, Web of Science, Scopus, China National Knowledge Infrastructure (CNKI), China Biomedical Literature Database (CBM), Wanfang database and Chinese Journal Fulltext Database (VIP) from Jan 1, 1975 to Oct 5, 2022, and in database of Medline（PubMed） from Jan 1, 1975 to Nov 5, 2022，in order to collect the studies related to neonatal screening of DMD using CK or CKMM. The QUADAS2 scale was used to evaluate the risk of bias and clinical applicability of the included literature. Data were extracted and then metaanalysis was performed using Stata15 and MetaDisc1.4 software. The sensitivity, specificity, positive likelihood ratio（PLR）, negative likelihood ratio（NLR）and diagnostic odds ratio (DOR) were pooled. Summary receiver operating characteristic curve (SROC) was made and the area under the curve (AUC) and Q index was calculated. Main outcome measures：Sensitivity and specificity. Results：Eleven studies were included in newborn screening for DMD using CK with a total of 1 351 953 neonatal samples. Metaanalysis showed that pooled sensitivity, specificity,PLR,NLR and DOR were 97%(95%CI:88%99%),100%(95%CI:100%100%),1 131(95%CI:3703 455),0.01(95%CI:0.000.19),16 476(95%CI:4 11565 963), respectively. The AUC and Q index were 0.995 4 and 0.974 0, respectively. Deeks test（P=0.12）indicating a small possibility of publication bias. Five studies were included in newborn screening for DMD using CKMM with a total of 156 547 neonatal samples.Metaanalysis showed pooled sensitivity, specificity, PLR,NLR and DOR were 100%（95%CI:100%100%）、100%（95%CI:100%100%），3 925（95%CI: 3 9253 925），0.00（95%CI:0.000.00）and 23 094(95%CI:5 77392 384).The AUC and Q index were 0.925 2 and 0.859 4, respectively. Conclusion：The application of serum CK or CKMM in screening neonatal DMD has high accuracy, which is helpful for early diagnosis of DMD.

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：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: 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：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：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.

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

Background This is a preliminary multi-center survey for the study on the impact of a pediatric infusion management program on the outcome of infusion therapy under a self-controlled pre-and post-experiment design. The management program is based on Clinical Practice Guideline on Infusion Therapy in Children. Objective To investigate the current situation of pediatric nurses′ knowledge, attitude and behavior related to infusion extravasation. Design Questionnaire survey. Methods Based on the theory of knowledge, attitude and behavior, an initial questionnaire with 23 items in 3 sections of knowledge, attitude and behavior was drawn up. After the item analysis, there were 6, 4 and 6 items kept for knowledge, attitude and behavior respectively. The content validity of the items in the attitude and behavior sections was 0.82 to 1.00, and the content validity of the questionnaire level was 0.92. KMO test coefficient of structural validity was 0.807 in attitude and behavior. The result of Bartlett test was P＜0.01 and all items are loaded on with only one main factor ＞ 0.5. The Cronbach's α coefficients of attitude and behavior sections are 0.752 and 0.818 respectively. The nurses participating in clinical work for over 40 weeks in the past year and performing infusion independently or under guidance were recruited from the pediatric wards of 9 hospitals with close academic exchanges with the Nursing Department of Children's Hospital of Fudan University to complete an electronic questionnaire through the platform of Wenjuanxing. Main outcome measures Scores of knowledge, attitude, and behavior. Results Among 3,395 sent questionnaires, 2,568 were returned, and 2,210 were valid. Among 2,210 respondents, 21.8%, 15.9%, 34.9%, 11.1% and 29.8% was respectively from the children's hospital affiliated to the university, the pediatric ward of university-affiliated general hospital, the provincial children's hospital, the municipal children's hospital and the municipal maternal and child health hospital. In terms of working experience, those who have worked for ≤5 years, 5 to 10 years, 10 to 15 years and >15 years accounted for 25.6%, 35.3%, 25.6% and 13.5% respectively. For professional titles, 66.1%, 31.6% and 2.4% of them was junior, intermediate and senior titles respectively. Charge nurses, specialists and teaching nurses, and head nurses accounted for 81.0%, 14.7% and 43% respectively. Among the respondents, 2.8% did not participate in infusion training, 41.0% only participated in a training organized by departments, 45.7% participated in both department-level and institute-level training at the same time, and 9.4% participated in the infusion training by departments, institutes and higher-level organizations at the same time. In total, 22.6% of the subjects only had used peripheral intravenous catheters; 14.9% had used both peripheral intravenous catheters and midline catheters at the same time; and 62.4% had used both peripheral venous access devices and central venous access devices at the same time. There was 82.9% only with experience in inserting peripheral intravenous catheters, 11.1% in inserting both peripheral intravenous catheters and midline catheters and 5.9% in inserting both peripheral venous access devices and central venous access devices. The total score of knowledge section was (12.98±6.95) with good, medium and poor grade accounting for 8.6%, 5.5% and 75.9% respectively. The total scores of attitude and behavior were (17.23±2.58) and （23.45±4.14) respectively. There was significant difference in the correlation test between knowledge section and attitude (r=0.066) and behavior section (r=0.100) (P=0.002). Multivariate linear regression analysis showed that hospital type, number of training levels and types of venous access devices used by nurses were the influencing factors of knowledge and behavior scores. The number of training levels is the influencing factor of attitude score of the three factors. Conclusion The knowledge, attitude and behavior of pediatric nurses about infusion extravasation did not show the trend of unity and order.

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.

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

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

Background Speech sound disorder（SSD）is a common cause of communication disorders in childhood with a high prevalence. For those untreated children the symptoms can persist into adulthood and affect the social communication eventually. Objective To analyze the clinical features of consonant errors in children with SSD. Design Case series report. Methods This study recruited the children who came to the department of Children's Healthcare in Chengdu Women's and Children's Central Hospital from January 1, 2020 to December 31, 2020 due to unclear pronunciation, who met the SSD diagnosis and whose language development was over 4 years old, and excluded other diseases that affected language function. Phonetic assessment was conducted by picture naming method. Consonants were classified and analyzed according to the pronunciation position and method. The formula for correct rate of consonants (PCC) was number of correct consonants /(number of correct consonants+number of wrong consonants) ×100%. 85%~100% were mild, 65%~85% were mild to moderate, 50%~65% were moderate to severe, and less than 50% were severe. Demographic characteristics such as age, gender and voice assessment results of SSD children were collected from the medical records. Main outcome measures PCC and consonant error types. Results A total of 222 SSD children were recruited in this study, including 67 females and 155 males. There were 111 children aged 4 to 5 years (50.0%), 66 aged 5 to 6 years (29.7%) and 45 aged 6 to 15 years (20.3%). The average PCC of male and female students was 43.3%±20.9% and 44.9%±18.9%, respectively, with no significant difference (P＞0.05). There was a linear relationship between age and the severity of SSD (P＜0.001), and the proportion of severe consonant errors decreased with age. In each age group, the average number of substitution errors was higher than that of ellipsis and distortion, and the average number of substitution errors decreased with the age, showing a low degree of correlation (P＜0.05, r=0.217). The average number of errors in pronunciation positions in a descending order was blade-palatal, blade-alveolar, supradental, velar, alveo-palatal, bilabial, and labiodental. The average number of labiodental, supradental, blade-alveolar and blade-palatal errors decreased with age. The average number of errors in pronunciation style in a descending order was affricate, fricative, plosive, nasal, and lateral. The average number of errors in affricate, fricative, and lateral in the 4-5 age group was higher than that in the other two age groups. Conclusion SSD in children was mainly moderate to severe and severe in all age groups, and children's speech intelligibility tended to improve with age. The types of errors in all age groups were mainly substitution. The types of errors in pronunciation parts and pronunciation methods were not significantly different between the groups of 5 to 6 and 6 to 15 years old, which should be paid attention to.

Background：Severe coronary artery lesions (CAL) caused by Kawasaki disease (KD) can lead to coronary events or death in children and has an important impact on long-term prognosis and quality of life. Objective：To summarize and analyze the medium-term and long-term clinical outcomes of KD children with severe CAL and provide the basis for long-term follow-up management and prognosis evaluation of KD children. Design：Cohort study. Methods：The HIS system of Children's Hospital of Fudan University was searched to include children < 18 years of age who were discharged from the hospital from January 2008 to December 2019 with a diagnosis of KD and were diagnosed with severe CAL due to KD by coronary angiography (CAG) in our hospital. Patients with other diseases causing severe CAL and affecting the prognosis of severe CAL were excluded. All children were followed up by senior cardiovascular specialists in the outpatient clinic and ward, and were given medical treatment. Children with severe coronary artery stenosis and myocardial ischemia were treated surgically after multidisciplinary discussion. Children with myocardial ischemia, myocardial infarction or death during diagnosis and follow-up were taken as the poor prognosis group, and the opposite was the good prognosis group. The poor prognosis and the evolution of CAL were observed, and the influencing factors of poor prognosis were analyzed. Main outcome measures：Poor prognosis and improvement of CAL. Results：A total of 144 children with severe CAL due to KD were included in this analysis. Among them, 117(81.2%) were males and 27 were females with a median KD onset age of 2.2(1.0, 4.5) years, a median follow-up time of 1.6(0, 3.4) years, and a disease duration of 5.0(3.0, 21.3) months at the diagnosis of severe CAL. A total of 276 coronary arteries were involved in 144 children with KD and severe CAL. Single coronary arteries and ≥2 coronary arteries were involved in 56 cases(38.9%) and 88 cases(61.1%) respectively. There were 122 cases of giant coronary artery aneurysm(GCAA), 8 cases of multiple small and medium-sized coronary artery aneurysms(CAA) in the single coronary artery, 6 cases of GCAA with multiple small and medium-sized CAA in the single coronary artery, and 8 cases of stenosis in all affected coronary arteries. Sixty-two cases developed coronary artery stenosis, including 31 cases of coronary artery occlusion. Fifty-four of 144 children(37.5%) developed poor prognosis, and myocardial ischemia was present in all 54 cases, 14 of which had developed recorded acute myocardial infarction at the ischemic myocardium, and one child died of severe heart failure due to myocardial infarction. The results of multivariate analysis showed that the risk of poor prognosis was 2.6 times higher in children with ≥2 coronary artery involvement than in those with only 1 coronary artery involvement(OR=2.602, 95% CI: 1.201 to 5.634), and 3 times higher in children with coronary artery stenosis than in those without coronary artery stenosis(OR=3.055, 95% CI: 1.450 to 6.437). Among 179 CAG, 114 patients(208 affected coronary arteries) underwent one CAG, and 30 patients(68 affected coronary arteries) underwent≥2 CAG. When 68 affected coronary arteries were first diagnosed, 51 of them were GCAA and the improvement rate was 4.0% at the last follow-up; 3 of them were multiple small and medium-sized CAAs and the improvement rate was 66.6% at the last follow-up; 2 were single small and medium-sized CAAs and developed stenosis(stenosis degree about 50%) until the last follow-up; and 12 were stenosis and did not improve until the last follow-up. Conclusions：GCAA is the main type of KD with severe CAL, and it is difficult to recover. The improvement rate of multiple small and medium-sized CAAs in the single coronary artery is high. Coronary artery stenosis and multivessel coronary artery involvement are factors leading to the poor prognosis of children with severe CAL caused by KD.

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.