Objective：We have upgraded the data analysis pipeline (Fudan pipeline 1.0) to Fudan pipeline 2.0 for high throughput sequencing which established in 2015. The purpose of this study is to compare the turn around time and accuracy of these two pipelines. Methods：In this study, 112 continuous samples from neonatal intensive care unit were recruited. Both Fudan pipeline 1.0 and 2.0 were used for the data analysis. We compared the results of preliminary analysis, time-consuming, and the accuracy between these two pipelines. And the main features of the Fudan pipeline 2.0 are explained in detail. Results：On the comparison of preliminary data analysis results, the variations to manual analysis step of Fudan pipeline 2.0 (an average of 25 variants) was significantly less than that of Fudan pipeline 1.0 (an average of 210 variants). On the comparison of efficiency, the turn around time of Fudan pipeline 2.0 (19.8h) was significantly shorter than that of Fudan pipeline 1.0 (78.8h). The diagnosis coincidence rate of Fudan pipeline 2.0 is 63.6% (7/11) for positive cases, and 84.2% (85/101) for negative cases with manual review. Conclusion：This study clearly shows the efficient, accurate and automated of Fudan pipeline 2.0 for genetic diagnosis with large sample size.

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.

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

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Objective The purpose of this cross-sectional study was to examine the prevalence of behavior problems and associated protective and risk factors among children aged 3 to 6 years in Huangpu district of Guangzhou. Methods A community-based sample of 1 170 children was assessed with the Strengths and Difficulties Questionnaire(SDQ), Behavioral Style Questionnaire(BSQ), Family Environment Scale(FES) and a self-administered questionnaire including demographic characteristicts and children′s pre-,peri- and postnatal condition. Results Totally 11.4%(134/1 170) children were rated as abnormal without significant gender differences. The most prevalent behavior problem was peer problem(23.2%), followed by hyperactivity(16.6%),conduct(11.8%),emotion(8.4%) and prosocial(8.4%). Multiple linear regression models explained 50% of the total variance of SDQ total difficulties score for children.Paternal educational,cohesion and intellectual-cultural orientation of family environment were significant protective factors against behaviour problems. Joint family,child′s medical history(congenital diseases,brain injury),temperamental low persistence, low adaptability, negative emotionality,low rhythmicity,high intensity and high activity were associated with higher SDQ total difficulties score (P<0.05). Conclusions This study is consistent with previously reported risk factors for child behavior problems, and supports the need for a focus on early intervention and prevention strategies in the child mental health field.

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

objective: To investigate the clinical and genetic features of Kabuki syndrome caused by KMT2D mutation and summarize the clinical features in neonate. Methods: Using Whole-Exome Sequencing (WES) and Clinical panel deep sequencing，combined with data analysis pipeline established by molecular diagnostic center of Children's Hospital of Fudan University, the clinical and molecular features of 6 children with KMT2D mutations were summarized. Databases including PubMed，CNKI，WanFang Database and VIP were searched to collect literature of KS, which describe the clinical features of neonatal period from April 2012 to April 2017. Results: Four males and two females were diagnosed as KS. Three cases were diagnosed by WES due to KS related manifestations were present and the families came to order trio-WES. One case was diagnosed by clinical neonatal panel screening. Another two cases were diagnosed by WES. Seven heterozygous mutations were detected in six patients with KS，mutations were located in exon 11, exon 39, exon 51 and exon 53 respectively. The types of mutations were one stop gained, four missenses and two frameshifts. Mutation of c.12697C>T（p.Q4233X）、c.16498C>T（p.R5500W）、c.16273G>A（p.E5425K）were reported as pathogenic mutations and had recorded in Human Gene Mutation Database (HGMD). Mutation of c.12696G>T(p.Q4232H), c.3495delC (p.Pro1165LeufsTer47), c.10881delT （p.Leu3627Argfs Ter31）and c.12560G>A（p.G418E）were novel, which predicted as harmful variants by SIFT, polyphen 2 and MutationTaster software. In a total of 18 literatures，together with the 2 cases in this study, there were 34 neonates were included. The most common clinical features were as follows: feeding problem was in 19cases, cardiac dysplasia in 20 cases, special appearance in 17 cases, skeletal dysplasia in 15 cases, hypoglycemia in 10 cases and hypotonia in 9 cases. Conclusion: The typical clinical features of KS are not shown in the neonatal period. This disease should be considered when the newborn has feeding problem, abnormal cardiac morphololy, special appearance and other clinical features. Genetic test can help to diagnose earlier in clinical. Early diagnosis can provide accurate information to clinic, may help patients to acquire appropriate treatment and family genetic counseling.

Objective To investigate the physical growth level and its difference of infants with different feeding patterns. Methods Data on breastfeeding, complementary feeding and physical growth in infants aged 1-<12 months were collected through the fifth physical development survey of children under 7 years old in nine cities of China in 2015. Feeding patterns for infants aged 1-<6 months were classified into exclusive breastfeeding, partial breastfeeding and formula feeding, and for infants aged 6-<12 months into continued breastfeeding and formula feeding. Weight, length and head circumferences were assessed among different feeding groups using analysis of variance or t test. Results A total of 59,170 infants aged 1-<12 months were included in this study. For infants aged 1-<6 months, exclusive breastfeeding, partial breastfeeding and formula feeding accounted for 48.6%, 37.4% and 14.0% respectively and for infants aged 6-<12 months, continued breastfeeding and formula feeding accounted for 59.9% and 40.1% respectively. At the age of 1-<6 months, exclusively breastfed infants were a little heavier than partially breastfed infants with the difference from 0.06 to 0.20 kg, and also a little heavier than formula-fed infants with the difference from 0.09 to 0.22 kg. At the age of 6-<12 months, continuously breastfed infants were a little shorter than formula-fed infants with the difference from -0.3 to -0.1 cm. Weight at 6-<12 months, length at 1-<6 months, and head circumferences at 1-<12 months were almost not of statistical significance among different feeding groups. The growth of weight, length and head circumferences for infants with different feeding patterns generally conformed to child growth standards required by World Heath Organization, but the average growth levels of weight and length were slightly higher. Conclusion Infants with different feeding Methods presented similar growth patterns in infancy. The growth performance of exclusively breastfed infants was slightly higher than that of partially breastfed and formula-fed infants in the first half of the first year, but the growth performance of continuously breastfed infants was slightly lower than that of formula-fed infants in the second half.

Background：There are few reported cases of hereditary pancreatitis (HP) in children in China. Objective：To summarize the clinical characteristics and genetic variations of HP in children. Design：Case series report. Methods：Acute pancreatitis (AP), chronic pancreatitis (CP), acute recurrent pancreatitis (ARP), and HP were diagnosed based on the relevant criteria established by the International Study Group of Pediatric Pancreatitis. Medical records were included for patients whose primary diagnosis was HP in the inpatient medical records of Beijing Children's Hospital, Capital Medical University, from June 2017 to September 2023. The following information was extracted from medical records and follow-up records: sex, age at onset, age at diagnosis, family history, clinical manifestations, serological findings, imaging findings, complications, medical treatment, endoscopic retrograde cholangiopancreatography (ERCP) treatment, short-term and long-term follow-up outcomes, and genetic mutation information. Main outcome measures：Clinical characteristics and genetic features. Results：A total of 48 patients with HP meeting the inclusion criteria were analyzed. Among them, 30(62.5%) were male, with a mean age of onset at (8.0±3.8) years and a mean age at diagnosis of (8.7±3.7) years. The onset age was between 0 and 7 years in 45.8% of cases. AP was the initial presentation in 33 patients (68.8%), while 46 patients (95.8%) experienced varying degrees of abdominal pain. Malnutrition was observed in 23 cases (47.9%). Imaging findings revealed pancreatic calcifications in 21 patients, pancreatic swelling in 15, pancreatic duct dilatation in 14, pancreatic divisum in 12, pancreatic duct stones in 8, and pancreatic pseudocysts in 5 cases (10.4%). A total of 17 patients underwent 18 ERCP procedures, with one initial treatment failure that was successfully treated upon reattempt. Postoperatively, 10 patients (58.8%) experienced recurrence within three months, and 14 patients (82.4%) had recurrence within one year of follow-up. All 48 HP patients underwent genetic testing. Mutations were identified in SPINK1 (33 cases, 68.8%), CFTR (7 cases, 14.6%), and PRSS1 (4 cases, 8.3%). The mutations were inherited from the mother in 23 cases (47.9%), from the father in 17 cases (35.4%), from both parents in 7 cases (14.6%), and were de novo in 1 case (2.1%). Protein structure prediction indicated that 36 cases (75%) had pathogenic or likely pathogenic variants, while 12 cases (25%) had variants of uncertain significance. Conclusion：In Chinese children with hereditary pancreatitis (HP), SPINK1 gene mutations account for a high proportion of cases and are associated with pancreatic calcifications and chronic pancreatitis. ERCP treatment plays a protective role in reducing long-term recurrence rates.

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Background：Previous Studies have focused on the associations between individual factors within the cerebral palsy (CP) population. However, there is limited research that systematically describes or constructs comprehensive networks for interaction analysis. Objective：To develop an innovative methodological framework with novel indicators, cut-off values, and decision pathways and to provide support for exploring the interactions between health-related factors in CP. Design：Mixed-Methods： study. Methods：A systematic literature search was conducted to identify relevant studies on associations or interactions between muscle tone and health-related factors in CP (Step 1). Characteristic data reflecting the effects or interactions of muscle tone were extracted from the selected studies (Step 2). Statistical analysis Methods： used to evaluate the relationships were identified and summarized (Step 3). A definition of muscle tone was established, and other health-related information associated with muscle tone was categorized according to various guideline dimensions (Step 4). Based on this information and multidisciplinary perspectives, indicators for evaluating relationships and their threshold values were proposed (Step 5). A logical framework for summarizing and identifying relationships was developed (Step 6), followed by internal data testing, adjustments, and refinements (Step 7). Main outcome measures：Methodology for identifying relationships between muscle tone and health-related factors in children and adolescents with CP. Results：The study extracted 2 327 rows of data from 106 articles. Of these, a total of 78 articles using correlations analysis included 1 668 data points, 44 using regression analysis included 450 data points, and 13 using other statistical Methods： included 209 data points. Following the established indicators and framework, we first selected data points within the same guideline dimensions. For each dimension, we classified each article into one of three outcomes (related, uncertain, or unrelated), and subsequently derived final judgments by summarizing the outcomes of each article. After summarizing, if the proportion of uncertain articles in a dimension is ≥1/3, the relationship between muscle tone and that guideline dimension is considered uncertain. Otherwise, we classified related and unrelated articles into four distributions (n∶n, 1∶n or n∶1 or 1∶1, 0∶n or n∶0, and 0∶1 or 1∶0) and derived judgments based on two additional indicators. The appropriate sample size is calculated if need. In practice, we applied the framework to the internal data and proposed that the muscle tone may interact with four dimensions (gross motor skills, muscle strength and endurance, secondary musculoskeletal disorder, and quality of life), but not with physical activity. The relationship between muscle tone and the dimensions of gait, participation, activities of daily living, and upper limb function remains unclear. Conclusion：This study introduced an original methodological approach for determining the relationships between muscle tone and other health-related factors in children with CP. A set of judgment indicators and threshold values were proposed, and a logical framework for identifying the relationships was developed.

Background: Sitting height and leg length are the useful indicators for the linear growth evaluation of children and adolescents, but the growth reference standards of the two indicators have not been reported. Objective: To study and formulate the growth reference of sitting height and leg length of Chinese children and adolescents aged 0-18 years. Design: A cross-sectional survey. Methods: Stature and sitting height of 92,494 healthy urban children aged 0-18 years were measured in two national surveys in 2005 in China—The National Survey on the Physical Growth and Development of Children in the Nine Cities of China (NSPGDC) and The Chinese National Survey on Students' Constitution and Health (CNSSCH). Leg length was calculated by height minus sitting height. Growth reference standards of sitting height and leg length were constructed using the LMS method. Main outcome measures: Reference values of sitting height and leg length. Results: The percentile and the Z-scores reference values of sitting height and leg length for Chinese boys and girls aged 0-18 years were shown and their growth charts were drawn. Sitting height increased about 14 cm, 6 cm and 4 cm during the first, second and third year after birth, respectively. After that, the annual increment of sitting height is nearly 2-3 cm. Then the increments became slightly higher at 11-13 years for boys and 9-11 years for girls and gradually became smaller and smaller. Sitting height nearly stopped increasing at the age of 17 years for boys and 15 years for girls. Leg length increased respectively about 11-12 cm and 6.5 cm during the first and second year after birth, then the annual increment was 4-5 cm during 2-5 years, and leg length stopped increasing nearly at 15 years for boys and 13 years for girls. Conclusion: The growth reference standards of sitting height and leg length were formulated, which provide more data and reference for perfecting the growth evaluation system of children and adolescents in China.

Background：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：Children with Philadelphia chromosome positive acute lymphoblastic leukemia (Ph+ALL) have a poor prognosis after relapse, and treatment is challenging. Olverembatinib has shown good efficacy in adult patients with relapsed Ph+ALL, but its efficacy and safety in children are not well defined. Objective：To evaluate the efficacy and safety of olverembatinib in children with Ph+ALL. Design： Case series report. Methods：A retrospective analysis was conducted on children with Ph+ALL admitted to the department of pediatrics of Peking University People's Hospital from January 2022 to July 2024, who were treated with olverembatinib. The effects, side effects, and outcomes of the treatment were analyzed. Main outcome measures：Complete remission (CR), minimal residual disease (MRD) negativity, major molecular response (MMR), and complete molecular response (CMR). Results：A total of eight pediatric patients with relapsed Ph+ALL were included in the analysis, comprising six males and two females, with a median age of 9 years. Among them, three had hematologic relapse, while five had molecular relapse before receiving olverembatinib. All patients achieved CR after one treatment cycle of olverembatinib, either as monotherapy or in combination with chemotherapy. Among the three patients with hematologic relapse, the MRD negativity rate was 100%, and the MMR rate was 66%. Among the five patients with molecular relapse, the MRD negativity rate, MMR rate, and CMR rate were all 100%.The median follow-up duration was 13 months, during which all eight patients maintained CR. The MRD negativity and MMR rates remained 100%, while the CMR rate was 75%. All patients survived throughout the follow up period. Notably, one patient experienced a relapse of central nervous system leukemia (CNSL) but achieved sustained cerebrospinal fluid MRD negativity after receiving olverembatinib monotherapy combined with a single intrathecal chemotherapy injection.The adverse effects observed during treatment were mainly attributed to the combined use of chemotherapy drugs. Olverembatinib monotherapy did not cause significant discomfort in most patients; however, one patient discontinued olverembatinib due to drug-related adverse reactions. Conclusion：For the children with relapse of Ph+ALL, olverembatinib monotherapy or in combination with chemotherapy shows good efficacy and safety.

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.

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Background：Over 100 cases of Arboleda-Tham syndrome caused by KAT6A gene mutations have been reported internationally. Objective： To summarize the clinical and genetic features of Arboleda-Tham syndrome caused by KAT6A gene mutations. Design：Case series report. Methods：Children with KAT6A gene pathogenic or possibly pathogenic mutation, detected by high-throughput sequencing in the Molecular Medicine Center of the Children's Hospital of Fudan University from April 2018 to April 2024 were enrolled. Clinical information and genetic testResults： were collected. Additionally, we conducted a literature search in PubMed, CNKI, and Wanfang databases using the keywords "KAT6A" and "Arboleda-Tham Syndrome" to identify case reports with clinical and genetic mutation data published from January 2015 to June 2024. Main outcome measures：Genotype and phenotype characteristics of pediatric patients with pathogenic KAT6A gene mutations. Results：his study included 13 cases, comprising 10 males and 3 females. Except for one neonate, all other 12 patients exhibited neurodevelopmental disorders, with all patients older than one year showing delayed language development. The age at genetic testing ranged from 5 days to 7 years and 8 months. Heterozygous pathogenic mutations in the KAT6A gene were identified in all 13 patients, including six frameshift mutations, four nonsense mutations, two missense mutations, and one copy number deletion. Among these, 11 mutations were novel, with G1549S and R1019* having been previously reported. An analysis combining the 13 cases from this study with previously reported 101 cases with complete clinical and genetic data revealed that 113 patients(100%) presented with developmental delay/intellectual disability and speech delay, 64.6% (73/113) exhibited abnormal muscle tone, 12.4%(14/113) experienced epilepsy, and 6.2%(8/113) had hematological abnormalities. Truncating mutations, including nonsense and frameshift mutations, were the most prevalent mutation type, accounting for 86%(98/114) of cases, with R1129*(12 cases) and R1024*(9 cases) identified as hotspot pathogenic variants. Genotype-phenotype correlation analysis of the 114 cases indicated that epilepsy was more common in the missense mutation group(3/13, 23.1%) compared to the truncating mutation group(11/98, 11.3%), while hematological abnormalities were observed exclusively in the truncating mutation group. Conclusion：Mutations in the KAT6A gene leading to Arboleda-Tham syndrome in affected children primarily manifest as developmental delay, abnormal muscle tone, epilepsy, and hematological abnormalities. The predominant type of genetic variation is truncating mutations.

ObjectiveTo analyze the risk factors for 28-day mortality in immunocompromised pediatric patients admitted to PICU for sepsis. MethodsWe conducted a case-control study, and retrospectively collected the clinical data of patients who were admitted to the PICU of Children's Hospital of Fudan University for sepsis. Patients were divided into immunocompetent group and immunocompromised group based on immune status and 28-day mortality was the primary outcome. ResultsFrom December 1st, 2015 to December 31st, 2018, 385 consecutive cases were diagnosed as sepsis at discharge, of which 251 fitted the eligibility criteria, and others were excluded due to ICU-acquired sepsis or being discharged within 24 h. We identified the immunocompetent group (n=141) and immunocompromised group (n=110). The 28-day mortality was 69.1% in immunocompromised patients. Compared with the immunocompetent patients, they showed a larger portion of in-patients, less age disparity and higher PRISM Ⅲ score, and they were more dependent on life support therapies (vasoactive agents, ventilation) and less likely to localize infection sites, the RRT treatment survive rate was 17.4% and none of the 5 ECMO receivers survived. Univariate analysis of 28-day mortality within two groups identified several common factors including septic shock, invasive-ventilation, CRRT, PRISM Ⅲ score, PICU length of stay, hospital stay,PICU-free time, therapy limitation within 24 h and overall therapy limitation, with "other comorbidities" unique to the immunocompetent patients and "vasoactive agents" unique to immunocompromised patients. Multivariate Cox regression revealed that PRISM Ⅲ score, invasive-ventilation and serum lactate above 2 mmol·L-1 were shared risk factors in both groups, and septic shock was also a predictor in the immunocompromised group. Conclusion28-day mortality in pediatric patients admitted to PICU for sepsis remained high, with the immunocompromised status more likely to succumb to death. PRISM Ⅲ score, invasive ventilation and serum lactate above 2 mmol·L-1 were strong predictors for short-term mortality, hence early recognition and effective management might improve patients clinical outcome.

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Background Baby body plethysmography is the gold standard for testing the functional residual volume and airway resistance, making it important for the evaluation of infant respiratory physiology. Objective To explore the influence of improving the operation skills of pulmonary function test (PFT) in plethysmography on the success rate of PFT. Design Quality improvement study. Methods PFTs were performed using the Jaeger MasterScreen BabyBody device (Erich Jaeger GmbH, v4.65, Würzburg, Germany) to examine tidal breathing flow volume loop (TBFVL) and plethysmographic functional residual capacity (FRCP). Before the improvement, the protocol of PFT were in accordance with the recommendations published by the American Thoracic Society (ATS) and the European Respiratory Society (ERS). On the basis of the previous protocol, improvement was described as increasing the dosage of sedatives (oral chloral hydrate) , touching or massaging the baby for 5 minutes before the test, and placing a slope pillow with 15 degree supine position. Continuous cases of PFT in pulmonary function room from January 2017 to January 2019 were included, and children with severe pneumonia caused by acute lower respiratory tract infection (ALRI) were excluded. The date of January 1, 2018 was set as the timing to differentiate before and after improvement. They were divided into neonatal pneumonia group and ALRI group. ALRI group was divided into the wheeze and non-wheezing subgroups. Main outcome measures The success rate of TBFVL and FRCP, and the failure rate of sedation. Results Totally 120 cases of neonatal pneumonia and 477 cases of ALRI were included. There were 31 cases failing to fall asleep after sedation, 3 cases with neonatal pneumonia and 28 cases with ALRI for both 14 cases in the wheezing and non-wheezing subgroups. Among 23 cases in the early awakening group who did not finish the PFT, there were 6 cases with neonatal pneumonia and 17 cases with ALRI for 5 cases in the wheezing and 12 cases in the non-wheezing subgroup. Although the success rate of TBFVL and FRCP had been improved with decreased rate of sedation failure in the neonatal pneumonia group, there was no significant difference compared with that before the improvement on PFT protocol. The success rate of TBFVL and FRCP had been improved with decreased rate of sedation failure in the non- wheezing and the wheezing subgroups after improvement on PFT protocol with statistical significance. Conclusion Improving the quality of PFT protocol of Baby body plethysmography can significantly increase the success rate of FRCP and TBFVL and reduce the failure rate of sedation.