Objective：To re-determine items difficulty order of the Fudan Chinese version gross motor function measure(GMFM), and to compare the responsiveness and precision with the GMFM-66, in order to improve the items difficulty order of the GMFM to suit children with cerebral palsy in all age groups better. Methods：The data used for the analysis in this study were from children and adolescents with cerebral palsy undergoing rehabilitation therapy and education in rehabilitation center of Children's hospital of Fudan University and other 21 cooperative units in Shanghai Children's Rehabilitation Cooperative Group from 2001 to 2017. Each one of the cases had at least one time GMFM assessment and was diagnosed as cerebral palsy after 18 months. GMFM assessment was performed by a designated therapist or physician in a quiet, independent, well-lit room using Fudan Chinese version GMFM-88.The GMFM-66 score was derived from GMAE (version 1.0). Each GMFM-88 item was converted into three sub-items, and the GMFM-88 was converted into GMFM-264 containing 264 test items, with a score point (0, 1) for each. The rating scale model in Rashi analysis was used to analyze the GMFM-264 test results and 264 items, and generate the improved Fudan Chinese GMFM scale items difficulty order.Stratified random sampling method was used to determine the subjects included in the analysis of responsiveness and precision, and the difference in the scores of GMFM-264 and GMFM-66 were used to compare the responsiveness and precision of two score methods by comparing each assessment results of the below 3-year-old group and the above 6-year-old group. Results：A total of 3 498 GMFM assessment results of 1 198 children with cerebral palsy were included in the analysis. Among them, 801 were males. The average age was (4.5±3.8) years old when they had their first assessment. Rasch analysis showed that the unsuitable items of the total items was 2.3% in GMFM-264 tiny items, indicating that most of the items in this scale have good unidimensionality and form improved Fudan Chinese version items difficulty order containing 264 tiny items. In the <3 year old group, the responsiveness and precision of GMFM-264 was significantly higher than that of GMFM-66. Conclusion：The improved Fudan Chinese GMFM items difficulty order expands the target pool for the development of gross motor intervention in children with cerebral palsy combined with standardized assessment, and improves the responsiveness and precision of GMFM in children with cerebral palsy, especially infants with cerebral palsy. The result+ provide a basic model and data for the further promotion of intelligent function assessment and intervention systems for children with cerebral palsy.
Objective：To assess the efficacy and safety of antenatal glucocorticoids for reducing neonatal respiratory distress syndrome after full-term(more than 37 weeks) elective caesarean section. Methods：Databases including PubMed,Embase, The Cochrane Library, ClinicalTrials.gov,CBM,WanFang Data,CNKI and VIP were searched to collect randomized controlled trials (RCTs) about prenatal glucocorticoids for preventing neonatal respiratory distress syndrome(RDS) after full-term elective cesarean section.Before delivery, experimental groups were treated with glucocorticoids(the type, dose, route of administration and course of treatment of drugs were not limited), and control groups were given a placebo or a blank control. We used the combination of subject headings and text words to search,all databases were searched from inception to April 19, 2018. The primary outcomes were the incidence of neonatal RDS and neonatal mortality, the second outcomes were the incidence of transient tachypnea of newborn(TTN),neonatal respiratory distress, admitted to NICU with respiratory distress, neonatal sepsis, maternal infection and adverse reactions.The RCT bias risk assessment tool recommended by the Cochrane Handbook was used to evaluate the bias risk of the included literatures. Then meta-analysis was conducted by RevMan 5.3 software. Results：A total of 4 RCTs papers, involving 3 893 singleton neonates were included. The overall quality of the 4 literatures was moderate. Meta-analysis showed that the incidence of RDS between the experimental group and control group was statistically significant difference (OR=0.45, 95%CI: 0.24-0.83), no significant difference between the two groups were shown on neonatal mortality. There were significant differences in the incidence of TTN (OR=0.41, 95%CI: 0.29-0.59), admitted to NICU with respiratory distress (OR=0.42, 95%CI: 0.29-0.63), neonatal respiratory distress (OR=0.34,95%CI:0.22-0.53). One article reported the incidence of neonatal sepsis and maternal infection between the two groups, and there was no significant differences. Mothers of the treatment groups had a low adverse reaction rate. Conclusion：Based on current clinical evidence,a course of antenatal glucocorticoids could be given to decrease the risk of neonatal RDS after term singleton elective cesarean section.
Objective：To explore the long-term efficacy of specific subcutaneous immunotherapy (SCIT) with standardized house dust mite on children with asthma and allergic rhinitis. Methods：This paper was a case series report for long-term follow-up of intervention effects. Children with house dust mite allergic asthma and allergic rhinitis received SCIT (T0) to a course of 30 or more months of treatment (T1)，at T0, T1, T2 (3 years after T1) and T3 (6 years after T1), either in asthma specialist out-patient or by telephone follow-up. Many indexes were assessed, including asthma symptom scores (ASS), rhinitis symptom score (RSS), total symptom score (TSS), total medication score (TMS), symptom medication score (SMS). Visual analogue scale (VAS) and improvement self-evaluation were also used. ASS, RSS, TSS and TMS were evaluated for nearly 4 weeks. VAS and the condition improved self-evaluation for the children or their parents were used to assess the timing of their own feelings for nearly 1 month. Results：From April 2006 to June 2011, 56 cases ( 41 male cases, average age 7.1 (5~12) years old) were diagnosed as dust mite allergic asthma and allergic rhinitis children in the Asthma specialist outpatient department, and received SCIT treatment ≥ 30 months, meanwhile ASS, RSS, TSS and VAS at T0 were collected retrospectively, and TSS and SMS were calculated. There were 51 cases (38 male cases) at T2 and 45 cases (33 male cases) at T3. All evaluation indexes at T1 were significantly different compared with those at T0. There were significant differences in the 2 composite indexes (TSS and SMS), which reflected the assessment of the illness between any two adjacent time points. In the improvement self-evaluation, the differences of allergic rhinitis and asthma at T1 (18.5% vs 75%), T2 (31.2% vs 84%), T3 (39.5% vs 80%) were statistically significant. In the condition of improving the self-assessment scale，the condition to evaluate allergic rhinitis is obviously worse than asthma. At T3 point, the RSS, TSS, SMS of girls are significantly lower than those of boys and the difference is statistically significant (P<0.05). Conclusion：For children with dust mite allergic asthma and allergic rhinitis, SCIT can improve the asthma and rhinitis symptom markedly, decrease medication and VAS score. The long-term effect can maintain for 6 years after the cessation of treatment. The RSS, TSS and SMS of female children were more effective than those of male children.
Objective：To evaluate the effect and side effect of the antiviral regimens consisting of ganciclovir and/or valganciclovir on congenital cytomegalovirus (CMV) infected neonates. Methods：Retrospective analyze the data of neonates with congenital CMV infection hospitalized in the Newborn Department of the Children's Hospital of Fudan University from March 2012 to May 2017. The clinical characteristics, liver function, CMV DNA, brain MRI, fundus examination and treatment results of 3 groups were evaluated and compared. Results：Twenty-eight neonates were diagnosed as congenital CMV infection. Of whom, nine were asymptomatic or with mild symptoms and had not been treated with antiviral therapy; the remaining nineteen cases were congenital CMV infection with moderate or severe symptoms; among them, eleven cases were treated with ganciclovir and/or valganciclovir ≤6 weeks; and eight cases were treated with ganciclovir and/or valganciclovir for 6 months.① When followed up to 6 months old, except 1 patient had moderate elevated bile acid, all the other 27 had recovered symptoms and signs except the central nervous system, liver function and blood routine examination. ② In neonates with asymptomatic congenital CMV infection or with mild symptoms, a left hearing loss case emerged at 6 month. In ≤6 weeks antiviral group, 2 CMV-related fundus lesions healed in 1 month old; 3/5 patients still had abnormal brain MRI image and 2/5 patients had hearing loss when 6 months old. In 6 months treated group, all 4 fundus lesionsrelated to congenital CMV infection healed at the end of 6 months follow up, while 2/3 case still had abnormal brain MRI image and 1/7 with hearing loss.③ No statistical difference was observed in central nervous system symptom between 6 weeks group and 6 months group.④ No ganciclovir and/or valganciclovir related granulocytopenia and liver dysfunction occurred during follow-up. Conclusion：Treatments with ganciclovir and/or valganciclovir for ≤6 weeks or 6 months could improve senorineural hearing loss and chorioretinitis; while no significant difference regarding improvement of these lesions were observed between ≤6 weeks and 6-months treated groups at 6 month old. It is suggested that, neonates with asymptomatic congenital CMV infection should be screened by ophthalmoscopic examination, auditory brainstem response and MRI, early active antiviral therapy is recommended for neonate with emerging symptom.
Objective：The relationship between heterogeneous executive function (EF) and parenting stress among school boys with attention deficit hyperactivity disorder(ADHD) was explored. Methods：In this case-control study, boys with ADHD were chosen as case group (subgroup of Children with EF deficits and subgroup of Children with intact EF), boys with normal development were chosen as control group. We used the STROOP color-word test, Wisconsin Card Sorting Task (WCST), Cambridge Neuropsychological Test Automatic Battery (CANTAB), Wechsler Intelligence Scale for Children-Fourth Edition (WISC-Ⅳ) to evaluate the executive function, and used Swanson Nolan and Pelham, Version Ⅳ(SNAP-Ⅳ) inattention and hyperactivity/impulsivity subscales to assess the ADHD symptom, SNAP-Ⅳ oppositional defiant subscale and Parent Symptom Questionnaire (PSQ) for the comorbidity, and Parenting Stress Index (PSI) for parenting stress. Results：Data from 104 drug-naive boys diagnosed with ADHD (mean age 9.95) and 47 boys showing normal development (mean age 10.79) were collected. Their age was statistically different. The differences in SNAP-Ⅳ scores, PSQ scores were all statistically significant. The EF differences between ADHD intact EF subgroup and EF deficit subgroup were all statistically significant, but there were no significant difference between intact EF subgroup and control group. Compared to control group, the PSI total scores and all the factor scores of ADHD group and both of the subgroups were significantly higher, but there were no difference between ADHD intact EF subgroup and EF deficit subgroup except for distractibility/hyperactivity factor. Conclusion：Overall, increased stress was found in ADHD boys' parents regardless of the EF subgroup. Having intact EF didn't improve the stress of parenting.
Objective：To investigate the RUNX1-RUNX1T1 transcript (fusion transcript) dynamics in pediatric acute myeloid leukemia (AML) and their correlation with patients' clinico-biological characteristics and long-term outcomes. Methods：In a retrospective cohort, all patients with RUNX1-RUNX1T1-positive AML at Beijing Children's Hospital (our hospital), from October 1st, 2006 to March 31st, 2015 were enrolled. Patients were divided into high-expression or low-expression groups according to ＞104 copies, ＞103 copies, ＞102 copies, ＞10 copies, ＞1 copy and ＞0 copy per 104 copies GUS at diagnosis (time point 0, TP0) and following MRD detective time points, after Induction Ⅰ(TP1), Induction Ⅱ (TP2), and after ConsolidationⅠ (TP3), Consolidation Ⅱ (TP4) and Consolidation Ⅲ (TP5), respectively. The follow-up deadline was December 31st, 2017. Chi-square were used to test the differences of clinical and biological characteristics between the subgroups, Kaplan-Meier method was used to analyse patients' overall survival (OS) and relapse free survival (RFS), and Log-rank test for comparing the difference. Cox's proportional hazards regression model was used to analyze the independent significance for OS and RFS. Results：52 patients were enrolled and 27 of them were male, the median age was 8(2~14). Two patients were lost to follow up at TP1. 21 patients died during the follow-up, the median follow-up time of other 29 patients were 62.2(34~134.3) months. ①There were no significant differences in age, gender, WBC, Hb, PLT count, blasts account in the bone marrow, immunophenotype except CD15(P=0.004) and MRD of TP1~TP5 between the high-expression patients(17/50) and low-expression patients(33/50). ②Univariate analysis showed that RUNX1-RUNX1T1 transcript at TP1 and TP5 were corelated with 5 year OS and RFS, the gender and PLT count at TP0 were corelated with 5 year OS and WBC count at TP0 were corelated with 5 year RFS. Multivariate analysis showed that the RUNX1-RUNX1T1 transcript level ＞103 copies per 104 GUS at TP1 was the independent risk factor for poor OS of RUNX1-RUNX1T1+ pediatric AML patients, P=0.036, hazard ratio (HR) was 0.095 and the 95% confidence interval(CI) was (0.011, 0.860). Conclusion：The fusion transcript level after the first induction therapy was the independent factor affecting long outcome in RUNX1-RUNX1T1+ pediatric AML.
Objective：To investigate the clinical outcome of haploidentical hematopoietic stem cell transplantation without in vitro T-cell depletion for children with acute leukemia. Methods：In Beijing Children's Hospital, Capital Medical University, from June 8, 2007 to May 4, 2015, 23 children with acute leukemia had been treated with haploidentical related hematopoietic stem cell transplantation without in vitro T-cell depletion, and 21 children with acute leukemia had been treated with matched sibling donor hematopoietic stem cell transplantation. Both groups used myeloablative preconditioning regime, and G-CSF mobilized hematopoietic stem cell. Graft versus host disease (GVHD) prophylaxis consisted of cyclosporine A, methotrexate with or without mycophenolate mofetil. To prevent hepatic vein occlusion disease (VOD), prostaglandin E combined with or without low molecular weight heparin was used. Results：All patients attained hematopoietic stem cell transplantation successfully. The median time of leukocyte recovery for haploidentical group and matched sibling group were (13.1 ±2.3) days and (12.5 ± 1.4) days, respectively(P>0.05). The median time of platelet recovery for haploidentical group and matched sibling group were (19.4 ± 8.0) days and (22.8 ± 7.7) days, respectively (P>0.05). The median follow-up time was (49.6 ± 30.3) months and (32.5 ± 31.6) months after transplantation, the overall survival rates were 69.5% (16/23) vs71.4% (15/21), the difference was not statistically significant (P>0.05). Acute GVHD clinical grading (Ⅰ~Ⅳ) was 65.2% (15/23) in haploidentical group and 23.8% (5/21) in matched sibling group, and the difference was statistically significant (P<0.05). Conclusion：It can be achieved the same clinical effect of haploidentical related hematopoietic stem cell transplantation without in vitro T-cell depletion in the treatment of children with leukemia, compared with matched sibling hematopoietic stem cell transplantation. The safety and efficacies of haploidentical group were close to the matched sibling group.
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.
Objective：To investigate the diagnosis key points of the rare complications after ventricular septal defect repair surgery by echocardiography. Methods：The echocardiography features of 34 cases with the rare complications diagnosed at Beijing Anzhen hospital after ventricular septal defect repair surgery between January 2013 and April 2018 were retrospectively reviewed. Results：In 34 patients, 28 patients were diagnosed as left ventricular-right atrial communication, 3 patients was diagnosed as aortic valve perforation with regurgitation, 1 patient was diagnosed as left ventricular-right atrial communication and aortic valve perforation, 2 patients were diagnosed as aortic-left atrial tunnel. In 34 patients, 6 patients underwent correction surgery, 5 patients with left ventricular-right atrial communication were healed without surgery and 23 patients were still follow-up. The echocardiography characters of left ventricular-right atrial communication: (1) A small defect was showed between tricuspid septal leaflet and mitral anterior leaflet in four-chamber view of apex and subxiphorid. The defect located above tricuspid ring; (2) Color Doppler showed abnormal blood flow signal between left ventricle and right atrium; (3) Continuous-wave Doppler showed a high-velocity jet during systole. The echocardiography characters of aortic valve perforation: (1) A defect was showed on right coronary artery cusp or noncoronary artery cusp in the long axis view of left ventricle and artery short view; (2) Color Doppler showed aortic valve regurgitation originating from the defect. The echocardiography characters of aortic-left atrial tunnel: (1) Color Doppler showed abnormal blood flow signal between aorta and left atrium in the long axis view of left ventricle, artery short view and five-chamber view;(2) Continuous-wave Doppler showed a high-velocity jet during double phase. Conclusion：By scanning different views and closely combining the features of the blood flow frequency spectrum, the abnormal blood flow signal can be accurately diagnosed after ventricular septal defect repair surgery.
Objective：To analyze the clinical characteritics, diagnosis and treatment based on a lupus mesenteric vasculitis (LMV) case. Methods：Clinical data of the patient with LMV were analyzed at rheumatology and immunology department of the capital institute of pediatrics. Wanfang database, Chinese Journal Full-text Database （CJFD）and China wip database were searched by the keywords: "lupus enteritis，lupus mesenteric vasculitis，children from the time when those were built up to December 2017. Results：A nine-year-old girl with LMV was in hospital, who presented with abdominal pain, vomiting and diarrhea over 2 months. Her diarrhea was about dozens of times a day and, at each time, the amount of stools was about 10ml to 100ml. The results of abdominal examination were abdominal swelling, total abdominal tenderness, bowel tone lower, shifting voiceless (+). In addition, lab examinations showed, ANA1:320 (granular type), dsDNA, Sm antibody (-), anti-SSA, SSB and RO-52 (3 +), blood C3, C4 reduced, mass proteinuria. Abdominal ultrasonography showed enlarged of bilateral renal pelvis, renal calices and ureter. The wall of urinary bladder was also thickening. The symptoms disappeared after CTX pulse and the oral MP and hydroxychloroquine. At 2 months (rotavirus infection), 12 months (unclean food) and 14 months (no obvious cause) after the treatment, Some symptoms appeared that these were abdominal pain, diarrhea, green watery mucus and then vomiting and bile samples. Abdominal CT scan with contrast showed bowel wall thickening, dilatation of intestinal segments, enhanced "target sign", "comb sign", and dilated bilateral renal pelvis calyces and ureter. Based on those findings, she was diagnosed with LMV. After given large doses of MP and CTX pulse, her symptoms disappeared. But at the third time of recurrence, MP pules was not show obvious effect. So rituximab was administered two times. There were 6 SCI references were found and Chinese literatures could not been found. Currently, 10 children LMV and 12 cases LMV in hospital have been reported in the international community. Four cases had not detail of clinical data. A summary of 6 cases with detail information were summarized. Conclusion：LMV in children was rare and most of them were school-age girls. LMV might be the first manifestation of SLE, and also be in the stage of SLE completely relief. The typical clinical manifestations of the disease were acute abdominal pain, bile vomiting, and large amount of dark green water samples. Abdominal enhanced CT scan was key in making the correct diagnosis of LMV. The disease was easy to combine with the urinary tract abnormal, and the active treatment could be restored. So operation should be avoided as could as possible. The title of anti-SSA and SSB antibody was higher, which might be the predicting factor of the LMV. All the disease combined with lupus nephritis, including nephritic level of proteinuria. Timely diagnosis becomes very important for the adequate management of this rare entity. MP pulse was crucial and, if there was poor response, MP pulse should be prolonged. LMV was easy to relapse and rituximab might be one of a choice if there was therapy-resistant.
Objective：To report one case of ATP8B1 deficiency (intrahepatic cholestasis in infants) combined with Pitt-Hopkins syndrome caused by heterozygous deletion at 18q21. Methods：To summarize the clinical characteristics of the infant and the results of chromosome microarray testing and genetic testing. Results：A three-month-old boy was admitted to the hospital because of jaundice more than two months. Physical examination revealed the infant with weight of 4 kg (< P3), mild-to-moderate jaundice of the skin and moderate jaundice of the sclera. Blood biochemical testing revealed the infant with increased total bilirubin and direct bilirubin, increased ALT, AST, TBA and AFP, and normal GGT and ALB, suggesting cholestasis with low GGT. Chromosome microarray testing revealed the infant had 11.6 Mb deletion in the long arm of chromosome 18 (18q21.2-q21.33) and 8p23.2 deletion in the short arm of chromosome 18 (8p23.2). The deletion region of chromosome 18 contained ATP8B1 and TCF4 genes, which were correlated with intrahepatic cholestasis and Pitt-Hopkins syndrome. Gene sequencing of ATP8B1 revealed 2 SNP, which were predicted for non-pathogenic mutations by the Mutationtaster software. The boy was administrated oral ursodeoxycholic acid and fat-soluble vitamins. When the boy was 1 year old, his jaundice was resolved and his liver function also returned to normal range. The boy was followed up to 2 years and 10 months and with height of 90 cm (P3~P10), weight of 12 kg (P3~P10), head circumference of 42.5 cm (< P3). At that time, the boy showed a special face including big mouth, thick lips, wide and high nose, protruding nasal tip, slightly forward jaw and obvious mental retardation and severe constipation. Conclusion：One children with intrahepatic cholestasis combined with Pitt-Hopkins syndrome is confirmed by chromosome microarray testing and gene sequencing, suggesting that molecular diagnosis should be paid attention to for unexplained cholestasis. Conventional gene exon sequencing may lead to the missed diagnosis of some cases with deletion of chromosome fragments. Therefore, chromosome microarray testing should be used in combination.
