ObjectiveTo deepen the understanding of the characteristics of very early onset inflammatory bowel disease (VEO-IBD) , an infant diagnosed as VEO-IBD due to IL-10RA mutation was reported. MethodsAn infant was dianosed as VEO-IBD based on her clinical manifestations and colonoscopy character. The whole exome sequencing (WES) was performed to confirm the gene deficiency, and the patient was treated by umbilical cord blood stem cell transplantation (UCBT).ResultsA 44-day-old, full-term, female infant remained healthy until developing diarrhea(up to 10 to 20 times per day) on postnatal day 8 with recurrent fever and severe malnutrition. The patient's older sister presented the similar manifestations (recurrent fever, diarrhea and thrush) at one month after birth and died of suspected urethral fistula at the age of 5 months. The patient displayed the perianal abscess which progressed to a fistula with the body weight going down to 2.6 kg 4 days after admission to Children's Hospital of Fudan University. Colonoscopy showed hyperplastic lesions in rectum, straight ulcerations and cobblestone-like appearance in sigmoid colon and descending colon. Thalidomide 6 mg, qd and mesalazine 150mg, qd were used to control intestinal inflammation with enteral and parenteral nutrition support. IL-10RA gene deficiency was confirmed by Sanger sequencing, and umbilical cord blood stem cell transplantation was performed. The stem cells were obtained from an unrelated sex-matched and 8/10 HLA allele-matched UCB. Chimerism was 95.7% 12 weeks after transplantation. IL-10RA gene deficiency and malfunction returning to normal were confirmed by Sanger sequencing and western blotting. The patient's formed stool appeared gradually with the body weigh increasing to 5.2 kg. Colonoscopy showed mucosal healing. At 10 months after transplantation, stool calprotectin was normal (72 μg·g-1).ConclusionThe umbilical cord blood stem cell transplantation is a promising treatment for VEO-IBD due to IL-10RA mutation. It is worth to gather more experiences.
ObjectiveTo explore the feasibility of the family-integrated-care (FICare) to preterm infants in the neonatal intensive care units (NICU) in China.MethodsThis was a parallel controlled clinical trial. Preterm infants who met the inclusion and exclusion criteria were cared either by FICare intervention (establishing FICare team, NICU ward rearrangement and renovation, mothers of infants were trained to do hand hygiene, skin care, oral cavity care, tube feeding, bathing for infants, kangaroo caring, weighing for infants, and breast feeding) or by the current routine no-parent way. The primary outcome was total hospital stay. The secondary outcomes were velocity of daily weight gain, day-of-life (DOL) of starting enteral feeds and full-feeding, rate of breast-feeding, rate of nosocomial infection, total period of oxygenation, medical expenses for hospitalization, re-admission rate with 30 days after discharge, Neonatal Behavior & Neurological Assessment (NBNA) score at corrected 37 weeks of gestation. Other outcomes were number of parent compliant, stressfulness grading of medical staff during working hours, and monthly number of NICU incident report, and extra expenses of the department for FICare.ResultsTo establish FICare team and to have NICU ward renovation for FICare caused extra billing to the department. Total hospital stay of FICare and control groups was (25.9±7.1) d and (29.2±6.0) d, respectively (P=0.035). There was no significant difference between two groups in DOL of starting enteral feeds and rate of nosocomial infection. Compared to control group, DOL of full-feeding of FICare group was faster, rate of breast-feeding was higher, velocity of daily weight gain was faster, total period of oxygenation was shorter, medical expenses for hospitalization was less, re-admission rate with 30 days after discharge was lower, and NBNA score at corrected 37 weeks of gestation was higher with significant difference. During the presence of FICare parents in the NICU ward, the stressfulness grading of nurses during working hours was reported to increase (6/6). But the number of volunteer nurses to join FICare increased by 7, and there was no medical complaint related to FICare. The number of NICU incident report decreased from 4 issues/month the same time in the previous year to 2.2 issues/month after FICare intervention.ConclusionIt is feasible to have FICare for preterm infants in the NICUs in China. It is safe to carry on the FICare study, but working stressfulness of medical staff and extra expenses of department will increase by implementing FICare.
Objective To describe the clinical manifestations and prognosis of children with anti-N-methyl-D-aspartate receptor encephalitis.Methods Clinical manifestations, lab examination, management and prognosis of children with anti-N-methyl-D-aspartate receptor encephalitis hospitalized in Neurology Department of Beijing Children′s Hospital from January 2012 to December 2014 were retrospectively analyzed and the effect at the last follow-up was assessed by Modified Rankin Scale (MRS).Results A total of 102 cases diagnosed as anti-N-methyl-D-aspartate receptor encephalitis with the average onset age of (7.5±4.0) years ranged from 6 months to 15.8 years were enrolled into the analysis including 38 males and 64 females. The average onset age of females was elder than that of males (P=0.009). Psychiatric disturbances was found in 40 cases and neurology disorder was found in 62 cases as the initial symptoms. The symptoms in acute stage included mental and behavior disorder (99/102，97.1%), dyskinesia (98/102，96.1%), speech disorder (91/102，89.2%), sleep disorder (79/102，77.5%) and central hypoventilation (7/102，6.9%), and there was no significant difference among different age groups. All cases received the first line therapy, 18(17.3%) cases received the second line therapy, 14 cases(15.9%) had sequelae (MRS≥3), 3 cases died and 4 cases relapsed. Conclusion Anti-N-methyl-D-aspartate receptor encephalitis happened in different age groups, clinical manifestations were similar to adult, most of cases had favourable prognosis, but young children and those secondary to virus encephalitis had poor prognosis.
Objective To systematically evaluate the diagnostic value of specimens via bronchoscopy for tuberculosis(TB) detection in children.Methods The PubMed，EMBASE, Ovid, Cochrane Library, CBM, CNKI and Wanfang database were systematically searched up to February 2016, and relevant references were manual screened. Two reviewers independently screened literatures according to the inclusion and exclusion criteria and extracted data, and assessed the risk of bias of included studies by QUADAS-2 tool. The sensitivity and specificity of test methods and specimens (bronchoalveolar lavage, bronchial brushing and tissue biopsy) via bronchoscopy were evaluated by gold standard(clinical and laboratory diagnosis). Meta-analysis was performed using Meta-Disc 1.4 software, and summary receiver operating characteristic curve (SROC) was drawn and area under the curve (AUC) and Q index were calculated. Deek′s funnel plots were drawn using Stata 12.0 software.Results A total of 14 studies were included involving 2 781 specimens (1 082 patients). ①Fourteen literatures reported bronchoscopy for the diagnosis of TB. The pooled sensitivity and specificity of bronchoscopy for tuberculosis detection were 0.38（95%CI：0.35-0.41）and 1.00（95%CI：0.99-1.00）, respectively. Then subgroup analysis was made by the types of specimens and test methods. The pooled sensitivity and specificity of tissue biopsy were 0.51（95%CI：0.40-0.61）and 1.00（95%CI：0.81-1.00） , respectively; The pooled sensitivity and specificity of culture, acid fast bacilli on smear and PCR for bronchoalveolar lavage were 0.36（95%CI：0.32-0.40）vs 1.00（95%CI：0.99-1.00）, 0.21（95%CI：0.15-0.28）vs 1.00（95%：0.98-1.00）and 0.58（95%CI：0.46-0.69）vs 1.00（95%CI：0.84-1.00）, respectively. ②Ten literatures reported gastric lavage for the diagnosis of tuberculosis, which exhibited heterogeneity（P<0.001,I2=93.3%）. The pooled sensitivity and specificity of gastric lavage for tuberculosis detection were 0.45（95%CI：0.40-0.49）and 1.00(95%CI：0.99-1.00), respectively. The pooled sensitivity and specificity of smear for gastric lavage were 0.52（95%CI：0.47-0.57）and 1.00（95%CI：0.98-1.00）, respectively. ③The SROC AUC of bronchoalveolar lavage and gastric lavage were 0.883 9 and 0.873 7, respectively; ④P values of the Deek′s test of culture and smear for bronchoalveolar lavage were 0.005 and 0.014. P value of the Deek′s test of gastric lavage was 0.147.Conclusion The value of bronchoscopy for the diagnosis of tuberculosis was definitive in children. Bronchoalveolar lavage for bronchoscopy was the most common specimen, but in terms of culture and smear, it wasn′t better than gastric lavage for tuberculosis detection.
Objective To explore the relationship between 6 common biomarkers and kawasaki disease (KD) with coronary artery lesions(CAL) in the acute phase.Methods Case-control studies from the database of Web of Science, PubMed, The Cochrane Library, EBSCO, China National Knowledge Infrastructure, Wanfang Chinese Periodical Database and VIP Information were recruited to summarize the association between 6 biomarkers (WBC, Hb, PLT, CRP, ESR, ALB) with CAL from January 1 2000 to April 30 2016, and the biomarkers were adjusted by multivariate regression analysis. According to the inclusion and exclusion criteria the studies were selected through EndNote X7 software. The quality of the studies was evaluated by Newcastle-Ottawa Scale(NOS).Stata 12.0 software was applied for the meta-analysis, OR and 95%CI were extracted from each study. The effect model was selected according to the heterogeneity results.Results Twelve clinical studies with a total of 4 900 patients,1 256 patients with CAL were identified.6 factors were included . Six studies were 7 points and 4 studies were 6 points. There was no statistical significance between WBC, Hb, CRP, ESR with CAL, the results of OR and 95%CI were as follows: 0.32 (0.02-4.91), 0.94 (0.88-1.01), 1.11（0.97-1.26）and 1.09(0.98-1.20). PLT and ALB were related to the CAL, the results were as follows: 1.020(1.001-1.039) and 0.87(0.80-0.95). PLT and ALB were used as random model.Conclusion The major risk factors for KD with CAL in the acute stage were increased PLT and decreased ALB.
Objective To investigate the epidemiology of pertussis in the children with protracted cough in Jinan.Methods Outpatients and inpatients with protracted cough visiting the Department of Respiratory of Jinan Children′s Hospital from January 1 to December 31 2015 were recruited to receive pertussis serum antibody and PCR detection. Information about the age of pertussis diagnosis, vaccination, season, clinical characteristics and prognosis was analyzed.Results Of 3 068 suspected cases with pertussis, 657 (21.4%) cases were clinically diagnosed as pertussis, of them, 545 (83.0%) cases were diagnosed by pertussis serum antibody and/or PCR. 247 (22.6%) cases aged from 0 to 3 months, 199 (18.9%) aged from 3 months to 1 year, 168 (19.8%) aged from 1 to 7 years, 43 (58.1%) aged from 7 to 14 years. The diagnostic rate in children aged from 7 to 14 years was significantly higher than other children. The vaccination rate in children aged from 3 months to 1 year with pertussis or non-pertussis was 45.7% (91/199) and 73.7% (622/856), and the vaccination rate was 73.2% (123/168) and 97.0% (658/678) in children aged from 1 to 7 years. The vaccination rates between children aged from 7 to 14 years with pertussis and non-pertussis were similar (41/43 vs 29/31). PCR testing was positive in 545 cases (17.8%), of them, 372 cases (12.1%) with positive serum antibody. The number of pertussis cases increased from May, with high level from July to September and decreased from October to December. Twenty-nine persons in the pertussis children family had clinical symptoms, of them 9 cases and their parents both with positive serum antibody or PCR results, 6 children were clinically diagnosed with negative but whose parents with positive serum antibody or PCR results. Of 657 children with clinical diagnosis, 215 (32.7%) had breathing, 298 (45.4%) with fever. Six cases died from pertussis encepholopathy (3 cases), asphyxia (1 case), heart failure (1 case), persisting mechanical ventilation (1 case, gave up treatment).Conclusion Pertussis accounted for a large proportion of the children under 14 years with protracted cough in Jinan, especially in the children aged from 7 to 14 years. Pertussis showed a certain seasonal trend in Jinan. To protect the prevalence of pertussis, some measures should be taken including early vaccination 2 months after birth and revaccination for the preschool children.
Objective By comparing genotype frequencies among public population databases and single pediatric center, the carrier frequency of autosomal recessive disease-causing genes was acquired in Translational Medicine Center of Children′s Hospital of Fudan University (TMCCHFU). These carrier frequencies could be used as a reference to estimate the Chinese population carrier frequency, and would provide essential information for the design of Chinese-specific disease-causing gene carrier screen panel.Methods The disease-causing autosomal recessive genes from OMIM, and known pathogenic disease-causing mutations from ClinVar and HGMD were summarized. The carrier frequency of disease-causing genes was calculated using local population data and public population databases seperately, and then compared with each other in further studies.Results The public database were filtered and 60 209 pathogenic mutations on 1 368 autosomal recessive disease-causing genes were found, and 1 016 of mutations on 408 genes were identified in 1 147 WES datasets from TMCCHFU. Compared with ExAC East Asian population (4 312 samples) and ExAC European population (33 301 samples), population-specific mutations were identified in each of the populations. Carrier frequencies in TMCCHFU showed more similarity with ExAC East Asian population than European population. Among genes with carrier frequency higher than 1%, 70 out of 81 genes (86.4%) from TMCCHFU overlapped with 70 out of 102 genes (68.6%) from ExAC East Asian population, while 37 out of 81 genes (45.7%) overlapped with 37 out of 136 genes (27.2%) from ExAC European population.Conclusion Through comparison with ExAC East Asian and European population, carrier frequency of disease-causing genes identified in TMCCHFU is much more similar with East Asian population than European population. The difference of carrier frequency among populations should not be ignored and makes it necessary to establish a Chinese-specific panel for genetic disease screen.
Objective To summarize and review the clinical data of an infant diagnosed as cerebrotendinous xanthomatosis (CTX) so as to identify the disease early and improve our understanding of cholestasis.Methods Clinical features of a 2-months old girl in cholestatic jaundice was reported at onset. Bile duct exploration and laboratory examinations were taken and she was finally diagnosed as CTX by urinary acid mass spectrometry analysis and CYP27A1 gene detection. Clinical features of similar cases from published literatures were retrieved and systematically summarized.Results A 2-months old girl was admitted to our hospital due to jaundice from one week after birth. Laboratory findings showed cholestasis jaundice, normal or mildly elevated TBA, mildly elevated GGT and TCH. Biliary atresia was excluded by bile duct exploration. Absence of cholesterol-27-hydroxylase activity measured by Urinary bile acid mass spectrometry analysis and pathogenic compound heterozygous mutations of CYP27A1 gene: p.R127W(c.379C＞C/T )and p.Q116X（c.346C＞C/T）were found and CTX was confirmed. She received cholic acid tablets therapy. Follow up was carried out for 9 months after discharging from the hospital, her jaundice faded and she had no discomfort. Three related literatures concerning CTX with cholestatic jaundice onset were searched with Pubmed database. Combined with this case, common manifestations were cholestasis jaundice of the second-third months after birth, normal or mildly elevated GGT, mildly elevated TBA and TCH.Conclusion CTX reports on the onset of cholestasis in infancy are extremely rare. It should be considered the possibility of this disease when normal or mildly elevated TBA, slightly elevated GGT and TCH. Diagnosis may be confirmed by urinary bile acid mass spectrometry and CYP27A1 gene detection.
Objective To assess the efficacy and safety of polyethylene glycol 4000 (PEG4000) in constipated children younger than 8 years.Methods The randomized controlled trials of PEG4000 compared with other active comparator in children younger than 8 years with primary chronic constipation were conducted by an electronic search of Cochrane library, PubMed, EMBASE, ISI Web of Science, VIP, and CNKI, with the retrieval time from January 1981 to April 2016. Results Four qualifying studies involving 344 children were identified. Two were comparisons of PEG4000 with lactulose, one with milk of magnesia and one with PEG-electrolyte(PEG-EL). Study duration ranged from 2 weeks to 12 weeks. Four studies described the generation of random sequence, the allocation concealment and reported the subjects lost to follow-up, 3/4 articles used double-blind method. ①There was no severe adverse reaction observed in four studies. The rate of at least one blood biochemical indexes outside normal of PEG4000 was similar between after and before treatment(35/39 vs 31/39). The incidence of diarrhea was lower in PEG4000 group (2/46 vs 12/43) than in milk of magnesia group; the incidence of nausea was lower in PEG4000 group compared to PEG-EL group (1/49 vs 9/42). ②The stool frenqency was similar in PEG4000 and lactulose groups(8.5 vs 11.5 per week), after four weeks follow up, PEG4000 group had great increase in stool frenqency than PEG-EL group［(9.2 ± 3.2) vs (7.8 ±2.4) times，P=0.025］ and PEG4000 group had significantly higher improvement compared with the patients in the milk of magnesia group (42/46 vs 28/43，P=0.003).Conclusion Limited scientific evidence demonstrated that for children younger than 8 years , PEG4000 use was more effective and tolerated than other active comparators.
Objective To analyse the clinical phenotype and genotype of tuberous sclerosis complex (TSC) and improve the diagnostic level of TSC.Methods Patients were retrospectively collected from Aug. 2013 to Sept. 2015 hospitalized in Children′s Hospital of Fudan University, who were diagnosed with 2012 revised diagnostic criteria for TSC. Data of clinical phenotype included brain, skin, heart, kidney and eyes were intercepted. Patients were divided into the age of <1 year, -3 years, -6 years, -13 years and -18 years groups, statistics was made to get detection rate and the correlation was analysed between genetic mutation and clinical phenotype.Results A total of 105 cases diagnosed as TSC were recruited into the study including 54 males and 51 females. Age of visit was ranged from 2 months to 13 years. ① Reason for the first visit: 83 cases (79.0%) for seizure, 8 cases (7.6%) for abnormal of skin and 5 cases (4.8%) for cardiac tumor. ②39 cases (37.1%) were diagnosed only with clinical phenotype; 47(44.8%) with clinical phenotype and genetic testing; 2 cases (1.9%) with clinical suspicious but gene positive. ③Clinical characteristics detection rate: Subependymal nodules were in 91/99 cases(91.9%), cortical dysplasias were in 81/99 cases(81.8%), which was similar with other different age groups. Hypomelanotic macules were in 97/105 cases(92.4%), angiofibromas were in 55 cases(52.4%), shagreen patch in 46 cases(43.8%), the detection rate of angiofibromas and shagreen patch rised with age. Cardiac rhabdomyomas were in 25/75 cases(33.3%)，the detection rate descended with age; renal lesions were in 14/71 cases(19.7%); ocular lesions were in 5/37 cases(13.5%). ④TSC1 mutation was detected in 15/66 cases (22.7%)，TSC2 mutation was detected in 34/66 cases (51.5%)；spasm was more common in patients with TSC2 mutation (29.4% vs 13.3%).Conclusion TSC is an extremely variable disease that can affect multiple important organs. The detection rates of brain lesion were similar among different age and cardiac rhabdomyomas decreased with age. Gene test conduced to the diagnosis of clinical suspect cases.
Objective In this study, whole-exome sequencing was used to identify pathogenic mutations in a newborn with cerebral dysplasia. Methods The exome targets of the patient′s DNA was captured with the SureSelct Human All Exon kit followed by sequencing with the Illumina HiSeq2000 platform. The data analysis pipeline of Children′s Hospital of Fudan University was used for the annotation and variant calling. The detected variant was confirmed with Sanger direct sequencing. Neurons were isolated from neonatal rats and the oxygen-glucose deprivation (OGD) model was established. The cultured neurons were divided into 2 control group (Sham+PBS and Sham+POSTN subgroups) and OGD group (OGD+PBS and OGD+POSTN subgroups). Immunofluorescence, LDH cytotoxicity detection, BrdU staining and TUNEL staining were used to detect the proliferation and apoptosis of cultured neurons.Results Whole-exome sequencing identified total of 532 151 variants in the proband, and revealed two novel compound heterozygous variants in exon 23:c.A2475T:p.G825G and exon 19:c.G2251A:p.E751K in POSTN (NM_006475) gene. Sanger direct sequencing confirmed these two variants. POSTN was expressed in the cultured rat neurons (MAP-2 and NeuN positive cells). LDH cytotoxicity in Sham+POSTN subgroup was compromised with Sham+PBS subgroup. However, POSTN protected neurons from LDH cytotoxicity in OGD groups. The neurons were treated with OGD for 2, 6, 12 days, compared with Sham+PBS subgroups, the proliferation of neurons was increased in OGD+PBS subgroup as well as apoptosis of neurons. After POSTN treatment, the number of proliferative neurons was markedly increased in OGD group, however, the apoptotic neuron number was significantly decreased.Conclusion POSTN treatment decreased LDH cytotoxicity, increased the proliferation and decreased apoptosis of OGD-treated neurons.
Objective To investigate the molecular and virulence characterization of Staphylococcus aureus(SA) isolated from neonates with skin and soft tissue infections(SSTIs) through one-year prospective surveillance study, and to provide the scientific evidence for prevention and control of SA infection. Methods Cases of SSTIs in neonates were prospectively collected from May 2015 to April 2016 in NICU of Beijing Children′s Hospital, the clinical data were recorded, the multilocus sequence typing(MLST) and Staphylococcal cassette chromosome mec(SCCmec) types were analyzed by multiplex polymerase chain reaction method, the spa type was analyzed by PCR. PCR was also used to test 23 virulence genes, including 21 superantigen genes, PVL gene and sasX gene.Results A total of 13 SA strains were collected, including 7 MRSA，the most common clone of MRSA was agrⅠ-ST59-SCCmecⅣ-t437. It was found that all strains contained at least two superantigen toxin genes, and 6 strains were PVL positive. SasX was not detected in any of the isolates. Conclusion The carrying rate of SA from SSTIs in neonates was low, the most common clone of MRSA was agrⅠ-ST59-SCCmecⅣ-t437, the carrying rate of superantigen was high.
