Objective To observe clinical progression in severe cases with enterovirus 71 (EV71) infection, attempt to explore the neurologic invasive pathways, and introspect on the " Clinical expert consensus of EV71 infection severe cases (referred to expert consensus) " after EV71 infection. Methods Unsurvival cases of EV71 infection were selected from nine hospitals in Guangxi (12 cases) from 2008 to 2010，and in Guangzhou Women and Children′s Medical Center (2 cases) from2011 to 2012, to analyze these 14 cases in clinical manifestations and features of autopsy. Results 14 unsurvival cases of EV71 infection, male: female =7∶7 , aged from 7 to 36 months, the average age was (19.0 ± 9.8) months. The autopsy common features of 14/14 cases were the brainstem cribriform necrosis and malacia formation, 10 cases involved in the medulla oblongata, and there were no inflammatory cells in other organs. Nine symptoms/signs (34.6%) in the expert consensus hadn′t been recorded. Both seizure and disturbance of consciousness in stage 4 had occurred with the symptoms / signs in stage 2 simultaneously. The symptoms/signs could be observed at the beginning were fever, rash, vomiting, startle, seizure, fatigue; 42.9% cases appeared various neurological symptoms orderly, simultaneously or alternately until death. The 12/14 cases average survival duration after onset of symptoms/ signs was 72.4 h, and after appearing any abnormal basic vital signs in stage 3(mean duration 65.5 h) was 6.9 h, and after appearing neurologic symptoms/ signs in stage 2 (mean duration 39.8 h) was 32.6 h. Conclusion ①The cause of death for confirmed EV71 infection was brainstem function failure; ②It is speculated that EV71 neurologic invasive pathways existed; ③It is recommended that neurologic specialist assessment for special clinical indicators is needed after EV71 infection; ④Seizure and confusion should be included in the earlier observation indicators; ⑤It is proposed that indicators of neurologic specialist assessment would be used in the fuller clinical staging study of EV71 infected neurologic involvement, to provide sufficient time of observation and intervention for clinicans.
Objective To investigate procalcitonin（PCT）and CRP as markers of systemic and localized bacterial infections. Methods The cases of infectious diseases were recruited retrospectively in a children' hospital. Severe sepsis, septicemia with positive blood culture were recruited as systemic bacterial infection group. Acute suppurative tonsillitis, urinary tract infection and pyogenic osteomyelitis and septic arthritis were recruited as localized bacterial infection group. Infectious mononucleosis, hand foot and mouth disease were recruited as viral infection group. The value and positive rates of serum PCT and CRP among these groups were compared. The receiver operator characteristic curve (ROC) was drawn for PCT and CRP to diagnose systemic and localized bacterial infections, and the sensitivity and specificity were evaluated and the area under roc curve (AUC) and 95%CI were analyzed. Results One hundred and forty eight cases were recruited, 19 in systemic bacterial infection group, 55 in localized bacterial infections group and 74 in viral infection group. ①The levels of serum CRP and PCT and the positive rate of PCT were lower in localized bacterial infection group than in systemic bacterial infection group（CRP: 21.35 vs 76.0 mg·L-1, P=0.001; PCT:0.10 vs 28.09 μg·L-1, 32.7% vs 100%, P<0.001）. The levels of serum CRP and the positive rate were higher in localized bacterial infection group than in viral infection group（21.35 vs 4.0 mg·L-1, P<0.001; 73.1% vs 27.0%, P<0.001). The levels and the positive rate of serum CRP were not significantly different in these two groups. There were no significant differences of WBC in three groups. The positive rate of WBC was higher in systemic bacterial infection group than in viral infection group（84.5% vs 54.0%，P=0.017),but no significant difference was found between systemic bacterial infection group and localized bacterial infection group. There were no significant differences between localized bacterial infection group and viral infection group. ②In patients with localized bacterial infection, the level and the positive rate of serum PCT were higher in systemic inflammatory response syndrome (SIRS) group than non-SIRS group（0.40 vs 0.08, P =0.002; 60.0% vs 17.1%, P =0.001）, but there was no significant difference in the level and the positive rate of serum CRP between two groups. ③The AUC of ROC was 0.99 for PCT and 0.84 for CRP to diagnose systemic bacterial infection. It was 0.54 for PCT and 0.78 for CRP to diagnose localized bacterial infection, respectively. Conclusions In our study, PCT was identified as a sensitive marker of systemic bacterial infection and localized bacterial infections progressing into sepsis. As an indicator of bacterial infection, CRP was batter than PCT in localized infections.
Objective To understand the epidemiological and clinical features of moderate and severe Japanese encephalitis (JE) in pediatric inpatients in Shanghai and assess the risk factors associated with the severity and prognosis of JE. Methods The clinical data from pediatric JE cases who acquired JE infection in Shanghai during 2002-2011 were retrospectively analyzed. JE was laboratory-confirmed based on the positive JEV-specific immunoglobulin M detection in serum and/or cerebral spinal fluid in clinical cases. Results A total of 73 children confirmed with JE were included in this study. the male-to-female ratio was 2.3:1 and the mean age was 5.1 years; 65 (89%) were migrant children; 12 (16.4%) had reliable records of JE vaccination; 69 (94.5%） lived in rural or suburban areas. All JE cases in Shanghai occurred in July and August with more severe cases occurring in early July. All JE cases had fever, followed by neck rigidity (82.2%), seizure (76.7%), headache (75.3%), vomiting (74%) and coma (47.9%). Six (8.2%) cases had secondary respiratory failure, and 3 (4.1%) deceased. Twenty (27.4%) had various disability at hospital discharge. The rates of disability or mortality at hospital discharge in moderate and severe JE were 13.0% and 84.2% (χ2=33.06，P<0.000 1). The median value of serum creatine kinase (CK) was significant higher in severe cases than in moderate cases (465 verse 105 U·L-1, Z=-3.173，P=0.001). The independent risk factors associated with the poor outcomes of JE at hospital discharge included multiple seizures (OR=29.3), coma (OR=253.6)，living near pigs farms (OR=16.9) and serum CK > 200 U·L-1 (OR=0.01). Conclusions The clinical classification of JE severity is useful to guide the appropriate management and predict the prognosis. Elevated serum CK is an important biochemical predictor for severe JE. Multiple seizures, coma, living near pig farms and serum CK>200 U·L-1 are the independent risk factors associated with severe JE and poor outcome. Reinforcement of JE immunization among the migrant children is crucial to reduce the morbidity and sequelae of JE in Shanghai.
Objective This study aimed to analyze the dynamic characteristics of group A rotavirus genotypes. Methods A total of 345 rotavirus-positive stool specimens were collected from inpatients under 5 years old hospitalized with acute gastroenteritis in Children′s Hospital of Fudan University from January 2008 to December 2011. Each fecal specimen was tested for rotavirus with a commercial enzyme immunoassay, and genotypes were characterized using multiplex nested reverse transcription polymerase chain reaction (RT-PCR). Results G genotypes: The predominant G genotype was G3 which accounted for 49.2%, 44.6% and 78.0% respectively in the year of 2008, 2009 and 2010. The prevalence of G9 was on an upward trend from 2008 to 2011, and dominated as the most common type in 2011(51.1%). G1 was detected each year with a varying prevalence of 8%-20%. G2 was rarely seen and G4 was not detected during the four years. Mixed G infections with G3+G9 were the most prevailing G-mixed types, followed by G3+G1. Otherwise, mixed-G infections with three different G genotypes were detected in 4 cases. P genotypes: P［8］ genotype was the dominant strain with prevalence of 55.6%, 60.0% and 68.1% respectively in the year of 2008, 2010 and 2011, whereas mixed P genotype was dominant in 2009(43.2%). P［4］ strains were prevalent in four years in a volatility way. P［6］ and P［9］ could also be found as minor types. Interestingly, P［10］ genotype was seen only in combination with P［8］. The major mixed P infection was genotype of P［4］+P［8］, and P［8］+P［10］ was assigned as follows. A high prevalence of P［8］G3 genotype was determined to be the major rotavirus genotype combination (24.3%) in Shanghai from 2008 to 2011 and the other prevalent genotypes included P［8］G9 and P［m］G3. P［8］G9 strains jumped as the most predominant type in 2011( 40.5%). Conclusions Compared with the data from the year of 2001-2007, this study shows new epidemiological characteristics of group A rotavirus genotypes during 2008-2011 in Shanghai, including ascending of G1 and G9 proportions, reduction of G3 and diversification of mixed infections. Therefore, it is highly essential to conduct continuous and systematic monitoring for rotavirus strains in anticipation of rotavirus vaccine introduction in Shanghai.
Objective Congenital heart disease (CHD) is the most common birth defect in humans. The genetic causes for CHD remain largely unknown. Tetralogy of Fallot (TOF) is one major component of conotruncal defects (CTD), a complex CHD induced by abnormal development of the outflow tract. Retinoid X receptor alpha (RXRA), a ligand-dependent transcript factor, plays a critical role in multiple aspects of cardiogenesis including the development of outflow tract (OFT). Taken together, RXRA may be a potential candidate gene of TOF. To date, RXRA gene promoter region has not been analyzed and reported in TOF patients. We hypothesized that the sequence variants within RXRA gene promoter region may change RXRA levels and the development of TOF. In this study, the promoter regions of RXRA gene were genetically analyzed. Methods Case group included DNA samples from patients with TOF, which had been confirmed by cardiac catheterization and surgery. Control group consisted of DNA samples from randomly selected healthy children. Genomic DNA was extracted from peripheral blood. PCR was used to amplify the 1 417 bp promoter region from genomic DNA. PCR products were sequenced by ABI Prism Bigdye system. Results The promoter regions of RXRA gene were genetically analyzed in 213 TOF patients and 500 healthy controls. One novel heterozygous mutation, -1 191A>AG (according to the transcription start site), was found in one TOF patients, but in none of controls. Three novel single-nucleotide polymorphisms, -1287C>CT, -800C>CA and -760C>CT were found in both TOF patients and controls. There were no statistically significant changes in the genotype and allele frequencies of the three SNPs between TOF patients and control group (P>0.05). Several transcription factor binding sites were found within the region containing these single-nucleotide variations by searching http://www.cbrc.jp/research/db/TFSEARCH.html. Conclusions The A at position -1 191 following C, and C at position -800 was followed by G, thus these single-nucleotide variations provided additional candidate cytosines (CpG) for methylation that may enhance the level of gene expression.The sequence variants within RXRA gene promoter may contribute to the TOF etiology by altering the expression levels of RXRA gene.
Objective To assess the reporting quality of systematic reviews(SRs)/meta-analyses(MAs) of interventions published in Chinese Journal of Evidence-Based Pediatrics and Pediatrics. Methods According to the inclusion and exclusion criteria, the basic data of SRs/MAs of intervention RCTs were collected . The preferential reporting items (PRISMA statement) for SRs/MAs were applied to assess report quality. Analyses were performed using Excel, RevMan5 and Meta-Analyst software. Results A total of 67 SRs/MAs were included. The PRISMA checklist score ranged from 12.0 to 24.5, the average score was 19.98±2.86. There has been some improvement in total score after the PRISMA publishing, but there was no significant difference. The impact of authors′ number to reporting quality wasn′t statistically different. The reporting quality of funding theses, authors′ number <2, written by clinicians, Chinese theses and published in Chinese Journal of Evidence-Based Pediatrics was better than non-funding theses, authors′ number ≥2, written by university, English theses and published in Pediatrics. The total score of included SRs/MAs published in Chinese Journal of Evidence-Based Pediatrics focused on high quality score (-27) (66.7%), low quality score (<15) documents were not found. 70.3% SRs/MAs published in Pediatrics focused on medium quality score (-21), low quality score (<15) documents was 13.5%. Conclusions The effort was valuable for selecting two magazines in learning, understanding, and executing the writing specification of SRs/MAs, there are a large space to further improve the reporting quality and normative publication.
Objective To evaluate the relationship between the MRI findings and clinical characteristics in full-term infants with neonatal hypoglycemia. Methods The clinical records of 22 neonates with isolated hypoglycemia who were referred to Children′ Hospital of Fudan University from June 1, 2008 to June 30, 2011 were reviewed retrospectively. The patients were divided into two groups according to the early magnetic resonance imaging (MRI) findings: MRI -group (n=9) were patients who showed normal brain imaging while MRI + group (n=13) were patients who showed abnormal brain imaging finding. The clinical characteristics of neonatal hypoglycemia were compared between two groups. The brain injury patterns identified from early MRI scans were presented. Results The frequencies of risk factors for hypoglycemia were similar in two groups (P=0.054). The duration when hypoglycemia was first detected was 1(0.5-17) h in MRI- group and 46.6(12.7-78.3) h in MRI+ group, respectively, P=0.000. MRI- group established stable blood glucose levels faster than the MRI+ group, (54.1±18.2) h vs (71.6±15.1) h, P=0.023. The occurrences of symptoms were more frequent in MRI + group than MRI - group (P=0.000). Among MRI +group, 10 had predominant bilateral parieto-occipital cortex and subcortical white matter abnormalities, 1 had unilateral occipital and parietal area lesions, 2 had punctate white matter lesions in periventricular region or centrum semiovale. Conclusions Screening and management of babies at risk for neonatal hypoglycemia are recommended. Infants who were identified less than 12 hours of postnatal age remained asymptomatic, and there were no changes in the MRI imaging. The duration from birth till establishment of the stable blood glucose levels might be suggestive of association with neuroimaging changes and long-term neurological changes. The most common area of hypoglycemia-associated brain injury was in the parietal and occipital lobes.
Objective To investigate CASP8AP2 expression in childhood acute lymphoblastic leukemia (ALL), its associations with clinical characteristics, and its prognostic significance for disease relapse. Methods Clinical data of patients with newly diagnosed childhood ALL were enrolled in Beijing Children′s Hospital from April 2008 to August 2009. Using real-time quantitative polymerase chain reaction (RQ-PCR), CASP8AP2 was quantitatively detected in 81 ALL patients, ABL was detected simultaneously and used as an internal control. The average Ct value of samples obtained from five pediatric ALL patients with long-term complete continuous remission (CCR>5 years) was used as a calibrator. The expression levels of CASP8AP2 were calculated by the 2-ΔΔCt method and presented as fold changes compared with that of the five CCR patients. Results Eighty-one children diagnosed with ALL were included in the study. The ratio of males to females was 1.6. ①The ROC curve of CASP8AP2 was made to predict the relapse of pediatric ALL, and the area under the curve (AUC) was 0.851(P<0.001). ② The expression of CASP8AP2 in the unfavorable prognosis group was significantly lower than that in the favorable prognosis group, （0.45±0.31） vs （0.77±0.35）,P=0.0021. ③ Using a cutoff value of 0.4760, CASP8AP2 may be divided into high- and low-expression groups. Significantly poorer event-free survival (EFS) (P<0.001) and overall survival (OS) (P<0.001) were found in the low-expression group. ④ Using the expressions of CASP8AP2 and minimal residual disease (MRD) as bases, samples were divided into three risk groups. Differences between groups were statistically significant and indicated the capacity to predict the relapse of disease (AUC=0.917, P<0.001). Conclusions The expression of CASP8AP2 could be an independent prognostic factor for pediatric ALL. Joint detection of CASP8AP2 and MRD could help predict outcomes more precisely and has the potenticals to be sued as an effective means in determining prognosis, monitoring the risk of recurrence, and guiding the treatment.
Objective To investiagte clinical manifestation and therapeutic methods of mitochondrial neurogastrointestinal encephalomyopathy((MNGIE),and improve the understanding and recognition of this disease. Methods Clinical data of the patient were collected, and mitochondrial respiratory chain enzyme activity of the peripheral white blood cells was examined,then the associated genes were sequenced according to the enzyme activity. The literatures were reviewed to summarize the clinical manifestation, treatment and prognosis of this disease. Results The initial symptoms were found 19 days after birth, including weight loss,refractory diarrhea,malnutrition and anemia.The mitochondrial respiratory chain composite enzyme test suggested the presence of mitochondrial respiratory chain composite enzyme defect, and peripheral white cell mitochondrial DNA sequencing confirmed A750G mutation at the MT-RNR1 locus,which led to rRNA structure change and resulted in the disease.After feeding with deep hydrolyzed protein milk, and treating with probiotics and vitamin B, the diarrhea improved and the child gained weight satisfactorily. Conclusions Children with early-onset refractory diarrhea should be considered as the possibility of MNGIE.
Objective To analyze MFN2 mutations and associated phenotypes in patients with charact-marry-tooth (CMT) type Ⅱ. Methods Children diagnosed as CMT 2 in Beijing Children's Hospital from 1998 to 2012 were included.Direct sequencing of the MFN2 gene and clinical investigations were performed in patients with MFN2 mutations. The clinical features, electrophysiological finding, labortory test and pathology of paitients with and without MFN2 mutations were analyzed. Results Twenty one cases with CMT 2 were included in the study.①No gene mutation was detected in 18 cases (male 14 cases, female 4 cases). The average age of the onset of the disease was 3.3 years. Nine of them involved in both proximal end and distal end of lower limb, seven cases involved in limbs, two cases could not walk, eight cases were with myophagism of proximal and distal ends of lower limb, mild sensory disturbance could be detected in four cases. Three different missense mutations were identified in 3 patients (male 2 cases, female 1 case). The age of onset ranged from 1.5 to 8 years, one had a family history of autosomal dominant inheritance. Myophagism of proximal and distal ends of lower limb could be found in all cases, foot drop with strephenopodia were observed in two cases, and all with sensory disturbance. ②Conduction velocity great than 38 m·s-1 of motor nerve and/or sensory nerve, or decreased amplitude could be detected in all cases. The decreased value of CAMP of common peroneal nerve and tibial nerve was higher in MFN2 gene mutation children than that in children without MFN2 mutation.③Sural nerve examination was performed in ten cases, one of them with MFN2 gene mutation, nine without MFN2 gene mutation, prominent mitochondrial abnormalities in both myelinated and unmyelinated nerve fibers were observed under electronic microscope. Conclusions MFN2 mutations was one of the causes of CMT2 with either dominant or recessive inheritance. The age of onset of patients with MFN2 gene mutation usually was before 10 years old.
Objective Congenital central hypoventilation syndrome (CCHS) is a rare autosomal dominant disorder characterized by failure in the autonomic control of breathing. Methods The clinical data of this patient were collected. The PHOX2B gene was analyzed by DNA sequecing in patient and his parents who were known with CCHS. Results According to the clinical data, this patient typically presented hypoventilation during sleeping, without any associated primary cardiac, pulmonary, neuromuscular or brainstem lesions,or any metabolic diseases. DNA sequencing of the PHOX2B gene showed expanded alleles containing polyalanine 25 repeats in the patient. Conclusions According to the clinical and genetic diagnosis, this patient presented CCHS. DNA sequencing of the PHOX2B gene identified a mutation in exon 3 (genotype of 20/25 ) in the patient but not in his parents.
Objective To understand the clinical and pathologic features of the hypersensitivity pneumonitis in children. Methods A case of nine years and six months old girl with hypersensitivity pneumonitis admitted to Beijing Children′Hospital in the April of 2012 was reviewed. Results The symptoms were cough for 4 months, short breath, no sputum and fevers, no dyspnean or digital clubbing. The diffused micronodules were found in the high-resolution CT of the bilateral lung. The cellular bronchiolitis and bronchiolocentric lymphocytic pneumonitis were presented in the pathology of the lung , the abundant foamy cells in the interstitium and giant cells in the interstitial spaces also were found in the pathology. No evidence of the tuberclusis and virus infection and connective tissue disease was found. The symptoms and abnormal of the HRCT findings were improved after 26 days avoidance of the environment exposure, and were improved evidently after two-week treatment of the corticosteroid. The patient was recovered almost completely after two months of the treatment. Conclusions The manifestation of the subacute hypersensitivity pneumonitis in the HRCT is diffused micronodules. Subacute hypersensitivity pneumonitis in children is well reponsible to the treatment of corticosteroid. Histological diagnosis of the hypersensitivity pneumonitis is predicated on the recognition of the poor formed granulomatous or giant cells in the interstitial spaces.
Objective To improve the understanding to acute purulent pericarditis caused by Streptococcus Pneumoniae(PPSP) ,to report a case of acute PPSP serotype 6A in a Chinese child and 16 reported cases by English literature on this topic up to now. Methods Clinical manifestation and prognosis of 17 patients（including our reported case in this article） with acute purulent pericarditis caused by Streptococcus Pneumoniae were retrospectively analyzed. Results A 14-month-old previously healthy boy had a history with 7-day-tachypnea and 3-day-cough. The levels of white blood cell (WBC) and C-reactive protein (CRP) were significantly high.A computed tomographic imaging of the chest and echocardiographic study showed massive pericardial fluid. Streptococcus Pneumoniae serotype 6A was recovered from pericardial fluid and was found to be sensitive to penicillin. The patient was diagnosed as PPSP and treated with intravenous infusion of cefamandole and linezolid successively. On the 19th day of hospitalization the patient was discharged in good general condition and with hemodynamically stable. Over 6 months follow-up, ultrasound cardiography only revealed a little thickening cardiac pericardium.Since 1990,only 16 cases of PPSP have been reported in children in the PubMed databases.17 cases (9 males，7 females，1 unknown) aged from 4 months to 17 years,10 cases were younger than 2 years old. Children were healthy without previous medical conditions and only 3cases had underlying diseases. Its clinical recognition was difficult due to insidiously subtle and varied presentations,but most of cases had fever, dyspnea and cough. The levels of WBC, neutrophil and C-reactive protein were very high. Pericardial fluid was often yellowish-brown and revealed typical manifestation of purulent pericarditis. Echocardiogram and chest CT/X ray showed a large amount of pericardial effusion,many cases showed pneumonia pleural effussion.8 cases were with penicillin susceptible strains, 1 case with penicillin drug resistant strains of S. pneumoniae.1 case of serotype 34, 2 cases of serotype 6A , 14 and 23F were reported respectively.3 cases were with cardiac tamponade.Effective drainage of the pericardium in combined with high dose intravenous antibiotics offered the best results.Most of cases were treated with vancomycin finally. In general，there was often a good outcome without sequelae, but 2 cases died. Conclusions In near 20 years，PPSP has been reported in the English literature，and tended to increase in the past 2 years. Its clinical recognition is difficult due to atypical and varied presentations, especially in pediatirc department. Children were often healthy in the past. Despite the serious morbidity, PPSP patients who received prompt treatment could achieve good prognosis without sequelae.
Objective The aim of the study was to examine whether asiatic acid could attenuate ischemia-reperfusion(I/R) induced lung injury in infant rabbits. Methods 60 New Zealand white rabbits aged from 15 to 21 days were subjected to sham operation, I/R, low dose asiatic acid plus I/R, medium dose asiatic acid puls IR, and high dose asiatic acid puls I/R. I/R was induced by clamping the right pulmonary hilum for 1 hour and then removal of the clamp for 4 hours. Asiatic acid was given 3 days before operation by 7.5mg, 15, 30 mg·kg-1 respectively. Production and expression of free radical species-hydroxyl radical (ROS-HR), malondialdehyde (MDA), superoxide dismutase (SOD), glutathione peroxidase (GSH-PX), myeloid differentiation factor-88(MyD-88), and muclear factors-κB(NF-κB) in the lung tissue were also evaluated. And temperature, hemodynamics, blood gases and neutrophil count were measured 2 hours after reperfusing. In addition, serum levels of interleukin-1β and tumor necrosis factor-α were measured during the ischemia-reperfusion process. Results The infant lungs in asiatic acid middle and high dose groups had less neutrophil infiltration, edema, swelled alveolar epithelial and endothelial cells under light and electron microscopes. ②Compared wtih I/R group, asiatic acid reduced the production of ROS-HR and MDA and improved the activities of GSH-PX and SOD markedly, siginificantly decreased the serum levels of interleukin- 1β and tumor necrosis factor-α at 4 h time point after reperfusion, as well as the MyD88 and NF-κB of lung were siginificantly decreased(P<0.05).③Asiatic acid middle and high dose groups had good effect of attenuating I/R. Conclusions Asiatic acid pretreatment reduced the lung damage induced by I/R in the infant rabbits.
