Objectives：To observe environmental determinants and the heritability of CD4+ and CD8+ T-lymphocyte subsets in 1 year-old healthy twins. Methods：Twins born at 5 compresive hospitals in Urumqi including the First Teaching Hospital of Xinjiang Medical University, Materal and Child Care Hospital of Urumqi City, People′s Hospital of Xinjiang Uygur Autonomous Region, the PLA Hospital of Xinjiang and the First People′s Hospital of Urumqi City were recruited based on the inclusion and exclusion criteria after obtaining inform consent. Demographic and general information, family history, paternal life styles, maternal gestational and birth information, as well as feeding and growth development information of infants were collected by interview and medical records. The growth and development examinations were performed by using national unified instruments and protocols. Venous whole blood samples (2 mL) were obtained from all subjects using EDTA-K3 tubes and CD4+ and CD8+ T cell counts were examined on the same day by flow cytometry. Zygosity was determined by DNA-based microsatellite markers. Conventional statistical analyses were performed using Stata 11.0 software for Windows. Structural equation model was used to estimate the relative contribution of genetic and environmental effects to the CD4+ and CD8+ T-lymphocyte subsets number using Mx program. Results：Totally 172 healthy pairs of twins were enrolled into the study, consisting of 82 monozygotic (MZ) (47.7%) and 90 dizygotic (DZ) pairs. There was a positive but weak correlation between CD4+ T cells counts and Apgar score in both MZ twins and DZ twins (rMZ=0.16, rDZ=0.14, P<0.05). After model fitting, AE model showed the best performance to the continuous phenotypes for both CD4+ and CD8+ T-lymphocyte counts, additive genetic effect (i.e. heritability) explained 61.8%(95%CI:38.3%~74.8%) and 57.3%(95%CI:34.5%~70.2%) of variations of CD4+ and CD8+ T-lymphocyte counts, respectively. Unique environmental effect explained 38.2%(95% CI: 20.4~52.8%) and 42.7%(95%CI: 26.2%~61.9%) of the variations, respectively. Conclusions：The heritability of CD4+ and CD8+ T-lymphocyte counts was 0.62 and 0.57 in 1-year old infants respectively. Perinatal and early life environmental factors, such as Apgar score may be associated with CD4+ and CD8+ T-lymphocyte counts.
Objectives：To assess the vitamin B12 nutritional status of 18 months old toddlers in impoverished area of China and to explore its correlation with different complementary foods. Methods：Data were drawn from a randomized controlled intervention trial that aimed to investigate the effect of different complementary infant foods. All subjects were recruited at 6 months of age and randomized to feed different complementary foods, meat, fortified cereal, and local made rice cereal. The intervention continued to children at the age of 18 months. The serum vitamin B12, homocysteine, and hemoglobin, as well as anthropometric parameters were measured at 18 months of age. Results：A total of 217 toddlers were included in the current analysis, 61 in meat group, 85 in fortified cereal group, and 71 in local made cereal group. The median level of serum vitamin B12 , homocysteine and toddlers was 342(85-2 700) pg·mL-1, 8.20(3.30-20.40) μmol·L-1 and 124(90-158) g·L-1,respectively. 85 (39.2%) toddlers had a serum vitamin B12 level < 300 pg·mL-1, 42 (19.4%) toddlers < 200 pg·mL-1; 26 (12.0%) toddlers had a homocysteine level > 12 μmol·L-1; 52 (24.0 %) toddlers had a hemoglobin level < 115 g·L-1. The toddlers in meat, fortified cereal, and local made cereal groups had a median serum vitamin B12 level of 335, 422 and 281 pg·mL-1, respectively. There was statistical difference among three groups (P=0.013). Among 85 toddlers who had a serum vitamin B12 level < 300 pg·mL-1, 39.34% (24) was in meat group, 28.2% (24) in fortified cereal group, and 52.1% (37) in cereal group. There was a significant difference among three groups (P=0.010). Conclusions：Vitamin B12 deficiency was common in toddlers in impoverished area. Inadequate dietary intake was the main reason of vitamin B12 deficiency in these toddlers. Both meat and fortified cereal could improve vitamin B12 nutritional status of toddlers.
Objectives：To investigate the distribution of causes of chronic cough in children in Wenzhou area, and to explore the potentially existed considerable issues in diagnosis. Methods：A prospective observational study was conducted in Yuying Children′s Hospital from Jan. 2008 to Dec. 2010. Patients presented to pediatric respiratory clinic with cough over 4 weeks were diagnosed and treated prospectively and procedurally. Follow-up was conducted by clinical interview or by telephone 2 weeks，1 month and 3 months after the first clinic visit. The final diagnosis and treatment were adjusted according to the follow-up results. Results：During the study period, totally 739 children with chronic cough were enrolled aged 8 months to 14 years old, including 174 cases (23.5%) aged 0-3 years，288 cases（39%) aged -6 years ,277 cases（37.5%) aged -14 years. The duration of chronic cough ranged from 4 weeks to 5 years. In the first-quarter of the year, there were 103 cases (13.9%), followed with second-quarter 247 cases (33.4%), third-quarter 96 cases (13.0%) and fourth-quarter 293 cases (39.7%). Finally, 680 cases(92.0%) were found with single cause, 45(6.1%) with double causes, 14 (1.9%) with unidentified causes. Main causes of chronic cough were upper airway cough syndrome (n=237, 32.1%), cough variant asthma (n=219, 29.6%), post infection cough (n=109, 14.8%), atopic cough (n=76, 10.3%), psychogenic cough (n=25, 3.4%), chronic cough due to gastroesophageal reflux (GERC)(n=9, 1.2%) and other causes (n=5, 0.7%). The proportions of causes differed among age groups (P＜0.05). The most common causes in children aged -3 years,-6 years and -14 years were post infection cough (n=58, 33.3%), upper airways cough syndrome (n=114, 28.5%) and cough variant asthma (n=103, 37.2%). Totally 675 cases were caused by the top 6 causes, 496 of them with the same initial and final diagnosis, the match ratio was 73.5%. Conclusions：The main causes of chronic cough in children in Wenzhou were upper airway cough syndrome,cough variant asthma, post infection cough and atopic cough. The etiologic constituent ratio differed with age.
Objectives：To study whether the abnormal global DNA methylation levels or disturbed promoter methylation pattern of DNA mismatched repair genes increases the incidence of neural tube defects (NTDs). Methods：A hospital-based case-control study was conducted in the Lvliang area of Shanxi Province, China. NTD-affected cases and controls matched in maternal age and gestational age were recruited from county hospitals and maternal and child health hospitals. All subjects were diagnosed by B-mode ultrasound and confirmed by autopsy. The methylation Quantification Ultra Kits (Epigentek) were used to determine the global DNA methylation levels in brain and skin tissues. The Methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA) kits were used to quantify the methylation levels of promoter regions of 7 DNA mismatched repair genes (MLH1，MSH2，MSH6，MSH3，MLH3，PMS2 and MGMT). Results:65 NTD-affected fetuses and 48 normal controls were collected. ① In brain tissue, global DNA methylation levels were significantly decreased in NTD compared with control group (5.3% vs 6.5%，P<0.001). DNA hypomethylation caused a significant 4.98-fold increased risk for NTDs (CI:1.42-17.53). No statistical difference was seen for skin tissue in two groups (13.3% vs 13.1%, P>0.05).② Compared with control group, NTDs group had significantly lower methylation levels in the promoter regions of MSH6（MSH6-301:2.5% vs 3.7%, P<0.05）and PMS2（PMS2-328:5.7% vs 6.7%; PMS2-142:2.0% vs 2.7%, P<0.05）. Conclusions:Global DNA hypomethylation in fetal brain tissue is associated with NTD-affected pregnancy. Disturbed methylation patterns in promoter regions of two mismatched repair genes, MSH6 and PMS2 are associated with NTD-affected pregnancy.
Objectives：To explore the significance of mesangial IgM deposition in childhood primary glomerulopathy. Methods：Clinical and renal pathological data were collected from patients with childhood primary glomerular diseases who had undergone renal biopsies at Peking University First Hospital from June 2005 to June 2011. Patients were divided into two groups: IgM deposit group comprised patients with mesangial IgM deposits and control group comprised patients without mesangial IgM deposits. A retrospective analysis was carried out on all children who met the criteria. Results：Of the 618 children with renal biopsy speciments, 125 children met both clinical and pathologic diagnosis. IgM deposit group included 76 cases, while control group contained 49 cases. There was no difference between the two groups in disease onset age, incidence of hypertension, renal insufficiency, serum total protein, serum albumin, serum cholesterol, CCr or kidney early injury parameters. Serum IgM was significantly higher in IgM deposition group than that in control group (P=0.038). Proteinuria in IgM deposit group was significantly more severe than that in control group (P=0.025). IgM deposit group had a significantly higher incidence of glomerular sclerosis and arteriole injury than control group (P=0.002, 0.039). Whereas the occurrence of glomerulopathy basement membrane thickness in IgM deposit group was significantly lower than that in control group（P=0.000）. There was no significant difference between the two groups when comparing the response to steroid treatment. During the follow-up period, there was no significant difference in the incidence of renal insufficiency between the two groups. Conclusions：The childhood primary glomerulopathy with mesangial IgM deposits has more severe proteinuria and pathological changes than that without mesangial IgM deposits. More attention should be paid on patients with mesangial IgM deposits and the possible histological transition to focal segmental glomerulosclerosis.
Objectives：To assess preterm birth on the intellectual development and the effect of early intervention. Methods：The Cochrane library,PubMed,EMBASE,Wanfang,CNKI and VIP were searched from January 1980 to November 2011. Two reviewers assessed the quality of included studies and extracted data. All included studies were graded on sequence generation,allocation concealment,blinding,incomplete outcome data,selective outcome reporting, and other sources of bias.Statistical analysis was performed employing RevMan 5.0.13 software. Heterogeneity of the included articles was tested to select proper effect model. Results：Eighteen studies were included to assess influence of preterm birth on intellectual development, fifteen studies were included to analyze the effect of early intervention to preterm infants. Sequence generation, allocation concealment, blinding, the integrity of outcome data, and selective outcome reporting were mentioned by 9, 9, 9, 12 and 10 studies respectively. None of studies mentioned other sources of bias. The intelligence quotient (IQ) of preterm infants was significantly lower than term infants, SMD=-11.62 (95％CI: -13.21 to -10.03). The stratified analysis on the relationship between IQ and gestational age (GA) showed that IQ was lower in lower GA. IQ reduced from 112.7 for infants with GA of 34-36 weeks to 82.1 for those with GA of 25 weeks. The effect of early intervention on preterm infants was evaluated based on MDI and PDI by using the Bayley Scales of Infant Development (BSID) at 6, 12, 18, 24, and 36 months at corrected GA. The results showed that MDI and PDI were increased obviously in the intervention group. Five studies reported that early intervention reduced the incidence of mental abnormalities in preterm infants (OR= 0.25，95％CI: 0.15 to 0.41). Conclusions：The results showed IQ of preterm infants was significantly lower than the term infants. Lower IQ was seen in infants with lower GA. Early intervention could significantly improve the IQ of preterm infants and reduce the incidence of mental abnormalities. Long term effect of early intervention on IQ needs long-term follow-up studies and evaluation.
Objectives:To investigate the diagnosis and therapy of congenital sucrase-isomaltase deficiency in children. Methods:The characteristics of clinical manifestation,diagnosis and effects of the therapy of three congenital sucrase-isomaltase deficiency cases were summarized. Results:In three children, aged 16 months to 19 months, the bowel movement was normal during breast feeding after birth, diarrhea began when weaning breast milk and fed on rice paste or rice porridge, the stool was yellow and watery-like or loose, 7-10 times a day. Physical examinations from the three children showed mild to moderate protein-energy malnutrition. Sucrose challenge tests showed the highest promoted postprandial blood glucose values compared with the fasting blood-glucose were 0.1 (2.0%), 0.1 (2.6%) and 0.9 (19.1%) mmol·L-1, respectively. All of the three children had yellow and watery-like stool 2-4 hours after the sucrose challenge tests. Compared with the fasting blood-glucose, glucose challenge tests showed the highest promoted postprandial blood glucose values were 1.5 (30.6%), 2.3 (65.7%) and 4.4 (107%) mmol·L-1, respectively. Nobody had diarrhea after the glucose challenge tests. When the three children got diagnosed, food containing sucrose and starch was stopped. One to two days after feeding with paste made of soybean and pork, the stool turned to be normal. Three cases had been misdiagnosed as long as 9 to 12 months. Congenital sucrase-isomaltase deficiency was easy to be misdiagnosed as lactose intolerence and milk-protein allergy, but lactose free formula and free amino acid formula could not improve the diarrhea respectively. It also should be differentiate with celiac disease, crohn′s disease, intestinal parasitosis,lymphoma and lymphosarcoma. Follow-up: The first case could tolerate small quantity rice and noodle when he was 3 years and 4 months old, and he could tolerate normal dose rice and noodle when he was 4 years and 4 months old. He still could not tolerate sucrose. The second case could tolerate small quantity rice and noodle when he was 3 years old . The third case could not tolerate rice and noodle till now (2 years and 1 month old). Conclusions:When congenital sucrase-isomaltase deficiency is suspected, the diagnosis can be made according to the classic history (diarrhea began after weaning the breast milk, the diarrhea can rapidly recovered after avoiding food containing sucrose and starch, along with a positive sucrose challenge test).
Objectives:To study the clinical manifestations, diagnosis and treatment of dilated cardiomyopathy with abnormal fatty acid metabolism in children. Methods:The clinical manifestations, laboratory examinations, treatment and follow-up evaluation of children identified as dilated cardiomyopathy with abnormal fatty acid metabolism at Beijing Anzhen Hospital from January 2007 to June 2011 were retrospectively reviewed. Results:Nine children were enrolled, including 5 males and 4 females, onset age ranging from 11 months to 18 years, course of disease from 0.5 to 4.5 years. Nine cases were all fatigued with one or more symptoms as muscle weakness (4 cases), limb proximal muscle atrophy (1 case), seizures (2 cases) and growth retardation (2 cases). Nine cases were all found with varying degrees of hepatomegaly accompanied by liver dysfunction (8 cases), elevated CK, CK-MB, increased lactate dehydrogenase (LDH) (7 cases), elevated lactic acid( 6 cases), hypoglycemia ( 2 cases), high blood ammonia ( 3 cases). Increased left ventricular end-diastolic diameter and decreased ejection fraction were measured by echocardiography in cases. Two cases showed myogenic damage by electromyography. Tandem mass spectrometry examination revealed that free carnitine was significantly higher in 1 case, normal in 3 cases while decreased in 5 cases; acylcarnitine increased in 7 cases, decreased in 1 case, normal in 1 case. The primary clinical diagnosis was carnitine palmitoyltransferase Ⅰ deficiency in 1 patient, systemic carnitine deficiency in 1 patient, multiple acyl-CoA dehydrogenase deficiency in 4 patients, long-chain acyl-CoA dehydrogenase deficiency in 3 patients. Based on conventional treatment of heart failure to all patients, supplement of L-carnitine and vitamin, dietary guidance including low-fat and preventing from starvation achieved better clinical, biochemical, cardiac imaging and function improvement. Conclusions:Metabolic screening should be performed in children with cardiomyopathy suspectedly secondary to fatty acid oxidation disorder. This may help define early diagnosis, therapeutic strategy and improve the prognosis.
Objectives:To understand the influence of measles vaccination on clinical manifestations of measles in children, different characteristics of measles in infants and children in order to improve early diagnosis of measles by analyzing the characteristics of measles cases with laboratory confirmed etiological data. Methods:Clinical data were collected from children who visited the Department of Outpatient Infectious Diseases and hospitalized with clinical diagnosis of measles and confirmed by measles specific IgM and measles virus N gene fragment from January 2002 to December 2010. Measles specific IgM antibodies were tested using serum samples with ELISA. Measles virus N gene fragment was amplified from specimens of throat swabs and fresh urine by reverse transcription-polymerase chain reaction (RT-PCR). Analyses were performed in vaccinated and unvaccinated cased separately. Results:① In total, 207 cases of measles in children with etiological diagnosis were analyzed, including 123 males and 84 females, 53 vaccinated and 154 unvaccinated. Age distribution ranged from 0 to 15 years, including 69 cases (33.3%) of younger than 8 months (who had not reached the age for primary measles vaccination), and 45 cases (21.7%) of younger than 1 year of age. ②Cases with Beijing local residency was more common in vaccinated group than that in unvaccinated group. The peak incidence was found in April for all cases in two groups. 15.4% (24/154) cases with known exposure history in measles unvaccinated group and in unvaccinated group and 16.9% (9/53) in measles vaccinated group, with no significant difference between two groups. ③The proportions of measles with symptoms of mucosa spots ( Koplik spots) and cough were significantly lower in vaccinated group than in unvaccinated group while the other symptoms had no significant difference between two groups. ④ Of 154 unvaccinated cases, 97 were younger than 1 and 57 older than 1 year old. Symptoms of eyes was more common in the subgroup older than 1 year of age. Conclusions:Measles cases with younger age have been increasing in recent years in Beijing. More and more measles cases for children have presented with atypical clinical manifestations. Most of the measles cases in this study were younger than 8 months of age which is before EPI for measles vaccination or older than 8 months of age but missed vaccination. The data indicated that strengthening measles immunization program was necessary, and early and rapid etiological diagnosis for atypical measles was important for early isolation of the cases.
Objectives：The aim of this study was to establish FeNO reference values for healthy school-aged children in Suzhou according to the international guidelines, and to assess the determinants of FeNO. Methods：Children aged 6-14 years were recruited from two public schools in Suzhou. The subjects completed a respiratory questionnaire, and were examined with measurements of FeNO, spirometry and blood eosinophil. Healthy children were screened to establish reference values of FeNO. FeNO was measured with a chemiluminescence analyzer according to American Thoracic Society guidelines (single breath online, exhalation flow 50 mL·s-1). The associations between different determinants (sex, age, height, weight, BMI, peripheral blood EOS count, FEV1/FVC, lung function) and FeNO were analyzed. Results：Finally, a total of 450 children participated in the study, and 225 children fulfilled the inclusion criteria of healthy subjects (107 boys and 118 girls). FeNO data were skewed, and met normal distribution after natural logarithm transformation. The geometric mean of FeNO in 225 children was 11 parts per billion (ppb) (95%CI: 5-28 ppb), the minimum value was below 5 ppb, and the maximum value was 83 ppb. The mean value was 11 ppb (95% CI：5-31 ppb) for boys and 11 ppb (95%CI: 5-25 ppb) for girls. In stepwise multiple regression analysis, peripheral blood EOS count was found to be the best independent variable for the regression equation for FeNO (r=0.291, P<0.000 1). Height (r=0.148, P=0.027) and FEV1 (r=0.138, P=0.038) were significantly correlated with FeNO. FeNO in children aged >9 years was significant higher than that in children aged ≤ 9 years(P=0.002). Sex, weight, BMI and FEV1/FVC were not associated with FeNO. Conclusions：FeNO reference values of healthy children aged 6 to 14 years in Suzhou should be considered to fall between the following ranges: 5-28 ppb, which is slightly higher than European and American children. FeNO levels in healthy school-aged children appear to be affected by EOS count and height significantly, followed by FEV1, and not influenced by sex, age, weight, BMI and FEV1/FVC.
Objectives：The role of NK cell function as an etiological or prognostic factor in EBV-HLH remains unclear. The present study tried to investigate the expression of NK cell surface activating receptors and CD107a in EBV-HLH patients. Methods：EBV-HLH patients and age- and sex-matched normal controls were selected from August 2009 to May 2011 in Beijing Children′s Hospital. Multicolored immunofluorescence flowcytometric analysis was performed to detect NK cellsurface activating receptors, perforin and IL-2 stimulated NK cells in peripheral blood from EBV-HLH patients and controls. Results:Eight cases were enrolled in EBV-HLH group and 8 normal children were enrolled in control group. ①There was no statistical difference between EBV-HLH patients and normal controls in NK cell surface activating receptors (NKP30, NKP46, NKG2D, DNAM-1 and 2B4), perforin or basic CD107a expression (P>0.05). ②There was no statistical difference in basic CD107a, CD107a/K562, CD107a/2B4/P815, CD107a/NKG2D/P815 or CD107a/2B4/NKG2D/P815 expression between EBV-HLH group and control group. ③Basic CD107a expression, CD107a/K562 and CD107a/NKG2D/P815 expression in normal controls significantly changed 48 hours after IL-2 stimulation, while such difference was not seen in EBV-HLH patients (P>0.05). Conclusions:The present results indicated that there may be some defects in responding to IL-2 in EBV-HLH patients.
Objectives:To study the clinical and pathological feature of the children infected with influenza A H1N1 virus. Methods:The clinical material and result of the autopsy of a died child infected with influenza A H1N1 virus were analyzed. Results:A child,one year and four months old, onset with fever and cough, progressed to dyspnea and lung failure in one day. The throat swab showed that the nucleic acid detection of influenza A H1N1 virus was positive by (real time PCR) RT-PCR recommended by WHO and National Influenza Reference Center of China. Streptococcus pneumoniae grew in the trachea secretion bacteria culture. Autopsy showed the main lesions in the lung. Gross: 90% of the section in the lung presented with consolidation, taupe, pleural adhesion wildly, involved pericardium exine. Microscopic: diffuse alveolar interstitial tissue was broadened，most of the alveolar walls were covered by substance like hyaline membrane,more than 90% of the alveolar spaces were full with inflammatory exudate，neutrophils，lymphocytes，monocytes and giant cells. Some of the alveoli collapsed and closed, some of the alveoli showed ectasia and fusion. Inflammatory exudate was found in the bronchiole and bronchial intralumen. There were more lymphocytic infiltration in tip of the wall. Lung membrane was edematous. There were more lymphocytic infiltration in tip of the tracheal mucosa, or focal mucosal erosion. There was no obvious pathological change in the brain,heart, liver, spleen , kidney, adrenal gland, pancreas or gastrointestinal tract. Conclusions:This H1N1 case with severe pneumonia was rapidly progressed and featured with pathological changes in his lung, such as inflammation, exudative and hyaline membrane formation. Main causes of the death were acute respiratory distress syndrome, respiratory and circulatory failure.
Objectives:To examine the normative baseline microglia (MG) development in C57B/L fetus and early infants especially the most vulnerable period of oligodendrocyte progenitor cells (OPCs) injury, and to explore the mechanisms of activated microglia dependent white matter injury following LPS -induced intrauterine infection. Methods:① The developmental profile of MG in mouse cerebral white matter was examined, immunocytochemistry with MG and OPCs specific markers (Tomato lectin and O4+) were used to identify the normal distribution of MG and its relationship with OPCs. ② Intrauterine infection brain injury model was established by intrauterine injection of LPS（5, 10 and 20 μg·mL-1 as group A, B and C）and compared with PBS control group to further verify the causal relationship of MG activation to OPCs damage using special antibodies to MG (CD68) and OPCs (O4+). ③ Western blotting was used to test the Toll like receptor-4 (TLR-4) protein expression in peri-ventricular white matter tissue. ④ Cytokine concentrations released by activated MG were measured by ELISA and the relationship to brain injury was analyzed. Results:① MG (Tomato lectin +) expression was low in the middle gestational age (GA) and the expression peaked at late GA and earlier after birth which was mainly distributed to the periventricular white matter and correlated closely to the development of OPCs between 10 gestational days and 0 day after birth (P0). ② Quantitative analysis with CD68+ and O4+ showed increased density of activated MG and OPCs proportionally in control group. There was a significant increase of CD68+ cells following increasing dose of LPS, but there was no significant difference between group B and C. Contrary to the significant increase of CD68＋ cells, there was a significant decrease of O4+ cells in group A, B and C. ③ No TLR-4 protein expression was found in control group, dose dependent significant increase of TLR-4 protein was found in group B and C. ④ Pro-cytokines IL-2 and TNF-α levels released by MG significantly increased with LPS dose increased, which were higher than control group, whereas the SOD levels were significantly lower than control group. Conclusions:The primary finding of a transient, developmental dependent overabundance of CD68-activated MG in the cerebral white matter of the C57B/L pups suggested a potential "priming" effect of this area on infectious brain insults characterized by activation of MG, particularly PVL.
