Objective To evaluate the safety of oral use of nimesulide in children. Methods Clinical studies involving nimesulide orally used in children were identified from PubMed，EMBASE，Cochrane Library（Issue 3th,2011）, Cochrance Clinical Trials Database (CENTRAL)，CBM, CNKI, VIP and Wanfang Database. Other resources were searched manually，including State Food and Drug Administration (SFDA) Drug Adverse Event Report, WHO Pharmaceuticals Newsletter, MHRA Drug Safety Update and FDA Drug safety Newsletter. Data were extracted and evaluated with a specifically data extraction form, the tool recommended by Cochrane was used for risk of bias assessment and RevMan 5.0 software was used for meta-analysis. Casuality of case reports was assessed with WHO-UMC system. Results Cohort study and case controlled study on safety of oral use of nimesulide were not retrieved. A total of 53 clinical studies were included, involving 43 prospective controlled studies, 9 case reports and 1 countrywide post-marketing surveillance report. Results of randomized controlled trials showed that adverse events reported in children using nimesulide included gastrointestinal reaction, hypothermia, skin rash, nervous system reaction (somnolence and irritability) and hepatic enzyme elevation. Nimesulide group had statistically lower incidence of gastrointestinal events, higher incidence of hypothermia and nervous system reaction and similar enzyme elevation compared with that using ibuprofen and paracetamol. ② Two out of 3 cases reported severe hepatotoxicity died，2/3 were probably and 1/3 was possiblely caused by nimesulide. ③ Surveillance of nimesulide in China had not been published by (SFDA). The countrywide post-marketing surveillance in India, involing 4 092 children, reported 13 cases with renal reaction, but no hepatotoxicity was reported. ④ China SFDA modified the instructions of nimesulide in 2008, baned its using in children under 1 year old and used not for more than 3 d for the fever. European Medicines Agency (EMA) assessed the risks and benefits of nimesulide in 2007, limited nimesulide using only for pain, not used for fever, the treatment not more than 15 d, and baned the using in children under 12 years old. Indian Health Ministry baned children aged under 12 years to use nimesulide in February 2011. Conclusions The incidence of gastrointestinal reaction of nimesulide by oral use in children may be less than that of ibuprofen and paracetamol, while the incidence of hypothermia and nervous system reaction may be more than that of ibuprofen. The incidence of hepatic enzyme elevation of nimesulide may be similar with that of ibuprofen and paracetamol. Further study on severe hepatotoxity is needed to understand its relation to nimesulide.
Objective Many countries analyzed the trend of hour-specific transcutaneous bilirubin after birth and developed hour-specific transcutaneous bilirubin nomogram for predicting the risk of neonatal hyperbilirubinemia. The predictive value of hour-specific transcutaneous bilirubin nomogram for neonatal hyperbilirubinemia was systematically reviewed. Methods The Cochrane library, PubMed, OVID, Springer, CNKI, VIP, Wanfang from January 1990 to March 2011 were searched. Two reviewers assessed the quality of including studies independantly, extracted data. Statistical analysis was performed employing Office Excel 2003 and SPSS 16.0. Results Ten studies were included. Six studies were assessed as B-class, four studies were C-class. The hour bilirubin percentile curve values of different countries and races showed some differences. India had the highest bilirubin percentile curve values, followed by Greece, Israel and China, and United States. In the high-risk areas, the rate of bilirubin within 24h after birth increased the fastest; the rate of bilirubin within 36 h after birth increased the fastest in the medium and low risk areas. India had the highest increased rate of bilirubin, followed by China, United States, Israel, and Greece. In the high-risk areas, the sensitivity of hour-specific transcutaneous bilirubin nomogram for predicting neonatal hyperbilirubinemia was 26.9%-75.0%, the specificity was 89.4%-97.3%; the sensitivity and specificity was 78.7%-100.0% and 48.3%%-82.3% respectively for the medium-risk areas, as well as 98.7%-100.0% and 24.4%-56.1% for low-risk areas. AUC was 0.766-0.990. Thailand had the highest accuracy for predicting neonatal hyperbilirubinemia, followed by India and China, and United States was the lowest. Conclusions The hour-specific transcutaneous bilirubin nomogram showed high predictive accuracy for neonatal hyperbilirubinemia, and was valuable in clinical application. The hour bilirubin percentile curve values vary among different countries and races. It is suggested that countries develop hour-specific transcutaneous bilirubin nomogram based on their own countries' value of bilirubin change and take it as the reference standard of intervention.
Objective To identify the patterns of peadiatric renal biopsy histopathology and its variation in the past 31 year in a single center and implication on modification to the clinical indications. Methods A retrospective study was done on all renal biopsies performed from January 1979 to December 2009. All the cases were recruited consecutively from Department of Nephrology and Rheumatism in Children's Hospital of Fudan University and were categorized into 3 periods: period Ⅰ (1979 to 1989), period Ⅱ (1990 to 1999) and period Ⅲ (2000 to 2009). Results A total of 1 419 renal biopsies were performed in 31 years. Mean age was (8.08±3.46) years (6 months-18 years). Major clinical presentations were haematuria (38.8%, 551/1 419), followed by primary nephrotic syndrome (30.9%, 439/1 419) and renal manifestations secondary to systemic diseases (23.8%, 338/1 419). Primary glomerulonephritis (PGN) accounted for 63.9% (907/1 419) of the total patients, secondary glomerulonephritis (SGN) 23.2% (329/1 419) and hereditary glomerulonephritis (HGN) 12.1% (172/1 419). Common causes of PGN were IgAN (26.6%, 241/907) (98 out of 241 were diffuse proliferative type) and MCD (23.0%, 209/907) (120 out of 209 with IgM deposition). FSGS only accounted for 3.0% (27/907). The percentage of IgAN was relatively high and that of FSGS was low. In SGN, HSN (47.1%, 155/329) (72 out of 155 were focal segmental proliferative type) ranked first and followed by LN (28.6%, 94/329) (43 out of 94 were diffuse proliferative LN). In HGN, thin basement membrane nephropathy (TBMN) accounted for 80.8% (139/172) and Alport syndrome accounted for 17.4% (30/172). During 31 years, the composition of PGN decreased while that of HGN increased MsPGN and HBV-GN were on the top in period Ⅰ and decreased in period Ⅱ and Ⅲ. IgAN and HSN had a rise in composition. Most haematuria with proteinuria patients had IgAN (42.6%, 84/197) while most isolated microscopic haematuria had TBMN (52.9%, 109/206). Most primary nephrotic syndrome patients especially steroid dependent and frequently relaps (SDFR) had MCD (61.8%, 97/157). Conclusions It is time for us to reflect the renal biopsy indication. For SDFR, the renal biopsy should be performed for those who are starting to use immunosuppressive drugs such as cyclosporin A or tacrolimus. The indication of renal biopsy for isolated microscopic hematuria should be stricter.
Objective To study the effect of birth weight on childhood and adulthood hypertension. Methods All study participants came from whole population of 3 198 subjects (1 700 males, 53.2%) of the national project of the 7th Five Year Plan, named "Beijing children and aadolescents blood pressure study (BBS)". Baseline study was conducted in 1987, and data including height, weight and blood pressure at baseline and 2010 (March 2010 to March 2011) were analyzed. Blood pressure was measured by auscultation on right arm. Korotkoff Ⅰ, Ⅳ and Ⅴ were recorded as systolic blood pressure (SBP) and diastolic blood pressure (DBP-K4 and DBP-K5). Birth weight, premature delivery and breast feeding were recalled by participants' mothers. Childhood hypertension was defined as SBP and（or） DBP equal to or greater than the 95th percentile for age and gender. Adulthood hypertension was diagnosed as SBP ≥140 mmHg and(or) DBP ≥90 mmHg or the subjects who were taking anti-hypertension drugs presently, according to the China Guideline for Hypertension Prevention and Control issued in 2009. Low birth weight was defined as <2 500 g and macrosomia as ≥4 000 g. Multiple regression models were used to analyze the influence of birth weight on childhood and adulthood blood pressure levels and hypertension. Results A total of 1 126 adults (35.2%) from the BBS cohort were followed up and participated the clinical examination ,among which 936 subjects (492 males, 52.6%) with valid birth weight were analyzed. The proportion of low birth weight and macrosomia were 3.2% (30/936) and 8.3% (78/936), respectively. The prevalence rates of hypertension at childhood and adulthood were 11.0% and 13.4%, respectively. Trend of negative correlation between birth weight and childhood and adulthood SBP was observed in female, but it did not reach statistical significance (P>0.05). Relationships between birth weight and childhood SBP and DBP varied among birth weight categories and genders. With age, body mass index, premature delivery and breast feeding adjusted, relative risks (RRs) of low birth weight predicting female hypertension in childhood and adulthood were 500(1.32-18.88) and 5.84(1.05-32.65), respectively. However, in male, low birth weight was not statistically correlated with hypertension at childhood or adulthood. The relationship between macrosomia and childhood or adulthood hypertension was not significant in either males or females. Conclusions Relationships between birth weight and childhood blood pressure differed in low birth weight, macrosomia and normal birth weight groups, or in males and females. Low birth weight may increase the risk of female hypertension at both childhood and adulthood.
Objective Human glutathione S-transferases (hGSTs) play a crucial role in the biological detoxification processes of drugs and xenobiotics. In drug metabolic process, the gene polymorphism caused by a homozygous or heterozygous deletion of the GSTM1 and GSTT1 genes was associated with the metabolic speed of glutathione S-transferases. The aim of this study was to investigate the association between gene polymorphisms and the metabolic phenotype of GSTM1 and GSTT1 in normal Chinese Han children, to provide an important theoretical basis for guiding the clinical treatment of drugs which metabolic by liver. Methods Chinese Han healthy children were identified who were randomly sampled from 2005 to 2010 in healthy center of Beijing Children's Hospital. The mean age of them was 5.425 years, ranged from 2 months to 14 years. The participants with positive history of diagnosed cancers, psychiatric disorders, asthma, cataract and cardiovascular disease showing significant association with hGSTs polymorphism were excluded. Demographic and medical information of these children was obtained from the patients' files. Genomic DNA was extracted from peripheral blood by EDTA anticoagulation, using a standard salting-out procedure. The concentration and purity of DNA were estimated spectrophotometrically. Genotyping was carried out by using traditional PCR-RFLP method. Further comparison between our existing data and previously reported frequencies in other ethnic populations, was performed to determine inter-ethnic differences. Results A total of 786 Chinese Han healthy children (486 males and 300 females) were enrolled into the study. In the study population, homozygous deletion (*0/*0) referring to slow metabolism was detected in 59.3% (n=466) for GSTM1 gene and 58.4% (n=459)for GSTT1 gene of the subjects, GSTM1 and GSTT1 homozygous deletions (*0/*0) respectively. The heterozygous deletion （*1/*0） referring to middle metabolism was detected in 34.0%(n=267) for GSTM1 gene and 35.1% (n=276) for GSTT1 gene of the subjects, respectively. The homozygote of non-deletion (*1/*1） referring to fast metabolism was detected in 6.7%(n= 53) for GSTM1 gene and 6.5%(n=51) for GSTT1 gene of the subjects, respectively.There was no co-expression of GSTM1 and GSTT1. And there were no significant statistical differences in gene copy number variation frequency between different genders. The comparisons of GSTM1 and GSTT1 gene genotype frequencies among worldwide populations showed different distribution patterns in Asians, Black and Caucasians. The homozygotes of deletion of the DNA fragments of interest for GSTM1 and GSTT1 gene were more common in Asia population. Conclusions In this study, GSTM1 and GSTT1 slow metabolism (indicated by *0/*0 genotype) was more prone in Chinese Han children. The distributions of GSTM1 and GSTT1 gene polymorphisms varied among different races or regions. It provided an important theoretical basis for formulate treatment plans which suitable for Chinese Han children aiming at the hepatic metabolism drugs. Meanwhile, individualized medical treatment may be fulfilled in Chinese Han children, such as antitubercular treatment. However, observing the frequencies of genetic polymorphism will be insufficient in the absence of any supporting clinical data on catalytic or functional activity concerning the effect of a given genetic variant on the future research, it is planed to present a complete analysis with respect to the role of these variants in influencing the serum levels and therapeutic efficacy of drugs.
Objective To investigate the levels of the enteroovirus 71 and C4 genetype antibody (EV71-lgG) among children in Guangzhou area, and the relationship between EV71-IgG and hand, foot and mouth disease (HFMD). Methods EV71 diagnostic antigen was prepared from EV71 C4 genotype samples isolated from children with HFMD in Children's Hospital, Guangzhou Women and Children's Medical Center to establish the method of diagnostic EV71-IgG kits and laboratory evaluation. Blood samples of healthy children confirmed to be without fever and symptoms of HFMD by physical examinations in our hospital were collected from January to March in 2010 to be tested for EV71-IgG antibody. Swab specimens were collected from outpatient and inpatient children with HFMD in our hospital in 2010 to be tested for specific EV71 nucleic acid. Results ① The cut-off value of kit established by our laborary was 0.148. Compared with the cell neutralization tests, the accordancy rate was 100% for positive rate and 92% for negative rate. There was no cross reaction with Coxsackie A16 virus antibody. ②Serum samples were from 819 healthy children, including 481 males and 338 females. EV71-IgG positive rate in children aged under 1 year was the highest (60%, 60/100), and EV71-IgG positive rates of -2-year-old, -3-year-old, -4-year-old, -5-year-old and -14-year-old groups were 39.3%（72/183）, 12.9%（15/116）, 27.1%（38/140）, 14.2%（16/113） and 22.8%（38/167）。There was no significant difference between different genders. ③ A total of 4 780 children with positive EV71 were enrolled, including 3 070 males and 1 718 females. There were 310（6.5%） children in <1-year-old group, 1 157（24.2%） in -2-year-old, 1 337（280%） in -3-year-old, 1 094（22.9%） in -4-year-old, 450（9.4%） in -5-year-old, 432（9.0%） in -14-year-old groups. ④ In each group EV71 - IgG antibody positive rate was opposite to the tendency of EV71 positive rate. In <1-year-old group, EV71 - IgG positive rate was the highest while EV71 positive rate was the lowest. In -3-year-old group, EV71 - IgG positive rate was the lowest while EV71 positive rate was the highest. Conclusions In Guangzhou area, EV71-IgG positive rate in children aged under 1 year was the highest. EV71 positive rate was significantly associated with EV71-IgG positive rate.
Objective To analyze the variation of blood glucose (BG) and relevant markers in critically ill children and its association with stress hyperglycemia． Methods Children aged under 14 years with critical disease in Guangzhou Women and Children's Medical Center PICU from January 2007 to April 2008 were enrolled. Within 24 h after entering PICU, recruited subjects were classified into hyperglycemia group and normoglycemia group according to BG greater than 6.1 mmol·L-1 or not. Additional healthy children attending regular physical examination in the same period were selected. Children in the two patient groups with BG<4.0 or >10.0 mmol·L-1 twice were excluded. BG, cortisol, growth hormones (GH), immune and cytokine levels and lipid profiles were measured dynamically on day 0 (the day admitted), day 3 and day 5 respectively. Results Ten children in normoglycemia group, 53 in hyperglycemia group and 15 in normal group were enrolled. ①In hyperglycemia group cortisol secretion peak was seen on day 0, and then declined. ②GH and insulin levels at 3 time points in hyperglycemia group were significantly higher than those in normoglycemia and control group. GH or IGF-1 levels in normoglycemia group did not differ significantly. ③The IGF-1 levels in hyperglycemia and normoglycemia groups kept increasing through day 0 to day 5, no significant difference between groups was observed. The IL-6 and triglyceride levels of hyperglycemia group on day 0 were significantly higher than those of other two groups, however, the high density lipoprotein cholesterol level was lower than that in normoglycemia group. ④Eight cases among hyperglycemia group died (8/53,15.1%). The BG, cortisol and insulin levels of the died cases were significantly higher than those of survival cases. Conclusions Elevated cortisol and insulin, accompanied abnormalities in cytokins and lipid profiles may be associated with the development of stress hyperglycemia in critically ill children, and may indicate poor prognosis.
Objective To investigate the methylation status of ITGAL gene promoter and the effects of mRNA expression in T cells of patients with biliary atresia (BA). Methods The BA infants were recruited from the patients diagnosed as BA by surgery at the Children's Hospital of Fudan University. At the same time, the control group was collected from the patients diagnosed as inguinal hernia by surgery from the same hospital. CD4+ and CD8+T cells were isolated from the peripheral venous blood of infants in BA and control groups. Of them the CD4+ and CD8+T cells of 5 infants with BA were cultured, and then treated with 5-azaC. Genomic DNA and mRNA were extracted from CD4+ and CD8+T cells. Bisulfite DNA sequencing was performed to determine the methylation status of ITGAL gene promoter. The mRNA expression of ITGAL was detected using RT-PCR. Results Twenty-five infants with BA (20 were divided into BA group, 5 were treated with 5-azaC) and 20 controls were analyzed. ①The promoter region (-250 to 250 bp) of the ITGAL gene was unmethylated in BA and control groups. The average methylation level of ITGAL gene promoter region (-1450 to -950 bp) in BA group was higher than that in control group (P<0.001 for CD4+T cells and P=0.02 for CD8+T cells). The average methylation levels from CD8+T cells in BA compared with that in control group and the levels from CD4+T cells compared with that from CD8+T cells in control group were not significantly different (P>0.05). The average methylation levels of ITGAL gene promoter were lower in CD4+ and CD8+T cells in 5-azaC treated group than those in 5-azaC untreated group (P<0.001). ②The mRNA expression of ITGAL in CD4+ T cells in BA group was lower than that in control group (P=0.007) and CD8+T cells in BA group (P=0.013). The mRNA expression of ITGAL in CD8+T cells between BA and control groups and the difference between CD4+ and CD8+T cells in control group were not significantly different (P=0.266 and 0.227). The mRNA expressions of ITGAL in CD4+ and CD8+T cells in 5-azaC treated group were higher than those in the 5-azaC untreated group (P=0.013 and 0.025). Conclusions ITGAL gene promoter in peripheral blood CD4+ T cells from infants with BA is significantly hypermethylated, which impacts the mRNA expression of ITGAL, and may cause the abnormal T cell function.
Objective To analyze the expression of insulin receptor sustrate 1 (IRS-1) and 2 (IRS-2) mRNAs and proteins of pancreas, liver and skeletal muscle tissue of intrauterine growth retardation (IUGR) rats, and to investigate the mechanism of insuline resistance development. Methods IUGR model was established by using gestational low-protein diet method. The model rats were then randomly divided into IUGR group and control group (receiving regular diet during pregnancy). IRS-1 and IRS-2 mRNAs were detected in pup rat pancreas, liver and skeletal muscle at 0, 3 and 8 weeks after birth. At the same time, the expressions of IRS-1 and IRS-2 proteins were examined with Western blot method. Fasting blood glucose, serum insulin levels were tested in pup rats at 3 and 8 weeks after birth, and insulin resistance index was calculated. Results ① The mean birth weight and body weight at the 3rd week of pup rats in IUGR group were significantly lower than that in control, whereas it reversed at the 8th week. ② The IRS-2 mRNA and protein expression levels among pancreas and liver tissue of IUGR group were lower than those of control group. There was no significant difference in IRS-1 mRNA and protein expression levels between IUGR and control groups. Skeletal muscle IRS-1 mRNA and protein expression levels at each time point were lower than those of control group. IRS-2 protein expression levels of IUGR group did not differ from control group. ③ Skeletal muscle IRS-1 mRNA and protein expression level decreased more than pancreas and liver at the 8th week. Liver IRS-2 mRNA and protein expression level decreased more than pancreas and skeletal muscle. ④ There was no signigicant difference in blood glucose between IUGR and control groups at the 8th week. The level of insulin and FIRI in IUGR group increased more than that in control group. Conclusions The IRS-1 and IR-2 mRNA and protein expression in pancreas,peripheral tissue and liver declined , with most significant decline in liver. It may be one of the mechanisms of insulin resistance.
Evidence mapping is an approach of summarizing research evidence, which has a comprehensive search focusing on a well definite question, summarize basic characteristics and research result of researches in the fields, displays the best evidence and the problems for the users, improves the effectiveness of health care research for decision-making managers, clinicians, guideline developers, patients, researchers, educators. The stages of the framework for conducting evidence mapping were: question development, question prioritization, evidence search & selection, data extraction, study appraisal & synthesis, evidence gaps analysis. Evidence mapping can help policymakers, clinicians, researchers, research organization select the study direction and present the best evidence for guideline maker, patients, and clinicians. However, evidence mapping do not assess the quality of included studies and affiliate the study data, just describe the characteristics and results of included studies, which made overall effect weak. Therefore, system of evidence mapping methodology should be further studied and improved.
Abstract: Bronchopulmonary dysplasia(BPD)is one of the most serious complications of premature infants.Corticosteroids is the most controversial application among the prevention and treatment of BPD. The application of corticosteroids therapy in premature respiratory system diseases was reported early in 1957. In the 1990s, Corticosteroids become the routine drug of the prevention and treatment of BPD. Since 1999, the use of corticosteroids started to decrease because of the corticosteroids therapy complications. In recent years, there are a lot of literatures on corticosteroids therapy BPD were reviewed and reported, but the results are different. The reports have positive results, also have negative results. So the suggestion is that the clinicians should use corticosteroids cautiously with the lowest dose and the shortest course of treatment possible.
