Objective To investigate the efficacy of eradication therapy and antimicrobial resistance rate of Helicobacter pylori (H.pylori) strains among children in Shanghai.Methods From 1st January 2014 to 19th September 2017, patients who were diagnosed as H.pylori infection, completed the eradication therapy and reassessed the H.pylori status in Children's Hospital of Fudan University were enrolled in the restrospective study. All data were extracted from medical record system of the hospital including sex, age at diagnosis, endoscopy findings, rapid urease test (RUT) results, histology findings, microbiological culture with anti-microbial susceptibility results, treatment composition and duration. H. pylori infection was evaluated at least 4 weeks after the completion of the treatment. Negative urea breath test (UBT) or RUT was indicated successful eradication.Results A total of 1 558 patients with the mean age of (8.5±3.1) years and male of 56.5% were enrolled in the study. Abdominal discomfort and non-ulcer disease were common manifestations occurred in 74.6% and 85.0% of the patients, respectively. All patients received the empiric treatment for two weeks (10 days for sequential therapy). Total eradication rate in first-line and rescue therapy was 56.7%(883/1 558). The successful eradication rate was 56.4%(751/1 331) in first-line therapy and 58.1%(132/227) in rescue therapy. No significant difference was observed between the two groups. For first-line therapy, the eradication rate was 57.9% (659/1 139) in OCA/OCAc therapy (omeparaole, clarithromycin and amoxicillin/amoxicillin-clavulanic acid), 31.8%(34/107) in OCM therapy (omeparaole, clarithromycin and metronidazole) and 68.2%(58/85) in other therapies. The eradication rate of OCM therapy was lower than that of the other two groups. For rescue therapy, the eradication rate was 57.6%(87/151) in OCA/OCAc therapy with bismuth, 52.3%(23/44) in OCM therapy with bismuth and 68.8%(22/32) in other therapies. No significant difference was observed among each two groups. The resistance rates to clarithromycin, metronidazole and amoxicillin in 579 strains were 31.8%, 45.1% and 1.4%, respectively. Double resistance rates to clarithromycin and metronidazole were 23.0%. There were 259 strains in successful theatment group and 320 strains in treatment failure group. The latter got higher resistance rates in clarithromycin (44.0% vs 21.9%), metronidazole (52.5% vs 39.1%) and double resistance (32.4% vs 15.3%). Four hundred and seventy-five strains were in first-line therapy group and 104 strains in rescue therapy group. The resistance rates in rescue therapy group were all higher than that in first-line therapy group with clarithromycin (42.3% vs 29.5%), metronidazole (55.8% vs 42.7%) and double resistance (34.6% vs 20.4%).Conclusion The eradication rate of standard triple therapy in children was only 56.4% because of the high resistance in clarithromycin and metronidazole. It may not be suitable as the first-line therapy in clinical practice. Whether increasing the compliance of the patients and the dose of drugs (PPI and amoxicillin) will improve the eradication rate needs further investigation.
Objective To investigate the effects of gestational weight gain (GWG) in women with systemic lupus erythematosus (SLE) on birth weight of their neonates.Methods SLE women and their neonates were recruited from Renji Hospital. Maternal demographic parameters (age, height, pre-pregnancy body weight, education level, GWG, past disease history, gestational age), clinical parameters at the first check-up (systolic and diastolic blood pressure, total cholesterol and triglycerides, fasting blood glucose), and neonatal sex, Apgar Score and birth weight were collected from medical records. Healthy pregnant women and their neonates were matched (1:3) based on age and education level as control. The relationship between GWG and neonatal birth weight was analyzed by the general linear regression.Results A total of 180 women (45 pregnant women with SLE and 135 healthy pregnant women) were included in the current study. The average age and birth weight were 29.0±3.0 years and 3 198.8±501.8 g, respectively. GWG was lower in SLE group than that in control group (12.4±5.5 kg vs 15.0±5.1 kg, P=0.004). The proportion of inadequate GWG in the SLE group was higher than that in the control group (37.8% vs 16.3%, P<0.01). A high GWG was associated with a larger birth weight in all participants. Compared with neonates whose mothers were in the lowest quartile group, neonates whose mothers were in the highest quartile were likely to get an extra birth weight (246.4±234.1g), however, it did not reach a significant difference.Conclusion GWG in SLE women was lower than that of healthy women, which might result in a low birth weight.
Objective To evaluate the clinical effect of professional-parent- hospitalized premature integrated education on extremely low birth weight infants.Methods The study design was historical comparative study. Two consecutive ELBW samples were selected from Children's Hospital of Fudan University. The routine nursing education program was conducted in control group (April 1, 2016 to February 28, 2017). A three-dimensional integrated education program was conducted in the experimental group (April 1, 2017 to March 31, 2018). The Beck Anxiety Inventory (BAI) and the Beck Depression Inventory Version 2 (BDI-II) were used as evaluation tools. The anxiety and depression levels of parents in different education programs were compared. The anxiety and depression levels of parents before discharge and at admission were also compared.Results There were 78 cases and 95 cases of ELBW in the control group and experimental group respectively. Sixty-four cases in the control group and 79 cases in the experimental group were chosen according to the inclusion criteria. The average gestational week of ELBW in the experimental group was less than that in the control group. The proportion of test-tube infants was higher and the duration of mechanical ventilation was longer than that of control group. The difference was statistically significant. However, the length of hospitalization was not longer than that of the control group, and the breast-feeding rate was significantly higher than that of the control group. There was no significant difference in BAI gross score[(18.9±9.8)vs (17.1±10.2)], BDI score[(17.2±8.8)vs (16.0±9.0)] , the number of cases of moderate and severe anxiety[(37/128) vs (36/158)] and depression[(38/128) vs (51/158)] between the experimental group and the control group at admission. The BAI gross scores of the experimental group and the control group at discharge were 11.0±6.5 and 8.5±2.3 lower than those at admission respectively, while BDI scores were 11.3±8.1 and 9.1±7.9 lower. The number of moderate to severe anxiety and depression decreased significantly, and the difference was statistically significant. The improvement values of anxiety and depression in the experimental group were better than those in the control group, and the difference was statistically significant. The scores of anxiety and depression of fathers at admission were higher than those of mothers, and the differences were statistically significant.Conclusion Three-dimensional integrated education program significantly reduced the level of anxiety and depression of ELBW parents. It has been well validated by the historical comparative study in the single-center.
ObjectiveIn order to improve the diagnosis and treatment of constrictive pericarditis (CP) in children by analyzing the etiology, misdiagnostic causes,clinical manifestations, diagnosis,treatment and prognosis of the disease.Methods From January 1996 to January 2018, 78 patients with confirmed CP were enrolled. Data on clinical characteristics, disease manifestations, treatment, and outcomes were collected and analyzed.Results Seventy-eight patients with CP were enrolled. There were 49 males with an average age of 9.4 (1 to 15.4) years and an average duration of 13.4 months (6 days to 7 years). There were 6 cases (7.7%) with history of tuberculosis before the disease, and there were 41 cases (52.6%) with no clear history of acute pericarditis. The first symptom was edema (61/78, 78.2%), and the most common sign was hepatomegaly (72/78, 92.3%). The etiology was unclear in 30 cases (38.4%). The main cause was paragonimiasis infection (19 cases, 24.4%) in patients with clear etiology. Twenty cases (25.6%) were misdiagnosed as other diseases. The positive rate of chest radiography was 70.5%(55/78); chest perspective was 92.3%(45/48); cardiac CT was 100% (31 /31); cardiac MRI was 100%(1/1), and echocardiography was 92.3%(72 /78). Sixty-one patients (78.2%) underwent surgery and were found that the pericardium was uneven. Pathological biopsy was performed in 60/61 surgical patients, with pericardial thickening in 59 cases (98.3%) and normalpericardial thickness in 1 case (1.7%). Pathological examination showed there were 48 cases of non-specific CP (80.0%), 6 cases of tuberculous pericarditis (10.0%), 4 cases of suppurative pericarditis (6.7%), and 2 cases of paragonimal pericarditis (3.3%). Of the 61 surgical patients, 60 were discharged and one died. Seventeen patients gave up surgery, 7 of whom lost contact, and 10 were dead.Conclusion Most of CP were of unknown cause, but in known causes paragonimiasis had a high incidence. The misdiagnosis rate of pediatric CP was high. Docters' better understanding of CP may reduce misdiagnosis. Pathological biopsy had low specificity in determining etiology. Echocardiography was still the first choice for the diagnosis of CP. Pericardial stripping is considered the best surgical procedure in the treatment of CP, and the prognosis is good.
Objective To investigate the clinical,immunological and genetic characteristics of hyper-IgM syndrome(HIgM)caused by copy number variation.Methods We collated the data of a child with HIgM syndrome caused by copy number variation of CD40LG and searched the literature at the same time.Results The patient had recurrent infection and opportunistic infection along with diarrhea,jaundice and portal vein cavernous degeneration. There was no positive family history. Next generation sequencing bioinformatics analysis revealed no pathogenic mutation but copy number variation showed a large deletion of CD40LG gene and PCR also showed no amplification of the cDNA.The level of IgG and IgA decreased and the blood routine test showed neutropenia.The expression of CD40L by flow cytometry was negative and the number of memory B cells and plasma cells reduced. CD40LG gene mutation is the most common pathogenic gene of HIgM syndrome, as well as copy number variation analysis,followed by AICDA gene.Conclusion For children with highly suspected XHIgM,but no suspicious CD40LG pathogenic mutation, it is necessary to consider copy number variation,especially that caused by CD40LG and AICDA gene.
Objective To investigate the characteristics of immunoglobulin (Ig) and T-cell receptor (TCR) gene rearrangement patterns in childhood T-cell acute lymphoblastic leukemia(T-ALL), and its correlation with the clinical and biological characteristics of the patients.Methods The study included 52 newly diagnosed pediatric T-ALL patients enrolled at Beijing Children's Hospital from January 1st, 2005 to December 31th, 2008. Analyze the Ig/TCR gene rearrangement of bone marrow mononuclear cells at diagnosis, including the incidence of TCRB, TCRG, TCRD and IgH gene rearrangements and types, germline fragment usage and junctional characteristics.According to the rearrangement of each gene, it was divided into positive and negative groups, and then the clinical and biological characteristics were compared between different groups.Results ① There were 37 males(71.2%) among the 52 children,aged from 1.8 to 16 years , with a median of 8 years,and the median WBC was 140.5 (2.7-667.1) ×109·L-1. There were 38 cases of IR(73.1%), and 14 cases of HR(26.9%). The follow-up time was 1.2 to 171.7 months and the median follow-up time was 136.3 months. There were 38 cases(73.1%) of long-term complete remission, 10 cases(19.2%) of recurrence and 4 cases(7.7%) of death from other cases. ②The incidence of TCRB, TCRG, TCRD and IgH clonal gene rearrangement was 85%, 85%, 38% and 21%, respectively. Ninety-four percent of the children were detected at least one gene rearrangement, and 88% of the children were at least examined two gene rearrangements. The TCRB, TCRD, TCRG, and IgH rearrangements were dominated by complete Vβ-(Dβ)-Jβ, Vδ-Jδ, VγI-Jγ1.3/2.3, and DH-JH incomplete rearrangement, respectively. Different combinations of germline gene segments resulted in the combinatorial diversity, and the deletion and random insertion of nucleotides at the junction sites created an enormous junctional diversity. ③Among the ten relapsed children, six were compared the Ig/TCR gene rearrangement pattern between diagnosis and recurrence,and four patients had recurrence of Ig/TCR gene rearrangement pattern at the time of initial diagnosis and two patients changed. ④The positive rates of SIL-TAL1 fusion gene were 0 in 11 patients with positive IgH rearrangement and 34.1% (14/41) in 41 children with negative IgH rearrangement,P=0.025 . ⑤The high-risk ratio of TCRB gene rearrangement positive group (20.5%, 9/44) was lower than that of negative group (62.5%, 5/8), P=0.025. The remission rate at the 33rd day of the TCRB or TCRG gene rearrangement positive group (89.4%, 42/44) was higher than that of the negative group (10.6%, 5/8), P=0.022, and the ratio of MRD level ≥10-3 on the 78th day (10.8%, 4/37) was lower than the negative group (50.0%, 3/6), P=0.045.Conclusion The usage of germline fragments of clonal Ig/TCR gene rearrangements and the DNA sequence of their junction regions were diverse, which was helpful for further screening of MRD markers of T-ALL in children.
Objective This study aimed to explore the pathogens and the antibiotic resistance in consecutive cases,and to provide a basis for the rational regarding antibiotic use.Methods We performed a retrospective chart review of all patients with pediatric hematology and oncology desease in Beijing Children's Hospital from January 2016 to June 2017. All patients were selected based on clinical presentation. Bacterial strains after removal of contaminated and colonized specimens were analyzed. The drug sensitivity test was determined by disk diffusion method or automatic instrument method according to the 2014 (CLSI) standard of American Clinical Laboratory Standardization Committee.Results Of all 2,188 strains isolated from 2,095 samples, 48.1% were gram-negative bacteria; 38.3% were gram-positive bacteria,and 13.6% were a fungal infection. The primary pathogens were gram-negative bacteria including Klebsiella pneumoniae,Pseudomonas aeruginosa, Enterobactercloacae, and Escherichia coli. Gram-positive bacteria were mainly coagulase-positive Staphylococcus epidermidis and human Staphylococcus. A total of methicillin-resistant Staphylococcus (MRS) gram-positive bacterial strains (41.6%,348/837) were identified, and Staphylococcus epidermidis (84.9%, 169/199) and human staphylococci (90.8%, 129/142) were the main types, but vancomycin- and linazolamide-resistant strains were not detected.Extended-spectrum β-lactamase-positive bacteria accounted for 31.9% (336/1 053)gram-negative bacteria, mainly K. pneumoniae(63.8%,134/210) and E. coli(92.8%, 90/97). As for gram-negative bacteria, there were 23.6% (248/1 053)carbapenem-resistant Enterobacteriaceae-positive bacteria, mainly K. pneumoniae(63.8%, 134/210),E. coli(51.5%, 50/97), and Enterobactercloacae(34.5%,38/110).The drug resistance rate for imipenem and meropenem was about or over 50%, but the resistance rate for tigecycline and amikacin was 0.9%-13.4% and 10%-26.8%, respectively. There were 86 Acinetobacter baumaniistrains, in which there were 32.6%(28/86) isolates drug-resistant A.baumanniistrains.The drug resistance rates of A. baumanii to carbapenem and polymyxin were 52.3%-58.1% and 1.2%.Conclusion Our report revealed a prevalence of pathogens of pediatric patients with hemato-oncological malignancies. The Gram-negative bacteria was the main pathogen. An increasing incidence of drug-resistant bacteria and opportunistic pathogens was demonstrated.
Objective To screen mutations in the coding region of DACT1 gene in patients with congenital heart disease (CHD) and to study their biological functions.Methods The subjects of study were from Chinese Han population in Shandong Province. CHD samples were collected from sporadic CHD patients diagnosed at the Cardiovascular Disease Institute in General Hospital of Jinan Military Region from Aug. 2008 to Jan. 2011. The samples collected from the patients with other syndromes or familial heart diseases were excluded. The control samples were collected from healthy children without CHD or familial heart diseases in the same hospital during the same time. ①Genomic DNAs were extracted from the CHD and control samples. The second-generation sequencing technology was used for target sequencing of 404 samples of CHD and 213 healthy controls for the exons of DACT1 gene. Bioinformatics methods were used to screen case-specific new missense mutations or rare missense mutations, which were further verified by Sanger Sequencing. ②The plasmids expressing wild type or mutant DACT1 genes were transfected into HEK293T cells and the effects of the mutants on the level of DACT1 protein were examined by Western blot. ③The effects of the mutations on canonical Wnt signaling and PCP signaling were evaluated by luciferase reporter assay.Results There were 404 CHD cases at the age of (2.9±2.7) years and 213 controls at the age of (7.1±3.7) years. The ratios of male to female for CHD and control samples were 1.2:1 and 1:1 respectively. Four novel or rare missen mutations, c.1486C>T (p.S441L), c.1598C>A (p.S478R), c.1659G>C (p.E499Q) and c.1891T>A (p.M576K), (thereafter called DACT1S441L, DACT1S478R, DACT1E499Q and DACT1M576K, respectively) were identified from three CHD samples. The four mutations were verified by Sanger sequencing. The mutations of DACT1S478R and DACT1E499Q occurred at highly conserved sites and the mutations of DACT1S441L and DACT1E499Q were predicted to be harmful. The four mutations have no effects on the protein levels of DACT1 mutant protein themselves, respectively. However, the mutation of DACT1E499Q attenuated the degradation of DVL2 protein and reduced the inhibition of the canonical Wnt signaling pathway and PCP signaling pathway.Conclusion DACT1E499Q mutation may contribute to the development of CHD by decreasing the inhibitation of Wnt signalings.
Objective To introduce a binomial-normal hierarchical model (BNHM) that is appropriate for meta-analysis of proportions, and explain how to fit the model with bayesian methods.Methods The BNHM and a normal-normal hierarchical model(NNHM)were explained. Random effects model was used to reanalyze two worked examples from literature in the framework of the BNHM and NNHM respectively. Bayesian and frequentist methods were used to fit the BNHM. The frequentist methods were used to fit the NNHM with standard inverse variance method for the two untransformed or logit transformed data of proportions.Results In the framework of BNHM, the point estimates and 95% credit interval(CI) of pooled proportions using the bayesian method were 0.057(0.039,0.077) and 0.799(0.693,0.897) respectively, and the between-study variances were 0.488 and 0.919 respectively. The point estimates and 95% confidence interval(CI) of pooled proportions using the frequentist method were 0.056(0.041,0.078) and 0.798(0.692,0.875) respectively, and the between-study variances were 0.400 and 0.589 respectively. In the framework of NNHM, for the logit transformed data, the point estimates and 95%CI of pooled proportions were 0.073(0.057,0.094) and 0.754(0.661,0.827) respectively, and the between-study variances were 0.170 and 0.301 respectively. For the untransformed data,the point estimates and 95%CI of pooled proportions were 0.049(0.032,0.065) and 0.804(0.719,0.888) respectively,and the between-study variances were 0.001 and 0.018 respectively.Conclusion Different models might give different results,and the NNHM might underestimate the between-study variances. Bayesian methods were preferable for the meta-analysis of proportions in the framework of BNHM.
Objective To introduce the meta-analysis method for the incidence data using the PROC NLMIXED program in SAS software.Methods A Binomial-Normal model (BNM) or Poisson-Normal model (PNM) based on the generalized linear mixed model (GLMM) was proposed by Stijnen et al., which was extremely convenient to achieve a random-effect meta-analysis of incidence data, especially when the meta-analysis incorporated zero-event studies. A systematic review of the risk of fatal adverse events in cancer patients treated with vascular endothelial growth factor receptor tyrosine kinase inhibitors published by Schutz et al. was used as an example data, and meta-analysis of the incidence data was performed using SAS software and programming code was provided.Results For the zero-event study, the PNM model could be used for meta-analysis without continuity correction. The deletion of the zero-event study could have a greater impact on the PNM model. Compared with the standard normal model, the PNM model or BNM model gave higher effect values, while the P values were smaller, resulting in better sensitivity.Conclusion Based on the generalized linear mixed-effects model, using the PROC NLMIXED in SAS to achieve the meta-analysis of incidence data is the preferred method.
Objective To explore the causal association between birth weight and childhood obesity by using the GWAS data and the Mendelian randomization (MR) method.Methods Based on the genetic data published by the Early Growth Genetics Consortium (EGG) (data acquisition time is October 20, 2018), the SNP with statistically significant association with birth weight was screened by MR-base platform. As instrumental variables (screening parameters P<5×10-8, linkage disequilibrium r2<0.1), birth weight and childhood obesity were determined by inverse variance weighted analysis (IVW), weighted median method and MR-Egger method, respectively (definition of childhood obesity: BMI≥95%). Forest maps and scatter plots were also applied.Results A total of 33 SNPs related to birth weight were screened. A total of 5,530 obese children and 8,318 normal children were included. IVW analysis: OR=1.79, 95% CI: 1.29~2.47, P=4.24×10-4; weighted median method: OR=1.30, 95% CI: 0.81~2.08, P=0.27; MR-Egger method: OR=1.73, 95% CI: 0.58~5.20, P=0.36. The result of IVW in the forest map showed that the genetic susceptibility of childhood obesity was related to the birth weight level. rs7964361, rs11765649, rs3780573 and rs1351394 showed that birth weight and childhood obesity were statistically significant. The scatter plot showed that the causal correlation estimates for the IVW method, the MR-Egger method, and the weighted median method were similar.Conclusion IVW analysis showed that there was a strong correlation between birth weight and childhood obesity, but the other two statistical methods found that the difference was not statistically significant, so the causal association remained to be supported by further evidence.
