FU pan, WANG Chuan-qing, YU Hui, XU Hong-mei, JING Chun-mei, DENG Ji-kui, ZHAO Rui-zhen, HUA Chun-zhen, CHEN Ying-hu, CHEN Xue-jun, ZHANG Ting, ZHANG Hong, CHEN Yi-ping, YANG Jin-hong, LIN Ai-wei, WANG Shi-fu, CAO Qing, WANG Xing, DENG Hui-ling, CAO San-cheng, HAO Jian-hua, GAO Wei, HUANG Yuan-yuan
Objective This study is aimed to investigate the antimicrobial resistance profiles of pathogens in Chinese children.Methods Clinical isolates were collected from 11 tertiary children hospitals in China in 2018. Antimicrobial susceptibility testing was carried out according to a unified protocol using Kirby-Bauer method or automated systems interpreted according to the criteria of Clinical and Laboratory Standards Institute (CLSI) 2017 breakpoints. Penicillin susceptibility of streptococcus pneumonia was detected by E-test.Results A total of 62,212 isolates were collected, of which 42.2% was gram-positive organisms and 57.8% was gram-negative organisms. Top-five pathogens were as follows, Streptococcus pneumonia (12.9%), Escherichia coli (12.4%), Haemophilus influenza (11.8%), Straphylococcus aureus (10.3%), and Moraxella catarrhalis (7.2%). In neonatal group, Straphylococcus aureus was the primary pathogen (17.0%). More than half of pathogens (57.0%) were seperated from respiratory tract, Streptococcus pneumonia and Streptococcus pyogenes were the primary pathogens isolated in lower and upper respiratory tract respectively. Carbapenem resistance Enterobacteriaceae(CRE) accounted for 8.7%. The detection rate of CRE in neonatal group was 16.8%, much higher than that in non-neonatal group (7.2%). CRE strains represented high-level resistances to many antibiotics. Carbapenem resistant Acinetobacter baumannii (CR-ab) was 63.2% in total and the rate in neonatal group was 35.2%, much lower than than in non-neonatal group (69.7%). Carbapenem resistant Pseudomonas aeruginosa (CR-pae) was 27.2% and showed no difference between neonatal (25.0%) and non-neonatal (27.3%) groups. The Methicillin-resistant Staphylococcus aureus (MRSA) and Coagulase negative staphylococci (MRCNS) were 34.9% and 77.3% respectively. We detected 0.1% penicillin non-susceptible β-hemolytic Streptococcus pyogenes. The penicillin non-susceptible rates of Streptococcus pneumonia (PNSP) from non-cerebrospinal fluid was 21.3%. The β-lactamase positive rate of Haemophilus pneumonia isolates was increased to 61.1%.Conclusion Respiratory infection was the most common pediatric infections. Carbapenem-resistant bacteria presented high-level resistance to various antibiotics. In neonatal group, CRE was higher than that in non-neonatal group but CR-ab was lower than that in non-neonatal group.
Objective To investigate the efficacy and adverse effects of sequential mycophenolate mafetil (MMF) after 3 months and 6 months of cyclophosphamide (CTX) in children with type Ⅲ or Ⅳ lupus nephritis (LN).Methods This is a non-randomized controlled trial. The objects were children with type Ⅲ or Ⅳ LN. Parents of these children were fully aware of the benefits and adverse effects of sequential MMF after 3 months (group A) and 6 months (group B) of CTX induction therapy. According to the parents' decision, these children were divided into group A and B. The efficacy and adverse events of the two groups were followed up for 1 year. The main outcome indicators of efficacy are as follows. Complete remission: blood routine, renal function, albumin, erythrocyte sedimentation rate are normal and C3≥0.73 g·L-1, C4≥0.1 g·L-1, anti-ds-DNA antibody is negative with two methods of immunofluorescence and ELISA. At the same time, 24 h urine protein should be lower than150 mg. Partial remission: Any one of the following is achieved:①24 h urine protein is 50% lower than that before treatment, and the total amount is <3.5 g·24 h-1.②Serum creatinine and urine protein/creatinine are improved by 50%.③Serum creatinine is improved by 50% and urinary protein/creatinine is <1.0. And laboratory tests are improved compared to before the treatment.Results Thirty three children were retrospectively analyzed. All the children were admitted to the Peking Union Medical College Hospital from January 2012 to January 2018. The age of onset, age of kidney biopsy, gender, season of onset, living environment, type of renal pathology, incidence of family history were similar in two groups. The efficacy and side effects have no significant difference between the two groups, at the end of treatment (3 months in group A, 6 months in group B) and 12 months after treatment. There was no significant difference in efficacy at 3 months between two groups. There was no significant difference in efficacy at 6 months and 1 year between two groups. At 3 months, the cumulative dose of CTX (mg·kg-1) were (94.0±20.5) and (104.1±34.8) respectively in group A and B. There was no significant difference (P=0.39). There was no correlation between the mean CTX cumulative amount and the efficacy at 3 months and 6 months(r= 0.95, P= 0.051). There was no significant difference in the incidence of adverse events between the two groups. The adverse events were mainly white blood cell reduction, infection, gastrointestinal discomfort and irregular menstruation. Hair loss and hemorrhagic cystitis did not happen because of CTX.Conclusions equencing of MMF after 3 months or 6 months of CTX treatment has no effect on efficacy and adverse effects for children with proliferative lupus nephritis.
Objective To analyze the clinical characteristics of IgA nephropathy and Henoch-Schonlein purpura nephritis in children, and to explore the value of its clinical and pathological classification.Methods Patients with the first onset of the IgA nephropathy or Henoch-Schonlein purpura nephritis , who hospitalized in our hospital from January 2014 to December 2018 were studied retrospectively to summarize their clinical data. The clinical and pathological classification of IgA nephropathy and Henoch-Schonlein was according to the criterion of Kidney Pathology Group of pediatric Branch of Chinese Medical Association.Results There were 255 cases of first IgA nephropathy and 212 cases of Henoch-Schonlein purpura nephritis included in this study. Nephritic syndrome type (45.5% vs 39.2%), hematuria and proteinuria type (41.2% vs 42.5%) were most common, while isolated proteinuria type and chronic nephritis were not seen in both IgA nephropathy and Henoch-Schonlein purpura nephritis group. Grades Ⅲ (52.4%~53.6% vs 51.8%~53.9%) and Ⅱ (35.3%~36.2% vs 34.6%~36.3%) were the most common pathological types in different clinical types (P>0.05). The prognosis between different clinical types was the same (99.1%~100% vs 97.6%~100%) (P>0.05).Conclusion The clinical and pathological classification of childhood IgA nephropathy and Henoch-Schonlein purpura nephritis in China is useless and it should be discussed further.
Objective To investigate the association between TGF-β3 polymorphisms and the susceptibility to non-syndromic cleft 1∶P with or without cleft palate (NSCL/P) in Asian population using Meta-analysis.Methods Electionic detabeses including PubMed, Cochrane Library, Embase, Chinese Science and Technology Academic Journal, Chinese Journal Full-text Database, Chinese Biomedical Literature Database and Wanfang database were searched for relevant literature from inception of databases to Januatr 2019. Two researchers selected the literature and extracted the data independently according to the inclusion and exclusion criteria. A Meta-analysis was performed using STATA12.0 software and publication bias test were performed by funnel Plots.Results A total of nine case-control studies were included in the present Meta-analysis, including 806 cases and 781 healthy control. Meta-analysis showed that there was significant association between TGF-β3 polymorphism and susceptibility to NSCL/P under allele model (G vs A: OR=1.23, 95%CI: 1.04-1.47), additive model (GG vs AA: OR=1.72, 95%CI: 1.17-2.55), Co-dominant model (GG vs GA: OR=1.50, 95%CI: 1.15-1.98) and dominant model (GG vs GA+AA: OR=1.50, 95%CI: 1.16-1.94). However, there was no significant association between them under recessive model (AA vs GA+GG: OR=0.97, 95%CI: 0.72-1.30).ConclusionTGF-β3 polymorphism is associated with an increased risk of NSCL/P in Asian population.
Objective To investigate the predictive value of adenovirus (ADV) load in the development of severe adenovirus pneumonia (SAP) to bronchiolitis obliterans (BO).Methods A total of 139 SAP children admitted to Children's Hospital of Chongqing Medical University from January 2015 to February 2019 were enrolled, of which 34 developed into BO and 105 did not. LASSO-logistic regression, restricted cubic spline model and decision curve analysis were used to evaluate the clinical predictive value of ADV load in the development of SAP to BO.Results The duration of fever, respiratory failure, invasive mechanical ventilation, ADV-DNA load of nasopharyngeal aspirate, PCT and bacterial infection were compared between the two groups (P<0.05). The variables were screened by LASSO-logistic regression, and multivariate logistic regression analysis showed that the ADV load of nasopharyngeal aspirate was an independent risk factor for SAP developing into BO (OR=1.247, 95% CI: 1.088~1.459, P=0.01). Restricted cubic spline analysis showed a linear dose-response relationship between the natural logarithm of the nasopharyngeal aspirate ADV load and the post-SAP developmental BO (linear test, P=0.69). Decision curve analysis showed that ADV load had important clinical value for the prediction of SAP developing into BO.Conclusion ADV load is an independent, dose-dependent risk factor for the development of childhood SAP to BO, and has important clinical value for the prediction of SAP developing into BO.
ZHAI Yi-hui, SHI Peng, RAO Jia, CHEN Jing, FANG Xiao-yan, MIAO Qian-fan, ZHANG Zhi-qing, LIU Jia-lu, TANG Xiao-shan, LIU Jiao-jiao, CAO Qi, GUO Wei, YE Cheng-jie, GE Xiao-ling, ZHANG Xiao-bo, SHEN Qian, XU Hong
Objective The front page of inpatient medical records consists of structured data domains including demography, diagnosis, procedures and hospitalization expenditure. To explore and develop an analysis method based on the medical big data of the front page of inpatient medical records and describe the brief characteristics of medical service provided by pediatric nephrology in a national children's medical center.Methods We performed a cross section study based on the data of the front page of the inpatient medical records from January 1, 2014 to December 31, 2018 derived from the pediatric nephrology department in the hospital information system (HIS). After data desensitization, the selected data elements on the structured front page were extracted, and the backup database DASF-PEKDI (a database searched by fields for pediatric kidney disease inpatients)was established. The ICD codes were mapped to a standardized version. The current addresses were simplified to provinces and cities. The repository of ICD diagnostic codes of renal (related) disease was established and classified into 14 categories: primary glomerular disease, secondary glomerular disease, genetic glomerular disease, renal tubular disease, urinary tract infection, congenital abnormality of kidney and urinary tract, urolithiasis, renal angiopathy, nocturnal enuresis, renal tumors, renal insufficiency / renal failure, renal replacement therapy, hematuria / proteinuria and others.Results In HIS of our hospital, 7,898 inpatient medical records of pediatric nephrology identified on the front page of inpatient medical records were retrieved. One thousand and ninety-one ICD-10 diagnostic codes were derived from DASF-PEKDI, among which 285 were diagnostic codes of renal (related) disease, including codes of diseases requiring differentiation with renal diseases, codes of morbidity and post-operational status. Among 285 diagnositic codes, 227 codes belonged to specific renal disease. Three codes of procedure (ICD-9-CM-3) were also included. Three thousand nine hundred and sixty three patients (7,898 cases) were discharged from department of pediatric nephrology, among which 90.1% (3,571 patients) were with renal (related) diseases, with a median age of 5.8 years (0-20 years), and 61.3% of them were male children. Among 7,898 cases, patients living outside Shanghai during the five years increased from 72.1% in 2014 to 85.7% in 2018. The average hospitalization cost was 13,716 RMB and the average hospitalization duration was 9.4 days. Primary nephrotic syndrome accounted for 78.1% of the primary glomerular disease. Henoch-Schonlein purpura nephritis and lupus nephritis accounted for 78.4% of secondary kidney disease. The proportion of CAKUT diagnosis increased from 9.3% in 2014 to 15.3% in 2018. Chronic kidney disease (stage 2-5) accounted for 90.7% of renal insufficiency / renal failure. The modality of renal replacement therapy includes peritoneal dialysis (62.2%), hemodialysis (12.6%) and kidney transplantation (25.2%).Conclusion The structured data elements on the front page of inpatient medical records provide a new tool to accelerate clinical study through data capture and analysis. The authors developed a front page based analysis method. The diagnosis spectrum of renal diseases on the front page of inpatient medical record needs to be standardized based on ICD-10 codes, and the database and classification of renal (related) diseases should be established, so as to further accurately analyze the demographic and characteristics of kidney disease of inpatients in the department of pediatric nephrology.
Objective To summarize the clinical features of severe gastrointestinal tract involvement and perforation in juvenile dermatomyositis (JDM).Methods Four cases of JDM with severe gastrointestinal tract involvement in our hospital were summarized. Relevant studies were reviewed.Results Four patients (P1-P4) were involved in the study with one boy and three girls, aged between 1.6 and 5 years. The onset of gastrointestinal involvement occurred between the 4th and 10th month after the diagnosis of JDM, and the primary symptom was abdominal pain. P1 had duodenal and transverse colon perforation; P2 had duodenal perforation combined with hepatic artery rupture; intestinal perforation site on P3 was unknown and P4 had thickened intestinal wall without perforation. Four cases had strong positive results for anti-NXP2 antibody (3+) and had been treated with steroids and/or immunosuppressants. P1 and P2 underwent surgical intervention and P4 received autologous hematopoietic stem cell transplantation(AHSCT)owing to their resistance to the traditional treatment. P1 experienced complete remission during follow-up for 2 years, but she died after repairing digestive tract fistula; P2 died of infection and duodenal fistula; P3 died of diffuse abdominal wall hemorrhage; P4 experienced complete remission after autologous stem cell transplantation. Twelve patients with JDM with gastrointestinal perforation from the literature were summarized. The primary symptom in the digestive tract was severe abdominal pain with or without fever and vomiting, which appeared between 2 months and 9 years after the diagnosis of JDM. Perforations were reported in the duodenum (8 patients), colon (3 patients), jejunum (1 patient), pylori area (1 patient), cervical area of the esophagus (1 patient) and an unclear location (1 patient), with perforations at multiple sites or recurrent perforations reported in five patients. None of them were tested for myositis-specific antibodies. Surgery was performed in 11 patients. Nine patients experienced relief of their symptoms; 3 patients died; 1 patient died of repeated intestinal perforation; 1 patient died of postoperative acute respiratory distress syndrome, and 1 patient of death was unknown.Conclusion Refractory JDM patients may suffer from intestinal perforation and the primary symptom of JDM with gastrointestinal complications was abdominal pain. Common intestine perforation was duodenal peritoneal perforation, and its clinical symptoms were atypical and prone to delay diagnosis. Our patients were positive for the anti-NXP2 antibody. Intestinal perforation has a high mortality rate. In particular, there is no effective procedure for duodenal perforation. Autologous stem cell transplantation might be an option to control the high mortality rate.
Objective To determine status of both Hippo and Wnt tumor suppressor pathways in Chinese hepatoblastoma (HB) specimens, and to test anti-tumor effect of selected drugs in a HB PDX model.Methods Immunohistochemistry (IHC) staining of 20 HB specimens with paired adjacent normal tissues were performed to detect the status of YAP and β-catenin. Cell experiments using HB cells (Huh6) were performed to test the effect of XAV939, a TNKS1/2 inhibitor, on YAP and β-catenin activity. A HB patient-derived xenograft (PDX) model was established to test the effect of XAV939 and other drugs on tumor development.Results Concurrent activation of YAP and β-catenin were observed in Chinese HB patient samples. XAV939 inactivated YAP and β-catenin by accumulating AMOT and AXIN1/2 in Huh6 cells. While Cisplatin and Sorafenib had obvious inhibition effect on PDX tumor growth, XAV939 alone had no obvious effect, and the combination of XAV939 with Cisplatin showed similar effect as Cisplatin single therapy.Conclusion While YAP and β-catenin were activated in Chinese HB patients, XAV939 did not show a significant inhibition on the growth of tumor in a HB PDX model as Cisplatin did. Further work is needed to explore the role of Hippo and Wnt pathways in HB development and to target these two pathways molecularly.
Objective To explore the changes of histone methylation of IL-4 gene and its roles in dysfunction of Th2 cells during acute pediatric Kawasaki disease (KD).Methods Forty-two children with KD were recruited in present study, while thirty-six age-matched healthy volunteer were as controls. Flow cytometry was performed to determine the frequencies of Th2 cells and levels of IL-4, phosphorylated STAT6 (pSTAT6) and GATA3 protein. Chromatin immunoprecipitation (ChIP) and quantitative PCR were used to evaluate trimethylation of histone H3 at lysine 4 at CNS1, HSⅡ and HSVa of IL-4 gene and binding levels of GATA3 and MLL1 with loci afore-mentioned in CD4+ T cells. Transcription levels of IL-4, IL-5, IL-13, IL-4Rα, IL-2Rγ and SOCS5 mRNA in CD4+ T cells were quantitated by real-time PCR. Plasma concentrations of IL-4, IL-5 and IL-13 were analyzed by enzyme-linked immunosorbent assay.Results (1) In comparison with healthy controls, the frequencies of Th2 cells, mRNA levels and plasma concentrations of Th2 cytokines (IL-4, IL-5 and IL-13) ,and methylation levels of H3K4me3 associated with IL-4 loci (CNS1, HSⅡ and HSVa) increased significantly in patients with acute KD(P<0.05). The items mentioned afore in patients with coronary artery lesions (CAL) were found to be higher than those without coronary artery lesions (NCAL), and restored to some extent after IVIG therapy (P<0.05). (2) ChIP results showed binding abilities of GATA-3 and MLL1 proteins with IL-4 gene loci (CNS1, HSⅡ and HSVa), were up-regulated remarkably in CD4+ T cells from patients with acute KD (P<0.05), and down-regulated after IVIG treatment(P<0.05). There are positive correlations between binding abilities of MLL1 protein with IL-4 loci (CNS1, HSⅡ and HSVa) and transcription level of IL-4 mRNA detected during acute KD (r=0.42, 0.33, 0.39, P<0.05). In parallel, binding abilities of GATA-3 and MLL1 with the three IL-4 loci in CAL group were higher than those in NCAL group (P<0.05). ⑶ During acute phase of KD, plasma levels of IL-4 protein, and expression levels of IL-4 signaling downstream molecules (IL-4Rα, IL-2Rγ、pSTAT6 and GATA-3) and negative regulator SOCS5 increased remarkably (P<0.05), and all the items decreased after IVIG treatment (P<0.05). Furthermore, the five items aforementioned in CAL group were higher than those in NCAL group, while the last items in CAL group was lower than that in NCAL group(P<0.05).Conclusion Excessive histone methylation of H3K4me3 with IL-4 gene might be one of initiative factors resulting in aberration of Th2 cells in KD.
Objective To analyze the clinical characteristics and surgical outcomes of total anomalous pulmonary venous drainage (TAPVD).Methods We reviewed patients with TAPVD from June 2012 to June 2018 who underwent surgical repair and met the inclusion criteria. The patients were classified into 2 groups: event and nonevent group. Data were analyzed with SPSS statistical software and median (range) was used to describe the data distributions which do not conform to normal distribution. The Mann-Whitney U test was used to compare differences between groups. Cox proportional hazards modeling was used to analyze associated risk factors for death and recurrent pulmonary venous obstruction (PVO).Results A total of 138 patients with TAPVD were recruited including 42 cases in event group and 96 cases in nonevent group. There were 65 cases with supracardiac type, 44 cases with intracardiac type, 19 cases with infracardiac type and 10 cases with mix type. A total of 138 patients underwent TAPVD repair at a median age of 50 days; patients younger than 1 month were 60 cases (43.5%) and younger than 6 months were 123 cases (89.1%).There were 63 cases (45.7%) with preoperative PVO and 41 cases (29.7%) with postoperative PVO. Infracardiac TAPVD, mixed TAPVD, younger age, preoperative PVO, emergency operation and prolonged cardiopulmonary bypass showed significant difference between the event and nonevent groups. The preoperative predictors of studied endpoints were infracardiac TAPVD (P=0.005), mixed TAPVD (P=0.014), preoperative PVO (P=0.020), younger than 1 month (P=0.009) and prolonged cardiopulmonary bypass (P=0.024).Conclusions upracardiac subtype is the most common type of TAPVD. Risk factors such as infracardiac, mixed TAPVD, preoperative PVO, younger than 1 month at repair and prolonged cardiopulmonary bypass, were associated with a poorer prognosis.
Objective To investigate the relationship between four adipokines (leptin, adiponectin, Nrg4 and ZAG) and obesity and related metabolic disorders.Methods Obese children aged from 5 to 14 years were recruited from Children's Health Department of Children's Hospital of Nanjing Medical University. We measured height, weight, WC, fat mass percentage (FM%) and blood pressure, then calculated waist height ratio (WHtR) and BMISDS. Indicators of glucose and lipid metabolism were measured. Serum adipokines levels were measured by enzyme-linked immunosorbent assays (ELISA).According to blood pressure, glucose and lipid metabolism indicators, obese children were divided into metabolically unhealthy obesity (MUO) and metabolically healthy obesity (MHO). Then association between serum adipokines, obesity and metabolic status was analyzed.Results A total of 192 obese children were recruited in the study (138 boys and 54 girls, 10.59±1.93 years), with average BMISDS of 2.86 (2.38, 3.26). Among the obese children, 164 cases (85.4%) were MUO and 28 cases (14.6%) were MHO. After adjusting for age, MUO children had lower adiponectin and Nrg4 levels compared to MHO children (all P<0.05). Serum leptin and ZAG levels were no significant difference between the two groups. Correlation analysis indicated that serum leptin levels in MUO group were positively correlated with BMISDS, FM% and WHtR (P<0.05). Serum adiponectin levels were negatively correlated with age, ALT, AST and HOMA-IR (P<0.05). Serum Nrg4 levels were negatively correlated with BMISDS, WHtR, ALT and AST(P<0.05). Serum ZAG levels were negatively correlated with FM% (P<0.05). Logistic regression analysis showed that serum adiponectin and Nrg4 were protective factors for metabolism in obese children. ROC analysis showed that the diagnostic cut-off points of serum adiponectin and Nrg4 evaluating metabolic abnormalities in obese children were 5.56 μg·mL-1 and 5.5 ng·mL-1, respectively.Conclusions erum leptin and ZAG levels in obese children and adolescents with metabolic disorders are closely related to fat mass, while adiponectin and Nrg4 levels are associated with the degree of metabolic disorders. These adipokines are important for identifying and interfering with the occurrence and development of metabolic disorders in obese children and adolescents.
Objective To evaluate the value of contrast-enhanced voiding urosonography in diagnosis and follow-up in pediatric vesicoureteral reflux(VUR).Methods Children with high risk of VUR admitted to Children's hospital of Fudan University between September 2018 and May 2019 were given Sulfur Hexafluoride Microbubbles (Sonovue) through bladder for CeVUS. The results of CeVUS examination combined with the clinical characteristics of children were analyzed.Results A total of 50 children received CeVUS examination, including 21 males (42%, 2 with isolated kidney) and 29 females (58%, 1 with isolated kidney).The median age of them is 25.0 (2.3~99.0) months. ①26 patients (50 PUUs) received CeVUS examination for the first time, and 15 /26 patients (57.7%) had VUR, among which 6 patients (23.1%) were low grade and 9 patients (34.6%) were high grade.VUR exists in 21/50 PUUs, and middle and high level (Ⅲ-Ⅴ) reflux accounted for 66.67%.② 24 patients(47 PUUs) had received MCU before and 24/47 (51.1%) PUUs still had reflux during the follow-up CeVUS examination.The follow-up interval between CeVUS and MCU in children with improved reflux was significantly longer than the time of children with worsening or similar reflux (19.1 month vs 12.2 months, P=0.02). ③ Among the children who received CeVUS, 14 cases have been found to have urinary or other malformations but VUR through early B-ultrasound and other examinations. In 9 cases, MCU examination indicated the presence of VUR before the CeVUS examination was completed.Conclusion Since CeVUS has no radiation, it can be used for diagnosis and follow-up of VUR. For follow-up patients, the frequency of examinations can be appropriately prolonged.
