FU Pan, HE Leiyan, WANG Chuanqing, YU Hui, XU Hongmei, JING Chunmei, DENG Jikui, ZHAO Ruizhen, HUA Chunzhen, CHEN Yinghu, CHEN Xuejun, ZHANG Ting, ZHANG Hong, CHEN Yiping, YANG Jinhong, LIN Aiwei, WANG Shifu, CAO Qing, WANG Xing, DENG Huiling, CAO Sancheng, HAO Jianhua, GAO Wei, HUANG Yuanyuan
Background Chinese Inspect Survey of Pediatric Consortium(ISPED) Surveillance program was established in 2015. The data of antibiotics resistance were collected from each hospital of ISPED and summarized every year to monitor the bacterial drug resistance among Chinese children. Objective This study is aimed to investigate the antimicrobial resistance profiles of pathogens in Chinese children and guide the reasonable use of antibiotics. Design This is a cross-sectional survey. Every hospital conducted the standard procedure of bacterial culture, identification and antimicrobial susceptibility test. The bacterial information and antibiotics resistance data were collected by lead hospital every year. All data were analyzed to reflect the current bacterial infection and drug resistance among children. Methods Clinical isolates were collected from 11 tertiary children hospitals in China in 2019. Antimicrobial susceptibility testing was carried out according to a unified protocol using Kirby-Bauer method or automated systems. Results were interpreted according to the criteria of Clinical and Laboratory Standards Institute (CLSI) 2019 breakpoints. Penicillin susceptibility of streptococcus pneumonia was detected by E-test. Main outcome measures Monitor and detect the distribution of bacteria strains in children and the changes of bacteria drug resistance, especially the multi-drug resistant bacteria among pediatric patients. Results A total of 76,287 isolates were collected, of which 41.0% was gram-positive organisms and 59.0% was gram-negative organisms. Top-five pathogens were as follows, Escherichia coli (12.5%), Streptococcus pneumonia (11.5%), Haemophilus influenza (11.5%), Straphylococcus aureus (11.2%), and Klebsiella pneunoniae (6.9%). Straphylococcus aureus and Streptococcus pneumonia was the primary pathogen in neonatal group and non-neonatal group respectively. Multi-drug resistant organisms (MDROs) were very common in children. The detection rate of Carbapenem resistance Enterobacteriaceae (CRE), Pseudomonas aeruginosa (CR-PA) and Acinetobacter baumannⅡ (CR-AB) was 8.7%, 23.2% and 54.0% respectively. CRE was higher in neonatal group (11.7%) than non-neonatal group (7.6%), while CR-PA and CR-AB was lower in neonatal group (19.2% and 30.4%) than non-neonatal group (23.2% and 57.7%). The rates of Methicillin-resistant Staphylococcus aureus (MRSA) and Coagulase negative staphylococci (MRCNS) were 35.0% and 76.4% respectively. Most of MDROs (CRE, CR-PA, CR-AB and MRSA) were seperated from respiratory tract. MDROs presented high-level drug resistances, especially CR-AB presenting >70% resistance to most antibiotics. The β-lactamase positive rate of Haemophilus influenza isolates was 63.9%. Conclusion MDROs were very common in children and it's necessary to establish an effective Multiple Disciplinary Team (MDT) to control the antimicrobial resistance in pediatric group.
Background The diagnostic utility of magnetic resonance (MR) diffusion tensor imaging (DTI) in the diagnosis of cortical and white matter lesions in children with focal cortical dysplasia (FCD) is unclear. Objective To evaluate the value of conventional MR and DTI in the diagnosis of FCD in children. Design The children with unilateral temporal lobe FCD confirmed by surgery and pathology were taken as the research objects, and the contralateral side of FCD and healthy children were taken as the control group. DTI parameters were compared in two groups. Methods The onset age and disease course of FCD and MR and DTI data of healthy children who have matched time of MR examination, age and gender were collected. The fractional anisotropy (FA) and apparent diffusion coefficient (ADC) of cortical and white matter of typical lesions on the affected and contralateral sides of FCD and in healthy children were measured. Main outcome measures AUC of ROC curve of DTI parameters on the affected and contralateral sides of FCD and in healthy children. Results There were 21 cases of FCD with an average age of 8.2 (1-16) years, an average age of 4.5 (1-8) years, an average course of disease of 5.8 (1-9) years, and 20 cases of healthy children with an average age of 7.9 (2-16) years. FA values of the affected cortex and white matter were significantly lower than those of the corresponding areas of the contralateral side and healthy chidren (P=0.029, 0.014, 0.018 and 0.007 respectively). ADC values of the affected cortex were significantly higher than those of the corresponding areas of the contralateral side and healthy children (P=0.001). ADC values of the affected white matter were not significantly different from those of the corresponding areas of the contralateral side and healthy children (P> 0.05). AUC of ROC curve of DTI parameters in FCD children compared with corresponding areas in healthy children was all larger than that of corresponding DTI parameters in comparison of two sides in children with FCD. The ADC value of the cortical area in the case group was positively correlated with the course of disease (r=0.762, P=0.013). The FA value in the white matter area was negatively correlated with the course of disease (r=-0.694, P=0.025), and positively correlated with the age of onset (r=0.705, P=0.017). Conclusion DTI parameters can reflect the microstructural differences among the affected side of FCD, the contralateral side of FCD and healthy children. Correlation of clinical factors can also be reflected. The comparison of the affected side of FCD and the corresponding areas in healthy children has high quality diagnostic utility, which is more significant than the comparison of the affected and contralateral sides of FCD under the same parameters. Therefore, it is of great significance to try to establish the reference values of FA (cortex and white matter) and ADC (cortex and white matter) in normal population.
Background A few cases of childhood primary nephrotic syndrome showed steroid-resistant nephrotic syndrome (SRNS) which was difficult to treat. For these cases of SRNS, after excluding genetic factors other agents were added such as calcineurin inhibitor and mycophenolate mofetil. However, there were no regular principles or unified therapeutic schedules. Objective To observe the therapeutic effects and safety of steroid combined with calcineurin inhibitors and mycophenolate mofetil on pediatric cases of steroid-resistant nephrotic syndrome. Design Retrospective non-randomized controlled study. Methods Data were collected from children with steroid-resistant nephrotic syndrome treated in the department of pediatrics of Peking University First Hospital from January 2014 to December 2020. After excluding genetic factors, they were divided into four groups as A (steroid + calcineurin inhibitor + mycophenolate mofetil, added sequentially), B (if steroid combined calcineurin inhibitor for over 3 months is ineffective, it will be replaced by steroid combined with mycophenolate mofetil for over 3 months. If there is still no effect, the triple therapy of steroid, calcineurin inhibitor and mycophenolate mofetil will be used.), C (calcineurin inhibitor + mycophenolate mofetil, withdrawal of steroid because of glucocorticoid diabetes or glaucoma) and D (steroid + calcineurin inhibitor + rituximab). Main observation parameters The time of urine protein changed negative, the time percentage of urine protein remained negative and average numbers of relapse. Results There were 39 pediatric cases of steroid-resistant nephrotic syndrome in this study, including 16, 8, 3 and 12 cases in group A, B, C and D, respectively. The urine protein negative rates of group A, B, C and D were 75.0% (12/16), 75.0% (6/8), 100% (3/3) and 75.0% (9/12), respectively. There was no difference on urine protein negative rate between four groups (P>0.05). However, the average time of urine protein conversed to negative was much less while the percentage of urine protein conversed to negative was much higher in groups A and D as compared to group B and C (P<0.05). There was no significant difference in the average time of urine protein conversed to negative and the percentage of urine protein conversed to negative between group A and group D (P>0.05). Conclusion Steroid combined with calcineurin inhibitors and mycophenolate mofetil showed better effects on some idiopathic steroid-resistant nephrotic syndrome in children.
Objective To report a case of Aicardi-Goutières syndrome type 7 (AGS7) in China and summarize the clinical characteristics of cases previously reported in other countries. Methods The clinical manifestations, the expression of type I interferon stimulated genes and results of whole-exome sequencing (WES) were retrospectively analyzed. We searched AGS7 caused by the mutation of IFIH1 or MDA5 in the databases of PubMed, Wanfang and CNKI. Clinical features and gene mutation spectrum were summarized. Results A 3-year-old boy experienced recurrent rash for more than 2 years since age of 6 months. Further assessment identified growth retardation, abnormal liver function, decreased white blood cells, increased erythrocyte sedimentation rate, basal ganglia calcification, leukodystrophy, pulmonary interstitial disease, subclinical hypothyroidism, and increased expression of interferon stimulated genes. WES revealed a de novo, heterozygous mutation in the IFIH1 gene(c.1016C>A, p.Ala339Asp). The diagnosis of AGS7 was made. Our literature review included 15 publications. A total of 31 patients, including our case, were reported. AGS7 could be characterized by myodystonia, paralysis, developmental backwardness, skin lesions, as well as abnormal auxiliary examination results, such as cytopenia, hypohepatia, thyroid dysfunction, intracranial calcification, leukoencephalopathy and encephalatrophy. A total of 17 pathogenic variants were reported in 31 cases, including 16 missense mutations and 1 nonsense mutation. But a well targeted relationship between genotype and phenotype was not found. It is not a self-limited disease. Five patients (15%.1) died of as cardiopulmonary complications, hemophagocytic syndrome, cirrhosis or pancreatitis. Conclusion AGS7 is a type I interferonopathies characterized by regression of development, and involvement of multiple organs, such as nervous system, blood, thyroid gland, liver, spleen and so on.
Background CircRNAs play an important part in various dieases. But circRNAs in pediatric asthma have not been reported so far. It had been reported that circHIPK3 promoted Th2 differentiation in allergic rhinitis. Objective To explore the expression and potential function of circHIPK3 in children with asthma. Design The study developed by firstly collecting peripheral blood mononuclear cells (PBMCs) from asthmatic patients and healthy controls. The expression of circHIPK3 was detected and the correlations between circHIPK3 and T cell's transcription factors were analyzed. Relative results were validated in asthma mice. Sequently, bioinformatics analysis was used to analyze possible mechanisms and correlation analysis was performed between circHIPK3 and clinical indicators. Methods Peripheral blood mononuclear cells (PBMCs) were collected from asthmatic patients and healthy controls from August 26,2017 to August 5,2019 in the outpatient respirology clinic at Children's Hospital of Fudan University.qRT-PCR was used for the detection of the expression of circHIPK3 and T-bet in the PBMCs.Pearson correlation analysis was used to analyze the correlation between circHIPK3 and T-bet.A cockroach extract (CRE)-induced asthma model was adopted in the experiment. The expression of circHIPK3 and T-bet in the mice lung were detected by qRT-PCR. Bioinformatics analysis was used to explore the potential mechanism between circHIPK3 and T-bet in children with asthma. Pearson correlation analysis was used to analyze the correlation between circHIPK3 and eosinophils in peripheral blood. Main outcome measures The main outcome measures were relative expression of circHIPK3 and T-bet, as well as the correlation coefficients between them. Results A total of 43 patients of mild asthma (35 males, median age 6.5 years) and 28 normal controls (22 males, median age 6.4 years) were evaluated. Comparing with healthy controls,the expression of circHIPK3 (t=4.627,P<0.001) and T-bet (t=2.727, P<0.01) were significantly decreased in asthmatic patients.circHIPK3 was positively correlated with T-bet in pediatric asthma patients (R=0.483 0, P=0.000 7). The results in lung remodeling in asthma mice were in accordance with those in human PBMCs. miR-485-3p was up-regulated in children with asthma by analysis of a reported GEO database. circHIPK3 could bind with miR-485-3p in a sponge way. T-bet was a predicted target of miR-485-3p. A negative correlation was detected between circHIPK3 and eosinophils in peripheral blood (R=-0.369 2, P=0.019 1). ConclusioncircHIPK3 was down-regulated in the asthmatic patients and mice, potentially regulating T-bet through sponge miR-485-3p.
