Objective：We analyzed the effect and safety of rituximab in children with primary refractory nephrotic syndrome (NS)and explored the factors related to the prognosis. Methods：Frequent relapsing-steroid dependent NS and calcineurin inhibitor (CNI)-sensitive steroid resistant NS patients, who received rituximab and had been followed up for more than 6 months from March 2011 to December 2016, were enrolled in this study. Rituximab was given for 1 or 2 doses. Glucocorticoid was gradually reduced in 3-5 months after treatment of rituximab, CNI was stopped within 1 month after treatment of rituximab. Some of the patients were added mycophenolate mofetil for 1-2 years. The factors that may influence the effect of rituximab (gender, age of onset, pathogenesis, different clinical types, pathological types, therapeutic dosages and whether to add with mycophenolate mofetil) were analyzed. Results：A total of 55 cases were enrolled in this study. Frequent relapsing-steroid dependent NS accounted for 70.9% (39 cases) and minimal change disease accounted for 81.6% (40 cases). Nineteen cases received one dose of rituximab and 36 cases were added mycophenolate mofetiltherapy. The age of using rituximab was 8.8±3.7 years, the median course of disease before rituximab was 38(26.0，61.0) months. Patients were followed for a mean duration of 28.0(17.0, 19.3) months. The relapses of urine protein after rituximab were declined from 2.0(1.0, 3.0) to 1.0(0, 1.5) in one year. The median remission duration was 10.3(5.9, 18.3) months, sustained remission rate was 74.5% and 43.6% at 6 months and 12 months, respectively. There was no statistically significant difference in efficacy between different clinical groups or patients received different dosages of rituximab. Mycophenolate mofetil therapy could improve the sustained remission rate to 94.4% and 58.3% at 6 months and 12 months, respectively. No patients had severe complications. Conclusion：Rituximab is effective and safe to treat the primary refractory NS in children. Mycophenolate mofetil can further improve the sustained remission time of urine protein.
Objective: To analyze the correlation and consistency of total bilirubin (TBil) values in newborns measured with blood gas analyzer and automatic biochemical analyzer. Methods: The infants admitted to Neonatal Department of Children's Hospital of Fudan University from December 1st 2017 to January 31st 2018 were enrolled，and on the first day of admission，TBil values were measured for the first time using blood gas analyzer and automatic biochemical analyzer simultaneously. Spearman's correlation coefficients and blandAltman plots were used to analyze the correlation and consistency of TBil values measured with both methods. Results:① A total of 123 infants were included. The TBil value measured with the automatic biochemical analyzer was 292.6±113.4 μmol·L-1, and the infants with TBil＜200, ~300, ~400 and >400 μmol·L-1 were 32, 33, 35 and 23 cases respectively. Compared with automatic biochemical analyzer, mean TBil values measured with the blood gas analyzer were lower (P＜0.001), whether in the total 123 cases or in subgroups with different TBil values.② Correlation coefficients of TBil of 123 infants and infants with TBil＜200, ~300, ~400 and >400 μmol·L-1 measured with the blood gas analyzer were 0.98, 0.88, 0.81, 0.78 and 0.88 respectively, P＜0.001. The overall biases were 30.9±25.6, 15.0±12.5, 23.0±18.3, 39.0±28.3 and 52.0±25.3 μmol·L-1 respectively; 95%CI were -19.2~81.0, -9.5~39.6, -12.9~58.9, -16.5~94.5 and 2.3~101.7 μmol·L-1 respectively; TBil values outside the 95%CI respectively accounted for 4% (5/123), 9% (3/32), 3% (1/33), 3% (1/35) and 4% (1/23). Conclusion: The values of TBil measured by blood gas analyzer have good linear correlation with the automatic biochemical analyzer, but the consistency is poor. Therefore, blood gas analyzer may only be used as an important supplement for the determination of TBil values measured with the automatic biochemical analyzer.
Objective：To analyze the relationship of VKORC1 gene polymorphism and warfarin maintenance dosage in Kawasaki disease children with coronary artery aneurysms aged from 6 months to 7 years. Methods：Clinical data of children under stable warfarin treatment for Kawasaki disease patients with coronary artery aneurysms and undergone genetic testing for VKORC1 were analyzed retrospectively. Associations of VKORC1 polymorphisms and clinical variables on warfarin maintenance dosage were assessed and a warfarin stable dosing algorithm was derived based on genetic and non-genetic factors. Results：Data of a total of 42 cases（0.5-6.7 years old）were collected. Thirty-five patients were male and 7 patients were female. The Warfarin maintenance dosage was 1.47±0.45 mg·d-1,and the weight-normalized Warfarin maintenance dosage was 0.11±0.033 mg·kg-1·d-1. The group comparing VKORC1 TT genotypes (0.10±0.021 mg·kg-1·d-1) required significantly lower daily doses than CT group (0.16±0.043 mg·kg-1·d-1）,P＜0.01. Compared with the children who underwent gene detection after warfarin, warfarin stability time was obviously shorten and the incidence of bleeding has a decreasing trend in children who underwent gene detection before warfarin. Two linear regression models were builed by setting different dependent variables: 1. Warfarin dose (mg·kg-1·d-1) =0.039+ 0.061×VKORC1 rs9923231(1 if TT,2 if CT), VKORC1 rs9923231 had significant influence on interindividual variation in warfarin stable dose, which contributed 43.8%. 2. Warfarin dose in (mg·d-1) =-0.407+0.088×weight+0.580×VKORC1 rs9923231(1if TT, 2 if CT）, In the full regression model, the combination of VKORC1 and weight explained 63.2% of dosing variability,VKORC1 and weight contributed 19.5％,43.7% respectively. The second warfarin stable dosing algorithm was superior to the first algorithm for higher R2. ConclusionIn：Kawasaki disease population with coronary artery aneurysms aged from 6 months to 7 years, VKORC1 is the main genetic factor relative to warfarin maintenance dosage. Weight is the main influence factor to warfarin maintenance dosage. The warfarin stable dosing algorithm may be useful for helping clinicians to prescribe warfarin with greater safety and efficiency.
Objective：To evaluate the effect of isothermal amplification chip method in lower respiratory tract pathogens detection. Methods：A total of 230 qualified sputum samples were collected. The pathogens were detected by using the isothermal amplification chip method and bacterial culture method. Mycobacterium tuberculosis was tested by using the Ziehl-Neelsen staining. Results：Pathogens were detected by using the isothermal amplification chip method in 182 specimens with the positive rate of 79.1%，which were mainly Methicillin-resistant staphylococcus aureus (33.8%), Haemophilus influenzae (27.7%), Streptococcus pneumoniae (22.5%). Of which, 77(33.5%) were single pathogen infection, 105(45.6%) were mixed infection and 48(20.9%) were pathogen negative. The positive rates of haemophilus influenzae, streptococcus pneumoniae, staphylococcus aureus and klebsiella pneumoniae detected using isothermal amplification chip were higher than culture. The total conformance rate of escherichia coli, klebsiella pneumoniae, pseudomonas aeruginosa, acinetobacter baumannii, and malt narrow-phagocytes by the two different methods were high. And the positive rate of mycoplasma pneumoniae detected by isothermal amplification chip (12.4%) was similar with that detected by argeted serological testing (11.8%). Conclusion：Isothermal amplification chip method is conducive to the rapid diagnosis of low respiratory tract infection of children and timely targeted treatment.
Objective：To study the clinical characteristics of raoultella ornithinolytica infection in children. Methods：The clinical features and drug susceptibility data of 5 cases with raoultella ornithinolytica infection were retrospectively analyzed and related literatures were reviewed. Results：Three of them were males and 2 females, aged from 3 months to 16 years. The primary diseases of 2 cases were congenital malformation, 2 were immunological related diseases and 1 was craniocerebral malignant tumor. Four children had mechanical ventilation history. Four cases had fever; 3 cases were positive for blood culture and 2 were positive for sputum culture. The leucocyte increased in 3 cases and decreased in 1 case. Two children were treated with ciprofloxacin, 1 with amikacin, and 2 with cephalosporin antibiotics. All of them were improved and discharged. Nine cases were retrieved from PubMed、Web of Science and 3 domestic databases, together with our 5 cases, 14 cases were analyzed. The primary diseases of the older children were mainly neoplastic related and immune related diseases, while infants and young children were mostly complicated with congenital malformation. Fever was the main symptom, neonatal infection was mainly manifested by dyspnea and hypoxemia, with multiple skin flushes and systemic erythema. Leukocyte usually increased obviously. Of 14 cases, 6 were ventilator-assisted, 5 had indwelling urethral catheters, 3 had surgical treatment or chemotherapy, and 1 had blood purification for many times. Blood culture was the main method of identification, which was highly sensitive to the three generation of cephalosporin, meropenem, amikacin, ciprofloxacin and levofloxacin. The prognosis was generally good, while patients with sepsis had multifunctional organ failure and died. Conclusion：Blood infecton is the main route of raoultella ornithinolytica in children. High risk population including patients with congenital multiple abnormalities, tumor and immunedeficiency, while invasive operations would increase the risk of infection. Early etiology identification is helpful to diagnosis and treatment, antibiotics preferred three generations of cephalosporins, carbapenems, quinolone and aminoglycoside. Patients with sepsis mostly had poor prognosis.
ObjectiveTo evaluate the ability of the pediatric critical illness score (PCIS) and the pediatric risk of mortality score Ⅲ (PRISM Ⅲ) in assessing the severity of the disease and the prognosis of children in intensive care unit (PICU). MethodsWe received continuous cases of PICU from Children's Hospital of Fudan University from July 21, 2016 to July 30, 2017. In PICU, PCIS and PRISM Ⅲ scores were obtained from the most abnormal recorded values of clinical data in the first 12 h. Cases were divided into the death groups, the transfer group and the automatic discharge group by PICU outcomes. Cases were divided into the non-survival group and the survival group by outcomes within 28 days after PICU (the cases in the automatic discharge group were followed up by telephone on the 28th day after PICU). The death subgroup of the automatic discharge group and the death group were the non-survival group; the survival subgroup of the automatic discharge group and the transfer group were the survival group. Age, the state before admission, the disease when entering the PICU, the source of the children, and the main cause, whether in the PICU received invasive mechanical ventilation treatment, PICU hospitalization time and other data were collected from medical history. Correlation analysis was done using Pearson correlation analysis, and logistic regression analysis was used to evaluate the predictive effect of each index on the outcomes of the two scoring systems. ResultsA total of 685 cases were included in the study. According to PICU outcomes, there were 100 cases in the death group, 442 cases in the transfer group, and 143 cases in the automatic discharge group. The following differences were statistically significant: age, pre-hospital status and PICU hospitalization time of the transfer group compared with the death group or the automatic discharge group; pre-hospital cardiopulmonary resuscitation of the death group compared with the automatic discharge group or the transfer group; the use of vasoactive drugs of the transfer group compared with the death group; trauma, tumor and other causes of the main cause in the automatic discharge group and the transfer group. According to the 28-day follow-up outcomes after PICU, the cases were divided into the non-survival group (n=218) and the survival group (n=467), including 118 cases of automatic discharge death subgroup and 25 cases of automatic discharge survival subgroup. Univariate analysis showed that respiratory rate, systolic blood pressure, pH, PaO2, and creatinine/urea nitrogen in the PCIS score were statistically different between the non-survival group and the survival group; systolic blood pressure, pH, acidosis, total content of CO2, PaO2, PaCO2, blood urea nitrogen, PT/APTT, PLT count and conscious state in the PRISM Ⅲ score were statistically different between the non-survival group and the survival group. ConclusionBoth PCIS and PRISM Ⅲ are suitable for the assessment of the severity of disease and the prognosis of children in PICU. Systolic blood pressure and pH have a greater effect on predicting outcomes of death and survival.
Objective：To translate the family member version of FPDR-BRS (Family Presence During Resuscitation Benefits-Risks) into Chinese, and test its reliability and validity. Methods：The English version of FPDR-BRS was translate and revise. The reliability and validity of the Chinses version of FPDR-BRS was investigated in 253 children (emergency gradeⅠ, Ⅱ, and critically ill) parents from May 2016 to November 2016. Results：The Chinese version of FPDR-BRS was analyzed in three aspects: critical group comparison, item and total score correlation and homogeneity test. The content validity index was 1.0; exploratory factor analysis was done in the two parts of the benefits and risks. The result of benefits scale showed that the Bartlett test value of KMO was 0.876 (P<0.01), principal component analysis extracted two main factors, which could explain the overall variance of 53.0%, the load factor ranged from 0.588 to 0.795, and could explain the 13 items of the original scale well, named as fully understand and actively respond. The Cronbach s' alpha coefficient of it was 0.873. The result of risks scale showed that the Bartlett test value of KMO was 0.883 (P<0.01), principal component analysis to extract 2 the main factors, can explain the overall variance of 64.5%, the factor loading ranged from 0.726 to 0.892, could explain the 10 items of the original scale well, named personal risk and personnel risk. The Cronbach s alpha Coefficient of it was 0.890. Conclusion：The Chinese version of FPDR-BRS has good reliability and validity, and thus can be used to evaluate the attitude and intention of the family members in the family presence.
Objective：To evaluate the reporting quality of clinical practice guidelines published in journals of mainland China in 2016, using Reporting Items for practice Guidelines in Healthcare (RIGHT) , in order to provide reference for Chinese scholars in reporting guidelines. Methods：The electronic databases of CBM (Chinese Biomedical Literature Database), CNKI (China National Knowledge Infrastructure) and Wan Fang Database from January to December 2016 were searched. Two authors independently selected studies, extracted data and the data was processed by Excel 2016 software. Results：Seventy-nine clinical practice guidelines were included. We found that among the seven domains of RIGHT, field one (basic information) had the highest reporting rate (52.7%). Field five (review and quality assurance) and field seven (funding, declaration and management of interest) had the lowest reporting rate (6.3%). All guidelines reported item 1a (identify the report as a guideline in the title). None of the guidelines reported item 9a-1 (how all contributors to the guideline development were selected), item 11b-1 (if the guideline developers used existing systematic reviews, reference these and describe how those reviews were identified and assessed), item 11b-2 (whether systematic reviews were updated), item 14a (whether values and preferences of the target population(s) were considered in the formulation of each recommendation), item 17 (whether the guideline was subjected to a quality assurance process) and item 18b (describe the role of funder(s) in the different stages of guideline development and in the dissemination and implementation of the recommendations). Conclusion：The reporting quality of clinical practice guidelines published in journals of mainland China in 2016 is low. It is suggested that the guideline developers should report guidelines in accordance with RIGHT during the guideline development process.
Objective：To characterize the microbiome in children with IL10RA deficiency who developed inflammatory bowel disease(IBD) at a very young age. Methods：Fecal samples were collected from three groups of children. IL10RA group included very early onset inflammatory bowel disease (VEO-IBD) patients with identified IL10RA deficiency. Symptomatic patients(SP) consisted of patients that presented with signs and symptoms suggestive of VEO-IBD but without gene mutation. And healthy controls(HC) were age-matched volunteers lacking evidence of disease. Microbial DNA was extracted from the fecal samples. All analysis was based on the 16S rRNA gene sequencing data. Results：We enrolled 17 IL10RA-deficient patients, 15 symptomatic patients, and 22 age-matched healthy children. We observed significantly reduced diversity in IL10RA at both the phylum and ordinal level of taxonomic classification. The Shannon index values for HC, SP, and IL10RA group were 2.37±0.57, 1.79±0.70, and 1.36±1.03 respectively. Accordingly, average Simpson index values were 0.19±0.11, 0.32±0.20, and 0.48±0.31 respectively. A balanced proportion of genera of Firmicutes and Bifidobacterium dominant Actinobacteria were observed in HC. But in SP and IL10RA group, Firmicutes were dominant by Enterococcus and Streptococcus. Compared with SP group, the proportion of Bifidobacterium was reduced in IL10RA group, but the proportion of Rothia was increased. Seventeen genera showed significance in comparisons of relative abundances between IL10RA group and the other groups. Interestingly, most of them were negatively associated with disease status. Conclusion：Intestinal microbiome in VEO-IBD with IL10RA deficiency had features different from the other groups, such as reduced diversity, large variation of the group, imbalanced structure and decreased abundance of symbionts.
Objective：To explore the role of exposure to PM2.5 on Th9 cell differentiation and its role in the pathology of asthma to provide evidence for causal relationship between air pollution and asthma and to find new treatment strategy for asthma. Methods：Mice were sensitized and challenged with cockroach extract (CRE) by intratracheal inhalation. Different dose of PM2.5 were inhaled by intratracheal injection during the challenging period. Cell counting in the bronchoalveolar lavage fluid (BALF), HE staining of lung tissues and resistance of airway were detected to evaluate the effect of PM2.5 on asthma. Th9 cells in the lung hilar lymphnodes was detected with flow cytometry. IL-9 expression in the lung tissues was detected with qRT-PCR. Th9 cells were differentiated in the presence of IL-4 and TGF-β with naive CD4+ T cells in vitro. IL-9，PU.1 and BATF were detected with qRT-PCR or flow cytometry. Results：The lung inflammation were significant enhanced in the PM2.5 together with allergen (CRE) group compared with CRE group. The total cell numbers, the number of eosinophils, granulocytes and lymphocytes in the BALF, lung inflammation, and airway resistance were significant increased in the PM2.5+CRE group compared with CRE group. There was more Th9 positive cells in lung hilar lymphonodes in the PM2.5+CRE group than CRE group. The IL-9 positive cells was more in the PM2.5+CRE group than CRE group in in-vitro experiment (52.0%±5.8% vs 31.7%±3.2%, P=0.000 4 ). PU.1 and BATF expression was also higher in the PM2.5+CRE group than CRE group. Conclusion：PM2.5 could enhance the inflammation of asthma and this may be related to its effect on Th9 cells differentiation.
Objective：To report a case of cryptogenic multifocal ulcerating stenosing enteritis (CMUSE), and to improve the cognition of this rare disease. Methods：Clinical characteristics, laboratory examination, imaging examination, endoscopic findings, pathological features and treatment of the patient with CMUSE from Children's Hospital of Fudan University were collected. The related literature was searched from Wanfang Data Service Platform, Chinese Biomedical Database, PubMed and EMBASE (up to June 2018) by using search terms ("cryptogenic multifocal ulcerating stenosing enteritis" OR CMUSE OR "cryptogenic, multifocal, ulcerous, and stenosing enteritis"). Results：We reported a male child who presented with repeated anaemia and melaena for more than 6 years. Capsule endoscopy of multifocal ulcerating stenosing and pathological features were compatible with CMUSE. Systemic corticosteroid was initiated at 2 mg·kg-1·d-1. The side effects of systemic corticosteroid about visual ambiguity were observed after one month. Then, the steroid was weaned, and azathioprine was initiated at 1 mg·kg-1·d-1 as a steroid-sparing agent. After following for 8 months, the patient was in the remission without anaemia, melaena and abdominal pain. According to literature, 68.6% of cases had an onset in youth and middle-age adults, and the main clinical manifestations were abdominal pain (67.9%), anaemia (32.1%) and gastrointestinal bleeding (18.5%). Capsule endoscopy had a risk retention rate of 37.9%, and the recurrence rate was high with the reoperation rate of 29.7%. Conclusion：The diagnosis of CMUSE should be considered in patients with unexplained recurrent melaena, anemia and small intestinal ulcers and stenosis. Endoscopy plays a vital role in the diagnosis. Glucocorticoid is effective, but easy to relapse.
Objective：To investigate the clinical features of urocanase deficiency caused by mutations in UROC1 gene. Methods：The clinical information and gene sequencing result of an urocanase deficiency patient that carried mutations in UROC1 gene was reported and the relative literature was reviewed. Results：The patient was a boy 1-year-1-month old, with complaint of 'unable to sit steadily without assistance or actively grasp objects'. He could hold his head up at 4.5 months, roll over at 6.5 months, actively found people at 8 months. Physical examination: slow response, internal strabismus, not good at tracking objects; hypertonia at upper limbs, hyperactive tendon reflex, cortical thumb sign. Concentration of folic acid was more than 25.2 ng·mL-1(reference value: 3.0-17.0 ng·mL-1). Head MRI scan presented increased extracerebral space and myelination development delay in bilateral temporal occipital lobe. LC–MS/MS assay of blood indicated increased concentration of histidine 116.075 μmol·L-1(reference value of 6 month - 1-year old babies is 0~79.3 μmol·L-1), with 1.464 times rate. The result of urine metabolic analysis was normal. Two mutations, one maternal missense mutation c.74G>A (p.G25E) and one paternal nonsense mutation c.74G>A (p.G25E) in UROC1 gene were discovered by gene sequencing. Both mutations are predicted to be deleterious on analysis. Searching on CNKI, Wanfang and PubMed databases, 3 English reports have been discovered, 4 cases of urocanase deficiency were reported. Including the case in our report, 5 cases have been reported till now. The diagnosis age of our patient is the youngest one, others were diagnosed at age 16, 9, 11 and 19 respectively; 2 male patients and 3 female patients have been reported; clinical features are all development delay and mental retardation with IQ less than 60. One patient was reported carrying compound heterozygous mutations c.209T>C and c.1348C>T in UROC1 gene. Conclusion：Mutations c.74G>A and c.854G>A might be novel pathogenic mutations in UROC1 gene that could cause abnormality in structure and function in urocanase. These mutations may cause urocanase deficiency.
Objective：To report a case of fructose-1,6-bisphosphatase deficiency diagnosed by genetic sequencing, and to improve the cognition of this rare disease and etiological diagnosis of status epilepticus (SE). Methods：Clinical data of the patient with FBP1 gene mutation from Children's Hospital of Fudan University were collected. The related literature was searched from Wanfang Data Service Platform, China National Knowledge Infrastructure and PubMed (up to October 2017) by using search terms "FBP1" and "Fructose-1,6-bisphosphatase deficiency". Results：A male patient with fructose bisphosphatase-1(FBP1) gene mutations who presented with SE and was misdiagnosed and treated with levetiracetam was reported. Genetic analysis of the family members revealed that the proband had compound heterozygous mutations of c.704delC and c.959dupG, which were inherited from his carrier parents, respectively. After genetic diagnosis, the patient was instructed to avoid prolonged fasting and to have fructose-free foods and finally withdrew from antiepileptic drugs. No seizures occurred during two years of follow-up. Sequencing of the amniotic fluid cells of the second child showed that the fetus only carried one heterozygous mutation which was inherited from the mother. According to the literature, 68.5% of cases had an onset in newborns or infancy, and the main causes were infection and inadequate intake. Main clinical manifestations were disturbance of consciousness, convulsions, gastrointestinal symptoms with hypoglycemia and lactic acidosis. Conclusion：For children manifested as recurrent SE with hypoglycemia, metabolic disorders should be considered. Correct diagnosis in early episodes is very important to improve the prognosis. Genetic counseling may be helpful to the family.
Objective：To investigate the clinical characteristics and gene information of Xia-Gibbs syndrome with AHDC1 mutaiton. Methods：A boy diagnosed of Xia-Gibbs syndrome confirmed by whole-exon sequencing (WES) which revealed a de novo mutation in AHDC1 was reported. His clinical data and gene mutation was summarized combined with cases retrieved from the related literatures. Results：This patient was first send to our clinic because of global development delay. He had no verbal words and was unable to creep. He had low-set ears and esotropia in left eye. Hypotonia was noted on physical examination. Patent foramen ovale (PFO) was detected by echocardiogram, and hydronephrosis (HN) was noted by renal ultrasound. Magnetic resonance imaging of brain revealed less white matter, thin corpus callosum. Bilateral and high amplitude delta waves was shown though an electroencephalogram. Whole exon sequencing indentied a de novo deletion mutation in AHDC1: c.750_753delCCTC, which probably leads to an even earlier stop of translation（p.T252Afs*7）.A total of 15 cases was retrieved from 6 literatures analyzed with AHDC1 mutation. The clinical phenotypes in all the effect individuals were dominated by mental retardation, mild craniofacial dysmorphism, hypotonia, respiratory and sleep disorders. Other similar medical features contained ataxia, epilepsy, autism, feeding difficulties and visual impairment. Thin corpus callosum was the majority brain anomaly observed by neurologic images. Totally 13 mutation sites had been reported and the most common type was truncating. Conclusion：Xia-Gibbs syndrome with AHDC1 mutation was characterized by severe mental retardation, facial dysmorphia，hypotonia and sleep apnea. Further functional expression still should be done to explore whether AHDC1 mutation plays a role in the cause of the PFO and hydronephrosis.
