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Several observational studies have reported associations between low levels of fat-soluble vitamins (A, D and E) and the incidence of pneumonia. Whether infection affects or negatively regulates serum vitamin levels remains controversial. Our aims were to develop and validate a simple-pretreatment and fast method to determine the serum levels of selected fat-soluble vitamins, namely vitamin A (retinol), vitamin D (25-OH-D

The purpose of this study is to understand children’s clinical characteristics with pertussis and analyze risk factors on critical pertussis patients. Demographic data from patients with pertussis at Children’s Hospital affiliated to the Capital Institute of Pediatrics between March 2011 and December 2018 were collected. We retrospectively gathered more information with the positive exposure, vaccination, antibiotic usage before diagnosis, clinical manifestation, laboratory tests, therapy, and complications for hospitalized children. We divided the patients into severe and non-severe groups, comparing related factors and clinical characteristics among each group. In particular, we summarize the clinical features of the severe patients before aggravation. A total of 967 pertussis cases were diagnosed, of which 227 were hospitalized. The onset age younger than 3 months old accounted for the highest proportion, and 126 patients received hospitalization. For those patients, the incidence of post-tussive vomiting, paroxysmal cyanosis, post-tussive heart rate decrease, hypoxemia, severe pneumonia, and mechanical ventilation was significantly higher than that in the ≥ 3-month-old group (p

Background Langerhans cell histiocytosis (LCH) is a rare neoplastic disease that occurs in both children and adults, and BRAF V600E is detected in up to 64% of the patients. Several studies have discussed the associations between BRAF V600E mutation and clinicopathological manifestations, but no clear conclusions have been drawn regarding the clinical significance of the mutation in pediatric patients. Results We retrieved the clinical information for 148 pediatric LCH patients and investigated the BRAF V600E mutation using next-generation sequencing alone or with droplet digital PCR. The overall positive rate of BRAF V600E was 60/148 (41%). The type of sample (peripheral blood and formalin-fixed paraffin-embedded tissue) used for testing was significantly associated with the BRAF V600E mutation status (p-value = 0.000 and 0.000). The risk of recurrence declined in patients who received targeted therapy (p-value = 0.006; hazard ratio 0.164, 95%CI: 0.046 to 0.583). However, no correlation was found between the BRAF V600E status and gender, age, stage, specific organ affected, TP53 mutation status, masses close to the lesion or recurrence. Conclusions This is the largest pediatric LCH study conducted with a Chinese population to date. BRAF V600E in LCH may occur less in East Asian populations than in other ethnic groups, regardless of age. Biopsy tissue is a more sensitive sample for BRAF mutation screening because not all of circulating DNA is tumoral. Approaches with low limit of detection or high sensitivity are recommended for mutation screening to avoid type I and II errors.

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Background Sepsis is a leading cause of pediatric morbidity and mortality worldwide. The aim of this study was to explore the association of decreased mitochondrial respiratory chain enzyme activities with the risk for pediatric sepsis, and explore their association with mortality among affected children. Methods A total of 50 incident cases with sepsis and 49 healthy controls participated in this study. The level of serum coenzyme Q10 was measured by high-performance liquid chromatography, and selected mitochondrial respiratory chain enzymes in WBC were measured using spectrophotometric. Logistic regression models were used to estimate odds ratio (OR) and 95% confidence interval (CI). Results The levels of CoQ10, complex II, complex I + III and FoF1-ATPase were significantly higher in healthy controls than in children with sepsis (p p p = 0.001, p = 0.004 and 0.001, respectively) in children with sepsis. Conclusions Our findings indicate the promising predictive contribution of low serum CoQ10 and complex I + III to the risk of pediatric sepsis and its associated mortality during hospitalization among Chinese children. Trial registration The trial was registered with www.chictr.org.cn, number ChiCTR-IOR-15006446 on May 05, 2015. Retrospectively registered.

Objective We determined the yield, genetic spectrum, and actual origin of de novo mutations (DNMs) for infantile spasms (ISs) in a Chinese cohort. The efficacy of levetiracetam (LEV) for STXBP1‐related ISs was explored also. Methods Targeted sequencing of 153 epilepsy‐related candidate genes was applied to 289 Chinese patients with undiagnosed ISs. Trio‐based amplicon deep sequencing was used for all DNMs to distinguish somatic/mosaic mutations from germline ones. Results Total of 26 DNMs were identified from 289 recruited Chinese patients with undiagnosed ISs. Among them, 24 DNMs were interpreted as pathogenic mutations based on American College of Medical Genetics and Genomics guidelines, contributing to 8.3% (24/289) of diagnosis yield in the Chinese IS cohort. CDKL5 and STXBP1 are the top genes with recurrent DNMs, accounting for 3.1% (9/289) of yield. Further deep resequencing for the trio members showed that 22.7% (5/22) of DNMs are actually somatic in the proband or a parent. These somatic carriers presented milder seizure attacks than those with true germline DNMs. After treatment with LEV for half a year, three patients with DNM in STXBP1 showed improved clinical symptoms, including seizure‐free and normal electroencephalogram, except for a patient with a second DNM in DIAPH3. Significance Our study confirmed the contribution and genetic spectrum of DNMs in Chinese IS patients. Somatic mutation account for a quarter of DNMs in IS cases. Treatment with LEV improved the prognosis of STXBP1‐related ISs., The contribution and genetic spectrum of de novo mutations (DNMs) was confirmed in infantile spasms (ISs). Somatic mutation accounted for 22.7% of DNMs in IS patients. Treatment with levetiracetam improved the prognosis of STXBP1‐related ISs.

Background Neurodevelopmental disorders (NDDs) are a group of disorders with high genetic and phenotypic heterogeneities. The 16p11.2 microdeletion has been implicated as an important genetic risk factor for NDDs. Methods Multiple genetic tests were used to detect the 16p11.2 microdeletion from 918 Chinese children with NDDs. Targeted sequencing of genes in the 16p11.2 interval was performed in all carriers of the 16p11.2 microdeletion, and whole‐genome expression profiling analysis was performed for the patient carriers and normal carriers in their intra‐family. Results Three patients carrying the 16p11.2 microdeletion were screened out, indicating a frequency of 0.33% for the 16p11.2 microdeletion in this cohort. We reviewed the neurodevelopmental trajectories of the 16p11.2 microdeletion carriers from childhood to puberty and confirmed that this microdeletion was associated with abnormal neurodevelopment, with varied neurodevelopmental phenotypes. A differential PRRT2 genotype (rs10204, T>C) was identified between patients and normal carriers of the 16p11.2 microdeletion. Moreover, the determination of differential whole‐genome expression profiling demonstrated the destruction of the top‐ranked network in neurogenesis and accounted for observation of abnormal neurodevelopmental phenotypes in the 16p11.2 microdeletion carriers. Conclusions We have provided the frequency of the 16p11.2 microdeletion in a Chinese pediatric NDD cohort with a variable NDD phenotype from childhood to puberty, which is useful for Chinese geneticists/pediatricians to conduct the 16p11.2 microdeletion testing in children with NDDs., We screened out three patients carrying 16p11.2 microdeletion from a Chinese pediatric NDD cohort, producing a frequency of 0.33% for 16p11.2 microdeletion, which is useful for Chinese geneticists/pediatricians before conducting the 16p11.2 microdeletion testing in children with NDDs. We reviewed the neurodevelopmental trajectories of these child carriers of 16p11.2 microdeletion from childhood to puberty and confirmed that this microdeletion was associated with abnormal neurodevelopmental outcomes, but with varied neurodevelopmental phenotypes. Furthermore, the determination of differential whole‐genome expression profiling between a patient carrier and their intra‐family normal carrier of 16p11.2 microdeletion demonstrated destruction of the top‐ranked network for nervous system development, thus accounting for the observed abnormal neurodevelopmental phenotypes in 16p11.2 microdeletion carriers.

Purpose To examine the overall genomic copy-number variant (CNV) landscape of Chinese pediatric patients with developmental disorders. Methods De-identified chromosomal microarray (CMA) data from 10,026 pediatric patients with developmental disorders were collected for re-evaluating the pathogenic CNV (pCNV) yields of different medical conditions and for comparing the frequency and phenotypic variability of genomic disorders between the Chinese and Western patient populations. Results The overall yield of pCNVs in the Chinese pediatric patient cohort was 21.37%, with variable yields for different disorders. Yields of pCNVs were positively associated with phenotypic complexity and intellectual disability/developmental delay (ID/DD) comorbidity for most disorders. The genomic burden and pCNV yield in neurodevelopmental disorders supported a female protective effect. However, the stratification analysis revealed that it was seen only in nonsyndromic ID/DD, not in nonsyndromic autism spectrum disorders or seizure. Furthermore, 15 known genomic disorders showed significantly different frequencies in Chinese and Western patient cohorts, and profiles of referred clinical features for 15 known genomic disorders were also significantly different in the two cohorts. Conclusion We defined the pCNV yields and profiles of the Chinese pediatric patients with different medical conditions and uncovered differences in the frequency and phenotypic diversity of genomic disorders between Chinese and Western patients.

Vancomycin is a glycopeptide antibiotic widely used against Gram-positive bacteria such as methicillin-resistant Staphylococcus aureus and coagulase-negative Staphylococcus. Several studies have found that in adults, continuous infusions of vancomycin showed earlier attainment of desired target drug concentrations and reduced nephrotoxicity relative to intermittent infusion. In the pediatric population, there is no consensus on the best vancomycin infusion method. The present study developed and validated a simple and cost-effective UPLC method to determine serum vancomycin levels in pediatric patients and applied it to the therapeutic drug monitoring of vancomycin in children who were treated with either continuous infusion or intermittent infusion of vancomycin. The sample preparation procedure involves only protein precipitation and filtration, and the UPLC method takes 5 min/sample. The assay was linear from 5 mg/L to 100 mg/L (R2 = 0.999). The precision and accuracy were determined at 4 concentration levels. The intraday variability (%CV) ranged from 1.23% to 6.01% (n = 6), and the interday variability ranged from 3.02% to 9.75% (n = 18). The accuracies were good and ranged from 91.21% to 112.63%. Serum vancomycin was stable at room temperature for 12 h or for 3 freeze/thaw cycles, and the processed sample was stable in an autosampler within 15.5 h.

Previous studies have demonstrated a potential role of STAT4 polymorphisms in increased juvenile idiopathic arthritis (JIA) risk in Caucasian populations; however, their role remains unclear in Han Chinese populations. We aimed to investigate single nucleotide polymorphisms (SNPs) of STAT4 and their role in JIA in Han Chinese populations.This study included 205 JIA cases and 267 healthy controls. MassArray high-throughput DNA analyser and mass spectrometry were used to analyse 16 STAT4 SNP sites. The relationship between these SNPs and JIA risk was calculated using multiple logistic regressions.The G allele of rs11893432 was associated with an increased risk of JIA (odds ratio [OR]: 1.73; 95% confidence interval [CI]: 1.03-2.88; p=0.037). This relationship was observed in oligoarticular JIA (OR: 2.75; 95% CI: 1.29-5.83; p=0.026), and not in polyarticular JIA or systemic JIA. The GG motif was significantly correlated with oligoarticular JIA risk,compared to the CC+CG motif (OR: 1.88; 95% CI: 1.06-3.32; p=0.034). The C allele of rs1018981 and the A allele of rs10931481 were associated with a greater risk of polyarticular JIA (C allele: [OR: 7.82; 95% CI: 1.06-57.74; p=0.044]; A allele: [OR: 2.86; 95% CI: 1.23, 6.65; p=0.039).The G allele of rs11893432 was significantly associated with JIA risk, particularly oligoarticular JIA, in Han Chinese populations. SNPs at rs1018981 and rs10931481 were correlated with higher risk of polyarticular JIA.

We assessed the relationship between serum 25-hydroxyvitamin D (25(OH)D) level and community-acquired pneumonia (CAP) among Chinese children. This observational study examined children aged 3 days to 14 years (n = 1582) from the Capital Institute of Pediatrics in 2009 to 2011. There were 797 children in the CAP group and 785 controls. The CAP group was divided into 2 groups: a pneumonia group and pneumonia-induced sepsis group. The serum 25(OH)D level was estimated using micro whole blood chemiluminescence. The average serum 25(OH)D level in all samples was 25.32 ± 14.07 ng/mL, with the CAP group showing a lower value than the control group (P

The mechanisms underpinning Kawasaki disease (KD) are incompletely understood. There is an unmet need for specific biomarkers for the early diagnosis of KD.Eighty-five KD patients suffering from acute-phase and subacute-phase KD, 40 healthy children, and 40 febrile children comprised the study cohort. An enzyme-linked immunosorbent assay was used to measure plasma levels of C1q, C1q-circulating immune complex (C1q-CIC), mannan-binding lectin-associated serine protease (MASP)-1, factor B, C4d, C3d, C5a, C5b-9 and CD59.Plasma concentrations of factor B and C5a in the acute phase were lower than those in healthy and febrile control groups (all P0.05). Compared with acute-phase KD patients, plasma concentrations of C1q, factor B, and C3d in KD patients were increased significantly (P0.05), but those of C4d, MASP-1 and CD59 decreased significantly (P0.05), in patients with sub-acute KD.These data suggest that more than one pathway in the complement system is activated in KD. Importantly, decreased plasma concentrations of factor B and C5a in the acute phase (6-10 d) could be employed as biomarkers for the early diagnosis of KD.

Vitamin D receptor (VDR) is a potential candidate gene for community-acquired pneumonia (CAP). Examining the susceptibility VDR gene for CAP is essential for early intervention, prevention of related complications, and improvement of outcome. A case-control study was performed to examine the association between rs2239185 of VDR gene and CAP among children in Chinese Han population. Polymerase chain reaction and direct sequencing were used to genotype rs2239185 in 91 CAP children and 94 healthy children. For rs2239185, individuals with TT genotype showed a significantly higher risk of CAP than those with CC plus CT genotypes (P = 0.008). The occurrence of T allele of rs2239185 was significantly more frequent in CAP children than those in normal controls (P = 0.045).We found through stratification analysis that CAP children with systemic inflammatory response syndrome (SIRS), leukocyte count (WBC) >10 × 109/L, C-reactive protein (CRP) >25 mg/L, procalcitonin (PCT) >2 ng/mL, and pediatric critical illness score

Aim Methylation abnormalities in T lymphocytes have been reported to correlate with systemic lupus erythematosus (SLE). Previous studies identified hypomethylation in the promoter of several genes linked to SLE. Long interspersed nucleotide element-1 (LINE-1) constitutes 17–25% of the human genome, and LINE-1 hypomethylation has been reported in SLE. Limited information is available regarding LINE-1 methylation in juvenile SLE (JSLE). Method Methylation levels of LINE-1 in peripheral blood mononuclear cells (PBMCs) from 59 JSLE and 47 control samples were examined by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. Total homocysteine (tHcy) concentrations in plasma were measured by immunoassay. Results Significant hypomethylation of LINE-1 was observed in PBMCs from JSLE patients (60.93% in cases compared with 62.88% in controls, P = 0.001). Significant LINE-1 hypomethylation was observed in active SLE compared to controls (60.66% vs. 62.88%, P = 0.001). According to other clinical parameters, a significant correlation was found between LINE-1 methylation levels and the Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2000) of the cases (r = −0.285, P = 0.032). The risk of JSLE increased with decreasing levels of LINE-1 methylation, with an odds ratio of 14.5 (95% CI: 2.8–75.6, P = 0.002). Cases had significantly higher plasma concentrations of tHcy than controls (15.11 vs. 11.02 μmol/L, P = 0.028); the correlation between LINE-1 methylation levels and tHcy was significant (r = −0.4, P = 0.013). Correlations between methylation levels of LINE-1 and complement component 3 were significant (r = 0.317, P = 0.044; r = 0.387, P = 0.031, in total JSLE and active JSLE, respectively). Conclusion Hypomethylation of LINE-1 is associated with risk of JSLE, and LINE-1 methylation levels were related to disease activity and clinical manifestations. The correlation between tHcy levels and LINE-1 methylation was significant.

Streptococcal infection and basal ganglia inflammation are hypothesized to be involved in Tourette’s syndrome (TS). There is a need for effective therapies for managing TS. We studied streptococcal infection and immunity in TS following immunomodulator (pidotimod) therapy. Blood samples from 58 patients with TS and 128 age-matched healthy controls enabled measurement of antistreptolysin O (ASO), T cells, natural killer (NK) cells, interleukin-6 (IL-6) and interleukin-8 (IL-8), and tumor necrosis factor-α (TNF-α). Forty-four patients with abnormal T cell numbers were divided into two groups and treated with pidotimod granules (pidotimod group, n = 20) or pidotimod plus dopaminergic receptor antagonists (combination group, n = 24). Yale Global Tic Severity Scale (YGTSS) scores and immunologic indices were assessed after treatment. An ASO >1:200 was found in 22.4 % of children with TS, 7.5 % of controls, and 38.9 % of children with both TS and attention deficit hyperactivity disorder (ADHD) compared to 15.0 % of children with TS alone (P

Background Tryptophan hydroxylase-2 (TPH2) is a potential candidate gene for screening tic disorder (TD). Methods A case–control study was performed to examine the association between the TPH2 gene and TD. The Sequenom® Mass ARRAY iPLEX GOLD System was used to genotype two single nucleotide polymorphisms (SNPs) of the TPH2 gene in 149 TD children and in 125 normal controls. Results For rs4565946, individuals with the TT genotype showed a significantly higher risk of TD than those with TC plus CC genotypes [odds ratio (OR) =3.077, 95% confidence interval (CI): 1.273–7.437; P = 0.009], as did male TD children with the TT genotype (OR = 3.228, 95% CI: 1.153–9.040; P = 0.020). The G allele of rs4570625 was significantly more frequent in TD children with higher levels of tic symptoms (Yale Global Tic Severity Scale, YGTSS) than those in controls among the male children (OR = 1.684, 95%: 1.097–2.583; P = 0.017]. TD children with severe tic symptoms had significantly higher frequencies of rs4546946 TT genotype than did normal controls in boys (OR = 3.292, 95% CI: 1.139–9.513; P = 0.022). We also found that genotype distributions of both SNPs were different between the Asian and European populations. Conclusions Our results indicated that the TT genotype of rs4565946 is a potential genetic risk factor for TD, and the allele G of rs4570625 might be associated with the severity of tic symptoms in boys. These polymorphisms might be susceptibility loci for TD in the Chinese Han population. Because of the confounding of co-existing attention deficit hyperactivity disorder (ADHD),these findings need to be confirmed by studies in much larger samples.