Lipidomic profiles in serum and urine in children with steroid sensitive nephrotic syndrome.

BACKGROUND: Steroid-sensitive nephrotic syndrome (SSNS) accounts for approximately 80% of cases of nephrotic syndrome. The involvement of aberrant lipid metabolism in early SSNS is poorly understood, warranting further investigation. This study aimed to explore alterations in lipid metabolism associated with SSNS pathogenesis. METHODS: A screening cohort containing serum (50 SSNS, 37 controls) and urine samples (27 SSNS, 26 controls) was analyzed by untargeted lipidomic profiling using UHPLC-QTOF-MS. Then, a validation cohort (20 SSNS, 56 controls) underwent further analysis to check the potential clinical application by ROC curve analysis. RESULTS: Lipidomic profiling of serum and urine samples revealed significant lipid alterations in SSNS patients, with the alterations in the serum samples being more significant. An elevated concentration of PE and PG and downregulated concentration of FA were observed in SSNS serum. A total of 38 dysregulated lipids and 5 lipid metabolic pathways were identified in the serum samples in SSNS patients. Validation in the second cohort confirmed differential regulation of nine kinds of lipids, including 5 up-regulated substances [SM d33:2 (m/z = 686.5361), SHexCer d34:1 (m/z = 779.521), PI 20:4_22:4 (m/z = 934.5558), Cer_NS d18:1_23:0 (m/z = 635.6216), and GM3 d36:1 (m/z = 1180.7431)], as well as 4 down-regulated substances: [CE 18:1 (m/z = 650.601), PE 38:6 (m/z = 763.5205), PC 17:0_20:4 (m/z = 795.5868) and EtherPC 16:2e_20:4 (m/z = 763.5498)]. CONCLUSIONS: Untargeted lipidomic analysis successfully identified specific lipid class changes in patients with SSNS, providing a deeper understanding of lipid alterations and underlying mechanisms associated with SSNS.

Construction of a mycelium sphere using a Fusarium strain isolate and Chlorella sp. for polyacrylamide biodegradation and inorganic carbon fixation.

In the context of global demand for carbon reduction, the formation of inorganic carbon (IC) in the wastewater from oil flooding becomes a potential threat. In this study, Chlorella sp. and Fusarium sp. were used to assemble a fungal-algal pellet to degrade polyacrylamide (PAM) and fix IC in synthetic oil-flooding wastewater. The results showed that the combination of Chlorella sp. and Fusarium sp. was more effective at degrading PAM and removing carbon than a monoculture. With PAM as the sole nitrogen source, the degradation of PAM by the consortium was enhanced up to 35.17 ± 0.86% and 21.63 ± 2.23% compared with the monocultures of fungi or microalgae, respectively. The degradation of the consortium was significantly enhanced by the addition of an external nitrogen source by up to 27.17 ± 2.27% and 22.86 ± 2.4% compared with the monoculture of fungi or microalgae, respectively. This may depend on the effect of synergy between the two species. For the removal of IC from the water, the removal efficiency of the consortium was higher than that of the microalgae by 38.5 ± 0.08%, which may be attributed to the ability of the fungi to aid in the adsorption of nutrients and its assimilation by the microalgae. Therefore, the Fusarium-Chlorella consortium can effectively degrade PAM, while simultaneously fixing carbon, which provides a feasible scheme for the treatment and carbon neutralization of the wastewater that contains PAM.

Immune microenvironment associated with the severity of Langerhans cell histiocytosis in children.

The aim of this study is to investigate the clinical potential of immune microenvironment in peripheral blood for the severity and therapeutic efficacy of Langerhans cell histiocytosis (LCH). A total of 200 newly diagnosed children with LCH during 10 years was enrolled for analysis in this study. Peripheral blood samples were acquired from patients before treatment in our hospital and immune indicators were detected by a four-color flow cytometer. The levels of CD3 + CD8 + T cell, CD3 + CD4 + HLA-DR + T cell, CD3 + CD8 + HLA-DR + T cell, IL-4, IL-6, IL-10 and IFN-γ in peripheral blood were markedly elevated in LCH patients vs. healthy controls. Patients with multiple system with risk organ involvement (MS-RO + ) exhibited higher levels in IL-6, IL-10 and IFN-γ, CD3 + CD4 + HLA-DR + T cell and CD3 + CD8 + HLA-DR + T cell, compared to those in patients without risk organ involvement (RO-). Patients who responded effectively to initial chemotherapy showed significantly lower levels of IL-4, IL-10, IFN-γ, CD3 + CD4 + HLA-DR + T cell and CD3 + CD8 + HLA-DR + T cell in peripheral blood, compared to those in patients who did not respond to initial chemotherapy. Furthermore, univariate analyses were performed that the higher levels of CD3 + CD4 + HLA-DR + T cells, CD3 + CD8 + HLA-DR + T cells and IL-10 in peripheral blood were related to non-response in LCH after initial chemotherapy. Immune microenvironment in peripheral blood may be associated with the severity and treatment response of LCH. The levels of CD3 + CD4 + HLA-DR + T cells, CD3 + CD8 + HLA-DR + T cells and IL-10 may be biomarkers to predict treatment response of LCH patients.

Metabolomic profiles in serum and urine uncover novel biomarkers in children with nephrotic syndrome.

BACKGROUND: Nephrotic syndrome is common in children and adults worldwide, and steroid-sensitive nephrotic syndrome (SSNS) accounts for 80%. Aberrant metabolism involvement in early SSNS is sparsely studied, and its pathogenesis remains unclear. Therefore, the goal of this study was to investigate the changes in initiated SSNS patients-related metabolites through serum and urine metabolomics and discover the novel potential metabolites and metabolic pathways. METHODS: Serum samples (27 SSNS and 56 controls) and urine samples (17 SSNS and 24 controls) were collected. Meanwhile, the non-targeted analyses were performed by ultra-high-performance liquid chromatography-quadrupole time of flight-mass spectrometry (UHPLC-QTOF-MS) to determine the changes in SSNS. We applied the causal inference model, the DoWhy model, to assess the causal effects of several selected metabolites. An ultraperformance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) was used to validate hits (D-mannitol, dulcitol, D-sorbitol, XMP, NADPH, NAD, bilirubin, and α-KG-like) in 41 SSNS and 43 controls. In addition, the metabolic pathways were explored. RESULTS: Compared to urine, the metabolism analysis of serum samples was more clearly discriminated at SSNS. 194 differential serum metabolites and five metabolic pathways were obtained in the SSNS group. Eight differential metabolites were identified by establishing the diagnostic model for SSNS, and four variables had a positive causal effect. After validation by targeted MS, except XMP, others have similar trends like the untargeted metabolic analysis. CONCLUSION: With untargeted metabolomics analysis and further targeted quantitative analysis, we found seven metabolites may be new biomarkers for risk prediction and early diagnosis for SSNS.

Proposal for High-Energy Cutoff Extension of Optical Harmonics of Solid Materials Using the Example of a One-Dimensional ZnO Crystal.

We propose a novel approach based on the subcycle injection of carriers to extend the high-energy cutoff in solid-state high harmonics. The mechanism is first examined by employing the standard single-cell semiconductor Bloch equation (SC SBE) method for one-dimensional (1D) Mathieu potential model for ZnO subjected to the intense linearly polarized midinfrared laser field and extreme-ultraviolet pulse. Then, we use coupled solution of Maxwell propagation equation and SC SBE to propagate the fundamental laser field through the sample, and find that the high-harmonics pulse train from the entrance section of the sample can inject carriers to the conduction bands with attosecond timing, subsequently leading to a dramatic extension of high-energy cutoff in harmonics from the backside. We predict that for a peak intensity at 2×10^{11} W/cm^{2}, as a result of the self-seeding, the high-energy cutoff shifts from 20th (7.75 eV) order to around 50th (19.38 eV) order harmonics.

Cytokine Gene Polymorphisms in Chinese Children with Idiopathic Nephrotic Syndrome.

BACKGROUND: Cytokines play a role in the progression of idiopathic-nephrotic syndrome (INS). OBJECTIVES: To investigate the association of different cytokine genes polymorphisms with INS incidence and response to steroid therapy in Chinese children. METHODS: 182 children with INS and 100 healthy controls were enrolled in this study. Blood genomic DNAs were used to analyze20 single nucleotide polymorphisms (SNPs) in 8 cytokine genes includingIL-21, IL-18, IL-6, IFN-γ, IL-4, IL-10, IL-17F, IL-17A d by multi-PCR with next-generation sequencing. RESULTS: Among 182 children with INS, 89 (48.6%) were steroid-sensitive (SS), 73 (39.9%) were steroid-dependent (SD) and 21 (11.5%) were steroid-resistant (SR). In 20 SNPs, IL-4-rs2243283 exhibited a significantly different genotype distribution between INS and the healthy controls (CC is a risk genotype: 66.5% of INS VS 51% of the control; OR=1.91, p=0.012). Patients carrying AG genotype (rs2275913, IL-17A) had a significantly higher risk of steroid-dependent response (69.1% of SD VS 46.4% of SS; OR=2.58, p=0.014). Similarly, patients carrying A allele of IL-10-rs1800872 (39.0% of SD VS 26.7% of SS; OR=1.76, p=0.018) and C allele of IL-10-rs1800896 (12.3% of SD VS 3.9% of SS; OR=3.44, p=0.004) had a higher risk of steroid-dependent response. However, none of these 20 SNPs showed a significant difference between SS group and SR group. CONCLUSION: Among the 20 cytokine gene SNPs, IL-4-rs2243283 might increase the susceptibility to INS in Chinese children; rs2275913 of IL-17A, rs1180972, and rs1800896 of IL-10 show association with the steroid -response in Chinese INS children.

Molecular characteristics of Clostridium difficile in children with acute gastroenteritis from Zhejiang.

BACKGROUND: Clostridium difficile infection (CDI) has an increasing pediatric prevalence worldwide. However, molecular characteristics of C. difficile in Chinese children with acute gastroenteritis have not been reported. METHODS: A five-year cross-sectional study was conducted in a tertiary children's hospital in Zhejiang. Consecutive stool specimens from outpatient children with acute gastroenteritis were cultured for C. difficile, and isolates then were analyzed for toxin genes, multi-locus sequence type and antimicrobial resistance. Diarrhea-related viruses were detected, and demographic data were collected. RESULTS: A total of 115 CDI cases (14.3%), and 69 co-infected cases with both viruses and toxigenic C. difficile, were found in the 804 stool samples. The 186 C. difficile isolates included 6 of toxin A-positive/toxin B-positive/binary toxin-positive (A+B+CDT+), 139 of A+B+CDT-, 3 of A-B+CDT+, 36 of A-B+CDT- and 2 of A-B-CDT-. Sequence types 26 (17.7%), 35 (11.3%), 39 (12.4%), 54 (16.7%), and 152 (11.3%) were major genotypes with significant differences among different antimicrobial resistances (Fisher's exact test, P < 0.001). The A-B+ isolates had significantly higher resistance, compared to erythromycin, rifampin, moxifloxacin, and gatifloxacin, than that of the A+B+ (χ2 = 7.78 to 29.26, P < 0.01). The positive CDI rate in infants (16.2%) was significantly higher than that of children over 1 year old (10.8%) (χ2 = 4.39, P = 0.036). CONCLUSIONS: CDI has been revealed as a major cause of acute gastroenteritis in children with various genotypes. The role of toxigenic C. difficile and risk factors of CDI should be emphatically considered in subsequent diarrhea surveillance in children from China.

Hemolytic specimens in complete blood cell count: Red cell parameters could be revised by plasma free hemoglobin.

INTRODUCTION: Hemolysis is the main cause of unqualified clinical samples. In this study, we established a method for detecting and evaluating hemolysis in whole blood test. We used a mathematical formula for correcting the influence of hemolysis on complete blood cell count (CBC) so as to avoid re-venipuncture and obtain more accurate parameters of red blood cell detection, reduce the burden of patients, and improve the efficiency of diagnosis and treatment. METHODS: Hemolytic samples were selected and then corrected using the new formula. Plasma free hemoglobin (fHB) was used as the criterion to determine the degree of hemolysis; the uncertainty of measurement is acceptable as the limit value of deviation between the measured value and the revised value. Hemolysis simulation analysis in vitro and continuous monitoring of clinical patients were used to verify the correction effect. RESULTS: A total of 83 clinical samples with hemolysis were collected and analyzed; fHB 1.4 g/L was selected as the unacceptable value for clinical hemolysis detection. In hemolytic samples, the red blood cell parameters corrected by formula are significantly different from those uncorrected and had a good consistency with those before hemolysis. CONCLUSION: The results show that the hemolysis phenomenon of CBC has a significant impact on routine blood testing. By using the new formula, the influence of hemolysis on erythrocyte and related parameters can be quickly and easily corrected, thus avoiding venipuncture again for re-examination, reducing diagnostic errors, and saving medical resources.

Evaluation of a commercial latex agglutination test for detecting rotavirus A and human adenovirus in children's stool specimens.

OBJECTIVES: Rotavirus A and human adenovirus are the two most common causes of infantile diarrhea; thus, it is of great importance to find out a rapid and accurate diagnostic method. This study aimed to evaluate the diagnostic significance of latex agglutination test for detection of rotavirus A and human adenovirus. METHODS: A prospective study was conducted on 214 diarrhea children from September 2018 to March 2019 in our hospital. Fresh stool samples were collected for detection of rotavirus A and human adenovirus by latex agglutination test and quantitative reverse transcription polymerase chain reaction (RT-qPCR). Then, the consistency of results detected by these two methods was analyzed． RESULTS: With performing the latex agglutination test, it was revealed that positive rates for detecting rotavirus A virus and human adenovirus were 23.83% (51/214) and 25.24% (54/214), respectively. Meanwhile, results of RT-qPCR showed that positive rates for detecting rotavirus A virus and human adenovirus were 58 (27.10%) and 59 (27.57%), respectively. Using RT-qPCR as the gold standard, the sensitivity and specificity of the latex agglutination test for detecting rotavirus A were 81.03% and 97.44%, and the corresponding values for detecting human adenovirus were 76.27% and 94.19%, respectively. CONCLUSION: This latex agglutination test showed a satisfactory consistency with RT-qPCR for detecting rotavirus A and human adenovirus. The mentioned commercial assay may be highly appropriate for rapid screening of rotavirus A and human adenovirus.

Changes and correlations of serum interleukins, adhesion molecules and soluble E-selectin in children with allergic rhinitis and asthma.

OBJECTIVE: To observe the changes and correlations of serum interleukins (ILs), adhesion molecules and soluble E-selectin (sE-selectin) in children with allergic rhinitis, asthma and both diseases. METHODS: A total of 45 children with allergic rhinitis, 40 with asthma and 45 with allergic rhinitis complicated with asthma treated from September 2016 to January 2018 were selected. Meanwhile, 30 healthy subjects who received physical examinations were included as a control group. The levels of serum IL-4, IL-5, IL-10, soluble intercellular adhesion molecule-1 (sICAM-1), soluble vascular adhesion molecule-1 (sVCAM-1), and sE-selectin were detected by double-antibody sandwich ELISA, and their correlations were subjected to Spearman's correlation analysis. RESULTS: The serum IL levels of allergic rhinitis, asthma and complication groups were significantly higher than those of control group (P<0.01), and the levels of complication group significantly exceeded those of asthma group (P<0.05). The serum levels of IL-5 and IL-10 in complication group significantly exceeded those of allergic rhinitis group (P<0.05). Compared with control group, serum sICAM-1, sVCAM-1, and sE-selectin levels significantly increased in other three groups (P<0.01). Such levels of complication group were significantly higher than those of allergic rhinitis and asthma groups (P<0.05). Serum IL-10 level was positively correlated with that of IL-4 (r=0.965, P<0.05), and sE-selectin level was positively correlated with those of sICAM-1 and sVCAM-1 (r=0.915, P<0.01; r=0.892, P<0.01). CONCLUSION: Serum IL-4, IL-5, IL-10, adhesion molecules and sE-selectin are all involved in the pathogenesis of allergic rhinitis and asthma, which can be used to evaluate the degrees of respiratory allergic diseases.

Rapid and sensitive identification of glycoprotein H genotypes in clinical human cytomegalovirus samples.

Human cytomegalovirus (HCMV) is a common pathogen that causes persistent infections in immune deficient patients and results in significant morbidity and mortality, particularly among transplant recipients and children. Different HCMV glycoprotein H (gH) genotypes may cause different diseases and affect the severity of these diseases. To develop a sensitive quantitative real-time PCR assay that could rapidly distinguish between two HCMV gH genotypes, primers were designed to target the conserved region of the gH gene. gH1 and gH2 probes were designed to target the two variable regions. Standard HCMV strains (AD169 and TOWNE) and 203 clinical urine samples from HCMV infected children were used for the present study. Based on the primer-probe set used to detect the target gH gene segment of HCMV, our quantitative real-time PCR assay specifically discriminated between HCMV gH1 and gH2 with a detection limit of approximately 10(2) viral copies/ml. Among the 203 clinical urine samples tested, 145 were gH1 positive, 56 were gH2 positive, and 2 were positive for both. Thus, we developed a gH gene-based real time-PCR method that could rapidly, stably, and specifically distinguish between two HCMV gH genotypes. We found HCMV gH1 to be common among children examined in Zhejiang, China.

Serum suPAR levels help differentiate steroid resistance from steroid-sensitive nephrotic syndrome in children.

BACKGROUND: Soluble urokinase plasminogen activator receptor (suPAR) has been regarded as a permeability factor in proteinuria, though its role in primary nephrotic syndrome remains to be elucidated further. METHODS: Plasma samples and clinical information from 176 children with primary nephrotic syndrome were collected and concentrations of suPAR were measured. We evaluated the correlation between suPAR concentrations and clinical features, and the value of the plasma suPAR level in predicting steroid-resistant nephrotic syndrome (SRNS). RESULTS: There is a significant difference in plasma suPAR concentration between SRNS and steroid-sensitive nephrotic syndrome (SSNS) groups (3,744.1 ± 2,226.0 vs. 2,153.5 ± 1,167.0, p < 0.05). The area under the curve (AUC) was 0.80, with p < 0.001 for the receiver operating characteristic (ROC) curve analysis using suPAR to predict SRNS. The suspicious range for predicting SRNS was estimated to be 1,907.0 pg/ml to 3,043.5 pg/ml (χ(2) = 14.775, p = 0.001). CONCLUSIONS: From ROC curve analysis, we demonstrated the significance of the suPAR level in predicting SRNS with a high specificity but low sensitivity. However, the clinical value of suPAR to predict steroid resistance and guide therapy remains to be investigated further.