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Background: Between 10 and 20% of Kawasaki disease (KD) patients are resistant to treatment with initial intravenous immunoglobulin (IVIG) and have a high risk of developing coronary artery lesions. Some studies have been conducted to identify predictive factors. However, the results are controversial. This study aims to identify the risk factors for IVIG-resistant KD patients in a Chinese population.Methods: We performed a retrospective analysis of medical records of consecutive KD patients from two medical centers in South China from January 2015 to December 2017. A total of 1281 KD patients were eligible for inclusion in this study and maintained follow-up for over 12 months. The KD patients were divided into two groups based on IVIG response. Clinical characteristics and laboratory variables were compared between the two groups. Multivariate logistic regression analysis was performed to identify the risk factors of IVIG resistance in KD patients.Results: Of the 1281 KD patients, 141 (11.0%) cases who were IVIG resistant to adjunctive therapies for primary treatment were classified as group 1. The remaining patients were in group 2 (n = 1140), classified as the control group. There was a significant difference in male to female ratio and the length of hospital stay between the two groups (P < 0.05). Group 1 had a higher white blood cell count (P=0.01) and C-reactive protein level (P < 0.01) before IVIG treatment than in group 2. Group 1 had a significantly higher white blood cell count and percentage of neutrophils after the IVIG infusion than in group 2 (P < 0.001). In addition, the mean values of C-reactive protein level and neutrophil percentage before and after treatment difference comparison were significantly different. Multivariate analysis showed that patients presenting with coronary artery lesions in the acute phase and a C-reactive protein level >100 mg/L at diagnosis were associated with IVIG resistance in KD. During the 12-month follow-up period, group 1 had an obviously higher incidence of coronary artery lesions than group 2, and the difference between the groups was statistically significant (P < 0.001).Conclusions: Patients presenting with coronary artery lesions in the acute phase and elevated C-reactive protein levels before IVIG treatment might be a useful and important value for predicting IVIG resistance in KD. Risk assessment based on coronary artery lesions and C-reactive protein levels prior to the treatment may improve the outcome of IVIG resistance. [ABSTRACT FROM AUTHOR]

The aim of this study was to investigate the effects of substituting soybean oil (SO) for fish oil (FO) on the performance, tissue fatty acid (FA) composition, plasma components, liver metabolic enzyme activity and mRNA levels of genes related to lipid metabolism in the liver of groupers (Epinephelus coioides). We formulated five isolipidic and isoproteic diets with increasing SO levels (0, 250, 500, 750 and 1000 g/kg, respectively). Triplicate groups of 30 groupers (initial mean body weight of 12.6 g/fish) were fed one of the diets twice daily, to apparent satiety across a feeding period of 56 days. The growth performance, whole‐body composition, and protein and lipid muscle contents did not differ across the dietary treatments. In contrast, the liver lipid content had positive linear and quadratic responses to the increasing dietary SO levels, but the liver protein content had the opposite trend, and the highest lipid value and lowest protein value occurred in the 250 and 1000 g/kg SO diets, respectively. There were no significant effects of increasing dietary SO inclusion levels on any of the plasma components and parameters of liver metabolic enzyme activity, except for acetyl coenzyme A carboxylase and hepatic lipase, which showed linear and quadratic responses to increasing dietary SO inclusion levels and peaked at 1000 and 250 g/kg SO inclusion level, respectively. However, the FA profiles of the dorsal muscle and liver generally reflected the FA profile of the diet. Furthermore, the mRNA levels of fas, acc, g6pd, lpl, pparα, cpt‐1, srebp‐1c, δ6fad and elovl5 in the liver exhibited positive linear and/or quadratic responses to dietary SO inclusion levels. However, negative linear and/or quadratic responses were observed for the mRNA levels of hsl and atgl in the liver, with increasing dietary SO inclusion levels. The mRNA levels of scd and fabp in the liver were not affected by the dietary SO inclusion level. These results indicate that FO could be replaced completely by SO without affecting growth. However, the inclusion of SO at levels higher than 500 g/kg could compromise the FA profile in the liver and flesh of the fish species. These results provide a novel insight into the potential utilization of SO in grouper feeds. [ABSTRACT FROM AUTHOR]

Background. Although intravenous immunoglobulin (IVIG) is expected to prevent coronary artery abnormalities of Kawasaki disease (KD) in the acute phase, the timing and effectiveness of IVIG remain to be determined. The association of timing of IVIG administration in KD patients with coronary artery abnormalities is evaluated in this cohort study. Methods. We systematically studied KD patients from two participating institutions between 2015 and 2017. To reveal the effectiveness of IVIG treatment, these patients were classified into four groups regarding the time of IVIG treatment. Primary outcome was coronary artery abnormalities by echo at diagnosis and 12 months follow-up; secondary outcomes included inflammatory markers. Results. A total of 1281 patients were included in this study. The best time of IVIG treatment cut-off values in 12 months follow-up for predicting coronary artery abnormalities was days 7.5 of illness onset. According to the best time of IVIG treatment cut-off values, all patients were classified into 4 groups. Group 1 was defined as earlier IVIG treatment administration on days ≤4 of the illness (n = 77). Group 2 was defined with days 5-7 (n = 817), group 3 with days 8-10 (n = 249), group 4 with days >10 (n = 138). A greater proportion of IVIG-resistant KD patients were group 4 than the other three groups, and there were significant differences (p < 0.05). The incidence of coronary artery lesions (CALs) and coronary artery aneurysms (CAAs) in group 3 and group 4 was higher than that in group 1 (p < 0.05) and group 2 (p < 0.05) during a 12-month follow-up. Additionally, the incidence of CALs in group 1 was higher than that in group 2 but without statistical significance (p > 0.05). The OR was significantly higher for those who started IVIG administration more than 7 days from the onset was positively associated with the occurrence of CALs (OR, 5.3; 95% CI, 2.0-13.9) and CAAs (OR, 13.5; 95% CI, 2.9-14.1) 12 months after initial onset. Multivariate regression revealed that the timing of IVIG treatment and IVIG-resistance was independent risk factors of CALs. Conclusions. IVIG treatment less than 7 days after illness onset are found to be sufficient for preventing developing coronary artery abnormalities in KD patients. Earlier IVIG treatment administration within 4 days may not increase the higher incidence of coronary artery abnormalities and IVIG resistance (Chinese Clinical Trial Registry:ChiCTR1800015800). [ABSTRACT FROM AUTHOR]

Background. Kawasaki disease (KD) is a systemic vasculitis of unknown etiology in children. Coronary artery abnormalities are the most common complications of KD. Recent evidence showed that genetic polymorphisms may lead to susceptibility to KD. Genetic variants in platelet glycoprotein have been reported to be associated with coronary artery disease. The aim of the present study is to investigate the correlation between the role of platelet glycoprotein and coronary artery aneurysms in KD patients. Methods. We did a case-control study that enrolled 818 KD patients and 1401 healthy children with the same age and sex from January 2013 to December 2016. Analysis of single-nucleotide polymorphism (rs1126643) of the platelet glycoprotein Ia/IIa C807T was performed by multiplex polymerase chain reactions in this study. Results. A significant difference in the genotype distribution between KD cases and controls was observed for the glycoprotein Ia/IIa C807T (rs1126643) polymorphism (p = 0.026). Compared with the healthy children, the rs1126643T allele carriers had odds ratio (OR) of 0.63 for developing KD (TT vs. CC: adjusted OR = 0.62, 95% confidence interval (CI) = 0.43–0.88, p = 0.0078 ; TT vs. CT/CC: adjusted OR = 0.63, 95% CI = 0.44–0.889, p = 0.0093). Furthermore, we also found that children less than 60 months of age and female patients with rs1126643 T allele carriers had an adjusted OR of 0.66 (95% CI = 0.46–0.95) for noncoronary artery aneurysm patients (p = 0.0242). Single-nucleotide polymorphism rs1126643 TT seems to represent a protective factor against KD in coronary artery aneurysm formation in multivariate analysis. Conclusions. The platelet glycoprotein Ia/IIa T allele carriers may have a protective effect on the risk of coronary artery aneurysms of KD patients, especially in females and children aged less than 60 months. These results may provide evidence for platelet glycoprotein Ia/IIa gene polymorphisms in the pathogenesis of KD patients. [ABSTRACT FROM AUTHOR]

There have been no robust data from clinical trials to guide the clinician in the choice of therapeutic agents for the child with intravenous immunoglobulin (IVIG) resistance. The treatment regimen for IVIG-resistant patients varies between institutions, and the best option has not yet been established. Therefore, in this trial, a total of 955 patients with Kawasaki disease (KD) were selected and were initially treated with IVIG (2 g/kg), of whom 80 (8.38%) assessed as IVIG resistant were randomly divided into two groups: Group A received the second IVIG treatment (n = 40), and Group B received methylprednisolone pulse therapy (MPT, n = 40). The whole fever time, duration of fever after retreatment, hospital days, medical costs, readmission rate, and laboratory examination difference (△) were calculated. Coronary artery lesion (CAL) outcomes were followed up over two years. Patients in the MPT group had shorter fever after retreatment and lower medical costs; more rapid declines in C-reactive protein (CRP), neutrophils (N%), and platelet (PLT) levels; and more rapid rise in sodium. However, they also probably had a higher incidence of treatment failure and CALs than the additional IVIG treatment group in the long-term follow-up. Caution is still required in the use of MPT to treat IVIG-resistant KD. [ABSTRACT FROM AUTHOR]

Alternative splicing plays a pivotal role in modulating the function of eukaryotic proteins. In the inner ear, many genes undergo alternative splicing, and errors in this process lead to hearing loss. Cadherin 23 (CDH23) forms part of the so-called tip links, which are indispensable for mechanoelectrical transduction (MET) in the hair cells. Cdh23 gene contains 69 exons, and exon 68 is subjected to alternative splicing. Exon 68 of the Cdh23 gene is spliced into its mRNA only in a few cell types including hair cells. The mechanism responsible for the alternative splicing of Cdh23 exon 68 remains elusive. In the present work, we performed a cell-based screening to look for splicing factors that regulate the splicing of Cdh23 exon 68. RBM24 and RBM38 were identified to enhance the inclusion of Cdh23 exon 68. The splicing of Cdh23 exon 68 is affected in Rbm24 knockdown or knockout cells. Moreover, we also found that PTBP1 inhibits the inclusion of Cdh23 exon 68. Taken together, we show here that alternative splicing of Cdh23 exon 68 is regulated by RBM24, RBM38, and PTBP1. [ABSTRACT FROM AUTHOR]

Kawasaki disease (KD) is an acute systemic vasculitis of childhood with prolonged fever, and the diagnosis of KD is mainly based on clinical criteria, which is prone to misdiagnosis with other febrile infectious (FI) diseases. Currently, there remain no effective molecular markers for KD diagnosis. In this study, we aimed to use a relative-expression-based method k-TSP and resampling framework to identify robust gene pair signatures to distinguish KD from bacterial and virus febrile infectious diseases. Our study pool consisted of 808 childhood patients from several studies and assigned to three groups, namely, the discovery set (n = 224), validation set-1 (n = 197), and validation set-2 (n = 387). We had identified 60 biologically relevant gene pairs and developed a top-ranked gene pair classifier (TRGP) using the first seven signatures, with the area under the receiver-operating characteristic curves (AUROC) of 0.947 (95% CI, 0.918-0.976), a sensitivity of 0.936 (95% CI, 0.872-0.987), and a specificity of 0.774 (95% CI, 0.705-0.836) in the discovery set. In the validation set-1, the TRGP classifier distinguished KD from FI with AUROC of 0.955 (95% CI, 0.919-0.991), a sensitivity of 0.959 (95% CI, 0.925-0.986), and a specificity of 0.863 (95% CI, 0.764-0.961). In the validation set-2, the predictive performance of classification was with an AUROC of 0.796 (95% CI, 0.747-0.845), a sensitivity of 0.797 (95% CI, 0.720-0.864), and a specificity of 0.661 (95% CI, 0.606-0.717). Our study reveals that gene pair signatures are robust across diverse studies and can be utilized as objective biomarkers to distinguish KD from FI, helping to develop a fast, simple, and effective molecular approach to improve the diagnosis of KD. [ABSTRACT FROM AUTHOR]

Aim. There are increasing evidence demonstrating that neutrophil-mediated inflammation plays a role in the etiology of type 2 diabetes. However, the molecular mechanisms by which neutrophils contribute to type 2 diabetes remain largely unknown. The aim of the present work was to identify possible changes in circulating neutrophils to better elucidate neutrophil involvement in human type 2 diabetes. Methods. Patients newly diagnosed with type 2 diabetes (n = 5) and age- and sex-matched healthy controls (n = 5) were recruited. Neutrophils were purified from type 2 diabetes patients and controls, and RNA sequencing (RNA-seq) was used for comprehensive transcriptome analysis. Differentially expressed genes (DEGs) were screened, and Gene Ontology (GO) and KEGG pathway enrichment analyses were performed. Real-time polymerase chain reaction (qPCR) was used for validation in external samples of type 2 diabetes patients (n = 8) and healthy controls (n = 8). Results. Gene expression analysis showed that, compared with neutrophils from healthy controls, there were 1990 upregulated DEGs and 1314 downregulated DEGs in neutrophils from type 2 diabetes patients. GO analysis demonstrated that the DEGs were mainly involved in myeloid leukocyte activation, T cell activation, adaptive immunity, and cytokine production. The top 20 enriched KEGG pathways included the cytokine-cytokine receptor interaction pathway, NF-κB signaling pathway, cell adhesion molecules, and chemokine signaling pathway. Furthermore, qPCR of genes related to neutrophil activation revealed that the expression of SELL, SELP, CXCR1, and S100A8 was significantly increased in neutrophils from type 2 diabetes patients compared with that in neutrophils from controls. Conclusions. Our study reveals an abnormal activation of circulating neutrophils at the transcriptome level in type 2 diabetes patients. These findings suggest a potential involvement of neutrophil dysfunction in the pathologic process of type 2 diabetes and provide insight into potential therapeutic targets for type 2 diabetes. [ABSTRACT FROM AUTHOR]

Children with Kawasaki disease (KD) resistant to intravenous immunoglobulin (IVIG) have a higher incidence of coronary artery lesions (CAL). Despite the association between Purinergic receptor P2Y12 (P2RY12) polymorphism, KD genetic susceptibility, and CAL complications being proved, few studies have assessed the relationship between P2RY12 polymorphisms and IVIG resistance in patients with KD. We recruited 148 KD patients with IVIG resistance and 611 with IVIG sensitivity and selected five P2RY12 polymorphisms: rs9859538, rs1491974, rs7637803, rs6809699, and rs2046934. A significant difference in the genotype distributions between patients was only observed for the rs6809699 A > C polymorphism (AC vs. AA: adjusted odds ratio (OR) = 0.48, 95% confidence interval (CI) = 0.27–0.84, P = 0.011 ; AC/CC vs. AA: adjusted OR = 0.47, 95% CI = 0.27–0.83, P = 0.0084). After adjusting for age and gender, the carriers of the rs6809699 C allele had OR of 0.44 to 0.49 for IVIG sensitivity (AC vs. AA: adjusted OR = 0.48, 95% confidence interval (CI) = 0.27–0.84, P = 0.011 ; AC/CC vs. AA: adjusted OR = 0.47, 95% CI = 0.27–0.83, P = 0.0084) compared to the carriers of a rs6809699 AA genotype, suggesting the protective effect of this SNP against IVIG resistance. Moreover, individuals with all five protective polymorphisms experienced a significantly decreased IVIG resistance compared to that of individuals with up to three protective polymorphisms (adjusted OR = 0.27, 95% CI = 0.13–0.57, P = 0.0006). Our results suggest that the P2RY12 rs6809699 polymorphism could be used as a biomarker to predict IVIG resistance in KD patients. [ABSTRACT FROM AUTHOR]

Objective. The aim of this study was to clarify the association of two single-nucleotide polymorphisms (SNPs) (rs11651270 and rs2670660) in the NLRP1 (NLR family pyrin domain containing 1) gene with type 1 diabetes (T1D) in the Chinese Han population. We hypothesize that mutations in the NLRP1 gene may affect the susceptibility to T1D. Materials and Methods. A case control study was designed, and participants fulfilling the diagnostic criteria of classical T1D as well as nondiabetic controls were enrolled in the study. The polymorphisms rs11651270 and rs2670660 were genotyped by polymerase chain reaction (PCR) and Sanger sequencing. Chi-squared test and logistic regression analysis were performed to compare the distributions of the allele and genotype between cases and controls. Kruskal-Wallis one-way ANOVA was used to compare the characteristics of different genotypes in participants with T1D. Results. A total of 510 participants with classical T1D as well as 531 nondiabetic controls were enrolled in the study. The two groups were matched in sex (p=0.418). The age (p<0.001) and BMI (p<0.001) were significantly lower in cases compared to controls. Significantly higher values were observed for fasting plasma glucose (FPG) (p<0.001) and 2 h postprandial plasma glucose (PPG) (p<0.001) in individuals with T1D. Regarding the allelic model, the minor allele C of rs11651270 was significantly associated with lower risk of T1D compared with the T allele (OR=0.714, 95% CI=0.579-0.882). Both rs11651270 and rs2670660 polymorphisms were associated with T1D in the Chinese Han population under a dominant model (OR=0.648, 95% CI=0.503-0.834 and OR=0.716, 95% CI=0.549-0.934, respectively) and an overdominant model (OR=0.663, 95% CI=0.511-0.860 and OR=0.711, 95% CI=0.541-0.935, respectively). Additionally, the polymorphism rs11651270 was also related to T1D in an additive model (OR=0.719, 95% CI=0.583-0.887). Most importantly, when we analyzed the clinical characteristics of T1D individuals with different genotypes, we found that the age of onset with the TT genotype at rs11651270 was younger than those with the other two genotypes (p=0.001). Conclusions. SNPs in the NLRP1 gene were associated with T1D, as well as the age of onset in the Chinese Han T1D individuals. Our study indicated that the NLRP1 gene might play a pivotal role in the etiopathogenesis of T1D and could be applied to genetic screening of T1D in the Chinese Han population. [ABSTRACT FROM AUTHOR]

PDZD7 is an important deafness gene, whose mutations are associated with syndromic and nonsyndromic hearing loss. PDZD7 contains multiple PDZ domains that are essential for organizing various proteins into protein complex. Several PDZD7-binding proteins have been identified, including usherin, ADGRV1, whirlin, harmonin, SANS and MYO7A, all belonging to USH proteins. Here, we report the identification of novel PDZD7-binding partners through yeast two-hybrid screening using the first two PDZ domains of PDZD7 as bait. Eleven proteins were identified, most of which have not been reported as PDZD7-binding partners before. Among the identified proteins, ADGRV1, gelsolin, and ß-catenin have been shown to play important roles in hearing, whereas the functions of other proteins in the inner ear remain elusive. We confirmed the expression of one candidate PDZD7-binding protein, CADM1, in the mouse inner ear and evaluated the auditory function of Cadm1 knockout mice by performing auditory brainstem response (ABR) measurement. Unexpectedly, Cadm1 knockout mice show normal hearing threshold, which might be explained by the possible compensation by its homologs that are also expressed in the inner ear. Taken together, our work identified several novel PDZD7-binding proteins, which will help us to further understand the role of PDZD7 in hearing transduction. [ABSTRACT FROM AUTHOR]

Protocadherin 15 (PCDH15) is a core component of hair cell tip-links and crucial for proper function of inner ear hair cells. Mutations of PCDH15 gene cause syndromic and nonsyndromic hearing loss. At present, the regulatory mechanisms responsible for the intracellular transportation of PCDH15 largely remain unknown. Here we show that PIST, a Golgi-associated, PDZ domain-containing protein, interacts with PCDH15. The interaction is mediated by the PDZ domain of PIST and the C-terminal PDZ domain-binding interface (PBI) of PCDH15. Through this interaction, PIST retains PCDH15 in the trans-Golgi network (TGN) and reduces the membrane expression of PCDH15. We have previously showed that PIST regulates the membrane expression of another tip-link component, cadherin 23 (CDH23). Taken together, our finding suggests that PIST regulates the intracellular trafficking and membrane targeting of the tip-link proteins CDH23 and PCDH15. [ABSTRACT FROM AUTHOR]

A novel correction method was demonstrated for measuring spectral irradiance of light sources with a narrow bandwidth. Using the correction method based on differential quadrature method, an estimate of the true value was achieved with measured values of seven adjacent points. The formula of this correction method was derived. Numerical simulations and experimental validation of this correction method were also performed, respectively. This correction method could be used in radiometry, photometry, colorimetry, and other spectrometry fields, especially in the spectrum measurement of LED lamp. [ABSTRACT FROM AUTHOR]

An improved antenna array pattern synthesis method using fast Fourier transform is proposed, which can be effectively applied to the synthesis of large planar arrays with periodic structure. Theoretical and simulative analyses show that the original FFT method has a low convergence rate and the converged solution can hardly fully meet the requirements of the desired pattern. A scaling factor is introduced to the original method. By choosing a proper value for the scaling factor, the convergence rate can be greatly improved and the final solution is able to fully meet the expectations. Simulation results are given to demonstrate the effectiveness of the proposed algorithm. [ABSTRACT FROM AUTHOR]

A computer simulation approach was developed to screen functional monomers for the rational design of molecularly imprinted polymers (MIPs). The proposed approach is based on a comparison of the binding energy of complexes, which are formed by the interaction between a template molecule and various functional monomers. According to the results of theoretical calculations, MIPs using thymopentin (TP5) as a template were prepared by a solution polymerization method, in which 2-methylacrylamide, N, N'-methylenebisacrylamide and poly(methylacrylic acid)/SiO2 were used as the functional monomer, cross-linker and support, respectively. Solid-phase extraction experiments were performed, and static and dynamic binding properties of the synthesized MIP (i.e. TP5-MIP) for TP5 were studied. Results show that TP5-MIP exhibits excellent binding affinity and specific selectivity for the template molecule (i.e. TP5). [ABSTRACT FROM AUTHOR]