Comparison of six Z-score formulas based on echocardiography for coronary artery lesions in Kawasaki disease.

GOAL: Kawasaki disease (KD) patients are at risk of developing the serious complication of coronary artery dilation (CAD). To diagnose CAD caused by KD, various Z-Score formulas are used worldwide. This paper aims to evaluate the differences and inclusiveness among the six most commonly used Z-Score formulas in diagnosing CAD in Suzhou, China. Additionally, the study seeks to compare the differences in CAD diagnosis among different high-risk factor groups. By doing so, this research provides a valuable reference for accurately diagnosing CAD in KD patients. METHOD: This paper presents a retrospective analysis of 1509 patients diagnosed with KD at the Children's Hospital of Soochow University between January 2018 and December 2020. We collected the patients' clinical and echocardiographic data and used six Z-Score formulas (Kobayashi et al., de Zorzi et al., Kurotobi et al., McCrindle et al., Olivieri et al., and Dallaire et al.) to diagnose the degree of CAD in different segments. We then compared the diagnostic differences and inclusiveness of these formulas, especially the diagnostic differences in medium to giant CAA. To achieve this, we divided the patients into groups based on their age (≤12 months, 13-30 months, and > 30 months) and fever duration (≤5 days, 6-7 days, 8-9 days, and ≥ 10 days). Using the McNemar test and the Kappa test, we compared the differences and the consistencies of CDA diagnosis among the six Z-Score formulas. Moreover, we used the Friedman test and Chi-square segmentation formula to compare the differences in age and number of fever duration between groups and to compare each Z-Score formula pair within the group. RESULTS: Except for the LMCA segment, where there were no statistically significant differences between de Zorzi formula and McCrindle formula, the Z-score formulas showed statistically significant differences in the degree of CAD diagnosis across all other segments. Inclusiveness assessment revealed that Kobayashi formula and Dallaire formula showed significantly higher rates of dilatation (6.58% and 5.32%), or of small aneurysms (6.52% and 4.52%) compared to other formulas (1.0%-1.73%). Medium aneurysms were also more likely to be identified with Kobayashi and Dallaire formulas (0.8% and 0.8%) compared to the remaining formulas (0.13-0.40%). There are significant differences in the diagnoses of medium to giant CAA made by these six formulas in LAD and RCA. The longer the duration of fever and the younger the age, the higher the diagnosis rates of CAD and CAA. There were no statistically significant differences between de Zorzi formula and McCrindle formula, de Zorzi formula and Oliveri formula, and Kurotobi formula and Dallaire formula within the four groups based on the duration of fever. Similarly, there were no statistically significant differences between Kobayashi formula and Dallaire formula, and between de Zorzi formula and Oliveri formula in the age groups of ≤12 months and 13-30 months. CONCLUSION: There are diagnostic differences among these six Z-score formulas, considering the aforementioned statistics. Kobayashi formula and Dallaire formula are more inclusive, and less likely to under-diagnose significant CAD. They perform evenly for dilatation only, for small aneurysms and the median size aneurysms, and that is for segments of LMCA, LAD and RCA. In addition, McCrindle formula joins the "inclusive" pack for LAD and RCA in the matter of CAD. The younger the age of the patients and the longer the duration of fever, the higher the diagnosis rates of CAD and CAA. Furthermore, the younger the age of the patients and the shorter the duration of fever, the greater the differences between the various formulas.

Transient changes in the ST-T waveform mimicking myocardial infarction in a child with near-drowning: a case report.

Drowning is a common cause of childhood morbidity and mortality worldwide. Anoxia, hypothermia, and metabolic acidosis are mainly responsible for this morbidity. Drowning may lead to multiple organ damage, especially cardiac damage, in cases in which severe hypothermia and hypoxemia occur. We report a case of a 4-year-old girl who was admitted to our hospital's Emergency Department because of drowning. She had elevated troponin I concentrations and ST-segment elevation with T wave inversion. However, cardiovascular computed tomography showed no obvious abnormalities in the coronary arteries. We suggest that cardiac damage in this situation is caused by coronary artery spasms. To the best of our knowledge, this is the first case of cardiac damage with electrocardiographic changes after drowning in a preschool child.

Prediction nomogram for coronary artery aneurysms at one month in Kawasaki disease.

BACKGROUND: Coronary status at one month after Kawasaki disease (KD) onset had a great significance. The present study aimed to establish a prediction model for coronary artery aneurysms (CAA) at one month in children with KD. METHODS: Patients with a diagnosis of KD between May 2017 and Dec 2018 were enrolled as the development cohort to build a prediction model. The model was validated by internal and external validation. Patients between Jan 2019 and Dec 2019 were enrolled as the validation cohort. The adaptive least absolute shrinkage and selection operator (LASSO) was used to select the possible predictors. Receiving operating characteristic curve (ROC), calibration plots, and decision curve analysis (DCA) were used to evaluate the performance of the model. The performance of the Son score was also assessed. RESULTS: LASSO regression demonstrated that age, sex, and CALs in the acute stage were predictors for CAA at one month. The area under the ROC (AUC) was 0.946 (95% confidence interval: 0.911-0.980) with a sensitivity of 92.5% and a specificity of 90.5%. The calibration curve and the DCA showed a favorable diagnostic performance. The internal and external validation proved the reliability of the prediction model. The AUC of our model and the Son score were 0.941 and 0.860, respectively (P < 0.001). CONCLUSION: Our prediction model for CAA at one month after disease onset in KD had an excellent predictive utility.

Bioinformatics analysis and identification of hub genes of neutrophils in Kawasaki disease: a pivotal study.

BACKGROUND: Kawasaki disease (KD) is considered the main contributor to acquired heart diseases in developed countries. However, the precise pathogenesis of KD remains unclear. Neutrophils play roles in KD. This study aimed to select hub genes in neutrophils in acute KD. METHODS: mRNA microarray of neutrophils from four acute KD patients and three healthy controls was performed to screen differentially expressed mRNAs (DE-mRNAs). DE-mRNAs were analyzed and predicted by Gene Ontology (GO), Kyoto Encyclopaedia of Genes and Genomes (KEGG) pathways, and protein-protein interaction networks. Real time-PCR was finally conducted to confirm the reliability and validity of the expression level of DE-mRNAs from blood samples of healthy controls and KD patients in both acute and convalescent stage. RESULTS: A total of 1950 DE-mRNAs including 1287 upregulated and 663 downregulated mRNAs were identified. GO and KEGG analyses revealed the DE-mRNAs were mainly enriched in the regulation of transcription from RNA polymerase II promoter, apoptotic process, intracellular signal transduction, protein phosphorylation, protein transport, metabolic pathways, carbon metabolism, lysosome, apoptosis, pyrimidine metabolism, alzheimer disease, prion disease, sphingolipid metabolism, huntington disease, glucagon signaling pathway, non-alcoholic fatty liver disease, pyruvate metabolism, sphingolipid signaling pathway, and peroxisome. Twenty hub DE-mRNAs were selected including GAPDH, GNB2L1, PTPRC, GART, HIST2H2AC, ACTG1, H2AFX, CREB1, ATP5A1, ENO1, RAC2, PKM, BCL2L1, ATP5B, MRPL13, SDHA, TLR4, RUVBL2, TXNRD1, and ITGAM. The real-time PCR results showed that BCL2L1 and ITGAM mRNA were upregulated in acute KD and were normalized in the convalescent stage. CONCLUSIONS: These findings may improve our understanding of neutrophils in KD. Key Points • Neutrophilic BCL2L1 and ITGAM mRNA were first reported to be correlated with the pathogenic mechanism of KD.

Risk-prediction models for intravenous immunoglobulin resistance in Kawasaki disease: Risk-of-Bias Assessment using PROBAST.

BACKGROUND: The prediction model of intravenous immunoglobulin (IVIG) resistance in Kawasaki disease can calculate the probability of IVIG resistance and provide a basis for clinical decision-making. We aim to assess the quality of these models developed in the children with Kawasaki disease. METHODS: Studies of prediction models for IVIG-resistant Kawasaki disease were identified through searches in the PubMed, Web of Science, and Embase databases. Two investigators independently performed literature screening, data extraction, quality evaluation, and discrepancies were settled by a statistician. The checklist for critical appraisal and data extraction for systematic reviews of prediction modeling studies (CHARMS) was used for data extraction, and the prediction models were evaluated using the Prediction Model Risk of Bias Assessment Tool (PROBAST). RESULTS: Seventeen studies meeting the selection criteria were included in the qualitative analysis. The top three predictors were neutrophil measurements (peripheral neutrophil count and neutrophil %), serum albumin level, and C-reactive protein (CRP) level. The reported area under the curve (AUC) values for the developed models ranged from 0.672 (95% confidence interval [CI]: 0.631-0.712) to 0.891 (95% CI: 0.837-0.945); The studies showed a high risk of bias (ROB) for modeling techniques, yielding a high overall ROB. CONCLUSION: IVIG resistance models for Kawasaki disease showed high ROB. An emphasis on improving their quality can provide high-quality evidence for clinical practice. IMPACT STATEMENT: This study systematically evaluated the risk of bias (ROB) of existing prediction models for intravenous immunoglobulin (IVIG) resistance in Kawasaki disease to provide guidance for future model development meeting clinical expectations. This is the first study to systematically evaluate the ROB of IVIG resistance in Kawasaki disease by using PROBAST. ROB may reduce model performance in different populations. Future prediction models should account for this problem, and PROBAST can help improve the methodological quality and applicability of prediction model development.

Linear ubiquitination improves NFAT1 protein stability and facilitates NFAT1 signalling in Kawasaki disease.

NFAT1 is known for its roles in T cell development and activation. So far, the phosphorylation of NFAT1 has been extensively studied, but the other post-translational modifications of NFAT1 remain largely unknown. In this study, we reported that NFAT1 is a linearly ubiquitinated substrate of linear ubiquitin chain assembly complex (LUBAC). LUBAC promoted NFAT1 linear ubiquitination, which in turn inhibited K48-linked polyubiquitination of NFAT1 and therefore increased NFAT1 protein stability. Interestingly, the linear ubiquitination levels of NFAT1 in patients with the Kawasaki disease were upregulated. Further studies demonstrated that the patients with the Kawasaki disease had increased mRNA levels of HOIL-1L. These findings revealed a linearly ubiquitinated substrate of LUBAC and an important biological function of NFAT1 linear ubiquitination in the Kawasaki disease and therefore may provide a novel strategy for the treatment of the Kawasaki disease.

Predicting immunoglobulin resistance in Kawasaki disease: an assessment of neutrophil to lymphocyte platelet ratio.

BACKGROUND: Kawasaki disease (KD) is an acute febrile illness of unknown etiology and predictors for intravenous immunoglobulin (IVIG) resistance have been widely explored in recent decades. Neutrophil to lymphocyte platelet ratio (NLPR) was reported to be associated with the outcomes in many diseases. However, its relationship with IVIG resistance has not be explored. METHODS: The medical data of patients diagnosed with KD in Children's Hospital of Soochow University between January 2019 and December 2020 were retrospectively reviewed and analyzed. Patients were trisected into three groups based on NLPR. Logistics regression was used to analyze the association between NLPR and IVIG resistance. Restricted cubic spine was used to exhibit the relationship. Sensitivity analysis and subgroup analysis were also carried out. RESULTS: A total of 803 patients were included in the present study (61.8% males; median age: 24 months). IVIG resistance occurred in 74 (9.2%) patients. Multivariable-adjusted analyses revealed higher NLPR (odds ratio [95% confidence interval]: 1.12 [1.00-1.24]) was an independent predictor of IVIG resistance, which was strengthened by sensitivity analyses. The association of NLPR and IVIG resistance was not modified by age, sex, CALs, or days of IVIG initiation ≤ 4. CONCLUSION: NLPR may be a valuable prognostic marker in KD patients with IVIG resistance.

Breastfeeding has no protective effects on the development of coronary artery lesions in Kawasaki disease: a retrospective cohort study.

BACKGROUND: Kawasaki disease (KD) is a self-limiting vasculitis with an unknown etiology. It has been reported that breastfeeding has a potential protective effect on KD development. However, whether breastfeeding has an effect on the development of coronary artery lesions (CALs) remains unclear. METHODS: We retrospectively reviewed the medical records of patients with the main diagnosis of KD hospitalized in our hospital from May 2017 to November 2018. Standardized telephone interviews were carried out to obtain feeding practices before KD was onset. RESULTS: Two hundred and ninety-three (51.6%) were exclusively breastfed, 223 (39.3%) were partially breastfed and 52 (9.2%) were formula fed. There were no significant differences in the characteristics regarding age, gender, incomplete KD, intravenous immunoglobulin (IVIG) resistance, and the laboratory variables among the three groups. With formula feeding as a reference, patients exclusively breastfed and partially breastfed seemed to have a higher incidence of CALs, even after adjusting confounders, but were not statistically significant. After grouping patients who were older than six months into formula feeding, partial breastfeeding for < 2 months, partial breastfeeding for ≥ 2 and < 4 months, partial breastfeeding for ≥ 4 and < 6 months and exclusively breastfeeding based on the length of breastfeeding, the results remained the same (P > 0.05). CONCLUSIONS: Breastfeeding has no protective effect on the development of CALs in KD.

Biogenesis, Trafficking, and Function of Small RNAs in Plants.

Small RNAs (sRNAs) encoded by plant genomes have received widespread attention because they can affect multiple biological processes. Different sRNAs that are synthesized in plant cells can move throughout the plants, transport to plant pathogens via extracellular vesicles (EVs), and transfer to mammals via food. Small RNAs function at the target sites through DNA methylation, RNA interference, and translational repression. In this article, we reviewed the systematic processes of sRNA biogenesis, trafficking, and the underlying mechanisms of its functions.

Diameters of phloem sieve elements can predict stem growth rates of woody plants.

Understanding forest dynamics is crucial to addressing climate change and reforestation challenges. Plant anatomy can help predict growth rates of woody plants, contributing key information on forest dynamics. Although features of the water-transport system (xylem) have long been used to predict plant growth, the potential contribution of carbon-transporting tissue (phloem) remains virtually unexplored. Here, we use data from 347 woody plant species to investigate whether species-specific stem diameter growth rates can be predicted by the diameter of both the xylem and phloem conducting cells when corrected for phylogenetic relatedness. We found positive correlations between growth rate, phloem sieve element diameter and xylem vessel diameter in liana species sampled in the field. Moreover, we obtained similar results for data extracted from the Xylem Database, an online repository of functional, anatomical and image data for woody plant species. Information from this database confirmed the correlation of sieve element diameter and growth rate across woody plants of various growth forms. Furthermore, we used data subsets to explore potential influences of biomes, growth forms and botanical family association. Subsequently, we combined anatomical and geoclimatic data to train an artificial neural network to predict growth rates. Our results demonstrate that sugar transport architecture is associated with growth rate to a similar degree as water-transport architecture. Furthermore, our results illustrate the potential value of artificial neural networks for modeling plant growth under future climatic scenarios.

Evaluation of Carotid Artery Elasticity in Early Stage of Kawasaki Disease by Two-Dimensional Speckle Tracking Imaging: A Pilot Study.

OBJECTIVES: Children with Kawasaki disease (KD) often develop impaired arterial function. The aim of the study was to assess the feasibility and efficacy of two-dimensional speckle tracking technique (2DSTI) for the evaluation of carotid artery elasticity in children with early-stage KD. METHODS: Children with KD (n = 97), age and sex-matched children with fever (n = 18), and healthy controls (n = 24) were included. Children with KD were subsequently divided into a coronary artery lesion group (CAL group, 27 cases) and a noncoronary artery lesion group (nCAL group, 70 cases) based on the results of echocardiography. The carotid circumferential peak strain (CCS) and carotid intima-media thickness (CIMT) for the children in each group were measured, and the laboratory indicators for each group were collected. RESULTS: The CCS of children with KD was lower than that of children with fever and healthy controls (P = .001 and .008), whereas CIMT was not significantly different among the groups. Moreover, the CCS of children in the CAL group was lower than that of children in the nCAL group and healthy controls (P = .001 and .000, respectively), whereas the CIMT of children in the CAL group was higher than that of children in the nCAL group (P = .014). In children with KD, CCS was negatively correlated with C-reactive protein (CRP) and alanine aminotransferase (ALT) (r = -.419, P = .001; and r = -.305, P = .003). However, CCS was negatively correlated with CRP (r = -.508, P = .007) but not ALT (r = -.176, P = .379) in children in the CAL group. CONCLUSION: CCS determined based on 2DSTI can reflect changes in the carotid artery elasticity function in the early stage of KD.

AST-to-ALT ratio and coronary artery lesions among patients with Kawasaki disease.

BACKGROUND: The aim of this study was to explore the associations between the aspartate aminotransferase-to-alanine aminotransferase ratio (AST/ALT) and coronary artery lesions (CALs) among patients with Kawasaki disease (KD). METHODS: Medical records of KD patients presenting to a single center between January 2019 and December 2020 were retrospectively collected and analyzed. Univariate, multivariable-adjusted analyses, subgroup analyses, restricted cubic spline test, and fitted curves were used to evaluate the associations between AST/ALT and CALs. RESULTS: A total of 831 patients were enrolled, of which 201 (24.2%) had CALs on admission and 21 (2.5%) developed CALs de novo after intravenous immunoglobulin (IVIG). Multivariable-adjusted analyses models revealed that a lower AST/ALT was associated with an increased risk of CALs on admission when AST/ALT was a continuous variable (P = 0.007) and when it was a categorical variable (P for trend = 0.004). Each unit increase in AST/ALT was associated with a 22% lower risk of CALs on admission (odds ratio = 0.78, 95% confidence interval 0.65-0.94). A negative linear relationship was noted between AST/ALT and the risk of CALs on admission in both observed and fitted models. However, such associations were not observed in AST/ALT and CALs de novo after IVIG. None of the variables significantly modified the association between AST/ALT and CALs on admission and CALs de novo after IVIG (P > 0.05). CONCLUSION: Our findings suggested that AST/ALT was a risk factor of CALs, but was not associated with progressive CALs.

Clinical characteristics of Kawasaki disease and concurrent pathogens during isolation in COVID-19 pandemic.

BACKGROUND: The aim of this study is to explore the characteristics of Kawasaki disease (KD) and concurrent pathogens due to a stay-at-home isolation policy during coronavirus disease 2019 (COVID-19) epidemic. METHODS: All patients with KD admitted between February and April in 2015-2020, were classified into before (group 1, in 2015-2019) and after (group 2, in 2020) isolation groups. A total of 4742 patients [with KD (n = 98) and non-KD (n = 4644)] referred to Mycoplasma pneumoniae (MP) and virus detection were analyzed in 2020. Clinical characteristics, laboratory data, and 13 pathogens were analyzed retrospectively. RESULTS: Group 2 had a significantly increased incidence of KD (0.11%) with 107 patients compared to that of group 1 (0.03%) with 493 patients. The comparisons of oral mucosal change, strawberry tongue, desquamation of the fingertips, cervical lymphadenopathy and neutrophil percentage decreased in group 2 compared to group 1. The infection rate of MP increased significantly in group 2 (34.7%) compared to group 1 (19.3%), while the positive rate of viruses decreased significantly in group 2 (5.3%) compared to group 1 (14.3%). In 2020, the positive rate of MP infection increased significantly in patients with KD compared to the increase in patients with non-KD. The infection rate of MP for younger children aged less than 3 years old was higher in group 2 than in group 1. CONCLUSION: Compared with the characteristics of KD from 2015 to 2019 years, the incidence of KD was increased in 2020 and was accompanied by a high incidence of MP infection, especially in younger children (less than 3 years old) during the isolation due to COVID-19 pandemic.

Neutropenia Is Not Associated With the Outcomes in Patients With Kawasaki Disease.

Objective: To investigate the outcomes of coronary artery lesions (CALs) and intravenous immunoglobulin (IVIG) resistance in patients with and without neutropenia during the disease course and to explore the relationships between Δ absolute neutrophils count (ΔANC) and the outcomes. Methods: We retrospectively reviewed the medical records of patients hospitalized in Children's Hospital of Soochow University with a main diagnosis of KD during January 2019 and December 2019. 1:4 propensity score matching was carried out to adjust the baseline characteristics. Smoothed plots and threshold effect analyses were performed to reveal the relationships between ΔANC and the outcomes. Results: Of the 438 patients enrolled, 75 (17.1%) were neutropenia cases and 363 (82.9%) were non-neutropenia cases. Patients with neutropenia were younger, had lower levels of initial ANC, white blood cell (WBC) count and C-reactive protein (CRP). Propensity score matching included 75 neutropenia and 247 non-neutropenia patients. No significant difference was found between neutropenia and non-neutropenia groups regarding CALs, coronary artery aneurysms, irregular coronary lumen, IVIG resistance and days of fever duration. There was a non-linear relationship between ΔANC and IVIG resistance. However, threshold effect analysis showed the incidence of IVIG resistance decreased with increasing ΔANC before the turning point (ΔANC = 1.6) (OR = 0.65, 95% CI = 0.50-0.8.4 P = 0.001). On the other hand, there was a linear relationship between ΔANC and CALs, even after adjusting the confounders (OR = 1.06, 95% CI = 1.02-1.11, P = 0.008). Conclusions: Neutropenia after IVIG was not exactly associated with the outcomes. However, ΔANC was in relation to CALs and IVIG resistance.

Bioinformatics identification of hub genes and signaling pathways regulated by intravenous immunoglobulin treatment in acute Kawasaki disease.

Kawasaki disease (KD) is an acute, self-limiting form of vasculitis commonly encountered in infants and young children. Intravenous immunoglobulin (IVIG) is the primary drug used for the treatment of KD, which may significantly reduce the occurrence of coronary artery lesions. However, the specific molecular profile changes of KD caused by IVIG treatment have remained elusive and require further research. The present study was designed to identify key genes, pathways and immune cells affected by IVIG treatment using multiple bioinformatics analysis methods. The results suggested that myeloid cells and neutrophils were affected by IVIG treatment. Kyoto Encyclopedia of Genes and Genomes pathway analysis identified that hematopoietic cell lineages and osteoclast differentiation may have an important role in the mechanism of action of IVIG treatment. Immune cell analysis indicated that the levels of monocytes, M1 macrophages, neutrophils and platelets were markedly changed in patients with KD after vs. prior to IVIG treatment. The key upregulated genes, including ZW10 interacting kinetochore protein, GINS complex subunit 1 and microRNA-30b-3p in whole blood cells of patients with KD following treatment with IVIG indicated that these IVIG-targeted molecules may have important roles in KD. In addition, these genes were further examined by literature review and indicated to be involved in cell proliferation, apoptosis and virus-related immune response in patients with KD. Therefore, the present results may provide novel insight into the mechanisms of action of IVIG treatment for KD.

In silico Identification of 10 Hub Genes and an miRNA-mRNA Regulatory Network in Acute Kawasaki Disease.

Kawasaki disease (KD) causes acute systemic vasculitis and has unknown etiology. Since the acute stage of KD is the most relevant, the aim of the present study was to identify hub genes in acute KD by bioinformatics analysis. We also aimed at constructing microRNA (miRNA)-messenger RNA (mRNA) regulatory networks associated with acute KD based on previously identified differentially expressed miRNAs (DE-miRNAs). DE-mRNAs in acute KD patients were screened using the mRNA expression profile data of GSE18606 from the Gene Expression Omnibus. The functional and pathway enrichment analysis of DE-mRNAs were performed with the DAVID database. Target genes of DE-miRNAs were predicted using the miRWalk database and their intersection with DE-mRNAs was obtained. From a protein-protein interaction (PPI) network established by the STRING database, Cytoscape software identified hub genes with the two topological analysis methods maximal clique centrality and Degree algorithm to construct a miRNA-hub gene network. A total of 1,063 DE-mRNAs were identified between acute KD and healthy individuals, 472 upregulated and 591 downregulated. The constructed PPI network with these DE-mRNAs identified 38 hub genes mostly enriched in pathways related to systemic lupus erythematosus, alcoholism, viral carcinogenesis, osteoclast differentiation, adipocytokine signaling pathway and tumor necrosis factor signaling pathway. Target genes were predicted for the up-regulated and down-regulated DE-miRNAs, 10,203, and 5,310, respectively. Subsequently, 355, and 130 overlapping target DE-mRNAs were obtained for upregulated and downregulated DE-miRNAs, respectively. PPI networks with these target DE-mRNAs produced 15 hub genes, six down-regulated and nine upregulated hub genes. Among these, ten genes (ATM, MDC1, CD59, CD177, TRPM2, FCAR, TSPAN14, LILRB2, SIRPA, and STAT3) were identified as hub genes in the PPI network of DE-mRNAs. Finally, we constructed the regulatory network of DE-miRNAs and hub genes, which suggested potential modulation of most hub genes by hsa-miR-4443 and hsa-miR-6510-5p. SP1 was predicted to potentially regulate most of DE-miRNAs. In conclusion, several hub genes are associated with acute KD. An miRNA-mRNA regulatory network potentially relevant for acute KD pathogenesis provides new insights into the underlying molecular mechanisms of acute KD. The latter may contribute to the diagnosis and treatment of acute KD.

Decreased Flow-Mediated Dilatation in Children With Type 1 Diabetes: A Systematic Review and Meta-Analysis.

Type 1 diabetes (T1DM) is a strong risk factor for the development of cardiovascular disease. Flow-mediated dilatation (FMD) is an early noninvasive marker of endothelial function and it predicts future cardiovascular disease. However, the changes in FMD among T1DM children are still controversial. The present meta-analysis aimed to investigate whether FMD is impaired in children with T1DM. PubMed, EMBASE, Cochrane library, and Web of Science were searched for studies comparing FMD in children with T1DM and healthy controls. The Newcastle-Ottawa quality assessment scale for case-control studies was used to assess study quality. Data were pooled using a random effects models to obtain the weighted mean differences (WMD) in FMD and 95% CIs. Overall, 19 studies with 1245 patients and 872 healthy controls were included in this meta-analysis. Children with T1DM had significantly lower FMDs compared with healthy controls (WMD: -2.58; 95% CI: -3.36 to -1.81; P < .001). Meta-regression analysis revealed that low-density lipoprotein cholesterol levels impacted the observed difference in FMD between T1DM and healthy children. This meta-analysis showed that T1DM children have impaired endothelial function, which indicates they are at higher risk of developing cardiovascular disease in later life.

Higher efficacy of infliximab than immunoglobulin on Kawasaki disease, a meta-analysis.

This meta-analysis evaluated the efficacy and safety of infliximab as initial therapy for patients with Kawasaki disease (KD) and intravenous immunoglobulin (IVIG) resistant KD. Studies of infliximab in KD, published between January 2004 and December 2019, were curated from PubMed, MEDLINE, and Cochrane Library. Data were analyzed using STATA Version 12.0. Of the 8 studies considered, 4 evaluated the effect of infliximab combined with IVIG as primary therapy in KD, and the remaining investigated the effect of infliximab in IVIG resistant patients. Infliximab was more effective than the control group, with the total summary odds ratio (OR) of 0.34 (95% confidence interval (CI): 0.19-0.62). The treatment resistance of the infliximab group was lower than the IVIG group (0.36 [95% CI: 0.14-0.92]) when infliximab was combined with IVIG as the initial treatment. However, infliximab treatment for IVIG resistant KD was more effective than the IVIG group (0.28 [95% CI: 0.12-0.66]). There was no significant increase in the incidence of coronary artery lesions. The total summary OR for the incidence of coronary artery lesions and infliximab treatment was 0.88 (95% CI: 0.48-1.62). There was no statistically significant difference in adverse events (AEs) when compared between the groups (0.71 [95% CI: 0.44-1.16]). Infliximab combined with IVIG reduced treatment resistance in KD patients vs. conventional IVIG therapy. Infliximab improved clinical course in IVIG resistant KD patients. Infliximab treatment did not reduce the incidence of coronary artery lesions and did not show any significant increase in the incidence of AEs. PROSPERO REGISTRATION NUMBER: CRD42020218554.

Leukocyte proteomics coupled with serum metabolomics identifies novel biomarkers and abnormal amino acid metabolism in Kawasaki disease.

Kawasaki disease (KD) is a systemic vasculitis that can lead to severe cardiovascular complications, whereas the development and clinical usage of specific biomarkers might help diagnose KD and avoid certain complications. To this end, the molecular profiles of acute KD patients with coronary artery lesions (CAL) were first investigated through leukocyte proteomics and serum metabolomics assays. A total of 269 differentially abundant proteins and 35 differentially abundant metabolites with the top fold-changed levels were identified in acute KD patients compared to those in the healthy controls. Among them, several highly promising candidate marker proteins and metabolites indicative of KD progression were further analysed, such as the increased proteins ALPL, NAMPT, and S100P, as well as the decreased proteins C1QB and apolipoprotein family members. Moreover, metabolites, including succinic acid, dGMP, hyaluronic acid, L-tryptophan, propionylcarnitine, inosine, and phosphorylcholine, were found to be highly accurate at distinguishing between KD patients and healthy controls. Interestingly, the abnormal expression levels of a distinct set of proteins and metabolites in acute KD patients can be restored to normal levels upon intravenous immunoglobulin (IVIG) treatment. Overall, this work has revealed novel biomarkers and abnormal amino-acid metabolism as a prominent feature involved in KD patients with CAL. SIGNIFICANCE: KD is frequently concomitant with the development of life-threatening coronary vasculitis. Here, the profiles of leukocyte proteomics and serum metabolomics in acute KD patients with CALs were first investigated, and several hub molecules identified here could be used as supplemental biomarkers for KD diagnosis. Moreover, the metabolomic abnormalities especially the amino acids are particularly prominent in KD patients. Interestingly, the abnormal expression levels of a distinct set of proteins and metabolites in acute KD patients can be restored to normal levels upon IVIG treatment. Therefore, these findings might help understand the IVIG activities and also the underlying mechanisms of IVIG-resistant patients, thereby providing a new perspective for the exploration of mechanisms related to KD.

Reduced pectin content of cell walls prevents stress-induced root cell elongation in Arabidopsis.

The primary cell walls of plants provide mechanical strength while maintaining the flexibility needed for cell extension growth. Cell extension involves loosening the bonds between cellulose microfibrils, hemicelluloses and pectins. Pectins have been implicated in this process, but it remains unclear if this depends on the abundance of certain pectins, their modifications, and/or structure. Here, cell wall-related mutants of the model plant Arabidopsis were characterized by biochemical and immunohistochemical methods and Fourier-transform infrared microspectroscopy. Mutants with reduced pectin or hemicellulose content showed no root cell elongation in response to simulated drought stress, in contrast to wild-type plants or mutants with reduced cellulose content. While no association was found between the degrees of pectin methylesterification and cell elongation, cell wall composition analysis suggested an important role of the pectin rhamnogalacturonan II (RGII), which was corroborated in experiments with the RGII-modifying chemical 2ß-deoxy-Kdo. The results were complemented by expression analysis of cell wall synthesis genes and microscopic analysis of cell wall porosity. It is concluded that a certain amount of pectin is necessary for stress-induced root cell elongation, and hypotheses regarding the mechanistic basis of this result are formulated.