Relationship between Baseline Serum Potassium and 1-Year Readmission in Pediatric Patients with Heart Failure: A Retrospective Cohort Study.

Pediatric heart failure (HF) is associated with high readmission rates, but the optimal serum potassium range for this population remains unclear. In this single-center retrospective cohort study, 180 pediatric patients hospitalized for HF between January 2016 and January 2022 were stratified into low-potassium (<3.7 mmol/L), middle-potassium (3.7-4.7 mmol/L), and high-potassium (≥4.7 mmol/L) groups based on the distribution of potassium levels in the study population. The primary outcome was readmission for HF within 1 year of discharge. Cox regression and restricted cubic spline models were used to assess the association between potassium levels and 1-year HF readmission rates. Notably, 38.9% of patients underwent 1 or more 1-year readmissions for HF within 1 year. The high-potassium group had a significantly higher readmission frequency than the middle-potassium group. In multivariate Cox regression models, potassium levels of ≥4.7 mmol/L were independently associated with increased 1-year readmission risk. A J-shaped relationship was observed between baseline potassium levels and 1-year readmission risk, with the lowest risk at 4.1 mmol/L. In pediatric patients with HF, a serum potassium level ≥ 4.7 mmol/L was independently associated with increased 1-year readmission risk. Maintaining potassium levels within a narrow range may improve outcomes in this population.

Evaluation of the Association Between Coronary Artery Aneurysms and Concomitant Infection in Patients With Kawasaki Disease.

We analyzed the relationship between recovery from coronary artery aneurysms (CAAs) and concurrent infections in patients with Kawasaki disease (KD). The estimated median time of aneurysm persistence between patients with and without infections was compared using Kaplan-Meier survival analyses. Risk factors associated with persistent CAAs at 2 years were identified using multivariable analyses. Co-infection was confirmed in 20.5% (106/518) of patients diagnosed with KD. No significant differences regarding treatment or coronary artery outcome were identified between patients with and without infections. The estimated median time of aneurysm persistence was higher in the co-infected group (9 vs. 6 months). A maximum Z-score ≥ 4.00 at 1 month had 78% sensitivity and 83% specificity in predicting CAAs without recovery within 1 year of onset, whereas the predictability was higher within 2 years of onset, with a Z-score ≥ 4.88 (sensitivity, 92%; specificity, 91%). Concomitant infections did not affect the response to treatment or coronary artery outcomes in patients with KD.

ITPKC polymorphism (rs7251246 T > C), coronary artery aneurysms, and thrombosis in patients with Kawasaki disease in a Southern Han Chinese population.

Objectives: Kawasaki disease (KD) is a commonly acquired pediatric systemic vasculitis disease resulting in coronary artery aneurysm (CAA). The relationship between the ITPKC polymorphism (rs7251246) and the severity and susceptibility to KD in the Han Chinese population in Southern China remains unclear. Methods: We enrolled 262 children as controls and 221 children with KD (46 [20.8%] with intravenous immunoglobulin resistance and 82 [37.1%] with CAA). The relationship between the ITPKC rs7251246 polymorphism, KD susceptibility, and CAA formation was investigated. Results: While the ITPKC rs7251246 T>C polymorphism was not significantly associated with KD susceptibility, it was significantly related to the CAA risk in children with KD [CC/CT vs. TT: adjusted odds ratio [OR] 2.089, 95% confidence interval [CI] 1.085-4.020]. Male children with the rs7251246 CT/TT genotype had a significantly lower risk of thrombosis [CT/TT vs. CC: adjusted OR 0.251, 95% CI 0.068-0.923]. Children with KD, especially those with CAA, had significantly downregulated ITPKC mRNA compared to healthy children. ITPKC mRNA levels were lower in children with CAA who developed thrombosis (P=0.039). In children with KD, the CC genotype showed lower mRNA levels of ITPKC (P=0.035). Conclusion: The ITPKC rs7251246 T>C polymorphism may be a risk factor for CAA and thrombosis in children with KD in the Han Chinese population, likely due to differences in mature mRNA levels caused by interference of RNA splicing. Dual antiplatelet therapy for thrombosis is recommended for male children with the rs7251246 CC genotype.

Risk Factors for Coronary Artery Aneurysm in a Chinese Pediatric Population with Kawasaki Disease at Low Risk of Intravenous Immunoglobulin Resistance: A Retrospective Cohort Study.

INTRODUCTION: Multiple scoring systems for predicting intravenous immunoglobulin (IVIG) resistance have been developed. Although low-scoring patients with Kawasaki disease (KD) have a favorable prognosis, many develop coronary artery aneurysms (CAAs). Herein, we determined the risk factors for CAA development among patients with KD with low risk of IVIG resistance. METHODS: We compared 14 scoring systems for predicting IVIG resistance among patients with KD hospitalized from 2003 to 2022. Patients were risk stratified using an optimal scoring system. Association between baseline characteristics and CAA development was assessed within the low-risk group. RESULTS: Overall, 664 pediatric patients with KD were included; 108 (16.3%) had IVIG resistance, and the Liping scoring system had the highest area under the curve (0.714). According to this system, 444 (66.9%) patients with KD were classified as having low risk of developing IVIG resistance (<5 points). CAA development was significantly associated with male sex (odds ratio [OR], 1.946; 95% CI: 1.015-3.730), age <6 months at fever onset (OR, 3.142; 95% CI: 1.028-9.608), and a baseline maximum Z score of ≥2.72 (OR, 3.451; 95% CI: 2.582-4.612). CAA incidence increased with the number of risk factors, and comparisons with a Kobayashi score of <5 points among patients with KD revealed similar results. CONCLUSIONS: Predicting the response to IVIG might help further reduce CAA development in patients with KD.

Prognostic nutritional index value in the prognosis of Kawasaki disease with coronary artery lesions.

Objectives: The prognostic nutritional index (PNI) is a purported predictor of intravenous immunoglobulin (IVIG) resistance and coronary artery aneurysm (CAA) development in patients with Kawasaki disease (KD). However, limited data exist on CAA regression. This study aimed to confirm whether the PNI is a predictor for CAA persistency in patients with KD. Methods: This retrospective study grouped 341 patients with KD based on the coronary artery status and time of aneurysm persistence. The clinical and laboratory parameters were compared, and multivariate logistic regression analysis was performed to identify the independent risk factors for persistent CAA. The receiver operating characteristic (ROC) curve was further used to assess the predictive values of the PNI in persistent CAA. Results: Among the study patients, 80 (23.5%) presented with CAA, including CAA persisting for 2 years in 17 patients (5.0%). Patients with CAA were more frequently treated with corticosteroids (p < 0.016). No statistically significant differences were found in the nutritional status and PNI among patients with or without coronary artery lesions, regardless of injury severity. Patients in the persistent CAA group presented with higher rates of overnutrition and showed lower PNI values and a higher incidence of thrombosis than those in the normal group (p < 0.05). The PNI and the maximum Z-score at 1 month of onset were significantly associated with CAA persisting for 2 years and may be used as predictors of persistent CAA. The area under the ROC curve was 0.708 (95% confidence interval, 0.569-0.847), and a 40.2 PNI cutoff yielded a sensitivity and specificity of 41 and 92%, respectively, for predicting CAA persisting for 2 years. Kaplan-Meier survival analysis revealed that the estimated median time of aneurysm persistence was significantly higher in patients with PNI values of ≤40 than in those with PNI values of >40 (hazard ratio, 2.958; 95% confidence interval, 1.601-5.464; p = 0.007). After sampling-time stratification, the PNI differed significantly between patients with and without persistent CAA when sampled on the second (p = 0.040), third (p = 0.028), and fourth days (p = 0.041) following disease onset. Conclusion: A lower PNI value is an independent risk factor for CAA persisting for 2 years in patients with KD, besides the maximum Z-score at 1 month after onset. Furthermore, the PNI obtained within 4 days from fever onset may possess greater predictive power for patients with persistent CAA.

Evaluation of laboratory predictors for intravenous immunoglobulin resistance and coronary artery aneurysm in Kawasaki Disease before and after therapy.

OBJECTIVES: We aimed to evaluate the clinical and laboratory characteristics of patients with Kawasaki disease (KD) before and after therapy. METHODS: Patients with KD were divided into different groups according to their responsiveness to initial intravenous immunoglobulin (IVIG) treatment and coronary status. The clinical and laboratory parameters before and after therapy were compared. Multivariate analysis was performed to identify the independent risk factors, and the receiver operating characteristic (ROC) curve was applied to assess and compare the prediction ability of risk factors and their fluctuations. RESULTS: Of the 153 patients included in the study, 41 (26.8%) had IVIG resistance and 37 (24.2%) had developed CAA. After stratifying by therapy response, the two groups differed in the levels of total bilirubin (TSB), albumin, and sodium, neutrophil-to-lymphocyte count ratio (NLR), platelet-to-lymphocyte count ratio (PLR), TSB-to-albumin (B/A) ratio, and prognostic nutritional index (PNI) before IVIG, and in the white blood cell count (WBC), neutrophil count, levels of hemoglobin, C-reactive protein (CRP), alanine aminotransferase (ALT), and albumin, NLR, PNI, capillary leakage index (CLI), and systemic immune-inflammation index (SII) after IVIG. Multivariate analysis revealed that the B/A ratio before IVIG and CLI and SII after IVIG were significantly and positively associated with IVIG resistance and that there was a larger decline in the B/A ratio and smaller decline in CLI and SII pre- and post-treatment in the IVIG-resistant group than in the IVIG-responsive group. However, no statistical differences in the fluctuations of the B/A ratio, CLI, and SII as well as all parameters before and after therapy were observed in patients with and without CAA. ROC curve analyses found a greater AUC value of post-treatment parameters (0.751 and 0.706 for CLI and SII, respectively) compared with pre-treatment parameters (0.654 for B/A ratio) in predicting IVIG resistance; however, the predictive ability of the fluctuations in risk factors before and after therapy was not superior to that of baseline values. CONCLUSIONS: The B/A ratio before IVIG and CLI and SII after IVIG were risk factors for IVIG resistance in patients with KD, independent of CAA development. Key Points • A high total bilirubin-to-albumin ratio before IVIG and high capillary leakage and systemic immune-inflammation indices after IVIG may indicate an increased risk of intravenous immunoglobulin resistance in patients with Kawasaki disease. • Post-treatment parameters were superior to pre-treatment parameters in terms of prediction; therefore, rapid and repeated assessment of risk factors before and after treatment must be considered in children in whom the vital signs and symptoms do not improve after treatment.

Extracardiovascular injury complications in Kawasaki disease.

Importance: Patients with Kawasaki disease (KD) experience various extracardiovascular injury complications, which may affect their outcomes. Objective: To investigate the incidence and clinical characteristics of extracardiovascular complications in children with KD. Methods: The clinical data of patients diagnosed with KD in the First Affiliated Hospital of Guangxi Medical University from January 2003 to January 2021 were reviewed. The clinical characteristics and extracardiovascular complications were compared among patients stratified by age, intravenous immunoglobulin (IVIG) therapy responsiveness, and coronary status. Results: A total of 511 patients with KD were included, 357 (69.9%) were aged 1-5 years. Children aged <1 year (21.5%) and boys (70.8%) were more likely to have coronary artery lesions (CALs). The incidence of incomplete KD was lowest in 1-5-year-old patients (19.6%). Involvement of the hematological system gradually decreased with age (<1 year, 51.8%; 1-5 years, 36.7%; >5 years, 29.5%), whereas the involvement of the joints gradually increased with age (<1 year, 2.7%; 1-5 years, 6.2%; >5 years, 20.5%). Nervous system involvement was more common in IVIG non-responders (15.7% [13/83] vs. 5.4% [23/428], P = 0.001). However, there were no significant differences in extracardiovascular injury complications between patients with or without CALs. Interpretation: KD can involve multiple organ injuries as well as cardiovascular complications, and nervous systerm involvement may be more common in patients unresponsive to IVIG.

Risk factors and coronary artery outcomes of coronary artery aneurysms differing in size and emergence time in children with Kawasaki disease.

Coronary artery aneurysm (CAA) is a serious cardiac complication arising from Kawasaki disease (KD) and is becoming the leading cause of acquired heart disease in children. The aim of this study was to determine the potential risk factors associated with coronary artery aneurysms (CAAs), which differ in size and emergence time, and track its regression within 3 years of onset. The laboratory data, clinical features, and coronary artery outcomes of patients, who were diagnosed with KD and received treatment from January 2003 to January 2019 were retrospectively analyzed. A total of 484 pediatric patients with KD were examined during the study period. Among them, 130 (26.9%) presented with CAA, including mid- to large-sized CAA in 38 patients (7.9%) and de novo CAA after intravenous immunoglobulin (IVIG) treatment in 22 patients (4.5%). Albumin-to-globin (A/G) ratio was significantly negatively associated with the absolute internal diameter of coronary artery at 1 month of onset and may be used as a predictor of mid- to large-sized CAA development in patients with KD. The area under the receiver operating characteristic curve was 0.637 (95% confidence interval: 0.551-0.724), and a cutoff of 1.32 yielded a sensitivity and specificity of 79 and 49%, respectively, for predicting mid- to large-sized CAA development. De novo CAA after IVIG may lead to an increased risk of developing progressive CAA [13 (59.1%) of 22 vs. 31 (28.7%) of 108; P = 0.006] and had significantly greater changes in both the magnitude of CAA dimension variation and maximum z-score of the coronary arteries at 2 and 4 weeks and then 3 months after onset (P < 0.001). Kaplan-Meier survival analysis revealed that the estimated median time of aneurysm persistence was significantly higher in the progressive CAA group than in the non-progressive CAA group (25 vs. 4 months, P < 0.001), as well as among the three groups of patients (giant CAA > medium-sized CAA > small-sized CAA, P < 0.001). Children with KD who had low A/G ratio were more likely to develop mid- to large-sized CAA. Nevertheless, de novo CAA after IVIG treatment may increase the risk of more severe arterial damage and development of progressive coronary artery damage; and both mid- to large-sized and de novo CAA could dramatically prolong coronary artery normalization time. Thus, aggressive risk modifications should be employed, and close monitoring with frequent echocardiography is needed for this vulnerable patient population.

Bioinformatic analysis of dysregulated circular RNAs in pediatric pulmonary hypertension linked congenital heart disease.

Background: Circular RNAs (circRNAs) may play important roles in the progression of pulmonary arterial hypertension. However, the potential roles they play in childhood pulmonary arterial hypertension associated congenital heart disease (CHD) progression remains unclear. Methods: Thirteen human plasma samples including eight from pulmonary arterial hypertension secondary to CHD patients and five from a control group were analyzed using the Arraystar Human circRNA array. The relative expression levels of five differentially expressed circRNAs in pulmonary arterial hypertension were detected using real-time polymerase chain reaction (PCR) analysis. In parallel, these levels were also taken on control samples from 32 CHD patients. We used miRanda and TargetScan software packages to predict potential microRNA (miRNA)targets, which were then combined into a circRNA-miRNA-messenger RNA (mRNA) network. Results: Twenty-seven circRNAs (three upregulated and 24 downregulated) were differentially expressed between the pulmonary arterial hypertension and control groups. Compared to control group levels, circ_003416 expression in the pulmonary arterial hypertension group was significantly downregulated, while circ_005372 expression, in contrast, was significantly upregulated. The differential expression of these circRNAs was mainly linked to variation in levels of oxidative phosphorylation and tight junction signaling. Conclusions: We identified one overexpressed and one underexpressed circRNA in plasma samples from children with CHD associated pulmonary arterial hypertension. Bioinformatic analysis indicated these dysregulated circRNAs might be associated with the occurrence and regulation of pulmonary arterial hypertension.

Risk Factors for Resistance to Intravenous Immunoglobulin Treatment and Coronary Artery Abnormalities in a Chinese Pediatric Population With Kawasaki Disease: A Retrospective Cohort Study.

Background: The factors predicting high-risk Kawasaki disease (KD) remain unclear. Therefore, we aimed to determine the risk factors for resistance to intravenous immunoglobulin (IVIG) treatment and coronary artery aneurysm (CAA) development in a Chinese pediatric population with high-risk KD. Methods: We compared the performances of 11 scoring systems that have been reported to predict IVIG resistance among patients with KD hospitalized from January 2013 through August 2021. Patients were risk-stratified based on the optimal scoring system. The association of baseline characteristics with IVIG treatment resistance and CAA development was investigated within the high-risk group of KD. Results: In total, 346 pediatric patients with KD were included, of whom 63 (18.2%) presented with IVIG resistance. The Kobayashi score and five Chinese scoring system scores (Tang et al., Yang et al., Lan et al., Liping et al., and Wu et al.) were significantly higher in the IVIG non-responsive KD group than in the IVIG responsive KD group, and the results of the receiver operating characteristic (ROC) curves analysis were observed to be highest in the Xie Liping scoring system for IVIG resistance (area under the curve, 0.650). Especially, 87 (25.1%) patients comprised the high-risk KD group based on this optimal scoring system (≥5 points). IVIG resistance was significantly associated with the total bilirubin-to-albumin ratio (B/A ratio) [odds ratio, 7.427; 95% confidence interval (CI): 1.022-53.951]. The area under the ROC was 0.703 (95% CI: 0.586-0.821), and the cutoff point was 0.383, which indicated a sensitivity and specificity for predicting treatment resistance of 58% and 80%, respectively. The serum albumin level (odds ratio, 1.401; 95% CI: 1.049-1.869) and Z score of the left main coronary artery (odds ratio, 9.023; 95% CI: 1.070-76.112) were independent predictors of CAA development. Conclusions: In the Chinese pediatric population with KD, the Xie Liping scoring system is the most appropriate method for identifying high-risk patients, and IVIG resistance could be predicted based on the B/A ratio. Serum albumin level and Z score of the left main coronary artery at baseline were warning indicators for CAA development. More intensified or adjunctive therapies and close follow-up should be considered for high-risk patients with these risk factors.

Effects of YM155 on the proliferation and apoptosis of pulmonary artery smooth muscle cells in a rat model of high pulmonary blood flow-induced pulmonary arterial hypertension.

INTRODUCTION: Proliferation and apoptosis of pulmonary artery smooth muscle cells (PASMCs) play an important role in the occurrence and development of pulmonary arterial hypertension (PAH). The purpose of this study was to investigate the effects of survivin inhibitor YM155 on the proliferation and apoptosis of PASMCs in rats with PAH induced by high pulmonary blood flow. METHODS: Thirty male Sprague-Dawley (SD) rats were randomly divided into control, model, and YM155 intervention groups. A rat model of PAH induced by high pulmonary blood flow was established, and it was confirmed by assessments of right-ventricular pressure (RVP) and right ventricular hypertrophy index (RVHI). Immunohistochemical staining and western blot analysis were used to detect the expression of survivin, and the proliferation and apoptosis of PASMCs. Lastly, the effects of in vivo treatment of YM155 were tested. RESULTS: The increased expression of survivin mRNA and protein were observed in the model group, accompanied by pulmonary arteriolar wall thickening, lumen stenosis, and perivascular inflammatory cell infiltration. Elevated expression of survivin and pulmonary vascular remodeling were significantly mitigated after YM155 treatment. Specifically, the YM155 intervention group had a significantly lower PASMC proliferation rate and a higher PASMC apoptotic rate. CONCLUSION: YM155 suppressed PASMC proliferation and promoted PASMC apoptosis by inhibiting survivin expression and thereby reducing pulmonary vascular remodeling in high pulmonary blood flow-induced PAH in vivo.

Expression and clinical significance of circular RNA hsa_circ_0003416 in pediatric pulmonary arterial hypertension associated with congenital heart disease.

BACKGROUND: Circular RNAs (circRNAs) have been found to be involved in the development of pulmonary arterial hypertension (PAH). However, their diagnostic value in pediatric PAH remains unclear. This study aimed to examine the characteristic expression of the circRNA hsa_circ_0003416 in the plasma of children with PAH caused by congenital heart disease (CHD); the potential of hsa_circ_0003416 as a diagnostic biomarker was also investigated. METHODS: The plasma expression levels of hsa_circ_0003416 were determined via quantitative reverse transcription-polymerase chain reaction in 50 CHD patients, 50 PAH patients, and 20 healthy subjects; the associations between hsa_circ_0003416 levels and clinical data were analyzed thereafter. Receiver operating characteristic curves were employed to determine the diagnostic capacity of this circRNA. RESULTS: Expression levels of hsa_circ_0003416 in plasma were lower in the PAH-CHD group than in the CHD and healthy control groups (p = 0.009 vs. healthy control group, p = 0.026 vs. CHD group). Moreover, hsa_circ_0003416 was found to be negatively associated with B-type natriuretic peptide (r = -0.342, p = 0.013). In addition, the area under the curve of hsa_circ_0003416 levels in plasma was 0.721 (95% confidence intervals = 0.585-0.857, p = 0.004), suggesting that it has a promising diagnostic value. CONCLUSIONS: Overall, hsa_circ_0003416 was found to be significantly downregulated in children with PAH-CHD and to be potent as a biomarker for PAH-CHD diagnosis.

Metabolic Reprogramming of the Right Ventricle and Pulmonary Arteries in a Flow-Associated Pulmonary Arterial Hypertension Rat Model.

Pulmonary arterial hypertension (PAH) is a complex devastating disease relevant to remarkable metabolic dysregulation. Although various research studies on PAH from a metabolic perspective have been emerging, pathogenesis of PAH varies in different categories. Research on metabolic reprogramming in flow-associated PAH remains insufficient. An untargeted metabolomic profiling platform was used to evaluate the metabolic profile of pulmonary arteries (PAs) as well as the right ventricle (RV) in a flow-associated PAH rat model in the present work. A total of 79 PAs and 128 RV metabolites were significantly altered in PAH rats, among which 39 metabolites were assessed as shared dysregulated metabolites in PAs and the RV. Pathway analysis elucidated that, in PAs of PAH rats, pathways of phenylalanine, tyrosine, and tryptophan biosynthesis and linoleic acid metabolism were significantly altered, while in the RV, arginine biosynthesis and linoleic acid metabolism were altered dramatically. Further integrated analysis of shared dysregulated PA and RV metabolites demonstrated that the linoleic acid metabolism and the arachidonic acid (AA) metabolism were the key pathways involved in the pathogenesis of flow-associated PAH. Results obtained from the present work indicate that the PAH pathogenesis could be mediated by widespread metabolic reprogramming. In particular, the dysregulation of AA metabolism may considerably contribute to the development of high blood flow-associated PAH.

Large-Scale Phylogenomic Analyses Reveal the Monophyly of Bryophytes and Neoproterozoic Origin of Land Plants.

The relationships among the four major embryophyte lineages (mosses, liverworts, hornworts, vascular plants) and the timing of the origin of land plants are enigmatic problems in plant evolution. Here, we resolve the monophyly of bryophytes by improving taxon sampling of hornworts and eliminating the effect of synonymous substitutions. We then estimate the divergence time of crown embryophytes based on three fossil calibration strategies, and reveal that maximum calibration constraints have a major effect on estimating the time of origin of land plants. Moreover, comparison of priors and posteriors provides a guide for evaluating the optimal calibration strategy. By considering the reliability of fossil calibrations and the influences of molecular data, we estimate that land plants originated in the Precambrian (980-682 Ma), much older than widely recognized. Our study highlights the important contribution of molecular data when faced with contentious fossil evidence, and that fossil calibrations used in estimating the timescale of plant evolution require critical scrutiny.

Lifestyle Clusters and Cardiometabolic Risks in Adolescents: A Chinese School-Based Study Using a Latent Class Analysis Approach.

Background: Unhealthy dietary and lifestyle behaviors are associated with a higher prevalence of non-communicable chronic diseases and higher mortality in adults. However, there remains some uncertainty about the magnitude of the associations between lifestyle behaviors and cardiovascular factors in adolescents. Methods: We conducted a school-based cross-sectional study of 895 Chinese adolescents aged 15-19 years. They participated in a questionnaire survey, physical examination, and blood sample collection. Latent class analysis (LCA) was used to identify heterogeneous subgroups of lifestyle behaviors. A set of 12 latent class indicators, which reflected lifestyle behaviors including dietary habits, physical activity, sleep duration, screen time, and pressure perception, were included in the analysis. Logistic regression analysis was performed to determine whether the derived classes were related to a cardiometabolic risk. Results: In total, 13.7 and 5.6% of the participants were overweight and obese, respectively, and 8.4 and 14.1% reported having pre-hypertension and hypertension, respectively. A two-class model provided the best fit with a healthy lifestyle pattern (65.8%) and a sub-healthy lifestyle pattern (34.2%). There were more female participants with a healthy lifestyle (56.2 vs. 43.8%), whereas there were more males with a sub-healthy lifestyle (45.4 vs. 54.6%), (all P = 0.002). Increased risk of cardiometabolic abnormality (BMI categories, blood pressure and lipids) was not significant across lifestyle patterns, except for waist circumference (70.5 vs 69.1 cm, P = 0.044). There was no significant difference in physical activity and intake of fruit and vegetable between the two patterns. Conclusion: Primary prevention based on lifestyle modification should target patterns of behaviors at high risk in adolescents. Due to the complex effect of lifestyle clusters on cardiometabolic risks, well-designed and prospective studies in adolescents are needed in the future.

Phylogenomic Insights into Deep Phylogeny of Angiosperms Based on Broad Nuclear Gene Sampling.

Angiosperms (flowering plants) are the most diverse and species-rich group of plants. The vast majority (∼99.95%) of angiosperms form a clade called Mesangiospermae, which is subdivided into five major groups: eudicots, monocots, magnoliids, Chloranthales, and Ceratophyllales. The relationships among these Mesangiospermae groups have been the subject of long debate. In this study, we assembled a phylogenomic dataset of 1594 genes from 151 angiosperm taxa, including representatives of all five lineages, to investigate the phylogeny of major angiosperm lineages under both coalescent- and concatenation-based methods. We dissected the phylogenetic signal and found that more than half of the genes lack phylogenetic information for the backbone of angiosperm phylogeny. We further removed the genes with weak phylogenetic signal and showed that eudicots, Ceratophyllales, and Chloranthales form a clade, with magnoliids and monocots being the next successive sister lineages. Similar frequencies of gene tree conflict are suggestive of incomplete lineage sorting along the backbone of the angiosperm phylogeny. Our analyses suggest that a fully bifurcating species tree may not be the best way to represent the early radiation of angiosperms. Meanwhile, we inferred that the crown-group angiosperms originated approximately between 255.1 and 222.2 million years ago, and Mesangiospermae diversified into the five extant groups in a short time span (∼27 million years) at the Early to Late Jurassic.

TMEM16A Regulates Pulmonary Arterial Smooth Muscle Cells Proliferation via p38MAPK/ERK Pathway in High Pulmonary Blood Flow-Induced Pulmonary Arterial Hypertension.

OBJECTIVE: Pulmonary arterial hypertension (PAH) is a complex disease of the small pulmonary arteries that is mainly characterized by vascular remodeling. It has been demonstrated that excessive proliferation of pulmonary arterial smooth muscle cells (PASMCs) plays a pivotal role in vascular remodeling during PAH. The present study was undertaken to explore the role of TMEM16A in regulating PASMCs proliferation in high pulmonary blood flow-induced PAH. METHODS: Aortocaval shunt surgery was undertaken to establish an animal model. Pulmonary artery pressure and pulmonary vascular structure remodeling (PVSR) were tested. Immunohistochemical staining and Western blot were performed to investigate the expression of TMEM16A. The proliferation of PASMCs was tested by the MTT assay. After treating PASMCs with TMEM16A-siRNA, the expression of proliferating cell nuclear antigen (PCNA), phosphorylated p38 mitogen-activated protein kinase (p-p38MAPK), and phosphorylated extracellular signal-regulated kinase (p-ERK) signaling in PASMCs were tested. RESULTS: PAH and PVSR developed 11 weeks postoperation. Elevated expression of TMEM16A accompanied by high expression of PCNA in pulmonary arteries of the shunt group was observed. The increased proliferation of PASMCs and increased expression of TMEM16A and PCNA, along with activated p-p38MAPK and p-ERK signaling in PASMCs of the shunt group, were all attenuated by siRNA-specific TMEM16A knockdown. CONCLUSION: TMEM16A regulates PASMCs proliferation in high pulmonary blood flow-induced PAH, and the p38MAPK/ERK signaling pathway is probably involved.

Adaptation to Extreme Antarctic Environments Revealed by the Genome of a Sea Ice Green Alga.

The unicellular green alga Chlamydomonas sp. ICE-L thrives in polar sea ice, where it tolerates extreme low temperatures, high salinity, and broad seasonal fluctuations in light conditions. Despite the high interest in biotechnological uses of this species, little is known about the adaptations that allow it to thrive in this harsh and complex environment. Here, we assembled a high-quality genome sequence of ∼542 Mb and found that retrotransposon proliferation contributed to the relatively large genome size of ICE-L when compared to other chlorophytes. Genomic features that may support the extremophilic lifestyle of this sea ice alga include massively expanded gene families involved in unsaturated fatty acid biosynthesis, DNA repair, photoprotection, ionic homeostasis, osmotic homeostasis, and reactive oxygen species detoxification. The acquisition of multiple ice binding proteins through putative horizontal gene transfer likely contributed to the origin of the psychrophilic lifestyle in ICE-L. Additional innovations include the significant upregulation under abiotic stress of several expanded ICE-L gene families, likely reflecting adaptive changes among diverse metabolic processes. Our analyses of the genome, transcriptome, and functional assays advance general understanding of the Antarctic green algae and offer potential explanations for how green plants adapt to extreme environments.

Outcomes of Kawasaki disease with giant coronary aneurysms: a single-centre study in southwest China.

BACKGROUND: Giant coronary aneurysms are the most severe complications of Kawasaki disease. There are few reports of outcomes from China. Most previous studies were based only on absolute aneurysmal dimensions. The aim of the present study was to catalog the outcomes of Kawasaki disease with giant coronary aneurysms in southwest China based on absolute dimensions and the z-score adjusted for body surface area. METHODS AND RESULTS: All patients diagnosed with giant coronary aneurysms (z-score ≥ 10 or absolute dimension ≥ 8 mm) between December, 2002 and December, 2018 were included. We retrospectively analysed patient characteristics and clinical data from 38 patients with giant coronary aneurysms. Over a median follow-up period of 30.5 months (range from 1.7 months to 22.3 years), including patients in chronic phase who had been diagnosed prior to 2002, eight patients had myocardial infarction, including two deaths and one patient with coronary artery bypass grafting. The 1-, 2-, and 5-year event-free rates were 0.63, 0.63, and 0.53 for thrombosis, respectively, and 0.86, 0.81, and 0.81 for major adverse cardiac events, respectively. The 1-, 2-, and 5-year regression-free rates were 0.94, 0.85, and 0.67, respectively. A total of 73.7% of patients remained active. CONCLUSION: In the early stages of Kawasaki disease, patients with giant coronary aneurysms often experience major cardiovascular events; however, they are also likely to have normalisation of the coronary internal luminal diameter. With long-term anticoagulation, close cardiologic monitoring, and prompt thrombolytic therapy, most patients can achieve disease-free periods.

Long-Term Outcome of Transcatheter Device Closure of Perimembranous Ventricular Septal Defects.

Background: Ventricular septal defect is a common congenital heart defect. Transcatheter closure of perimembranous ventricular septal defect (pmVSD) is an effective method alternative to surgical closure. The aim of the study is to evaluate the procedural result, early and long-term follow-up outcome of transcatheter closure of pmVSD. Methods: From January 2005 to December 2016, we retrospectively identified the patients who underwent transcatheter device closure of pmVSD. All patients underwent transthoracic echocardiography (TTE) and electrocardiogram (ECG) before and after the procedure. Follow-up evaluation was done at 1, 3, 6, 12 months and yearly thereafter with TTE and ECG. Results: Total 186 patients (95 male, 91 female) had catheter-based intervention of pmVSD. The mean age at the time of procedure was 5.4 ± 2.8 years (range 2~14 years) and the mean weight was 18.1 ± 6.7 kg (range 10.5~43 kg). The mean size of the implanted device was 8.4 ± 2.1 mm (range 5~16 mm). The device was successfully implanted in 180 patients (96.8%). Immediate post-procedural echocardiography showed complete occlusion in all but one patient had trivial residual shunt. Total early adverse events occurred in 16 patients (8.9%). Only in two patients it was significant, complete AVB occurred in a 9 years old boy, managed with temporary pacemaker and one patient had complete left bundle branch block, recovered fully after steroid therapy. During a median follow-up period of 18.4 months (range 6~120 months), no serious adverse events and complete AVB were encountered. Conclusion: In our experience, The incidence of serious adverse event is low and no late onset of complete AVB with excellent success rate and follow-up results, confirming the transcatheter closure of pmVSD is a valuable alternative to surgical closure in selected patients.