Diagnostic Value of 99mTc-MIBI Myocardial Perfusion Imaging in Detecting Myocardial Ischemia of Children with Kawasaki Disease and Coronary Artery Lesions.

Pediatric patients with coronary artery lesions (CALs) after Kawasaki disease (KD) may be complicated with myocardial ischemia. Although previous studies in adults have proven the diagnostic value of 99mTc-MIBI myocardial perfusion imaging (MPI) for ischemic heart disease, its feasibility and accuracy in this pediatric population remain uncertain. In this retrospective study, we collected data of 177 pediatric patients (Age range: 6 months to 14 years) who had undergone MPI and coronary artery angiography (CAG) between July 2019 and February 2023. Using the positive result of CAG as the reference standard of myocardial ischemia, we compared the results of 99mTc-MIBI MPI with other non-invasive examinations, including cardiac magnetic resonance imaging (CMRI), echocardiogram, and comprehensive electrocardiogram-related examinations. All patients finished adenosine triphosphate stress MPI without major side effects. The sensitivity of MPI was 79.17%, which was greater than CMRI and echocardiogram (P < 0.05). The negative predictive value and the accuracy of MPI were 89.9% and 71.75%, indicating the advantages over others. Composite monitoring strategy of MPI and CMRI effectively improved the diagnostic performance (P < 0.001). In 4 cases diagnosed with myocardial ischemia by "MPI + CMRI," despite the absence of significant stenosis, multiple giant coronary artery aneurysms (GCAA) were all observed in CAG. 99mTc-MIBI MPI is the preferred non-invasive examination for detecting myocardial ischemia in pediatric patients with CAL after KD. When combined with CMRI, it can enhance diagnostic accuracy. Multiple GCAAs without stenosis may be an isolated risk factor of myocardial ischemia.

Maternal Obesity and Kawasaki Disease-like Vasculitis: A New Perspective on Cardiovascular Injury and Inflammatory Response in Offspring Male Mice.

Maternal obesity affects the risk of cardiovascular disease and inflammatory response in offspring. However, the impact of maternal obesity on offspring with Kawasaki disease (KD), the leading cause of childhood acquired heart disease, is still an understudied area. This study aimed to elucidate the impact of maternal obesity on offspring in KD-like vasculitis and the underlying mechanisms. Offspring of obese female mice and normal diet dams were randomly divided into two subgroups. The pups were injected intraperitoneally with either Candida albicans water-soluble fraction (CAWS) or phosphate buffered saline (PBS) to establish the obesity (OB)-CAWS group, OB group, wild type (WT)-CAWS group, and WT group. Their weight was monitored during the study. After four weeks, echocardiography was applied to obtain the alternation of cardiac structures. Mouse cytokine panel, Hematoxylin-Eosin (HE) staining, western blot, and real-time qPCR were used to study the pathological changes and protein and RNA expression alternations. Based on the study of pathology, serology and molecular biology, maternal obesity lead to more severe vasculitis and induced altered cardiac structure in the offspring mice and promoted the expression of pro-inflammatory cytokines through activating the NF-κB signaling pathway. Maternal obesity aggravated the inflammatory response of offspring mice in KD-like vasculitis.

Melatonin alleviates vascular endothelial cell damage by regulating an autophagy-apoptosis axis in Kawasaki disease.

OBJECTIVES: Melatonin has been reported to be an appropriate candidate for mitigating various cardiovascular injuries, owing to its versatility. This study aimed to explore the role of melatonin in Kawasaki disease (KD)-associated vasculitis and its underlying mechanisms. MATERIAL AND METHODS: The role of melatonin was evaluated in human coronary artery endothelial cells (HCAECs), peripheral blood mononuclear cells from KD patients, human THP1 cell line in vitro, and a Candida albicans water-soluble fraction (CAWS)-induced KD mouse model in vivo. Cell proliferation assay, cell apoptosis assay, cell co-culture, RNA extraction, RNA sequencing, reverse transcription quantitative PCR, enzyme-linked immunosorbent assay (ELISA), transwell assay, western blot, dual-luciferase reporter assay, and autophagic flux assay were performed to investigate the function and regulatory mechanisms of melatonin in vitro, while haematoxylin and eosin staining, Verhoeff's van Gieson staining, ELISA, and immunohistochemical analysis were performed to detect the effect of melatonin in vivo. RESULTS: Melatonin suppressed cell apoptosis directly reduced the expression of endothelial cell damage markers in HCAECs, and alleviated vasculitis in the CAWS-induced KD mouse model. Mechanistically, melatonin promoted autophagy by activating the melatonin/ melatonin receptor (MT)/cAMP-response element binding protein (CREB) pathway and upregulating the expression of autophagy-related gene-3, thereby suppressing cell apoptosis in an autophagy-dependent manner. Additionally, melatonin decreased the production of pro-inflammatory cytokines in macrophages and indirectly reduced the immunopathological damage of HCAECs. CONCLUSIONS: This study revealed that melatonin protects vascular endothelial cells in KD, by suppressing cell apoptosis in an autophagy-dependent manner and reducing the immunopathological damage mediated by macrophages.

Protective effect of antioxidants on cardiac function in adult offspring exposed to prenatal overnutrition.

Maternal overnutrition-induced fetal programming predisposes offspring to cardiovascular health issues throughout life. Understanding how these adverse cardiovascular effects are regulated at the maternal-fetal crosstalk will provide insight into the mechanisms of these cardiovascular diseases, which will help in further identifying potential targets for intervention. Here, we uncover a role of oxidative stress caused by prenatal overnutrition in governing cardiac damage. Mice exposed to maternal obesity showed remarkable pathological cardiomyocyte hypertrophy (pmale < 0.001, Cohen's dmale = 1.77; pfemale < 0.001, Cohen's dfemale = 1.94), increased collagen content (pmale < 0.001, Cohen's dmale = 2.13; pfemale < 0.001, Cohen's dfemale = 2.71), and increased levels of transforming growth factor ß (TGF-ß) (pmale < 0.001, Cohen's dmale = 3.02; pfemale < 0.001, Cohen's dfemale = 4.52), as well as left ventricular dysfunction in adulthood. To cope with increased oxidative stress in the myocardial tissue of offspring from obese mothers, we sought to decrease the effect of oxidative stress and prevent the development of these cardiovascular conditions with use of the antioxidant N-acetylcysteine during pregnancy. As predicted, after treatment with the antioxidant, there was greatly mitigated cardiomyocyte hypertrophy (pmale < 0.001, Cohen's dmale = 1.31; pfemale < 0.001, Cohen's dfemale = 0.82) and cardiac fibrosis, including decreased composition of collagen fibers (pmale < 0.01, Cohen's dmale = 1.45; pfemale < 0.05, Cohen's dfemale = 1.23) and reduced levels of TGF-ß (pmale < 0.05, Cohen's dmale = 1.83; pfemale < 0.01, Cohen's dfemale = 3.81). We also observed improved left ventricle contractile function together with the alleviation of enhanced oxidative stress in the myocardial tissue of offspring. Collectively, these results established a crucial role of oxidative stress in prenatal overnutrition-associated ventricular remodeling and cardiac dysfunction. Our findings provided an important target for intervention of cardiovascular disease in overnutrition-related fetal programming.

Effects of the Leptin-Mediated MAPK/ERK Signaling Pathway on Collagen II Expression in Knee Cartilage of Newborn Male Mice from Obese Maternal Offspring.

Epidemiological data suggest that various noncommunicable diseases develop as a result of altered maternal metabolic and physiological status due to exposure to several adverse factors during pregnancy. However, evidence for intrauterine exposure factors and mechanisms underlying the origin of early cartilage disease in chronic osteoarthritic disease is still lacking. In this study, we found that persistent overnutrition during pregnancy in obese mothers led to cartilage damage in neonatal male mice. This was mainly characterized by increased apoptosis with decreased expression of chondrocyte collagen II and low expression of Runx family transcription factor 2 (RUNX2) and SRY-box transcription factor 9 (SOX9). This reduction was also found to be associated with high leptin expression in newborn male mice of obese maternal offspring. Furthermore, the administration of leptin and mitogen-activated protein kinase (MAPK)-extracellular signal-regulated kinase (ERK) inhibitors in primary chondrocytes showed that leptin mediated MAPK/ERK signaling activation and thus affected the key regulators of cartilage matrix metallopeptidase 1 (MMP1) and tissue inhibitor of metalloproteinase 1 (TIMP1), thereby altering the expression of collagen II in mouse cartilage. Altogether, this study provided insights into the molecular mechanisms of cartilage-related disease development and also new clues and evidence for the fetogenetic origin of cartilage diseases.

N-acetylcysteine protects neonatal mice from ventricular hypertrophy induced by maternal obesity in a sex-specific manner.

BACKGROUND: Maternal obesity induces adverse cardiac programming in offspring, and effective interventions are needed to prevent cardiovascular ill-health. Herein we hypothesized that exposure to maternal obesogenic diet-induced obesity in mice results in left ventricular remodelling and hypertrophy in early childhood, and that maternal N-acetylcysteine (NAC) treatment alleviates these effects in a sex-dependent manner. METHODS AND RESULTS: The maternal obesity was induced in mice by the consumption of a Western diet accompanied by a 20 % sucrose solution. To determine the effect of NAC on the cardiac outcomes induced by maternal obesity, obese dams were continuously exposed to the obesogenic diet, with or without the oral NAC treatment during pregnancy. Left ventricular remodelling and hypertrophy occurred as early as 7 days after birth in the male offspring of obese dams (O-OB) compared with controls (O-CO). An over-expression of key genes and markers related to cardiac fibrosis accompanied by more disorganized myofibrils was observed in the hearts of neonatal male O-OB mice. When we next evaluated the level of oxidative stress in the hearts of neonatal mice, the activity of enzymatic antioxidants declined and expression of NOX enzyme complex was up-regulated in O-OB offspring hearts, but was normal in the offspring of NAC treated mice (O-OB/NAC). Maternal obesity also activated cardiac Akt and mammalian target of rapamycin (mTOR) signalling in offspring, and NAC treatment restored offspring cardiac Akt-mTOR signalling to normal irrespective of sex. NAC treatment did not prevent cardiomyocyte hypertrophy but did alleviate increased heart weight, interventricular septal thickness, and collagen content in male O-OB/NAC pups. CONCLUSIONS: Collectively, our results indicated that NAC blunted cardiac fibrosis and related ventricular hypertrophy of male neonatal offspring in the setting of maternal obesity, potentially acting by reducing oxidative stress. The present study provides a basis for investigating the role of NAC in nutrition-related cardiac programming.

Upregulation of miRNA-23a-3p rescues high glucose-induced cell apoptosis and proliferation inhibition in cardiomyocytes.

Maternal hyperglycemia potentially inhibits the development of the fetal heart by suppressing cardiomyocyte proliferation and promoting apoptosis. Different studies have indicated that miRNAs are key regulators of cardiomyocyte proliferation, differentiation, and apoptosis and play a protective role in a variety of cardiovascular diseases. However, the biological function of miRNA-23a in hyperglycemia-related cardiomyocyte injury is not fully understood. The present study investigated the effect of miRNA-23a-3p on cell proliferation and apoptosis in a myocardial injury model induced by high glucose. H9c2 cardiomyocytes were exposed to high glucose to establish an in vitro myocardial injury model and then transfected with miRNA-23a-3p mimics. After miRNA-23a-3p transfection, lens-free microscopy was used to dynamically monitor cell numbers and confluence and calculate the cell cycle duration. CCK-8 and EdU incorporation assays were performed to detect cell proliferation. Flow cytometry was used to measured cell apoptosis. Upregulation of miRNA-23a-3p significantly alleviated high glucose-induced cell apoptosis and cell proliferation inhibition (p < 0.01 and p < 0.0001, respectively). The cell cycle of the miRNA-23a-3p mimics group was significantly shorter than that of the negative control group (p < 0.01). The expression of cell cycle-activating and apoptosis inhibition-associated factors Ccna2, Ccne1, and Bcl-2 was downregulated by high glucose and upregulated by miRNA-23a-3p overexpression in high glucose-injured H9c2 cells. miRNA-23a-3p mimics transfection before high glucose treatment had a significantly greater benefit than transfection after high glucose treatment (p < 0.0001), and the rescue effect of miRNA-23a-3p increased as the concentration increased. This study suggests that miRNA-23a-3p exerted a dose- and time-dependent protective effect on high glucose-induced H9c2 cardiomyocyte injury.

[Causes and clinical features of children with traumatic brain injury: a retrospective analysis of 126 cases].

OBJECTIVE: To investigate the causes and clinical features of children with traumatic brain injury (TBI) who need hospitalization or emergency observation. METHODS: A retrospective analysis was performed for the clinical data of 126 children with TBI who were admitted to the emergency department from January 1, 2014 to August 31, 2016, including causes of injury and clinical features. RESULTS: Of the 126 children, there were 95 boys and 31 girls, with a mean age of 2.8 years (range 0.8-5.5 years). The children aged <1 year accounted for 38.1% (48/126), and 26 children died. The two most common types of TBI were epidural hematoma (54.0%) and subarachnoid hemorrhage (50.8%). Of the 126 children, 83 (65.9%) had a Glasgow Coma Scale score of ≤8 within 24 hours after admission. There were different causes of TBI and places where TBI occurred in different age groups. The two leading causes of TBI were falls (51.6%) and road traffic injuries (42.9%). Compared with those in the other age groups, the children in the age <1 year group were most likely to experience injury due to falls (46%; P=0.023). Thirty-five percent of all TBI due to road traffic injuries occurred in the children aged 3-6 years (P<0.001). Most TBI cases occurred at home (47.6%) or on roads/streets (45.2%). Among those who experienced TBI at home, the children aged <1 year accounted for the highest proportion of 48% (P=0.002), and 53% of the patients aged 3-6 years experienced TBI on roads/streets. The most common cause of death in children with TBI was road traffic injury, which accounted for 69%. Among those who died, the children aged <1 year accounted for the highest proportion (62%). CONCLUSIONS: There are different causes of TBI and places where TBI occurs in different age groups. Among children with TBI, the children aged <1 year account for the highest proportion and have the highest number of deaths, with falls at home as the most common cause of TBI. Children aged 3-6 years tend to suffer TBI due to road traffic injury. Road traffic injury is the leading cause of death.

Alpha B-crystallin C-802G polymorphism and colorectal cancer susceptibility and clinical outcome in Chinese population.

Colorectal cancer (CRC) is one of the most prevalent cancers worldwide and Alpha B-crystallin (CRYAB) protein has been identified as a prognostic biomarker for CRC. We evaluated CRYAB C-802G (rs14133)polymorphism in association with CRC risk and survival in Chinese population. We genotyped for CRYAB C-802G (rs14133), A-1215G (rs2228387) and intron 2 (rs2070894), and assessed their associations with CRC in a case-control study of 441 CRC cases and 500 healthy controls. We also analyzed this polymorphism in relation to overall survival in CRC patients. A significantly different frequency distribution was found in CRYAB C-802G genotypes, but not in A-1215G and intron2 genotypes, between the cases and the controls. Under multivariable logistic regression adjusted for age and gender, CG/GG genotype carriers were associated with increased risk of CRC (OR 1.754, 95% CI 1.338-2.301, P < 0.001) when compared with CC genotype carriers. Multivariate Cox proportional hazards model showed that patients with CG/GG genotype had significant shorter survival time than those with CC genotype, after adjustment for gender and TNM stage (HR 2.347, 95% CI 1.719-3.204, P < 0.001), and after adjustment for gender and tumor grade (HR 2.871, 95% CI 2.121-3.887, P < 0.001), respectively. Our results demonstrated that CG/GG at CRYAB C-802G is correlated with CRC susceptibility and this polymorphism may be an useful marker for clinical outcome of CRC.

Long noncoding RNA BLACAT1 modulates ABCB1 to promote oxaliplatin resistance of gastric cancer via sponging miR-361.

Long non-coding RNAs (lncRNAs) have emerged as novel gene regulators in multiple tumorigenesis and chemoresistance. However, their potential roles and molecular mechanisms in gastric cancer chemoresistance remain unclear. In present study, our team investigated the role and potential regulatory mechanism of lncRNA s bladder cancer associated transcript-1 (BLACAT1) in the gastric cancer chemoresistance. Results showed that BLACAT1 expression was up-regulated in the oxaliplatin (OXA) resistant gastric cancer tissue and cells compared with OXA-sensitive tissue and parental cell lines. In vitro, BLACAT1 knockdown decreased the expression levels of drug resistance related genes and ABCB1 protein. Besides, BLACAT1 knockdown significantly promoted apoptosis and down-regulated the invasion and the IC50 value of oxaliplatin. In vivo, BLACAT1 knockdown suppressed the tumor growth of gastric cancer cells. Bioinformatics tools and luciferase assay indicated that miR-361 both targeted 3?-UTR of BLACAT1 and ABCB1mRNA, suggesting the BLACAT1/miR-361/ABCB1 regulatory pathway. In summary, our results conclude that BLACAT1 accelerates the oxaliplatin-resistance of gastric cancer via promoting ABCB1 protein expression by targeting miR-361, providing a novel insight for the chemoresistance of gastric cancer.