Single-Cell Transcriptome Reveals Potential Mechanisms for Coronary Artery Lesions in Kawasaki Disease.

BACKGROUND: Coronary artery lesions (CALs) are the most common and major complication of Kawasaki disease (KD) in developed countries. However, the underlying immunologic mechanisms of CAL development in KD remain unclear. METHODS: Here, we conducted single-cell transcriptome analyses of 212 210 peripheral blood mononuclear cells collected from a cross-sectional cohort of 16 children, including 4 patients with KD with CALs, 5 patients with KD without CALs, 4 healthy controls, and 3 febrile controls. RESULTS: KD altered the proportion of peripheral blood mononuclear cells, including an increasing trend in inflammatory cells (megakaryocytes and monocytes) and a decreasing trend in lymphocytes (eg, CD4+ T, CD8+ T, mucosal-associated invariant T, natural killer, and γδ T cells), highlighting the potential presence of lymphopenia phenomenon in KD. Our data indicated the presence of inflammatory cytokine storm in patients with KD with CALs, caused by systemic upregulation of TNFSF13B (tumor necrosis factor superfamily member 13b), CXCL16 (C-X-C motif chemokine ligand 16), TNFSF10 (tumor necrosis factor superfamily member 10), and IL1RN (interleukin 1 receptor antagonist), mainly produced by monocytes (especially for the Mono_CD14-CD16 cluster) and megakaryocytes. We also found that myeloid cells of patients with KD, particularly in those with CALs, might play a role in vascular injury (eg, increased MMP [matrix metalloproteinase] 9, MMP17, and MMP25) and immune cell recruitment. The immune landscape of patients with KD with CALs was featured by lower exhaustion levels in natural killer cells, a high cytotoxic state in the CD8_Pro cluster, and activation of the complement system in monocytes. Additionally, the activation of B cells was more pronounced in the early stage of KD. CONCLUSIONS: Collectively, this study provides a comprehensive understanding of the roles of various immune cells and inflammatory cytokine storms in the development of CALs in KD and offers a valuable resource for identifying novel therapeutic targets for patients with KD with CALs.

Development of a prediction model for progression of coronary artery lesions in Kawasaki disease.

BACKGROUNDS: This study aimed to identify risk factors for the progression of coronary artery lesions (CALs) in children with Kawasaki disease (KD) and to develop a nomogram prediction model. METHODS: This is a retrospective case-control study in which the participants were categorized into three groups based on the changes of the maximum Z score (Zmax) of coronary arteries at the 1-month follow-up compared with the baseline Zmax: CALs-progressed, CALs-improved, and CALs-unchanged. RESULTS: Of total 387 patients, 65 (27%), 319 (73%), and 3 (0.7%) patients were categorized into CALs-progressed group, CALs-improved group, and CALs-unchanged group, respectively. Six independent factors associated with CALs progression were identified, including initial IVIG resistance, baseline Zmax, the number of coronary arteries involved, C-reactive protein, albumin, and soluble interleukin-2 receptor (odds ratio: 7.19, 1.51, 2.32, 1.52, 0.86, and 1.46, respectively; all P-values < 0.01). The nomogram prediction model including these six independent risk factors yielded an area under the curve (AUC) of 0.80 (95% confidence interval, 0.74 to 0.86). The accuracy of this model reached 81.7% after the Monte-Carlo Bootstrapping 1000 repetitions. CONCLUSIONS: The nomogram prediction model can identify children at high risk for the progression of CALs at early stages. IMPACT: Six independent factors associated with CALs progression were identified, including initial IVIG resistance, baseline Zmax, the number of coronary arteries involved, CRP, ALB, and sIL-2R. The prediction model we constructed can identify children at high risk for the progression of CALs at early stages and help clinicians make individualized treatment plans. Prospective, multi-centered studies with larger sample sizes are warranted to validate the power of this prediction model in children with KD.

Effects of a PRECEDE-PROCEED Model-Based Intervention on Fatigue in Patients With Coronary Heart Disease: A Randomized Controlled Trial.

OBJECTIVE: This research aimed to determine how a 12-week PRECEDE-PROCEED model-based intervention affected fatigue in patients with coronary heart disease. METHODS: This cluster randomized controlled trial recruited participants diagnosed with coronary heart disease at 2 community health centers in China. Participants in the control group (n = 36) received routine health education, whereas those in the intervention group (n = 38) were given a 12-week PRECEDE-PROCEED model-based intervention and routine health education. The intervention consisted of 6 training sessions on coronary heart disease, fatigue, fatigue management, self-management skills and social support. A primary outcome (fatigue) and 4 secondary outcomes (knowledge of fatigue, self-management, quality of life and body mass index) were assessed using the Fatigue Scale-14, Fatigue Cognitive Questionnaire for Patients with Coronary Heart Disease, Coronary Artery Disease Self-Management Scale, Chinese Cardiovascular Questionnaire of Quality of Life, and electronic weighing scale, respectively. Data were collected 3 times over 12 weeks. RESULTS: Compared with the control group, the intervention group showed a statistically significant improvement in the level of fatigue (8.72 vs 7.06, P < .001), knowledge of fatigue (P < .001), self-management skills (P < .001), and quality of life (P < .001). However, there was no significant difference in body mass index between the 2 groups (P = .504). CONCLUSIONS: The findings suggest that a well-designed intervention based on the PRECEDE-PROCEED model could alleviate fatigue symptoms and increase knowledge of fatigue, self-management skills and quality of life in patients with coronary heart disease.

CYP2C19 polymorphisms and lipoproteins associated with clopidogrel resistance in children with Kawasaki disease in China: A prospective study.

Background: CYP2C19 genetic variation and clinical factors have been proved to be related with clopidogrel resistance (CR) in adults, while the presence of CR in children with Kawasaki disease (KD) was seldom reported. Our objective was to evaluate KD patients' response to clopidogrel treatment and determine whether CYP2C19 gene polymorphisms and laboratory indicators are associated with CR in this population. Methods: This was a prospective and single-center study. We recruited children with KD hospitalized in the cardiology department at the Children's Hospital Capital Institute of Pediatrics between January 2019 and October 2021, and the distribution of the CYP2C19 gene polymorphisms was assessed. According to the light transmission aggregometry (LTA) test results, KD patients who were treated with clopidogrel were divided into CR group and non-CR (NCR) group. We also analyzed the influence of CYP2C19 gene polymorphisms and laboratory indicators on CR in children with KD. Results: (1) A total of 346 children with KD were evaluated for the genotypic and phenotypic distributions of CYP2C19. Loss-of-function (LOF) mutated allele was included in 56.9% of CYP2C19 genotypes, and their corresponding phenotypes were intermediate metabolizers (46.2%) and poor metabolizers (10.7%). (2) The incidence of CR in this study population was 31.4%. The multivariate logistic regression showed that carrying CYP2C19 LOF allele (OR, 3.922; 95%CI, 1.504-10.282; P = 0.005) and high levels of low-density lipoprotein (OR, 1.675; 95%CI, 1.069-2.623; P = 0.024) were independent risk factor for CR, while low levels of high-density lipoprotein (OR, 0.120; 95%CI, 0.020, 0.734; P = 0.022) was an independent protective factor for CR. The area under the receiver operator characteristic curve of the multivariate logistic regression model (including high-density lipoprotein, low-density lipoprotein, and CYP2C19 LOF allele carriers) for predicting CR was 0.769 (95% CI, 0.674-0.863; P < 0.001). The sensitivity and specificity were 70.3 and 74.0%, respectively. Conclusion: Carrying CYP2C19 LOF allele, low levels of high-density lipoprotein, and high levels of low-density lipoprotein were independent risk factors for CR in children with KD in China. This may benefit pediatricians in choosing appropriate individualized antiplatelet therapy.

Factors Affecting the Exercise Capacity in Pediatric Primary Hypertension.

Purpose: Exercise training is crucial to the early intervention of pediatric primary hypertension (PHT). However, much less is known about exercise capacity in this disease. This work investigated the exercise capacity in pediatric PHT and analyzed the factors affecting exercise capacity. Methods: The study enrolled children with PHT at the Children's Hospital Capital Institute of Pediatrics between July 2017 and July 2020. The Bruce protocol of the treadmill exercise test (TET) was used to assess exercise capacity. Multivariate ordinal logistic regression and generalized linear models were used to analyze factors affecting exercise capacity. Results: Of 190 patients, 146 (76.8%) were male, and the median age was 13 (11, 14). Most children accomplished TET and achieved the submaximal heart rates (189 [99.5%]). Children with lower resting diastolic blood pressure (DBP) and 24 h average diastolic blood pressure (ADBP) could achieve a TET stage of 6 or more, whereas children with higher DBP and ADBP could only achieve a TET stage of 3 (P all < 0.05). Children with lower DBP and 24 h ADBP were also associated with greater metabolic equivalents (METs; r = -0.237, r = -0.179, P all < 0.05). The completion of TET stages was negatively associated with female (OR = 0.163), younger age (OR = 1.198), greater body mass index (BMI, OR = 0.921), and higher 24 h ADBP (OR = 0.952, P all < 0.05). In addition, METs were negatively associated with female (ß = -1.909), younger age (ß = 0.282), greater BMI (ß = -0.134), and higher 24 h ADBP (ß = -0.063, P all < 0.05). Conclusions: Exercise capacity was impaired among pediatric PHT patients. Female gender, younger age, greater BMI, and higher 24 h ADBP are independently associated with the exercise capacity in pediatric PHT. These findings may help developing scientific exercise prescriptions for pediatric PHT.

Secondary prevention of coronary heart disease: The effect of a nursing intervention using Cox's interaction model of client health behaviour.

AIMS: Secondary prevention of coronary heart disease is of utmost importance to facilitate people to achieve health outcomes and behaviours. This study was to investigate the effect of a nursing intervention based on Cox's interaction model of client health behaviour to improve health outcomes and behaviours of secondary prevention of coronary heart disease. DESIGN: This study is a cluster randomised controlled trial. METHODS: Participants were recruited between August and November 2019 in two community settings in Hengyang city, Hunan province, China. Participants in the intervention group received a nursing intervention based on Cox's interaction model of client health behaviour and routine health education, while those in the control group received routine health education only. The outcome variables included self-management, physical activity, medication compliance, anxiety, sexual knowledge, the ability to identify sexual health education needs, blood pressure, body mass index (BMI), and low-density lipoprotein cholesterol (LDL-C). The influential statistical tests applied to analyse the data included χ2 tests and t tests. RESULTS: Seventy-seven participants completed this study. Compared with the control group (n = 40), the intervention group (n = 37) showed statistically significant better health outcomes and behaviours regarding self-management, physical activity (except for high energy consumption), medication compliance, anxiety, sexual knowledge, the ability to identify sexual health education needs, systolic blood pressure, BMI, and LDL-C. However, there was no statistically significant difference in diastolic blood pressure and high energy consumption for physical activity. CONCLUSION: A well-developed nursing intervention based on Cox's interaction model of client health behaviour could successfully improve health outcomes and behaviours of secondary prevention of coronary heart disease. Such an intervention may be incorporated into community healthcare practice by nurses to improve patient care. IMPACT: This study provides a valuable insight to facilitate further development of effective nursing interventions to improve secondary prevention of coronary heart disease in community settings.

N6-Adenosine Methylation (m6A) RNA Modification: an Emerging Role in Cardiovascular Diseases.

N6-methyladenosine (m6A) is the most abundant and prevalent epigenetic modification of mRNA in mammals. This dynamic modification is regulated by m6A methyltransferases and demethylases, which control the fate of target mRNAs through influencing splicing, translation and decay. Recent studies suggest that m6A modification plays an important role in the progress of cardiac remodeling and cardiomyocyte contractile function. However, the exact roles of m6A in cardiovascular diseases (CVDs) have not been fully explained. In this review, we summarize the current roles of the m6A methylation in the progress of CVDs, such as cardiac remodeling, heart failure, atherosclerosis (AS), and congenital heart disease. Furthermore, we seek to explore the potential risk mechanisms of m6A in CVDs, including obesity, inflammation, adipogenesis, insulin resistance (IR), hypertension, and type 2 diabetes mellitus (T2DM), which may provide novel therapeutic targets for the treatment of CVDs.

Development and validation of a Chinese-language instrument measuring empowerment needs of patients after a percutaneous coronary intervention.

Patient empowerment has been shown to have some positive impacts on self-efficacy, self-esteem, and recovery. However, information about the empowerment needs of patients after a percutaneous coronary intervention is scarce. The aim of this study was to develop a Chinese-language instrument to measure empowerment needs of such patients. The initial instrument was generated based on a literature review and interviews with patients after a percutaneous coronary intervention procedure. Content validity was tested with a panel of experts using the Delphi method. In total, 226 patients were recruited for psychometric tests using the revised instrument. Expert authority coefficient was 0.92, and content validity index was 0.95. The internal consistency reliability was demonstrated by Cronbach's α coefficients (0.86 for the total score, 0.66-0.74 for the dimensions). The newly developed 19-item, five-dimension instrument has shown satisfactory validity (face/content validity and construct validity) and internal consistency reliability. The instrument could help clinical nurses who have close contact with patients after a percutaneous coronary intervention to gain a better understanding of their empowerment needs and could help develop appropriate health education to address such needs.

Nobiletin reduces LPL-mediated lipid accumulation and pro-inflammatory cytokine secretion through upregulation of miR-590 expression.

Nobiletin has protective effects on cardiovascular diseases, but the mechanism is not clear. In this study, we examined whether nobiletin affects the expression of miR-590/LPL and its relative effects on lipid accumulation and pro-inflammatory cytokine secretion in human THP-1 macrophages. RT-qPCR analysis showed that nobiletin increased the expression of miR-590. Western blot analysis showed that nobiletin-suppressed LPL expression was enhanced by miR-590 mimic and abrogated by miR-590 inhibitor. Oil Red O staining and high-performance liquid chromatography assays showed that nobiletin attenuated lipid accumulation in macrophages. Treatment with nobiletin and miR-590 mimic decreased cellular lipid accumulation, whereas treatment with miR-590 inhibitor increased cellular lipid accumulation. ELISA illustrated that nobiletin alleviated pro-inflammatory cytokine secretion in macrophages as measured by, which was reduced by miR-590 mimic and increased by miR-590 inhibitor. In conclusion, nobiletin may alleviate lipid accumulation and secretion of pro-inflammatory cytokines by enhancing the inhibitory effect of miR-590 on LPL expression, suggesting a promising strategy for potential drug development for atherosclerosis.