Effect of Bedside Ultrasound-Guided Versus Fluoroscopy-Guided Transvenous Cardiac Temporary Pacing in Children with Bradyarrhythmia.

To compare the efficacy and safety of bedside ultrasound-guided and fluoroscopy-guided transvenous cardiac temporary pacing in the treatment of bradyarrhythmia in children. Children treated by temporary intravenous cardiac pacing from January 2016 to June 2023 in Hunan Provincial Children's Hospital were enrolled, and the characteristics and data of the cases were summarized. Patients were divided into bedside ultrasound-guided group (ultrasound group) and fluoroscopy-guided group (fluoroscopy group) according to the implantation guidance methods. The efficacy, safety, and incidence of complications in children were compared, and follow-up analysis was carried out. A total of 30 children were enrolled, including 18 males and 12 females, with a median age of 5.5 (2.9, 10.0) years and a median weight of 18.7 (12.7, 32.7) kg. The most common primary diseases were fulminant myocarditis (13/30 cases) and congenital high-grade AVB (10/30 cases). Among them, the proportion of congenital high AVB in the fluoroscopy group was significantly higher than that in the ultrasound group, and the difference was statistically significant (p = 0.007). The implantation process was successful in all 30 children. From the time of pacing decision to implantation, the median time of ultrasound group was 56 (30, 60) min and that of fluoroscopy group was 154 (78,180) min, with a statistically significant difference (P < 0.001). A total of 5 cases developed complications. There was no statistically significant difference between the two groups (P > 0.05). Compared with traditional fluoroscopic temporary pacing, bedside ultrasound-guided temporary pacing technology can effectively shorten the operation time and reduce the occurrence of complications and has become a better choice for children's emergency and critical care treatment. The right internal jugular vein is preferred for intravenous implantation.

[Research progress of right ventricular strain imaging evaluation technology in pulmonary arterial hypertension]. / å³å¿ƒå®¤åº”å˜å½±åƒè¯„ä¼°æŠ€æœ¯åœ¨è‚ºåŠ¨è„‰é«˜åŽ‹ä¸­çš„ç ”ç©¶è¿›å±•.

Pulmonary arterial hypertension (PAH) has a subtle onset, rapid progression, and high mortality rate. Imaging evaluation is an important diagnostic and follow-up method for PAH patients. Right ventricular (RV) strain evaluation can identify early changes in RV function and predict the prognosis. Currently, various methods such as tissue Doppler imaging, velocity vector imaging, speckle tracking imaging, and cardiac magnetic resonance imaging can be used to evaluate RV strain in PAH patients. This article aims to summarize the research progress of RV strain imaging evaluation technology in PAH patients, in order to provide a basis for clinical diagnosis and follow-up of PAH patients.

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Pulmonary arterial hypertension (PAH) is a severe disease characterized by abnormal pulmonary vascular remodeling and increased right ventricular pressure load, posing a significant threat to patient health. While some pathological mechanisms of PAH have been revealed, the deeper mechanisms of pathogenesis remain to be elucidated. In recent years, bioinformatics has provided a powerful tool for a deeper understanding of the complex mechanisms of PAH through the integration of techniques such as multi-omics analysis, artificial intelligence, and Mendelian randomization. This review focuses on the bioinformatics methods and technologies used in PAH research, summarizing their current applications in the study of disease mechanisms, diagnosis, and prognosis assessment. Additionally, it analyzes the existing challenges faced by bioinformatics and its potential applications in the clinical and basic research fields of PAH in the future.

Lactylation: novel epigenetic regulatory and therapeutic opportunities.

Lactate, which is an end product of glycolysis, has traditionally been considered a metabolic waste. However, numerous studies have demonstrated that lactate serves metabolic and nonmetabolic functions in physiological processes and multiple diseases. Cancer and pulmonary arterial hypertension have been shown to undergo metabolic reprogramming, which is accompanied by increased lactate production. Metabolic reprogramming and epigenetic modifications have been extensively linked; furthermore, posttranslational modifications of histones caused by metabolites play a vital role in epigenetic alterations. In this paper, we reviewed recent research on lactate-induced histone modifications and provided a new vision about the metabolic effect of glycolysis. Based on our review, the cross talk between the metabolome and epigenome induced by glycolysis may indicate novel epigenetic regulatory and therapeutic opportunities. There is a magnificent progress in the interaction between metabolomics and epigenomics in recent decades, but many questions still remained to be investigated. Lactylation is found in different pathophysiological states and leads to diverse biological effects; however, only a few mechanisms of lactylation have been illustrated. Further research on lactylation would provide us with a better understanding of the cross talk between metabolomics and epigenomics.

LncRNA ROR promotes NLRP3-mediated cardiomyocyte pyroptosis by upregulating FOXP1 via interactions with PTBP1.

OBJECTIVE: The purpose of this design was to explore the specific role and related mechanism of long noncoding RNA (lncRNA) regulators of reprogramming (ROR) in viral myocarditis (VMC). METHODS: AC16 cells were infected with coxsackievirus B3 (CVB3) to establish a VMC cell model in vitro. The release of interleukin (IL)-1ß and IL-18 was evaluated by enzyme-linked immunosorbent assay (ELISA). Gene expression was calculated using quantitative real-time (qRT)-PCR. Cell pyroptosis was determined by flow cytometry and Western blot assays. Cell counting Kit-8 (CCK-8) detected cell viability. The molecular associations were verified by employing RNA immunoprecipitation (RIP), RNA pulldown and chromatin immunoprecipitation (ChIP) assays. RESULTS: The lncRNA ROR was more highly expressed in CVB3 virus-infected AC16 cells than in controls. Knockdown of ROR markedly rescued cell viability and reduced the release of IL-1ß and IL-18, cell pyroptosis and pyroptotic proteins such as NLRP3, ASC and cleaved caspase 1. Mechanistically, ROR destroyed the mRNA stability of Forkhead Box P Factor 1 (FOXP1) by binding polypyrimidine tract binding protein 1 (PTBP1). FOXP1 repressed the transcription of NLRP3 by directly interacting with its promoter. Importantly, coinhibition of FOXP1 impeded the protective role of ROR silencing in CVB3-infected AC16 cells. CONCLUSION: In conclusion, these findings elucidated that ROR knockdown inhibited CVB3-induced cardiomyocyte inflammation and NLRP3-mediated pyroptosis by regulating the PTBP1/FOXP1 axis, implying that ROR might be a new inducer in CVB3-infected VMC.

CD38: A Potential Therapeutic Target in Cardiovascular Disease.

Substantial research has demonstrated the association between cardiovascular disease and the dysregulation of intracellular calcium, ageing, reduction in nicotinamide adenine dinucleotide NAD+ content, and decrease in sirtuin activity. CD38, which comprises the soluble type, type II, and type III, is the main NADase in mammals. This molecule catalyses the production of cyclic adenosine diphosphate ribose (cADPR), nicotinic acid adenine dinucleotide phosphate (NAADP), and adenosine diphosphate ribose (ADPR), which stimulate the release of Ca2+, accompanied by NAD+ consumption and decreased sirtuin activity. Therefore, the relationship between cardiovascular disease and CD38 has been attracting increased attention. In this review, we summarize the structure, regulation, function, targeted drug development, and current research on CD38 in the cardiac context. More importantly, we provide original views about the as yet elusive mechanisms of CD38 action in certain cardiovascular disease models. Based on our review, we predict that CD38 may serve as a novel therapeutic target in cardiovascular disease in the future.

Compliance with aspirin in paediatric CHD post-percutaneous transcatheter occlusion: a cross-sectional study.

BACKGROUND: Predictors of compliance with aspirin in children following cardiac catheterisation have not been identified. The aim of this study is to identify the caregivers' knowledge, compliance with aspirin medication, and predictors of compliance with aspirin in children with Congenital Heart Disease (CHD) post-percutaneous transcatheter occlusion. METHODS: A cross-sectional explorative design was adopted using a self-administered questionnaire and conducted between May 2017 and May 2018. Recruited were 220 caregivers of children with CHD post-percutaneous transcatheter occlusion. Questionnaires included child and caregivers' characteristics, a self-designed and tested knowledge about aspirin scale (scoring scale 0-2), and the 8-item Morisky Medication Adherence Scale (scoring scale 0-8). Data were analysed using multivariate binary logistic regression analysis to identify predictors of compliance with aspirin. RESULTS: Of the 220 eligible children and caregivers, 210 (95.5%) responded and 209 surveys were included in the analysis. The mean score of knowledge was 7.25 (standard deviation 2.27). The mean score of compliance was 5.65 (standard deviation 1.36). Child's age, length of aspirin use, health insurance policies, relationship to child, monthly income, and knowledge about aspirin of caregivers were independent predictors of compliance with aspirin (p < 0.05). CONCLUSION: Caregivers of children with CHD had an adequate level of knowledge about aspirin. Compliance to aspirin medication reported by caregivers was low. Predictors of medium to high compliance with aspirin were related to the child's age and socio-economic reasons. Further studies are needed to identify effective strategies to improve knowledge, compliance with medication, and long-term outcomes of children with CHD.

Three-dimensional printing models in congenital heart disease education for medical students: a controlled comparative study.

BACKGROUND: This study sought to assess, using subjective (self-assessment) and objective (MCQ) methods, the efficacy of using heart models with ventricular septal defect lesions produced with three-dimensional printing technology in a congenital heart disease curriculum for medical students. METHODS: Three computed tomography datasets of three subtypes of ventricular septal defects (perimembranous, subarterial and muscular, one for each) were obtained and processed for building into and printing out 3D models. Then a total of 63 medical students in one class were randomly allocated to two groups (32 students in the experimental, and 31 the control). The two groups participated in a seminar with or without a 3D heart model, respectively. Assessment of this curriculum was carried out using Likert-type questionnaires as well as an objective multiple choice question test assessing both knowledge acquisition, and structural conceptualization. Open-ended questions were also provided for getting advice and suggestion on 3D model utilization in CHD education. RESULTS: With these 3D models, feedback shown in the questionnaires from students in experimental group was significantly more positive than their classmates in the control. And the test results also showed a significant difference in structural conceptualization in favor of the experimental group. CONCLUSION: It is effective to use heart models created using current 3D printing technology for congenital heart disease education. It stimulates students' interest in congenital heart disease and improves the outcomes of medical education.

PDGF Promotes the Warburg Effect in Pulmonary Arterial Smooth Muscle Cells via Activation of the PI3K/AKT/mTOR/HIF-1α Signaling Pathway.

BACKGROUND/AIMS: The enhanced proliferation of pulmonary arterial smooth muscle cells (PASMCs) is a central pathological component in pulmonary arterial hypertension (PAH). Both the Warburg effect and platelet-derived growth factor (PDGF) are involved in the proliferation of PASMCs. However, the mechanism underlying the crosstalk between the Warburg effect and PDGF during PASMC proliferation is still unknown. We hypothesized that PDGF promotes the Warburg effect via activating the phosphatidylinositol 3-kinase (PI3K) signaling pathway and hypoxia-inducible factor 1-α (HIF-1α) in proliferative PASMCs. METHODS: PASMCs were derived from pulmonary arteries of SD rats; cell viability, the presence of metabolites, and metabolic enzyme activities assay were determined by MTT assays, kit assays and western blot analysis, respectively. RESULTS: PDGF promoted PASMC proliferation in a dose- and time-dependent manner, accompanied by an enhanced Warburg effect. Treatment with PDGFR antagonists, Warburg effect inhibitor and PDK1 inhibitor significantly inhibited PI3K signaling activation, HIF-1α expression and PASMC proliferation induced by PDGF, respectively. Furthermore, treatment with PI3K signaling pathway inhibitors remarkably suppressed PDGF-induced PASMC proliferation and the Warburg effect. CONCLUSION: microplate reader (Biotek, Winooski The Warburg effect plays a critical role in PDGF-induced PASMC proliferation and is mediated by activation of the PI3K signaling pathway and HIF-1α.

Transcatheter Closure of Coronary Artery Fistulae: Considerations and Approaches Based on Fistula Origin.

OBJECTIVES: To investigate technical approaches for transcatheter closure of coronary artery fistula based on anatomic type of the fistula. BACKGROUND: The variability in coronary artery fistulae (CAF) anatomy that necessitates different transcatheter closure (TCC) approaches has not been well documented. METHODS: Records of patients with CAF who underwent TCC at 2 centers were reviewed for technical details and procedural outcome. CAF were classified as proximal and distal. TCC approaches employed were arterio-venous or arterio-arterial loop, retrograde arterial, and antegrade venous. RESULTS: Eighteen patients with CAF, mean age 12.6 years (0.07-60), 11 male (61%), underwent TCC. All CAF drained predominantly into the right side of the heart. Types of CAF were proximal in 15 and distal in 3 patients. CAF calibers were large in 7, medium in 9, and small in 2 patients. The arterio-venous loop approach was used in the majority of the cases (11 patients) and the CAF size were medium to large. The retrograde arterial approach was used in 4; of these, 3 patients had small to medium sized CAF. In 2 patients with long tortuous CAF an antegrade venous approach was employed. TCC was successful in 17 of the 18 patients (94.4%). There were no peri-procedural deaths or vascular complications. CONCLUSIONS: This study documents transcatheter closure approaches for CAF and device selection based on fistula origin. The choices of TCC technique and device selection vary, and are primarily determined by the heterogeneous anatomic characteristics of the fistulae.

[Transcatheter closure in various types of congenital coronary artery fistula: a follow-up study].

OBJECTIVE: To evaluate the short- and medium-term efficacy, complications, and anti-coagulation therapies related to transcatheter closure (TCC) of coronary artery fistula (CAF) in children. METHODS: We conducted a retrospective review of the medical records of 12 children with CAF who underwent TCC between January 2006 and January 2014, focusing on details such as preoperative, radiographic, and postoperative follow-up data, to record closure methods for CAF, anti-coagulation therapies, postoperative complications, and results of auxiliary examinations. RESULTS: Among the 12 cases who underwent successful TCC and whose age was 1-158 months, four patients had proximal/medium-sized CAF, five had proximal/large CAF, and three had distal/medium-sized CAF. The mean period of postoperative follow-up was 3.5±2.4 years. Eleven patients took aspirin for 6 months post closure, and one took it for 18 months. Neither coronary thrombosis nor interventional complications were found. Left ventricular ejection fraction, cardiothoracic ratio, pulmonary artery pressure, and the diameters of coronary artery lesions decreased post TCC. CONCLUSIONS: TCC is feasible and safe in proximal and distal/medium-sized CAF patients. Postoperative anti-coagulation with aspirin may prevent short- and medium-term thrombosis, but treatment course and safety need to be investigated by further follow-ups.

Subspecialty surveillance of long-term course of small and moderate muscular ventricular septal defect: heterogenous practices, low yield.

BACKGROUND: No expert consensus guides practice for intensity of ongoing pediatric cardiology surveillance of hemodynamically insignificant small and moderate muscular ventricular septal defect (mVSD). Therefore, despite the well-established benign natural history of mVSD, there is potential for widely divergent follow up practices. The purpose of this investigation was to evaluate (1) variations in follow up of mVSD within an academic children's hospital based pediatric cardiology practice, and (2) the frequency of active medical or surgical management resulting from follow up of mVSD. METHODS: We retrospectively reviewed records of 600 patients with isolated mVSD echocardiographically diagnosed between 2006 and 2012. Large mVSD were excluded (n = 4). Patient age, gender, echocardiographic findings, provider, recommendations for follow up, and medical and surgical management were tabulated at initial and follow up visits. Independent associations with follow up recommendations were sought using multivariate analysis. RESULTS: Initial echocardiography showed small single mVSD in 509 (85%), multiple small mVSD in 60 (10%), and small-to-moderate or moderate single mVSD in 31 (5%). The mean age at diagnosis was 15.9 months (0-18.5 years) and 25.7 months (0-18.5 years) at last follow up. There was slight female predominance (56.3%). Fourteen pediatric cardiology providers recommended 316 follow up visits, 259 of which were actually accomplished. There were 37 other unplanned follow up visits. No medical or surgical management changes were associated with any of the follow up visits. The proportion of patients for whom follow up was advised varied among providers from 11 to 100%. Independent associations with recommendation for follow up were limited to the identity and clinical volume of the provider, age of the patient, and the presence of multiple, small-to-moderate, or moderate mVSD. CONCLUSIONS: In this large series of moderate or smaller mVSD, pediatric cardiology follow up was commonly recommended but resulted in no active medical or surgical management. Major provider based inconsistency in intensity of follow up of mVSD was identified, but is difficult to justify.

Clinical characteristics and follow-up of complex arrhythmias associated with RYR2 gene mutations in children.

Objective: The aim of this study was to analyze the diagnosis, treatment, and follow-up of six cases of complex arrhythmias associated with RYR2 gene mutations in children. Method: A retrospective analysis was conducted on six children diagnosed with complex arrhythmias associated with RYR2 gene mutations. The study included an analysis of the age of onset, initial symptoms, electrocardiographic characteristics, genetic results, treatment course, and follow-up outcomes. Results: Among the six cases included in the study, there were four males and two females, with an average age of 3.5 ± 0.5 years. The average time from initial symptoms to diagnosis was 2.7 ± 1.3 years. The most common clinical manifestation was syncope, with exercise and emotions being the main triggers. All six children had de novo missense mutations in the RYR2 gene identified through whole-exome sequencing. In Holter electrocardiogram, atrial arrhythmias and sinoatrial node dysfunction were commonly observed in younger children. Four patients underwent exercise stress testing, with two experiencing bidirectional ventricular premature contractions and two experiencing bidirectional ventricular tachycardia and polymorphic ventricular tachycardia. Initial treatment involved oral propranolol or metoprolol. If arrhythmias persisted, flecainide or propafenone was added as adjunctive therapy. Two patients received permanent cardiac pacemaker treatment (single chamber ventricular pacemaker, VVI). All patients survived, with three experiencing occasional syncope during treatment. The follow-up period ranged from 12 to 37 months, with an average follow-up time of 24.3 ± 3.7 months. Conclusion: Complex arrhythmias associated with RYR2 gene mutations in children can present with various clinical manifestations. Atrial arrhythmias combined with sinoatrial node dysfunction are commonly observed in younger children, and the combination of pharmacological therapy and cardiac pacemaker treatment yields favourable treatment outcomes.

Causal association of depression, anxiety, cognitive performance, the brain cortical structure with pulmonary arterial hypertension: A Mendelian randomization study.

BACKGROUND: Patients with pulmonary arterial hypertension (PAH) often present with anxiety, depression and cognitive deterioration. Structural changes in the cerebral cortex in PAH patients have also been reported in observational studies. METHODS: PAH genome-wide association (GWAS) including 162,962 European individuals was used to assess genetically determined PAH. GWAS summary statistics were obtained for cognitive performance, depression, anxiety and alterations in cortical thickness (TH) or surface area (SA) of the brain cortex, respectively. Two-sample Mendelian randomization (MR) was performed. Finally, sensitivity analyses including Cochran's Q test, MR-Egger intercept test, leave-one-out analyses, and funnel plot was performed. RESULTS: PAH had no causal relationship with depression, anxiety, and cognitive performance. At the global level, PAH was not associated with SA or TH of the brain cortex; at the functional regional level, PAH increased TH of insula (P = 0.015), pars triangularis (P = 0.037) and pars opercularis (P = 0.010) without global weighted. After global weighted, PAH increased TH of insula (P = 0.004), pars triangularis (P = 0.032), pars opercularis (P = 0.007) and rostral middle frontal gyrus (P = 0.022) while reducing TH of inferior parietal (P = 0.004), superior parietal (P = 0.031) and lateral occipital gyrus (P = 0.033). No heterogeneity and pleiotropy were detected. LIMITATIONS: The enrolled patients were all European and the causal relationship between PAH and the structure of the cerebral cortex in other populations remains unknown. CONCLUSION: Causal relationship between PAH and the brain cortical structure was implied, thus providing novel insights into the PAH associated neuropsychiatric symptoms.

The prognostic value of prognostic nutritional index in postoperative onset of PAH in children with isolated VSD: a prospective cohort study based on propensity score matching analysis.

Background: The mechanism of pulmonary arterial hypertension (PAH) after surgery/intervention for isolated venticlular septal defect (VSD) in children is unknown. Reliable prognostic indicators for predicting postoperative PAH are urgently needed. Prognostic nutration index (PNI) is widely used to predict postoperative complications and survival in adults, but it is unclear whether it can be used as an indicator of prognosis in children. Methods: A total of 251 children underwent VSD repair surgery or interventional closure in Hunan Children's Hospital from 2020 to 2023 were collected. A 1:1 propensity score matching (PSM) analysis was performed using the nearest neighbor method with a caliper size of 0.2 Logistics regression analysis is used to examine factors associated with the development of PAH. Results: The cut-off value for PNI was determined as 58.0. After 1:1 PSM analysis, 49 patients in the low PNI group were matched with high PNI group. Children in the low PNI group had higher risk of postoperative PAH (P = 0.002) than those in the high PNI group. Multivariate logistics regression analysis showed that PNI (RR: 0.903, 95% CI: 0.816-0.999, P = 0.049) and tricuspid regurgitation velocity (RR: 4.743, 95% CI: 1.131-19.897, P = 0.033) were independent prognostic factors for the development of PAH. Conclusion: PNI can be used as a prognostic indicator for PAH development after surgery/intervention in children with isolated VSD.

High-intensity Focused Ultrasound-A New Choice to Conduct Pulmonary Artery Denervation.

This research aimed to explore whether high-intensity focused ultrasound (HIFU) could conduct pulmonary artery denervation (PADN). HIFU was performed in pulmonary arteries of 6 normotensive rabbits at dose of 250W, 6 times for each rabbit, and an additional 6 rabbits served as controls. Then ATEPH was induced in both groups by intravenous infusion of autogeneic thrombus. Hemodynamics and ultrasonography parameters were measured by right heart catheter and echocardiography pre- and post-establishment of ATEPH models in both groups. Histological analysis and immunohistochemistry of tyrosine hydroxylase (TH) were also performed. After PADN procedures, 5 rabbits were successfully conducted PADN, of which ablation zone was also observed in right auricle or right lung in 4 rabbits. Ablation zone was detected only in right lung in 1 rabbit. Compared with control group, milder right heart hemodynamic changes were found in PADN group, accompanied by improved ultrasound parameters in PADN group. HIFU can acutly damage SNs around pulmonary artery successfully, which may be a new choice to conduct PADN. However, the accuracy of HIFU with PADN needs to be improved.

Evaluation of right ventricular longitudinal strain in pediatric patients with pulmonary hypertension by two-dimensional speckle-tracking echocardiography.

Objectives: We aimed to investigate the association between right ventricular longitudinal strain measured by two-dimensional speckle-tracking echocardiography (2D-STE) and right heart catheterization data in pediatric patients with pulmonary hypertension (PH). Methods: Two groups were evaluated, each consisting of 58 patients. Group 1, patients with PH; Group 2, normal matched controls. Data were collected from 58 patients with PH who underwent invasive hemodynamic evaluation. Standard transthoracic echocardiographic assessment was performed in all patients under the same circumstances. All patients underwent 2D-STE, and off-line analysis generated right ventricle longitudinal strain (RVLS) and right ventricular free wall strain (RVFW) and collected echocardiographic conventional parameters of right ventricular function, including the control group. The relationship between invasive characteristics and right ventricular function parameters was analyzed. Results: In all, 58 PH patients were included in our study. The mean pulmonary artery pressure (mPAP) and pulmonary vascular resistance (PVR) were strongly correlated with right ventricular free wall strain (RVFW) and right ventricular longitudinal strain (RVLS), moderately correlated with the right ventricle myocardial performance index (Tei index), weakly correlated with the transverse diameter of the right ventricle (RV) and the transverse diameter of the right atrium (RA), and moderately negatively correlated with right ventricular fractional area change (RVFAC). In terms of segments of the right ventricular free wall, the basal segment had the highest correlation coefficient with mPAP and PVR (r = 0.413, 0.523, 0.578, r = 0.421, 0.533, 0.575, p < 0.05, respectively). Tricuspid annular plane systolic excursion (TAPSE), main pulmonary artery diameter (MPA), peak systolic velocity of the right ventricle (RV-S'), and RA area parameters were not associated with mPAP and PVR (p > 0.05). Conclusions: Right ventricular longitudinal strain is a reliable indicator to evaluate right ventricular function in pediatric patients with PH. It can provide valuable reference information for the clinical judgment of the status and severity of the disease in children.

Case Report: Identification of microduplication in the chromosomal 2p16.1p15 region in an infant suffering from pulmonary arterial hypertension.

This study reports the first case of a patient with chromosomal 2p16.1p15 microduplication syndrome complicated by pulmonary arterial hypertension (PAH). A female infant was admitted to the hospital suffering from dyskinesia and developmental delay, and conventional echocardiography revealed an atrial septal defect (ASD), which was not taken seriously or treated at that time. Two years later, preoperative right heart catheterization for ASD closure revealed a mean pulmonary artery pressure (mPAP) of 45 mmHg. The mPAP was reduced, and the condition was stabilized after drug therapy. A genomic copy number duplication (3×) of at least 2.58 Mb in the 2p16.1p15 region on the paternal chromosome was revealed. Multiple Online Mendelian Inheritance in Man (OMIM) genes are involved in this genomic region, such as BCL11A, EHBP1, FAM161A, PEX13, and REL. EHBP1 promotes a molecular phenotypic transformation of pulmonary vascular endothelial cells and is thought to be involved in the rapidly developing PAH of this infant. Collectively, our findings contribute to the knowledge of the genes involved and the clinical manifestations of the 2p16.1p15 microduplication syndrome. Moreover, clinicians should be alert to the possibility of PAH and take early drug intervention when facing patients with 2p16.1p15 microduplications.

Comprehensive analysis of m6A methylomes in idiopathic pulmonary arterial hypertension.

Idiopathic pulmonary arterial hypertension (IPAH) is a serious and fatal disease. Recently, m6A has been reported to play an important role in the lungs of IPAH patients and experimental pulmonary hypertension models. However, the meaning of m6A mRNAs in the peripheral blood of IPAH patients remains largely unexplored. We aimed to construct a transcriptome-wide map of m6A mRNAs in the peripheral blood of IPAH patients. M6A RNA Methylation Quantification Kit was utilized to measure the total m6A levels in the peripheral blood of IPAH patients. A combination of MeRIP-seq, RNA-seq and bioinformatics analysis was utilized to select m6A-modified hub genes of IPAH. MeRIP-qPCR and RT-qPCR were used to measure the m6A levels and mRNA levels of TP53, RPS27A, SMAD3 and FoxO3 in IPAH patients. Western blot was performed to assess the protein levels of m6A related regulators and m6A related genes in experimental PH animal models, hypoxia-treated and PDGF-BB induced PASMCs. We found that the total m6A levels were increased in peripheral blood of IPAH patients and verified that m6A levels of RPS27A and SMAD3 were significantly elevated and m6A levels of TP53 and FoxO3 were significantly reduced. The mRNA or protein levels of RPS27A, SMAD3, TP53 and FoxO3 were changed in human blood samples, experimental PH animal models and PDGF-BB induced PASMCs. Moreover, METTL3 and YTHDF1 were increased in the hypoxia induced pulmonary hypertension rat model, hypoxia-treated and PDGF-BB induced PASMCs. These finding suggested that m6A may play an important role in IPAH.