BackgroundsAsthma is a chronic inflammatory disease affecting airways, usually starting in childhood. Its cause remains unclear.ObjectiveWe aim to elucidate the role of immune dysregulation in the pathogenesis of pediatric asthma.MethodsIn this study, we used single-cell RNA sequencing to analyze peripheral blood mononuclear cells (PBMCs) from three pediatric asthma patients and four age-matched healthy controls to investigate the cellular etiology of childhood asthma.ResultsThe overall expression patterns of PBMCs from the three asthma patients indicate that both innate and adaptive immunity are imbalanced and abnormally activated in childhood asthma. Analysis of hematopoietic stem and progenitor cells (HSPCs) expression profiles further reveals that HSPCs from asthma patients tend to express immunity-related genes earlier. The cell developmental trajectories observed in asthma patients show an abnormal immune cell development pattern. Dysregulated lymphoid lineage development is observed in all three patients but there is no identical abnormal pattern for each patient. Pseudo-time analysis of gene expression demonstrates that JUN, a gene controlling cell cycle progression, is repressed in asthma patients while SPI1, an essential gene for lymphoid lineage development along with six inflammatory response related genes (S100A8, S100A9, S100A12, IL7R, IL32, and CCL5), exhibit various aberrant expression trajectories in asthmatic individuals. S100A8, S100A9, S100A12, and RETN are universally upregulated in various cell types of asthma patients. The analyses of cell-cell communication further elucidate the contributory roles of dendritic cells and CD14+ monocytes in the development and heterogeneity of asthma, as they exhibit increased reception and transmission of annexin and resistin signals in the asthma group. The resistin protein-protein interaction network analysis further suggests that SQSTM1, HSPA5 and A2M might serve as the potential therapeutic targets in childhood asthma.ConclusionsOur scRNA-Seq analyses unveil childhood asthma as a complex disease with immune-related heterogenicities, characterized by dysregulated lymphoid cell development, a common feature that may offer a novel research direction for comprehensively understanding the key molecular mechanisms underlying childhood asthma.

Objectives Coronary artery anomalies are rare both in coronary angiogram and computed tomography angiography. Hypertrophic cardiomyopathy (HCM) is the most frequent inherited cardiac disease. The phenotype of HCM associated with anomalous coronary origin is not commonly seen especially in children.Case presentation We describe a case series of two children with HCM combined right coronary artery (RCA) originated from left coronary sinus. Case 1 was a 9-month-old female with TTN gene heterozygous mutation (p.R16724L) who exhibited cardiac insufficiency. Case 2 was a 12-year-old male with MYBPC3 gene heterozygous mutation (p.R820Q) who only exhibited intermittent chest pain. A total of 7 HCM cases with RCA originated from left coronary sinus have been reported with our literature review. Case 1 is the youngest child patient in our report until now. Moreover, the echocardiogram of case 1 is similar with restrictive cardiomyopathy (RCM) and it demonstrates the progression of HCM to heart failure. So, HCM with TTN gene mutation may exhibit cardiac insufficiency more early. And the gene mutation site of TTN has never been reported in previous HCM cases.Conclusions HCM coexisted with anomalous origin of RCA has different clinical presentation, and it maybe due to different gene mutation.

BackgroundThe etiology of Kawasaki disease (KD) remains unclear. Hematopoietic stem and progenitor cells (HSPCs) serve as the precursor cells for a multitude of immune cells. Investigating their initial transcriptional status may help uncover the aberrant immune mechanisms underlying KD.MethodsInduced pluripotent stem cells (iPSCs) were reprogrammed from peripheral blood mononuclear cells (PBMCs) isolated from patients with KD and febrile individuals, followed by directed differentiation into HSPCs. We performed bulk RNA-sequencing to compare transcriptomic profiles of iPSC-derived HSPCs between the two groups, with further comparison against integrated HSPC data from public KD single-cell datasets.ResultsWe recruited three patients with KD prior to Intravenous immunoglobulin (IVIG) therapy and three febrile control patients, and successfully established an iPSC-derived HSPCs disease model. Transcriptomic profiling revealed elevated immune and inflammatory response signatures in iPSC-derived HSPCs from patients with KD compared with those from febrile individuals. In addition, in vitro-generated KD iPSC-HSPCs exhibited partial transcriptional features similar to in vivo HSPCs isolated from PBMCs of patients with KD. Gene Set Enrichment Analysis (GSEA) further revealed that gene sets associated with B-cell developmental processes were transcriptionally downregulated in iPSC-derived HSPCs from patients with KD relative to febrile controls.ConclusionsiPSC-derived HSPCs from patients with KD display altered immune-inflammatory transcriptional profiles and suppressed B-cell developmental signatures at the transcriptomic level. These preliminary findings suggest that early hematopoietic immune dysregulation may contribute to KD pathogenesis. We propose that these iPSC-derived HSPCs could be a good cellular model for studying the etiology of KD in vitro. These findings are preliminary, constrained by the small sample size and limited to transcriptomic analysis only. Further studies with larger cohorts and functional experiments are needed to verify these results.

Background:Kawasaki Disease (KD) is a vasculitis syndrome featured with a high and persistent fever in children. It is the leading cause of coronary artery lesions (CALs) for children in developed countries. Methods:Single-cell RNA sequencing analyses were performed for the peripheral blood mononuclear cells from three KD non-CAL patients before/after IVIG treatment (KD BT and KD AT), three KD CAL patients before IVIG treatment (CAL BT), and three KD CAL patients after IVIG treatment (CAL AT). Results:Overall expression analyses show immunoglobulin and adaptive immunity related genes are commonly upregulated in CAL BT and AT patients while antimicrobial and innate immunity related genes are commonly downregulated in them. Pseudo-time analyses demonstrate that CAL BT patients have a disorganized cell development trajectory with multiple overlapped cell linages and CAL AT patients have a dysregulated B cell developmental trajectory featured with a mixed monocyte and B lineage. In gene branch pseudo-time analyses, the repressed expression of SPI1 and MT2A are found in CAL BT patients, which is similar to their expression patterns in KD BT patients; while the early elevated expression of SPI1 and MT2A could partly explain the dysregulated B cell development in CAL AT patients. Cell communication analyses demonstrates that CAL BT patients have the lower number of inferred cell-to-cell interactions and the weakest interaction strength among four groups, whereas CD14 monocytes in CAL AT and KD BT patients have strong cell-to-cell interaction strength which may contribute to CAL or KD pathogenesis. In the monocytes of CAL patients, MCH-II is a significantly increased signal and RESISTIN is a significantly decreased signal compared to non-CAL counterpart. Conclusions:Our results suggest that MCH-II is a bad signal for indicating CAL development while RESISTIN is a good signal for protecting from CAL development.

Here, using single-cell RNA sequencing, we profile peripheral blood mononuclear cells (PBMCs) from three patients with onset asthma and four age-matched healthy controls to investigate the cellular etiology of childhood asthma. We find that very few differentially expressed genes (DEGs) in hematopoietic stem and progenitor cells (HSPCs) are common among three asthma cases, but the common ones are functionally related to the S100A gene family. Furthermore, GO analyses show that the heterogeneous DEGs in HSPCs in three asthma cases can be categorized into the biological processes of immunity and immune responses, which indicates that different DEGs converge on a common pathological base. The overall cellular expression profiles demonstrate that pro-inflammatory mediators and immunoglobulin receptors have a high expression level and interferon alpha induced protein has a low expression level in mononuclear macrophages of acute asthma. The cell developmental trajectories in three asthma cases exhibit an abnormal immune cell development pattern compared to the developmental trajectory in health control. T-cell development in acute asthma is especially dysregulated for three cases with three different T-cell branching patterns. We also find that the innate lymphoid cells (ILCs) in three asthma cases have a low expression level in housekeeping genes. Our scRNA-seq analyses for three asthma patients reveal a complex cellular etiology for childhood asthma and provide a new research direction for the comprehensive and systematic study of effector cells and key molecular mechanisms of childhood asthma.### Competing Interest StatementThe authors have declared no competing interest.### Funding StatementThis study was funded by Jinshan Distinct key medical specialty project (JSZK2023A04) and Institute of Pediatric Infection, Immunity, and Critical Care Medicine Cultivate Research Project.### Author DeclarationsI confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.YesThe details of the IRB/oversight body that provided approval or exemption for the research described are given below:The Ethics Committee of Shanghai Children's Hospital (Protocol Numbers: 2019R081, 2022R029-F-01) gave approval for this work.I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals.YesI understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).YesI have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable.YesAll data produced in the present study are available upon reasonable request to the authors

This paper comprehensively compares the Kawasaki disease (KD) guidelines from seven countries/regions, including China, Argentina, Europe, Italy, Japan, Spain, and the United States, as retrieved from the PubMed database. It analyzes the similarities and differences in KD diagnosis and treatment among these guidelines. The results show that all guidelines consistently recommend a single infusion of immunoglobulin at a dosage of 2 g/kg as the first-line treatment for KD, and none advocate for the routine use of methylprednisolone or prednisone as standalone first-line treatment options for KD. However, there are some differences among the guidelines regarding classification, diagnostic criteria, and specific treatment methods for KD. Therefore, it is essential to further strengthen international collaboration in guideline development and conduct multicenter clinical research in the future, aiming to achieve a higher level of expert consensus, thereby promoting the enhancement of KD diagnosis and treatment.

BackgroundKawasaki disease (KD) is an acute systemic vasculitis that can lead to acquired heart disease in children mostly from in developed countries. The previous research showed that B cells in KD patients underwent a profound change in both the cell numbers and types after intravenous immunoglobulin (IVIG) therapy.MethodsWe performed the single-cell RNA-sequencing for the peripheral blood mononuclear cells (PBMCs) from three febrile patients and three KD patients to investigate the possible mechanism underlying B cell developmental dysfunction in KD. The pseudo-time analysis was employed to study the developmental trajectories of the PBMCs in febrile control and KD patients.ResultsOverall single-cell expression profiles show that the biological processes of immunity, B cell activation pathway and their related biological entities are repressed in KD patients before IVIG treatment compared to febrile patient and KD patients after IVIG treatment. The differentially expressed gene analyses further demonstrate that B cell signaling pathway is downregulated in B cells and plasma blast cells of KD patients before treatment while cell cycle genes and MYC gene are upregulated in dendritic cells (DCs) and hematopoietic stem and progenitor cells (HSPCs) of KD patients before treatment. The biological process of immune response is upregulated in the HSPCs of KD patients before treatment in our dataset while the biological process of inflammatory response is upregulated in the HSPCs of KD patients before treatment in GSE168732 dataset. Single-cell trajectory analyses demonstrate that KD patients before treatment have a shortened developmental path in which B cells and T cells are failed to differentiate into separate lineages. HSPD1 and HSPE1 genes show an elevated expression level in the early cell development stage of KD patients before treatment accompanied with the repression of MYC, SPI1, MT2A and UBE2C genes. Our analyses of all B cells from KD patients before treatment show most of B cells are arrested in a transitional state with an ill developmental path compared with febrile patients and KD patients after treatment.ConclusionOur results indicate that the immune premature HSPCs accompanied with the abnormal expression dynamics of cell cycle and SPI1 genes are the mechanism underlying B cell developmental dysfunction in KD patients.

Introduction and aim. Kawasaki disease (KD) is an acute vasculitis with unknown etiology, usually occurring in chil dren under 5 years old. This article will summarize the three consensuses formulated in China about KD. Material and methods. English databases for consensus search include UpToDate, BMJ Clinical Evidence, National Guideline Clearinghouse, Joanna Briggs Institute Library, Cochrane Library, and PubMed, etc.; Chinese databases in clude China Biomedical Literature Service, China Knowledge Network, Wanfang database, etc. All literature searches ended on February 28, 2022. Analysis of the literature. KD is a common acquired heart disease in children and can lead to severe complications such as coronary injury. However, intravenous immunoglobulin (IVIG) combined with oral aspirin (Asp) is currently recognized as the most effective treatment in KD acute stage and the first-line treatment to prevent cardiovascular complications. Glucocorticoid (GC) is mainly used for KD patients with a high risk of coronary artery aneurysm (CAA), no immunoglobulin response, and confirmed CAA. There are already consensus guidelines on diagnosing and treat ing KD in different countries. This article summarizes the relevant expert consensus on aspirin, glucocorticoids and IVIG for the treatment of Kawasaki disease in China. Conclusion. Still, there are inconsistent opinions in the literature on the mechanism, optimal timing, and dosage of medication for KD.

Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a hereditary heart disease characterized by bidirectional or polymorphic ventricular tachycardia and an increased risk of sudden cardiac death. Although trans-2,3-enoyl-CoA reductase like (TECRL) is a newly reported pathogenic gene leading to CPVT that can influence intracellular calcium regulation, the unidentified mechanism underlying the pathogenesis of TECRL deficiency-mediated CPVT remains mainly elusive. In the present study, Tecrl knockout (KO) mice were established and the differentially expressed genes (DEGs) were investigated by RNA-sequencing from the heart tissues. In addition, 857 DEGs were identified in Tecrl KO mice. Subsequently, a weighted gene co-expression network analysis was conducted to discern the pivotal pathways implicated in the Tecrl-mediated regulatory network. Moreover, pathway mapping analyses demonstrated that essential metabolism-related pathways were significantly enriched, notably the fatty acid metabolic process and calcium regulation. Collectively, the data suggested a synergistic relationship between Tecrl deficiency and cardiometabolic and calcium regulation during the development of CPVT. Therefore, further studies on the potential function of TECRL in cardiac tissues would be beneficial to elucidate the pathogenesis of CPVT.

目的 住院医师规范化培训(简称住培)是医学生毕业后教育的重要组成部分,是完成医学生到临床医生转变的重要阶段.在儿外科住培中,医学模拟教学作为理论教学与实践教学的桥梁,正成为主流的教学手段之一.PDCA(plan-do-check-action)理论因其先进性被引入多个学科建设管理中,在医学教育领域也得到推广并获得成功.但目前基于PDCA理论指导模拟实训的相关研究较少报道,故本文拟基于PDCA循环对儿外科专业基地模拟实训效能进行研究,探讨该模式在儿外科住培中的作用.方法 选取2020年、2021年结业的儿外科住院医师17名作为观察组,采用PDCA循环模拟教学;2018、2019年结业的儿外科住院医师20人作为对照组,采用单纯模拟教学.分析两组住院医师考核成绩及教学满意度差异.结果 观察组住院医师考核成绩、实操能力及教学满意度均高于对照组(P<0.05).结论 应用PDCA循环模式有利于提高儿外科住培模拟实训的教学效果,是有效提高其临床技能的方法.

BACKGROUND:Inhibition of fatty acid synthase (FAS) plays a crucial protective role in pulmonary hypertension (PH). Our aim was to identify novel metabolites in mice with hypoxia-induced PH after treatment with C75 (FAS inhibitor) and to confirm the presence of these metabolites in paediatric patients with PH.METHODS:The PH mouse model was built by chronic hypoxia and ovalbumin (OVA) assistance. Untargeted metabolomics was used to analyse mouse serum. Six children with PH and six relative controls (patients without lung and heart disease) were selected in Shanghai Children's Hospital and they all performed blood tandem mass spectrometry during hospitalization.RESULTS:First, a total of 29 differential metabolites, including lipid metabolites, polyamine, and glutamine were identified as differential metabolites in the hypoxia group compared with the control group. After C75 treatment, symptoms were partially relieved in the PH mouse, and 15 differential metabolites, including lipid metabolites, polyamine, and glutamine were identified in the hypoxia + C75 group compared with the hypoxia group. These differential metabolites were enriched in arginine and glycerolipid metabolism through metabolite set enrichment analyses and were involved in excessive cell proliferation, which was a characteristic of PH. Second, glutamine and caproyl carnitine levels were increased in paediatric patients with PH.CONCLUSIONS:FAS may be a potential PH therapeutic target. Lipid metabolites, polyamine, and glutamine, are closely related to PH. Putrescine and glutamine might be biomarkers for PH.

Accurate segmentation is a basic and crucial step for medical image processing and analysis. In the last few years, U-Net, and its variants, have become widely adopted models in medical image segmentation tasks. However, the multiple training parameters of these models determines high computation complexity, which is impractical for further applications. In this paper, by introducing depthwise separable convolution and attention mechanism into U-shaped architecture, we propose a novel lightweight neural network (DSCA-Net) for medical image segmentation. Three attention modules are created to improve its segmentation performance. Firstly, Pooling Attention (PA) module is utilized to reduce the loss of consecutive down-sampling operations. Secondly, for capturing critical context information, based on attention mechanism and convolution operation, we propose Context Attention (CA) module instead of concatenation operations. Finally, Multiscale Edge Attention (MEA) module is used to emphasize multi-level representative scale edge features for final prediction. The number of parameters in our network is 2.2 M, which is 71.6% less than U-Net. Experiment results across four public datasets show the potential and the dice coefficients are improved by 5.49% for ISIC 2018, 4.28% for thyroid, 1.61% for lung and 9.31% for nuclei compared with U-Net.

OBJECTIVES:To investigate mRNA and long non-coding RNA (lncRNA) expression profiles in monocrotaline (MCT)- mice.MATERIALS AND METHODS:Lung tissues (Control-Vehicle, MCT-Vehicle, and MCT-C75) were examined by high-throughput sequencing (HTS). Aberrantly expressed mRNAs and lncRNAs were analyzed by bioinformatics. Cell proliferation and cell cycle analysis were performed to detect the potential protective effects of C75, an inhibitor of fatty acid synthase. The signaling pathways associated with inflammatory responses were verified by real time-PCR.RESULTS:RNA sequencing data reveals 285 differentially expressed genes (DEGs) and 147 lncRNAs in the MCT-Vehicle group compared to the control. After five-week of C75 treatment, 514 DEGs and 84 lncRNAs are aberrant compared to the MCT-Vehicle group. Analysis of DEGs and lncRNA target genes reveals that they were enriched in pathways related to cell cycle, cell division, and vascular smooth muscle contraction that contributes to the PAH pathological process. Subsequently, the expression of eight DEGs and three lncRNAs is verified using RT-PCR. Differentially expressed lncRNAs (ENSMUSG00000110393.2, Gm38850, ENSMUSG00000100465.1, ENSMUSG00000110399.1) may associate in PAH pathogenesis as suggested by co-expression network analysis. C75 can protect against MCT-induced PAH through its anti-inflammatory and anti-proliferation.CONCLUSIONS:These DEGs and lncRNAs can be considered as novel candidate regulators of PAH pathogenesis. We propose that C75 treatment can partially reverse PAH pathogenesis through modulating cell cycle, cell proliferation, and anti-inflammatory.

目的 依据川崎病（Kawasaki disease, KD）标准数据模型调查KD患儿的相关资料，探索基于标准数据集和隐私计算环境的医学人工智能算法比较模式。方法 选取2017年1月—2021年12月在上海市儿童医院住院的初诊为KD的998例患儿资料，其中包括不完全KD。根据KD的诊断标准和静脉注射免疫球蛋白（intravenous immunoglobulin, IVIG）治疗无应答诊断标准，分析KD患儿的性别、月龄和实际IVIG治疗无应答患儿比例。依据KD标准数据模型，构建标准数据集，部署安全计算环境，检验KD高危预测模型在不同发热天数患儿中的诊断一致性，并对比IVIG治疗无应答预测模型与Kobayashi预测模型的预测效率，评价2个模型的AUC的ROC及灵敏度和特异度。结果 本研究纳入的患儿月龄为（31.45±23.51）个月。其中，男性639例（64.03%）,女性359例（35.97%）。IVIG治疗实际无应答患儿99例（99/998,9.92%）,其中男性65例（65.66%）,女性34例（34.34%）。根据KD高危预测模型判定为KD高危的患儿931例（931/998,93.29%）,其中在发热病程＜5 d的326例患儿中，被判定为KD高危的患儿312例（95.71%）;在病程≥5 d的672例患儿中，被判定为KD高危的患儿619例（92.11%）。根据IVIG治疗无应答预测模型评分系统，将患儿分为IVIG无应答型KD组（683例）和IVIG敏感型KD组（315例）。与IVIG敏感型KD组相比，IVIG无应答型KD组的纤维蛋白原降解产物（FDP）、血清白蛋白和AST水平均显著升高（P值均＜0.01）,中性粒细胞与淋巴细胞比值（NLR）显著降低（P＜0.01）。IVIG治疗无应答预测模型和Kobayashi预测模型的ROC的AUC分别为0.72（95%CI为0.67～0.78）和0.66（95%CI为0.58～0.70）。IVIG治疗无应答预测模型的灵敏度和特异度均为0.73,Kobayashi预测模型的灵敏度和特异度分别为0.29和0.89。结论 本研究使用院内搭建的隐私计算环境对KD标准数据集进行处理分析，表明IVIG治疗无应答预测模型预测汉族KD患儿IVIG治疗无应答的效率略优于Kobayashi预测模型。

Hypertrophic cardiomyopathy (HCM) is an autosomal dominant cardiomyopathy, which is one of the most common reasons for cardiac arrest in children or adolescents. It is characterized by ventricular hypertrophy (usually left ventricle), small ventricular cavity, and reduced ventricular diastolic compliance found by echocardiography in the absence of abnormal load (such as hypertension or aortic stenosis). HCM is usually caused by mutations in genes encoding sarcomere or sarcomere-related genes. Whole exome sequencing (WES) is performed to identify probable causative genes. Through WES, we identified LIM domain-binding protein 3 (LDB3) mutations (R547Q and P323S) respectively in an 11-year-old HCM girl and a 6-year-old HCM boy. Neural network analyses showed that the LDB3 (R547Q and P323S) mutation decreased its protein stability, with confidence scores of −0.9211 and −0.8967. The STRUM server also confirmed that the mutation decreased its protein stability. Thus, LDB3 mutation may be associated with heritable HCM. To our knowledge, this is the first time to report LDB3 heterozygous variants (R547Q and P323S) responsible for heritable HCM.

目的 评估超重/肥胖儿童的自主神经功能情况.方法 通过研究动态心电图的心率变异性(HRV)及心率减速力(DC)指标,平板运动试验的运动当量、达峰值心率(HRmax)的运动时间、运动终止后第一分钟心率恢复(HRR 1)、恢复至静息心率时间、静息期收缩压、运动峰值收缩压及运动恢复期第三分钟收缩压指标来评估肥胖儿童的自主神经功能.结果 肥胖组儿童31例,男23例、女8例,平均年龄(10.4±2.6)岁;超重组69例,男35例、女34例,平均年龄(10.9±2.7)岁;对照组100例,男57例、女43例,平均年龄(10.2±2.7)岁.超重、肥胖与对照组三组儿童之间正常RR间期标准(SDNN)、相邻RR间期差值的均方根(RMSSD)、5 min均值标准差(SDANN)、NN 50占所有NN间期个数的百分数(pNN 50)、低频功率(LF)/高频功率(HF)、心率减速力(DC)值的差异均有统计学意义(P<0.05).超重、肥胖与对照组三组儿童之间达HRmax运动时间、运动当量、HRR 1/HRmax、恢复至静息心率时间、静息期收缩压、运动峰值收缩压、恢复期第三分钟收缩压/峰值收缩压的差异均有统计学意义(P<0.05).结论 超重/肥胖儿童存在心脏自主神经功能紊乱,尤其迷走神经功能的受损,需要引起足够重视,积极干预,预防心血管事件的发生.

块匹配法是利用超声心动图对心肌进行斑点跟踪定量分析最为常见、有效的方法,块匹配法中模板块大小对斑点跟踪精度有很大的影响,然而现有算法中模板块大小都是由经验来确定,不仅造成斑点跟踪精度较差而且缺乏自适应性.本文提出一种用于超声心动图块匹配斑点跟踪的模板块大小自适应估计方法.首先利用双向跟踪准确度估计跟踪误差,然后根据不同大小块的双向跟踪准确度自适应地确定块匹配中模板块的大小,解决了模板块大小自适应的问题.通过与传统固定模板块大小的方法比较,采用自适应模板块大小方法的斑点跟踪结果在精确度和稳定性上都取得了更好的结果,其中斑点跟踪平均误差由2.5±0.2下降为1.1±0.1,为心脏功能临床诊断和治疗提供了更为可靠的相关参数.

新时代青年作为医院发展的中坚力量,是促进医院发展的重要生力军.共青团组织作为医院工作的重要组成部分,其主要服务对象就是青年,关系到医院青年的向心力和凝聚力.本文采用问卷调研的方式,了解医学青年参与医院共青团活动的现状以及他们对医院未来共青团活动的诉求和建议,探究医院共青团组织如何厚植青年理想信念,凝聚青春正能量;围绕医院中心工作,展现青年新作为;加强青年文化建设,推动工作新局面,这将有助于探讨科学有效的路径发挥青年在医院建设中的生力军作用,促进公立医院高质量发展.

Abstract Objectives: To investigate mRNA and long non-coding RNA (lncRNA) expression profiles in monocrotaline (MCT)- mice. Materials and Methods: Lung tissues (Control-Vehicle, MCT-Vehicle, and MCT-C75) were examined by high-throughput sequencing (HTS). Aberrantly expressed mRNAs and lncRNAs were analysed by bioinformatics. Cell proliferation and cell cycle analysis were performed to detect the potential protective effects of C75, an inhibitor of fatty acid synthase. The signal pathways associated with inflammatory responses were verified by RT-PCR. Results: RNA sequencing data reveals 285 differentially expressed genes (DEGs) and 147 lncRNAs in the MCT-Vehicle group compared to the control group. After five-week of C75 treatment, 514 DEGs and 84 lncRNAs are aberrant compared to the MCT-Vehicle group. Analysis of DEGs and lncRNA target genes reveals that they were enriched in pathways related to cell cycle, cell division, and vascular smooth muscle contraction that contributes to the PAH pathological process. Subsequently, the expression of eight DEGs and three lncRNAs is verified using RT-PCR. Differentially expressed lncRNAs (ENSMUSG00000110393.2, Gm38850, ENSMUSG00000100465.1, ENSMUSG00000110399.1) may associate in PAH pathogenesis as suggested by co-expression network analysis. C75 can protect against MCT-induced PAH through its anti-inflammatory and anti-proliferation. Conclusions: These DEGs and lncRNAs can be considered as novel candidate regulators of PAH pathogenesis. We propose that C75 treatment can partially reverse PAH pathogenesis through modulating cell cycle, cell proliferation, and anti-inflammatory.

Sudden cardiac death (SCD) caused by ventricular arrhythmias is the leading cause of mortality of cardiovascular disease. Mutation in TECRL, an endoplasmic reticulum protein, was first reported in catecholaminergic polymorphic ventricular tachycardia during which a patient succumbed to SCD. Using loss- and gain-of-function approaches, we investigated the role of TECRL in murine and human cardiomyocytes. Tecrl (knockout, KO) mouse shows significantly aggravated cardiac dysfunction, evidenced by the decrease of ejection fraction and fractional shortening. Mechanistically, TECRL deficiency impairs mitochondrial respiration, which is characterized by reduced adenosine triphosphate production, increased fatty acid synthase (FAS) and reactive oxygen species production, along with decreased MFN2, p-AKT (Ser473), and NRF2 expressions. Overexpression of TECRL induces mitochondrial respiration, in PI3K/AKT dependent manner. TECRL regulates mitochondrial function mainly through PI3K/AKT signaling and the mitochondrial fusion protein MFN2. Apoptosis inducing factor (AIF) and cytochrome C (Cyc) is released from the mitochondria into the cytoplasm after siTECRL infection, as demonstrated by immunofluorescent staining and western blotting. Herein, we propose a previously unrecognized TECRL mechanism in regulating CPVT and may provide possible support for therapeutic target in CPVT.