Single-Nucleus Multiomic Analyses Identifies Gene Regulatory Dynamics of Phenotypic Modulation in Human Aneurysmal Aortic Root.

Aortic root aneurysm is a potentially life-threatening condition that may lead to aortic rupture and is often associated with genetic syndromes, such as Marfan syndrome (MFS). Although studies with MFS animal models have provided valuable insights into the pathogenesis of aortic root aneurysms, this understanding of the transcriptomic and epigenomic landscape in human aortic root tissue remains incomplete. This knowledge gap has impeded the development of effective targeted therapies.

Rare loss-of-function variants in matrisome genes are enriched in Ebstein's anomaly.

Ebstein's anomaly, a rare congenital heart disease, is distinguished by the failure of embryological delamination of the tricuspid valve leaflets from the underlying primitive right ventricle myocardium. Gaining insight into the genetic basis of Ebstein's anomaly allows a more precise definition of its pathogenesis. In this study, two distinct cohorts from the Chinese Han population were included: a case-control cohort consisting of 82 unrelated cases and 125 controls without cardiac phenotypes and a trio cohort comprising 36 parent-offspring trios.

Heterozygous nonsense variants in laminin subunit 3α resulting in Ebstein's anomaly.

Ebstein's anomaly is a rare congenital heart disease characterized by tricuspid valve downward displacement and is associated with additional cardiac phenotypes such as left ventricle non-compaction. The genetic basis of Ebstein's anomaly has yet to be fully elucidated, although several genes (e.g.

Molecular characterization and clinical investigation of patients with heritable thoracic aortic aneurysm and dissection.

Objectives: Thoracic aortic aneurysm and dissection has a genetic predisposition and a variety of clinical manifestations. This study aimed to investigate the clinical and molecular characterizations of patients with thoracic aortic aneurysm and dissection and further explore the relationship between the genotype and phenotype, as well as their postoperative outcomes.

Methods: A total of 1095 individuals with thoracic aortic aneurysm and dissection admitted to our hospital between 2013 and 2022 were included.

HTAADVar: Aggregation and fully automated clinical interpretation of genetic variants in heritable thoracic aortic aneurysm and dissection.

Purpose: Early detection and pathogenicity interpretation of disease-associated variants are crucial but challenging in molecular diagnosis, especially for insidious and life-threatening diseases, such as heritable thoracic aortic aneurysm and dissection (HTAAD). In this study, we developed HTAADVar, an unbiased and fully automated system for the molecular diagnosis of HTAAD.

Methods: We developed HTAADVar (http://htaadvar.

Inhibition of immunoglobulin E attenuates pulmonary hypertension.

Pulmonary hypertension (PH) is a severe cardiopulmonary disease characterized by pulmonary vascular remodeling. Immunoglobulin E (IgE) is known to participate in aortic vascular remodeling, but whether IgE mediates pulmonary vascular disease is unknown. In the present study, we found serum IgE elevation in pulmonary arterial hypertension (PAH) patients, hypoxia-induced PH mice and monocrotaline-induced PH rats.

Metabolomic Profile Reveals That Ceramide Metabolic Disturbance Plays an Important Role in Thoracic Aortic Dissection.

Aims: Thoracic aortic dissection (TAD) is a life-threatening disease with no effective drug therapy thus far. New therapeutic targets and indications for timely surgical intervention are urgently needed. Our aim is to investigate new pathological mechanisms and potential biomarkers of TAD through global metabolomic profiling of aortic aneurysm and dissection patients.

Novel LTBP3 mutations associated with thoracic aortic aneurysms and dissections.

Background: Thoracic aortic aneurysm and dissection (TAAD) is a hidden-onset but life-threatening disorder with high clinical variability and genetic heterogeneity. In recent years, an increasing number of genes have been identified to be related to TAAD. However, some genes remain uncertain because of limited case reports and/or functional studies.

Pollution Distribution of Potentially Toxic Elements in a Karstic River Affected by Manganese Mining in Changyang, Western Hubei, Central China.

This study investigated the distribution, pollution level and potential ecological risk of potentially toxic elements (PTEs) from manganese mining in a karstic Danshui River, in Changyang, Western Hubei, Central China. River water and sediments were collected for seven PTEs measurement (As, Cd, Cr, Cu, Mn, Pb and Zn), as well as pH and Eh of the river water were measured. Results showed that the major pollutant was Mn, the river water environment was mainly acidic and oxidizing (288 < Eh, pH < 6.

P-Selectin Glycoprotein Ligand-1 Deficiency Protects Against Aortic Aneurysm Formation Induced by DOCA Plus Salt.

Purpose: P-selectin glycoprotein ligand-1 (PSGL-1) acts as a crucial regulator for the inflammatory cells infiltration by mediating the adhesion of leukocytes. However, the role of PSGL-1 in aortic aneurysm remains elusive. Here, we investigated the role of PSGL-1 in aortic aneurysm (AA) development.

Clinical characteristics and survival of Chinese patients diagnosed with pulmonary arterial hypertension who carry BMPR2 or EIF2KAK4 variants.

Background: Variants in the gene encoding bone morphogenetic protein receptor type II (BMPR2) are the most common genetic cause of pulmonary arterial hypertension (PAH), whereas biallelic variants in the eukaryotic translation initiation factor 2 alpha kinase 4 gene (EIF2AK4) are described in pulmonary veno-occlusive disease/pulmonary capillary haemangiomatosis (PVOD/PCH). Racial background may influence the clinical characteristics of patients diagnosed with PAH or PVOD/PCH. Here, we compared the clinical characteristics and survival between patients with BMPR2 variants or EIF2AK4 variants in a Chinese population.

Transcriptome analysis and functional identification of adipose-derived mesenchymal stem cells in secondary lymphedema.

Background: Secondary lymphedema is a common condition that affects patients with malignant tumors. Conservative treatments fail to provide lasting relief because they do not address the underlying pathological accumulation of excessive fat. Our aim is to clarify the molecular mechanisms of abnormal adipogenic differentiation in lymphedema adipose tissue.

Reversible splenial lesion syndrome (RESLES) due to acute intermittent porphyria with a novel mutation in the hydroxymethylbilane synthase gene.

Background: Reversible splenial lesion syndrome (RESLES) is a clinico-radiological syndrome characterized by the presence of reversible lesions specifically involving the splenium of the corpus callosum (SCC). The cause of RESLES is unknown. However, infectious-related mild encephalitis/encephalopathy (MERS) with a reversible splenial lesion remains the most common cause of reversible splenial lesions.

Exosomal miR-423-5p mediates the proangiogenic activity of human adipose-derived stem cells by targeting Sufu.

Background: Human adipose-derived stem cells (hADSCs) are an important source of cells for regenerative medicine. Evidence of extensive interactions with the surrounding microenvironment has led researchers to focus more on hADSCs as activating agents of regenerative pathways, rather than simply replacing damaged cells. Several studies have found that functional miRNAs can be packaged into exosomes and transferred from donor cells into recipient cells, indicating that transported miRNAs may be a new class of cell-to-cell regulatory species.

Perioperative urinary thromboxane metabolites and outcome of coronary artery bypass grafting: a nested case-control study.

Objective: As a marker of in vivo thromboxane generation, high-level urinary thromboxane metabolites (TXA-M) increase the occurrence of cardiovascular events in high-risk patients. To investigate whether perioperative urinary TXA-M level is associated with major adverse cardiac and cerebrovascular events (MACCE) after coronary artery bypass graft (CABG) surgery, we designed a nested case-control study.

Design: Observational, nested case-control study.

Genetic analyses in a cohort of 191 pulmonary arterial hypertension patients.

Background: Pulmonary arterial hypertension (PAH) is a progressive and fatal disorder associated with high pulmonary artery pressure. Genetic testing enables early diagnosis and offers an opportunity for family screening. To identify genetic mutations and help make a precise diagnosis, we performed genetic testing in 191 probands with PAH and tried to analyze the genotype-phenotype correlation.

Reversible MRI findings in a case of acute intermittent porphyria with a novel mutation in the porphobilinogen deaminase gene.

Acute intermittent porphyria (AIP) is an autosomal dominant disorder caused by a partial deficiency of porphobilinogen deaminase (PBGD), the third enzyme in the of heme biosynthetic pathway. It can affect the autonomic, peripheral, and central nervous system. Posterior reversible encephalopathy syndrome is a clinicoradiological entity characterized by headache, seizures, altered consciousness, and visual disorder associated with potentially reversible neuroradiological abnormalities predominantly in the parieto-occipital lobes.

A novel PROS1 mutation, c.74dupA, was identified in a protein S deficiency family.

Protein S is a vitamin K-dependent plasma glycoprotein that acts as an anticoagulant, and its deficiency usually predisposes individuals to venous thromboembolism. Hereditary protein S deficiency is an autosomal dominant disorder caused by a PROS1 mutation. Herein, we described a novel PROS1 frameshift mutation, c.

Genetic testing of the FBN1 gene in Chinese patients with Marfan/Marfan-like syndrome.

Marfan syndrome (MFS) is an autosomal dominant connective tissue disorder typically involving the ocular, skeletal and cardiovascular systems, and aortic aneurysms/dissection mainly contributes to its mortality. Here, we performed genetic testing of the FBN1 gene in 39 Chinese probands with Marfan/Marfan-like syndrome and their related family members by Sanger sequencing. In total, 29 pathogenic/likely pathogenic FBN1 mutations, including 17 novel ones, were identified.

Genetic testing of 10 patients with features of Loeys-Dietz syndrome.

Inherited aortopathy, characterized with a high risk of fetal aortic aneurysms/dissections, could occur secondary to several syndromes. To identify genetic mutations and help to give a precise diagnosis, we performed a gene panel testing, involving 15 genes related to inherited aortopathy. Here we reported 10 patients, combining with the genetic testing results, were diagnosed or suspected with Loeys-Dietz syndrome, which would be the largest group of Loeys-Dietz syndrome ever reported in China till now.

A pharmacogenetics-based warfarin maintenance dosing algorithm from Northern Chinese patients.

Inconsistent associations with warfarin dose were observed in genetic variants except VKORC1 haplotype and CYP2C9*3 in Chinese people, and few studies on warfarin dose algorithm was performed in a large Chinese Han population lived in Northern China. Of 787 consenting patients with heart-valve replacements who were receiving long-term warfarin maintenance therapy, 20 related Single nucleotide polymorphisms were genotyped. Only VKORC1 and CYP2C9 SNPs were observed to be significantly associated with warfarin dose.