High clinical utility of long-read sequencing for precise diagnosis of congenital adrenal hyperplasia in 322 probands.

Background: The molecular genetic diagnosis of congenital adrenal hyperplasia (CAH) is very challenging due to the high homology between the CYP21A2 gene and its pseudogene CYP21A1P.

Methodology: This study aims to assess the clinical efficacy of targeted long-read sequencing (T-LRS) by comparing it with a control method based on the combined assay (NGS, Multiplex ligation-dependent probe amplification and Sanger sequencing) and to introduce T-LRS as a first-tier diagnostic test for suspected CAH patients to improve the precise diagnosis of CAH.

Results: A large cohort of 562 participants including 322 probands and 240 family members was enrolled for the perspective (96 probands) and prospective study (226 probands).

Structural characterization of polysaccharides from Polygonatum Sibiricum and effect on alleviating hyperlipidemia in egg yolk emulsion-induced mice.

Polysaccharides are the major bioactive composition of Polygonatum sibiricum (P. sibiricum). However, the structural and functional identifications of these polysaccharides were still limited.

Skeletal overgrowth in a pre-pubescent child treated with pan-FGFR inhibitor.

Fibroblast growth factors and their receptors (FGFR) have major roles in both human growth and oncogenesis. In adults, therapeutic FGFR inhibitors have been successful against tumors that carry somatic FGFR mutations. In pediatric patients, trials testing these anti-tumor FGFR inhibitor therapeutics are underway, with several recent reports suggesting modest positive responses.

Effects of aquatic exercise intervention on executive function and brain-derived neurotrophic factor of children with autism spectrum disorder.

Background: Limited knowledge exists regarding the effectiveness of aquatic exercise intervention for improving executive function (EF) in children with autism spectrum disorder (ASD). Additionally, the impact of aquatic exercise on brain-derived neurotrophic factor (BDNF) in children with ASD requires further investigation.

Aims: This study aimed to explore the effects of a 12-week aquatic exercise intervention on core EF and BDNF levels in children with ASD.

Interaction between the gut microbiota and colonic enteroendocrine cells regulates host metabolism.

Nutrient handling is an essential function of the gastrointestinal tract. Hormonal responses of small intestinal enteroendocrine cells (EECs) have been extensively studied but much less is known about the role of colonic EECs in metabolic regulation. To address this core question, we investigated a mouse model deficient in colonic EECs.

Immunopeptidome mining reveals a novel ERS-induced target in T1D.

Autoreactive CD8 T cells play a key role in type 1 diabetes (T1D), but the antigen spectrum that activates autoreactive CD8 T cells remains unclear. Endoplasmic reticulum stress (ERS) has been implicated in β-cell autoantigen generation. Here, we analyzed the major histocompatibility complex class I (MHC-I)-associated immunopeptidome (MIP) of islet β-cells under steady and ERS conditions and found that ERS reshaped the MIP of β-cells and promoted the MHC-I presentation of a panel of conventional self-peptides.

Four novel mutations identification in 17 beta-hydroxysteroid dehydrogenase-3 deficiency and our clinical experience: possible benefits of early treatment.

Introduction: Individuals with 17-beta-hydroxysteroid dehydrogenase type 3 (17β-HSD3) deficiency face a multitude of challenges, primarily concerning genital appearance, potential malignancy risks, and fertility issues. This study reports our findings from an investigation involving five individuals affected by 17β-HSD3 deficiency, ranging in age from pre-adolescence to adolescence. Notably, we identified four previously unreported mutations in these subjects.

Effects of Aquatic Exercise and Floor Curling on Balance Ability and Lower Limb Muscle Strength in Children with Intellectual Disabilities: A Pilot Study in China.

Children with intellectual disabilities often face challenges in balance ability and lower limb muscle strength, which negatively impact their daily lives and motor function. Therefore, it is crucial to enhance the balance ability and lower limb muscle strength of children with intellectual disabilities. This study aimed to investigate the effects of a 12-week aquatic exercise and floor curling intervention on the balance ability and lower limb muscle strength of children with intellectual disabilities.

En masse organoid phenotyping informs metabolic-associated genetic susceptibility to NASH.

Genotype-phenotype associations for common diseases are often compounded by pleiotropy and metabolic state. Here, we devised a pooled human organoid-panel of steatohepatitis to investigate the impact of metabolic status on genotype-phenotype association. En masse population-based phenotypic analysis under insulin insensitive conditions predicted key non-alcoholic steatohepatitis (NASH)-genetic factors including the glucokinase regulatory protein (GCKR)-rs1260326:C>T.

Three cases of 3β-hydroxysteroid dehydrogenase deficiency: Clinical analysis.

Background: 3β-HSD deficiency is a rare type of congenital adrenal hyperplasia (CAH), which is caused by HSD3B2 gene mutations.

Objectives: In order to improve the understanding and diagnosis of the disease, we analyzed and summarized the clinical characteristics, genetic variants and treatment for 3 children with 3β-HSD deficiency in this study.

Material And Methods: A summary of the clinical data, hormone levels (17-hydroxyprogesterone, adrenocorticotropic hormone, cortisol, testosterone, dehydroepiandrosterone, androstenedione, renin, and aldosterone), therapeutic drugs, and gene sequencing results from 3 3β-HSD deficiency patients was created.

Anti-diabetic compounds from the seeds of Psoralea corylifolia.

A new aurone named (2Z)-2-[(4'-hydroxyphenyl) methylene]-6-hydroxy-7-prenyl-3(2H)-benzofurane (1), two new flavonoids named (2S)-7-methoxy-6-(2-hydroxy-3-methylbut-3-en-1-yl)-2-(4-hydroxyphenyl)chroman-4-one (2), (2S)-4'-hydroxyl-7-hydroxymethylene-6-(2″,3″-epoxy-3″-methylbutyl)flavanone (3), and a new coumestan named bavacoumestan E (4), together with eleven known compounds (5-15), were isolated from the seeds of Psoralea corylifolia. The chemical structures were elucidated by spectroscopic and physico-chemical analyses. All isolates were evaluated for in vitro inhibitory activity against DGAT, PTP1B and α-glucosidase.

Analysis of bone mass and its relationship with body composition in school-aged children and adolescents based on stage of puberty and site specificity: A retrospective case-control study.

The aim of this study was to better understand the relationship of bone mass with body composition based on different stages of puberty and to illuminate the contribution of site-specific fat mass and lean mass (FM and LM) compared with bone mass in school-aged children and adolescents in Chongqing, China.A total of 1179 healthy subjects of both sexes were recruited. Bone mineral content (BMC), bone mineral density (BMD), bone area, and both FM and LM were measured by dual-energy X-ray absorptiometry (DXA).

Waist-to-height ratio remains an accurate and practical way of identifying cardiometabolic risks in children and adolescents.

Aim: We evaluated how effectively the waist-to-height ratio (WHtR) identified cardiometabolic risk (CMR) in children and adolescents, compared with the tri-ponderal mass index, percentage of body fat and other obesity indexes.

Methods: Eligible subjects were recruited from three metropolitan regions of China from May 2013 to June 2014. Subjects with at least three of the following abnormalities - hypertension, dyslipidemia, elevated fasting blood glucose and central obesity - were defined as CMR1 and children with at least two were defined as CMR2.

MicroRNA-142-3p inhibits high-glucose-induced endothelial-to-mesenchymal transition through targeting TGF-β1/Smad pathway in primary human aortic endothelial cells.

Myocardial fibrosis is an important pathological feature of diabetic cardiomyopathy (DCM) and endothelial-to-mesenchymal transition (EndMT) is an essential process for myocardial fibrosis. Recent studies have demonstrated an association between miRs and DCM. Therefore, the aim of this study is to investigate the role and the mechanism of miRNAs in the process of EndMT.

[Novel PHEX gene mutations in patients with X-linked hypophosphatemic rickets: an analysis of 2 cases].

Objective: To investigate PHEX gene mutations in 2 patients with X-linked hypophosphatemic rickets (XLH) and their families and to clarify the genetic etiology.

Methods: A retrospective analysis was performed for the clinical data of two patients with XLH. High-throughput sequencing was used to detect the PHEX gene, a pathogenic gene of XLH.

Functional characteristics of reversibly immortalized hepatic progenitor cells derived from mouse embryonic liver.

Background/aims: Liver is a vital organ and retains its regeneration capability throughout adulthood, which requires contributions from different cell populations, including liver precursors and intrahepatic stem cells. To overcome the mortality of hepatic progenitors (iHPs) in vitro, we aim to establish reversibly immortalized hepatic progenitor cells from mouse embryonic liver.

Methods And Results: Using retroviral system to stably express SV40 T antigen flanked with Cre/LoxP sites, we establish a repertoire of iHP clones with varied differentiation potential.

Noggin resistance contributes to the potent osteogenic capability of BMP9 in mesenchymal stem cells.

Mesenchymal stem cells (MSCs) are multipotent progenitors and can differentiate into osteogenic, chondrogenic, and adipogenic lineages. Bone morphogenetic proteins (BMPs) play important roles in stem cell proliferation and differentiation. We recently demonstrated that BMP9 is a potent but less understood osteogenic factor.

Cross-talk between EGF and BMP9 signalling pathways regulates the osteogenic differentiation of mesenchymal stem cells.

Mesenchymal stem cells (MSCs) are multipotent progenitors, which give rise to several lineages, including bone, cartilage and fat. Epidermal growth factor (EGF) stimulates cell growth, proliferation and differentiation. EGF acts by binding with high affinity to epidermal growth factor receptor (EGFR) on the cell surface and stimulating the intrinsic protein tyrosine kinase activity of its receptor, which initiates a signal transduction cascade causing a variety of biochemical changes within the cell and regulating cell proliferation and differentiation.

Establishment and characterization of the reversibly immortalized mouse fetal heart progenitors.

Objective: Progenitor cell-based cardiomyocyte regeneration holds great promise of repairing an injured heart. Although cardiomyogenic differentiation has been reported for a variety of progenitor cell types, the biological factors that regulate effective cardiomyogenesis remain largely undefined. Primary cardiomyogenic progenitors (CPs) have a limited life span in culture, hampering the CPs' in vitro and in vivo studies.

Growth hormone synergizes with BMP9 in osteogenic differentiation by activating the JAK/STAT/IGF1 pathway in murine multilineage cells.

Growth hormone (GH) is usually released by somatotrophs in the anterior pituitary in response to the GH-releasing hormone and plays an important role in skeleton development and postnatal growth. However, it is unclear if extrapituitary GH exerts any effect on murine multilineage cells (MMCs). MMCs are multipotent progenitors that give rise to several lineages, including bone, cartilage, and fat.

Mesenchymal stem cells: Molecular characteristics and clinical applications.

Mesenchymal stem cells (MSCs) are non-hematopoietic stem cells with the capacity to differentiate into tissues of both mesenchymal and non-mesenchymal origin. MSCs can differentiate into osteoblastic, chondrogenic, and adipogenic lineages, although recent studies have demonstrated that MSCs are also able to differentiate into other lineages, including neuronal and cardiomyogenic lineages. Since their original isolation from the bone marrow, MSCs have been successfully harvested from many other tissues.

BMP-9 induced osteogenic differentiation of mesenchymal stem cells: molecular mechanism and therapeutic potential.

Promoting osteogenic differentiation and efficacious bone regeneration have the potential to revolutionize the treatment of orthopaedic and musculoskeletal disorders. Mesenchymal Stem Cells (MSCs) are bone marrow progenitor cells that have the capacity to differentiate along osteogenic, chondrogenic, myogenic, and adipogenic lineages. Differentiation along these lineages is a tightly controlled process that is in part regulated by the Bone Morphogenetic Proteins (BMPs).

Defective osteogenic differentiation in the development of osteosarcoma.

Osteosarcoma (OS) is associated with poor prognosis due to its high incidence of metastasis and chemoresistance. It often arises in areas of rapid bone growth in long bones during the adolescent growth spurt. Although certain genetic conditions and alterations increase the risk of developing OS, the molecular pathogenesis is poorly understood.

Mesenchymal Progenitor Cells and Their Orthopedic Applications: Forging a Path towards Clinical Trials.

Mesenchymal progenitor cells (MPCs) are nonhematopoietic multipotent cells capable of differentiating into mesenchymal and nonmesenchymal lineages. While they can be isolated from various tissues, MPCs isolated from the bone marrow are best characterized. These cells represent a subset of bone marrow stromal cells (BMSCs) which, in addition to their differentiation potential, are critical in supporting proliferation and differentiation of hematopoietic cells.