Identification of Eukaryotic Translation Initiation Factor 4B as a Novel Candidate Gene for Congenital Hypothyroidism.

Context: Congenital hypothyroidism (CH) is the most common endocrine disorder in neonates, but its etiology is still poorly understood.

Objective: We performed whole exome sequencing to identify a novel causative gene for CH and functional studies to validate its role in the occurrence of CH.

Methods: Whole exome sequencing in 98 CH patients not harboring known CH candidate genes and bioinformatic analysis were performed.

Deficiency of the HGF/Met pathway leads to thyroid dysgenesis by impeding late thyroid expansion.

The mechanisms of bifurcation, a key step in thyroid development, are largely unknown. Here we find three zebrafish lines from a forward genetic screening with similar thyroid dysgenesis phenotypes and identify a stop-gain mutation in hgfa and two missense mutations in met by positional cloning from these zebrafish lines. The elongation of the thyroid primordium along the pharyngeal midline was dramatically disrupted in these zebrafish lines carrying a mutation in hgfa or met.

Variant Screening and Phenotype Analysis in 367 Chinese Patients With Congenital Hypothyroidism.

Background: Genetic defects in the human thyroid-stimulating hormone (TSH) receptor () gene can cause congenital hypothyroidism (CH). However, the biological functions and comprehensive genotype-phenotype relationships for most variants associated with CH remain unexplored. We aimed to identify variants in Chinese patients with CH, analyze the functions of the variants, and explore the relationships between genotypes and clinical phenotypes.

Contactin 6, A Novel Causative Gene for Congenital Hypothyroidism, Mediates Thyroid Hormone Biosynthesis Through Notch Signaling.

Congenital hypothyroidism (CH) is the most common neonatal metabolic disorder. In patients with CH in China, thyroid dyshormonogenesis is more common than thyroid dysgenesis; however, the genetic causes of CH due to thyroid dyshormonogenesis remain largely unknown. Therefore, we aimed at identifying novel candidate causative genes for CH.

Genetic Screening and Functional Analysis of Thyroid Peroxidase Variants in Chinese Patients with Congenital Hypothyroidism.

Introduction: Congenital hypothyroidism (CH), the most common neonatal endocrine disorder worldwide, can be caused by variants in the thyroid peroxidase (TPO) gene. This study aimed to identify TPO variants in Chinese patients with CH, analyze their impact on TPO function, and establish relationships between TPO genotypes and clinical characteristics.

Methods: A total of 328 patients with CH were screened for TPO variants by performing whole-exome sequencing.

Pathogenic variations in and contribute to congenital hypothyroidism due to dyshormonogenesis by regulating the Notch signalling pathway.

Background: In several countries, thyroid dyshormonogenesis is more common than thyroid dysgenesis in patients with congenital hypothyroidism (CH). However, known pathogenic genes are limited to those directly involved in hormone biosynthesis. The aetiology and pathogenesis of thyroid dyshormonogenesis remain unknown in many patients.

The transcription factor regulates pituitary development in zebrafish.

Background: ISL LIM homeobox 2, also known as insulin gene enhancer protein ISL-2 (), is a transcription factor gene that participates in a wide range of developmental events. However, the role of in the hypothalamus-pituitary-thyroid axis is largely unknown. In the present study, we characterized the expression patterns of and revealed its regulative role during embryogenesis using zebrafish.

Large-scale forward genetic screening of zebrafish affecting thyroid development.

The thyroid follicular cells originate from the foregut endoderm and elucidating which genes and signaling pathways regulate their development is crucial for understanding developmental disorders as well as diseases in adulthood. We exploited unique advantages of the zebrafish model to carry an ENU-based forward mutagenesis screen aiming at identifying genes involved in the development and function of the thyroid follicular cells. ENU is an excellent chemical mutagen due to its high mutation efficiency and an indiscriminate selection of genes.

T Cell Receptor Repertoire Analysis Reveals Signatures of T Cell Responses to Human .

Characterization of T cell receptor (TCR) repertoires is essential for understanding the mechanisms of infection involving T cell adaptive immunity. The characteristics of TCR sequences and distinctive signatures of T cell subsets in tuberculous patients are still unclear. By combining single-cell TCR sequencing (sc-TCR seq) with single-cell RNA sequencing (sc-RNA seq) and flow cytometry to characterize T cells in tuberculous pleural effusions (TPEs), we identified 41,718 CD3 T cells in TPEs and paired blood samples, including 30,515 CD4 T cells and 11,203 CD8 T cells.

Single-cell analysis of diverse immune phenotypes in malignant pleural effusion.

The complex interactions among different immune cells have important functions in the development of malignant pleural effusion (MPE). Here we perform single-cell RNA sequencing on 62,382 cells from MPE patients induced by non-small cell lung cancer to describe the composition, lineage, and functional states of infiltrating immune cells in MPE. Immune cells in MPE display a number of transcriptional signatures enriched for regulatory T cells, B cells, macrophages, and dendritic cells compared to corresponding counterparts in blood.

The mutation screening in candidate genes related to thyroid dysgenesis by targeted next-generation sequencing panel in the Chinese congenital hypothyroidism.

Objective: Congenital hypothyroidism (CH) is known to be due to thyroid dyshormonogenesis (DH), which is mostly inherited in an autosomal recessive inheritance pattern or thyroid dysgenesis (TD), whose inheritance pattern is controversial and whose molecular etiology remains poorly understood.

Design And Methods: The variants in 37 candidate genes of CH, including 25 genes related to TD, were screened by targeted exon sequencing in 205 Chinese patients whose CH cannot be explained by biallelic variants in genes related to DH. The inheritance pattern of the genes was analyzed in family trios or quartets.

Genetic Manipulation on Zebrafish duox Recapitulate the Clinical Manifestations of Congenital Hypothyroidism.

Congenital hypothyroidism (CH) is a highly prevalent but treatable neonatal endocrine disorder. Thyroid dyshormonogenesis is the main cause of congenital hypothyroidism in Chinese CH patients, and DUOX2 is the most frequent mutated gene involved in H2O2 production. In humans, the primary sources for H2O2 production are DUOX1 and DUOX2, while in zebrafish there is only a single orthologue for DUOX1 and DUOX2.

Novel Compound Heterozygous Pathogenic Mutations of in a Chinese Patient With Congenital Hypothyroidism.

Background And Objectives: Defects in the human sodium/iodide symporter () gene have been reported to be one of the causes of congenital hypothyroidism (CH). We aimed to identify mutations in Chinese patients with CH and to evaluate the function of the mutation.

Methods: Two hundred and seventy-three patients with primary CH were screened for mutations in using next-generation sequencing.

Nebulization in the Treatment of COVID-19: A Randomized, Double-Blind, Placebo-Controlled Trial.

Severe acute respiratory syndrome coronavirus 2 infection is associated with strong infectiousness and has no effective therapy. We aimed to explore the efficacy and safety of nebulization in the treatment of Coronavirus Disease 2019 (COVID-19). In this randomized, double-blind, placebo-controlled clinical trial, we included 31 adult patients with moderate COVID-19 who were admitted to the Fourth People's Hospital of Nanning (Nanning, China) between January 22, 2020 and February 17, 2020.

Molecular and clinical genetics of the transcription factor GLIS3 in Chinese congenital hypothyroidism.

The transcription factor GLIS3 is an important factor in hormone biosynthesis and thyroid development, and mutations in GLIS3 are relatively rare. Deletions of more than one of the 11 exons of GLIS3 occur in most patients with various extrathyroidal abnormalities and congenital hypothyroidism (CH), and only 18 missense variants of GLIS3 related to thyroid disease have been reported. The aim of this study was to report the family history and molecular basis of patients with CH who carry GLIS3 variants.

Compression methods after femoral artery puncture: A protocol for systematic review and network meta-analysis.

Background: Vascular complications at the puncture site is a common complication after femoral artery puncture. It will not only affect the postoperative effect and patient comfort, but also may endanger the life of the patient. The effective compression hemostasis methods at the puncture site can improve the comfort of the patient, shorten the hospital stay, and reduce the burden on the medical staff.

Anti-IFN-γ autoantibodies underlie disseminated Talaromyces marneffei infections.

Talaromyces marneffei causes life-threatening opportunistic infections, mainly in Southeast Asia and South China. T. marneffei mainly infects patients with human immunodeficiency virus (HIV) but also infects individuals without known immunosuppression.

Candidate gene associations reveal sex-specific Graves' disease risk alleles among Chinese Han populations.

Background: With several susceptibility single nucleotide polymorphisms identified by case-control association studies, Graves' disease is one of the most common forms of autoimmune thyroid disease. In this study, we aimed to determine whether any observed differences in genetic associations are influenced by sex in Chinese Han populations.

Methods: A total of 8,835 patients with Graves' disease and 9,936 sex-matched healthy controls were enrolled in the study.

The TPO mutation screening and genotype-phenotype analysis in 230 Chinese patients with congenital hypothyroidism.

Inborn defects in thyroid hormone biosynthesis contribute to nearly half of congenital hypothyroidism (CH) cases in China. The thyroid peroxidase (TPO) mutation is one of the most frequent mutations that results in thyroid dyshormonogenesis. In this study, 35 non-synonymous mutations in 15 TPO sites, including 6 novel mutations, were identified in 230 Chinese patients with CH.

Involvement of LeMDR, an ATP-binding cassette protein gene, in shikonin transport and biosynthesis in Lithospermum erythrorhizon.

Background: Shikonin is a naphthoquinone secondary metabolite with important medicinal value and is found in Lithospermum erythrorhizon. Considering the limited knowledge on the membrane transport mechanism of shikonin, this study investigated such molecular mechanism.

Results: We successfully isolated an ATP-binding cassette protein gene, LeMDR, from L.

Transcriptome analysis explores genes related to shikonin biosynthesis in Lithospermeae plants and provides insights into Boraginales' evolutionary history.

Shikonin and its derivatives extracted from Lithospermeae plants' red roots have current applications in food and pharmaceutical industries. Previous studies have cloned some genes related to shikonin biosynthesis. However, most genes related to shikonin biosynthesis remain unclear, because the lack of the genome/transcriptome of the Lithospermeae plants.