Functional variant of the carboxypeptidase M (CPM) gene may affect silica-related pneumoconiosis susceptibility by its expression: a multistage case-control study.

ObjectivesIn a genome-wide association study, we discovered chromosome 12q15 (defined as rs73329476) as a silica-related pneumoconiosis susceptibility region. However, the causal variants in this region have not yet been reported.MethodsWe systematically screened eight potentially functional single-neucleotide polymorphism (SNPs) in the genes near rs73329476 (carboxypeptidase M (CPM) and cleavage and polyadenylation specific factor 6 (CPSF6)) in a case-control study including 177 cases with silicosis and 204 healthy controls, matched to cases with years of silica dust exposure. We evaluated the associations between these eight SNPs and the development of silicosis. Luciferase reporter gene assays were performed to test the effects of selected SNP on the activity of CPM in the promoter. In addition, a two-stage case-control study was performed to investigate the expression differences of the two genes in peripheral blood leucocytes from a total of 64 cases with silicosis and 64 healthy controls with similar years of silica dust exposure as the cases.ResultsWe found a strong association between the mutant rs12812500 G allele and the susceptibility of silicosis (OR=1.45, 95% CI 1.03 to 2.04, p=0.034), while luciferase reporter gene assays indicated that the mutant G allele of rs12812500 is strongly associated with increased luciferase levels compared with the wild-type C allele (p<0.01). Moreover, the mRNA (peripheral blood leucocytes) expression of the CPM gene was significantly higher in subjects with silicosis compared with healthy controls.ConclusionsThe rs12812500 variant of the CPM gene may increase silicosis susceptibility by affecting the expression of CPM, which may contribute to silicosis susceptibility with biological plausibility

Mouse Embryonic Fibroblasts-Derived Extracellular Matrix Facilitates Expansion of Inner Ear-Derived Cells

Objective: Previous reports showed that mouse embryonic fibroblasts (MEFs) could support pluripotent stem cell selfrenewaland maintain their pluripotency. The goal of this study was to reveal whether the decellularized extracellularmatrix derived from MEFs (MEF-ECM) is beneficial to promote the proliferation of inner ear-derived cells.Materials and Methods: In this experimental study, we prepared a cell-free MEF-ECM through decellularization.Scanning electron microscope (SEM) and immunofluorescent staining were conducted for phenotype characterization.Organs of Corti were dissected from postnatal day 2 and the inner ear-derived cells were obtained. The identificationof inner ear-derived cells was conducted by using reverse transcription-polymerase chain reaction (RT-PCR). Cellcounting kit-8 (CCK-8) was used to evaluate the proliferation capability of inner ear-derived cells cultured on the MEFECMand tissue culture plate (TCP).Results: The MEF-ECM was clearly observed after decellularization via SEM, and the immunofluorescence stainingresults revealed that MEF-ECM was composed of three proteins, including collagen I, fibronectin and laminin. Mostimportantly, the results of CCK-8 showed that compared with TCP, MEF-ECM could effectively facilitate the proliferationof inner ear-derived cells.Conclusion: The discovery of the potential of MEF-ECM in promoting inner ear-derived cell proliferation indicatesthat the decellularized matrix microenvironment may play a vital role in keeping proliferation ability of these cells. Ourfindings indicate that the use of MEF-ECM may serve as a novel approach for expanding inner ear-derived cells andpotentially facilitating the clinical application of inner ear-derived cells for hearing loss in the future

Analysis of etiology and clinical features of spontaneous downbeat nystagmus: a retrospective study

ObjectiveTo investigate the topical diagnosis, possible etiology and mechanism of spontaneous downbeat nystagmus (sDBN) patients with dizziness/vertigo.MethodsThe clinical features of dizziness/vertigo patients accompanied with DBN were retrospectively reviewed in the Vertigo Center of our hospital from January 2018 to March 2021. The clinical features of dizziness/vertigo patients accompanied with DBN were reviewed. Comprehensive VNG, bithermal caloric testing, video-head-impulse test (vHIT), vestibular-evoked myogenic potentials (VEMP), head magnetic resonance imaging (MRI), three-dimensional fluid-attenuated incersion recovery magnetic resonance imaging (3D-FLAIR MRI) in the inner ear, serum immunology and other examinations were to determine the lesion site, and analyze its possible etiology and mechanism.ResultsA total of 54 patients were included. Among them, 70.4% (n = 38) of DBN patients were diagnosed with episodic vestibular syndrome (EVS), 22.2% (n = 12) with chronic vestibular syndrome (CVS), and 7.4% (n = 4) with acute vestibular syndrome (AVS). Among all the patients, 51.9% of DBN patients had clear etiology, with central lesions of 29.6% and peripheral diseases of 22.2%. The most common diseases in DBN patients were cerebellar lesions (13.0%, n = 7) and vestibular migraine (13.0%, n = 7), followed by benign positional paroxysmal vertigo (7.4%, n = 4) and drug-related dizziness/vertigo (5.6%, n = 3). The other 48.1% of the patients had unknown etiology. 53.8% (14/26) of patients with idiopathic DBN had decreased semicircular canal function, with 42.9% (6/14) decreased posterior semicircular canal function. The posterior semicircular canal gain in DBN patients decreased compared to the anterior semicircular canal in the same conjugate plane. Patients with peripheral DBN were more prone to horizontal/torsional nystagmus during positional testing.ConclusionIn our study, DBN patients have a relative decrease in posterior semicircular canal gain, which is possibly a particular result found in a subset of downbeat nystagmus patients. The changes in nystagmus during positional testing may be helpful in distinguishing between peripheral and central causes

Literature Review on the Development of Public-Private-Partnership Leisure Sightseeing Agriculture

Comprehensive use of content analysis method and quantitative visualization analysis method, taking journal papers and master's thesis in the field of PPP of CNKI database as samples, through content analysis of research topics, research nature, and analysis of authors, literature discipline distribution, research hotspots and other fields, To discuss the trend characteristics of research and development in the field of PPP leisure agriculture in my country