m6A modification regulates lung fibroblast-to-myofibroblast transition through modulating KCNH6 mRNA translation.

Idiopathic pulmonary fibrosis (IPF) is a chronic, fatal lung disease characterized by progressive and non-reversible abnormal matrix deposition in lung parenchyma. Myofibroblasts originating mainly from resident fibroblasts via fibroblast-to-myofibroblast transition (FMT) are the dominant collagen-producing cells in pulmonary fibrosis. N6-methyladenosine (m6A) modification has been implicated in various biological processes. However, the role of m6A modification in pulmonary fibrosis remains elusive. In this study, we reveal that m6A modification is upregulated in a bleomycin (BLM)-induced pulmonary fibrosis mouse model, FMT-derived myofibroblasts, and IPF patient lung samples. Lowering m6A levels through silencing methyltransferase-like 3 (METTL3) inhibits the FMT process in vitro and in vivo. Mechanistically, KCNH6 is involved in the m6A-regulated FMT process. m6A modification regulates the expression of KCNH6 by modulating its translation in a YTH-domain family 1 (YTHDF1)-dependent manner. Together, our study highlights the critical role of m6A modification in pulmonary fibrosis. Manipulation of m6A modification through targeting METTL3 may become a promising strategy for the treatment of pulmonary fibrosis.

Long-Term Changes of Urinary Exosomal Peptide Levels After Thyroidectomy in Patients with Thyroid Cancer: A Prospective Observational Study.

Background: The recurrence rate of thyroid cancer can be as high as 30%. The purpose of this study was to examine changes of urine exosomal peptide levels after thyroidectomy in patients with thyroid cancer to determine if levels can predict the risk of recurrence. Methods: Patients >20 years old as newly diagnosed with papillary thyroid cancer who had received a thyroidectomy were recruited. Urine samples were collected at 12 months after enrollment to the study, and 1 year later. Urine exosomes containing different peptides were identified and compared. Results: A total of 70 patients were enrolled in the study, and were classified by the interval between surgery and enrollment: 42 patients with < 5 years between surgery and enrollment, 14 patients between 5-10 years, and 14 patients longer than 10 years. No recurrence was observed in any patient during the 2 years after enrollment. No significant differences were found in the levels of serum proteins or urine exosomal peptides between groups, or between intervals. Known risk factors for high-risk thyroid cancer had only a mild correlation with serum protein levels and urine exosomal peptides. Conclusion: Our study revealed the long-term basal fluctuation ranges of serum proteins and urine exosomal peptides in patients with thyroid cancer who underwent thyroidectomy. For high-risk patients after thyroidectomy, concentrations of serum proteins or urine exosomal peptides within the ranges may indicate there is a lower risk of thyroid cancer recurrence during long-term follow-up. Trial Registration: ClinicalTrials.gov: NCT03488134.

Urinary Exosomal Tissue TIMP and Angiopoietin-1 Are Preoperative Novel Biomarkers of Well-Differentiated Thyroid Cancer.

Finding non-invasive and sensitive biomarkers for early screening of high-risk patients remains important in clinical practice. A higher concentration of urine exosomal thyroglobulin protein was found in late-stage patients with thyroid carcinoma compared to those with early stage in our previous study. This prospective study aims to find new prognostic biomarkers before surgery for decision-making with this platform. We enrolled patients newly diagnosed with papillary and follicular cancer from 2017 to 2018. Preoperative urine samples were collected and the exosomal proteins were analyzed. The association of the concentration of urine exosomal proteins with lymph node metastasis and MACIS score (metastasis, age, completeness of resection, invasion, and size) was analyzed with multiple logistic regression. In total, 21 patients were included, with a mean age of 51.29 ± 10.29 years and a majority of female patients (85.71%). The concentration of urine exosomal TIMP (tissue inhibitor of metalloproteinase) was significantly higher in patients with lymph node metastasis (p = 0.01). Multiple logistic regression analysis showed association of urine exosomal TIMP (adjusted odds ratio (aOR): 3.09, 95% confidence interval (CI): 0.99-9.6, p = 0.052), angiopoietin-1 (aOR: 2.24, 95% CI: 0.97-5.15, p = 0.058) with lymph node metastasis. However, no association was noted between MACIS score and various urine exosomal protein candidates. Preoperative urine exosomal data could suggest certain peptides having the potential as prognostic indicators for screening patients with high-risk before surgery. Further study with a large cohort and long follow-up is needed to identify the application of urine exosomal proteins on prognostic prediction.

A comparison of visual acuity measured by ETDRS chart and Standard Logarithmic Visual Acuity chart among outpatients.

AIM: To compare the results of visual acuity (VA) measured by Early Treatment Diabetic Retinopathy Study (ETDRS) chart, 5 m Standard Logarithm Visual Acuity (5SL) chart, and 2.5 m Standard Logarithm Visual Acuity (2.5SL) chart in outpatients of age 12-80y. METHODS: Each patient (totally 2000 outpatients) had both eyes tested with ETDRS chart at 4 m, 5SL chart at 5 m, and 2.5SL chart at 2.5 m in random order. The VA values of outpatients were categorized by ages. VA values were expressed by logMAR recording method. RESULTS: The mean VA results of ETDRS charts, 5SL, and 2.5SL chart were 0.52±0.28, 0.50±0.30, and 0.46±0.28 logMAR, respectively. There was a statistically significant difference in the three eye charts in the whole group (P<0.001). For all subjects, the correlation of VA tested with three charts was statistically significant (Spearman correlation coefficient=0.944, 0.937, 0.946, all P<0.001). Bland-Altman analysis shows the 95% limits of agreement between the 5SL and 2.5SL chart were -0.182 to 0.210, -0.139 to 0.251, and -0.151 to 0.235 logMAR, respectively). CONCLUSION: The agreement between the three eye charts is not high. The VA measured by 5SL chart is slightly better than that by ETDRS chart and 5SL chart would be a suitable alternative when ETDRS chart are not available in the clinical situation. The VA measured by 2.5SL chart is about 0.5 line better than VA tested with ETDRS chart, which may overestimate VA.