Pulmonary hypertension (PH) is a group of syndromes characterized by irreversible vascular remodeling and persistent elevation of pulmonary vascular resistance and pressure, leading to ultimately right heart failure and even death. Current therapeutic strategies mainly focus on symptoms alleviation by stimulating pulmonary vessel dilation. Unfortunately, the mechanism and interventional management of vascular remodeling are still yet unrevealed. Hypoxia plays a central role in the pathogenesis of PH and numerous studies have shown the relationship between PH and hypoxia-inducible factors family. EPAS1, known as hypoxia-inducible factor-2 alpha (HIF-2α), functions as a transcription factor participating in various cellular pathways. However, the detailed mechanism of EPAS1 has not been fully and systematically described. This article exhibited a comprehensive summary of EPAS1 including the molecular structure, biological function and regulatory network in PH and other relevant cardiovascular diseases, and furthermore, provided theoretical reference for the potential novel target for future PH intervention.

Background: Pulmonary arterial hypertension (PAH) is a progressive disease characterized by pulmonary vascular remodeling. The development of PAH involves N6-methyladenosine (m6A) modification. However, the functional role of m6A regulators in PAH and the underlying regulatory mechanisms remain unknown so far.Methods: Microarray data (GSE149713) for monocrotaline induced PAH (MCT-PAH) rat models were downloaded and screened for differentially expressed genes (DEGs) and m6A regulators. Next, we screened for differentially expressed m6A regulators in endothelial cells (ECs), smooth muscle cells (SMCs), fibroblasts, interstitial macrophages, NK cells, B cells, T cells, regulatory T cells (Tregs) using scRNA sequencing data. The target DEGs of m6A regulators in ECs, SMCs, fibroblasts, and Tregs were functionally annotated using the Gene Ontology (GO) functional analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. In addition, the cellular interaction analysis was performed to reveal the receptor—ligand pairs regulated by m6A regulators. Pseudo-time trajectory analyses were performed and a ceRNA network of lncRNAs-miRNAs-mRNAs was constructed in SMCs. Furthermore, the RNA transcriptome sequencing data for the SMCs isolated from idiopathic PAH (IPAH) patients (GSE144274) were validated for differentially expressed m6A regulators. Moreover, the HNRNPA2B1 levels in the lung samples from PAH patients and MCT-PAH were determined using immunohistochemistry.Results: The m6A regulators were observed to be dysregulated in PAH. HNRNPA2B1expression level was increased in the PASMCs of scRNAs and IPAH patients. The target DEGs of HNRNPA2B1 were enriched in the regulation of muscle cell differentiation and vasculature development in PASMCs. The HNRNPA2B1 expression levels determined were consistent with the proliferation-related and collagen synthesis-related gene COL4A1. Moreover, the predicted transcription factors (TFs) foxd2/3 and NFκB could be involved in the regulation of HNRNPA2B1. HNRNPA2B1 might be regulating SMCs proliferation and phenotypic transition via rno-miR-330–3p/TGFβR3 and rno-miR-125a-3p/slc39a1. In addition, HNRNPA2B1 was observed to be highly expressed in the lung samples from MCT-PAH rat models and patients with PAH.Conclusion: In summary, the present study identified certain key functional m6A regulators that are involved in pulmonary vascular remodeling. The investigation of m6A patterns might be promising and provide biomarkers for diagnosis and treatment of PAH in the future.

Purpose: To determine whether TCF-1+ PD-1+ CD8+T cells are associated with the response to PD-1 blockade in non-small cell lung cancer (NSCLC) patients. Methods: We investigated the expression of TCF-1+ PD-1+ CD8+T cells and elucidated their predictive role in NSCLC patients. Pretreatment specimens from fifteen advanced NSCLC patients who underwent PD-1 immunotherapy or combined with chemotherapies were analyzed. The frequency of TCF-1+ cells in PD-1+ CD8+T cells were determined in these biospecimens by using multi-label immunofluorescence staining and multi-spectral acquisition technology. The clinical role of TCF-1+PD-1+CD8+T cells were evaluated via analyzing our patients’ clinic parameters and public NSCLC database. Results: A high frequency of TCF-1+ PD-1+ CD8+T cells were identified in responders compared with non-responders (p=0.0427), and the patients with high expression of this cell subset had durable clinical benefit of anti-PD-1 therapy. There were no significant association between the expression of TCF-1+ PD-1+ CD8+T cells and patients’ age, gender, smoking history, pathologic type and genetic status. In univariate logistic regression analysis, high frequency of TCF-1+ PD-1+ CD8+T cells were significantly correlated with patients’ benefit of PD-1 blockade (p=0.035). Conclusion: Our study indicated that TCF-1+ PD-1+ CD8+T cells are associated with the response to PD-1 blockade, and may be a predictor of anti-PD-1 therapy.

Objective: We aimed to describe the features of 220 nonemergency (mild or common type) COVID-19 patients from a shelter hospital, as well as evaluate the efficiency of antiviral drug, Arbidol in their disease progressions.Methods: Basic clinical characteristics were described and the efficacy of Arbidol was evaluated based on gender, age, maximum body temperature of the patients.Results: Basically, males had a higher risk of fever and more onset symptoms than females. Arbidol could accelerate fever recovery and viral shedding in respiratory specimens, particularly in males. Arbidol also contributed to shorter hospital stay without obvious adverse reactions.Conclusions: In the retrospective COVID-19 cohort, gender was one of the important factors affecting patient's conditions. Arbidol showed several beneficial effects in these patients, especially in males. This study brought more researches enlightenment in understanding the emerging infectious disease.