Neutrophil extracellular traps activate lung fibroblast to induce polymyositis-related interstitial lung diseases via TLR9-miR-7-Smad2 pathway.

Excessive neutrophil extracellular trap (NET) formation may contribute to polymyositis (PM)-associated interstitial lung diseases (ILD), but the underlying mechanism is not fully revealed. In this study, we found that NET accelerated the progression of ILD and promoted pulmonary fibrosis (PF) in vivo. miR-7 expression was down-regulated in lung tissue of PM group than control group, and NETs further decreased miR-7 expression. TLR9 and Smad2 were up-regulated in lung tissue of PM group than control group, and NETs further increased TLR9 and Smad2 expressions. In vitro experiments showed that PMA-treated NETs accelerated the proliferation of LF and their differentiation into myofibroblast (MF), whereas DNase I decreased the promotion effect of NETs. Neutrophil extracellular trap components myeloperoxidase (MPO) and histone 3 also promoted the proliferation and differentiation of LF. In addition, we demonstrated that TLR9 involved in the regulation of NETs on LF proliferation and differentiation, and confirmed the interaction between miR-7 and Smad2 in LF. Finally, miR-7-Smad2 pathway was confirmed to be involved in the regulation of TLR9 on LF proliferation and differentiation. Therefore, NETs promote PM-related ILD, and TLR9-miR-7-Smad2 signalling pathway is involved in the proliferation of LFs and their differentiation into MFs.

[Clinical analysis of suspected COVID-19 patients with anxiety and depression].

OBJECTIVE: To explore the risk factors of anxiety and depression in patients with suspected coronavirus disease 2019 (COVID-19) so as to achieve early intervention and better clinical prognosis. METHODS: Seventy-six patients with suspected COVID-19 in fever isolation wards of Second Hospital of Lanzhou University were enrolled From January 31, 2020 to February 22, 2020. Their clinical baseline data were collected. The anxiety of patients was assessed by Hamilton Anxiety Scale, and the depression of patients was assessed by Hamilton Depression Scale. Multivariate Logistic regression analysis was performed to explore the risk factors of anxiety and depression in these patients. RESULTS: Female patients are more likely to have anxiety (OR=3.206, 95%CI: 1.073-9.583, P<0.05) and depression (OR=9.111, 95%CI: 2.143-38.729, P<0.01) than male patients; patients with known contact history of epidemic area and personnel in epidemic area are more likely to have depression (OR=3.267, 95%CI: 1.082-9.597, P<0.05). CONCLUSIONS: During the isolation treatment of suspected COVID-19 patients, early psychological intervention should be carried out for the female patients with known contact history of epidemic area and personnel in epidemic area, and drug treatment should be given in advance if necessary.

COL8A1 Promotes NSCLC Progression Through IFIT1/IFIT3-Mediated EGFR Activation.

Activation of EGFR is a major risk factor for non-small cell lung cancer (NSCLC). Understanding the molecular events promoting EGFR activation can help us gain more insights into the progression of NSCLC. In this study, we demonstrate that collagen type VIII alpha 1 chain (COL8A1), an extracellular matrix component, was overexpressed in NSCLC. In NSCLC cells, knockdown of COL8A1 suppressed cell growth, cycle progression, and migration, and induced cell apoptosis. While COL8A1 overexpression promoted cell proliferation and inhibited cell apoptosis. In addition, we found that COL8A1 depletion reduced interferon response signaling and downregulated (IFIT1) and interferon-induced proteins with tetratricopeptide repeats 3 (IFIT3). Moreover, we indicated that COL8A1 could upregulate IFIT1 and IFIT3 mediated EGFR activation in vitro and in vivo. Lastly, there was a positive correlation among COL8A1, IFIT1, and IFIT3 expression, and EGFR activity in patients with NSCLC. Overall, our data demonstrate that COL8A1 contributes to NSCLC proliferation and invasion through EGFR activation, dependent on IFIT1 and IFIT3 expression.

Biomarkers for detecting malignant pleural mesothelioma: Protocol for a reanalysis of published data based on systematic reviews of diagnostic test accuracy.

BACKGROUND: Malignant pleural mesothelioma (MPM) is a highly invasive tumor caused primarily by asbestos exposure. In recent decades, the incidence of MPM has shown an increasing trend, posing a great threat to human health. Although there is currently no effective way to treat MPM, patients can survive for more than 5 years if the tumor is removed early. Several systematic reviews (SRs) have evaluated the diagnostic value of biomarkers for diagnosing MPM. However, no studies have been conducted to analyze the quality of these SRs and it remains unclear which biomarker is the excellent diagnostic test. This study aims to assess the methodological quality of the SRs and reanalyze the published data based on SRs to find the optimal biomarker for the early diagnosis of MPM. METHODS: A systematic search will be performed in PubMed, Embase.com, the Cochrane Library of Systematic Reviews, and Web of Science to identify SRs reporting value of biomarkers for detecting MPM. We will evaluate the risk of bias of the included SRs according to the Assessment of Multiple Systematic Reviews-2 (AMSTAR-2) instrument. Standard pairwise meta-analysis and adjusted indirect comparison will be used to compare the diagnostic value of different biomarkers. RESULTS: The results of this study will be submitted to a peer-reviewed journal for publication. CONCLUSION: This study will reanalyze the published data based on SRs to find a biomarker with the superior diagnostic performance for the diagnosis of MPM. ETHICS AND DISSEMINATION: Ethics approval and patient consent are not required as this study is an overview based on published systematic reviews. PROSPERO REGISTRATION NUMBER: CRD42019125880.

Cytotoxic activity of an octadecenoic acid extract from Euphorbia kansui (Euphorbiaceae) on human tumour cell strains.

We have investigated the cytotoxic and antitumour activity of an octadecenoic acid extract, mainly containing oleic and linoleic acids, from Euphorbia kansui on human gastric (SGC-7901), hepatocellular carcinoma (BEL-7402), and leukaemia (HL-60) tumour cell strains. Significant and dose-dependent antiproliferation effects were observed on tumour cells from the dose of 3.2 microg mL(-1), which were comparable with or better than those of the common antitumour agent 5-fluorouracil. Results from the clone formation assay and flow cytometry indicated that the mixture of octadecenoic acids resulted in a dose-dependent reduction in the number of tumour cells and significantly inhibited cell proliferation, with induced apoptosis and G(0)/G(1) phase cell cycle arrest. Also, the octadecenoic acids could not only cause cell apoptosis/necrosis but also functionally and structurally damage the tumour cell membrane and cell ultra-structures. These observations encourage further clinical evaluation of the inhibitory effects of octadecenoic acids on various forms of cancer.

[Clinical research of selective bronchial artery infusion and chemotherapy of lung cancer].

BACKGROUND: To study the effect of selective bronchial artery infusion (BAI) and chemotherapy in the treatment of patients with intermediate and advanced lung cancer. METHODS: Forty-five cases of advanced lung cancer were treated by BAI, which were compared with 40 cases of advanced lung cancer treated by systemic chemotherapy. RESULTS: The response rate of BAI (33/44, 75.0%) was better than that of systemic chemotherapy (20/40, 50.0%)( P < 0.05). The side-effect of BAI was lower than that of systemic chemotherapy ( P < 0.05), but one case occured paraplegia after BAI. The response rate of small cell undifferentiated lung cancer, squamous cell carcinoma and adenocarcinoma was 94.5% (17/18), 66.6% (14/21) and 40.0% (2/5) respectively in the BAI group. Significant difference of the response rate was found in squamous cell carcinoma and adenocarcinoma between the two groups ( P < 0.05). CONCLUSIONS: BAI has better response rate and less toxicity than systemic chemotherapy in intermediate and advanced lung cancer, especially in patients with squamous cell carcinoma. Small cell undifferentiated lung carcinoma should be treated by systemic chemotherapy firstly and then BAI. Adenocarcinoma should be treated by BAI firstly and then other therapy.