Pancreatic cancer (PaCa) is one of the most fatal malignancies of the digestive system, and most patients are diagnosed at advanced stages due to the lack of specific and effective tumor-related biomarkers for the early detection of PaCa. miR-492 has been found to be upregulated in PaCa tumor tissue and may serve as a potential therapeutic target. However, the molecular mechanisms by which miR-492 promotes PaCa tumor growth and progression are unclear. In this study, we first found that miR-492 in enhancer loci activated neighboring genes (NR2C1/NDUFA12/TMCC3) and promoted PaCa cell proliferation, migration, and invasion in vitro. We also observed that miR-492-activating genes significantly enriched the TGF-β/Smad3 signaling pathway in PaCa to promote epithelial-mesenchymal transition (EMT) during tumorigenesis and development. Using CRISPR–Cas9 and ChIP assays, we further observed that miR-492 acted as an enhancer trigger, and that antagomiR-492 repressed PaCa tumorigenesis in vivo, decreased the expression levels of serum TGF-β, and suppressed the EMT process by downregulating the expression of NR2C1. Our results demonstrate that miR-492, as an enhancer trigger, facilitates PaCa progression via the NR2C1-TGF-β/Smad3 pathway.
Objectives We aimed to develop a simple algorithm helps early identification of SARS-CoV-2 infection patients with severe progression tendency. Methods 322 SARS-COV-2 infection patients were respectively enrolled. The univariable and multivariable analysis were computed to identify the independent predictors of severe progression, and the prediction model was established based on independent predictors. The areas under the ROC curves (AUROCs) were used to evaluate the diagnostic performances. Results Of 322 confirmed SARS-COV-2 infection patients, 11 were diagnosed as severe cases on admission, 15 developed to severe cases after admission, and 296 were non-severe cases. The multivariable analysis identified age (OR=1.061, p=0.028), lactate dehydrogenase (LDH) (OR=1.006, p=0.037), and CD4 count (OR=0.993, p=0.006) as the independent predictors of severe progression. Consequently, the age-LDH-CD4 algorithm was derived as (age×LDH)/CD4. The AUROC of the age-LDH-CD4 model was significantly higher than that of single CD4 count, LDH, or age (0.92, 0.85, 0.80, and 0.75, respectively). The age-LDH-CD4 model ≥ 82 has high sensitive (81%) and specific (93%) for the early identification of patients with severe progression tendency following SARS-CoV-2 infection. Conclusions The age-LDH-CD4 model is a simple algorithm for early identifying cases with severe progression tendency in SARS-CoV-2 infection patients, and warrants further validation.
Background/aims: This study is to evaluate the effect of proton pump inhibitors on the course of common COVID-19.Methods: Clinical data of common COVID-19 patients admitted to the Shanghai Public Health Clinical Center for treatment from January 20, 2020 to March 16, 2020 were collected. A retrospective study was conducted and the patients were divided into two groups according to whether they used proton pump inhibitors or not. The differences in SARS-CoV-2 clearance and hospital stay between the two groups were compared by univariate and multivariate analyses.Results: A total of 154 COVID-19 common cases were included in this study, including 80 males (51.9%), 35 patients (22.7%) in the proton pump inhibitors group, and 119 patients (77.3%) in the control group. In the proton pump inhibitors group and the control group, the duration of the SARS-CoV-2 clearance were 7(6-9) and 7(6-11) days, and the duration of the hospital stay was 21(16-25) and 20(15-26) days, respectively. There was no significant difference between the two groups in the cumulative incidence of the SARS-CoV-2 clearance and the discharge, all P > 0.05. Multivariate analysis showed that chronic gastropathy prolonged the duration of SARS-CoV-2 clearance, the HR was 20.924(3.547-123.447). Hypertension, chronic obstructive pulmonary disease, chronic liver disease and malignant tumor all increased the duration of hospital stay for COVID-19, and the HR were 1.820 (1.073-3.085), 4.370 (1.205-15.844), 9.011 (2.681-30.290) and 5.270 (1.237-22.456), respectively; the duration of the hospital stay in COVID-19 patients was shortened by the SARS-CoV-2 clearance, and the HR was 0.907 (0.869-0.947); all P < 0.05.Conclusion: Proton pump inhibitors use has no effect on the prolonging or shortening of the course of adults hospitalized with COVID-19.
Metagenomic next generation sequencing (mNGS) holds promise as a diagnostic tool for unbiased pathogen identification and precision medicine. However, its medical utility depends largely on the assay simplicity and reproducibility. In the current study, we aimed to develop a streamlined Illumina and Oxford Nanopore-based DNA/RNA library preparation protocol and rapid data analysis pipeline. The Illumina sequencing based mNGS method was first developed and evaluated using a set of samples with known etiology. Its sensitivity for RNA virus (Influenza A, H1N1) was <6.4×102 EID50/mL, and a good correlation between viral loads and mapped reads was observed. Then the rapid turnaround time of Nanopore sequencing was testified by sequencing of an Influenza A virus and Adenoviruses. Further, 11 respiratory swabs or sputum samples pre-tested for a panel of pathogens were analyzed and the pathogens identified by illumina sequencing showed 81.8% concordance with qPCR-based results. Additional sequencing of cerebrospinal fluid (CSF) samples from HIV-1 positive patients with meningitis/encephalitis detected HIV-1 RNA and toxoplasma gondii sequences. In conclusion, we have developed a simplified protocol which realized facile metagenomic sequencing of a variety of clinical samples and pathogen identification in a clinically meaningful time frame.
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