Identification and development of a five-gene signature to improve the prediction of mechanical ventilator-free days for patients with COVID-19.

OBJECTIVE: Coronavirus disease 2019 (COVID-19) is a highly contagious infectious disease caused by the newly discovered severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Severe COVID-19 infection causes complications in the respiratory tract, which results in pulmonary failure, thus requiring prolonged mechanical ventilation (MV). An increase in the number of patients with COVID-19 poses numerous challenges to the healthcare system, including the shortage of MV facilities. Despite continued efforts to improve COVID-19 diagnosis and treatment, no study has established a reliable predictive model for the risk assessment of deteriorating COVID-19 cases. MATERIALS AND METHODS: We extracted the expression profiles and clinical data of the GSE157103, GSE116560 and GSE21802 cohorts from the Gene Expression Omnibus database. Differentially expressed genes (DEGs) were identified as the intersection of the resulting differential genes as analysed via limma, edgeR and DESeq2 R packages. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed using the R package 'clusterProfiler'. Variables closely related to MV were examined using univariate Cox regression analysis, and significant variables were subjected to least absolute shrinkage and selection operator regression (LASSO) analysis for the construction of a risk model. Kaplan-Meier analysis and receiver operating characteristic (ROC) curves were generated to verify the predictive values of the risk model. RESULTS: We identified 198 unigenes that were differentially expressed in COVID-19 samples. Moreover, a five-gene signature (BTN3A1, GPR35, HAAO, SLC2A6 and TEX2) was constructed to predict the ventilator-free days of patients with COVID-19. In our study, we used the five-gene signature to calculate the risk score (MV score) for each patient. The results revealed a statistical correlation between the MV score and the scores of the Acute Physiology and Chronic Health Evaluation and Sequential Organ Failure Assessment of patients with COVID-19. Kaplan-Meier analysis revealed that the number of ventilator-free days was significantly reduced in the low-MVscore group compared to the high-MVscore group. The ROC curves revealed that our model had a good performance, and the areas under the ROC curve were 0.93 (3-week ROC) and 0.97 (4-week ROC). The 'Limma' package analysis revealed 71 upregulated genes and 59 downregulated genes in the high-MV score group compared to the low-MV score group. These DEGs were mainly enriched in cytokine signalling in immune system and cellular response to cytokine stimulus. CONCLUSIONS: This study identified a five-gene signature that can predict the length of ventilator-free days for patients with COVID-19.

LncRNA UNC5B-AS1 promotes malignant progression of prostate cancer by competitive binding to caspase-9.

OBJECTIVE: This study aims to investigate the expression of LncRNA UNC5B-AS1 in prostate cancer (PCa) and to further investigate whether it can prompt malignant progression of PCa via regulating caspase-9. PATIENTS AND METHODS: Quantitative Real Time-Polymerase Chain Reaction (qRT-PCR) was conducted to examine UNC5B-AS1 expression in 50 pairs of tumor tissue specimens and paracancerous ones collected from PCa patients, and the interplay between UNC5B-AS1 expression and clinical indicators of PCa was also analyzed. Meanwhile, UNC5B-AS1 levels in PCa cell lines were also further verified by qRT-PCR. In addition, UNC5B-AS1 knockdown model was constructed using lentivirus in PCa cell lines, and cell counting kit-8 (CCK-8), 5-Ethynyl-2'-deoxyuridine (EdU), transwell and flow cytometry assays were performed to figure out the impact of UNC5B-AS1 on the biological function of PCa cells. Finally, cell recovery experiment was conducted to explore the underlying mechanism and the association between UNC5B-AS1 and caspase-9. RESULTS: QRT-PCR results suggested that UNC5B-AS1 expression in PCa tissue samples was remarkably higher than in adjacent ones, with a statistically significant difference. Compared with patients with low expression of UNC5B-AS1, patients with highly-expressed UNC5B-AS1 had a higher incidence of distant metastasis and more advanced pathological stage. At the same time, proliferation and invasion, as well as migration ability of cells in sh-UNC5B-AS1 group, was conspicuously attenuated while cell apoptosis ability was conversely enhanced. Furthermore, qRT-PCR results revealed that caspase-9 and UNC5B-AS1 showed a negative correlation in gene expression level in PCa tissues. The results of the luciferase reporter gene experiment demonstrated that UNC5B-AS1 can be targeted by caspase-9 through their binding site. Additionally, cell recovery experiment indicated that UNC5B-AS1 and caspase-9 can be mutually regulated, which then together affect the malignant progression of PCa. CONCLUSIONS: UNC5B-AS1 expression was found remarkably increased in both PCa tissues and cell lines, which was remarkably associated with pathological stage and incidence of distant metastasis of PCa patients. In addition, UNC5B-AS1 was able to accelerate the malignant progression of PCa by modulating caspase-9 expression.

Radiofrequency thermocoagulation combined with pulsed radiofrequency helps relieve postoperative complications of trigeminal neuralgia.

Trigeminal neuralgia is a sudden, severe condition characterized by stabbing and recurrent pain. Radiofrequency thermocoagulation (RFT) and pulsed radiofrequency (PRF) are common surgical interventions used to treat trigeminal neuralgia. This study aimed to investigate the therapeutic effects and associated complications of a combination of RFT and PRF in the treatment of trigeminal neuralgia. Computed tomography-guided percutaneous RFT of the Gasserian ganglion was performed on 80 patients with trigeminal neuralgia. Patients were randomly assigned to either group A (RFT at 70°C) or group B (RFT at 75°C). Patients in each group were divided into 2 subgroups, receiving percutaneous RFT (240 s) with or without PRF (42°C, 2 Hz, 240 s). Six months later, pain relief and complication status were evaluated. There was no significant difference in visual analogue scores among groups with RFT at 70° or 75°C, with or without PRF. Data showed that facial numbness and postoperative masticatory muscle weakness recovered more rapidly in patients receiving combined RFT and PRF treatment. Decreased corneal reflex was relieved to a significantly greater extent in groups receiving PRF than those without. Thus, compared to the use of RFT at 75°C alone, the combination of PRF and RFT helped eliminate postoperative complications, such as facial numbness, masticatory muscle weakness, and decreased corneal reflex, indicating that it could be useful for surgically treating trigeminal neuralgia.