Background: Although many genes related to epithelial-mesenchymal transition (EMT) have been explored in hepatocellular carcinoma (HCC), their prognostic significance still needs further analysis.Methods: Differentially expressed EMT-related genes were obtained through the integrated analysis of 4 Gene expression omnibus (GEO) datasets. The univariate Cox regression and Lasso Cox regression models are utilized to determine the EMT-related gene signature. Based on the results of multivariate Cox regression, a predictive nomogram is established. Time-dependent ROC curve and calibration curve are used to show the distinguishing ability and consistency of the nomogram. Finally, we explored the correlation between EMT risk score and immune immunity.Results: We identified a nine EMT-related gene signature to predict the survival outcome of HCC patients. Based on the EMT risk score’s median, HCC patients in each dataset were divided into high and low-risk groups. The survival outcomes of HCC patients in the high-risk group were significantly worse than those in the low-risk group. The prediction nomogram based on the EMT risk score has better distinguishing ability and consistency. High EMT risk score was related to immune infiltration.Conclusion: The nomogram based on the EMT risk score can reliably predict the survival outcome of HCC patients, thereby providing benefits for medical decisions.
Objective: To observe the efficacy and safety of postoperative long-term low-dose oral administration of clarithromycin in patients with refractory chronic rhinosinusitis (RCRS), to explore the characteristics of postoperative microbiota in the nasal cavity in patients with RCRS, and to compare the differences and changes in microbiota in the nasal cavity before and after medication. Methods: This was a prospective, self-controlled study. Eighteen patients with RCRS who had persistent symptoms after endoscopic sinus surgery and standard therapy with normal immunoglobulin E and eosinophil level were included. Low dose (250 mg, once daily) clarithromycin was orally administrated for 12 weeks. Symptom severity and endoscopic findings were evaluated before, after 4 weeks, and 12 weeks of treatment, and nasal cavity microbiota was analyzed simultaneously. Results: A total of 18 patients with RCRS were enrolled and 17 patients completed the study. Four weeks after oral administration of clarithromycin, significant improvement was observed in subjective symptoms including nasal congestion, rhinorrhea, postnasal drip, and general discomfort, as well as endoscopic findings including general surgical cavity condition, rhinedema, and rhinorrhea ( P < .05). After continuous treatment to the 12th week, symptoms showed significant improvement compared with baseline, and endoscopic score showed significant improvement compared with both baseline and 4 weeks after treatment. Analysis of middle nasal meatus flora revealed a significant decrease of Streptococcus pneumoniae after 12 weeks of clarithromycin treatment ( P < .05), while the richness, composition, and diversity were similar before and after treatment. Patients enrolled experienced no adverse drug reaction or allergic reaction, nor clinical significant liver function impairment observed. Conclusion: Postoperative low-dose long-term oral administration of clarithromycin in patients with RCRS can improve the clinical symptoms and facilitate the mucosal epithelialization, with good tolerance and safety. The efficacy of clarithromycin in patients with RCRS may be related to its regulatory effect on nasal cavity microbiota.
Purpose: This study aimed to explore the expression of E2Fs gene family in thyroid cancer(THCA) patients, and systematically analyze the relationship between E2Fs gene and immune cell infiltration and prognosis of THCA patients. Methods: We utilized the UALCAN, cBioPortal, Kaplan-Meier Plotter, Human Protein Atlas, GEPIA, Metascape, Linkedomics and TIMER online databases to explore the transcription level, protein level, genetic alteration and the biological functions of E2Fs, and its relationship with the prognosis and infiltration of immune cell in thyroid cancer patients. Results: ① The expressions of E2F1/7 were significantly increased in the tumor group, while the expressions of E2F4/5 were greatly decreased. ②The mutation rate of E2Fs was 32.93% in patients with THCA, and the mutation of E2Fs was significantly associated with shorter disease-specific survival (P=0.0187) and progression-free survival (P=0.0147). ③Higher expression in transcription and protein levels of E2F1 (HR=0.15, 95%CI: 0.05-0.47, P=0.00015) and E2F2 (HR=37, 95%CI: 0.14-1.00, P= 0.041) were significantly associated with longer overall survival of THCA patients. ④The expression level of E2F1 was positively correlated with infiltration of B cells (Cor = 0.156, p =5.69e-4) and CD8+ T cells (Cor = 0.096, p = 3.35e-2). The expression level of E2F2 was positively correlated with infiltration of B cells (Cor = 0.433, p =2.01e-2), CD8+ T cells (Cor = 0.296, p =2.55e-11), CD4+ T cells (Cor = 0.213, p =1.97e-6), Macrophages (Cor = 0.277, p =4.94e-10), neutrophils (Cor = 0.362, p =1.35e-16) and dendritic cells (Cor = 0.479, p =3.98e-29). Conclusions: E2F1/2 were potential the prognostic markers of THCA patients. Their functions may be related to cell cycle and DNA replication signaling pathways, and promoting multiple immune cell infiltration.
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