Simin Liang

Background: Clear cell renal cell carcinoma (ccRCC) has the highest morbidity among renal cell carcinoma (RCC) subtypes. While existing clinical pharmacological intervention strategies have achieved certain efficacy, challenges including inevitable drug resistance and intricate immune heterogeneity of ccRCC continue to hinder their biomedical application. Therefore, developing novel immunotherapeutic agents and identifying patients who can gain the greatest benefits from these therapies are urgent issues.Methods: To address these challenges, mRNA expression profile and clinical data of ccRCC were obtained from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. These data were integrated and randomly allocated into training and test sets. Immune-related differentially expressed genes (IRDEGs) were used to construct an immune-related gene prognostic index (IRGPI). Both prognostic performance metrics and immune phenotyping were employed to evaluate the effectiveness of the model. Furthermore, model IRDEGs (mIRDEGs) in two risk subgroups were leveraged to select potential therapeutic compounds. Afterwards, network pharmacology and molecular docking techniques were used to elucidate the anti-cancer mechanisms of Zebularine (Zeb). Finally, the anti-cancer efficacy of Zeb was validated through in vivo and in vitro experiments.Results: Our constructed IRGPI exhibited superior prognostic performance. The drug screening revealed Zeb potentially targets the PI3K-Akt signaling pathway to exert its anti-cancer effects. Subsequent experimental validation corroborated these theoretical findings.Conclusion: This study presents a prognostic model to evaluate immune cell infiltration and predict the prognosis of ccRCC patients. The identified small molecule compound provides a novel therapeutic avenue for treating ccRCC patients.

Background: Renal cell carcinoma (RCC) is one of the most common malignant tumors of the urinary system, of which the clear cell renal cell carcinoma (ccRCC) accounts for the most subtypes. The increasing discoveries of abundant autophagy-related long non-coding RNAs (ARLNRs) lead to a resurgent interest in evaluating their potential on prognosis prediction. Based on a large number of ccRCC gene samples from TCGA and clinics, ARLNRs analysis will provide a novel perspective into this field. Methods: We calculated the autophagy scores of each sample according to the expression levels of autophagy-related genes (ARGs) and screened the survival-related ARLNRs (sARLNRs) of ccRCC patients by Cox regression analysis. The high-risk group and the low-risk group were distinguished by the median score of the autophagy-related risk score (ARRS) model. The functional annotations were detected by gene set enrichment analysis (GSEA) and principal component analysis (PCA). The expression levels of two kinds of sARLNRs in the renal tumor and adjacent normal tissues and cell lines were verified. Results: There were 146 ARLNRs selected by Pearson analysis. A total of 30 sARLNRs were remarkably correlated with the clinical outcomes of ccRCC patients. Eleven sARLNRs (AC002553.1, AC092611.2, AL360181.2, AP002807.1, AC098484.1, AL513218.1, AC008735.2, MHENCR, AC020907.4, AC011462.4, and AC008870.2) with the highest prognosis value were recruited to establish the ARRS in which the overall survival (OS) in the high-risk group was shorter than that in the low-risk group. ARRS could be treated as an independent prognostic factor and has significant correlations with OS. The distributions of autophagy genes were different between the high-risk group and the low-risk group. In addition, we also found that the expression levels of AC098484.1 in ccRCC cell lines and tumor tissues were lower than those in HK-2 and adjacent normal tissues, but AL513218.1 showed the inverse level. Furthermore, the AC098484.1 expressed decreasingly with the more advanced T-stages, but AL513218.1 gradually increased. Conclusion: Our study identified and verified some sARLNRs with clinical significances and revealed their potential values on predicting prognoses of ccRCC patients, which may provide a novel perspective for autophagy-related research and clinical decisions.

The spread of coronavirus disease 2019 (COVID-19) around the world has put a heavy burden on human society and is also a great challenge facing medical staff. This study aimed to assess the difficulties faced by health care personnel (HCP) in using personal protective equipment (PPE) in clinical practice during the COVID-19 outbreak in Wuhan, China. One hundred twenty medical staff from the First Affiliated Hospital of Chongqing Medical University presented to the Wuhan First Hospital to provide medical assistance, from whom 20 HCP volunteered to participate in a focus group discussion attended by infection control nurse leaders. Participants’ responses and discussions were recorded, and the content was analyzed for themes. Observed difficulties included inappropriate PPE sizes, the design of the PPE and its complexity of use, doubts related to the quality and effectiveness of PPE, potential risks during doffing, space layout between clean and contaminated area, and poor comfort with PPE use. Other factors, such as the support environment, management, processes, preparedness, HCP, and equipment can also have a positive or negative impact on the use of PPE. Future efforts to optimize PPE use should focus on strengthening training for HCP using real items for increasing compliance with standardized protocols, improving PPE design, and performing further research on the risks, benefits, and best practices of PPE use.