Background: Frontline health professionals are a COVID-19-susceptible population during the outbreak of COVID-19, but prophylactic drugs against SARS-CoV-2 infection are to be explored. Method: Frontline health professionals diagnosed with COVID-19 before February 9, 2020 in Tongji Hospital, Wuhan, China and the same amount of controls in the uninfected group were included in this study. Clinical and laboratory data were collected with standardized forms. Results: A total of 164 subjects were included in this study, 82 cases in the infected group and 82 controls in the uninfected group, with a median age of 37 years, including 63 males and 101 females. Nineteen (23.2%) patients in the infected group were administered oral arbidol, and 48 (58.5%) in the uninfected group (OR = 0.214, 95% CI 0.109–0.420). The cumulative uninfected rate of health professionals in the arbidol group was significantly higher than that of individuals in the non-arbidol group (log-rank test, χ² = 98.74; P < 0.001). Forty-eight patients (58.5%) in the infection group were hospitalized, with a median age of 39 (31–49) years, of whom 7 (14.6%) were prophylactically administered arbidol. Thirty-four patients (41.5%) with mild symptoms were treated outside the hospital, among which the median age was 34 (30–39) years, and twelve patients (35.3%) took prophylactic oral arbidol. The hospitalization rate was significantly associated with age (P = 0.024) and oral arbidol administration (OR = 0.313, 95% CI 0.108–0.909). In the age-matched case-control study, the hospitalization rate was not significantly associated with arbidol administration (P = 0.091). Conclusion: Prophylactic oral arbidol was associated with a lower incidence of SARS-CoV-2 infection but not hospitalization rate in health professionals, providing a basis for the selection of prophylactic drugs for high-risk populations.

Background: Novel non-invasive biomarkers are urgently required to improve the diagnostic sensitivity and specificity of prostate cancer (PCa). Therefore, the diagnostic value of following candidate genes (ERG, PCA3, ARV7, PSMA, CK19, and EpCAM) were estimated by testing mRNAs from urinary exosomes of patients with primary PCa.Methods: Exosomes were obtained using size-exclusion chromatography (SEC), out of which RNAs were extracted, then analyzed by quantitative reverse transcription-polymerase chain reaction according to manufacturer’s protocol.Results: The expression of urinary exosomal ERG, PCA3, PSMA, CK19, and EpCAM were significantly increased in patients with PCa compared with healthy males. In addition, the levels of urinary exosomal ERG, ARV7, and PSMA were intimately correlated with the Gleason score in PCa patients (P < 0.05). The receiver operating characteristic curves (ROCs) showed that urinary exosomal ERG, PCA3, PSMA, CK19, and EpCAM were able to distinguish patients with PCa from healthy individuals with the area under the curve (AUC) of 0.782, 0.783, 0.772, 0.731, and 0.739, respectively. Urinary exosomal PCA3 and PSMA distinguished PCa patients from healthy individuals with an AUC of 0.870. Combination of urinary exosomal PCA3, PSMA with serum PSA and PI-RADS achieved higher AUC compared with PSA alone (0.914 and 0.846, respectively). Kaplan-Meier curves demonstrated that PCA3, ARV7, and EpCAM were associated in androgen-deprivation therapy (ADT) failure time which is defined as from the initiation of ADT in hormone-sensitive stage to the development of castration-resistant prostate cancer.Conclusion: These findings suggested that mRNAs from urinary exosomes have the potential in serving as novel and non-invasive indicators for PCa diagnosis and prediction.

Background: Immune checkpoint inhibitors (ICIs) are the standard of care for metastatic renal cell carcinoma (RCC); however, most patients develop de novo or acquired resistance to ICIs. Oxidative phosphorylation (OXPHOS) has been rarely explored as a potential target for correcting ICI resistance. Methods: We systematically analyzed RNA sequencing and clinical data from CheckMate, JAVELIN Renal 101, and NCT01358721 clinical trials, and clinicopathological data of 25 patients from Tongji Hospital to investigate the relationship between OXPHOS and ICI resistance. The Ndufb8-knockdown Renca cell line was derived to determine the effect of OXPHOS on RCC immunotherapy in vivo. Results: An analysis of the CheckMate series data revealed that high OXPHOS levels are risk factors for ICI in patients with RCC, but are affected by thevon Hippel-Lindau protein (VHL) and hypoxia-inducible factor-1α status. This result is consistent with correlation between clinicopathological characteristics and prognostic observations at our institute. Knockdown of the mitochondrial complex I subunit Ndufb8 of the Renca cell line had no effect on cell growth and migration in vitro, but slowed down cell growth in vivo. Among anti-programmed death ligand 1 (PD-L1)-treated BALB/c mice, shNdufb8 Renca tumors grew slower than shControl Renca tumors and the corresponding mice survived longer. Flow cytometry revealed that CD8⁺ T cells in shNdufb8 Renca tumors, which were exposed to a lower degree of hypoxia and expressed less programmed death-1 (PD-1) and T-cell immunoglobulin domain and mucin domain 3 (TIM-3), secreted more interferon-γ after stimulation. Immunofluorescence demonstrated that the shNdufb8 Renca tumors had a higher proportion of CD8⁺ T cells and the proportion of these cells was lower in the hypoxic area. Conclusions: OXPHOS is a reliable predictor of immunotherapy response in RCC and is more pronounced in metastatic lesions. RCC cells generate a hypoxic tumor microenvironment and inhibit T-cell function through oxidative metabolism, thereby leading to immunotherapy resistance.

Background: Kidney cancer undergoes a dramatic metabolic shift and has demonstrated responsiveness to immunotherapeutic intervention. However, metabolic classification and the associations between metabolic alterations and immune infiltration in Renal cell carcinoma still remain elucidative. Methods: Unsupervised consensus clustering was conducted on the TCGA cohorts for metabolic classification. GESA, mRNAsi, prognosis, clinical features, mutation load, immune infiltration and differentially expressed gene differences among different clusters were compared. The prognosis model and nomograms were constructed based on metabolic gene signatures and verified using external ICGC datasets. Immunohistochemical results from Human Protein Atlas database and Tongji hospital were used to validate gene expression levels in normal tissues and tumor samples. CCK8, apoptosis analysis, qPCR, subcutaneously implanted murine models and flowcytometry analysis were applied to investigate the roles of ACAA2 in tumor progression and anti-tumor immunity. Results: Renal cell carcinoma was classified into 3 metabolic subclusters and the subcluster with low metabolic profiles displayed the poorest prognosis, highest invasiveness and AJCC grade, enhanced immune infiltration but suppressive immunophenotypes. ACAA2, ACAT1, ASRGL1, AKR1B10, ABCC2, ANGPTL4 were identified to construct the 6 gene-signature prognosis model and verified both internally and externally with ICGC cohorts. ACAA2 was demonstrated as a tumor suppressor and was associated with higher immune infiltration and elevated PD-1 expression of CD8⁺ T cells. Conclusions: Our research proposed a new metabolic classification method for RCC and revealed intrinsic associations between metabolic phenotypes and immune profiles. The identified gene signatures might serve as key factors bridging tumor metabolism and tumor immunity and warrant further in-depth investigations.

UroVysion^TM is a fluorescence in situ hybridization assay that was developed for the detection of bladder cancer (UC accounted for 90%) in urine specimens. It consists of fluorescently labeled DNA probes to the pericentromeric regions of chromosomes 3, 7, 17 and to the 9p21 band location of the P16 tumor suppressor gene, which was approved by the Food and Drug Administration (FDA) in 2001 and 2005, respectively, for urine detection in patients with suspected bladder cancer and postoperative recurrence monitoring. Furthermore, recent studies also demonstrated that U-FISH was useful for assessing superficial bladder cancer patients’ response to Bacillus Calmette–Guérin therapy and in detecting upper tract urothelial carcinoma. Therefore, positive U-FISH was well known to urologists as a molecular cytogenetic technique for the detection of UC. However, with the continuous enrichment of clinical studies at home and abroad, U-FISH has shown a broader application space in the detection of various urinary primary tumors and even metastatic tumors. This review focuses on summarizing the research status of U-FISH in UC, non-urothelial carcinoma and metastatic tumor, so as to strengthen urologists’ more comprehensive understanding of the application value of U-FISH and better complete the accurate diagnosis and treatment of urological cancers.