Comprehensive analysis of E47­like factors and verification of ELF4 in clear cell renal cell carcinoma.

Clear cell renal cell carcinoma (ccRCC) is the most prominent subtype of renal cancer and E47-like factors (ELFs) are important in tumorigenesis; however, the specific role of key ELFs in ccRCC remains unclear. The present study comprehensively analyzed RNA sequencing and clinical data from multiple databases, and identified differentially expressed ELFs (ELF3-5) in ccRCC. The DNA promoter methylation, genetic variation and clinical significance of ELF3-5 in ccRCC were analyzed using the cBioPortal and UALCAN databases. The association between ELF3-5 and multiple immune cell infiltration was analyzed using Tumor Immune Estimation Resource. Subsequently, ELF4 was selected and its association with biological functions was assessed. Cell counting kit-8 (CCK-8), colony formation, Transwell, macrophage chemotaxis and polarization assays were conducted to validate the functions of ELF4. Notably, the mRNA expression levels of ELF4 were significantly upregulated in ccRCC, whereas ELF3 and ELF5 mRNA expression levels were significantly downregulated. Clinical significance analysis revealed that ELF4 showed a high clinical significance with tumor grade, clear cell type A and B subtypes, and incidence rates of amplification in genetic variation. Further analyses indicated that ELF4 may be involved in multiple immune cell differentiation. Additionally, cell experiments revealed that ELF4 inhibition downregulated 769-P and 786-O proliferation, migration and invasion. Knockdown of ELF4 in cancer cells also inhibited M2 macrophage polarization and chemotaxis towards 769-P and 786-O cells. Conclusively, the present findings indicated the clinical significance of ELF4 in ccRCC, and verified its key role in driving cell proliferation, migration and invasion, and promoting M2 macrophage polarization and chemotaxis in ccRCC.

TREM-1 as a potential prognostic biomarker associated with immune infiltration in clear cell renal cell carcinoma.

BACKGROUND: The tumor immune microenvironment plays a crucial role in the efficacy of various therapeutics. However, their correlation is not yet completely understood in Clear cell renal cell carcinoma (ccRCC). This study aimed to investigate the potential of TREM-1 as a potential novel biomarker for ccRCC. METHODS: We constructed a ccRCC immune prognostic signature. The clinical characteristics, the status of the tumor microenvironment, and immune infiltration were analyzed through the ESTIMATE and CIBERSORT algorithms for the hub gene, while the Gene Set Enrichment Analysis and PPI analysis were performed to predict the function of the hub gene. Immunohistochemical staining was used to detect the expression of TREM-1 in renal clear cell carcinoma tissues. RESULTS: The CIBERSORT and ESTIMATE algorithms revealed that TREM-1 was correlated with the infiltration of 12 types of immune cells. Therefore, it was determined that TREM-1 was involved in numerous classical pathways in the immune response via GSEA analysis. In Immunohistochemical staining, we found that the expression of TREM-1 was significantly upregulated with increasing tumor grade in renal clear cell carcinoma, and elevated TREM-1 expression was associated with poor prognosis. CONCLUSIONS: The results suggest that TREM-1 may act as an implicit novel prognostic biomarker in ccRCC that could be utilized to facilitate immunotherapeutic strategy.

Development of a novel nomogram for predicting clinically significant prostate cancer with the prostate health index and multiparametric MRI.

Introduction: On prostate biopsy, multiparametric magnetic resonance imaging (mpMRI) and the Prostate Health Index (PHI) have allowed prediction of clinically significant prostate cancer (csPCa). Methods: To predict the likelihood of csPCa, we created a nomogram based on a multivariate model that included PHI and mpMRI. We assessed 315 males who were scheduled for prostate biopsies. Results: We used the Prostate Imaging Reporting and Data System version 2 (PI-RADS V2) to assess mpMRI and optimize PHI testing prior to biopsy. Univariate analysis showed that csPCa may be identified by PHI with a cut-off value of 77.77, PHID with 2.36, and PI-RADS with 3 as the best threshold. Multivariable logistic models for predicting csPCa were developed using PI-RADS, free PSA (fPSA), PHI, and prostate volume. A multivariate model that included PI-RADS, fPSA, PHI, and prostate volume had the best accuracy (AUC: 0.882). Decision curve analysis (DCA), which was carried out to verify the nomogram's clinical applicability, showed an ideal advantage (13.35% higher than the model that include PI-RADS only). Discussion: In conclusion, the nomogram based on PHI and mpMRI is a valuable tool for predicting csPCa while avoiding unnecessary biopsy as much as possible.

Association between health behaviours and the COVID-19 vaccination: risk compensation among healthcare workers in Taizhou, China.

This study is conducted to explore the association between health behaviors and the COVID-19 vaccination based on the risk compensation concept among health-care workers in Taizhou, China. We conducted a self-administered online survey to estimate the health behaviors among the staff in a tertiary hospital in Taizhou, China, from May 18 to 21 May 2021. A total of 592 out of 660 subjects (89.7%) responded to the questionnaire after receiving an e-poster on WeChat. Subjects who had been inoculated with the COVID-19 vaccine were asked to mention the differences in their health behaviors before and after the vaccination. The results showed that there were no statistical differences in health behaviors between vaccinated and unvaccinated groups, except in terms of the type of gloves they used (62.8% in the vaccinated group and 49.2% in the unvaccinated group, p = .048). Subjects who received earlier COVID-19 vaccinations exhibited better health behaviors (22.40% increased for duration of wearing masks (P = .007), 25.40% increased for times of washing hands (P = .01), and 20.90% increased for times of wearing gloves (P = .01)). Subjects also revealed better health behaviors (washing hands, wearing gloves, and wearing masks) after vaccination compared to that before. In conclusion, concept of risk compensation was not applied in our findings. The health behaviors did not reduce after the COVID-19 vaccination, which even may improve health behaviors among health-care workers in the hospital setting.

The Significance of INHBE Expression in the Cancer Cells of Clear-Cell Renal Cell Carcinoma.

BACKGROUND: Activins and inhibins are structurally related dimeric glycoprotein hormones belonging to the transforming growth factor-ß superfamily but whether they are also involved in malignancy is far from clear. No study has reported the expression of INHBE in kidney cancer. The purpose of this study was to examine the expressions of INHBE in the tumor tissue of patients with clear-cell renal cell carcinoma (ccRCC) and to explore the pathologic significance. METHODS: The INHBE mRNA expression in the tumor tissue of ccRCC patients was analyzed by using RNA sequencing data from the TCGA database. To examine the expression of inhibin ßE protein, 241 ccRCC patients were recruited and immunohistochemistry was performed on the tumor tissue of these patients along with 39 normal renal samples. The association between the inhibin ßE expression level and patient's clinicopathological indices was evaluated. RESULTS: In the normal renal tissue, inhibin ßE was found to be expressed mainly by renal tubular epithelial cells. In the tumor tissue, inhibin ßE was expressed mainly in cancer cells. The expressions of INHBE mRNA and protein in the tumor tissue of ccRCC patients increased significantly compared with those in normal renal samples. There was a significant correlation between the level of inhibin ßE in the tumor tissue and tumor grade. Patients with a lower inhibin ßE expression in the tumor tissue were found to have a longer overall survival and disease-specific survival. CONCLUSIONS: INHBE might be involved in the pathogenesis of ccRCC and function as a tumor promoter.

Antibiotic Sensitivity of Proteus mirabilis Urinary Tract Infection in Patients with Urinary Calculi.

Background: The study's objective was to determine Proteus mirabilis susceptibility in individuals with urinary tract infections and stones to antibiotics and prescribe optimal antimicrobial treatment. Methods: Nonrepetitive Proteus mirabilis strains were isolated from urine specimens obtained from 317 patients diagnosed with urinary stones from January, 2018, to December, 2021. A VITEK mass spectrometer was used for species identification, and a VITEK-compact 2 automatic microbial system was used for the antimicrobial susceptibility test (AST). Susceptibility to imipenem and cefoperazone/sodium sulbactam was tested by the disc diffusion method (K-B method). The antibiotic sensitivity of the strains was analyzed by sex and season. Results: A total of 317 patients were reviewed: 202 females (63.7%) and 115 males (36.3%). Proteus mirabilis infections were observed during spring (21.8%, n = 69), summer (26.2%, n = 83), autumn (33.8%, n = 107), and winter (18.2%, n = 57). Proteus mirabilis infections in females were diagnosed most often during the fall (24.3%, n = 77) and during the summer in males (11.0%, n = 35) (p = 0.010). Female patients responded best to levofloxacin (p = 0.014), and male patients responded best to sulfamethoxazole (p = 0.023). Seasonal variation in antibiotic sensitivity was confirmed, with significantly higher rates in the winter for cefuroxime (p = 0.002) and sulfamethoxazole (p = 0.002). Significant seasonal increases were also found in levofloxacin sensitivity during the summer (p = 0.005). Conclusions: Highly effective antibiotics such as cefoxitin and ceftazidime should be used empirically by considering antibiotic sensitivity changes by sex, season, and year. Regional studies should be conducted frequently.

Pelvic lipomatosis with cystitis glandularis managed with cyclooxygenase-2 inhibitor: A case report.

BACKGROUND: Pelvic lipomatosis (PL) is a rare benign condition with characteristic overgrowth of histologically benign fat and invasion and compression of pelvic organs, often leading to non-specific lower urinary tract symptoms (LUTS). Approximately 40% of patients with PL have cystitis glandularis (CG). The cause of PL combined with CG is poorly understood, and there is currently no effective treatment. Refractory CG with upper urinary tract obstruction even requires partial or radical bladder resection. CASE SUMMARY: In this case, a patient suffering from PL with CG was treated by transurethral resection of bladder tumour (TUR-BT) and oral administration of celecoxib, a selective cyclooxygenase-2 (COX-2) inhibitor. The LUTS were alleviated, and the cystoscopy results improved significantly. Immunohistochemistry showed up-regulated COX-2 expression in the epithelium of TUR-BT samples, suggesting that COX-2 may participate in the pathophysiological process of PL combined with CG. CONCLUSION: We report for the first time that celecoxib may be an effective treatment strategy for PL combined with refractory CG.

LncRNA PCGEM1 promotes renal carcinoma progression by targeting miR-433-3p to regulate FGF2 expression.

Long non-coding RNAs (lncRNAs) are implicated in the development of carcinomas, containing renal carcinoma. The competing endogenous RNA (ceRNA) network is well-known in modulating the pathological and physiological processes of tumors. Still and all, the function role of oncogenic lncRNA PCGEM1 prostate-specific transcript (PCGEM1) in renal carcinoma was undefined till now. This paper aimed to figure out the role and mechanism of PCGEM1 in renal carcinoma. In this study, PCGEM1 was observed to be lifted in renal carcinoma cells. Loss-of-function experiments displayed that silencing of PCGEM1 repressed cell proliferation and migration, and activated apoptosis in renal carcinoma. FISH assay and subcellular fractionation assay indicated that PCGEM1 was largely located in the cytoplasm. As demonstrated, PCGEM1 interacted with microRNA433-3p (miR-433-3p). Subsequently, luciferase reporter and RIP experiments together with qRT-PCR certified that PCGEM1 and fibroblast growth factor 2 (FGF2) functioned as ceRNA for miR-433-3p, leading to the upregulation of FGF2 expression. Finally, rescue assays exhibited that FGF2 overexpression rescued the inhibited cell progression caused by PCGEM1 downregulation. MiR-433-3p inhibitor could reverse the cell growth and migration caused by PCGEM1 downregulation. The present research investigated the molecular mechanism underlying PCGEM1 in renal carcinoma, exposing a PCGEM1-mediated therapy for the treatment of patients with renal carcinoma.

Ubiquitin ligase SMURF1 functions as a prognostic marker and promotes growth and metastasis of clear cell renal cell carcinoma.

Smad ubiquitin regulatory factor 1 (SMURF1), a recently identified E3 ubiquitin ligase, targets substrate proteins for ubiquitination and proteasomal degradation. Previous studies have reported that SMURF1 also functions as an oncogene in human cancers. However, the clinical value of SMURF1 and its role in clear cell renal cell carcinoma (ccRCC) are unknown. SMURF1 expression was analyzed in 100 cases of ccRCC and matched tumor-adjacent specimens. SMURF1 was prominently overexpressed in ccRCC specimens compared with tumor-adjacent specimens. Increased levels of SMURF1 were also observed in ccRCC cell lines. Clinicopathological detection verified that SMURF1 expression was associated with advanced tumor node metastasis stage, large tumor size and vascular invasion of ccRCC patients. Moreover, Kaplan-Meier analysis found that SMURF1 elevation led to adverse overall survival and disease-free survival. Multivariate Cox regression analysis revealed that SMURF1 expression was an independent marker for prognosis prediction. Further experiments illustrated that SMURF1 knockdown significantly inhibited growth and metastasis of 769P cells, while SMURF1 overexpression promoted proliferation, migration and invasion in OSRC-2 cells. Mechanistically, SMURF1 inversely regulated the expression of DAB2 interacting protein, which negatively mediated the activation of both the ERK/RSK1 and PI3K/AKT/mTOR pathways in ccRCC cells. Taken together, these results suggest that SMURF1 might be a promising biomarker and target for novel treatment of human ccRCC.

Comparison between zoledronic acid and clodronate in the treatment of prostate cancer patients with bone metastases.

The aim of this study is to compare the efficacy and safety between zoledronic acid (ZA) and clodronate (CA) in the treatment of bone metastases for prostate cancer patients. We conducted a prospective study in recruiting 137 prostate cancer patients with bone metastases from 2008 to 2010. All men were well responding to first-line hormone therapy (PSA < 2 ng/mL); Patients were randomly assigned to receive zoledronic acid (4 mg over a 30 min infusion) every 1 month or to take 4 tablets per day of clodronate (1,600 mg) for up to 3 years. Bone mineral density (BMD) was measured by dual-energy X-ray absorptiometry at femoral neck, lumbar spine, and total hip, together with visual analog scale score were evaluated on baseline and 6, 12, 24, and 36 months, respectively. Toxicity and skeletal-related events (SREs) happened in both groups during this period were recorded down and compared. The ZA group had better bone progression-free survival (BPFS) (31 months vs 22 months, P = 0.04), but no statistical evidence of benefit was observed in terms of overall survival rate. The ZA group significantly increased lumbar spine BMD (4.5 ± 2.3 % vs CA group 2.3 ± 3.9 % P = 0.03), had a better response on pain-relieve effect (92 vs 76 % P = 0.002) and a rapid pain palliation (9 months vs 13 months P = 0.03). The CA group reported more gastrointestinal cases. However, the ZA group required more dose modifications. As compared to clodronate, Zoledronic acid has advantages on extending BPFS, better bone pain control and lumbar spine BMD performance for prostate cancer patients with bone metastases. The overall survival rate and SREs rate are similar.