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Background The encapsulation of circular RNAs (circRNAs) into extracellular vesicles (EVs) enables their involvement in intercellular communication and exerts an influence on the malignant advancement of various tumors. However, the regulatory role of EVs-circRNA in renal cell carcinoma (RCC) remains elusive. Methods The in vitro and in vivo functional experiments were implemented to measure the effects of circEHD2 on the phenotype of RCC. The functional role of EVs-circEHD2 on the activation of fibroblasts was assessed by collagen contraction assay, western blotting, and enzyme-linked immunosorbent assay (ELISA). The mechanism was investigated by RNA pull-down assay, RNA immunoprecipitation, chromatin isolation by RNA purification, luciferase assay, and co-immunoprecipitation assay. Results We demonstrated that circEHD2 was upregulated in RCC tissues and serum EVs of RCC patients with metastasis. Silencing circEHD2 inhibited tumor growth in vitro and in vivo. Mechanistic studies indicated that FUS RNA -binding protein (FUS) accelerated the cyclization of circEHD2, then circEHD2 interacts with tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein eta (YWHAH), which acts as a bridge to recruit circEHD2 and Yes1-associated transcriptional regulator (YAP) to the promoter of SRY-box transcription factor 9 (SOX9); this results in the sustained activation of SOX9. Heterogeneous nuclear ribonucleoprotein A2/B1 (hnRNPA2B1) regulates the package of circEHD2 into EVs, then EVs-circEHD2 transmits to fibroblasts, converting fibroblasts to cancer-associated fibroblasts (CAFs). Activated CAFs promote the metastasis of RCC by secreting pro-inflammatory cytokines such as IL-6. Furthermore, antisense oligonucleotides (ASOs) targeting circEHD2 exhibited a strong inhibition of tumor growth in vivo. Conclusions The circEHD2/YWHAH/YAP/SOX9 signaling pathway accelerates the growth of RCC. EVs-circEHD2 facilitates the metastasis of RCC by converting fibroblasts to CAFs. Our results suggest that EVs-circEHD2 may be a useful biomarker and therapeutic target for RCC.

Metabolic syndrome (MS) is an increasing public health concern because of rapid lifestyle changes. Although there have been previous studies on the prevalence of MS in China, the prevalence may have changed with lifestyle changes over the last decade. To update this prevalence, we performed a cross-sectional survey among adults over 18 years old across China from May 2013 to July 2014. Participants underwent questionnaires and provided blood and urine samples for analysis. MS was defined according to the criteria of the China Diabetes Society. A total of 12570 individuals (45.2% men) with an average age of 48.8±15.3 (18-96) years were selected and invited to participate in the study. In total, 9310 (40.7% men) individuals completed the investigation, with a response rate of 74.1%. The prevalence of MS in China was 14.39% [95% confidence interval (CI): -3.75-32.53%], and the age-adjusted prevalence was 9.82% (95% CI: 9.03-10.61%; 7.78% in men and 6.76% in women; 7.39% in rural residents and 6.98% in urban residents). The highest prevalence occurred among adults aged 50-59 years (1.95%, 95% CI: 1.40-2.50%), and the lowest prevalence occurred among adults aged 40-49 years (0.74%, 95% CI: 0.38-1.10%); the prevalence was the highest in the south region and lowest in the east region (4.46% and 1.23%, respectively). The results of logistic regression analyses showed that age, urolithiasis, hyperuricemia, coronary artery disease, thiazide drugs intake, family history of diabetes and hypertension were all significantly associated with an increased risk of metabolic syndrome (OR>1). In addition, education, vitamin D intake and family history of urolithiasis are all protective factors (OR<1). Our results indicate that there was a high prevalence of MS in Chinese adults. Compared to the previous study 10 years ago, some preventive strategies have worked; however, further work on the prevention and treatment of MS remains necessary.

The aim of this study was to elucidate the correlation between m6A modification and the tumor immune microenvironment (TIME) in prostate cancer (PCa) and to identify the m6A regulation patterns suitable for immune checkpoint inhibitors (ICIs) therapy. We evaluated the m6A regulation patterns of PCa based on 24 m6A regulators and correlated these modification patterns with TIME characteristics. Three distinct m6A regulation patterns were determined in PCa. The m6A regulators cluster with the best prognosis had significantly increased METTL14 and ZC3H13 expression and was characterized by low mutation rate, tumor heterogeneity, and neoantigens. The m6A regulators cluster with a poor prognosis had markedly high KIAA1429 and HNRNPA2B1 expression and was characterized by high intratumor heterogeneity and Th2 cell infiltration, while low Th17 cell infiltration and Macrophages M1/M2. The m6Ascore was constructed to quantify the m6A modification pattern of individual PCa patients based on m6A-associated genes. We found that the low-m6Ascore group with poor prognosis had a higher immunotherapeutic response rate than the high-m6Ascore group. The low-m6Ascore group was more likely to benefit from ICIs therapy. This study was determined that immunotherapy is more effective in low-m6Ascore PCa patients with poor prognosis.

Kidney stone is a chronic metabolic disease that caused by many factors, especially by the metabolic disturbances of urine compositions, but the metabolic profiling of the urine from kidney stone patients remains poorly explored. In the present study, 1H NMR spectroscopy and multivariate pattern recognition analytical techniques were combined to explore the metabolic profiling of the urine from kidney stone patients. A total of 216 urine samples obtained from kidney stone patients (n = 110) and healthy controls (n = 106) were investigated. The results indicated that principal component analysis (PCA) and partial least-squares discriminant analysis (PLS-DA) models were capable of distinguishing kidney stone patients from healthy controls. In addition, a total of 15 metabolites was obviously different in concentration between the two groups. Furthermore, four metabolic pathways, including glyoxylate and dicarboxylate metabolism, glycine, serine and threonine metabolism, phenylalanine metabolism and citrate cycle (TCA cycle), were closely associated with kidney stone. Together, our results established a preliminary metabolic profiling of the urine from kidney stone patients via using 1H NMR-based analytical techniques for the first time and provided a novel method for recognizing and observing the kidney stone disease.

There has been significant uncertainty in the selection of candidates for cytoreductive nephrectomy (CN) in patients with metastatic renal cell carcinoma (mRCC). This report investigates the influence of site-specific metastases (bone, brain, liver, and lung) on the survival benefit of CN. Within the Surveillance, Epidemiology and End Results database (2010-2014), 1113 mRCC patients treated with CN (n = 618) or no surgery (NS, n = 495) met the selection criteria. 168 pairs of patients using propensity scores were matched to balance the selection bias of undergoing CN. Multivariable competing risks regression analysis was used to calculate cancer-specific mortality (CSM) and overall survival (OS). Cases were subdivided to investigate the advantages of each procedure. Before or after matching, CN led to better OS and lower CSM in Kaplan-Meier analysis. In matched cohort, decreased CSM after CN compared to without CN were consistently found in most subgroups stratified by age, T stage, and patients with ≤2 site-specific metastases. However, patients with ≥ 3 site-specific metastases, or patients with ≥cT3 stage combined with ≥ 2 site-specific metastases were not benefit from the cytoreductive nephrectomy. The potential benefit of CN disappeared in patients with ≥ 3 site-specific metastases, or patients with ≥cT3 combined with ≥ 2 site-specific metastases.

BackgroundRecent studies have focused on the correlation between N6-methyladenosine (m6A) modification and specific tumor-infiltrating immune cells. However, the potential roles of m6A modification in the tumor immune landscape remain elusive.MethodsWe comprehensively evaluated the m6A modification patterns and tumor immune landscape of 513 clear cell renal cell carcinoma (ccRCC) patients, and correlated the m6A modification patterns with the immune landscape. The m6Ascore was established using principal component analysis. Multivariate Cox regression analysis was performed to evaluate the prognostic value of the m6Ascore.ResultsWe identified three m6Aclusters—characterized by differences in Th17 signature, extent of intratumor heterogeneity, overall cell proliferation, aneuploidy, expression of immunomodulatory genes, overall somatic copy number alterations, and prognosis. The m6Ascore was established to quantify the m6A modification pattern of individual ccRCC patients. Further analyses revealed that the m6Ascore was an independent prognostic factor of ccRCC. Finally, we verified the prognostic value of the m6Ascore in the programmed cell death protein 1 (PD-1) blockade therapy of patients with advanced ccRCC.ConclusionsThis study demonstrated the correlation between m6A modification and the tumor immune landscape in ccRCC. The comprehensive evaluation of m6A modification patterns in individual ccRCC patients enhances our understanding of the tumor immune landscape and provides a new approach toward new and improved immunotherapeutic strategies for ccRCC patients.

The aim of this study was to determine whether the presence or degree of hydronephrosis (HN) affects the stone disintegration efficacy of shock wave lithotripsy (SWL). A comprehensive literature search using PubMed, Embase, Cochrane Library, and Web of Science was conducted to retrieve relevant studies. Risk ratios (RRs) and mean differences (MDs) with corresponding 95% confidence intervals (CIs) were calculated for comparisons of outcomes of interest. In total, seven comparative studies with 2033 patients were included. Overall results indicated no significant difference in stone-free rate (SFR) and retreatment rate between two groups. Subgroup analysis further revealed: (1) compared with moderate or severe HN, non-HN SWL brought significantly lower retreatment rate (RR 0.67, 95%CI 0.52–0.87, P = 0.002 and RR 0.55, 95%CI: 0.40–0.76, P = 0.0003, respectively) and shorter clearance time (MD − 3.80, 95%CI − 5.81 to − 1.79, P = 0.0002 and MD – 5.93, 95%CI − 10.29 to − 1.57, P = 0.008, respectively); (2) SWLs performed without stone-induced HN or with artificial HN were associated with significantly higher SFR (RR 1.11, 95%CI 1.04−1.18, P = 0.001 and RR 0.93, 95%CI 0.87−0.99, P = 0.02, respectively); (3) non-HN SWL brought significantly higher SFR than HN group when treating proximal ureteral stones (RR 1.14, 95%CI 1.04–1.24, P = 0.005). Generally, SWLs performed with HN were shown to offer similar stone disintegration efficacy to those without HN. However, it seemed preferable to perform SWL: (1) without severe to moderate HN or stone-induced HN; (2) with artificial HN; (3) without HN when treating proximal ureteral stones.

Clear cell renal cell carcinoma (ccRCC) is the most common subtype of renal cell carcinoma (RCC), and is frequently accompanied by the genetic features of von Hippel–Lindau (VHL) loss. VHL loss increases the expression of hypoxia-inducible factors (HIFs) and their targets, including epidermal growth factor (EGF), vascular endothelial growth factor (VEGF), and platelet-derived growth factor (PDGF). The primary treatment for metastatic RCC (mRCC) is molecular-targeted therapy, especially anti-angiogenic therapy. VEGF monoclonal antibodies and VEGF receptor (VEGFR) tyrosine kinase inhibitors (TKIs) are the main drugs used in anti-angiogenic therapy. However, crosstalk between VEGFR and other tyrosine kinase or downstream pathways produce resistance to TKI treatment, and the multi-target inhibitors, HIF inhibitors or combination strategies are promising strategies for mRCC. HIFs are upstream of the crosstalk between the growth factors, and these factors may regulate the expression of VEGR, EGF, PDGF and other growth factors. The frequent VHL loss in ccRCC increases HIF expression, and HIFs may be an ideal candidate to overcome the TKI resistance. The combination of HIF inhibitors and immune checkpoint inhibitors is also anticipated. Various clinical trials of programmed cell death protein 1 inhibitors are planned. The present study reviews the effects of current and potential TKIs on mRCC, with a focus on VEGF/VEGFR and other targets for mRCC therapy.

Prostate cancer (PCa) is a common urinary malignancy, whose molecular mechanism has not been fully elucidated. We aimed to screen for key genes and biological pathways related to PCa using bioinformatics method. Differentially expressed genes (DEGs) were filtered out from the GSE103512 dataset and subjected to the gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses. The protein-protein interactions (PPI) network was constructed, following by the identification of hub genes. The results of former studies were compared with ours. The relative expression levels of hub genes were examined in The Cancer Genome Atlas (TCGA) and Oncomine public databases. The University of California Santa Cruz Xena online tools were used to study whether the expression of hub genes was correlated with the survival of PCa patients from TCGA cohorts. Totally, 252 (186 upregulated and 66 downregulated) DEGs were identified. GO analysis enriched mainly in \"oxidation-reduction process\" and \"positive regulation of transcription from RNA polymerase II promoter\"; KEGG pathway analysis enriched mostly in \"metabolic pathways\" and \"protein digestion and absorption.\" Kallikrein-related peptidase 3, cadherin 1 (CDH1), Kallikrein-related peptidase 2 (KLK2), forkhead box A1 (FOXA1), and epithelial cell adhesion molecule (EPCAM) were identified as hub genes from the PPI network. CDH1, FOXA1, and EPCAM were validated by other relevant gene expression omnibus datasets. All hub genes were validated by both TCGA and Oncomine except KLK2. Two additional top DEGs (ABCC4 and SLPI) were found to be associated with the prognosis of PCa patients. This study excavated the key genes and pathways in PCa, which might be biomarkers for diagnosis, prognosis, and potential therapeutic targets.

Background Upper urinary tract stones is the most common diseases in urology. Percutaneous nephrolithotomy (PCNL) and ureteroscopic lithotripsy (fURL) are common treatment, but both their efficacy and safety are controversial. Thus we aim to evaluate the efficacy and safety of PCNL and fURL in the treatment of upper urinary tract stones, providing a reference for clinical work. Methods PubMed, Web of Science, Embase and CNKI were searched through Apr. 1, 2019 to identify eligible studies. Data were analyzed by using RevMan 5.3 and Stata 12.0 software. Pooled relative risks (RRs) or weighted mean difference (WMD) with 95% confidence intervals (CIs) were calculated using fixed or random effects methods. Publication bias and sensitivity analysis were performed. Results Four randomized controlled trials (RCTs), fifteen cohort studies involving 1822 patients were included. Stone-free rate of PCNL was significantly high than that of fURL (RR: 1.07; 95% CI: 1.03, 1.12; P  = 0.0004). The decline of hemoglobin in PCNL was significantly high than that of fURL (WMD: 1.07; 95% CI: 0.54, 1.61; P  < 0.0001). The number of blood transfusion was significantly greater in the PCNL compared to the fURL (RR: 5.04; 95% CI: 1.78, 14.24; P  = 0.002). The incidence of postoperative bleeding or hematuria showed greater significantly difference in the PCNL compared to the fURL (RR: 2.72; 95% CI: 1.55, 4.75; P  = 0.0005). Operation time, fever, infection, perforation, requiring drug analgesia was not significantly different between two surgical procedures. Conclusions In the treatment of upper urinary tract stones, the stones clearance rate of PCNL is higher than fURL, and the safety of fURL is higher than PCNL.