Diagnostic Accuracy and Interobserver Agreement of PI-RADS Version 2 and Version 2.1 for the Detection of Transition Zone Prostate Cancers.

BACKGROUND. PI-RADS version 2.1 (v2.1) introduced a number of key changes to the assessment of transition zone (TZ) lesions. OBJECTIVE. The purpose of this study was to evaluate interobserver agreement and diagnostic accuracy for detecting TZ prostate cancer (PCa) and clinically significant PCa (csPCa) by use of PI-RADS v2 and PI-RADS v2.1 among radiologists with different levels of experience. METHODS. This retrospective study included 355 biopsy-naïve patients who from January 2017 to March 2020 underwent prostate MRI that showed a TZ lesion and underwent subsequent biopsy. PCa was diagnosed in 93 patients (International Society of Urological Pathology [ISUP] grade group 1, n = 34; ISUP grade group ≥ 2, n = 59) and non-cancerous lesions in 262 patients. Five radiologists with varying experience in prostate MRI scored lesions using PI-RADS v2 and PI-RADS v2.1 in sessions separated by at least 4 weeks. Interobserver agreement was evaluated with kappa and Kendall W statistics. ROC curve analysis was used to evaluate performance in detection of TZ PCa and csPCa. RESULTS. Interobserver agreement among all readers was higher for PI-RADS v2.1 than for PI-RADS v2 (mean weighted κ = 0.700 vs 0.622; Kendall W = 0.805 vs 0.728; p = .03). The pooled AUC values for detecting TZ PCa and csPCa were higher among all readers using PI-RADS v2.1 (0.866 vs 0.827 for TZ PCa; 0.929 vs 0.899 for TZ csPCa; p < .001). For detecting TZ PCa, the pooled sensitivity, specificity, and accuracy were 86.9%, 79.4%, and 75.4% among all readers for PI-RADS v2.1 compared with 79.4%, 71.8%, and 73.8% for PI-RADS v2. For detecting TZ csPCa, the pooled sensitivity, specificity, and accuracy were 84.8%, 90.9%, and 89.9% among all readers for PI-RADS v2.1 compared with 81.4%, 89.9%, and 88.5% for PI-RADS v2. Reader 1, who had the least experience, had the lowest sensitivity, specificity, and accuracy (78.0%, 89.2%, and 87.3%). Reader 5, who had the most experience, had the highest sensitivity, specificity, and accuracy (88.1%, 92.9%, and 92.1%) in detecting csPCa. CONCLUSION. PI-RADS v2.1 had better interobserver agreement and diagnostic accuracy than PI-RADS v2 for evaluating TZ lesions. Reader experience continues to affect the performance of prostate MRI interpretation with PI-RADS v2.1. CLINICAL IMPACT. PI-RADS v2.1 is more accurate and reproducible than PI-RADS v2 for the diagnosis of TZ PCa.

LncRNA SNHG3 promotes bladder cancer proliferation and metastasis through miR-515-5p/GINS2 axis.

Growing evidence suggests that long non-coding RNAs (lncRNAs) are associated with carcinogenesis. LncRNA small nucleolar RNA host gene 3 (SNHG3) is up-regulated in various cancers and positively associated with poor prognosis of these cancers. However, the precise role of lncRNA SNHG3 in bladder cancer (Bca) remains unclear. In our research, we first reported that lncRNA SNHG3 was up-regulated in bladder cancer tissues and positively related to poor clinical prognosis. Moreover, knockdown of lncRNA SNHG3 significantly suppressed the proliferation, migration, invasion and EMT process of Bca cells in vitro and vivo. Mechanistically, we revealed that suppression of SNHG3 evidently enhanced miR-515-5p expression and decreased GINS2 expression at posttranscriptional levels. Moreover, SNHG3 positively regulated GINS2 expression by sponging miR-515-5p under a competing endogenous RNA (ceRNA) mechanism. To sum up, our study suggested lncRNA SNHG3 acted as a microRNA sponge and an oncogenic role in the progression of bladder cancer.

Blockage of O-linked GlcNAcylation induces AMPK-dependent autophagy in bladder cancer cells.

BACKGROUND: High levels of the post-translational modification O-GlcNAcylation (O-GlcNAc) are found in multiple cancers, including bladder cancer. Autophagy, which can be induced by stress from post-translational modifications, plays a critical role in maintaining cellular homeostasis and regulating tumorigenesis. The impact of O-GlcNAcylation on autophagy in bladder cancer remains unclear. Here, we evaluate the change in autophagic activity in response to O-GlcNAcylation and explore the potential mechanisms. METHODS: O-GlcNAcylation levels in bladder cancer cells were altered through pharmacological or genetic manipulations: treating with 6-diazo-5-oxo-norleucine (DON) or thiamet-G (TG) or up- and downregulation of O-GlcNAc transferase (OGT) or O-GlcNAcase (OGA). Autophagy was determined using fluorescence microscopy and western blotting. Co-immunoprecipitation (Co-IP) assays were performed to evaluate whether the autophagy regulator AMP-activated protein kinase (AMPK) was O-GlcNAc modified. RESULTS: Cellular autophagic flux was strikingly enhanced as a result of O-GlcNAcylation suppression, whereas it decreased at high O-GlcNAcylation levels. Phosphorylation of AMPK increased after the suppression of O-GlcNAcylation. We found that O-GlcNAcylation of AMPK suppressed the activity of this regulator, thereby inhibiting ULK1 activity and autophagy. CONCLUSION: We characterized a new function of O-GlcNAcylation in the suppression of autophagy via regulation of AMPK. GRAPHICAL ABSTRACT: Blockage of O-linked GlcNAcylation induces AMPK dependent autophagy in bladder cancer cells.

Coexpression Analysis of the EZH2 Gene Using The Cancer Genome Atlas and Oncomine Databases Identifies Coexpressed Genes Involved in Biological Networks in Breast Cancer, Glioblastoma, and Prostate Cancer.

BACKGROUND This study aimed to perform coexpression analysis of the EZH2 gene using The Cancer Genome Atlas (TCGA) and the Oncomine databases to identify coexpressed genes involved in biological networks in breast cancer, glioblastoma, and prostate cancer, with functional analysis of the EZH2 gene in the C4-2 human prostate cancer cell line in vitro. MATERIAL AND METHODS Data from TCGA and Oncomine databases were analyzed to determine the expression of EZH2 and the top five coexpressed genes in breast cancer, glioblastoma, and prostate cancer and the clinical significance the coexpressed genes. Gene Ontology (GO) analysis was performed to predict the functions and pathways of EZH2 using pathway annotation. The role of EZH2 in the C4-2 human prostate cancer cell line was studied in vitro. RESULTS Analysis of 16 micro-arrays identified 185 genes that were coexpressed with EZH2. The top five coexpressed genes were MCM4, KIAA0101, MKI67, RRM2, and CDC25a. Increased expression of these genes and EZH2 were associated with reduced survival. Coexpressed genes were involved in biological networks associated with the cell cycle, mitosis, and DNA damage. The effects of EZH2 on prostate cancer cell was validated in vitro as knockdown of EZH2 resulted in a G2/M cell cycle arrest, increased DNA damage, and reduced colony number. CONCLUSIONS Coexpression analysis of EZH2 identified its role in the cell cycle, mitosis, and DNA repair. The molecular mechanisms involved in EZH2 gene expression in the cell response to DNA damage requires further study to determine whether EZH2 is a potential human cancer biomarker.

Evaluation of clinical effects of microsurgical subinguinal varicocelectomy with and without testicular delivery.

The aim of this study was to access whether microsurgical subinguinal varicocelectomy (MSV) with testicular delivery has a better therapeutic effect than MSV without testicular delivery, including semen quality, serum testosterone (T) level and International Index of Erectile Function (IIEF)-5 score in infertility male patients with varicocele. In this prospective study, 181 patients were included and they chose the treatment by themselves. A total of 114 patients who received MSV without testicular delivery (TD) and 67 patients who received MSV with TD were followed-up 6 months after the operation. Semen parameters, serum T level and IIEF-5 scores were recorded before and 6 months after the operation. Results showed that MSV with or without TD could improve semen quality, serum T level and IIEF-5 score. For semen quality 6 months after the operation, there was no significant difference between patients received MSV with or without TD. But in patients with varicocele of grade III, MSV without testicular delivery improved the sperm concentration and motility more. And patients received MSV without TD have a higher T level 6 months after the operation, especially in patients ≤27 years. MSV with TD is not superior to that without, but this should be verified in more samples and a better designed randomised controlled study in the future.

Greenlight high-performance system (HPS) 120-W laser vaporization versus transurethral resection of the prostate for the treatment of benign prostatic hyperplasia: a meta-analysis of the published results of randomized controlled trials.

To assess the efficacy and the safety of Greenlight(TM) high-performance system (HPS) 120-W laser photoselective vaporization of the prostate (PVP) compared with transurethral resection of the prostate (TURP) for treatment of benign prostatic hyperplasia (BPH). The related original studies only including randomized controlled trials were searched by databases MEDLINE, EMBASE, Google Scholar, and the Cochrane Controlled Trial Register. The databases were updated till July 2014. The risk ratio, mean difference, and their corresponding 95% confidence intervals were calculated. Risk of bias of the enrolled trials were assessed according to Cochrane Handbook. A total of four trials involving 559 patients were enrolled. Statistical analysis was performed by software Review Manager (V5.3.3). There was no significant difference in International Prostate Symptom Score (IPSS) and maximum flow rate (Qmax) between PVP and TURP at 6-, 12-, and 24-month follow-up. Patients in the PVP group were associated with significantly lower risk of capsule perforation (risk ratio (RR) = 0.06, 95% confidence interval (95%CI) = 0.01 to 0.46; p = 0.007), significantly lower transfusion requirements (RR = 0.12, 95%CI = 0.03 to 0.43; p = 0.001), a shorter catheterization time (mean difference (MD) = -41.93, 95%CI = -54.87 to -28.99; p < 0.00001), and a shorter duration of hospital stay (MD = -2.09, 95%CI = -2.58 to -1.59; p < 0.00001) than that in the TURP group. In the TURP group, the patients were associated with a lower risk of re-operation (RR = 3.68, 95%CI = 1.04 to 13.00; p = 0.04) and a shorter operative time (MD = 9.28, 95%CI = 2.80 to 15.75; p = 0.005) than those in the PVP group. In addition, no statistically significant differences were detected between groups in terms of the rates of transurethral resection syndrome, urethral stricture, bladder neck contracture, incontinence, and infection. Greenlight(TM) 120-W laser PVP is as effective as TURP for symptom reduction and improvement of the quality of life. Laser PVP shows advantages over TURP in terms of intraoperative safety, whereas TURP is found to have a shorter operative time and lower re-operative risk.

Ailanthone suppresses cell proliferation of renal cell carcinoma partially via inhibition of EZH2.

BACKGROUND: Ailanthone (Ail) extracted from medicinal plants has played an anticancer role in multiple cancers, while there is no research about Ail in renal cell carcinoma (RCC). METHODS: In the present study, we performed CCK-8 and flow cytometry to assess the effect of Ail on cell viability, apoptosis and cycle. We also performed tandem mass tags (TMT)-labeled quantitative proteomic technology and bioinformatic analysis to identify the functional pathway and proteins of Ail in RCC. RESULTS: The results showed Ail could inhibit cell viability and induce cell apoptosis. Proteomic profiling identified 1732 differentially expressed proteins in cells treated with Ail, compared to the negative control group. Gene ontology function annotation and Gene Set Enrichment Analysis (GSEA) were performed to identified the involved biological processes, molecular function and pathway. Results of GSEA proved the enrichment of Deps in EZH2 targets. The comparison between Deps and EZH2 co-expressed genes revealed 44 overlapped genes and we identified 4 hub genes (CDC20, CEP55, TOP2A, and UBE2C) associated with RCC progression. The molecular docking study revealed a moderate to tight binding potential of Ail and EZH2, and western blotting showed EZH2 was suppressed after cells treated with Ail. CONCLUSION: Altogether, we identified the anticancer role of Ail in RCC, including inhibition of cell proliferation and induction of apoptosis. The results also screened the key proteins mediate the function of Ail, which have laid a theoretical foundation for elucidating the applications of Ail in clinical research.

The clinical significance and anti-tumor role of PRKG1 in bladder cancer.

Introduction: cGMP-dependent protein kinase 1 (PRKG1) has shown to be associated with some tumorigenesis, while the role of PRKG1 in bladder cancer is unclear. Methods: To investigate the biological and clinical significance of PRKG1 in bladder cancer, we detected the expression of PRKG1 and explored the function of PRKG1 in bladder cancer cells. The PRKG1 transcripts data was downloaded from The Cancer Genome Atlas (TCGA) database, and immunohistochemistry staining was conducted on formalin-fixed paraffin-embedded (FFPE) sample tissues. Relationship between clinical characteristics of patients and expression of PRKG1 was analyzed in FFPE samples, TCGA database, and GSE19423 dataset. PRKG1 was over-expressed, and cell proliferation, migration, invasion, apoptosis, and spheroidizing ability were then detected. Chemosensitivity to cisplatin was detected with cell viability, and half-maximal drug inhibitory concentration (IC50) was calculated. In addition, the relation between PRKG1 expression and the infiltration level of tumor immune cells in tumor microenvironment were analyzed. Results: The results showed expression of PRKG1 was lower in bladder cancer, compared with normal tissues both at protein and transcript levels. Lower PRKG1 expression was related to higher tumor grade, T stage, and muscle invasion, also predicted worse overall survival and recurrence free survival in patients treated with Bacillus Calmette-Guerin (BCG) intravesical immunotherapy. Analysis of tumor immune cells infiltration showed lower PRKG1 was associated with non-inflamed tumor microenvironment. Conclusion: The present study firstly identified the anti-tumor role and tumor immune regulatory role of PRKG1, also found loss of PRKG1 could be used as a prognosis factor. The present study provided a potential biomarker and therapy target to bladder cancer.

Chronic oral administration of L-carnitine induces testicular injury: in vivo evidence.

PURPOSE: While L-carnitine is commonly used to treat oligoasthenozoospermia, concerns have been raised regarding its potential harm to spermatogenesis. This study aims to investigate the potential testicular toxicity of long-term oral administration of L-carnitine. METHODS: In this study, we refer to the clinical adult dosage and mode of L-carnitine administration, and after converting to mouse doses, mice were daily intragastrical administered L-carnitine to investigate whether it was harmful to the testis. The investigation involved assessing its potential testicular toxicity through histopathological staining, sperm motility analysis, and quantitative real-time PCR. RESULTS: Our results showed that L-carnitine increased sperm motility after 14 days of continuous administration, but increased luminal exfoliated spermatogenic cells occurred in the testis, and TUNEL results showed increased apoptotic cells. Compared with the control group, the mRNA expression of the spermatogenic cell marker at each stage was decreased in mice treated for 14 consecutive days of L-carnitine. After 50 days of continuous administration followed by 14 days of drug withdrawal, the total sperm motility of mice was almost 0, and a large number of abnormal eosinophilic spermatogenic cells appeared in the testis. These indicate that oral L-carnitine for more than 14 days impairs spermatogenesis in mice, and sudden discontinuation of administration results in substantial death of established spermatogenic cell populations. CONCLUSION: Our findings suggest that chronic oral administration of L-carnitine impairs spermatogenic function in the testis. The oral administration of L-carnitine to enhance sperm motility should not exceed the 2/5 point of the spermatogenic cycle.

Erratum: CircNT5E promotes the proliferation and migration of bladder cancer via sponging miR-502-5p: Erratum.

[This corrects the article DOI: 10.7150/jca.53385.].

Comprehensive Analysis of Prognostic Value and Immune Infiltration of TFAP2 Family Members in Bladder Cancer from Database and FFPE Sample.

Background: Bladder cancer (BLCA) is one of the common malignant tumors worldwide. Recent studies have shown that Transcription factor activating protein-2(TFAP2) family proteins plays a bidirectional regulatory role in the process of tumorigenesis versus evolution by regulating the expression of tumor associated genes. However, little is known about the function of distinct TFAP2s proteins in patient with BLCA. Methods: Formalin-fixed paraffin-embedded (FFPE) sample tissues and clinical data of 240 patients with bladder cancer were collected for immunohistochemical analysis. The Human Protein Atlas, Gene Expression Profiling Interactive Analysis (GEPIA), Shiny Methylation Analysis Resource Tool (SMART), Kaplan-Meier plotter, cBioPortal, Metascape, LinkedOmics, TIMER and CIBERSORT were utilized to analyze differential expression, prognostic value, genetic alteration and immune cell infiltration of TFAP2 family in patients with BLCA. Results: Our study found that TFAP2 family proteins are generally expressed higher in BLCA tissues than in normal tissues. However, they show different trends in the growth, metastasis and survival prognosis of BLCA. TFAP2A and TFAP2C was associated with worse clinical stage and prognosis in BLCA patients, while TFAP2B, TFAP2D and TFAP2E showed the opposite trend. Importantly, the functions of the differentially expressed TFAP2s were primarily related to the developmental process, reproductive process, response to stimulus and immune system process, etc. Moreover, TFAP2 family was significantly correlated with the infiltration of six immune cell types and might regulate TAM polarization. Conclusion: TFAP2 family might be an important regulator of immune cell infiltration and a valuable prognostic biomarker in patients with BLCA.

Exosomal miR-93-5p as an important driver of bladder cancer progression.

Background: Tumor-derived exosomes are involved in the process of tumor metastasis and angiogenesis. MicroRNAs (miRNAs) are the most widely investigated factors in exosomes. Therefore, we hope to find a new therapeutic target in bladder cancer (BLCA), which has high incidence rate and mortality. Methods: Exosomal microRNA(miR)-93-5p expression level, downstream target molecules, and biological functions were examined with bioinformatics technology. Exosomes were extracted by sequential differential centrifugation and verified by transmission electron microscopy. The exosomal miR-93-5p on cell proliferation, invasion, and angiogenesis abilities in 5637 and T24 cells was determined by Cell Counting Kit 8 (CCK-8), colony-forming assay, Transwell assay, and vascular ring formation assay. A mouse xenograft model with intratumor injection was adopted to evaluate the correlation between BLCA-derived exosomes and tumor growth in vivo. Results: The results revealed that exosomes play an important role in the biological progression of BLCA, with miR-93-5p being a particularly important molecule. Compared to normal cells, more malignant cells release more exosomal miR-93-5p, and tumor-derived exosomal miR-93-5p could significantly promote cell proliferation, invasion, and angiogenesis in vitro and in vivo. We identified phosphatase and tensin homolog (PTEN) as the most significant target of miR-93-5p in BLCA and human umbilical vein endothelial cells. Conclusions: Our study successfully revealed the biological role and mechanism of BLCA-derived exosomes in tumor progression. Target at tumor exosomes and exosomal miR-93-5p may be an effective treatment in BLCA.

circSPECC1 promotes bladder cancer progression via regulating miR-136-5p/GNAS axis.

BACKGROUND: An increasing body of evidence suggest that circRNAs modulate various gene expression at the posttranscriptional level, affecting the development of cancers. Previous study suggested that circSPECC1 acted as an oncogene in some tumors, promoting the growth and metastasis of cancer cells. However, the role of circSPECC1 in bladder cancer (Bca) remains unknown. METHODS: RT-qPCR assay was applied to detect the expresion level of circRNA, miRNA and mRNA in Bca tissues and cells. CCK-8, cell colony formation and wound-healing assay were peformed to detect the effect of circSPECC1 on cell proliferation and migration. Nuclear mass separation, dual-luciferase reporter and RNA pull-down assay were used to investigate the molecular mechanisms underlying circSPECC1. RESULTS: In this study, we found that circSPECC1 was significantly up-regulated in Bca tissues and cell lines. Increased expression of circSPECC1 contribute to poor prognosis of Bca. Further tests showed that knockdown of circSPECC1 impaired the proliferation and migration of Bca cells. Mechanically, circSPECC1 sponged miR-136-5p to promote the mRNA and protein expression of GNAS. Besides, enforced expression of GNAS significantly reversed the proliferation and migration inhibition mediated by circSPECC1 suppression. CONCLUSION: In general, our study suggested that circSPECC1 contributed to the growth and metastasis of Bca and it is possible to become an ideal non-invasive biomarker for diagnosis and effective therapeutic target for treatment.

Evaluation of a novel biodegradable ureteral stent produced from polyurethane and magnesium alloys.

Indwelling ureteral stents represent a very frequently used procedure in urological clinical practice that ensures the drainage of urine from the upper urinary tract. However, the stents could result in many stent-associated complications, such as encrustation and patient discomfort. We developed a new type of biodegradable ureteral stents produced from degradable polyurethane and magnesium alloys. In the present study, we investigated the biocompatibility and the property of degradation of the biodegradable ureteral stents. We evaluated the cytotoxicity of biodegradable ureteral stent by the MTT assay in vitro. The rabbit dorsal muscle embedding test was used to assess the biocompatibility of the degradable stents. Inflammation and fibrosis of muscle tissue were noted to evaluate compatibility at 1, 2, 4, 6 weeks after stents implanted in muscle. The degradation of the biodegradable ureteral stents was assessed by measuring the weight loss of the samples in AUS (artificial urine solution). For validating the degradation property of degradable stents in vivo, we inserted a degradable stent or a conventional biostable stent into Bama pigs. Furthermore, blood studies, liver function tests, renal function tests, urine studies, and computerized tomography (CT) were performed postoperatively. Our study confirms that the degradable polyurethane-based biodegradable ureteral stent has good biocompatibility. Our biodegradable ureteral stents were completely degraded within 4 weeks and provided a better ability of drainage than conventional stents. They hold promise for decreasing the need for a secondary procedure and stent related morbidity, such as infections.

circMBOAT2 serves as the sponge of miR-433-3p to promote the progression of bladder cancer.

BACKGROUND: Bladder cancer (Bca) is the most common cancer in urinary system. Recent studies revealed that circular RNAs (circRNAs) play vital roles in the development and progression of cancers. circMBOAT2 serves as an oncogenic gene in various kinds of cancer, promoting cell growth and metastasis. Nevertheless, the biological function of circMBOAT2 in Bca has not been reported. METHODS: qRT-PCR was used to measure the mRNA, circRNA and miRNA expression levels in Bca tissues and cells. Loss-of function experiments were carried to investigate the effect of circMBOAT2 on cell proliferation and migration. Nuclear mass separation, RNA pull-down and dual-luciferase reporter were performed to the molecular mechanisms underlying the functions of circMBOAT2. RESULTS: In this research, we identified that circMBOAT2 expression was increased in Bca tissues and positively corelated with unfavorable prognosis. In vitro assay demonstrated that suppression of circMBOAT2 impaired the proliferation and migration of Bca cells. Mechanically, circMBOAT2 was predominantly spread in cytoplasm and it sponged miR-433-3p to strengthen CREB1 expression. CONCLUSION: Hence, our study suggested that circMBOAT2 may serve as an oncogene in the development and progression of Bca and it will be the novel tumor biomarker and therapeutic target for Bca.

Use of miR­145 and testicular nuclear receptor 4 inhibition to reduce chemoresistance to docetaxel in prostate cancer.

The human testicular nuclear receptor 4 (TR4) is a critical regulatory gene for the progression of prostate cancer (PCa). Although it has been revealed that TR4 causes chemoresistance in PCa via the activation of octamer­binding transcription factor 4 (OCT4), the detailed mechanism remains unexplored. In the present study, it was revealed that inhibition of TR4 by shRNA in PCa enhanced the sensitivity to docetaxel in vitro and in vivo. TR4 induced the downregulation of miR­145 by directly binding it to the promoter of miR­145, which was confirmed by chromatin immunoprecipitation analysis and luciferase assay. The overexpression of miR­145 suppressed both the chemoresistance and the expression of OCT4 mRNA and protein. Additionally, the TR4 shRNA mediated re­sensitization to docetaxel, along with the downregulated expression of OCT4, were reversed by the concurrent inhibition of miR­145. The luciferase assay revealed that the activity of the wild­type OCT4 3' untranslated region reporter was suppressed. This suppression diminished when the miR­145 response element mutated. These findings suggest an undescribed regulatory pathway in PCa, by which TR4 directly suppressed the expression of miR­145, thereby inhibiting its direct target OCT4, leading to the promotion of chemoresistance in PCa.

A nomogram based on PI-RADS v2.1 and clinical indicators for predicting clinically significant prostate cancer in the transition zone.

BACKGROUND: This study attempted to develop a nomogram for predicting clinically significant prostate cancer (cs-PCa) in the transition zone (TZ) with the Prostate Imaging Reporting and Data System version 2.1 (PI-RADS v2.1) score based on biparametric magnetic resonance imaging (bp-MRI) and clinical indicators. METHODS: We retrospectively reviewed 383 patients with suspicious prostate lesions in the TZ as a training cohort and 128 patients as the validation cohort from January 2015 to March 2020. Multivariable logistic regression analysis was performed to determine independent predictors for building a nomogram, and the performance of the nomogram was assessed by the area under the receiver operating characteristic curve (AUC), the calibration curve and decision curve. RESULTS: The PI-RADS v2.1 score and prostate-specific antigen density (PSAD) were independent predictors of TZ cs-PCa. The prediction model had a significantly higher AUC (0.936) than the individual predictors (0.914 for PI-RADS v2.1 score, P=0.045, 0.842 for PSAD, P<0.001). The nomogram showed good discrimination (AUC of 0.936 in the training cohort and 0.963 in the validation cohort) and favorable calibration. When the PI-RADS v2.1 score was combined with PSAD, the diagnostic sensitivity and specificity were 80.7% and 93.8%, respectively, which were better than those of the PI-RADS v2.1 score (sensitivity, 74.2%; specificity, 92.5%) and PSAD (sensitivity, 66.1%; specificity, 88.2%). CONCLUSIONS: The newly constructed nomogram exhibits satisfactory predictive accuracy and consistency for TZ cs-PCa. PI-RADS v2.1 based on bp-MRI is a strong predictor in the detection of TZ cs-PCa. Adding PSAD to PI-RADS v2.1 could improve its diagnostic performance, thereby avoiding unnecessary biopsies.

The Role of PSA Density among PI-RADS v2.1 Categories to Avoid an Unnecessary Transition Zone Biopsy in Patients with PSA 4-20 ng/mL.

OBJECTIVE: To evaluate the role of prostate-specific antigen density (PSAD) in different Prostate Imaging Reporting and Data System version 2.1 (PI-RADS v2.1) categories to avoid an unnecessary biopsy in transition zone (TZ) patients with PSA ranging from 4 to 20 ng/mL. MATERIALS AND METHODS: In this retrospective and single-center study, 333 biopsy-naïve patients with TZ lesions who underwent biparametric magnetic resonance imaging (bp-MRI) were analyzed from January 2016 to March 2020. Multivariate logistic regression analyses were performed to determine independent predictors of clinically significant prostate cancer (cs-PCa). The receiver operating characteristic (ROC) curve was used to compare diagnostic performance. RESULTS: PI-RADS v2.1 and PSAD were the independent predictors for TZ cs-PCa in patients with PSA 4-20 ng/mL. 0.9% (2/213), 10.0% (7/70), and 48.0% (24/50) of PI-RADS v2.1 score 1-2, 3, and 4-5 had TZ cs-PCa. However, for patients with PI-RADS v2.1 score 1-2, there were no obvious changes in the detection of TZ cs-PCa (0.8% (1/129), 1.3% (1/75), and 0.0% (0/9)) combining with different PSAD stratification (PSAD < 0.15, 0.15-0.29, and ≥0.30 ng/mL/mL). For patients with PI-RADS v2.1 score ≥ 3, the TZ cs-PCa detection rate significantly varied according to different PSAD stratification. A PI-RADS v2.1 score 3 and PSAD < 0.15 and 0.15-0.29 ng/mL/mL had 8.6% (3/35) and 3.7% (1/27) of TZ cs-PCa, while a PI-RADS v2.1 score 3 and PSAD ≥ 0.30 ng/mL/mL had a higher TZ cs-PCa detection rate (37.5% (3/8)). A PI-RADS v2.1 score 4-5 and PSAD <0.15 ng/mL/mL had no cs-PCa (0.0% (0/9)). In contrast, a PI-RADS v2.1 score 4-5 and PSAD 0.15-0.29 and ≥0.30 ng/mL/mL had the highest cs-PCa detection rate (50.0% (10/20), 66.7% (14/21)). It showed the highest AUC in the combination of PI-RADS v2.1 and PSAD (0.910), which was significantly higher than PI-RADS v2.1 (0.889, P = 0.039) or PSAD (0.803, P < 0.001). CONCLUSIONS: For TZ patients with PSA 4-20 ng/mL, PI-RADS v2.1 score ≤ 2 can avoid an unnecessary biopsy regardless of PSAD. PI-RADS v2.1 score ≥ 3 may avoid an unnecessary biopsy after combining with PSAD. PI-RADS v2.1 combined with PSAD could significantly improve diagnostic performance.

CircNT5E promotes the proliferation and migration of bladder cancer via sponging miR-502-5p.

Accumulating evidence suggest that circRNA RNAs (circRNAs) play important roles in tumor formation and development. circNT5E has been shown to be an oncogenic gene in several types of cancer, and the high expression of circNT5E lead to tumorigenesis and cancer progression. However, the precise role of circNT5E in bladder cancer (Bca) has not been characterized. In this study, we observed that circNT5E expression was augmented in Bca tissues compared with that in adjacent normal tissues, and its expression level was positively associated with larger tumor size and lower survival rate. Further experiments showed that suppression of circNT5E restrained the growth and metastasis of Bca cells in vitro. circNT5E was mainly distributed in the cytoplasm and it captured miR-502-5p to increase HOXC8 mRNA and protein expression. Moreover, decreased miR-502-5p obviously reversed the circNT5E silencing-mediated inhibition of Bca cell growth and migration. Thus, this study suggested that circNT5E may act as a pro-oncogene in the development and progression of Bca and it may become a useful tumor biomarker and promising therapeutic target for Bca treatment.

A 90-Day Oral Toxicity Study of the Ethanol Extract from Eupatorium japonicum Thunb and Foeniculum vulgare in Rats.

Eupatorium japonicum Thunb and Foeniculum vulgare are two of the most widely used folk herbs and constituents in many traditional Chinese herbal formulas. Nonetheless, little toxicological and safety information associated with following daily repeated exposure is obtained according to previous research. The present study was performed to assess the toxicity of ethanol extract from Eupatorium japonicum Thunb and Foeniculum vulgare (EFE) in male rats administered by dietary oral gavage at target doses of 0.39, 0.78, and 1.56 g/kg body weight/day for 90 days. There were no significant adverse effects on clinical signs, body weight, food conversion efficiency, and vital hematological indices. However, some hematology and biochemical indices such as WCV, MCH, MCHC, LY, MPV, T-CHO, as well as TG revealed significant changes in Sprague-Dawley rats and organ weights in lung and spleen showed diminished in male rats. Necropsy and histopathology findings suggested that no significant differences in absolute weights were found in all organs except lung and spleen, and no treatment-related alteration was identified in any organs. All results obtained in the present study indicated that the proper use of EFE in traditional medicine at oral dosages up to 1.56 g/kg/day body weight may harbor no prolonged toxicity to rats. However, further studies of EFE are still necessary to assess its oral safety in patients.