Effective Diagnosis of Prostate Cancer Based on mRNAs From Urinary Exosomes.

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.

MiR-5195-3p functions as a tumor suppressor in prostate cancer via targeting CCNL1.

BACKGROUND: Accumulating evidence indicates that miR-5195-3p exerts tumor-suppressive roles in several tumors. However, the clinical significance and biological function of miR-5195-3p in prostate cancer (PCa) have not been reported yet. METHODS: The expression levels of miR-5195-3p and Cyclin L1 (CCNL1) were determined using quantitative real-time PCR in clinical specimens and cell lines. The clinical significance of miR-5195-3p in patients with PCa was evaluated using Kaplan-Meier survival analysis and Cox regression models. Cell proliferation and cell cycle distribution were measured by CCK-8 assay and flow cytometry, respectively. The association between miR-5195-3p and CCNL1 was analyzed by luciferase reporter assay. RESULTS: MiR-5195-3p expression levels were significantly downregulated in 69 paired PCa tissues compared with matched adjacent normal tissues. The decreased miR-5195-3p expression was associated with Gleason score and TNM stage, as well as worse survival prognosis. The in vitro experiments showed that miR-5195-3p overexpression suppressed the proliferation and cell cycle G1/S transition in PC-3 and DU145 cells. Elevated miR-5195-3p abundance obviously impaired tumor formation in vivo using PC-3 xenografts. Mechanistically, CCNL1 was a direct target of miR-5195-3p in PCa cells, which was inversely correlated with miR-5195-3p in PCa tissues. Importantly, CCNL1 knockdown imitated, while overexpression reversed, the effects of miR-5195-3p overexpression on PCa cell proliferation and cell cycle G1/S transition. CONCLUSIONS: Our data suggest that miR-5195-3p functions as a tumor suppressor by targeting CCNL1 in PCa.

Identification of a DNA Repair Gene Signature and Establishment of a Prognostic Nomogram Predicting Biochemical-Recurrence-Free Survival of Prostate Cancer.

Background: The incidence of prostate cancer (PCa) is high and increasing worldwide. The prognosis of PCa is relatively good, but it is important to identify the patients with a high risk of biochemical recurrence (BCR) so that additional treatment could be applied. Method: Level 3 mRNA expression and clinicopathological data were obtained from The Cancer Genome Atlas (TCGA) to serve as training data. The GSE84042 dataset was used as a validation set. Univariate Cox, lasso Cox, and stepwise multivariate Cox regression were applied to identify a DNA repair gene (DRG) signature. The performance of the DRG signature was assessed based on Kaplan-Meier curve, receiver operating characteristic (ROC), and Harrell's concordance index (C-index). Furtherly, a prognostic nomogram was established and evaluated likewise. Results: A novel four DRG signature was established to predict BCR of PCa, which included POLM, NUDT15, AEN, and HELQ. The ROC and C index presented good performance in both training dataset and validation dataset. The patients were stratified by the signature into high- and low-risk groups with distinct BCR survival. Multivariate Cox analysis revealed that the DRG signature is an independent prognostic factor for PCa. Also, the DRG signature high-risk was related to a higher homologous recombination deficiency (HRD) score. The nomogram, incorporating the DRG signature and clinicopathological parameters, was able to predict the BCR with high efficiency and showed superior performance compared to models that consisted of only clinicopathological parameters. Conclusion: Our study identified a DRG signature and established a prognostic nomogram, which were reliable in predicting the BCR of PCa. This model could help with individualized treatment and medical decision making.

Partial and Radical Nephrectomy Provides Equivalent Oncologic Outcomes in pT3a Renal Cell Carcinoma: A Population-Based Study.

PURPOSE: To compare the cause-specific survival (CSS) and overall survival (OS) of patients with localized T3a renal cell carcinoma (RCC) after partial nephrectomy (PN) or radical nephrectomy (RN). METHODS: We obtained the demographic and clinicopathological data of 7,127 patients with localized T3a RCC and who underwent PN or RN from the Surveillance, Epidemiology, and End Results (SEER) database. These patients were divided into fat invasion cohort and venous invasion cohort for subsequent analysis. Kaplan-Meier analysis (KMA) and univariate and multivariate Cox proportional hazards regression analyses were used to evaluate the effects of PN or RN on OS and CSS. Meanwhile, 65 cases with clinical T1 (cT1) RCC upstaged to pathological T3a (pT3a) who were treated in Tongji Hospital (TJH) from 2011 to 2020 and underwent PN or RN were identified. RESULTS: In the study cohort, 2,085 (29.3%) patients died during the 1-172 months' follow-up, of whom 1,155 (16.2%) died of RCC. In the two cohorts of fat invasion and venous invasion, KMA indicated that the PN group had favorable survival (p < 0.001). However, after propensity score matching (PSM), univariate and multivariate Cox regression analyses showed that the PN and RN groups had comparable CSS in the fat invasion cohort (p = 0.075) and the venous invasion cohort (p = 0.190). During 1-104 months of follow-up, 9 cases in the Tongji cohort had disease recurrence. There was no significant difference in recurrence-free survival between the RN group and the PN group (p = 0.170). CONCLUSIONS: Our analysis showed that after balancing these factors, patients with localized pT3a RCC receiving PN or RN can achieve comparable oncologic outcomes. PN is safe for selected T3a patients.

Prognostic Value of Androgen Receptor Splice Variant 7 in the Treatment of Metastatic Castration-Resistant Prostate Cancer: A Systematic Review and Meta-Analysis.

BACKGROUND: The prognostic value of androgen receptor splice variant 7 (AR-V7) for the treatment response of metastatic castration-resistant prostate cancer (mCRPC) remains unclear. In this study, we aimed to synthesize relevant studies that assessed the prognostic value of AR-V7 status for the treatment response of mCRPC patients treated with androgen receptor signalling inhibitors (ARSis) and chemotherapy. METHODS: We searched the PubMed, Embase, and MEDLINE databases by using the keywords AR-V7 and prostate cancer to identify relevant studies published before 25 September 2019. The main outcomes were prostate-specific antigen (PSA) response, progression-free survival (PFS), and overall survival (OS). Pooled odds ratios (ORs) and hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated using a random effects model. The quality of the included studies was assessed using the Newcastle-Ottawa Quality Assessment Scale. RESULTS: A total of 1,545 patients from 21 studies were included. For the mCRPC patients treated with ARSis, AR-V7-positive patients had a lower PSA response rate (OR 6.01, 95% CI 2.88-12.51; P < 0.001), shorter PFS (HR 2.56, 95% CI 1.80-3.64; P < 0.001) and shorter OS (HR 4.28, 95% CI 2.92-6.27; P < 0.001) than AR-V7-negative patients. Although AR-V7-positive patients treated with chemotherapy also had a lower PSA response rate (OR 2.23, 95% CI 1.38-3.62; P = 0.001) and shorter OS than AR-V7-negative patients (HR 1.60, 95% CI 1.02-2.53; P = 0.043), there was no significant difference in PFS (HR 1.05, 95% CI 0.74-1.49; P = 0.796) between these groups. Furthermore, AR-V7-positive patients receiving ARSis had a shorter median OS than those receiving chemotherapy (HR 3.50, 95% CI 1.98-6.20; P < 0.001); There was no significant difference among AR-V7-negative patients (HR 1.30, 95% CI 0.64-2.62; P = 0.47). CONCLUSIONS: AR-V7 is a potential biomarker of treatment resistance in mCRPC patients. AR-V7-positive mCRPC patients had poorer treatment outcomes than AR-V7-nagetive patients when treated with ARSis. AR-V7-positive patients have better outcomes when treated with taxane than ARSis. Furthermore, the ability of AR-V7 status to predict treatment outcomes varies from different detection methods. The detection of AR-V7 before treatment is important for the selection of treatment modalities for mCRPC patients.

Leucocyte Subsets Effectively Predict the Clinical Outcome of Patients With COVID-19 Pneumonia: A Retrospective Case-Control Study.

Background: The clinical characteristics of coronavirus disease 2019 (COVID-19) have been well-studied, while effective predictors for clinical outcome and research on underlying mechanisms are scarce. Methods: Hospitalized COVID-19 pneumonia patients with definitive clinical outcome (cured or died) were retrospectively studied. The diagnostic performance of the leucocyte subsets and other parameters were compared using the area under the receiver operating characteristic curve (AUC). Further, the correlations between leucocyte subsets and inflammation-related factors associated with clinical outcome were subsequently investigated. Results: Among 95 subjects included, 56 patients were cured, and 39 died. Older age, elevated aspartate aminotransferase, total bilirubin, serum lactate dehydrogenase, blood urea nitrogen, prothrombin time, D-dimer, Procalcitonin, and C-reactive protein levels, decreased albumin, elevated serum cytokines (IL2R, IL6, IL8, IL10, and TNF-α) levels, and a decreased lymphocyte count indicated poor outcome in patients with COVID-19 pneumonia. Lymphocyte subset (lymphocytes, T cells, helper T cells, suppressor T cells, natural killer cells, T cells+B cells+NK cells) counts were positively associated with clinical outcome (AUC: 0.777; AUC: 0.925; AUC: 0.900; AUC: 0.902; AUC: 0.877; AUC: 0.918, resp.). The neutrophil-to-lymphocyte ratio (NLR), neutrophil to T lymphocyte count ratio (NTR), neutrophil percentage to T lymphocyte ratio (NpTR) effectively predicted mortality (AUC: 0.900; AUC: 0.905; AUC: 0.932, resp.). Binary logistic regression showed that NpTR was an independent prognostic factor for mortality. Serum IL6 levels were positively correlated with leucocyte count, neutrophil count, and eosinophil count and negatively correlated with lymphocyte count. Conclusion: These results indicate that leucocyte subsets predict the clinical outcome of patients with COVID-19 pneumonia with high efficiency. Non-self-limiting inflammatory response is involved in the development of fatal pneumonia.

Optimal Evacuation Strategy for Parking Lots Considering the Dynamic Background Traffic Flows.

An optimal evacuation strategy for parking lots can shorten evacuation times and reduce casualties and economic loss. However, the impact of dynamic background traffic flows in a road network on the evacuation plan is rarely taken into account in existing approaches. This research develops an optimal evacuation model with total evacuation time minimization by dividing the evacuation process in a parking lot into two periods. In the first period, a queuing theory is used to estimate the queuing time, and in the second period, a traffic flow equilibrium model and an intersection delay model are employed to simulate vehicles' route choice. To deal with these models, a modified ant colony algorithm is developed. The results of a numerical example prove that the proposed method has an advantage in improving evacuation efficiency. The results also show that background traffic flows affect not only vehicles' average queuing time in parking lots but also optimal evacuation route choice. Additionally, a sensitivity analysis indicates that the minimum threshold of headway time that allows vehicles out of a parking lot to merge into the background traffic flows on the roads connecting the exits has a great impact on average queuing time, average travel time, and total evacuation time.

Risk Factors Affecting Traffic Accidents at Urban Weaving Sections: Evidence from China.

As a critical configuration of interchanges, the weaving section is inclined to be involved in more traffic accidents, which may bring about severe casualties. To identify the factors associated with traffic accidents at the weaving section, we employed the multinomial logistic regression approach to identify the correlation between six categories of risk factors (drivers' attributes, weather conditions, traffic characteristics, driving behavior, vehicle types and temporal-spatial distribution) and four types of traffic accidents (rear-end, side wipe, collision with fixtures and rollover) based on 768 accident samples of an observed weaving section from 2016 to 2018. The modeling results show that drivers' gender and age, weather condition, traffic density, weaving ratio, vehicle speed, lane change behavior, private cars, season, time period, day of week and accident location are important factors affecting traffic accidents at the weaving section, but they have different contributions to the four traffic accident types. The results also show that traffic density of ≥31 vehicle/100 m has the highest risk of causing rear-end accidents, weaving ration of ≥41% has the highest possibility to bring about a side wipe incident, collision with fixtures is the most likely to happen in snowy weather, and rollover is the most likely incident to occur in rainy weather.

Mini-Percutaneous Nephrolithotomy with Ureter Catheter: A Safe and Effective form of mPCNL Offers Better Quality of Life.

OBJECTIVE: To compare outcomes and postoperative quality of life (QoL) among patients with kidney stone who received mini-percutaneous nephrolithotomy (mPCNL), partial tubeless mPCNL or mPCNL with ureter catheter in a prospective randomized clinical trial. METHODS: From May 2017 to December 2017, 60 patients with kidney stone who underwent mPCNL were randomized into 3 groups: Group I (mPCNL), Group II (partial tubeless mPCNL), Group III (mPCNL with ureter catheter). We evaluated perioperative characteristics, stone clearance, analgesic requirements and QoL by using the Wisconsin Stone QOL questionnaire. RESULTS: The age, gender, stone diameter, body mass index, length of operation, drop in hemoglobin and stone-free rates for the 3 groups were similar among these groups. However, the postoperative visual analog scale and the analgesic requirement in Group II were significantly the lowest (p < 0.05). According to Wisconsin Stone QOL questionnaire, compared to Group I, statistical significant difference in the QoL was seen in Group II and III, indicating a meaningful and immediate improvement in the postoperative QoL following mPCNL. CONCLUSION: Compared with standard and partial tubeless mPCNL, mPCNL with ureter catheter is a safe and useful form of mPCNL, which can offer better QoL and is more cost effective.

Robotic-assisted Laparoscopic Nephrectomy with Vein Thrombectomy: Initial Experience and Outcomes from a Single Surgeon.

This study was designed to explore the safety and feasibility of robotic-assisted laparoscopic nephrectomy with vein thrombectomy (RAL-NVT) for the treatment of renal cell carcinoma (RCC) with venous tumor thrombus (VTT). Clinical data of 6 patients treated with RAL-NVT between July 2016 and November 2017 in our hospital were retrospectively collected and analyzed. There were 5 males and 1 female with their age ranging from 48 years to 68 years. Five renal tumors were right-sided and one left-sided. Three cases fell in level 0 VTT, one in level I and two in level II. Preoperative imaging revealed lymph node involvement in 1 case and distant metastasis in 2 cases. For RCC with level 0 VTT, the renal vein of the affected side was adequately and carefully dissected around the thrombus to the proximity of inferior vena cava (IVC) and was ligated with Hem-o-loks without cross-clamping the IVC. For level I and II VTT, the IVC was crossclamped cephalically and caudally around the tumor thrombus and all tributaries were sequentially blocked to ensure the safe retrieval of VTT. All operations were successfully completed without conversion to open operation. The mean operative time was 150 (115-230) min. Cross-clamping of the IVC happened in 3 cases, and the blocking time was 14, 19 and 20 min, respectively. The mean estimated blood loss during the operation was 400 (200-580) mL. The peritoneal drainage tube was removed 5 to 9 days after the operation, and all patients were postoperatively discharged at 6 to 11 days. Postoperative pathological analysis confirmed that the RCCs were comprised of 4 clear cell RCCs, 1 papillary cell RCC, and 1 medullary cell RCC; 2 cases were Fuhrman grade II, 3 cases grade III, and 1 case undefined grade. No recurrence or progression was observed during the follow-up of 4.2 (3-6) months. We concluded that RAL-NVT is highly challenging but safe and feasible for the treatment of RCC with VTT.

Research progress of percutaneous nephrolithotomy.

Percutaneous nephrolithotomy (PCNL) is generally accepted as the gold standard treatment for the treatment of large kidney stones (> 2 cm). For nearly 40 years, with the continuous progress of technology and the constant updating of ideas, PCNL has made great progress. In this review, we discuss the current research progress, recent advancement and hot spot of the whole process of PCNL including anesthesia, position, puncture, dilation, lithotripsy approaches, perfusate, tube placement, hospitalization time, drug, treatment of residual stones, prognosis judgment and operation evaluation by summarizing the related research in this article.

MiR-514a-3p inhibits cell proliferation and epithelial-mesenchymal transition by targeting EGFR in clear cell renal cell carcinoma.

PURPOSE: Dysregulation of miR-514a-3p has been reported in multiple human malignancies. However, its biological function and molecular mechanisms in renal cell cancer (RCC) remain unclear. The aims of this study were to explore the role of miR-514a-3p and its potential mechanism in human RCC. METHODS: The expression level of miR-514a-3p was quantified by real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR) in 20 cases of paired ccRCC and adjacent normal tissues and RCC cell lines. The role of miR-514a-3p in RCC cells was further evaluated by functional analyses. Western blot was applied to probe into the biological mechanism of miR-514a-3p in RCC cells. RESULTS: The qRT-PCR results confirmed that miR-514a-3p was dramatically down-regulated in ccRCC specimens. Restoration of miR-514a-3p expression might distinctively suppress cell proliferation, viability, migration and invasion in comparison with negative control in RCC cells and negatively regulate the proteins related to epithelial-mesenchymal transition (EMT), such as E-Cadherin, N-Cadherin and Vimentin. Results of luciferase reporter assay and Western blot analysis identified that miR-514a-3p might inversely regulate the expression of epidermal growth factor receptor (EGFR) directly by binding to its 3'-untranslated region (3'-UTR) at the translational level. Further studies showed that the phenotypic changes of RCC cells caused by miR-514a-3p occurred through EGFR/MAPK/ERK pathway rather than PI3K/AKT signaling. Moreover, the inhibitory effect of miR-514a-3p was also confirmed in vivo study. CONCLUSIONS: MiR-514a-3p is a novel tumor suppressor in ccRCC and potentially functions through EGFR/MAPK/ERK pathway.