Endogenously Gated DNA Walking Machine for Prescreened MicroRNA Detection in Extracellular Vesicles.

Tumor-derived extracellular vesicle (T-EV) microRNAs have been investigated as promising biomarkers in clinical diagnosis as well as disease progression monitoring. However, the expression profiles of microRNA in different tissues vary widely, the precise monitoring of microRNA levels in EVs originating from diseased tissues is susceptible to background interference, thus remains a challenge. Conventional assays require extensive processing, such as EV isolation and even sample lysis, which is both slow and laborious, and the cumbersome pretreatment could spoil the downstream analysis. To address this issue, we developed a generalizable strategy for T-EVs-selective activation and therefore specific amplified microRNA imaging. The conditional signal amplification is established by integrating a traditional DNA walker system with endogenously activated motif to achieve sensitized microRNA imaging in T-EVs. The preorganized endogenous activation with additional sensing criteria narrowed the scope against the complex specimens, and the amplified sensing with reduced off-target signals was supposed to be sensitive to monitor the tiny changes of microRNA expression during the disease course, which holds great potential for accurate diagnosis and prognosis.

Construction of a prognostic 6-gene signature for breast cancer based on multi-omics and single-cell data.

Background: Breast cancer (BC) is one of the females' most common malignant tumors there are large individual differences in its prognosis. We intended to uncover novel useful genetic biomarkers and a risk signature for BC to aid determining clinical strategies. Methods: A combined significance (p combined) was calculated for each gene by Fisher's method based on the RNA-seq, CNV, and DNA methylation data from TCGA-BRCA. Genes with a p combined< 0.01 were subjected to univariate cox and Lasso regression, whereby an RS signature was established. The predicted performance of the RS signature would be assessed in GSE7390 and GSE20685, and emphatically analyzed in triple-negative breast cancer (TNBC) patients, while the expression of immune checkpoints and drug sensitivity were also examined. GSE176078, a single-cell dataset, was used to validate the differences in cellular composition in tumors between TNBC patients with different RS. Results: The RS signature consisted of C15orf52, C1orf228, CEL, FUZ, PAK6, and SIRPG showed good performance. It could distinguish the prognosis of patients well, even stratified by disease stages or subtypes and also showed a stronger predictive ability than traditional clinical indicators. The down-regulated expressions of many immune checkpoints, while the decreased sensitivity of many antitumor drugs was observed in TNBC patients with higher RS. The overall cells and lymphocytes composition differed between patients with different RS, which could facilitate a more personalized treatment. Conclusion: The six genes RS signature established based on multi-omics data exhibited well performance in predicting the prognosis of BC patients, regardless of disease stages or subtypes. Contributing to a more personalized treatment, our signature might benefit the outcome of BC patients.

KL is a favorable prognostic factor related immune for clear cell renal cell carcinoma.

BACKGROUND: Clear cell renal cell carcinoma (ccRCC) is a prevalent cancer in adult urology, often leading to metastasis and poor prognosis. Recently, advances in tumor immunology and aging research have opened up new possibilities for the treatment of kidney cancer. Therefore, the identification of potential targets and prognostic biomarkers for immunotherapy has become increasingly urgent. METHODS: Using GSE168845 data, we identified immune-aging-associated differentially expressed genes (IAR-DEGs) by intersecting differentially expressed immune-related genes and aging-related genes. The prognostic value of IAR-DEGs was determined via univariate and multivariate Cox regression analysis, revealing KL as an independent prognostic factor for ccRCC. We also investigated the correlation between KL and various immune-related factors, including immune cell infiltration, immune score, immune checkpoint, MSI, and TIED score. To confirm the expression of KL in ccRCC, we conducted qRT-PCR assays on both ccRCC cell lines and clinical tissue samples, and compared KL expression levels between normal kidney cell line (HK-2) and ACHN, a ccRCC cell line. Finally, we assessed KL protein expression levels in tissues using immunohistochemistry (IHC). RESULTS: In this study, we utilized Venn diagram analysis to identify 17 co-expressed immune-aging related DEGs from GSE168845, import database, and MSigDB database. GO and KEGG analysis revealed that the functions of the 17 IAR-DEGs were primarily related to "aging". Univariate and multivariate Cox analysis validated these 17 genes, and KL was determined to be an independent prognostic factor for ccRCC. The downregulation of KL was observed in ccRCC tissues and was negatively associated with T stage, M stage, pathological stage, and histologic grade (p < 0.05). This downregulation indicated disease deterioration and a shortened overall survival period. Our calibration curves and nomogram demonstrated the excellent predictive potential of KL. GSEA analysis showed that KL gene mediated immune and aging-related pathways, and was significantly correlated with immune infiltration and MS and TIED score. More research has revealed a significant reduction in KL mRNA expression levels in human renal cancer cells, particularly in ccRCC tissues compared to adjacent normal kidney tissues. Moreover, immunohistochemistry data have demonstrated a marked decrease in KL protein expression levels in ccRCC cells when compared to adjacent normal tissues. CONCLUSIONS: KL was a potential aging-related target for immunotherapy and valid prognostic biomarker for ccRCC patients.

Clinicopathological characteristics of HER2-low breast cancer: a retrospective study.

Human Epidermal Growth Factor Receptor-2 (HER2)-negative breast cancers (BCs) contain HER2-low and HER2-zero ones. HER2-low breast cancer has been receiving wide-spread concerns as the marvelous effect of novel anti-HER2 antibody-drug conjugates, however, the characteristic remains unknown. Our aim was to explore the differences of clinicopathological indicators and survival outcomes between HER2-low and HER2-0 breast cancers. We retrospectively analyzed 501 invasive breast cancer patients with complete data on HER2 status from 2017 to 2021 in our single center, of whom 415 HER2 negative patients were included for subsequent analysis. Each cohort was further divided into hormone receptor (HR) positive and HR negative subgroup. Clinicopathological factors and survival outcomes were collected and compared between HER2-low BCs and HER2-0 BCs. HER2-low BCs was obviously higher in HR positive BCs, with 277 (90.5%) HER2-low HR positive patients, 29 (9.5%) HER2-low HR negative patients, 68 (62.4%) HER2-0 HR positive patients and 41 (37.6%) HER2-0 HR negative patients (P < 0.001). Significant differences between HER2-low BCs and Her2-0 BCs were observed in lymph node ratio (LNR) (mean rank, 215 vs. 188 P = 0.014), estrogen receptor (ER)expression (90.5% vs. 62.4% P < 0.001), progesterone receptor (PR) expression (84.3% vs. 56.9% P < 0.001), Ki-67 expression (46.4% vs. 61.5% P < 0.001), androgen receptor (AR) expression (68% vs. 50.5% P < 0.001), adjuvant chemotherapy (69% vs. 79.8% P = 0.03). HER2-low BCs had lower histological grade than HER2-0 BCs, with grade I-II (68.7% vs. 43.1%) and grade III (22.2% vs. 43.1%) P < 0.01. No statistical differences were detected between the two groups for DFS and DDFS. Our results demonstrated that HR and AR status was closely related to HER2-low breast cancers. Further exploration about survival prognosis of HER2-low breast cancer is badly needed.

Design of intermittent continuous measurement of radon concentration in water.

The U.S. Environmental Protection Agency established the maximum contaminant level limit for radon concentration in drinking water as 11.1 Bq L-1. A new device based on the bubbling method with a 290 mL sample bottle was designed for intermittent continuous measurement of water radon concentration. A STM32 is used to control the switch of the water pump and the valves. The Water-Radon-Measurement software written in C# is to connect RAD7 and calculate the water radon concentration automatically.

Immune-enhancing activity of polysaccharides and flavonoids derived from Phellinus igniarius YASH1.

Introduction: Phellinus igniarius (P. igniarius) (Sanghuang) is a widely used traditional Chinese medicine fungus, and its natural products have great potential for clinical application in immune enhancement. This study aimed to explore the immune-enhancing activity and underlying mechanisms of the polysaccharides and flavonoids derived from Phellinus igniarius (P. igniarius) and to provide a theoretical and experimental basis for the development of novel drugs. Methods: Wild P. igniarius YASH1 from the Loess Plateau in Yan'an region was collected, and polysaccharides and total flavonoids were extracted, isolated and identified from mycelium and sporophore. In vitro antioxidant activity was detected through the scavenging activity of hydroxyl radicals and total antioxidant capacity. Cell Counting Kit-8 and trypan blue detection kit were used to detect the effect of extract polysaccharides and flavonoids on the proliferation and phagocytosis ability of immune cells. To assess the effect of the drugs on cytokine secretion by immune cells and immune recovery in immunocompromised mice, the expression of interleukin (IL)-2, IL-6, interferon (IFN)-γ, and tumor necrosis factor (TNF)-α were examined at the cellular and animal levels. The species composition, abundance of gut microbiota and the altered content of short-chain fatty acids in the feces were analyzed to elucidate the possible mechanisms of drugs by 16S ribosomal RNA (rRNA) amplifiers sequencing and liquid chromatography-tandem mass spectrometry (LC-MS/MS). Results: Both polysaccharides and flavonoids derived from mycelium or sporophore had antioxidant activity and may stimulate the expression and secretion of IL-2, IL-6, and IFN-γ in immune cells while inhibiting TNF-α expression and secretion and increasing IL-2, IL-6, and IFN- γ expression levels in mice. Furthermore, polysaccharides and flavonoids from mycelium and sporophore showed different effects on the metabolic response of intestinal short-chain fatty acids (SCFAs) in mice, and the use of these drugs remarkably changed the species composition and abundance of intestinal flora in mice. Discussion: Polysaccharides and flavonoids from P. igniarius YASH1 mycelium and sporophore have in vitro antioxidant activity, and they affect the promotion of cell proliferation, stimulation of IL-2, IL-6, and IFN-γ secretion, and inhibition of TNF-α expression in immune cells. Polysaccharides and flavonoids from P. igniarius YASH1 may enhance immunity in immunocompromised mice and remarkably affect the intestinal flora and content of SCFAs.

The Value of Circulating Tumor Cells and Tumor Markers Detection in Lung Cancer Diagnosis.

OBJECTIVE: Circulating tumor cells are complete tumor cells with multi-scale analysis values that present a high potential for lung cancer diagnosis. To enhance the accuracy of lung cancer diagnosis, we detected circulating tumor cells by the innovated conical micro filter integrated microfluidic system. METHODS: We recruited 45 subjects of study, including 22 lung cancer patients, 2 precancerous patients, the control group including 14 healthy participants, and 7 patients with lung benign lesions in this prospective study. We calculated the area under the receiver operating characteristic curve of circulating tumor cells, cytokeratin19 fragment, carcinoma embryonic antigen, squamous cell carcinoma, neuron-specific enolase, and their combination, respectively, while compared the circulating tumor cells levels between vein blood and arterial blood. A conical shape filter embedded in a microfluidic chip was used to improve the detection capability of circulating tumor cells. RESULTS: The study indicated that the sensitivity, specificity, positive predictive value, and negative predictive value of circulating tumor cells detection were 81.8%, 90.5%, 90.0%, and 82.6%, respectively. The circulating tumor cells level of lung cancer patient was significantly higher than that of the control group (P < .05). The area under the curve of circulating tumor cells, cytokeratin19 fragment, carcinoma embryonic antigen, squamous cell carcinoma, and neuron-specific enolase alone was 0.838, 0.760, 0.705, 0.614, and 0.636, respectively. The combination area under the curve of the 4 tumor markers (cytokeratin19 fragment, carcinoma embryonic antigen, squamous cell carcinoma, and neuron-specific enolase) was 0.805 less than that of circulating tumor cells alone. Together, the total area under the curve of circulating tumor cell and the 4 tumor markers were 0.847, showing the highest area under the curve value among all biomarkers. In addition, this study found that there was no significant difference in positive rate of circulating tumor cell between arterial and venous blood samples. CONCLUSION: The circulating tumor cells detection technology by conical micro filter integrated microfluidic could be used for lung cancer diagnosis with high sensitivity and specificity. Complementary combination of circulating tumor cells and conventional 4 lung cancer markers could enhance the clinical application accuracy. Venous blood should be used as a routine sample for circulating tumor cells detections.

Development and external validation of a novel nomogram to predict prostate cancer in biopsy-naïve patients with PSA <10 ng/ml and PI-RADS v2.1 = 3 lesions.

OBJECTIVE: To develop and externally validate a novel nomogram in biopsy-naïve patients with prostate-specific antigen (PSA) <10 ng/ml and PI-RADS v2.1 = 3 lesions. METHODS: We retrospectively collected 307 men that underwent initial biopsy from October 2015 to January 2022 in Cohort 1 (The First Affiliated Hospital of Soochow University). External cohort (Cohort 2, Kunshan Hospital) included 109 men that met our criteria from July 2016 to June 2021. By Slicer-3D Software, the volume of all lesions was divided into two subgroups (PI-RADS v2.1 = 3a and 3b). Logistic regression analysis was performed to screen for variables and construct nomogram by analyzing clinical data from Cohort 1. Receiver operating characteristics curve analysis, calibration plot and decision curve analysis (DCA) were plotted to validate the nomogram in external cohort. RESULTS: A total of 70 (22.8%) patients was diagnosed with prostate cancer in Institution 1. Among them, 34 (11.1%) had clinically significant prostate cancer (csPCa). Age, prostate-specific antigen density, digital rectal examination, PI-RADS v2.1 = 3 subgroups (3a and 3b) and apparent diffusion coefficient (ADC, <750 mm2 /s) were predictive factors for prostate cancer (PCa) and csPCa. High area under the curve of the nomogram was found in Cohort 1 and Cohort 2 for PCa (0.857 vs. 0.850) and for csPCa (0.896 vs. 0.893). Calibration curves showed excellent agreement between the predicted probability and actual risk for the models in internal and external validation. The DCA demonstrated net benefit of our nomogram. CONCLUSION: Until now, this is the first nomogram that predicts PCa and csPCa in biopsy-naïve patients with PSA <10 ng/ml and PI-RADS v2.1 = 3 lesions. Furthermore, PI-RADS v2.1 = 3 subgroups were considered to be an independent risk factor in our model. Our nomogram may assist urologists in biopsy decision making for these so-called "double gray zone" patients.

Two-sample Mendelian randomization study reveals no causal relationship between inflammatory bowel disease and urological cancers.

Background: The relationship between inflammatory bowel disease (IBD) and urological cancers has been identified in epidemiological and observational studies, while the causality remains uncertain. We examined whether IBD is causally associated with urological cancers in a Mendelian randomization (MR) study. Methods: The causal relationship between IBD, its main subtypes, and urological cancers was investigated using genome-wide association study data. To obtain more reliable conclusions, all outcomes were divided into training and validation sets. Eligible single-nucleotide polymorphisms were selected as instrumental variables based on MR analysis assumptions. The inverse variance-weighted (IVW) method was employed as the main method along with four other complementary methods. Results: In this two-sample MR study, no genetic evidence for the causal effect of IBD on urological cancers was found in either the training or validation sets using the IVW method. Similarly, we did not observe any significant association between Crohn's disease or ulcerative colitis and urological cancers. The results of the other methods are in accordance with those obtained using the IVW method. Conclusion: In this study, we confirmed that IBD is not a causal genetic risk factor for urological cancer in a European population.

Oncological safety of reconstruction with autologous fat grafting in breast cancer patients: a systematic review and meta-analysis.

To evaluate the oncological safety of autologous fat grafting and its effect on disease-free survival and local recurrence in breast cancer patients with autologous fat grafting (AFG) reconstruction. A literature search was performed using the Pubmed, Medline, Web of Science, and Cochrane libraries from January 2011 to March 2020, in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, to identify all relevant studies involving the application of autologous fat grafting in breast cancer reconstruction procedures. The primary outcome of the meta-analysis was a difference in incidence rates of locoregional recurrence and disease-free survival (DFS) between patients who had autologous fat grafting and controls. A total of 11 studies were included. Eight studies reported local-regional recurrences (LRR) and five studies reported disease-free survival (DFS) in 5,886 patients. Our meta-analysis of all included studies about survival outcomes showed AFG was not associated with increased LRR and DFS. Pooled hazard ratios (HRs) (95% CIs) for LRR and DFS were 1.26 (0.90-1.76) and 1.27 (0.96-1.69), respectively. According to the published literature, autologous fat grafting did not result in an increased rate of LRR and DFS in patients with breast cancer. Autologous fat grafting can, therefore, be performed safely in breast reconstruction after breast cancer.

Prognostic values of the core components of the mammalian circadian clock in prostate cancer.

BACKGROUND: Prostate cancer (PC) is one of the most common malignancies in males. Extensive and complex connections between circadian rhythm and cancer were found. Nonetheless, in PC, the potential role of the core components of the mammalian circadian clock (CCMCCs) in prognosis prediction has not been fully clarified. METHODS: We firstly collected 605 patients with PC from The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) databases. Survival analysis was carried out for each CCMCC. Then, we investigated the prognostic ability of CCMCCs by Cox regression analysis. Independent prognostic signatures were extracted for the establishment of the circadian clock-based risk score model. We explored the predictive performance of the risk score model in the TCGA training cohort and the independent GEO dataset. Finally, the relationships between risk score and clinicopathological parameters, biological processes, and signaling pathways were evaluated. RESULTS: The expression levels of CCMCCs were widely correlated with age, tumor status, lymph node status, disease-free survival (DFS), progression-free survival (PFS), and overall survival (OS). Nine circadian clock genes, including CSNK1D, BTRC, CLOCK, CSNK1E, FBXL3, PRKAA2, DBP, NR1D2, and RORB, were identified as vital prognostic factors in PC and were used to construct the circadian clock-based risk score model. For DFS, the area under the 3-year or 5-year receiver operating characteristic curves ranged from 0.728 to 0.821, suggesting better predictive performance. When compared with T3-4N1 stage, PC patients at T2N0 stage might be benefited more from the circadian clock-based risk score model. Furthermore, a high circadian clock-based risk score indicated shorter DFS (p < 0.0001), early progression (p < 0.0001), and higher 5-year death rate (p = 0.007) in PC. The risk score was related to tumor status (p < 0.001), lymph node status (p < 0.001), and ribosome-related biogenesis and pathways. CONCLUSIONS: The vital roles of circadian clock genes in clinical outcomes were fully depicted. The circadian clock-based risk score model could reflect and predict the prognosis of patients with PC.

STC1 is a Novel Biomarker Associated with Immune Characteristics and Prognosis of Bladder Cancer.

BACKGROUND: Stanniocalcin-1 (STC1) is a well-studied oncogene that promotes different types of cancer progression. However, the expression status of STC1, the values of STC1 on prognosis, and its immune characteristic in bladder cancer (BLCA) have not been well examined. METHODS: The expression of STC1 and its clinicopathological as well as immune characteristics in BLCA samples were firstly identified in The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) databases. Immunohistochemistry (IHC) performed on the tissue microarray (TMA) slide was further used to validate the expression of STC1 and its relationship with immune features in 16 non-muscle invasive bladder cancer (NMIBC) samples and 42 muscle invasive bladder cancer (MIBC) samples. RESULTS: The expression of STC1 was upregulated in higher stage BLCA. High STC1 expression also predicted poor prognosis in BLCA. Subsequently, the TMA validated the expression and prognostic value of STC1 in BLCA. Bioinformatics analysis demonstrated that STC1 and common immune checkpoints as well as immune markers of various immune cells were positively correlated in TCGA. In addition, IHC data from the TMA further validated that tumor cells with higher STC1 level tended to express higher PDL1 as well as increased infiltration of CD3+ T cells. CONCLUSION: To our knowledge, this is the first comprehensive study that investigates the clinical and immune characteristics of STC1 in BLCA. It may provide new insight into the function of STC1 in regulating tumor immune microenvironment. Further studies are warranted to uncover the potential mechanisms that mediate STC1 expression and tumor immunity in BLCA.

Identification of a Novel Ferroptosis-Related Gene Prognostic Signature in Bladder Cancer.

BACKGROUND: Ferroptosis is a newly found non-apoptotic forms of cell death that plays an important role in tumors. However, the prognostic value of ferroptosis-related genes (FRG) in bladder cancer (BLCA) have not been well examined. METHODS: FRG data and clinical information were collected from The Cancer Genome Atlas (TCGA). Then, significantly different FRGs were investigated by functional enrichment analyses. The prognostic FRG signature was identified by univariate cox regression and least absolute shrinkage and selection operator (LASSO) analysis, which was validated in TCGA cohort and Gene Expression Omnibus (GEO) cohort. Subsequently, the nomogram integrating risk scores and clinical parameters were established and evaluated. Additionally, Gene Set Enrichment Analyses (GSEA) was performed to explore the potential molecular mechanisms underlying our prognostic FRG signature. Finally, the expression of three key FRGs was verified in clinical specimens. RESULTS: Thirty-two significantly different FRGs were identified from TCGA-BLCA cohort. Enrichment analyses showed that these genes were mainly related to the ferroptosis. Seven genes (TFRC, G6PD, SLC38A1, ZEB1, SCD, SRC, and PRDX6) were then identified to develop a prognostic signature. The Kaplan-Meier analysis confirmed the predictive value of the signature for overall survival (OS) in both TCGA and GEO cohort. A nomogram integrating age and risk scores was established and demonstrated high predictive accuracy, which was validated through calibration curves and receiver operating characteristic (ROC) curve [area under the curve (AUC) = 0.690]. GSEA showed that molecular alteration in the high- or low-risk group was closely associated with ferroptosis. Finally, experimental results confirmed the expression of SCD, SRC, and PRDX6 in BLCA. CONCLUSION: Herein, we identified a novel FRG prognostic signature that maybe involved in BLCA. It showed high values in predicting OS, and targeting these FRGs may be an alternative for BLCA treatment. Further experimental studies are warranted to uncover the mechanisms that these FRGs mediate BLCA progression.

Parallel comparison of R.E.N.A.L., PADUA, and C-index scoring systems in predicting outcomes after partial nephrectomy: A systematic review and meta-analysis.

OBJECTIVE: To parallelly compare the applicability of the radius, exophytic/endophytic, nearness, anterior/posterior, location nephrometry score (R.E.N.A.L.), the Preoperative Aspects and Dimensions Used for an Anatomical (PADUA), and the centrality index (C-index) scoring systems in predicting clinical outcomes after partial nephrectomy (PN). METHODS: We searched EMBASE, PubMed, Ovid, and Web of Science to perform a meta-analysis examining the correlation coefficients between three nephrometry scores (NSs) and warm ischemia time (WIT), estimated blood loss (EBL), operation time (OT), length of stay (LOS), and absolute change in eGFR (ACE) up to 25 January 2021. RESULTS: In total, 13 studies including 1496 patients met the criteria for further analysis. Overall, all scoring systems had statistically significant correlations with the WIT, EBL, OT, ACE and LOS and ACE, except for the correlation between PADUA and LOS (r = 0.16 [-0.00, 0.31], p > 0.05). The C-index had the strongest correlation with WIT (r = -0.35 [-0.43, -0.26], p < 0.05) and ACE (r = -0.29 [-0.48, -0.10], p < 0.05). Weak correlations were observed between OT as well as EBL and each scoring system. Publication bias was observed in PADUA score predicting ACE (p = 0.04) and high heterogeneity was found in some of our results. CONCLUSION: Until now, this is the first meta-analysis that parallelly compares these three scoring systems in predicting outcomes after PN. We found that all NSs showed a statistically significant correlation with WIT, EBL, OT, and ACE. Moreover, the C-index scoring system is the best predictor of WIT and ACE. Due to the existence of publication bias and high heterogeneity, more well-designed and large-scale studies are warranted for validation.

Performance of 18F-DCFPyL PET/CT Imaging in Early Detection of Biochemically Recurrent Prostate Cancer: A Systematic Review and Meta-Analysis.

Background: Prostate-specific membrane antigen (PSMA)-targeted 2-(3-{1-carboxy-5-[(6-[18F] fluoro-pyridine-3-carbonyl)-amino]-pentyl}-ureido)-pentanedioic acid (18F-DCFPyL) positron emission tomography/computed tomography (PET/CT) has shown advantages in primary staging, restaging, and metastasis detection of prostate cancer (PCa). However, little is known about the role of 18F-DCFPyL PET/CT in biochemically recurrent prostate cancer (BRPCa). Hence, we performed a systematic review and meta-analysis to evaluate 18F-DCFPyL PET/CT as first-line imaging modality in early detection of BRPCa. Methods: A comprehensive literature search of PubMed, Web of Science, Embase, and Cochrane Library was conducted until December 2020. The pooled detection rate on a per-person basis and together with 95% confidence interval (CI) was calculated. Furthermore, a prostate-specific antigen (PSA)-stratified performance of detection positivity was obtained to assess the sensitivity of 18F-DCFPyL PET/CT in BRPCa with different PSA levels. Results: A total of nine eligible studies (844 patients) were included in this meta-analysis. The pooled detection rate (DR) of 18F-DCFPyL PET/CT in BRPCa was 81% (95% CI: 76.9-85.1%). The pooled DR was 88.8% for PSA ≥ 0.5 ng/ml (95% CI: 86.2-91.3%) and 47.2% for PSA < 0.5 ng/ml (95% CI: 32.6-61.8%). We also noticed that the regional lymph node was the most common site with local recurrence compared with other sites (45.8%, 95% CI: 42.1-49.6%). Statistical heterogeneity and publication bias were found. Conclusion: The results suggest that 18F-DCFPyL PET/CT has a relatively high detection rate in BRPCa. The results also indicate that imaging with 18F-DCFPyL may exhibit improved sensitivity in BRPCa with increased PSA levels. Considering the publication bias, further large-scale multicenter studies are warranted for validation.

Efficacy and Safety of Transurethral Laser Surgery Versus Transurethral Resection for Non-Muscle-Invasive Bladder Cancer: A Meta-Analysis and Systematic Review.

OBJECTIVE: To compare the efficacy and safety of transurethral laser surgery and transurethral resection of a bladder tumor (TURBT) for non-muscle-invasive bladder cancer (NMIBC). MATERIAL AND METHODS: A research was carried out in Medline via PubMed, EMBASE, the Cochrane Library, and Web of Science up to October 20, 2019, to identify articles related to transurethral laser surgery and TURBT for NMIBC. All analyses were done using RevMan5.3 and Stata14. RESULTS: A total of 17 studies involving 2,439 participants were included. The analysis showed no significant difference in operation times (mean difference = -0.2; 95% CI -2.29 to 1.89; p = 0.85) or occurrences of urethral stricture (OR = 0.7; 95% CI 0.24-2.06; p = 0.52). Transurethral laser surgery was associated with a lower incidence of obturator nerve reflex (OR = 0.04; 95% CI 0.02-0.09; p < 0.00001) and bladder perforation (OR = 0.09; 95% CI 0.04-0.23; p < 0.00001), a higher rate of detrusor muscle acquisition (OR = 5.28; 95% CI 2.42-11.49; p < 0.0001), shorter catheterization (mean difference = -1.05; 95% CI -1.41 to -0.68; p < 0.00001) and hospitalization times (mean difference = -0.96; 95% CI -1.59 to -0.33; p = 0.003), and lower rates of bladder irrigation (OR = 0.21; 95% CI 0.13-0.35; p < 0.00001) and recurrence both at 12 months (OR = 0.66; 95% CI 0.48-0.9, p = 0.008) and at 24 months (OR = 0.6; 95% CI 0.41-0.86; p = 0.005). CONCLUSIONS: Transurethral laser surgery for NMIBC, as compared to TURBT, is associated with a lower incidence of complications, a lower recurrence rate, and faster postoperative recovery.

Risk Factors of Infectious Complications following Ureteroscopy: A Systematic Review and Meta-Analysis.

OBJECTIVE: To investigate the potential risk factors of infectious complications following ureteroscopy (URS). MATERIALS AND METHODS: Studies reporting risk factors of infectious complications following URS were searched via PubMed, EMBASE, Cochrane Library, and Web of Science databases up to August 30, 2019. OR or mean difference (MD) with 95% CI was calculated to assess the potential risk factors. RESULTS: A total of 14 studies containing 9,532 patients were included. Positive preoperative urine culture was the most significant risk factor (OR 2.95, 95% CI 1.96-4.43, p < 0.01), followed by female gender (OR 1.95, 95% CI 1.48-2.57, p < 0.01), diabetes mellitus (OR 1.55, 95% CI 1.13-2.13, p < 0.01), pre- and postoperative stent (OR 1.53, 95% CI 1.11-2.11, p = 0.01, OR 1.44, 95% CI 1.01-2.03, p = 0.04, relatively), and extended operative time (MD -11.54, 95% CI -16.10 to 6.98, p < 0.01). Age (MD -2.59, 95% CI -5.36 to 0.18, p = 0.07), cumulative stone diameter (MD -1.54; 95% CI -4.63 to 1.55, p = 0.33), and renal insufficiency (OR 1.22, 95% CI 0.80-1.88, p = 0.36) were not the potential risk factors. CONCLUSION: The prevalence of infectious complications following URS was correlated with female gender, diabetes mellitus, preoperative urine culture, pre- and postoperative stent insertion, and extended operative time. Publication bias and high heterogeneity were observed in some risk factors. Further studies are warranted for a valid conclusion.

A novel nomogram combined PIRADS v2 and neutrophil-to-lymphocyte ratio to predict the risk of clinically significant prostate cancer in men with PSA < 10 ng/ml at first biopsy.

OBJECTIVE: To determine whether Prostate Imaging-Reporting and Data System version 2 (PIRADS v2) and neutrophil-to-lymphocyte ratio(NLR) improve the detection of clinically significant prostate cancer(csCaP) in men with prostate-specific antigen (PSA) <10 ng/ml at first biopsy. METHODS: Univariable and multivariable binary logistic regression analysis were used to screen for independent risk factors of csCaP. The multivariable model based on the risk factors was to build the nomogram predicting csCaP and assessed by receiver operator characteristic curve analysis, calibration plot, and decision curve analysis. RESULTS: This retrospective study included 335 men with PSA < 10 ng/ml who underwent initial biopsy. A total of 78 (23.3%) men had csCaP. The nomogram was built based on the multivariable model including age, digital rectal examination, free prostate-specific antigen, PIRADS v2, and NLR. It had high area under the curve of 0.876 and was well calibrated in internal validation. Decision curve analysis also demonstrated that it would improve the prediction of csCaP. CONCLUSION: PIRADS v2 and NLR improve the detection of csCaP in men with PSA < 10 ng/ml at first biopsy. Due to lack of external validation, relatively small cohort and homogenous population, the study has several limitations. Despite of this, the nomogram based on our study is a promising tool for patients to understand their risk of csCaP and for urologists to make clinical decisions.

Extracorporeal shock wave therapy is effective in treating chronic plantar fasciitis: A meta-analysis of RCTs.

BACKGROUND: Plantar fasciitis (PF) is the most common reason for heel pain. The efficacy of extracorporeal shock wave therapy (ESWT) as an ideal alternative to conservative treatments and surgery is controversial, and almost all previous articles compared general ESWT with placebo without indicating the kind of shock wave. We undertook a meta-analysis to compare the efficacy of general ESWT, focused shock wave (FSW), and radial shock wave (RSW) with placebo, to assess their effectiveness in chronic PF. METHODS: The PubMed, Medline, EmBase, Web of Science, and Cochrane library databases were searched for studies comparing FSW or RSW therapy with placebo in chronic PF. Clinical outcomes included the odds ratios (ORs) of pain relief, pain reduction, and complications. Relevant data were analyzed using RevMan v5.3. RESULTS: Nine studies involving 935 patients were included. ESWT had higher improvement rates than the placebo group (OR 2.58, 95% confidence interval [CI] 1.97-3.39, P < .00001). ESWT had markedly lower standardized mean difference than placebo, with heterogeneity observed (standardized mean difference 1.01, 95% CI -0.01 to 2.03, P = .05, I = 96%, P < .00001). FSW and RSW therapies had greater therapeutic success in pain relief than the placebo group (OR 2.17, 95% CI 1.49-3.16, P < .0001; OR 4.63, 95% CI 1.30-16.46, P = .02), but significant heterogeneity was observed in RSW therapy versus placebo (I = 81%, P = .005). CONCLUSION: This meta-analysis suggested that FSW therapy can relieve pain in chronic PF as an ideal alternative option; meanwhile, no firm conclusions of general ESWT and RSW effectiveness can be drawn. Due to variations in the included studies, additional trials are needed to validate these conclusions.