Regional location of lymph node metastases predicts survival in patients with de novo metastatic prostate cancer.

To report the regional locations of metastases and to estimate the prognostic value of the pattern of regional metastases in men with metastatic hormone-sensitive prostate cancer (mHSPC), we retrospectively analyzed 870 mHSPC patients between November 28, 2009, and February 4, 2021, from West China Hospital in Chengdu, China. The patients were initially classified into 5 subgroups according to metastatic patterns as follows: simple bone metastases (G1), concomitant bone and regional lymph node (LN) metastases (G2), concomitant bone and nonregional LN (NRLN) metastases (G3), lung metastases (G4), and liver metastases (G5). In addition, patients in the G3 group were subclassified as G3a and G3b based on the LN metastatic plane (below or above the diaphragm, respectively). The associations of different metastatic patterns with castration-resistant prostate cancer-free survival (CFS) and overall survival (OS) were analyzed by univariate and multivariate analyses. The results showed that patients in G1 and G2 had relatively favorable clinical outcomes, patients in G3a and G4 had intermediate prognoses, and patients in G3b and G5 had the worst survival outcomes. We observed that patients in G3b had outcomes comparable to those in G5 but had a significantly worse prognosis than patients in G3a (median CFS: 8.2 months vs 14.3 months, P = 0.015; median OS: 38.1 months vs 45.8 months, P = 0.038). In conclusion, metastatic site can predict the prognosis of patients with mHSPC, and the presence of concomitant bone and NRLN metastases is a valuable prognostic factor. Furthermore, our findings indicate that the farther the NRLNs are located, the more aggressive the disease is.

NMDAR in bladder smooth muscle is not a pharmacotherapy target for overactive bladder in mice.

Overactive bladder (OAB) is a common condition that affects a significant patient population. The N-methyl-D-aspartate receptor (NMDAR) has a role in developing bladder overactivity, pharmacological inhibition of which inhibits bladder overactivity. The common pathogenesis of OAB involves bladder smooth muscle (BSM) overactivity. In this study, a smooth muscle-specific NMDAR knockout (SMNRKO) mouse model was generated. The bladders from SMNRKO mice displayed normal size and weight with an intact bladder wall and well-arranged BSM bundles. Besides, SMNRKO mice had normal voiding patterns and urodynamics and BSM contractility, indicating that NMDAR in BSM was not essential for normal physiological bladder morphology and function. Unexpectedly, cyclophosphamide (CYP)-treated SMNRKO and wild-type (WT) mice had similar pathological changes in the bladder. Furthermore, SMNRKO mice displayed similar altered voiding patterns and urodynamic abnormalities and impaired BSM contractility compared with WT mice after CYP treatment. MK801 partially reversed the pathological bladder morphology and improved bladder dysfunction induced by CYP, but did not cause apparent differences between WT mice and SMNRKO mice, suggesting that NMDAR in BSM was not involved in pathological bladder morphology and function. Moreover, the direct instillation of NMDAR agonists or antagonists into the CYP-induced OAB did not affect bladder urodynamic function, indicating that NMDAR in BSM was not the pharmacotherapy target of MK801 for CYP-induced cystitis. The findings indicated that NMDAR in BSM was not essential for normal physiological or pathological bladder morphology and function, and MK801 improving pathological bladder function was not mediated by an action on NMDAR in BSM.

Development of nanotechnology in andrology.

Since first introduced in 1980s, nanotechnology has always been the eye-catching point as its providing us with new approaches to explore the microscopic world. Many nanotechnology-associated novel technologies have been brought into clinical use in the past decades and uncountable patients benefited from them, which convinces us of a bright prospect of nanotechnology in the field of medicine. In this review, literatures concerning nanotechnology applications in andrology were retrieved and we made a comprehensive discussion on drug delivery, gene therapy and stem cell therapy use in andrology, which calls for the engagement of nanotechnology.

Carbon dots-based fluorescent turn off/on sensor for highly selective and sensitive detection of Hg2+ and biothiols.

In this work, sodium salicylate and ethylenediamine (EDA) are used as the precursors to synthesize green fluorescent carbon dots (CDs). The CDs have some attractive properties, including better oxidation resistance, good water solubility, and excellent stability in high ionic strength solutions in a pH range of 6.0-10.0. Compared to other metal ions, only Hg2+ can quench the fluorescence of CDs, and with the introduction of biothiols, the fluorescence of the CDs/Hg2+ system can be recovered. Therefore, a turn off/on fluorescent sensor is constructed using CDs as a fluorescent probe, and the sensor is applied to the detection of Hg2+ and biothiols (glutathione, homocysteine and cysteine). In addition, the fluorescent sensor exhibits excellent selectivity and sensitivity. The linear range of Hg2+ is 0.05-10 µM with the detection limit of 44 nM. Glutathione, homocysteine, and cysteine have a linear response in the range of 0.5-10 µM with the limit of detection of 80, 76, and 69 nM, respectively. Furthermore, the fluorescence method is successfully used to detect Hg2+ in actual water samples and biothiols in human plasma.

Construction of an effective ratiometric fluorescent sensing platform for specific and visual detection of mercury ions based on target-triggered the inhibition on inner filter effect.

Sensitive and selective determination of mercury ion (Hg2+) is critical for human health and environmental monitoring. Herein we construct an effective ratiometric fluorescent sensing platform by combining green fluorescent polymer carbon dots (PCDs) and red fluorescent tetraphenylporphyrin tetrasulfonic acid hydrate (TPPS) for specific and visual detection of Hg2+. The fluorescence of PCDs can be quenched by TPPS through inner filter effect (IEF). In the presence of both Mn2+ and Hg2+, however, Hg2+ can expedite the complexation of TPPS and Mn2+, which causes the decrease in both fluorescence and absorption of TPPS, accompanied by the fluorescence recovery of PCDs due to the subdued IFE between TPPS and PCDs. Based on the change of fluorescence signal, a ratiometric fluorescent sensing platform is constructed for specific and visual detection of Hg2+. The proposed approach presents a fine linear range for Hg2+ over the range of 10-200 nM with a detection limit of 0.038 nM. Moreover, an easily distinguishable fluorescence color change from pink to green with the increase of Hg2+ concentration can be observed by the naked eye under a UV lamp. Such a simple and effective method shows great potential for visual sensing of Hg2+ in on-site and resource-limited settings.

Proton-controlled synthesis of red-emitting carbon dots and application for hematin detection in human erythrocytes.

The Red-emitting nitrogen-doped carbon dots (N-CDs) are synthesized using o-phenylenediamine by a one-step method, and can serve as a fluorescent probe for "turn off" detection of hematin in human red cells. The red-emitting N-CDs can be obtained only in acidic conditions and the emission of the red-emitting N-CDs is pH-dependent, indicating proton-controlled synthesis and emission. The red-emitting N-CDs are 2.7 nm in mean size and have a uniform dispersion and exhibit a high quantum yield (12.8%) and great optical properties. The developed sensing system for hematin displays a linear response from 0.4 to 32 µM with a detection limit of 0.18 µM. Importantly, this fluorescent probe demonstrates a good potential practicability for the quantitative detection of hematin in complex matrixes. Graphical abstract ᅟ.

Green fluorescent carbon quantum dots as a label-free probe for rapid and sensitive detection of hematin.

Hematin is an oxidized form of heme, and the abnormal levels of hematin in the human body can lead to various inflammatory lesions. Hence, there is still a need to establish a rapid, sensitive and efficient method for hematin detection. Herein, the green fluorescent carbon quantum dots (CQDs) are synthesized by using L-cysteine and hydrogen peroxide as precursors. The synthesized CQDs exhibit some fascinating characters including excellent water solubility, high fluorescence quantum yield, and good stability in a broad pH range of 7.0-11.0 and high ionic strength solution. Excitingly, the fluorescence of CQDs can be rapidly and selectively quenched by hematin via the inner filter effect. Moreover, the detection of hematin by the CQDs fluorescent probe shows a good linearity in the concentration range of 0.5-30 µM with a minimum detection limit of 0.1 µM. Finally, the proposed approach is successfully applied to detect hematin in human blood samples.

pH-mediated reversible fluorescence nanoswitch based on inner filter effect induced fluorescence quenching for selective and visual detection of 4-nitrophenol.

Being a common hazardous waste, 4-nitrophenol (4-NP) has caused a serious threat to humans and environment. Therefore, rapid and selective detection of 4-NP, especially using a simple and portable instrument, is highly desired for human health and environmental monitoring. Herein, we develop a novel pH-mediated reversible fluorescence nanoswitch for selectively detecting 4-NP by using water-soluble fluorescent polymer carbon dots (PCDs) as a probe. The fluorescence of PCDs can be quenched by 4-NP via inner filter effect (IFE) because its excitation spectrum well overlaps with the absorption spectrum of 4-NP under alkaline condition. However, an obvious blue shift of the absorption peak of 4-NP occurs under acidic condition, causing the fluorescence recovery of PCDs due to the disappearance of IFE. On the basis of this principle, a pH-mediated reversible fluorescence nanoswitch was constructed and a broad linear range was obtained from 0.5 to 60 µM with a detection limit of 0.26 µM for 4-NP. Furthermore, this approach was successfully applied to detect 4-NP in real water samples and a portable polyamide film-based sensor was developed for visual detection of 4-NP, which offers a promising platform for the detection of 4-NP in on-site and resource-poor settings.

Low-intensity extracorporeal shock wave therapy for erectile dysfunction after radical prostatectomy: a review of preclinical studies.

Low-intensity extracorporeal shock wave therapy (LI-ESWT) is a novel treatment for erectile dysfunction (ED). Its ability to improve erectile function has been shown in patients with vasculogenic ED by many randomized-controlled trials against sham procedures. However, the role of LI-ESWT in ED caused by radical prostatectomy (RP) is still questionable because this type of ED was excluded from nearly all clinical studies; it has been investigated in only a few small single-arm trials. This review summarizes preclinical studies on mechanisms of action of LI-ESWT for ED and neurological diseases to explore the potential of this treatment for nerve-impaired ED after RP.

Short-term efficacy and safety of low-intensity extracorporeal shock wave therapy in erectile dysfunction: a systematic review and meta-analysis

ABSTRACT Aim: The role of low-intensity extracorporeal shock wave therapy (LI-ESWT) in erectile dysfunction (ED) is not clearly determined. The purpose of this study is to investigate the short-term efficacy and safety of LI-ESWT for ED patients. Materials and Methods: Relevant studies were searched in Medline, Embase, Cochrane Library, China National Knowledge Infrastructure (CNKI), WANFANG and VIP databases. Effective rate in terms of International Index of Erectile Function-Erectile Function Domain (IIEF-EF) and Erectile Hardness Score (EHS) at about 1XSmonth after LI-ESWT was extracted from eligible studies for meta-analysis to calculate risk ratio (RR) of effective treatment in ED patients treated by LI-ESWT compared to those receiving sham-treatment. Results: Overall fifteen studies were included in the review, of which four randomized controlled trials (RCTs) were for meta-analysis. Effective treatment was 8.31 [95°/o confidence interval (CI): 3.88-17.78] times more effective in the LI-ESWT group (n=176) than in the sham-treatment group (n= 101) at about 1 month after the intervention in terms of EHS, while it was 2.50 (95% CI: 0.74-8.45) times more in the treatment group (n= 121) than in the control group (n=89) in terms of IIEF-EF. Nine-week protocol with energy density of 0.09mJ/mm2 and 1500 pluses seemed to have better therapeutic effect than five-week protocol. No significant adverse event was reported. Conclusion: LI-ESWT, as a noninvasive treatment, has potential short-term therapeutic effect on patients with organic ED irrespective of sensitivity to PDE5is. Owing to the limited number and quality of the studies, more large-scale, well-designed and longterm follow-up time studies are needed to confirm our analysis.

Short-term efficacy and safety of low-intensity extracorporeal shock wave therapy in erectile dysfunction: a systematic review and meta-analysis.

AIM: The role of low-intensity extracorporeal shock wave therapy (LI-ESWT) in erectile dysfunction (ED) is not clearly determined. The purpose of this study is to investigate the short-term efficacy and safety of LI-ESWT for ED patients. MATERIALS AND METHODS: Relevant studies were searched in Medline, Embase, Cochrane Library, China National Knowledge Infrastructure (CNKI), WANFANG and VIP databases. Effective rate in terms of International Index of Erectile Function-Erectile Function Domain (IIEF-EF) and Erectile Hardness Score (EHS) at about 1month after LI-ESWT was extracted from eligible studies for meta-analysis to calculate risk ratio (RR) of effective treatment in ED patients treated by LI-ESWT compared to those receiving sham-treatment. RESULTS: Overall fifteen studies were included in the review, of which four randomized controlled trials (RCTs) were for meta-analysis. Effective treatment was 8.31 [95% confidence interval (CI): 3.88-17.78] times more effective in the LI-ESWT group (n=176) than in the sham-treatment group (n=101) at about 1 month after the intervention in terms of EHS, while it was 2.50 (95% CI: 0.74-8.45) times more in the treatment group (n=121) than in the control group (n=89) in terms of IIEF-EF. Nine-week protocol with energy density of 0.09mJ/mm2 and 1500 pluses seemed to have better therapeutic effect than five-week protocol. No significant adverse event was reported. CONCLUSION: LI-ESWT, as a noninvasive treatment, has potential short-term therapeutic effect on patients with organic ED irrespective of sensitivity to PDE5is. Owing to the limited number and quality of the studies, more large-scale, well-designed and long-term follow-up time studies are needed to confirm our analysis.

Clinicopathological Characteristics, Treatment, and Prognosis of Rarely Primary Epididymal Adenocarcinoma: A Review and Update.

Primary epididymal adenocarcinoma (PEA) is exceedingly rare. Only 22 cases had been published worldwide by 2008; nearly 80% of these cases were reported before 2007. In order to investigate the current clinical status of PEA, we search for relevant literatures with "epididymis and adenocarcinoma" and "epididymal and adenocarcinoma" as keywords published between January 1997 and November 2017 in PubMed. As a result, 17 cases are identified. We review these cases and summarize new and important perspectives about the clinicopathological characteristics, diagnosis, treatment, and prognosis of PEA in the present review.

Radiocolloid-based dynamic sentinel lymph node biopsy in penile cancer with clinically negative inguinal lymph node: an updated systematic review and meta-analysis.

PURPOSE: More literatures regarding radiocolloid-based dynamic sentinel lymph node biopsy (DSNB) in penile cancer with clinically negative groin (cN0) have been published since previous meta-analysis in 2012. This updated meta-analysis was to assess the accuracy of the procedure in penile cancer with cN0 disease and explore its relative factors on the basis of current evidences. MATERIALS AND METHODS: We performed a review of PubMed, Ovid/Embase, and the Cochrane Library in March 2016 according to the Preferred Reporting Items for Systematic Review and Meta-analysis (PRISMA) statement. Study quality was evaluated by the use of the Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2). A random effects model was used for statistical pooling. Publication bias was evaluated by the use of funnel plot and Egger's test. Meta-regression, subgroup and sensitivity analysis were conducted to explore the sources of heterogeneity. RESULTS: A total of 27 articles were included. Two articles had two different cohorts and each cohort was considered a separate study. Overall 29 studies were used for sensitivity and negative predictive value (NPV) meta-analysis. The pooled sensitivity and NPV was 88 % (95 % CI 84-90 %) and 99 % (98-99 %), respectively. Meta-regression and subgroup analysis revealed that the use of preoperative ultrasonic scan (USS) ± fine-needle aspiration cytology (FNAC), surgical exploration of wound for suspicious lymph nodes (LN), immunohistochemistry (IHC) and extensive experience were significantly associated with the improved sensitivity of DSNB. CONCLUSIONS: Radiocolloid-based DSNB is a promising staging modality to detect inguinal micrometastasis in penile cancer without clinically positive inguinal LN. Preoperative USS ± FNAC and surgical exploration are effective supplements to exclude potentially clinical involvement, and IHC makes the diagnosis of occult metastasis in SLN more likely. The multidisciplinary and multistep procedure should be performed by skilled teams in specialized centers.

[Minimally invasive techniques in the treatment of benign prostatic hyperplasia: An update].

Lower urinary tract symptoms (LUTS) resulting from benign prostatic hyperplasia (BPH) obviously impair the quality of life of middle-aged and elderly men. Current management of BPH includes wait-and-watch, medical therapy, and conventional surgery. As a new approach, minimally invasive surgery has been playing an increasingly important role in the management of BPH, with potential advantages of less operative trauma, quicker recovery, lower risk of postoperative complications and higher quality of life. This review mainly discusses prostatic urethral lift (Urolift® System), transurethral water vapor therapy (Rezum® System) and robot-guided high-energy water ablation (PROCEPT Aquablation™ System).

[Prostatic urethral lift: A novel minimally invasive treatment for benign prostatic hyperplasia].

Benign prostatic hyperplasia (BPH) and BPH-induced lower urinary tract symptoms (LUTS) are common factors influencing the quality of life (QOL) of elderly males. In case of undesirable or adverse effects of medication, many BPH patients seek surgical treatment. Transurethral resection of the prostate (TURP), though evidently effective for BPH, fails to preserve the sexual function and therefore reduces the QOL of the patients. Moreover, some elderly patients with comorbidities may be unfit for TURP. Prostatic urethral lift (PUL) is a newly developed surgical procedure for the treatment of LUTS secondary to BPH. With the advantages of minimal invasiveness, low rate of peri- and post-operative complications, and maximal preservation of patients' erectile and ejaculatory functions, PUL is winning more and more attention from the clinicians and patients.