The EPR effect of 41 renal tumors collected from clinical patients were analyzed via perfusion strategy, correlating the EPR effect in human tumors with that in animal models and confirming that more ...than 87 % of the examined renal tumors possess the considerable EPR effect, which yet showed significant diversity and heterogeneity in different patients.
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•An ex vivo perfusion model was developed for real-time investigation of the EPR effect in human renal tumors via X-ray computed tomography (CT).•The EPR in human solid tumors was positively correlated with that in animal models.•Considerable EPR effect was observed in more than 87% of human renal tumors, which showed significant diversity and heterogeneity.
The enhanced permeability and retention (EPR) effect in human solid tumors is being increasingly questioned due to the failure of many nanomedicines in their clinical translation. Herein, we developed an ex vivo perfusion model for real-time investigation of the EPR effect in human renal tumors via X-ray computed tomography (CT), proving the EPR in human solid tumors and correlating the EPR effect in human tumors with that in animal models. Unexpectedly, more than 87 % of human renal tumors displayed a considerable EPR effect, which yet showed significant diversity and heterogeneity in different patients. For the first time, we unraveled that the EPR effect in renal tumors was positively correlated with the tumor size, and tumors from male patients exhibited a significantly higher EPR effect. This ex vivo model provides an efficient strategy for investigating the EPR effect in human tumors. Our results may provide a theoretical basis for the development of anticancer nanomedicines in the future.
Type 2 diabetes mellitus erectile dysfunction (T2DMED) is one of the common complications of type 2 diabetes mellitus (T2DM). Icariside II (ICA II), a flavonoid derived from Epimedium, has been shown ...to improve erectile function in T2DMED rats.
To investigate the effect of ICA II and metformin (MET) on penile erectile function, mitochondrial autophagy, glucose-lipid metabolism in rats with T2DMED.
In the control and T2DMED groups, rats were administered normal saline. In the MET group, rats were administered MET for 0.2 g/kg/day. In the ICA II+MET group, rats were administered ICA II for 10 mg/kg/day and MET for 0.2 g/kg/day.
The number of mating rats, number of erectile rats, erection rate, erection frequency, intracorneal pressure, and intracorneal pressure/mean arterial pressure in the ICA II+MET group and control group were significantly higher than corresponding values in than T2DMED group. The absolute values of fasting plasma glucose, glycated haemoglobin in the ICA II+MET group, MET group, and control group were significantly lower than in the T2DMED group. The advanced glycation end product (AGE) values in the ICA II+MET group and the MET group were lower than in the T2DMED group. The receptors for the AGE values and angiotensin II values in the ICA II+MET group were lower than in the T2DMED and MET groups. The high-density lipoprotein values, testosterone values, nitric oxide synthase activity, and cyclic guanosine monophosphate content in the ICA II+MET and control groups were higher than in the T2DMED group. The low-density lipoprotein values, triglyceride values, estradiol values, and total cholesterol values in the ICA II+MET and control groups were lower than in the T2DMED group.
ICA II could increase erectile function and smooth muscle cell/collagen fibril proportions, decreased mitochondrial autophagy, and AGE concentrations and improve lipid metabolism, nitric oxide synthase activity, cyclic guanosine monophosphate content, testosterone, estradiol, and Ang II in rat with T2DMED.
Zhang J, Li S, Zhang S, et al. Effect of Icariside II and Metformin on Penile Erectile Function, Histological Structure, Mitochondrial Autophagy, Glucose-Lipid Metabolism, Angiotensin II and Sex Hormone in Type 2 Diabetic Rats With Erectile Dysfunction. J Sex Med 2020;8:168–177.
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Recently, zwitterionic materials have been developed as alternatives to PEG for prolonging the circulation time of nanoparticles without triggering immune responses. However, ...zwitterionic coatings also hindered the interactions between nanoparticles and tumor cells, leading to less efficient uptake of nanoparticles by cancer cells. Such effect significantly limited the applications of zwitterionic materials for the purposes of drug delivery and the development to novel therapeutic agents. To overcome these issues, surface-adaptive mixed-shell micelles (MSMs) with poly(2-methacryloyloxyethyl phosphorylcholine) (PMPC)/poly(β-amino ester) (PAE) heterogeneous surfaces were constructed. Owing to the synergistic effect of zwitterionic coatings and micro-phase-separated surfaces, PMPC mixed-shell micelles exhibited the improved blood circulation time compared to single-PEG-shell micelles (PEGSMs) and single-PMPC-shell micelles (PMPCSMs). Moreover, such MSMs can convert their surface to positively charged ones in response to the acidic tumor microenvironment, leading to a significant enhancement in cellular uptake of MSMs by tumor cells. This strategy demonstrated a general approach to enhance the cellular uptake of zwitterionic nanoparticles without compromising their long circulating capability, providing a practical method for improving the tumor-targeting efficiency of particulate drug delivery systems.
Herein we demonstrate a general strategy to integrate non-fouling zwitterionic surface on the nanoparticles without compromising their capability of tumor accumulation, by constructing a surface-adaptive mixed-shell micelles (MSMs) with poly(2-methacryloyloxyethyl phosphorylcholine) (PMPC)/poly(β-amino ester) (PAE) heterogeneous surfaces. At the blood pH (7.4), PAE chains collapsed to the inner of the shell due to the deprotonation, and the forming micro-phase separation structure was synergistic with zwitterionic surface to prolong the circulation time of MSMs in the blood. While at the tumor sites, PAE was protonated, and the positively charged surface of MSMs enhanced cellular uptake. This self-assembly-based strategy is compatible to other zwitterionic materials, endowing a great flexibility for the construction of responsive drug delivery systems particularly to the novel chemotherapeutic agents.
Prostate cancer is the second most common cancer in men worldwide
. Over the past decade, large-scale integrative genomics efforts have enhanced our understanding of this disease by characterizing ...its genetic and epigenetic landscape in thousands of patients
. However, most tumours profiled in these studies were obtained from patients from Western populations. Here we produced and analysed whole-genome, whole-transcriptome and DNA methylation data for 208 pairs of tumour tissue samples and matched healthy control tissue from Chinese patients with primary prostate cancer. Systematic comparison with published data from 2,554 prostate tumours revealed that the genomic alteration signatures in Chinese patients were markedly distinct from those of Western cohorts: specifically, 41% of tumours contained mutations in FOXA1 and 18% each had deletions in ZNF292 and CHD1. Alterations of the genome and epigenome were correlated and were predictive of disease phenotype and progression. Coding and noncoding mutations, as well as epimutations, converged on pathways that are important for prostate cancer, providing insights into this devastating disease. These discoveries underscore the importance of including population context in constructing comprehensive genomic maps for disease.
Ultrasound-guided renal access for percutaneous nephrolithotomy (PCNL) is a safe, effective, and low-cost procedure commonly performed worldwide, but a technique underutilized by urologists in the ...United States. The purpose of this article is to familiarize the practicing urologist with methods for ultrasound guidance for percutaneous renal access. We discuss two alternative techniques for gaining renal access for PCNL under ultrasound guidance. We also describe a novel technique of using the puncture needle to reposition residual stone fragments to avoid additional tract dilation. With appropriate training, ultrasound-guided renal access for PCNL can lead to reduced radiation exposure, accurate renal access, and excellent stone-free success rates and clinical outcomes.
To investigate the effect of hypertension on the (enhanced permeability and retention, EPR) effect induced by polymer nanomicelles in renal cell carcinoma in vitro.
A total of 80 patients with renal ...cell carcinoma treated at the Department of Urology Surgery in the Dept. of Urology of the Affiliated Hospital of Hebei University from Oct. 2019 to Oct. 2020, were analyzed retrospectively. The hypertension group (experimental group) included 40 patients, and the normal blood pressure group (control group) included 40 patients. The diagnosis of renal clear cell carcinoma was confirmed by preoperative auxiliary examinations, such as ultrasonography and CT combined with postoperative pathological analysis. All patients underwent laparoscopic radical nephrectomy for renal cell carcinoma. Polymer nanomicelles (loaded with prolonium iodide) were perfused into the resected kidney specimens within the specified time. The iodine enrichment of polymer nanomicelles in renal tumors was assessed by CT scanning. The peak EPR effect and the time to the peak were statistically compared between the two groups.
No significant differences were found in age, sex, location of kidney disease, tumor location or tumor size between the two groups (
0.05). The peak (
±
) of the EPR effect in experimental group was 3.60±0.95 ug/cm
and 3.01±0.96 ug/cm
in control group, respectively. There was significant difference between the two groups (
0.05). The time to the peak of the EPR effect was 3.76±0.75 h in experimental group and 3.82±0.93 hour in control group, respectively. No statistically significant difference was found in the time to the peak of the EPR effect between the two groups (
0.05).
Hypertension has a certain effect on the EPR effect induced by polymer nanomicelles in renal cell carcinoma in vitro.
Bladder cancer is one of the most aggressive urothelial tumors. Previous studies have suggested that epithelial–mesenchymal transition (EMT) contributes to bladder cancer progression. However, the ...regulatory network of EMT in bladder cancer remains elusive. In this study, we found Yin Yang 1 (YY1) is a critical regulator of EMT in bladder cancer. First, we showed that YY1 was upregulated in bladder cancer tissues than that in adjacent normal tissues. Then, we proved that YY1 promoted EMT of bladder cancer cells. Further experiments indicated that YY1 affected the EMT of bladder cancer through transforming growth factor-β (TGFβ) signaling pathway. Taken together, our study identifies YY1 as a key EMT driver in bladder cancer, suggesting it as a potential therapeutic target.
Benign prostatic hyperplasia (BPH) is a common chronic progressive disease resulting in urinary obstruction in aging men. It comes to more and more patients with massive BPH with the aging of society ...and extension of life expectancy.
The aim of the study was to compare the clinical efficacy, safety, and complications between transurethral bipolar plasmakinetic enucleation of the prostate (PKEP) and transurethral resection of the prostate (TURP) in the treatment of massive BPH.
Patients with BPH were divided into the PKEP group and the TURP group randomly. Intraoperative blood loss (BL), operation time (OT), resected tissue weight (RTW), gland resection ratio (GRR), postoperative indwelling ureter time (IUT), bladder fistula time (BFT) and hospital stay time (HST), preoperative and postoperative serum sodium concentration (SSC), hemoglobin concentration (HGB), prostate weight (PW), postvoid residual (PVR), maximum urinary flow rate (Qmax), international prostate symptom score (IPSS), quality of life (QOL), International Index of Erectile Function (IIEF), and other complications were analyzed and compared respectively.
There was no statistical difference in preoperative IPSS, preoperative QOL score, preoperative PVR, preoperative Qmax, postoperative QOL score, postoperative PVR, postoperative Qmax, IPSS difference value (DV), Qmax DV, and PVR DV between the PKEP group and the TURP group (p > 0.05). OT, BL, IUT, BFT, HST, and postoperative IPSS in the PKEP group were significantly lower than that in the TURP group (p < 0.01). RTW and GRR in the PKEP group were significantly higher than that in the TURP group (p < 0.01). QOL DV in the PKEP group was higher than that in the TURP group (p < 0.05). There was statistical difference in SSC DV between the PKEP group and the TURP group (p < 0.05). There was significant statistical difference in postoperative PW, postoperative HGB, PW DV, and HGB DV between the PKEP group and the TURP group (p < 0.01). There was significant statistical difference in IPSS, QOL, PVR, and Qmax between postoperative value and preoperative value in both groups (p < 0.01). The incidence of transurethral resection syndrome, obturator nerve reflex, transient urinary incontinence, and retrograde ejaculation between the PKEP group and the TURP group has no statistical difference (p > 0.05). Capsule perforation, blood transfusion, secondary hemorrhage, bladder neck contracture, and urethral stricture in the PKEP group were lower than that in the TURP group (p < 0.05). Bladder spasm in the PKEP group was significantly lower than that in the TURP group (p < 0.01). There was no statistical difference in preoperative and postoperative IIEF-5, effective erectile frequency, telotism average tension, sustainable telotism average time, and sexual dissatisfaction between the PKEP group and the TURP group (p > 0.05).
PKEP and TURP have similar clinical efficacy in the treatment of massive BPH. PKEP has advantages in shorter OT, less BL, more GRR, and fewer complications, but the long-term therapeutic effect of PKEP needs further follow-up.
To explore the establishment of a scoring system that can provide a reference for clinical decision making regarding the endoscopic treatment of 1-2 cm lower pole stones (LPS).
The data of patients ...with renal calculi who were treated with percutaneous nephrolithotomy (PCNL) or retrograde intrarenal surgery (RIRS) in three hospitals from January 2013 to December 2017 were analyzed retrospectively. Multivariable logistic analysis was performed to determine the statistically significant indicators and regression coefficients, which were used to construct the scoring system. The stone-free rate (SFR) and postoperative complication rates of PCNL and RIRS within the two fractional segments of the scoring system were compared to select the optimal procedures.
A total of 137 patients in the PCNL group and 152 patients in the RIRS group were included in this study. Five factors were found to be most predictive of endoscopic treatment choice: stone number, stone diameter, infundibulopelvic angle (IPA), infundibular length (IL), and infundibular width (IW), yielding a total score ranging from 0-5. In the 0-2 segments, the RIRS group had better outcomes than the PCNL group in terms of the postoperative complication rates (6.8% versus 18.0%, P = .026). In segments 3-5, the SFR of the PCNL group was significantly higher than that of the RIRS group (88.5% versus 70.6%, P = .017).
Our scoring system was based on the patient's preoperative imaging examination to measure the stone number, stone diameter, IPA, IL and IW. RIRS was recommended at 0-2 segments, and PCNL was recommended at 3-5 segments. This new scoring system is expected to provide guidance for urologists to make endoscopic treatment decisions for 1-2 cm LPS.
Purpose
The goal of this study is to evaluate the efficacy and safety of modified triangular double-J (DJ) stent in 1–2 cm renal or ureter calculi after retrograde intrarenal surgery (RIRS) via a ...randomized, controlled clinical study.
Methods
A total of 196 patients with 1–2 cm renal or ureter calculi who were performed RIRS and received 7Fr modified triangular DJ stents (100 cases) or 6Fr normal DJ stents (96 cases). All operations were performed by experienced surgeons. The clinical characteristics and outcomes were analyzed.
Results
There were no significant differences between two groups in terms of age, gender, BMI, location, hydronephrosis, urea WBC, urea RBC, BUN, Cr, laser emission time, operation time, Hb loss, postoperative BUN, postoperative Cr. Patients who received modified triangular DJ stents were shown to have higher stone-free rate (
p
= 0.038), but lower general health (
p
= 0.004).
Conclusion
The modified triangular 7Fr DJ stents were more efficient for patients underwent RIRS than 6Fr normal DJ stents.
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