Epithelial cells derived exosomal miR-203a-3p facilitates stromal inflammation of type IIIA chronic prostatitis/chronic pelvic pain syndrome by targeting DUSP5 and increasing MCP-1 generation.

Increased proinflammatory cytokines and infiltration of inflammatory cells in the stroma are important pathological features of type IIIA chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS-A), and the interaction between stromal cells and other cells in the inflammatory microenvironment is closely related to the inflammatory process of CP/CPPS-A. However, the interaction between stromal and epithelial cells remains unclear. In this study, inflammatory prostate epithelial cells (PECs) released miR-203a-3p-rich exosomes and facilitated prostate stromal cells (PSCs) inflammation by upregulating MCP-1 expression. Mechanistically, DUSP5 was identified as a novel target gene of miR-203a-3p and regulated PSCs inflammation through the ERK1/2/MCP-1 signaling pathway. Meanwhile, the effect of exosomes derived from prostatic fluids of CP/CPPS-A patients was consistent with that of exosomes derived from inflammatory PECs. Importantly, we demonstrated that miR-203a-3p antagomirs-loaded exosomes derived from PECs targeted the prostate and alleviated prostatitis by inhibiting the DUSP5-ERK1/2 pathway. Collectively, our findings provide new insights into underlying the interaction between PECs and PSCs in CP/CPPS-A, providing a promising therapeutic strategy for CP/CPPS-A.

Spatial heterogeneity of tumor microenvironment influences the prognosis of clear cell renal cell carcinoma.

BACKGROUND: Clear cell renal cell carcinoma (ccRCC) is an immunologically and histologically diverse tumor. However, how the structural heterogeneity of tumor microenvironment (TME) affects cancer progression and treatment response remains unclear. Hence, we characterized the TME architectures of ccRCC tissues using imaging mass cytometry (IMC) and explored their associations with clinical outcome and therapeutic response. METHODS: Using IMC, we profiled the TME landscape of ccRCC and paracancerous tissue by measuring 17 markers involved in tissue architecture, immune cell and immune activation. In the ccRCC tissue, we identified distinct immune architectures of ccRCC tissue based on the mix score and performed cellular neighborhood (CN) analysis to subdivide TME phenotypes. Moreover, we assessed the relationship between the different TME phenotypes and ccRCC patient survival, clinical features and treatment response. RESULTS: We found that ccRCC tissues had higher levels of CD8+ T cells, CD163- macrophages, Treg cells, endothelial cells, and fibroblasts than paracancerous tissues. Immune infiltrates in ccRCC tissues distinctly showed clustered and scattered patterns. Within the clustered pattern, we identified two subtypes with different clinical outcomes based on CN analysis. The TLS-like phenotype had cell communities resembling tertiary lymphoid structures, characterized by cell-cell interactions of CD8+ T cells-B cells and GZMB+CD8+ T cells-B cells, which exhibited anti-tumor features and favorable outcomes, while the Macrophage/T-clustered phenotype with macrophage- or T cell-dominated cell communities had a poor prognosis. Patients with scattered immune architecture could be further divided into scattered-CN-hot and scattered-CN-cold phenotypes based on the presence or absence of immune CNs, but both had a better prognosis than the macrophage/T-clustered phenotype. We further analyzed the relationship between the TME phenotypes and treatment response in five metastatic ccRCC patients treated with sunitinib, and found that all three responders were scattered-CN-hot phenotype while both non-responders were macrophage/T-clustered phenotype. CONCLUSION: Our study revealed the structural heterogeneity of TME in ccRCC and its impact on clinical outcome and personalized treatment. These findings highlight the potential of IMC and CN analysis for characterizing TME structural units in cancer research.

Gene mutation profiling and clinical significances in patients with renal cell carcinoma.

OBJECTIVES: The pathological mechanisms of patients with Renal Cell Carcinoma (RCC) remain defined. This study aimed to evaluate relationships between the landscape of gene mutations and their clinical significance in RCC patients. METHODS: Tissue and peripheral blood samples of 42 patients with RCC were collected and performed for the Next Generation Sequencing (NGS) with Geneseeq PrimeTM 425-gene panel probes. Their landscapes of gene mutation were analyzed. We also carried out an evaluation of Tumor-Node-Metastasis (TNM) staging, RENAL nephelometry score, surgery, and targeted drug treatment of patients. Then we compared the correlations of landscape in gene mutations and the prognosis. RESULTS: The most common gene alternations, including BAP1, PBRM1, SETD2, CSF1R, NPM1, EGFR, POLE, RB1, and VHL genes, were identified in tissue and blood samples of 75% of patients. EGFR, POLE, and RB1 gene mutations frequently occurred in relapsed and metastatic patients. BAP1, CCND2, KRAS, PTPN11, ERBB2/3, JAK2, and POLE were presented in the patients with > 9 RENAL nephelometry score. Univariable analysis indicated that SETD2, BAP1, and PBRM1 genes were key factors for Disease-Free Survival (DFS). Multivariable analysis confirmed that mutated SETD1, NPM1, and CSF1R were critical factors for the Progression Free Survival (PFS) of RCC patients with target therapy. CONCLUSIONS: Wild-type PBRM1 and mutated BAP1 in patients with RCC were strongly associated with the outcomes of the patient. The PFS of the patients with SETD2, NPM1, and CSF1R mutations were significantly shorter than those patients without variants.

Glucocorticoid nanoformulations relieve chronic pelvic pain syndrome and may alleviate depression in mice.

BACKGROUND: Chronic pelvic pain syndrome (CPPS) is a typical symptom of chronic prostatitis (CP) in males that may cause abnormal urination, sexual dysfunction, or depression and significantly affect the quality of life of the patient. Currently, there is no effective treatment for CPPS due to its recurrence and intractability. For synergistic CPPS therapy, we developed pH/reactive oxygen species (ROS) dual-responsive dexamethasone (Dex) nanoformulations using a ROS-responsive moiety and phytochemical modified α-cyclodextrin (α-CD) as the carrier. RESULTS: Dex release from the nanoformulations can be controlled in acidic and/or ROS-rich microenvironments. The fabricated Dex nanoformulations can also be efficiently internalized by lipopolysaccharide (LPS)-stimulated macrophages, prostatic epithelial cells, and stromal cells. Moreover, the levels of proinflammatory factors (e.g., TNF-α, IL-1ß, and IL-17 A) in these cells were significantly decreased by Dex nanoformulations treatment through the release of Dex, phytochemical and elimination of ROS. In vivo experiments demonstrated notable accumulation of the Dex nanoformulations in prostate tissue to alleviate the symptoms of CPPS through the downregulation of proinflammatory factors. Interestingly, depression in mice may be relieved due to alleviation of their pelvic pain. CONCLUSION: We fabricated Dex nanoformulations for the effective management of CPPS and alleviation of depression in mice.

Comparison of antegrade robotic assisted VS laparoscopic inguinal lymphadenectomy for penile cancer.

BACKGROUND: Minimally invasive modifications of inguinal lymphadenectomy (IL), including laparoscopic IL (LIL) and robotic-assisted IL (RAIL), have been utilized for penile cancer. Comparative study is necessary to guide the decision about which minimally invasive technique to select for IL. Therefore we compared RAIL with LIL performed via an antegrade approach in terms of perioperative outcomes. METHODS: We conducted a retrospective study of 43 patients who underwent RAIL (n = 20) or LIL (n = 23) for penile cancer from 2016 to 2020. The key surgical procedures and techniques are described. Complications were graded by the Clavien-Dindo classification, and operative time, estimated blood loss (EBL), lymph nodal yield, nodal positivity, postoperative drain duration, and disease recurrence during follow-up were assessed. Categorical variables were compared using chi-squared whereas continuous variables were compared by t-tests. RESULTS: The operative time for RAIL was significantly shorter than that of LIL (median 83 vs 95 min). Significantly less blood loss was reported with RAIL than with LIL (median 10 vs 35 ml). Lymph node yield, pathological positive nodes, the hospital stay, postoperative drain duration, postoperative complications and recurrence were similar for RAIL and LIL. CONCLUSIONS: For patients with penile cancer, perioperative outcomes of RAIL and LIL were similar, but there was less blood loss, a shorter operative time for robotic cases.

Gene mutation profiling and clinical significances in patients with renal cell carcinoma

Abstract Objectives The pathological mechanisms of patients with Renal Cell Carcinoma (RCC) remain defined. This study aimed to evaluate relationships between the landscape of gene mutations and their clinical significance in RCC patients. Methods Tissue and peripheral blood samples of 42 patients with RCC were collected and performed for the Next Generation Sequencing (NGS) with Geneseeq PrimeTM 425-gene panel probes. Their landscapes of gene mutation were analyzed. We also carried out an evaluation of Tumor-Node-Metastasis (TNM) staging, RENAL nephelometry score, surgery, and targeted drug treatment of patients. Then we compared the correlations of landscape in gene mutations and the prognosis. Results The most common gene alternations, including BAP1, PBRM1, SETD2, CSF1R, NPM1, EGFR, POLE, RB1, and VHL genes, were identified in tissue and blood samples of 75% of patients. EGFR, POLE, and RB1 gene mutations frequently occurred in relapsed and metastatic patients. BAP1, CCND2, KRAS, PTPN11, ERBB2/3, JAK2, and POLE were presented in the patients with > 9 RENAL nephelometry score. Univariable analysis indicated that SETD2, BAP1, and PBRM1 genes were key factors for Disease-Free Survival (DFS). Multivariable analysis confirmed that mutated SETD1, NPM1, and CSF1R were critical factors for the Progression Free Survival (PFS) of RCC patients with target therapy. Conclusions Wild-type PBRM1 and mutated BAP1 in patients with RCC were strongly associated with the outcomes of the patient. The PFS of the patients with SETD2, NPM1, and CSF1R mutations were significantly shorter than those patients without variants.

Photoselective sharp enucleation of the prostate with a front-firing 532-nm laser versus photoselective vaporization of the prostate in the treatment of benign prostatic hyperplasia: a randomised controlled trial with 1-year followup results.

BACKGROUND: We designed a new surgical procedure to treat benign prostatic hyperplasia(BPH). In order to verify its effectiveness and safety, we constructed this randomized controlled trial to compare the efficacy of our innovative enucleation technique- photoselective sharp enucleation of the prostate (PSEP), with a front-firing 532-nm laser and the traditional technique-photoselective vaporization of the prostate (PVP) in the treatment of BPH. METHODS: A total of 154 consecutive patients diagnosed with bladder outlet obstruction secondary to BPH in our center from June 2018 to April 2019 were randomly divided into the PSEP group (n = 77) and the PVP group (n = 77) and were treated surgically with either PSEP or PVP. All patients were assessed preoperatively and followed up at 1, 6, and 12 months postoperatively. The international prostate symptom score,quality-of-life score, postvoid residual urine volume, maximum urine flow rate, prostate volume, prostate-specific antigen, and adverse events were compared. RESULTS: The lower urinary tract symptoms in both groups were significantly improved compared with the baseline at 1, 6, and 12 months postoperatively. The PSEP and PVP groups had an equivalent International Prostate Symptom Score, quality-of-life score, postvoid residual urine volume, maximum urine flow rate, prostate-specific antigen at each follow-up (P > 0.05). The median operative time in the PSEP group was significantly shorter than that in the PVP group (35 min vs. 47 min, P < 0.001). At 6 and 12 months after surgery, the median PV in the PSEP group was smaller than that in the PVP group (P < 0.05). Complication rates were comparable between the groups. CONCLUSION: Both PSEP and PVP can achieve good efficacy and safety in the treatment of BPH. PSEP can remove more tissue than PVP and is associated with higher efficiency. In addition, PSEP eliminates the problem of lack of tissue samples associated with PVP. TRIAL REGISTRATION: Chinese Clinical Trial Registry, identifie:ChiCTR1800015867, date:25/04/2018.

In vivo targeting capacities of different nanoparticles to prostate tissues based on a mouse model of chronic bacterial prostatitis.

Chronic bacterial prostatitis usually occurs in men and seriously affects the quality of life of patients. The efficacy of chronic bacterial prostatitis treatment is limited by the difficulty for free drugs (e.g., antibiotics) to penetrate the prostate epithelium and target inflammatory tissues. The advent of nanotechnology offers the possibility to address this issue, such as the development of targeted nanoparticle delivery strategies that may overcome these important limitations. The physicochemical properties of nanoparticles, such as particle size, shape and surface modification ligands, determine their targeting effectiveness. In this study, nanoparticles with different physicochemical properties were prepared to explore and confirm their targeting capacities to inflammatory prostate tissues of chronic bacterial prostatitis, focusing on the effects of size and different modification ligands on the targeting performance. In vivo and ex vivo imaging results verified that folic acid-modified nanoparticles with a particle size of 180-190 nm via tail intravenous injection had the optimal targeting efficiency to prostate tissues. Our results provide an experimental basis and reference value for targeted therapy of prostate-related diseases with nanotechnology in the future.

One-step coordination of metal-phenolic networks as antibacterial coatings with sustainable and controllable copper release for urinary catheter applications.

Catheter-associated urinary tract infections (CAUTIs) draw great concern due to increased demand for urinary catheters in hospitalization. Encrustation caused by urinary pathogens, especially Proteus mirabilis, results in blocking of the catheter lumen and further infections. In this study, a facile and low-cost surface modification strategy of urinary catheters was developed using one-step coordination of tannic acid (TA) and copper ions. The copper content of the coating could be manipulated by the number of TA-Cu (TC) layers, and the coating released copper in a pH-responsive manner. The coating exhibited high antibacterial efficiency (killed >99% of planktonic bacteria, and reduced biofilm coverage to <1% after 24 h) due to the synergistic antimicrobial effect of TA and copper ions. In vivo study with a rabbit model indicated that with two TC layers, the coated catheter could effectively inhibit bacterial growth in urine and colonization on the surface, and reduce encrustation formation. In addition, the TC-coated catheter exhibited better tissue compatibility compared to the unmodified catheter, probably due to the antibacterial performance of the coating. Such a straightforward coating strategy with good in vitro and in vivo antibacterial properties and biocompatibility holds great promise for combating CAUTIs in clinical practice.

Antibiotic-loaded reactive oxygen species-responsive nanomedicine for effective management of chronic bacterial prostatitis.

Chronic bacterial prostatitis (CBP) occurs frequently in the male population and significantly influences quality of life. Antibiotics are the main strategy for managing chronic bacterial prostatitis; however, most antibiotics have low efficacy due to their poor penetration of prostate tissues. To overcome this challenge, we fabricated cefpodoxime proxetil (CPD)-loaded reactive oxygen species (ROS)-responsive nanoparticles (NPs) for targeted treatment of CBP. These NPs were modified with folic acid (FA) and could be effectively internalized by bacteria-infected macrophages and prostatic epithelial cells because of the high expression of folate receptors (FRs) in these cells. In vitro cellular assays demonstrated that the CPD-loaded nanomedicine can obviously reduce proinflammatory cytokine expression in cells since the nanomedicine can efficiently eradicate cellular bacteria. In vivo imaging results verified that FA-modified nanomedicines can penetrate the prostatic epithelium and accumulate in the glandular lumen because FRs overexpression was also observed in the prostate tissues of CBP mice. Animal experiments demonstrated that FA-modified nanomedicine can remarkably relieve pelvic pain in CBP mice and dramatically decrease proinflammatory cytokine expression in prostate tissues via eradication of bacteria and scavenging of ROS. Our results provide a new strategy to deliver antibiotics for targeted therapy of CBP. STATEMENT OF SIGNIFICANCE: To overcome poor penetration of antibiotics in prostatic tissues, we developed an antibiotics-loaded ROS-responsive NPs for targeted treatment of CBP. We demonstrated that both bacteria-infected macrophages and prostatic epithelial cells have FRs overexpression, thus FA-modified NPs can be efficiently internalized by these cells. FA-modified NPs can penetrate the prostatic epithelium and accumulate in the glandular lumen via FRs-mediated endocytosis, and the accumulated NPs can smartly release their payload under high ROS microenvironment. A distinguished therapy outcome was obtained in murine CBP model since CPD-loaded NPs can efficiently eradicate the resident bacteria in prostate tissues and downregulate proinflammatory cytokine expression. Our work provides a practicable strategy to expand the application of antibiotics for management of CBP.

Preliminary Functional Outcome Following Robotic Intracorporeal Orthotopic Ileal Neobladder Suspension with Round Ligaments in Women with Bladder Cancer.

BACKGROUND: Chronic urinary retention (CUR) is a frequent complication after orthotopic neobladder (ONB) reconstruction in women. To decrease CUR, several open surgical modifications to provide back support to the ONB have been established on the basis of pelvic anatomical differences between females and males. OBJECTIVE: To illustrate our technique for robotic intracorporeal reconfiguration of ONB as integrated into our open surgical approach to provide back support to the ONB with round ligaments in women. DESIGN, SETTING, AND PARTICIPANTS: From November 2017 to April 2021, 28 patients underwent robotic intracorporeal ONB with a minimum of 6 mo of follow-up at a single centre. SURGICAL PROCEDURE: We performed robotic radical cystectomy, pelvic lymphadenectomy, and a complete intracorporeal ONB suspended with round ligaments (rONB). Our surgical procedure is demonstrated in the accompanying video. MEASUREMENTS: Demographics and clinical and pathological data were collected. Perioperative and 90-d complications and 6-mo functional outcomes were compared for the rONB group (n = 12) and the patients receiving a traditional ONB (tONB; n = 16). RESULTS AND LIMITATIONS: The median total operative time was 305 min (interquartile range [IQR] 270-370) for tONB and 303 min (IQR 287-330) for rONB. The median estimated blood loss was 325 ml (IQR 200-700) for tONB and 350 ml (IQR 262-600) for rONB. Some 50% of the tONB group and 41.7% of the rONB group experienced low-grade complications. A total of 12.5% tONB and 8.3% rONB patients experienced high-grade complications with neobladder-vaginal fistula. The cumulative risk of CUR was 37.5% in the tONB group and 16.7% in the rONB group. This study is limited by the small sample size and the short follow-up period. CONCLUSIONS: We established a feasible surgical technique for a robotic intracorporeal ONB configuration suspended with round ligaments. This may prevent the occurrence of emptying dysfunction in women. PATIENT SUMMARY: We describe our stepwise technique for creating a new bladder within the body that is suspended with round ligaments. Patients undergoing removal of the bladder for bladder cancer may benefit from this technique in terms of better urinary function and the advantages of a robotic surgical approach.

Prostatic fluid exosome-mediated microRNA-155 promotes the pathogenesis of type IIIA chronic prostatitis.

BACKGROUND: The latest research has shown that exosomes play an important role in cell-to-cell communication and are closely related to the occurrence of many chronic inflammatory diseases. However, no studies have clarified whether exosomes are involved in the pathogenesis of aseptic inflammation, type IIIA chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS-A). This study aimed to explore the relationship between prostatic fluid exosomes and CP/CPPS-A and reveal new pathogenesis. METHODS: Our group collected prostatic fluid samples from CP/CPPS-A patients and normal adult men. Electron microscope, quantitative PCR (qPCR), Western Blot, nanoparticle tracking analysis, hematoxylin-and-eosin (HE) staining, immunofluorescence staining and miRNA-155 functional analysis were used to verify the role of exosomes in CP/CPPS-A in vivo and in vitro. RESULTS: Exosomes were abundantly enriched in the prostatic fluid of CP/CPPS-A patients and selectively overloaded with microRNA-155 (miRNA-155). These exosomes were taken up by prostatic stromal cells in large quantities. They activated interleukin (IL)-8 and tumor necrosis factor-alpha (TNF-α) expression in vitro, and the integrity of the exosomes' plasma membrane is a necessary condition for information transmission by exosomes. In in vivo experiments, histological results showed that prostatic fluid exosomes induced prostatitis in rats. Also, immunofluorescence staining showed excessive activation of IL-8, TNF-α, and inducible nitric oxide synthase (iNOS). CONCLUSIONS: Exosomes in the prostatic fluid and the miRNA-155 contained therein were may be involved with the pathogenesis of CP/CPPS-A.

Photoselective sharp enucleation of the prostate with a front-firing 532-nm laser: an innovative surgical technique for benign prostatic hyperplasia-a single-center study of 475 cases.

PURPOSE: To describe the novel technique of photoselective sharp enucleation of the prostate (PSEP) with a front-firing 532-nm laser and evaluate its efficacy and safety. METHODS: A seven-step standardized surgical procedure was established, and PSEP was performed in an en bloc or lobulate manner according to the size of the middle lobe of the prostate. The following clinical data of 583 patients who underwent PSEP in our center from November 2016 to May 2018 were retrospectively reviewed: maximum flow rate (Qmax), International Prostate Symptom Score (IPSS), quality of life score (Qols), post-void residual volume (PVR), prostate volume, operation time, serum prostate-specific antigen (PSA) concentration, and complications at 1, 6, and 12 months postoperatively. RESULTS: Of the 583 patients, 475 had complete clinical information and were included in the study. The median operation time was 39 min. There were significant improvements in the Qmax, IPSS, Qols, PVR and PSA concentration at each follow-up time point postoperatively. Postoperative hemorrhage occurred in 22 patients (4.6%), urinary retention in 29 (6.1%), urinary tract infection in 55 (11.6%), bladder neck contracture in 8 (1.7%), urethral strictures in 11 (2.3%), and stress urinary incontinence in 9 (1.9%). CONCLUSIONS: PSEP is effective and safe for the treatment of benign prostatic hyperplasia. The innovative technique integrates the excellent hemostatic property of the 532-nm laser and the high efficiency of enucleation. It decreases the occurrence of postoperative incontinence associated with "blunt" enucleation of 532-nm laser and eliminates the lack of tissue samples problem associated with photoselective vaporization of the prostate.

Round ligament suspending treatment in orthotopic ileal-neobladder after radical cystectomy in women: a single-centre prospective randomised trial.

OBJECTIVES: To compare the occurrence of emptying dysfunction between surgical techniques for orthotopic neobladder suspended with round ligament (rONB) and the standard procedure (sONB). PATIENTS AND METHODS: A prospective randomised controlled trial was performed in a single centre of female patients undergoing creation of an ONB using rONB or sONB. Patients were followed for ≥24 months after ONB. The primary endpoints were significant post-void residual urine volume (sPVR) and need for clean intermittent catheterisation (CIC) at 24 months postoperatively. The secondary endpoints included early and late complications, urodynamic profile, and ONB continence. RESULTS: Between January 2011 and October 2017, the trial enrolled 85 patients, of whom 82 were randomised. A total of 41 patients had a rONB and 41 a sONB. At 24 months, 17 of the 37 patients with a sONB and nine of the 39 patients with a rONB had a sPVR. The cumulative risk of a sPVR was significantly lower in the rONB group (23.1%) vs the sONB group (45.9%) (hazard ratio [HR] 0.43, 95% confidence interval [CI], 0.19-0.96; P = 0.040). In all, 15 of the 37 patients with a sONB and four of the 39 patients with a rONB needed CIC. The cumulative risk of requiring CIC was significantly lower in the rONB group (10.3%) vs the sONB group (40.5%) (HR 0.22, 95% CI 0.07-0.67; P = 0.008) at 24 months. Multivariable Cox regression analysis also showed that the rONB type was an independently protective factor for sPVR and CIC. The rates of early (0-90 days) and late complication (>90 days) were 54.1% and 13.5% in the sONB group, and 64.1% and 10.3% in the rONB group, respectively. There were no significant differences in complications, urodynamic profile or ONB continence. A major limitation is the small sample size at a single centre. CONCLUSION: Posterior support with round ligament for an ONB significantly improved the emptying of the ONB and resulted in a reduced need for CIC. The surgical modification is a feasible and safe technique without additional complication-related surgeries.

Approaches for the synthesis of o-nitrobenzyl and coumarin linkers for use in photocleavable biomaterials and bioconjugates and their biomedical applications.

Photocleavable biomaterials and bioconjugates are particularly interesting because light sources are easy to obtain and the responsiveness of materials is convenient to control. In recent years, various photocleavable biomaterials and bioconjugates have been synthesized for the control of payload release, regulation of biomolecule activity, 3D cell culture, and investigation of molecular mechanisms. Photocleavable linkers are crucial components of photocleavable biomaterials, which significantly influence the photoresponsive capabilities of materials. Photosensitive molecules, such as o-nitrobenzyls and coumarins, have been extensively developed as photocleavable linkers. In the present review, we provide comprehensive knowledge regarding the synthetic strategies of o-nitrobenzyl and coumarin derived linkers with various functional groups and their applications for the construction of photocleavable biomaterials and bioconjugates. Finally, the biomedical applications of o-nitrobenzyl and coumarin-based photocleavable biomaterials and bioconjugates will be summarized and discussed.

Clinical efficacy of submucosal injection of triamcinolone acetonide in the treatment of type II/III interstitial cystitis/bladder pain syndrome.

BACKGROUND: To evaluate the efficacy of submucosal injection of triamcinolone acetonide for the treatment of type II/III interstitial cystitis/bladder pain syndrome. METHODS: A retrospective analysis of the clinical data of type II/III interstitial cystitis/bladder pain syndrome patients treated in our department from April 2016 to August 2018 was conducted, and changes in International Prostate Symptom Scores and the Pelvic Pain and Urgency/Frequency symptom scale after surgery were evaluated to explore factors that may affect patient outcomes. RESULTS: A total of 27 female patients and 8 male patients were enrolled, with type II patients accounting for 62.9% of the sample, and the median follow-up duration was 31 months (range: 12-40 months). Twenty-two patients (74.3%) had significantly improved questionnaire scores at 4 weeks postoperatively. Treatment efficacy was sustained for at least 1 year in 15 patients, and persistent effectiveness was noted in 10 (28.6%) patients. Patients with an advanced age (p = 0.015), high pain scores (p = 0.040), and higher International Prostate Symptom Scores (p = 0.037) and Pelvic Pain and Urgency/Frequency symptom scale scores (p = 0.020) were more likely to benefit from submucosal injection of triamcinolone acetonide. Gender, disease duration, and the presence of Hunner's lesions had no predictive value for treatment outcomes. CONCLUSION: Submucosal injection of triamcinolone acetonide can improve the clinical symptoms and quality of life in both men and women with type II/III interstitial cystitis/bladder pain syndrome. Patients with an advanced age and more severe interstitial cystitis/bladder pain syndrome related symptoms may benefit more from triamcinolone acetonide injection.

Reduced Ca2+ spark activity contributes to detrusor overactivity of rats with partial bladder outlet obstruction.

We tested whether or not altered Ca2+ spark activity accounted for detrusor overactivity (DO) of Wistar rats after partial bladder outlet obstruction (PBOO). We constructed a DO model through PBOO and studied the Ca2+ spark activity of detrusor. By way of using confocal microscopy and the patch-clamp technique, Ca2+ sparks and spontaneous transient outward currents (STOCs) in detrusor myocytes were measured respectively. Our results indicated that Ca2+ spark activity and STOCs were significantly reduced in the DO detrusor myocytes compared to unafflicted control cells, and both of these had levels that were remarkably increased by applications of caffeine (10 µM), a RyR agonist, in DO myocytes. In addition, measures of detrusor contractions were also recorded by using freshly isolated detrusor strips. These results indicated that the spontaneous contraction of DO detrusor was significantly enhanced, and that the effect of caffeine (10 µM) upon detrusor contractions was reversed by applications of iberiotoxin (100 nM) which is a BK channel blocker. Western blotting (WB) analyses indicated that the levels of expression of ryanodine receptor type 2 (RyR2) and FK506 binding protein 12.6 (FKBP12.6) in bladder muscle were respectively decreased and increased in the samples from DO rats. Thus, we considered in the rat DO model wherein PBOO, the reduced Ca2+ spark activity in detrusor myocytes partly contributed to overactive detrusor contractions. The impaired Ca2+ spark activity may have resulted from decreased RyR2 expression and increased FKBP12.6 expression. Such novel findings in our research might help to provide means for better treatment outcomes for patients afflicted by bladder dysfunction.

Refinement Surgical Technique, and Perioperative and Functional Outcomes in Patients With Robotic Intracorporeal Hautmann Orthotopic Neobladder.

OBJECTIVE: To illustrate our refinement technique for robotic intracorporeal orthotopic Hautmann neobladder with adherence to open surgical principles and evaluate perioperative and functional outcomes. PATIENTS AND METHODS: Robot-assisted radical cystectomy with intracorporeal Hautmann orthotopic neobladder was performed by the same surgeon in 40 patients with bladder cancer from November 2017 to March 2019. Baseline demographics, pathologic data, 90-day complications, and functional outcomes at both 6 and 12 months were evaluated with questionnaire and urodynamic analysis. RESULTS: Median follow-up was 14 months (range 4-20). Median operative time was 320 (230-500) minutes, and the estimated blood loss was 300 (100-2000) mL. No conversion to the open technique was reported. The overall 90-day complication rate was 45%, and the high-grade complication rate was only 10%. The daytime satisfactory continence rate was 90% at both 6 months (30 patients) and 12 months (20 patients), while the night-time satisfactory continence rate was 76.7% and 80.0% at 6 months and 12 months, respectively. One patient underwent clean intermittent catheterization. The cohort had minimal postvoid residual volume, normal compliance, and a mean capacity of 328.7 cm3 (range 170-500) at 6 months postoperatively. CONCLUSION: Our preliminary data indicate that robotic intracorporeal Hautmann neobladder configuration is a feasible surgical technique and can achieve a low pressure and sufficient capacity for satisfactory early voiding patterns. Refinement of the stepwise process can effectively decrease the time of the operation. Long-term functional and oncological outcomes remain to be evaluated with longer follow-up and more cases.

Simvastatin alleviated diabetes mellitus-induced erectile dysfunction in rats by enhancing AMPK pathway-induced autophagy.

BACKGROUND: Diabetes mellitus-induced erectile dysfunction is a common diabetic complication, and new therapeutics and the pathogenesis of diabetes mellitus-induced erectile dysfunction need to be investigated. OBJECTIVES: The aim was to investigate the pathogenesis of diabetes mellitus-induced erectile dysfunction and the pharmacological mechanism of simvastatin treatment in diabetes mellitus-induced erectile dysfunction model rats. MATERIALS AND METHODS: A total of 86 male Sprague Dawley rats aged 8 weeks old were used in this study. The rats were divided into three groups: control (normal), diabetes mellitus-induced erectile dysfunction (streptozotocin-injected), and diabetes mellitus-induced erectile dysfunction + simvastatin (sim). Each group was subdivided into two subgroups for in vitro and in vivo analyses. A bioinformatics method was used to detect differences in gene expression in the corpus cavernosum between normal and diabetes mellitus-induced erectile dysfunction rats. Erectile function was measured by a cavernous nerve electrostimulation test. Corpus cavernosum fibrosis was assessed by Masson staining and Western blotting. Immunofluorescence and Western blotting were performed to explore the differential expression of autophagy-related genes and the AMPK-SKP2-CARM1 pathway genes in rat cavernous smooth muscle cells and the corpus cavernosum. The autophagosomes of the corpus cavernosum tissue were observed by transmission electron microscopy. RESULTS: Autophagy-related genes and pathways (the AMPK and FoxO pathway) were identified by bioinformatics analysis and confirmed at the protein level. Simvastatin, an AMPK agonist, was used to treat diabetes mellitus-induced erectile dysfunction rats for 8 weeks, demonstrating that erectile function was improved for 80.5% (P < .05) of rats. Corpus cavernosum fibrosis was alleviated (P < .05), and autophagy was further enhanced (P < .05); these results might be partially caused by AMPK-SKP2-CARM1 pathway activation (P < .05). DISCUSSION AND CONCLUSION: Simvastatin could enhance protective autophagy by activating the AMPK-SKP2-CARM1 pathway to improve erectile function in diabetes mellitus-induced erectile dysfunction rats.