[Effect of transurethral thuliumlaser vapoenucleation of the prostate with low-power conventional pulse mode on sexual function in patients with benign prostatic hyperplasia].

OBJECTIVE: To explore the effect of a novel transurethral thulium laser vapoenucleation of the prostate with low-power conventional pulse mode (LP-ThuVEP) on sexual function in patients with benign prostatic hyperplasia (BPH). METHODS: 89 BPH patients admitted to Department of Urology, Jintan People's Hospital, Affiliated to Jiangsu University, from January 2022 to June 2023 were selected and randomly divided into the LP-ThuLEP group (45 cases) and the transurethral plasma kinetic resection of the prostate (TUPKRP) group (44 cases). Perioperative indicators were recorded, and the IPSS, Qmax, Qavg, PVR, and QoL of the two groups of patients before surgery and 3 months and 6 months after surgery were comparatively analyzed. The effect of surgery on male sexual function was evaluated through the International Index of Erectile Function-5 (IIEF-5) score and the Male Sexual Health Questionnaire-Ejaculatory Dysfunction (MSHQ-EjD) score. RESULTS: Compared with the TUPKRP group, the LP-ThuVEP group had no statistically significant difference in operation time (P>0.05), but there were statistical differences in bladder irrigation time and indwelling urinary catheter time (P<0.05) and significant statistical differences in the decrease in hemoglobin on the day of surgery and the disappearance time of gross hematuria induced by defecation after surgery (P<0.001). The perioperative complications of the two groups were comparable. Among the urinary tract symptom indicators, the LP-ThuVEP group had statistically significant differences in IPSS score, QoL score, and PVR compared with the TUPKRP group 3 months after surgery (P<0.05). In terms of male sexual function, there was a statistical difference in IIEF-5 scores between the two groups at 3 months and 6 months after surgery (P<0.05); Except that there was no statistical difference in the ejaculation-related satisfaction scores between the two groups at 3 months after surgery (P>0.05), there had all significant statistical differences in ejaculation function and satisfaction scores between and within the groups at 3 months and 6 months after surgery (P<0.001). CONCLUSION: Compared with TUPKRP, the LP-ThuVEP can also effectively relieve urinary tract obstruction caused by BPH and has the advantages of less damage and faster recovery of erectile function and ejaculatory function of patients.

Tumor-associated macrophages in direct contact with prostate cancer cells promote malignant proliferation and metastasis through NOTCH1 pathway.

Background: M2 macrophages are well accepted to promote cancer progression in the prostate cancer (PCa). Paracrine is the principally studied mode of communication between M2 macrophages and tumor cells. In addition to this, we present here a novel model to demonstrate these cellular communications. Methods: PCa cells were co-cultured with THP-1/ human peripheral blood mononuclear cells derived M2 macrophages in direct contact manner. Cancer cell proliferation and invasion were examined to explain how direct contact communicates. Cell-based findings were validated in two xenograft models and patients samples. Results: M2 macrophage direct contact induced a higher proliferation and invasion in PCa cells when compared with noncontact coculture manner. In direct contact manner, NOTCH1 pathway was greatly activated in PCa cells, induced by elevated γ-secretase activity and higher coactivator MAML2 expression. Additionally, blocking γ-secretase activity and depletion of MAML2 completely abolished M2 macrophage direct contact-mediated PCa cell proliferation and invasion. In vivo, inhibiting NOTCH1 signalling impaired M2 macrophage-mediated PCa tumor growth and lung metastasis. Notably, M2 macrophage infiltration as well as high NOTCH1 signaling in cancer cells indicated more aggressive features and worse survival in PCa patients. Conclusion: Our results demonstrated the cell-cell direct contact pattern is an important way in PCa microenvironment cell communication. In this manner, elevated γ-secretase activity and MAML2 expression induced higher NOTCH1 signalling in PCa cells, which increased tumor cells proliferation and invasion. This potentially provided a therapeutic target for PCa.

Peripheral zone PSA density: a predominant variable to improve prostate cancer detection efficiency in men with PSA higher than 4 ng ml-1.

To improve the diagnostic efficiency of prostate cancer (PCa) and reduce unnecessary biopsies, we defined and analyzed the diagnostic efficiency of peripheral zone prostate-specific antigen (PSA) density (PZ-PSAD). Patients who underwent systematic 12-core prostate biopsies in Shanghai General Hospital (Shanghai, China) between January 2012 and January 2018 were retrospectively identified (n = 529). Another group of patients with benign prostatic hyperplasia (n = 100) were randomly preselected to obtain the PSA density of the non-PCa cohort (N-PSAD). Prostate volumes and transition zone volumes were measured using multiparameter magnetic resonance imaging (mpMRI) and were combined with PSA and N-PSAD to obtain the PZ-PSAD from a specific algorithm. Receiver operating characteristic (ROC) curve analysis was used to assess the PCa detection efficiency in patients stratified by PSA level, and the area under the ROC curve (AUC) of PZ-PSAD was higher than that of PSA, PSA density (PSAD), and transition zone PSA density (TZ-PSAD). PZ-PSAD could amend the diagnosis for more than half of the patients with inaccurate transrectal ultrasonography (TRUS) and mpMRI results. When TRUS and mpMRI findings were ambiguous to predict PCa (PIRADS score ≤3), PZ-PSAD could increase the positive rate of biopsy from 21.7% to 54.7%, and help 63.8% (150/235) of patients avoid unnecessary prostate biopsy. In patients whose PSA was 4.0-10.0 ng ml-1, 10.1-20.0 ng ml-1, and >20.0 ng ml-1, the ideal PZ-PSAD cut-off value for predicting clinically significant PCa was 0.019 ng ml-2, 0.297 ng ml-2, and 1.180 ng ml-2, respectively (sensitivity >90%). Compared with PSA, PSAD, and TZ-PSAD, the efficiency of PZ-PSAD for predicting PCa is the highest, leading to fewer missed diagnoses and unnecessary biopsies.

5-ARI induces autophagy of prostate epithelial cells through suppressing IGF-1 expression in prostate fibroblasts.

OBJECTIVES: 5α-reductase inhibitor (5-ARI) is a commonly used medicine in the treatment of lower urinary tract symptoms (LUTS) associated with benign prostatic hyperplasia (BPH). Our study mainly focuses on the mechanism of BPH development after 5ARI treatment. MATERIALS AND METHODS: Prostate specimens from patients were collected. Insulin-like growth factor 1 (IGF-1), Beclin-1, LC3 levels, was analysed by immunohistochemistry. The role IGF-1 on autophagic flux in prostate epithelial cells was studied. Additionally, effect of autophagy on recombinant grafts consisting of prostate stromal and epithelial cells in nude mice was investigated. RESULTS: We demonstrated that IGF-1 expression is down-regulated in prostate fibroblasts after long-term 5-ARI application. A decrease in IGF-1 levels was found to activate autophagic flux through the mTOR pathway in prostate epithelial cells, while the inhibition of IGF-1 receptor function induced autophagy in prostate epithelial cells. In addition, we revealed that blocking autophagic flux initiation can reduce the volume of recombinant grafts in vivo. Finally, our findings suggest that long-term 5-ARI application reduces IGF-1 secretion by prostatic stromal cells, thereby inducing autophagy of prostatic epithelial cells, which is one of the mechanisms underlying BPH pathogenesis and progression. CONCLUSIONS: Focusing on the autophagy induced by low levels of IGF-1 in prostatic epithelial cells, after elucidating AR signalling impairment of prostate stromal cells, might provide a novel strategy for the treatment and prevention of BPH development.

Porous Se@SiO2 nanosphere-coated catheter accelerates prostatic urethra wound healing by modulating macrophage polarization through reactive oxygen species-NF-κB pathway inhibition.

Benign prostatic hyperplasia (BPH) patients experience complications after surgery. We studied oxidative stress scavenging by porous Se@SiO2 nanospheres in prostatic urethra wound healing after transurethral resection of the prostate (TURP). Beagle dogs were randomly distributed into two groups after establishing TURP models. Wound recovery and oxidative stress levels were evaluated. Re-epithelialization and the macrophage distribution at the wound site were assessed by histology. The mechanism by which porous Se@SiO2 nanospheres regulated macrophage polarization was investigated by qRT-PCR, western blotting, flow cytometry, immunofluorescence and dual luciferase reporter gene assays. Our results demonstrated that Porous Se@SiO2 nanosphere-coated catheters advance re-epithelization of the prostatic urethra, accelerating wound healing in beagle dogs after TURP, and improve the antioxidant capacity to inhibit oxidative stress and induced an M2 phenotype transition of macrophages at the wound. By restraining the function of reactive oxygen species (ROS), porous Se@SiO2 nanospheres downregulated Ikk, IκB and p65 phosphorylation to block the downstream NF-κB pathway in macrophages in vitro. Since activation of NF-κB signaling cascades drives macrophage polarization, porous Se@SiO2 nanospheres promoted macrophage phenotype conversion from M1 to M2. Our findings suggest that porous Se@SiO2 nanosphere-coated catheters promote postoperative wound recovery in the prostatic urethra by promoting macrophage polarization toward the M2 phenotype through suppression of the ROS-NF-κB pathway, attenuating the inflammatory response. STATEMENT OF SIGNIFICANCE: The inability to effectively control post-operative inflammatory responses after surgical treatment of benign prostatic hyperplasia (BPH) remains a challenge to researchers and surgeons, as it can lead to indirect cell death and ultimately delay wound healing. Macrophages at the wound site work as pivotal regulators of local inflammatory response. Here, we designed and produced a new type of catheter with a coating of porous Se@SiO2 nanosphere and demonstrated its role in promoting prostatic urethra wound repair by shifting macrophage polarization toward the anti-inflammatory M2 phenotype via suppressing ROS-NF-κB pathway. These results indicate that the use of porous Se@SiO2 nanosphere-coated catheter may provide a therapeutic strategy for postoperative complications during prostatic urethra wound healing to improve patient quality of life.

M1 macrophage mediated increased reactive oxygen species (ROS) influence wound healing via the MAPK signaling in vitro and in vivo.

Thulium laser resection of the prostate (TmLRP), a major treatment for benign prostatic hyperplasia (BPH), has several postoperative complications that affect the patients' quality of life. The aim of this study was to investigate the effect of the M1 macrophage-secreted reactive oxygen species (ROS) on prostatic wound healing, and the role of MAPK signaling in this process. A co-culture model in vitro was established using macrophages and prostate epithelial or stromal cells. Cell proliferation, migration, apoptosis, MAPK pathway-related gene expression levels were evaluated by standard assays. In addition, an in vivo model of prostatectomy was established in beagles by subjecting them to TmLRP, and were either treated with N-acetyl-L-cysteine (NAC) and or placebo. Wound healing and re-epithelialization were analyzed histopathologically in both groups, in addition to macrophage polarization, oxidative stress levels and MAPK pathway-related proteins expressions. Intracellular ROS levels were significantly increased in the prostate epithelial and stromal cells following co-culture with M1-like macrophages and H2O2 exposure via MAPK activation, which affected their proliferation, migration and apoptosis, and delayed the wound healing process. The cellular functions and wound healing capacity of the prostate cells were restored by blocking or clearing the macrophage-secreted ROS. In the beagle model, increased ROS levels impaired cellular functions, and appropriate removing ROS accelerated the wound healing process.

Androgen Deprivation Accelerates the Prostatic Urethra Wound Healing After Thulium Laser Resection of the Prostate by Promoting Re-Epithelialization and Regulating the Macrophage Polarization.

BACKGROUND: Complications after a thulium laser resection of the prostate (TmLRP) are related to re-epithelialization of the prostatic urethra. Since prostate growth and development are induced by androgen, the aim of this study was to determine the role and explore the mechanism of androgen in wound healing of the prostatic urethra. METHODS: Beagles that received TmLRPs were randomly distributed into a castration group, a testosterone undecanoate (TU) group, and a control group. The prostate wound was assessed once a week using a cystoscope. Histological analysis was then carried out to study the re-epithelialization of the prostatic urethra in each group. The inflammatory response in the wound tissue and urine was also investigated. RESULTS: The healing of the prostatic urethra after a TmLRP was more rapid in the castration group and slower in the TU group than that in the control group. Castration accelerated re-epithelialization by promoting basal cell proliferation in the wound surface and beneath the wound and by accelerating the differentiation of basal cells into urothelial cells. Castration reduced the duration of the inflammatory phase and induced the conversion of M1 macrophages to M2 macrophages, thus accelerating the maturation of the wound. By contrast, androgen supplementation enhanced the inflammatory response and prolonged the inflammatory phase. Moreover, the anti-inflammatory phase was delayed and weakened. CONCLUSION: Androgen deprivation promotes re-epithelialization of the wound, regulates the inflammatory response, and accelerates wound healing of the prostatic urethra after a TmLRP. Prostate 77:708-717, 2017. © 2017 Wiley Periodicals, Inc.

MiR-185 attenuates androgen receptor function in prostate cancer indirectly by targeting bromodomain containing 8 isoform 2, an androgen receptor co-activator.

OBJECTIVES: Aberrant androgen receptor (AR) signaling functions are implicated in prostate cancer (PCa) pathogenesis. Here, we studied interactions between miR-185 and the bromodomain containing 8 isoform 2 (BRD8 ISO2) to investigate indirect mechanisms of miR-185 with respect to AR function through BRD8 ISO2 in PCa. METHODS: Putative miRNA response element (MRE) of miR-185 in 3'-untranslated region (3'-UTR) of BRD8 ISO2 mRNA was predicted by software and confirmed using dual-luciferase assays and Ago2 immunoprecipitation. BRD8 and AR expression were determined by qRT-PCR and Western blot in PCa cells and tissues. MMTV-Fluc reporter plasmids and dual-luciferase assays were used to evaluate AR activity. RESULTS: MRE prediction, dual-luciferase assays and Ago2 immunoprecipitation confirmed that miR-185 is capable of binding the 3'-UTR of BRD8 ISO2 mRNA. QRT-PCR and Western blot indicated that BRD8 ISO2 expression is decreased by miR-185 mimic transfection while increased by miR-185 inhibitor transfection. MMTV-Fluc reporter assays revealed that miR-185 can attenuate AR function by suppressing BRD8 ISO2. Additionally, Pearson's correlation analyses confirmed that BRD8 ISO2 mRNA expression is inversely correlated with miR-185 expression in clinical specimens. CONCLUSION: In addition to suppression of AR expression, miR-185 can attenuate AR function indirectly by suppressing BRD8 ISO2. MiR-185 and BRD8 ISO2 may be possible therapeutic targets for PCa treatment.

Long non-coding RNA lnc-MX1-1 is associated with poor clinical features and promotes cellular proliferation and invasiveness in prostate cancer.

Long non-coding RNAs (lncRNAs) are emerging as key molecules in human cancer genesis and progression, including prostate cancer. Large amount of lncRNAs have been found that differentially expressed between prostate cancer tissues and normal prostate tissues. Whether these lncRNAs could serve as a novel biomarker for prostate cancer diagnosis or prognosis, and their biological functions in prostate cancer need further investigation. In the present study, we identified that lncRNA lnc-MX1-1 is over-expressed in prostate cancer tissues compared with their adjacent normal prostate tissues by gene expression array profiling. The expression of lnc-MX1-1 in 60 prostate cancer cases was determined by real-time quantitative PCR and the correlations between lnc-MX1-1 expression and patients' clinical features were further analyzed. Next, we impaired lnc-MX1-1 expression using RNAi in LNCaP and 22Rv1 prostate cancer cells to explore the effects of lnc-MX1-1 on proliferation and invasiveness of the cells. Our results showed that there was a significant association between over-expression of lnc-MX1-1 and patients' clinical features such as PSA, Gleason score, metastasis, and recurrence free survival. Moreover, knockdown of lnc-MX1-1 reduced both proliferation and invasiveness of LNCaP and 22Rv1 cells. In conclusion, the results suggest that lnc-MX1-1 may serve as a potential biomarker and therapeutic target for prostate cancer.

Inhibition of fatty-acid synthase suppresses P-AKT and induces apoptosis in bladder cancer.

OBJECTIVE: To investigate the role of fatty acid synthase (FASN) in bladder transitional cell carcinoma (BTCC). METHODS: FASN expression was investigated in non-muscle-invasive BTCC tissue specimens by immunohistochemistry and BTCC cell lines by Western blot. After treatment with FASN-siRNA or FASN inhibitor cerulenin (Cer), the proliferation and apoptosis of BTCC cell lines 5637 and 253 J were determined by cell counting Kit-8 (CCK8) assay and flow cytometry respectively. The expression of p-AKT, cyclin D1 (CCND1), and apoptosis-related proteins were detected by Western blot. RESULTS: High levels of FASN expression were observed in 59% (32/54) of non-muscle-invasive BTCC tissue specimens, and FASN expression was associated with histologic grade (P < .05) and recurrence (P < .05). FASN expression was high in 6 BTCC cell lines. FASN inhibitor Cer and FASN-siRNA produced the increased apoptosis and decreased proliferation of bladder cancer cells, and caused inactivity of AKT and downregulation of CCND1. Furthermore, treatment of BTCC cell lines with Cer resulted in apoptosis via the caspase-dependent pathway involving inactivation of antiapoptotic bcl-2 protein. CONCLUSION: Our data suggest that FASN plays an important role in BTCC development. Targeting FASN may be a new therapeutic strategy for BTCC.

[Analysis of N-E cadherin switch as an independent predictive parameter of bladder cancer survival outcomes].

OBJECTIVE: To explore the expression patterns of cadherins (N-cadherin and E-cadherin) in urothelial carcinomas and understand the values of N-E cadherin switch in the predictions of postoperative recurrence and prognosis. METHODS: The expressions of N-cadherin and E-cadherin were measured by immunohistochemistry in 64 transurethral bladder tumor resection (TURBT) or partial cystectomy samples (48 cases) in 2005 by the method of streptavidin-biotin peroxidase. RESULTS: A positive expression of N-cadherin and a negative expression of E-cadherin were noted in 27 (42.2%) and 16 (25.0%) specimens respectively. Patients with more poorly differentiated bladder cancer were accompanied with a higher expression of N-cadherin and a lower expression of E-cadherin (both P < 0.05). A positive expression of N-cadherin decreased the recurrence-free and cancer-related survival rates while a negative expression of E-cadherin was correlated with a lower cancer-related survival rate (all P < 0.05). No significant association was found between the expression of E-cadherin and the recurrence-free survival rate. Furthermore, the N-E cadherin switch (a negative expression of E-cadherin and a positive expression of N-cadherin) showed a higher predictive power in both recurrence-free and cancer-related survival according to multivariate analysis (HR = 0.428, 95%CI: 0.217 - 0.845, HR = 0.098, 95%CI: 0.013 - 0.767). No significant association was found between the expressions of two cadherins and postoperative progression. CONCLUSION: Although the expressions of E-cadherin and N-cadherin appear to be correlated with survival outcomes in bladder cancer, N-E cadherin switch may be a better predicator for postoperative recurrence and cancer-related survival.

Prenatal exposure to di-n-butyl phthalate induces anorectal malformations in male rat offspring.

The objectives of this study were to investigate the dysplasia, histological malformations, and genetic abnormalities in male rats induced by maternal exposure to di-n-butyl phthalate (DBP). Here we report novel findings concerning developmental abnormalities resulting from prenatal exposure to DBP, which leads to significant anorectal malformations (ARMs) in male rat offspring. The incidence of ARMs was 39.5% in male offspring and all abnormal pups were complicated with secondary megacolon. General images, histological analysis and anatomy examination confirmed the malformation. The development abnormalities such as decreased bodyweight (BW) and anogenital distance (AGD), shortened body lengths (with tail removed), as well as increased abdominal circumference were observed at different developmental stages of ARMs in male rat. The developmental abnormalities in both solid organs (brain, heart, liver, spleen, lung and kidney) and reproductive organs (testes and epididymis) of abnormal pubs on PND35 were also investigated. In addition, the serum testosterone (T) level of ARMs in male rats on PND1 was significantly lower than that of controls with accompanying reduced expression of androgen receptor (AR), sonic hedgehog (Shh) and bone morphogenetic protein 4 (Bmp4) mRNA from tissues of the terminal rectum. These results conclusively demonstrate for the first time that in utero exposure to DBP leads to an increased likelihood for the development of ARMs and subsequent complicating megacolon in male rat offspring.

[Long-term efficacy of tubularized peritoneal free grafts as ureteral mucosal substitutes in dogs].

OBJECTIVE: To investigate the long-term efficacy of ureteral reconstruction with tubularized peritoneal free grafts for the treatment of avulsion of ureteral mucosa in animal models. METHODS: The model of avulsion of ureteral mucosa was established in 12 adult dogs. Then they were divided into Group A (n = 6, length of avulsed mucosa at 4 cm) and Group B (n = 6, length of avulsed mucosa at 6 cm). And the tubularized peritoneal free grafts and ureteral stents were implanted into the injured ureters. The curative effect was observed by intravenous urethrogram (IVU) and histological examination at Week 24 post-operation. RESULTS: Severe stenosis was observed by IVU in 1 dogs in Groups A and B respectively. In the remaining 10 dogs, IVU showed normal size and morphology of kidneys. There was no hydronephrosis. And no obvious stricture of ureteral part was observed for mucosa substitutes made of peritoneal free grafts. In all 10 dogs without stenosis of both groups, peritoneal membrane was replaced by integrated transitional epithelium. And there was no obvious stricture. Collagen fibers were arranged parallel to mucosal surface. CONCLUSION: For avulsion of ureteral mucosa under 6 cm, reconstruction with tubularized peritoneal free grafts as mucosa substitutes is an effective method. And its long-term efficacy is satisfactory.

[Cystic lymphangioma of the spermatic cord in old man: a case report and review of the literature].

OBJECTIVE: To investigate the clinical and pathological features, diagnosis and treatment of cystic lymphangioma of the spermatic cord. METHODS: One case of cystic lymphangioma of the spermatic cord in a 71-year-old patient was retrospectively analyzed and the relevant literature was reviewed. RESULTS: The patient, presented with spermatic cord hydrocele, was treated by local excision of the tumor, which was pathologically diagnosed as cystic lymphangioma. No relapse was found during a 3-month follow-up after the operation. CONCLUSION: Lymphangioma of the spermatic cord is a benign tumor. Preoperation ultrasonography and CT are important for determining the location and nature of lymphangioma. Surgical excision is an effective option for the treatment of cystic lymphangioma of the spermatic cord.

[Effects of different reconstruction methods in treatment of avulsion of ureteral mucosa: experiment with dogs].

OBJECTIVE: To investigate the curative effects of different reconstruction methods in the treatment of avulsion of ureteral mucosa. METHODS: Twenty adult dogs were randomly divided into 4 equal groups: Group III (control group in which the ureter was incised and a ureteral stent was placed therein), Group II (the ureter was incised and a ureteral mucosal avulsion about 5 cm in length was created and the avulsed mucosa was replaced to the original position and a ureteral stent was placed in addition), Group III (a piece of bladder mucosa was incised and grafted to the avulsed ureter mucosa and a ureteral stent was placed in addition), and Group IV (a tubularized peritoneal free graft and a ureteral stent were placed in the avulsed ureter). Ten weeks later intravenous pyelography (IVP) was conducted to observe the images of ureter. Then the dogs were killed and pathological examination of the reconstructed ureter was conducted. RESULTS: IVP showed atresia and stenosis in all control group dogs. No obvious stenosis was observed in Groups II and IV. Pathological examination showed that the newly grown mucosa was similar to the normal ureter structure in Groups II and IV. In Group III one dog died, slight distension of ureter superior to the reconstructed part was found in 2 dogs, and no obvious stenosis was observed in 3 dogs. CONCLUSION: Orthotopic replacement and tabularized peritoneal free grafting with placement of ureter stent are effective in treatment of avulsion of ureter mucosa. Bladder mucosa can be used as selectable material.