Safety of low-intensity extracorporeal shock wave therapy in prostate disorders: in vitro and in vivo evidence.

ABSTRACT: Recent evidence suggests that low-intensity extracorporeal shock wave therapy (Li-ESWT) is a promising treatment for chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS); however, its safety in pelvic organs, particularly prostate tissues and cells, remains unclear. The current study evaluates the risks of prostate cell damage or oncogenesis following the administration of Li-ESWT for prostatitis. To this end, a robust in vitro model (Cell Counting Kit-8 [CCK-8] assay, clone formation assay, cell scratch assay, lactate dehydrogenase [LDH] release assay, flow cytometry, and immunoblotting assay) was designed to examine the effects of Li-ESWT on cell proliferation, clonogenicity, migration, membrane integrity, and DNA damage. Exome sequencing of Li-ESWT-treated cells was performed to determine the risk of carcinogenesis. Furthermore, an in vivo rat model (n = 20) was employed to assess the effects of Li-ESWT on cancer biomarkers (carcinoembryonic antigen [CEA], Ki67, proliferating cell nuclear antigen [PCNA], and gamma-H2A histone family member X, phosphorylation of the H2AX Ser-139 [γ-H2AX]) in prostate tissue. Based on our findings, Li-ESWT promotes cellular growth and motility without inducing significant cell membrane or DNA damage or alterations. Genetic analyses did not demonstrate an increase in mutations, and no damage to prostate tissue or upregulation of cancer biomarkers was detected in vivo. This comprehensive in vitro and in vivo assessment confirms the safety of Li-ESWT in managing prostate disorders.

Identification of miRNA signature in cancer-associated fibroblast to predict recurrent prostate cancer.

BACKGROUND: Cancer-associated fibroblasts (CAFs) are one of the major components of prostate stromal cells, which play a crucial part in tumor development and treatment resistance. This study aimed to establish a model of CAFs-related microRNAs (miRNAs) to assess prognostic differences, tumor microenvironments, and screening of anticancer drugs by integrating data from single-cell RNA sequencing (scRNA-seq) and bulk RNA sequencing (buRNA-seq). METHODS: scRNA-seq and buRNA-seq data of primary prostate cancer (PCa) were downloaded from Gene Expression Omnibus and The Cancer Genome Atlas databases. Statistical methods including Least absolute shrinkage and selection operator (Lasso), Lasso penalized, Random Forest, Random Forest Combination, and Support Vector Machine (SVM) were performed to select hub miRNAs. Pathway analyses and assessment of infiltrating immune cells were conducted using Gene Set Enrichment Analysis and the CIBERSORT algorithm. The expression of CAFs-related miRNAs in fibroblast cell lines were validated through quantitative real-time PCR. Cell Counting Kit 8 (CCK8), wound-healing, clone formation, and cell migration assays were used to explore cell proliferation, growth, and migration in vitro. A mouse xenograft model was established to investigate the effect of CAFs on tumor growth in vivo. RESULTS: Through single-cell transcriptomics analysis in 34 PCa patients, 89 CAFs-related mRNAs were identified. A prognostic model based on 9 CAFs-related miRNAs (hsa-miR-1258, hsa-miR-133b, hsa-miR-222-3p, hsa-miR-145-3p, hsa-miR-493-5p, hsa-miR-96-5p, hsa-miR-15b-5p, hsa-miR-106b-5p, and hsa-miR-191-5p) was established to predict biochemical recurrence (BCR). We have determined through two prediction methods that NVP-TAE684 may be the optimal targeted therapy drug for treating CAFs. Downregulation of hsa-miR-106b-5p in CAFs significantly suppressed cell proliferation, migration, and colony formation in vitro. In vivo studies using a xenograft model further confirmed that hsa-miR-106b-5p downregulation significantly reduced tumor growth. CONCLUSION: Our findings conducted an integrated bioinformatic analysis to develop a CAFs-related miRNAs model that provides prognostic insights into individualized and precise treatment for prostate adenocarcinoma patients. Downregulation of miR-106b-5p in CAFs significantly suppressed tumor growth, suggesting a potential therapeutic target for cancer treatment.

Sertraline Alleviates Chronic Prostatitis by Regulating the TRPV1 Channel.

Introduction: Although sertraline has been widely used for chronic prostatitis (CP), the mechanisms are unclear. Herein, we explored the mechanisms of sertraline in treating CP. Methods: Network pharmacology methods were used to explore the potential targets and molecular mechanisms. LPS was used to stimulate RWPE-1 cells to construct an in vitro model of CP. An experimental autoimmune prostatitis (EAP) mice model was built. CCK-8 assay, EdU assay, BrdU detection, and Tunel assay were performed to evaluate the proliferation and apoptosis process of cells or tissues, respectively. DCFH-DA and Fluo-4 fluorescence probes were used to detect intracellular ROS and calcium concentrations. Von Frey filaments and open-field tests were utilized to evaluate pain response and depressive-like behavior of mice. Histopathology was evaluated through hematoxylin and eosin staining. RT-qPCR, Western blot, immunofluorescence, and immunohistochemistry were utilized to evaluate the transcription, expression, and location of related proteins. Molecular dynamics (MD) simulation and surface plasmon resonance (SPR) assay were performed to measure the binding capacity of sertraline and related proteins. Results: Through a network pharmacology analysis, 27 potential targets of sertraline for CP were obtained, and 5 key targets (CHRM1, ADRA1B, HTR2B, HTR2A, and TRPV1) were finally identified. Functional experiments suggested that TRPV1 was involved in the proliferation, apoptosis inhibition, and ROS production of LPS-induced RWPE-1 cells. In vitro experiments showed that sertraline significantly inhibited cell proliferation, ROS generation, and transcription of inflammation cytokines of LPS-induced RWPE-1 cells. Additionally, sertraline markedly promoted the apoptosis level of LPS-stimulated RWPE-1 cells and elevated the expression level of BAX while reducing the expression levels of Bcl2 and Caspase-3. MD simulation and SPR assay confirmed the direct binding of sertraline to TRPV1. Moreover, sertraline significantly down-regulated the expression level of TRPV1 and inhibited calcium influx of LPS-induced RWPE-1 cells. TRPV1 agonist (Capsaicin) significantly restored the effects on proliferation, apoptosis, ROS production, and calcium influx of sertraline on LPS-induced RWPE-1 cells. Mice experiments demonstrated that sertraline treatment could reduce pain response, improve depression-like symptoms, and relieve local prostate inflammation of EAP mice, as well as down-regulated the expression level of TRPV1, inhibit the proliferation, and promote apoptosis of prostate tissues in EAP mice. Discussion: The results revealed the anti-inflammatory effect of sertraline for RWPE-1 cells and EAP mice, and the potential mechanism was regulating the TRPV1 channel. It indicated that sertraline might serve as a complementary anti-inflammatory agent for CP.

Comparative evaluation of reproductive organ-preserving versus standard radical cystectomy in female: a meta-analysis and systematic review of perioperative, oncological, and functional outcomes.

BACKGROUND: To evaluate the perioperative, oncological, and functional outcomes of reproductive organ-preserving radical cystectomy (ROPRC) compared to standard radical cystectomy (SRC) in the treatment of female bladder cancer. METHODS: A systematic search was conducted in November 2023 across several scientific databases. We executed a systematic review and cumulative meta-analysis of the primary outcomes of interest, adhering to the PRISMA and AMSTAR guidelines. The study was registered in PROSPERO (CRD42024501522). RESULTS: The meta-analysis included 10 studies with a total of 2015 participants. ROPRC showed a significant reduction in operative time and postoperative fasting period compared to SRC (MD - 45.69, 95% CI - 78.91 ~ - 12.47, p = 0.007, and MD - 0.69, 95% CI - 1.25 ~ - 0.13, p = 0.02, respectively). Functional outcomes, both daytime continence rate (OR 4.94, 95% CI 1.53 ~ 15.91, p = 0.008) and nighttime continence rate (OR 5.91, 95% CI 1.94 ~ 18.01, p = 0.002), and sexual function measured by the Female Sexual Function Index (MD 5.72, 95% CI 0.19 ~ 11.26, p = 0.04), were significantly improved in the ROPRC group. There were no significant differences between ROPRC and SRC in terms of estimated blood loss, length of hospital stay, overall postoperative complications, minor complications or major complications. Oncologically, both procedures showed comparable outcomes with no significant differences in positive surgical margins, tumor recurrence rates, overall survival, cancer-specific survival, recurrence-free survival, or progression-free survival. CONCLUSIONS: ROPRC is a viable and effective alternative to SRC in female bladder cancer patients, offering enhanced functional outcomes and similar oncological safety. These findings suggest that ROPRC can improve the quality of life in female bladder cancer patients without compromising the efficacy of cancer treatment.

Comparative effectiveness of multiple androgen receptor signaling inhibitor medicines with androgen deprivation therapy for metastatic hormone-sensitive prostate cancer: a study in the real world.

Background: The current treatment strategy for metastatic Hormone-Sensitive Prostate Cancer (mHSPC) is the combination of Androgen Receptor Signaling Inhibitors (ARSIs) medicines with androgen deprivation therapy (ADT). However, there is a lack of real-world data comparing the efficacy of different ARSI pharmaceuticals. Therefore, the objective of this study was to compare the effectiveness and safety of bicalutamide, abiraterone, enzalutamide, and apalutamide in combination with ADT for patients with mHSPC. Methods: We retrospectively analyzed 82 patients diagnosed with mHSPC, including 18 patients treated with abiraterone acetate with prednisone, 21 patients with enzalutamide, 20 patients with apalutamide, and 23 patients with bicalutamide. We evaluated PSA progression-free survival (PSA-PFS), imaging progression-free survival (r PFS), castration resistance progression-free survival (CRPC-PFS), and overall survival (OS) using Kaplan-Meier survival analyses. Additionally, we explored relevant factors affecting prognosis through univariate and multivariate Cox risk-proportionality models. PSA response rates at 3, 6, and 12 months, nadir PSA levels (nPSA), and time to nadir (TTN) in different medication subgroups after treatment were documented, and we used one-way ANOVA to determine the effect of these measures on patient prognosis. Results: In comparison with bicalutamide, both enzalutamide and apalutamide have shown significant advantages in delaying disease progression among mHSPC patients. Specifically, enzalutamide has been found to significantly prolong PSA-PFS (HR 2.244; 95% CI 1.366-3.685, p=0.001), rPFS (HR 2.539; 95% CI 1.181-5.461; p= 0.007), CRPC-PFS (HR 2.131; 95% CI 1.295-3.506; p= 0.003), and OS (HR 2.06; 95% CI 1.183-3.585; P=0.005). Similarly, apalutamide has significantly extended PSA-PFS (HR 5.071; 95% CI 1.711-15.032; P= 0.003) and CRPC-PFS (HR 6.724; 95% CI 1.976-22.878; P=0.002) among patients. On the other hand, the use of abiraterone in combination with ADT did not demonstrate a significant advantage in delaying diseases progression when compared with the other three agents in mHSPC patients. There were no significant differences in overall adverse event rates among the four pharmaceuticals in terms of safety. Additionally, the observation of PSA kinetics revealed that enzalutamide, apalutamide, and abiraterone acetate had a significant advantage in achieving deep PSA response (PSA ≤ 0.2 ng/ml) compared with bicalutamide (p=0.007 at 12 months). Enzalutamide and apalutamide exhibited preeminence efficacy, with no substantial difference observed between the two medications. Conclusions: Abiraterone, enzalutamide, and apalutamide were found to significantly reduce and stabilize PSA levels in mHSPC patients more quickly and thoroughly than bicalutamide. Furthermore, enzalutamide and apalutamide were found to significantly prolong survival and delay disease progression in mHSPC patients compared with bicalutamide. It should be noted that abiraterone did not demonstrate a significant advantage in delaying disease compared with enzalutamide and apalutamide. After conducting drug toxicity analyses, it was determined that there were no significant differences among the four drugs.

Network pharmacological analysis and experimental study of melatonin in chronic prostatitis/chronic pelvic pain syndrome.

This study is aimed at exploring the potential mechanisms of melatonin (MT) in treating chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) using network pharmacology and experimental study. The target genes of MT were acquired from the Swiss Target Prediction, SuperPred, SEA, and PharmMapper databases, and the CP/CPPS targets were collected based on OMIM, DisGeNET, and GeneCards databases. The intersection of MT and CP/CPPS target genes was analyzed. A PPI network was constructed using Cytoscape to identify core targets. The shared targets underwent GO and KEGG enrichment analyses by Using R software. Molecular docking of MT with core targets was performed using AutoDock and PyMOL. GROMACS software was used for molecular dynamics simulation. And using cell experiments to verify the potential effect of MT in CP/CPPS. Network pharmacology analysis reveals 284 shared targets between MT and CP/CPPS, with AKT1, SRC, HSP90AA1, PTGS2, BCL2L1, ALB, CASP3, NFKB1, HIF1A, and ESR1 identified as key targets. Enrichment analysis indicates that MT affects CP/CPPS through various biological processes, and pathway analysis emphasizes the significance of PI3K-Akt, MAPK, Ras, FoxO, HIF-1, EGFR, and apoptosis pathways. Molecular docking confirms strong binding between MT and core targets. It is worth noting that the molecular dynamics simulation showed that the average binding free energy of AKT1, PTGS2, ALB, HSP90AA1 proteins, and MT was - 26.15, - 29.48, - 18.59, and - 20.09 kcal/mol, respectively. These results indicated that AKT1, PTGS2, ALB, and HSP90AA1 proteins were strongly bound to MT. Cell experiments demonstrate that MT can inhibit the secretion of IL-1ß, IL-6, and TNF-α in LPS-induced RWPE-1 cells, alleviate inflammation, and suppress cell apoptosis and oxidative stress. Network pharmacology, molecular docking, molecular dynamics simulation, and cell experiments showed that MT could play a role in CP/CPPS by regulating multiple targets and pathways. These findings provide an important scientific basis for further exploration of the molecular mechanism and clinical application of MT in CP/CPPS treatment and are expected to provide new ideas and directions for the development of novel therapeutic strategies.

Hypoxia-mediated attenuation of EGLN2 inhibition of the NF-κB signaling pathway leads to the formation of a loop between HIF-1α and MUC1-C promoting chemoresistance in bladder cancer.

The expression pattern of MUC1-C in tumors is closely linked to tumor progression; however, its specific mechanism remains unclear. The expression of MUC1-C in cancer and adjacent normal tissues was detected using immunohistochemistry and Western blot. The IC50 of cells to gemcitabine was determined using the CCK8 assay. The effects of hypoxia and MUC1-C on the behavioral and metabolic characteristics of bladder cancer cells were investigated. Gene expression was assessed through Western blot and polymerase chain reaction. The relationship between the genes was analyzed by co-immunoprecipitation, immunofluorescence and Western blot. Finally, the role of the EGLN2 and NF-κB signaling pathways in the interaction between MUC1-C and hypoxia-inducible factor-1α (HIF-1α) was investigated. MUC1-C expression is significantly higher in bladder cancer tissues than in adjacent normal tissues, particularly in large-volume tumors, and is closely correlated with clinical features such as tumor grade. Tumor volume-mediated hypoxia resulted in increased expression of MUC1-C and HIF-1α in bladder cancer cells. Under stimulation of hypoxia, the inhibitory effect of EGLN2 on the NF-κB signaling pathway was weakened, allowing NF-κB to promote the positive feedback formation of MUC1-C and HIF-1α. Simultaneously, EGLN2-mediated degradation of HIF-1α was reduced. This ultimately led to elevated HIF-1α-mediated downstream gene expression, promoting increased glucose uptake and glycolysis, and ultimately resulting in heightened chemotherapy resistance and malignancy.

Risk factors of high fluid absorption in patients treated with mini-PCNL: a single-center prospective study.

BACKGROUND: The factors influencing fluid absorption in mini-percutaneous nephrolithotripsy (mini-PCNL) are still unknown. We aim to investigate the factors that influence irrigation fluid absorption during mini-PCNL. METHODS: A total of 94 patients who underwent mini-PCNL were included in this prospective study. The endoscopic surgical monitoring system (ESMS) was used to measure the volume of irrigation fluid absorbed during the procedure. Irrigating time, the total volume of irrigation fluid, stone size, S.T.O.N.E. score, hemoglobin, electrolyte levels, and postoperative complications were recorded. RESULTS: A significant correlation was observed between fluid absorption and the presence of postoperative fever, and based on this phenomenon, patients were divided into low and high fluid absorption groups. The serum creatinine level in the high fluid absorption group was significantly high (7 vs. 16.5, p = 0.02). Significant differences were observed between the low and high fluid absorption groups in terms of mean stone size (21.70 mm vs. 26.78 mm), presence of stone burden ≥ 800 mm2 (4% vs. 23%), S.T.O.N.E. score > 8 (4% vs. 38%), the fluid used > 18,596 ml (19% vs. 78%), irrigation time (55.61 min vs. 91.28 min), and perfusion rate (24% vs. 45%) (all p < 0.05). The rates of postoperative fever and SIRS in the high fluid absorption group were significantly high (p < 0.05). CONCLUSIONS: Mean stone size, presence of stone burden ≥ 800 mm2, S.T.O.N.E. score > 8, the fluid used > 18596 mL, irrigation time, and perfusion rate are risk factors of intraoperative fluid absorption in mini-PCNL.

HER2 Affects the Biological Behaviours of Bladder Cancer Cells and is Closely Associated with the Progression and Prognosis of Bladder Cancer.

OBJECTIVE: Given the growing recognition of molecular targets in oncology, this study aimed to examine the expression pattern and prognostic significance of human epidermal growth factor receptor-2 (HER2) in bladder cancer (BC) and the effects of HER2 knockdown on the biological behaviours of BC cells. METHODS: A total of 126 BC tissue samples and 20 samples of normal bladder mucosa were collected for immunohistochemical staining. The clinicopathological data were obtained from patients with BC. HER2 was knocked down in two BC cell lines (T24 and 5637) using lentiviral delivery of short hairpin RNA (shRNA), referred to as shHER2, with a blank control group (shCtrl) for comparison. A range of assays, including cell counting kit-8, colony formation, transwell, wound healing, and flow cytometry, were performed to assess the effects of HER2 knockdown on the proliferation, migration, cell cycle entry, and apoptosis of BC cells. RESULTS: The study revealed a notable overexpression rate of HER2 in BC tissues (57.1%) than in normal bladder mucosa (0%) (p < 0.001). HER2 overexpression was associated with tumour number (p < 0.0001), pathological grade (p < 0.0001), lymph node metastasis (p = 0.040), distant metastasis (p = 0.037), overall survival (p = 0.0006), and recurrence-free survival (RFS) (p < 0.0001). In contrast, no significant association was identified between HER2 overexpression and demographic factors such as sex (p = 0.687), age (p = 0.430), tumour size (p = 0.053), or T stage (p = 0.134). Furthermore, the experimental knockdown of HER2 in BC cells inhibited the proliferation and migration and promoted their apoptosis and cell cycle arrest in the G1 phase. CONCLUSIONS: The findings suggest HER2 as a potential therapeutic target for BC and underscore the promise of developing anti-HER2-targeting strategies for BC management.

Transperitoneal vs retroperitoneal laparoscopic radical nephrectomy: a double-arm, parallel-group randomized clinical trial.

OBJECTIVE: To compare the outcomes of patients undergoing Retroperitoneal laparoscopic Radical nephrectomy (RLRN) and Transperitoneal laparoscopic Radical nephrectomy (TLRN). METHODS: A total of 120 patients with localized renal cell carcinoma were randomized into either RLRN or TLRN group. Mainly by comparing the patient perioperative related data, surgical specimen integrity, pathological results and tumor results. RESULTS: Each group comprised 60 patients. The two group were equivalent in terms of perioperative and pathological outcomes. The mean integrity score was significantly lower in the RLRN group than TLRN group. With a median follow-up of 36.4 months after the operation, Kaplan-Meier survival analysis showed no significant difference between RLRN and TLRN in overall survival (89.8% vs. 88.5%; P = 0.898), recurrence-free survival (77.9% vs. 87.7%; P = 0.180), and cancer-specific survival (91.4% vs. 98.3%; P = 0.153). In clinical T2 subgroup, the recurrence rate and recurrence-free survival in the RLRN group was significantly worse than that in the TLRN group (43.2% vs. 76.7%, P = 0.046). Univariate and multivariate COX regression analysis showed that RLRN (HR: 3.35; 95%CI: 1.12-10.03; P = 0.030), male (HR: 4.01; 95%CI: 1.07-14.99; P = 0.039) and tumor size (HR: 1.23; 95%CI: 1.01-1.51; P = 0.042) were independent risk factor for recurrence-free survival. CONCLUSIONS: Our study showed that although RLRN versus TLRN had roughly similar efficacy, TLRN outperformed RLRN in terms of surgical specimen integrity. TLRN was also significantly better than RLRN in controlling tumor recurrence for clinical T2 and above cases. TRIAL REGISTRATION: Chinese Clinical Trial Registry ( https://www.chictr.org.cn/showproj.html?proj=24400 ), identifier: ChiCTR1800014431, date: 13/01/2018.

Perioperative outcomes and continence following robotic-assisted radical cystectomy with mainz pouch II urinary diversion in patients with bladder cancer.

PURPOSE: To present the widely unknown perioperative outcomes and continence status of bladder cancer patients following robotic-assisted radical cystectomy (RARC) with Mainz pouch II urinary diversion (UD). MATERIALS AND METHODS: From November 2020 to December 2023, 37 bladder cancer patients who underwent RARC with Mainz pouch II UD were retrospectively assessed (ChiCTR2300070279). The results, which included patient demographics, perioperative data, continence, and complications (early ≤ 30 days and late ≤ 30 days) were reported using the RC-pentafecta criteria. RC-pentafecta criteria included ≥ 16 lymph nodes removed, negative soft tissue surgical margins, absence of major (Grade III-IV) complication at 90 days, absence of clinical recurrence at ≤ 12 months, and absence of long-term UD-related sequelae. A numeric rating scale assessed patient satisfaction with urinary continence 30 days after surgery. The validated Patient Assessment of Constipation Symptoms (PAC-SYM) questionnaire was used to evaluate bowel function. The Kaplan-Meier curve was used to evaluate overall survival (OS). RESULTS: Of the 37 patients evaluated over a median (range) follow-up period of 23.0 (12.0-36.5) months. The median (range) age was 65 (40-81) years. The median (range) time to urinary continence after surgery was 2.3 (1.5-6) months. Of the 37 patients, 31 (83.8%) were continent both during the day and at night, 34 (91.9%) were continent during the day, 32 (86.5%) were continent at night, 35 (94.6%) were satisfied with their urinary continence status, and 21 (56.8%) were very satisfied. The mean (range) voiding frequency was 6 (4-10) during the day and 3 (2-5.5) at night. The mean (range) PAC-SYM total score was 9.50 (4.00-15.00). In 12 (32.4%) of the patients, RC-pentafecta was achieved, and achieving RC-pentafecta was linked to better satisfaction scores (7.3 vs. 5.5, p = 0.034). There was no significant difference between RC-pentafecta and No RC-pentafecta groups in terms of OS (25.6 vs. 21.5 months, p = 0.16). 7 (19.4%) patients experienced late complications. CONCLUSIONS: Mainz pouch II UD following RARC in bladder cancer patients results in a satisfactory continence rate. Achieving RC-pentafecta was correlated with better satisfaction scores. The intracorporeal approach to Mainz pouch II UD is beneficial for female patients due to its reduced invasiveness. TRIAL REGISTRATION: ChiCTR2300070279; Registration: 07/04/2023, Last updated version: 01/06/2023. Retrospectively registered.

HER2 Affects the Biological Behaviours of Bladder Cancer Cells and is Closely Associated with the Progression and Prognosis of Bladder Cancer

Objective: Given the growing recognition of molecular targets in oncology, this study aimed to examine the expression pattern and prognostic significance of human epidermal growth factor receptor-2 (HER2) in bladder cancer (BC) and the effects of HER2 knockdown on the biological behaviours of BC cells. Methods: A total of 126 BC tissue samples and 20 samples of normal bladder mucosa were collected for immunohistochemical staining. The clinicopathological data were obtained from patients with BC. HER2 was knocked down in two BC cell lines (T24 and 5637) using lentiviral delivery of short hairpin RNA (shRNA), referred to as shHER2, with a blank control group (shCtrl) for comparison. A range of assays, including cell counting kit-8, colony formation, transwell, wound healing, and flow cytometry, were performed to assess the effects of HER2 knockdown on the proliferation, migration, cell cycle entry, and apoptosis of BC cells. Results: The study revealed a notable overexpression rate of HER2 in BC tissues (57.1%) than in normal bladder mucosa (0%) (p < 0.001). HER2 overexpression was associated with tumour number (p < 0.0001), pathological grade (p < 0.0001), lymph node metastasis (p = 0.040), distant metastasis (p = 0.037), overall survival (p = 0.0006), and recurrence-free survival (RFS) (p < 0.0001). In contrast, no significant association was identified between HER2 overexpression and demographic factors such as sex (p = 0.687), age (p = 0.430), tumour size (p = 0.053), or T stage (p = 0.134). Furthermore, the experimental knockdown of HER2 in BC cells inhibited the proliferation and migration and promoted their apoptosis and cell cycle arrest in the G1 phase. Conclusions: The findings suggest HER2 as a potential therapeutic target for BC and underscore the promise of developing anti-HER2-targeting strategies for BC management (AU)

Device-assisted intravesical chemotherapy versus bacillus Calmette-Guerin for intermediate or high-risk non-muscle invasive bladder cancer: a systematic reviewer and meta-analysis.

PURPOSE: To investigate the effectiveness and safety of device-assisted intravesical chemotherapy compared to Bacillus Calmette-Guerin (BCG) in the treatment of patients with intermediate- and high-risk non-muscle-invasive bladder cancer (NMIBC). METHODS: In February 2023, a systematic search was conducted on the PubMed, Cochrane, and Embase databases. Following the PRISMA guidelines, a systematic review and meta-analysis of the primary outcomes of interest were performed. The review was prospectively registered on PROSPERO under the registration number CRD42023398559. RESULTS: A total of 10 studies involving 1160 patients were included. The results of the meta-analysis showed that compared to BCG, device-assisted chemotherapy had a lower recurrence rate (OR: 0.63, 95% CI: 0.48-0.84, p = 0.001), longer recurrence-free survival (OR: 0.64, 95% CI: 0.47-0.88, p = 0.006), and lower incidence of fever (OR: 0.18, 95% CI: 0.08-0.44, p = 0.0002). However, no significant differences were observed between the two groups in terms of progression, overall survival, progression-free survival, disease-free survival, overall adverse events, serious adverse events, hematuria, allergy, and general discomfort. Subgroup analysis revealed that neither chemohyperthermia (CHT) nor electromotive drug administration (EMDA) showed statistically significant differences in oncological outcomes compared to BCG. Regarding adverse events, both CHT and EMDA groups showed lower rates of fever compared to the BCG group (OR: 0.26, 95% CI: 0.10-0.67, p = 0.005, and OR: 0.14, 95% CI: 0.05-0.37, p < 0.0001, respectively). No significant differences were observed in the remaining adverse events between either the CHT or EMDA group and the BCG group. CONCLUSION: Device-assisted intravesical chemotherapy appears to be a safe and viable alternative to BCG for patients with intermediate and high-risk NMIBC, showing comparable oncological outcomes and adverse events.

The methodological quality assessment of systematic reviews/meta-analyses of chronic prostatitis/chronic pelvic pain syndrome using AMSTAR2.

BACKGROUND: This study aimed to assess the methodological quality of the systematic reviews/meta-analyses (SRs/MAs) of chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) using A Measurement Tool to Assess systematic Reviews (AMSTAR2) and to explore the potential influencing factors. METHODS: PubMed, EMBASE and Cochrane Library databases were searched for relevant studies. AMSTAR2 was used for evaluating the methodological quality of eligible SRs/MAs. Differences between methodological characteristics of SRs/MAs were compared using chi-square tests. The intra-class correlation coefficient (ICC) was used to assess reviewer agreement in the pre-experiment. Multivariate regression analysis was used to identify potential factors affecting methodological quality. RESULTS: A total of 45 SRs/MAs were included. After AMSTAR2 evaluation, only two (4.4%) of 45 SRs/MAs were moderate, three (6.7%) were rated as low quality, and the remainder 40 (88.9%) were rated as critically low quality. Among the 16 items of AMSTAR2, item 3 and item 10 had the poorest adherence. Item 4 received the most significant number of "Partial Yes" responses. Univariable analysis indicated that there were significant differences in methodological quality in SRs between different continents (P = 0.027) as well as between preregistered SRs and those that were not (P = 0.004). However, in multivariate analysis, there was no significant association between methodological quality and the following research characteristics: publication year, continent, whether reporting followed Preferred Reporting Items for Systematic Reviews (PRISMA), preregistration, funding support, randomized controlled trials (RCT) enrollment, whether SR was published in the Cochrane Database of Systematic Reviews (CDSR), and whether with meta-analysis. Additionally, subgroup analysis based on interventional SRs/MAs showed that continent was independently associated with the methodological quality of SRs/MAs of CP/CPPS via univariable and multivariate analysis. CONCLUSIONS: Our study demonstrates that the methodological quality of SRs/MAs of CP/CPPS was generally poor. SRs/MAs of CP/CPPS should adopt the AMSTAR2 to enhance their methodological quality.

Glial Cells of the Central Nervous System: A Potential Target in Chronic Prostatitis/Chronic Pelvic Pain Syndrome.

Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is one of the most common diseases of the male urological system while the etiology and treatment of CP/CPPS remain a thorny issue. Cumulative research suggested a potentially important role of glial cells in CP/CPPS. This narrative review retrospected literature and grasped the research process about glial cells and CP/CPPS. Three types of glial cells showed a crucial connection with general pain and psychosocial symptoms. Microglia might also be involved in lower urinary tract symptoms. Only microglia and astrocytes have been studied in the animal model of CP/CPPS. Activated microglia and reactive astrocytes were found to be involved in both pain and psychosocial symptoms of CP/CPPS. The possible mechanism might be to mediate the production of some inflammatory mediators and their interaction with neurons. Glial cells provide a new insight to understand the cause of complex symptoms of CP/CPPS and might become a novel target to develop new treatment options. However, the activation and action mechanism of glial cells in CP/CPPS needs to be further explored.