Bone marrow mesenchymal stem cells therapy on bilateral pelvic nerve crush-induced voiding dysfunction in rats.

INTRODUCTION AND HYPOTHESIS: Neurogenic voiding dysfunction can be induced after radical pelvic surgery and severely affects patients' quality of life. This study aims to investigate the effects of bone marrow mesenchymal stem cells (BMSCs) on neurogenic voiding dysfunction in male rats and explore the underlying mechanisms. METHODS: Thirty 4-week-old male Sprague-Dawley rats were randomly divided into three groups: (1) sham-operated (sham, n = 10), (2) intrabladder wall injection of phosphate buffer solution (PBS) after bilateral pelvic nerve crush (BPNC+PBS, n = 10), and (3) intrabladder wall injection of BMSCs after bilateral pelvic nerve crush (BPNC+BMSCs, n = 10). Four weeks postoperatively, functional and morphological examinations were performed. RESULTS: Compared to the sham group, BPNC rats manifested significant augmentation in the frequency of non-voiding contractions and postvoid residual and bladder capacity, and they had decreases in intravesical pressure and voiding efficiency. However, they were markedly improved after BMSC injection. Masson's trichrome staining showed that the ratio of collagen area in bladder wall tissue significantly increased in the BPNC+PBS group but was reduced following BMSC injection. BPNC increased the protein expression of TGF-ß1, Smad2/3, and collagen I/III but decreased the expression of α-SMA. BMSC injection stimulated higher expression levels of α-SMA and lower expression levels of the other target proteins. The expression levels of vesicular acetylcholine transporters were reduced at 4 weeks post-BPNC, whereas injection of BMSCs boosted the expression quantity. CONCLUSIONS: BMSC therapy suppressed detrusor fibrosis, improved intravesical pressure and voiding efficiency, and partially restored voiding function in male rats after BPNC.

[Relationship of prostate volume and inflammatory cell infiltration with the positive rate of prostate biopsy].

OBJECTIVE: To investigate the factors influencing the positive rate of prostate biopsy and its relationship with the prostate volume and inflammatory cell infiltration (ICI). METHODS: We retrospectively analyzed the clinical data on 230 cases of double-plane transrectal ultrasound-guided prostate biopsy in our Department of Urology, including the patients' age, body mass index (BMI), serum total prostate-specific antigen (tPSA), PSA density (PSAD), prostate volume, and ICI in the prostate tissue. We also investigated the relationship of the above factors with the pathological results of prostate biopsy by binary logistic regression analysis. RESULTS: The positive rate of prostate biopsy was 38.7% (89/230) in the total number of cases, 28.57% (n = 56) in the 196 cases with tPSA < 100 µg/L, and 97.06% (n = 33) in the 34 cases with tPSA ≥ 100 µg/L. Binary logistic regression analysis showed that the positive rate of prostate biopsy in those with tPSA < 100 µg/L was correlated positively with age (P < 0.01, OR = 1.09), tPSA (P < 0.01, OR = 1.04) and PSAD (P < 0.01, OR = 10.04), negatively with the prostate volume (P < 0.01, OR = 0.98) and ICI (P < 0.01, OR = 0.22), but not with BMI (P > 0.05). As a predictor of positive prostate biopsy, tPSA > 10 µg/L exhibited a sensitivity of 82.14% and a specificity of 35.71%, while PSAD > 0.26 showed a sensitivity of 78.57% and a specificity of 71.43%. CONCLUSIONS: Non-specific elevation of the tPSA level induced by increased prostate volume and inflammatory cell infiltration may lead to unnecessary biopsies in some patients. As a predictor of positive prostate biopsy, PSAD > 0.26 has a higher clinical application value than tPSA > 10 µg/L.

Identification of an immune subtype-related prognostic signature of clear cell renal cell carcinoma based on single-cell sequencing analysis.

Background: There is growing evidence that immune cells are strongly associated with the prognosis and treatment of clear cell renal cell carcinoma (ccRCC). Our aim is to construct an immune subtype-related model to predict the prognosis of ccRCC patients and to provide guidance for finding appropriate treatment strategies. Methods: Based on single-cell analysis of the GSE152938 dataset from the GEO database, we defined the immune subtype-related genes in ccRCC. Immediately afterwards, we used Cox regression and Lasso regression to build a prognostic model based on TCGA database. Then, we carried out a series of evaluation analyses around the model. Finally, we proved the role of VMP1 in ccRCC by cellular assays. Result: Initially, based on TCGA ccRCC patient data and GEO ccRCC single-cell data, we successfully constructed a prognostic model consisting of five genes. Survival analysis showed that the higher the risk score, the worse the prognosis. We also found that the model had high predictive accuracy for patient prognosis through ROC analysis. In addition, we found that patients in the high-risk group had stronger immune cell infiltration and higher levels of immune checkpoint gene expression. Finally, cellular experiments demonstrated that when the VMP1 gene was knocked down, 786-O cells showed reduced proliferation, migration, and invasion ability and increased levels of apoptosis. Conclusion: Our study can provide a reference for the diagnosis and treatment of patients with ccRCC.

Efficacy of peripheral electrical nerve stimulation on improvements of urodynamics and voiding diary in patients with neurogenic lower urinary tract dysfunction: a systematic review and meta-analysis.

BACKGROUND: Peripheral electrical nerve stimulation is a routinely recommended treatment for non-neurogenic overactive bladder but has not been approved for patients with neurogenic lower urinary tract dysfunction (NLUTD). This systematic review and meta-analysis was to elucidate the efficacy and safety of electrostimulation and thus provide firm evidence for treating NLUTD. MATERIALS AND METHODS: We systematically performed the literature search through PubMed, Web of Science, and Cochrane Library databases in March 2022. The eligible studies were identified across the inclusion criteria and the data on urodynamic outcomes, voiding diary parameters, and safety was collected to quantitatively synthesize the pooled mean differences (MDs) with 95% CIs. Subgroup analyses and sensitivity analyses were subsequently used to investigate the possible heterogeneity. This report was achieved in accordance with the preferred reporting items for systematic reviews and meta-analyses statement. RESULTS: A total of 10 studies involving 464 subjects and 8 studies with 400 patients were included for systematic review and meta-analysis, respectively. The pooled effect estimates indicated that electrostimulation could significantly improve urodynamic outcomes, including maximum cystometric capacity (MD=55.72, 95% CI 15.73, 95.72), maximum flow rate (MD=4.71, 95% CI 1.78, 7.65), maximal detrusor pressure (MD=-10.59, 95% CI -11.45, -9.73), voided volume (MD=58.14, 95% CI 42.97, 73.31), and post-void residual (MD=-32.46, 95% CI -46.63, -18.29); for voiding diary parameters, patients undergoing electrostimulation showed lower MDs of incontinence episodes per 24 h (MD=-2.45, 95% CI -4.69, -0.20) and overactive bladder symptom score (MD=-4.46, 95% CI -6.00, -2.91). In addition to surface redness and swelling, no stimulation-related severe adverse events were reported else. CONCLUSIONS: The current evidence demonstrated that peripheral electrical nerve stimulation might be effective and safe for managing NLUTD, whereas more reliable data from large-scale randomized controlled trials are necessary to strengthen this concept.

Development and validation of a novel nomogram predicting clinically significant prostate cancer in biopsy-naive men based on multi-institutional analysis.

BACKGROUND: Prediction of clinically significant prostate cancer (csPCa) is essential to select biopsy-naive patients for prostate biopsy. This study was to develop and validate a nomogram based on clinicodemographic parameters and exclude csPCa using prostate-specific antigen density (PSAD) stratification. METHODS: Independent predictors were determined via univariate and multivariate logistic analysis and adopted for developing a predictive nomogram, which was assessed in terms of discrimination, calibration, and net benefit. Different PSAD thresholds were used for deciding immediate biopsies in patients with Prostate Imaging-Reporting and Data System (PI-RADS) 3 lesions. RESULTS: A total of 932 consecutive patients who underwent ultrasound-guided transperineal cognitive biopsy were enrolled in our study. In the development cohort, age (odds ratio [OR], 1.075; 95% confidence interval [CI], 1.036-1.114), PSAD (OR, 6.003; 95% CI, 2.826-12.751), and PI-RADS (OR, 3.419; 95% CI, 2.453-4.766) were significant predictors for csPCa. On internal and external validation, this nomogram showed high areas under the curve of 0.943, 0.922, and 0.897, and low Brier scores of 0.092, 0.102, and 0.133 and insignificant unreliability tests of 0.713, 0.490, and 0.859, respectively. Decision curve analysis revealed this model could markedly improve clinical net benefit. The probability of excluding csPCa was 98.51% in patients with PI-RADS 3 lesions and PSAD <0.2 ng/ml2 . CONCLUSION: This novel nomogram including age, PSAD, and PI-RADS could be applied to accurately predict csPCa, and 44.08% of patients with equivocal imaging findings plus PSAD <0.2 ng/ml2 could safely forgo biopsy.

Neoadjuvant Chemohormonal Therapy in Prostate Cancer Before Radical Prostatectomy: A Systematic Review and Meta-Analysis.

Objective: This meta-analysis was to investigate the effects of neoadjuvant chemohormonal therapy (NCHT) on patients with prostate cancer (PCa) before radical prostatectomy (RP) and attempt to provide meaningful evidence. Methods: A systematic search was performed using the PubMed, Web of Science, and Cochrane Library databases in February 2022 based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The relevant studies were critically screened and we extracted the data of demography, postoperative pathology, and survival to calculate the pooled effect sizes. Subgroup analyses and sensitivity analyses were used to explore the source of heterogeneity. Results: Six identified studies involving 1717 subjects were included according to the selection criteria. There was no significant difference between NCHT plus RP and RP alone groups regarding lymph node involvement (risk ratio [RR]=1.03, 95% confidence interval [CI]: 0.57-1.87, P=0.92). However, NCHT prior to RP significantly decreased the rates of positive surgical margin (PSM, RR=0.35, 95% CI: 0.22-0.55, P<0.0001) and seminal vesicle invasion (SVI, RR=0.78, 95% CI: 0.65-0.95, P=0.01), and increase pathological downstaging (RR=1.64, 95% CI: 1.17-2.29, P=0.004). Additionally, biochemical recurrence-free survival (BRFS) and overall survival (OS) were significantly prolonged under the administration of NCHT (HR=0.54, 95% CI: 0.34-0.85, P=0.008 and HR=0.67, 95% CI: 0.48-0.94, P=0.02, respectively). Conclusions: Compared to the RP alone group, patients with NCHT plus RP showed significant improvements in PSM, SVI, pathological downstaging, BRFS, and OS, whereas further multicenter randomized controlled trials are needed to consolidate this concept.

Expression of miR-410 in peripheral blood of patients with clear cell renal cell carcinoma and its effect on proliferation and invasion of Caki-2 cells.

PURPOSE: To explore the significance of miR-410 expression in clear cell renal cell carcinoma (CCRCC) and its biological function in CCRCC. METHODS: A total of 113 patients with CCRCC admitted to our hospital and 113 healthy individuals over the same period were enrolled. MiR-410 in the tissues and serum of patients with CCRCC was quantified, and the diagnostic value of miR-410 in CCRCC and the relationship between miR-410 and prognosis of patients with CCRCC were analyzed. In addition, miR-410 mimic and miR-410 inhibitor were adopted to regulate miR-410 in CCRCC cells (Caki-2), and then the changes in the proliferation, migration, invasion, and cell cycle of Caki-2 cells were determined. Moreover, tumorigenicity in nude mice was carried out to determine the effect of miR-410 on the tumor growth of CCRCC. RESULTS: MiR-410 was expressed at a high level in CCRCC patients, and had a high diagnostic accuracy [area under the curve (AUC) = 0.916]. In addition, miR-410 was an independent risk factor for the survival prognosis of patients with CCRCC, and its high expression indicated poor prognosis of the patients. Inhibiting miR-410 suppressed cell proliferation, cycle progression, migration, invasion and tumor growth in vivo and promoted cell apoptosis. CONCLUSION: MiR-410 is a possible biological indicator for the diagnosis and prognosis of CCRCC, and is also an independent risk factor for the survival prognosis of CCRCC patients. In addition, miR-410 plays a role as an oncogene in CCRCC and promotes the malignant progression of CCRCC.

Establishment of animal model manifested as bladder neurogenic changes generated by bilateral pelvic nerve injury in male rats.

PURPOSE: To establish a male rat model of neurogenic bladder after bilateral pelvic nerve injury (BPNI) and investigate the factors associated with onset of neurogenic bladder. METHODS: Twenty-four 8-week-old male Sprague-Dawley rats were randomly divided into three groups (n = 8 rats per group). Rats in 4-week and 8-week nerve injury group underwent BPNI, while rats in the sham group underwent a sham operation. Bladder functional analysis were performed and then bladders tissues were harvested for morphological examination and investigating the mRNA expression levels of target genes in all rats. RESULTS: The bladder weight significantly increased in rats following BPNI. Functional analysis revealed non-voiding contractions and decreased detrusor contractility following BPNI, manifested as elevated post-void residual and bladder capacity while reduced maximum voiding pressure and voiding efficiency. The collagen area in bladder tissue and mRNA expression levels of target genes significantly increased at 4 or 8 weeks post-BPNI except Smad3. At 4 weeks post-BPNI, expression levels of vesicular acetylcholine transporter were reduced, then returned to baseline at 8 weeks. Expression levels of tyrosine hydroxylase were reduced at both 4 and 8 weeks post-BPNI. CONCLUSIONS: A neurogenic bladder animal model was successfully established by performing BPNI in male rats, characterized by impaired voiding function, bladder detrusor fibrosis, and reduced neurotransmitter release.

Construction and Validation of a Clinical Predictive Nomogram for Improving the Cancer Detection of Prostate Naive Biopsy Based on Chinese Multicenter Clinical Data.

OBJECTIVES: Prostate biopsy is a common approach for the diagnosis of prostate cancer (PCa) in patients with suspicious PCa. In order to increase the detection rate of prostate naive biopsy, we constructed two effective nomograms for predicting the diagnosis of PCa and clinically significant PCa (csPCa) prior to biopsy. MATERIALS AND METHODS: The data of 1,428 patients who underwent prostate biopsy in three Chinese medical centers from January 2018 to June 2021 were used to conduct this retrospective study. The KD cohort, which consisted of 701 patients, was used for model construction and internal validation; the DF cohort, which consisted of 385 patients, and the ZD cohort, which consisted of 342 patients, were used for external validation. Independent predictors were selected by univariate and multivariate binary logistic regression analysis and adopted for establishing the predictive nomogram. The apparent performance of the model was evaluated via internal validation and geographically external validation. For assessing the clinical utility of our model, decision curve analysis was also performed. RESULTS: The results of univariate and multivariate logistic regression analysis showed prostate-specific antigen density (PSAD) (P<0.001, OR:2.102, 95%CI:1.687-2.620) and prostate imaging-reporting and data system (PI-RADS) grade (P<0.001, OR:4.528, 95%CI:2.752-7.453) were independent predictors of PCa before biopsy. Therefore, a nomogram composed of PSAD and PI-RADS grade was constructed. Internal validation in the developed cohort showed that the nomogram had good discrimination (AUC=0.804), and the calibration curve indicated that the predicted incidence was consistent with the observed incidence of PCa; the brier score was 0.172. External validation was performed in the DF and ZD cohorts. The AUC values were 0.884 and 0.882, in the DF and ZD cohorts, respectively. Calibration curves elucidated greatly predicted the accuracy of PCa in the two validation cohorts; the brier scores were 0.129 in the DF cohort and 0.131 in the ZD cohort. Decision curve analysis showed that our model can add net benefits for patients. A separated predicted model for csPCa was also established and validated. The apparent performance of our nomogram for PCa was also assessed in three different PSA groups, and the results were as good as we expected. CONCLUSIONS: In this study, we put forward two simple and convenient clinical predictive models comprised of PSAD and PI-RADS grade with excellent reproducibility and generalizability. They provide a novel calculator for the prediction of the diagnosis of an individual patient with suspicious PCa.

Establishing a novel prediction model for improving the positive rate of prostate biopsy.

BACKGROUND: At present, prostate-specific antigen (PSA) is the primary evaluation index for judging the necessity of prostate cancer (PCa) biopsy. However, there is a high false-positive rate and a low predictive value due to many interference factors. In this study, we tried to find a novel prediction model that could improve the positive rate of prostate biopsy and reduce unnecessary biopsy. METHODS: We retrospectively studied 237 patients, including their age, body mass index (BMI), PSA, prostate volume (PV), prostate imaging-reporting and data system (PI-RADS) v2 score, neutrophil-lymphocyte ratio (NLR), biopsy Gleason score (BGS), and other information. The univariate and multivariate logistic analyses were used to screen out indicators related to PCa. After establishing a prediction formula model, we used receiver operating characteristic (ROC) curves to assess its prediction performance. RESULTS: Our study found that age, PSA, PI-RADS v2 score, and diabetes significantly correlated with PCa. Based on multivariate logistic regression analysis results, we created the following prediction formula: Y = 2.599 × PI-RADS v2 score + 1.766 × diabetes + 0.052 × age + 1.005 × PSAD - 9.119. ROC curves showed the formula's threshold was 0.3543. The composite formula had an excellent capacity to detect PCa with the area under the curve (AUC) of 0.91. In addition, the composite formula also achieved significantly better sensitivity, specificity, and diagnostic accuracy than PSA, PSA density (PSAD), and PI-RADS v2 score alone. CONCLUSIONS: Our predictive formula predicted performance better than PSA, PSAD, and PI-RADS v2 score. It can thus contribute to the diagnosis of PCa and be used as an indicator for prostate biopsy, thereby reducing unnecessary biopsy.