Clinical practice guideline for transurethral plasmakinetic resection of prostate for benign prostatic hyperplasia (2021 Edition).

Benign prostatic hyperplasia (BPH) is highly prevalent among older men, impacting on their quality of life, sexual function, and genitourinary health, and has become an important global burden of disease. Transurethral plasmakinetic resection of prostate (TUPKP) is one of the foremost surgical procedures for the treatment of BPH. It has become well established in clinical practice with good efficacy and safety. In 2018, we issued the guideline "2018 Standard Edition". However much new direct evidence has now emerged and this may change some of previous recommendations. The time is ripe to develop new evidence-based guidelines, so we formed a working group of clinical experts and methodologists. The steering group members posed 31 questions relevant to the management of TUPKP for BPH covering the following areas: questions relevant to the perioperative period (preoperative, intraoperative, and postoperative) of TUPKP in the treatment of BPH, postoperative complications and the level of surgeons' surgical skill. We searched the literature for direct evidence on the management of TUPKP for BPH, and assessed its certainty generated recommendations using the grade criteria by the European Association of Urology. Recommendations were either strong or weak, or in the form of an ungraded consensus-based statement. Finally, we issued 36 statements. Among them, 23 carried strong recommendations, and 13 carried weak recommendations for the stated procedure. They covered questions relevant to the aforementioned three areas. The preoperative period for TUPKP in the treatment of BPH included indications and contraindications for TUPKP, precautions for preoperative preparation in patients with renal impairment and urinary tract infection due to urinary retention, and preoperative prophylactic use of antibiotics. Questions relevant to the intraoperative period incorporated surgical operation techniques and prevention and management of bladder explosion. The application to different populations incorporating the efficacy and safety of TUPKP in the treatment of normal volume (< 80 ml) and large-volume (≥ 80 ml) BPH compared with transurethral urethral resection prostate, transurethral plasmakinetic enucleation of prostate and open prostatectomy; the efficacy and safety of TUPKP in high-risk populations and among people taking anticoagulant (antithrombotic) drugs. Questions relevant to the postoperative period incorporated the time and speed of flushing, the time indwelling catheters are needed, principles of postoperative therapeutic use of antibiotics, follow-up time and follow-up content. Questions related to complications incorporated types of complications and their incidence, postoperative leukocyturia, the treatment measures for the perforation and extravasation of the capsule, transurethral resection syndrome, postoperative bleeding, urinary catheter blockage, bladder spasm, overactive bladder, urinary incontinence, urethral stricture, rectal injury during surgery, postoperative erectile dysfunction and retrograde ejaculation. Final questions were related to surgeons' skills when performing TUPKP for the treatment of BPH. We hope these recommendations can help support healthcare workers caring for patients having TUPKP for the treatment of BPH.

Role of p-ERK1/2 in Benign Prostatic Hyperplasia during Hyperinsulinemia.

PURPOSE: Using a rat model of hyperinsulinemia, the present study investigated the role of p-ERK1/2 in benign prostatic hyperplasia (BPH). MATERIALS AND METHODS: Forty male Sprague-Dawley rats were randomly selected and assigned to four groups: high fat diet (HFD)+BPH (n=10), HFD (n=10), BPH (n=10), and control (n=10) groups. Hyperinsulinemia was induced by HFD feeding, while BPH was induced using testosterone propionate. Plasma glucose, plasma insulin and bodyweight were examined weekly. Immunohistochemistry (IHC) and western blot analysis were used to analyze the expression of ERK1/2 and p-ERK1/2 in rat prostates. RESULTS: Plasma glucose and plasma insulin levels were significantly greater in the HFD+BPH and HFD groups, when compared to the other two groups (P<0.05). Prostate weights were significantly greater in the HFD+BPH, HFD and BPH groups, than in the control group (P<0.05). IHC and western blot analysis revealed that p-ERK1/2 expression was greater in the HFD+BPH group than in the other three groups (P<0.05). CONCLUSION: Androgens plus a hyperinsulinemic condition induced by HFD can result in prostatic cell hyperplasia, and this mechanism may be correlated to the upregulation of p-ERK1/2. Further investigations of this possibility are required.

Identification of potential novel differentially-expressed genes and their role in invasion and migration in renal cell carcinoma.

Clear cell renal cell carcinoma (ccRCC) remains one of the most common cancer types globally, and while it has been extensively studied, the molecular basis for its pathology remains incompletely understood. Herein, we profiled three previously published datasets (GSE66272, GSE100666, and GSE105261) in a single integrated analysis aimed at identifying disease-associated patterns of gene expression that may offer mechanistic insight into the drivers of this disease. We pooled expression data from 39 normal kidney samples and 39 kidney tumors, leading us to identify 310 differentially expressed genes (DEGs) that were linked to kidney cancer in all three analyzed datasets. Of these genes, 133 and 177 were up- and down-regulated, respectively, in cancer samples. We then incorporated these DEGs into a protein-protein interaction network with the STRING and Cytoscape tools, and we were able to identify signaling pathways significantly enriched for these DEGs. The relationship between DEG expression and ccRCC patient survival was further evaluated using a Kaplan-Meier approach, leading us to identify TIMP1 as an independent prognostic factor in ccRCC patients. When TIMP1 expression was disrupted in ccRCC cell lines, this impaired their migratory and invasive capabilities. In summary, we employed an integrative bioinformatics approach to identify ccRCC-related DEGs and associated signaling pathways. Together these findings offer novel insight into the mechanistic basis for ccRCC, potentially helping to identify novel therapeutic targets for the treatment of this deadly disease.

Quercetin protects against chronic prostatitis in rat model through NF-κB and MAPK signaling pathways.

BACKGROUND: Chronic Prostatitis/Chronic Pelvic Pain Syndrome (CP/CPPS) is a common disease of urology, of which the pathogenesis and therapy remain to be further elucidated. Quercetin has been reported to improve the symptoms of CP/CPPS patients. We aimed to verify the therapeutic effect of quercetin on CP/CPPS and identify the mechanism responsible for it. METHODS: A novel CP/CPPS model induced with Complete Freund Adjuvant in Sprague Dawley rats was established and the prostates and blood specimens were harvested for further measurement after oral administration of quercetin for 4 weeks. RESULTS: Increased prostate index and infiltration of lymphocytes, up-regulated expression of IL-1ß, IL-2, IL-6, IL-17A, MCP1, and TNFα, decreased T-SOD, CAT, GSH-PX, and increased MDA, enhanced phosphorylation of NF-κB, P38, ERK1/2, and SAPK/JNK were detected in CP/CPPS rat model. Quercetin was identified to ameliorate the histo-pathologic changes, decrease the expression of pro-inflammatory cytokines IL-1ß, IL-2, IL-6, IL-17A, MCP1, and TNFα, improve anti-oxidant capacity, and suppress the phosphorylation of NF-κB and MAPKs. CONCLUSIONS: Quercetin has specific protective effect on CP/CPPS, which is mediated by anti-inflammation, anti-oxidation, and at least partly through NF-κB and MAPK signaling pathways.

DLX1, a binding protein of beta-catenin, promoted the growth and migration of prostate cancer cells.

Several studies have indicated the involvement of DLX1 in the progression of prostate cancer. However, the functions of DLX1 in the prostate cancer and the underlying molecular mechanism remains largely unknown. In this study, we have shown that DLX1 was up-regulated in the prostate clinical samples. DLX1 promoted the growth, migration and colony formation of prostate cancer cells by activating beta-catenin/TCF signaling. DLX1 interacted with beta-catenin and enhanced the interaction between beta-catenin and TCF4. Taken together, this study demonstrated that DLX1 exerted the oncogenic roles on the prostate cancer by activating beta-catenin/TCF signaling.

Identification of hub genes and pathways associated with bladder cancer based on co-expression network analysis.

The aim of the present study was to identify hub genes and signaling pathways associated with bladder cancer (BC) utilizing centrality analysis and pathway enrichment analysis. The differentially expressed genes (DEGs) were screened from the ArrayExpress database between normal subjects and BC patients. Co-expression networks of BC were constructed using differentially co-expressed genes and links, and hub genes were investigated by degree centrality analysis of co-expression networks in BC. The enriched signaling pathways were investigated by Kyoto Encyclopedia of Genes and Genomes database analysis based on the DEGs. The hub gene expression in BC tissues was validated using reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and western blotting. A total of 329 DEGs were screened, including 147 upregulated and 182 downregulated genes. The co-expression network constructed between BC and normal controls consisted of 182 nodes and 434 edges, and the two genes in each gene pair were differentially co-expressed genes. Centrality analysis of co-expression networks suggested that the top 5 hub genes with high degree included lectin, galactoside-binding, soluble, 4 (LGALS4), protein tyrosine phosphatase, receptor type N2 (PTPRN2), transmembrane protease, serine 11E (TMPRSS11E), tripartite motif containing 31 (TRIM31) and potassium voltage-gated channel subfamily D member 3 (KCND3). Pathway analysis revealed that the 329 DEGs were significantly enriched in 5 terms (cell cycle, DNA replication, oocyte meiosis, p53 signaling pathway and peroxisome proliferator-activated receptor signaling pathway). According to RT-qPCR and western blot analysis, 4/5 hub genes were significantly expressed, including LGALS4, PTPRN2, TMPRSS11E, TRIM31; however, KCND3 was not significantly expressed. In the present study, 5 hub genes were successfully identified (LGALS4, PTPRN2, TMPRSS11E, TRIM31 and KCND3) and 5 biological pathways that may be underlying biomarkers for early diagnosis and treatment associated with bladder cancer were revealed.

Clinical characteristics and pathology of thyroid-like follicular carcinoma of the kidney: Report of 3 cases and a literature review.

Thyroid-like follicular carcinoma (TLFC) of the kidney is an extremely rare type of renal tumor, which has not been classified under a known subtype of renal cell carcinoma. It is histologically similar to the primary thyroid follicular carcinoma; however, the characteristics lack thyroid immunohistochemical markers. The aim of the present study was to illustrate the clinical characteristics of 3 new cases along with a review of the literature. The patients were compared with regards to gender, age, location and size of the tumor, imageology, morphology, immunohistochemistry and prognosis. According to the limited data, TLFC occurs mainly in young women and its clinical manifestations have no difference with other renal tumors. Its imageological features resemble a large spectrum of benign and malignant renal and extra-renal conditions, which should be eliminated in the diagnostic process. Confirmed diagnosis depends on the examination of pathology and immunohistochemistry. Surgical ablation is the preferred therapeutic method. Currently, TLFC has a relatively good prognosis; however, this conclusion requires further cases and long-term follow-ups. Improving the understanding of TLFC can help avoid misdiagnosis and prevent inappropriate treatment.

The complete mitochondrial genome sequence of the prostate adenocarcinoma rat R3327.

The prostate adenocarcinoma of the Copenhagen rat (R3327) is recognized as a suitable model for human prostate carcinoma. In this study, we sequenced its complete mitogenome and total length of the genome was 16,310 bp (GenBank Accession Number KM820831). It contains 13 protein-coding genes, 2 ribosomal RNA genes, and 22 transfer RNA genes. This mitochondrial genome sequence will provide new genetic resource into prostate adenocarcinoma disease.

Metabolic behavior prediction of pazopanib by cytochrome P450 (CYP) 3A4 by molecular docking.

Metabolism-mediated drug adverse effects (e.g., drug-drug interaction, bioactivation, etc.) strongly limit the utilization of clinical drugs. The present study aims to predict the metabolic capability of cytochrome P450 (CYP) 3A4 toward pazopanib which is an excellent drug exhibiting therapeutic role toward various cancers especially for ovarian cancer. Pazopanib can be well docked into the activity cavity of CYP3A4, and the interaction structure in pazopanib was methyl group located besides nitrogen in the five-membered ring. The distance between the hydrogen atom in methyl group and active center is 3.64 Å. The interaction amino acid is Glu374. Furthermore, both pazopanib and ketoconazole were docked into the activity cavity of CYP3A4 to compare their binding potential. The distance between ketoconazole and activity center (2.10 Å) is closer than the distance between pazopanib and activity center of CYP3A4, indicating the easy influence of CYP3A4 inhibitor toward the metabolism of pazopanib. All these data were helpful for the clinical application of pazopanib, and R&D of other tinib drug candidates as new anti-tumor drugs.

[Expressions of hypoxia inducible factor 1 alpha and P53 in the epididymis of varicocele rats].

OBJECTIVE: To investigate the mechanism of epididymal hypofunction of rats with varicocele (VC) by observing the changes in the epididymal index, motility of epididymal sperm, expressions of hypoxia-inducible factor 1 alpha (HIF-1 alpha) and the tumor suppressor protein p53, and epididymal epithelial cells. METHODS: Ninety SD rats were equally randomized to a VC model (A), a sham operation (B), and a normal control group (C). At 49 days after surgery, all the rats were executed after weighing. Then the volume of the left epididymis was obtained, the epididymal sperm motility was detected by computer-assisted sperm analysis (CASA), the expressions of HIF-1 alpha and p53 in the epididymal tissue were determined by Western-blot, and the epididymal epithelial cells were observed by HE staining. RESULTS: VC models were successfully established in 27 of the rats. One-way ANOVA test showed no statistically significant differences in the epididymis index among groups A ([40.53 +/- 1.76] x 10 (-5)) , B ([43.31 1.58] x 10( -5)) , and C ( [44. 10 +/- 2.62] x 10 -5) (P > 0.05). Sperm motility and the percentage of progressively motile sperm were significantly lower in group A ([71.86 +/- 5.07]% and [42. 26 +/-4.45]%) than in B ([78.51 4.50]% and [49.08 +/-4. 19]% ) and C ( [79.24 +/- 2.70] % and [52. 23+/- 2. 23] % ) (both P <0.05) , while the expressions of HTF-1 a and p53 were remarkably higher in A (1.74 +/- 0. 16 and 1.71 +/- 0. 11) than in B (0.32 +/- 0. 08 and 0.56 +/- 0.13) and C (0.12 +/- 0. 03 and 0.25 +/-0.06) (both P < 0.05). The epididymal epithelial cells in group A were obviously decreased in number and arranged in loose and disorderly patterns as compared with those in B and C. CONCLUSION: Varicocele can cause hypoxia in the epididymal tissue, which in turn may lead to epididymal hypofunction.

Increased expression of miR-222 is associated with poor prognosis in bladder cancer.

BACKGROUND: MicroRNA-222 (miR-222) has been shown to play a potential oncogenic role in bladder cancer. The aim of this study was to evaluate the expression of miR-222 in bladder cancer and its potential relevance to clinicopathological characteristics and patient survival. METHODS: Surgical specimens of cancer tissue and adjacent normal tissue were obtained from 97 patients with bladder cancer. The relative expression levels of miR-222 in the cancer and the normal adjacent tissue were measured by quantitative reverse-transcriptase PCR. We analyzed their correlation with clinicopathological parameters and prognostic value. RESULTS: The expression level of miR-222 was significantly higher in tumor tissues than in corresponding non-cancerous tissues (5.46 ± 1.45 versus 1.92 ± 0.65, P < 0.0001), and a high expression of miR-222 was found to be significantly associated with tumor grade (P = 0.003) and tumor stage (P = 0.005). The miR-222 expression level was classified as high or low in relation to the median value (cutoff value = 5.15). Kaplan-Meier analysis showed that patients with higher levels of miR-222 had significantly poorer survival than those with lower expression of this miRNA in patients, with a 5-year overall survival of 29.53% and 52.75%, respectively (P = 0.0034). In the multivariate Cox proportional hazards analysis, which included miR-222 level, tumor grade, tumor stage, and tumor number, high miR-222 expression was independently associated with poor survival (P < 0.001; hazard ratio 6.17; 95% CI 2.33 to 10.39). CONCLUSION: miR-222 overexpression is involved in the poor prognosis of bladder cancer and can be used as a biomarker for selection of cases requiring special attention.

Characteristics of urinary tract infection pathogens and their in vitro susceptibility to antimicrobial agents in China: data from a multicenter study.

OBJECTIVE: This study assessed the characteristics of pathogens identified in clinical isolates from patients with urinary tract infection (UTI) and their in vitro sensitivity to commonly used antibiotics in the clinical setting in China. DESIGN AND SETTING: Multicenter study was conducted between January and December 2011 in 12 hospitals in China. PARTICIPANTS: Urine samples were collected from 356 symptomatic patients treated in the study hospitals for acute uncomplicated cystitis, recurrent UTI or complicated UTI. PRIMARY AND SECONDARY OUTCOME MEASURES: Minimal inhibitory concentrations (MICs) were measured using broth microdilution according to the Clinical and Laboratory Standards Institute 2011 guidelines. Thirteen antimicrobial agents were tested: fosfomycin tromethamine, levofloxacin, moxifloxacin, cefdinir, cefixime, cefaclor, cefprozil, cefuroxime, amoxicillin/clavulanic acid, cefotaxime, azithromycin, nitrofurantoin and oxacillin. Escherichia coli isolates were screened and extended spectrum ß-lactamases (ESBL) production was confirmed by a double-disk synergy test. RESULTS: 198 urine samples were culture-positive and 175 isolates were included in the final analysis. E coli was detected in 50% of cultures, followed by Staphylococcus epidermidis (9%), Enterococcus faecalis (9%) and Klebsiella pneumoniae (5%). The detection rate of ESBL-producing E coli was 53%. Resistance to levofloxacin was the most common among all the isolates. Nitrofurantoin and fosfomycin tromethamine had the greatest activity against E coli; overall, 92% and 91% of isolates were susceptible to these antimicrobials. E faecalis had the highest susceptibility rates to fosfomycin tromethamine (100%). CONCLUSIONS: The most frequently identified pathogens in our patients were ESBL-producing E coli and E faecalis. Fosfomycin tromethamine and nitrofurantoin showed a good antimicrobial activity against UTI pathogens. They may represent good options for the empiric treatment of patients with UTI.

Evaluation of three-dose fosfomycin tromethamine in the treatment of patients with urinary tract infections: an uncontrolled, open-label, multicentre study.

OBJECTIVE: To evaluate the clinical and microbiological efficacy and safety of three doses of 3 g fosfomycin tromethamine administered orally to treat lower urinary tract infections. DESIGN AND PARTICIPANTS: This prospective, uncontrolled, open-label study was conducted in 12 medical centres in China, between January and December 2011. According to the diagnosis criteria of Chinese Guidelines on Urological Infections, patients (18-70 years) with acute uncomplicated cystitis, recurrent lower urinary tract infection or complicated lower urinary tract infection received three doses of 3 g fosfomycin tromethamine orally, at days 1, 3 and 5. PRIMARY AND SECONDARY OUTCOME MEASURES: Efficacy endpoints (clinical efficacy, microbiological efficacy and overall efficacy) were evaluated on day 15. Clinical symptoms, physical signs, urinalysis, liver and kidney function, patient records and evaluation of adverse events (AEs) and serious AEs up to day 15 were evaluated for analysis of safety. RESULTS: 361 patients were included in the full analysis set, 356 in the safety analysis set and 335 in the per-protocol set (PPS). In the PPS, the clinical efficacy rates at day 15 for acute uncomplicated cystitis, recurrent lower urinary tract infection and complicated lower urinary tract infection were 94.71% (179/189), 77.22% (61/79) and 62.69% (42/67), respectively. The microbiological efficacy rates (day 15) were 97.65% (83/85), 94.44% (34/36) and 83.87% (26/31), respectively. The overall efficacy rates (day 15) were 95.29% (81/85), 77.78% (28/36) and 64.52% (20/31), respectively. 20/356 (5.6%) patients reported drug-related AEs, the most common being diarrhoea. No serious drug-related AEs were reported. CONCLUSIONS: This fosfomycin tromethamine dosing regimen showed clinical and microbiological efficacy with some AEs and good tolerability in patients with acute uncomplicated cystitis, recurrent lower urinary tract infection and complicated lower urinary tract infection.