American journal of clinical and experimental urology最新文献

Long non-coding RNAs (lncRNAs) primarily engage with mRNA, DNA, proteins, and microRNAs (miRNAs), thereby regulating gene expression; however, its specific role in diabetic erectile dysfunction (DED) has not been studied. This study aims to investigate the effects and mechanisms of LncRNA CRYM-AS1 in DED. The differential target gene LncRNA CRYM-AS1 was identified in the penile tissues of rats with DED through bioinformatics analyses. A KEGG signaling pathway enrichment analysis suggested a potential association between LncRNA CRYM-AS1 and the Hippo-YAP1 pathway. Real-time fluorescent quantitative PCR (RT-qPCR) results indicated a significantly lower expression of LncRNA CRYM-AS1 in the penile tissue of DED rats compared to the control group. Western Blot and immunohistochemistry (IHC) staining results demonstrated significantly elevated protein expression levels of YAP1, Caspase3, BAX, and Bcl-2, with a decreased Bcl-2/BAX ratio. CCK8 cell viability results showed a significant decrease in cell viability in the high glucose group at 4 days of modeling, and compared with the normal glucose group, RT-qPCR results showed that the expression of LncRNA CRYM-AS1 in the high glucose group in human umbilical vein endothelial cells (HUVECs) was significantly reduced; Western Blot results showed that the protein expression of YAP1, Cleaved-caspase3 and BAX was significantly up-regulated, and the protein expression of Bcl-2 was significantly down-regulated in the high glucose group. Compared with the empty vector group, RT-qPCR results after transfection of siLncRNA CRYM-AS1 showed that the expression of LncRNA CRYM-AS1 was down-regulated, the mRNA and protein expression of YAP1, Caspase3, Cleaved-caspase3, BAX, and Bcl-2 were significantly up-regulated, and the Bcl-2/BAX ratio decreased. Flow cytometry results showed that the apoptosis rate of HUVECs increased after interference. Low expression of LncRNA CRYM-AS1 may activate the Hippo-YAP1 signaling pathway to regulate apoptosis in HUVECs, leading to ED development, and the discovery of new target genes may provide new therapeutic targets to regulate diabetic erectile disfunction.

Prostate cancer (PCa) is the most common cancer and second leading cause of cancer death in American men. Most patients with metastatic disease respond initially to androgen deprivation therapy (ADT), but almost inevitably progress to castration resistant prostate cancer (CRPC). Identification of markers and drivers of mCRPC that (a) represent a progenitor-type cancer cell population (b) persist in castration resistant disease (c) are actionable targets expressed on the cell surface, and (d) are induced by hypoxia, is required to facilitate the development of novel targeted therapies. We identified prostatic acid phosphatase (PAP), particularly the transmembrane form (TMPAP), as one such potential target. PAP is both a phosphatase and a 5'ectonucleotidase that generates adenosine. We herein demonstrate that PAP is expressed early on during fetal development and persists in castration-resistant disease. The VCaP and VCaP-enzalutamide-resistant PCa cell lines express secretory (sPAP) and TMPAP. Androgens downregulate while hypoxia upregulates PAP expression. In vivo, PAP persists in hypoxic areas of castration-resistant tumors. Knockdown of PAP decreases VCaP migration and colony formation. Finally, treatment of VCaP tumor-bearing mice with inhibitors of adenosine receptors reduces tumor growth. This data demonstrates that TMPAP is a novel therapeutic target in advanced prostate cancer.

Though early antibiotic sulfonamides had poor urine solubility and resulted in urine crystalluria and urolithiasis, sulfamethoxazole urolithiasis is a rare phenomenon. In our case report, we describe a patient with N4-acetyl-sulfamethoxazole (metabolite of sulfamethoxazole) urolithiasis that developed after prolonged exposure to trimethoprim/sulfamethoxazole (TMP-SMX). Prior to stone formation, our patient had a total colectomy and end ileostomy created after an episode of toxic megacolon secondary Clostridium difficile. He also had benign prostatic hypertrophy and chronic urinary retention. These specific metabolic conditions, including dehydration leading to higher urinary concentration, urinary stasis, and low urinary pH may have predisposed our patient to this rare condition. Our patient's stones were then imaged under light microscopy and scanning electron microscopy (SEM). It was found to be comprised of rectangular shaped crystals. To our knowledge, this is the first time these stone crystals have been imaged with SEM.

Background: Urinary tract and male genital organ lymphoid neoplasms are uncommon, accounting for less than 5% of all primary extranodal lymphomas. There have only been a few small case series and isolated case reports describing the primary sites and subtypes of these neoplasms. The aim of the study is to investigate the pathological characteristics of patients diagnosed with primary Genitourinary (GU) lymphoma in at two major hospitals.

Material and methods: We obtained cases that were diagnosed with primary GU lymphomas between 2005 and 2020. Pathology and immunohistochemistry slides were retrieved and reviewed, additional immunohistochemical markers were done on selected cases.

Result: Herein we present a study of 11 patients. The mean age at diagnosis time was 46 years (range 24-71 years). Among urinary bladder, and ureter lymphomas, a slight female predominance was noted (3:2). Pathologic lymphoma subtype observed in our study were diffuse large B-cell lymphoma (DLBCL) (36%); mucosa-associated lymphoid tissue (MALT) lymphoma (18%); acute lymphoblastic lymphoma (B-LBL) (9%); high-grade B-cell lymphomas (27%) one of them with histomorphology of Burkitt-like large cell type, and a case of high-grade lymphoma, unclassifiable (9%). At the initial time of presentation, patients were commonly presented with non-specific signs and symptoms.

Conclusion: Even though this study reaffirms the prevalence of DLBCL in GU system, it also sheds light on the variable range of lymphomas that can arise in these sites. The variety of subtypes highlights the significance of thoroughly characterizing lymphoma classifications through ancillary studies such as immunohistochemistry and other molecular/cytogenetic tests if needed, as they are crucial for achieving an accurate pathology diagnosis.

Purpose: Targeted prostate biopsies are increasingly being performed by urologists in the United States including those in the Pennsylvania Urologic Regional Collaborative, a physician-led data-sharing and quality improvement collaborative. To evaluate the performance of MRI guided fusion needle prostate biopsies in the collaborative, we analyzed the variability by practice in rates of detection of clinically significant prostate cancer and patient characteristics associated with detection of clinically significant prostate cancer.

Methods: We analyzed 857 first-time MRI fusion biopsy procedures performed at five practices (minimum 20 procedures) between 2015 and 2019. We used chi-square analysis for baseline patient characteristics and Grade Group (GG) ≥ 3 tumor detection rates by practice. Multivariable logistic regression was used to estimate the odds of clinically significant cancer detection when adjusting for baseline patient characteristics.

Results: Approximately 15% of men undergoing targeted MRI guided biopsy were ≤ 59 years old. Median prostate specific antigen (PSA) was 6.8 ng/ml. Detection rates for GG ≥ 3 tumors ranged from 14.3% to 28.3% (P = 0.02) across practices. However, the odds of GG ≥ 3 tumor detection did not differ significantly between practices after adjusting for clinical and radiographic factors. Overall, increased likelihood of detecting a GG ≥ 3 tumor was associated with increased age, DRE abnormalities, higher PSA, smaller gland volume and PI-RADS ≥ 4 MRI lesions. There was an 81% concordance rate between PI-RADS ≥ 4 and Gleason grade ≥ 3 prostate cancer.

Conclusion: We demonstrate the value of obtaining pre-biopsy MRI given high concordance between presence of suspicious lesions and MRI-targeted biopsy detection of clinically significant prostate cancer. Variability of baseline patient characteristics among practices may account for the observed differences in clinically significant cancer detection rates. These findings can aid standardization and quality improvement efforts within the collaborative.

Prostate cancer is the second leading cause of cancer-related deaths among men worldwide. With heavy androgen deprivation therapies, prostate cancer may shift to androgen receptor negative and neuroendocrine negative subtype of castration resistant prostate cancer, defined as double-negative prostate cancer. Double-negative prostate cancer is associated with poor prognosis and disease mortality. The molecular mechanisms underlying the emergence of double-negative prostate cancer remain poorly understood. Here, we demonstrate that Ubiquitin C-Terminal Hydrolase L1 (UCH-L1), is negatively correlated with androgen receptor levels in prostate cancer patients. UCH-L1 plays a functional role in tumorigenesis and metastasis in double-negative prostate cancer. Knock-down of UCH-L1 decreases double-negative prostate cancer colony formation in vitro and tumor growth in vivo. Moreover, decrease of UCH-L1 significantly delays cell migration in vitro and spontaneous metastasis and metastatic colonization in vivo. Proteomic analysis revealed that mTORC1 signaling, androgen response signaling and MYC targets are the top three decreased pathways upon UCH-L1 decrease. Further, treatment with LDN-57444, a UCH-L1 small molecule inhibitor, impairs double-negative prostate cancer cell colony formation, migration in vitro, and metastatic colonization in vivo. Our study reveals that UCH-L1 is an important regulator of double-negative prostate cancer tumor growth and progression, providing a promising therapeutic target for this subtype of metastatic prostate cancer.

Prophylactic antibiotics are commonly used to prevent infections and complications during surgeries. In this study inflammatory responses and infectious complications after utilizing antibiotic-loaded irrigation compared with intravenous (IV) prophylactic antibiotics. Eighty-eight participants with ureteral stones enrolled in this prospective randomized controlled trial. Participants were allocated into two groups, namely "standard" with 45 participants, and "antibiotic-loaded" with 43 participants. The "standard" group received standard normal saline irrigation with 1 gram of IV ceftriaxone 30 minutes before in transurethral ureterolithotripsy (TUL), while the "antibiotic-loaded" group received ceftriaxone-added irrigation fluid and did not receive any IV antibiotics. The laboratory tests, including Complete Blood Count (CBC), Erythrocyte Sedimentation Rate (ESR), C-reactive protein (CRP), venous blood gas (VBG), IL-6, creatinine, sodium, potassium, SIRS score, and urine culture were recorded. The continuous variables are described using either mean (standard deviation (SD)) or median (interquartile range (IQR)) and the t-test and Mann-Whitney test are used to infer them. The discrete variables are reported as numbers (percentages) and the Chi-squared test is applied to them. Statistical analyses were performed by the SPSS software (V.26, IBM) with a considering significance criterion of 0.05. Statistically differences were not found in postoperative inflammatory and infectious complications among the two groups (P>0.05) including SIRS score (P=0.385), WBC (P=0.589), IL-6 (P=0.365), ESR (P=0.171), CRP (P=0.279), Platelet (P=0.501), positive urine culture (P=0.922), and post-operative fever (P=0.162). Administering antibiotic-loaded irrigation fluid was as safe and effective as IV ceftriaxone in TUL and could be a reasonable alternative for IV antibiotics.

This case study emphasizes the critical role of accurate diagnosis and tailored management strategies in successfully treating bladder injuries, particularly in complex cases. We present a patient with trigonal involvement and a Grade V injury that did not respond to conservative treatment, underscoring the need for precise surgical management. However, considering the patient's condition and the variability in surgical approaches, a less invasive intervention was chosen, leading to successful management using an external catheter to allow the bladder to heal without direct contact with urine. This innovative approach resulted in complete recovery without surgery, demonstrating the potential for positive outcomes even in complex cases. The study reiterates the importance of prompt recognition and appropriate management to prevent adverse outcomes associated with bladder trauma, underscoring the significance of close clinical monitoring and individualized treatment strategies for successful outcomes.

Background: Genetic factors are thought to play a major role in erectile dysfunction (ED), but the search for specific ED-related genes remains a mysterious area characterised by limited and inconclusive research.

Methods: Whole blood expression quantitative trait loci (eQTLs) and the GWAS data related to the genetics of ED are derived from a Finnish database, Finngen, which contains a dataset of 1154 cases and 94024 controls, culminating in a total of 95178 individuals under scrutiny. Based on these pooled data, a Mendelian randomisation (MR) analysis of ED was performed. Subsequent analyses of PPI and single cell type expression help identify potential pathogenic genes, revealing the function of genes and their association with phenotypes.

Results: After SMR analysis, 110 ED-associated genes were screened, of which MDM4 Degree had the highest value with an OR of 1.8453076, was displaced on chromosome 1, and had a risk of promoting ED. Single-cell sequencing analysis results demonstrate the expression of the MDM4 gene in six cell types, further confirming the role of the MDM4 gene in ED.

Conclusions: Our study showed that among the 110 genes associated with ED, MDM4 was highly associated with an increased risk of ED. These findings strongly support personalised treatment strategies decision-making for ED patients.

Emphysematous pyelonephritis (EPN) is a rare infectious disease affecting the renal and perirenal tissues, wherein gas formation occurs in the renal parenchyma, perinephric tissues, or collecting systems. It can be life threatening with mortality rates upto 60%. Here, we report a case series of EPN during the COVID pandemic with COVID test-positive patients who were diagnosed based on clinical signs, symptoms, and CT scans. One patient was conservatively managed, one underwent nephrectomy, and the others were treated with percutaneous drainage and pigtailing. Despite being critically ill, all the patients recovered uneventfully. Owning to the rarity of the lesion and variations in the clinical spectrum, the diagnosis of EPN is challenging. EPN requires early diagnosis and prompt management. The interventional technique depends on the clinical status of the patient and the severity of the lesion. Although the threshold of intervention is low in normal clinical practice, in covid patients, we tried to manage patients conservatively and intervened only when unavoidable.