Risk factors for erectile dysfunction in diabetes mellitus: a systematic review and meta-analysis.

Background: Previous studies have established that diabetes mellitus (DM) markedly raises the risk of developing erectile dysfunction (ED). Despite extensive investigations, the risk factors associated with ED in diabetic men have yet to be unequivocally determined, owing to incongruent and inconclusive results reported in various studies. Objective: The objective of this systematic review and meta-analysis was to assess the risk factors for ED in men with DM. Methods: A comprehensive systematic review was conducted, encompassing studies published in the PubMed, Scopus and Embase databases up to August 24th, 2023. All studies examining the risk factors of ED in patients with DM were included in the analysis. To identify significant variations among the risk factors, odds ratios (ORs) and their corresponding 95% confidence intervals (CIs) were employed. The risk of bias was evaluated using the Newcastle-Ottawa Scale(NOS) for longitudinal studies and the Agency for Healthcare Research and Quality Scale(AHRQ) for cross-sectional studies. Results: A total of 58 studies, including a substantial participant pool of 66,925 individuals diagnosed with DM, both with or without ED, were included in the meta-analysis. Mean age (OR: 1.31, 95% CI=1.24-1.37), smoking status (OR: 1.32, 95% CI=1.18-1.47), HbA1C (OR: 1.44, 95% CI=1.28-1.62), duration of DM (OR: 1.39, 95% CI=1.29-1.50), diabetic neuropathy (OR: 3.47, 95% CI=2.16-5.56), diabetic retinopathy (OR: 3.01, 95% CI=2.02-4.48), diabetic foot (OR: 3.96, 95% CI=2.87-5.47), cardiovascular disease (OR: 1.92, 95% CI=1.71-2.16), hypertension (OR: 1.74, 95% CI=1.52-2.00), microvascular disease (OR: 2.14, 95% CI=1.61-2.85), vascular disease (OR: 2.75, 95% CI=2.35-3.21), nephropathy (OR: 2.67, 95% CI=2.06-3.46), depression (OR: 1.82, 95% CI=1.04-3.20), metabolic syndrome (OR: 2.22, 95% CI=1.98-2.49), and diuretic treatment (OR: 2.42, 95% CI=1.38-4.22) were associated with increased risk factors of ED in men with DM. Conclusion: Our study indicates that in men with DM, several risk factors for ED have been identified, including mean age, HbA1C, duration of DM, diabetic neuropathy, diabetic retinopathy, diabetic foot, cardiovascular disease, hypertension, microvascular disease, vascular disease, nephropathy, depression, metabolic syndrome, and diuretic treatment. By clarifying the connection between these risk factors and ED, clinicians and scientific experts can intervene and address these risk factors, ultimately reducing the occurrence of ED and improving patient management.

Causal associations between prostate diseases, renal diseases, renal function, and erectile dysfunction risk: a 2-sample Mendelian randomization study.

Background: Previous observational studies have found a potential link between prostate disease, particularly prostate cancer (PCa), and kidney disease, specifically chronic renal disease (CKD), in relation to erectile dysfunction (ED), yet the causal relationship between these factors remains uncertain. Aim: The study sought to explore the potential causal association between prostate diseases, renal diseases, renal function, and risk of ED. Methods: In this study, 5 analytical approaches were employed to explore the causal relationships between various prostate diseases (PCa and benign prostatic hyperplasia), renal diseases (CKD, immunoglobulin A nephropathy, membranous nephropathy, nephrotic syndrome, and kidney ureter calculi), as well as 8 renal function parameters, with regard to ED. All data pertaining to exposure and outcome factors were acquired from publicly accessible genome-wide association studies. The methods used encompassed inverse variance weighting, MR-Egger, weighted median, simple mode, and weighted mode residual sum and outlier techniques. The MR-Egger intercept test was utilized to assess pleiotropy, while Cochran's Q statistic was employed to measure heterogeneity. Outcomes: We employed inverse variance weighting MR as the primary statistical method to assess the causal relationship between exposure factors and ED. Results: Genetically predicted PCa demonstrated a causal association with an elevated risk of ED (odds ratio, 1.125; 95% confidence interval, 1.066-1.186; P < .0001). However, no compelling evidence was found to support associations between genetically determined benign prostatic hyperplasia, CKD, immunoglobulin A nephropathy, membranous nephropathy, nephrotic syndrome, kidney ureter calculi, and the renal function parameters investigated, and the risk of ED. Clinical Implications: The risk of ED is considerably amplified in patients diagnosed with PCa, thereby highlighting the importance of addressing ED as a significant concern for clinicians treating individuals with PCa. Strengths and Limitations: This study's strength lies in validating the PCa-ED association using genetic analysis, while its limitation is the heterogeneity in study results. Conclusion: The results of this study suggest a potential link between PCa and a higher risk of ED.

Novel heterotopic continental ileal reservoir based on the Mitrofanoff principle: a case report and review of the literature.

For patients undergoing radical cystectomy with standard lymphadenectomy for bladder cancer, appropriate urinary diversion (with a pouch and conduit) improves postoperative quality of life, reduces postoperative complications, and prolongs survival. We developed a novel heterotopic ileal reservoir to achieve these goals. This report describes the methodology involved and the incidence of intraoperative and postoperative complications. Three patients who underwent novel heterotopic ileal reservoir creation following radical cystectomy and standard lymphadenectomy (for bladder cancer) were evaluated. The ileum served as a pouch in which the ureters and appendix were implanted by extramural tunnelling. The appendix served as a conduit and pelvic reperitonealization was performed. Operative times, intraoperative blood loss, time to intestinal function recovery, incidence of intestinal obstruction and ureteric reflux, and bladder volumes and continence levels were evaluated. The surgical intervention was successful with operation times ranging 410-525 min, blood loss ranging 300-700 ml, and recovery time for intestinal function ranging 3-5 days. The postoperative hospitalization time was 11-15 days. Subileus occurred in patient B, who recovered after fasting and fluid replacement. Patients B and C achieved complete continence 6 weeks after surgery, while patient A experienced umbilical urine leakage with catheterization time intervals that exceeded 4 h. At 3 months after surgery, the bladder capacities of all patients ranged 250-370 ml. Follow-up cystography suggested the presence of bilateral ureteral reflux in patient A, with mild and moderate reflux on the left right sides, respectively. All patients achieved complete continence. Patients were followed for 3-9 months postoperatively; chest and abdominal computed tomography and cystography showed absence of hydronephrosis, recurrence, or distant metastasis during this period. The novel heterotopic continent ileal reservoir described in this study may be suitable for selected patients. The surgical procedure is safe when performed by well-trained and highly experienced urologists.

FTO-stabilized miR-139-5p targets ZNF217 to suppress prostate cancer cell malignancies by inactivating the PI3K/Akt/mTOR signal pathway.

As one of the most important demethylases for RNA N6-methyladenosine (m6A) modifications, fat mass and obesity-associated protein (FTO) plays anti-cancer role during prostate cancer (PC), but it is still unclear the detailed molecular mechanisms. Here, this study verified that FTO inactivated the tumor-accelerating PI3K/Akt/mTOR pathway to hamper PC development through regulating the downstream miR-139-5p/zinc finger protein 217 (ZNF217) axis. Through performing clinical analysis, it was revealed that FTO was apparently ablated in the cancerous tissues compared to the normal tissues collected from PC patients, and patients with high-expressed FTO predicted a favorable prognosis. Functional experiments confirmed that overexpression of FTO suppressed cell proliferation, mitosis, epithelial-mesenchymal transition (EMT), tumorigenesis and lung metastasis both in vitro and in vivo. The following mechanical experiments verified that FTO stabilized miR-139-5p to increase its expression levels in a m6A-dependent manner, and elevated miR-139-5p induced degradation of ZNF217 through binding to ZNF217 mRNA, resulting in the inactivation of the PI3K/Akt/mTOR signal pathway. Finally, our rescuing experiments confirmed that overexpressed FTO-induced tumor-suppressing effects on PC cells were abrogated by miR-139-5p ablation and ZNF217 overexpression. Collectively, this study firstly validated that FTO exerted its anti-tumor effects in PC through regulating the miR-139-5p/ZNF217 axis in a m6A-dependent manner, providing novel biomarkers for the advancement of anti-cancer agents for PC treatment.

The association between sexual dysfunction and prostate cancer: a systematic review and meta-analysis.

BACKGROUND: Whether there is a connection between sexual dysfunction (SD) and prostate cancer (PCa) is controversial. AIM: We sought to review the interrelationship between SD and PCa and to determine whether there is a definitive risk of men developing PCa after suffering from SD. METHODS: A complete search of the PubMed, Web of Science, Ovid MEDLINE, Embase, and Cochrane Library databases was performed to search for eligible studies published up to October 2022. The protocol for this meta-analysis is available from PROSPERO (ID: CRD42022342381). OUTCOMES: The associations between SD and the risk of PCa were assessed by calculating pooled ORs with 95% CIs, and the standard mean difference (SMD) and its 95% CI were used to assess the relationship between SD and prostate-specific antigen (PSA) levels or prostate volume (PV). Random-effects models were used to account for potential heterogeneity, and the Newcastle-Ottawa Scale (NOS) was used to evaluate the quality of the included studies. RESULTS: Twenty studies involving 215,626 individuals were included in our meta-analysis. Compared with controls, subjects with SD had a 1.62-fold increased risk of PCa (OR = 1.62, 95% CI, 1.77-2.23, P = .003; heterogeneity: I2 = 97.8%, P < .001). Patients with SD had higher PSA levels than controls (SMD =0.07, 95% CI, 0.00 to 0.13, P = .041; heterogeneity: I2 = 55.6%, P = .027). However, there was no association between SD and PV (SMD = 0.03, 95% CI, -0.05 to 0.11, P = .122; heterogeneity: I2 = 48.5%, P = .100). CLINICAL IMPLICATIONS: Current evidence confirms a potential link between SD and the risk of PCa and that SD in PCa patients should be of concern to clinicians. STRENGTHS AND LIMITATIONS: The strength of this study is that it is to our knowledge the first meta-analysis of studies on the risk of PCa in men with SD. A limitation is that most of the studies included in this meta-analysis focused on ED. CONCLUSION: Our systematic review and meta-analysis results suggest that men with SD have a higher risk of PCa and higher PSA levels than men without SD. However, this is merely inferential, and causality cannot be determined based on the current data. Further longitudinal studies should be performed to validate our preliminary findings.

Circular RNA UBAP2 promotes the proliferation of prostate cancer cells via the miR-1244/MAP3K2 axis.

Prostate cancer (PCa) is a common male malignant disease with a high incidence, which can seriously affect the quality of life of patients. The survival rate of patients with PCa has improved to 98.6%; however, new insights for the molecular mechanism are still urgently required. Circular RNA (circ)UBAP2 is a tumor-associated circRNA that has been demonstrated to promote the progression of various types of cancer. CircUBAP2 has been demonstrated to be significantly upregulated in PCa, but its role in the progression of PCa remains unclear. The present study aimed to provide an improved understanding of the regulatory mechanism of circUBAP2 in PCa. circUBAP2 expression was identified to be upregulated in four PCa cell lines and clinical tissues by using reverse transcription-quantitative PCR analysis. Binding sites analysis and luciferase reporter gene assay indicated that the microRNA(miR)-1244/MAP3K2 axis was the target of circUBAP2. Gain-of-function assays revealed that circUBAP2 promoted the proliferation of PCa cells by sponging miR-1244 and promoting the MAP3K2 axis. The present findings may be essential for providing new strategies in the diagnosis and targeted therapy of PCa.

Up-regulation of DRAM2 promotes tolerance of bladder transitional cell carcinoma to gemcitabine.

INTRODUCTION: Bladder transitional cell carcinoma (BTCC) is one of the most prevalent human malignant diseases. Gemcitabine is commonly applied in the treatment of BTCC while acquired gemcitabine resistance has caused a severe impediment to recovery. This study aimed to investigate the function of DRAM2 in regulating gemcitabine resistance of BTCC. MATERIAL AND METHODS: GSE77883 was introduced to screen out the differentially expressed autophagy-related genes in T24 cells and gemcitabine-resistant T24-GEM cells. After establishing T24-GEM cells ourselves, aberrant expression of DRAM2 was detected by qRT-PCR and Western blot. After stably manipulating the expression of DRAM2 in T24 and T24-GEM cells, the changes of cell biological functions under gemcitabine treatment were compared, including cell viability, apoptosis and autophagy, using colony formation, flow cytometry and electron microscopy respectively. RESULTS: DRAM2 was up-regulated in gemcitabine-resistant T24-GEM cells. Silencing of DRAM2 in T24-GEM cells inhibited the cell autophagy induced by treatment with gemcitabine and contributed to attenuated gemcitabine resistance. Also, overexpression of DRAM2 in T24 cells enhanced the autophagy, strengthened the chemoresistance and decreased the cell apoptosis rate under the treatment with gemcitabine. CONCLUSIONS: Our data suggested that downregulation of DRAM2 rescued the sensitivity of T24-GEM cells to gemcitabine, providing an appropriate therapeutic target for BTCC treatment.

Functional analysis of serum microRNAs miR-21 and miR-106a in renal cell carcinoma.

OBJECTIVE: microRNAs (miRNAs) plays an important role in tumor development and progression and act as oncogenes or tumor suppressor genes in the carcinogenesis process. miRNA is stable in serum, and recent studies have demonstrated the feasibility of using circulating miRNA as biomarkers in cancer patients. However, currently, no serum biomarkers for the early diagnosis and prognosis of renal cell carcinoma (RCC) have been reported. Therefore, a new molecular marker for early diagnosis and evaluation of recurrence after surgery is required. Our purpose was to identify miRNA signatures that could distinguish the serum of RCC patients from matched healthy controls and validate identified miRNAs as potential biomarkers for RCC. METHOD: Serum samples from 30 RCC patients were collected before and 1 month after surgery. 30 cancer-free blood donor volunteers with no history of any cancer were recruited from the same institute. miR-21 and miR-106a expression levels were determined by real-time PCR. RESULT: The serum miR-21 level was significantly higher in RCC patients (median, 8.34) than in healthy control individuals (median, 0.70; p= 0.001). A month after surgery, serum miR-21 levels (median, 0.69) were significantly reduced (p= 0.032). The serum miR-106a level was higher in RCC patients (median, 8.99) compared with controls (median, 0.96; p= 0.000), while miR-106a levels (median, 1.01) were reduced a month after surgery (p= 0.028). The expression level of miR-21 and miR-106 a in RCC patients increased significantly, while miR-21 and miR-106a decreased after surgery. This outcome suggests that serum miR-21 and miR-106a expression level was closely related with kidney cancer tissue. CONCLUSION: We conclude that serum miR-21 and miR106a are expected to be molecular markers for RCC.

Impact of smoking status and cumulative smoking exposure on tumor recurrence of non-muscle-invasive bladder cancer.

OBJECTIVE: To investigate the effect of smoking status, cumulative smoking exposure and smoking cessation on the outcomes of patient with non-muscle-invasive bladder cancer (NMIBC). METHODS: We collected smoking data from 484 patients with NMIBC who were treated with transurethral resection (TUR); smoking status was categorized as (never smokers vs current smokers vs former smokers). Cumulative smoking exposure was categorized as high smoking exposure (cigarette index ≥400) versus low smoking exposure (cigarette index <400). Association with outcomes was examined by multivariable analyses after adjusting for the effects of standard clinicopathologic factors, and the Kaplan-Meier method was used to estimate the effect of smoking status and cumulative smoking exposure on RFS. RESULTS: A total of 168 (34.7 %) patients were never smoker, 121 (25 %) patients were current smokers, and 195 (40.3 %) patients were former smokers. The median follow-up was 25 months. By multivariate analysis, pathological grade (p = 0.013), history of recurrence (p < 0.001), number of tumors (p < 0.001) and size of tumors (p = 0.013) were significantly associated with tumor recurrence; nevertheless, smoking status did not influence tumor recurrence (p = 0.063). Among current and former smokers, cumulative smoking exposure was significantly associated with tumor recurrence (p < 0.001), compared to current smokers, patients with smoking cessation ≥10 years had a lower risk of tumor recurrence [hazard ratio (HR) 0.456, p = 0.007]. CONCLUSIONS: Smoking affects the prognosis of patient with NMIBC, which is still controversial; however, among ever smokers, a high cumulative exposure smoking can significantly increase the risk of tumor recurrence. Quitting smoking might be associated with a lower recurrence rate for patients with NMIBC.

Culture and Identification of Mouse Bone Marrow-Derived Dendritic Cells and Their Capability to Induce T Lymphocyte Proliferation.

BACKGROUND: The aim of this study was to establish a culture method for mouse dendritic cells (DCs) in vitro and observe their morphology at different growth stages and their ability to induce the proliferation of T lymphocytes. MATERIAL/METHODS: Granulocyte-macrophage colony stimulating factor (GM-CSF) and interleukin-4 (IL-4) were used in combination to induce differentiation of mouse bone marrow (BM) mononucleocytes into DCs. The derived DCs were then assessed for morphology, phenotype, and function. RESULTS: The mouse BM-derived mononucleocytes had altered cell morphology 3 days after induction by GM-CSF and IL-4 and grew into colonies. Typical dendrites appeared 8 days after induction. Many mature DCs were generated, with typical dendritic morphology observed under scanning electron microscopy. Expression levels of CD11c, a specific marker of BM-derived DCs, and of co-stimulatory molecules such as CD40, CD80, CD86, and MHC-II were elevated in the mature DCs. Furthermore, the mature DCs displayed a strong potency in stimulating the proliferation of syngenic or allogenic T lymphocytes. CONCLUSIONS: Mouse BM-derived mononucleocytes cultured in vitro can produce a large number of DCs, as well as immature DCs, in high purity. The described in vitro culture method lays a foundation for further investigations of anti-tumor vaccines.

Differential expression and clinical significance of serum protein among patients with clear-cell renal cell carcinoma.

BACKGROUND AND OBJECTIVE: Looking for tumor markers by using protein chip technology is one of the hot topics, but many studies are still limited on short term detection of differential expressed proteins before and after surgery among patients with RCC. This study analyzed differential expressed serum protein and its clinical significance with clear-cell renal cell carcinoma to further measurement of the rule of variable expressing. METHODS: Eighty-nine patients with clear-cell renal cell carcinoma who underwent surgery from November 2013 to 2014 and postoperatively confirmed by pathology were entered in RCC group, 100 healthy volunteers and patients without RCC who underwent medical examination in the same period were entered in control group. The serum protein were analyzed in both group before surgery and every regular follow-up period in 1 year after surgery with RCC group. The surface-enhanced laser desorption ionization time of flight mass spectrometry (SELDI-TOF-MS) and weak cation exchange protein chip (CM10) technology systems were used for identifying differential expressed serum protein in RCC group and controls. The linear support vector machine (SVM) was applied to establish the diagnostic model of protein fingerprints and the leave-one-out cross validation was used for determining model discriminating effect. The differential expressed proteins were analyzed by ZUCI-PDAS protein spectral data analysis system. RESULTS: Five kinds of proteins were identified as potential biomarker, ultimately. The M/Z of these proteins was 15953, 7987, 9304, 8948, 5911, respectively. There were significant difference on expression level of these proteins with two groups preoperatively (P< 0.05). Comparison of all postoperative expression levels to preoperative one and each differential level mutually between a year in postoperative period also revealed statistical significance (P< 0.05). With taking identified proteins as biomarker, the sensitivity and specificity in predicting clear-cell renal cell carcinoma was 88.8% (79/89) and 91.0% (91/100), respectively. CONCLUSION: The corresponding specific protein was Bcl-2 family apoptosis regulatory proteins, WAP four-disulfide core protein, Krueppel-like factor 8, monocyte chemotactic protein-1, serum amyloid ß -protein-4, respectively, and will may serve as tumor markers of kidney cancer. These proteins manifests high predictive value for clear-cell renal cell carcinoma, and may contribute to therapeutic evaluation, prognosis and targeted therapy for clear-cell renal cell carcinoma.

Diagnosis and surgical treatment of renal hydatid disease: a retrospective analysis of 30 cases.

Echinococcosis (CE) is an infection which is caused by the larval stage of a tapeworm and is endemic in stockbreeding regions of developing countries. The kidney is the most commonly affected organ in the urinary tract. However, reports on renal hydatid disease are limited in the literature, and usually there are no specific clinical characteristics and promising operative methods. The purpose of this study is to assess the most appropriate surgical technique for the patient with urinary tract CE. We retrospectively analyzed thirty patients with renal hydatid cysts who received different surgical treatments in the urology department of the First Affiliated Hospital of Xinjiang Medical University from February 1985 to April 2010. Twenty patients were males and ten were females. The diagnostic accuracy was 74%, 87.5%, and 66.6% respectively by using of ultrasound, CT, and laboratory tests. Thirty patients were followed up for 1-15 years after surgery. One patient experienced a recurrence of renal CE. The ultrasound, CT, and immunological tests are an important means of diagnosis. The surgical treatment principle of renal hydatid should be based on residual renal function, hydatid cyst size, number, location, and surgical techniques to determine the surgical plan to retain the renal function.

Expression of chemokine receptor 4 was associated with poor survival in renal cell carcinoma.

Chemokines and their receptors are known to play important roles in tumor growth and metastasis of many malignancies. Recently, CC chemokine receptor 4 (CCR4) has been described as a prognostic marker in various tumors. However, the possible role of CCR4 in clear cell renal cell carcinoma (ccRCC) has not been well elucidated. In this study, we detected the expression of CCR4 in 53 ccRCC by immunohistochemistry and correlated it with clinicopathological parameters and prognosis. Immunohistochemistry was used to determine the expression of CCR4 in 53 ccRCC and 11 renal contusion tissue specimens. CCR4 expression between carcinoma and normal renal tissues was evaluated by χ(2) test. Correlation between CCR4 and clinicopathological data was tested by χ(2) test. Univariate survival analysis was performed by the Kaplan-Meier method, and differences among the groups were analyzed by the log-rank test. CCR4 expression in ccRCC tissue was significantly higher compared with normal renal tissue samples (χ(2) = 4.392, P = 0.036). CCR4 was correlated with the clinicopathological features including tumor stage (P = 0.009), lymph node metastasis (P = 0.003) and distant metastasis (P = 0.031). Further, CCR4 was the only dependent affecting factor in lymph node metastasis (P = 0.014). Univariate analysis showed that tumor stage, lymph node metastasis, distant metastasis and CCR4 were influential factors for poor prognosis in ccRCC patients; multivariate analysis revealed that CCR4 (P = 0.007) was the only independent risk factor for prognosis. In addition, Kaplan-Meier curve for overall survival (OS) indicated that prognosis was unfavorable for patients who had high CCR4 expression level (P = 0.010). CCR4 was correlated with tumor aggressive behavior in ccRCC. It might be involved in lymph node metastasis and have influence on patients' OS. Further research is needed to determine the potential of CCR4.