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LncRNA growth arrest specific 5 (GAS5) has been confirmed to play an essential role in a number of biological processes, such as tumor regulation and gene transcription. GAS5 has been shown to be a tumor suppressor gene in many types of cancer, but its specific mechanism of action in bladder cancer (BC) remains to be elucidated. In this study, we explored the biological properties of GAS5 in BC and its mechanism of action in BC. We analyzed the expression of GAS5 in 50 pairs of BC tissues and found that GAS5 was low expressed in BC tissues compared with normal mucosal tissues. In vitro and in vivo experiments showed that GAS5 could affect the proliferation and migration of BC cells. Nucleoplasmic isolation assays and fluorescence in situ hybridization (FISH) assays demonstrated the localization of GAS5 in cell cytoplasm. Chromatin isolation by RNA purification (ChIRP), RNA immunoprecipitation (RIP) and luciferase assay demonstrated the target binding relationship of GAS5 with miR-18a-5p. Rescue experiments demonstrated that GAS5 promoted the proliferation and migration of BC cells through target binding of miR-18a-5p. Moreover, miR-18a-5p bound to its targets AXIN2 and GSK3β, which in turn affected the expression of Wnt/β-catenin pathway-related proteins. Our findings demonstrate that GAS5 regulates Wnt/β-catenin pathway activity by regulating the miR-18a-5p/AXIN2/GSK3β axis to modulate BC progression, providing a new potential therapeutic strategy for the treatment of BC.

Background Many studies have reported a possible strong relationship between poor sleep quality, sleep disruption, sleep disorders, and erectile dysfunction (ED). Aim This study aimed to investigate the relationship between sleep quality and ED. Methods Patients diagnosed with ED by the International Index of Erectile Function-5 (IIEF-5) questionnaire and 72 healthy adult men were included. Participants completed the questionnaire, underwent a detailed physical examination, and provided blood samples. All enrolled subjects then wore the Fitbit Charge 2 that monitored sleep throughout the night. Outcomes Primary outcome measures included scores on the IIEF-5, General Anxiety Disorder-7 (GAD-7) scale, Patient Health Questionnaire-9 (PHQ-9), Pittsburgh Sleep Quality Index (PSQI), and sleep monitoring parameters obtained from Fitbit Charge 2. Results Finally, a total of 107 ED patients and 72 healthy adult men were enrolled in this study. Univariate analysis indicated that the GAD-7 (P < .001), PHQ-9 (P < .001), and PSQI scores (P < .001) significantly differed according to the presence/absence of ED. Further multiple logistic regression analysis showed that the PHQ-9 (odds ratio [OR]: 1.227, 95% confidence interval [CI]: 1.070-1.407; P = .003) and PSQI scores (OR: 1.220, 95%CI: 1.116-1.334; P < .001) were independent risk factors for ED. Analysis of objective sleep monitoring parameters showed that total sleep time (TST) (P = .001), sleep onset latency (SOL) (P = .026), deep sleep (N3) duration (P = .011) and rapid eye movement (REM) sleep duration (P < .001) were significantly differed between the 2 groups, with durations in the ED group significantly lower than those in the non-ED group. In addition, receiver operating characteristic (ROC) curve analysis indicated that the REM sleep duration had the highest area under the curve (AUC: 0.728) of all sleep parameters, with a P value < .001, a sensitivity of 72.2% and a specificity of 73.8%. Clinical Implications Urologists and andrologists should be aware of impacted sleep quality and depression in ED patients. Strengths & Limitations The strength of this study is that the relationship between sleep quality and ED was assessed with both a subjective scale and an objective sleep monitoring tool. However, our study only described an association between sleep quality and ED and did not establish a causal relationship. Conclusion Sleep parameters are strongly associated with ED, indicating that poor sleep quality may increase the likelihood of ED.

C-reactive protein (CRP), as a marker of inflammation, may be closely related to erectile dysfunction (ED), however, there is no meta-analysis exists for it.We aimed to verify the relationship between CRP and erectile dysfunction and to explore the changes of CRP levels in ED patients after first-line treatment.We searched databases including the Cochrane Library, PubMed, and MEDLINE to identify studies up to January 1, 2022. We performed a comprehensive analysis of the included studies by STATA software and calculated standardized mean differences (SMDs) and their corresponding 95% confidence intervals.A total of 12 studies were included and the analysis showed that CRP levels were higher significantly in patients with erectile dysfunction than the healthy controls (p 0.001) and decreased by a mean of 0.38 mg/L after first-line PDE5i drug treatment (p = 0.001).This novel meta-analysis suggests that CRP is statistically significantly associated with erectile dysfunction and may be a predictor or risk factor for the assessment of ED. However, further original studies with large sample sizes are needed to validate this.

Background A connection between multiple sclerosis (MS) and erectile dysfunction (ED) has been debatable. Aim To assess the pooled prevalence of ED among men with MS and whether MS was a risk factor for ED. Methods A systematic review of the literature was conducted in PubMed, Scopus, Web of Science, and the Cochrane Library to find relevant English-language studies published up to February 2022 that assessed the prevalence of ED in MS patients. Two authors independently evaluated the full text of the enrolled studies to determine eligibility, and if there was disagreement, the decision was made by a third author after discussion. Assessment tools adapted for prevalence studies were used to evaluate the quality of cross-sectional studies, and the quality of case-control studies was assessed by Newcastle-Ottawa scale. The relative risk (RR) and its 95% confidence interval (CI) were used to assess the strength of association between MS and the risk of ED. The sources of heterogeneity were investigated by subgroup analysis. Sensitivity analysis was conducted to evaluate the stability of the results. Outcomes The pooled prevalence of ED in MS patients as well as 95% CIs were estimated, and the RR and its 95% CI were used to assess the strength of association between MS and the risk of ED. Results Sixteen studies included collectively gave information about ED in 2,760 MS men, resulting in a pooled prevalence of 49% (95% CI = 42–56%) for ED with a large heterogeneity. Synthesis of results revealed that MS was significantly associated with an increased risk of ED (RR = 3.17, 95% CI = 2.31–4.36, P < .001; heterogeneity: I2 = 0.0%, P = .716). The pooled prevalence estimates of ED were 55, 63, and 57% in the age >40, IIEF diagnostic tool, and mean disease duration >10 years subgroups, respectively. Clinical Implications The present meta-analysis indicates that MS patients had a significantly increased risk of ED, which should raise awareness of the potential association between MS and ED by clinicians. Strengths & Limitations This is the first meta-analysis to provide the global prevalence of ED in MS patients and to demonstrate that MS is a risk factor for ED. However, all enrolled studies were observational in design, which may reduce the robustness of this evidence. Conclusion Results of this meta-analysis showed that ED was highly prevalent in adult men with MS and MS was a potential risk factor for ED development.

Objective. To assess the correlation between the drug resistance of Klebsiella pneumoniae and antimicrobial drug usage. Methods. The drug resistance rate of Klebsiella pneumoniae and the antimicrobial drug dosage of inpatients admitted to The Second Affiliated Hospital of Wannan Medical College from January 2016 to December 2020 were retrospectively recorded, and their correlation was analyzed using the Pearson method. Results. There are 6493 strains of Gram-negative bacteria, including 1272 strains of Klebsiella pneumoniae, ranking first in respiratory medicine. Klebsiella pneumoniae showed an overall increasing trend in resistance to piperacillin/tazobactam and ampicillin/sulbactam and a high resistance to aztreonam, ceftazidime, and ciprofloxacin (all P < 0.05 ). The top 3 antimicrobial drugs used in 2016–2020 were β-lactams, quinolones, and macrolides. The rates of resistance to piperacillin/tazobactam, cefoperazone/sulbactam, and ampicillin/sulbactam were highly positively correlated with the use of β-lactams. The use of carbapenems and glycopeptides was negatively correlated with the resistance to ciprofloxacin, and the resistance to ceftazidime had a high positive correlation with the use of glycopeptides and carbapenems. Conclusion. The use of antimicrobial drugs is correlated with the resistance rate of Klebsiella pneumoniae. To reduce bacterial drug resistance, the rational use of antimicrobial drugs requires joint control through multiple departments to improve the clinical use of antimicrobial drugs and improve in-hospital control.

Platinum-based chemotherapy is a widely used strategy for bladder cancer (BCa) treatment. However, its clinical efficacy is affected by chemotherapy resistance via complex molecular mechanisms. Therefore, there is an urgent need to explore new targets for BCa therapy. Here, we showed that bromodomain-4 protein (BRD4) expression is upregulated in BCa tissues and cells. Inhibition of BRD4 attenuated the migration and invasion of BCa cells, which was rescued by the Sonic hedgehog (SHH) pathway activator recombinant human Sonic hedgehog peptide (rhSHH). We further found that cisplatin (DDP) suppressed the migration and invasion of BCa cells in vitro and inhibited tumor growth in vivo. However, overexpression of BRD4 weakened the pharmacological effects of DDP. In brief, our research revealed that BRD4 promotes migration and invasion by positively regulating the SHH pathway, drives DDP resistance in BCa, and is a novel therapeutic target for the treatment of BCa.

Sleep is a fundamental biological requirement, and lack of sleep has increasingly been recognized to cause metabolic consequences and adversely affect immune function. Recent articles have pointed to how sleep and sexual functions may be interlinked, involving inflammation, vascular alterations, tissue damage, and endothelial dysfunction.We examined the effect of paradoxical sleep deprivation on sexual behavior and hemogram parameters in male rats. In addition, we also explored whether 7 days of recovery sleep is sufficient to offset these detriments.Male rats were given sexual experience through training. At the fifth test, the sexually vigorous males were randomly separated into three experimental groups: paradoxical sleep deprivation (rats submitted to 96 h of paradoxical sleep deprivation, n = 6), recovery sleep (recovery sleep 7 days after paradoxical sleep deprivation, n = 6), and control (n = 10). We evaluated the sexual behaviors of three groups. Blood samples were collected to analyze hemogram parameters.In this study, we recognized that repeated copulatory tests can lead to changes in sexual behavior over time. We found that 96 h of acute sleep deprivation impaired the sexual behavior of male rats. Our results demonstrated that 96 h of paradoxical sleep deprivation also increased levels of white blood cell subpopulations, in particular neutrophils. Recovery sleep after sleep deprivation has a certain reversal effect on white blood cell subgroups and impairment of sexual behavior, with some signs that not all levels were back to baseline even after 7 days of recovery.In general, we found that 96 h of paradoxical sleep deprivation impaired the sexual behavior of male rats. Our results demonstrated that paradoxical sleep deprivation can cause systemic inflammation by affecting white blood cell subpopulations, in particular neutrophils. Seven days of recovery sleep after sleep deprivation has a certain reversal effect to these impairments.

Increasing evidence suggests that microRNAs (miRNAs) play critical roles in bladder tumorigenesis and development by combining with the 3' untranslated regions (3'-UTRs) of the corresponding mRNAs to negatively regulate gene expression. The role of miR-182-5p in bladder cancer (BC) remains unclear. Therefore, this study aimed to clarify the functional role of miR-182-5p in BC. We predicted candidate mRNAs for miR-182-5p via three databases (TarBase, ENCORI, and miRDB). Dual-luciferase reporter assays and target prediction confirmed FOXF2 as a potential target of miR-182-5p. Quantitative RT-PCR (qRT-PCR) showed that endogenous miR-182-5p expression was significantly upregulated in BC cell lines and clinical samples of BC patients. IHC, western blotting, and qRT-PCR assays indicated that FOXF2 expression was concurrently downregulated in BC tissues and BC cell lines. Gain- and loss-of-function studies showed that the overexpression of miR-182-5p enhanced the proliferation and migration of BC cells, while the downregulation of miR-182-5p showed the opposite results. The effects induced by miR-182-5p were attenuated with the restoration of FOXF2 expression. In BC cells, the upregulation of miR-182-5p not only decreased FOXF2 expression but also markedly increased Sonic hedgehog (SHH) pathway levels. These findings suggested that FOXF2 directly binds to miR-182-5p and that miR-182-5p acts as a tumor promoter in BC genesis and metastasis by targeting FOXF2. In addition, miR-182-5p plays a pro-cancer role by downregulating FOXF2 and activating the SHH pathway.

Background Studies have demonstrated that allicin may play critical roles in the procession of ischemia–reperfusion(I/R) injury. The purpose of this study was to investigate the protective effects of allicin on renal I/R injury by attenuating oxidative stress and apoptosis. Methods To establish a model of renal I/R, the right kidney underwent 12 h reperfusion after 45 min ischemia, allicin was administered intraperitoneally at concentrations of 40, 50 or 60 mg/kg. NRK-52E cells were treated with allicin at concentrations of 1, 3 or 5 μM in 24 h hypoxia/ 6 h reoxygenation(H/R) treatments. Indicators of HE, oxidative stress, apoptosis were measured to evaluate the effect of aliicin on renal I/R injury. Results Allicin protected renal I/R injury by ameliorating histological injury and decreasing the oxidative stress in renal tissues. Meanwhile, allicin significantly downregulated the expression of Bax and caspase-3, upregulated the expression of Bcl-2 in I/R renal tissues and H/R treated NRK-52E cells. Conclusions Allicin may exert anti-apoptotic and antioxidative effects to promote renal function recovery in I/R renal tissues and H/R treated NRK-52E cells. Taken together, allicin may be a potential novel therapy option for future renal injury protection.

This study aimed to assess the relationship between 25(OH) levels and erectile dysfunction (ED), particularly arteriogenic ED (A-ED). From September 2020 to January 2022, 150 patients diagnosed with ED by the International Index of Erectile Function-5 (IIEF-5) questionnaire were included. All patients were classified as organic ED and psychological ED by nocturnal penile tumescence and rigidity (NPTR) examination. Organic ED patients were divided into A-ED and NA-ED by penile doppler ultrasound (PDU) examination. Finally, 150 patients complaining of ED were enrolled in our study. 25(OH)D levels were significantly lower in patients with organic ED (18.24 ± 6.04 ng/ml) than in patients with psychogenic ED (20.90 ± 8.79 ng/ml) (p = 0.032). In A-ED and NA-ED, the mean of peak systolic flow velocity (PSV) values was 18.94 ± 5.28 cm/s and 51.57 ± 15.42 cm/s (p 0.001), and the mean of 25(OH)D was 15.66 ± 5.86 ng/ml and 20.48 ± 5.90 ng/ml, respectively (p 0.001). The results showed that 25(OH)D levels were positively correlated with IIEF-5 scores and the PSV values in A-ED patients. The 25(OH)D cut-off value differentiating between A-ED and NA-ED was 15.05 ng/ml. Low 25(OH)D levels may be an independent risk factor for ED, especially A-ED. ED patients should routinely undergo serum 25(OH)D level measurement, and 25(OH)D replacement therapy is necessary for patients with low vitamin D levels.

This study aims to investigate the role of nocturnal penile tumescence and rigidity (NPTR) and laboratory features in patients with mild, moderate and severe ED and then explored the correlation between ED severity with certain blood count parameters such as WBC and NLR. A total of 86 ED patients (age 29.8 ± 7.09 years) were enrolled. Classification of ED severity according to IIEF-5 scores was as follows: mild ED, 43.02% (37/86); moderate ED, 27.91% (24/86) and severe ED, 29.07% (25/86). Patients with moderate and severe ED had declined IIEF-5 scores and increased GAD-7 and PHQ-9 scores compared with mild ED. The mean NLR value of the mild, moderate and severe ED groups was 1.43 ± 0.39, 1.74 ± 0.45 and 2.0 ± 0.58, respectively. Stratification analysis according to NPTR results indicated that there was a significant difference in WBC and NLR between the two groups. Patients with abnormal NPTR had increased WBC and NLR levels compared with the normal groups. Multivariate logistic regression analysis suggested that severe ED (OR [95% CI]: 5.736 [1.248-26.354]), WBC (OR [95% CI]: 1.676 [1.094-2.567]) and NLR (OR [95% CI]: 5.595 [1.478-21.178]) were identified as independent risk factors for severe ED (abnormal NPTR results). In conclusion, this study indicates a significant difference in NLR, PLR, PDW, MPV and HDL between the mild, moderate and severe ED groups. The WBC and NLR are significantly increased in patients with severe ED (abnormal NPTR results) and it can be available as a quick, easy and cheap investigation compared with the RigiScan to evaluate the severity of ED with good sensitivity and specificity, which is important for the diagnosis and evaluation of ED.

The aim of the present study was to test the hypothesis that recovery sleep could counteract the detrimental effects of sleep deprivation (SD) on male rats' fertility.Twenty-two rats were housed in groups of six per cage with unrestricted access to food and water in a room. The modified multiple platform method was used to induce SD in rats over a 96-hour period. We examined the effect of SD on semen quality, reproductive hormones, and testicular histology in adult male rats. Then, we investigated the effect of 7 days recovery sleep on impaired reproductive function induced by SD.After the acclimation period, 22 rats were randomly separated into three experimental groups (SD, recovery sleep, and the control groups). Ninety-six hours of SD resulted in a significant decrease in sperm motility (24.33±10.93In conclusion, 96 hours of SD deteriorated the parameters of sperm motility and the number of morphologically normal sperm in rats, probably due to the decrease in serum testosterone levels and the disruption of testicular tissue structure when compared to the control group. After 7 days of recovery sleep, semen parameter, especially sperm motility and testosterone levels did not return to baseline levels compared to the control group.

Several hematologic parameters have been shown to be strongly associated with cardiovascular disease, yet few studies were conducted to assess their relationship with atherogenic erectile dysfunction.To find out the differences in hematological parameters between patients with atherogenic erectile dysfunction and healthy controls through as comprehensive a hematological examination as possible and try to assess and predict atherogenic erectile dysfunction using possible indicators.We collected hematological parameters in detail from 105 healthy controls and 183 patients with erectile dysfunction (119 patients with atherogenic erectile dysfunction patients and 64 patients with venous erectile dysfunction) who were selected by nocturnal penile tumescence and rigidity and color duplex doppler ultrasound.Statistically significant differences were found between the atherogenic erectile dysfunction and venous erectile dysfunction groups in platelet to lymphocyte ratio, neutrophil to lymphocyte ratio, and mean platelet volume (all p lt; 0.01). When comparing atherogenic erectile dysfunction with the healthy population, we found statistically significant differences between the two groups in white blood cell, neutrophil to lymphocyte ratio, platelet to lymphocyte ratio, mean platelet volume, triglycerides, high-density lipoprotein cholesterol, and non-high-density lipoprotein cholesterol (neutrophil to lymphocyte ratio, platelet to lymphocyte ratio, mean platelet volume, triglycerides, and high-density lipoprotein cholesterol, p lt; 0.01; white blood cell, p = 0.024; non-high-density lipoprotein cholesterol, p = 0.036). Receiver operator characteristic curve analysis showed that neutrophil to lymphocyte ratio and platelet to lymphocyte ratio had the highest diagnostic value (neutrophil to lymphocyte ratio: area under the curve = 0.810, p lt; 0.001, cut-off = 1.995; platelet to lymphocyte ratio: area under the curve = 0.782, p lt; 0.001, cut-off = 126.3).Several hematological parameters (white blood cell, platelet to lymphocyte ratio, neutrophil to lymphocyte ratio, mean platelet volume, triglycerides, high-density lipoprotein cholesterol, and non-high-density lipoprotein cholesterol) can be considered markers of atherogenic erectile dysfunction, while these parameters were not significantly different in venous erectile dysfunction compared to healthy subjects. This suggests that hematological examinations may be a convenient and effective method to help evaluate and diagnose atherogenic erectile dysfunction.

Numerous studies conducted to study the role of testosterone in erectile dysfunction (ED) extensively, but less is known of the association between estradiol level and ED. To assess the strong association between estradiol and ED by quantitatively synthesizing all studies evaluating the relationship between estradiol and ED. An extensive literature search was conducted by two authors independently in three electronic databases, including PubMed, Web of Science and Cochrane Library, up to January 10, 2021. The Patient Population or Problem, Intervention, Comparison, Outcomes and Setting (PICOS) were used for inclusion criteria to identify studies. The Newcastle-Ottawa Scale was applied to assess the quality of studies. The standardized mean difference (SMD) and their corresponding 95% confidence intervals (95% CIs) were used to compare the estradiol level between ED patients and healthy subjects, and the pooled OR and 95%CI were used to evaluate the strong association between estradiol level and ED. Finally, six studies were included in this meta-analysis, satisfying predefined inclusion criteria. Five studies were considered to be high quality, and only one was judged of moderate quality. The estradiol level of ED patients was statistically higher than that in healthy subjects (SMD 0.45, 95%CI 0.28-0.63, p0.0001). The pooled OR demonstrated that the estradiol was correlated to the ED significantly (OR 1.08, 95%CI 1.05-1.12, p0.0001). Subgroup analyses were conducted based on age, diagnosis way, country, sample size, detection method and estradiol level. There was no substantial change in the result of SMD ranging from 0.41 (95% CI 0.31-0.51) to 0.53 (95% CI 0.44-0.62) when performing sensitivity analysis. No publication bias was detected by the Begg test or Egger test. This meta-analysis demonstrated that the estradiol level is correlated to ED significantly.

Bladder cancer (BCa) is one of the most common cancers in men and is a major threat to the lives and health of older men. Many studies have shown that miR-7, as an important tumor suppressor gene, could directly inhibit some pathways involved in the development of cancer. MiR-7-5p, which was assessed in this study, consists of one arm of miR-7 and acts as a cancer suppressor gene in multiple cancer types. Autophagy, as a common biological process, plays dual roles in the process of cancer. Chemotherapy resistance is a problem in the treatment of BCa. In this study, the data showed that miR-7-5p was obviously down-regulated in BCa tissues and cells compared to their respective controls. In addition, miR-7-5p mimic effectively inhibited migration, invasion and autophagy both in vitro and in vivo. In the mechanistic study, miR-7-5p targeted autophagy-related gene ATG7 to inhibit its expression, which in turn inhibited autophagy. Finally, the migration of BCa cells was inhibited, and chemosensitivity was improved. Overall, our results provide evidence of the role of miR-7-5p as a cancer suppressor gene in BCa and provide new opportunities for the treatment of BCa.

Background Erectile dysfunction (ED) may be common in patients with inflammatory bowel disease (IBD), but its prevalence and risk factors still remain debatable. Aim To evaluate the prevalence of ED in the IBD population and the potential role of risk factors in the development of ED. Methods An extensive search in the PubMed, Cochrane Library, and Web of Science was performed to identify relevant English-language articles published up to December 2021 that evaluated the prevalence of ED on IBD patients. The included studies were evaluated by 2 independent reviewers for eligibility. We used an adapted Assessment Tool for Prevalence Studies to evaluate the quality of enrolled studies. Data were analyzed and graphed using the STATA software (version 16.0; Stata Corporation, College Station, TX, USA). The ORs with 95% CIs were pooled using a fixed or random-effects model according to heterogeneity. Subgroup analysis was performed to explore the source of heterogeneity. Sensitivity analysis was conducted to evaluate the stability of the results. Outcomes The pooled prevalence of ED in IBD patients was calculated, and the OR value and 95% CIs were used to assess the strength of the association between IBD-related risk factors and ED. Results Fourteen studies included 32,858 individuals totally were enrolled for this meta-analysis. The overall pooled prevalence estimate of ED in IBD patients was 27% (95% CI: 20–34%). Operation (OR 1.28; 95% CI: 1.17–1.39; P < .00001; I2 = 0.0%), disease activity (OR 2.06; 95% CI: 1.07–3.05; P < .00001), and depression (crude OR 3.31; 95% CI: 1.08–5.54; P = .004; I2 = 0.0%) significantly increase the risk of ED in people with IBD. The association of depression and ED was further confirmed by calculating the pooled estimates of adjusted OR (1.58; 95% CI: 0.05–3.12; P < .05; I2 = 0.0%). The pooled prevalence estimates of ED were 30, 33, and 17% in the age Clinical Implications IBD patients had a significantly increased prevalence of ED, indicating that erectile function in men with IBD should be concerned by clinicians. Strengths & Limitations The strength of this study is that this is the first meta-analysis to assess the global prevalence and risk factors of ED in IBD patients. A limitation is that the results after pooling the included articles showed significant heterogeneity. Conclusion The results of our meta-analysis and systematic review provide evidence of the high prevalence and risk factors of ED in IBD patients.

Background. The spondin-2 (SPON2) gene is overexpressed in multiple malignant tumors and may promote tumor aggressiveness. However, its expression profile and functional roles in clear cell renal cell carcinoma (ccRCC) are still unclear. Methods. SPON2 expression in ccRCC was evaluated using expression data from TCGA and GEO databases, then confirmed by local patient population (94 patients). The clinical significance of SPON2 expression was evaluated. Downregulation of SPON2 was performed using small-interfering RNA (siRNA). The effects of SPON2 silencing on cell proliferation, apoptosis, invasion, and migration in vitro were investigated. Results. SPON2 was overexpressed in the majority of the ccRCC at both mRNA and protein levels. SPON2 expression was significantly correlated with stage, grade, and recurrence (all P<0.05) in patients with localized ccRCC. The receiver operating characteristic (ROC) curve showed that SPON2 expression could serve as a predictor of recurrence. SPON2 expression was significantly associated with recurrence-free survival (RFS) in patients with localized ccRCC. Knocking down SPON2 resulted in suppressed cell invasion and migration in vitro. Conclusion. SPON2 expression might function as a prognostic biomarker in patients with localized ccRCC.

Treatment of advanced kidney renal clear cell carcinoma (KIRC) remains challenging in clinic. The functional role and prognostic significance of MFN2 in KIRC are still unclear.In this study, we first performed a bioinformatic analysis to determine the expression level and prognostic value of MFN2 in KIRC using The Cancer Genome Atlas (TCGA) dataset, and then validated the MFN2 mRNA expression in our cohort of clinical tissue samples and cell lines of KIRC via RT-qPCR. Cox regression model was used to identify the independent prognostic factors. A nomogram was constructed to predict the prognosis of KIRC patients. Gene set enrichment analysis (GSEA) was performed to predict the involved functional pathways of MFN2 co-expressed genes. The association between MFN2 expression level and immune cell infiltration was assessed using the TIMER and the TIDISB databases. In addition, cell proliferation and migration abilities of two KIRC cell lines with MFN2 overexpression were evaluated by MTS and wound healing assays, respectively.Downregulation of MFN2 was observed in KIRC tissues and cell lines compared to the normal controls. Kaplan-Meier curve analysis indicated an inferior survival outcomes in KIRC patients with lower MFN2 expression, uncovering the tumor-suppressive role of MFN2 in KIRC. Cox regression results showed that higher MFN2 expression was one of the independent protective factors in KIRC. Besides, function predictive analysis revealed that MFN2 co-expressed genes were enriched in the biological processes of energy metabolism and autophagy. Moreover, MFN2 expression was observed to be significantly associated with immune cell infiltration and a variety of markers of tumor infiltrating immune cells (TIICs) including multiple immune checkpoints in KIRC tissues. Finally, MFN2 overexpression significantly inhibited cell proliferation and migration abilities of two KIRC cell lines examined.Generally, our data suggested that MFN2 may serve as a potential prognostic biomarker and therapeutic target in KIRC.

e17040 Background: Abiraterone acetate is approved for the treatment of metastatic castration-resistant prostate cancer (mCRPC). However, the originator abiraterone acetate (ZYTIGA) is observed to be with relatively low bioavailability and high pharmacokinetic variability. Abiraterone Acetate Tablets (I), in which Sodium N-[8-(2-hydroxy-benzoyl) amino] caprylate (SNAC) was added in the formulation as an absorption enhancer, was therefore developed by using nanocrystal technology to enhance the dissolution rate of pharmaceutical compounds, leading to the improvement of the low oral bioavailability and significant food effects. Methods: Patients with mCRPC were randomized (1:1) to receive either Abiraterone Acetate Tablets (I) 300 mg daily plus 5 mg prednisone orally twice daily, or ZYTIGA 1000 mg once daily plus 5 mg prednisone orally twice daily for 84 days. The primary endpoint was serum testosterone concentration (Day 9/10). Secondary endpoints included serum prostate-specific antigen (PSA), pharmacokinetics and adverse events. Results: 68 patients with a median age of 71 (52-84 yrs) (n = 34 in each group) were enrolled in the full analysis set (FAS). The least square geometric mean of Day 9/10 serum testosterone concentration (rounded-up by 1 ng/dl) in Abiraterone Acetate Tablets (I) and ZYTIGA groups was 1.053 (95% CI, 1.006-1.102) and 1.000 (95% CI, 0.956-1.046), respectively. The geometric mean ratio between two groups was 1.053 (90% CI, 0.998-1.110) and the 90% CI fell within 80.0% to 125.0% equivalence limits. The PSA-50 response rate was also similar on Days 28, 56 and 84 (46.9% vs 50.0%, 65.6% vs 57.6%, 71.9% vs 67.7%). Compared with ZYTIGAlabel, no new safety concerns were observed in Abiraterone Acetate Tablets (I). In addition, Abiraterone Acetate Tablets (I) group was observed to be with lower frequency of treatment-emergent adverse events (TEAEs) of any grade (76.5% vs 85.7%), grade ≥3 TEAEs (8.8% vs 22.9%), and grade ≥3 treatment-related adverse events (TRAEs) (5.9% vs 14.3%). Conclusions: Therapeutic equivalence between Abiraterone Acetate Tablets (I) 300 mg and ZYTIGA 1000 mg was confirmed by Day 9/10 serum testosterone concentration in mCRPC patients. Abiraterone Acetate Tablets (I) also showed a trend of improvement in safety profile. Clinical trial information: NCT04862091.

Abnormal RNA methylation and dysregulation of miRNA are frequently occurred in bladder cancer. Melittin is a potential drug candidate for intravesical chemotherapy against bladder cancer. However, the underlying epigenetic mechanism by which melittin-induced anti-tumor effect remains unclear. Here, we showed that melittin selectively induced apoptosis of bladder cancer cells in a METTL3-dependent manner. Ectopic expression of METTL3 significantly blocked melittin-induced apoptosis in vitro and in vivo. MicroRNA-sequence analysis identified miR-146a-5p suppression contributed to the melittin-induced selective antitumor effect. Further investigation revealed that METTL3-guided m6A modification methylated pri-miR-146 at the flanking sequence, which was responsible for the pri-miR-146 maturation. Moreover, NUMB/NOTCH2 axis was identified as a downstream target signal that mediated the pro-survival role of miR-146a-5p in bladder cancer cells. Importantly, METTL3 and miR-146a-5p were positively correlated with recurrence and poor prognosis of patients with bladder cancer. Our study indicates that METTL3 acts as a fate determinant that controls the sensitivity of bladder cancer cells to melittin treatment. Moreover, METTL3/miR-146a-5p/NUMB/NOTCH2 axis plays an oncogenic role in bladder cancer pathogenesis and could be a potential therapeutic target for recurrent bladder cancer treatment.

Background: To evaluate the efficacy of flexible ureteroscopic lithotripsy (FURSL) based on the concept of enhanced recovery after surgery (ERAS).Methods: 435 patients with upper urinary calculi between 2017-2020 were retrospectively analysed and assigned to ERAS group (ERAS management) and control group (traditional management). Operative time, postoperative ambulation time, postoperative hospital stay, total cost of hospitalization, postoperative complications and stone removal were compared. Results: 427 cases were successfully performed FURSL procedure with 4 cases of ERAS group (n = 216) and 4 cases of control group (n = 219) failed respectively. No postoperative complications occurred in either group except for fever and hematuria. There were no significant difference in postoperative fever and stone removal between the two groups (all p > 0.05). The patients in ERAS group had shorter operative time, shorter postoperative ambulation time, less postoperative severe hematuria, shorter postoperative hospital stay and lower total cost of hospitalization than those in control group (all p < 0.05).Conclusions: FURSL based on the concept of ERAS for the treatment of upper urinary tract calculi is safe and reliable, with rapid postoperative recovery, low cost of hospitalization and worthy of clinical promotion.

Li Cheng,1,* Hao Wang,2,* Zicheng Wang,3 Houbao Huang,1 Dong Zhuo,1 Jian Lin4 1Department of Urology, The First Affiliated Hospital, Yijishan Hospital of Wannan Medical College, Wuhu, Anhui Province, People’s Republic of China; 2Department of Geriatrics, Peking University First Hospital, Beijing, People’s Republic of China; 3Department of Urology, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui Province, People’s Republic of China; 4Department of Urology, Peking University First Hospital, Beijing, People’s Republic of China*These authors contributed equally to this workCorrespondence: Li Cheng Email chenglibjmu@163.comIntroduction: Bladder cancer is a lethal human malignancy. Currently, treatment for bladder cancer is limited. The anti-tumor effects of leflunomide have attracted much more concern in multiple human cancers.Materials and Methods: This study evaluated the anti-tumor effects of leflunomide on cell viability, colony formation, apoptosis, and cell cycle in two human bladder carcinoma cell lines, 5637 and T24. Meanwhile, the underlying mechanism including PI3K/Akt signaling pathway and autophagy modulation was also identified.Results: Leflunomide markedly inhibited the growth of both bladder cancer cell lines and induced apoptosis and cell cycle arrest in S phase. The phosphorylation levels of Akt and P70S6K in both cell lines were significantly down-regulated with leflunomide treatment. Furthermore, the deceased formation of autophagosomes and the accumulation of LC3II and P62 suggested the blockade of autophagy by leflunomide. Modulation of autophagy with rapamycin and chloroquine markedly attenuated and enhanced the cytostatic effects of leflunomide, respectively.Conclusion: Leflunomide significantly reduced the cell viability of bladder cancer cells via inducing apoptosis and cell cycle arrest and suppressing the PI3K/Akt signaling pathway. In addition, the blockade of autophagy was observed, and autophagy inhibition enhanced leflunomide-mediating anti-tumor effects. Our data presented here offer novel ideas for comprehensive therapeutic regimes on bladder cancer.Keywords: leflunomide, autophagy, PI3K/Akt pathway, anti-tumor, bladder cancer

Introduction. CD146 is a membrane signal receptor in tumor-induced angiogenesis. However, limited studies have focused on the CD146 promoter polymorphisms in clear cell renal cell carcinoma (ccRCC). Purpose. The purpose of this study was to investigate the association between polymorphisms located in the promoter region of the CD146 gene and characteristics of ccRCC in Chinese population. The association between the CD146 promoter polymorphisms and CD146 expression was also investigated in ccRCC. Materials and Methods. A total of 600 samples including 300 ccRCC patients and 300 healthy controls were collected for analysis of the CD146 promoter polymorphisms by direct sequence. The CD146 expressions were measured by qRT-PCR. Results. We had not found any significant differences in genotypic and allelic frequencies of CD146 promoter polymorphisms between ccRCC patients and controls. The rs3923594 was associated with stage and metastasis (300 cases) and recurrence (263 cases) of ccRCC in Chinese population. A significant association was also observed between the rs3923594 and CD146 expression (227 cases) in ccRCC. Conclusions. CD146 promoter polymorphisms were not associated with the risk of ccRCC in Chinese population. The rs3923594 was an independent predictor of recurrence in Chinese patients with localized ccRCC.

Background Let-7 is one of the earliest discovered microRNAs(miRNAs) and has been reported to be down-regulated in multiple malignant tumors. The effects and molecular mechanisms of let-7i in bladder cancer are still unclear. This study was to investigate the effects and potential mechanisms of let-7i on bladder cancer cells. Methods Total RNA was extracted from bladder cancer cell lines. The expression levels of let-7i and HMGA1 were examined by quantitative real-time PCR. Cell viability was detected using the CCK-8 and colony formation assays, while transwell and wound healing assays were used to evaluate migration ability. Luciferase reporter assay and western blot were used to confirm the target gene of let-7i. Results Compared with the SV-40 immortalized human uroepithelial cell line (SV-HUC-1), bladder cancer cell lines T24 and 5637 had low levels of let-7i expression, but high levels of high mobility group protein A1 (HMGA1) expression. Transfection of cell lines T24 and 5637 with let-7i mimic suppressed cell proliferation and migration. Luciferase reporter assay confirmed HMGA1 may be one of the target genes of let-7i-5p. Protein and mRNA expression of HMGA1 was significantly downregulated in let-7i mimic transfected cell lines T24 and 5637. Conclusions Up-regulation of let-7i suppressed proliferation and migration of the human bladder cancer cell lines T24 and 5637 by targeting HMGA1. These findings suggest that let-7i might be considered as a novel therapeutic target for bladder cancer.

BACKGROUND This study aimed to evaluate the risk factors associated with the development of urolithiasis in a population in Southern China. MATERIAL AND METHODS A questionnaire-based study was conducted between March 2017 to April 2018 that included 1,519 patients in Southern China and included questions on patient demographics, diet, and lifestyle. Patients were divided into the urolithiasis group who had urinary calculi and the control group. RESULTS There were 829 patients (54.6%) in the urolithiasis group and 690 patients (45.4%) in the control group. Using a chi-squared (χ²) test, 13 variables were found to be significantly associated with urolithiasis, including age, physical activity, and dietary factors that included high sodium, protein, fat, lean meat, vegetables, pickled food, fluid intake, drinking habits and tea consumption, and frequency and duration of physical exercise. Multivariate logistic regression analysis showed that dietary factors, including vegetables (OR, 0.856; 95% CI, 0.769-0.948), pickled foods (OR, 1.271; 95% CI, 1.030-1.357), and animal protein intake (OR, 1.138; 95% CI, 1.031-1.258), drinking strong tea (OR, 0.793; 95% CI, 0.702-0.897), fluid intake (OR, 0.758; 95% CI, 0.644-0.816), and duration of physical exercise (OR, 0.840; 95% CI, 0.808-0.973) were significantly associated with the occurrence of urolithiasis and were independent risk factors. CONCLUSIONS High consumptions of pickled foods and animal protein were the main risk factors for the development of urolithiasis in a population of southern China, but high fluid intake with a preference for strong tea, a diet of vegetables, and physical exercise were protective factors.

Gang Feng,1,2 Hui-Min Ma,1 Hou-Bao Huang,3 Ya-Wei Li,3 Peng Zhang,1 Jian-Jun Huang,1 Long Cheng,1,2 Guo-Rong Li4 1Clinical Laboratory, The First Affiliated Hospital of Wannan Medical College, Wuhu 241001, Anhui, China; 2Anhui Province Key Laboratory of Active Biological Macro-molecules Research, Wannan Medical College, Wuhu 241002, Anhui, China; 3Department of Urology, The First Affiliated Hospital of Wannan Medical College, Wuhu 241001, Anhui, China; 4Department of Urology, North Hospital, CHU of Saint-Etienne, Saint-Etienne 42055, France Background and aims: COL5A1 has been identified to be involved in metastasis of clear cell renal cell carcinoma (ccRCC) by bioinformatic analysis. This study aimed to investigate COL5A1 expression and its clinical significance in ccRCC. The function of COL5A1 in ccRCC was further investigated. Methods: COL5A1 expression was examined in 256 ccRCC tissues and paired adjacent normal renal tissues by immunohistochemistry and real-time quantitative PCR. The clinical significance of COL5A1 expression was evaluated. Downregulation of COL5A1 was achieved using siRNA. The effects of COL5A1 silencing on cell proliferation, apoptosis, migration, invasion in vitro, and tumor growth in vivo were investigated. Results: COL5A1 expression was upregulated in the majority of the ccRCC tissues at both protein and mRNA levels. COL5A1 expression was significantly correlated with tumor diameter, tumor stage, tumor grade, distant metastasis, recurrence, necrosis, and sarcomatoid (all P

Bufalin has been demonstrated to possess a wide range of pharmacological effects. Among these is its antitumour effect, which has been confirmed in multiple organs or tissues and provoked many concerns. However, its cytostatic effect and underlying mechanism in bladder cancer has not thoroughly been elucidated. This study aimed to investigate the hypothesis that Bufalin induces cell apoptosis and inhibits cell growth in bladder cancer through the inactivation of Na+/K+-ATPase (NKA). In the current study, it was demonstrated that Bufalin remarkably inhibited cell viability and induced cell apoptosis in bladder cancer cell line T24. Subsequently, we found that the expression of NKA was significantly supressed in Bufalin-treated cells and the NKA-α3 isoform was most sensitive to Bufalin among all α subunits of NKA. By transfection with NKA-α3 overexpressing plasmids, the expression of the NKA-α3 subunit was upregulated and NKA-α3 overexpression was found to markedly attenuated Bufalin-induced cell apoptosis in T24 cells, suggesting NKA-α3 played a critical role in Bufalin-induced cell apoptosis. Taken together, the present study confirmed that Bufalin promotes tumour apoptosis and inhibits tumour growth in bladder cancer in vitro, and this antitumour effect may be ascribed to the inactivation of NKA.

PURPOSE: The objective of this study is to determine whether or not plasma cfDNA levels can predict efficacy of sorafenib in patient with metastatic cRCC.MATERIALS AND METHODS: Plasma cfDNA levels were quantified by quantitative real-time PCR at six different time-points (before treatment, 4 weeks, 8 weeks, 12 weeks, 16 weeks, and 24 weeks) in 18 metastatic cRCC patients receiving sorafenib, as assessed by CT examination according to RECIST 1.1.RESULTS: A significantly lower plasma cfDNA level, measured from 8 weeks to 24 weeks, was found in patients with remission or stable disease than in those with progression. Higher levels in plasma cfDNA levels during the course of treatment indicated poor outcome. For predicting progression, a sensitivity of 66.7% was achieved at 100% specificity using cfDNA levels at 8 weeks.CONCLUSIONS: Monitoring of plasma cfDNA levels during the course of sorafenib therapy could identify metastatic cRCC patients who are likely to exhibit a poor response at an early stage.

To investigate whether CD146 gene expression could provide useful information to predict early recurrence after nephrectomy. This study included 84 patients with clear cell renal cell carcinoma (cRCC), and 44 subjects without tumor were used as controls. Quantitative RT-PCR was used to measure the CD146 gene expression. The mean value of CD146 expression in patients with metastatic cRCC (0.0438 ± 0.0024) was significantly higher than in those with localized cRCC (0.0374 ± 0.0012, P = 0.018) or in controls (0.0344 ± 0.0010, P = 0.001). Of patients with localized cRCC, those with recurrence had a significantly higher CD146 expression than those without recurrence (P = 0.029). The univariate analysis showed that CD146 was associated with early recurrence. The recurrence-free survival curve indicated that patients with a high CD146 expression had a significantly higher recurrence rate than those with a low CD146 expression (P = 0.018). CD146 gene expression can be useful for predicting early recurrence and stratifying the patients into risk groups for possible adjuvant treatment.

Objectives To investigate whether CD133 messenger ribonucleic acid (mRNA) could provide useful information to identify metastasis or predict recurrence in patients with clear cell renal cell carcinoma (cRCC). Methods and materials This study included 86 patients with cRCC and 30 healthy controls. Real-time reverse transcriptase-polymerase chain reaction was used to quantify CD133 mRNA in peripheral blood mononuclear cells before nephrectomy. Results The average CD133 mRNA in patients with metastatic cRCC (1.546±0.291) was significantly higher than that in those with localized cRCC (1.034±0.316, P = 0.022) or in controls (0.042±0.028, P = 0.001). Metastasis could be identified with a sensitivity of 82.6% at specificity of 69.8% by CD133 mRNA. Among patients with localized cRCC, there was a significant difference in CD133 mRNA between the patients with recurrence (1.136±0.127) and without recurrence (1.010±0.091, P = 0.047). Recurrence could be identified with a sensitivity of 75.0% at specificity of 61.8%. Patients with a higher CD133 mRNA had a significantly higher recurrence rate than those with a low CD133 mRNA ( P = 0.019). Conclusions CD133 mRNA can be useful for identifying metastasis, predicting recurrence, and stratifying the patients into different risk groups for possible adjuvant treatment.

PURPOSE: The objective of this study is to determine whether or not plasma cfDNA levels can predict efficacy of sorafenib in patient with metastatic cRCC. MATERIALS AND METHODS: Plasma cfDNA levels were quantified by quantitative real-time PCR at six different time-points (before treatment, 4 weeks, 8 weeks, 12 weeks, 16 weeks, and 24 weeks) in 18 metastatic cRCC patients receiving sorafenib, as assessed by CT examination according to RECIST 1.1. RESULTS: A significantly lower plasma cfDNA level, measured from 8 weeks to 24 weeks, was found in patients with remission or stable disease than in those with progression. Higher levels in plasma cfDNA levels during the course of treatment indicated poor outcome. For predicting progression, a sensitivity of 66.7% was achieved at 100% specificity using cfDNA levels at 8 weeks. CONCLUSIONS: Monitoring of plasma cfDNA levels during the course of sorafenib therapy could identify metastatic cRCC patients who are likely to exhibit a poor response at an early stage.