The functions and mechanisms of RNA modification in prostate: Current status and future perspectives.

The increasing incidence and mortality of prostate cancer worldwide significantly impact the life span of male patients, emphasizing the urgency of understanding its pathogenic mechanism and associated molecular changes that regulate tumor progression for effective prevention and treatment. RNA modification, an important post-transcriptional regulatory process, profoundly influences tumor cell growth and metabolism, shaping cell fate. Over 170 RNA modification methods are known, with prominent research focusing on N6-methyladenosine, N7-methylguanosine, N1-methyladenosine, 5-methylcytidine, pseudouridine, and N4-acetylcytidine modifications. These alterations intricately regulate coding and non-coding RNA post-transcriptionally, affecting the stability of RNA and protein expression levels. This article delves into the latest advancements and challenges associated with various RNA modifications in prostate cancer tumor cells, tumor microenvironment, and core signaling molecule androgen receptors. It aims to provide new research targets and avenues for molecular diagnosis, treatment strategies, and improvement of the prognosis in prostate cancer.

Isolation of endophytes from Dioscorea nipponica Makino for stimulating diosgenin production and plant growth.

KEY MESSAGE: Both bacterial and fungal endophytes exhibited one or more plant growth-promoting (PGP) traits. Among these strains, the Paenibacillus peoriae SYbr421 strain demonstrated the greatest activity in the direct biotransformation of tuber powder from D. nipponica into diosgenin. Endophytes play crucial roles in shaping active metabolites within plants, significantly influencing both the quality and yield of host plants. Dioscorea nipponica Makino accumulates abundant steroidal saponins, which can be hydrolyzed to produce diosgenin. However, our understanding of the associated endophytes and their contributions to plant growth and diosgenin production is limited. The present study aimed to assess the PGP ability and potential of diosgenin biotransformation by endophytes isolates associated with D. nipponica for the efficient improvement of plant growth and development of a clean and effective approach for producing the valuable drug diosgenin. Eighteen bacterial endophytes were classified into six genera through sequencing and phylogenetic analysis of the 16S rDNA gene. Similarly, 12 fungal endophytes were categorized into 5 genera based on sequencing and phylogenetic analysis of the ITS rDNA gene. Pure culture experiments revealed that 30 isolated endophytic strains exhibited one or more PGP traits, such as nitrogen fixation, phosphate solubilization, siderophore synthesis, and IAA production. One strain of endophytic bacteria, P. peoriae SYbr421, effectively directly biotransformed the saponin components in D. nipponica. Moreover, a high yield of diosgenin (3.50%) was obtained at an inoculum size of 4% after 6 days of fermentation. Thus, SYbr421 could be used for a cleaner and more eco-friendly diosgenin production process. In addition, based on the assessment of growth-promoting isolates and seed germination results, the strains SYbr421, SYfr1321, and SYfl221 were selected for greenhouse experiments. The results revealed that the inoculation of these promising isolates significantly increased the plant height and fresh weight of the leaves and roots compared to the control plants. These findings underscore the importance of preparing PGP bioinoculants from selected isolates as an additional option for sustainable diosgenin production.

Effect of tumor CD276 expression on infiltrating immune cells and clinicopathological features of prostate cancer.

BACKGROUND: Advanced prostate cancer (PCa) is often resistant to immunotherapy. In this study, we examined the role of CD276 in mediating immunotherapeutic effects through changes in immune cell infiltration. METHODS: Using transcriptomic and proteomic analyses, CD276 was identified as a potential target for immunotherapy. Subsequent in vivo and in vitro experiments confirmed its role as a potential mediator of immunotherapeutic effects. RESULTS: Multi-omic analysis suggested that CD276 was identified as a key molecule regulating the immune microenvironment (IM). In vivo experiments revealed that CD276 knockdown was found to enhance CD8+ T cell infiltration into the IM. Immunohistochemical analysis of PCa samples further confirmed the same findings. CONCLUSION: CD276 was found to inhibit the enrichment of CD8+ T cells in PCa. Thus, CD276 inhibitors may be potential targets for immunotherapy.

Erratum: Depletion of CDC5L inhibits bladder cancer tumorigenesis: Erratum.

[This corrects the article DOI: 10.7150/jca.32850.].

Combination of preoperative plasma fibrinogen and neutrophil-to-lymphocyte ratio to predict the prognosis for patients undergoing laparoscopic nephrectomy for renal cell carcinoma.

This study was conducted to investigate the prognostic significance of a combination of fibrinogen and neutrophil-to-lymphocyte ratio (NLR) named the F-NLR score as a novel indicator and further create nomograms for predicting the prognosis of patients with renal cell carcinoma (RCC) treated with laparoscopic nephrectomy. A total of 425 patients with RCC who underwent laparoscopic nephrectomy were included in this study. Then, we divided the patients based on the cut-off values of their F-NLR score into three categories: F-NLR 2 (both high fibrinogen and NLR), F-NLR 0 (both low fibrinogen and NLR), and F-NLR 1 (remaining patients). Cox regression analysis was performed to investigate the predictive performance of the F-NLR score on overall survival (OS) and cancer-specific survival (CSS). Predictive nomograms of F-NLR were established and internally validated. Time-dependent receiver operating characteristic (ROC) curve analysis was performed to assess the predictive accuracy of the nomogram, NLR, and fibrinogen as prognostic markers. The F-NLR 0, 1, and 2 groups included 226 (53.2%), 147 (34.6%), and 52 (12.2%) patients, respectively. Cox regression analysis showed that a high F-NLR score was significantly associated with poor prognosis and acted as an independent prognostic factor for OS and CSS (all P < 0.05). Predictive nomograms with F-NLR for OS (C-index: 0.773) and CSS (C-index: 0.838) were well developed. Time-dependent ROC results showed that nomograms containing F-NLR had better predictive performance than NLR and fibrinogen. F-NLR score was a novel effective prognostic biomarker for patients with RCC undergoing laparoscopic nephrectomy.

Efficacy of Transcutaneous Electrical Nerve Stimulation in the Management of Neurogenic Overactive Bladder: A Randomized Controlled Trial.

OBJECTIVE: The aim of the study was to investigate the therapeutic effect of transcutaneous electrical nerve stimulation on neurogenic overactive bladder that is refractory to pharmacotherapy. METHODS: This randomized trial recruited 83 participants with neurogenic overactive bladder that were nonresponsive to 3-mo first-line anticholinergic drug treatment. Participants were randomized into treatment and control groups. Transcutaneous electrical nerve stimulation current consisting of biphasic square wave with pulse durations of 150 µs and pulse frequency set at 20 Hz were applied to for 30 mins once a day for 90 days. Stimulation was provided over the lateral aspect of the sacrum bilaterally of the electrodes. Patients in the transcutaneous electrical nerve stimulation group stopped taking the anticholinergic drugs. The control group continued to receive anticholinergic drugs for 90 days. The participants' Overactive Bladder Symptom Score, the Medical Outcomes Study 36-Item Short-Form Health Survey scores, urodynamic values, and voiding diary data were assessed before and after the therapy. RESULTS: The transcutaneous electrical nerve stimulation treatment group had significantly decreased Overactive Bladder Symptom scores compared with the control group (P < 0.001); in addition, half of the Medical Outcomes Study 36-Item Short-Form Health Survey scores were significantly improved in the transcutaneous electrical nerve stimulation group (P < 0.05). The patients treated with transcutaneous electrical nerve stimulation improved significantly voiding diary parameters at P < 0.05. Similarly, urodynamic values at P < 0.05 favored the experimental group over the control group. CONCLUSIONS: Applying daily transcutaneous electrical nerve stimulation over the sacral region for 90 days to patient with neurogenic overactive bladder improved overactive bladder symptoms of patients whose response to anticholinergic drugs is far inferior. TO CLAIM CME CREDITS: Complete the self-assessment activity and evaluation online at http://www.physiatry.org/JournalCME. CME OBJECTIVES: Upon completion of this article, the reader should be able to: (1) Determine the therapeutic effect of transcutaneous electrical nerve stimulation (TENS) on neurogenic overactive bladder (NOAB); (2) Demonstrate the effectiveness of reflex suppression of the bladder using the TENS applied over the sacral region as a stimulation location; and (3) Confirm the TENS method using biphasic square waves with pulse durations of 150 µs and pulse frequencies of 20 Hz as applied is shown to be superior to anticholinergic drugs in managing NOAB. LEVEL: Advanced. ACCREDITATION: The Association of Academic Physiatrists is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians.The Association of Academic Physiatrists designates this journal-based CME activity for a maximum of 1.0 AMA PRA Category 1 Credit(s)™. Physicians should only claim credit commensurate with the extent of their participation in the activity.

The development and assessment of a predicting nomogram for the recovery of immediate urinary continence following laparoscopic radical prostatectomy.

Purpose: This study aimed to develop a nomogram to predict the recovery of immediate urinary continence in laparoscopic radical prostatectomy (LRP) patients. Methods: A prediction model was developed based on a dataset of 154 LRP patients. Immediate urinary continence was defined as free from using pads within 7 days after the removal of the urinary catheter. The least absolute shrinkage and selection operator regression (LASSO) model was applied to screen the features. Multivariate logistic regression analysis was used to establish prediction model integrating the features selected from the LASSO regression analysis. Receiver operating curve (ROC), calibration and decision curve analysis (DCA) were used to assess the model's discrimination, calibration and clinical utility. Results: The identified features of the prediction model included age, body mass index (BMI) and three pelvic anatomic parameters measured by MRI: membranous urethral length (MUL), intravesical prostatic protrusion length (IPPL) and puborectalis muscle width (PMW). The nomogram showed good discrimination with an are under the curve(AUC) of 0.914 (95% CI, 0.865-0.959, p < 0.001). Moreover, good calibration was showed in the model. Lastly, DCA showed that the nomogram was clinically useful. Conclusion: The developed novel nomogram that can predict the possibility for post-prostatectomy patients to recover immediate urinary continence could be used as a counseling tool to explain urinary incontinence to patients after LRP.

Development of nomograms related to inflammatory biomarkers to estimate the prognosis of bladder cancer after radical cystectomy.

BACKGROUND: Bladder cancer is one of the most common carcinomas and it brings about huge social economic burden. There is not a reliable way to predict the prognosis of bladder patients. We develop the nomogram to predict the prognosis of bladder cancer patients. METHODS: A total of 127 bladder cancer patients after radical cystectomy were studied retrospectively. Their clinicopathological data were collected for statistical analysis. RESULTS: The level of albumin/globulin ratio (AGR), C-reactive protein/albumin ratio (CAR), neutrophil to lymphocyte ratio (NLR) and platelet to lymphocyte ratio (PLR) associated with pathological and hematological parameters like T stage and hemoglobin. Furthermore, the AGR was associated with overall survival (OS) and CAR, NLR, and PLR were associated with both OS and progression-free survival (PFS) (P<0.05). The multivariate analysis revealed that tobacco smoking, tumor T stage, M stage, NLR, CAR, and AGR were all independent predictors for OS of patients and tobacco smoking, tumor T stage, NLR, CAR, and AGR were independent predictors for PFS of patients. In addition, AGR, CAR, and NLR, as well as, the clinicopathological parameters in the development of nomograms with a C index of 0.901 (95% CI: 0.505-1.269) for OS, and 0.807 (95% CI: 0.755-0.858) for PFS. The nomograms were able to provide a prognosis of the OS with the area under the curve (AUC) =0.86. Further, tests assessed the PFS with the AUC =0.84. CONCLUSIONS: This study demonstrates that the nomograms of the inflammatory biomarkers were able to predict prognosis of bladder cancer patients after radical cystectomy.

Extreme body mass index is associated with poor survival outcomes after radical cystectomy: a retrospective cohort study in a Chinese population.

BACKGROUND: Body mass index (BMI) has been evidenced to be a significant prognostic factor in multiple cancers. This retrospective study aimed to investigate the association between BMI and survival outcomes after radical cystectomy (RC) in patients with bladder cancer (BCa). METHODS: Clinical and pathological parameters of patients who were diagnosed with BCa and received RC between 2010 and 2018 were collected. The associations between BMI at surgery and clinicopathological features were examined. The prognostic value of BCa for overall survival (OS) and cancer-specific survival (CSS) was examined using the Kaplan-Meier method and Cox regression models. RESULTS: Among the 217 patients enrolled in this study, 13 (6.0%), 121 (55.8%), 60 (27.6%), and 23 (10.6%) had a BMI value of <18.5 kg/m2 (underweight), 18.5-23.9 kg/m2 (normal), 24-27.9 kg/m2 (overweight), and ≥28 kg/m2 (obese), respectively. Underweight and obese patients tended to have poorer survival after RC than normal and overweight patients (P<0.05). Multivariable Cox regression revealed that extreme BMI was an independent predictor of both OS (BMI <18.5 vs. 18.5-27.9 kg/m2, OR =2.675, 95% CI: 1.131-6.327, P=0.025; BMI ≥28 vs. 18.5-27.9 kg/m2, OR =3.693, 95% CI: 1.589-8.583, P=0.002) and CSS (BMI <18.5 vs. 18.5-27.9 kg/m2, OR =3.012, 95% CI: 1.180-7.687, P=0.021; BMI ≥28 vs. 18.5-27.9 kg/m2, OR =3.801, 95% CI: 1.526-9.469, P=0.004), along with tumor stage and urinary diversion type. CONCLUSIONS: Being underweight or obese is associated with a poor prognosis in patients with BCa undergoing RC. For patients who are preparing to undergo RC for BCa, controlling the BMI index through diet or exercise before surgery may contribute to the surgical curative effect and an improved prognosis.

ID2 Inhibits Bladder Cancer Progression and Metastasis via PI3K/AKT Signaling Pathway.

Background: Inhibitors of DNA-binding (ID) proteins are important regulators of cell proliferation and differentiation. The aim of this study was to evaluated the role of ID proteins in bladder cancer (BCa) and related molecular mechanisms. Methods: The TCGA database was analyzed for the expression and clinical significance of ID proteins. The expression of ID2 was determined by qRT-PCR, immunohistochemical staining and western blot. The role of ID2 was determined by CCK-8, colony formation, wound healing, transwell and xenograft tumor assays, and the potential mechanism of ID2 in BCa was investigated by RNA sequencing. Results: ID2 expression was significantly downregulated in TCGA database and clinical samples, and high ID2 expression was associated with low-grade tumor staging and correlated with better overall survival, disease specific survival (DSS) and progress free interval (PFI). In vivo and in vitro experiments showed that knockdown of ID2 promoted proliferation, migration, invasion and metastasis of BCa cells, while overexpression of ID2 significantly inhibited cell proliferation, migration, invasion and metastasis. Mechanistically, ID2 acts as a tumor suppressor through PI3K/AKT signaling pathway to inhibit the progression and metastasis of BCa. Conclusion: Our results suggest that ID2 exerts tumor suppressive effects in BCa through PI3K/AKT signaling pathway, and altered ID2 expression can be used as a biomarker of BCa progression and metastasis.

Combination of Total Psoas Index and Albumin-Globulin Score for the Prognosis Prediction of Bladder Cancer Patients After Radical Cystectomy: A Population-Based Study.

BACKGROUND: Sarcopenia as the loss of skeletal muscle mass is related with poor postoperative survival. This work purposed to evaluate the prognostic prediction of the total psoas index (TPI), albumin-globulin score (AGS), and the combination of TPI and AGS (CTA) in bladder cancer (BCa) patients after radical cystectomy. METHODS: BCa patients that received radical cystectomy between 2012 and 2020 were retrieved from our medical center. The calculation of TPI was based on the plain computed tomography images. The predictive effects of TPI, AGS, and CTA grade on survival of BCa patients were analyzed and compared with the albumin-globulin ratio (AGR) through the receiver operating characteristic (ROC) curves. A nomogram was further established based on the Cox regression results from CTA grade and clinicopathological characteristics, which are verified by the decision curve analysis (DCA). RESULTS: A total of 112 eligible patients diagnosed as BCa were included in this study for retrospective analysis. The patients with lower TPI or higher AGS grade (1/2) contained poorer overall survival (OS) and disease-free survival (DFS). Divided by CTA grade, there were 35 (31.25%) patients in grade 1 associated with the best postoperative prognosis, which was accompanied with increased TPI and decreased AGS. The CTA grade could better predict postoperative outcomes compared with TPI, AGR, and AGS for the highest area under the curve (AUC; 0.674 of OS and 0.681 of DFS). The 3- and 5-year OS and DFS nomograms were conducted based on CTA grade and clinical variables, with a higher predictive performance than the TNM stage. CONCLUSION: This study revealed that the novel index CTA functioned as an effective prognostic predictor for postoperative OS and DFS of BCa patients after radical cystectomy. Preoperative assessment of CTA would contribute to optimizing clinical therapies.

Long Noncoding RNA SNHG1 Activates Autophagy and Promotes Cell Invasion in Bladder Cancer.

LncRNAs play important roles in bladder cancer. However, only a few studies report on the correlation between lncRNAs expression and autophagy in bladder cancer. This study aimed to explore the effect of lncRNA on autophagy in bladder cancer. The findings showed high expression of SNHG1 in the bladder cancer cells and tumor tissues. The high expression of SNHG1 was positively correlated with bladder cancer cell invasion, proliferation, and autophagy. This finding implies that SNHG1 promotes bladder cancer cell invasion and proliferation via autophagy. Further analysis of the mechanism of action of SNHG1 showed that it functions as a sponge of miRNA-493 in bladder cancer. miRNA-493 binds on the 3' -UTR of ATG14 mRNA thus affecting ATG14 protein expression, which is implicated in autophagy. These findings are supported by previous preclinical studies using multiple Bca cell lines and TCGA, which demonstrate that SNHG1 plays an oncogenic role by acting as a sponge of miR-493-5p or as its ceRNA. Upregulation of SNHG1 promotes proliferation, invasion, and autophagy of bladder cancer cells through the miR-493-5p/ATG14/autophagy pathway. Therefore, SNHG1 may act as a potential therapeutic target for the treatment of bladder cancer.

Relationship between urine specific gravity and the prevalence rate of kidney stone.

BACKGROUND: The purpose of this study was to evaluate the relationship between urine specific gravity (USG) and the prevalence rate of kidney stone. METHODS: We conducted a cross-sectional study of adult participants (≥20 years) of the National Health and Nutrition Examination Survey (NHANES) from 2007 to 2008. The USG was divided into three groups: <1.008, 1.008-1.020 and >1.020. Univariate and multivariate logistic regression analysis was used to determine the effect of USG on the prevalence rate of kidney stone. RESULTS: A total of 4,791 patients were included in this study, of which 464 (9.7%) reported a history of kidney stone. Univariate logistic regression analysis showed that age, gender, race, hypertension, diabetes, body mass index (BMI), estimated glomerular filtration rate (eGFR), USG and urine creatinine were closely related to the prevalence of kidney stones. After adjusting for known confounding factors, multivariate logistic regression showed that the prevalence rate of kidney stone increased with the increase of USG (1.008-1.020 vs. <1.008, OR =1.31, 95% CI, 0.09-1.91, P=0.155; >1.020 vs. <1.008, OR =1.71, 95% CI, 1.16-2.54, P=0.007). CONCLUSIONS: The increase of USG was significantly correlated with self-reported kidney stone. This finding helps to identify risk factors for kidney stones as early as possible in the United States.

Prognostic Significance of Modified Advanced Lung Cancer Inflammation Index in Patients With Renal Cell Carcinoma Undergoing Laparoscopic Nephrectomy: A Multi-Institutional, Propensity Score Matching Cohort Study.

BACKGROUND: We conducted a multi-institutional clinical study to assess the prognostic value of the advanced lung cancer inflammatory index (ALI) and modified ALI (mALI) in patients with renal cell carcinoma (RCC). METHODS: We collected 440 patients who underwent laparoscopic nephrectomy at three centers from 2014 to 2019. ALI was defined as body mass index (BMI) × serum albumin (ALB)/neutrophil-to-lymphocyte ratio (NLR) and mALI as L3 muscle index × ALB/NLR. Kaplan-Meier curves, receiver operating characteristic (ROC) curves and Cox survival analysis were used to assess the effect of ALI and mALI on overall survival (OS). In addition, we performed 1:1 propensity score matching (PSM) for the high mALI and low mALI groups to further explore the impact of mALI on survival in RCC patients. RESULTS: The optimal cut-off values for ALI and mALI were 40.6 and 83.0, respectively. Based on the cut-off values, we divided the patients into high ALI and low ALI groups, high mALI and low mALI groups. ALI and mALI were significantly associated with the AJCC stage, Fuhrman grade, T stage, and M stage. Low ALI (p = 0.002) or low mALI (p < 0.001) was associated with poorer prognosis. ROC curves showed that mALI was a better predictor of OS than ALI. Multivariate Cox regression analysis showed that low mALI (aHR = 2.22; 95% CI 1.19-4.13, p = 0.012) was an independent risk factor for OS in RCC patients who underwent nephrectomy, while ALI (aHR = 1.40; 95% CI 0.73-2.66, p = 0.309) was not significantly associated. Furthermore, after PSM analysis, we found that mALI remained an independent risk factor for OS (aHR = 2.88; 95% CI 1.33-6.26, p = 0.007) in patients with RCC. CONCLUSIONS: For RCC patients undergoing laparoscopic nephrectomy, low ALI and low mALI were associated with poor prognosis, and preoperative mALI can be used as a potential independent prognostic indicator for RCC patients.

Polyfluoroalkyl chemicals and the risk of kidney stones in US adults: A population-based study.

The potential nephrotoxicity of polyfluoroalkyl chemicals (PFCs) have received extensive attention. However, the relationship between PFCs and the risk of kidney stones remain unclear. This study aimed to examine the level of PFCs in the US population and its relationship with the risk of kidney stones. We investigated the serum levels of six PFCs in 8453 adult participants (≥20 years) from the National Health and Nutrition Examination Survey (NHANES) between 2007 and 2016, including perfluorodecanoic acid (PFDE), perfluorohexane sulfonic acid (PFHS), 2-(N-methyl-perfluorooctane sulfonamido) acetate (MPAH), perfluorononanoic acid (PFNA), perfluoroundecanoic acid (PFUA), and perfluorododecanoic acid (PFDO). Logistic regression model was used to evaluate the correlation between PFCs and kidney stones. Of the 8453 participants, 787 self-reported a history of kidney stones. After adjusting for gender, age, race, education, marital status, body mass index (BMI), hypertension, diabetes and estimated glomerular filtration rate (eGFR), we found that total PFCs and PFHS were positively correlated with the risk of kidney stones. Compared with the lowest tertile, the odds ratios with 95% confidence intervals (CI) with increasing tertiles were 1.30 (95% CI,1.08-1.59, p = 0.007) and 1.25 (95 CI%,1.00-1.52, p = 0.024) for total PFCs and 1.24 (95 CI%,1.03-1.51, p = 0.032), and 1.35 (95 CI,1.10-1.68, p = 0.005) for PFHS. Our study shows that total PFCs and PFHS were associated with an increased risk of kidney stones.

Cost-effectiveness analysis of two kinds of bladder cancer urinary diversion: Studer versus Bricker.

BACKGROUND: The purpose of our study was to evaluated the cost-effectiveness of two bladder cancer (BCa) urinary diversions: Studer and Bricker. METHODS: The study included 44 patients with Studer and 40 patients with Bricker. Collected and analyzed the patient's basic characteristics, health care costs, and prognosis survival. The quality-adjusted life-year (QALY) were calculated and verified by the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core-30 (EORTC QLQ-C30, Version 3, Chinese version). Cost-effectiveness depends on the incremental cost per QALY. The incremental cost-effectiveness ratio (ICER) was determined using the cost/QALY. RESULTS: We found the average total cost of the Studer group was $7,173.7±1,390.8, and the Bricker group was $6,545.2±1,458.4. There were significant differences in hospitalization time, total hospitalization expenses, bed cost, comprehensive medical service charge and drugs cost (all P<0.05). The hospitalization time, total hospitalization expenses, bed cost, comprehensive medical service charge, surgical treatment cost and drugs cost in Studer group were higher than those in Bricker group, while there was no significant difference in postoperative complications between the two groups (P=0.858). The ICER of Studer group and Bricker group were $8,535.6±2,027.6/QALY and $11,158.2±2,944.9/QALY, respectively. The ICER of Studer group over Bricker group was $2,514.0/QALY. CONCLUSIONS: We found the Studer group had higher hospitalization time, total hospitalization expenses, bed cost, comprehensive medical service charge, surgical treatment cost, and drugs cost than the Bricker group, but the Studer group had a higher ICER than the Bricker group.

Depletion of CDC5L inhibits bladder cancer tumorigenesis.

Cell division cycle 5-like (CDC5L) protein is a cell cycle regulator of the G2/M transition and has been reported to participate in the catalytic step of pre-messenger RNA (mRNA) splicing and DNA damage repair. Recently, CDC5L was also found to act as a candidate oncogene in osteosarcoma and cervical tumours. However, the role of CDC5L expression in bladder cancer remains unclear. Here, we analysed the expression and clinical significance of CDC5L in bladder cancer tissues. The expression of CDC5L in fresh bladder cancer tissues and paraffin-embedded slices was evaluated by western blot and immunohistochemistry, respectively. We found that CDC5L was highly expressed in bladder cancer. The expression of CDC5L was significantly associated with bladder cancer pathology grade and Ki67 expression. Univariate and multivariate analyses showed that high CDC5L expression was an independent prognostic factor for the survival of bladder cancer patients. To determine whether CDC5L could regulate the proliferation of bladder cancer cells, we transfected bladder cancer cells with an interfering RNA targeting CDC5L and then investigated cell proliferation with a cell counting kit (CCK)-8, flow cytometry assays, colony formation and xenograft assay analyses. Our results indicate that knockdown of CDC5L inhibits proliferation of bladder cancer cells. In addition, reduced expression of CDC5L induced apoptosis of bladder cancer cells and inhibited their migration, invasion and EMT. These findings suggest that CDC5L might play an important role in bladder cancer and thus be a promising therapeutic target of bladder cancer.

Cystatin C in Evaluating Renal Function in Ureteral Calculi Hydronephrosis in Adults.

BACKGROUND: Serum cystatin C (CysC) is still becoming used as a marker of renal function but is far from being commonly used worldwide. The purpose of this study was to characterize the ureteral calculi patients with hydronephrosis-caused CysC changes in renal function. METHODS: To better reflect the changes of renal function, we constructed models of ureteral obstruction in rats to mimic the hydronephrosis caused by human ureteral calculi. Moreover, our study included 200 patients diagnosed with ureteral calculi in our hospital between June 2017 and 2018. We compared the estimated glomerular filtration rate using different equations based on CysC and/or serum creatinine (SCr). RESULTS: We found that the expression of CysC and SCr increased with the prolonged obstruction time by enzyme linked immunosorbent assay. Moreover, quantitative real-time polymerase chain reaction, Western blot and immunohistochemistry further demonstrated that the expression of CysC increases with the degree of hydronephrosis. Among 200 patients with ureteral calculi, 40 (20.0%) had no hydronephrosis, 110 (55.0%) had mild hydronephrosis, 32 (16.0%) had moderate hydronephrosis and 18 (9.0%) had severe hydronephrosis. As the degree of hydronephrosis increased, the expression of neutrophil percentage, CysC, blood urea nitrogen, SCr and serum uric acid also increased. Multivariate analyses demonstrated that only CysC was an independent risk factor for hydronephrosis (p = 0.003). In addition, CysC and the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) CysC equation showed the highest veracity in renal function estimation of patients with hydronephrosis caused by ureteral calculus. CONCLUSION: For patients with hydronephrosis caused by ureteral calculi, CysC better reflects the changes in renal function, and the CKD-EPI CysC equation has the highest accuracy.

Analysis of the clinical effect and long-term follow-up results of retroperitoneal laparoscopic ureterolithotomy in the treatment of complicated upper ureteral calculi (report of 206 cases followed for 10 years).

PURPOSE: To summarize the experience of retroperitoneal laparoscopic ureterolithotomy (RLU) in the treatment of upper ureteral calculi and long-term follow-up results and compare them with ureteroscopic lithotomy (URL) and percutaneous nephrolithotomy (PCNL). METHODS: The clinical data of 585 patients with complex upper ureteral calculi who met the inclusion criteria from January 2006 to December 2017 were retrospectively analyzed. There were 206 cases treated with RLU, 201 cases treated with URL and 178 cases treated with PCNL. The operation time, hospitalization time, stone clearance rate, incidence of postoperative complications and recurrence rate were observed and compared among the three groups. RESULTS: Among 585 eligible patients, 206 cases were treated with RLU, 201 cases were treated with URL and 178 cases were treated with PCNL. The stone clearance rate (98.54%), postoperative complication types and rate (0.97%) in the RLU group were superior to those in the URL group and the PCNL group (P < 0.05). There was no significant difference in the recurrence rate (3.88%) between the RLU group and the other two groups (P > 0.05). CONCLUSION: Retroperitoneal laparoscopic ureterolithotomy has many advantages in the treatment of upper ureteral calculi, including high stone clearance rate, less complications especially in ureteral stricture. Retroperitoneal laparoscopic ureterolithotomy is also safe to treat upper ureteral calculi accompanied with severe urinary tract infection.