Association of socioeconomic status and overactive bladder in US adults: a cross-sectional analysis of nationally representative data.

Background: Socioeconomic status inequality is an important variable in the emergence of urological diseases in humans. This study set out to investigate the association between the prevalence of overactive bladder (OAB) and the poverty income ratio (PIR) that served as a more influential indicator of socioeconomic status compared to education and occupation. Method: Data from the National Health and Nutrition Examination Survey (NHANES) conducted from 2007 to 2020 were used in this cross-sectional study. The association between the PIR and OAB was examined using weighted multivariate logistic regression and weighted restricted cubic splines (RCS). Additionally, interaction analysis was used for investigation to the connections between PIR and OAB in various covariate groups in order to confirm the stability of the results. Results: We observed a noteworthy inverse association between PIR and OAB after adjusting for potential confounding variables (OR = 0.87, 95% CI, 0.84-0.90, p < 0.0001). PIR was transformed into categorical variables, and the association held steady after that (1.0 < PIR <4.0 vs. PIR ≤ 1.0, OR = 0.70, 95% CI =0.63-0.77, p < 0.0001; PIR ≥ 4.0 vs. PIR ≤ 1.0, OR = 0.56, 95% CI =0.48-0.65, p < 0.0001). Additionally, RCS analysis showed that PIR and OAB had a negative nonlinear response relationship. Subgroup analyses showed that the inverse association between PIR and prevalence of OAB was stronger in obese than in nonobese individuals (P for interaction < 0.05). Conclusion: In our study, we observed a significant negative association between the PIR and the prevalence of OAB. In the future, PIR could be used as a reference standard to develop strategies to prevent and treat OAB.

Liposome-coated nanoparticle triggers prostate cancer ferroptosis through synergetic chemodynamic-gas therapy.

Ferroptosis has attracted much attention for tumor treatment. It has been recently identified that castration-resistant prostate cancer (CRPC) is vulnerable to ferroptosis inducers. Notably, chemodynamic therapy (CDT), triggered by metal ions, could easily induce ferroptosis via a Fenton/Fenton-like reaction, but its efficiency was highly dependent on the intracellular H2O2 concentration, posing significant changes for its clinical translation. Herein, we attached glucose oxidase (GOx) onto the surface of manganese sulfide (MnS) and developed therapeutic nanocomposites (Lpo@MnS-GOx) after encapsulating with liposome. Upon internalization by cancer cells, the released GOx could transform glucose into gluconic acid (GA) and H2O2. Notably, the generated GA stimulates the degradation of MnS, followed by the promotion of the release of H2S and Mn2+, whereas the produced H2O2 can amplify the Fenton-like response initiated by Mn2+. The enhanced CDT combined with the gas therapy effect could simultaneously promote the accumulation of reactive oxygen species and finally induce ferroptosis and exhibit an excellent anti-tumor effect. Consequently, these Lpo@MnS-GOx NPs with enhanced ferroptosis-induced effect will find great potential for CRPC cancer treatment.

A machine learning framework develops a DNA replication stress model for predicting clinical outcomes and therapeutic vulnerability in primary prostate cancer.

Recent studies have identified DNA replication stress as an important feature of advanced prostate cancer (PCa). The identification of biomarkers for DNA replication stress could therefore facilitate risk stratification and help inform treatment options for PCa. Here, we designed a robust machine learning-based framework to comprehensively explore the impact of DNA replication stress on prognosis and treatment in 5 PCa bulk transcriptomic cohorts with a total of 905 patients. Bootstrap resampling-based univariate Cox regression and Boruta algorithm were applied to select a subset of DNA replication stress genes that were more clinically relevant. Next, we benchmarked 7 survival-related machine-learning algorithms for PCa recurrence using nested cross-validation. Multi-omic and drug sensitivity data were also utilized to characterize PCa with various DNA replication stress. We found that the hyperparameter-tuned eXtreme Gradient Boosting model outperformed other tuned models and was therefore used to establish a robust replication stress signature (RSS). RSS demonstrated superior performance over most clinical features and other PCa signatures in predicting PCa recurrence across cohorts. Lower RSS was characterized by enriched metabolism pathways, high androgen activity, and a favorable prognosis. In contrast, higher RSS was significantly associated with TP53, RB1, and PTEN deletion, exhibited increased proliferation and DNA replication stress, and was more immune-suppressive with a higher chance of immunotherapy response. In silico screening identified 13 potential targets (e.g. TOP2A, CDK9, and RRM2) from 2249 druggable targets, and 2 therapeutic agents (irinotecan and topotecan) for RSS-high patients. Additionally, RSS-high patients were more responsive to taxane-based chemotherapy and Poly (ADP-ribose) polymerase inhibitors, whereas RSS-low patients were more sensitive to androgen deprivation therapy. In conclusion, a robust machine-learning framework was used to reveal the great potential of RSS for personalized risk stratification and therapeutic implications in PCa.

A novel ferroptosis-related 12-gene signature predicts clinical prognosis and reveals immune relevancy in clear cell renal cell carcinoma.

BACKGROUND: Clear cell renal cell carcinoma (ccRCC) is still highly aggressive and lethal even with various therapeutic approaches. As the kidney is an iron metabolism-related organ, exploring and assessing the clinical value of ferroptosis, an iron-dependent regulated cell death, is practical and important. METHODS: Prognostic ferroptosis-related differentially expressed genes (DEGs) were identified from the KIRC cohort in the cancer genome atlas (TCGA) database, from which a prognostic signature was established using Lasso-penalized Cox regression analysis. Each patient in the KIRC cohort and the E-MTAB-1980 cohort (from the ArrayExpress database) was assigned a calculated signature-correlated risk score and categorized to be either in the high- or low-risk group divided by the median risk score in the KIRC cohort. Then, the independent prognostic value of the signature was further assessed by Kaplan-Meier (K-M) survival, time-dependent receiver operating characteristic (ROC) and Cox regression analyses based on overall survival (OS) in both cohorts. Finally, risk-related DEGs were identified in both cohorts and subjected to enrichment analyses for Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) and immune infiltration. RESULTS: Among 60 ferroptosis-related genes, 32 prognostic DEGs were identified, from which we constructed a prognostic 12-gene signature with CARS1, HMGCR, CHAC1, GOT1, CD44, STEAP3, AKR1C1, CBS, DPP4, FANCD2, SLC1A5 and NCOA4. Patients in both cohorts were divided into high- and low-risk groups, which were visually distributed in two sets and had positive-risk-related mortality. The K-M survival and the ROC curves validated that the signature has prognostic value with P < 0.05 and area under the curve > 0.7 in both cohorts, respectively. Multivariate Cox regression further confirmed the risk score as an independent prognostic predictor for OS. Commonly enriched terms in GO and KEGG not only showed a high iron correlation but also, interestingly, immune relevance of 3 immune cells (macrophages, mast cells and regulatory T cells) and 1 immune-related function (antigen processing cell co-stimulation). CONCLUSION: We established a novel 12 ferroptosis-related-gene signature that was proven to be an independent prognostic predictor for OS and inferred to be related to tumour immunity in ccRCC; however, the underlying mechanism is still poorly characterized and needs further exploration.

Dietary and lifestyle factors for primary prevention of nephrolithiasis: a systematic review and meta-analysis.

BACKGROUND: Dietary and lifestyle factors may play an important role in the increasing prevalence of nephrolithiasis. We aimed to review and quantify the associations between lifestyle factors and incident nephrolithiasis and suggest lifestyle changes for the primary prevention of nephrolithiasis. METHODS: PubMed, EMBASE, and Cochrane Library were searched up to May 2019, for observational studies and randomized controlled trials (RCTs) that assessed modifiable lifestyle factors and risk of nephrolithiasis in adults. Pooled relative risks (RRs) and 95% confidence intervals (CIs) were computed using a random effects model. The I2 statistic was employed to evaluate heterogeneity. Subgroup analysis, sensitivity analysis and meta-regression were also conducted whenever possible. RESULTS: Fifty relevant articles with 1,322,133 participants and 21,030 cases in total were identified. Prominent risk factors for incident stones were body mass index (1.39,1.27-1.52), dietary sodium (1.38, 1.21-1.56), fructose, meat, animal protein, and soda. In contrast, protective factors included fluid intake (0.55, 0.51-0.60), a Dietary Approaches to Stop Hypertension (DASH) style diet (0.69, 0.64-0.75), alcohol (0.69, 0.56-0.85), water, coffee, tea, vegetables, fruits, dietary fiber, dietary calcium (0.83, 0.76-0.90), and potassium. Vitamin D (1.22, 1.01-1.49) and calcium (1.16, 1.00-1.35) supplementation alone increased the risk of stones in meta-analyses of observational studies, but not in RCTs, where the cosupplementation conferred significant risk. CONCLUSIONS: Several modifiable factors, notably fluid intake, dietary patterns, and obesity, were significantly associated with nephrolithiasis. Long-term RCTs are required to investigate the cost-effectiveness of dietary patterns for stone prevention. The independent and combined effects of vitamin D and calcium supplementation on nephrolithiasis need further elucidation.

Identification of cell division cycle 20 as a candidate biomarker and potential therapeutic target in bladder cancer using bioinformatics analysis.

PURPOSE: As bladder cancer (BC) is very heterogeneous and complicated in the genetic level, exploring genes to serve as biomarkers and therapeutic targets is practical. MATERIALS AND METHODS: We searched Gene Expression Omnibus (GEO) and downloaded the eligible microarray datasets. After intersection analysis for identified differentially expressed genes (DEGs) of included datasets, overlapped DEGs were identified and subsequently analyzed with Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), Protein-Protein Interaction (PPI) and hub genes identification. Hub genes were further analyzed with mRNA expression comparation in Oncomine and Gene Expression Profiling Interactive Analysis (GEPIA) database, proteomics-based validation in The Human Protein Atlas (THPA) and survival analysis in GEO and Oncolnc database. RESULTS: We analyzed five eligible GEO datasets and identified 76 overlapped DEGs mapped into PPI network with 459 edges which were mainly enriched in cell cycle pathway and related terms in GO and KEGG analysis. Among five identified hub genes, which are Cyclin-Dependent Kinase 1 (CDK1), Ubiquitin-Conjugating Enzyme E2 C (UBE2C), Cell Division Cycle 20 (CDC20), Microtubule Nucleation Factor (TPX2) and Cell Division Cycle Associated 8 (CDCA8); CDC20 and CDCA8 were confirmed as significant in mRNA expression comparation and proteomics-based validation. However, only CDC20 was considered prognostically significant in both GEO and Oncolnc database. CONCLUSIONS: CDC20 and CDCA8 were identified as candidate diagnostic biomarkers for BC in the present study; however, only CDC20 was validated as prognostically valuable and may possibly serve as a candidate prognostic biomarker and potential therapeutic target. Still, further validation studies are essential and indispensable.

Associations between nephrolithiasis and diabetes mellitus, hypertension and gallstones: A meta-analysis of cohort studies.

AIM: To review and clarify the strengths and directions of associations between nephrolithiasis and hypertension (HTN), diabetes mellitus (DM) and gallstones (GS) given the inconsistent results reported in cohort studies. METHODS: Relevant literature was searched in PubMed and EMBASE from inception to July 2019, for cohort studies that examined the relationships between kidney stones and these three diseases among adults. Pooled relative risks (RRs) were calculated by maximally adjusted risk estimates using a random effect model. Subgroup analysis, meta-regression and sensitivity analysis were conducted whenever appropriate. RESULTS: Of 3537 papers, 21 articles with each including 1 to 3 cohorts were identified. In this meta-analysis, nephrolithiasis was reciprocally linked to HTN, DM and GS. Kidney stones were significantly associated with 31%, 33% and 46% higher risks of incident HTN, DM and GS whereas GS was associated with a significantly higher risk of nephrolithiasis (RR: 1.49; 95% CI, 1.28-1.73), followed by HTN (RR: 1.30; 95% CI, 1.11-1.52) and DM (RR: 1.18; 95% CI, 1.07-1.29). Also, females with DM (RR: 1.29; 95% CI, 1.08-1.55) were more likely to develop kidney stones than diabetic male patients (RR: 0.91; 95% CI, 0.75-1.10). CONCLUSION: Although additional studies are needed to confirm these findings and elucidate the mechanisms, this study revealed possible bidirectional associations between nephrolithiasis and HTN, diabetes and GS, which reinforced the notion of nephrolithiasis as a systemic disease that requires comprehensive investigations.

Bladder cancer survival nomogram: Development and validation of a prediction tool, using the SEER and TCGA databases.

Bladder cancer (BC) is a common malignancy associated with high morbidity and mortality, however, accurate and convenient risk assessment tools applicable to BC patients are currently lacking. Previous studies using nomograms to evaluate bladder cancer (BC) survival have been based on small samples. Using a large dataset, this study aimed to construct more precise clinical nomograms to effectively predict bladder cancer survival.Data on patients with pathologically-confirmed bladder cancer were extracted from the Surveillance, Epidemiology, and End Results (SEER) database. Additional BC patient data for an external validation cohort were extracted from the Cancer Genome Atlas (TCGA) database. Clinical parameters that constituted potential risk factors were reviewed and analyzed using univariate and multivariate Cox proportional hazards regression. A nomogram was constructed with parameters that significantly correlated with the overall survival (OS). Prognostic performance of a nomogram was assessed using the concordance index (c-index), area under the receiver operating characteristic curve (AUC), and a calibration curve. The model was then tested with data from an internal and external validation cohort. Patients' survival was analyzed and compared with the Kaplan-Meier (KM) method.Multivariate Cox regression showed that age, sex, race, stage_T1, stage_T2a, stage_T2b, stage_T3a, stage_Ta, stage_Tis, stage_N, stage_M were independent predictors of BC survival. A nomogram was constructed based on these factors. The c-index of the nomogram was 0.7916 (95% confidence interval CI, 0.79-0.80). The calibration curve showed excellent agreement between the predicted and observed values. The c-index for the internal validation cohort was 0.7917 (95% CI 0.79-0.80), which was higher than for the training cohort, suggesting robustness of the model. For the training cohort, the AUC for the 3- and the 5-year survival was 0.82 and 0.813, respectively. The c-index for the TNM-based model was superior to that for the AJCC-TNM classification.The models presented in this study might be suitable for clinical use, supporting clinicians in their individualized assessment of expected survival in BC patients. They might also be used as a layered tool for clinical research.

Vimentin Overexpressions Induced by Cell Hypoxia Promote Vasculogenic Mimicry by Renal Cell Carcinoma Cells.

Vasculogenic mimicry (VM), the novel approach for tumor cells to obtain blood supply, was reported to be involved in antiangiogenic resistance and poor prognosis in renal cell carcinoma (RCC). However, the molecular mechanisms underlying VM formed by RCC cells are still not clearly depicted. In the present study, we found that OS-RC-2 acquired the VM forming ability accompanied with the increased expressions of Vimentin and AXL and decreased expression of E-Cadherin by CoCl2 treatment. Downregulation of Vimentin by siRNA severely impaired the capability of OS-RC-2 and 786-O to form VM structures induced by cell hypoxia in vitro. Moreover, knockdown of Vimentin inhibited cell migration and invasion, which could be prompted by hypoxia induction in RCC cells. In our clear cell RCC tissues, we found that VM was positively correlated with Vimentin overexpression and both predicted poor prognosis. In conclusion, Vimentin plays an important role in hypoxia induced VM formation of RCC cells and targeted Vimentin might be beneficial for RCC therapy.

Bladder preservation approach versus radical cystectomy for high-grade non-muscle-invasive bladder cancer: a meta-analysis of cohort studies.

BACKGROUND: High-grade non-muscle-invasive bladder cancer is superficial; nonetheless, it is an aggressive cancer. Proper management strategy selection following transurethral resection between bladder preservation (BP) and radical cystectomy (RC) could result in delayed or excessive treatment. Hence, selecting the optimal treatment modality remains controversial to date. METHODS: We searched MEDLINE, The Cochrane Library, EMBASE, China National Knowledge Infrastructure, and Wanfang database through 12 April 2018. Quality and publication bias were assessed using the Newcastle-Ottawa Scale and Begg's/Egger's test. We collected 2-year, 5-year, 10-year, and 15-year survival rate and hazard ratio (HR) for overall survival (OS), cancer-specific survival (CSS), and progression-free survival (PFS). Using the Review Manager 5.2 software, we used the odds ratio (OR) of specific years and HR for meta-analysis. Subgroup analysis was performed by the original tumor state, radical cystectomy timing, bladder preservation modality, and age. RESULTS: In total, 11 cohorts with 1735 patients were selected for the meta-analysis. All OR of OS supported BP as a better treatment option; however, all OR of PFS had no significant differences. As for CSS, only the 15-year OR reflected a statistical significance preferring RC. Subgroup analysis showed that BP is more appropriate for patients older than 65 and G3 tumor. Limited data demonstrated that late RC (> 3 months) is more effective compared to early RC (< 3 months) and intravesical Bacillus Calmette-Guerin was not statistically different from that of RC. The mixed BP modalities were significantly better compared to RC in OS and worse in CSS, with both having a very low evidence strength. CONCLUSIONS: BP is a superior treatment modality compare to RC, especially for older patients and T1G3 or lower grade tumors. However, the superior BP modality was unclear. Conversely, RC could be a better option for younger patients. More specifically, late RC may be more beneficial but had a very-low-level of evidence. Quality of life should be considered equal to survival outcome; hence, post-treatment follow-up needs to be performed. Prospective randomized studies should be performed to overcome the limitations of this meta-analysis study. REGISTRATION: Registration ID is CRD42018093491 .

In vitro anti-tumor activity of the tanshinone IIA against SKOV3 cells.

The aim of this study was to determine the anti-tumour activity of tanshinone IIA in SKOV3 cells. Results suggested that tanshinone IIA could significantly inhibit (IC50 value  =  19.6 µM) the proliferation and induce apoptosis of SKOV3 cells as demonstrated by flow cytometry analysis. In addition, tanshinone IIA treatment induced G2/M phase cell cycle arrest in SKOV3 cells. The results of Western blotting indicated that tanshinone IIA can suppress the expression of anti-apoptotic protein Bcl-2, increase (0.28 vs. 0.62) the expression of pro-apoptotic protein Bax (0.83 vs. 0.24) in SKOV3 cells. It can be concluded that the tanshinone IIA may be a possible therapeutic candidate having cytotoxic and anti-tumour potential.

Effects of puerarin in STZ-induced diabetic rats by oxidative stress and the TGF-ß1/Smad2 pathway.

The present study aimed to investigate the effects of pueraria on streptozotocine (STZ)-induced renal damage and its possible mechanisms. Wistar rats were randomly divided into five groups: the normal control group, diabetes untreated model group, two dosages (140 and 200 mg per kg bw per day) of puerarin treatment groups and a positive control group. Rats were studied 30 days after the STZ treatment, and the diabetes untreated model group presented significantly higher kidney index, blood glucose, triglyceride (TG), total cholesterol (TC), malondialdehyde (MDA), interferon-γ (IFN-γ), and IFN-γ/IL-4 levels, lower body weight, fasting blood insulin (FPI), IL-4, superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px) and nitric oxide (NO) levels and worse renal function (higher blood urea nitrogen (BUN), serum creatinine (SCr), urine protein (UP) levels and glomerular extracellular matrix (relative area)) compared with the normal control group (p < 0.05). Furthermore, RT-FQ-PCR and western blot analyses showed that TGF-ß1, Smad2, CTGF and FN protein and mRNA expression was significantly increased in the diabetes untreated model group compared with the normal control group. In contrast, the puerarin treatment dose-dependently significantly decreased the kidney index, blood glucose, TG, TC, MDA, IFN-γ, and IFN-γ/IL-4 levels, increased the body weight, FPI, IL-4, SOD, CAT, GSH-Px and NO levels and improved the renal function (lower BUN, SCr, UP levels and glomerular extracellular matrix (relative area)) in puerarin treatment groups (p < 0.05). In addition, the mRNA and protein expression of TGF-ß1, Smad2, CTGF and FN was downregulated. It can be concluded that puerarin exerted its anti-diabetic effect on the STZ-treated rats through the inhibition of the TGF-ß1/Smad2 pathway.

Optimization of extraction of Eucommia ulmoides polysaccharides by response surface methodology.

In this study, extraction yield of Eucommia ulmoides polysaccharides was optimized by the utilization of response surface methodology (RSM). Based on contour plots and variance analysis, optimum operational conditions for maximizing extraction yield were found to be extraction time 80 min, ratio of water to raw material 3, and extraction number 3. Then, we investigated the protective effect of the E. ulmoides polysaccharides on the tissue peroxidative damage and abnormal antioxidant levels in ischemia reperfusion (IR) induced renal toxicity in male albino rabbits. Decrease in all the enzymes (superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px), glutathione reductase (GR)) and non-enzymatic antioxidant (glutathione (GSH)), along with an increase in the lipid peroxidative index (malondialdehyde) was found in all the renal ischemia reperfusion (RIR) rabbits as compared with normal controls. The findings indicate that the extract of E. ulmoides polysaccharides can protect the kidney against IR induced oxidative damage in rabbits.

Chemical characterization of Lycium barbarum polysaccharides and its inhibition against liver oxidative injury of high-fat mice.

In this study, we investigated chemical structure of Lycium barbarum polysaccharides and its modulatory effect on oxidative stress in high-fat mice. The polysaccharides mainly contained xylose and glucose. Little amount of rhamnose, mannose and galactose was observed. The Lycium barbarum polysaccharides had IR bands at 800-1200 cm(-1), 1450-1800 cm(-1), 2500-3000 cm(-1), and 3200-3600 cm(-1), which were distinctive absorptions of polysaccharides. Rats are fed with high-fat diet for 2 months. Results showed that blood and liver antioxidant enzymes activities and GSH level in model mice significantly decreased, and MDA level significantly increased (P<0.01) compared to normal control mice. Administration of Lycium barbarum polysaccharides significantly increased antioxidant enzymes activities and decreased MDA level in mice (P<0.01) compared to model group.

Effects of Glycyrrhiza glabra polysaccharides on immune and antioxidant activities in high-fat mice.

The purpose of this study was to investigate the immune and antioxidant activities of Glycyrrhiza glabra polysaccharides (GGP) in rats fed high-fat diet. The experiment was performed on four groups of growing Kunming mice. The results of the experiment showed a statistically significant decrease in serum antioxidant enzyme activities in high-fat group. Administration of GGP dose-dependently significantly enhanced immune and antioxidant enzyme activities in the GGP-treated mice compared to the high-fat model mice. It is concluded that GGP treatment can enhance immune activities, and reduce oxidative stress in high-fat mice.