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Abstract Background Epidemiological studies have revealed a significant association between impaired kidney function and certain mental disorders, particularly bipolar disorder (BIP) and major depressive disorder (MDD). However, the evidence regarding shared genetics and causality is limited due to residual confounding and reverse causation. Methods In this study, we conducted a large-scale genome-wide cross-trait association study to investigate the genetic overlap between 5 kidney function biomarkers (eGFRcrea, eGFRcys, blood urea nitrogen (BUN), serum urate, and UACR) and 2 mental disorders (MDD, BIP). Summary-level data of European ancestry were extracted from UK Biobank, Chronic Kidney Disease Genetics Consortium, and Psychiatric Genomics Consortium. Results Using LD score regression, we found moderate but significant genetic correlations between kidney function biomarker traits on BIP and MDD. Cross-trait meta-analysis identified 1 to 19 independent significant loci that were found shared among 10 pairs of 5 kidney function biomarkers traits and 2 mental disorders. Among them, 3 novel genes: SUFU, IBSP, and PTPRJ, were also identified in transcriptome-wide association study analysis (TWAS), most of which were observed in the nervous and digestive systems (FDR

BackgroundBenign prostatic hyperplasia (BPH) is a common disease occurring in elderly and middle-aged men, and cardiovascular diseases (CVDs) are one of the major causes of death worldwide. Many observational studies examined have found a strong association between BPH and CVDs, but the causal relationship between them is unclear. The aim of this study was to determine the causal relationship between BPH and CVDs, specifically five diseases: stroke, coronary heart disease (CHD), heart failure, myocardial infarction (MI), and atrial fibrillation (AF).MethodsIn this study, we obtained single nucleotide polymorphisms (SNPs) of patients with BPH from the UK Biobank database and patients with CVDs from the UK Biobank, the HERMES Consortium, and the FinnGen Genome Database, each used as a genetic tool for a Mendelian randomization (MR) study. We used conventional MR analysis to assess potential causal direction between BPH and CVDs, as well as MR-Egger, MR-PRESSO, model-based estimation (MBE) and weighted median methods for sensitivity analysis.ResultsUsing a bidirectional two-sample MR study, we found that BPH patients had an increased risk of developing CHD (ConMix OR = 1.152, 95% CI: 1.011–1.235, p = 0.035) and MI (ConMix OR = 1.107.95% CI: 1.022–1.164, p = 0.013), but a decreased risk of stroke (ConMix OR = 0.872, 95% CI: 0.797–0.926, p = 0.002). The reverse study was not statistically significant and further research may be needed.ConclusionOur study suggests a potential causal relationship between BPH and CVDs. BPH appears to be a risk factor for CHD and MI, but it may be protective against stroke. There was no evidence of a causal association in the reverse study, and a larger sample size was needed in follow-up to further explore the potential association.

Abstract Background The mutational pattern of homologous recombination repair (HRR)‐associated gene alterations in Chinese urothelial carcinoma (UC) necessitates comprehensive sequencing efforts, and the clinical implications of HRR gene mutations in UC remain to be elucidated. Materials and Methods We delineated the mutational landscape of 343 Chinese UC patients from West China Hospital and 822 patients from The Cancer Genome Atlas (TCGA) using next‐generation sequencing (NGS). Data from 182 metastatic UC patients from MSK‐IMPACT cohort were used to assess the association between HRR mutations and immunotherapy efficacy. Comprehensive transcriptomic analysis was performed to explore the impact of HRR mutations on tumor immune microenvironment. Results Among Chinese UC patients, 34% harbored HRR gene mutations, with BRCA2, ATM, BRCA1, CDK12, and RAD51C being the most prevalently mutated genes. Mutational signatures contributing to UC differed between patients with and without HRR mutations. Signature 22 for exposure to aristolochic acid was only observed in Chinese UC patients. The presence of HRR mutations was correlated with higher tumor mutational burden, neoantigen burden, and PD‐L1 expression. Importantly, patients with HRR mutations exhibited significantly improved prognosis following immunotherapy compared to those without HRR mutations. Conclusions Our findings provide valuable insights into the genomic landscape of Chinese UC patients and underscore the molecular rationale for utilizing immunotherapy in UC patients with HRR mutations.

Background: Partial bladder outlet obstruction (pBOO) causes deposition of extracellular matrix (ECM), promotes bladder fibrosis, and decreases bladder compliance. Methods: To investigate the effect of β-adrenoceptor (ADRB) on the ECM deposition of pBOO rat model and explore its underlying mechanism, human bladder smooth muscle cells (hBSMCs) were exposed to the pathological hydrostatic pressure (100 cm H2O) for 6 h, reverse transcription-polymerase chain reaction (RT-PCR) and western blotting were employed. Then the rats of sham operation and pBOO model were treated with vehicle or ADRB agonists for 3 weeks, and the alterations of the bladder were observed via Masson staining and immunohistochemical analysis. Results: 100 cm H2O hydrostatic pressure significantly upregulated the expression of collagen I (COL1), collagen III (COL3) and fibronectin (FN), and downregulated the expression of ADRB2 and ADRB3 of hBSMCs at 6 h. The agonists of ADRB2 and ADRB3, Formoterol and BRL 37344, decreased COL1 and FN expression of hBSMCs under 100 cm H2O for 6 h compared with the cells exposed to hydrostatic pressure only. As the classic downstream pathways of ADRB, the EPAC pathway inhibited COL1 and FN expression of hBSMCs via regulating SMAD3 and SMAD2 activities, respectively. In pBOO rats, Procaterol (ADRB2 agonist), and Mirabegron (ADRB3 agonist) inhibited the formation of collagen and decreased the expression of FN and COL1 in the bladders of pBOO rats. Conclusions: The bladder fibrosis of pBOO and deposition of hBSMCs ECM under hydrostatic pressure were regulated by ADRB2, and ADRB3 via EPAC/SMAD2/FN and EPAC/SMAD3/COL1 pathways, these findings pave an avenue for effective treatment of pBOO.

Abstract Ferroptosis is a recently discovered form of regulated cell death characterized by its distinct dependence on iron and the peroxidation of lipids within cellular membranes. Ferroptosis plays a crucial role in physiological and pathological situations and has attracted the attention of numerous scientists. Ferroptosis suppressive protein 1 (FSP1) is one of the main regulators that negatively regulates ferroptosis through the GPX4‐independent FSP1–CoQ10–NAD(P)H axis and is a potential therapeutic target for ferroptosis‐related diseases. However, the crystal structure of FSP1 has not been resolved, which hinders the development of therapeutic strategies targeting FSP1. To unravel this puzzle, we purified the human FSP1 (hFSP1) protein using the baculovirus eukaryotic cell expression system and solved its crystal structure at a resolution of 1.75 Å. Furthermore, we evaluated the oxidoreductase activity of hFSP1 with NADH as the substrate and identified E156 as the key amino acid in maintaining hFSP1 activity. Interestingly, our results indicated that hFSP1 exists and functions in a monomeric state. Mutagenesis analysis revealed the critical role of the C‐terminal domain in the binding of substrate. These findings significantly enhance our understanding of the functional mechanism of FSP1 and provide a precise model for further drug development.

Abstract Detrusor underactivity (DUA) is a common and thorny problem in urology, which severely impairs patients’ bladder function and quality of life. However, its underlying pathophysiological mechanism remains unclear. Hence, we sequenced 69,973 cells from five controls and nine patients with bladder dysfunction using single‐cell RNA sequencing. Twelve distinct cell types were identified and they showed high cellular and functional heterogeneity among each group. Among them, fibroblasts, macrophages, and epithelial cells had the most intercellular communications. Their aberrant gene expressions and altered intercellular interactions were mainly involved in extracellular matrix organization, inflammation/immune regulation, and cellular injury. Further re‐cluster analysis revealed an accumulation of the RBFOX1+ fibroblasts and RIPOR2+ macrophages in dysfunctional bladder wall, which mediated bladder remodeling through dysfunctional extracellular matrix organization and inflammation/immune reaction. Besides, the subtype of the epithelial cells was significantly altered. They underwent an intricate process including inflammation, damage, and repair during bladder remodeling. Overall, this work constructed the first single‐cell atlas for obstruction‐induced DUA, which could provide a valuable resource for deciphering the cellular heterogeneity and function changes in DUA, as well as potential strategies for bladder function improvement.

Background: Urinary incontinence (UI) is a common health problem that affects the quality of life and health of millions of people in the United States (US). We aimed to investigate the association between sitting time and UI symptoms in the US population. Methods: A cross-sectional survey of participants aged 20 and above from the National Health and Nutrition Examination Survey 2007–2018 was performed. A self-report questionnaire that reported complete data on UI, sitting time and covariates was included. Weighted multivariable logistic and regression models were used to assess the association between sitting time and UI symptoms. Results: A total of 22,916 participants were enrolled. Prolonged sitting time was associated with urgency UI (UUI, odds ratio [OR] = 1.2, 95% confidence interval [CI] = 1.1 to 1.3, p = 0.001). Compared with patients with sitting a time shorter than 7 hours (h), moderate recreational activity modified the association between sitting time and mixed UI in males in the fully adjusted model (OR = 2.5, 95% CI = 1.4 to 4.5, p = 0.002). A sitting time over 7 h was related to mixed UI (MUI, OR = 1.6, 95% CI = 1.1 to 2.2, p = 0.01) in males, and stress UI (SUI, OR = 0.9, 95% CI = 0.8 to 0.98, p = 0.03) in females. However, no significant difference was found among the UI, SUI, and MUI groups in fully adjusted model. Conclusions: A prolonged sitting time (≥7 h) was associated with UUI symptoms in all populations, SUI symptoms in females and MUI symptoms in males compared with sitting time lower than 7 h. Compared with those sit shorter than 7 h, moderate recreational activity may be a modifier between prolonged sitting and MUI symptoms in male participants, which warrants further studies for confirmation.

Purpose: No consensus exists about the causal relationship between vitamin D (VD) and male factor infertility due to heterogeneity and confounding factors even in randomized controlled trials (RCTs). This study aimed to investigate the causal association between 25 hydroxyvitamin D (25OHD) levels and male factor infertility through Mendelian randomization (MR) and provide complementary information for optimization of future RCTs. Materials and Methods: Two-sample MR analyses with four steps were performed. Single-nucleotide polymorphisms (SNPs) for VD were extracted from 417,580 Europeans in the UK Biobank, and the summary-level data of male factor infertility (825 cases and 85,722 controls) were extracted from the FinnGen. Results: Totally 99 SNPs robustly associated with the 25OHD were included, and a 1-unit increase in genetically predicted natural-log transformed 25OHD levels was associated with decreased risk of male factor infertility (odds ratio [OR], 0.62; 95% confidence interval [CI], 0.44–0.89; p=0.010), which was consistent in all three sensitivity analyses (MR-Egger, weighted median, and weighted mode methods). The conclusion still stands after removing SNPs which explained more variation in the male factor infertility than the 25OHD (OR, 0.61; 95% CI, 0.42–0.88; p=0.009; n=62), and which were associated with confounders (body mass index, type 2 diabetes, smoking, and coronary artery diseases) of male factor infertility (OR, 0.58; 95% CI, 0.39–0.85; p=0.005; n=55). Conclusions: VD supplement to increase serum 25OHD levels may be clinically beneficial for male factor infertility in the general population. The well-designed RCTs should be performed in priority to address this question.

Abstract Background The impact of fibroblasts on the immune system provides insight into the function of fibroblasts. In various tissue microenvironments, multiple fibroblast subtypes interact with immunocytes by secreting growth factors, cytokines, and chemokines, leading to wound healing, fibrosis, and escape of cancer immune surveillance. However, the specific mechanisms involved in the fibroblast‐immunocyte interaction network have not yet been fully elucidated. Main body and conclusion Therefore, we systematically reviewed the molecular mechanisms of fibroblast‐immunocyte interactions in fibrosis, from the history of cellular evolution and cell subtype divisions to the regulatory networks between fibroblasts and immunocytes. We also discuss how these communications function in different tissue and organ statuses, as well as potential therapies targeting the reciprocal fibroblast‐immunocyte interplay in fibrosis. A comprehensive understanding of these functional cells under pathophysiological conditions and the mechanisms by which they communicate may lead to the development of effective and specific therapies targeting fibrosis.

Abstract Background Fumarate hydratase–deficient renal cell carcinoma (FH-RCC) is a rare highly aggressive subtype of kidney cancer for which the distinct genomic, transcriptomic, and evolutionary relationships between metastatic and primary lesions are still unclear. Methods In this study, whole-exome, RNA-seq, and DNA methylation sequencing were performed on primary-metastatic paired specimens from 19 FH-RCC cases, including 23 primary and 35 matched metastatic lesions. Phylogenetic and clonal evolutionary analyses were used to investigate the evolutionary characteristics of FH-RCC. Transcriptomic analyses, immunohistochemistry, and multiple immunofluorescence experiments were performed to identify the tumor microenvironmental features of metastatic lesions. Results Paired primary and metastatic lesions generally showed similar characteristics of tumor mutation burden, tumor neoantigen burden, microsatellite instability score, CNV burden, and genome instability index. Notably, we identified an FH-mutated founding MRCA (the most recent common ancestor) clone that dominated the early evolutionary trajectories in FH-RCC. Although both primary and metastatic lesions manifested high immunogenicity, metastatic lesions exhibited higher enrichment of T effector cells and immune-related chemokines, together with upregulation of PD-L1, TIGIT, and BTLA. In addition, we found that concurrent NF2 mutation may be associated with bone metastasis and upregulation of cell cycle signature in metastatic lesions. Furthermore, although in FH-RCC metastatic lesions in general shared similar CpG island methylator phenotype with primary lesions, we found metastatic lesions displaying hypomethylated chemokine and immune checkpoints related genomic loci. Conclusions Overall, our study demonstrated the genomic, epigenomic, and transcriptomic features of metastatic lesions in FH-RCC and revealed their early evolutionary trajectory. These results provided multi-omics evidence portraying the progression of FH-RCC.

Abstract Background Many observational epidemiology studies discovered that kidney cancer and impaired kidney function have a bidirectional relationship. However, it remains unclear whether these two kinds of traits are causally linked. In this study, we aimed to investigate the bidirectional causal relation between kidney cancer and kidney function biomarkers (creatinine‐based estimated glomerular filtration rate (eGFRcrea), cystatin C‐based estimated glomerular filtration rate (eGFRcys), blood urea nitrogen (BUN), serum urate, and urinary albumin‐to‐creatinine ratio (UACR)). Methods For both directions, single‐nucleotide polymorphisms (SNPs), as genetic instruments, for the five kidney function traits were selected from up to 1,004,040 individuals, and SNPs for kidney cancer were from 408,786 participants(1338 cases). In the main analysis, we applied two state‐of‐the‐art MR methods, namely, contamination mixture and Robust Adjusted Profile Score to downweight the effect of weak instrument bias, pleiotropy, and extreme outliers. We additionally conducted traditional MR analyses as sensitivity analyses. Summary‐level data of European ancestry were extracted from UK Biobank, Chronic Kidney Disease Genetics Consortium, and Kaiser Permanente. Results Based on 99 SNPs, we found that the eGFRcrea had a significant negative causal effect on the risk of kidney cancer (OR = 0.007, 95% CI:2.6 × 10−4–0.569, p = 0.041). After adjusting for body composition or diabetes, urate had a significant negative causal effect on kidney cancer (OR

TFE3-translocation renal cell carcinoma (TFE3-tRCC) is a rare subtype of kidney cancer with no standard treatment options for the advanced disease. Here, the authors perform genomic and transcriptomic profiling of 63 untreated primary TFE3-tRCC tumours and reveal potential therapeutic targets.

The relationship between vitamin E intake or circulating α-tocopherol and various health outcomes is still debatable and uncertain. We conducted an umbrella review to identify the relationships between vitamin E intake or circulating tocopherol and health outcomes by merging and recalculating earlier meta-analyses. The connections that were found to be statistically significant were then classified into different evidence levels based on p values, between-study heterogeneity, prediction intervals, and small study effects. We finally included 32 eligible meta-analyses with four vitamin E sources and 64 unique health outcomes. Only the association between circulating α-tocopherol and wheeze or asthma in children was substantiated by consistent evidence. Suggestive evidence was suggested for seven results on endothelial function (supplemental vitamin E): serum C-reactive protein (CRP) concentrations (supplemental vitamin E), cervical cancer (dietary vitamin E), esophageal cancer (dietary vitamin E), cervical intraepithelial neoplasia (CIN, dietary vitamin E), pancreatic cancer (total vitamin E intake), and colorectal cancer (circulating α-tocopherol levels); all of these showed a protective effect consistent with the vitamin E source. In conclusion, our work has indicated that vitamin E is protective for several particular health outcomes. Further prospective studies are required when other factors that may contribute to bias are considered.

BackgroundStudies have reported that diabetes is related to the prognosis of upper tract urothelial carcinoma (UTUC) after radical nephroureterectomy (RNU), but this conclusion is still controversial. Here, we performed a meta-analysis to comprehensively explore the association between diabetes and UTUC prognosis.MethodsIn November 2020, we searched PubMed, Web of science and the Cochrane Library to find relevant studies that evaluated the effect of diabetes on the prognosis of UTUC. The Newcastle Ottawa Scale was used to assess the quality of the literature. Review Manager 5.3 was used to pool cancer-specific survival (CSS), overall survival (OS), recurrence-free survival (RFS) and intravesical recurrence (IVR).ResultsA total of 10 studies with 11,303 patients were included in this meta-analysis. Our pooled results showed that diabetes did not affect the survival outcome of UTUC, including CSS (HR: 1.33, 95% CI: 0.89-1.98; P = 0.16), OS (HR: 1.18, 95% CI: 0.77-1.80; P = 0.45) and RFS (HR: 1.37, 95% CI: 0.91-2.05; P = 0.13). However, diabetes increased the risk of IVR of UTUC patients (HR: 1.26, 95% CI: 1.11-1.43; P = 0.0004).ConclusionAlthough diabetes has no significant impact on the survival outcomes of UTUC after RNU, it increases the risk of IVR. Therefore, special attention should be paid to monitoring the IVR for UTUC patients with diabetes and the necessity of appropriate intravesical adjuvant treatment when needed.

Abstract Background Although the indications of minimally invasive treatments for pediatric urolithiasis are similar to those in adults, it is still crucial to make the right treatment decision due to the special considerations of children. This review aims to evaluate the efficacy and safety of extracorporeal shockwave lithotripsy (SWL), percutaneous nephrolithotomy (PCNL), and retrograde intrarenal surgery (RIRS) in the management of pediatric upper urinary tract stones. Methods EMBASE, PubMed, and the Cochrane Library were searched from their first available date to March 2018. The studies that meet the inclusive criteria were included. The efficacy and safety of the treatments were assessed by means of meta-analysis of the stone free rate (SFR), complication rate, effectiveness quotient (EQ) and secondary outcome indicators. Results A total of 13 comparative studies were identified for data analysis. PCNL presented a significantly higher SFR compared with SWL. Similarly, the single-session SFR of RIRS was significantly higher than SWL. However, no significant difference was found between RIRS and SWL in the overall SFR. There was no significant difference between PCNL and RIRS in the SFR. Furthermore, no significant differences in complication rates were found among the three therapies. Compared with the other two treatments, PCNL had a longer operative time, fluoroscopy time and hospital stay. SWL had a shorter hospital stay, higher retreatment rate and auxiliary rate in comparison with the other two treatments. The present data also showed that PCNL presented a higher EQ than the other two treatments, and RIRS had a lower efficiency than SWL and PCNL. In the subgroup analysis of pediatric patients with stone ≤20 mm, the comparative results were similar to those described above, except for the higher complication rate of PCNL than SWL. Conclusions Although SWL as an outpatient procedure provides shorter hospital stay and reduces operative time, it has a lower SFR and higher retreatment rate than the other two treatments. PCNL exhibits a higher SFR and EQ than SWL; nevertheless, it has a longer operative time and fluoroscopy time than the other two procedures. RIRS offers a similar SFR as PCNL but a lower efficiency than PCNL.

Abstract Background Conflicting evidence exists regarding the effect of hypertension on the prognosis of metastatic renal cell carcinoma (mRCC) patients treated with tyrosine kinase inhibitors (TKIs). This study aimed to assess the predictive value of TKIs-induced hypertension in patients with mRCC. Methods This study was registered in PROSPERO (CRD42019129593). PubMed, Embase, Web of Science and the Cochrane Library database were searched with terms: “renal cell carcinoma”, “hypertension”, “blood pressure”, “tyrosine kinase inhibitor”, “sunitinib”, “axitinib”, “sorafenib” and “pazopanib” until March 21, 2019. Hazard Ratios (HR) and 95% confidence intervals (CI) for progression-free survival (PFS) or overall survival (OS) were extracted and analyzed with Stata 15.0 software. Heterogeneity was assessed using the I2 value. Meta-regression, subgroup analysis and sensitivity analysis were also performed to explore heterogeneity. Publication bias was assessed with funnel plots and precisely assessed by Egger’s and Begg’s tests. The quality of evidence of outcomes was generated according to the Grading of Recommendations Assessment, Development, and Evaluation (GRADE). Results A total of 4661 patients from 22 studies were included in the study. The results showed that the increase of blood pressure was an effective predictor for longer PFS (HR = 0.59, 95% CI: 0.48–0.71, p < 0.001; I2 = 77.3%) and OS (HR = 0.57, 95% CI: 0.45–0.70, p < 0.001; I2 = 77.4%) of patients with mRCC. Subgroup analysis revealed that patients receiving sunitinib and pazopanib could have longer PFS and OS. Conclusions This study indicated that TKIs-induced hypertension may be a good predictor for better prognosis of patients with mRCC receiving TKIs treatment, especially using sunitinib or pazopanib.

Abstract Background Barbed sutures can avoid knot tying and speed the suture placement in the PN(partial nephrectomy). On account of the impact on clinical outcomes are ambiguous, this study is determined to identify the application of barbed suture during PN. Methods ClinicalTrials.gov, Cochrane Register of Clinical Studies, PubMed and EMBASE were searched for RCTs(randomized controlled trials) and cohort studies focusing on the comparison of barbed and traditional sutures in PN(last updated on Feb in 2015). According to Cochrane Library’s suggestion, quality assessment was performed. Review Manager was applied to analyze all the data and sensitivity analyses were performed through omitting each study sequentially. Results Eight cohort studies and none of RCTs proved eligible (risk of bias: moderate to low,431 patients). Warm ischemia time(MD = − 6.55,95% CI -8.86 to − 4.24, P

Objective: To compare the efficacy and safety of current systemic combination therapies for patients with mHSPC and help select candidates for optimal treatment.Methods: Databases of MEDLINE and EMBASE, Cochrane Central Register of Controlled Trials, and Clinical Trial.gov were searched for eligible studies. Direct and network meta-analysis were conducted to compare various systemic combination therapies and the surface under the cumulative ranking curve (SUCRA) was generated for treatment ranking. Subgroup analyses were performed according to the extent of metastasis. Adverse events (AEs) were compared among the effective treatments.Results: Ten trials with 16 publications were included in this network meta-analysis. Direct and network meta-analysis consistently suggested that androgen-deprivation therapy (ADT) combined with docetaxel, abiraterone, enzalutamide, or apalutamide could significantly improve overall survival (OS) and failure-free survival (FFS) compared to ADT alone in men with mHSPC. SUCRA analysis demonstrated the superiority of ADT plus abiraterone or enzalutamide over other therapies. Subgroup analyses indicated that additional abiraterone to ADT had the highest ranking in patients with high-volume diseases or visceral metastases and enzalutamide plus ADT outperformed other treatments in patients with low-volume diseases or without visceral metastases. Different combination therapies had variable AE profiles and ADT in addition with docetaxel or abiraterone had the highest risk of AEs.Conclusion: ADT plus docetaxel, abiraterone, enzalutamide, or apalutamide were associated with significantly improved survival in patients with mHSPC. ADT plus abiraterone or enzalutamide appeared to be the most effective treatments. Clinicians should balance the efficacy, potential AEs, and disease status to select the optimal treatment.

In Asia, about 1%–19.1% of the population suffer from urolithiasis. However, due to variations in socio-economic status and geographic locations, the prevalence and incidence have changed in different countries or regions over the years. The research for risk factors of urinary tract stones is of predominant importance. In this review, we find the prevalence of urolithiasis is 5%–19.1% in West Asia, Southeast Asia, South Asia, as well as some developed countries (South Korea and Japan), whereas, it is only 1%–8% in most part of East Asia and North Asia. The recurrence rate ranges from 21% to 53% after 3–5 years. Calcium oxalate (75%–90%) is the most frequent component of calculi, followed by uric acid (5%−20%), calcium phosphate (6%−13%), struvite (2%−15%), apatite (1%) and cystine (0.5%−1%). The incidence of urolithiasis reaches its peak in population aged over 30 years. Males are more likely to suffer from urinary calculi. Because of different dietary habits or genetic background, differences of prevalence among races or nationalities also exist. Genetic mutation of specific locus may contribute to the formation of different kinds of calculi. Dietary habits (westernized dietary habits and less fluid intake), as well as climatic factors (hot temperature and many hours of exposure to sunshine) play a crucial role in the development of stones. Other diseases, especially metabolic syndrome, may also contribute to urinary tract stones. Keywords: Urolithiasis, Epidemiology, Prevalence, Incidence, Component, Risk factors

Background/Aims: Overactive bladder associated with bladder outlet obstruction (BOO) is a highly prevalent condition, which is usually treated with antimuscarinics. However, the potential effects of antimuscarinics on the structure and function of bladder have not been investigated thus far. Methods: Sprague-Dawley(R) rats accepted bladder neck obstruction surgery or sham surgery, and then received treatment of three different antimuscarinics (Solifenacin, Darifenacin, and Tolterodine) or vehicle. After 3, 6 and 12 weeks, the bladder function and structure were measured. The effect of antimuscarinics on cellular alteration in vitro was observed under mechanical stimulation. Bladder morphology were examined by immunohistochemistry, and the bladder function were investigated by cystometry and strip contractility test. The expression of muscarinic receptors and inflammatory cytokines were measured by PCR and Western blotting. Results: Here we demonstrate, both in vitro and in vivo, that antimuscarinics are protective regulators for the bladder structure and function. Antimuscarinics decrease the weight of bladders with BOO. Antimuscarinics improve the voiding parameter and enhance the contraction of bladder smooth muscle. The results also show that antimuscarinics inhibit the proliferation of bladder smooth muscle cells both in vivo and in vitro, it can reduce the collagen deposition and inflammatory cytokines in bladders with BOO. During this process, the expression of M2 and M3 receptors was altered by antimuscarinics. Conclusion: Antimuscarinics could reverse the structural and functional changes of BOO bladder wall at cellular and tissue level, and the alteration of M2 and M3 receptors may be involved in this biological process.

Background: Kidney stones are among the most common urological conditions affecting ~9% of the world population. Although some unhealthy diets and unhealthy lifestyles are reportedly risk factors for kidney stone, the association between daily sitting time and kidney stone has not been explored. Materials and Methods: This large-scale, cross-sectional study was conducted using data from the National Health and Nutrition Examination Survey (NHANES) database 2007-2016. Kidney stone history and daily sitting time were retrieved from the questionnaire and 24 hour (h) recall interviews. Logistic regression and subgroup analysis were conducted to investigate the association. The analysis was further stratified by vigorous recreational activity. Results: A total of 19 188 participants aged =20 years with complete information were included in this study. The overall prevalence of kidney stone was 9.6%. Among participants without vigorous recreational activity, a trend towards an increasing prevalence of kidney stone was observed with increased daily sitting time. However, the trend was not observed in individuals who participated in vigorous recreational activity, as they experienced a decreased risk of kidney stone despite having a daily sitting time of 6-8 h (crude model OR=0.659, 95% CI: 0.457-0.950, P=0.028), indicating that vigorous recreational activity may partially attenuate the detrimental effect of prolonged sitting time. Conclusion: Our study revealed an increasing trend of prevalence of kidney stone with increased daily sitting time among the population not performing vigorous recreational activity despite the difference was nonsignificant. Vigorous recreational activity may modify the association between daily sitting time and kidney stone. More prospective cohort studies are warranted to further examine this association. [ABSTRACT FROM AUTHOR]

Background: Circulating tumor DNA (ctDNA) has emerged as a noninvasive technique that provides valuable insights into molecular profiles and tumor disease management. This study aimed to evaluate the prognostic significance of circulating tumor DNA (ctDNA) in urothelial carcinoma (UC) through a systematic review and meta-analysis. Methods: A comprehensive search was conducted in MEDLINE, EMBASE, and the Cochrane Library from the inception to December 2023. Studies investigating the prognostic value of ctDNA in UC were included. Hazard ratios (HRs) of disease-free survival (DFS) and overall survival (OS) were extracted. Overall meta-analysis and subgroup exploration stratified by metastatic status, ctDNA sampling time, treatment type, and detection method was performed using the R software (version 4.2.2). Results: A total of 16 studies with 1725 patients were included. Fourteen studies assessed the association between baseline ctDNA status and patient outcomes. Patients with elevated ctDNA levels exhibited significantly worse DFS (HR=6.26; 95% CI: 3.71-10.58, P<0.001) and OS (HR=4.23; 95% CI: 2.72-6.57, P<0.001) regardless of metastatic status, ctDNA sampling time, treatment type, and detectionmethods. Six studies evaluated the prognostic value of ctDNA dynamics in UC. Patients who showed a decrease or clearance in ctDNA levels during treatment or observation demonstrated more favorable DFS (HR=0.26, 95% CI: 0.17-0.41, P<0.001) and OS (HR=0.21, 95% CI: 0.11-0.38, P<0.001) compared to those who did not. The association remained consistent across the subgroup analysis based onmetastatic status and detectionmethods. In the immune checkpoint inhibitor-treated setting, both lower baseline ctDNA level and ctDNA decrease during the treatment were significantly associated with more favorable oncologic outcomes. Furthermore, specific gene mutations such as FGFR3 identified in ctDNA also demonstrated predictive value in UC patients. Conclusion: This meta-analysis demonstrates a strong association of ctDNA status and its dynamic change with survival outcomes in UC, suggesting substantial clinical utility of ctDNA testing in prognosis prediction and decision making in this setting. [ABSTRACT FROM AUTHOR]

Objectives: Various new positions for percutaneous nephrolithotomy (PCNL) were proposed to reduce the limitations of the traditional position. This study was aimed to evaluate the efficacy and safety of the different PCNL positions. Methods: PubMed, Embase, Web of Science, and the Cochrane Library were searched for relevant randomized controlled trials (RCTs) up to 18 April 2023. The authors collected five common surgical positions used for PCNL: oblique supine position (OSP), supine position (SP), flank position (FP), split-leg oblique supine/flank position (SLP), and prone position (PP). Paired and network meta-analysis were conducted to compare relevant outcomes, including complications, operative time, stone-free rates, hospital stay, and hemoglobin loss among these different positions. Results: The study included 17 RCTs with a total of 1841 patients. The result demonstrated that SLP significantly outperformed in terms of decreasing operation time (FP vs SLP MD-MD-41.65; OSP vs SLP MD 28.97; PP vs SLP MD 34.94), hospital stay, and hemoglobin loss. Ranking probabilities showed SLP had highest stone-free rate. Prone position was more likely to occur complications than others. Based on SMAA model, the benefit-risk analysis suggested the SLP was the optimal position in PCNL. Conclusions: For PCNL, the split-leg, flank, supine, and OSPs are as secure as the prone position. Further RCTs are necessary to confirm the outstanding safety and efficacy of split-leg position. Besides, the position should be selected regard for the patient's demands, the surgeon's preference and learning curve. [ABSTRACT FROM AUTHOR]

Background: Management of complicated posterior urethral stricture is challenging. Modified transperineal anastomotic urethroplasty (TAU) with bulbocavernosus flap interposition and human fibrin sealant provides another treatment option. The authors aimed to evaluate whether this technique could improve the success rate in the complicated posterior urethral stricture reconstruction in this study. Materials and methods: Between 2016 and 2019, 48 patients underwent either conventional or modified TAU. The criteria for success included both the absence of clinical symptoms and no need for further surgical intervention during follow-up. Results: Twelve patients underwent the modified TAU (group A) using bulbocavernosus flap interposition and human fibrin sealant. Thirty-six patients underwent the traditional end-to-end anastomotic urethroplasty (group B). Follow-up was 24.3-57.2 months. The patients in group A had a higher surgery success rate compared to the patients in group B (91.7 vs. 63.9%, P=0.067), with a quasisignificant result. Besides, no postoperative complications were observed in group A, while two individuals in group B had urinary incontinence, but the difference was not significant (0 vs. 5.6%, P= 0.404). Conclusion: Based on the preliminary results, modified TAU with bulbocavernosus flap interposition and human fibrin sealant is a safe and feasible technique for complicated posterior urethral stricture reconstruction. [ABSTRACT FROM AUTHOR]

Methylation modifications help better understand the pathogenesis of upper tract urothelial carcinoma. A total of 11 eligible studies regarding DNA methylation alterations were included in this meta-analysis. Twelve methylated genes were found to be significant in the diagnosis or prognostic outcome of UTUC, including tumor recurrence, progression, and mortality. Candidate biomarkers with essential diagnosis and prognosis function might provide precision medicine references for personalized therapies. Purpose: Numerous studies suggested methylation modifications play an important role in upper tract urothelial carcinoma (UTUC), but few have depicted DNA methylation architecture on the pathological process of UTUC. We aimed to better understand the pathogenesis of UTUC and provide precision medicine references when managing UTUC patients. Methods: PubMed, Cochrane Library, EMBASE, and Scopus were searched for UTUC until December 31, 2020. Methodological quality assessment was conducted according to NIH recommendations. Meta-analysis was conducted to assess the prognostic effect of methylated genes. Kaplan-Meier survival analyses were performed to validate methylated genes and cytosine-phosphate-guanine (CpG) sites. Results: Eleven studies (3619 patients) were eligible to investigate 12 methylated genes and 10 CpGs. The quality of all the studies was fair to good. Meta-analysis found the pooled effect of eligible methylated genes had a low risk of tumor recurrence (HR = 0 ·67; 95% CI: 0 ·51-0 ·87; P = ·003), but a high risk of tumor progression (HR = 1 ·60; 95% CI: 1 ·17-2 ·18; P = ·003) and cancer-specific mortality (HR = 1 ·35; 95% CI: 1 ·06-1 ·72; P = ·01). For individual methylation status of GDF15, HSPA2, RASSF1A, TMEFF2, and VIM, the pooled effect of each gene was found pleiotropic on both diagnosis and prognosis. Survival analysis suggested higher methylation of SPARCL1 had a better disease-specific survival (P = ·048). Conclusion: We combined metaanalysis and Kaplan-Meier survival analysis using the most updated evidence on the methylation of UTUC. Candidate biomarkers with essential diagnosis and prognosis function might provide precision medicine references for personalized therapies. [ABSTRACT FROM AUTHOR]