A new technique for the treatment of ureteric stricture after kidney transplantation.

OBJECTIVE: To evaluate the safety and effectiveness of endoscopic treatments with Allium® metal ureteric stent (AMUS) for ureteric strictures after kidney transplantation (KT). PATIENTS AND METHODS: In a prospective manner, we gathered clinical data from 68 patients who underwent endoscopic treatments with AMUS for ureteric strictures after KT between January 2019 and March 2022. The definition of surgical success was the unobstructed drainage of the AMUS, or in cases where there was AMUS migration, occlusion or encrustation and subsequently removed, there is no worsening of renal hydronephrosis in the patient during the follow-up period. RESULTS: Based on the specific circumstances of the ureteric strictures, three distinct types of surgery were selected for treatment. The overall success rate of endoscopic treatments for ureteric strictures following KT was 90% (61/68) during a follow-up period of 1 year. Surgical complications included haematuria (18%), pain (10%), urinary tract infections (7.4%), and lower urinary tract symptoms (7.4%). The incidences of stent migration, occlusion, and encrustation were 10%, 2.9%, and 1.5%, respectively. Postoperatively, significant improvements were observed in various parameters. At 1 month after surgery, there was a notable decrease in blood creatinine levels (105.5 vs 90.4 mol/L), urea nitrogen levels (6.6 vs 5.4 mmol/L), and hydronephrosis volume (64.4 vs 43.9 mL). Additionally, the serum estimated glomerular filtration rate increased from 49.5 to 64.4 mL/min/1.73 m2. The follow-up results of patients at 1 year after surgery were similar to those observed at 1 month after surgery. CONCLUSIONS: Systemic endoscopic treatments with AMUS were found to be safe and effective for ureteric strictures after KT with short-term follow-ups. This technique offers a novel option for the treatment of post-KT strictures.

Association between daily sitting time and kidney stones based on the National Health and Nutrition Examination Survey (NHANES) 2007-2016: A cross-sectional study.

BACKGROUND: Kidney stones are among the most common urological conditions affecting approximately 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 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 19188 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 to 8 hours (crude model OR=0.659, 95% CI: 0.457 to 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.

UPK3A+ umbrella cell damage mediated by TLR3-NR2F6 triggers programmed destruction of urothelium in Hunner-type interstitial cystitis/painful bladder syndrome.

Urothelial damage and barrier dysfunction emerge as the foremost mechanisms in Hunner-type interstitial cystitis/bladder pain syndrome (HIC). Although treatments aimed at urothelial regeneration and repair have been employed, their therapeutic effectiveness remains limited due to the inadequate understanding of specific cell types involved in damage and the lack of specific molecular targets within these mechanisms. Therefore, we harnessed single-cell RNA sequencing to elucidate the heterogeneity and developmental trajectory of urothelial cells within HIC bladders. Through reclustering, we identified eight distinct clusters of urothelial cells. There was a significant reduction in UPK3A+ umbrella cells and a simultaneous increase in progenitor-like pluripotent cells (PPCs) within the HIC bladder. Pseudotime analysis of the urothelial cells in the HIC bladder revealed that cells faced challenges in differentiating into UPK3A+ umbrella cells, while PPCs exhibited substantial proliferation to compensate for the loss of UPK3A+ umbrella cells. The urothelium in HIC remains unrepaired, despite the substantial proliferation of PPCs. Thus, we propose that inhibiting the pivotal signaling pathways responsible for the injury to UPK3A+ umbrella cells is paramount for restoring the urothelial barrier and alleviating lower urinary tract symptoms in HIC patients. Subsequently, we identified key molecular pathways (TLR3 and NR2F6) associated with the injury of UPK3A+ umbrella cells in HIC urothelium. Finally, we conducted in vitro and in vivo experiments to confirm the potential of the TLR3-NR2F6 axis as a promising therapeutic target for HIC. These findings hold the potential to inhibit urothelial injury, providing promising clues for early diagnosis and functional bladder self-repair strategies for HIC patients. © 2024 The Pathological Society of Great Britain and Ireland.

Association between Sitting Time and Urinary Incontinence in the US population: Data from the National Health and Nutrition Examination Survey (NHANES) 2007 to 2018.

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.

Crosstalk between fibroblasts and immunocytes in fibrosis: From molecular mechanisms to clinical trials.

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.

Metal ureteral stents for ureteral stricture: 2 years of experience with 246 cases.

BACKGROUND: Metal ureteral stents (MUS) has gained popularity as an endoscopic treatment alternative for the management of ureteral strictures. The aim of this study was to evaluate the safety, efficacy, and tolerability of MUS for treating ureteral strictures and to identify any factors that could influence the success of this intervention. METHODS: This study is a prospective analysis of the efficacy and safety of MUS for treating ureteral strictures in a single-center setting. The study enrolled 246 patients who had been diagnosed with ureteral strictures and had undergone MUS placement between January 2019 and July 2021. The patients were followed-up for a duration of 2 years. RESULTS: The overall success rate of MUS placement was 71.7%. Furthermore, the success rate of ureteral strictures after kidney transplantation (78.2%) was significantly higher than common ureteral strictures (73.0%) or recurrent ureteral strictures (67.6%). Additionally, postsurgery, there was a considerable reduction in hydronephrosis volume (68.9±96.1 vs. 32.1±48.8 cm 3 ), blood creatinine level (103.7±49.8 vs. 94.4±47.5 mol/l) and urea nitrogen level (6.7±7.2 vs. 5.1±2.4 mmol/l). The study also reported that the rate of adverse events associated with MUS was relatively low, included hematuria (7.9%), pain (6.8%), urinary tract infection (6.4%), and lower urinary tract symptoms (5.3%). CONCLUSIONS: MUS appear to be a safe and effective treatment option for ureteral strictures, with a high success rate and low complication rate. These results have important implications for the management of ureteral strictures and can help guide clinical decision-making in the selection of treatment options.

ß-Adrenoceptors regulate urothelial inflammation and zonula occludens in the bladder outlet obstruction model.

BACKGROUND: The purpose of this study was to evaluate the effects of ß-adrenoceptors (ADRBs) on the urothelial inflammation and zonula occludens (ZO) in a rat PBOO model and in an in vitro model. METHODS: The PBOO model was established by ligating the bladder neck of rats. Twenty rats were divided into 4 groups: sham operation, PBOO + normal saline, PBOO + ADRB2 agonist, PBOO + ADRB3 agonist. PBOO rats were with treated with ADRBs agonists for 3 weeks. Human urothelial cells (HUCs) were subjected to ADRBs agonist treatment or hydrostatic pressure in an in vitro model. RESULTS: In the PBOO group, there was a significant increase in the expression of MCP-1, IL-6 and RANTES compared to the sham group. By contrast, there was a post-PBOO decline in the expression of ZO-1 and ZO-2 in the urothelium. ADRB2 or ADRB3 agonists exhibited downregulated inflammatory cytokine expression and increased ZO expression in the PBOO model. The regulation of inflammation and ZO by ADRB2 and ADRB3 agonists in an in vitro model was found consistent with that in the PBOO model. Moreover, RhoA and ROCK inhibitors suppressed the expression of hydrostatic pressure-induced inflammatory cytokines. Additionally, RhoA agonist reversed the inhibitory effect of ADRBs agonists on the inflammatory secretion from HUCs. CONCLUSIONS: ADRB2 and ADRB3 agonists increased ZO protein expression in HUCs in a rat PBOO model and in an in vitro model. Furthermore, ADRB2 and ADRB3 agonists inhibited the secretion of inflammatory cytokines from HUCs by regulating the RhoA/ROCK signaling pathways.

Association Between Sleep Duration and Urinary Incontinence in Female Adults: A Cross-sectional Study in National Health and Nutrition Examination Survey 2007-2018.

OBJECTIVE: To elaborate on the effect of sleep duration on urinary incontinence (UI), we investigated the association between sleep duration with the risk of UI from the National Health and Nutrition Examination Survey (NHANES) dataset. METHODS: A cross-sectional survey of female participants aged 20years old and above were enrolled from the year 2007-2018. We performed weighted multivariable logistic regression models to assess the association between sleep duration and UI. RESULTS: A total of 6838 female participants were included. Compared with sleep duration less than 6 hours, other sleep duration was found to be not significantly correlated with total UI, stress urinary incontinence, and mixed urinary incontinence in all three models Compared to sleep duration less than 6 hours, multivariate regression demonstrated that moderate sleep (6-8 hours) indicated a lower urgent urinary incontinence (UUI, odds ratio=0.764, 95% confidence interval=0.620-0.944, P = .013). Inadequate sleep (<6 hours) indicated a higher UUI (odds ratio=1.308, 95% confidence interval=1.060-1.614, P = .013) compared to moderate sleep duration (6-8 hours). The association might be modified by the family income-to-poverty ratio. CONCLUSION: Inadequate sleep (<6 hours) was associated with a higher incidence of UUI. A moderate sleep duration (6-8 hours) was related to a lower rate of UUI. Further studies are warranted for clinical prevention and treatment guidance.

Association between marijuana use and kidney stone: a cross-sectional study of NHANES 2009 to 2018.

Objective: The purpose of this investigation is to determine whether regular marijuana use is related to history of kidney stones in the US population. Methods: Data were obtained from the National Health and Nutrition Examination Survey (NHANES) from 2009 to 2018. Kidney stone and marijuana use data were collected from self-report questionnaires. Multivariate logistic regression and multiple sensitivity analyses were applied to examine the relationship between marijuana usage and kidney stones. Results: There are approximately 26.04% of the US population have admitted to using marijuana in their lifetime. Compared with none regular users, those with a higher frequency of marijuana use were more males, more non-Hispanic races, lower than high school education, overweight, no recreational activity, without diabetes mellitus, and more coronary heart disease. After adjusting for potential confounders, multivariate regression analysis demonstrated that marijuana use was inversely correlated to kidney stones in males (Odds ratio [OR] = 0.72, 95% Confidence interval [CI] = 0.54-0.97). One to seven times/week regular consumption of marijuana was associated with kidney stones in males (OR = 0.62, 95% CI = 0.43-0.89). Sensitivity analyses validated the robustness of our outcomes. Conclusion: Our findings revealed that regular marijuana male users were inversely associated with kidney stones. Marijuana use one to six times/week was inversely related to the risk of kidney stones in males. Further studies are required to explore the dose and type associations of marijuana with kidney stones.

Association between urinary phthalate metabolites and nephrolithiasis in adults: A cross-sectional analysis with NHANES 2007-2018.

Nephrolithiasis is highly prevalent and brings health and economic burdens to patients. The augmentation of nephrolithiasis may be associated with exposure to phthalate metabolites. However, few studies investigated the effect of various phthalates exposure on nephrolithiasis. We analyzed data from 7139 participants aged 20 years or above from the National Health and Nutrition Examination Survey (NHANES) 2007-2018. Serum calcium level-stratified univariate and multivariate linear regression analyses were performed to explore the relationship between urinary phthalate metabolites and nephrolithiasis. As a result, the prevalence of nephrolithiasis was approximately 9.96%. After adjusting for confounding factors, associations were found between serum calcium concentration with monoethyl phthalate (P = 0.012) and mono-isobutyl phthalate (P = 0.003) compared with tertile 1 (T1). In adjusted analysis, nephrolithiasis was positively associated with middle and high tertiles of mono benzyl phthalate (P < 0.05) compare with low tertile group. Furthermore, high-level exposure to mono-isobutyl phthalate had a similar positive association with nephrolithiasis (P = 0.028). Our findings provide evidence that exposure to certain phthalate metabolites (i.e. MiBP and MBzP) may be associated with a high risk of nephrolithiasis depending on serum calcium level.

Cellular mechanotransduction in health and diseases: from molecular mechanism to therapeutic targets.

Cellular mechanotransduction, a critical regulator of numerous biological processes, is the conversion from mechanical signals to biochemical signals regarding cell activities and metabolism. Typical mechanical cues in organisms include hydrostatic pressure, fluid shear stress, tensile force, extracellular matrix stiffness or tissue elasticity, and extracellular fluid viscosity. Mechanotransduction has been expected to trigger multiple biological processes, such as embryonic development, tissue repair and regeneration. However, prolonged excessive mechanical stimulation can result in pathological processes, such as multi-organ fibrosis, tumorigenesis, and cancer immunotherapy resistance. Although the associations between mechanical cues and normal tissue homeostasis or diseases have been identified, the regulatory mechanisms among different mechanical cues are not yet comprehensively illustrated, and no effective therapies are currently available targeting mechanical cue-related signaling. This review systematically summarizes the characteristics and regulatory mechanisms of typical mechanical cues in normal conditions and diseases with the updated evidence. The key effectors responding to mechanical stimulations are listed, such as Piezo channels, integrins, Yes-associated protein (YAP) /transcriptional coactivator with PDZ-binding motif (TAZ), and transient receptor potential vanilloid 4 (TRPV4). We also reviewed the key signaling pathways, therapeutic targets and cutting-edge clinical applications of diseases related to mechanical cues.

The association of dietary intake of riboflavin and thiamine with kidney stone: a cross-sectional survey of NHANES 2007-2018.

BACKGROUND: Kidney stone disease (KSD) is a common condition that affects 10% population in the United States (US). The relationship between thiamine and riboflavin intake and KSD has not been well-studied. We aimed to investigate the prevalence of KSD and the association between dietary thiamine and riboflavin intake with KSD in the US population. METHODS: This large-scale, cross-sectional study included subjects from the National Health and Nutrition Examination Survey (NHANES) 2007-2018. KSD and dietary intake were collected from questionnaires and 24-hour recall interviews. Logistic regression and sensitivity analyses were performed to investigate the association. RESULTS: This study included 26,786 adult participants with a mean age of 50.12 ± 17.61 years old. The prevalence of KSD was 9.62%. After adjusting for all potential covariates, we found that higher riboflavin intake was negatively related to KSD compared with dietary intake of riboflavin < 2 mg/day in the fully-adjusted model (OR = 0.541, 95% CI = 0.368 to 0.795, P = 0.002). After stratifying by gender and age, we found that the impact of riboflavin on KSD still existed in all age subgroups (P < 0.05) but only in males (P = 0.001). No such associations were found between dietary intake of thiamine and KSD in any of the subgroups. CONCLUSIONS: Our study suggested that a high intake of riboflavin is independently inversely associated with kidney stones, especially in male population. No association was found between dietary intake of thiamine and KSD. Further studies are needed to confirm our results and explore the causal relationships.

Which frequency is better for pediatric shock wave lithotripsy? Low intermediate or high: A systematic review and meta-analysis.

Background: To explore the optimal frequency for pediatric extracorporeal shock wave lithotripsy (ESWL) in the treatment of upper urinary stones. Methods: A systematic literature search was undertaken using PubMed, Embase, Web of Science and Cochrane Central Register of Controlled Trials databases to identify eligible studies published before January 2023. Primary outcomes were perioperative efficacy parameters, including ESWL time, anesthesia time for ESWL sessions, success rates after each session, additional interventions needed, and treatment sessions per patient. Secondary outcomes were postoperative complications and efficiency quotient. Results: Four controlled studies involving 263 pediatric patients were enrolled in our meta-analysis. In the comparison between the low-frequency and intermediate-frequency groups, we observed no significant difference as regards anesthesia time for ESWL session (WMD = -4.98, 95% CI -21.55∼11.58, p = 0.56), success rates after ESWL sessions (first session: OR = 0.02 95%CI -0.12∼0.17, p = 0.74; second session: OR = 1.04 95%CI 0.56∼1.90, p = 0.91; third session: OR = 1.62 95%CI 0.73∼3.60, p = 0.24), treatment sessions needed (WMD = 0.08 95%CI -0.21∼0.36, p = 0.60), additional interventions after ESWL (OR=0.99 95%CI 0.40∼2.47, p = 0.99) and rates of Clavien grade 2 complications (OR = 0.92 95%CI 0.18∼4.69, p = 0.92). However, the intermediate-frequency group may exhibit potential benefits in Clavien grade 1 complications. In the comparison between intermediate-frequency and high-frequency, the eligible studies exhibited higher success rates in the intermediate-frequency group after the first session, the second session and the third session. More sessions may be required in the high-frequency group. With respect to other perioperative, postoperative parameters and major complications, the results were similar. Conclusions: Intermediate-frequency and low-frequency had similar success rates and seemed to be the optimal frequency for pediatric ESWL. Nevertheless, future large-volume, well-designed RCTs are awaited to confirm and update the findings of this analysis. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/, identifier: CRD42022333646.

Association between the systemic immune-inflammation index and kidney stone: A cross-sectional study of NHANES 2007-2018.

Background: The incidence rate of kidney stones increased over the past decades globally, which brought medical expenditure and social burden. The systemic immune-inflammatory index (SII) was initially identified as a prognosis of multiple diseases. We performed an updated analysis on the impact of SII on kidney stones. Methods: This compensatory cross-sectional study enrolled participants from the National Health and Nutrition Examination Survey 2007-2018. Univariate and multivariate logistic regression analyses were performed to investigate the association between SII and kidney stones. Results: Of the 22220 participants, the mean (SD) age was 49.45 ± 17.36 years old, with a 9.87% incidence rate of kidney stones. A fully adjusted model showed that SII higher than 330 x 109/L was parallel associated with kidney stones (Odds ratio [OR] = 1.282, 95% Confidence interval [CI] = 1.023 to 1.608, P = 0.034) in adults aged 20-50. However, no difference was found in the elderly subgroup. Multiple imputation analyses confirmed the robustness of our results. Conclusions: Our findings suggested SII was positively associated with a high risk of kidney stones in US adults aged less than 50. The outcome compensated for previous studies that still needed more large-scale prospective cohorts for validation.

YAP-mediated mechanotransduction in urinary bladder remodeling: Based on RNA-seq and CUT&Tag.

Yes-associated protein (YAP) is an important transcriptional coactivator binding to transcriptional factors that engage in many downstream gene transcription. Partial bladder outlet obstruction (pBOO) causes a massive burden to patients and finally leads to bladder fibrosis. Several cell types engage in the pBOO pathological process, including urothelial cells, smooth muscle cells, and fibroblasts. To clarify the function of YAP in bladder fibrosis, we performed the RNA-seq and CUT&Tag of the bladder smooth muscle cell to analyze the YAP ablation of human bladder smooth muscle cells (hBdSMCs) and immunoprecipitation of YAP. 141 differentially expressed genes (DEGs) were identified through RNA-seq between YAP-knockdown and nature control. After matching with the results of CUT&Tag, 36 genes were regulated directly by YAP. Then we identified the hub genes in the DEGs, including CDCA5, CENPA, DTL, NCAPH, and NEIL3, that contribute to cell proliferation. Thus, our study provides a regulatory network of YAP in smooth muscle proliferation. The possible effects of YAP on hBdSMC might be a vital target for pBOO-associated bladder fibrosis.

Survivin knockdown alleviates pathological hydrostatic pressure-induced bladder smooth muscle cell dysfunction and BOO-induced bladder remodeling via autophagy.

Aim: Bladder outlet obstruction (BOO) leads to bladder wall remodeling accompanying the progression from inflammation to fibrosis where pathological hydrostatic pressure (HP)-induced alteration of bladder smooth muscle cells (BSMCs) hypertrophic and excessive extracellular matrix (ECM) deposition play a pivotal role. Recently, we have predicted survivin (BIRC5) as a potential hub gene that might be critical during bladder fibrosis by bioinformatics analyses from rat BOO bladder, but its function during BOO progression remains unknown. Here, we investigated the role of survivin protein on bladder dysfunction of BOO both in vitro and in vivo. Methods: Sprague-Dawley female rats were divided into three groups: control group, BOO group, and BOO followed by the treatment with YM155 group. Bladder morphology and function were evaluated by Masson staining and urodynamic testing. To elucidate the underlying mechanism, hBSMCs were subjected to pathological HP of 200 cm H2O and co-cultured with the presence or absence of survivin siRNA and/or autophagy inhibitor 3-MA. Autophagy was evaluated by the detection of Beclin1 and LC3B-II expression, proliferation was conducted by the EdU analysis and PCNA expression, and fibrosis was assessed by the examination of Col 1 and Fn expression. Results: BOO led to a gradual alteration of hypertrophy and fibrosis of the bladder, and subsequently induced bladder dysfunction accompanied by increased survivin expression, while these histological and function changes were attenuated by the treatment with YM155. HP significantly increased survivin expression, upregulated Col1 and Fn expression, enhanced proliferation, and downregulated autophagy markers, but these changes were partially abolished by survivin siRNA treatment, which was consistent with the results of the BOO rat experiment. In addition, the anti-fibrotic and anti-proliferative effects of the survivin siRNA treatment on hBSMCs were diminished after the inhibition of autophagy by the treatment with 3-MA. Conclusion: In summary, the upregulation of survivin increased cell proliferation and fibrotic protein expression of hBSMC and drove the onset of bladder remodeling through autophagy during BOO. Targeting survivin in pathological hBSMCs could be a promising way to anti-fibrotic therapeutic approach in bladder remodeling secondary to BOO.

YAP/Smad3 promotes pathological extracellular matrix microenviroment-induced bladder smooth muscle proliferation in bladder fibrosis progression.

Fibrosis is a chronic inflammation process with excess extracellular matrix (ECM) deposition that cannot be reversed. Patients suffer from bladder dysfunction caused by bladder fibrosis. Moreover, the interactive mechanisms between ECM and bladder fibrosis are still obscure. Hence, we assessed the pivotal effect of Yes-associated protein (YAP) on the proliferation of bladder smooth muscle in fibrosis process. We identified that stiff ECM increased the expression and translocation of YAP in the nucleus of human bladder smooth muscle cell (hBdSMC). Sequencings and proteomics revealed that YAP bound to Smad3 and promoted the proliferation of hBdSMC via MAPK/ERK signaling pathway in stiff ECM. Moreover, CUT and TAG sequencing and dual-luciferase assays demonstrated that Smad3 inhibited the transcription of JUN. The YAP inhibitor CA3 was used in a partial bladder outlet obstruction (pBOO) rat model. The results showed that CA3 attenuated bladder smooth muscle proliferation. Collectively, YAP binding with Smad3 in the nucleus inhibited the transcription of JUN, and promoted the proliferation of bladder smooth muscle through the MAPK/ERK signaling pathway. The current study identified a novel mechanism of mechanical force induced bladder fibrosis that provided insights in YAP-associated organ fibrosis.

A rare case report of multifocal para-aortic and para-vesical paragangliomas.

Background: Paragangliomas (PGLs) are uncommon tumors of uncertain malignant potential. Multifocal paragangliomas are scarcely reported in the literature. Case summary: A 25-year-old male patient was reported for the first time with multifocal para-aortic and para-vesical PGLs. The diagnosis was identified by blood catecholamine tests and enhanced CT scan and MIBG scintigraphy. A resection surgery was performed for treatment and the immunochemistry test of the tumors presented the features of PGL. Conclusion: A case of multifocal para-aortic and para-vesical PGLs confirmed by the catecholamine test, enhanced CT, and MIBG scintigraphy is presented. The cooperation of experienced surgeons, anesthesiologists, and endocrinologists was critical in treatment.

A bibliometric analysis of top-cited journal articles in interstitial cystitis and bladder pain syndrome.

INTRODUCTION AND HYPOTHESIS: To identify and compare the top-cited articles from all indexed journals and urology-nephrology and obstetrics-gynecology journals in the Institute for Scientific Information Web of Science's Citation Index Expanded on interstitial cystitis and bladder pain syndrome (IC/BPS). METHODS: Cross-sectional bibliometric analysis of top-cited articles in Web of ScienceTM (WoS) from 1900-2022. The articles were retrieved by the MeSH terms from NCBI. The characteristics of top 100 cited articles from all indexed journals and specialized journals were evaluated. RESULTS: A total of 5547 articles were collected from 1115 journals, in which 3225 articles were from 141 urological and gynecological specialized journals. The USA and the UK were the top two origins for articles on interstitial cystitis. The articles from non-specialized journals were more frequently cited than those from specialized journals (median [IQR], 221.5 [189.8-313.5] vs 131.0 [126.0-142.8], P < 0.0001). The citation number per year showed similar results (median [IQR], 239.9 [194.5-311.8] vs 132.0 [126.7-140.5], P < 0.0001). There were many more open-access articles in non-specialized than specialized journals (P = 0.0018). CONCLUSIONS: The current study initially queried the articles published on WoS on IC/BPS by the number of citations to identify the differences between two journal categories. The characteristics and trends of research were analyzed by citations to provide insights into the current research status and future direction.