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.

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.

Actomyosin Activity and Piezo1 Activity Synergistically Drive Urinary System Fibroblast Activation.

Mechanical cues play a crucial role in activating myofibroblasts from quiescent fibroblasts during fibrosis, and the stiffness of the extracellular matrix is of significant importance in this process. While intracellular force mediated by myosin II and calcium influx regulated by Piezo1 are the primary mechanisms by which cells sense and respond to mechanical forces, their intercellular mechanical interaction remains to be elucidated. Here, hydrogels with tunable substrate are used to systematically investigate the crosstalk of myosin II and Piezo1 in fibroblast to myofibroblast transition (FMT). The findings reveal that the two distinct signaling pathways are integrated to convert mechanical stiffness signals into biochemical signals during bladder-specific FMT. Moreover, it is demonstrated that the crosstalk between myosin II and Piezo1 sensing mechanisms synergistically establishes a sustained feed-forward loop that contributes to chromatin remodeling, induces the expression of downstream target genes, and ultimately exacerbates FMT, in which the intracellular force activates Piezo1 by PI3K/PIP3 pathway-mediated membrane tension and the Piezo1-regulated calcium influx enhances intracellular force by the classical FAK/RhoA/ROCK pathway. Finally, the multifunctional Piezo1 in the complex feedback circuit of FMT drives to further identify that targeting Piezo1 as a therapeutic option for ameliorating bladder fibrosis and dysfunction.

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.

Perioperative Safety of Bladder Hydrodistention in Patients on Antithrombotic Therapy.

IMPORTANCE: Bladder hydrodistention (BH) is commonly used to diagnose and treat patients with interstitial cystitis/bladder pain syndrome (IC/BPS), but the overall assessment of bleeding complications for patients taking antithrombotics is lacking. OBJECTIVES: The study aimed to investigate if perioperative complications were more common in patients with IC/BPS receiving antithrombotic therapy after BH. STUDY DESIGN: We retrospectively reviewed patients with IC/BPS who underwent hydrodistention during January 2010 and May 2021. Patients with and without antithrombotic drugs were identified and grouped, and their medical records were reviewed. Perioperative data and symptom scores were assessed. The rates of complications in the 2 groups were recorded at 3 months and at the last visit postoperatively. RESULTS: A total of 387 patients were eventually included. Among them, 29 (7.5%) patients were receiving systemic antithrombotic therapy and 358 (92.5%) were not. Compared with the non-antithrombotic group, patients receiving antithrombotic therapy demonstrated a longer hospital stay ( P = 0.033) and a longer catheterization time ( P = 0.034). Moreover, the patients with antithrombotic drugs had increased odds of bladder tamponade (odds ratio, 6.76; P = 0.019) and urinary retention (odds ratio, 5.79; P = 0.033) both 3 months postoperatively and last follow-up, but this is not statistically different between patients with and without Hunner lesions. No thromboembolic events were identified during the study period. CONCLUSIONS: Although a small number of patients with IC/BPS needed anticoagulants, longer hospital stays, longer catheterization time, and increased odds of bladder tamponade and urinary retention were observed in patients receiving antithrombotic therapy. Still, a comprehensive management scheme to balance bleeding complications and antithrombotic agents is needed for individuals.

Antifibrotic Effects of Tetrahedral Framework Nucleic Acids by Inhibiting Macrophage Polarization and Macrophage-Myofibroblast Transition in Bladder Remodeling.

Bladder outlet obstruction (BOO) is a prevalent condition arising from urethral stricture, posterior urethral valves, and benign prostatic hyperplasia. Long-term obstruction can lead to bladder remodeling, which is characterized by inflammatory cell infiltration, detrusor hypertrophy, and fibrosis. Until now, there are no efficacious therapeutic options for BOO-induced remodeling. Tetrahedral framework nucleic acids (tFNAs) are a type of novel 3D DNA nanomaterials that possess excellent antifibrotic effects. Here, to determine the treatment effects of tFNAs on BOO-induced remodeling is aimed. Four single-strand DNAs are self-assembled to form tetrahedral framework DNA nanostructures, and the antifibrotic effects of tFNAs are investigated in an in vivo BOO animal model and an in vitro transforming growth factor beta1 (TGF-ß1)-induced fibrosis model. The results demonstrated that tFNAs could ameliorate BOO-induced bladder fibrosis and dysfunction by inhibiting M2 macrophage polarization and the macrophage-myofibroblast transition (MMT) process. Furthermore, tFNAs regulate M2 polarization and the MMT process by deactivating the signal transducer and activator of transcription (Stat) and TGF-ß1/small mothers against decapentaplegic (Smad) pathways, respectively. This is the first study to reveal that tFNAs might be a promising nanomaterial for the treatment of BOO-induced remodeling.

The association between heavy metal exposure and erectile dysfunction in the United States.

Literature regarding the impacts of heavy metal exposure on erectile dysfunction (ED) is scarce. We aimed to evaluate the correlation between 10 urinary metals and ED in a large, nationally representative adult male sample. The dataset was extracted from the National Health and Nutrition Examination Survey (NHANES) during the period of 2001-2002 and 2003-2004. Weighted proportions and multivariable logistic regression analysis adjusted for confounding variables were utilized to determine the relationship between metal exposure and ED. Weighted quantile sum (WQS) regression was utilized to evaluate the impact of a mixture of urinary metals on ED. A total of 1328 participants were included in our study. In multivariable logistic regression analysis, cobalt (Co) and antimony (Sb) were positively associated with ED (odds ratio [OR]: 1.36, 95% confidence interval [CI]: 1.10-1.73, P = 0.020; and OR: 1.41, 95% CI: 1.12-1.77, P = 0.018, respectively) after full adjustment. Men in tertile 4 for Co (OR: 1.49, 95% CI: 1.02-2.41, P for trend = 0.012) and Sb (OR: 1.53, 95% CI: 1.08-2.40, P for trend = 0.041) had significantly higher odds of ED than those in tertile 1. Furthermore, the WQS index was significantly linked with increased odds of ED after full adjustment (OR: 1.31, 95% CI: 1.04-1.72, P < 0.05). Our study expanded on previous literature indicating the possible role of heavy metal exposure in the etiology of ED. The evaluation of heavy metal exposure should be included in the risk assessment of ED.

Remodelling landscape of tissue-engineered bladder with porcine small intestine submucosa using single-cell RNA sequencing.

OBJECTIVE: Bioscaffolds are widely used for tissue engineering, but failed and inconsistent preclinical results have hampered the clinical use of bioscaffolds for tissue engineering. We aimed to construct a cellular remodelling landscape and to identify the key cell subpopulations and important genes driving bladder remodelling. METHODS: Twenty-four reconstructed mouse bladders using porcine small intestinal submucosa (PSIS) were harvested at 1, 3, and 6 weeks to perform single-cell RNA sequencing. Cell types were identified and their differentially expressed genes (DEGs) at each stage were used for functional analysis. Immunofluorescence was used to validate the specific cell type. RESULTS: The remodelling landscape included 13 cell types. Among them, fibroblasts, smooth muscle cells (SMCs), endothelial cells, and macrophages had the most communications with other cells. In the process of regeneration, DEGs of fibroblasts at 1, 3, and 6 weeks were mainly involved in wound healing, extracellular matrix organization, and regulation of development growth, respectively. Among these cells, Saa3+ fibroblasts might mediate tissue remodelling. The DEGs of SMCs at 1, 3, and 6 weeks were mainly involved in the inflammatory response, muscle cell proliferation, and mesenchyme development, respectively. Moreover, we found that Notch3+ SMCs potentially modulated contractility. From 1 to 6 weeks, synchronous development of endothelial cells was observed by trajectory analysis. CONCLUSIONS: A remoulding landscape was successfully constructed and findings might help surficial modifications of PSIS and find a better alternative. However, more in vivo and in vitro studies are needed to further validate these results.

The association between urinary organophosphate insecticide metabolites and erectile dysfunction in the United States.

Organophosphate (OP) insecticides are the main chemicals used in agriculture for pest elimination, and they have been linked with many diseases. However, there is no literature regarding the impacts of organophosphate insecticide metabolite exposure on erectile dysfunction (ED). We aimed to evaluate the correlation between 4 urinary organophosphate insecticide metabolites and the presence of ED in a representative sample of men aged 20 and older. The dataset including a total of 555 subjects was obtained from the National Health and Nutrition Examination Survey (NHANES) 2003-2004. ED was assessed by a question from a self-report questionnaire. Weighted proportions and multivariable logistic regression analysis were utilized to examine the relationship between organophosphate insecticide metabolite exposure and ED. In multivariable logistic regression analysis, diethylphosphate (DEP) was positively correlated with ED (OR 1.07; 95% CI 1.01-1.14; P = 0.033) after full adjustment. Men in DEP tertile 4 had a significant 33% higher risk of ED than those in tertile 1. Furthermore, in a subgroup analysis, our results showed that higher DEP levels were significantly associated with ED in the young age group (20 ≤ age ≤ 39). Our study revealed a significant association between organophosphate insecticide metabolite exposure and an increased risk of ED. Moreover, the correlations were more evident in the young age group. The evaluation of urinary organophosphate insecticide metabolite exposure should be included in the risk assessment of ED. Further study to investigate the underlying mechanism, such as how long the urinary metabolite is present, whether ED is reversible in this population by lowering DEP concentrations, and how exposure to this metabolite affects erectile tissue, is warranted.

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.

Food Insecurity May be an Independent Risk Factor Associated With Erectile Dysfunction in the United States: Analysis of the National Health and Nutrition Examination Survey Data.

INTRODUCTION: While food insecurity is a global public health problem associated with obesity, diabetes, hypertension and coronary heart disease, literature regarding the relationship between food insecurity and erectile dysfunction (ED) is scarce. AIM: We aimed to determine the associations between food insecurity and ED in the National Health and Nutrition Examination Survey. METHODS: Data was extracted from 3,891 participants (aged ≥ 20 years) with ED in the 2001-2004 National Health and Nutrition Examination Survey. Multivariable logistic regression analysis with sampling weights was conducted to evaluate the associations. MAIN OUTCOME MEASURE: Food security was assessed utilizing the Household Food Security Module. A single-question self-report from the Massachusetts Male Aging Study was utilized to evaluate ED status. RESULTS: Approximately 10.2% of individuals had food insecurity. Food insecurity was significantly associated with ED after full adjustment (odds ratio [OR] 1.56; 95% confidence interval [95% CI] 1.16-2.09; P = .003). Men with very low food insecurity had 59% higher risks of ED compared with those having high food security (OR 1.59; 95% CI 1.13-2.27; P = .006). Moreover, the associations were stronger in the old people (age ≥ 60) (OR 2.15; 95% CI 1.26-3.66; P = .004). CONCLUSIONS: Food insecurity might be associated with higher risks of developing ED. Wang W, Chen J, Peng L, et al. Food Insecurity May be an Independent Risk Factor Associated With Erectile Dysfunction in the United States: Analysis of the National Health and Nutrition Examination Survey Data. Sex Med 2022;10:100549.

The Association Between 2, 4-Dichlorophenoxyacetic Acid and Erectile Dysfunction.

Background: 2, 4-dichlorophenoxyacetic acid (2,4-D) is one of the most frequently used herbicides in the world, and it has been linked with low testosterone; however, studies regarding its effect on erectile function are limited. The current study aimed to determine the association between the 2,4-D exposure and erectile dysfunction (ED) in men from the National Health and Nutrition Examination Survey (NHANES). Methods: We analyzed data for urinary 2,4-D levels from 1,311 men (>20 years of age) in the NHANES 2001-2004. ED was assessed by a single, validated survey question. Multivariable logistic regression analysis utilizing sampling weights was performed to determine the relationship between 2,4-D exposure and ED. Results: Multivariable logistic regression models demonstrated no statistically significant association between 2,4-D exposure and ED after full adjustment [odds ratio (OR) 1.02; 95% CI 0.77-1.36; P = 0.882)]. Men in the 2,4-D quartile 4 groups were not associated with an increased risk of ED (OR 1.13; 95% CI 0.74-1.75; P for trend = 0.481). Furthermore, the association between urinary 2,4-D level and ED was not significant in the subgroup analysis stratified by age, BMI, cardiovascular disease, hypertension, diabetes, and high cholesterol. Conclusion: We demonstrated that there was no association between 2,4-D exposure and ED. Further studies are warranted to corroborate our results.

The Association Between Metabolic Syndrome and Prostate Cancer Risk: A Large-Scale Investigation and Study of Chinese.

Background: To investigate the association between metabolic syndrome (MetS) and its components and prostate cancer (PCa). Methods: This study enrolled 482 943 consecutive men who underwent routine health checkups at the Health Management Center of West China Hospital Between 2010 and 2017. For patients with elevated prostate-specific antigen (PSA) levels or color Doppler ultrasound indicating abnormal prostates, we recommended prostate puncture and follow-up. We used the chi-square test and independent t-test for categorical variables and continuous variables, respectively. We used logistic regression analysis to evaluate the effects of MetS and its components on prostate cancer risk. Results: We found that the incidence of PCa in Chinese men over 40 years of age was 0.1%. Among the 85882 participants, 31.5% (27016/85882) of the patients were diagnosed with MetS. PCa was associated with older age, higher PSA levels, lighter weight and shorter height, hypertension, elevated fasting blood glucose (FBG) and HDL cholesterol level, lower triglycerides. After excluded the interference of other factors in multivariate logistic analysis, we found that MetS, hypertension, hyperlipidemia, hyperglycemia, and obesity were not related to the risk of PCa. High age and PSA levels were risk factors for prostate cancer. Conclusions: High age and PSA levels were risk factors for prostate cancer. MetS, hypertension, hyperlipidemia, hyperglycemia, and obesity were not related to the risk of PCa.

Integrating single-cell RNA sequencing with spatial transcriptomics reveals immune landscape for interstitial cystitis.

Interstitial cystitis (IC) is a severely debilitating and chronic disorder with unclear etiology and pathophysiology, which makes the diagnosis difficult and treatment challenging. To investigate the role of immunity in IC bladders, we sequenced 135,091 CD45+ immune cells from 15 female patients with IC and 9 controls with stress urinary incontinence using single-cell RNA sequencing (scRNA-seq). 22 immune subpopulations were identified in the constructed landscape. Among them, M2-like macrophages, inflammatory CD14+ macrophages, and conventional dendritic cells had the most communications with other immune cells. Then, a significant increase of central memory CD4+ T cells, regulatory T cells, GZMK+CD8+ T cells, activated B cells, un-switched memory B cells, and neutrophils, and a significant decrease of CD8+ effector T cells, Th17 cells, follicular helper T cells, switched memory B cells, transitional B cells, and macrophages were noted in IC bladders. The enrichment analysis identified a virus-related response during the dynamic change of cell proportion, furthermore, the human polyomavirus-2 was detected with a positive rate of 95% in urine of patients with IC. By integrating the results of scRNA-seq with spatial transcriptomics, we found nearly all immune subpopulations were enriched in the urothelial region or located close to fibroblasts in IC bladders, but they were discovered around urothelium and smooth muscle cells in control bladders. These findings depict the immune landscape for IC and might provide valuable insights into the pathophysiology of IC.

Ureteroscopy Is Equally Efficient and Safe in Obese and Morbidly Obese Patients: A Systematic Review and Meta-Analysis.

BACKGROUND: Ureteroscopy (URS) has been established as an effective treatment for stones in obese patients (OP). However, recent studies found that the efficacy of the procedure may be lower in patients with higher body mass index (BMI). In the current study, we aim to determine if obesity might influence the effectiveness and safety of URS. METHODS: In May 2021, a comprehensive search was conducted in the PubMed, EMBASE, Web of Science, Cochrane Library, and ClinicalTrials.gov to find eligible studies. Stone-free rate (SFR), operative time, length of stay, and complication rate were assessed utilizing RevMan 5.3. RESULTS: Thirteen studies involving 4,583 normal-weight patients (NWP), 2,465 OP, and 291 morbidly OP (MOP) were included. Pooled results showed that statistically similar SFR existed between OP and NWP [odds ratio (OR): 1.09; 95% CI: 0.79, 1.52; p = 0.59], and between MOP and NWP (OR: 1.03; 95% CI: 0.46, 2.31; p = 0.95). The operation time was similar between OP and NWP [mean difference (MD): -2.27; 95% CI: -8.98, 4.43; p = 0.51], and between MOP and NWP (MD: 4.85; 95% CI: -5.78, 15.47; p = 0.37). In addition, no significant difference regarding length of stay existed between OP and NWP (MD: -0.07; 95% CI: -0.20, 0.07; p = 0.33), and between MOP and NWP (MD: -0.06; 95% CI: -0.25, 0.14; p = 0.58). Furthermore, we observed similar minor complication rate between OP and NWP (OR: 1.04; 95% CI: 0.81, 1.32; p = 0.78), and between MOP and NWP (OR: 1.29; 95% CI: 0.80, 2.08; p = 0.30). The differences concerning major complication rate between OP and NWP (OR: 0.97; 95% CI: 0.39, 2.43; p = 0.95), and between MOP and NWP (OR: 2.01; 95% CI: 0.55, 7.30; p = 0.29) were also not significant. CONCLUSIONS: Our study demonstrated that URS performed in MOP and OP appears to have the same efficacy and safety as well as in NWP group.