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.

Aggressive alternative splicing events discovered in cecum ligation and puncture induced lung injury.

AIMS: Acute lung injury (ALI) induced by sepsis and its complications have high morbidity and mortality rates globally. The objective of this study was to enhance our understanding of the underlying mechanism of ALI by identifying potential splicing events that are regulated in this condition. MATERIALS AND METHODS: The CLP mouse model was utilized for mRNA sequencing, and the expression and splicing data were analyzed. Verification of the changes in expression and splicing induced by CLP was conducted using qPCR and RT-PCR. RESULTS: Our results showed that splicing-related genes were regulated, suggesting that splicing regulation may be a key mechanism in ALI. We also found that more than 2900 genes displayed alternative splicing in the lungs of mice with sepsis. Using RT-PCR, we verified that TLR4 and other genes had differential splicing isoforms in the lungs of mice with sepsis. We confirmed the presence of TLR4-s in the lungs of mice with sepsis using RNA-fluorescence in situ hybridization. CONCLUSION: Our results suggest that sepsis-induced ALI can significantly alter splicing in the lungs of mice. The list of DASGs and splicing factors is valuable for further study in the search for new treatment approaches for sepsis-induced ALI.

Diagnostic value of transperineal ultrasound in patients with stress urinary incontinence (SUI): a systematic review and meta-analysis.

PURPOSE: We aimed to analyze the diagnostic value of transperineal ultrasound in patients with stress urinary incontinence (SUI) using evidence-based methods. METHODS: A comprehensive search of the studies on the diagnosis of SUI by transperineal ultrasound in PubMed, EMBASE, MEDLINE, Cochrane library, Medicine, Web of Science, and clinicaltrials.gov databases on August 1, 2022. Studies were included if they met the inclusion criteria and were evaluated by different quality evaluation methods according to study types. Various ultrasound parameters were collected and counted to analyze and judge the diagnostic value of transperineal ultrasound in SUI patients. RESULTS: A total of 13 studies with 1563 participants were finally included. The combined statistics showed no significant difference in age and parity among the included patients, and the BMI of the SUI group was slightly higher than that of the normal population (MD 1.20, 95%CI 0.68-1.72). The results indicated that compared with the normal population, the α angle (MD 15.56, 95%CI 9.93-21.90), ß angle (at rest: MD 10.02 mm, 95%CI 1.95-18.09; at Valsalva: MD 22.40 mm, 95%CI 13.79-31.01), bladder neck descent (MD 6.82 mm, 95%CI 4.49-9.14), area of hiatus (MD 2.83 cm2, 95%CI 0.71-4.94) and bladder neck funneling (RR 4.71, 95%CI 1.08-20.62) of SUI patients were significantly different, which illustrated the potential value of transperineal ultrasound in diagnosing SUI. CONCLUSION: Evidence-based medicine was applied to statistically analyze published articles on the diagnostic value of transperineal ultrasound in SUI. The results suggested that transperineal ultrasound had application value in the diagnosis of SUI and had the potential to become a routine examination method to assist clinical decision-making.

Effect of vaginal energy-based treatment on female stress urinary incontinence: a systematic review and meta-analysis of randomized controlled trials.

PURPOSE: To evaluate the efficacy and safety of vaginal energy-based therapies in treating female SUI. METHODS: The PubMed, EMBASE, Web of Science, and Scopus databases were searched up to September 2022 to identify RCTs comparing energy-based therapies with placebo intervention in treating female SUI. The primary outcome was International Consultation on Incontinence Questionnaire-Short Form (ICIQ-SF) score. Secondary outcomes included the 1-h pad test and cure rate. RESULTS: A total of 577 patients from 6 studies were included in the meta-analysis. Energy-based therapies did not significantly improve the ICIQ-SF score at all visits (≤ 1 month: SMD, -0.39; 95% CI - 0.80 to 0.03; P = 0.07; 3 months: SMD, - 1.32; 95% CI - 4.07 to 1.43; P = 0.35; 6 months: SMD, - 0.39; 95% CI - 0.91 to 0.12; P = 0.14). The subgroup analysis showed that there was no significant improvement in ICIQ-SF score in the CO2 laser group compared to the placebo group at all visits (≤ 1 month: SMD, - 0.13; 95% CI - 0.59 to 0.34; P = 0.59; 3 months: SMD, - 1.50; 95% CI - 3.91 to 0.92; P = 0.22; 6 months: SMD, 0.13; 95% CI - 0.47 to 0.72; P = 0.67). Meta-analysis was not performed in Er: YAG laser and radiofrequency therapy due to insufficient trials. CONCLUSION: Based on the limited clinical evidence, our meta-analysis showed no prior efficacy of energy-based therapy over placebo intervention. However, the results of this meta-analysis should be taken with caution due to the limited amount of available evidence and the heterogeneity among the included studies. PROSPERO REGISTRATION NUMBER: CRD42022360471.

Comparative study of absorbable suture and permanent suture in sacrocolpopexy: a meta-analysis and systematic review.

INTRODUCTION AND HYPOTHESIS: The aim of this study was to compare the surgical results and the complications of absorbable suture (AS) versus permanent suture (PS) in sacrocolpopexy (SCP). METHODS: We systematically searched PubMed, Embase, ClinicalTrials.gov, and the Cochrane Library Central Register of Controlled Trials for articles in which researchers compared AS with PS in SCP. The primary outcomes were the surgical success rate and suture-related complications (suture exposure/erosion, mesh erosion, and suture removal). All analyses were performed with Review Manager 5.3. RESULTS: Four articles involving 689 patients were ultimately included. Our findings demonstrated that AS had similar surgical success rates to those of PS (OR=1.34; 95% CI, 0.60-2.96) and no significant differences in failure rates were noted between the two groups (OR=0.75; 95% CI, 0.34-1.66). Subgroup analyses in patients with anatomical failure revealed no significant differences in recurrent posterior prolapse (OR=0.33; 95% CI, 0.05-2.10) or in recurrent apical (OR=0.64; 95% CI, 0.03-13.66) or anterior prolapse (OR=0.45; 95% CI, 0.13-1.57). However, the AS group were at a lower risk of suture exposure/erosion (OR=0.18; 95% CI, 0.06-0.58) and a lower suture removal rate (OR=0.14; 95% CI, 0.03-0.61) and retreatment (OR=0.36; 95% CI, 0.16-0.82), but the mesh erosion was not significantly different (OR=1.00; 95% CI, 0.49-2.08). CONCLUSIONS: The data showed that AS had a similar success rate, less exposure/erosion, and were less likely to be removed and require retreatment than PS, which supported the notion that AS is as effective as PS but safer.

Bladder Sonomorphological Tests in Diagnosing Bladder Outlet Obstruction in Patients with Lower Urinary Tract Symptoms: A Systematic Review and Meta-Analysis.

AIMS: We aimed to investigate the accuracy of bladder sonomorphological parameters including detrusor wall thickness (DWT) and ultrasound-estimated bladder weight (UEBW) for diagnosing bladder outlet obstruction (BOO) in patients with lower urinary tract symptoms (LUTS). METHODS: A comprehensive search was conducted through databases including PubMed, EMBASE, MEDLINE, Cochrane Library, Medicine, China Knowledge Network (CNKI), China Biomedical Literature Database, Wanfang Database, the Chongqing VIP Chinese Science, and Technology Periodical Database (VIP) to select studies assessing the diagnostic accuracy of DWT and UEBW to diagnose BOO in adults with LUTS. Databases were searched from inception to 2020 without restriction. Study quality was assessed using Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2), and measures of accuracy were calculated using random-effects model. RESULTS: The initial search included 84 publications, of which 78 publications were screened, and 16 studies with 1,847 patients finally contained diagnostic data. The results from 10 out of 16 studies assessing DWT showed a pooled sensitivity (SSY) of 0.68 (95% CI, 0.56-0.78) and specificity (SPY) of 0.91 (95% CI, 0.82-0.96) with I2 values of 93%, while 6 studies evaluating UEBW were analyzed with a SSY of 0.88 (95% CI, 0.78-0.93) and SPY of 0.81 (95% CI, 0.67-0.90) with I2 values of 83%. CONCLUSIONS: DWT shows high SPY, and UEBW performs high SSY of diagnosing BOO. Further well-designed studies are needed to evaluate the utilization of DWT and UEBW for the diagnosis of BOO.

High plasma levels of pro-inflammatory factors interleukin-17 and interleukin-23 are associated with poor outcome of cardiac-arrest patients: a single center experience.

BACKGROUND: Systemic inflammation is an important feature of post-cardiac arrest syndrome (PCAS). This study was designed to determine whether the plasma concentrations of some circulating pro-inflammatory cytokines (interleukin-17 [IL-8], IL-22, IL-23 and IL-33) are of value in predicting the outcome of patients after return of spontaneous circulation (ROSC) during the post-cardiac arrest period. METHODS: This was a prospective observational clinical study. In total, 21 patients (survivors, n = 10; non-survivors, n = 11) who experienced cardiac arrest and successful ROSC with expected survival of at least 7 days were consecutively enrolled from January 2016 to December 2017. Of the 21 enrolled patients, ten survived were designated "survivors". The other eleven patients died between 2 days and 1 months post ROSC. Venous blood was drawn at three time-points: baseline (< 1 h post ROSC), 2 days post ROSC and 7 days post ROSC. Plasma IL-8, IL-22, IL-23 and IL-33 were determined using commercial enzyme-linked immunosorbent assays. RESULTS: Plasma creatinine levels, but aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels, were elevated in non-survivors compared with survivors. Plasma levels of IL-17, IL-22, IL-23 and IL-33 of the 21 total patients did not change at 2 or 7 days post ROSC compared to baseline. In survivors, the plasma levels of IL-17 and IL-23 at 2 or 7 days post ROSC were lower than baseline. In non-survivors, plasma levels of IL-17 increased compared with baseline. Receiver operating characteristic curve analysis showed that the plasma levels of IL-17 and IL-23 at 2 or 7 days post ROSC were able to predict the mortality of PCAS patients, and positively correlated with Acute Physiology and Chronic Health Evaluation (APACHE)-II score and time to ROSC. CONCLUSION: These results provide the first evidence that the elevated plasma IL-17 and IL-23 levels are associated with poor outcome in PCAS patients. The role of IL-17/IL-23 axis post ROSC is worth paying attention to in PCAS patients. TRIAL REGISTRATION: Clinicaltrial.govNCT02297776, 2014-11-21.

Tetramethylpyrazine alleviates LPS-induced inflammatory injury in HUVECs by inhibiting Rho/ROCK pathway.

Endothelial dysfunction plays an important role in the pathogenesis of acute lung injury (ALI). Tetramethylpyrazine (TMP) has been reported to attenuate harmful changes in ALI rats. However, the effects of TMP on endothelial cell injury and its underlying mechanisms remain unknown. In this study, human umbilical vein endothelial cells (HUVECs) induced by lipopolysaccharide (LPS) was used as an inflammatory injury model, also served as LPS group. HUVECs pretreated with TMP for 2 h before induced by LPS was served as LPS + TMP group. Untreated HUVECs was served as control group. After incubation with LPS for 12 h, cell viability and morphology, cell apoptosis rate, CD31-positive endothelial microparticles (EMPs) release, proinflammatory cytokines secretion, and ROCK II expression were evaluated. Compared with LPS group, TMP pretreatment improved cell viability and morphology. Besides, cell apoptosis rate, CD31-positive EMPs amount, TNF-α and IL-1ß concentrates, and ROCK II mRNA and protein levels in LPS + TMP group were significantly decreased when compared with LPS group. To further confirm the mechanism, HUVECs in all the above groups were pretreated with Y27632 (ROCK II inhibitor) for 30 min before grouping, then treated as above. No significant differences in cell apoptosis rate, CD31-positive EMPs amount, and ROCK II expression between Y27632 + LPS group and Y27632 + LPS + TMP group were found. To sum up, our study found that TMP alleviated LPS-induced inflammatory injury in HUVECs by inhibiting Rho/ROCK pathway.

PPM1D silencing by RNA interference inhibits the proliferation of lung cancer cells.

BACKGROUND: PPM1D (protein phosphatase, Mg2+/Mn2+ dependent, 1D) has been reported to be involved in multiple human tumors. This study was designed to investigate the functional role of PPM1D in lung cancer cells. METHODS: Expression levels of PPM1D were analyzed in A549 and H1299 cells by real-time PCR and Western blotting. Lentivirus-mediated short hairpin RNA (shRNA) was used to knock down PPM1D expression in both cell lines. The effects of PPM1D on lung cancer cell growth were investigated by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide), colony formation and flow cytometry assays. RESULTS: Knockdown of PPM1D in lung cancer cells resulted in decreased cell proliferation and impaired colony formation ability. Moreover, flow cytometry analysis showed that knockdown of PPM1D arrested cell cycle at the G0/G1 phase. Furthermore, PPM1D silencing downregulated the expression of cyclin B1 in H1299 cells. Therefore, it is reasonable to speculate that the mechanisms by which PPM1D knockdown alleviates cell growth may be partly via the induction of cell cycle arrest due to the suppression of cyclin B1. CONCLUSIONS: These results suggest that PPM1D silencing by RNA interference (RNAi) may be a potential therapeutic approach for the treatment of lung cancer.

Long-term outcomes of surgical interventions for stress urinary incontinence: a systematic review and network meta-analysis.

BACKGROUND: Stress urinary incontinence is common among women, and surgical interventions have significantly improved patients' symptoms. The long-term effectiveness of these surgeries is increasingly drawing attention, yet it remains sparsely documented in the literature. OBJECTIVE: To compare the long-term effectiveness and safety of retropubic tension-free vaginal tape (TVT-RP), tension-free vaginal tape-obturator (TVT-O), transobturator tape (TOT), single-incision sling (SIS), Burch colposuspension, and pubovaginal sling (PVS). METHODS: A comprehensive and systematic literature review was conducted in PubMed, EMBASE, MEDLINE, Cochrane Library, Medicine, and clinicaltrials.gov from inception to May 2023. Selected trials were evaluated for potential bias using the Cochrane tool. Treatment modalities were compared using network meta-analysis to assess objective success rate, subjective success rate, and complications as outcomes. RESULTS: A total of 37 studies involving 5720 patients were included. No significant statistical differences were found among the interventions regarding objective success rate. PVS had the highest surface under the cumulative ranking curve SUCRA value (93.1). For subjective success rate, TVT-RP, TVT-O, and PVS demonstrated superiority over SIS, with PVS having the highest SUCRA value (80.1). SIS had lower overall complication and pain rates compared to other methods, with statistical significance. There were no differences in reoperation rate, exposure rate, and urinary tract infection occurrence among the surgical approaches. CONCLUSIONS: In terms of long-term effectiveness and safety, TVT-RP and TVT-O appear to be the preferred options for patients opting for synthetic slings, while for patients seeking nonsynthetic slings, PVS may represent the optimal choice.

Deterministic Single-Cell Encapsulation in PEG Norbornene Microgels for Promoting Anti-Inflammatory Response and Therapeutic Delivery of Mesenchymal Stromal Cells.

Tissue engineering at single-cell resolution has enhanced therapeutic efficacy. Droplet microfluidics offers a powerful platform that allows deterministic single-cell encapsulation into aqueous droplets, yet the direct encapsulation of cells into microgels remains challenging. Here, the design of a microfluidic device that is capable of single-cell encapsulation within polyethylene glycol norbornene (PEGNB) hydrogels on-chip is reported. Cells are first ordered in media within a straight microchannel via inertial focusing, followed by the introduction of PEGNB solution from two separate, converging channels. Droplets are thoroughly mixed by passage through a serpentine channel, and microgels are formed by photo-photopolymerization. This platform uniquely enables both single-cell encapsulation and excellent cell viability post-photo-polymerization. More than 90% of singly encapsulated mesenchymal stromal cells (MSCs) remain alive for 7 days. Notably, singly encapsulated MSCs have elevated expression levels in genes that code anti-inflammatory cytokines, for example, IL-10 and TGF-ß, thus enhancing the secretion of proteins of interest. Following injection into a mouse model with induced inflammation, singly encapsulated MSCs show a strong retention rate in vivo, reduce overall inflammation, and mitigate liver damage. These translational results indicate that deterministic single-cell encapsulation could find use in a broad spectrum of tissue engineering applications.

Nafamostat mesylate versus regional citrate anticoagulation for continuous renal replacement therapy in patients at high risk of bleeding: a retrospective single-center study.

PURPOSE: The choice of continuous renal replacement therapy (CRRT) anticoagulation program for patients at high risk of bleeding has always been a complex problem in clinical practice. Clinical regimens include regional citrate anticoagulation (RCA) and nafamostat mesylate (NM). This study aimed to evaluate the efficacy and safety of these two anticoagulants for CRRT in patients at high risk of bleeding to guide their clinical use better. PATIENTS AND METHODS: Between January 2021 and December 2022, 307 patients were screened for this study. Forty-six patients were finally enrolled: 22 in the regional citrate anticoagulation group and 24 in the nafamostat mesylate group. We collected patients' baseline characteristics, laboratory indicators before CRRT, and CRRT-related data. We then performed a statistical analysis of the data from both groups of patients. RESULTS: In our study, the baseline characteristics did not differ significantly between the two groups; the baseline laboratory indicators before CRRT of patients in the two groups were not significantly different. The duration of CRRT was 600 min in the regional citrate anticoagulation (RCA) group, 615 min in the nafamostat mesylate (NM) group; the success rate was 90.7% in the RCA group, and 85.6% in the NM group, the anticoagulant efficacy between the two groups was comparable. There was no significant difference in the safety of anticoagulation between the two groups. We used Generalized Estimating Equations (GEE) to test whether different anticoagulation methods significantly affected the success rate of CRRT and found no statistical difference between RCA and NM. CONCLUSION: Our study suggests that nafamostat mesylate's anticoagulant efficacy and safety are not inferior to regional citrate anticoagulation for continuous renal replacement therapy in patients at high risk of bleeding.

Causal Relationship between Mitochondrial-Associated Proteins and Sepsis in ICU Patients: A Mendelian Randomization Study.

BACKGROUND: The alarming mortality rate of sepsis in ICUs has garnered significant attention. The precise etiology remains elusive. Mitochondria, often referred to as the cellular powerhouses, have been postulated to have a dysfunctional role, correlating with the onset and progression of sepsis. However, the exact causal relationship remains to be defined. METHOD: Employing the Mendelian randomization approach, this study systematically analyzed data from the IEUOpenGWAS and UKbiobank databases concerning mitochondrial function-related proteins and their association with sepsis, aiming to delineate the causal relationship between the two. RESULTS: The findings underscored a statistically significant association of GrpE1 with sepsis, registering a P value of 0.005 and an OR of 0.499 (95% CI: 0.307-0.810). Likewise, HTRA2, ISCU, and CUP3 each manifested significant associations with sepsis, yielding OR values of 0.585, 0.637, and 0.634, respectively. These results suggest potential implications of the aforementioned proteins in the pathogenesis of sepsis. CONCLUSION: The present study furnishes novel evidence elucidating the roles of GrpE1, HTRA2, ISCU, and CUP3 in the pathophysiology of sepsis. Such insights pave the way for a deeper understanding of the pathological mechanisms underpinning sepsis and hint at promising therapeutic strategies for the future.

Beneficial impact of cardiac heavy metal scavenger metallothionein in sepsis-provoked cardiac anomalies dependent upon regulation of endoplasmic reticulum stress and ferroptosis but not autophagy.

AIMS: Sepsis represents a profound proinflammatory response with a major contribution from oxidative injury. Here we evaluated possible impact of heavy metal scavenger metallothionein (MT) on endotoxin lipopolysaccharide (LPS)-induced oxidative stress, endoplasmic reticulum (ER) stress, autophagy, and ferroptosis enroute to myocardial injury along with interplay among these stress domains. MATERIALS AND METHODS: Echocardiographic, cardiomyocyte mechanical and intracellular Ca2+ responses were monitored in myocardia from WT and transgenic mice with cardiac-selective MT overexpression challenged with LPS. Oxidative stress, stress signaling (p38, ERK, JNK), ER stress, autophagy, and ferroptosis were scrutinized. KEY FINDINGS: RNAseq analysis revealed discrepant patterns in ferroptosis between LPS-exposed and normal murine hearts. LPS insult enlarged LV end systolic dimension, suppressed fractional shortening, ejection fraction, maximal velocity of shortening/relengthening and peak shortening, as well as elongated relengthening along with dampened intracellular Ca2+ release and reuptake. In addition, LPS triggered oxidative stress (lowered glutathione/glutathione disulfide ratio and O2- production), activation of stress cascades (p38, ERK, JNK), ER stress (GRP78, PERK, Gadd153, and IRE1α), inflammation (TNFα and iNOS), unchecked autophagy (LCB3, Beclin-1 and Atg7), ferroptosis (GPx4 and SLC7A11) and interstitial fibrosis. Although MT overexpression itself did not reveal response on cardiac function, it attenuated or mitigated LPS-evoked alterations in echocardiographic, cardiomyocyte contractile and intracellular Ca2+ characteristics, O2- production, TNFα level, ER stress and ferroptosis (without affecting autophagy, elevated AMP/ATP ratio, and iNOS). In vitro evidence revealed beneficial effects of suppression of oxidative stress, ER stress and ferroptosis against LPS-elicited myocardial anomalies. SIGNIFICANCE: These data strongly support the therapeutic promises of MT and ferroptosis in septic cardiomyopathy.

Single-cell transcriptomics reveal the remodeling landscape of bladder in patients with obstruction-induced detrusor underactivity.

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.

The new checklist to evaluate educational value of YouTube surgical videos of transurethral resection of the prostate.

Background: Transurethral resection of the prostate (TURP) is a widespread, effective way to treat benign prostatic hyperplasia (BPH). Many medical students and junior clinicians increasingly turn to easily accessible online resources to learn this technique, such as videos on YouTube. This study assessed the educational value of YouTube videos about TURP, which are popular among many young surgeons. Methods: We searched YouTube as of August 2, 2022 for videos fulfilling the search terms "transurethral resection of the prostate", "benign prostatic hyperplasia", "BPH", "TURP", "benign prostatic enlargement", "bladder outlet obstruction" and "lower urinary tract symptom". We assessed the educational value of the identified videos using a custom-designed checklist. Results: We identified 47 relevant videos, 20 of which were posted after July 1, 2020. The average number of views was 576,379±208,535 (range, 54-1,385,713). The average quality score of the videos was 7.38±2.53 (range, 4-12) on a 15-point scale, and 20 were judged to be of low educational quality. Quality scores correlated positively with the number of likes (R=0.596, P<0.01). Conclusions: The educational value of most TURP videos on YouTube appears to be low, with most lacking detailed explanations of preoperative preparations and the surgical procedure. High-quality video resources about TURP need to be developed for medical students and junior surgeons. Standard quality criteria should also be developed and disseminated to ensure the production of accurate learning resources for junior clinicians.

The effectiveness and safety of oral medications, onabotulinumtoxinA (three doses) and transcutaneous tibial nerve stimulation as non or minimally invasive treatment for the management of neurogenic detrusor overactivity in adults: a systematic review and network meta-analysis.

BACKGROUND: Oral medications, onabotulinumtoxinA injections, and transcutaneous tibial nerve stimulation (TTNS) are recommended by the American Urological Association/Society of Urodynamics, Female Pelvic Medicine and Urogenital Reconstruction guidelines as non or minimally invasive treatments for patients with neurogenic detrusor overactivity (NDO) without treatment hierarchy. OBJECTIVE: The objective was to compare and rank the effectiveness and safety of oral medications, three doses of onabotulinumtoxinA, and TTNS on improving urodynamic outcomes in patient-reported outcomes and safety outcomes in patients with NDO. METHODS: The authors searched PubMed, EMBASE, MEDLINE, Cochrane Library, Medicine, and clinicaltrials.gov, from their inception to October 2022 and included randomized controlled studies on the drug, onabotulinumtoxinA, and TTNS for the treatment of patients with NDO. Outcomes included urodynamic parameters, voiding diary, quality of life changes, adverse event rate and postvoid residual. RESULTS: A total of 26 articles and 2938 patients were included in the statistics. Regarding effectiveness, all interventions except TTNS and α-blockers were statistically different for the placebo group. The urodynamic outcome and patient-reported outcome suggested that onabotulinumtoxinA injection (urodynamic outcome: onabotulinumtoxinA 200 U, the mean surface under the cumulative ranking curve (SUCRA): 87.4; patient-reported outcome: onabotulinumtoxinA 100 U, mean SUCRA: 89.8) was the most effective treatment, and the safety outcome suggested that TTNS (SUCRA: 83.3) was the safest. Cluster analysis found that antimuscarinics and ß3-adrenoceptor-agonists possessed good effectiveness and safety. CONCLUSION: OnabotulinumtoxinA injection is probably the most effective way to treat patients with NDO, with increasing effectiveness but decreasing safety as the dose rises. The effectiveness of α-blockers and TTNS was not statistically different from the placebo group. Antimuscarinics and ß3-adrenoceptor-agonists have good effectiveness and safety.

Causal associations of gut microbiota and metabolites on sepsis: a two-sample Mendelian randomization study.

Background: Sepsis stands as a dire medical condition, arising when the body's immune response to infection spirals into overdrive, paving the way for potential organ damage and potential mortality. With intestinal flora's known impact on sepsis but a dearth of comprehensive data, our study embarked on a two-sample Mendelian randomization analysis to probe the causal link between gut microbiota and their metabolites with severe sepsis patients who succumbed within a 28-day span. Methods: Leveraging data from Genome-wide association study (GWAS) and combining it with data from 2,076 European descendants in the Framingham Heart Study, single-nucleotide polymorphisms (SNPs) were employed as Instrumental Variables (IVs) to discern gene loci affiliated with metabolites. GWAS summary statistics for sepsis were extracted from the UK Biobank consortium. Results: In this extensive exploration, 93 distinct genome-wide significant SNPs correlated with gut microbial metabolites and specific bacterial traits were identified for IVs construction. Notably, a substantial link between Coprococcus2 and both the incidence (OR of 0.80, 95% CI: 0.68-0.94, P=0.007) and the 28-day mortality rate (OR 0.48, 95% CI: 0.27-0.85, P=0.013) of sepsis was observed. The metabolite α-hydroxybutyrate displayed a marked association with sepsis onset (OR=1.08, 95% CI: 1.02-1.15, P=0.006) and its 28-day mortality rate (OR=1.17, 95% CI: 1.01-1.36, P=0.029). Conclusion: This research unveils the intricate interplay between the gut microbial consortium, especially the genus Coprococcus, and the metabolite α-hydroxybutyrate in the milieu of sepsis. The findings illuminate the pivotal role of intestinal microbiota and their metabolites in sepsis' pathogenesis, offering fresh insights for future research and hinting at novel strategies for sepsis' diagnosis, therapeutic interventions, and prognostic assessments.

Identification of circRNA-miRNA-mRNA network as biomarkers for interstitial cystitis/bladder pain syndrome.

Interstitial cystitis/bladder pain syndrome (IC/BPS) is a long-lasting and incapacitating disease, and the exact factors that affect its onset and advancement are still uncertain. Thus, the main aim was to explore new biomarkers and possible therapeutic targets for IC/BPS. Next-generation high-throughput sequencing experiments were performed on bladder tissues. Based on the interactions between circRNA and miRNA, as well as miRNA and mRNA, candidates were selected to build a network of circRNA-miRNA-mRNA. The STRING database and Cytoscape software were utilized to build a protein-protein interaction (PPI) network to pinpoint the hub genes associated with IC/BPS. The expression levels of circRNA and miRNA in the network were confirmed through quantitative polymerase chain reaction. Western blot was applied to confirm the stability of the lipopolysaccharide-induced IC/BPS model, and the effect of overexpression of circ.5863 by lentivirus on inflammation. Ten circRNA-miRNA interactions involving three circRNAs and six miRNAs were identified, and IFIT3 and RSAD2 were identified as hub genes in the resulting PPI network with 19 nodes. Circ.5863 showed a statistically significant decrease in the constructed model, which is consistent with the sequencing results, and overexpression via lentiviral transfection of circ.5863 was found to alleviate inflammation damage. In this study, a circRNA-miRNA-mRNA network was successfully constructed, and IFIT3 and RSAD2 were identified as hub genes. Our findings suggest that circ.5863 can mitigate inflammation damage in IC/BPS. The identified marker genes may serve as valuable targets for future research aimed at developing diagnostic tools and more effective therapies for IC/BPS.

Sacrospinous Ligament Fixation vs Uterosacral Ligaments Suspension for Pelvic Organ Prolapse: A Systematic Review and Meta-Analysis.

OBJECTIVE: To compare the effectiveness and safety of sacrospinous ligament fixation (SSLF) and uterosacral ligaments suspension (ULS) for surgical correction of pelvic organ prolapse (POP). METHODS: Comparative studies were identified in PubMed, EMBASE, MEDLINE, Cochrane library, Medicine and clinicaltrials.gov databases. Randomized controlled trials, prospective and retrospective cohort studies were included. Primary outcomes were collected including anatomical success rate (Defined as anterior or posterior vaginal wall beyond the hymen), surgical success rate, recurrence and total complication rate, while secondary outcomes were specific complications rates. Data were analyzed using Revman (Version 5.4). RESULTS: After searching databases and removing the duplicate studies, a total of 57 articles had entered the screening stage. Finally, 9 moderate and high quality studies (4 randomized controlled trials and 5 retrospective studies) with 4516 participants were included. For primary outcomes, there was no statistical difference between the 2 groups regarding surgical success rate (RR = 1.00; 95% CI: 0.91-1.01; I2 = 0%; P =.98), anatomical success (RR = 0.90; 95% CI: 0.78-1.05; I2 = 61%; P =.19), recurrence rate (RR = 1.26; 95% CI: 0.85-1.87; I2 = 75%; P =.24) and total complication rate (RR = 1.07; 95% CI: 0.89-1.28; I2 = 33%; P =.47). Subgroup analysis regarding different follow-up times (1,2 and 5 years) and stages (Stage 2 and stage 3-4) found similar results in primary outcomes. CONCLUSION: In conclusion, SSLF and ULS have the same efficacy and safety for patients. However, SSLF seems to have lower complication rates of vaginal granulation tissue and urethral injury and is gradually favored by surgeons because of its short operation time and simple operation. We still need more high-quality research, especially in terms of the incidence of complications.