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.

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.

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.

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.

Educational value assessment of YouTube surgical videos of tension-free vaginal tape obturator (TVT-O) and trans-obturator vaginal tape (TOT).

BACKGROUND: YouTube, as a widely used video website around the world, contains a large number of surgical teaching videos, providing a good platform for doctors to learn surgery, but its content and quality are uneven. Tension-free vaginal tape obturator (TVT-O) and trans-obturator vaginal tape (TOT) are common surgical methods for the treatment of stress urinary incontinence (SUI), and there are many videos on YouTube teaching these procedures. We aimed to assess the educational value of surgical videos of TVT-O and TOT on YouTube. METHODS: A comprehensive search was conducted for "tension-free vaginal tape obturator" and "trans-obturator vaginal tape" on YouTube on August 22. After referring to LAParoscopic surgery Video Educational GuidelineS (LAP-VEGaS) and previous studies, we developed a checklist containing 5 major items and 18 minor items. SPSS 26 was applied to data and correlation analysis. RESULTS: A total of 36 videos were assessed. The average number of days available was 1,956.6 days (range, 190-4,152 days) and the average length was 9.7 min (range, 1.8-73.6 min, SD: 13.65). Video definition is divided into high, moderate and low, accounting for 22%, 36% and 42% respectively. The average score of the included videos was 7.39 (range, 3-16, SD: 3.57). The correlation analysis indicated that the video quality score has a certain correlation with the length of the video, but has no significant correlation with other factors and there was no significant correlation between audience likes and other factors. CONCLUSIONS: On YouTube, we still lack high educational value videos about TVT-O and TOT, and the existing videos are deficient in the explanation of critical steps, the key points of patients' perioperative management, and the application of auxiliary teaching tools. This further indicates the importance of improving educational videos of surgery, and an authoritative checklist for urologic surgery.

Educational value assessment of YouTube surgical videos of green light laser vaporization of the prostate.

Background: YouTube is commonly used by doctors to learn surgery. To date, no studies have evaluated the quality of videos on photoselective vaporization of the prostate (PVP) for benign prostatic hyperplasia (BPH) on YouTube. Our aim was to assess the educational value of YouTube videos regarding PVP. Methods: "Green light laser vaporization of the prostate" and "photoselective vaporization of the prostate (PVP)" were searched by 2 authors on YouTube on February 14, 2022. Based on the Laparoscopic Surgery Video Educational Guidelines and previous studies, a checklist that included 4 major and 16 minor items was developed. SPSS version 26 (IBM Corp., Armonk, NY, USA) was used to analyze the data using correlation analysis. Results: A total of 74 surgical videos were assessed. The mean number of days available for educational videos was 2,607 days (range, 156-5,854 days), with the earliest videos dating back to 2006 and the latest to 2021. The average length was 12.69 minutes (range, 0.73-123.7, SD 21.25). The majority of videos originated in the United States, and the video definition was divided into high, moderate, and low, accounting for 21.6%, 66.2%, and 12.2% of the videos, respectively. The average numbers of likes and dislikes for videos were 34.26 (SD 87.96) and 0, respectively. The average score of the videos was 6.65 (range, 2-12, SD 2.79). The correlation analysis indicated that the number of views of these videos was related to the number of online days and likes. The scores of videos were related to the number of likes, and the annual average number of views was related to both the number of views and the number of surgeon likes. Conclusions: There is a lack of high-quality surgical videos of green laser vaporization of the prostate on YouTube. More detailed explanations of the key steps of the operation are needed. We hope that more videos with higher educational value will be published in the future to help surgeons master this technology.

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.

Use of in-bed cycling combined with passive joint activity in acute respiratory failure patients receiving mechanical ventilation.

BACKGROUND: This study aimed to investigate the use of in-bed cycling combined with passive joint movement of upper limbs in patients with acute respiratory failure (ARF) in Department of Intensive Care Unit (ICU). METHODS: One hundred and seven patients receiving mechanical ventilation (MV) for ARF were randomly divided into the intervention group and the control group. Patients in the control group received routine intensive care. In the intervention group, the lower extremity in-bed cycling was combined with the upper extremity passive joint activities. RESULTS: The time of MV, ICU stay, and incidence of ICU-acquired weakness (ICU-AW) were significantly lower, but the Barthel index score was markedly higher in the intervention group than in the control group (P<0.05). CONCLUSIONS: The in-bed cycling combined with passive joint movement of upper limbs is safe and feasible in patients with ARF. It can reduce the duration of MV, ICU stay and incidence of ICU-AW as well as improve their ability to live independently.

Plasma Adipokines in Patients Resuscitated from Cardiac Arrest: Difference of Visfatin between Survivors and Nonsurvivors.

BACKGROUND: Adipokines are a group of cytokines or peptides secreted by adipose tissue to exert numerous biological functions. In the present study, we measured the plasma levels of four adipokines (adiponectin, leptin, fatty acid-binding protein 4 (FABP4), and visfatin) in cardiac arrest patients following return of spontaneous circulation (ROSC). METHODS: Totally, 21 patients who experienced cardiac arrest and successful ROSC with expected survival of at least 48 hours (from January 2016 to December 2017) were consecutively enrolled into this prospective observational clinical study. Of the 21 enrolled patients, ten survived, and other eleven died between 2 days and 6 months post ROSC. Venous blood was drawn at three time points: baseline (<1 hour post ROSC), 2 days post ROSC, and 7 days post ROSC. Plasma concentrations of adiponectin, leptin, FABP4, and visfatin were determined using commercial enzyme-linked immunosorbent assays. RESULTS: The plasma visfatin levels at 2 or 7 days post ROSC increased significantly compared with the baseline (P < 0.01), while plasma levels of adiponectin, leptin, and FABP4 did not change. Moreover, plasma visfatin levels in survivors at 2 or 7 days post ROSC were higher than those in nonsurvivors (P < 0.01). Plasma visfatin levels at 2 or 7 days post ROSC were negatively correlated with Acute Physiology and Chronic Health Evaluation (APACHE) II score and time to ROSC. Moreover, receiver operating characteristic curve analysis showed that the plasma visfatin levels at 2 or 7 days post ROSC were good predictors for survival of the patients. CONCLUSION: Elevated plasma visfatin levels may be a marker for better outcome of cardiac arrest patients post ROSC.

Noninvasive monitoring of intra-abdominal pressure by measuring abdominal wall tension.

BACKGROUND: Noninvasive monitoring of intra-abdominal pressure (IAP) by measuring abdominal wall tension (AWT) was effective and feasible in previous postmortem and animal studies. This study aimed to investigate the feasibility of the AWT method for noninvasively monitoring IAP in the intensive care unit (ICU). METHODS: In this prospective study, we observed patients with detained urethral catheters in the ICU of Shanghai Tenth People's Hospital between April 2011 and March 2013. The correlation between AWT and urinary bladder pressure (UBP) was analyzed by linear regression analysis. The effects of respiratory and body position on AWT were evaluated using the paired samples t test, whereas the effects of gender and body mass index (BMI) on baseline AWT (IAP<12 mmHg) were assessed using one-way analysis of variance. RESULTS: A total of 51 patients were studied. A significant linear correlation was observed between AWT and UBP (R=0.986, P<0.01); the regression equation was Y=-1.369+9.57X (P<0.01). There were significant differences among the different respiratory phases and body positions (P<0.01). However, gender and BMI had no significant effects on baseline AWT (P=0.457 and 0.313, respectively). CONCLUSIONS: There was a significant linear correlation between AWT and UBP and respiratory phase, whereas body position had significant effects on AWT but gender and BMI did not. Therefore, AWT could serve as a simple, rapid, accurate, and important method to monitor IAP in critically ill patients.

Effect of carbon dioxide pneumoperitoneum on human renal cell carcinoma proliferation and metastasis in an orthotropic xenograft nude mouse model.

INTRODUCTION: This study aimed to explore the effect of carbon dioxide (CO2) pneumoperitoneum on tumor proliferation and metastasis in an orthotropic xenograft nude mice model of human renal cell carcinoma (RCC) and evaluate the safety of CO2 pneumoperitoneum laparoscopy for treating RCC. MATERIAL AND METHODS: RCC 786-0 cells were injected to establish an orthotropic xenograft model. Fifty nude mice were given orthotropic inoculations and randomized to five groups: group A (control); group B (CO2 pneumoperitoneum for 2 h); group C (CO2 pneumoperitoneum for 4 h); group D (CO2 pneumoperitoneum for 4 h and 24 h after waking); group E (CO2 pneumoperitoneum for 4 h and 48 h after waking). The proliferation status was observed in RCC specimens by immunohistochemical staining for Ki67. The protein levels of hypoxia-inducible factor-1α (HIF-1α) and vascular endothelial growth factor (VEGF) were examined by western blotting. RESULTS: All groups showed similar Ki67-positive staining in RCC samples (p > 0.05). The relative expression of HIF-1α and VEGF gradually increased in both group B and group C, as compared with group A, but only the difference between group C and group A reached statistical significance (p < 0.05). The protein levels of HIF-1α and VEGF decreased in both group D and group E, as compared with group B and group C; however, the differences between group D, group E, and group A did not reach statistical significance (p > 0.05). CONCLUSIONS: In an orthotropic xenograft nude mice model of RCC, CO2 pneumoperitoneum has no effect on expression of the cellular proliferation marker Ki67. However, CO2 pneumoperitoneum rapidly induces transient expression of HIF-1α and VEGF. Thus, CO2 pneumoperitoneum laparoscopy may be a safe method for treating RCC.