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.

Resolving neuroinflammatory and social deficits in ASD model mice: Dexmedetomidine downregulates NF-κB/IL-6 pathway via α2AR.

Autism spectrum disorder (ASD) is a neurodevelopmental disorder that severely affects individuals' daily life and social development. Unfortunately, there are currently no effective treatments for ASD. Dexmedetomidine (DEX) is a selective agonist of α2 adrenergic receptor (α2AR) and is widely used as a first-line medication for sedation and hypnosis in clinical practice. In recent years, there have been reports suggesting its potential positive effects on improving emotional and cognitive functions. However, whether dexmedetomidine has therapeutic effects on the core symptoms of ASD, namely social deficits and repetitive behaviors, remains to be investigated. In the present study, we employed various behavioral tests to assess the phenotypes of animals, including the three-chamber, self-grooming, marble burying, open field, and elevated plus maze. Additionally, electrophysiological recordings, western blotting, qPCR were mainly used to investigate and validate the potential mechanisms underlying the role of dexmedetomidine. We found that intraperitoneal injection of dexmedetomidine in ASD model mice-BTBR T+ Itpr3tf/J (BTBR) mice could adaptively improve their social deficits. Further, we observed a significant reduction in c-Fos positive signals and interleukin-6 (IL-6) expression level in the prelimbic cortex (PrL) of the BTBR mice treated with dexmedetomidine. Enhancing or inhibiting the action of IL-6 directly affects the social behavior of BTBR mice. Mechanistically, we have found that NF-κB p65 is a key pathway regulating IL-6 expression in the PrL region. In addition, we have confirmed that the α2AR acts as a receptor switch mediating the beneficial effects of dexmedetomidine in improving social deficits. This study provides the first evidence of the beneficial effects of dexmedetomidine on core symptoms of ASD and offers a theoretical basis and potential therapeutic approach for the clinical treatment of ASD.

The design and evaluation of a quick checklist for urodynamic quality control: A prospective single-center small sample study.

PURPOSE: To design a quick checklist for urodynamic study (UDS), aiming to reduce the occurrence of errors in the process, which may help to increase the quality of UDS. And further to analyze the effectiveness of this quick checklist for UDS quality control. METHODS: First, a quick checklist for uroflow study and pressure-flow study was developed, based on the International Continence Society-Good Urodynamic Practice standards, our previous studies, and recent literature, as well as expert suggestions. Then, patients who underwent UDS between January 2023 to February 2023 were randomly assigned to a study group or a control group. For the study group, the quick checklist was used throughout the UDS process, while the control group did not. The main artefacts were chosen to verify the effectiveness of the quick checklist for improving the UDS quality. RESULTS: The quick checklist comprised three subtypes: checklist for patients, checklist for environment and device, and checklist for UDS test process. 38 UDS traces per group were included. The incidence of missing the standard cough test decreased significantly from 18.4% to 0 (p = 0.012), with the checklist implementation. The baseline drift frequency rate also declined significantly from 39.5% to 5.3% (p < 0.05). Volume < 150 mL on uroflow study occurred in 68.4% of cases and its frequency rate decreased significantly with checklist implementation (p < 0.05). CONCLUSION: A quick checklist for quality control of UDS was developed. The quick checklist as a convenient, quick, and easy used urodynamic quality control method, may help to reduce the technical artefacts and improve fundamental urodynamic quality control. Future research with a larger sample size is needed to confirm the effectiveness of the checklist.

Seed-borne bacterial synthetic community resists seed pathogenic fungi and promotes plant growth.

AIMS: In this study, the control effects of synthetic microbial communities composed of peanut seed bacteria against seed aflatoxin contamination caused by Aspergillus flavus and root rot by Fusarium oxysporum were evaluated. METHODS AND RESULTS: Potentially conserved microbial synthetic communities (C), growth-promoting synthetic communities (S), and combined synthetic communities (CS) of peanut seeds were constructed after 16S rRNA Illumina sequencing, strain isolation, and measurement of plant growth promotion indicators. Three synthetic communities showed resistance to root rot and CS had the best effect after inoculating into peanut seedlings. This was achieved by increased defense enzyme activity and activated salicylic acid (SA)-related, systematically induced resistance in peanuts. In addition, CS also inhibited the reproduction of A. flavus on peanut seeds and the production of aflatoxin. These effects are related to bacterial degradation of toxins and destruction of mycelia. CONCLUSIONS: Inoculation with a synthetic community composed of seed bacteria can help host peanuts resist the invasion of seeds by A. flavus and seedlings by F. oxysporum and promote the growth of peanut seedlings.

NFATc2-dependent epigenetic downregulation of the TSC2/Beclin-1 pathway is involved in neuropathic pain induced by oxaliplatin.

Neuropathic pain is a common dose-limiting side effect of oxaliplatin, which hampers the effective treatment of tumors. Here, we found that upregulation of transcription factor NFATc2 decreased the expression of Beclin-1, a critical molecule in autophagy, in the spinal dorsal horn, and contributed to neuropathic pain following oxaliplatin treatment. Meanwhile, manipulating autophagy levels by intrathecal injection of rapamycin (RAPA) or 3-methyladenine (3-MA) differentially altered mechanical allodynia in oxaliplatin-treated or naïve rats. Utilizing chromatin immunoprecipitation-sequencing (ChIP-seq) assay combined with bioinformatics analysis, we found that NFATc2 negatively regulated the transcription of tuberous sclerosis complex protein 2 (TSC2), which contributed to the oxaliplatin-induced Beclin-1 downregulation. Further assays revealed that NFATc2 regulated histone H4 acetylation and methylation in the TSC2 promoter site 1 in rats' dorsal horns with oxaliplatin treatment. These results suggested that NFATc2 mediated the epigenetic downregulation of the TSC2/Beclin-1 autophagy pathway and contributed to oxaliplatin-induced mechanical allodynia, which provided a new therapeutic insight for chemotherapy-induced neuropathic pain.

MiR-672-5p-Mediated Upregulation of REEP6 in Spinal Dorsal Horn Participates in Bortezomib-Induced Neuropathic Pain in Rats.

Evidence shows that miRNAs are deeply involved in nervous system diseases, but whether miRNAs contribute to the bortezomib (BTZ)-induced neuropathic pain remains unclear. We aimed to investigate whether miRNAs contribute to bortezomib (BTZ)-induced neuropathic pain and explore the related downstream cascades. The level of miRNAs in the spinal dorsal horn was explored using miRNA microarray and PCR. MiR-672-5p was significantly downregulated in dorsal horn neurons in the rats with BTZ treatment. Intrathecal injection of miR-672-5p agomir blunted the increase of the amplitude and frequency of sEPSCs in dorsal horn neurons and mechanical allodynia induced by BTZ. In addition, the knockdown of miR-672-5p by intrathecal injection of antagomir increased the amplitude and frequency of sEPSCs in dorsal horn neurons and decreased the mechanical withdrawal threshold in naïve rats. Furthermore, silico analysis and the data from subsequent assays indicated that REEP6, a potential miR-672-5p-regulating molecule, was increased in the spinal dorsal horn of rats with BTZ-induced neuropathic pain. Blocking REEP6 alleviated the mechanical pain behavior induced by BTZ, whereas overexpressing REEP6 induced pain hypersensitivity in naïve rats. Importantly, we further found that miR-672-5p was expressed in the REEP6-positive cells, and overexpression or knockdown of miR-672-5p reversely regulated the REEP6 expression. Bioinformatics analysis and double-luciferase reporter assay showed the existence of interaction sites between REEP6 mRNA and miR-672-5p. Overall, our study demonstrated that miR-672-5p directly regulated the expression of REEP6, which participated in the neuronal hyperexcitability in the spinal dorsal horn and neuropathic pain following BTZ treatment. This signaling pathway may potentially serve as a novel therapeutic avenue for chemotherapeutic-induced mechanical hypersensitivity.

Immunogenicity of COVID-19 vaccines in chronic liver disease patients and liver transplant recipients: A systematic review and meta-analysis.

BACKGROUND AND AIMS: Chronic liver disease (CLD) patients and liver transplant (LT) recipients have an increased risk of morbidity and mortality from coronavirus disease 2019 (COVID-19). The immunogenicity of COVID-19 vaccines in CLD patients and LT recipients is poorly understood. The present study aimed to evaluate the immunogenicity of COVID-19 vaccines in CLD patients and LT recipients. METHODS: We searched electronic databases for eligible studies. Two reviewers independently conducted the literature search, extracted the data and assessed the risk of bias of included studies. The rates of detectable immune response were pooled from single-arm studies. For comparative studies, we compared the rates of detectable immune response between patients and healthy controls. The meta-analysis was conducted using the Stata software with a random-effects model. RESULTS: In total, 19 observational studies involving 4191 participants met the inclusion criteria. The pooled rates of detectable humoral immune response after two doses of COVID-19 vaccination in CLD patients and LT recipients were 95% (95% confidence interval [CI] = 88%-99%) and 66% (95% CI = 57%-74%) respectively. After two doses of vaccination, the humoral immune response rate was similar in CLD patients and healthy controls (risk ratio [RR] = 0.96; 95% CI = 0.90-1.02; p = .14). In contrast, LT recipients had a lower humoral immune response rate after two doses of vaccination than healthy controls (RR = 0.68; 95% CI = 0.59-0.77; p < .01). CONCLUSIONS: Our meta-analysis demonstrated that COVID-19 vaccination induced strong humoral immune responses in CLD patients but poor humoral immune responses in LT recipients.

Statistical process control for the analysis of quality control in urodynamics: A potential new approach for quality review of urodynamics.

PURPOSE: To analyze quality control in urodynamic studies, using a proportion control chart (p-chart) for statistical process control. MATERIALS AND METHODS: This single-center study was conducted at the Urodynamic Center of West China Hospital, Sichuan University. We randomly selected 15 samples from each month in 2020, and 180 urodynamic traces were finally enrolled. We used the p-chart of statistical process control for analysis. We calculated the proportion of the incidence of a selected set of artefacts in the monthly urodynamic study process, including non-standard zero setting, no cough test, incomplete records of all measurements by urodynamicists, catheter displacement, and baseline drift. Through the specific calculation formula of statistical process control, we obtained the values of the center line, lower control limit, and upper control limit. RESULTS: All data points of each artefact were within zone A. However, one outlier was found in the p-chart of all artefacts in October, which might have been caused by inexperienced operators. CONCLUSIONS: Statistical process control may play an important role in the process control of urodynamic studies and guide us in identifying the cause of poor quality in process management.

Correlation between obesity-related measurements and initial and initial resting intravesical and abdominal pressures in urodynamic study using air-filled catheter system.

OBJECTIVES: To establish the initial (before pressure equilibrium) and initial resting intravesical and abdominal pressure in the sitting position using air-filled catheters, to assess the correlation between these pressures and obesity-related measurements, and to estimate if obesity-related measurements can be a guide to interpret initial and initial resting pressures in urodynamic testing. METHODS: Patients with non-neurogenic lower urinary tract symptoms referred for urodynamic testing in our center were consecutively enrolled in a prospective study from August 2022 to October 2022. The correlation between the initial and initial resting pressures (before and after pressure equilibrium) and obesity-related measurements were analyzed using Pearson's correlation coefficient and multiple linear regression analysis. RESULTS: Ninety-eight patients aged 56 ± 16 were studied. The 95% range of the initial intravesical and abdominal pressure were 18-42 cmH2 O and 21-60 cmH2 O, respectively. The initial resting intravesical, abdominal, and detrusor pressure in the 95% range were 17-41, 16-42, and -5 to 4 cmH2 O, respectively. Over the multiple analysis, abdominal fat thickness, and body mass index (BMI) correlated independently with initial intravesical pressure, and only visceral fat grade correlated with initial abdominal pressure. BMI correlated independently with initial resting intravesical pressure. CONCLUSIONS: Our results determined the ranges of values of both initial and initial resting pressures in the air-charged system. Meanwhile, the present study indicated the obesity-related measurements may be used as a guide to interpret the initial and initial resting pressures in urodynamic testing, and may provide a reference for the quality control of these pressures.

Evaluation of the effectiveness of four alternative approaches for the classical cough test during a urodynamic study in the context of the COVID-19 global pandemic.

BACKGROUD: To evaluate four different alternatives to the classical cough test during a urodynamic study in the context of the COVID-19 pandemic. METHODS: Patients who needed to undergo a urodynamic study (UDS) at the West China Hospital of Sichuan University between April 2021 and May 2021 were randomly selected according to the inclusion and exclusion criteria. During the UDS process, we used four alternative methods to the "cough test": 1) quickly pressing the bladder area, 2) performing the Valsalva maneuver, 3) performing the Kegel maneuver, and 4) letting the patient close their mouth while performing the cough test. The "cough" waveform amplitudes and characteristics of the graphics were obtained and compared with the classical cough test. RESULTS: A total of 120 patients (89 men, 31 women) were included in the study. There was no significant difference between the cough waveform amplitude induced by the Valsalva maneuver compared with the classical cough test (P = 0.182); there was no significant difference between the cough waveform amplitude induced by the cough test with the mouth closed and the classical cough test (P = 0.342); there was no significant difference between pressing quickly on the bladder area and the classical method (P = 0.076); and there was a significant difference between the data obtained by the Kegel maneuver and the classical method (P < 0.05). The average "cough" amplitudes obtained were 73.14 ± 22.48 cm H2O, 66.17 ± 17.12 cm H2O, 82.93 ± 18.95 cm H2O, 26.50 ± 8.68 cm H2O, and 68.90 ± 20.32 cm H2O by the classical cough test, by quickly pressing the bladder area, by the Valsalva maneuver, by the Kegel maneuver, and by coughing with a closed mouth, respectively. CONCLUSION: Quickly pressing the bladder area, performing the Valsalva maneuver, and letting the patient close their mouth while performing the cough test can all provide effective cough waveforms and amplitudes. TRIAL REGISTRATION: No. 2021-183.

Effects of intraoperative Magnesium sulfate infusion on emergency agitation during general anesthesia in patients undergoing radical mastectomy: a randomized controlled study.

BACKGROUND: Emergency agitation is a common postoperative complication in patients under general anesthesia, which can lead to unpredictable damages such as shedding of drainage tube and bleeding from the wound. The purpose of the study is to investigate whether intraoperative infusion of Magnesium Sulfate reduces the incidence of emergency agitation (EA) in patients undergoing radical mastectomy, and to evaluate its safety and efficacy. METHODS: A total of 70 patients were randomly assigned to two groups: the Magnesium group (M group) and the control group (C group). After a routine intravenous anesthetic induction, patients in the M group received a 30 mg/kg bolus of intravenous magnesium during the first hour and then a continuous infusion of 10 mg/kg ×h until the end of the surgery, patients in the C group received 0.9% saline at the same volume and rate. The sedation-agitation scale (SAS) and the visual analogue scale were used to assess agitation and pain, respectively. RESULTS: Compared to the C group, the M group reduced the incidence of EA significantly (odds ratio 0.26, 95% confidence interval 0.09-0.71, P = 0.009). The postoperative pain score of the magnesium sulfate group(0(0,1)) was lower than that of the control group(2(0,3)) at T0 (P = 0.011). Additionally, the M group required a lower dosage of remifentanil during surgery compared to the C group(300.4 ± 84 versus 559.3 ± 184 µg, respectively, P<0.001). CONCLUSIONS: the intraoperative infusion of magnesium sulfate is a safe and effective method for reducing the incidence of emergency agitation in patients undergoing radical mastectomy. TRAIL REGISTRATION: The study was registered in Chictr.org with the identifier: ChiCTR2300070595 on 18/04/2023.

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.

Cynasibirolide A, One New Humulanolide Sesquiterpene from Cynanchum acutum subsp. sibiricum.

Cynasibirolide A (1), one new humulanolide sesquiterpene, together with four known analogs, asteriscanolide (2), (1S,8S)-8-hydroxyhumula-2Z,6E,9E-trien-1,12-olide (3), (1S,7R)-8-oxohumula-2Z,9E-dien-1,12-olide (4), and (+)-6,7,9,10-tetrahydroasteriscunolide (5) were isolated from the roots and rhizomes of Cynanchum acutum subsp. sibiricum. Their structures and configurations were elucidated by spectroscopic methods, including 2D-NMR techniques, and the structure of 1 was confirmed by single-crystal X-ray diffraction. All compounds were evaluated for their anti-complementary activity in vitro, and compound 3 exhibited anti-complement effect with CH50 value of 0.45 mM.

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.

Bevacizumab Combined with S-1 and Raltitrexed for Patients with Metastatic Colorectal Cancer Refractory to Standard Therapies: A Phase II Study.

LESSONS LEARNED: Bevacizumab combined with S-1 and raltitrexed demonstrated positive antitumor efficacy and acceptable toxicity. This combination might represent a treatment option for refractory metastatic colorectal cancer. BACKGROUND: In patients with metastatic colorectal cancer (mCRC) refractory to standard therapies, S-1 plus raltitrexed showed a good objective response rate (ORR) and significant survival benefit in our previous study. In the present study, we assessed the activity and safety of bevacizumab combined with S-1 and raltitrexed. METHODS: This investigator-initiated, open-label, single-arm, phase II trial was performed at West China Hospital in China. Patients with mCRC who had disease progression after fluoropyrimidine, irinotecan, and oxaliplatin and had at least one measurable lesion were eligible for this trial. Anti-epidermal growth factor receptor (EGFR) (for tumors with wild-type RAS) and anti-vascular endothelial growth factor (VEGF) therapy in the first or second line was allowed, but patients who had been treated with bevacizumab across two consecutive chemotherapy regimens were excluded. Patients received bevacizumab (7.5 mg/kg on day 1), oral S-1 (80-120 mg per day for 14 days), and raltitrexed (3 mg/m2 on day 1) every 3 weeks. The primary endpoint was ORR. Secondary endpoints included progression-free survival (PFS), overall survival (OS), and toxicity. RESULTS: From September 2015 to November 2019, 44 patients were enrolled. Tumor response evaluation was available in 44 patients at the time of the analysis. There were no complete responses; the ORR was 15.9%, and the disease control rate was 54.5%. Median PFS and OS were 110 days (95% confidence interval [CI], 65.0-155.0) and 367 days (95% CI, 310.4-423.6), respectively. The combination was well tolerated. CONCLUSION: Bevacizumab combined with S-1 and raltitrexed showed promising antitumor activity and safety in refractory mCRC.

Revascularization of Coronary Artery Chronic Total Occlusion by Active Antegrade Reverse Wire Technique.

OBJECTIVES: To assess the effectiveness and safety of ARW for vascular recanalization in CTO patients. BACKGROUND: Chronic total occlusion (CTO) of coronary artery accompanied with large branch distal to the occluded segment (<2 mm) is one of the challenges physicians are facing during the coronary intervention. In cases where the antegrade wire passed the occluded segment reaching the branch vessel, but could not access the main vessel through various adjustments, application of active antegrade reverse wire technique (ARW) could be considered. Patients and Methods. A total of 301 consecutive CTO patients who received the antegrade percutaneous coronary intervention (PCI) between December 2015 and December 2019 at our institution were included, of whom 11 were treated with ARW (10 successfully) for vascular recanalization. The applicability and safety of ARW were assessed. RESULTS: Among the 301 CTO patients who received antegrade vascular recanalization, 11 were treated with ARW. ARW was successful in 10 patients as follows: from the diagonal branch (D) to anterior descending branch (LAD) in 4 patients; from the septal branch (S) to LAD in 1 patient; from D to S and LAD in 1 patient; from the circumflex branch (LCX) to obtuse marginal branch (OM) in 1 patient; from OM to LCX in 1 patient; from a posterior descending artery (PDA) to the posterior lateral vein (PLV) in 2 patients. Yet, ARW in patient with RCAm CTO failed, while the consequent retrograde PCI succeeded. The mean J-CTO score of the 11 patients was 2.7 ± 0.65, among whom eight were accompanied with calcifications. Sion Black and Fielder XTR reverse wires were used in 9 and 2 patients, respectively. No loss of side branches or severe procedure-related complications occurred in 11 patients. CONCLUSION: Therefore, ARW can improve procedural efficiency and should be popularized for further application.

Identification of key genes in human urothelial cells corresponding to interstitial cystitis/bladder pain syndrome in a lipopolysaccharide-induced cystitis model.

AIMS: The cellular functions of bladder urothelial cells in interstitial cystitis/bladder pain syndrome (IC/BPS) have not been well revealed and understood. Thus, the study aims to identify key genes and significant pathways in urothelium corresponding to IC/BPS in a lipopolysaccharide (LPS)-induced cystitis model and provide novel clues related to diagnosis and treatment of IC/BPS. METHODS: Human urothelial cells (HUCs) were incubated with LPS (50 µg/ml for 24 h). Microarray was applied to analyze the differentially expressed genes (DEGs) between HUCs under LPS treatment and the control group. DEGs in the two groups were identified and then used for enrichment analysis. Subsequently, protein-protein interaction (PPI) network based on DEGs was constructed. Lastly, the top five key genes were identified through the Cytoscape (version 3.7.2) using the "Clustering Coefficient" algorithm. RESULTS: One hundred and seventy-one DEGs (96 upregulated genes and 75 downregulated genes) were identified between the LPS treatment and control group. The established PPI network was composed of 169 nodes and 678 edges. Moreover, C19orf33, TRIM31, MUC21, ELF3, and IFI27 were identified as hub genes in the PPI network. Subsequently, a statistically increased expression level of TRIM31 and ELF3 was validated by real-time quantitative-polymerase chain reaction and immunohistochemistry in bladder tissues from 20 patients with IC/BPS. CONCLUSIONS: TRIM31 and ELF3 may be the two hub genes in urothelium corresponding to IC/BPS. More studies are warranted to further validate the findings. The identified marker genes may be useful targets for further studies to develop diagnostic tools and more effective therapies for a broader group of women with IC/PBS.

Is imidafenacin an alternative to current antimuscarinic drugs for patients with overactive bladder syndrome?

PURPOSE: Previous studies have included a limited number of randomized controlled trials (RCTs) and compared limited parameters after treatment with imidafenacin and other anticholinergic drugs (ADs) for overactive bladder syndrome (OAB), and controversy about the superiority of these ADs still remains. We aim to update the evidence and provide better clinical guidance. METHODS: A systematic search of PubMed, Embase, ClinicalTrial.gov and Cochrane Library Central Register of Controlled Trials was conducted from January 2007 to April 2019. Meta-analysis of all published RCTs comparing imidafenacin with other ADs in patients with OAB was performed. The primary outcomes were the changes in OAB symptoms and OAB symptom score (OABSS). Secondary outcomes included adverse events (AEs) and the dropout rate related to AEs. RESULTS: A total of 6 studies including 7 RCTs involving 1430 patients with mean follow-up of 23.43 weeks were included. All ADs improved OAB symptoms. Regarding efficacy, these drugs had similar efficacy in voids, urgency episodes, urgency incontinence episodes, incontinence episodes and OABSS. However, imidafenacin performed better in the reduction of nocturia episodes (MD = -0.24, 95% CI -0.44 to -0.04, P = 0.02). Moreover, imidafenacin was associated with a statistically lower dry mouth rate (RR = 0.87, 95% CI 0.75-1.00, P = 0.04), lower constipation rate (RR = 0.68, 95% CI 0.50-0.93, P = 0.01) and lower AE-related withdrawal rate (RR = 0.51, 95% CI 0.29-0.89, P = 0.02). There was no significant difference in terms of other complications. CONCLUSIONS: In conclusion, imidafenacin was comparable to other ADs in the treatment of OAB. Moreover, imidafenacin presented a lower dry mouth rate, lower constipation rate and higher adherence and persistence.

Efficacy and safety comparison of pharmacotherapies for interstitial cystitis and bladder pain syndrome: a systematic review and Bayesian network meta-analysis.

INTRODUCTION AND HYPOTHESIS: The objective was to compare the clinical efficacy and safety of pharmacological interventions for interstitial cystitis and bladder pain syndrome (IC/BPS) with direct and indirect evidence from randomized trials. METHODS: We searched PubMed, the Cochrane library, and EMBASE for randomized controlled trials (RCTs) that assessed the pharmacological therapies for IC/BPS. Primary efficacy outcomes included ICSI (O'Leary Sant Interstitial Cystitis Symptom Index), ICPI (O'Leary Sant Interstitial Cystitis Problem Index), 24-h micturition frequency, visual analog scale (VAS), and Likert score for pain. Safety outcomes are total adverse events (AEs, intravesical instillation, and others), gastrointestinal symptoms, headache, pain, and urinary symptoms. A systematic review and Bayesian network meta-analysis were performed. RESULTS: A total of 23 RCTs with 1,871 participants were identified. The ICSI was significantly reduced in the amitriptyline group (MD = -4.9, 95% CI: -9.0 to -0.76), the cyclosporine A group (MD = -7.9, 95% CI: -13.0 to -3.0) and the certolizumab pegol group (MD = -3.6, 95% CI:-6.5 to -0.63) compared with placebo group. Moreover, for ICPI, cyclosporine A showed superior benefit compared to placebo (MD = -7.6, 95% CI: -13 to -2.3). VAS score improved significantly in cyclosporine A group than pentosan polysulfate sodium (MD = 3.09, 95% CI: 0.13 to 6.07). None of the agents revealed a significant alleviation of 24-h micturition frequency. In terms of safety outcomes, the incidence rate on urinary symptoms for botulinum toxin A was the only variate higher than chondroitin sulfate (MD = -2.02, 95% CI: -4.99 to 0.66) and placebo (MD = -1.60, 95% CI:-3.83 to 0.17). No significant difference was found among the other treatments. CONCLUSIONS: Cyclosporine A might be superior to other pharmacological treatments in efficacy. Amitriptyline and certolizumab pegol were capable of lowering the ICSI as well.

Metabolic syndrome in women with and without interstitial cystitis/bladder pain syndrome.

INTRODUCTION AND HYPOTHESIS: The aim of this study was to compare the frequency of metabolic syndrome (MetS) in patients with and without interstitial cystitis/bladder pain syndrome (IC/BPS). METHODS: This case-control study evaluated the indicators of MetS in 287 females with IC/BPS and in 287 females without IC/BPS in West China Hospital between January 2010 and January 2020. Then, the number of voids per day, frequency of night urination, O'Leary-Sant Interstitial Cystitis Symptom/Problem Index, and visual analog scale were examined in the two groups. RESULTS: Based on both the National Cholesterol Education Program Adult Treatment Panel III recommendations and the International Diabetes Federation criteria, the distribution of MetS was statistically higher in patients with IC/BPS than in the control group, with 34.8% vs 17.8% (P < 0.0001) and 34.2% vs 20.9% (P = 0.0005), respectively. Regarding symptom scores, the IC/BPS group demonstrated significantly higher scores than the control group in all aspects (P < 0.0001). More patients with anxiety (P < 0.0001), insomnia (P < 0.0001), hypertension (P = 0.0001), and diabetes mellitus (P = 0.017) were observed in the IC/BPS group. Moreover, the findings indicated that patients with IC/BPS had a higher BMI (P = 0.0001) and larger waist circumference (P = 0.0001). Blood tests presented a significantly higher level of fasting glycemia, serum cystatin-C, and triglycerides in patients with IC/BPS. Furthermore, higher ORs for the occurrence of MetS among cases were observed, although this was not statistically significant. CONCLUSIONS: MetS frequency was relatively high in patients with IC/BPS. Further research is needed to understand the common pathophysiologic mechanism of IC/BPS and MetS.