This study aimed to provide evidence of persistent uropathogenic Escherichia coli(UPEC) in female patients with recurrent urinary tract infection(UTI) after antibiotic therapy. We collected biopsies of the bladder...This study aimed to provide evidence of persistent uropathogenic Escherichia coli(UPEC) in female patients with recurrent urinary tract infection(UTI) after antibiotic therapy. We collected biopsies of the bladder, and clean-catch urine samples from 32 women who had episodes of recurrent UTI and were given antibiotic therapy. Urine samples and biopsies were analyzed by conventional bacteriological techniques. Phylogenetic group and 16 virulence factors(VFs) of UPEC were determined using polymerase chain reaction(PCR). The infection capability of UPEC was confirmed in a mouse model. Immunofluorescence and electron microscopy were used to detect intracellular bacterial communities(IBCs) in the mouse model. The results showed that all urine specimens were detected sterile. E. coli was found in 6 of 32 biopsies(18.75%), and was identified to be UPEC by PCR. Different VFs associated with the formation of IBCs were identified in all six UPEC isolates. Each UPEC isolate was capable of forming IBCs within the bladder epithelial cells of mice. In conclusion, UPEC with distinctive pathological traits and the capability of IBC formation was first found in the bladders of women after antibiotic therapy, suggesting that the IBC pathogenic pathway may occur in humans and it plays an important role in UTI recurrence.展开更多
[Objective] This research aimed at studying the mechanism of the occurrence of epithelial cell loss in bladders of prenatal and postnatal mice. [Method] Bladder epithelia of 1-2-day-old newborn Kunming mice and mice a...[Objective] This research aimed at studying the mechanism of the occurrence of epithelial cell loss in bladders of prenatal and postnatal mice. [Method] Bladder epithelia of 1-2-day-old newborn Kunming mice and mice at later period of embryonic development were acquired, and paraffin sections of such epithelia were then made for Mallory's coloration and ordinary optical microscopic observation. The acquired bladder epithelia were made into frozen sections, which were then colored by DAPI and labeled in situ by Terminal-deoxynucleoitidyl Transferase Mediated Nick End Labeling(TUNEL) for fluorescent microscopic observation. DNA electrophoresis and TUNEL in situ labeling were conducted on the acquired urine exfoliated cells. [Result] The results showed that the complete three layers of cells occurred in 20-day-old mouse embryos, whereas no superficial cells resided in the bladder epithelia of newborn mice and no cells exfoliating were observed. Cells exfoliating from the bladder epithelia of newborn mice were observed, and they exhibited the phenomenon of apoptosis. There were apoptosis existed in the urine cells of newborn mice. [Conclusion] Therefore, the results showed that a few days before and after their birth, mice witnessed the process of cell exfoliation in their bladder epithelia and the exfoliated cells showed typical characteristics of apoptosis.展开更多
Introduction: The ureteral ostia may not be easily identified in urological endoscopic procedures, leading to an incomplete diagnosis of urinary tract diseases or a predisposition to iatrogenic lesions. The purpose of...Introduction: The ureteral ostia may not be easily identified in urological endoscopic procedures, leading to an incomplete diagnosis of urinary tract diseases or a predisposition to iatrogenic lesions. The purpose of our study is to evaluate the anatomical distribution of ureteralostia in normal bladders and those with thickened walls. Materials and Methods: We dissected 30 vesical-prostate blocks from human cadavers and identified the ostia of the bladder trigone. A computerized morphometric analysis was performed to measure the thickness of the detrusor muscle, the distances between the ureteral ostia themselves and the distances between each ureteral ostium (left—LUO and right—RUO) and the internal urethral ostium (IUO). The angle formed between the IUO and LUO/RUO was also recorded as well as the volume of the prostates. Results: Fifteen bladders with a non-thickened detrusor (6 mm) were identified. The average prostatic volume of the dissected blocks was 23.7 cm3. The distance between ureteral ostia, the distance from IUO to LUO, the distance from IUO to RUO and the angle formed between IUO and LUO/RUO in normal and thickened bladder were, respectively, 1.9 cm/2.2 cm (p = 0.09), 1.6 cm/1.6 cm (p = 0.82), 1.6 cm/1.7 cm (p = 0.79) and 77/91 (p = 0.17). Conclusions: Our study shows that there is no significant difference in the position of bladder ostia in healthy and thickened bladders. We believe that our findings may facilitate locating the ureteral orifices in situations where endoscopic identification is difficult.展开更多
We introduce a modified surgical technique for internal ureteroileal stenting to improve cosmesis in patients undergoing ileal neobladder. Internal ureteric stents are secured to the tip of the urethral catheter with ...We introduce a modified surgical technique for internal ureteroileal stenting to improve cosmesis in patients undergoing ileal neobladder. Internal ureteric stents are secured to the tip of the urethral catheter with nonabsorbable suture facilitating removal of the stents postoperatively 2-3 weeks along with the urethral catheter. This surgical modification was applied to 21 patients of whom no significant surgical or infectious complication due to single urethral catheter was observed. Internal ureteral stenting is simple, safe and inexpensive alternative to conventional methods to support ureteroileal anastomosis in patients undergoing orthotopic bladder substitution.展开更多
BACKGROUND The incidence of diabetic atherosclerosis(DMA)is increasing worldwide,but its pathogenesis remains incompletely understood.In addition to cardiovascular complications,bladder dysfunction is one of the commo...BACKGROUND The incidence of diabetic atherosclerosis(DMA)is increasing worldwide,but its pathogenesis remains incompletely understood.In addition to cardiovascular complications,bladder dysfunction is one of the common comorbidities associated with DMA but is often refractory to current treatments.AIM To investigate the therapeutic effect of human amniotic fluid stem cell-derived extracellular vesicles(hAFSC-EVs)on the recovery of bladder dysfunction in DMA rats.METHODS Eighty rats were divided into normal control,streptozotocin-induced diabetic rats,diabetic rats subjected to arterial balloon endothelial injury of common iliac artery(DMA),and DMA rats treated with hAFSC-EVs(DMA+hAFSC-EVs).At 4 weeks and 12 weeks after DMA induction,levels of blood glucose,total cholesterol,triglyceride,high-density lipoprotein cholesterol,low-density lipoprotein cholesterol,homeostasis model assessment(HOMA)-insulin resistance,and HOMA-βwere measured.Cystometry,common iliac artery wall thickness,and bladder tumor necrosis factor(TNF)-α,interleukin(IL)-6,transforming growth factor(TGF)-β1,Smad3,connective tissue growth factor(CTGF)and fibronectin were also evaluated.RESULTS Bladder weight and blood glucose,triglyceride,HOMA-insulin resistance,common iliac artery intima thickness,voided volume,intercontraction interval,bladder capacity,and mRNA expression of TNF-α,IL-6,TGF-β1,Smad3,CTGF and fibronectin were significantly increased at 4 weeks and 12 weeks after induction,while the HOMA-βlevel decreased at 4 weeks and 12 weeks,and the high-density lipoprotein cholesterol level decreased at 12 weeks.hAFSC-EVs treatment in DMA rats significantly reduced bladder weight and blood glucose,thickness of common iliac arterial intima,voided volume,intercontraction interval and bladder capacity at 4 weeks.The mRNA expression of TNF-α,TGF-β1,and CTGF in DMA rats treated with hAFSC-EVs were significantly decreased at 4 weeks,while the mRNA expressions of IL-6 and Smad3 were significantly decreased 12 weeks.CONCLUSION hAFSC-EVs treatment can help restore DMA-induced bladder dysfunction,which is associated with lowered blood glucose levels,reduced arterial wall thickness,and decreased TNF-α,IL-6,TGF-β1,Smad3,and CTGF expression.展开更多
Salt bladders,specialized structures on the surface of quinoa leaves,secrete Na+to mitigate the effects of the plant from abiotic stresses,particularly salt exposure.Understanding the development of these structures i...Salt bladders,specialized structures on the surface of quinoa leaves,secrete Na+to mitigate the effects of the plant from abiotic stresses,particularly salt exposure.Understanding the development of these structures is crucial for elucidating quinoa’s salt tolerance mechanisms.In this study,we employed transmission electron microscopy to detail cellular differentiation across the developmental stages of quinoa salt bladders.To further explore the developmental trajectory and underlying molecular mechanisms,we conducted single-cell RNA sequencing on quinoa protoplasts derived from young leaves.This allowed us to construct a cellular atlas,identifying 13 distinct cell clusters.Through pseudotime analysis,we mapped the developmental pathways of salt bladders and identified regulatory factors involved in cell fate decisions.GO and KEGG enrichment analyses,as well as experimental results,revealed the impacts of salt stress and the deprivation of sulfur and nitrogen on the development of quinoa salt bladders.Analysis of the transcription factor interaction network in pre-stalk cells(pre-SC),stalk cells(SC),and epidermal bladder cells(EBCs)indicated that TCP5,YAB5,NAC078,SCL8,GT-3B,and T1P17.40 play crucial roles in EBC development.Based on our findings,we developed an informative model elucidating salt bladder formation.This study provides a vital resource for mapping quinoa leaf cells and contributes to our understanding of its salt tolerance mechanisms.展开更多
Background::Since 2019,a novel coronavirus named 2019 novel coronavirus(2019-nCoV)has emerged worldwide.Apart from fever and respiratory complications,acute kidney injury has been observed in a few patients with coron...Background::Since 2019,a novel coronavirus named 2019 novel coronavirus(2019-nCoV)has emerged worldwide.Apart from fever and respiratory complications,acute kidney injury has been observed in a few patients with coronavirus disease 2019.Furthermore,according to recent findings,the virus has been detected in urine.Angiotensin-converting enzyme II(ACE2)has been proposed to serve as the receptor for the entry of 2019-nCoV,which is the same as that for the severe acute respiratory syndrome.This study aimed to investigate the possible cause of kidney damage and the potential route of 2019-nCoV infection in the urinary system.Methods::We used both published kidney and bladder cell atlas data and new independent kidney single-cell RNA sequencing data generated in-house to evaluate ACE2 gene expression in all cell types in healthy kidneys and bladders.The Pearson correlation coefficients between ACE2 and all other genes were first generated.Then,genes with r values larger than 0.1 and P values smaller than 0.01 were deemed significant co-expression genes with ACE2.Results::Our results showed the enriched expression of ACE2 in all subtypes of proximal tubule(PT)cells of the kidney.ACE2 expression was found in 5.12%,5.80%,and 14.38%of the proximal convoluted tubule cells,PT cells,and proximal straight tubule cells,respectively,in three published kidney cell atlas datasets.In addition,ACE2 expression was also confirmed in 12.05%,6.80%,and 10.20%of cells of the proximal convoluted tubule,PT,and proximal straight tubule,respectively,in our own two healthy kidney samples.For the analysis of public data from three bladder samples,ACE2 expression was low but detectable in bladder epithelial cells.Only 0.25%and 1.28%of intermediate cells and umbrella cells,respectively,had ACE2 expression.Conclusion::This study has provided bioinformatics evidence of the potential route of 2019-nCoV infection in the urinary system.展开更多
Schwann cell transplantation is considered one of the most promising cell-based therapy to repair injured spinal cord due to its unique growth-promoting and myelin-forming properties.A the Food and Drug Administration...Schwann cell transplantation is considered one of the most promising cell-based therapy to repair injured spinal cord due to its unique growth-promoting and myelin-forming properties.A the Food and Drug Administration-approved Phase I clinical trial has been conducted to evaluate the safety of transplanted human autologous Schwann cells to treat patients with spinal cord injury.A major challenge for Schwann cell transplantation is that grafted Schwann cells are confined within the lesion cavity,and they do not migrate into the host environment due to the inhibitory barrier formed by injury-induced glial scar,thus limiting axonal reentry into the host spinal cord.Here we introduce a combinatorial strategy by suppressing the inhibitory extracellular environment with injection of lentivirus-mediated transfection of chondroitinase ABC gene at the rostral and caudal borders of the lesion site and simultaneously leveraging the repair capacity of transplanted Schwann cells in adult rats following a mid-thoracic contusive spinal cord injury.We report that when the glial scar was degraded by chondroitinase ABC at the rostral and caudal lesion borders,Schwann cells migrated for considerable distances in both rostral and caudal directions.Such Schwann cell migration led to enhanced axonal regrowth,including the serotonergic and dopaminergic axons originating from supraspinal regions,and promoted recovery of locomotor and urinary bladder functions.Importantly,the Schwann cell survival and axonal regrowth persisted up to 6 months after the injury,even when treatment was delayed for 3 months to mimic chronic spinal cord injury.These findings collectively show promising evidence for a combinatorial strategy with chondroitinase ABC and Schwann cells in promoting remodeling and recovery of function following spinal cord injury.展开更多
BACKGROUND Urinary system tumors often cause negative psychological symptoms,such as depression and dysphoria which significantly impact immune function and indirectly affect cancer prognosis.While epirubicin(EPI)is r...BACKGROUND Urinary system tumors often cause negative psychological symptoms,such as depression and dysphoria which significantly impact immune function and indirectly affect cancer prognosis.While epirubicin(EPI)is recommended by the European Association of Urology and can improve prognosis,its long-term use can cause toxic side effects,reduce treatment compliance,and increase psycho-logical burden.Therefore,an appropriate intervention mode is necessary.METHODS This was a retrospective study including 110 patients with urinary system tumors and depression admitted to Zhumadian Central Hospital between March 2021 and July 2023.Patients were divided into conventional(n=55)and joint inter-vention(n=55)groups.The conventional group received mitomycin and routine nursing,while the joint intervention group received EPI and mindfulness intervention.Both groups underwent three cycles of chemotherapy.Immune function(CD4+cells,CD8+cells,CD4+/CD8+ratio),tumor marker levels[urinary bladder cancer antigen(UBC),bladder tumor antigen(BTA)and nuclear matrix protein 22(NMP22)],quality of life questionnaire-core 30(QLQ-C30),17-item Hamilton depression scale(HAMD-17),and cancer-related fatigue[cancer fatigue scale(CFS)]were assessed.Adverse reactions and nursing satisfaction were recorded and evaluated.RESULTS Post-intervention,CD4+,CD8+,and CD4+/CD8+levels increased in both groups,with the joint intervention group showing more significant improvement(P<0.05).Tumor marker levels(NMP22,BTA,and UBC)were lower in the joint intervention group compared to the conventional group(P<0.05).The joint intervention group also showed a greater reduction in HAMD-17 scores(9.38±3.12 vs 15.45±4.86,P<0.05),higher QLQ-C30 scores,and lower CFS scores(both P<0.05).Additionally,the joint intervention group had a lower incidence of adverse reactions and higher nursing satisfaction(P<0.05).CONCLUSION EPI combined with mindfulness intervention significantly improved clinical outcomes in patients with urinary system tumors and depression and is worthy of clinical application.展开更多
Objective The present study evaluated the effects of deep acupuncture at Weizhong acupoint(BL40)on bladder function and brain activity in a rat model of overactive bladder(OAB),and investigated the possible mechanisms...Objective The present study evaluated the effects of deep acupuncture at Weizhong acupoint(BL40)on bladder function and brain activity in a rat model of overactive bladder(OAB),and investigated the possible mechanisms around the acupuncture area that initiate the effects of acupuncture.Methods Adult female Sprague-Dawley rats were randomly divided into six groups,comprising a control group,model group,group treated with deep acupuncture at BL40,group treated with shallow acupuncture at BL40,group treated with acupuncture at non-acupoint next to BL40,and group treated with acupuncture at Xuanzhong(GB39).Urodynamic evaluation was used to observe the urination,and functional magnetic resonance imaging was used to observe the brain activation.The mechanism of acupuncture at BL40 in regulating bladder function was explored by toluidine blue staining and enzyme-linked immunosorbent assay,and the mechanism was verified by stabilizing mast cells(MCs)or blocking tibial nerve.Results Deep acupuncture at BL40 significantly increased the intercontraction interval in OAB rats and enhanced the mean amplitude of low frequency fluctuation of primary motor cortex(M1),periaquaductal gray matter(PAG),and pontine micturition center(PMC).It also increased the zero-lag functional connectivity between M1 and PAG and between PAG and PMC.Shallow acupuncture at BL40 and acupuncture at non-acupoint or GB39 had no effect on these indexes.Further studies suggested that deep acupuncture at BL40 increased the number and degranulation rate of MCs as well as the contents of 5-hydroxytryptamine,substance P,and histamine in the tissues around BL40.Blocking the tibial nerve by lidocaine injection or inhibiting MC degranulation by sodium cromoglycate injection obstructed the effects of acupuncture on restoring urinary function and modulating brain activation in OAB rats.Conclusion Deep acupuncture at BL40 may be more effective for inhibiting OAB by promoting degranulation of MCs around the acupoint and stimulating tibial nerve,thereby regulating the activation of the brain area that controls the lower urinary tract.展开更多
Clinical bladder evaluation is a cost-effective,non-invasive method for diagnosing and managing urinary dysfunction,particularly in patients with neurogenic bladder or other impairments.This process aims to assess bla...Clinical bladder evaluation is a cost-effective,non-invasive method for diagnosing and managing urinary dysfunction,particularly in patients with neurogenic bladder or other impairments.This process aims to assess bladder capacity,storage,and voiding functions through simple,realistic,and resource-friendly approaches.It involves a structured series of steps,from history-taking and physical examination to bladder-emptying procedures,monitoring urine leaks,assessing reflex voiding,measuring post-void residual(PVR),and calculating total bladder capacity.These evaluations help differentiate between upper motor neuron and lower motor neuron bladder dysfunction,providing critical insights for tailored management.The interpretation of findings focuses on identifying bladder type,assessing leak timing and volume,evaluating reflex voiding,and measuring PVR and total bladder capacity.The results guide interventions such as timing selfclean intermittent catheterization,adjusting fluid intake,and using bladder diaries to monitor patterns.Clinical bladder evaluation is particularly advantageous in low-resource settings,as it avoids the risks and costs associated with urodynamic studies while reflecting real-life patient conditions more effectively.Despite its benefits,no validation studies currently exist for clinical bladder assessment,and its parameters,like maximum voided volume,remain underexplored compared to urodynamic measures.Given the accessibility,affordability,and practicality of this approach,it holds promise for widespread application,especially in primary care settings and among economically disadvantaged populations.This editorial describes the process step-by-step and highlights its role in improving patient outcomes while minimizing complications.展开更多
Introduction:Non–muscle-invasive bladder cancer(NMIBC)is a common malignancy worldwide.While Bacillus Calmette-Guérin(BCG)is standard of care for treatment for most patients with high-risk NMIBC,many will either...Introduction:Non–muscle-invasive bladder cancer(NMIBC)is a common malignancy worldwide.While Bacillus Calmette-Guérin(BCG)is standard of care for treatment for most patients with high-risk NMIBC,many will either not respond to BCG initially or will eventually develop BCG-unresponsive disease.A treatment option in BCG-unresponsive disease is nadofaragene firadenovec-vncg(Adstiladrin),a nonreplicating adenoviral vector–based gene therapy approved by the US Food and Drug Administration(FDA)for the treatment of adults with high-risk BCGunresponsive NMIBC with carcinoma in situ with or without papillary tumors.Objective:To review safety outcomes of participants who received the FDA-approved dose of nadofaragene firadenovec(3×10^(11)vp/mL)across phase 2(NCT01687244)and phase 3(NCT02773849)studies.Methods:Data from the phase 2 and phase 3 studies were collected and analyzed.The findings were reported using descriptive statistics to summarize the key outcomes observed across studies.Results:Common adverse events(AEs)among nadofaragene firadenovec recipients were leakage of fluid around the urinary catheter,fatigue,bladder spasm,chills,dysuria,and micturition urgency.Most study drug–related AEs were mild and localized,with no grade 4 or 5 study drug–related AEs observed in either study.Study drug–related AEs were generally transient,with most study drug–related AEs having a median duration of≤2.0 days in the phase 3 study.Discontinuation rates due to study drug–related AEs were low,with none(0%)in the phase 2 study and three(1.9%)in the phase 3 study.No specific postmarketing surveillance was required by the FDA besides routine pharmacovigilance monitoring;no new real-world safety signals have been observed.Conclusion:Nadofaragene firadenovec demonstrated a favorable and tolerable safety profile across its clinical study program,allowing for broad patient selection among those with high-risk BCG-unresponsive NMIBC.展开更多
Dear Editor,Primary bladder neck obstruction(PBNO)affects approximately 28%–54%of men[1].Its etiology remains unclear.Symptoms of PBNO present as voiding(e.g.,decreased force of stream,hesitancy,intermittent stream,a...Dear Editor,Primary bladder neck obstruction(PBNO)affects approximately 28%–54%of men[1].Its etiology remains unclear.Symptoms of PBNO present as voiding(e.g.,decreased force of stream,hesitancy,intermittent stream,and incomplete emptying),storage(e.g.,frequency,urgency,urge incontinence,and nocturia),or a combination of both[2].Untreated PBNO can lead to bladder dysfunction,bladder diverticula,hydronephrosis,and impaired renal function[3].展开更多
The published article titled“Puerarin inhibits proliferation and induces apoptosis by upregulation of miR-16 in bladder cancer cell line T24”has been retracted from Oncology Research,Vol.26,No.8,2018,pp.1227–1234.
Background:The COVID-19 pandemic disrupted healthcare systems globally,raising concerns about delayed cancer diagnosis and treatment.In France,transurethral resection of bladder tumors(TURBT)was prioritized in nationa...Background:The COVID-19 pandemic disrupted healthcare systems globally,raising concerns about delayed cancer diagnosis and treatment.In France,transurethral resection of bladder tumors(TURBT)was prioritized in national urology guidelines to ensure the timely management of urothelial carcinoma.This study aimed to assess the impact of care reorganization on tumor staging,recurrence,palliative care,and mortality in bladder cancer patients from the pre-pandemic through late-pandemic periods.Methods:We conducted a retrospective multicenter study including all patients who underwent TURBT with histologically confirmed urothelial carcinoma between April and December of 2019(pre-pandemic),2020(early pandemic),2021(mid-pandemic),and 2022(late pandemic)in two French institutions.TURBT indications were categorized as diagnostic,palliative,or staging.Clinical and pathological data were compared across the four periods.Statistical analyses included Chi-square tests,Estimated Annual Percentage Change(EAPC),and multivariable logistic regression adjusted for age,sex,ASA score,and center.Results:A total of 790 TURBT procedures were analyzed.The proportion of muscle-invasive bladder cancer(pT≥2)declined over time(18.7%in 2019 to 13.2%in 2022;p=0.63),while superficial tumors(pTa)increased(57.2%to 65.5%).All-cause mortality significantly decreased from 38.0%in 2019 to 22.0%in 2020,20.5%in 2021,and 19.5%in 2022(p=0.006).EAPC showed a significant annual decline in mortality(–24.3%,p=0.004).In multivariable analysis,2020,2021,and 2022 were each associated with significantly lower odds of mortality compared to 2019.Recurrence rates remained stable across all periods(p=0.93).Interhospital variation persisted in mortality and recurrence.Conclusions:Despite the pandemic,urothelial bladder cancer outcomes did not worsen through 2022.On the contrary,timely reorganization,prioritization of TURBT,and triage strategies were associated with reduced mortality and palliative care needs,highlighting the resilience of cancer care when guided by adaptive health policies.展开更多
Objective:To observe the effect of Xipayimaizibizi oral liquid(XP)in an overactive bladder(OAB)experimental rat model and to explore its pharmacological mechanisms.Methods:Network pharmacology was used to explore the ...Objective:To observe the effect of Xipayimaizibizi oral liquid(XP)in an overactive bladder(OAB)experimental rat model and to explore its pharmacological mechanisms.Methods:Network pharmacology was used to explore the potential mechanisms of action of XP.The rats underwent bladder outlet obstruction surgery and were administered the corresponding drug concentrations by gavage for 4 weeks.The study observed the body weight,water intake,bladder and kidney indices(to evaluate their general status),urination behavior pattern(to observe frequency and urgency),and urodynamics(to measure bladder parameters).Hematoxylin and eosin and Masson's trichome staining were used to observe changes in the bladder structure.Enzyme-linked immunosorbent assay was used to measure the levels of nerve growth factor,brain-derived neurotrophic factor,and acetylcholine in the urine.The key targets involved in these mechanisms were validated using reverse transcription-quantitative polymerase chain reaction,immunohistochemistry,and western blot in vivo/vitro experiments.Result:Network pharmacological analysis predicted that XP may alleviate OAB by affecting the cholinergic synapse and calcium signaling pathways.XP treatment significantly reduced the bladder index,improved urine behavior and urodynamic parameters,decreased the neurotransmitters in urine,and reduced the thickness of the bladder wall and collagen ratio.These results indicate that XP can alleviate OAB symptoms and improve the bladder structure.In vivo/vitro experiments further demonstrated that XP can inhibit targets,such as muscarinic acetylcholine receptor 2,and participate in cholinergic synapses to further regulate the parasympathetic nervous system.It can also reduce the overexpression of Ca^(2+) caused by agonists,inhibit targets such as transient receptor potential vanilloid type 1,and participate in calcium signaling pathways to maintain Ca^(2+) homeostasis.Conclusion:These results suggest that XP inhibited bladder overactivity by maintaining Ca^(2+) homeostasis and regulating the parasympathetic nervous system.展开更多
When Julian Bird was 60,he was diagnosed(诊断)with cancer of the bladder.He had a series of unpleasant operations,and the doctor predicted that he was likely to die pretty soon.After 34 years as a psychiatrist(精神科...When Julian Bird was 60,he was diagnosed(诊断)with cancer of the bladder.He had a series of unpleasant operations,and the doctor predicted that he was likely to die pretty soon.After 34 years as a psychiatrist(精神科医生),in that intense state of mind,he began to daydream about becoming a professional actor.展开更多
Introduction: The therapeutic approach to benign prostatic hyperplasia (BPH) has evolved profoundly. Surgical treatment is reserved for complicated cases and the reference surgical technique is transurethral resection...Introduction: The therapeutic approach to benign prostatic hyperplasia (BPH) has evolved profoundly. Surgical treatment is reserved for complicated cases and the reference surgical technique is transurethral resection of the prostate (TURP). This work aims to study the epidemiological, clinical and therapeutic aspects of monopolar transurethral resection of the prostate in our department. Materials and Methods: We conducted a descriptive study with retrospective data collection over a 12-month period from November 1, 2023 to December 31, 2024. The urology unit, an integral part of the surgery department, of the Sino-Guinean Friendship Hospital in Conakry served as the setting for this study. It included 27 patients with benign prostatic hypertrophy treated surgically by monopolar transurethral resection and having a usable medical record. The parameters studied were epidemiological, clinics and therapeutic. Results: The mean age of the patients was 68.57 ± 5.7 years with extremes from 50 to 79 years. The peak frequency was observed between 70 and 79 years (48.15%). All our patients had lower urinary tract disorders, i.e. 100% of cases. On digital rectal examination, an increase in the volume of the prostate of benign appearance was observed in all cases. The mean prostate volume was 43.7 cc on ultrasound with extremes from 34 cc to 58 cc. The total PSA level was less than 4 ng/ml in the majority of cases. The postoperative course was generally uncomplicated (n = 26) with removal of the urinary catheter on the second postoperative day (D2). However, one peroperative complication was observed in one patient;it was a bladder breach, leading to the passage of glycine into the peritoneum. Conclusion: Transurethral resection of the prostate has reduced the length of hospital stay of our patients, as well as the comorbidities associated with the treatment. The complications associated with it are rare but potentially serious. Its performance requires in-depth mastery of the endoscopic anatomy of the lower urinary tract as well as technical operative expertise.展开更多
BACKGROUNDΒ-elemene is widely used to treat a variety of cancers,including bladder cancer(BLCA).However,the anti-cancer target,effective constituents and mechanism was unclear.AIM To investigate the therapeutic effec...BACKGROUNDΒ-elemene is widely used to treat a variety of cancers,including bladder cancer(BLCA).However,the anti-cancer target,effective constituents and mechanism was unclear.AIM To investigate the therapeutic effect and underlying mechanism ofβ-elemene in BLCA.METHODS We first mined the GEPIA2 database to explore the association between the GM3(ST3 Beta-Galactoside Alpha-2,3-Sialyltransferase 5,GM3,ST3GAL5)gene and BLCA.Second,we performed in vitro experiments using BLCA cells to verify the inhibitory effect and targets therapy ofβ-elemene on BLCA.RESULTS Our results revealed a significantly reduced expression of GM3 in BLCA tissues.Notably,BLCA patients with higher GM3 expression exhibited prolonged overall survival and disease-free survival.In vitro studies demonstrated thatβ-elemene significantly affected BLCA cell viability,leading to a marked upregulation of GM3 expression,increased apoptotic cell populations,and a notable reduction in cell migration and invasion.WB analysis showed thatβ-elemene enhanced GM3 protein expression while simultaneously decreasing phosphorylated epidermal growth factor receptor(p-EGFR)levels.Additionally,overexpression or RNAi of GM3 in BLCA cells resulted in corresponding changes in epidermal growth factor receptor and p-EGFR expression levels.CONCLUSION This study provides preliminary evidence for further investigation into the molecular mechanisms ofβ-elemene in the treatment of BLCA.展开更多
Background:Studies have reported the special value of PANoptosis in cancer,but there is no study on the prognostic and therapeutic effects of PANoptosis in bladder cancer(BLCA).This study aimed to explore the role of ...Background:Studies have reported the special value of PANoptosis in cancer,but there is no study on the prognostic and therapeutic effects of PANoptosis in bladder cancer(BLCA).This study aimed to explore the role of PANoptosis in BLCA heterogeneity and its impact on clinical outcomes and immunotherapy response while establishing a robust prognostic model based on PANoptosis-related features.Methods:Gene expression profiles and clinical data were collected from public databases.Spatial heterogeneity of cell death pathways in BLCA was evaluated.Consensus clustering was performed based on identified PANoptosis genes.Cell death pathway scores,molecular,and pathway activation differences between different groups were compared.Protein-protein interaction(PPI)network construction was constructed,and immune-related gene sets,tumor immune dysfunction and exclusion(TIDE)scores,and SubMap analysis were used to evaluate immunomodulator expression and immunotherapy efficacy.Ten machine learning algorithms were utilized to develop the most accurate predictive risk model,and a nomogram was created for clinical application.Results:BLCA demonstrated a spatially heterogeneous distribution of pyroptosis,apoptosis,and necroptosis.Notably,T effector cells significantly colocalized with total apoptosis.Two PANoptosis modes were identified:high PANoptosis(high.PANO)and low PANoptosis(low.PANO).High.PANO was associated with worse clinical outcomes and advanced tumor stage,and increased activation of immune-related and cell death pathways.It also showed increased infiltration of immune cells,elevated expression of immunomodulatory factors,and enhanced responsiveness to the immunotherapy.The PANoptosis-related machine learning prognostic signature(PMLS)exhibited strong predictive power for outcomes in BLCA.CSPG4 was identified as a key gene underlying prognostic and therapeutic differences.Conclusion:PANoptosis shapes distinct prognostic and immunological phenotypes in BLCA.PMLS offers a reliable prognostic tool.CSPG4 may represent a potential therapeutic target in PANoptosis-driven BLCA.展开更多
文摘This study aimed to provide evidence of persistent uropathogenic Escherichia coli(UPEC) in female patients with recurrent urinary tract infection(UTI) after antibiotic therapy. We collected biopsies of the bladder, and clean-catch urine samples from 32 women who had episodes of recurrent UTI and were given antibiotic therapy. Urine samples and biopsies were analyzed by conventional bacteriological techniques. Phylogenetic group and 16 virulence factors(VFs) of UPEC were determined using polymerase chain reaction(PCR). The infection capability of UPEC was confirmed in a mouse model. Immunofluorescence and electron microscopy were used to detect intracellular bacterial communities(IBCs) in the mouse model. The results showed that all urine specimens were detected sterile. E. coli was found in 6 of 32 biopsies(18.75%), and was identified to be UPEC by PCR. Different VFs associated with the formation of IBCs were identified in all six UPEC isolates. Each UPEC isolate was capable of forming IBCs within the bladder epithelial cells of mice. In conclusion, UPEC with distinctive pathological traits and the capability of IBC formation was first found in the bladders of women after antibiotic therapy, suggesting that the IBC pathogenic pathway may occur in humans and it plays an important role in UTI recurrence.
基金Supported by the Key Scientific and Technological Project of Henan Province(162102110092)
文摘[Objective] This research aimed at studying the mechanism of the occurrence of epithelial cell loss in bladders of prenatal and postnatal mice. [Method] Bladder epithelia of 1-2-day-old newborn Kunming mice and mice at later period of embryonic development were acquired, and paraffin sections of such epithelia were then made for Mallory's coloration and ordinary optical microscopic observation. The acquired bladder epithelia were made into frozen sections, which were then colored by DAPI and labeled in situ by Terminal-deoxynucleoitidyl Transferase Mediated Nick End Labeling(TUNEL) for fluorescent microscopic observation. DNA electrophoresis and TUNEL in situ labeling were conducted on the acquired urine exfoliated cells. [Result] The results showed that the complete three layers of cells occurred in 20-day-old mouse embryos, whereas no superficial cells resided in the bladder epithelia of newborn mice and no cells exfoliating were observed. Cells exfoliating from the bladder epithelia of newborn mice were observed, and they exhibited the phenomenon of apoptosis. There were apoptosis existed in the urine cells of newborn mice. [Conclusion] Therefore, the results showed that a few days before and after their birth, mice witnessed the process of cell exfoliation in their bladder epithelia and the exfoliated cells showed typical characteristics of apoptosis.
文摘Introduction: The ureteral ostia may not be easily identified in urological endoscopic procedures, leading to an incomplete diagnosis of urinary tract diseases or a predisposition to iatrogenic lesions. The purpose of our study is to evaluate the anatomical distribution of ureteralostia in normal bladders and those with thickened walls. Materials and Methods: We dissected 30 vesical-prostate blocks from human cadavers and identified the ostia of the bladder trigone. A computerized morphometric analysis was performed to measure the thickness of the detrusor muscle, the distances between the ureteral ostia themselves and the distances between each ureteral ostium (left—LUO and right—RUO) and the internal urethral ostium (IUO). The angle formed between the IUO and LUO/RUO was also recorded as well as the volume of the prostates. Results: Fifteen bladders with a non-thickened detrusor (6 mm) were identified. The average prostatic volume of the dissected blocks was 23.7 cm3. The distance between ureteral ostia, the distance from IUO to LUO, the distance from IUO to RUO and the angle formed between IUO and LUO/RUO in normal and thickened bladder were, respectively, 1.9 cm/2.2 cm (p = 0.09), 1.6 cm/1.6 cm (p = 0.82), 1.6 cm/1.7 cm (p = 0.79) and 77/91 (p = 0.17). Conclusions: Our study shows that there is no significant difference in the position of bladder ostia in healthy and thickened bladders. We believe that our findings may facilitate locating the ureteral orifices in situations where endoscopic identification is difficult.
文摘We introduce a modified surgical technique for internal ureteroileal stenting to improve cosmesis in patients undergoing ileal neobladder. Internal ureteric stents are secured to the tip of the urethral catheter with nonabsorbable suture facilitating removal of the stents postoperatively 2-3 weeks along with the urethral catheter. This surgical modification was applied to 21 patients of whom no significant surgical or infectious complication due to single urethral catheter was observed. Internal ureteral stenting is simple, safe and inexpensive alternative to conventional methods to support ureteroileal anastomosis in patients undergoing orthotopic bladder substitution.
基金the Ministry of Science and Technology Taiwan,No.MOST 109-2314-B-182A-091,No.NSTC 112-2314-B-182A-062, No.NSTC 113-2314-B-182A-125.
文摘BACKGROUND The incidence of diabetic atherosclerosis(DMA)is increasing worldwide,but its pathogenesis remains incompletely understood.In addition to cardiovascular complications,bladder dysfunction is one of the common comorbidities associated with DMA but is often refractory to current treatments.AIM To investigate the therapeutic effect of human amniotic fluid stem cell-derived extracellular vesicles(hAFSC-EVs)on the recovery of bladder dysfunction in DMA rats.METHODS Eighty rats were divided into normal control,streptozotocin-induced diabetic rats,diabetic rats subjected to arterial balloon endothelial injury of common iliac artery(DMA),and DMA rats treated with hAFSC-EVs(DMA+hAFSC-EVs).At 4 weeks and 12 weeks after DMA induction,levels of blood glucose,total cholesterol,triglyceride,high-density lipoprotein cholesterol,low-density lipoprotein cholesterol,homeostasis model assessment(HOMA)-insulin resistance,and HOMA-βwere measured.Cystometry,common iliac artery wall thickness,and bladder tumor necrosis factor(TNF)-α,interleukin(IL)-6,transforming growth factor(TGF)-β1,Smad3,connective tissue growth factor(CTGF)and fibronectin were also evaluated.RESULTS Bladder weight and blood glucose,triglyceride,HOMA-insulin resistance,common iliac artery intima thickness,voided volume,intercontraction interval,bladder capacity,and mRNA expression of TNF-α,IL-6,TGF-β1,Smad3,CTGF and fibronectin were significantly increased at 4 weeks and 12 weeks after induction,while the HOMA-βlevel decreased at 4 weeks and 12 weeks,and the high-density lipoprotein cholesterol level decreased at 12 weeks.hAFSC-EVs treatment in DMA rats significantly reduced bladder weight and blood glucose,thickness of common iliac arterial intima,voided volume,intercontraction interval and bladder capacity at 4 weeks.The mRNA expression of TNF-α,TGF-β1,and CTGF in DMA rats treated with hAFSC-EVs were significantly decreased at 4 weeks,while the mRNA expressions of IL-6 and Smad3 were significantly decreased 12 weeks.CONCLUSION hAFSC-EVs treatment can help restore DMA-induced bladder dysfunction,which is associated with lowered blood glucose levels,reduced arterial wall thickness,and decreased TNF-α,IL-6,TGF-β1,Smad3,and CTGF expression.
基金supported by the National Key Research and Development Program of China(No.2022YFD1200300).
文摘Salt bladders,specialized structures on the surface of quinoa leaves,secrete Na+to mitigate the effects of the plant from abiotic stresses,particularly salt exposure.Understanding the development of these structures is crucial for elucidating quinoa’s salt tolerance mechanisms.In this study,we employed transmission electron microscopy to detail cellular differentiation across the developmental stages of quinoa salt bladders.To further explore the developmental trajectory and underlying molecular mechanisms,we conducted single-cell RNA sequencing on quinoa protoplasts derived from young leaves.This allowed us to construct a cellular atlas,identifying 13 distinct cell clusters.Through pseudotime analysis,we mapped the developmental pathways of salt bladders and identified regulatory factors involved in cell fate decisions.GO and KEGG enrichment analyses,as well as experimental results,revealed the impacts of salt stress and the deprivation of sulfur and nitrogen on the development of quinoa salt bladders.Analysis of the transcription factor interaction network in pre-stalk cells(pre-SC),stalk cells(SC),and epidermal bladder cells(EBCs)indicated that TCP5,YAB5,NAC078,SCL8,GT-3B,and T1P17.40 play crucial roles in EBC development.Based on our findings,we developed an informative model elucidating salt bladder formation.This study provides a vital resource for mapping quinoa leaf cells and contributes to our understanding of its salt tolerance mechanisms.
基金the Project of Health Commission of Hunan Province(No.C2019184)the National Natural Science Foundation of China(No.81800641).
文摘Background::Since 2019,a novel coronavirus named 2019 novel coronavirus(2019-nCoV)has emerged worldwide.Apart from fever and respiratory complications,acute kidney injury has been observed in a few patients with coronavirus disease 2019.Furthermore,according to recent findings,the virus has been detected in urine.Angiotensin-converting enzyme II(ACE2)has been proposed to serve as the receptor for the entry of 2019-nCoV,which is the same as that for the severe acute respiratory syndrome.This study aimed to investigate the possible cause of kidney damage and the potential route of 2019-nCoV infection in the urinary system.Methods::We used both published kidney and bladder cell atlas data and new independent kidney single-cell RNA sequencing data generated in-house to evaluate ACE2 gene expression in all cell types in healthy kidneys and bladders.The Pearson correlation coefficients between ACE2 and all other genes were first generated.Then,genes with r values larger than 0.1 and P values smaller than 0.01 were deemed significant co-expression genes with ACE2.Results::Our results showed the enriched expression of ACE2 in all subtypes of proximal tubule(PT)cells of the kidney.ACE2 expression was found in 5.12%,5.80%,and 14.38%of the proximal convoluted tubule cells,PT cells,and proximal straight tubule cells,respectively,in three published kidney cell atlas datasets.In addition,ACE2 expression was also confirmed in 12.05%,6.80%,and 10.20%of cells of the proximal convoluted tubule,PT,and proximal straight tubule,respectively,in our own two healthy kidney samples.For the analysis of public data from three bladder samples,ACE2 expression was low but detectable in bladder epithelial cells.Only 0.25%and 1.28%of intermediate cells and umbrella cells,respectively,had ACE2 expression.Conclusion::This study has provided bioinformatics evidence of the potential route of 2019-nCoV infection in the urinary system.
基金supported in part by NIH R01 NS100531,R01 NS103481NIH R21NS130241(to LD)+3 种基金Merit Review Award I01 BX002356,I01 BX003705 from the U.S.Department of Veterans AffairsIndiana Spinal Cord and Brain Injury Research Foundation(No.19919)Mari Hulman George Endowment Funds(to XMX)Indiana Spinal Cord&Brain Injury Research Fund from ISDH(to NKL and LD)。
文摘Schwann cell transplantation is considered one of the most promising cell-based therapy to repair injured spinal cord due to its unique growth-promoting and myelin-forming properties.A the Food and Drug Administration-approved Phase I clinical trial has been conducted to evaluate the safety of transplanted human autologous Schwann cells to treat patients with spinal cord injury.A major challenge for Schwann cell transplantation is that grafted Schwann cells are confined within the lesion cavity,and they do not migrate into the host environment due to the inhibitory barrier formed by injury-induced glial scar,thus limiting axonal reentry into the host spinal cord.Here we introduce a combinatorial strategy by suppressing the inhibitory extracellular environment with injection of lentivirus-mediated transfection of chondroitinase ABC gene at the rostral and caudal borders of the lesion site and simultaneously leveraging the repair capacity of transplanted Schwann cells in adult rats following a mid-thoracic contusive spinal cord injury.We report that when the glial scar was degraded by chondroitinase ABC at the rostral and caudal lesion borders,Schwann cells migrated for considerable distances in both rostral and caudal directions.Such Schwann cell migration led to enhanced axonal regrowth,including the serotonergic and dopaminergic axons originating from supraspinal regions,and promoted recovery of locomotor and urinary bladder functions.Importantly,the Schwann cell survival and axonal regrowth persisted up to 6 months after the injury,even when treatment was delayed for 3 months to mimic chronic spinal cord injury.These findings collectively show promising evidence for a combinatorial strategy with chondroitinase ABC and Schwann cells in promoting remodeling and recovery of function following spinal cord injury.
文摘BACKGROUND Urinary system tumors often cause negative psychological symptoms,such as depression and dysphoria which significantly impact immune function and indirectly affect cancer prognosis.While epirubicin(EPI)is recommended by the European Association of Urology and can improve prognosis,its long-term use can cause toxic side effects,reduce treatment compliance,and increase psycho-logical burden.Therefore,an appropriate intervention mode is necessary.METHODS This was a retrospective study including 110 patients with urinary system tumors and depression admitted to Zhumadian Central Hospital between March 2021 and July 2023.Patients were divided into conventional(n=55)and joint inter-vention(n=55)groups.The conventional group received mitomycin and routine nursing,while the joint intervention group received EPI and mindfulness intervention.Both groups underwent three cycles of chemotherapy.Immune function(CD4+cells,CD8+cells,CD4+/CD8+ratio),tumor marker levels[urinary bladder cancer antigen(UBC),bladder tumor antigen(BTA)and nuclear matrix protein 22(NMP22)],quality of life questionnaire-core 30(QLQ-C30),17-item Hamilton depression scale(HAMD-17),and cancer-related fatigue[cancer fatigue scale(CFS)]were assessed.Adverse reactions and nursing satisfaction were recorded and evaluated.RESULTS Post-intervention,CD4+,CD8+,and CD4+/CD8+levels increased in both groups,with the joint intervention group showing more significant improvement(P<0.05).Tumor marker levels(NMP22,BTA,and UBC)were lower in the joint intervention group compared to the conventional group(P<0.05).The joint intervention group also showed a greater reduction in HAMD-17 scores(9.38±3.12 vs 15.45±4.86,P<0.05),higher QLQ-C30 scores,and lower CFS scores(both P<0.05).Additionally,the joint intervention group had a lower incidence of adverse reactions and higher nursing satisfaction(P<0.05).CONCLUSION EPI combined with mindfulness intervention significantly improved clinical outcomes in patients with urinary system tumors and depression and is worthy of clinical application.
基金supported by grants from the Shanghai Science and Technology Commission(No.21ZR1461000)Shanghai Municipal Health Commission(No.ZY[2021–2023]−0204).
文摘Objective The present study evaluated the effects of deep acupuncture at Weizhong acupoint(BL40)on bladder function and brain activity in a rat model of overactive bladder(OAB),and investigated the possible mechanisms around the acupuncture area that initiate the effects of acupuncture.Methods Adult female Sprague-Dawley rats were randomly divided into six groups,comprising a control group,model group,group treated with deep acupuncture at BL40,group treated with shallow acupuncture at BL40,group treated with acupuncture at non-acupoint next to BL40,and group treated with acupuncture at Xuanzhong(GB39).Urodynamic evaluation was used to observe the urination,and functional magnetic resonance imaging was used to observe the brain activation.The mechanism of acupuncture at BL40 in regulating bladder function was explored by toluidine blue staining and enzyme-linked immunosorbent assay,and the mechanism was verified by stabilizing mast cells(MCs)or blocking tibial nerve.Results Deep acupuncture at BL40 significantly increased the intercontraction interval in OAB rats and enhanced the mean amplitude of low frequency fluctuation of primary motor cortex(M1),periaquaductal gray matter(PAG),and pontine micturition center(PMC).It also increased the zero-lag functional connectivity between M1 and PAG and between PAG and PMC.Shallow acupuncture at BL40 and acupuncture at non-acupoint or GB39 had no effect on these indexes.Further studies suggested that deep acupuncture at BL40 increased the number and degranulation rate of MCs as well as the contents of 5-hydroxytryptamine,substance P,and histamine in the tissues around BL40.Blocking the tibial nerve by lidocaine injection or inhibiting MC degranulation by sodium cromoglycate injection obstructed the effects of acupuncture on restoring urinary function and modulating brain activation in OAB rats.Conclusion Deep acupuncture at BL40 may be more effective for inhibiting OAB by promoting degranulation of MCs around the acupoint and stimulating tibial nerve,thereby regulating the activation of the brain area that controls the lower urinary tract.
文摘Clinical bladder evaluation is a cost-effective,non-invasive method for diagnosing and managing urinary dysfunction,particularly in patients with neurogenic bladder or other impairments.This process aims to assess bladder capacity,storage,and voiding functions through simple,realistic,and resource-friendly approaches.It involves a structured series of steps,from history-taking and physical examination to bladder-emptying procedures,monitoring urine leaks,assessing reflex voiding,measuring post-void residual(PVR),and calculating total bladder capacity.These evaluations help differentiate between upper motor neuron and lower motor neuron bladder dysfunction,providing critical insights for tailored management.The interpretation of findings focuses on identifying bladder type,assessing leak timing and volume,evaluating reflex voiding,and measuring PVR and total bladder capacity.The results guide interventions such as timing selfclean intermittent catheterization,adjusting fluid intake,and using bladder diaries to monitor patterns.Clinical bladder evaluation is particularly advantageous in low-resource settings,as it avoids the risks and costs associated with urodynamic studies while reflecting real-life patient conditions more effectively.Despite its benefits,no validation studies currently exist for clinical bladder assessment,and its parameters,like maximum voided volume,remain underexplored compared to urodynamic measures.Given the accessibility,affordability,and practicality of this approach,it holds promise for widespread application,especially in primary care settings and among economically disadvantaged populations.This editorial describes the process step-by-step and highlights its role in improving patient outcomes while minimizing complications.
基金This work was supported by Ferring Pharmaceuticals Inc.
文摘Introduction:Non–muscle-invasive bladder cancer(NMIBC)is a common malignancy worldwide.While Bacillus Calmette-Guérin(BCG)is standard of care for treatment for most patients with high-risk NMIBC,many will either not respond to BCG initially or will eventually develop BCG-unresponsive disease.A treatment option in BCG-unresponsive disease is nadofaragene firadenovec-vncg(Adstiladrin),a nonreplicating adenoviral vector–based gene therapy approved by the US Food and Drug Administration(FDA)for the treatment of adults with high-risk BCGunresponsive NMIBC with carcinoma in situ with or without papillary tumors.Objective:To review safety outcomes of participants who received the FDA-approved dose of nadofaragene firadenovec(3×10^(11)vp/mL)across phase 2(NCT01687244)and phase 3(NCT02773849)studies.Methods:Data from the phase 2 and phase 3 studies were collected and analyzed.The findings were reported using descriptive statistics to summarize the key outcomes observed across studies.Results:Common adverse events(AEs)among nadofaragene firadenovec recipients were leakage of fluid around the urinary catheter,fatigue,bladder spasm,chills,dysuria,and micturition urgency.Most study drug–related AEs were mild and localized,with no grade 4 or 5 study drug–related AEs observed in either study.Study drug–related AEs were generally transient,with most study drug–related AEs having a median duration of≤2.0 days in the phase 3 study.Discontinuation rates due to study drug–related AEs were low,with none(0%)in the phase 2 study and three(1.9%)in the phase 3 study.No specific postmarketing surveillance was required by the FDA besides routine pharmacovigilance monitoring;no new real-world safety signals have been observed.Conclusion:Nadofaragene firadenovec demonstrated a favorable and tolerable safety profile across its clinical study program,allowing for broad patient selection among those with high-risk BCG-unresponsive NMIBC.
文摘Dear Editor,Primary bladder neck obstruction(PBNO)affects approximately 28%–54%of men[1].Its etiology remains unclear.Symptoms of PBNO present as voiding(e.g.,decreased force of stream,hesitancy,intermittent stream,and incomplete emptying),storage(e.g.,frequency,urgency,urge incontinence,and nocturia),or a combination of both[2].Untreated PBNO can lead to bladder dysfunction,bladder diverticula,hydronephrosis,and impaired renal function[3].
文摘The published article titled“Puerarin inhibits proliferation and induces apoptosis by upregulation of miR-16 in bladder cancer cell line T24”has been retracted from Oncology Research,Vol.26,No.8,2018,pp.1227–1234.
文摘Background:The COVID-19 pandemic disrupted healthcare systems globally,raising concerns about delayed cancer diagnosis and treatment.In France,transurethral resection of bladder tumors(TURBT)was prioritized in national urology guidelines to ensure the timely management of urothelial carcinoma.This study aimed to assess the impact of care reorganization on tumor staging,recurrence,palliative care,and mortality in bladder cancer patients from the pre-pandemic through late-pandemic periods.Methods:We conducted a retrospective multicenter study including all patients who underwent TURBT with histologically confirmed urothelial carcinoma between April and December of 2019(pre-pandemic),2020(early pandemic),2021(mid-pandemic),and 2022(late pandemic)in two French institutions.TURBT indications were categorized as diagnostic,palliative,or staging.Clinical and pathological data were compared across the four periods.Statistical analyses included Chi-square tests,Estimated Annual Percentage Change(EAPC),and multivariable logistic regression adjusted for age,sex,ASA score,and center.Results:A total of 790 TURBT procedures were analyzed.The proportion of muscle-invasive bladder cancer(pT≥2)declined over time(18.7%in 2019 to 13.2%in 2022;p=0.63),while superficial tumors(pTa)increased(57.2%to 65.5%).All-cause mortality significantly decreased from 38.0%in 2019 to 22.0%in 2020,20.5%in 2021,and 19.5%in 2022(p=0.006).EAPC showed a significant annual decline in mortality(–24.3%,p=0.004).In multivariable analysis,2020,2021,and 2022 were each associated with significantly lower odds of mortality compared to 2019.Recurrence rates remained stable across all periods(p=0.93).Interhospital variation persisted in mortality and recurrence.Conclusions:Despite the pandemic,urothelial bladder cancer outcomes did not worsen through 2022.On the contrary,timely reorganization,prioritization of TURBT,and triage strategies were associated with reduced mortality and palliative care needs,highlighting the resilience of cancer care when guided by adaptive health policies.
基金supported by the Natural Science Foundation in Xinjiang Uygur Autonomous Region(Urumqi,China,2023D01F38).
文摘Objective:To observe the effect of Xipayimaizibizi oral liquid(XP)in an overactive bladder(OAB)experimental rat model and to explore its pharmacological mechanisms.Methods:Network pharmacology was used to explore the potential mechanisms of action of XP.The rats underwent bladder outlet obstruction surgery and were administered the corresponding drug concentrations by gavage for 4 weeks.The study observed the body weight,water intake,bladder and kidney indices(to evaluate their general status),urination behavior pattern(to observe frequency and urgency),and urodynamics(to measure bladder parameters).Hematoxylin and eosin and Masson's trichome staining were used to observe changes in the bladder structure.Enzyme-linked immunosorbent assay was used to measure the levels of nerve growth factor,brain-derived neurotrophic factor,and acetylcholine in the urine.The key targets involved in these mechanisms were validated using reverse transcription-quantitative polymerase chain reaction,immunohistochemistry,and western blot in vivo/vitro experiments.Result:Network pharmacological analysis predicted that XP may alleviate OAB by affecting the cholinergic synapse and calcium signaling pathways.XP treatment significantly reduced the bladder index,improved urine behavior and urodynamic parameters,decreased the neurotransmitters in urine,and reduced the thickness of the bladder wall and collagen ratio.These results indicate that XP can alleviate OAB symptoms and improve the bladder structure.In vivo/vitro experiments further demonstrated that XP can inhibit targets,such as muscarinic acetylcholine receptor 2,and participate in cholinergic synapses to further regulate the parasympathetic nervous system.It can also reduce the overexpression of Ca^(2+) caused by agonists,inhibit targets such as transient receptor potential vanilloid type 1,and participate in calcium signaling pathways to maintain Ca^(2+) homeostasis.Conclusion:These results suggest that XP inhibited bladder overactivity by maintaining Ca^(2+) homeostasis and regulating the parasympathetic nervous system.
文摘When Julian Bird was 60,he was diagnosed(诊断)with cancer of the bladder.He had a series of unpleasant operations,and the doctor predicted that he was likely to die pretty soon.After 34 years as a psychiatrist(精神科医生),in that intense state of mind,he began to daydream about becoming a professional actor.
文摘Introduction: The therapeutic approach to benign prostatic hyperplasia (BPH) has evolved profoundly. Surgical treatment is reserved for complicated cases and the reference surgical technique is transurethral resection of the prostate (TURP). This work aims to study the epidemiological, clinical and therapeutic aspects of monopolar transurethral resection of the prostate in our department. Materials and Methods: We conducted a descriptive study with retrospective data collection over a 12-month period from November 1, 2023 to December 31, 2024. The urology unit, an integral part of the surgery department, of the Sino-Guinean Friendship Hospital in Conakry served as the setting for this study. It included 27 patients with benign prostatic hypertrophy treated surgically by monopolar transurethral resection and having a usable medical record. The parameters studied were epidemiological, clinics and therapeutic. Results: The mean age of the patients was 68.57 ± 5.7 years with extremes from 50 to 79 years. The peak frequency was observed between 70 and 79 years (48.15%). All our patients had lower urinary tract disorders, i.e. 100% of cases. On digital rectal examination, an increase in the volume of the prostate of benign appearance was observed in all cases. The mean prostate volume was 43.7 cc on ultrasound with extremes from 34 cc to 58 cc. The total PSA level was less than 4 ng/ml in the majority of cases. The postoperative course was generally uncomplicated (n = 26) with removal of the urinary catheter on the second postoperative day (D2). However, one peroperative complication was observed in one patient;it was a bladder breach, leading to the passage of glycine into the peritoneum. Conclusion: Transurethral resection of the prostate has reduced the length of hospital stay of our patients, as well as the comorbidities associated with the treatment. The complications associated with it are rare but potentially serious. Its performance requires in-depth mastery of the endoscopic anatomy of the lower urinary tract as well as technical operative expertise.
基金Supported by the Zhejiang Provincial Traditional Chinese Medicine Foundation,No.2021ZA021 and No.2022ZZ005.
文摘BACKGROUNDΒ-elemene is widely used to treat a variety of cancers,including bladder cancer(BLCA).However,the anti-cancer target,effective constituents and mechanism was unclear.AIM To investigate the therapeutic effect and underlying mechanism ofβ-elemene in BLCA.METHODS We first mined the GEPIA2 database to explore the association between the GM3(ST3 Beta-Galactoside Alpha-2,3-Sialyltransferase 5,GM3,ST3GAL5)gene and BLCA.Second,we performed in vitro experiments using BLCA cells to verify the inhibitory effect and targets therapy ofβ-elemene on BLCA.RESULTS Our results revealed a significantly reduced expression of GM3 in BLCA tissues.Notably,BLCA patients with higher GM3 expression exhibited prolonged overall survival and disease-free survival.In vitro studies demonstrated thatβ-elemene significantly affected BLCA cell viability,leading to a marked upregulation of GM3 expression,increased apoptotic cell populations,and a notable reduction in cell migration and invasion.WB analysis showed thatβ-elemene enhanced GM3 protein expression while simultaneously decreasing phosphorylated epidermal growth factor receptor(p-EGFR)levels.Additionally,overexpression or RNAi of GM3 in BLCA cells resulted in corresponding changes in epidermal growth factor receptor and p-EGFR expression levels.CONCLUSION This study provides preliminary evidence for further investigation into the molecular mechanisms ofβ-elemene in the treatment of BLCA.
基金supported by grants from the National Natural Science Foundation of China(No.82172741)Shanghai Municipal Health Bureau(No.2020CXJQ03).
文摘Background:Studies have reported the special value of PANoptosis in cancer,but there is no study on the prognostic and therapeutic effects of PANoptosis in bladder cancer(BLCA).This study aimed to explore the role of PANoptosis in BLCA heterogeneity and its impact on clinical outcomes and immunotherapy response while establishing a robust prognostic model based on PANoptosis-related features.Methods:Gene expression profiles and clinical data were collected from public databases.Spatial heterogeneity of cell death pathways in BLCA was evaluated.Consensus clustering was performed based on identified PANoptosis genes.Cell death pathway scores,molecular,and pathway activation differences between different groups were compared.Protein-protein interaction(PPI)network construction was constructed,and immune-related gene sets,tumor immune dysfunction and exclusion(TIDE)scores,and SubMap analysis were used to evaluate immunomodulator expression and immunotherapy efficacy.Ten machine learning algorithms were utilized to develop the most accurate predictive risk model,and a nomogram was created for clinical application.Results:BLCA demonstrated a spatially heterogeneous distribution of pyroptosis,apoptosis,and necroptosis.Notably,T effector cells significantly colocalized with total apoptosis.Two PANoptosis modes were identified:high PANoptosis(high.PANO)and low PANoptosis(low.PANO).High.PANO was associated with worse clinical outcomes and advanced tumor stage,and increased activation of immune-related and cell death pathways.It also showed increased infiltration of immune cells,elevated expression of immunomodulatory factors,and enhanced responsiveness to the immunotherapy.The PANoptosis-related machine learning prognostic signature(PMLS)exhibited strong predictive power for outcomes in BLCA.CSPG4 was identified as a key gene underlying prognostic and therapeutic differences.Conclusion:PANoptosis shapes distinct prognostic and immunological phenotypes in BLCA.PMLS offers a reliable prognostic tool.CSPG4 may represent a potential therapeutic target in PANoptosis-driven BLCA.