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
Objective:Based on the theory of“Taiyang governs tendons”,to explore the effect of acupuncture at points of the Bladder Meridian of Foot-Taiyang on the expression of serum inflammatory factors in rabbit models of ce...Objective:Based on the theory of“Taiyang governs tendons”,to explore the effect of acupuncture at points of the Bladder Meridian of Foot-Taiyang on the expression of serum inflammatory factors in rabbit models of cervical spondylosis.Methods:Thirty New Zealand white rabbits were randomly divided into a blank group,a model group,and a treatment group,with 10 rabbits in each group.The models of cervical spondylosis in the model group and treatment group were established by long-term head-down flexion combined with cold-damp stimulation.After modeling,the treatment group received acupuncture at three points(Kunlun,Weizhong,and Feishu)on the Bladder Meridian of Foot-Taiyang,once a day for 20 minutes each time,for 14 consecutive days;the model group and blank group received no therapeutic intervention.After the intervention,cardiac blood was collected from all rabbits to detect the expression levels of serum inflammatory factors IL-6,TNF-α,and IL-1β.Meanwhile,cervical muscle tissue was collected,stained with HE,and the morphological changes of the posterior cervical muscle tissue in each group were observed under an optical microscope.Results:After modeling,the levels of inflammatory factors in the serum of rabbits in the model group and treatment group were significantly increased compared with those before modeling,with a statistically significant difference(p<0.01).After intervention,the serum inflammatory factors in the treatment group decreased significantly compared with those in the model group,and the difference was statistically significant(p<0.01).Conclusion:Acupuncture at points of the Bladder Meridian of Foot-Taiyang in rabbit models of cervical spondylosis can reduce the serum levels of inflammatory factors TNF-α,IL-1β,and IL-6.展开更多
Artificial intelligence(AI)is transforming the diagnostic landscape of malignant tumors in the urinary system,including prostate cancer,bladder cancer,and renal cell carcinoma(RCC).By integrating imaging,pathology,and...Artificial intelligence(AI)is transforming the diagnostic landscape of malignant tumors in the urinary system,including prostate cancer,bladder cancer,and renal cell carcinoma(RCC).By integrating imaging,pathology,and molecular data,AI enhances the precision and reproducibility of tumor detection,grading,and risk stratification.In prostate cancer,AI-assisted multiparametric Magnetic resonance imaging(MRI)and digital pathology systems improve lesion localization and Gleason scoring.For bladder cancer,deep learning-based cystoscopy and radiomics models from Computed tomography/magnetic resonance imaging(CT/MRI)enable real-time lesion segmentation and non-invasive biomarker prediction,such as Programmed Cell Death-Ligand 1(PD-L1)expression.In RCC,AI,combined with CT/MRI and multi-omics data,aids in subtype classification and prognostic prediction,supporting personalized therapy.However,despite these promising advances,challenges such as data standardization,model generalizability,interpretability,and regulatory compliance hinder AI’s clinical translation.This review outlines the current state of AI in urological cancer diagnosis and prognosis,its technological innovations,and the clinical challenges and opportunities that lie ahead.展开更多
Objective:While cisplatin-based chemotherapy is pivotal for advanced bladder cancer,acquired resistance remains a major obstacle.This study investigates key molecular drivers of this resistance and potential reversal ...Objective:While cisplatin-based chemotherapy is pivotal for advanced bladder cancer,acquired resistance remains a major obstacle.This study investigates key molecular drivers of this resistance and potential reversal strategies.Methods:We established GC(Gemcitabine and Cisplatin)-resistant T24-R and UC3-R cell lines from T24 and UM-UC-3(UC3)cells.Transcriptomic and proteomic analyses identified differentially expressed molecules.Apoptosis and cell viability were assessed by flow cytometry and CCK-8(Cell Counting Kit-8)assays,while RT-qPCR(Reverse Transcription Quantitative Polymerase Chain Reaction)and Western blot analyzed gene and protein expression.Immunofluorescence evaluated FAK(Focal Adhesion Kinase)phosphorylation,and a xenograft mouse model validated the findings in vivo.Results:Integrated transcriptomic and proteomic analysis identified FN1(fibronectin)as a consistently upregulated top candidate in resistant cells(T24-R transcript log_(2)FC=2.8,protein log_(2)FC=0.9;UC3-R transcript log_(2)FC=3.7;all p<0.001).Knockdown of FN1 reduced chemoresistance(Resistance Index:5.2 in T24-R and 2.0 in UC3-R cells,p<0.001)and enhanced apoptosis(approximately 4.5-fold in T24-R and 7.5-fold in UC3-R,p<0.001).ITGB4(Integrin Subunit Beta 4)was upregulated in resistant cells(transcript log_(2)FC:4.2 in T24-R and 3.03 in UC3-R;protein log_(2)FC:0.67 in T24-R;all p<0.01).Critically,ITGB4 knockdown abolished the chemoresistance promoted by exogenous FN1,which was associated with increased FAK(Y397)phosphorylation.Conclusion:Our results demonstrate that the FN1-ITGB4 axis drives chemoresistance in bladder cancer via FAK signaling.Targeting this axis represents a promising strategy to overcome chemoresistance.展开更多
Overview:Surgical management of benign prostatic hyperplasia(BPH)has evolved significantly,incorporating various minimally invasive procedures aimed at reducing morbidity and optimizing patient outcomes.Despite advanc...Overview:Surgical management of benign prostatic hyperplasia(BPH)has evolved significantly,incorporating various minimally invasive procedures aimed at reducing morbidity and optimizing patient outcomes.Despite advancements,transurethral approaches continue to pose risks such as urethral strictures and urinary incontinence due to mechanical and thermal stress.To address these limitations,the Suprapubic Transvesical Adenoma Resection of the Prostate(STARP)was developed,offering a direct suprapubic route that bypasses the urethra entirely.Recent studies have validated STAR-P as both feasible and safe,emphasizing advantages such as enhanced visualization of the urinary sphincter,minimized urethral trauma,effective hemostasis,and reduced operative stress.The procedure utilizes specially designed instrumentation,including a large-caliber bipolar resectoscope(42 Fr),allowing the efficient removal of substantial adenoma tissue in fewer resection passes compared to traditional methods.Objectives:This article provides a comprehensive,step-by-step description of the STAR-P technique.The primary objective is to detail patient selection criteria,preoperative assessments,procedural steps including mini-open suprapubic access,specialized instrumentation usage,resection techniques,and postoperative management protocols.Highlighting technical considerations and procedural innovations aims to inform urologists about the potential benefits of STAR-P,particularly in patients at higher risk for urethral complications or those with large prostate volumes.By documenting the procedural intricacies and outcomes clearly and thoroughly,we seek to encourage informed adoption of STAR-P as an alternative,effective surgical approach for managing benign prostatic hyperplasia,thus contributing to the evolving landscape ofminimally invasive urological surgery.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
Gall bladder cancer(GBC)remains a highly aggressive disease,with an overall 5-year dismal survival rate of 15%-20%.Its asymptomatic nature in very early stages and non-specific clinical presentations pose significant ...Gall bladder cancer(GBC)remains a highly aggressive disease,with an overall 5-year dismal survival rate of 15%-20%.Its asymptomatic nature in very early stages and non-specific clinical presentations pose significant challenges to timely detection.Consequently,GBC often presents late,making it one of the most challenging cancers to manage.Surgery offers the best chance for long-term survival;however,only 10%of GBC patients are candidates for upfront resection,with the majority presenting in locally advanced or metastatic stages.Further-more,GBC is generally resistant to chemotherapy and radiotherapy,limiting the effectiveness of systemic therapy.Therefore,early diagnosis is crucial to offer the best treatment through surgical resection and to improve the outcome.Recent advancements in imaging technologies,biomarker discovery,and molecular diagnostics offer promising avenues for enhancing detection rates.Though non-invasive,most of them lack specificity,and the majority fail as an early diagnostic tool.This review examines the current status of early detection strategies for GBC,addresses the limitations of existing approaches,and explores the newer emer-ging diagnostic tools and techniques and how they can be exploited in future for its early detection.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
OBJECTIVE:To investigate whether electroacupuncture(EA)therapy for overactive bladder(OAB)exerts its effect by modulating mechanosensitive channels in the urothelium,thereby improving bladder sensory function.METHODS:...OBJECTIVE:To investigate whether electroacupuncture(EA)therapy for overactive bladder(OAB)exerts its effect by modulating mechanosensitive channels in the urothelium,thereby improving bladder sensory function.METHODS:In this study,a rat model of OAB was created by using intraperitoneal injections of cyclophosphamide.We performed either EA or bladder perfusion with HC-067047[a transient receptor potential vanilloid 4(TRPV4)antagonist]and assessed the efficacy of electroacupuncture in the treatment of OAB in rats via urodynamic determination and Void spot assay.tissue morphology,distribution and expression of the TRPV4protein and the amount of adenosine triphosphate(ATP)and Ca2+released from urothelial cells in each group of rats were observed to identify the mechanism by which electroacupuncture improves OAB in rats.RESULTS:EA ameliorated bladder function and voiding behaviour,improved bladder uroepithelial tissue morphology,and significantly reduced the immunofluorescence intensity and the mRNA and protein expression levels of TRPV4 in the uroepithelium of OAB rats.Moreover,the simulated mechanical stimulationinduced increases in Ca^(2+)concentration and the release of ATP and acetylcholine(Ach)from bladder urothelial cells were inhibited.The changes in EA followed the same trend as those in HC-067047.CONCLUSIONS:These results suggest that EA inhibits bladder sensory function by downregulating the expression of mechanically activated TRPV4 ion channels distributed in bladder urothelial cells,which correspondingly decreases the inward flow of extracellular Ca^(2+)and reduces the release of ATP and Ach,thereby attenuating excitatory signals.展开更多
Rational design of multifunctional nanoplatforms capable of combining therapeutic effects with real-time monitoring of drug distribution and tumor status is emerging as a promising approach in cancer nanomedicine.Here...Rational design of multifunctional nanoplatforms capable of combining therapeutic effects with real-time monitoring of drug distribution and tumor status is emerging as a promising approach in cancer nanomedicine.Here,we introduce pyropheophorbide a-bisaminoquinoline conjugate lipid nanoparticles(PPBC LNPs)as a bimodal system for image-guided phototherapy in bladder cancer treatment.PPBC LNPs not only demonstrate both powerful photodynamic and photothermal effects upon light activation,but also exhibit potent autophagy blockage,effectively inducing bladder cancer cell death.Furthermore,PPBC LNPs possess remarkable photoacoustic(PA)and fluorescence(FL)imaging capabilities,enabling imaging with high-resolution,deep tissue penetration and high sensitivity for tracking drug biodistribution and phototherapy efficacy.Specifically,PA imaging confirms the efficient accumulation of PPBC LNPs within tumor and predicts therapeutic outcomes of photodynamic therapy,while FL imaging confirms their prolonged retention at the tumor site for up to 6 days.PPBC LNPs significantly suppress bladder tumor growth,with several tumors completely ablated following just two doses of the nanoparticles and laser treatment.Additionally,PPBC LNPs were formulated with lipid-based excipients and assembled using microfluidic technology to enhance biocompatibility,stability,and scalability,showing potential for clinical translation.This versatile nanoparticle represents a promising candidate for further development in bladder cancer therapy.展开更多
Immune checkpoint inhibitors(ICIs)play a significant role in tumor treatment,but the immune-related adverse events(irAEs),which brings about have also attracted much attention.Among them,toxic epidermal necrolysis(TEN...Immune checkpoint inhibitors(ICIs)play a significant role in tumor treatment,but the immune-related adverse events(irAEs),which brings about have also attracted much attention.Among them,toxic epidermal necrolysis(TEN)is one of the most severe skin toxic reactions.This article reports a case of a bladder cancer patient who developed TEN after receiving ICIs treatment.The male patient was diagnosed with bladder cancer in November 2023.On April 29,2024,he was admitted to the Third Hospital of Changsha for antitumor treatment.In May 2024,he developed immune-related myocarditis after treatment with toripalimab.On July 6,2024,the patient switched to envafolimab treatment,and on July 16,he developed rashes and eventually progressed to TEN.After treatment with glucocorticoids and related symptomatic measures,the patient improved.TEN is a rare but serious irAE in ICIs treatment.Suspected patients should be intervened early,and patients who have already developed it should be actively treated,in order to enhance the understanding and management of TEN caused by ICIs treatment.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
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Yunnan Provincial High-Level Traditional Chinese Medicine Talent Training ProjectYunnan Provincial Department of Science and Technology Traditional Chinese Medicine Basic Research Joint Special Project(Project No.:202101AZ070001-138)。
文摘Objective:Based on the theory of“Taiyang governs tendons”,to explore the effect of acupuncture at points of the Bladder Meridian of Foot-Taiyang on the expression of serum inflammatory factors in rabbit models of cervical spondylosis.Methods:Thirty New Zealand white rabbits were randomly divided into a blank group,a model group,and a treatment group,with 10 rabbits in each group.The models of cervical spondylosis in the model group and treatment group were established by long-term head-down flexion combined with cold-damp stimulation.After modeling,the treatment group received acupuncture at three points(Kunlun,Weizhong,and Feishu)on the Bladder Meridian of Foot-Taiyang,once a day for 20 minutes each time,for 14 consecutive days;the model group and blank group received no therapeutic intervention.After the intervention,cardiac blood was collected from all rabbits to detect the expression levels of serum inflammatory factors IL-6,TNF-α,and IL-1β.Meanwhile,cervical muscle tissue was collected,stained with HE,and the morphological changes of the posterior cervical muscle tissue in each group were observed under an optical microscope.Results:After modeling,the levels of inflammatory factors in the serum of rabbits in the model group and treatment group were significantly increased compared with those before modeling,with a statistically significant difference(p<0.01).After intervention,the serum inflammatory factors in the treatment group decreased significantly compared with those in the model group,and the difference was statistically significant(p<0.01).Conclusion:Acupuncture at points of the Bladder Meridian of Foot-Taiyang in rabbit models of cervical spondylosis can reduce the serum levels of inflammatory factors TNF-α,IL-1β,and IL-6.
基金supported by grants from the Hangzhou Key Project for Agricultural and Social Development under Grant No.20231203A12(JZ)the General Program of the Scientific Research Special Project for Post-Marketing Clinical Research of Innovative Drugs,Development Center for Medical Science&Technology,National Health Commission of the People’s Republic of China under Grant No.WKZX2024CX104202(JZ).
文摘Artificial intelligence(AI)is transforming the diagnostic landscape of malignant tumors in the urinary system,including prostate cancer,bladder cancer,and renal cell carcinoma(RCC).By integrating imaging,pathology,and molecular data,AI enhances the precision and reproducibility of tumor detection,grading,and risk stratification.In prostate cancer,AI-assisted multiparametric Magnetic resonance imaging(MRI)and digital pathology systems improve lesion localization and Gleason scoring.For bladder cancer,deep learning-based cystoscopy and radiomics models from Computed tomography/magnetic resonance imaging(CT/MRI)enable real-time lesion segmentation and non-invasive biomarker prediction,such as Programmed Cell Death-Ligand 1(PD-L1)expression.In RCC,AI,combined with CT/MRI and multi-omics data,aids in subtype classification and prognostic prediction,supporting personalized therapy.However,despite these promising advances,challenges such as data standardization,model generalizability,interpretability,and regulatory compliance hinder AI’s clinical translation.This review outlines the current state of AI in urological cancer diagnosis and prognosis,its technological innovations,and the clinical challenges and opportunities that lie ahead.
基金supported by grants from the National Natural Science Foundation of China(82372881 to Weiyang He)the Chongqing Biomedicine Key R&D Project(CSTB2021TIAD-KPX0041 to Weiyang He).
文摘Objective:While cisplatin-based chemotherapy is pivotal for advanced bladder cancer,acquired resistance remains a major obstacle.This study investigates key molecular drivers of this resistance and potential reversal strategies.Methods:We established GC(Gemcitabine and Cisplatin)-resistant T24-R and UC3-R cell lines from T24 and UM-UC-3(UC3)cells.Transcriptomic and proteomic analyses identified differentially expressed molecules.Apoptosis and cell viability were assessed by flow cytometry and CCK-8(Cell Counting Kit-8)assays,while RT-qPCR(Reverse Transcription Quantitative Polymerase Chain Reaction)and Western blot analyzed gene and protein expression.Immunofluorescence evaluated FAK(Focal Adhesion Kinase)phosphorylation,and a xenograft mouse model validated the findings in vivo.Results:Integrated transcriptomic and proteomic analysis identified FN1(fibronectin)as a consistently upregulated top candidate in resistant cells(T24-R transcript log_(2)FC=2.8,protein log_(2)FC=0.9;UC3-R transcript log_(2)FC=3.7;all p<0.001).Knockdown of FN1 reduced chemoresistance(Resistance Index:5.2 in T24-R and 2.0 in UC3-R cells,p<0.001)and enhanced apoptosis(approximately 4.5-fold in T24-R and 7.5-fold in UC3-R,p<0.001).ITGB4(Integrin Subunit Beta 4)was upregulated in resistant cells(transcript log_(2)FC:4.2 in T24-R and 3.03 in UC3-R;protein log_(2)FC:0.67 in T24-R;all p<0.01).Critically,ITGB4 knockdown abolished the chemoresistance promoted by exogenous FN1,which was associated with increased FAK(Y397)phosphorylation.Conclusion:Our results demonstrate that the FN1-ITGB4 axis drives chemoresistance in bladder cancer via FAK signaling.Targeting this axis represents a promising strategy to overcome chemoresistance.
文摘Overview:Surgical management of benign prostatic hyperplasia(BPH)has evolved significantly,incorporating various minimally invasive procedures aimed at reducing morbidity and optimizing patient outcomes.Despite advancements,transurethral approaches continue to pose risks such as urethral strictures and urinary incontinence due to mechanical and thermal stress.To address these limitations,the Suprapubic Transvesical Adenoma Resection of the Prostate(STARP)was developed,offering a direct suprapubic route that bypasses the urethra entirely.Recent studies have validated STAR-P as both feasible and safe,emphasizing advantages such as enhanced visualization of the urinary sphincter,minimized urethral trauma,effective hemostasis,and reduced operative stress.The procedure utilizes specially designed instrumentation,including a large-caliber bipolar resectoscope(42 Fr),allowing the efficient removal of substantial adenoma tissue in fewer resection passes compared to traditional methods.Objectives:This article provides a comprehensive,step-by-step description of the STAR-P technique.The primary objective is to detail patient selection criteria,preoperative assessments,procedural steps including mini-open suprapubic access,specialized instrumentation usage,resection techniques,and postoperative management protocols.Highlighting technical considerations and procedural innovations aims to inform urologists about the potential benefits of STAR-P,particularly in patients at higher risk for urethral complications or those with large prostate volumes.By documenting the procedural intricacies and outcomes clearly and thoroughly,we seek to encourage informed adoption of STAR-P as an alternative,effective surgical approach for managing benign prostatic hyperplasia,thus contributing to the evolving landscape ofminimally invasive urological surgery.
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.
文摘Gall bladder cancer(GBC)remains a highly aggressive disease,with an overall 5-year dismal survival rate of 15%-20%.Its asymptomatic nature in very early stages and non-specific clinical presentations pose significant challenges to timely detection.Consequently,GBC often presents late,making it one of the most challenging cancers to manage.Surgery offers the best chance for long-term survival;however,only 10%of GBC patients are candidates for upfront resection,with the majority presenting in locally advanced or metastatic stages.Further-more,GBC is generally resistant to chemotherapy and radiotherapy,limiting the effectiveness of systemic therapy.Therefore,early diagnosis is crucial to offer the best treatment through surgical resection and to improve the outcome.Recent advancements in imaging technologies,biomarker discovery,and molecular diagnostics offer promising avenues for enhancing detection rates.Though non-invasive,most of them lack specificity,and the majority fail as an early diagnostic tool.This review examines the current status of early detection strategies for GBC,addresses the limitations of existing approaches,and explores the newer emer-ging diagnostic tools and techniques and how they can be exploited in future for its early detection.
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.
基金Natural Science Foundation-funded Project:Research on the Effect of Acupuncture in Regulating Bladder Excitability based on the Generation and Transmission of Afferent Information from Urinary Control(No.82174516)Investigation into the Mechanism of Acupuncture-regulated Bladder Excitability based on Sensory Nerve Mechanotransduction Signaling(No.82474645)。
文摘OBJECTIVE:To investigate whether electroacupuncture(EA)therapy for overactive bladder(OAB)exerts its effect by modulating mechanosensitive channels in the urothelium,thereby improving bladder sensory function.METHODS:In this study,a rat model of OAB was created by using intraperitoneal injections of cyclophosphamide.We performed either EA or bladder perfusion with HC-067047[a transient receptor potential vanilloid 4(TRPV4)antagonist]and assessed the efficacy of electroacupuncture in the treatment of OAB in rats via urodynamic determination and Void spot assay.tissue morphology,distribution and expression of the TRPV4protein and the amount of adenosine triphosphate(ATP)and Ca2+released from urothelial cells in each group of rats were observed to identify the mechanism by which electroacupuncture improves OAB in rats.RESULTS:EA ameliorated bladder function and voiding behaviour,improved bladder uroepithelial tissue morphology,and significantly reduced the immunofluorescence intensity and the mRNA and protein expression levels of TRPV4 in the uroepithelium of OAB rats.Moreover,the simulated mechanical stimulationinduced increases in Ca^(2+)concentration and the release of ATP and acetylcholine(Ach)from bladder urothelial cells were inhibited.The changes in EA followed the same trend as those in HC-067047.CONCLUSIONS:These results suggest that EA inhibits bladder sensory function by downregulating the expression of mechanically activated TRPV4 ion channels distributed in bladder urothelial cells,which correspondingly decreases the inward flow of extracellular Ca^(2+)and reduces the release of ATP and Ach,thereby attenuating excitatory signals.
文摘Rational design of multifunctional nanoplatforms capable of combining therapeutic effects with real-time monitoring of drug distribution and tumor status is emerging as a promising approach in cancer nanomedicine.Here,we introduce pyropheophorbide a-bisaminoquinoline conjugate lipid nanoparticles(PPBC LNPs)as a bimodal system for image-guided phototherapy in bladder cancer treatment.PPBC LNPs not only demonstrate both powerful photodynamic and photothermal effects upon light activation,but also exhibit potent autophagy blockage,effectively inducing bladder cancer cell death.Furthermore,PPBC LNPs possess remarkable photoacoustic(PA)and fluorescence(FL)imaging capabilities,enabling imaging with high-resolution,deep tissue penetration and high sensitivity for tracking drug biodistribution and phototherapy efficacy.Specifically,PA imaging confirms the efficient accumulation of PPBC LNPs within tumor and predicts therapeutic outcomes of photodynamic therapy,while FL imaging confirms their prolonged retention at the tumor site for up to 6 days.PPBC LNPs significantly suppress bladder tumor growth,with several tumors completely ablated following just two doses of the nanoparticles and laser treatment.Additionally,PPBC LNPs were formulated with lipid-based excipients and assembled using microfluidic technology to enhance biocompatibility,stability,and scalability,showing potential for clinical translation.This versatile nanoparticle represents a promising candidate for further development in bladder cancer therapy.
基金supported by Research Project of Health Commission of Hunan Province,China(D202313016450)。
文摘Immune checkpoint inhibitors(ICIs)play a significant role in tumor treatment,but the immune-related adverse events(irAEs),which brings about have also attracted much attention.Among them,toxic epidermal necrolysis(TEN)is one of the most severe skin toxic reactions.This article reports a case of a bladder cancer patient who developed TEN after receiving ICIs treatment.The male patient was diagnosed with bladder cancer in November 2023.On April 29,2024,he was admitted to the Third Hospital of Changsha for antitumor treatment.In May 2024,he developed immune-related myocarditis after treatment with toripalimab.On July 6,2024,the patient switched to envafolimab treatment,and on July 16,he developed rashes and eventually progressed to TEN.After treatment with glucocorticoids and related symptomatic measures,the patient improved.TEN is a rare but serious irAE in ICIs treatment.Suspected patients should be intervened early,and patients who have already developed it should be actively treated,in order to enhance the understanding and management of TEN caused by ICIs treatment.
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.
