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
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
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: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
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
Objective: To explore the current status and influencing factors of supportive care needs in patients with muscle-invasive bladder cancer after surgery, and to provide a reference for the development of targeted inter...Objective: To explore the current status and influencing factors of supportive care needs in patients with muscle-invasive bladder cancer after surgery, and to provide a reference for the development of targeted intervention strPan ategies. Methods: A general data questionnaire and supportive care needs scale were used to investigate 107 patients with muscle-invasive bladder cancer after surgery. Results: The total score of supportive care needs in patients with muscle-invasive bladder cancer after surgery was (98.48 ± 9.07). Multiple linear regression analysis showed that age, primary caregiver, medical payment method, number of hospitalizations and postoperative time were important influencing factors of supportive care needs in patients with muscle-invasive bladder cancer after surgery (P Conclusion: The supportive care needs of patients with muscle-invasive bladder cancer after surgery are at a low level. Medical staff should identify them early, pay more attention to young patients, patients without medical insurance and patients with multiple hospitalizations, and provide targeted nursing measures to meet their supportive care needs.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.
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
Objective:This study aimed to explore the anticancer potential of Cannabis sativa(C.sativa)strains,specifically PARIS,Dairy Queen(DQ),and super cannabidiol(sCBD),on bladder cancer cells.Given the increasing interest i...Objective:This study aimed to explore the anticancer potential of Cannabis sativa(C.sativa)strains,specifically PARIS,Dairy Queen(DQ),and super cannabidiol(sCBD),on bladder cancer cells.Given the increasing interest in cannabinoids like cannabichromene(CBC)and delta-9-tetrahydrocannabinol(THC)for their therapeutic properties,we evaluated their cytotoxic effects on urothelial carcinoma(UC)cell lines and their ability to inhibit cell migration and induce apoptosis in both two-dimensional cell models and three-dimensional ex vivo organ cultures(EVOCs).Methods:C.sativa strains were screened for their cytotoxicity against UC cell lines(HTB-4 and HTB-9)using XTT assays.Their phytocannabinoid content was analyzed using high-performance liquid chromatography.We employed fluorescence-activated cell-sorting to determine apoptosis and cell cycle,migration assays to determine cell migration,and EVOCs to evaluate the cytotoxic effect on UC.Gene expression was determined by quantitative polymerase chain reaction.Results:Three commercial C.sativa strains,PARIS,DQ,and sCBD,were found to have the most potent anticancer effects on bladder cancer cells.All extracts contain CBC and THC at different concentrations.In XTT assays on UC cell lines,PARIS had a half-maximal inhibitory concentration(IC50)of 21.58 mg/mL,while DQ and sCBD had similar cytotoxic activity with IC_(50) values for 48-h treatment of 17.99 mg/mL and 17.88 mg/mL,respectively.DQ and sCBD extracts were found to significantly reduce cell migration and increase the percentage of cells in S phase and G_(2)/M phase within the cell population.In EVOCs,the extracts initiated cell death with the expression of apoptosis-related genes increased following exposure to treatment.Conclusion:The findings suggest that C.sativa strains PARIS,DQ,and sCBD,containing CBC and THC,exhibit significant anticancer activity against UC cell lines and ex vivo models.These results underscore the therapeutic potential of CBC-and THC-rich C.sativa extracts in bladder cancer treatment.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
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
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
Background:Bladder cancer prognosis remains suboptimal despite advancements in research.Current molecular subtyping methods are resource-intensive,highlighting the need for efficient,cost-effective approaches to predi...Background:Bladder cancer prognosis remains suboptimal despite advancements in research.Current molecular subtyping methods are resource-intensive,highlighting the need for efficient,cost-effective approaches to predict BCa molecular subtypes.Method:We developed a predictive model for BCa molecular subtypes using machine learning(ML)and pathomics derived from Hematoxylin-Eosin stained pathological slides.A cohort of 353 patients from TCGA was employed,and image features were extracted for analysis.Pathomic signatures were constructed using the LASSO Cox regression algorithm,and a pathomic-clinical nomogram was developed and validated in training and testing cohorts.Results:Seventy distinct image features were identified from 150 pathomic signatures.The model demonstrated robust predictive ability,with AUCs of 0.833 and 0.822 in the training and validation cohorts,respectively.The addition of pathomic score,N stage,and M stage improved the model’s discrimination,achieving AUCs of 0.877 and 0.794 in the training and validation cohorts.Limitations include the lack of an external validation cohort.Conclusion:Our ML-based pathomics model shows promise in predicting BCa molecular subtypes and has the potential to enhance prognosis prediction and inform treatment strategies,marking a significant step towards precision medicine for BCa.展开更多
Objective:To systematically review the most recent scientific literature regarding modern strategies for organ preservation in the treatment of non-metastatic muscle-invasive bladder cancer.Methods:Literature search w...Objective:To systematically review the most recent scientific literature regarding modern strategies for organ preservation in the treatment of non-metastatic muscle-invasive bladder cancer.Methods:Literature search was made using PubMed,Google Scholar,EMBASE,Wiley Library,and ClinicalTrials.gov following the recommendations of the Preferred Reporting Items for Systematic reviews and Meta-Analyses statement.The primary outcome was 5-year overall survival rate,which was addressed by a systematic review and meta-analysis.The risk of bias and quality of evidence were assessed according to the Cochrane Collaboration and the Grading of Recommendations,Assessment,Development and Evaluation system.Results:The evidence is consistent in showing that 5-year survival of trimodality therapy is similar to radical cystectomy in selected patients,ranging between 29%and 73%.Patients undergoing bladder-sparing therapy were found to have better outcomes in terms of quality of life and sociability than those undergoing radical cystectomy.Immunotherapy is establishing itself as a strategy for organ-preservation treatment,showing complete response rates between 42%and 100%.However,most of these results have been obtained from ongoing clinical trials.Furthermore,there are still no studies comparing the efficacy among the different available therapies.Conclusion:Although radical cystectomy remains the gold standard treatment for muscle-invasive bladder cancer,its significant morbidity has prompted the exploration of alternative therapies.In this context,bladder preservation therapies,though supported by limited literature,emerge as a potential alternative that could offer comparable oncological outcomes in selected patients.展开更多
Objective:Bladder cancer(BCa)is a prevalent malignant tumor in the urinary system.Molecular subtyping,utilizing molecular characteristics,represents a novel classification system that has demonstrated its efficacy in ...Objective:Bladder cancer(BCa)is a prevalent malignant tumor in the urinary system.Molecular subtyping,utilizing molecular characteristics,represents a novel classification system that has demonstrated its efficacy in tumor diagnosis and treatment.Given the critical role of molecular subtyping in the BCa treatment,acquiring a comprehensive understanding is imperative for guiding treatment decisions,optimizing risk assessment systems,and ultimately improving patient prognosis.Methods:In this review,we provide a comprehensive overview of the research progress in molecular subtyping of BCa,with a primary focus on discussing its utility in guiding various treatment modalities including neoadjuvant chemotherapy,neoadjuvant immunotherapy,and targeted therapy.In addition,this review also covers the trimodality treatment,antibody-drug conjugates,and the treatment of small cell BCa.Results:We present a comprehensive overview of the responsiveness or resistance of different molecular subtypes of BCa to various therapeutic modalities.The basal subtype demonstrates favorable sensitivity to neoadjuvant chemotherapy across multiple classification systems,whereas the luminal infiltrated subtype exhibits potential susceptibility to immunotherapy.In terms of targeted therapy,the basal-like and the basal/squamous subtypes in some classifications have shown notable responsiveness to epidermal growth factor receptor-targeted therapy.Moreover,the luminal subtype in the University of Texas M.D.Anderson Cancer Center classification,the luminal papillary subtypes according to the Cancer Genome Atlas Research Network classification in 2017,and the luminal unstable type in the 2019 Molecular Subtyping classification show potential for the fibroblast growth factor receptor 3-targeted treatment.Conclusion:The significance and impact of BCa molecular subtyping in guiding treatment,evaluating progression,and predicting prognosis are increasingly acknowledged.Accurate subtyping and broad application can bring good benefits to clinical decision-making,risk assessment,and prognostic evaluation.展开更多
Introduction:Radical cystectomy with pelvic node dissection remains the standard of care for muscle-invasive bladder carcinoma(MIBC);however,there is a growing interest in bladder preservation alternatives among the e...Introduction:Radical cystectomy with pelvic node dissection remains the standard of care for muscle-invasive bladder carcinoma(MIBC);however,there is a growing interest in bladder preservation alternatives among the elderly population.Guidelines indicate that partial cystectomy(PC)combined with pelvic node dissection(LND)can be considered as an alternative in carefully selected individuals.Using the National Cancer Database,we analyzed the overall survival(OS)between PC with and without LND among octogenarians.Methods:We identified octogenarians with localized muscle-invasive bladder carcinoma(cT2-3N0M0)and urothelial histology who underwent PC with or without LND between 2004 and 2018.Based on the number of lymph nodes removed(LNR),the LND group was further subdivided into<10 and>=10 lymph node groups.A propensity-matched Kaplan-Meier survival analysis was performed to compare OS between these groups.Results:Among 2573 patients who underwent PC,492 octogenarians met our selection criteria.208(42.2%)had LND,while 284(57.8%)had no LND.Within the LND group,53(25.5%)had<10 LNR,and 155(74.5%)had>=10 LNR.The median OS for the matched LND and non-LND groups was 36.9 and 33.4 months(p=0.96),respectively.Similarly,<10 LNR and>=10 LNR had 36.9 and 43.5 months(p=0.42),respectively.Multivariate Cox regression analysis revealed no difference in the risk of mortality.Conclusion:Among octogenarians who underwent PC,there was no significant difference in OS between those with or without LND,and between<10 or>=10 LNR groups.Therefore,the role and extent of LND after PC need further exploration in this subset of the population.展开更多
BACKGROUND An ileal neobladder is a standardized form of urinary diversion that provides acceptable outcomes in terms of long-term quality of life.Urothelial carcinomas(UCs)arising in the ileal neobladder are extremel...BACKGROUND An ileal neobladder is a standardized form of urinary diversion that provides acceptable outcomes in terms of long-term quality of life.Urothelial carcinomas(UCs)arising in the ileal neobladder are extremely rare,and few reports on this have been published in the English language.CASE SUMMARY We report a case of UC that developed in the ileal neobladder of a 63-year-old man.The patient was diagnosed with UC in situ and underwent radical cystoprostatectomy and ileal neobladder creation.Ten years after the surgery and neoadjuvant chemotherapy,an UC developed in the ileal neobladder.CONCLUSION Ileal neobladder urothelial carcinoma can originate from the implanted urothelium and the intestinal mucosa can migrate intraluminally.展开更多
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 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.
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.
文摘Objective: To explore the current status and influencing factors of supportive care needs in patients with muscle-invasive bladder cancer after surgery, and to provide a reference for the development of targeted intervention strPan ategies. Methods: A general data questionnaire and supportive care needs scale were used to investigate 107 patients with muscle-invasive bladder cancer after surgery. Results: The total score of supportive care needs in patients with muscle-invasive bladder cancer after surgery was (98.48 ± 9.07). Multiple linear regression analysis showed that age, primary caregiver, medical payment method, number of hospitalizations and postoperative time were important influencing factors of supportive care needs in patients with muscle-invasive bladder cancer after surgery (P Conclusion: The supportive care needs of patients with muscle-invasive bladder cancer after surgery are at a low level. Medical staff should identify them early, pay more attention to young patients, patients without medical insurance and patients with multiple hospitalizations, and provide targeted nursing measures to meet their supportive care needs.
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Objective:This study aimed to explore the anticancer potential of Cannabis sativa(C.sativa)strains,specifically PARIS,Dairy Queen(DQ),and super cannabidiol(sCBD),on bladder cancer cells.Given the increasing interest in cannabinoids like cannabichromene(CBC)and delta-9-tetrahydrocannabinol(THC)for their therapeutic properties,we evaluated their cytotoxic effects on urothelial carcinoma(UC)cell lines and their ability to inhibit cell migration and induce apoptosis in both two-dimensional cell models and three-dimensional ex vivo organ cultures(EVOCs).Methods:C.sativa strains were screened for their cytotoxicity against UC cell lines(HTB-4 and HTB-9)using XTT assays.Their phytocannabinoid content was analyzed using high-performance liquid chromatography.We employed fluorescence-activated cell-sorting to determine apoptosis and cell cycle,migration assays to determine cell migration,and EVOCs to evaluate the cytotoxic effect on UC.Gene expression was determined by quantitative polymerase chain reaction.Results:Three commercial C.sativa strains,PARIS,DQ,and sCBD,were found to have the most potent anticancer effects on bladder cancer cells.All extracts contain CBC and THC at different concentrations.In XTT assays on UC cell lines,PARIS had a half-maximal inhibitory concentration(IC50)of 21.58 mg/mL,while DQ and sCBD had similar cytotoxic activity with IC_(50) values for 48-h treatment of 17.99 mg/mL and 17.88 mg/mL,respectively.DQ and sCBD extracts were found to significantly reduce cell migration and increase the percentage of cells in S phase and G_(2)/M phase within the cell population.In EVOCs,the extracts initiated cell death with the expression of apoptosis-related genes increased following exposure to treatment.Conclusion:The findings suggest that C.sativa strains PARIS,DQ,and sCBD,containing CBC and THC,exhibit significant anticancer activity against UC cell lines and ex vivo models.These results underscore the therapeutic potential of CBC-and THC-rich C.sativa extracts in bladder cancer treatment.
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 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.
基金supported by the Guangzhou Municipal Basic Research Program Jointly Funded by City,University,and Enterprise Special Project(2024A03J0907)the Natural Science Foundation of Guangdong Province(2024A1515013201)+1 种基金the National Natural Science Foundation of China(82203720,82203188,82002682,81972731,81773026,81972383)the Science and Technology Project of Zhongshan Municipality(No.2024B1032).
文摘Background:Bladder cancer prognosis remains suboptimal despite advancements in research.Current molecular subtyping methods are resource-intensive,highlighting the need for efficient,cost-effective approaches to predict BCa molecular subtypes.Method:We developed a predictive model for BCa molecular subtypes using machine learning(ML)and pathomics derived from Hematoxylin-Eosin stained pathological slides.A cohort of 353 patients from TCGA was employed,and image features were extracted for analysis.Pathomic signatures were constructed using the LASSO Cox regression algorithm,and a pathomic-clinical nomogram was developed and validated in training and testing cohorts.Results:Seventy distinct image features were identified from 150 pathomic signatures.The model demonstrated robust predictive ability,with AUCs of 0.833 and 0.822 in the training and validation cohorts,respectively.The addition of pathomic score,N stage,and M stage improved the model’s discrimination,achieving AUCs of 0.877 and 0.794 in the training and validation cohorts.Limitations include the lack of an external validation cohort.Conclusion:Our ML-based pathomics model shows promise in predicting BCa molecular subtypes and has the potential to enhance prognosis prediction and inform treatment strategies,marking a significant step towards precision medicine for BCa.
文摘Objective:To systematically review the most recent scientific literature regarding modern strategies for organ preservation in the treatment of non-metastatic muscle-invasive bladder cancer.Methods:Literature search was made using PubMed,Google Scholar,EMBASE,Wiley Library,and ClinicalTrials.gov following the recommendations of the Preferred Reporting Items for Systematic reviews and Meta-Analyses statement.The primary outcome was 5-year overall survival rate,which was addressed by a systematic review and meta-analysis.The risk of bias and quality of evidence were assessed according to the Cochrane Collaboration and the Grading of Recommendations,Assessment,Development and Evaluation system.Results:The evidence is consistent in showing that 5-year survival of trimodality therapy is similar to radical cystectomy in selected patients,ranging between 29%and 73%.Patients undergoing bladder-sparing therapy were found to have better outcomes in terms of quality of life and sociability than those undergoing radical cystectomy.Immunotherapy is establishing itself as a strategy for organ-preservation treatment,showing complete response rates between 42%and 100%.However,most of these results have been obtained from ongoing clinical trials.Furthermore,there are still no studies comparing the efficacy among the different available therapies.Conclusion:Although radical cystectomy remains the gold standard treatment for muscle-invasive bladder cancer,its significant morbidity has prompted the exploration of alternative therapies.In this context,bladder preservation therapies,though supported by limited literature,emerge as a potential alternative that could offer comparable oncological outcomes in selected patients.
基金supported by the grants from the National Natural Science Foundation of China(82273132 to Liu B).
文摘Objective:Bladder cancer(BCa)is a prevalent malignant tumor in the urinary system.Molecular subtyping,utilizing molecular characteristics,represents a novel classification system that has demonstrated its efficacy in tumor diagnosis and treatment.Given the critical role of molecular subtyping in the BCa treatment,acquiring a comprehensive understanding is imperative for guiding treatment decisions,optimizing risk assessment systems,and ultimately improving patient prognosis.Methods:In this review,we provide a comprehensive overview of the research progress in molecular subtyping of BCa,with a primary focus on discussing its utility in guiding various treatment modalities including neoadjuvant chemotherapy,neoadjuvant immunotherapy,and targeted therapy.In addition,this review also covers the trimodality treatment,antibody-drug conjugates,and the treatment of small cell BCa.Results:We present a comprehensive overview of the responsiveness or resistance of different molecular subtypes of BCa to various therapeutic modalities.The basal subtype demonstrates favorable sensitivity to neoadjuvant chemotherapy across multiple classification systems,whereas the luminal infiltrated subtype exhibits potential susceptibility to immunotherapy.In terms of targeted therapy,the basal-like and the basal/squamous subtypes in some classifications have shown notable responsiveness to epidermal growth factor receptor-targeted therapy.Moreover,the luminal subtype in the University of Texas M.D.Anderson Cancer Center classification,the luminal papillary subtypes according to the Cancer Genome Atlas Research Network classification in 2017,and the luminal unstable type in the 2019 Molecular Subtyping classification show potential for the fibroblast growth factor receptor 3-targeted treatment.Conclusion:The significance and impact of BCa molecular subtyping in guiding treatment,evaluating progression,and predicting prognosis are increasingly acknowledged.Accurate subtyping and broad application can bring good benefits to clinical decision-making,risk assessment,and prognostic evaluation.
文摘Introduction:Radical cystectomy with pelvic node dissection remains the standard of care for muscle-invasive bladder carcinoma(MIBC);however,there is a growing interest in bladder preservation alternatives among the elderly population.Guidelines indicate that partial cystectomy(PC)combined with pelvic node dissection(LND)can be considered as an alternative in carefully selected individuals.Using the National Cancer Database,we analyzed the overall survival(OS)between PC with and without LND among octogenarians.Methods:We identified octogenarians with localized muscle-invasive bladder carcinoma(cT2-3N0M0)and urothelial histology who underwent PC with or without LND between 2004 and 2018.Based on the number of lymph nodes removed(LNR),the LND group was further subdivided into<10 and>=10 lymph node groups.A propensity-matched Kaplan-Meier survival analysis was performed to compare OS between these groups.Results:Among 2573 patients who underwent PC,492 octogenarians met our selection criteria.208(42.2%)had LND,while 284(57.8%)had no LND.Within the LND group,53(25.5%)had<10 LNR,and 155(74.5%)had>=10 LNR.The median OS for the matched LND and non-LND groups was 36.9 and 33.4 months(p=0.96),respectively.Similarly,<10 LNR and>=10 LNR had 36.9 and 43.5 months(p=0.42),respectively.Multivariate Cox regression analysis revealed no difference in the risk of mortality.Conclusion:Among octogenarians who underwent PC,there was no significant difference in OS between those with or without LND,and between<10 or>=10 LNR groups.Therefore,the role and extent of LND after PC need further exploration in this subset of the population.
文摘BACKGROUND An ileal neobladder is a standardized form of urinary diversion that provides acceptable outcomes in terms of long-term quality of life.Urothelial carcinomas(UCs)arising in the ileal neobladder are extremely rare,and few reports on this have been published in the English language.CASE SUMMARY We report a case of UC that developed in the ileal neobladder of a 63-year-old man.The patient was diagnosed with UC in situ and underwent radical cystoprostatectomy and ileal neobladder creation.Ten years after the surgery and neoadjuvant chemotherapy,an UC developed in the ileal neobladder.CONCLUSION Ileal neobladder urothelial carcinoma can originate from the implanted urothelium and the intestinal mucosa can migrate intraluminally.
