Stem cell treatment may enhance erectile dysfunction(ED)in individuals with cavernous nerve injury(CNI).Nevertheless,no investigations have directly ascertained the implications of varying amounts of human umbilical c...Stem cell treatment may enhance erectile dysfunction(ED)in individuals with cavernous nerve injury(CNI).Nevertheless,no investigations have directly ascertained the implications of varying amounts of human umbilical cord-derived mesenchymal stem cells(HUC-MSCs)on ED.We compare the efficacy of three various doses of HUC-MSCs as a therapeutic strategy for ED.Sprague–Dawley rats(total=175)were randomly allocated into five groups.A total of 35 rats underwent sham surgery and 140 rats endured bilateral CNI and were treated with vehicles or doses of HUC-MSCs(1×106 cells,5×106 cells,and 1×107 cells in 0.1 ml,respectively).Penile tissues were harvested for histological analysis on 1 day,3 days,7 days,14 days,28 days,60 days,and 90 days postsurgery.It was found that varying dosages of HUC-MSCs enhanced the erectile function of rats with bilateral CNI and ED.Moreover,there was no significant disparity in the effectiveness of various dosages of HUC-MSCs.However,the expression of endothelial markers(rat endothelial cell antigen-1[RECA-1]and endothelial nitric oxide synthase[eNOS]),smooth muscle markers(alpha smooth muscle actin[α-SMA]and desmin),and neural markers(neurofilament[RECA-1]and neurogenic nitric oxide synthase[nNOS])increased significantly with prolonged treatment time.Masson’s staining demonstrated an increased in the smooth muscle cell(SMC)/collagen ratio.Significant changes were detected in the microstructures of various types of cells.In vivo imaging system(IVIS)analysis showed that at the 1st day,the HUC-MSCs implanted moved to the site of damage.Additionally,the oxidative stress levels were dramatically reduced in the penises of rats administered with HUC-MSCs.展开更多
Stem cell therapy is a potentially promising option for erectile dysfunction; however, its risk of tumorigenicity is a clinical hurdle and the risk is positively related to the number of injected cells. Our previous s...Stem cell therapy is a potentially promising option for erectile dysfunction; however, its risk of tumorigenicity is a clinical hurdle and the risk is positively related to the number of injected cells. Our previous study showed that nanotechnology improved adipose-derived stem cell （ADSC） therapy for erectile dysfunction of cavernous nerve injury （CNI） by attracting cells in the corpus cavernosum. These results indicated the possibility of using a reduced dosage of ADSCs for intracavernous injection. In this exploratory study, we used lower dosage （2 × 105 cells） of ADSCs for intracavernous injection （ICI） and the nanotechnology approach. Intracavernous pressure and mean arterial pressure were measured at day 28 to assess erectile function. The low-dose ADSC therapy group showed favorable treatment effects, and nanotechnology further improved these effects. In vivo imaging of ICI cells revealed that the fluorescein signals of NanoShuttle-bound ADSCs （NanoADSCs） were much stronger than those of ADSCs at days 0, 1, and 3. Both immunofluorescence and Western blot analysis showed a significant increase in smooth muscle, endothelium, and nerve tissue in the ADSC group compared to that in the CNI group; further improvement was achieved with assisted nanotechnology. These findings demonstrate that nanotechnology can be used to further improve the effect of small dosage of ADSCs to improve erectile function. Abundant NanoADSCs remain in the corpus cavernosum in vivo for at least 3 days. The mechanism of erectile function improvement may be related to the regeneration of the smooth muscle, endothelium, and nerve tissues.展开更多
Postprostatectomy erectile dysfunction(pPED)remains a current problem despite improvements in surgical techniques.Vacuum therapy is clinically confirmed as a type of pPED rehabilitation.However,its underlying mechanis...Postprostatectomy erectile dysfunction(pPED)remains a current problem despite improvements in surgical techniques.Vacuum therapy is clinically confirmed as a type of pPED rehabilitation.However,its underlying mechanisms are incompletely understood.Recently,autophagy and apoptosis were extensively studied in erectile dysfunction resulting from diabetes,senescence,and androgen deprivation but not in the context of pPED and vacuum therapy.Therefore,this study was designed to investigate the roles of autophagy and apoptosis in pPED and vacuum therapy.Twenty-four adult male Sprague-Dawley rats were randomly divided into three groups:the control group,bilateral cavernous nerve crush(BCNC)group,and BCNC+vacuum group.After 4 weeks of treatment,intracavernosal pressure was used to evaluate erectile function.Real-time quantitative polymerase chain reaction,western blot,and immunohistochemistry were used to measure the molecular expression.TdT-mediated dUTP nick-end labeling staining was used to assess apoptosis.Transmission electron microscopy was used to observe autophagosomes.After treatment,compared with those of the BCNC group,erectile function and cavernosal hypoxia had statistically significantly improved(P<0.05).Apoptosis and the relative protein expression of B-cell lymphoma-2-associated X and cleaved Caspase3 were decreased(P<0.05).Autophagy-related molecules such as phosphorylated unc-51-like autophagy-activating kinase 1(Ser757)and p62 were decreased.Beclinl,microtubule-associated protein 1 light chain 3 A/B,and autophagosomes were increased(P<0.05).Besides,the phosphatidylinositol 3-kinase/AKT/mammalian target of rapamycin signaling pathway,as a negative regulator of autophagy to some degree,was inhibited.This study revealed that vacuum therapy ameliorated pPED in BCNC rats by inhibiting apoptosis and activating autophagy.展开更多
Cancer continues to pose a formidable challenge in global health,with conventional treatments such as chemotherapy and radiotherapy often resulting in severe toxicities that significantly degrade patients’quality of ...Cancer continues to pose a formidable challenge in global health,with conventional treatments such as chemotherapy and radiotherapy often resulting in severe toxicities that significantly degrade patients’quality of life and restrict therapeutic outcomes.Addressing this pressing issue,this review presents a thorough and systematic analysis of innovative and emerging strategies designed to minimize the toxicity induced by treatment,while maintaining or even enhancing antitumor efficacy.The focus is on six promising therapeutic approaches:combination therapies utilizing natural bioactive products,molecularly targeted therapies,immunotherapies,nanotechnology-mediated drug delivery systems,adjunct traditional Chinese medicine interventions,and low-dose spatiotemporally concerted regimens.Each approach employs unique mechanisms—such as enhanced targeting precision,immune system activation,tumor microenvironment reprogramming,and multi-component synergistic effects—to mitigate damage to normal tissues and reduce systemic adverse reactions.Despite promising preclinical and clinical advancements,several challenges persist,including drug resistance,high economic costs,a lack of reliable predictive biomarkers,and complexities in clinical translation and regulatory approval.Looking ahead,the incorporation of artificial intelligence,multi-omics profiling,and novel biomimetic nanotechnologies offers unprecedented opportunities for developing highly personalized,low-toxicity treatment frameworks.This review highlights a fundamental shift in oncology towards precision medicine that balances efficacy with safety,demonstrating the transformative potential of these strategies in shaping the future of cancer therapy and enhancing patient care globally.展开更多
Prostate cancer is the second most common malignancy and the sixth leading cause of cancer-related death in men worldwide.Radical prostatectomy(RP)is the standard treatment for localized prostate cancer,but the proced...Prostate cancer is the second most common malignancy and the sixth leading cause of cancer-related death in men worldwide.Radical prostatectomy(RP)is the standard treatment for localized prostate cancer,but the procedure often results in postoperative erectile dysfunction(ED).The poor efficacy of phosphodiesterase 5 inhibitors after surgery highlights the need to develop new therapies to enhance cavernous nerve regeneration and improve the erectile function of these patients.In the present study,we aimed to examine the potential of heparin-binding epidermal growth factor-like growth factor(HB-EGF)in preserving erectile function in cavernous nerve injury(CNI)mice.We found that HB-EGF expression was reduced significantly on the 1st day after CNI in penile tissue.Ex vivo and in vitro studies showed that HB-EGF promotes major pelvic ganglion neurite sprouting and neuro-2a(N2a)cell migration.In vivo studies showed that exogenous HB-EGF treatment significantly restored the erectile function of CNI mice to 86.9%of sham levels.Immunofluorescence staining showed that mural and neuronal cells were preserved by inducing cell proliferation and reducing apoptosis and reactive oxygen species production.Western blot analysis showed that HB-EGF upregulated protein kinase B and extracellular signal-regulated kinase activation and neurotrophic factor expression.Overall,HB-EGF is a major promising therapeutic agent for treating ED in postoperative RP.展开更多
BACKGROUND Hepatic hemangioma represents the most common benign primary hepatic neo-plasm.Although most such tumors are small and asymptomatic,giant cavernous hemangioma(GCH)is frequently symptomatic,and needs interve...BACKGROUND Hepatic hemangioma represents the most common benign primary hepatic neo-plasm.Although most such tumors are small and asymptomatic,giant cavernous hemangioma(GCH)is frequently symptomatic,and needs intervention.More-over,diffuse hepatic hemangiomatosis(DHH)is not rare in the liver parenchyma adjacent to a GCH.The management strategy for hepatic hemangiomas can differ depending on the presence of associated hemangiomatosis and the amount and distribution of the residual hepatic parenchyma.CASE SUMMARY Herein,we report two patients with GCH coexistent with DHH successfully treated by laparoscopic microwave ablation.The two GCHs were ablated com-pletely and the ablated zone atrophied obviously in imaging follow-ups after ablation.Surprisingly,there was a trend toward gradual reduction and dimini-shment of DHH.CONCLUSION Thermal ablation treatment might be an effective and less invasive treatment for GCH coexistent with DHH around the hemangioma.展开更多
Developmental venous anomalies(DVAs)are benign congenital veins that collect normal brain drainage into a single outlet.Cerebral cavernous malformations(CMs)are clusters of thin-walled capillary cavities prone to blee...Developmental venous anomalies(DVAs)are benign congenital veins that collect normal brain drainage into a single outlet.Cerebral cavernous malformations(CMs)are clusters of thin-walled capillary cavities prone to bleeding.When both lesions coexist,the DVA’s altered venous pressure and flow can promote CM formation or rupture.Detecting a DVA abutting an otherwise unexplained intracerebral hemorrhage can therefore raise suspicion of an occult CM as a likely cause,a clue which may be invaluable for daily clinical practice.The main focus of this review is to acknowledge the hallmark imaging appearances of DVAs and CMs,as well as their coexistence,explore the clinical consequences of mixed lesions,and emphasize that recognizing their partnership is vital for an accurate,timely diagnosis and appropriately targeted management.展开更多
BACKGROUND Transjugular intrahepatic portosystemic shunt(TIPS)is contraindicated for patients with cavernous transformation of the portal vein(CTPV)due to high surgery-related mortality risk.However,surgically assiste...BACKGROUND Transjugular intrahepatic portosystemic shunt(TIPS)is contraindicated for patients with cavernous transformation of the portal vein(CTPV)due to high surgery-related mortality risk.However,surgically assisted TIPS(SATIPS)can significantly reduce the risk.AIM To evaluate the clinical efficacy of SATIPS,this study was conducted.METHODS One hundred and seven patients with CTPV and esophagogastric variceal bleeding were recruited from January 2023 to December 2024.The patients were recruited from three different hospitals.Overall,54 patients received SATIPS treatment(SATIPS group),while 53 patients did not receive SATIPS and underwent prophylactic endoscopic sclerosing ligation(control group).Subsequently,survival rates,incidence rates of gastrointestinal bleeding,incidence of hepatic encephalopathy rate,and the incidence of liver failure after treatment in both groups at 3 and 6 months were observed.RESULTS The survival rates for the SATIPS and control groups were 94.4%and 92.5%at 3 months(P value=0.72)and 94.4%and 73.6%at 6 months(P value=0.0051)respectively.The incidence of liver failure was 3.7%and 9.4%at 3 months(P value=0.26)and 3.7%and18.9%at 6 months(P value=0.016);the incidence of gastrointestinal bleeding was 5.6%and 37.7%at 3 months(P value<0.001)and 9.3%and 47.2%(P value<0.001)at 6 months;and the incidence of hepatic encephalopathy was 3.7%and 17.0%at 3 months(P value=0.026)and 7.4%and 26.4%at 6 months(P value=0.026)respectively.CONCLUSION For patients with CTPV,there were no optimal treatment.Regarding long-term efficacy,SATIPS can significantly reduce the rate of rebleeding,hepatic encephalopathy and liver failure,and is associated with better survival.展开更多
Objective:The following article explores our evolving understandings of the role of regenerative technology as an effective penile rehabilitation tool in men with erectile dysfunction(ED)in the setting of prostate can...Objective:The following article explores our evolving understandings of the role of regenerative technology as an effective penile rehabilitation tool in men with erectile dysfunction(ED)in the setting of prostate cancer(PCa)treatment and PCa survivorship.Methods:This narrative clinical review paper summarizes what is currently known about various modalities of regenerative therapy in restoring spontaneous erectile function(EF)in men following PCa treatment with an emphasis on penile rehabilitation strategies.Results:Conventional medical therapy often does not reverse underlying endothelial dysfunction or promote neuro-vasculogenesis to preserve penile health in men with ED.Over the past decade,there has been considerable interest in the role of regenerative therapy to restore endothelial dysfunction and ED without future dependency on medical therapy.Regenerative therapy can be classified into cellular-based(immunomodulators,stem cells,and platelet-rich plasma),biomaterials(nerve graft transfer),and device-related technology(low-intensity shockwave).Although published literature shows early promise in the role of regenerative technology for ED,there is a paucity of high-quality clinical trials in the setting of penile rehabilitation and PCa survivorship to support their use as standard care and be adopted in clinical guidelines.展开更多
BACKGROUND Chemotherapy-induced cardiotoxicity is a significant complication in cancer therapy,limiting treatment efficacy and worsening patient outcomes.Recent studies have implicated the gut microbiome and its key m...BACKGROUND Chemotherapy-induced cardiotoxicity is a significant complication in cancer therapy,limiting treatment efficacy and worsening patient outcomes.Recent studies have implicated the gut microbiome and its key metabolites,such as shortchain fatty acids(SCFAs)and trimethylamine-N-oxide(TMAO),in mediating inflammation,oxidative stress,and cardiac damage.The gut-heart axis is increasingly recognized as a pivotal pathway linking microbiota dysregulation to chemotherapy-related cardiac dysfunction.AIM To systematically review existing evidence on the role of gut microbiome alterations in chemotherapy-induced cardiotoxicity and evaluate emerging microbiome-based therapeutic strategies aimed at mitigating cardiovascular risk in cancer patients.METHODS A systematic literature search was conducted in PubMed,Scopus,and Web of Science for studies published between January 2013 and December 2024.Studies were included if they examined chemotherapy-induced cardiotoxicity in relation to gut microbiota composition,microbial metabolites(e.g.,SCFAs,TMAO),or microbiome-targeted interventions.Selection followed Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines.Data extraction focused on microbiota alterations,mechanistic pathways,cardiac outcomes,and quality assessments using standardized risk-of-bias tools.RESULTS Eighteen studies met the inclusion criteria.Chemotherapy was consistently associated with gut dysbiosis characterized by reduced SCFA-producing bacteria and increased TMAO-producing strains.This imbalance contributed to gut barrier disruption,systemic inflammation,and oxidative stress,all of which promote myocardial damage.SCFA depletion weakened anti-inflammatory responses,while elevated TMAO levels exacerbated cardiac fibrosis and dysfunction.Preclinical studies showed promising cardioprotective effects from probiotics,prebiotics,dietary interventions,and fecal microbiota transplantation,though human data remain limited.CONCLUSION Gut microbiome dysregulation plays a crucial role in the development of chemotherapy-induced cardiotoxicity.Altered microbial composition and metabolite production trigger systemic inflammation and cardiac injury.Microbiome-targeted therapies represent a promising preventive and therapeutic approach in cardio-oncology,warranting further clinical validation through well-designed trials.展开更多
Cardiovascular disease remains the leading global cause of mortality,projected to increase by 73.4%from 2025 to 2050 despite declining age-standardized rates.Contemporary interventions,such as percutaneous coronary in...Cardiovascular disease remains the leading global cause of mortality,projected to increase by 73.4%from 2025 to 2050 despite declining age-standardized rates.Contemporary interventions,such as percutaneous coronary intervention and statins,reduce major adverse cardiovascular events(MACE)by 25%-30%,yet a 20%five-year MACE risk persists in high-risk cohorts.These approaches,histor-ically focused on luminal stenosis,fail to address systemic atherogenesis drivers like endothelial dysfunction and inflammation.Specifically,dietary linoleic acid restriction(<5 g/day)reduces oxidized low-density lipoprotein by approximately 15%by limiting peroxidation-prone bisallylic bonds,mitigating arterial inflam-mation,a key atherogenic trigger.Enhanced external counterpulsation,through pulsatile shear stress,enhances nitric oxide-mediated coronary perfusion,alle-viating angina in approximately 70%of refractory cases unresponsive to revascu-larization.Nanoparticle-facilitated chelation targets atherosclerotic plaques with precision,reducing calcium content by up to 30%in preclinical models,offering a novel avenue for lesion reversal.These innovations collectively address residual risk by tackling root causes,oxidative stress,endothelial dysfunction,and plaque instability,potentially halving MACE rates with widespread adoption.Despite promising preliminary data,gaps remain in long-term safety and scalability.Robust clinical trials are needed to validate these approaches,which collectively aim to transform cardiovascular disease management by prioritizing prevention and vascular restoration,potentially reducing coronary events to a public health rarity.展开更多
Regenerative medicine is a promising therapeutic avenue for previously incurable diseases.As the risk of chronic and degenerative diseases significantly increases with age,the elderly population represents a major coh...Regenerative medicine is a promising therapeutic avenue for previously incurable diseases.As the risk of chronic and degenerative diseases significantly increases with age,the elderly population represents a major cohort for stem cell-based therapies.However,the regenerative potential of stem cells significantly decreases with advanced age and deteriorating health status of the donor.Therefore,the efficacy of autologous stem cell therapy is significantly compromised in older patients.To overcome these limitations,alternative strategies have been used to restore the age-and disease-depleted function of stem cells.These methods aim to restore the therapeutic efficacy of aged stem cells for autologous use.This article explores the effect of donor age and health status on the regenerative potential of stem cells.It further highlights the limitations of stem cell-based therapy for autologous treatment in the elderly.A comprehensive insight into the potential strategies to address the“age”and“disease”compromised regenerative potential of autologous stem cells is also presented.The information provided here serves as a valuable resource for physicians and patients for optimization of stem cellbased autologous therapy for aged patients.展开更多
Tau plays a crucial role in several neurodegenerative diseases,collectively referred to as tauopathies.Therefore,targeting potential pathological changes in tau could enable useful therapeutic interventions.However,ta...Tau plays a crucial role in several neurodegenerative diseases,collectively referred to as tauopathies.Therefore,targeting potential pathological changes in tau could enable useful therapeutic interventions.However,tau is not an easy target because it dynamically interacts with microtubules and other cellular components,which presents a challenge for tau-targeted drugs.New cellular models could aid the development of mechanism-based tau-targeted therapies.展开更多
Therapy discontinuation in inflammatory bowel disease,particularly involving immunomodulators,biologics,and small molecules,remains a controversial and evolving topic.This letter reflects on developments following the...Therapy discontinuation in inflammatory bowel disease,particularly involving immunomodulators,biologics,and small molecules,remains a controversial and evolving topic.This letter reflects on developments following the publication by Meštrovićet al,emphasizing the complex balance between risks of relapse,antidrug antibody formation,and potential complications of long-term immunosuppression.Recent evidence underscores high relapse rates following withdrawal-especially of anti-tumor necrosis factor agents-and highlights the lack of robust data for newer biologics.Updated guidelines from European Crohn’s and Colitis Organization,British Society of Gastroenterology,and American College of Gastroenterology all support cautious and individualized approaches,with strict criteria and close follow-up,particularly in Crohn’s disease.For ulcerative colitis,therapeutic cycling remains insufficiently addressed.We proposed a flowchart to support clinical decision-making and stress the importance of shared decisionmaking in the era of personalized medicine since,despite new drug classes and evolving strategies,the therapeutic ceiling in inflammatory bowel disease has yet to be fully overcome.展开更多
The development of highly effective therapeutics is a priority in addressing the escalating threat that cancer poses to human health.Cyclodextrins(CDs) with exceptional biocompatibility and devisable structural hierar...The development of highly effective therapeutics is a priority in addressing the escalating threat that cancer poses to human health.Cyclodextrins(CDs) with exceptional biocompatibility and devisable structural hierarchy are emerging as versatile building blocks for engineered drug delivery systems,showing a promising prospect in cancer therapy.CDs enable precise synthesis of functionalized polymers with tailored architectures,endowing their excellent stability and large surface area to prolong drug circulation,enhance solubility,and increase targeting efficiency.Recently,CD-based nanotherapeutics has shown transformative potential in chemotherapy,phototherapy,immunotherapy,gene therapy and other codelivery systems of combination therapy.This review will introduce the types of CD-based nanotherapeutics,systematically summarize their design methods and anticancer application,and further discuss the prospects and challenges,providing a roadmap for advancing CD nanotechnology toward cancer therapeutics.展开更多
BACKGROUND The liver represents a common site of distant metastasis in patients with esophageal cancer(EC).Conventional chemotherapy(CMT)presents limited efficacy for EC,and EC patients with liver metastases typically...BACKGROUND The liver represents a common site of distant metastasis in patients with esophageal cancer(EC).Conventional chemotherapy(CMT)presents limited efficacy for EC,and EC patients with liver metastases typically experience a poor prognosis,highlighting an urgent need to explore novel treatment approaches.This study evaluated the overall efficacy and safety of CMT vs CMT combined with immune checkpoint inhibitors(ICIs)in the treatment of EC patients with liver metastases.Furthermore,prognostic factors influencing outcomes in this patient population were identified.AIM To evaluate the efficacy and safety of first-line chemoimmunotherapy for EC patients with liver metastases and to analyze prognostic factors.METHODS This retrospective study included 126 EC patients with liver metastases at Zhejiang Cancer Hospital between 2014 and 2024.Patients receiving CMT were compared with those receiving CMT+ICI.Analyzed variables included clinicopathological features,treatment history,characteristics of metastasis,systemic and local treatments,overall survival(OS),and treatment-related adverse events(TRAEs).Prognostic factors were evaluated using univariate and multivariate Cox proportional-hazards regression models.Finally,efficacy outcomes and TRAE profiles were compared between the two groups.RESULTS A significant difference in median OS was identified between the two groups(10.8 months in the CMT group vs 20.8 months in the CMT+ICI group,P=0.004).The CMT+ICI group also demonstrated a significantly longer median progression-free survival of 11.7 months(P<0.001).Patients receiving combination therapy exhibited significantly improved systemic objective response rate and disease control rate.Multivariate analysis identified key factors significantly influencing OS in EC patients with liver metastases:Karnofsky Performance Status score≥70,receipt of local therapy for liver metastases,and the number of cycles of CMT and immunotherapy received.Furthermore,the incidence of TRAEs did not significantly differ between the CMT+ICI and CMT groups.CONCLUSION For EC patients with liver metastases,the combination of CMT and ICIs demonstrates significantly superior efficacy compared with CMT alone,while maintaining manageable TRAEs.展开更多
Experimental therapies targeting immune and stromal cells,such as mast cells,cancer-associated fibroblasts,dendritic cells,and tumor endothelial cells,in the treatment of gastrointestinal solid tumors pose new and com...Experimental therapies targeting immune and stromal cells,such as mast cells,cancer-associated fibroblasts,dendritic cells,and tumor endothelial cells,in the treatment of gastrointestinal solid tumors pose new and complex surgical and medico-legal challenges.These innovative treatments require that informed consent not be limited to simple acceptance of the medical procedure,but instead reflect a true relational and cognitive process grounded in understanding,free choice,and the ability to revoke consent at any time.In particular,it is essential that the patient understands the experimental nature of the therapy,its development stage,potential benefits and risks,as well as the implications for their health and personal dignity.In the case of stromal cell-based treatments,which may exert complex immunomodulatory effects or activate angiogenic pathways that are not yet fully understood,patients must be made fully aware that they are participating in a non-standardized therapy whose outcomes,whether beneficial or harmful,cannot yet be predicted with certainty.This requires particularly careful medical communication,using simple yet scientifically accurate explanations delivered in appropriate language,along with a final verification of the patient’s actual understanding.展开更多
Despite demonstrating significant anti-tumor potential as an artemisinin derivative,artesunate faces delivery efficiency challenges due to low water solubility and insufficient targeting specificity.To improve the del...Despite demonstrating significant anti-tumor potential as an artemisinin derivative,artesunate faces delivery efficiency challenges due to low water solubility and insufficient targeting specificity.To improve the delivery efficiency,we engineered three artesunate(ART) derivatives,AC_(15)-L(linear),AC_(15)-B(branched),and AC_(15)-C(cyclic) with distinct aliphatic chain architectures.Unexpectedly,we observed that AC_(15)-C exhibited superior cytotoxicity against 4T1 breast cancer cells,and had the highest binding affinity for Lon protease 1(LONP1)(-72.6 kcal/mol).Subsequently,disulfide bond-containing lipid-PEG(DSPESS-PEG2K) modified chain architecture-engineered ART derivatives nanoassemblies(NAs) were developed to mitigate solubility-related limitations while enhancing targeting precision.Molecular docking and experimental validation demonstrated that ART derivatives inhibited LONP1 through hydrophobic interactions while preserved Fe^(2+)-mediated Fenton-like reaction activity.In vitro and in vivo evaluations demonstrated that AC_(15)-C NAs outperformed free ART and other NAs,suppressing 4T1 tumor growth via dual action:LONP1-directed mitochondrial proteostasis collapse and reactive oxygen species(ROS) amplification through Fe^(2+)-ART interactions.This study elucidated a novel anti-tumor mechanism of ART through the rational design of derivatives with spatially configured aliphatic chains,and developed reductionresponsive NAs to provide an advanced delivery strategy.展开更多
Mongolian medicine posits that disruptions to the natural balance of the three roots and seven elements within the human body may lead to ocular disorders,vision impairment,and ultimately myopia.China’s children and ...Mongolian medicine posits that disruptions to the natural balance of the three roots and seven elements within the human body may lead to ocular disorders,vision impairment,and ultimately myopia.China’s children and adolescents not only exhibit high myopia rates but also face increasingly prominent issues of younger onset and severe progression,which critically impact the nation’s future and require urgent attention.Myopia prevention constitutes a systematic project.Traditional Mongolian moxibustion therapy works by applying heat stimulation to specific acupoints to warm meridians,harmonize Qi-blood circulation,regulate elemental balance,thereby enhancing immunity for disease prevention.This holistic approach features non-invasive application with minimal side effects.However,current interventions in myopia management through this method still face challenges including inconsistent operational protocols and insufficiently systematic collaborative research.This paper reviews recent advancements in early intervention using Mongolian moxibustion therapy for myopia,providing insights to optimize myopia prevention strategies.展开更多
Thermally activated delayed fluorescence(TADF) emitters show great potential in photodynamic therapy(PDT) and bioimaging,leveraging their structural adaptability,efficient reverse intersystem crossing(RISC),robust pho...Thermally activated delayed fluorescence(TADF) emitters show great potential in photodynamic therapy(PDT) and bioimaging,leveraging their structural adaptability,efficient reverse intersystem crossing(RISC),robust photosensitizing capability,and high photoluminescence quantum yields(PLQYs).Herein,we developed a new class of donor-acceptor-donor(D-A-D)-type TADF materials by connecting the highly twisted indolizine-benzophenone electron acceptors with a series of electron donors including phenoxazine,phenothiazine and 9,9-dimethyl-9,10-dihydroacridine.These materials exhibit enhanced TADF properties,aggregation-induced emission(AIE),alongside high reactive oxygen species(ROS) generation efficiency,effectively mitigating aggregation-caused quenching observed in traditional fluorophores.Among them,IDP-p-PXZ,incorporating the phenoxazine donor,stands out with the smallest singlet-triplet splitting energy(ΔE_(ST)) and the highest spin-orbit coupling matrix elements(SOCMEs).Upon encapsulation into 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-2000](DSPE-PEG2000) nanoparticles(NPs),IDP-p-PXZ demonstrates extended delayed fluorescence lifetimes in air,an exceptionally fast intersystem crossing(ISC) rate constant(k_(ISC)) of 3.4×10^(7)s^(-1),and a radiative rate constant(k_(r)) of 5.05×10^(6)s^(-1).These NPs exhibit superior biocompatibility,efficient cellular internalization,and potent ROS production,enabling effective simultaneous PDT and confocal fluorescence imaging in HeLa cells.展开更多
基金supported by the Xuzhou City 2022 Special Program for Promoting Science and Technology Innovation(grant No.KC22096)Shandong Provincial Hospital Research Incubation Fund(No.2022FY063).
文摘Stem cell treatment may enhance erectile dysfunction(ED)in individuals with cavernous nerve injury(CNI).Nevertheless,no investigations have directly ascertained the implications of varying amounts of human umbilical cord-derived mesenchymal stem cells(HUC-MSCs)on ED.We compare the efficacy of three various doses of HUC-MSCs as a therapeutic strategy for ED.Sprague–Dawley rats(total=175)were randomly allocated into five groups.A total of 35 rats underwent sham surgery and 140 rats endured bilateral CNI and were treated with vehicles or doses of HUC-MSCs(1×106 cells,5×106 cells,and 1×107 cells in 0.1 ml,respectively).Penile tissues were harvested for histological analysis on 1 day,3 days,7 days,14 days,28 days,60 days,and 90 days postsurgery.It was found that varying dosages of HUC-MSCs enhanced the erectile function of rats with bilateral CNI and ED.Moreover,there was no significant disparity in the effectiveness of various dosages of HUC-MSCs.However,the expression of endothelial markers(rat endothelial cell antigen-1[RECA-1]and endothelial nitric oxide synthase[eNOS]),smooth muscle markers(alpha smooth muscle actin[α-SMA]and desmin),and neural markers(neurofilament[RECA-1]and neurogenic nitric oxide synthase[nNOS])increased significantly with prolonged treatment time.Masson’s staining demonstrated an increased in the smooth muscle cell(SMC)/collagen ratio.Significant changes were detected in the microstructures of various types of cells.In vivo imaging system(IVIS)analysis showed that at the 1st day,the HUC-MSCs implanted moved to the site of damage.Additionally,the oxidative stress levels were dramatically reduced in the penises of rats administered with HUC-MSCs.
基金This research was supported by the Beijing Natural Science Foundation （Grant No. 7174362） and the National Natural Science Foundation of China （Grant No. 81601272）.
文摘Stem cell therapy is a potentially promising option for erectile dysfunction; however, its risk of tumorigenicity is a clinical hurdle and the risk is positively related to the number of injected cells. Our previous study showed that nanotechnology improved adipose-derived stem cell （ADSC） therapy for erectile dysfunction of cavernous nerve injury （CNI） by attracting cells in the corpus cavernosum. These results indicated the possibility of using a reduced dosage of ADSCs for intracavernous injection. In this exploratory study, we used lower dosage （2 × 105 cells） of ADSCs for intracavernous injection （ICI） and the nanotechnology approach. Intracavernous pressure and mean arterial pressure were measured at day 28 to assess erectile function. The low-dose ADSC therapy group showed favorable treatment effects, and nanotechnology further improved these effects. In vivo imaging of ICI cells revealed that the fluorescein signals of NanoShuttle-bound ADSCs （NanoADSCs） were much stronger than those of ADSCs at days 0, 1, and 3. Both immunofluorescence and Western blot analysis showed a significant increase in smooth muscle, endothelium, and nerve tissue in the ADSC group compared to that in the CNI group; further improvement was achieved with assisted nanotechnology. These findings demonstrate that nanotechnology can be used to further improve the effect of small dosage of ADSCs to improve erectile function. Abundant NanoADSCs remain in the corpus cavernosum in vivo for at least 3 days. The mechanism of erectile function improvement may be related to the regeneration of the smooth muscle, endothelium, and nerve tissues.
基金the Natural Science Foundation of China(No.81871147 and No.82071639)the Sichuan Science and Technology Program(No.2018SZ0019 and No,2018TJPT0018).
文摘Postprostatectomy erectile dysfunction(pPED)remains a current problem despite improvements in surgical techniques.Vacuum therapy is clinically confirmed as a type of pPED rehabilitation.However,its underlying mechanisms are incompletely understood.Recently,autophagy and apoptosis were extensively studied in erectile dysfunction resulting from diabetes,senescence,and androgen deprivation but not in the context of pPED and vacuum therapy.Therefore,this study was designed to investigate the roles of autophagy and apoptosis in pPED and vacuum therapy.Twenty-four adult male Sprague-Dawley rats were randomly divided into three groups:the control group,bilateral cavernous nerve crush(BCNC)group,and BCNC+vacuum group.After 4 weeks of treatment,intracavernosal pressure was used to evaluate erectile function.Real-time quantitative polymerase chain reaction,western blot,and immunohistochemistry were used to measure the molecular expression.TdT-mediated dUTP nick-end labeling staining was used to assess apoptosis.Transmission electron microscopy was used to observe autophagosomes.After treatment,compared with those of the BCNC group,erectile function and cavernosal hypoxia had statistically significantly improved(P<0.05).Apoptosis and the relative protein expression of B-cell lymphoma-2-associated X and cleaved Caspase3 were decreased(P<0.05).Autophagy-related molecules such as phosphorylated unc-51-like autophagy-activating kinase 1(Ser757)and p62 were decreased.Beclinl,microtubule-associated protein 1 light chain 3 A/B,and autophagosomes were increased(P<0.05).Besides,the phosphatidylinositol 3-kinase/AKT/mammalian target of rapamycin signaling pathway,as a negative regulator of autophagy to some degree,was inhibited.This study revealed that vacuum therapy ameliorated pPED in BCNC rats by inhibiting apoptosis and activating autophagy.
文摘Cancer continues to pose a formidable challenge in global health,with conventional treatments such as chemotherapy and radiotherapy often resulting in severe toxicities that significantly degrade patients’quality of life and restrict therapeutic outcomes.Addressing this pressing issue,this review presents a thorough and systematic analysis of innovative and emerging strategies designed to minimize the toxicity induced by treatment,while maintaining or even enhancing antitumor efficacy.The focus is on six promising therapeutic approaches:combination therapies utilizing natural bioactive products,molecularly targeted therapies,immunotherapies,nanotechnology-mediated drug delivery systems,adjunct traditional Chinese medicine interventions,and low-dose spatiotemporally concerted regimens.Each approach employs unique mechanisms—such as enhanced targeting precision,immune system activation,tumor microenvironment reprogramming,and multi-component synergistic effects—to mitigate damage to normal tissues and reduce systemic adverse reactions.Despite promising preclinical and clinical advancements,several challenges persist,including drug resistance,high economic costs,a lack of reliable predictive biomarkers,and complexities in clinical translation and regulatory approval.Looking ahead,the incorporation of artificial intelligence,multi-omics profiling,and novel biomimetic nanotechnologies offers unprecedented opportunities for developing highly personalized,low-toxicity treatment frameworks.This review highlights a fundamental shift in oncology towards precision medicine that balances efficacy with safety,demonstrating the transformative potential of these strategies in shaping the future of cancer therapy and enhancing patient care globally.
文摘Prostate cancer is the second most common malignancy and the sixth leading cause of cancer-related death in men worldwide.Radical prostatectomy(RP)is the standard treatment for localized prostate cancer,but the procedure often results in postoperative erectile dysfunction(ED).The poor efficacy of phosphodiesterase 5 inhibitors after surgery highlights the need to develop new therapies to enhance cavernous nerve regeneration and improve the erectile function of these patients.In the present study,we aimed to examine the potential of heparin-binding epidermal growth factor-like growth factor(HB-EGF)in preserving erectile function in cavernous nerve injury(CNI)mice.We found that HB-EGF expression was reduced significantly on the 1st day after CNI in penile tissue.Ex vivo and in vitro studies showed that HB-EGF promotes major pelvic ganglion neurite sprouting and neuro-2a(N2a)cell migration.In vivo studies showed that exogenous HB-EGF treatment significantly restored the erectile function of CNI mice to 86.9%of sham levels.Immunofluorescence staining showed that mural and neuronal cells were preserved by inducing cell proliferation and reducing apoptosis and reactive oxygen species production.Western blot analysis showed that HB-EGF upregulated protein kinase B and extracellular signal-regulated kinase activation and neurotrophic factor expression.Overall,HB-EGF is a major promising therapeutic agent for treating ED in postoperative RP.
文摘BACKGROUND Hepatic hemangioma represents the most common benign primary hepatic neo-plasm.Although most such tumors are small and asymptomatic,giant cavernous hemangioma(GCH)is frequently symptomatic,and needs intervention.More-over,diffuse hepatic hemangiomatosis(DHH)is not rare in the liver parenchyma adjacent to a GCH.The management strategy for hepatic hemangiomas can differ depending on the presence of associated hemangiomatosis and the amount and distribution of the residual hepatic parenchyma.CASE SUMMARY Herein,we report two patients with GCH coexistent with DHH successfully treated by laparoscopic microwave ablation.The two GCHs were ablated com-pletely and the ablated zone atrophied obviously in imaging follow-ups after ablation.Surprisingly,there was a trend toward gradual reduction and dimini-shment of DHH.CONCLUSION Thermal ablation treatment might be an effective and less invasive treatment for GCH coexistent with DHH around the hemangioma.
文摘Developmental venous anomalies(DVAs)are benign congenital veins that collect normal brain drainage into a single outlet.Cerebral cavernous malformations(CMs)are clusters of thin-walled capillary cavities prone to bleeding.When both lesions coexist,the DVA’s altered venous pressure and flow can promote CM formation or rupture.Detecting a DVA abutting an otherwise unexplained intracerebral hemorrhage can therefore raise suspicion of an occult CM as a likely cause,a clue which may be invaluable for daily clinical practice.The main focus of this review is to acknowledge the hallmark imaging appearances of DVAs and CMs,as well as their coexistence,explore the clinical consequences of mixed lesions,and emphasize that recognizing their partnership is vital for an accurate,timely diagnosis and appropriately targeted management.
文摘BACKGROUND Transjugular intrahepatic portosystemic shunt(TIPS)is contraindicated for patients with cavernous transformation of the portal vein(CTPV)due to high surgery-related mortality risk.However,surgically assisted TIPS(SATIPS)can significantly reduce the risk.AIM To evaluate the clinical efficacy of SATIPS,this study was conducted.METHODS One hundred and seven patients with CTPV and esophagogastric variceal bleeding were recruited from January 2023 to December 2024.The patients were recruited from three different hospitals.Overall,54 patients received SATIPS treatment(SATIPS group),while 53 patients did not receive SATIPS and underwent prophylactic endoscopic sclerosing ligation(control group).Subsequently,survival rates,incidence rates of gastrointestinal bleeding,incidence of hepatic encephalopathy rate,and the incidence of liver failure after treatment in both groups at 3 and 6 months were observed.RESULTS The survival rates for the SATIPS and control groups were 94.4%and 92.5%at 3 months(P value=0.72)and 94.4%and 73.6%at 6 months(P value=0.0051)respectively.The incidence of liver failure was 3.7%and 9.4%at 3 months(P value=0.26)and 3.7%and18.9%at 6 months(P value=0.016);the incidence of gastrointestinal bleeding was 5.6%and 37.7%at 3 months(P value<0.001)and 9.3%and 47.2%(P value<0.001)at 6 months;and the incidence of hepatic encephalopathy was 3.7%and 17.0%at 3 months(P value=0.026)and 7.4%and 26.4%at 6 months(P value=0.026)respectively.CONCLUSION For patients with CTPV,there were no optimal treatment.Regarding long-term efficacy,SATIPS can significantly reduce the rate of rebleeding,hepatic encephalopathy and liver failure,and is associated with better survival.
文摘Objective:The following article explores our evolving understandings of the role of regenerative technology as an effective penile rehabilitation tool in men with erectile dysfunction(ED)in the setting of prostate cancer(PCa)treatment and PCa survivorship.Methods:This narrative clinical review paper summarizes what is currently known about various modalities of regenerative therapy in restoring spontaneous erectile function(EF)in men following PCa treatment with an emphasis on penile rehabilitation strategies.Results:Conventional medical therapy often does not reverse underlying endothelial dysfunction or promote neuro-vasculogenesis to preserve penile health in men with ED.Over the past decade,there has been considerable interest in the role of regenerative therapy to restore endothelial dysfunction and ED without future dependency on medical therapy.Regenerative therapy can be classified into cellular-based(immunomodulators,stem cells,and platelet-rich plasma),biomaterials(nerve graft transfer),and device-related technology(low-intensity shockwave).Although published literature shows early promise in the role of regenerative technology for ED,there is a paucity of high-quality clinical trials in the setting of penile rehabilitation and PCa survivorship to support their use as standard care and be adopted in clinical guidelines.
文摘BACKGROUND Chemotherapy-induced cardiotoxicity is a significant complication in cancer therapy,limiting treatment efficacy and worsening patient outcomes.Recent studies have implicated the gut microbiome and its key metabolites,such as shortchain fatty acids(SCFAs)and trimethylamine-N-oxide(TMAO),in mediating inflammation,oxidative stress,and cardiac damage.The gut-heart axis is increasingly recognized as a pivotal pathway linking microbiota dysregulation to chemotherapy-related cardiac dysfunction.AIM To systematically review existing evidence on the role of gut microbiome alterations in chemotherapy-induced cardiotoxicity and evaluate emerging microbiome-based therapeutic strategies aimed at mitigating cardiovascular risk in cancer patients.METHODS A systematic literature search was conducted in PubMed,Scopus,and Web of Science for studies published between January 2013 and December 2024.Studies were included if they examined chemotherapy-induced cardiotoxicity in relation to gut microbiota composition,microbial metabolites(e.g.,SCFAs,TMAO),or microbiome-targeted interventions.Selection followed Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines.Data extraction focused on microbiota alterations,mechanistic pathways,cardiac outcomes,and quality assessments using standardized risk-of-bias tools.RESULTS Eighteen studies met the inclusion criteria.Chemotherapy was consistently associated with gut dysbiosis characterized by reduced SCFA-producing bacteria and increased TMAO-producing strains.This imbalance contributed to gut barrier disruption,systemic inflammation,and oxidative stress,all of which promote myocardial damage.SCFA depletion weakened anti-inflammatory responses,while elevated TMAO levels exacerbated cardiac fibrosis and dysfunction.Preclinical studies showed promising cardioprotective effects from probiotics,prebiotics,dietary interventions,and fecal microbiota transplantation,though human data remain limited.CONCLUSION Gut microbiome dysregulation plays a crucial role in the development of chemotherapy-induced cardiotoxicity.Altered microbial composition and metabolite production trigger systemic inflammation and cardiac injury.Microbiome-targeted therapies represent a promising preventive and therapeutic approach in cardio-oncology,warranting further clinical validation through well-designed trials.
文摘Cardiovascular disease remains the leading global cause of mortality,projected to increase by 73.4%from 2025 to 2050 despite declining age-standardized rates.Contemporary interventions,such as percutaneous coronary intervention and statins,reduce major adverse cardiovascular events(MACE)by 25%-30%,yet a 20%five-year MACE risk persists in high-risk cohorts.These approaches,histor-ically focused on luminal stenosis,fail to address systemic atherogenesis drivers like endothelial dysfunction and inflammation.Specifically,dietary linoleic acid restriction(<5 g/day)reduces oxidized low-density lipoprotein by approximately 15%by limiting peroxidation-prone bisallylic bonds,mitigating arterial inflam-mation,a key atherogenic trigger.Enhanced external counterpulsation,through pulsatile shear stress,enhances nitric oxide-mediated coronary perfusion,alle-viating angina in approximately 70%of refractory cases unresponsive to revascu-larization.Nanoparticle-facilitated chelation targets atherosclerotic plaques with precision,reducing calcium content by up to 30%in preclinical models,offering a novel avenue for lesion reversal.These innovations collectively address residual risk by tackling root causes,oxidative stress,endothelial dysfunction,and plaque instability,potentially halving MACE rates with widespread adoption.Despite promising preliminary data,gaps remain in long-term safety and scalability.Robust clinical trials are needed to validate these approaches,which collectively aim to transform cardiovascular disease management by prioritizing prevention and vascular restoration,potentially reducing coronary events to a public health rarity.
文摘Regenerative medicine is a promising therapeutic avenue for previously incurable diseases.As the risk of chronic and degenerative diseases significantly increases with age,the elderly population represents a major cohort for stem cell-based therapies.However,the regenerative potential of stem cells significantly decreases with advanced age and deteriorating health status of the donor.Therefore,the efficacy of autologous stem cell therapy is significantly compromised in older patients.To overcome these limitations,alternative strategies have been used to restore the age-and disease-depleted function of stem cells.These methods aim to restore the therapeutic efficacy of aged stem cells for autologous use.This article explores the effect of donor age and health status on the regenerative potential of stem cells.It further highlights the limitations of stem cell-based therapy for autologous treatment in the elderly.A comprehensive insight into the potential strategies to address the“age”and“disease”compromised regenerative potential of autologous stem cells is also presented.The information provided here serves as a valuable resource for physicians and patients for optimization of stem cellbased autologous therapy for aged patients.
文摘Tau plays a crucial role in several neurodegenerative diseases,collectively referred to as tauopathies.Therefore,targeting potential pathological changes in tau could enable useful therapeutic interventions.However,tau is not an easy target because it dynamically interacts with microtubules and other cellular components,which presents a challenge for tau-targeted drugs.New cellular models could aid the development of mechanism-based tau-targeted therapies.
文摘Therapy discontinuation in inflammatory bowel disease,particularly involving immunomodulators,biologics,and small molecules,remains a controversial and evolving topic.This letter reflects on developments following the publication by Meštrovićet al,emphasizing the complex balance between risks of relapse,antidrug antibody formation,and potential complications of long-term immunosuppression.Recent evidence underscores high relapse rates following withdrawal-especially of anti-tumor necrosis factor agents-and highlights the lack of robust data for newer biologics.Updated guidelines from European Crohn’s and Colitis Organization,British Society of Gastroenterology,and American College of Gastroenterology all support cautious and individualized approaches,with strict criteria and close follow-up,particularly in Crohn’s disease.For ulcerative colitis,therapeutic cycling remains insufficiently addressed.We proposed a flowchart to support clinical decision-making and stress the importance of shared decisionmaking in the era of personalized medicine since,despite new drug classes and evolving strategies,the therapeutic ceiling in inflammatory bowel disease has yet to be fully overcome.
基金financially supported by National Natural Science Foundation of China (No.3240117,X.S)Sichuan Science and Technology Program (No.2024YFFK0345,Z.X)+3 种基金Natural Science Foundation of Chongqing (No.CSTB2024NSCQ-MSX0046,F.R)Startup Fund of Chongqing Normal University (No.23XLB036,F.R)National College Student Innovation and Entrepreneurship Program of Southwest University (No.202410635109,Y.Z)Guangdong High-level Hospital Construction Fund。
文摘The development of highly effective therapeutics is a priority in addressing the escalating threat that cancer poses to human health.Cyclodextrins(CDs) with exceptional biocompatibility and devisable structural hierarchy are emerging as versatile building blocks for engineered drug delivery systems,showing a promising prospect in cancer therapy.CDs enable precise synthesis of functionalized polymers with tailored architectures,endowing their excellent stability and large surface area to prolong drug circulation,enhance solubility,and increase targeting efficiency.Recently,CD-based nanotherapeutics has shown transformative potential in chemotherapy,phototherapy,immunotherapy,gene therapy and other codelivery systems of combination therapy.This review will introduce the types of CD-based nanotherapeutics,systematically summarize their design methods and anticancer application,and further discuss the prospects and challenges,providing a roadmap for advancing CD nanotechnology toward cancer therapeutics.
基金Supported by National Natural Science Foundation of China,No.82303672Zhejiang Provincial Health Commission and Zhejiang Provincial Administration of Traditional Chinese Medicine through the Targeted Project for Medical and Health Research,No.2025ZL017and China Primary Health Care Foundation,No.ZLMY20240311001ZJ.
文摘BACKGROUND The liver represents a common site of distant metastasis in patients with esophageal cancer(EC).Conventional chemotherapy(CMT)presents limited efficacy for EC,and EC patients with liver metastases typically experience a poor prognosis,highlighting an urgent need to explore novel treatment approaches.This study evaluated the overall efficacy and safety of CMT vs CMT combined with immune checkpoint inhibitors(ICIs)in the treatment of EC patients with liver metastases.Furthermore,prognostic factors influencing outcomes in this patient population were identified.AIM To evaluate the efficacy and safety of first-line chemoimmunotherapy for EC patients with liver metastases and to analyze prognostic factors.METHODS This retrospective study included 126 EC patients with liver metastases at Zhejiang Cancer Hospital between 2014 and 2024.Patients receiving CMT were compared with those receiving CMT+ICI.Analyzed variables included clinicopathological features,treatment history,characteristics of metastasis,systemic and local treatments,overall survival(OS),and treatment-related adverse events(TRAEs).Prognostic factors were evaluated using univariate and multivariate Cox proportional-hazards regression models.Finally,efficacy outcomes and TRAE profiles were compared between the two groups.RESULTS A significant difference in median OS was identified between the two groups(10.8 months in the CMT group vs 20.8 months in the CMT+ICI group,P=0.004).The CMT+ICI group also demonstrated a significantly longer median progression-free survival of 11.7 months(P<0.001).Patients receiving combination therapy exhibited significantly improved systemic objective response rate and disease control rate.Multivariate analysis identified key factors significantly influencing OS in EC patients with liver metastases:Karnofsky Performance Status score≥70,receipt of local therapy for liver metastases,and the number of cycles of CMT and immunotherapy received.Furthermore,the incidence of TRAEs did not significantly differ between the CMT+ICI and CMT groups.CONCLUSION For EC patients with liver metastases,the combination of CMT and ICIs demonstrates significantly superior efficacy compared with CMT alone,while maintaining manageable TRAEs.
文摘Experimental therapies targeting immune and stromal cells,such as mast cells,cancer-associated fibroblasts,dendritic cells,and tumor endothelial cells,in the treatment of gastrointestinal solid tumors pose new and complex surgical and medico-legal challenges.These innovative treatments require that informed consent not be limited to simple acceptance of the medical procedure,but instead reflect a true relational and cognitive process grounded in understanding,free choice,and the ability to revoke consent at any time.In particular,it is essential that the patient understands the experimental nature of the therapy,its development stage,potential benefits and risks,as well as the implications for their health and personal dignity.In the case of stromal cell-based treatments,which may exert complex immunomodulatory effects or activate angiogenic pathways that are not yet fully understood,patients must be made fully aware that they are participating in a non-standardized therapy whose outcomes,whether beneficial or harmful,cannot yet be predicted with certainty.This requires particularly careful medical communication,using simple yet scientifically accurate explanations delivered in appropriate language,along with a final verification of the patient’s actual understanding.
基金financially supported by the Liaoning Revitalization Talents Program (No.XLYC2403107)the Excellent Youth Science Foundation of Liaoning Province (No.2024JH3/10200046)the Basic Scientific Research Project of Liaoning Provincial Department of Education (No.LJ212410163015)。
文摘Despite demonstrating significant anti-tumor potential as an artemisinin derivative,artesunate faces delivery efficiency challenges due to low water solubility and insufficient targeting specificity.To improve the delivery efficiency,we engineered three artesunate(ART) derivatives,AC_(15)-L(linear),AC_(15)-B(branched),and AC_(15)-C(cyclic) with distinct aliphatic chain architectures.Unexpectedly,we observed that AC_(15)-C exhibited superior cytotoxicity against 4T1 breast cancer cells,and had the highest binding affinity for Lon protease 1(LONP1)(-72.6 kcal/mol).Subsequently,disulfide bond-containing lipid-PEG(DSPESS-PEG2K) modified chain architecture-engineered ART derivatives nanoassemblies(NAs) were developed to mitigate solubility-related limitations while enhancing targeting precision.Molecular docking and experimental validation demonstrated that ART derivatives inhibited LONP1 through hydrophobic interactions while preserved Fe^(2+)-mediated Fenton-like reaction activity.In vitro and in vivo evaluations demonstrated that AC_(15)-C NAs outperformed free ART and other NAs,suppressing 4T1 tumor growth via dual action:LONP1-directed mitochondrial proteostasis collapse and reactive oxygen species(ROS) amplification through Fe^(2+)-ART interactions.This study elucidated a novel anti-tumor mechanism of ART through the rational design of derivatives with spatially configured aliphatic chains,and developed reductionresponsive NAs to provide an advanced delivery strategy.
文摘Mongolian medicine posits that disruptions to the natural balance of the three roots and seven elements within the human body may lead to ocular disorders,vision impairment,and ultimately myopia.China’s children and adolescents not only exhibit high myopia rates but also face increasingly prominent issues of younger onset and severe progression,which critically impact the nation’s future and require urgent attention.Myopia prevention constitutes a systematic project.Traditional Mongolian moxibustion therapy works by applying heat stimulation to specific acupoints to warm meridians,harmonize Qi-blood circulation,regulate elemental balance,thereby enhancing immunity for disease prevention.This holistic approach features non-invasive application with minimal side effects.However,current interventions in myopia management through this method still face challenges including inconsistent operational protocols and insufficiently systematic collaborative research.This paper reviews recent advancements in early intervention using Mongolian moxibustion therapy for myopia,providing insights to optimize myopia prevention strategies.
基金supported by the National Natural Science Foundation of China (No.22405062)the Guangdong Basic and Applied Basic Research Foundation (No.2021A1515110869)+2 种基金the Shenzhen Science and Technology Program (No.ZDSYS20210623091813040)Innovation Program of Zhanjiang (No.2020LHJH005)Funds for Ph.D.researchers of Guangdong Medical University in 2025 (No.4SG25007G)。
文摘Thermally activated delayed fluorescence(TADF) emitters show great potential in photodynamic therapy(PDT) and bioimaging,leveraging their structural adaptability,efficient reverse intersystem crossing(RISC),robust photosensitizing capability,and high photoluminescence quantum yields(PLQYs).Herein,we developed a new class of donor-acceptor-donor(D-A-D)-type TADF materials by connecting the highly twisted indolizine-benzophenone electron acceptors with a series of electron donors including phenoxazine,phenothiazine and 9,9-dimethyl-9,10-dihydroacridine.These materials exhibit enhanced TADF properties,aggregation-induced emission(AIE),alongside high reactive oxygen species(ROS) generation efficiency,effectively mitigating aggregation-caused quenching observed in traditional fluorophores.Among them,IDP-p-PXZ,incorporating the phenoxazine donor,stands out with the smallest singlet-triplet splitting energy(ΔE_(ST)) and the highest spin-orbit coupling matrix elements(SOCMEs).Upon encapsulation into 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-2000](DSPE-PEG2000) nanoparticles(NPs),IDP-p-PXZ demonstrates extended delayed fluorescence lifetimes in air,an exceptionally fast intersystem crossing(ISC) rate constant(k_(ISC)) of 3.4×10^(7)s^(-1),and a radiative rate constant(k_(r)) of 5.05×10^(6)s^(-1).These NPs exhibit superior biocompatibility,efficient cellular internalization,and potent ROS production,enabling effective simultaneous PDT and confocal fluorescence imaging in HeLa cells.
