Objective:To investigate the anti-tumor effects of an E1B55KD-deleted oncolytic adenovirus,H101,in combination with a humanized anti-PD-1(Programmed cell death protein 1)monoclonal antibody,Camrelizumab.Methods:Anti-t...Objective:To investigate the anti-tumor effects of an E1B55KD-deleted oncolytic adenovirus,H101,in combination with a humanized anti-PD-1(Programmed cell death protein 1)monoclonal antibody,Camrelizumab.Methods:Anti-tumor efficacy of intratumoral injection of H101 or/and intraperitoneal injection of Camrelizumab were evaluated in an immune system humanized NOD Prkdc^(scid) Il2rg^(-/-)mice subcutaneous(S.C.)tumor model,established with human glioblastoma of unknown origin cell line U87-MG,and human bladder cancer cell line T24 and YTS-1.The mechanism by which H101 induced anti-tumor immunity were also investigated.Results:Combining H101 with Camrelizumab demonstrated more potent anti-tumor effects than monotherapy in mouse S.C.tumor model.Increased tumor-infiltrating T cells were observed in the combined treatment group.H101 infection decreased the expression of CD47 in cancer cells,thereby promoting macrophages to phagocytose cancer cells.Following the H101-mediated activation of macrophages,increased levels of cytokines,including TNF,IL-12 and IFN-γwere observed.Moreover,when induced THP-1 cells were co-cultured with H101-treated cancer cells,expression of IFN-γwas increased in T cells.Elimination of IL-12 using an anti-IL-12 antibody abolished IFN-γproduction from T cells.In addition,infection with H101 increased PD-L1 expression in YTS-1 cells.These results suggested that H101 may act synergistically to enhance the therapeutic efficacy of PD-1 blockade in cancer via suppressing CD47 signaling,which may promote macrophages to phagocytose tumor cells and activate CD8^(+)T cells.Conclusion:The combination of H101 with PD-1 blockade exhibits potential as a novel strategy for the treatment of cancer.展开更多
Dysfunction of anti-tumor immune responses is crucial for cancer progression. Immune checkpoint blockade(ICB), which can potentiate T cell responses, is an effective strategy for the normalization of host anti-tumor i...Dysfunction of anti-tumor immune responses is crucial for cancer progression. Immune checkpoint blockade(ICB), which can potentiate T cell responses, is an effective strategy for the normalization of host anti-tumor immunity. In recent years, immune checkpoints, expressed on both tumor cells and immune cells, have been identified;some of them have exhibited potential druggability and have been approved by the US Food and Drug Administration(FDA) for clinical treatment. However, limited responses and immune-related adverse events(ir AEs) cannot be ignored. This review outlines the development and applications of ICBs, potential strategies for overcoming resistance, and future directions for ICB-based cancer immunotherapy.展开更多
In the past decade,immunotherapies targeting cytotoxic T-lymphocyte antigen-4(CTLA-4),programmed cell death 1(PD-1),and PD-1 ligand(PD-L1)have been approved for solid tumors.However,some patients demonstrate suboptima...In the past decade,immunotherapies targeting cytotoxic T-lymphocyte antigen-4(CTLA-4),programmed cell death 1(PD-1),and PD-1 ligand(PD-L1)have been approved for solid tumors.However,some patients demonstrate suboptimal clinical outcomes due to resistance.The tumor microenvironment(TME)significantly affects the efficiency of immunotherapy by mediating interactions between tumor and non-tumor cells,including dendritic cells,T cells,B cells,macrophages,neutrophils,NK cells,and myeloid-derived suppressor cells(MDSCs).These non-tumor cells often exhibit two phenotypes with altered functions,and tumor cells drives their transition towards tumor promotion through tumor-education.Tumor-educated cells(TECs)are cells influenced by tumor cells,which acquire immune-suppressive phenotypes and promote tumor progression through resistance to anticancer therapies.These cells undergo modifications in response to signals from the tumor,which can influence their roles in tumor progression.Their dynamic interactions with tumor cells contribute to the reshaping of the TME,facilitating cancer growth and immune modulation.This review summarizes research on TECs in TME,explores mechanisms related to tumor education,and discusses their role in tumor progression and immunotherapy resistance.Additionally,potential therapeutic approaches targeting these cells are also reviewed,which may complement current treatment strategies.展开更多
BACKGROUND Irreversible electroporation(IRE)is a novel local tumor ablation approach with the potential to activate the host’s immune system.However,this approach is insufficient to prevent cancer progression,and com...BACKGROUND Irreversible electroporation(IRE)is a novel local tumor ablation approach with the potential to activate the host’s immune system.However,this approach is insufficient to prevent cancer progression,and complementary approaches are required for effective immunotherapy.AIM To assess the immunomodulatory effects and mechanism of IRE combined antiprogrammed cell death protein 1(PD-1)treatment in subcutaneous pancreatic cancer models.METHODS C57BL-6 tumor-bearing mice were randomly divided into four groups:Control group;IRE group;anti-PD-1 group;and IRE+anti-PD-1 group.Tumor-infiltrating T,B,and natural killer cell levels and plasma concentrations of T helper type 1 cytokines(interleukin-2,interferon-γ,and tumor necrosis factor-α)were evaluated.Real-time PCR was used to determine the expression of CD8(marker of CD8+T cells)in tumor tissues of the mice of all groups at different points of time.The growth curves of tumors were drawn.RESULTS The results demonstrated that the IRE+anti-PD-1 group exhibited significantly higher percentages of T lymphocyte infiltration,including CD4+and CD8+T cells compared with the control group.Additionally,the IRE+anti-PD-1 group showed increased infiltration of natural killer and B cells,elevated cytokine levels,and higher CD8 mRNA expression.Tumor volume was significantly reduced in the IRE+anti-PD-1 group,indicating a more pronounced therapeutic effect.CONCLUSION The combination of IRE and anti-PD-1 therapy promotes CD8+T cell immunity responses,leading to a more effective reduction in tumor volume and improved therapeutic outcomes,which provides a new direction for ablation and immunotherapy of pancreatic cancer.展开更多
BACKGROUND Gastric cancer(GC)is one of the most common malignancies worldwide,and Helicobacter pylori(HP)infection is a well-established risk factor for its development.Programmed death-ligand 1(PD-L1)expression is a ...BACKGROUND Gastric cancer(GC)is one of the most common malignancies worldwide,and Helicobacter pylori(HP)infection is a well-established risk factor for its development.Programmed death-ligand 1(PD-L1)expression is a crucial biomarker for predicting the efficacy of immune checkpoint inhibitors in cancer treatment.While HP infection and PD-L1 expression in GC may be linked,the relationship between them remains unclear,in part because there have been conflicting results reported from various studies.AIM To perform a meta-analysis to assess the relationship between HP and PD-L1 expression in patients with GC.METHODS A systematic literature review was conducted using PubMed,Embase,Cochrane Library,and Web of Science databases.Observational studies that examined the association between HP infection and PD-L1 expression in patients with GC were included.Odds ratios and 95%confidence intervals were calculated to estimate the association.Heterogeneity was assessed using Cochrane’s Q test and I²statistic.A random-effects model was used due to significant heterogeneity across studies.RESULTS Fourteen studies involving a total of 3069 patients with GC were included.The pooled analysis showed a significant association between HP infection and increased PD-L1 expression in GC tissues(odd ratio=1.69,95%confidence interval:1.24-2.29,P<0.001,I^(2)=59%).Sensitivity analyses confirmed the robustness of these findings.Subgroup analyses did not show significant variation based on geographic region,sample size,or method of PD-L1 assessment.Publication bias was minimal,as shown by funnel plots and Egger’s regression test.CONCLUSION HP infection is associated with increased PD-L1 expression in GC,suggesting that HP status may influence the response to programmed cell death protein 1/PD-L1 blockade therapy.展开更多
BACKGROUND Since the advent of the 20th century,alongside the progression of medical science and technological advancements,immunotherapy has emerged as a pivotal thera-peutic approach for tumor patients subsequent to...BACKGROUND Since the advent of the 20th century,alongside the progression of medical science and technological advancements,immunotherapy has emerged as a pivotal thera-peutic approach for tumor patients subsequent to undergoing radiotherapy and chemotherapy.Arimab(camrelizumab),a flagship drug in the realm of immuno-therapy,functions as a monoclonal antibody specifically targeting the progra-mmed death protein 1(PD-1).This drug engages with the human PD-1 receptor,effectively inhibiting the PD-1/programmed death ligand 1 signaling pathway.This inhibition results in the restoration of T cell activity and the induction of an anti-tumour response.However,it is noteworthy that such interference could lead to immune-related adverse events resembling autoimmune reactions.The grow-ing availability and clinical use of immune checkpoint inhibitors have raised sig-nificant clinical concerns regarding their safety.Numerous instances of immune-related adverse reactions and the associated management strategies have been extensively reported.Timely identification and diagnosis,coupled with multidi-sciplinary consultation and the prompt administration of immunosuppressants,can effectively address severe immune-related adverse reactions.CASE SUMMARY Arimab(camrelizumab),a monoclonal antibody targeting programmed death protein 1(PD-1),disrupts the PD-1/programmed death ligand 1(PD-L1)inter-action,reactivating T cell function and triggering anti-tumor immunity.However,this disruption may trigger immune-mediated adverse events akin to autoim-mune disorders.Approximately 2.8%of such events manifest as immune-related dermatologic reactions,with 0.7%classified as grade 3,which are infrequently documented.Here,this study describes a case of grade 3 bullous dermatitis occur-ring 15 days after initiating camrelizumab therapy.The patient,a 67-year-old male with oesophageal squamous cell carcinoma,received camrelizumab plus paclitaxel alongside chemotherapy and radiotherapy in early 2022.Due to disease progression,maintenance monotherapy with camrelizumab(200 mg)commenced in June 2022.On the fourth cycle,15 days into treatment,the patient presented with an immune-checkpoint inhibitor-related rash,despite unremarkable test results.Dermatology and pharmacy consultations were conducted,leading to glucocorticoid therapy,topical interventions,and supportive care.Gastric mucosal protection,nutritional supplementation,and other adjunctive treatments were also provided.The patient's symptoms resolved within 15 days post-discharge,resulting in discontinuation of camrelizumab.Like other PD-1 inhibitors,camrelizumab is associated with immune-mediated dermatitis.Thus,optimal management of these events requires a multidisciplinary approach,vigilant monitoring,regular evalua-tions,prompt glucocorticoid administration,and specialized dermatologic care.CONCLUSION The increasing adoption of immune checkpoint inhibitors in clinical practice has prompted substantial concerns about their safety profile.A wide range of immune-related adverse events and corresponding management stra-tegies have been well-documented.Early recognition and accurate diagnosis,combined with interdisciplinary collaboration and swift initiation of immunosuppressive therapy,are essential in managing severe immune-related adverse reactions effectively.This report details the treatment trajectory and outcome of a case involving immune-related cutaneous adverse reactions,providing pertinent clinical insights for future cases.展开更多
There is growing evidence that interleukin(IL)-6 plays an important role in neurological and psychiatric disorders.This editorial comments on the study published in the recent issue of the World Journal of Psychiatry,...There is growing evidence that interleukin(IL)-6 plays an important role in neurological and psychiatric disorders.This editorial comments on the study published in the recent issue of the World Journal of Psychiatry,which employed Mendelian randomization to identify a causal relationship between IL-6 receptor blockade and decreased epilepsy incidence.The purpose of this editorial is to highlight the dual effects of IL-6 in epilepsy and its related neuropsychiatric comorbidities.IL-6 plays a critical role in the facilitation of epileptogenesis and maintenance of epileptic seizures and is implicated in neuroinflammatory proce-sses associated with epilepsy.Furthermore,IL-6 significantly influences mood regulation and cognitive dysfunction in patients with epilepsy,highlighting its involvement in neuropsychiatric comorbidities.In summary,IL-6 is not only a pivotal factor in the pathogenesis of epilepsy but also significantly contributes to the emergence of epilepsy-related neuropsychiatric complications.Future resear-ch should prioritize elucidating the specific mechanisms by which IL-6 operates across different subtypes,stages and neuropsychiatric comorbidities of epilepsy,with the aim of developing more precise and effective interventions.Furthermore,the potential of IL-6 as a biomarker for the early diagnosis and prognosis of epile-psy warrants further investigation.展开更多
BACKGROUND Bradycardia,renal failure,atrioventricular nodal blockade,shock,and hyper-kalemia(BRASH)syndrome is an acronym used to describe a constellation of BRASH.It is an underrecognized phenomenon that can be deadl...BACKGROUND Bradycardia,renal failure,atrioventricular nodal blockade,shock,and hyper-kalemia(BRASH)syndrome is an acronym used to describe a constellation of BRASH.It is an underrecognized phenomenon that can be deadly if not appro-priately managed in a timely manner.This case highlights the importance of rapid diagnosis and reviews a multitude of treatment options in a uniquely severe case of BRASH syndrome.CASE SUMMARY We present a case of a 54-year-old male on a beta-blocker and angiotensin-con-verting enzyme inhibitor who presented with one day history of nausea,vomi-ting,and shortness of breath.Upon presentation,he was bradycardic and hypotensive,requiring transcutaneous pacing.Initial electrocardiogram showed atrial fibrillation with ventricular rate in 30’s.He was found to have acute kidney injury,hyperkalemia,and metabolic acidosis.He was successfully treated with multiple potassium lowering agents,continuous renal replacement therapy,four pressors,mechanical ventilation,and transvenous pacing with complete recovery prior to discharge.CONCLUSION Increased awareness of BRASH syndrome may improve outcomes through timely diagnosis and aggressive intervention.展开更多
Integrating photodynamic therapy(PDT)with immunosuppression reversal represents a promising synergistic approach to boost cancer immunotherapy.However,the complicated components and cumbersome preparation procedures o...Integrating photodynamic therapy(PDT)with immunosuppression reversal represents a promising synergistic approach to boost cancer immunotherapy.However,the complicated components and cumbersome preparation procedures of the currently developed nano drug delivery systems heavily hinder their further clinical translation.Herein,a reactive oxygen species(ROS)/photo dual-responsive amphipathic prodrug(denoted as PPTN)was designed and synthesized by linking NLG919,an indoleamine-2,3-dioxygenase(IDO)inhibitor,with the photosensitizer protoporphyrin IX(PpIX)by a thioketal moiety,and further modifying with mPEG2k.PPTN could self-assemble into nanoscale unimolecular micelles in aqueous solution without additional excipients,increasing tumor accumulation while effectively addressing the pronounced hydrophobicity challenge of PpIX.Upon light exposure,PPTN generated ROS,not only directly damaging cancer cells,but also trigger the breakage of thioketal bond to accelerate simultaneous release of NLG919.Therefore,PPTN potentially act as a promising ROS/photo dual-responsive carrier-free prodrug delivery system for controllable drug release and specific tumor therapy.Moreover,PPTN induced simultaneous PDT-triggered immunogenic cell death(ICD)effect and specific IDO blockade to boost immune response,exhibiting potent suppression efficacy against primary and distant tumors.Overall,with the superiorities of easily controllable preparation procedures,synchronous drug delivery and ROS/photo dual-responsiveness,such a prodrug unimolecular micelle may represent a promising nanoplatform for photoactivated-immunotherapy.展开更多
BACKGROUND:BRASH syndrome(Bradycardia,Renal failure,AV nodal blockade,Shock,and Hyperkalemia)is a recently described clinical entity characterized by synergistic interaction between AV nodal blocking medications and h...BACKGROUND:BRASH syndrome(Bradycardia,Renal failure,AV nodal blockade,Shock,and Hyperkalemia)is a recently described clinical entity characterized by synergistic interaction between AV nodal blocking medications and hyperkalemia.Despite increasing recognition,its clinical characteristics,risk factors,and outcomes remain poorly defined.The rationale of this review is to provide clinicians an upto-date overview of the most commonly encountered risk factors,triggers,clinical pictures,usual lab values,complications and outcomes,via the systemic analysis of currently published cases.METHODS:A systematic review was conducted using MEDLINE,Web of Science,and Cochrane Library databases through December 2024.Case reports,case series,and conference abstracts involving adult patients with BRASH syndrome were included.Data extraction focused on demographics,clinical presentations,laboratory findings,management strategies,and outcomes.RESULTS:Analysis included 131 patients from 111 published cases.Mean age was(71±13)years,with female predominance(58.1%).Hypertension(77.0%),chronic kidney disease(48.4%),and diabetes mellitus(46.7%)were the most common comorbidities.Beta-blockers were the predominant medication(76.5%).Most common presenting symptoms were syncope(17.9%),generalized weakness(16.2%),and altered mental status(11.9%).Mean potassium level was 6.6 mEq/L,with more than half of cases presenting with non-severe hyperkalemia(<6.5 mEq/L).Management often required multimodal therapy,with 50.8% of patients requiring vasopressors and 31.6% requiring hemodialysis.CONCLUSION:This systematic review provides the most comprehensive analysis of BRASH syndrome to date,demonstrating that while potentially serious,outcomes are generally favorable with appropriate recognition and management.The syndrome can develop even with modest hyperkalemia,particularly in elderly patients with multiple comorbidities.Early recognition and systematic management addressing all components of the syndrome appear crucial for optimal outcomes.展开更多
Tumor blockade therapy inhibits tumor progression by cutting off essential supplies of nutrients,oxygen,and biomolecules from the surrounding microenvironments.Inspired by natural processes,tumor biomineralization has...Tumor blockade therapy inhibits tumor progression by cutting off essential supplies of nutrients,oxygen,and biomolecules from the surrounding microenvironments.Inspired by natural processes,tumor biomineralization has evolved due to its biocompatibility,self-reinforcing capability,and penetrationindependent mechanism.However,the selective induction of tumor biomineralization using synthetic tools presents a significant challenge.Herein,a metabolic glycoengineering-assistant tumor biomineralization strategy was developed.Specifically,the azido group(N_(3))was introduced onto the cytomembrane by incubating tumor cells with glycose analog Ac4ManNAz.In addition,a bisphosphonate-containing polymer,dibenzocyclooctyne-poly(ethylene glycol)-alendronate(DBCO-PEG-ALN,DBPA)was synthesized,which attached to the tumor cell surface via"click chemistry"reaction between DBCO and N_(3).Subsequently,the bisphosphonate group on the cell surface chelated with positively charged ions in the microenvironments,triggering a consecutive process of biomineralization.This physical barrier significantly reduced tumor cell viability and mobility in a calcium ion concentration-dependent manner,suggesting its potential as an effective anti-tumor strategy for in vivo applications.展开更多
Mitochondria provides adenosine triphosphate for multiple vital movements to ensure tumor cell proliferation.Compared to the broadly used method of inducing DNA replication arrest to kill cancer,inducing mitochondria ...Mitochondria provides adenosine triphosphate for multiple vital movements to ensure tumor cell proliferation.Compared to the broadly used method of inducing DNA replication arrest to kill cancer,inducing mitochondria damage to cause energy shortage is quite promising as it can inhibit tumor cell bioactivities,increase intracellular accumulation of toxic drugs,eventually sensitize chemotherapy and even reverse drug resistance.Breaking the balance of glutathione(GSH)and reactive oxygen species(ROS)contents have been proven efficient in destroying mitochondria respectively.Herein,apigenin,a GSH efflux reagent,and 2-deoxy-5-fluorouridine 5-monophosphate sodium salt(FdUMP)that could induce toxic ROS were co-delivered by constructed lipid nanoparticles,noted as Lip@AF.An immune-checkpoint inhibition reagent CD276 antibody was modified onto the surface of Lip@AF with high reaction specificity(noted asαCD276-Lip@AF)to enhance the recognition of immune cells to tumor.Results showed that the redox balancewas destroyed,leading to severe injury to mitochondria and cell membrane.Furthermore,synergistic DNA/RNA replication inhibition caused by inhibiting the function of thymidylate synthase were observed.Eventually,significantly enhanced cytotoxicity was achieved by combining multiple mechanisms including ferroptosis,apoptosis and pyroptosis.In vivo,strengthen tumor growth inhibitionwas achieved byαCD276-Lip@AF with high biosafety,providing new sights in enhancing chemotherapy sensitiveness and achieving high-performance chemo-immunotherapy.展开更多
Esophageal squamous cell carcinoma(ESCC)remains a daunting global health concern.It is marked by aggressive progression and poor survival.While immunotherapy has emerged as a promising treatment modality,both primary ...Esophageal squamous cell carcinoma(ESCC)remains a daunting global health concern.It is marked by aggressive progression and poor survival.While immunotherapy has emerged as a promising treatment modality,both primary and acquired resistance continue to limit its clinical impact,leaving many patients without durable benefits(e.g.,CheckMate-648,ESCORT-1st).This review explains resistance mechanisms and suggests new strategies to improve outcomes.These mechanisms include immunosuppressive cells(Treg cells,myeloid-derived suppressor cells),inhibitory cytokines,molecular alterations involving programmed death 1/programmed death-ligand 1 signaling,and impaired antigen presentation.We also highlight key clinical trials—for example,CheckMate-648 and ESCORT-1st—that reveal both the potential and pitfalls of current immune checkpoint blockade strategies,underscoring the need for robust predictive biomarkers.Moreover,we examine cutting-edge tactics to overcome resistance,including combination regimens,tumor microenvironment remodeling,and tailored treatment approaches rooted in the patient’s unique genomic and immunologic landscape.展开更多
Gastrointestinal(GI)cancers are prevalent globally,with leading incidence and mortality rates among malignant tumors.Despite notable advancements in surgical resection,radiotherapy,and chemotherapy,the overall surviva...Gastrointestinal(GI)cancers are prevalent globally,with leading incidence and mortality rates among malignant tumors.Despite notable advancements in surgical resection,radiotherapy,and chemotherapy,the overall survival rates remain low.Hence,it is imperative to explore alternative approaches that enhance patient outcomes.Cluster of differentiation 47(CD47),serving as an early diagnostic marker,is predominantly overexpressed in GI cancers and associated with poor prognosis.Targeting the CD47-signal regulatory protein alpha(SIRPa)signaling pathway may provide a novel strategy for GI cancers treatment.This study summarizes current knowledge of the structure and function of CD47 and SIRPa,their roles in signaling pathways,the prognostic significance of CD47,therapeutic strategies targeting the CD47-SIRPα signaling pathway in GI cancer,and highlights key issues for future investigations.展开更多
The circuit quantum electrodynamics(QED)system has brought us into an ultrastrong and deep coupling regime in the light-matter interaction community,in which the quantum effect has attracted significant interest.In th...The circuit quantum electrodynamics(QED)system has brought us into an ultrastrong and deep coupling regime in the light-matter interaction community,in which the quantum effect has attracted significant interest.In this study,we theoretically investigated the photon blockade phenomenon in a double-transmon system operating in an ultrastrong coupling regime.We considered the effect of the counter-rotating wave terms in the interaction Hamiltonian and derived the master equation in the eigenpresentation.We found that photon blockade occurred in only one of the eigenmodes,and the counter-rotating wave terms enhanced the blockade by reducing the minimum value of the second-order correlation function.This study will be beneficial for the design of single-photon devices in circuit QED systems,especially in the ultrastrong coupling regime.展开更多
The BRASH syndrome,an acronym for bradycardia,renal failure,atrioventricular(AV)nodal blockade,shock,and hyperkalemia,was first described as a distinct clinical entity in 2016 by Josh Farkas.[1]He proposed a vicious p...The BRASH syndrome,an acronym for bradycardia,renal failure,atrioventricular(AV)nodal blockade,shock,and hyperkalemia,was first described as a distinct clinical entity in 2016 by Josh Farkas.[1]He proposed a vicious pathophysiological cycle driven by the synergy between AV nodal blockade and hyperkalemia.展开更多
The vortex dynamics after the initial ring dark solitons in two-component ultracold Rydberg atomic systems have been investigated.The two parameters characterizing the Rydberg long-range interaction—namely,the Rydber...The vortex dynamics after the initial ring dark solitons in two-component ultracold Rydberg atomic systems have been investigated.The two parameters characterizing the Rydberg long-range interaction—namely,the Rydberg strength and the blockade radius—along with the initial depth,are identified as the main factors that affect the vortex dynamics.In the absence of Rydberg soft-core potential and spin-orbit coupling,the late vortex dipoles move along x-or y-axis first.However,this work demonstrates that,with certain Rydberg strength and blockade radius,the late vortex dipoles move towards the edge at an oblique angle to the coordinate axes,and it reveals that the Rydberg nonlocal nonlinear interaction shortens the lifetime of late vortices.When the intra-component and inter-component Rydberg strengths are different,the backgrounds of the two components gradually complement each other,and the lifetime of late vortices is significantly shortened.The presented results show that the Rydberg dressing breaks the rule that the initial average depth determines the number and paths of vortices.The motion features of vortex dipoles in the ultracold Rydberg atomic system have been ascertained,and their directions of movement can be predicted to some degree based on the rotation directions and initial positions of the vortices.展开更多
We present work on a cavity-driven QED system combining an asymmetrical Fabry–Perot cavity and N two-level atoms(TLAs)and show the convenience of simplifying from distinguishable atoms to undistinguishable bosons whe...We present work on a cavity-driven QED system combining an asymmetrical Fabry–Perot cavity and N two-level atoms(TLAs)and show the convenience of simplifying from distinguishable atoms to undistinguishable bosons when the atoms are prepared in the same initial state.Such simplification is valid even when the atoms are not prepared in the inphase condition,since any partial in-phase initial state will evolve into the ground state through a relaxation process.Thus,we get a reduced group of differential equations by introducing the Dicke states,and the under-zero Lyapunov exponents verify its stability.We also work out the collective unconventional photon blockade(UCPB)and get two kinds of giant nonreciprocal UCPBs(NUCPBs)in the weak-driving approximation.Results show that we can employ N noninteracting bosonic atoms to generate a collective UCPB instead of a monoatomic UCPB as the UCPB conditions do not vary with the number of atoms.Furthermore,the forward giant NUCPB only occurring for N larger than a certain number as well as the backward giant NUCPB are controllable by the cavity asymmetry and by the number of atoms.Our findings suggest a prospective approach to the generation of quantum nonreciprocity by N identical atoms.展开更多
We read with great interest the recent article by Xing et al,which describes the synergy between irreversible electroporation and anti-programmed death-1 therapy in a murine hepatocellular carcinoma model.The study of...We read with great interest the recent article by Xing et al,which describes the synergy between irreversible electroporation and anti-programmed death-1 therapy in a murine hepatocellular carcinoma model.The study offers valuable mechanistic insights into local ablation,enhancing the efficacy of immune checkpoint blockade.However,critical methodological limitations and an overstatement of mechanistic conclusions warrant cautious interpretation.We recommend clarifying experimental details,optimizing murine models,applying more robust statistical analyses,and tempering conclusions to reflect the correlative nature of the findings.Further work should investigate immune mechanisms,durability of response,and safety in clinically relevant models to maximize translational potential.These refinements will strengthen the study’s impact in advancing ablation-immunotherapy strategies in hepatocellular carcinoma.展开更多
BACKGROUND Irreversible electroporation(IRE)represents an innovative localized technique for tumor ablation,possessing the capacity to activate the immune response of the host.However,this method alone is inadequate t...BACKGROUND Irreversible electroporation(IRE)represents an innovative localized technique for tumor ablation,possessing the capacity to activate the immune response of the host.However,this method alone is inadequate to halt cancer progression,necessitating the integration of additional strategies to achieve effective immuno-therapy.AIM To investigate the effects and underlying mechanisms of antitumor immunity derived from the synergistic application of IRE and anti-programmed cell death protein 1(PD-1)therapy within a murine model of hepatocellular carcinoma.METHODS C57BL-6 mice with tumor growth were divided into four separate cohorts:Control group;IRE group;Anti-PD-1 group;And IRE+anti-PD-1 group.The infiltration levels of T,B,and natural killer cells within the tumors,as well as the plasma concentrations of T helper type 1 cytokines(interleukin-2,interferon-γ,and tumor necrosis factor-β),were evaluated.Real-time polymerase chain reaction was utilized to quantify the expression of cluster of differentiation(CD)8(a marker indicative of CD8+T cells)in the tumor specimens of the mice at various temporal intervals.Tumor growth trajectories were charted.RESULTS The results indicated that the IRE+anti-PD-1 group exhibited significantly heightened percentages of T lymphocyte infiltration,particularly CD4+and CD8+T cells,when compared to the control cohort.Additionally,this group displayed increased infiltration of natural killer and B cells,augmented cytokine levels,and elevated CD8 messenger RNA expression.A marked decrease in tumor volume was noted in the IRE+anti-PD-1 group,indicating enhanced therapeutic efficacy.CONCLUSION The combined application of IRE and checkpoint blockade elicits an antitumor immune response,leading to a more substantial reduction in tumor volume and improved therapeutic outcomes,thereby establishing a novel avenue for the ablation and immunotherapy of hepatocellular carcinoma.展开更多
基金supported by Techpool Bio-Pharma Co.,Ltd.(grant no.AKR-S005).
文摘Objective:To investigate the anti-tumor effects of an E1B55KD-deleted oncolytic adenovirus,H101,in combination with a humanized anti-PD-1(Programmed cell death protein 1)monoclonal antibody,Camrelizumab.Methods:Anti-tumor efficacy of intratumoral injection of H101 or/and intraperitoneal injection of Camrelizumab were evaluated in an immune system humanized NOD Prkdc^(scid) Il2rg^(-/-)mice subcutaneous(S.C.)tumor model,established with human glioblastoma of unknown origin cell line U87-MG,and human bladder cancer cell line T24 and YTS-1.The mechanism by which H101 induced anti-tumor immunity were also investigated.Results:Combining H101 with Camrelizumab demonstrated more potent anti-tumor effects than monotherapy in mouse S.C.tumor model.Increased tumor-infiltrating T cells were observed in the combined treatment group.H101 infection decreased the expression of CD47 in cancer cells,thereby promoting macrophages to phagocytose cancer cells.Following the H101-mediated activation of macrophages,increased levels of cytokines,including TNF,IL-12 and IFN-γwere observed.Moreover,when induced THP-1 cells were co-cultured with H101-treated cancer cells,expression of IFN-γwas increased in T cells.Elimination of IL-12 using an anti-IL-12 antibody abolished IFN-γproduction from T cells.In addition,infection with H101 increased PD-L1 expression in YTS-1 cells.These results suggested that H101 may act synergistically to enhance the therapeutic efficacy of PD-1 blockade in cancer via suppressing CD47 signaling,which may promote macrophages to phagocytose tumor cells and activate CD8^(+)T cells.Conclusion:The combination of H101 with PD-1 blockade exhibits potential as a novel strategy for the treatment of cancer.
基金supported by the National Key Research and Development Program of China(No.2022YFE0102100)the National Natural Science Foundation of China(Nos.U22A20307 and 81930041)。
文摘Dysfunction of anti-tumor immune responses is crucial for cancer progression. Immune checkpoint blockade(ICB), which can potentiate T cell responses, is an effective strategy for the normalization of host anti-tumor immunity. In recent years, immune checkpoints, expressed on both tumor cells and immune cells, have been identified;some of them have exhibited potential druggability and have been approved by the US Food and Drug Administration(FDA) for clinical treatment. However, limited responses and immune-related adverse events(ir AEs) cannot be ignored. This review outlines the development and applications of ICBs, potential strategies for overcoming resistance, and future directions for ICB-based cancer immunotherapy.
基金supported by the NIH/NCI grants(No.P01CA257907)the Educational Department of Hunan Province for Excellent Youth Scholars(No.23B0011)。
文摘In the past decade,immunotherapies targeting cytotoxic T-lymphocyte antigen-4(CTLA-4),programmed cell death 1(PD-1),and PD-1 ligand(PD-L1)have been approved for solid tumors.However,some patients demonstrate suboptimal clinical outcomes due to resistance.The tumor microenvironment(TME)significantly affects the efficiency of immunotherapy by mediating interactions between tumor and non-tumor cells,including dendritic cells,T cells,B cells,macrophages,neutrophils,NK cells,and myeloid-derived suppressor cells(MDSCs).These non-tumor cells often exhibit two phenotypes with altered functions,and tumor cells drives their transition towards tumor promotion through tumor-education.Tumor-educated cells(TECs)are cells influenced by tumor cells,which acquire immune-suppressive phenotypes and promote tumor progression through resistance to anticancer therapies.These cells undergo modifications in response to signals from the tumor,which can influence their roles in tumor progression.Their dynamic interactions with tumor cells contribute to the reshaping of the TME,facilitating cancer growth and immune modulation.This review summarizes research on TECs in TME,explores mechanisms related to tumor education,and discusses their role in tumor progression and immunotherapy resistance.Additionally,potential therapeutic approaches targeting these cells are also reviewed,which may complement current treatment strategies.
基金Science and Technology Program of Guangzhou,No.202102010077International Science Foundation of Guangzhou Fuda Cancer Hospital,No.Y2020-ZD-03.
文摘BACKGROUND Irreversible electroporation(IRE)is a novel local tumor ablation approach with the potential to activate the host’s immune system.However,this approach is insufficient to prevent cancer progression,and complementary approaches are required for effective immunotherapy.AIM To assess the immunomodulatory effects and mechanism of IRE combined antiprogrammed cell death protein 1(PD-1)treatment in subcutaneous pancreatic cancer models.METHODS C57BL-6 tumor-bearing mice were randomly divided into four groups:Control group;IRE group;anti-PD-1 group;and IRE+anti-PD-1 group.Tumor-infiltrating T,B,and natural killer cell levels and plasma concentrations of T helper type 1 cytokines(interleukin-2,interferon-γ,and tumor necrosis factor-α)were evaluated.Real-time PCR was used to determine the expression of CD8(marker of CD8+T cells)in tumor tissues of the mice of all groups at different points of time.The growth curves of tumors were drawn.RESULTS The results demonstrated that the IRE+anti-PD-1 group exhibited significantly higher percentages of T lymphocyte infiltration,including CD4+and CD8+T cells compared with the control group.Additionally,the IRE+anti-PD-1 group showed increased infiltration of natural killer and B cells,elevated cytokine levels,and higher CD8 mRNA expression.Tumor volume was significantly reduced in the IRE+anti-PD-1 group,indicating a more pronounced therapeutic effect.CONCLUSION The combination of IRE and anti-PD-1 therapy promotes CD8+T cell immunity responses,leading to a more effective reduction in tumor volume and improved therapeutic outcomes,which provides a new direction for ablation and immunotherapy of pancreatic cancer.
文摘BACKGROUND Gastric cancer(GC)is one of the most common malignancies worldwide,and Helicobacter pylori(HP)infection is a well-established risk factor for its development.Programmed death-ligand 1(PD-L1)expression is a crucial biomarker for predicting the efficacy of immune checkpoint inhibitors in cancer treatment.While HP infection and PD-L1 expression in GC may be linked,the relationship between them remains unclear,in part because there have been conflicting results reported from various studies.AIM To perform a meta-analysis to assess the relationship between HP and PD-L1 expression in patients with GC.METHODS A systematic literature review was conducted using PubMed,Embase,Cochrane Library,and Web of Science databases.Observational studies that examined the association between HP infection and PD-L1 expression in patients with GC were included.Odds ratios and 95%confidence intervals were calculated to estimate the association.Heterogeneity was assessed using Cochrane’s Q test and I²statistic.A random-effects model was used due to significant heterogeneity across studies.RESULTS Fourteen studies involving a total of 3069 patients with GC were included.The pooled analysis showed a significant association between HP infection and increased PD-L1 expression in GC tissues(odd ratio=1.69,95%confidence interval:1.24-2.29,P<0.001,I^(2)=59%).Sensitivity analyses confirmed the robustness of these findings.Subgroup analyses did not show significant variation based on geographic region,sample size,or method of PD-L1 assessment.Publication bias was minimal,as shown by funnel plots and Egger’s regression test.CONCLUSION HP infection is associated with increased PD-L1 expression in GC,suggesting that HP status may influence the response to programmed cell death protein 1/PD-L1 blockade therapy.
文摘BACKGROUND Since the advent of the 20th century,alongside the progression of medical science and technological advancements,immunotherapy has emerged as a pivotal thera-peutic approach for tumor patients subsequent to undergoing radiotherapy and chemotherapy.Arimab(camrelizumab),a flagship drug in the realm of immuno-therapy,functions as a monoclonal antibody specifically targeting the progra-mmed death protein 1(PD-1).This drug engages with the human PD-1 receptor,effectively inhibiting the PD-1/programmed death ligand 1 signaling pathway.This inhibition results in the restoration of T cell activity and the induction of an anti-tumour response.However,it is noteworthy that such interference could lead to immune-related adverse events resembling autoimmune reactions.The grow-ing availability and clinical use of immune checkpoint inhibitors have raised sig-nificant clinical concerns regarding their safety.Numerous instances of immune-related adverse reactions and the associated management strategies have been extensively reported.Timely identification and diagnosis,coupled with multidi-sciplinary consultation and the prompt administration of immunosuppressants,can effectively address severe immune-related adverse reactions.CASE SUMMARY Arimab(camrelizumab),a monoclonal antibody targeting programmed death protein 1(PD-1),disrupts the PD-1/programmed death ligand 1(PD-L1)inter-action,reactivating T cell function and triggering anti-tumor immunity.However,this disruption may trigger immune-mediated adverse events akin to autoim-mune disorders.Approximately 2.8%of such events manifest as immune-related dermatologic reactions,with 0.7%classified as grade 3,which are infrequently documented.Here,this study describes a case of grade 3 bullous dermatitis occur-ring 15 days after initiating camrelizumab therapy.The patient,a 67-year-old male with oesophageal squamous cell carcinoma,received camrelizumab plus paclitaxel alongside chemotherapy and radiotherapy in early 2022.Due to disease progression,maintenance monotherapy with camrelizumab(200 mg)commenced in June 2022.On the fourth cycle,15 days into treatment,the patient presented with an immune-checkpoint inhibitor-related rash,despite unremarkable test results.Dermatology and pharmacy consultations were conducted,leading to glucocorticoid therapy,topical interventions,and supportive care.Gastric mucosal protection,nutritional supplementation,and other adjunctive treatments were also provided.The patient's symptoms resolved within 15 days post-discharge,resulting in discontinuation of camrelizumab.Like other PD-1 inhibitors,camrelizumab is associated with immune-mediated dermatitis.Thus,optimal management of these events requires a multidisciplinary approach,vigilant monitoring,regular evalua-tions,prompt glucocorticoid administration,and specialized dermatologic care.CONCLUSION The increasing adoption of immune checkpoint inhibitors in clinical practice has prompted substantial concerns about their safety profile.A wide range of immune-related adverse events and corresponding management stra-tegies have been well-documented.Early recognition and accurate diagnosis,combined with interdisciplinary collaboration and swift initiation of immunosuppressive therapy,are essential in managing severe immune-related adverse reactions effectively.This report details the treatment trajectory and outcome of a case involving immune-related cutaneous adverse reactions,providing pertinent clinical insights for future cases.
文摘There is growing evidence that interleukin(IL)-6 plays an important role in neurological and psychiatric disorders.This editorial comments on the study published in the recent issue of the World Journal of Psychiatry,which employed Mendelian randomization to identify a causal relationship between IL-6 receptor blockade and decreased epilepsy incidence.The purpose of this editorial is to highlight the dual effects of IL-6 in epilepsy and its related neuropsychiatric comorbidities.IL-6 plays a critical role in the facilitation of epileptogenesis and maintenance of epileptic seizures and is implicated in neuroinflammatory proce-sses associated with epilepsy.Furthermore,IL-6 significantly influences mood regulation and cognitive dysfunction in patients with epilepsy,highlighting its involvement in neuropsychiatric comorbidities.In summary,IL-6 is not only a pivotal factor in the pathogenesis of epilepsy but also significantly contributes to the emergence of epilepsy-related neuropsychiatric complications.Future resear-ch should prioritize elucidating the specific mechanisms by which IL-6 operates across different subtypes,stages and neuropsychiatric comorbidities of epilepsy,with the aim of developing more precise and effective interventions.Furthermore,the potential of IL-6 as a biomarker for the early diagnosis and prognosis of epile-psy warrants further investigation.
文摘BACKGROUND Bradycardia,renal failure,atrioventricular nodal blockade,shock,and hyper-kalemia(BRASH)syndrome is an acronym used to describe a constellation of BRASH.It is an underrecognized phenomenon that can be deadly if not appro-priately managed in a timely manner.This case highlights the importance of rapid diagnosis and reviews a multitude of treatment options in a uniquely severe case of BRASH syndrome.CASE SUMMARY We present a case of a 54-year-old male on a beta-blocker and angiotensin-con-verting enzyme inhibitor who presented with one day history of nausea,vomi-ting,and shortness of breath.Upon presentation,he was bradycardic and hypotensive,requiring transcutaneous pacing.Initial electrocardiogram showed atrial fibrillation with ventricular rate in 30’s.He was found to have acute kidney injury,hyperkalemia,and metabolic acidosis.He was successfully treated with multiple potassium lowering agents,continuous renal replacement therapy,four pressors,mechanical ventilation,and transvenous pacing with complete recovery prior to discharge.CONCLUSION Increased awareness of BRASH syndrome may improve outcomes through timely diagnosis and aggressive intervention.
基金supported by the National Natural Science Foundation of China(82373811,82574333,82504683)Natural Science Foundation of Guangdong Province(2024A1515012132).
文摘Integrating photodynamic therapy(PDT)with immunosuppression reversal represents a promising synergistic approach to boost cancer immunotherapy.However,the complicated components and cumbersome preparation procedures of the currently developed nano drug delivery systems heavily hinder their further clinical translation.Herein,a reactive oxygen species(ROS)/photo dual-responsive amphipathic prodrug(denoted as PPTN)was designed and synthesized by linking NLG919,an indoleamine-2,3-dioxygenase(IDO)inhibitor,with the photosensitizer protoporphyrin IX(PpIX)by a thioketal moiety,and further modifying with mPEG2k.PPTN could self-assemble into nanoscale unimolecular micelles in aqueous solution without additional excipients,increasing tumor accumulation while effectively addressing the pronounced hydrophobicity challenge of PpIX.Upon light exposure,PPTN generated ROS,not only directly damaging cancer cells,but also trigger the breakage of thioketal bond to accelerate simultaneous release of NLG919.Therefore,PPTN potentially act as a promising ROS/photo dual-responsive carrier-free prodrug delivery system for controllable drug release and specific tumor therapy.Moreover,PPTN induced simultaneous PDT-triggered immunogenic cell death(ICD)effect and specific IDO blockade to boost immune response,exhibiting potent suppression efficacy against primary and distant tumors.Overall,with the superiorities of easily controllable preparation procedures,synchronous drug delivery and ROS/photo dual-responsiveness,such a prodrug unimolecular micelle may represent a promising nanoplatform for photoactivated-immunotherapy.
文摘BACKGROUND:BRASH syndrome(Bradycardia,Renal failure,AV nodal blockade,Shock,and Hyperkalemia)is a recently described clinical entity characterized by synergistic interaction between AV nodal blocking medications and hyperkalemia.Despite increasing recognition,its clinical characteristics,risk factors,and outcomes remain poorly defined.The rationale of this review is to provide clinicians an upto-date overview of the most commonly encountered risk factors,triggers,clinical pictures,usual lab values,complications and outcomes,via the systemic analysis of currently published cases.METHODS:A systematic review was conducted using MEDLINE,Web of Science,and Cochrane Library databases through December 2024.Case reports,case series,and conference abstracts involving adult patients with BRASH syndrome were included.Data extraction focused on demographics,clinical presentations,laboratory findings,management strategies,and outcomes.RESULTS:Analysis included 131 patients from 111 published cases.Mean age was(71±13)years,with female predominance(58.1%).Hypertension(77.0%),chronic kidney disease(48.4%),and diabetes mellitus(46.7%)were the most common comorbidities.Beta-blockers were the predominant medication(76.5%).Most common presenting symptoms were syncope(17.9%),generalized weakness(16.2%),and altered mental status(11.9%).Mean potassium level was 6.6 mEq/L,with more than half of cases presenting with non-severe hyperkalemia(<6.5 mEq/L).Management often required multimodal therapy,with 50.8% of patients requiring vasopressors and 31.6% requiring hemodialysis.CONCLUSION:This systematic review provides the most comprehensive analysis of BRASH syndrome to date,demonstrating that while potentially serious,outcomes are generally favorable with appropriate recognition and management.The syndrome can develop even with modest hyperkalemia,particularly in elderly patients with multiple comorbidities.Early recognition and systematic management addressing all components of the syndrome appear crucial for optimal outcomes.
基金supported by the National Natural Science Foundation of China(Nos.U23A20591 and 52273158)the Science and Technology Development Program of Jilin Province(Nos.20240101002JJ and 20210504001GH).
文摘Tumor blockade therapy inhibits tumor progression by cutting off essential supplies of nutrients,oxygen,and biomolecules from the surrounding microenvironments.Inspired by natural processes,tumor biomineralization has evolved due to its biocompatibility,self-reinforcing capability,and penetrationindependent mechanism.However,the selective induction of tumor biomineralization using synthetic tools presents a significant challenge.Herein,a metabolic glycoengineering-assistant tumor biomineralization strategy was developed.Specifically,the azido group(N_(3))was introduced onto the cytomembrane by incubating tumor cells with glycose analog Ac4ManNAz.In addition,a bisphosphonate-containing polymer,dibenzocyclooctyne-poly(ethylene glycol)-alendronate(DBCO-PEG-ALN,DBPA)was synthesized,which attached to the tumor cell surface via"click chemistry"reaction between DBCO and N_(3).Subsequently,the bisphosphonate group on the cell surface chelated with positively charged ions in the microenvironments,triggering a consecutive process of biomineralization.This physical barrier significantly reduced tumor cell viability and mobility in a calcium ion concentration-dependent manner,suggesting its potential as an effective anti-tumor strategy for in vivo applications.
基金financially supported by the National Natural Science Foundation of China(82173769)Tianjin Science Foundation for Distinguished Young Scholars(24JCJQJC00050)+2 种基金Applied Basic Research Multi-Investment Foundation of Tianjin(21JCYBJC01540)the National Natural Science Foundation of China(82300336)the Science&Technology Development Fund of Tianjin Education Commission for Higher Education(2019KJ178).
文摘Mitochondria provides adenosine triphosphate for multiple vital movements to ensure tumor cell proliferation.Compared to the broadly used method of inducing DNA replication arrest to kill cancer,inducing mitochondria damage to cause energy shortage is quite promising as it can inhibit tumor cell bioactivities,increase intracellular accumulation of toxic drugs,eventually sensitize chemotherapy and even reverse drug resistance.Breaking the balance of glutathione(GSH)and reactive oxygen species(ROS)contents have been proven efficient in destroying mitochondria respectively.Herein,apigenin,a GSH efflux reagent,and 2-deoxy-5-fluorouridine 5-monophosphate sodium salt(FdUMP)that could induce toxic ROS were co-delivered by constructed lipid nanoparticles,noted as Lip@AF.An immune-checkpoint inhibition reagent CD276 antibody was modified onto the surface of Lip@AF with high reaction specificity(noted asαCD276-Lip@AF)to enhance the recognition of immune cells to tumor.Results showed that the redox balancewas destroyed,leading to severe injury to mitochondria and cell membrane.Furthermore,synergistic DNA/RNA replication inhibition caused by inhibiting the function of thymidylate synthase were observed.Eventually,significantly enhanced cytotoxicity was achieved by combining multiple mechanisms including ferroptosis,apoptosis and pyroptosis.In vivo,strengthen tumor growth inhibitionwas achieved byαCD276-Lip@AF with high biosafety,providing new sights in enhancing chemotherapy sensitiveness and achieving high-performance chemo-immunotherapy.
文摘Esophageal squamous cell carcinoma(ESCC)remains a daunting global health concern.It is marked by aggressive progression and poor survival.While immunotherapy has emerged as a promising treatment modality,both primary and acquired resistance continue to limit its clinical impact,leaving many patients without durable benefits(e.g.,CheckMate-648,ESCORT-1st).This review explains resistance mechanisms and suggests new strategies to improve outcomes.These mechanisms include immunosuppressive cells(Treg cells,myeloid-derived suppressor cells),inhibitory cytokines,molecular alterations involving programmed death 1/programmed death-ligand 1 signaling,and impaired antigen presentation.We also highlight key clinical trials—for example,CheckMate-648 and ESCORT-1st—that reveal both the potential and pitfalls of current immune checkpoint blockade strategies,underscoring the need for robust predictive biomarkers.Moreover,we examine cutting-edge tactics to overcome resistance,including combination regimens,tumor microenvironment remodeling,and tailored treatment approaches rooted in the patient’s unique genomic and immunologic landscape.
基金supported by the Fundamental Research Funds for the Central Universities,China(Grant Nos.:2023CDJXY-009 and 2023CDJYGRH-YB07)the National Natural Science Foundation of China(Grant No.:82172888)the Natural Science Foundation Project of Chongqing Science and Technology Commission(Grant No.:cstc2020jcyj-msxmX0154).
文摘Gastrointestinal(GI)cancers are prevalent globally,with leading incidence and mortality rates among malignant tumors.Despite notable advancements in surgical resection,radiotherapy,and chemotherapy,the overall survival rates remain low.Hence,it is imperative to explore alternative approaches that enhance patient outcomes.Cluster of differentiation 47(CD47),serving as an early diagnostic marker,is predominantly overexpressed in GI cancers and associated with poor prognosis.Targeting the CD47-signal regulatory protein alpha(SIRPa)signaling pathway may provide a novel strategy for GI cancers treatment.This study summarizes current knowledge of the structure and function of CD47 and SIRPa,their roles in signaling pathways,the prognostic significance of CD47,therapeutic strategies targeting the CD47-SIRPα signaling pathway in GI cancer,and highlights key issues for future investigations.
基金supported by the National Science Foundation of China(Grant No.12105026)Climbing Plan of Changchun University(Grant No.ZKP202010)Educational Commission of Jilin Province of China(Grant No.JJKH20230663KJ)。
文摘The circuit quantum electrodynamics(QED)system has brought us into an ultrastrong and deep coupling regime in the light-matter interaction community,in which the quantum effect has attracted significant interest.In this study,we theoretically investigated the photon blockade phenomenon in a double-transmon system operating in an ultrastrong coupling regime.We considered the effect of the counter-rotating wave terms in the interaction Hamiltonian and derived the master equation in the eigenpresentation.We found that photon blockade occurred in only one of the eigenmodes,and the counter-rotating wave terms enhanced the blockade by reducing the minimum value of the second-order correlation function.This study will be beneficial for the design of single-photon devices in circuit QED systems,especially in the ultrastrong coupling regime.
文摘The BRASH syndrome,an acronym for bradycardia,renal failure,atrioventricular(AV)nodal blockade,shock,and hyperkalemia,was first described as a distinct clinical entity in 2016 by Josh Farkas.[1]He proposed a vicious pathophysiological cycle driven by the synergy between AV nodal blockade and hyperkalemia.
基金supported by the Natural Science Foundation of Hubei Province of China(Grant No.2025AFB370)。
文摘The vortex dynamics after the initial ring dark solitons in two-component ultracold Rydberg atomic systems have been investigated.The two parameters characterizing the Rydberg long-range interaction—namely,the Rydberg strength and the blockade radius—along with the initial depth,are identified as the main factors that affect the vortex dynamics.In the absence of Rydberg soft-core potential and spin-orbit coupling,the late vortex dipoles move along x-or y-axis first.However,this work demonstrates that,with certain Rydberg strength and blockade radius,the late vortex dipoles move towards the edge at an oblique angle to the coordinate axes,and it reveals that the Rydberg nonlocal nonlinear interaction shortens the lifetime of late vortices.When the intra-component and inter-component Rydberg strengths are different,the backgrounds of the two components gradually complement each other,and the lifetime of late vortices is significantly shortened.The presented results show that the Rydberg dressing breaks the rule that the initial average depth determines the number and paths of vortices.The motion features of vortex dipoles in the ultracold Rydberg atomic system have been ascertained,and their directions of movement can be predicted to some degree based on the rotation directions and initial positions of the vortices.
基金Project supported by the National Natural Science Foundation of China(Grant Nos.12164022 and 12174288)Natural Science Foundation of Jiangxi Province of China(Grant No.20232BAB201044)+1 种基金Scientific Research Foundation of the Education Department of Jiangxi Province of China(Grant No.GJJ211039)China Postdoctoral Science Foundation(Grant No.2023M732028)。
文摘We present work on a cavity-driven QED system combining an asymmetrical Fabry–Perot cavity and N two-level atoms(TLAs)and show the convenience of simplifying from distinguishable atoms to undistinguishable bosons when the atoms are prepared in the same initial state.Such simplification is valid even when the atoms are not prepared in the inphase condition,since any partial in-phase initial state will evolve into the ground state through a relaxation process.Thus,we get a reduced group of differential equations by introducing the Dicke states,and the under-zero Lyapunov exponents verify its stability.We also work out the collective unconventional photon blockade(UCPB)and get two kinds of giant nonreciprocal UCPBs(NUCPBs)in the weak-driving approximation.Results show that we can employ N noninteracting bosonic atoms to generate a collective UCPB instead of a monoatomic UCPB as the UCPB conditions do not vary with the number of atoms.Furthermore,the forward giant NUCPB only occurring for N larger than a certain number as well as the backward giant NUCPB are controllable by the cavity asymmetry and by the number of atoms.Our findings suggest a prospective approach to the generation of quantum nonreciprocity by N identical atoms.
文摘We read with great interest the recent article by Xing et al,which describes the synergy between irreversible electroporation and anti-programmed death-1 therapy in a murine hepatocellular carcinoma model.The study offers valuable mechanistic insights into local ablation,enhancing the efficacy of immune checkpoint blockade.However,critical methodological limitations and an overstatement of mechanistic conclusions warrant cautious interpretation.We recommend clarifying experimental details,optimizing murine models,applying more robust statistical analyses,and tempering conclusions to reflect the correlative nature of the findings.Further work should investigate immune mechanisms,durability of response,and safety in clinically relevant models to maximize translational potential.These refinements will strengthen the study’s impact in advancing ablation-immunotherapy strategies in hepatocellular carcinoma.
基金Supported by the Science and Technology Program of Guangzhou,No.202201020024.
文摘BACKGROUND Irreversible electroporation(IRE)represents an innovative localized technique for tumor ablation,possessing the capacity to activate the immune response of the host.However,this method alone is inadequate to halt cancer progression,necessitating the integration of additional strategies to achieve effective immuno-therapy.AIM To investigate the effects and underlying mechanisms of antitumor immunity derived from the synergistic application of IRE and anti-programmed cell death protein 1(PD-1)therapy within a murine model of hepatocellular carcinoma.METHODS C57BL-6 mice with tumor growth were divided into four separate cohorts:Control group;IRE group;Anti-PD-1 group;And IRE+anti-PD-1 group.The infiltration levels of T,B,and natural killer cells within the tumors,as well as the plasma concentrations of T helper type 1 cytokines(interleukin-2,interferon-γ,and tumor necrosis factor-β),were evaluated.Real-time polymerase chain reaction was utilized to quantify the expression of cluster of differentiation(CD)8(a marker indicative of CD8+T cells)in the tumor specimens of the mice at various temporal intervals.Tumor growth trajectories were charted.RESULTS The results indicated that the IRE+anti-PD-1 group exhibited significantly heightened percentages of T lymphocyte infiltration,particularly CD4+and CD8+T cells,when compared to the control cohort.Additionally,this group displayed increased infiltration of natural killer and B cells,augmented cytokine levels,and elevated CD8 messenger RNA expression.A marked decrease in tumor volume was noted in the IRE+anti-PD-1 group,indicating enhanced therapeutic efficacy.CONCLUSION The combined application of IRE and checkpoint blockade elicits an antitumor immune response,leading to a more substantial reduction in tumor volume and improved therapeutic outcomes,thereby establishing a novel avenue for the ablation and immunotherapy of hepatocellular carcinoma.
