International Conference on Intelligent Systems（ICIS2005，2005年国际智能系统大会）于2005年12月1-3日在马来西亚吉隆坡举行。此次会议由马来西亚高等教育部批准，马来西来国家石油公司Petronas主赞助，Universiti Teknologi Petr...International Conference on Intelligent Systems（ICIS2005，2005年国际智能系统大会）于2005年12月1-3日在马来西亚吉隆坡举行。此次会议由马来西亚高等教育部批准，马来西来国家石油公司Petronas主赞助，Universiti Teknologi Petronas主办。参加会议的有来自中国、美国、日本、英国、马来西亚、印度等30个国家的200余篇论文作者及相关领域的研究人员。马来西来高等教育部部长Y．B．Dato’Sri Dr Haji Shafie Hj．Mohd Salleh亲临开幕式并致欢迎辞。展开更多
创新是一个民族进步的灵魂,是国家兴旺发达的不竭动力。2017年创新研究国际会议（The International Conference on Innovation Studies,ICIS2017）将于2017年6月24—26日在清华大学经济管理学院召开。本会议由清华大学技术创新研究中...创新是一个民族进步的灵魂,是国家兴旺发达的不竭动力。2017年创新研究国际会议（The International Conference on Innovation Studies,ICIS2017）将于2017年6月24—26日在清华大学经济管理学院召开。本会议由清华大学技术创新研究中心主任陈劲教授发起,国际创新学研究领域的著名领军学者、＂领先用户＂概念提出者Eric von Hippel教授作为特约嘉宾,将主持＂开放式创新与用户创新分会＂（1天）。展开更多
Background:While the treatment of metastatic renal cell carcinoma(mRCC)is evolving due to immune checkpoint inhibitors(ICIs),optimal strategies for later lines of therapy have yet to be defined.The combination of lenv...Background:While the treatment of metastatic renal cell carcinoma(mRCC)is evolving due to immune checkpoint inhibitors(ICIs),optimal strategies for later lines of therapy have yet to be defined.The combination of lenvatinib and everolimus represents a viable option,and the present review aimed to summarize its activity,effectiveness,and safety.Methods:A systematic review of the literature was conducted using PubMed,targeting studies published between 2018 and 2025.Eligible studies included English-language prospective and retrospective trials reporting survival outcomes in mRCC patients treated with lenvatinib and everolimus after at least one ICI-containing regimen.Results:Nine studies met the inclusion criteria,encompassing a total of 441 patients.The lenvatinib and everolimus combination was primarily used in the third and subsequent lines of therapy.Median overall survival ranged from 7.5 to 24.5 months,while median progression-free survival was more consistent,between 6.1 and 6.7 months,except for one study reporting 12.9 months.Objective response rates varied widely(14.0%–55.7%).Adverse events of grade≥3 did not exceed the expected rate,with diarrhoea and proteinuria as the most reported events.Dose reductions and treatment discontinuations due to toxicity occurred but were generally lower than in prior pivotal trials.Conclusions:Real-world evidence suggests that lenvatinib and everolimus represent an effective and safe option after ICI failure in mRCC patients.Nevertheless,the lack of randomized phase III trials and the heterogeneity of existing studies highlight the need for more robust prospective research to guide post-ICI therapeutic strategies.展开更多
1.A visitor flings hot water into the freezing cold air at Axan UNESCO Global Geopark,Xing'an League,Inner Mongolia Autonomous Region,January 1,20262.Visitors clad in red floatation suits float on the icy cold Lak...1.A visitor flings hot water into the freezing cold air at Axan UNESCO Global Geopark,Xing'an League,Inner Mongolia Autonomous Region,January 1,20262.Visitors clad in red floatation suits float on the icy cold Lake Yuehai,Yuehai Wetland Park,Yinchuan,capital of Ningxia Hui Autonomous Region,January 1,2026.展开更多
目的:本研究目的旨在探讨抗PD-1/PD-L1 (程序性细胞死亡蛋白-1,Programmed cell death-1/程序性死亡配体-1,Programmed death-ligand 1)治疗后发生心血管毒性死亡的风险因素,并以此构建预测模型。方法:本研究为单中心回顾性研究,通过系...目的:本研究目的旨在探讨抗PD-1/PD-L1 (程序性细胞死亡蛋白-1,Programmed cell death-1/程序性死亡配体-1,Programmed death-ligand 1)治疗后发生心血管毒性死亡的风险因素,并以此构建预测模型。方法:本研究为单中心回顾性研究,通过系统性回顾方法筛选2018年10月至2023年10月在青岛大学附属医院接受抗PD-1/PD-L1免疫治疗后的2665例实体肿瘤患者的病例资料观察180天,其中发生心血管毒性的33例,根据是否发生抗PD-1/PD-L1治疗心血管毒性死亡为结局,以是否发生死亡分为死亡组和存活组。采用单因素Cox回归分析其风险因素并控制相关混杂因素后构建预测模型绘制列线图。最后,利用受试者工作特征曲线(Receiver Operating Characteristic, ROC)、决策曲线分析法(Decision Curve Analysis, DCA)、校准曲线(Calibration Curve, CC)进行内部评价和内部验证。结果:1) 淋巴细胞计数、单核细胞计数、血小板计数、合并糖尿病、免疫检查点抑制剂种类、彩超室壁运动异常在心血管毒性存活组和死亡组间的差异均有统计学意义(均p Purpose: This study aimed to investigate risk factors for death from cardiovascular toxicity following anti-PD-1/PD-L1 therapy and develop a predictive model. Methods: This study was a single-center retrospective study, which screened the case data of 2665 patients with solid tumors after receiving anti-PD-1/PD-L1 immunotherapy at the Affiliated Hospital of Qingdao University for 180 days of observation by a systematic retrospective method, 33 cases of cardiovascular toxicity, and the outcome was based on whether or not death from cardiovascular toxicity of anti-PD-1/PD-L1 therapy occurred as the outcome categorized into death and survival groups. A one-way Cox regression analysis was used to analyze the risk factors and control for relevant confounders, and a predictive model was constructed to draw a column-line graph. Finally, Receiver Operating Characteristic (ROC), Decision Curve Analysis (DCA), and Calibration Curve (CC) were used for internal evaluation and internal validation. Results: 1) Lymphocyte, Platelet, Diabetes, Types of immune checkpoint inhibitors, Echocardiographic ventricular wall motion abnormalities and monocyte differences between two groups: those with death from cardiovascular toxicity and those without were statistically significant (all p < 0.05). 2) Univariate Cox regression identified diabetes (HR = 6.03, 95% CI 1.67~21.77, p = 0.006), Types of immune checkpoint inhibitors (HR = 6.62, 95% CI 1.69~25.89, p = 0.007), Echocardiographic ventricular wall motion abnormalities (HR = 4.61, 95% CI 1.19~17.85, p = 0.027), monocyte HR = 0.02, 95% CI 0.00~0.49, p = 0.015) as significant predictors. 3) Multivariate analysis confirmed monocyte (HR = 0.02, 95% CI 0.00~0.77, p = 0.036) as an independent predictor. 4) A predictive model for the risk of death from cardiovascular toxicity was constructed by including 4 variables (p < 0.05) from univariate Cox regression in a nomogram, with an AUC of 0.88 and 95% CI of 0.75 to 1.00. Conclusion: 1) Diabetes, Types of immune checkpoint inhibitors, Echocardiographic ventricular wall motion abnormalities and monocyte were significant predictors of death from cardiovascular toxicity. 2) Monocyte was an independent protective factor, after adjusting for other covariates. 3) A predictive model for the risk of cardiovascular toxic death was constructed by incorporating 4 variables from univariate Cox regression into a nomogram, and this model had good precision, discrimination, accuracy, and clinical benefit effects.展开更多
Hepatocellular carcinoma(HCC)is a highly aggressive malignancy,largely driven by an immunosuppres-sive tumor microenvironment(TME)that facilitates tumor growth,immune escape,and resistance to therapy.Although immunoth...Hepatocellular carcinoma(HCC)is a highly aggressive malignancy,largely driven by an immunosuppres-sive tumor microenvironment(TME)that facilitates tumor growth,immune escape,and resistance to therapy.Although immunotherapy—particularly immune checkpoint inhibitors(ICIs)—has transformed the therapeutic landscape by restoring T cell-mediated anti-tumor responses,their clinical benefit as monotherapy remains suboptimal.This limitation is primarily attributed to immunosuppressive components within the TME,including tumor-associated macrophages,regulatory T cells(Tregs),and myeloid-derived suppressor cells(MDSCs).To address these challenges,combination strategies have been explored,such as dual checkpoint blockade targeting programmed cell death protein 1(PD-1),programmed death-ligand 1(PD-L1),and cytotoxic T-lymphocyte-associated antigen 4(CTLA-4),as well as synergistic use of ICIs with anti-angiogenic agents or TME-targeted interventions.These approaches have shown encouraging potential in enhancing immune efficacy.This review outlines the complex crosstalk between the TME and immunotherapeutic responses in HCC,emphasizing how combination regimens may overcome immune resistance.Furthermore,we discuss the remaining hurdles,including therapeutic resistance and immune-related adverse events,and propose future directions involving TME-associated biomarkers and individualized treatment strategies to improve patient outcomes.展开更多
Non-small cell lung cancer(NSCLC)accounts for the majority of lung cancer cases and remains the leading cause of cancer-related mortality worldwide.Firstly,this review explores the limitations of conventional therapie...Non-small cell lung cancer(NSCLC)accounts for the majority of lung cancer cases and remains the leading cause of cancer-related mortality worldwide.Firstly,this review explores the limitations of conventional therapies,chemotherapy,radiotherapy,and surgery,focusing on the development of drug resistance and significant toxicity that often hinder their efficacy.Thereafter,advancements in targeted therapies,such as immune checkpoint inhibitors(ICIs)and tyrosine kinase inhibitors(TKIs),are discussed,highlighting their impact on improving outcomes for patients with specific genetic mutations,including c-ros oncogene 1 receptor tyrosine kinase(ROS1),anaplastic lymphoma kinase(ALK),and epidermal growth factor receptor(EGFR).Additionally,the emergence of novel immunotherapies and phytochemicals is examined,emphasizing their potential to overcome therapeutic resistance,particularly in advanced-stage diseases.The review also delves into the role of next-generation sequencing(NGS)in enabling personalized treatment approaches and explores the clinical potential of innovative agents,such as bispecific T-cell engagers(BiTEs)and antibody-drug conjugates(ADCs).Finally,we address the socioeconomic barriers that limit the accessibility of these therapies in low-resource settings and propose future research directions aimed at improving the long-term efficacy and accessibility of these treatments.展开更多
Background:immune checkpoint inhibitors(ICIs)have revolutionized the treatment of metastatic urothelial carcinoma(mUC),significantly improving survival outcomes.However,a subset of patients do not respond to ICIs,prom...Background:immune checkpoint inhibitors(ICIs)have revolutionized the treatment of metastatic urothelial carcinoma(mUC),significantly improving survival outcomes.However,a subset of patients do not respond to ICIs,prompting research into potential predictive factors.Commonly prescribed medications such as corticosteroids,proton-pump inhibitors(PPIs),antibiotics(Abs),antihypertensives,and analgesics may influence ICI effectiveness.Methods:we conducted a literature search on PubMed to investigate the impact of concomitant medications on the outcomes of patients with mUC,treated with ICIs.We selected the most relevant studies and performed a narrative review.Results:corticosteroids,PPIs and Abs have been associated with reduced survival in ICI-treated patients,including those with mUC.In contrast,antihypertensive agents like renin-angiotensin system inhibitors and betablockers may enhance ICI efficacy,though evidence remains inconclusive.The impact of other medications,such as statins,metformin,and analgesics,on ICI outcomes is less clear,with some data suggesting a detrimental impact on immune response.Conclusions:this narrative review synthesizes current evidence on how concomitant medications affect outcomes in mUC patients treated with ICIs.展开更多
Thrombotic thrombocytopenic purpura(TTP)is a rare and life-threatening form of thrombotic microangiopathy,primarily caused by a deficiency of ADAMTS-13 activity.Immune-related adverse events(irAEs)are autoimmune toxic...Thrombotic thrombocytopenic purpura(TTP)is a rare and life-threatening form of thrombotic microangiopathy,primarily caused by a deficiency of ADAMTS-13 activity.Immune-related adverse events(irAEs)are autoimmune toxicities mediated by the use of immune checkpoint inhibitors(ICIs).Here,the study reports a case of thrombotic thrombocytopenic purpura that developed in a patient with renal cell carcinoma and vertebral metastasis following combined treatment with Toripalimab and Pazopanib.The patient received Toripalimab in combination with Pazopanib after undergoing radical nephrectomy for right renal cell carcinoma.Five days later,a generalized erythematous rash appeared,partly confluent,accompanied by congestion and swelling of both palpebral and bulbar conjunctiva.Based on the clinical presentation and laboratory results showing thrombocytopenia and hemolytic anemia,the diagnosis of TTP was established.The condition was considered an adverse effect associated with the combination therapy of Toripalimab and Pazopanib.Plasma exchange and high-dose intravenous immunoglobulin therapy were promptly initiated.The treatment regimen was subsequently modified to Axitinib combined with radiotherapy,leading to a gradual recovery of platelet counts.This report highlights the potential risk of TTP associated with combined ICI and TKI therapy,and underscores the importance of early recognition and timely management of this potentially fatal complication.展开更多
Immune checkpoint inhibitor(ICI)has limited efficacy in the treatment of immune“cold”tumors.Due to insufficient T cell infiltration and heterogeneous programmed death ligand 1(PD-L1)expression,the ORR is only 5%–8%...Immune checkpoint inhibitor(ICI)has limited efficacy in the treatment of immune“cold”tumors.Due to insufficient T cell infiltration and heterogeneous programmed death ligand 1(PD-L1)expression,the ORR is only 5%–8%compared with 30%–40%of“hot”tumors.This article reviews the synergistic mechanism,clinical efficacy and optimization strategy of oncolytic virus(OVs)combined with ICIs in the treatment of refractory malignant tumors.Systematic analysis of mechanistic interactions across tumor types and clinical trial data demonstrates that OVs transform the immunosuppressive microenvironment by inducing immunogenic cell death and activating innate immunity.Concurrently,ICIs enhance adaptive immunity by reversing T-cell exhaustion and expanding T-cell diversity.Clinical trials in melanoma,head and neck cancer and breast cancer showed superior efficacy.The Objective Response Rate(ORR)of combination therapy was 39%–62%,while the ORR of ICI monotherapy was 18%.Treatment heterogeneity is mainly attributed to virus-related factors,including targeting specificity and replication efficiency,tumor characteristics,such as antigen presenting ability and mutation load,and host immune status,including preexisting antiviral antibodies and microbiome composition.This combined approach represents a paradigm shift in cancer immunotherapy,which effectively transforms immune“cold”tumors into“hot”tumors through the continuous activation of innate and adaptive immune responses.In the future,it is expected to improve the therapeutic effect of treatment-resistant malignant tumors through the integration of immune regulatory molecules,accurate biomarkers to guide the treatment scheme and triple combination strategy by a new generation of engineering viruses.展开更多
全名:哥白尼期刊数据库(ICI World of Journal)、哥白尼精选期刊数据库(ICI Master List)所属国家及机构:波兰哥白尼国际数据机构(Index Copernicus International,简称ICI)收录形式及规模:创建于1999年,由波兰的Index Copernicus Inter...全名:哥白尼期刊数据库(ICI World of Journal)、哥白尼精选期刊数据库(ICI Master List)所属国家及机构:波兰哥白尼国际数据机构(Index Copernicus International,简称ICI)收录形式及规模:创建于1999年,由波兰的Index Copernicus International(ICI)组织运营。ICI World of Journals是全球第三大国际数据库。目前,数据库中注册的期刊超过4.5万种,每月使用人次超过7万,来自150个国家。期刊需先进入ICI World of Journals,方可申请ICI Master List的录入。展开更多
A new cyclic prefix(CP)-based nonoverlapping FBMC-QAM(CP-NO-FBMC-QAM)system with two prototype filters is proposed in this paper,which satisfies complex orthogonality conditions and good frequency energy confinement a...A new cyclic prefix(CP)-based nonoverlapping FBMC-QAM(CP-NO-FBMC-QAM)system with two prototype filters is proposed in this paper,which satisfies complex orthogonality conditions and good frequency energy confinement at the same time.We analyze its inter-carrier interference/inter-symbol interference(ICI/ISI)over multipath channels.Owing to the additional CP,the ISI of received symbols over multipath channels is eliminated in the proposed system,and the resulting improvement in the signal-to-interference ratio(SIR)performance is evaluated by theoretical analysis.Moreover,for the ICI caused by multipath propagation in received symbols,we develop a method that eliminates the ICI by frequency-domain channel estimation and equalization before the receiver filtering process.The proposed CP-NO-FBMC-QAM system and ICI cancellation method(ICICM)are validated by comparisons of implementation complexity,power spectral density(PSD),bit error rate(BER)and channel estimation performance with conventional CP-based orthogonal frequency division multiplexing(CP-OFDM)and FBMC-QAM systems.展开更多
文摘International Conference on Intelligent Systems（ICIS2005，2005年国际智能系统大会）于2005年12月1-3日在马来西亚吉隆坡举行。此次会议由马来西亚高等教育部批准，马来西来国家石油公司Petronas主赞助，Universiti Teknologi Petronas主办。参加会议的有来自中国、美国、日本、英国、马来西亚、印度等30个国家的200余篇论文作者及相关领域的研究人员。马来西来高等教育部部长Y．B．Dato’Sri Dr Haji Shafie Hj．Mohd Salleh亲临开幕式并致欢迎辞。
文摘创新是一个民族进步的灵魂,是国家兴旺发达的不竭动力。2017年创新研究国际会议（The International Conference on Innovation Studies,ICIS2017）将于2017年6月24—26日在清华大学经济管理学院召开。本会议由清华大学技术创新研究中心主任陈劲教授发起,国际创新学研究领域的著名领军学者、＂领先用户＂概念提出者Eric von Hippel教授作为特约嘉宾,将主持＂开放式创新与用户创新分会＂（1天）。
文摘Background:While the treatment of metastatic renal cell carcinoma(mRCC)is evolving due to immune checkpoint inhibitors(ICIs),optimal strategies for later lines of therapy have yet to be defined.The combination of lenvatinib and everolimus represents a viable option,and the present review aimed to summarize its activity,effectiveness,and safety.Methods:A systematic review of the literature was conducted using PubMed,targeting studies published between 2018 and 2025.Eligible studies included English-language prospective and retrospective trials reporting survival outcomes in mRCC patients treated with lenvatinib and everolimus after at least one ICI-containing regimen.Results:Nine studies met the inclusion criteria,encompassing a total of 441 patients.The lenvatinib and everolimus combination was primarily used in the third and subsequent lines of therapy.Median overall survival ranged from 7.5 to 24.5 months,while median progression-free survival was more consistent,between 6.1 and 6.7 months,except for one study reporting 12.9 months.Objective response rates varied widely(14.0%–55.7%).Adverse events of grade≥3 did not exceed the expected rate,with diarrhoea and proteinuria as the most reported events.Dose reductions and treatment discontinuations due to toxicity occurred but were generally lower than in prior pivotal trials.Conclusions:Real-world evidence suggests that lenvatinib and everolimus represent an effective and safe option after ICI failure in mRCC patients.Nevertheless,the lack of randomized phase III trials and the heterogeneity of existing studies highlight the need for more robust prospective research to guide post-ICI therapeutic strategies.
文摘1.A visitor flings hot water into the freezing cold air at Axan UNESCO Global Geopark,Xing'an League,Inner Mongolia Autonomous Region,January 1,20262.Visitors clad in red floatation suits float on the icy cold Lake Yuehai,Yuehai Wetland Park,Yinchuan,capital of Ningxia Hui Autonomous Region,January 1,2026.
文摘目的:本研究目的旨在探讨抗PD-1/PD-L1 (程序性细胞死亡蛋白-1,Programmed cell death-1/程序性死亡配体-1,Programmed death-ligand 1)治疗后发生心血管毒性死亡的风险因素,并以此构建预测模型。方法:本研究为单中心回顾性研究,通过系统性回顾方法筛选2018年10月至2023年10月在青岛大学附属医院接受抗PD-1/PD-L1免疫治疗后的2665例实体肿瘤患者的病例资料观察180天,其中发生心血管毒性的33例,根据是否发生抗PD-1/PD-L1治疗心血管毒性死亡为结局,以是否发生死亡分为死亡组和存活组。采用单因素Cox回归分析其风险因素并控制相关混杂因素后构建预测模型绘制列线图。最后,利用受试者工作特征曲线(Receiver Operating Characteristic, ROC)、决策曲线分析法(Decision Curve Analysis, DCA)、校准曲线(Calibration Curve, CC)进行内部评价和内部验证。结果:1) 淋巴细胞计数、单核细胞计数、血小板计数、合并糖尿病、免疫检查点抑制剂种类、彩超室壁运动异常在心血管毒性存活组和死亡组间的差异均有统计学意义(均p Purpose: This study aimed to investigate risk factors for death from cardiovascular toxicity following anti-PD-1/PD-L1 therapy and develop a predictive model. Methods: This study was a single-center retrospective study, which screened the case data of 2665 patients with solid tumors after receiving anti-PD-1/PD-L1 immunotherapy at the Affiliated Hospital of Qingdao University for 180 days of observation by a systematic retrospective method, 33 cases of cardiovascular toxicity, and the outcome was based on whether or not death from cardiovascular toxicity of anti-PD-1/PD-L1 therapy occurred as the outcome categorized into death and survival groups. A one-way Cox regression analysis was used to analyze the risk factors and control for relevant confounders, and a predictive model was constructed to draw a column-line graph. Finally, Receiver Operating Characteristic (ROC), Decision Curve Analysis (DCA), and Calibration Curve (CC) were used for internal evaluation and internal validation. Results: 1) Lymphocyte, Platelet, Diabetes, Types of immune checkpoint inhibitors, Echocardiographic ventricular wall motion abnormalities and monocyte differences between two groups: those with death from cardiovascular toxicity and those without were statistically significant (all p < 0.05). 2) Univariate Cox regression identified diabetes (HR = 6.03, 95% CI 1.67~21.77, p = 0.006), Types of immune checkpoint inhibitors (HR = 6.62, 95% CI 1.69~25.89, p = 0.007), Echocardiographic ventricular wall motion abnormalities (HR = 4.61, 95% CI 1.19~17.85, p = 0.027), monocyte HR = 0.02, 95% CI 0.00~0.49, p = 0.015) as significant predictors. 3) Multivariate analysis confirmed monocyte (HR = 0.02, 95% CI 0.00~0.77, p = 0.036) as an independent predictor. 4) A predictive model for the risk of death from cardiovascular toxicity was constructed by including 4 variables (p < 0.05) from univariate Cox regression in a nomogram, with an AUC of 0.88 and 95% CI of 0.75 to 1.00. Conclusion: 1) Diabetes, Types of immune checkpoint inhibitors, Echocardiographic ventricular wall motion abnormalities and monocyte were significant predictors of death from cardiovascular toxicity. 2) Monocyte was an independent protective factor, after adjusting for other covariates. 3) A predictive model for the risk of cardiovascular toxic death was constructed by incorporating 4 variables from univariate Cox regression into a nomogram, and this model had good precision, discrimination, accuracy, and clinical benefit effects.
基金supported by Guangdong Basic and Applied Basic Research Foundation(2024A1515012993)the Project of Hunan Provincial Health Commission(No.D202303078877).
文摘Hepatocellular carcinoma(HCC)is a highly aggressive malignancy,largely driven by an immunosuppres-sive tumor microenvironment(TME)that facilitates tumor growth,immune escape,and resistance to therapy.Although immunotherapy—particularly immune checkpoint inhibitors(ICIs)—has transformed the therapeutic landscape by restoring T cell-mediated anti-tumor responses,their clinical benefit as monotherapy remains suboptimal.This limitation is primarily attributed to immunosuppressive components within the TME,including tumor-associated macrophages,regulatory T cells(Tregs),and myeloid-derived suppressor cells(MDSCs).To address these challenges,combination strategies have been explored,such as dual checkpoint blockade targeting programmed cell death protein 1(PD-1),programmed death-ligand 1(PD-L1),and cytotoxic T-lymphocyte-associated antigen 4(CTLA-4),as well as synergistic use of ICIs with anti-angiogenic agents or TME-targeted interventions.These approaches have shown encouraging potential in enhancing immune efficacy.This review outlines the complex crosstalk between the TME and immunotherapeutic responses in HCC,emphasizing how combination regimens may overcome immune resistance.Furthermore,we discuss the remaining hurdles,including therapeutic resistance and immune-related adverse events,and propose future directions involving TME-associated biomarkers and individualized treatment strategies to improve patient outcomes.
文摘Non-small cell lung cancer(NSCLC)accounts for the majority of lung cancer cases and remains the leading cause of cancer-related mortality worldwide.Firstly,this review explores the limitations of conventional therapies,chemotherapy,radiotherapy,and surgery,focusing on the development of drug resistance and significant toxicity that often hinder their efficacy.Thereafter,advancements in targeted therapies,such as immune checkpoint inhibitors(ICIs)and tyrosine kinase inhibitors(TKIs),are discussed,highlighting their impact on improving outcomes for patients with specific genetic mutations,including c-ros oncogene 1 receptor tyrosine kinase(ROS1),anaplastic lymphoma kinase(ALK),and epidermal growth factor receptor(EGFR).Additionally,the emergence of novel immunotherapies and phytochemicals is examined,emphasizing their potential to overcome therapeutic resistance,particularly in advanced-stage diseases.The review also delves into the role of next-generation sequencing(NGS)in enabling personalized treatment approaches and explores the clinical potential of innovative agents,such as bispecific T-cell engagers(BiTEs)and antibody-drug conjugates(ADCs).Finally,we address the socioeconomic barriers that limit the accessibility of these therapies in low-resource settings and propose future research directions aimed at improving the long-term efficacy and accessibility of these treatments.
文摘Background:immune checkpoint inhibitors(ICIs)have revolutionized the treatment of metastatic urothelial carcinoma(mUC),significantly improving survival outcomes.However,a subset of patients do not respond to ICIs,prompting research into potential predictive factors.Commonly prescribed medications such as corticosteroids,proton-pump inhibitors(PPIs),antibiotics(Abs),antihypertensives,and analgesics may influence ICI effectiveness.Methods:we conducted a literature search on PubMed to investigate the impact of concomitant medications on the outcomes of patients with mUC,treated with ICIs.We selected the most relevant studies and performed a narrative review.Results:corticosteroids,PPIs and Abs have been associated with reduced survival in ICI-treated patients,including those with mUC.In contrast,antihypertensive agents like renin-angiotensin system inhibitors and betablockers may enhance ICI efficacy,though evidence remains inconclusive.The impact of other medications,such as statins,metformin,and analgesics,on ICI outcomes is less clear,with some data suggesting a detrimental impact on immune response.Conclusions:this narrative review synthesizes current evidence on how concomitant medications affect outcomes in mUC patients treated with ICIs.
基金Natural Science Foundation of Gansu Province(Project No.:24JRRA615)Outstanding Talent Recruitment Program and the Doctoral Start-up Fund of Gansu Provincial Central Hospital(Project No.:GMCCH2024-2-6)。
文摘Thrombotic thrombocytopenic purpura(TTP)is a rare and life-threatening form of thrombotic microangiopathy,primarily caused by a deficiency of ADAMTS-13 activity.Immune-related adverse events(irAEs)are autoimmune toxicities mediated by the use of immune checkpoint inhibitors(ICIs).Here,the study reports a case of thrombotic thrombocytopenic purpura that developed in a patient with renal cell carcinoma and vertebral metastasis following combined treatment with Toripalimab and Pazopanib.The patient received Toripalimab in combination with Pazopanib after undergoing radical nephrectomy for right renal cell carcinoma.Five days later,a generalized erythematous rash appeared,partly confluent,accompanied by congestion and swelling of both palpebral and bulbar conjunctiva.Based on the clinical presentation and laboratory results showing thrombocytopenia and hemolytic anemia,the diagnosis of TTP was established.The condition was considered an adverse effect associated with the combination therapy of Toripalimab and Pazopanib.Plasma exchange and high-dose intravenous immunoglobulin therapy were promptly initiated.The treatment regimen was subsequently modified to Axitinib combined with radiotherapy,leading to a gradual recovery of platelet counts.This report highlights the potential risk of TTP associated with combined ICI and TKI therapy,and underscores the importance of early recognition and timely management of this potentially fatal complication.
基金supported in part by grants from the National Natural Science Foundation ofChina(Nos.82260462,82460606,32360046)Yunnan Fundamental Research Kunming Medical University Joint Projects(Nos.202201AY0700001-144,202301AY070001-115)+2 种基金Yunnan Fundamental Research Projects(No.202201AT070269)Yunnan health training project of high level talents(Nos.D-2024007,H-2024023)Graduate Innovation Fund of Kunming Medical University(No.2025S100).
文摘Immune checkpoint inhibitor(ICI)has limited efficacy in the treatment of immune“cold”tumors.Due to insufficient T cell infiltration and heterogeneous programmed death ligand 1(PD-L1)expression,the ORR is only 5%–8%compared with 30%–40%of“hot”tumors.This article reviews the synergistic mechanism,clinical efficacy and optimization strategy of oncolytic virus(OVs)combined with ICIs in the treatment of refractory malignant tumors.Systematic analysis of mechanistic interactions across tumor types and clinical trial data demonstrates that OVs transform the immunosuppressive microenvironment by inducing immunogenic cell death and activating innate immunity.Concurrently,ICIs enhance adaptive immunity by reversing T-cell exhaustion and expanding T-cell diversity.Clinical trials in melanoma,head and neck cancer and breast cancer showed superior efficacy.The Objective Response Rate(ORR)of combination therapy was 39%–62%,while the ORR of ICI monotherapy was 18%.Treatment heterogeneity is mainly attributed to virus-related factors,including targeting specificity and replication efficiency,tumor characteristics,such as antigen presenting ability and mutation load,and host immune status,including preexisting antiviral antibodies and microbiome composition.This combined approach represents a paradigm shift in cancer immunotherapy,which effectively transforms immune“cold”tumors into“hot”tumors through the continuous activation of innate and adaptive immune responses.In the future,it is expected to improve the therapeutic effect of treatment-resistant malignant tumors through the integration of immune regulatory molecules,accurate biomarkers to guide the treatment scheme and triple combination strategy by a new generation of engineering viruses.
文摘全名:哥白尼期刊数据库(ICI World of Journal)、哥白尼精选期刊数据库(ICI Master List)所属国家及机构:波兰哥白尼国际数据机构(Index Copernicus International,简称ICI)收录形式及规模:创建于1999年,由波兰的Index Copernicus International(ICI)组织运营。ICI World of Journals是全球第三大国际数据库。目前,数据库中注册的期刊超过4.5万种,每月使用人次超过7万,来自150个国家。期刊需先进入ICI World of Journals,方可申请ICI Master List的录入。
文摘A new cyclic prefix(CP)-based nonoverlapping FBMC-QAM(CP-NO-FBMC-QAM)system with two prototype filters is proposed in this paper,which satisfies complex orthogonality conditions and good frequency energy confinement at the same time.We analyze its inter-carrier interference/inter-symbol interference(ICI/ISI)over multipath channels.Owing to the additional CP,the ISI of received symbols over multipath channels is eliminated in the proposed system,and the resulting improvement in the signal-to-interference ratio(SIR)performance is evaluated by theoretical analysis.Moreover,for the ICI caused by multipath propagation in received symbols,we develop a method that eliminates the ICI by frequency-domain channel estimation and equalization before the receiver filtering process.The proposed CP-NO-FBMC-QAM system and ICI cancellation method(ICICM)are validated by comparisons of implementation complexity,power spectral density(PSD),bit error rate(BER)and channel estimation performance with conventional CP-based orthogonal frequency division multiplexing(CP-OFDM)and FBMC-QAM systems.
