Direct acting antivirals(DAAs)have revolutionized the treatment of hepatitis C virus(HCV)infection,achieving high rates(≥95%)of sustained virological response,with a good safety profile and high compliance rates.Cons...Direct acting antivirals(DAAs)have revolutionized the treatment of hepatitis C virus(HCV)infection,achieving high rates(≥95%)of sustained virological response,with a good safety profile and high compliance rates.Consequently,it had been expected that viral clearance will reduce morbidity and mortality rates,as well as the risk of hepatocellular carcinoma(HCC).However,since 2016,concerns have been raised over an unexpected high rate of HCC occurrence and recurrence after DAA therapy,which led to an avalanche of studies with contradictory results.We aimed to review the most recent and relevant articles regarding the risk of HCC after DAA treatment and identify the associated risk factors.展开更多
Chronic infections with the hepatitis B and C viruses have significant worldwide health and economic impacts.Previous treatments for hepatitis C such as interferon and ribavirin therapy were ineffective and poorly tol...Chronic infections with the hepatitis B and C viruses have significant worldwide health and economic impacts.Previous treatments for hepatitis C such as interferon and ribavirin therapy were ineffective and poorly tolerated by patients.The introduction of directly acting curative antiviral therapy for hepatitis C and the wider use of nucleos(t)ide analogues for suppression of chronic Hepatitis B infection have resulted in many positive developments.Decreasing the prevalence of hepatitis B and C have concurrently reduced transmission rates and hence,the number of new infections.Antiviral treatments have decreased the rates of liver decompensation and as a result,lowered hospitalisation and mortality rates for both chronic hepatitis B and C infection.The quality of life of chronically infected patients has also been improved significantly by modern treatment.Antiviral therapy has stopped the progression of liver disease to cirrhosis in certain patient cohorts and prevented ongoing hepatocellular damage in patients with existing cirrhosis.Longer term benefits of antiviral therapy include a reduced risk of developing hepatocellular carcinoma and decreased number of patients requiring liver transplantation.This review article assesses the literature and summarises the impact of modern antiviral therapy of chronic hepatitis B and C on clinical outcomes from liver disease.展开更多
Background:Gastric Cancer(GC)is the 5th most prevalent and 4th most deadly neoplasm globally.Immunotherapy has emerged as a promising treatment approach in GC,potentially improving positive clinical outcomes while add...Background:Gastric Cancer(GC)is the 5th most prevalent and 4th most deadly neoplasm globally.Immunotherapy has emerged as a promising treatment approach in GC,potentially improving positive clinical outcomes while addressing the limitations of conventional therapies.GC immunotherapy modalities consist of adoptive cell therapy(ACT),cancer vaccines,and immune checkpoint inhibitors(ICI).Objectives:This systematic review aims to provide an overview of the advances in immune-based therapeutic approaches in GC,highlighting the potential of this therapy as a strategy for GC treatment.Methods:Key studies investigating several immunotherapeutic agents and combination therapies were searched in PUBMED and included in this study.Specific cancer outcomes related to disease progression or survival were analyzed.Results:After screening 236 studies,the results revealed that immunotherapy,particularly the ICI pembrolizumab,demonstrated promising efficacy in the treatment of GC,as several studies reported improved OS,PFS,and objective response rate with the use of pembrolizumab alone or in combination with other treatment modalities.Conclusion:Safety analysis showed that immunotherapy was mostly well-tolerated,with manageable adverse events and relatively good safety profiles.Nonetheless,further research is required to understand the mechanisms of tumor resistance better and identify predictive biomarkers that can direct treatment optimization.展开更多
Tumor recurrence is one of the major life-threatening complications after liver transplantation for liver cancer.In addition to the common mechanisms underlying tumor recurrence,another unavoidable problem is that the...Tumor recurrence is one of the major life-threatening complications after liver transplantation for liver cancer.In addition to the common mechanisms underlying tumor recurrence,another unavoidable problem is that the immunosuppressive therapeutic regimen after transplantation could promote tumor recurrence and metastasis.Transplant oncology is an emerging field that addresses oncological challenges in transplantation.In this context,a comprehensive therapeutic management approach is required to balance the anti-tumor treatment and immunosuppressive status of recipients.Double-negative T cells(DNTs)are a cluster of heterogeneous cells mainly consisting of two subsets stratified by T cell receptor(TCR)type.Among them,TCRαβ^(+)DNTs are considered to induce immune suppression in immune-mediated diseases,while TCRγδ^(+)DNTs are widely recognized as tumor killers.As a composite cell therapy,healthy donor-derived DNTs can be propagated to therapeutic numbers in vitro and applied for the treatment of several malignancies without impairing normal tissues or being rejected by the host.In this work,we summarized the biological characteristics and functions of DNTs in oncology,immunology,and transplantation.Based on the multiple roles of DNTs,we propose that a new balance could be achieved in liver transplant oncology using them as an off-the-shelf adoptive cell therapy(ACT).展开更多
This study aimed to confirm the hierarchical factor structure and the criterion validity of the Brief Mental Flexibility Questionnaire(BMFQ)in the South African context.Three hundred and eighty-five employees from a p...This study aimed to confirm the hierarchical factor structure and the criterion validity of the Brief Mental Flexibility Questionnaire(BMFQ)in the South African context.Three hundred and eighty-five employees from a public institution in South Africa participated in the study.Confirmatory factor analysis affirmed the structural validity of the measure,comprising a general factor of mentalflexibility and six distinct processes consistent with acceptance and commitment therapy(ACT):cognitive,affective,perceptual,attentional,motivational,and behavioralflexibility.Multiple regression analysis revealed differential predictive weights of these dimensions for general mental health,with cognitiveflexibility as the primary predictor.Motivationalflexibility emerged as the strongest predictor of adaptive performance.The BMFQ offers practitioners the ability to measure an individual’s overall mentalflexibility score alongside specificflexibility dimensions,enabling targeted interventions,employee comparisons,and organisational trend analysis.展开更多
Insufficient infiltration of T cells severely compromises the antitumor efficacy of adoptive cell therapy(ACT)against solid tumors.Here,we present a facile immune cell surface engineering strategy aiming to substantia...Insufficient infiltration of T cells severely compromises the antitumor efficacy of adoptive cell therapy(ACT)against solid tumors.Here,we present a facile immune cell surface engineering strategy aiming to substantially enhance the anti-tumor efficacy of Th9-mediated ACT by rapidly identifying tumor-specific binding ligands and improving the infiltration of infused cells into solid tumors.Non-genetic decoration of Th9 cells with tumor-targeting peptide screened from phage display not only allowed precise targeted ACT against highly heterogeneous solid tumors but also substantially enhanced infiltration of CD8+T cells,which led to improved antitumor outcomes.Mechanistically,infusion of Th9 cells modified with tumor-specific binding ligands facilitated the enhanced distribution of tumor-killing cells and remodeled the immunosuppressive microenvironment of solid tumors via IL-9 mediated immunomodulation.Overall,we presented a simple,cost-effective,and cell-friendly strategy to enhance the efficacy of ACT against solid tumors with the potential to complement the current ACT.展开更多
文摘Direct acting antivirals(DAAs)have revolutionized the treatment of hepatitis C virus(HCV)infection,achieving high rates(≥95%)of sustained virological response,with a good safety profile and high compliance rates.Consequently,it had been expected that viral clearance will reduce morbidity and mortality rates,as well as the risk of hepatocellular carcinoma(HCC).However,since 2016,concerns have been raised over an unexpected high rate of HCC occurrence and recurrence after DAA therapy,which led to an avalanche of studies with contradictory results.We aimed to review the most recent and relevant articles regarding the risk of HCC after DAA treatment and identify the associated risk factors.
文摘Chronic infections with the hepatitis B and C viruses have significant worldwide health and economic impacts.Previous treatments for hepatitis C such as interferon and ribavirin therapy were ineffective and poorly tolerated by patients.The introduction of directly acting curative antiviral therapy for hepatitis C and the wider use of nucleos(t)ide analogues for suppression of chronic Hepatitis B infection have resulted in many positive developments.Decreasing the prevalence of hepatitis B and C have concurrently reduced transmission rates and hence,the number of new infections.Antiviral treatments have decreased the rates of liver decompensation and as a result,lowered hospitalisation and mortality rates for both chronic hepatitis B and C infection.The quality of life of chronically infected patients has also been improved significantly by modern treatment.Antiviral therapy has stopped the progression of liver disease to cirrhosis in certain patient cohorts and prevented ongoing hepatocellular damage in patients with existing cirrhosis.Longer term benefits of antiviral therapy include a reduced risk of developing hepatocellular carcinoma and decreased number of patients requiring liver transplantation.This review article assesses the literature and summarises the impact of modern antiviral therapy of chronic hepatitis B and C on clinical outcomes from liver disease.
文摘Background:Gastric Cancer(GC)is the 5th most prevalent and 4th most deadly neoplasm globally.Immunotherapy has emerged as a promising treatment approach in GC,potentially improving positive clinical outcomes while addressing the limitations of conventional therapies.GC immunotherapy modalities consist of adoptive cell therapy(ACT),cancer vaccines,and immune checkpoint inhibitors(ICI).Objectives:This systematic review aims to provide an overview of the advances in immune-based therapeutic approaches in GC,highlighting the potential of this therapy as a strategy for GC treatment.Methods:Key studies investigating several immunotherapeutic agents and combination therapies were searched in PUBMED and included in this study.Specific cancer outcomes related to disease progression or survival were analyzed.Results:After screening 236 studies,the results revealed that immunotherapy,particularly the ICI pembrolizumab,demonstrated promising efficacy in the treatment of GC,as several studies reported improved OS,PFS,and objective response rate with the use of pembrolizumab alone or in combination with other treatment modalities.Conclusion:Safety analysis showed that immunotherapy was mostly well-tolerated,with manageable adverse events and relatively good safety profiles.Nonetheless,further research is required to understand the mechanisms of tumor resistance better and identify predictive biomarkers that can direct treatment optimization.
基金supported by the Key Research&Development Plan of Zhejiang Province(Nos.2019C03050 and 2021C03118)the National Key Research and Development Program of China(No.2021YFA1100500)the National Natural Science Foundation of China(No.92159202)。
文摘Tumor recurrence is one of the major life-threatening complications after liver transplantation for liver cancer.In addition to the common mechanisms underlying tumor recurrence,another unavoidable problem is that the immunosuppressive therapeutic regimen after transplantation could promote tumor recurrence and metastasis.Transplant oncology is an emerging field that addresses oncological challenges in transplantation.In this context,a comprehensive therapeutic management approach is required to balance the anti-tumor treatment and immunosuppressive status of recipients.Double-negative T cells(DNTs)are a cluster of heterogeneous cells mainly consisting of two subsets stratified by T cell receptor(TCR)type.Among them,TCRαβ^(+)DNTs are considered to induce immune suppression in immune-mediated diseases,while TCRγδ^(+)DNTs are widely recognized as tumor killers.As a composite cell therapy,healthy donor-derived DNTs can be propagated to therapeutic numbers in vitro and applied for the treatment of several malignancies without impairing normal tissues or being rejected by the host.In this work,we summarized the biological characteristics and functions of DNTs in oncology,immunology,and transplantation.Based on the multiple roles of DNTs,we propose that a new balance could be achieved in liver transplant oncology using them as an off-the-shelf adoptive cell therapy(ACT).
文摘This study aimed to confirm the hierarchical factor structure and the criterion validity of the Brief Mental Flexibility Questionnaire(BMFQ)in the South African context.Three hundred and eighty-five employees from a public institution in South Africa participated in the study.Confirmatory factor analysis affirmed the structural validity of the measure,comprising a general factor of mentalflexibility and six distinct processes consistent with acceptance and commitment therapy(ACT):cognitive,affective,perceptual,attentional,motivational,and behavioralflexibility.Multiple regression analysis revealed differential predictive weights of these dimensions for general mental health,with cognitiveflexibility as the primary predictor.Motivationalflexibility emerged as the strongest predictor of adaptive performance.The BMFQ offers practitioners the ability to measure an individual’s overall mentalflexibility score alongside specificflexibility dimensions,enabling targeted interventions,employee comparisons,and organisational trend analysis.
基金This work was supported by National Natural Science Foundation of China(81872173,82072959,31870959,and 82102855)Zhejiang Province Natural Science Foundation(LY20H160018,LD21H160002,and LY19H160045).
文摘Insufficient infiltration of T cells severely compromises the antitumor efficacy of adoptive cell therapy(ACT)against solid tumors.Here,we present a facile immune cell surface engineering strategy aiming to substantially enhance the anti-tumor efficacy of Th9-mediated ACT by rapidly identifying tumor-specific binding ligands and improving the infiltration of infused cells into solid tumors.Non-genetic decoration of Th9 cells with tumor-targeting peptide screened from phage display not only allowed precise targeted ACT against highly heterogeneous solid tumors but also substantially enhanced infiltration of CD8+T cells,which led to improved antitumor outcomes.Mechanistically,infusion of Th9 cells modified with tumor-specific binding ligands facilitated the enhanced distribution of tumor-killing cells and remodeled the immunosuppressive microenvironment of solid tumors via IL-9 mediated immunomodulation.Overall,we presented a simple,cost-effective,and cell-friendly strategy to enhance the efficacy of ACT against solid tumors with the potential to complement the current ACT.
