Adult T-cell lymphoblastic lymphoma(T-LBL)is a rare and aggressive subtype of non-Hodgkin’s lymphoma that differs from pediatric T-LBL and has a worse prognosis.Due to its rarity,little is known about the genetic and...Adult T-cell lymphoblastic lymphoma(T-LBL)is a rare and aggressive subtype of non-Hodgkin’s lymphoma that differs from pediatric T-LBL and has a worse prognosis.Due to its rarity,little is known about the genetic and molecular characteristics,optimal treatment modalities,and prognostic factors of adult T-LBL.Therefore,we summarized the existing studies to comprehensively discuss the above issues in this review.Genetic mutations of NOTCH1/FBXW7,PTEN,RAS,and KMT2D,together with abnormal activation of signaling pathways,such as the JAK-STAT signaling pathway were described.We also discussed the therapeutic modalities.Once diagnosed,adult T-LBL patients should receive intensive or pediatric acute lymphoblastic leukemia regimen and central nervous system prophylaxis as soon as possible,and cranial radiation-free protocols are appropriate.Mediastinal radiotherapy improves clinical outcomes,but adverse events are of concern.Hematopoietic stem cell transplantation may be considered for adult T-LBL patients with high-risk factors or those with relapsed/refractory disease.Besides,several novel prognostic models have been constructed,such as the 5-miRNAs-based classifier,11-gene-based classifier,and 4-CpG-based classifier,which have presented significant prognostic value in adult T-LBL.展开更多
The screening of colorectal cancer(CRC)is pivotal for both the prevention and treatment of this disease,significantly improving early-stage tumor detection rates.This advancement not only boosts survival rates and qua...The screening of colorectal cancer(CRC)is pivotal for both the prevention and treatment of this disease,significantly improving early-stage tumor detection rates.This advancement not only boosts survival rates and quality of life for patients but also reduces the costs associated with treatment.However,the adoption of CRC screening methods faces numerous challenges,including the technical limitations of both noninvasive and invasive methods in terms of sensitivity and specificity.Moreover,socioeconomic factors such as regional disparities,economic conditions,and varying levels of awareness affect screening uptake.The coronavirus disease 2019 pandemic further intensified these challenges,leading to reduced screening participation and increased waiting periods.Additionally,the growing prevalence of early-onset CRC necessitates innovative screening approaches.In response,research into new methodologies,including artificial intelligence-based systems,aims to improve the precision and accessibility of screening.Proactive measures by governments and health organizations to enhance CRC screening efforts are underway,including increased advocacy,improved service delivery,and international cooperation.The role of technological innovation and global health collaboration in advancing CRC screening is undeniable.Technologies such as artificial intelligence and gene sequencing are set to revolutionize CRC screening,making a significant impact on the fight against this disease.Given the rise in early-onset CRC,it is crucial for screening strategies to continually evolve,ensuring their effectiveness and applicability.展开更多
At the cellular level, reduced kidney perfusion in atherosclerotic renal arthery disease (ARVD), induces hypoxia, activation of the renin-angiotensin-aldosterone system (RAAS) and cytokine activation. Impaired blood f...At the cellular level, reduced kidney perfusion in atherosclerotic renal arthery disease (ARVD), induces hypoxia, activation of the renin-angiotensin-aldosterone system (RAAS) and cytokine activation. Impaired blood flow in the kidneys creates a microenvironment triggering significant cytokine production, contributing to vascular damage and endothelial disfunction. Interactions between cytokines and endothelial, glomerular, and tubular cells often result in increased vessel permeability, and fibrosis, and contribute to the development of chronic kidney disease (CKD). Molecules such as endothelins, prostaglandins, and nitric oxide play a crucial role at the molecular level. The imbalance between vasoconstrictor and vasodilator factors contributes to vascular dysfunction. Oxidative stress and inflammatory processes at the cellular level contribute to endothelial damage and structural changes in blood vessels. Mineralocorticoid receptor antagonists (MRAs) therapy in the context of ARVD holds promise in reducing fibrosis, promoting angiogenesis and enhancing overall outcomes in patients with this pathology. Recent data also indicates the antioxidative, anti-inflammatory, and antifibrotic effects of SGLT2 inhibitors. They reduce oxidative stress caused by hypoxic conditions and enhance renal perfusion, contributing to the preservation of cellular function. Studies employing Blood Oxygen Level-Dependent (BOLD) imaging have identified adaptations to reduced blood flow, volume, and glomerular filtration rate in post-stenotic kidneys that preserve oxygenation in the medulla and cortex during medical therapy. Data from the literature indicate that despite the partial recovery of renal hypoxia and restoration of blood flow after revascularization, inflammatory cytokines and injury biomarkers remain elevated, and the glomerular filtration rate (GFR) does not recover in ARVD. Restoration of vascular patency alone has failed to reverse tubulointerstitial damage and partially explains the limited clinical benefit of renal stenting. Considering these findings, BOLD MR imaging emerges as a technique capable of providing insights into the critical juncture of irreversibility in ARVD. However, further research is needed to monitor renal hypoxia following renal artery stenting and the inflammatory response over an extended period in conjunction with optimal therapy involving MRAs and SGLT2 agonists. The aim of research at the molecular level enables the identification of potential therapeutic modalities targeting specific molecular pathways, opening the door to innovative approaches in treating renovascular hypertension.展开更多
Dear Editor,Ischemic stroke,a well-known age-related disorder(Cai et al.,2022b),resulting from the occlusion of cerebral blood vessels and the ensuing neuronal damage,has emerged as a leading cause of mortality and di...Dear Editor,Ischemic stroke,a well-known age-related disorder(Cai et al.,2022b),resulting from the occlusion of cerebral blood vessels and the ensuing neuronal damage,has emerged as a leading cause of mortality and disability worldwide(Zhang and Chopp,2009).It represents a significant global health challenge.The pursuit of innovative treatment strategies for ischemic stroke has become an urgent scientific priority.Stem cell therapy has gained prominence as a promising therapeutic modality for attenuating ischemic brain injury and facilitating repair in affected regions(Zhu et al.,2023).Among these,mesenchymal stem cells(MSCs)have garnered particular attention for their potential in ischemic stroke therapy,attributed to their capacity to secrete therapeutic biomolecules that provide neuroprotection,stimulate angiogenesis,and modulate immune responses(Stonesifer et al.,2017).Despite their promise,a multitude of challenges impede the realization of MSCs'therapeutic potential.展开更多
Hypoxia is a hallmark of solid tumors,and it significantly impairs the overall anticancer efficacy,particularly photodynamic therapy(PDT).Herein,a catalase-like nanovesicle with near-infrared light-responsiveness,that...Hypoxia is a hallmark of solid tumors,and it significantly impairs the overall anticancer efficacy,particularly photodynamic therapy(PDT).Herein,a catalase-like nanovesicle with near-infrared light-responsiveness,that is,platinum/gold nanoshell encapsulated chlorin e6(Ce6)/resveratrol(Res)liposome(Pt@Au-Ce6/Res-Lip),was developed to surmount this intractable issue.The Pt@Au-Ce6/Res-Lip can decompose overexpressed H_(2)O_(2)in tumor microenvironment to produce vast amounts of O_(2)for further enhancement of the PDT.Under the 808 nm laser irradiation,the Au nanoshells induced hyperthermia at the lesion site to ablate tumor cells,simultaneously inducing the controlled release of photosensitizer Ce6 and chemotherapeutic agent Res.Moreover,stimulated by 660 nm laser,numerous reactive oxygen species were formed to induce apoptosis and necrosis of tumor cells.With the cascade of trimodal therapeutic modality options(chemotherapy,photothermal therapy,and PDT),the Pt@Au-Ce6/Res-Lip showed ultrahigh tumor inhabitation rate in in vitro and in vivo studies,signifying that the Pt@AuCe6/Res-Lip nanovesicle is a promising candidate for effective cancer therapy.展开更多
基金This work was supported by the Special Support Program of Sun Yat-sen University Cancer Center(PT19020401)the Science and Technology Planning Project of Guangzhou,China(202002030205)the Clinical Oncology Foundation of Chinese Society of Clinical Oncology(Y-XD2019-124).
文摘Adult T-cell lymphoblastic lymphoma(T-LBL)is a rare and aggressive subtype of non-Hodgkin’s lymphoma that differs from pediatric T-LBL and has a worse prognosis.Due to its rarity,little is known about the genetic and molecular characteristics,optimal treatment modalities,and prognostic factors of adult T-LBL.Therefore,we summarized the existing studies to comprehensively discuss the above issues in this review.Genetic mutations of NOTCH1/FBXW7,PTEN,RAS,and KMT2D,together with abnormal activation of signaling pathways,such as the JAK-STAT signaling pathway were described.We also discussed the therapeutic modalities.Once diagnosed,adult T-LBL patients should receive intensive or pediatric acute lymphoblastic leukemia regimen and central nervous system prophylaxis as soon as possible,and cranial radiation-free protocols are appropriate.Mediastinal radiotherapy improves clinical outcomes,but adverse events are of concern.Hematopoietic stem cell transplantation may be considered for adult T-LBL patients with high-risk factors or those with relapsed/refractory disease.Besides,several novel prognostic models have been constructed,such as the 5-miRNAs-based classifier,11-gene-based classifier,and 4-CpG-based classifier,which have presented significant prognostic value in adult T-LBL.
文摘The screening of colorectal cancer(CRC)is pivotal for both the prevention and treatment of this disease,significantly improving early-stage tumor detection rates.This advancement not only boosts survival rates and quality of life for patients but also reduces the costs associated with treatment.However,the adoption of CRC screening methods faces numerous challenges,including the technical limitations of both noninvasive and invasive methods in terms of sensitivity and specificity.Moreover,socioeconomic factors such as regional disparities,economic conditions,and varying levels of awareness affect screening uptake.The coronavirus disease 2019 pandemic further intensified these challenges,leading to reduced screening participation and increased waiting periods.Additionally,the growing prevalence of early-onset CRC necessitates innovative screening approaches.In response,research into new methodologies,including artificial intelligence-based systems,aims to improve the precision and accessibility of screening.Proactive measures by governments and health organizations to enhance CRC screening efforts are underway,including increased advocacy,improved service delivery,and international cooperation.The role of technological innovation and global health collaboration in advancing CRC screening is undeniable.Technologies such as artificial intelligence and gene sequencing are set to revolutionize CRC screening,making a significant impact on the fight against this disease.Given the rise in early-onset CRC,it is crucial for screening strategies to continually evolve,ensuring their effectiveness and applicability.
文摘At the cellular level, reduced kidney perfusion in atherosclerotic renal arthery disease (ARVD), induces hypoxia, activation of the renin-angiotensin-aldosterone system (RAAS) and cytokine activation. Impaired blood flow in the kidneys creates a microenvironment triggering significant cytokine production, contributing to vascular damage and endothelial disfunction. Interactions between cytokines and endothelial, glomerular, and tubular cells often result in increased vessel permeability, and fibrosis, and contribute to the development of chronic kidney disease (CKD). Molecules such as endothelins, prostaglandins, and nitric oxide play a crucial role at the molecular level. The imbalance between vasoconstrictor and vasodilator factors contributes to vascular dysfunction. Oxidative stress and inflammatory processes at the cellular level contribute to endothelial damage and structural changes in blood vessels. Mineralocorticoid receptor antagonists (MRAs) therapy in the context of ARVD holds promise in reducing fibrosis, promoting angiogenesis and enhancing overall outcomes in patients with this pathology. Recent data also indicates the antioxidative, anti-inflammatory, and antifibrotic effects of SGLT2 inhibitors. They reduce oxidative stress caused by hypoxic conditions and enhance renal perfusion, contributing to the preservation of cellular function. Studies employing Blood Oxygen Level-Dependent (BOLD) imaging have identified adaptations to reduced blood flow, volume, and glomerular filtration rate in post-stenotic kidneys that preserve oxygenation in the medulla and cortex during medical therapy. Data from the literature indicate that despite the partial recovery of renal hypoxia and restoration of blood flow after revascularization, inflammatory cytokines and injury biomarkers remain elevated, and the glomerular filtration rate (GFR) does not recover in ARVD. Restoration of vascular patency alone has failed to reverse tubulointerstitial damage and partially explains the limited clinical benefit of renal stenting. Considering these findings, BOLD MR imaging emerges as a technique capable of providing insights into the critical juncture of irreversibility in ARVD. However, further research is needed to monitor renal hypoxia following renal artery stenting and the inflammatory response over an extended period in conjunction with optimal therapy involving MRAs and SGLT2 agonists. The aim of research at the molecular level enables the identification of potential therapeutic modalities targeting specific molecular pathways, opening the door to innovative approaches in treating renovascular hypertension.
基金supported by the National Key R&D Program of China STI2030-Major Projects-2021ZD0202400the National Natural Science Foundation of China (Grant Nos. 82125011, 81921006, 92149301, 92168201, 82122024)+11 种基金the National Key Research and Development Program of China (2020YFA0804000, 2022YFA1103700, 2020YFA0112200, 2022YFA1103802, 2021YFF1201000, 2023YFC3605400)the National Natural Science Foundation of China (82330044, 32341001, 92049304, 92049116, 32121001, 82192863, 82361148131, 82071588, 82361148130, 8231101626, 82201727, 82488301)CAS Project for Young Scientists in Basic Research (YSBR-076, YSBR-012)the Program of the Beijing Natural Science Foundation (Z230011, Z240018, JQ24044)the Informatization Plan of Chinese Academy of Sciences (CAS-WX2022SDC-XK14)New Cornerstone Science Foundation through the XPLORER PRIZE (2021-1045)Beijing Municipal Public Welfare Development and Reform Pilot Project for Medical Research Institutes (JYY2023-13)CAS Youth Interdisciplinary Team,Key Laboratory of Alzheimer’s Disease of Zhejiang Province (ZJAD-2024001)Excellent Young Talents Program of Capital Medical University (12300927)the Project for Technology Development of Beijing-affiliated Medical Research Institutes (11000023T000002036310)Excellent Young Talents Training Program for the Construction of Beijing Municipal University Teacher Team (BPHR202203105)Beijing Hospitals Authority Youth Programme (QML20230806)
文摘Dear Editor,Ischemic stroke,a well-known age-related disorder(Cai et al.,2022b),resulting from the occlusion of cerebral blood vessels and the ensuing neuronal damage,has emerged as a leading cause of mortality and disability worldwide(Zhang and Chopp,2009).It represents a significant global health challenge.The pursuit of innovative treatment strategies for ischemic stroke has become an urgent scientific priority.Stem cell therapy has gained prominence as a promising therapeutic modality for attenuating ischemic brain injury and facilitating repair in affected regions(Zhu et al.,2023).Among these,mesenchymal stem cells(MSCs)have garnered particular attention for their potential in ischemic stroke therapy,attributed to their capacity to secrete therapeutic biomolecules that provide neuroprotection,stimulate angiogenesis,and modulate immune responses(Stonesifer et al.,2017).Despite their promise,a multitude of challenges impede the realization of MSCs'therapeutic potential.
基金the National Natural Science Foundation(21776238,21476190,and 31801198)Hebei province Natural fund key projects(B2019203479)。
文摘Hypoxia is a hallmark of solid tumors,and it significantly impairs the overall anticancer efficacy,particularly photodynamic therapy(PDT).Herein,a catalase-like nanovesicle with near-infrared light-responsiveness,that is,platinum/gold nanoshell encapsulated chlorin e6(Ce6)/resveratrol(Res)liposome(Pt@Au-Ce6/Res-Lip),was developed to surmount this intractable issue.The Pt@Au-Ce6/Res-Lip can decompose overexpressed H_(2)O_(2)in tumor microenvironment to produce vast amounts of O_(2)for further enhancement of the PDT.Under the 808 nm laser irradiation,the Au nanoshells induced hyperthermia at the lesion site to ablate tumor cells,simultaneously inducing the controlled release of photosensitizer Ce6 and chemotherapeutic agent Res.Moreover,stimulated by 660 nm laser,numerous reactive oxygen species were formed to induce apoptosis and necrosis of tumor cells.With the cascade of trimodal therapeutic modality options(chemotherapy,photothermal therapy,and PDT),the Pt@Au-Ce6/Res-Lip showed ultrahigh tumor inhabitation rate in in vitro and in vivo studies,signifying that the Pt@AuCe6/Res-Lip nanovesicle is a promising candidate for effective cancer therapy.
