An upconversion nanoparticle(NaErF_(4)∶Yb/Tm@NaLuF_(4)∶Yb@NaLuF_(4)∶Nd/Yb@NaLuF_(4),noted as UC)was designed,emitting strong red light by 808 nm laser.The mesoporous silica(mSiO_(2))shell co‑doped with chlorin e6(C...An upconversion nanoparticle(NaErF_(4)∶Yb/Tm@NaLuF_(4)∶Yb@NaLuF_(4)∶Nd/Yb@NaLuF_(4),noted as UC)was designed,emitting strong red light by 808 nm laser.The mesoporous silica(mSiO_(2))shell co‑doped with chlorin e6(Ce6)and triethoxy(1H,1H,2H,2H‑nonafluorohexyl)silane(TFS)was coated on the outer layer of UC,and then a layer of HKUST‑1 shell was coated.The obtained nanocomposite UC@Ce6/TFS@mSiO_(2)@HKUST‑1(noted as UCTSH)was used for the synergistic treatment of chemodynamic therapy(CDT)and photodynamic therapy(PDT).Interestingly,the nanostructures can specifically re lease Cu^(2+)in the acidic tumor microenvironment.Cu^(2+)reacts with excess hydrogen peroxide(H_(2)O_(2))in the tumor microenvironment to form cytotoxic hydroxyl radical.Secondly,Ce6,with the action of oxygen‑carrying TFS,selectively produces a large amount of singlet oxygen by 808 nm laser irradiation.UCTSH can enhance the anti‑tumor effects of PDT and CDT by increasing the production level of reactive oxygen species,without causing damage to normal cells.展开更多
Cancer continues to pose a formidable challenge in global health,with conventional treatments such as chemotherapy and radiotherapy often resulting in severe toxicities that significantly degrade patients’quality of ...Cancer continues to pose a formidable challenge in global health,with conventional treatments such as chemotherapy and radiotherapy often resulting in severe toxicities that significantly degrade patients’quality of life and restrict therapeutic outcomes.Addressing this pressing issue,this review presents a thorough and systematic analysis of innovative and emerging strategies designed to minimize the toxicity induced by treatment,while maintaining or even enhancing antitumor efficacy.The focus is on six promising therapeutic approaches:combination therapies utilizing natural bioactive products,molecularly targeted therapies,immunotherapies,nanotechnology-mediated drug delivery systems,adjunct traditional Chinese medicine interventions,and low-dose spatiotemporally concerted regimens.Each approach employs unique mechanisms—such as enhanced targeting precision,immune system activation,tumor microenvironment reprogramming,and multi-component synergistic effects—to mitigate damage to normal tissues and reduce systemic adverse reactions.Despite promising preclinical and clinical advancements,several challenges persist,including drug resistance,high economic costs,a lack of reliable predictive biomarkers,and complexities in clinical translation and regulatory approval.Looking ahead,the incorporation of artificial intelligence,multi-omics profiling,and novel biomimetic nanotechnologies offers unprecedented opportunities for developing highly personalized,low-toxicity treatment frameworks.This review highlights a fundamental shift in oncology towards precision medicine that balances efficacy with safety,demonstrating the transformative potential of these strategies in shaping the future of cancer therapy and enhancing patient care globally.展开更多
Cardiovascular disease remains the leading global cause of mortality,projected to increase by 73.4%from 2025 to 2050 despite declining age-standardized rates.Contemporary interventions,such as percutaneous coronary in...Cardiovascular disease remains the leading global cause of mortality,projected to increase by 73.4%from 2025 to 2050 despite declining age-standardized rates.Contemporary interventions,such as percutaneous coronary intervention and statins,reduce major adverse cardiovascular events(MACE)by 25%-30%,yet a 20%five-year MACE risk persists in high-risk cohorts.These approaches,histor-ically focused on luminal stenosis,fail to address systemic atherogenesis drivers like endothelial dysfunction and inflammation.Specifically,dietary linoleic acid restriction(<5 g/day)reduces oxidized low-density lipoprotein by approximately 15%by limiting peroxidation-prone bisallylic bonds,mitigating arterial inflam-mation,a key atherogenic trigger.Enhanced external counterpulsation,through pulsatile shear stress,enhances nitric oxide-mediated coronary perfusion,alle-viating angina in approximately 70%of refractory cases unresponsive to revascu-larization.Nanoparticle-facilitated chelation targets atherosclerotic plaques with precision,reducing calcium content by up to 30%in preclinical models,offering a novel avenue for lesion reversal.These innovations collectively address residual risk by tackling root causes,oxidative stress,endothelial dysfunction,and plaque instability,potentially halving MACE rates with widespread adoption.Despite promising preliminary data,gaps remain in long-term safety and scalability.Robust clinical trials are needed to validate these approaches,which collectively aim to transform cardiovascular disease management by prioritizing prevention and vascular restoration,potentially reducing coronary events to a public health rarity.展开更多
Tau plays a crucial role in several neurodegenerative diseases,collectively referred to as tauopathies.Therefore,targeting potential pathological changes in tau could enable useful therapeutic interventions.However,ta...Tau plays a crucial role in several neurodegenerative diseases,collectively referred to as tauopathies.Therefore,targeting potential pathological changes in tau could enable useful therapeutic interventions.However,tau is not an easy target because it dynamically interacts with microtubules and other cellular components,which presents a challenge for tau-targeted drugs.New cellular models could aid the development of mechanism-based tau-targeted therapies.展开更多
Traditional Chinese medicine has opened new pathways and provided fresh perspectives for the treatment of uremic pruritus(UP)through syndrome differentiation and treatment.This paper summarizes the clinical experience...Traditional Chinese medicine has opened new pathways and provided fresh perspectives for the treatment of uremic pruritus(UP)through syndrome differentiation and treatment.This paper summarizes the clinical experience of Professor Li Qi in treating this condition.Professor Li Qi points out that the fundamental pathogenesis of UP lies in yang deficiency of the spleen and kidney.On this basis,either external cold entering the interior or yang deficiency leading to cold congelation may result in malnutrition of the skin,thereby triggering pruritus.In clinical practice,slight sweating therapy is applied to release the exterior and expel pathogenic factors or to warm and resolve cold fluid retention,achieving satisfactory therapeutic outcomes.展开更多
Serbisütherapy(ST)is a distinctive external treatment modality within traditional Mongolian medicine(TMM),historically developed within a nomadic cultural framework.This study presents a comprehensive philologica...Serbisütherapy(ST)is a distinctive external treatment modality within traditional Mongolian medicine(TMM),historically developed within a nomadic cultural framework.This study presents a comprehensive philological and historical analysis of ST,tracing its evolution from early battlefield applications to contemporary clinical use.By critically examining classical Mongolian medical texts alongside modern case studies,we aim to systematize ST’s therapeutic methods,indications,and limitations,while exploring its mechanisms of action through both traditional theory and modern biomedical perspectives.ST has undergone significant transformation,shifting from whole-body cavity immersion in the 13th century to targeted,organ-specific applications in modern practice.Its four primary methods–Covering,Mounted,Organ Placement,and Suction–demonstrate efficacy in treating cold-natured diseases,musculoskeletal disorders,gynecological conditions,and certain emergencies.ST embodies the core principles of TMM,particularly the balance of the“Three Roots”and the correction of cold-induced pathologies through heat.Despite challenges related to standardization,cultural translation,and regulatory acceptance,ST holds translational potential for integrative medicine.Future research should prioritize mechanistic validation,clinical standardization,and the development of biocompatible thermal technologies to bridge traditional practice with modern healthcare systems.展开更多
BACKGROUND Due to the dry and cold climate,the obvious temperature difference between day and night,and the low oxygen content of the air in the plateau area,people are prone to upper respiratory tract diseases,and of...BACKGROUND Due to the dry and cold climate,the obvious temperature difference between day and night,and the low oxygen content of the air in the plateau area,people are prone to upper respiratory tract diseases,and often the condition is prolonged,and the patients are prone to anxiety and uneasiness,which may be related to the harshness of the plateau environment,somatic discomfort due to the lack of oxygen,anxiety about the disease,and other factors.AIM To investigate the effects of cognitive behavioral therapy(CBT)on anxiety,sleep disorders,and hypoxia tolerance in patients with high-altitude respiratory diseases.METHODS A total of 2337 patients with high-altitude-related respiratory diseases treated at our hospital between November 2023 and January 2024 were selected as the study subjects.The subjects’pre-high-altitude residential altitude was approximately 1700 meters.They were divided into two groups.Both groups were given symptomatic treatment,and the control group implemented conventional nursing intervention,while the research group simultaneously conducted CBT intervention;assessed the degree of health knowledge of the two groups,and applied the Hamilton Anxiety Scale and the Pittsburgh Sleep Quality Index to assess the anxiety and sleep quality of the patients before and after the intervention,respectively.It also observed the length and efficiency of sleep,and detected the level of serum hypoxia inducible factor-1α,erythropoietin(EPO)and clinical intervention before and after intervention.EPO levels,and investigated satisfaction with the clinical intervention.RESULTS The rate of excellent health knowledge in the intervention group was 93.64%,which was higher than that in the control group(74.23%;P<0.05).Before the intervention,there was no significant difference in Hamilton Anxiety Scale and Pittsburgh Sleep Quality Index scores between the two groups(P>0.05),and after the intervention,the scores of the study group were significantly lower than those of the control group(P<0.05).There was no significant difference in sleep duration and sleep efficiency between the groups before the intervention(P>0.05),and after the intervention,the scores of the study group were significantly larger than those of the control group(P<0.05).There was no significant difference in serum hypoxia inducible factor-1αand EPO between the two groups before intervention(P>0.05),and both research groups were significantly lower than the control group after intervention(P<0.05).According to the questionnaire survey,the intervention satisfaction of the study group was 95.53%,which was higher than that of the control group(80.14%;P<0.05).CONCLUSION The CBT intervention in the treatment of patients with high-altitude-related respiratory diseases helps improve patients'health knowledge,relieve anxiety,improve sleep quality and hypoxia tolerance,and improve nursing satisfaction.展开更多
BACKGROUND Approximately 30%of patients with head and neck cancer experience adverse effects caused by anxiety and depression.Considering the high prevalence,implementing customized interventions to ease adverse emoti...BACKGROUND Approximately 30%of patients with head and neck cancer experience adverse effects caused by anxiety and depression.Considering the high prevalence,implementing customized interventions to ease adverse emotional states is imperative.AIM To evaluate the efficacy of cognitive behavioral therapy(CBT)-based psychological interventions in improving the psychological well-being and quality of life(QoL)of patients with laryngeal carcinoma.METHODS This study enrolled 120 patients admitted from February 2022 to February 2024.The control group,comprising 50 participants,received standard supportive psychological care,while the research group,consisting 70 participants,underwent CBT-based interventions.Several clinical outcomes were systematically assessed that included postoperative recovery metrics(duration of tracheostomy and nasogastric tube dependence and length of hospitalization),psychological status(Self-Rating Anxiety Scale and Self-Rating Depression Scale),nutritional markers(serum albumin and hemoglobin levels),sleep quality(Self-Rating Scale of Sleep and Athens Insomnia Scale),and QoL(Functional Assessment of Cancer Therapy-Head and Neck).RESULTS The results demonstrated that the research group experienced superior outcomes,with significantly reduced durations of tracheostomy and nasogastric tube dependence,as well as shorter hospital stays,compared with the control group.Additionally,the research group exhibited markedly lower post-intervention Self-Rating Anxiety Scale,Self-Rating Depression Scale,Self-Rating Scale of Sleep,and Athens Insomnia Scale scores,along with minimal but higher change in serum albumin and hemoglobin levels compared with the control group.All five domains of Functional Assessment of Cancer Therapy-Head and Neck showed notable improvements in the research group,exceeding those observed in the control group.CONCLUSION CBT-based psychological support positively affects the mental well-being and QoL of patients with laryngeal carcinoma,highlighting its potential for broader clinical application.展开更多
Background:Drama therapy as a discipline in clinical and public health areas dates back to movements in the Netherlands,Great Britain and the United States of America in the 1960s.Today,drama therapy comprises a huge ...Background:Drama therapy as a discipline in clinical and public health areas dates back to movements in the Netherlands,Great Britain and the United States of America in the 1960s.Today,drama therapy comprises a huge variety of methods and is applied in numerous medical domains such as psychiatry,pediatrics and neurogeriatrics.Nonetheless,historical and philosophical considerations suggest that at all times dramatic arts have encompassed curative potential and helped to promote mental health.Regarding this perspective,the present article aims to explore the spirit of drama therapy in ancient Chinese and Greek cultures.Methods:Involving cross-cultural psychiatry and medical anthropology,comparative research centred around salutary momentums inhering in drama and dramatic practices in Ancient China and Greece.The entire research process consisted of three phases:(i)screening of ancient Chinese and Greek dramatic rituals and arts to select phenomena and genres with pathological,therapeutic and mental health relevance;(ii)medical ontological processing,in particular from a psychopathological,psychiatric,psychotherapeutic and mental health scientific point of view,to explore and elucidate their curative and preventative features;(iii)transdisciplinary considerations about the evolution of drama therapy,as well as their diverse modes of artistic and medical reasoning.Results:The research process resulted in the identification of five(functional)roots of drama therapy,as well as public health benefits of dramatic arts:(i)dramatic rituals,stage-trance settings and spiritual immersion,(ii)mise-en-scène of divine spheres and alternative worlds,as well as scenic imagination and creative fusion of reality and fantasy,desire and satisfaction,(iii)anthropologic ontology,search of meaning and self-actualisation‘beyond codes and conventions’,(iv)personality traits and differential psychological symbolism,aesthetic self-exploration and auxiliary egos,(v)introjection and role-identity,inventive ways to tackle life problems,‘working through’and catharsis.Conclusion:Interdisciplinary constructivist reasoning suggests that dramatic arts and drama therapy share similar health promoting potential and innate therapeutic power.This calls for further research(i)to explore the entire spectrum of curative factors inhering in dramatic entities,(ii)to explain how drama-based interventions may alleviate mental-health issues alongside culturally sensitive differential diagnostic guidelines,and(iii)to optimise beneficial effects through advanced drama therapeutic settings.The present study suggests that dramatic arts shall also be studied with regard to public health challenges,self-regulation and self-care,mental resilience,well-being and quality of life,and emphatically advocates intensified collaboration between drama theory and drama therapy.展开更多
The human retina,a complex and highly specialized structure,includes multiple cell types that work synergistically to generate and transmit visual signals.However,genetic predisposition or age-related degeneration can...The human retina,a complex and highly specialized structure,includes multiple cell types that work synergistically to generate and transmit visual signals.However,genetic predisposition or age-related degeneration can lead to retinal damage that severely impairs vision or causes blindness.Treatment options for retinal diseases are limited,and there is an urgent need for innovative therapeutic strategies.Cell and gene therapies are promising because of the efficacy of delivery systems that transport therapeutic genes to targeted retinal cells.Gene delivery systems hold great promise for treating retinal diseases by enabling the targeted delivery of therapeutic genes to affected cells or by converting endogenous cells into functional ones to facilitate nerve regeneration,potentially restoring vision.This review focuses on two principal categories of gene delivery vectors used in the treatment of retinal diseases:viral and non-viral systems.Viral vectors,including lentiviruses and adeno-associated viruses,exploit the innate ability of viruses to infiltrate cells,which is followed by the introduction of therapeutic genetic material into target cells for gene correction.Lentiviruses can accommodate exogenous genes up to 8 kb in length,but their mechanism of integration into the host genome presents insertion mutation risks.Conversely,adeno-associated viruses are safer,as they exist as episomes in the nucleus,yet their limited packaging capacity constrains their application to a narrower spectrum of diseases,which necessitates the exploration of alternative delivery methods.In parallel,progress has also occurred in the development of novel non-viral delivery systems,particularly those based on liposomal technology.Manipulation of the ratios of hydrophilic and hydrophobic molecules within liposomes and the development of new lipid formulations have led to the creation of advanced non-viral vectors.These innovative systems include solid lipid nanoparticles,polymer nanoparticles,dendrimers,polymeric micelles,and polymeric nanoparticles.Compared with their viral counterparts,non-viral delivery systems offer markedly enhanced loading capacities that enable the direct delivery of nucleic acids,mRNA,or protein molecules into cells.This bypasses the need for DNA transcription and processing,which significantly enhances therapeutic efficiency.Nevertheless,the immunogenic potential and accumulation toxicity associated with non-viral particulate systems necessitates continued optimization to reduce adverse effects in vivo.This review explores the various delivery systems for retinal therapies and retinal nerve regeneration,and details the characteristics,advantages,limitations,and clinical applications of each vector type.By systematically outlining these factors,our goal is to guide the selection of the optimal delivery tool for a specific retinal disease,which will enhance treatment efficacy and improve patient outcomes while paving the way for more effective and targeted therapeutic interventions.展开更多
Effective treatment methods for stroke,a common cerebrovascular disease with a high mortality rate,are still being sought.Exosome therapy,a form of acellular therapy,has demonstrated promising efficacy in various dise...Effective treatment methods for stroke,a common cerebrovascular disease with a high mortality rate,are still being sought.Exosome therapy,a form of acellular therapy,has demonstrated promising efficacy in various diseases in animal models;however,there is currently insufficient evidence to guide the clinical application of exosome in patients with stroke.This article reviews the progress of exosome applications in stroke treatment.It aims to elucidate the significant potential value of exosomes in stroke therapy and provide a reference for their clinical translation.At present,many studies on exosome-based therapies for stroke are actively underway.Regarding preclinical research,exosomes,as bioactive substances with diverse sources,currently favor stem cells as their origin.Due to their high plasticity,exosomes can be effectively modified through various physical,chemical,and genetic engineering methods to enhance their efficacy.In animal models of stroke,exosome therapy can reduce neuroinflammatory responses,alleviate oxidative stress damage,and inhibit programmed cell death.Additionally,exosomes can promote angiogenesis,repair and regenerate damaged white matter fiber bundles,and facilitate the migration and differentiation of neural stem cells,aiding the repair process.We also summarize new directions for the application of exosomes,specifically the exosome intervention through the ventricular-meningeal lymphatic system.The review findings suggest that the treatment paradigm for stroke is poised for transformation.展开更多
Parkinson’s disease(PD)is the second most common neurodegenerative disorder.The progressive degeneration of dopamine(DA)producing neurons in the midbrain is the pathological hallmark,which leads to debilitating motor...Parkinson’s disease(PD)is the second most common neurodegenerative disorder.The progressive degeneration of dopamine(DA)producing neurons in the midbrain is the pathological hallmark,which leads to debilitating motor symptoms,including tremors,rigidity,and bradykinesia.Drug treatments,such as levodopa,provide symptomatic relief.However,they do not halt disease progression,and their effectiveness diminishes over time(reviewed in Poewe et al.,2017).展开更多
Myasthenia gravis is a chronic autoimmune disorder that affects the neuromuscular junction leading to fluctuating skeletal muscle fatigability. The majority of myasthenia gravis patients have detectable antibodies in ...Myasthenia gravis is a chronic autoimmune disorder that affects the neuromuscular junction leading to fluctuating skeletal muscle fatigability. The majority of myasthenia gravis patients have detectable antibodies in their serum, targeting acetylcholine receptor, muscle-specific kinase, or related proteins. Current treatment for myasthenia gravis involves symptomatic therapy, immunosuppressive drugs such as corticosteroids, azathioprine, and mycophenolate mofetil, and thymectomy, which is primarily indicated in patients with thymoma or thymic hyperplasia. However, this condition continues to pose significant challenges including an unpredictable and variable disease progression, differing response to individual therapies, and substantial longterm side effects associated with standard treatments(including an increased risk of infections, osteoporosis, and diabetes), underscoring the necessity for a more personalized approach to treatment. Furthermore, about fifteen percent of patients, called “refractory myasthenia gravis patients”, do not respond adequately to standard therapies. In this context, the introduction of molecular therapies has marked a significant advance in myasthenia gravis management. Advances in understanding myasthenia gravis pathogenesis, especially the role of pathogenic antibodies, have driven the development of these biological drugs, which offer more selective, rapid, and safer alternatives to traditional immunosuppressants. This review aims to provide a comprehensive overview of emerging therapeutic strategies targeting specific immune pathways in myasthenia gravis, with a particular focus on preclinical evidence, therapeutic rationale, and clinical translation of B-cell depletion therapies, neonatal Fc receptor inhibitors, and complement inhibitors.展开更多
The rise of the aging population parallels the rapidly increasing cases of neurological disorders. This puts pressure on scientists and physicians to find novel methods that can prevent and treat neurodegeneration. Th...The rise of the aging population parallels the rapidly increasing cases of neurological disorders. This puts pressure on scientists and physicians to find novel methods that can prevent and treat neurodegeneration. The brain is made up of a complex network of different cell types that work in tandem to maintain systemic homeostasis.展开更多
AAV-PHP.eB is an artificial adeno-associated virus(AAV)that crosses the blood-brain barrier and targets neurons more efficiently than other AAVs when administered systematically.While AAV-PHP.eB has been used in vario...AAV-PHP.eB is an artificial adeno-associated virus(AAV)that crosses the blood-brain barrier and targets neurons more efficiently than other AAVs when administered systematically.While AAV-PHP.eB has been used in various disease models,its cellular tropism in cerebrovascular diseases remains unclear.In the present study,we aimed to elucidate the tropism of AAV-PHP.eB for different cell types in the brain in a mouse model of ischemic stroke and evaluate its effectiveness in mediating basic fibroblast growth factor(bFGF)gene therapy.Mice were injected intravenously with AAV-PHP.eB either 14 days prior to(pre-stroke)or 1 day following(post-stroke)transient middle cerebral artery occlusion.Notably,we observed a shift in tropism from neurons to endothelial cells with post-stroke administration of AAV-PHP.eB-mNeonGreen(mNG).This endothelial cell tropism correlated strongly with expression of the endothelial membrane receptor lymphocyte antigen 6 family member A(Ly6A).Furthermore,AAV-PHP.eB-mediated overexpression of bFGF markedly improved neurobehavioral outcomes and promoted long-term neurogenesis and angiogenesis post-ischemic stroke.Our findings underscore the significance of considering potential tropism shifts when utilizing AAV-PHP.eB-mediated gene therapy in neurological diseases and suggest a promising new strategy for bFGF gene therapy in stroke treatment.展开更多
Background:In patients with autoimmune hemolytic anemia(AIHA),the risk of relapse is high owing to persistent autoreactive B-cell activity.Multirefractory AIHA is a more advanced stage of disease that is defined by a ...Background:In patients with autoimmune hemolytic anemia(AIHA),the risk of relapse is high owing to persistent autoreactive B-cell activity.Multirefractory AIHA is a more advanced stage of disease that is defined by a lack of response to at least three lines of therapy.CD19-directed chimeric antigen receptor(CAR)T-cell therapy results in profound B-cell depletion and may be a useful approach to achieving drug-free remission in multirefractory AIHA.展开更多
Pancreatic adenocarcinoma remains a most deadly malignancy, with an overall 5-year survival of 5%. A subset of patients will be diagnosed with potentially resectable disease, and while complete surgical resection prov...Pancreatic adenocarcinoma remains a most deadly malignancy, with an overall 5-year survival of 5%. A subset of patients will be diagnosed with potentially resectable disease, and while complete surgical resection provides the only chance at cure, data from trials of postoperative chemoradiation and/or chemotherapy demonstrate a modest survival advantage over those patients who undergo resection alone. As such, most practitioners believe that completion of multimodality therapy is the optimal treatment. However, the sequence of surgery, chemotherapy and radiation therapy is frequently debated, as patients may benefit from a neoadjuvant approach by initiating chemotherapy and/or chemoradiation prior to resection. Here we review the rationale for neoadjuvant therapy, which includes a higher rate of completion of multimodality therapy, minimizing the risk of unnecessary surgical resection for patients who develop early metastatic disease, improved surgical outcomes and the potential for longer overall survival. However, there are no prospective, randomized studies of the neoadjuvant approach compared to a surgeryfirst strategy; the established and ongoing investigations of neoadjuvant therapy for pancreatic cancer are discussed in detail. Lastly, as the future of therapeutic regimens is likely to entail patient-specific genetic and molecular analyses, and the treatment that is best applied based on those data, a review of clinically relevant biomarkers in pancreatic cancer is also presented.展开更多
Although antagonists of tumor necrosis factor have resulted in major therapeutic benefits in inflammatory bowel disease, the magnitude and durability of response are variable. Similar to previously available drugs suc...Although antagonists of tumor necrosis factor have resulted in major therapeutic benefits in inflammatory bowel disease, the magnitude and durability of response are variable. Similar to previously available drugs such as 5-aminosalicylates and immunomodulators, the therapeutic effect is not universal leaving many people searching for options. The development of newer agents has benefited from advances in the understanding of the pathophysiology of the disease. Uncontrolled activation of the acquired immune system has an important role, and lymphocytes, cytokines, and adhesion molecules are broadly targeted for therapeutic intervention. There is increasing evidence of an important role of the innate immune system and the intestinal epithelium, and the therapeutic paradigm is also shifting from immunosuppression to the reinforcement of the intestinal barrier, and modification of the disease process. In this review, we explore the limitation of current therapy as well as mechanisms of actions of new drugs and the efficacy and adverse events from data from clinical trials.展开更多
Hepatocellular carcinoma(HCC) is a common, increasingly prevalent malignancy. For all but the smallest lesions, surgical removal of cancer via resection or liver transplantation(LT) is considered the most feasible pat...Hepatocellular carcinoma(HCC) is a common, increasingly prevalent malignancy. For all but the smallest lesions, surgical removal of cancer via resection or liver transplantation(LT) is considered the most feasible pathway to cure. Resection- even with favorable survival- is associated with a fairly high rate of recurrence, perhaps since most HCCs occur in the setting of cirrhosis. LT offers the advantage of removing not only the cancer but the diseased liver from which the cancer has arisen, and LT outperforms resection for survival with selected patients. Since time waiting for LT is time during which HCC can progress, locoregional therapy(LRT) is widely employed by transplant centers. The purpose of LRT is either to bridge patients to LT by preventing progression and waitlist dropout, or to downstage patients who slightly exceed standard eligibility criteria initially but can fall within it after treatment. Transarterial chemoembolization and radiofrequency ablation have been the most widely utilized LRTs to date, with favorable efficacy and safety as a bridge to LT(and for the former, as a downstaging modality). The list of potentially effective LRTs has expanded in recent years, and includes transarterial chemoembolization with drug-eluting beads, radioembolization and novel forms of extracorporal therapy. Herein we appraise the various LRT modalities for HCC, and their potential roles in specific clinical scenarios in patients awaiting LT.展开更多
The last decade witnessed a significant progress in understanding the biology and immunology of colorectal cancer alongside with the technical innovations in radiotherapy.The stepwise implementation of intensitymodula...The last decade witnessed a significant progress in understanding the biology and immunology of colorectal cancer alongside with the technical innovations in radiotherapy.The stepwise implementation of intensitymodulated and image-guided radiation therapy by means of megavolt computed tomography and helical tomotherapy enabled us to anatomically sculpt dose delivery,reducing treatment related toxicity.In addition,the administration of a simultaneous integrated boost offers excellent local control rates.The novel challenge is the development of treatment strategies for medically inoperable patient and organ preserving approaches.However,distant control remains unsatisfactory and indicates an urgent need for biomarkers that predict the risk of tumor spread.The expected benefit of target?ed therapies that exploit the tumor genome alone is so far hindered by high cost techniques and pharmaceuticals,hence hardly justifying rather modest improvements in patient outcomes.On the other hand,the immune landscape of colorectal cancer is now better clarified with regard to the immunosuppressive network that promotes immune escape.Both N2 neutrophils and myeloid-derived suppressor cells(MDSC)emerge as useful clinical biomarkers of poor prognosis,while the growing list of anti-MDSC agents shows promising ability to boost antitumor T-cell immunity in preclinical settings.Therefore,integration of genetic and immune biomarkers is the next logical step towards effective targeted therapies in the context of personalized cancer treatment.展开更多
文摘An upconversion nanoparticle(NaErF_(4)∶Yb/Tm@NaLuF_(4)∶Yb@NaLuF_(4)∶Nd/Yb@NaLuF_(4),noted as UC)was designed,emitting strong red light by 808 nm laser.The mesoporous silica(mSiO_(2))shell co‑doped with chlorin e6(Ce6)and triethoxy(1H,1H,2H,2H‑nonafluorohexyl)silane(TFS)was coated on the outer layer of UC,and then a layer of HKUST‑1 shell was coated.The obtained nanocomposite UC@Ce6/TFS@mSiO_(2)@HKUST‑1(noted as UCTSH)was used for the synergistic treatment of chemodynamic therapy(CDT)and photodynamic therapy(PDT).Interestingly,the nanostructures can specifically re lease Cu^(2+)in the acidic tumor microenvironment.Cu^(2+)reacts with excess hydrogen peroxide(H_(2)O_(2))in the tumor microenvironment to form cytotoxic hydroxyl radical.Secondly,Ce6,with the action of oxygen‑carrying TFS,selectively produces a large amount of singlet oxygen by 808 nm laser irradiation.UCTSH can enhance the anti‑tumor effects of PDT and CDT by increasing the production level of reactive oxygen species,without causing damage to normal cells.
文摘Cancer continues to pose a formidable challenge in global health,with conventional treatments such as chemotherapy and radiotherapy often resulting in severe toxicities that significantly degrade patients’quality of life and restrict therapeutic outcomes.Addressing this pressing issue,this review presents a thorough and systematic analysis of innovative and emerging strategies designed to minimize the toxicity induced by treatment,while maintaining or even enhancing antitumor efficacy.The focus is on six promising therapeutic approaches:combination therapies utilizing natural bioactive products,molecularly targeted therapies,immunotherapies,nanotechnology-mediated drug delivery systems,adjunct traditional Chinese medicine interventions,and low-dose spatiotemporally concerted regimens.Each approach employs unique mechanisms—such as enhanced targeting precision,immune system activation,tumor microenvironment reprogramming,and multi-component synergistic effects—to mitigate damage to normal tissues and reduce systemic adverse reactions.Despite promising preclinical and clinical advancements,several challenges persist,including drug resistance,high economic costs,a lack of reliable predictive biomarkers,and complexities in clinical translation and regulatory approval.Looking ahead,the incorporation of artificial intelligence,multi-omics profiling,and novel biomimetic nanotechnologies offers unprecedented opportunities for developing highly personalized,low-toxicity treatment frameworks.This review highlights a fundamental shift in oncology towards precision medicine that balances efficacy with safety,demonstrating the transformative potential of these strategies in shaping the future of cancer therapy and enhancing patient care globally.
文摘Cardiovascular disease remains the leading global cause of mortality,projected to increase by 73.4%from 2025 to 2050 despite declining age-standardized rates.Contemporary interventions,such as percutaneous coronary intervention and statins,reduce major adverse cardiovascular events(MACE)by 25%-30%,yet a 20%five-year MACE risk persists in high-risk cohorts.These approaches,histor-ically focused on luminal stenosis,fail to address systemic atherogenesis drivers like endothelial dysfunction and inflammation.Specifically,dietary linoleic acid restriction(<5 g/day)reduces oxidized low-density lipoprotein by approximately 15%by limiting peroxidation-prone bisallylic bonds,mitigating arterial inflam-mation,a key atherogenic trigger.Enhanced external counterpulsation,through pulsatile shear stress,enhances nitric oxide-mediated coronary perfusion,alle-viating angina in approximately 70%of refractory cases unresponsive to revascu-larization.Nanoparticle-facilitated chelation targets atherosclerotic plaques with precision,reducing calcium content by up to 30%in preclinical models,offering a novel avenue for lesion reversal.These innovations collectively address residual risk by tackling root causes,oxidative stress,endothelial dysfunction,and plaque instability,potentially halving MACE rates with widespread adoption.Despite promising preliminary data,gaps remain in long-term safety and scalability.Robust clinical trials are needed to validate these approaches,which collectively aim to transform cardiovascular disease management by prioritizing prevention and vascular restoration,potentially reducing coronary events to a public health rarity.
文摘Tau plays a crucial role in several neurodegenerative diseases,collectively referred to as tauopathies.Therefore,targeting potential pathological changes in tau could enable useful therapeutic interventions.However,tau is not an easy target because it dynamically interacts with microtubules and other cellular components,which presents a challenge for tau-targeted drugs.New cellular models could aid the development of mechanism-based tau-targeted therapies.
基金Supported by National Program for Inheriting the Academic Experience of Senior TCM Experts(Seventh Batch),National Administration of Traditional Chinese Medicine([2022]No.76)Yunnan Provincial Collaborative Research Project on Major and Difficult Diseases with Integrated Traditional Chinese and Western Medicine(Yun Cai She No.163[2024])-Chronic Renal Failure(300072)Yunnan Provincial Senior TCM Expert Li Qi Heritage Studio Project.
文摘Traditional Chinese medicine has opened new pathways and provided fresh perspectives for the treatment of uremic pruritus(UP)through syndrome differentiation and treatment.This paper summarizes the clinical experience of Professor Li Qi in treating this condition.Professor Li Qi points out that the fundamental pathogenesis of UP lies in yang deficiency of the spleen and kidney.On this basis,either external cold entering the interior or yang deficiency leading to cold congelation may result in malnutrition of the skin,thereby triggering pruritus.In clinical practice,slight sweating therapy is applied to release the exterior and expel pathogenic factors or to warm and resolve cold fluid retention,achieving satisfactory therapeutic outcomes.
基金supported by The China Ethnic Medicine Association Research Grant(No.2023MY055-81)Science and Technology Program of the Joint Fund of Scientific Research for the Public Hospitals of Inner Mongolia Academy of Medical Sciences(2023GLLHD177,2023GLLH0174)Inner Mongolia Autonomous Region Regional Medical Center for Specialized Care(2025).
文摘Serbisütherapy(ST)is a distinctive external treatment modality within traditional Mongolian medicine(TMM),historically developed within a nomadic cultural framework.This study presents a comprehensive philological and historical analysis of ST,tracing its evolution from early battlefield applications to contemporary clinical use.By critically examining classical Mongolian medical texts alongside modern case studies,we aim to systematize ST’s therapeutic methods,indications,and limitations,while exploring its mechanisms of action through both traditional theory and modern biomedical perspectives.ST has undergone significant transformation,shifting from whole-body cavity immersion in the 13th century to targeted,organ-specific applications in modern practice.Its four primary methods–Covering,Mounted,Organ Placement,and Suction–demonstrate efficacy in treating cold-natured diseases,musculoskeletal disorders,gynecological conditions,and certain emergencies.ST embodies the core principles of TMM,particularly the balance of the“Three Roots”and the correction of cold-induced pathologies through heat.Despite challenges related to standardization,cultural translation,and regulatory acceptance,ST holds translational potential for integrative medicine.Future research should prioritize mechanistic validation,clinical standardization,and the development of biocompatible thermal technologies to bridge traditional practice with modern healthcare systems.
基金Supported by Army Logistics Department Health Bureau Project,No.QJGYXYJZX-012.
文摘BACKGROUND Due to the dry and cold climate,the obvious temperature difference between day and night,and the low oxygen content of the air in the plateau area,people are prone to upper respiratory tract diseases,and often the condition is prolonged,and the patients are prone to anxiety and uneasiness,which may be related to the harshness of the plateau environment,somatic discomfort due to the lack of oxygen,anxiety about the disease,and other factors.AIM To investigate the effects of cognitive behavioral therapy(CBT)on anxiety,sleep disorders,and hypoxia tolerance in patients with high-altitude respiratory diseases.METHODS A total of 2337 patients with high-altitude-related respiratory diseases treated at our hospital between November 2023 and January 2024 were selected as the study subjects.The subjects’pre-high-altitude residential altitude was approximately 1700 meters.They were divided into two groups.Both groups were given symptomatic treatment,and the control group implemented conventional nursing intervention,while the research group simultaneously conducted CBT intervention;assessed the degree of health knowledge of the two groups,and applied the Hamilton Anxiety Scale and the Pittsburgh Sleep Quality Index to assess the anxiety and sleep quality of the patients before and after the intervention,respectively.It also observed the length and efficiency of sleep,and detected the level of serum hypoxia inducible factor-1α,erythropoietin(EPO)and clinical intervention before and after intervention.EPO levels,and investigated satisfaction with the clinical intervention.RESULTS The rate of excellent health knowledge in the intervention group was 93.64%,which was higher than that in the control group(74.23%;P<0.05).Before the intervention,there was no significant difference in Hamilton Anxiety Scale and Pittsburgh Sleep Quality Index scores between the two groups(P>0.05),and after the intervention,the scores of the study group were significantly lower than those of the control group(P<0.05).There was no significant difference in sleep duration and sleep efficiency between the groups before the intervention(P>0.05),and after the intervention,the scores of the study group were significantly larger than those of the control group(P<0.05).There was no significant difference in serum hypoxia inducible factor-1αand EPO between the two groups before intervention(P>0.05),and both research groups were significantly lower than the control group after intervention(P<0.05).According to the questionnaire survey,the intervention satisfaction of the study group was 95.53%,which was higher than that of the control group(80.14%;P<0.05).CONCLUSION The CBT intervention in the treatment of patients with high-altitude-related respiratory diseases helps improve patients'health knowledge,relieve anxiety,improve sleep quality and hypoxia tolerance,and improve nursing satisfaction.
文摘BACKGROUND Approximately 30%of patients with head and neck cancer experience adverse effects caused by anxiety and depression.Considering the high prevalence,implementing customized interventions to ease adverse emotional states is imperative.AIM To evaluate the efficacy of cognitive behavioral therapy(CBT)-based psychological interventions in improving the psychological well-being and quality of life(QoL)of patients with laryngeal carcinoma.METHODS This study enrolled 120 patients admitted from February 2022 to February 2024.The control group,comprising 50 participants,received standard supportive psychological care,while the research group,consisting 70 participants,underwent CBT-based interventions.Several clinical outcomes were systematically assessed that included postoperative recovery metrics(duration of tracheostomy and nasogastric tube dependence and length of hospitalization),psychological status(Self-Rating Anxiety Scale and Self-Rating Depression Scale),nutritional markers(serum albumin and hemoglobin levels),sleep quality(Self-Rating Scale of Sleep and Athens Insomnia Scale),and QoL(Functional Assessment of Cancer Therapy-Head and Neck).RESULTS The results demonstrated that the research group experienced superior outcomes,with significantly reduced durations of tracheostomy and nasogastric tube dependence,as well as shorter hospital stays,compared with the control group.Additionally,the research group exhibited markedly lower post-intervention Self-Rating Anxiety Scale,Self-Rating Depression Scale,Self-Rating Scale of Sleep,and Athens Insomnia Scale scores,along with minimal but higher change in serum albumin and hemoglobin levels compared with the control group.All five domains of Functional Assessment of Cancer Therapy-Head and Neck showed notable improvements in the research group,exceeding those observed in the control group.CONCLUSION CBT-based psychological support positively affects the mental well-being and QoL of patients with laryngeal carcinoma,highlighting its potential for broader clinical application.
文摘Background:Drama therapy as a discipline in clinical and public health areas dates back to movements in the Netherlands,Great Britain and the United States of America in the 1960s.Today,drama therapy comprises a huge variety of methods and is applied in numerous medical domains such as psychiatry,pediatrics and neurogeriatrics.Nonetheless,historical and philosophical considerations suggest that at all times dramatic arts have encompassed curative potential and helped to promote mental health.Regarding this perspective,the present article aims to explore the spirit of drama therapy in ancient Chinese and Greek cultures.Methods:Involving cross-cultural psychiatry and medical anthropology,comparative research centred around salutary momentums inhering in drama and dramatic practices in Ancient China and Greece.The entire research process consisted of three phases:(i)screening of ancient Chinese and Greek dramatic rituals and arts to select phenomena and genres with pathological,therapeutic and mental health relevance;(ii)medical ontological processing,in particular from a psychopathological,psychiatric,psychotherapeutic and mental health scientific point of view,to explore and elucidate their curative and preventative features;(iii)transdisciplinary considerations about the evolution of drama therapy,as well as their diverse modes of artistic and medical reasoning.Results:The research process resulted in the identification of five(functional)roots of drama therapy,as well as public health benefits of dramatic arts:(i)dramatic rituals,stage-trance settings and spiritual immersion,(ii)mise-en-scène of divine spheres and alternative worlds,as well as scenic imagination and creative fusion of reality and fantasy,desire and satisfaction,(iii)anthropologic ontology,search of meaning and self-actualisation‘beyond codes and conventions’,(iv)personality traits and differential psychological symbolism,aesthetic self-exploration and auxiliary egos,(v)introjection and role-identity,inventive ways to tackle life problems,‘working through’and catharsis.Conclusion:Interdisciplinary constructivist reasoning suggests that dramatic arts and drama therapy share similar health promoting potential and innate therapeutic power.This calls for further research(i)to explore the entire spectrum of curative factors inhering in dramatic entities,(ii)to explain how drama-based interventions may alleviate mental-health issues alongside culturally sensitive differential diagnostic guidelines,and(iii)to optimise beneficial effects through advanced drama therapeutic settings.The present study suggests that dramatic arts shall also be studied with regard to public health challenges,self-regulation and self-care,mental resilience,well-being and quality of life,and emphatically advocates intensified collaboration between drama theory and drama therapy.
基金Hongguang Wu,Both authors contributed equally to this work and share first authorshipLing Dong,Both authors contributed equally to this work and share first authorship。
文摘The human retina,a complex and highly specialized structure,includes multiple cell types that work synergistically to generate and transmit visual signals.However,genetic predisposition or age-related degeneration can lead to retinal damage that severely impairs vision or causes blindness.Treatment options for retinal diseases are limited,and there is an urgent need for innovative therapeutic strategies.Cell and gene therapies are promising because of the efficacy of delivery systems that transport therapeutic genes to targeted retinal cells.Gene delivery systems hold great promise for treating retinal diseases by enabling the targeted delivery of therapeutic genes to affected cells or by converting endogenous cells into functional ones to facilitate nerve regeneration,potentially restoring vision.This review focuses on two principal categories of gene delivery vectors used in the treatment of retinal diseases:viral and non-viral systems.Viral vectors,including lentiviruses and adeno-associated viruses,exploit the innate ability of viruses to infiltrate cells,which is followed by the introduction of therapeutic genetic material into target cells for gene correction.Lentiviruses can accommodate exogenous genes up to 8 kb in length,but their mechanism of integration into the host genome presents insertion mutation risks.Conversely,adeno-associated viruses are safer,as they exist as episomes in the nucleus,yet their limited packaging capacity constrains their application to a narrower spectrum of diseases,which necessitates the exploration of alternative delivery methods.In parallel,progress has also occurred in the development of novel non-viral delivery systems,particularly those based on liposomal technology.Manipulation of the ratios of hydrophilic and hydrophobic molecules within liposomes and the development of new lipid formulations have led to the creation of advanced non-viral vectors.These innovative systems include solid lipid nanoparticles,polymer nanoparticles,dendrimers,polymeric micelles,and polymeric nanoparticles.Compared with their viral counterparts,non-viral delivery systems offer markedly enhanced loading capacities that enable the direct delivery of nucleic acids,mRNA,or protein molecules into cells.This bypasses the need for DNA transcription and processing,which significantly enhances therapeutic efficiency.Nevertheless,the immunogenic potential and accumulation toxicity associated with non-viral particulate systems necessitates continued optimization to reduce adverse effects in vivo.This review explores the various delivery systems for retinal therapies and retinal nerve regeneration,and details the characteristics,advantages,limitations,and clinical applications of each vector type.By systematically outlining these factors,our goal is to guide the selection of the optimal delivery tool for a specific retinal disease,which will enhance treatment efficacy and improve patient outcomes while paving the way for more effective and targeted therapeutic interventions.
基金supported by the Natural Science Foundation of Chongqing,No.CSTB2023NSCQ-mSX0561(to WL).
文摘Effective treatment methods for stroke,a common cerebrovascular disease with a high mortality rate,are still being sought.Exosome therapy,a form of acellular therapy,has demonstrated promising efficacy in various diseases in animal models;however,there is currently insufficient evidence to guide the clinical application of exosome in patients with stroke.This article reviews the progress of exosome applications in stroke treatment.It aims to elucidate the significant potential value of exosomes in stroke therapy and provide a reference for their clinical translation.At present,many studies on exosome-based therapies for stroke are actively underway.Regarding preclinical research,exosomes,as bioactive substances with diverse sources,currently favor stem cells as their origin.Due to their high plasticity,exosomes can be effectively modified through various physical,chemical,and genetic engineering methods to enhance their efficacy.In animal models of stroke,exosome therapy can reduce neuroinflammatory responses,alleviate oxidative stress damage,and inhibit programmed cell death.Additionally,exosomes can promote angiogenesis,repair and regenerate damaged white matter fiber bundles,and facilitate the migration and differentiation of neural stem cells,aiding the repair process.We also summarize new directions for the application of exosomes,specifically the exosome intervention through the ventricular-meningeal lymphatic system.The review findings suggest that the treatment paradigm for stroke is poised for transformation.
基金supported by the DGIST start-up funds from the Ministry of Science and ICT(2024010330)a National Research Foundation of Korea(NRF)grant funded by the Korea Government(MSIT)(No.RS-2024-00351442)(to TWK).
文摘Parkinson’s disease(PD)is the second most common neurodegenerative disorder.The progressive degeneration of dopamine(DA)producing neurons in the midbrain is the pathological hallmark,which leads to debilitating motor symptoms,including tremors,rigidity,and bradykinesia.Drug treatments,such as levodopa,provide symptomatic relief.However,they do not halt disease progression,and their effectiveness diminishes over time(reviewed in Poewe et al.,2017).
文摘Myasthenia gravis is a chronic autoimmune disorder that affects the neuromuscular junction leading to fluctuating skeletal muscle fatigability. The majority of myasthenia gravis patients have detectable antibodies in their serum, targeting acetylcholine receptor, muscle-specific kinase, or related proteins. Current treatment for myasthenia gravis involves symptomatic therapy, immunosuppressive drugs such as corticosteroids, azathioprine, and mycophenolate mofetil, and thymectomy, which is primarily indicated in patients with thymoma or thymic hyperplasia. However, this condition continues to pose significant challenges including an unpredictable and variable disease progression, differing response to individual therapies, and substantial longterm side effects associated with standard treatments(including an increased risk of infections, osteoporosis, and diabetes), underscoring the necessity for a more personalized approach to treatment. Furthermore, about fifteen percent of patients, called “refractory myasthenia gravis patients”, do not respond adequately to standard therapies. In this context, the introduction of molecular therapies has marked a significant advance in myasthenia gravis management. Advances in understanding myasthenia gravis pathogenesis, especially the role of pathogenic antibodies, have driven the development of these biological drugs, which offer more selective, rapid, and safer alternatives to traditional immunosuppressants. This review aims to provide a comprehensive overview of emerging therapeutic strategies targeting specific immune pathways in myasthenia gravis, with a particular focus on preclinical evidence, therapeutic rationale, and clinical translation of B-cell depletion therapies, neonatal Fc receptor inhibitors, and complement inhibitors.
文摘The rise of the aging population parallels the rapidly increasing cases of neurological disorders. This puts pressure on scientists and physicians to find novel methods that can prevent and treat neurodegeneration. The brain is made up of a complex network of different cell types that work in tandem to maintain systemic homeostasis.
基金supported by the National Natural Science Foundation of China,Nos.81870921(to YW),81974179(to ZZ),82271320(to ZZ),82071284(to YT)National Key R&D Program of China,No.2022YFA1603600(to ZZ),2019YFA0112000(to YT)+1 种基金Scientific Research and Innovation Program of Shanghai Education Commission,No.2019-01-07-00-02-E00064(to GYY)Scientific and Technological Innovation Act Program of Shanghai Science and Technology Commission,No.20JC1411900(to GYY).
文摘AAV-PHP.eB is an artificial adeno-associated virus(AAV)that crosses the blood-brain barrier and targets neurons more efficiently than other AAVs when administered systematically.While AAV-PHP.eB has been used in various disease models,its cellular tropism in cerebrovascular diseases remains unclear.In the present study,we aimed to elucidate the tropism of AAV-PHP.eB for different cell types in the brain in a mouse model of ischemic stroke and evaluate its effectiveness in mediating basic fibroblast growth factor(bFGF)gene therapy.Mice were injected intravenously with AAV-PHP.eB either 14 days prior to(pre-stroke)or 1 day following(post-stroke)transient middle cerebral artery occlusion.Notably,we observed a shift in tropism from neurons to endothelial cells with post-stroke administration of AAV-PHP.eB-mNeonGreen(mNG).This endothelial cell tropism correlated strongly with expression of the endothelial membrane receptor lymphocyte antigen 6 family member A(Ly6A).Furthermore,AAV-PHP.eB-mediated overexpression of bFGF markedly improved neurobehavioral outcomes and promoted long-term neurogenesis and angiogenesis post-ischemic stroke.Our findings underscore the significance of considering potential tropism shifts when utilizing AAV-PHP.eB-mediated gene therapy in neurological diseases and suggest a promising new strategy for bFGF gene therapy in stroke treatment.
文摘Background:In patients with autoimmune hemolytic anemia(AIHA),the risk of relapse is high owing to persistent autoreactive B-cell activity.Multirefractory AIHA is a more advanced stage of disease that is defined by a lack of response to at least three lines of therapy.CD19-directed chimeric antigen receptor(CAR)T-cell therapy results in profound B-cell depletion and may be a useful approach to achieving drug-free remission in multirefractory AIHA.
文摘Pancreatic adenocarcinoma remains a most deadly malignancy, with an overall 5-year survival of 5%. A subset of patients will be diagnosed with potentially resectable disease, and while complete surgical resection provides the only chance at cure, data from trials of postoperative chemoradiation and/or chemotherapy demonstrate a modest survival advantage over those patients who undergo resection alone. As such, most practitioners believe that completion of multimodality therapy is the optimal treatment. However, the sequence of surgery, chemotherapy and radiation therapy is frequently debated, as patients may benefit from a neoadjuvant approach by initiating chemotherapy and/or chemoradiation prior to resection. Here we review the rationale for neoadjuvant therapy, which includes a higher rate of completion of multimodality therapy, minimizing the risk of unnecessary surgical resection for patients who develop early metastatic disease, improved surgical outcomes and the potential for longer overall survival. However, there are no prospective, randomized studies of the neoadjuvant approach compared to a surgeryfirst strategy; the established and ongoing investigations of neoadjuvant therapy for pancreatic cancer are discussed in detail. Lastly, as the future of therapeutic regimens is likely to entail patient-specific genetic and molecular analyses, and the treatment that is best applied based on those data, a review of clinically relevant biomarkers in pancreatic cancer is also presented.
文摘Although antagonists of tumor necrosis factor have resulted in major therapeutic benefits in inflammatory bowel disease, the magnitude and durability of response are variable. Similar to previously available drugs such as 5-aminosalicylates and immunomodulators, the therapeutic effect is not universal leaving many people searching for options. The development of newer agents has benefited from advances in the understanding of the pathophysiology of the disease. Uncontrolled activation of the acquired immune system has an important role, and lymphocytes, cytokines, and adhesion molecules are broadly targeted for therapeutic intervention. There is increasing evidence of an important role of the innate immune system and the intestinal epithelium, and the therapeutic paradigm is also shifting from immunosuppression to the reinforcement of the intestinal barrier, and modification of the disease process. In this review, we explore the limitation of current therapy as well as mechanisms of actions of new drugs and the efficacy and adverse events from data from clinical trials.
文摘Hepatocellular carcinoma(HCC) is a common, increasingly prevalent malignancy. For all but the smallest lesions, surgical removal of cancer via resection or liver transplantation(LT) is considered the most feasible pathway to cure. Resection- even with favorable survival- is associated with a fairly high rate of recurrence, perhaps since most HCCs occur in the setting of cirrhosis. LT offers the advantage of removing not only the cancer but the diseased liver from which the cancer has arisen, and LT outperforms resection for survival with selected patients. Since time waiting for LT is time during which HCC can progress, locoregional therapy(LRT) is widely employed by transplant centers. The purpose of LRT is either to bridge patients to LT by preventing progression and waitlist dropout, or to downstage patients who slightly exceed standard eligibility criteria initially but can fall within it after treatment. Transarterial chemoembolization and radiofrequency ablation have been the most widely utilized LRTs to date, with favorable efficacy and safety as a bridge to LT(and for the former, as a downstaging modality). The list of potentially effective LRTs has expanded in recent years, and includes transarterial chemoembolization with drug-eluting beads, radioembolization and novel forms of extracorporal therapy. Herein we appraise the various LRT modalities for HCC, and their potential roles in specific clinical scenarios in patients awaiting LT.
基金Supported by Grants from the Vlaamse Liga tegen Kanker
文摘The last decade witnessed a significant progress in understanding the biology and immunology of colorectal cancer alongside with the technical innovations in radiotherapy.The stepwise implementation of intensitymodulated and image-guided radiation therapy by means of megavolt computed tomography and helical tomotherapy enabled us to anatomically sculpt dose delivery,reducing treatment related toxicity.In addition,the administration of a simultaneous integrated boost offers excellent local control rates.The novel challenge is the development of treatment strategies for medically inoperable patient and organ preserving approaches.However,distant control remains unsatisfactory and indicates an urgent need for biomarkers that predict the risk of tumor spread.The expected benefit of target?ed therapies that exploit the tumor genome alone is so far hindered by high cost techniques and pharmaceuticals,hence hardly justifying rather modest improvements in patient outcomes.On the other hand,the immune landscape of colorectal cancer is now better clarified with regard to the immunosuppressive network that promotes immune escape.Both N2 neutrophils and myeloid-derived suppressor cells(MDSC)emerge as useful clinical biomarkers of poor prognosis,while the growing list of anti-MDSC agents shows promising ability to boost antitumor T-cell immunity in preclinical settings.Therefore,integration of genetic and immune biomarkers is the next logical step towards effective targeted therapies in the context of personalized cancer treatment.
