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
Chronic,non-healing wounds represent a significant challenge for healthcare systems worldwide,often requiring significant human and financial resources.Chronic wounds arise from the complex interplay of underlying com...Chronic,non-healing wounds represent a significant challenge for healthcare systems worldwide,often requiring significant human and financial resources.Chronic wounds arise from the complex interplay of underlying comorbidities,such as diabetes or vascular diseases,lifestyle factors,and genetic risk profiles which may predispose extremities to local ischemia.Injuries are further exacerbated by bacterial colonization and the formation of biofilms.Infection,consequently,perpetuates a chronic inflammatory microenvironment,preventing the progression and completion of normal wound healing.The current standard of care(SOC)for chronic wounds involves surgical debridement along with localized wound irrigation,which requires inpatient care under general anesthesia.This could be followed by,if necessary,defect coverage via a reconstructive ladder utilizing wound debridement along with skin graft,local,or free flap techniques once the wound conditions are stabilized and adequate blood supply is restored.To promote physiological wound healing,a variety of approaches have been subjected to translational research.Beyond conventional wound healing drugs and devices that currently supplement treatments,cellular and immunotherapies have emerged as promising therapeutics that can behave as tailored therapies with cell-or molecule-specific wound healing properties.However,in contrast to the clinical omnipresence of chronic wound healing disorders,there remains a shortage of studies condensing the current body of evidence on cellular therapies and immunotherapies for chronic wounds.This review provides a comprehensive exploration of current therapies,experimental approaches,and translational studies,offering insights into their efficacy and limitations.Ultimately,we hope this line of research may serve as an evidence-based foundation to guide further experimental and translational approaches and optimize patient care long-term.展开更多
[Objectives]This meta-analysis evaluated the efficacy of Traditional Chinese Medicine(TCM)manual therapies(Tuina,Daoyin,acupotomology)for idiopathic scoliosis(IS),with dual focus on radiographic outcomes(Cobb angle,ve...[Objectives]This meta-analysis evaluated the efficacy of Traditional Chinese Medicine(TCM)manual therapies(Tuina,Daoyin,acupotomology)for idiopathic scoliosis(IS),with dual focus on radiographic outcomes(Cobb angle,vertebral rotation)and patient-centered metrics(pain,disability,quality of life).[Methods]This study systematically searched PubMed,Cochrane Library,EMBASE,Web of Science,CNKI,Wanfang,and VIP databases(from inception to July 2025)for randomized controlled trials(RCTs)comparing TCM manual therapies against controls(bracing,exercise,sham,or no intervention).Two reviewers independently extracted data and assessed methodological quality using the PEDro scale.Meta-analyses employed random-effects models(Stata 18)to calculate Hedges'g with 95%confidence intervals(CI).Heterogeneity was quantified via I 2 statistics,and subgroup analyses examined intervention types(standalone versus combined)and control groups.[Results]Radiographic outcomes:TCM therapies significantly reduced Cobb angle(Hedges'g=-0.93;95%CI:-1.37,-0.49;p<0.001)and vertebral torsion rotation(VTR;g=-0.71;95%CI:-0.91,-0.51;p<0.001)versus controls;patient-centered outcomes:substantial pain reduction(VAS:g=-1.47;95%CI:-2.64,-0.30;p=0.01)and disability improvement(ODI:g=-1.10;95%CI:-1.57,-0.64;p<0.001)were observed.Quality of life(SRS-22)showed non-significant gains(g=2.01;95%CI:-0.43,4.45;p=0.11).[Conclusions]TCM manual therapies significantly improve spinal alignment and reduce pain/disability in IS patients,particularly when integrated with exercise regimens.While results support their role as complementary interventions,standardization of protocols and long-term efficacy studies are needed for clinical implementation.展开更多
BACKGROUND Autoimmune hepatitis(AIH)is typically treated with immunomodulators and steroids.However,some patients are refractory to these treatments,necessitating alternative approaches.Biological therapies have recen...BACKGROUND Autoimmune hepatitis(AIH)is typically treated with immunomodulators and steroids.However,some patients are refractory to these treatments,necessitating alternative approaches.Biological therapies have recently been explored for these difficult cases.AIM To assess the efficacy and safety of biologics in AIH,focusing on patients unresponsive to standard treatments and evaluating outcomes such as serological markers and histological remission.METHODS A case-based systematic review was performed following the PRISMA protocol to evaluate the efficacy and safety of biological therapies in AIH.The primary focus was on serological improvement and histological remission.The secondary focus was on assessing therapy safety and additional outcomes.A standardized search command was applied to MEDLINE,EMBASE,and Cochrane Library databases to identify relevant studies.Inclusion criteria encompassed adult AIH patients treated with biologics.Data were analyzed based on demographics,prior treatments,and therapy-related outcomes.A narrative synthesis was employed to address biases and provide a comprehensive overview of the evidence.RESULTS A total of 352 studies were reviewed,with 30 selected for detailed analysis.Key findings revealed that Belimumab led to a favourable response in five out of eight AIH patients across two studies.Rituximab demonstrated high efficacy,with 41 out of 45 patients showing significant improvement across six studies.Basiliximab was assessed in a single study,where the sole patient treated experienced a beneficial outcome.Additionally,a notable number of AIH cases were induced by anti-tumor necrosis factor(TNF)medications,including 16 cases associated with infliximab and four cases with adalimumab.All these cases showed improvement upon withdrawal of the biologic agent.CONCLUSION Belimumab and Rituximab show promise as effective alternatives for managing refractory AIH,demonstrating significant improvements in clinical outcomes and liver function.However,the variability in patient responses to different therapies highlights the need for personalized treatment strategies.The risk of AIH induced by anti-TNF therapies underscores the need for vigilant monitoring and prompt symptom recognition.These findings support the incorporation of biologic agents into AIH treatment protocols,particularly for patients who do not respond to conventional therapies.展开更多
Introduction:Current international guidelines encourage cancer patients to engage in physical activity and recommend mind-body therapies(MBTs)as a method for treating cancer-related pain(CRP).However,the most effectiv...Introduction:Current international guidelines encourage cancer patients to engage in physical activity and recommend mind-body therapies(MBTs)as a method for treating cancer-related pain(CRP).However,the most effective MBTs for improving CRP in this population remain unknown.Therefore,this network meta-analysis(NMA)aimed to assess and rank the relative efficacy of different MBTs for CRP,and to conduct subgroup analyses according to different cancer types and stages of treatment.Content:Eight electronic databases were searched for randomized controlled trials(RCTs)that compared differentMBTs to improve pain in adults living with cancer.RCTs were evaluated using the Cochrane risk of bias tool.A random effects network meta-analysis was performed within a frequentist framework.Of the 4,916 articles retrieved and screened against the selection criteria.36 studies with a total 2,387 participants were eligible to be included in the analysis.Qigong demonstrated significantly greater effects than Usual care(standardized mean difference[SMD]-0.85,95% confidence interval[CI]-1.46 to -0.24),Waitlist(SMD−0.93,-1.77 to -0.08),and Massage(SMD-1.71,-3.20 to -0.23),with the highest surface under the cumulative ranking value of 86.5%,was ranked first.It was preceded by Conventional exercise(75.2%),Taichi(74.9%),with Massage having the lowest rank(7.2%).In a subgroup analysis of breast cancer,Taichi(89.6%),Conventional exercise(68.4%),and Pilates(68.3%)ranked as the top three.Summary and outlook:This network meta-analysis indicates that Qigong and Tai Chi are among the most effective mind–body therapies(MBTs)for managing cancer-related pain and may serve as complementary adjuvant treatments for patients with cancer.展开更多
BACKGROUND Anemia is a prevalent and challenging complication in patients with hematologic and solid malignancies,which stems from the direct effects of malignancy,treatment-induced toxicities,and systemic inflammatio...BACKGROUND Anemia is a prevalent and challenging complication in patients with hematologic and solid malignancies,which stems from the direct effects of malignancy,treatment-induced toxicities,and systemic inflammation.It affects patients’survival,functional status,and quality of life profoundly.Recent literature has highlighted the emerging role of the gut microbiome in the pathogenesis of cancer-associated anemia.The gut microbiota,through its intricate interplay with iron metabolism,inflammatory pathways,and immune modulation,may either exacerbate or ameliorate anemia depending on its composition,and functional integrity.Dysbiosis,characterized by disruption in the gut microbial ecosystem,is very common in cancer patients.This microbial imbalance is implicated in anemia causation through diminished iron absorption,persistent low-grade inflammation,and suppression of erythropoiesis.AIM To consolidate current evidence regarding the interplay between gut microbiome and anemia in the setting of malignancies.It aims to provide a detailed exploration of the mechanistic links between dysbiosis and anemia,identifies unique challenges associated with various cancer types,and evaluates the efficacy of microbiome-focused therapies.Through this integrative approach,the review seeks to establish a foundation for innovative clinical strategies aimed at mitigating anemia and improving patient outcomes in oncology.METHODS A literature search was performed using multiple databases,including Google Scholar,PubMed,Scopus,and Web of Science,using a combination of keywords and Boolean operators to refine results.Keywords included“cancerassociated anemia”,“gut microbiome”,“intestinal microbiota”,“iron metabolism”,“gut dysbiosis”,“short-chain fatty acids”,“hematopoiesis”,“probiotics”,“prebiotics”,and“fecal microbiota transplantation”.Articles published in English between 2000 and December 2024 were included,with a focus on contemporary and relevant findings.RESULTS Therapeutic strategies aimed at restoration of gut microbial homeostasis,such as probiotics,prebiotics,dietary interventions,and fecal microbiota transplantation(FMT),can inhibit anemia-causing pathways by enhancing microbial diversity,suppressing detrimental flora,reducing systemic inflammation and optimizing nutrient absorption.CONCLUSION Gut dysbiosis causes anemia and impairs response to chemotherapy in cancer patients.Microbiome-centered interventions,such as probiotics,prebiotics,dietary modifications,and FMT,have shown efficacy in restoring microbial balance,reducing inflammation,and enhancing nutrient bioavailability.Emerging approaches,including engineered probiotics and bacteriophage therapies,are promising precision-based,customizable solutions for various microbiome compositions and imbalances.Future research should focus on integrating microbiometargeted strategies with established anemia therapies.展开更多
Depression is a prevalent neuropsychiatric disorder characterized by persistent sadness,anhedonia,guilt,fatigue,and impaired concentration.Although pharmacotherapy and psychotherapy can be effective,their utility is l...Depression is a prevalent neuropsychiatric disorder characterized by persistent sadness,anhedonia,guilt,fatigue,and impaired concentration.Although pharmacotherapy and psychotherapy can be effective,their utility is limited by adverse effects and significant inter-individual variability.Non-pharmacological therapies from traditional medicine have emerged as promising adjuncts owing to their favorable safety profiles,minimal side effects,and high patient compliance.These therapies,including acupoint stimulation,meditation,and yoga,produce antidepressant effects by reducing neuroinflammation,modulating neurotransmitter release,enhancing neuroplasticity,and regulating the gut-brain axis.This review summarizes clinical applications and mechanistic insights of traditional medicine’s non-pharmacological therapies for depression,providing a scientific rationale for their integration into comprehensive management.展开更多
Osteoarthritis(OA)is one of the most common degenerative and age-related diseases in joints,which affects 654 million people worldwide.Current therapies could not fundamentally reverse the pathologic process of OA due...Osteoarthritis(OA)is one of the most common degenerative and age-related diseases in joints,which affects 654 million people worldwide.Current therapies could not fundamentally reverse the pathologic process of OA due to the complex pathogenesis.Although OA mechanisms have been investigated on a large scale over the past decade,the OA pathology correlated with aging-associated changes is still largely unrevealed.Therefore,in-depth analysis of the aging microenvironment and aging-related molecular mechanisms in OA may offer additional strategies for clinical prevention and treatment.In this review,we discuss the potential pathogenesis of OA in light of aging-associated changes and summarize three main components of the aging microenvironment of the OA joint:immune homeostatic imbalance,cellular senescence,and stem cell exhaustion,which could be induced by aging and further exacerbate OA progression.Additionally,it is emphasized that immune homeostatic imbalance appears before established OA,which occurs in the early stage and is the therapeutic window of opportunity for better clinical outcomes.Importantly,we evaluate recent therapeutic targets and promising interventions against these components,as well as the challenges and prospects for precise and individualized therapies of OA patients,which we believe would guide the construction of novel combined strategies targeting aging-related factors against OA for better treatments in the future.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
Extracorporeal therapies have a definite role in patients with acute liver failure,acute on-chronic liver failure,and progressive chronic liver disease.They act as a bridge-to-transplant in these patients.With the inc...Extracorporeal therapies have a definite role in patients with acute liver failure,acute on-chronic liver failure,and progressive chronic liver disease.They act as a bridge-to-transplant in these patients.With the increasing success of liver transplantation,the immediate postoperative complication spectrum continues to expand.Extracorporeal therapies can play an important role in managing these complications.However,the literature on extracorporeal therapies in the postliver transplant period is limited.This review article discussed various extracorporeal therapies that are still evolving or marred by limited evidence but can improve patient outcomes.These extracorporeal therapies can be divided into two subgroups:(1)Therapies for infective complications.Endotoxin and cytokine adsorption columns;and(2)Therapies for noninfective complications like small for size syndrome,primary allograft nonfunction,early allograft dysfunction,hyperacute rejection,hepatopulmonary syndrome,etc.(plasma exchange,double plasma molecular adsorption,molecular adsorbent recirculation system,and extracorporeal membrane oxygenation,among others).展开更多
Obesity is a chronic,multifactorial disease closely linked to a spectrum of cardiometabolic disorders,with its global prevalence rising at an alarming rate.In recent years,minimally invasive,safe,and effective endosco...Obesity is a chronic,multifactorial disease closely linked to a spectrum of cardiometabolic disorders,with its global prevalence rising at an alarming rate.In recent years,minimally invasive,safe,and effective endoscopic bariatric therapies have gained significant attention as alternatives to conventional surgical interventions.This review provides a comprehensive overview of various endoscopic weight-loss procedures,evaluating their advantages and limitations in comparison to surgical approaches to assist clinicians in optimizing patientspecific treatment strategies.Endoscopic bariatric therapies,including intragastric balloons,duodenal-jejunal bypass sleeves,endoscopic sleeve gastroplasty,gastric remodeling procedures,and interventions aimed at delaying gastric emptying are systematically reviewed.The efficacy,safety profiles,and clinical applicability are all synthesized.Endoscopic bariatric therapies exhibit distinct advantages and limitations,with varying indications and contraindications.As part of a multidisciplinary approach to obesity management,these procedures should be integrated with lifestyle modifications and nutritional counseling to maximize therapeutic benefits.Future research should focus on the long-term efficacy,safety,and patient-reported outcomes to refine clinical practice and optimize the role of endoscopic interventions in obesity treatment.展开更多
BACKGROUND:Whether lipid-modifying drugs directly impact the outcome of sepsis remains uncertain.Therefore,systematic investigations are needed to explore the potential impact of lipid-related therapies on sepsis outc...BACKGROUND:Whether lipid-modifying drugs directly impact the outcome of sepsis remains uncertain.Therefore,systematic investigations are needed to explore the potential impact of lipid-related therapies on sepsis outcomes and to elucidate the underlying mechanisms involving circulating inflammatory cytokines,which may play critical roles in the pathogenesis of sepsis.This study aimed to utilize drug-target Mendelian randomization to assess the direct causal effects of genetically proxied lipid-modifying therapies on sepsis outcomes.METHODS:First,a two-sample Mendelian randomization study was conducted to validate the causal associations among high-density lipoprotein cholesterol(HDL-C),low-density lipoprotein cholesterol(LDL-C),and sepsis.A subsequent drug-target Mendelian randomization study assessed the direct causal effects of genetical y proxied lipid-modifying therapies on the risk of sepsis,sepsis-related critical care admission,and sepsis-related death.The identified lipid-modifying drug targets were subsequently explored for direct causal relationships with 36 circulating inflammatory cytokines.Finally,enrichment analyses of the identified cytokines were conducted to explore the potential relationships of lipid-modifying drugs with the inflammatory response.RESULTS:Genetically proxied cholesteryl ester transfer protein(CETP) inhibitors were significantly associated with sepsis-related critical care admission(OR=0.84,95% CI [0.74,0.95],P=0.008,) and sepsisrelated death(OR=0.68,95% CI [0.52,0.88],P=0.004).The genetically proxied CETP inhibitors were strongly associated with the levels of 15 circulating inflammatory cytokines.Enrichment analyses indicated that CETP inhibitors may modulate inflammatory cytokines and influence the inflammatory response pathway.CONCLUSION:This study supports a causal effect of genetically proxied CETP inhibitors in reducing the risk of sepsis-related critical care admission and death.These findings suggest that the underlying mechanism may involve the modulation of some circulating inflammatory cytokines,influencing the inflammatory response pathway.展开更多
Respiratory syncytial virus(RSV)is one of the most common viruses leading to lower respiratory tract infections(LRTIs)in children and elderly individuals worldwide.Although significant progress in the prevention and t...Respiratory syncytial virus(RSV)is one of the most common viruses leading to lower respiratory tract infections(LRTIs)in children and elderly individuals worldwide.Although significant progress in the prevention and treatment of RSV infection was made in 2023,with two anti-RSV vaccines and one monoclonal antibody approved by the FDA,there is still a lack of postinfection therapeutic drugs in clinical practice,especially for the pediatric population.In recent years,with an increasing understanding of the pathogenic mechanisms of RSV,drugs and drug candidates,have shown great potential for clinical application.In this review,we categorize and discuss promising anti-RSV drug candidates that have been in preclinical or clinical development over the last five years.展开更多
Objective:This study explores the mechanism and clinical efficacy of combined external therapies of traditional Chinese medicine(such as moxibustion,acupoint application,etc.)in intervening renal Yang deficiency hyper...Objective:This study explores the mechanism and clinical efficacy of combined external therapies of traditional Chinese medicine(such as moxibustion,acupoint application,etc.)in intervening renal Yang deficiency hypertension through regulating the renin-angiotensin-aldosterone system(RASS).Methods:Sixty-one patients with renal Yang deficiency hypertension admitted to the hospital were selected as the study subjects.They were divided into a Western medicine combined with external therapies of traditional Chinese medicine group(n=30)and a conventional Western medicine treatment group(n=31)based on a random number table method.The enrollment information,blood pressure changes,and differences in aldosterone,angiotensin II,and renin activity during follow-up were compared between the two groups.Results:There were no statistically significant differences in gender,past history,pre-study medication,hypertension grading,aldosterone,angiotensin II,renin activity levels,and blood pressure between the two groups at baseline(P>0.05).Aldosterone,angiotensin II,and renin activity levels were significantly reduced in both groups after treatment compared to pre-treatment levels.Moreover,the aldosterone,angiotensin II,and renin activity levels in the Western medicine combined with external therapies of traditional Chinese medicine group were significantly lower than those in the conventional Western medicine treatment group,with statistically significant differences(P<0.05).Conclusion:Western medicine combined with external therapies of traditional Chinese medicine may regulate the RASS system through multiple targets,restoring renal Yang Qi transformation function and providing a new strategy for the integrated treatment of renal Yang deficiency hypertension with Chinese and Western medicine.展开更多
In the contemporary medical landscape,the burgeoning interest in natural therapies,particularly for managing gastrointestinal disorders,has brought traditional Chinese medicine(TCM)to the forefront.This article explai...In the contemporary medical landscape,the burgeoning interest in natural therapies,particularly for managing gastrointestinal disorders,has brought traditional Chinese medicine(TCM)to the forefront.This article explains the core principles and clinical applications of TCM in treating these conditions,furthering the discourse through an examination of integrated TCM strategies,as demonstrated in the study by Zhou et al.While TCM has shown promising clinical outcomes,it encounters significant hurdles in standardization,mechanistic research,and clinical validation.Future investigations should aim to solidify the scientific underpinnings of TCM and expand its use in gastrointestinal disease management,striving for a seamless fusion of traditional and contemporary medical practices.展开更多
In recent years,the progression of stem cell therapies has shown great promise in advancing the nascent field of regenerative medicine.Considering the non-regenerative nature of the mature central nervous system,the c...In recent years,the progression of stem cell therapies has shown great promise in advancing the nascent field of regenerative medicine.Considering the non-regenerative nature of the mature central nervous system,the concept that“blank”cells could be reprogrammed and functionally integrated into host neural networks remained intriguing.Previous work has also demonstrated the ability of such cells to stimulate intrinsic growth programs in post-mitotic cells,such as neurons.While embryonic stem cells demonstrated great potential in treating central nervous system pathologies,ethical and technical concerns remained.These barriers,along with the clear necessity for this type of treatment,ultimately prompted the advent of induced pluripotent stem cells.The advantage of pluripotent cells in central nervous system regeneration is multifaceted,permitting differentiation into neural stem cells,neural progenitor cells,glia,and various neuronal subpopulations.The precise spatiotemporal application of extrinsic growth factors in vitro,in addition to microenvironmental signaling in vivo,influences the efficiency of this directed differentiation.While the pluri-or multipotency of these cells is appealing,it also poses the risk of unregulated differentiation and teratoma formation.Cells of the neuroectodermal lineage,such as neuronal subpopulations and glia,have been explored with varying degrees of success.Although the risk of cancer or teratoma formation is greatly reduced,each subpopulation varies in effectiveness and is influenced by a myriad of factors,such as the timing of the transplant,pathology type,and the ratio of accompanying progenitor cells.Furthermore,successful transplantation requires innovative approaches to develop delivery vectors that can mitigate cell death and support integration.Lastly,host immune responses to allogeneic grafts must be thoroughly characterized and further developed to reduce the need for immunosuppression.Translation to a clinical setting will involve careful consideration when assessing both physiologic and functional outcomes.This review will highlight both successes and challenges faced when using human induced pluripotent stem cell-derived cell transplantation therapies to promote endogenous regeneration.展开更多
Use of immunomodulating agents to prevent the progression of autoimmuneβ-cell damage leading to type 1 diabetes mellitus(T1DM)is an interesting area for research.These include non-specific anti-inflammatory agents,im...Use of immunomodulating agents to prevent the progression of autoimmuneβ-cell damage leading to type 1 diabetes mellitus(T1DM)is an interesting area for research.These include non-specific anti-inflammatory agents,immunologic vaccination and anti-inflammatory agents targeting specific immune cells or cytokines.Teplizumab is an anti-CD3-molecule that binds to and leads to the disappearance of the CD3/TCR complex and rendering the T cell anergic to its target antigen.Preclinical and clinical trials have demonstrated its efficacy in reducing the decline in serum C-peptide levels and the need for insulin therapy if used early in the disease process of T1DM.The benefits have been apparent as early as six months to as long as seven years after therapy.It has recently been approved by the Food and Drug Administration to delay the onset of clinical(stage 3)type 1 diabetes in children above 8 years of age.In their recent metaanalysis published in the World Journal of Diabetes,Ma et al found that those in the teplizumab treatment group have a greater likelihood of reduction in insulin use,change in C-peptide response,and better glycemic control compared to the control group with a good safety profile.However,all the included randomized control trials have been conducted in high-income countries.High cost of therapy and unknown utility of the molecule in stage 3 disease limit its widespread use.展开更多
The integration of advanced diagnostic and therapeutic capabilities in oncology has given rise to phototheranostics,a field that combines the precision of imaging with the selectivity of light-activated treatments.Due...The integration of advanced diagnostic and therapeutic capabilities in oncology has given rise to phototheranostics,a field that combines the precision of imaging with the selectivity of light-activated treatments.Due to their pronounced near-infrared(NIR)absorption,tunable molecular structures,and commendable stability,organic photovoltaic non-fullerene acceptors(NFAs)represent a promising frontier in cancer management.Despite the great potential of NFAs in phototheranostics,there is currently a lack of systematic reviews in this field.This review provides a meticulous examination of the current state of NFAs in the field of phototheranostics,highlighting the strategic approaches to spectral red-shifting that enhance tissue penetration and therapeutic efficacy.It dissects the link between molecular architecture and performance across key therapeutic and diagnostic modalities,including photothermal therapy(PTT),photodynamic therapy(PDT),and fluorescence imaging(FLI).In addition,the review presents a concise analysis of the challenges and milestones in the clinical translation of NFAs,offering insights into the innovations required to overcome existing barriers.展开更多
Parkinson’s disease is a complex,progressive neurodegenerative disorder primarily characterized by the degeneration of dopaminergic neurons in the substantia nigra,leading to motor and non-motor symptoms.While sympto...Parkinson’s disease is a complex,progressive neurodegenerative disorder primarily characterized by the degeneration of dopaminergic neurons in the substantia nigra,leading to motor and non-motor symptoms.While symptomatic treatments such as levodopa and monoamine oxidase-B inhibitors offer short-term relief,they do not halt disease progression.In recent years,significant advances have been made in understanding the molecular mechanisms underlying Parkinson’s disease,including alpha-synuclein aggregation,mitochondrial dysfunction,neuroinflammation,and lysosomal impairment.These insights have spurred the development of targeted therapeutic strategies aimed at modifying disease progression.This review comprehensively explores emerging approaches such as gene and cell therapies,LRRK2 inhibitors,alpha-synuclein immunotherapy,and gut microbiota modulation.We also discuss the therapeutic potential of mitophagy activators,digital biomarkers,and neuromodulation techniques.Each therapeutic strategy is critically evaluated in the context of underlying pathophysiological mechanisms.Special attention is given to recent clinical trials(2023–2025),translational gaps,and the potential of personalized medicine in Parkinson’s disease management.Furthermore,we examine the integration of multi-omics data and digital tools in advancing precision therapeutics.Overall,this review highlights current challenges and future prospects in the journey toward disease-modifying interventions that move beyond symptomatic relief.展开更多
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 grants from the German Research Foundation (DFG)
文摘Chronic,non-healing wounds represent a significant challenge for healthcare systems worldwide,often requiring significant human and financial resources.Chronic wounds arise from the complex interplay of underlying comorbidities,such as diabetes or vascular diseases,lifestyle factors,and genetic risk profiles which may predispose extremities to local ischemia.Injuries are further exacerbated by bacterial colonization and the formation of biofilms.Infection,consequently,perpetuates a chronic inflammatory microenvironment,preventing the progression and completion of normal wound healing.The current standard of care(SOC)for chronic wounds involves surgical debridement along with localized wound irrigation,which requires inpatient care under general anesthesia.This could be followed by,if necessary,defect coverage via a reconstructive ladder utilizing wound debridement along with skin graft,local,or free flap techniques once the wound conditions are stabilized and adequate blood supply is restored.To promote physiological wound healing,a variety of approaches have been subjected to translational research.Beyond conventional wound healing drugs and devices that currently supplement treatments,cellular and immunotherapies have emerged as promising therapeutics that can behave as tailored therapies with cell-or molecule-specific wound healing properties.However,in contrast to the clinical omnipresence of chronic wound healing disorders,there remains a shortage of studies condensing the current body of evidence on cellular therapies and immunotherapies for chronic wounds.This review provides a comprehensive exploration of current therapies,experimental approaches,and translational studies,offering insights into their efficacy and limitations.Ultimately,we hope this line of research may serve as an evidence-based foundation to guide further experimental and translational approaches and optimize patient care long-term.
文摘[Objectives]This meta-analysis evaluated the efficacy of Traditional Chinese Medicine(TCM)manual therapies(Tuina,Daoyin,acupotomology)for idiopathic scoliosis(IS),with dual focus on radiographic outcomes(Cobb angle,vertebral rotation)and patient-centered metrics(pain,disability,quality of life).[Methods]This study systematically searched PubMed,Cochrane Library,EMBASE,Web of Science,CNKI,Wanfang,and VIP databases(from inception to July 2025)for randomized controlled trials(RCTs)comparing TCM manual therapies against controls(bracing,exercise,sham,or no intervention).Two reviewers independently extracted data and assessed methodological quality using the PEDro scale.Meta-analyses employed random-effects models(Stata 18)to calculate Hedges'g with 95%confidence intervals(CI).Heterogeneity was quantified via I 2 statistics,and subgroup analyses examined intervention types(standalone versus combined)and control groups.[Results]Radiographic outcomes:TCM therapies significantly reduced Cobb angle(Hedges'g=-0.93;95%CI:-1.37,-0.49;p<0.001)and vertebral torsion rotation(VTR;g=-0.71;95%CI:-0.91,-0.51;p<0.001)versus controls;patient-centered outcomes:substantial pain reduction(VAS:g=-1.47;95%CI:-2.64,-0.30;p=0.01)and disability improvement(ODI:g=-1.10;95%CI:-1.57,-0.64;p<0.001)were observed.Quality of life(SRS-22)showed non-significant gains(g=2.01;95%CI:-0.43,4.45;p=0.11).[Conclusions]TCM manual therapies significantly improve spinal alignment and reduce pain/disability in IS patients,particularly when integrated with exercise regimens.While results support their role as complementary interventions,standardization of protocols and long-term efficacy studies are needed for clinical implementation.
文摘BACKGROUND Autoimmune hepatitis(AIH)is typically treated with immunomodulators and steroids.However,some patients are refractory to these treatments,necessitating alternative approaches.Biological therapies have recently been explored for these difficult cases.AIM To assess the efficacy and safety of biologics in AIH,focusing on patients unresponsive to standard treatments and evaluating outcomes such as serological markers and histological remission.METHODS A case-based systematic review was performed following the PRISMA protocol to evaluate the efficacy and safety of biological therapies in AIH.The primary focus was on serological improvement and histological remission.The secondary focus was on assessing therapy safety and additional outcomes.A standardized search command was applied to MEDLINE,EMBASE,and Cochrane Library databases to identify relevant studies.Inclusion criteria encompassed adult AIH patients treated with biologics.Data were analyzed based on demographics,prior treatments,and therapy-related outcomes.A narrative synthesis was employed to address biases and provide a comprehensive overview of the evidence.RESULTS A total of 352 studies were reviewed,with 30 selected for detailed analysis.Key findings revealed that Belimumab led to a favourable response in five out of eight AIH patients across two studies.Rituximab demonstrated high efficacy,with 41 out of 45 patients showing significant improvement across six studies.Basiliximab was assessed in a single study,where the sole patient treated experienced a beneficial outcome.Additionally,a notable number of AIH cases were induced by anti-tumor necrosis factor(TNF)medications,including 16 cases associated with infliximab and four cases with adalimumab.All these cases showed improvement upon withdrawal of the biologic agent.CONCLUSION Belimumab and Rituximab show promise as effective alternatives for managing refractory AIH,demonstrating significant improvements in clinical outcomes and liver function.However,the variability in patient responses to different therapies highlights the need for personalized treatment strategies.The risk of AIH induced by anti-TNF therapies underscores the need for vigilant monitoring and prompt symptom recognition.These findings support the incorporation of biologic agents into AIH treatment protocols,particularly for patients who do not respond to conventional therapies.
基金supported by the program of Guangdong Provincial Clinical Research Center for Rehabilitation Medicine(2023B110003)the Research Foundation of Traditional Chinese Medicine Bureau of Guangdong Province(20231,067)the Guangdong Hopson-Pearl River Education Development Foundation(No.H20190116202012724).
文摘Introduction:Current international guidelines encourage cancer patients to engage in physical activity and recommend mind-body therapies(MBTs)as a method for treating cancer-related pain(CRP).However,the most effective MBTs for improving CRP in this population remain unknown.Therefore,this network meta-analysis(NMA)aimed to assess and rank the relative efficacy of different MBTs for CRP,and to conduct subgroup analyses according to different cancer types and stages of treatment.Content:Eight electronic databases were searched for randomized controlled trials(RCTs)that compared differentMBTs to improve pain in adults living with cancer.RCTs were evaluated using the Cochrane risk of bias tool.A random effects network meta-analysis was performed within a frequentist framework.Of the 4,916 articles retrieved and screened against the selection criteria.36 studies with a total 2,387 participants were eligible to be included in the analysis.Qigong demonstrated significantly greater effects than Usual care(standardized mean difference[SMD]-0.85,95% confidence interval[CI]-1.46 to -0.24),Waitlist(SMD−0.93,-1.77 to -0.08),and Massage(SMD-1.71,-3.20 to -0.23),with the highest surface under the cumulative ranking value of 86.5%,was ranked first.It was preceded by Conventional exercise(75.2%),Taichi(74.9%),with Massage having the lowest rank(7.2%).In a subgroup analysis of breast cancer,Taichi(89.6%),Conventional exercise(68.4%),and Pilates(68.3%)ranked as the top three.Summary and outlook:This network meta-analysis indicates that Qigong and Tai Chi are among the most effective mind–body therapies(MBTs)for managing cancer-related pain and may serve as complementary adjuvant treatments for patients with cancer.
文摘BACKGROUND Anemia is a prevalent and challenging complication in patients with hematologic and solid malignancies,which stems from the direct effects of malignancy,treatment-induced toxicities,and systemic inflammation.It affects patients’survival,functional status,and quality of life profoundly.Recent literature has highlighted the emerging role of the gut microbiome in the pathogenesis of cancer-associated anemia.The gut microbiota,through its intricate interplay with iron metabolism,inflammatory pathways,and immune modulation,may either exacerbate or ameliorate anemia depending on its composition,and functional integrity.Dysbiosis,characterized by disruption in the gut microbial ecosystem,is very common in cancer patients.This microbial imbalance is implicated in anemia causation through diminished iron absorption,persistent low-grade inflammation,and suppression of erythropoiesis.AIM To consolidate current evidence regarding the interplay between gut microbiome and anemia in the setting of malignancies.It aims to provide a detailed exploration of the mechanistic links between dysbiosis and anemia,identifies unique challenges associated with various cancer types,and evaluates the efficacy of microbiome-focused therapies.Through this integrative approach,the review seeks to establish a foundation for innovative clinical strategies aimed at mitigating anemia and improving patient outcomes in oncology.METHODS A literature search was performed using multiple databases,including Google Scholar,PubMed,Scopus,and Web of Science,using a combination of keywords and Boolean operators to refine results.Keywords included“cancerassociated anemia”,“gut microbiome”,“intestinal microbiota”,“iron metabolism”,“gut dysbiosis”,“short-chain fatty acids”,“hematopoiesis”,“probiotics”,“prebiotics”,and“fecal microbiota transplantation”.Articles published in English between 2000 and December 2024 were included,with a focus on contemporary and relevant findings.RESULTS Therapeutic strategies aimed at restoration of gut microbial homeostasis,such as probiotics,prebiotics,dietary interventions,and fecal microbiota transplantation(FMT),can inhibit anemia-causing pathways by enhancing microbial diversity,suppressing detrimental flora,reducing systemic inflammation and optimizing nutrient absorption.CONCLUSION Gut dysbiosis causes anemia and impairs response to chemotherapy in cancer patients.Microbiome-centered interventions,such as probiotics,prebiotics,dietary modifications,and FMT,have shown efficacy in restoring microbial balance,reducing inflammation,and enhancing nutrient bioavailability.Emerging approaches,including engineered probiotics and bacteriophage therapies,are promising precision-based,customizable solutions for various microbiome compositions and imbalances.Future research should focus on integrating microbiometargeted strategies with established anemia therapies.
基金supported by the Beijing Natural Science Foundation(7244491)Beijing TCM Science and Technology Development Fund Project(BJZYON-2023-05)+2 种基金Fundamental Research Funds for the Central Public Welfare Research Institutes(ZZ15-YQ-048,ZZ-YQ2023006)Innovation Team and Talents Cultivation Program of National Administration of Traditional Chinese Medicine(ZYYCXTD-D-202409)Science and Technology Innovation Project of the Institute of Acupuncture and Moxibustion,China Academy of Chinese Medical Sciences(CIZJS2025023).
文摘Depression is a prevalent neuropsychiatric disorder characterized by persistent sadness,anhedonia,guilt,fatigue,and impaired concentration.Although pharmacotherapy and psychotherapy can be effective,their utility is limited by adverse effects and significant inter-individual variability.Non-pharmacological therapies from traditional medicine have emerged as promising adjuncts owing to their favorable safety profiles,minimal side effects,and high patient compliance.These therapies,including acupoint stimulation,meditation,and yoga,produce antidepressant effects by reducing neuroinflammation,modulating neurotransmitter release,enhancing neuroplasticity,and regulating the gut-brain axis.This review summarizes clinical applications and mechanistic insights of traditional medicine’s non-pharmacological therapies for depression,providing a scientific rationale for their integration into comprehensive management.
基金supported by grants from National Natural Science Foundation of China(32370892)Science and Technology Commission of Shanghai Municipality(23141901200)+3 种基金Shanghai Natural Science Foundation(24ZR1450100)Health Commission of Shanghai Municipality(2022JC029)Biomaterials and Regenerative Medicine Institute Cooperative Research Project,Shanghai Jiaotong University School of Medicine(2022LHA11)Talent-Introduction Program of Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine(2022YJRC05).
文摘Osteoarthritis(OA)is one of the most common degenerative and age-related diseases in joints,which affects 654 million people worldwide.Current therapies could not fundamentally reverse the pathologic process of OA due to the complex pathogenesis.Although OA mechanisms have been investigated on a large scale over the past decade,the OA pathology correlated with aging-associated changes is still largely unrevealed.Therefore,in-depth analysis of the aging microenvironment and aging-related molecular mechanisms in OA may offer additional strategies for clinical prevention and treatment.In this review,we discuss the potential pathogenesis of OA in light of aging-associated changes and summarize three main components of the aging microenvironment of the OA joint:immune homeostatic imbalance,cellular senescence,and stem cell exhaustion,which could be induced by aging and further exacerbate OA progression.Additionally,it is emphasized that immune homeostatic imbalance appears before established OA,which occurs in the early stage and is the therapeutic window of opportunity for better clinical outcomes.Importantly,we evaluate recent therapeutic targets and promising interventions against these components,as well as the challenges and prospects for precise and individualized therapies of OA patients,which we believe would guide the construction of novel combined strategies targeting aging-related factors against OA for better treatments in the future.
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Extracorporeal therapies have a definite role in patients with acute liver failure,acute on-chronic liver failure,and progressive chronic liver disease.They act as a bridge-to-transplant in these patients.With the increasing success of liver transplantation,the immediate postoperative complication spectrum continues to expand.Extracorporeal therapies can play an important role in managing these complications.However,the literature on extracorporeal therapies in the postliver transplant period is limited.This review article discussed various extracorporeal therapies that are still evolving or marred by limited evidence but can improve patient outcomes.These extracorporeal therapies can be divided into two subgroups:(1)Therapies for infective complications.Endotoxin and cytokine adsorption columns;and(2)Therapies for noninfective complications like small for size syndrome,primary allograft nonfunction,early allograft dysfunction,hyperacute rejection,hepatopulmonary syndrome,etc.(plasma exchange,double plasma molecular adsorption,molecular adsorbent recirculation system,and extracorporeal membrane oxygenation,among others).
基金Supported by National Natural Science Foundation of China,No.81602056 and No.82273393the Young Talents Promotion Project of Shandong Medical Association in 2023,No.2023-GJ-0087.
文摘Obesity is a chronic,multifactorial disease closely linked to a spectrum of cardiometabolic disorders,with its global prevalence rising at an alarming rate.In recent years,minimally invasive,safe,and effective endoscopic bariatric therapies have gained significant attention as alternatives to conventional surgical interventions.This review provides a comprehensive overview of various endoscopic weight-loss procedures,evaluating their advantages and limitations in comparison to surgical approaches to assist clinicians in optimizing patientspecific treatment strategies.Endoscopic bariatric therapies,including intragastric balloons,duodenal-jejunal bypass sleeves,endoscopic sleeve gastroplasty,gastric remodeling procedures,and interventions aimed at delaying gastric emptying are systematically reviewed.The efficacy,safety profiles,and clinical applicability are all synthesized.Endoscopic bariatric therapies exhibit distinct advantages and limitations,with varying indications and contraindications.As part of a multidisciplinary approach to obesity management,these procedures should be integrated with lifestyle modifications and nutritional counseling to maximize therapeutic benefits.Future research should focus on the long-term efficacy,safety,and patient-reported outcomes to refine clinical practice and optimize the role of endoscopic interventions in obesity treatment.
文摘BACKGROUND:Whether lipid-modifying drugs directly impact the outcome of sepsis remains uncertain.Therefore,systematic investigations are needed to explore the potential impact of lipid-related therapies on sepsis outcomes and to elucidate the underlying mechanisms involving circulating inflammatory cytokines,which may play critical roles in the pathogenesis of sepsis.This study aimed to utilize drug-target Mendelian randomization to assess the direct causal effects of genetically proxied lipid-modifying therapies on sepsis outcomes.METHODS:First,a two-sample Mendelian randomization study was conducted to validate the causal associations among high-density lipoprotein cholesterol(HDL-C),low-density lipoprotein cholesterol(LDL-C),and sepsis.A subsequent drug-target Mendelian randomization study assessed the direct causal effects of genetical y proxied lipid-modifying therapies on the risk of sepsis,sepsis-related critical care admission,and sepsis-related death.The identified lipid-modifying drug targets were subsequently explored for direct causal relationships with 36 circulating inflammatory cytokines.Finally,enrichment analyses of the identified cytokines were conducted to explore the potential relationships of lipid-modifying drugs with the inflammatory response.RESULTS:Genetically proxied cholesteryl ester transfer protein(CETP) inhibitors were significantly associated with sepsis-related critical care admission(OR=0.84,95% CI [0.74,0.95],P=0.008,) and sepsisrelated death(OR=0.68,95% CI [0.52,0.88],P=0.004).The genetically proxied CETP inhibitors were strongly associated with the levels of 15 circulating inflammatory cytokines.Enrichment analyses indicated that CETP inhibitors may modulate inflammatory cytokines and influence the inflammatory response pathway.CONCLUSION:This study supports a causal effect of genetically proxied CETP inhibitors in reducing the risk of sepsis-related critical care admission and death.These findings suggest that the underlying mechanism may involve the modulation of some circulating inflammatory cytokines,influencing the inflammatory response pathway.
基金funded by the Beijing Natural Science Foundation(5242007,L222076,L246011)the High-level Public Health Technical Talents Project by the Beijing Municipal Commission of Health(Key discipline personnel-02-05)+1 种基金the CAMS Innovation Fund for Medical Sciences(CIFMS,2019-12M-5-026,2022-I2M-CoV19-006)the Reform and Development of the Beijing Municipal Health Commission,and the Respiratory Research Project of the National Clinical Research Center for Respiratory Diseases(HXZX-202106).
文摘Respiratory syncytial virus(RSV)is one of the most common viruses leading to lower respiratory tract infections(LRTIs)in children and elderly individuals worldwide.Although significant progress in the prevention and treatment of RSV infection was made in 2023,with two anti-RSV vaccines and one monoclonal antibody approved by the FDA,there is still a lack of postinfection therapeutic drugs in clinical practice,especially for the pediatric population.In recent years,with an increasing understanding of the pathogenic mechanisms of RSV,drugs and drug candidates,have shown great potential for clinical application.In this review,we categorize and discuss promising anti-RSV drug candidates that have been in preclinical or clinical development over the last five years.
文摘Objective:This study explores the mechanism and clinical efficacy of combined external therapies of traditional Chinese medicine(such as moxibustion,acupoint application,etc.)in intervening renal Yang deficiency hypertension through regulating the renin-angiotensin-aldosterone system(RASS).Methods:Sixty-one patients with renal Yang deficiency hypertension admitted to the hospital were selected as the study subjects.They were divided into a Western medicine combined with external therapies of traditional Chinese medicine group(n=30)and a conventional Western medicine treatment group(n=31)based on a random number table method.The enrollment information,blood pressure changes,and differences in aldosterone,angiotensin II,and renin activity during follow-up were compared between the two groups.Results:There were no statistically significant differences in gender,past history,pre-study medication,hypertension grading,aldosterone,angiotensin II,renin activity levels,and blood pressure between the two groups at baseline(P>0.05).Aldosterone,angiotensin II,and renin activity levels were significantly reduced in both groups after treatment compared to pre-treatment levels.Moreover,the aldosterone,angiotensin II,and renin activity levels in the Western medicine combined with external therapies of traditional Chinese medicine group were significantly lower than those in the conventional Western medicine treatment group,with statistically significant differences(P<0.05).Conclusion:Western medicine combined with external therapies of traditional Chinese medicine may regulate the RASS system through multiple targets,restoring renal Yang Qi transformation function and providing a new strategy for the integrated treatment of renal Yang deficiency hypertension with Chinese and Western medicine.
基金Supported by the 2023 Government Funded Project of the Outstanding Talents Training Program in Clinical Medicine,No.ZF2023165Key Research and Development Projects of Hebei Province,No.18277731DNatural Science Foundation of Hebei Province,No.H202423105.
文摘In the contemporary medical landscape,the burgeoning interest in natural therapies,particularly for managing gastrointestinal disorders,has brought traditional Chinese medicine(TCM)to the forefront.This article explains the core principles and clinical applications of TCM in treating these conditions,furthering the discourse through an examination of integrated TCM strategies,as demonstrated in the study by Zhou et al.While TCM has shown promising clinical outcomes,it encounters significant hurdles in standardization,mechanistic research,and clinical validation.Future investigations should aim to solidify the scientific underpinnings of TCM and expand its use in gastrointestinal disease management,striving for a seamless fusion of traditional and contemporary medical practices.
基金supported by Ohio State Start Up FundNational Institutes of Health(NIH)+12 种基金Department of Defense(DoD)Wings for Life Spinal Cord Research Foundation,Wings for Life Spinal Cord Research Foundation(Austria)California Institute of Regenerative Medicine(CIRM)International Spinal Research Trust(United Kingdom)Stanford University Bio-X Program Interdisciplinary Initiatives Seed Grant IIP-7Dennis Chan FoundationKlein Family FundLucile Packard Foundation for Children's HealthStanford Institute for Neuro-Innovation and Translational Neurosciences(SINTN)Saunders Family Neuroscience FundJames Doty Neurosurgery FundHearst Neuroscience FundEileen Bond Research Fund(to GP)。
文摘In recent years,the progression of stem cell therapies has shown great promise in advancing the nascent field of regenerative medicine.Considering the non-regenerative nature of the mature central nervous system,the concept that“blank”cells could be reprogrammed and functionally integrated into host neural networks remained intriguing.Previous work has also demonstrated the ability of such cells to stimulate intrinsic growth programs in post-mitotic cells,such as neurons.While embryonic stem cells demonstrated great potential in treating central nervous system pathologies,ethical and technical concerns remained.These barriers,along with the clear necessity for this type of treatment,ultimately prompted the advent of induced pluripotent stem cells.The advantage of pluripotent cells in central nervous system regeneration is multifaceted,permitting differentiation into neural stem cells,neural progenitor cells,glia,and various neuronal subpopulations.The precise spatiotemporal application of extrinsic growth factors in vitro,in addition to microenvironmental signaling in vivo,influences the efficiency of this directed differentiation.While the pluri-or multipotency of these cells is appealing,it also poses the risk of unregulated differentiation and teratoma formation.Cells of the neuroectodermal lineage,such as neuronal subpopulations and glia,have been explored with varying degrees of success.Although the risk of cancer or teratoma formation is greatly reduced,each subpopulation varies in effectiveness and is influenced by a myriad of factors,such as the timing of the transplant,pathology type,and the ratio of accompanying progenitor cells.Furthermore,successful transplantation requires innovative approaches to develop delivery vectors that can mitigate cell death and support integration.Lastly,host immune responses to allogeneic grafts must be thoroughly characterized and further developed to reduce the need for immunosuppression.Translation to a clinical setting will involve careful consideration when assessing both physiologic and functional outcomes.This review will highlight both successes and challenges faced when using human induced pluripotent stem cell-derived cell transplantation therapies to promote endogenous regeneration.
文摘Use of immunomodulating agents to prevent the progression of autoimmuneβ-cell damage leading to type 1 diabetes mellitus(T1DM)is an interesting area for research.These include non-specific anti-inflammatory agents,immunologic vaccination and anti-inflammatory agents targeting specific immune cells or cytokines.Teplizumab is an anti-CD3-molecule that binds to and leads to the disappearance of the CD3/TCR complex and rendering the T cell anergic to its target antigen.Preclinical and clinical trials have demonstrated its efficacy in reducing the decline in serum C-peptide levels and the need for insulin therapy if used early in the disease process of T1DM.The benefits have been apparent as early as six months to as long as seven years after therapy.It has recently been approved by the Food and Drug Administration to delay the onset of clinical(stage 3)type 1 diabetes in children above 8 years of age.In their recent metaanalysis published in the World Journal of Diabetes,Ma et al found that those in the teplizumab treatment group have a greater likelihood of reduction in insulin use,change in C-peptide response,and better glycemic control compared to the control group with a good safety profile.However,all the included randomized control trials have been conducted in high-income countries.High cost of therapy and unknown utility of the molecule in stage 3 disease limit its widespread use.
基金supported by the Natural Science Foundation of Zhejiang Province(Nos.LZ23B040001,LY23E030003 and LY24B030005)the National Natural Science Foundation of China(No.22105222)+1 种基金the Interdisciplinary Research Project of Hangzhou Normal University(No.2024JCXK05)the Jiangsu Key Laboratory of Advanced Functional Polymer Design and Application,Soochow University。
文摘The integration of advanced diagnostic and therapeutic capabilities in oncology has given rise to phototheranostics,a field that combines the precision of imaging with the selectivity of light-activated treatments.Due to their pronounced near-infrared(NIR)absorption,tunable molecular structures,and commendable stability,organic photovoltaic non-fullerene acceptors(NFAs)represent a promising frontier in cancer management.Despite the great potential of NFAs in phototheranostics,there is currently a lack of systematic reviews in this field.This review provides a meticulous examination of the current state of NFAs in the field of phototheranostics,highlighting the strategic approaches to spectral red-shifting that enhance tissue penetration and therapeutic efficacy.It dissects the link between molecular architecture and performance across key therapeutic and diagnostic modalities,including photothermal therapy(PTT),photodynamic therapy(PDT),and fluorescence imaging(FLI).In addition,the review presents a concise analysis of the challenges and milestones in the clinical translation of NFAs,offering insights into the innovations required to overcome existing barriers.
文摘Parkinson’s disease is a complex,progressive neurodegenerative disorder primarily characterized by the degeneration of dopaminergic neurons in the substantia nigra,leading to motor and non-motor symptoms.While symptomatic treatments such as levodopa and monoamine oxidase-B inhibitors offer short-term relief,they do not halt disease progression.In recent years,significant advances have been made in understanding the molecular mechanisms underlying Parkinson’s disease,including alpha-synuclein aggregation,mitochondrial dysfunction,neuroinflammation,and lysosomal impairment.These insights have spurred the development of targeted therapeutic strategies aimed at modifying disease progression.This review comprehensively explores emerging approaches such as gene and cell therapies,LRRK2 inhibitors,alpha-synuclein immunotherapy,and gut microbiota modulation.We also discuss the therapeutic potential of mitophagy activators,digital biomarkers,and neuromodulation techniques.Each therapeutic strategy is critically evaluated in the context of underlying pathophysiological mechanisms.Special attention is given to recent clinical trials(2023–2025),translational gaps,and the potential of personalized medicine in Parkinson’s disease management.Furthermore,we examine the integration of multi-omics data and digital tools in advancing precision therapeutics.Overall,this review highlights current challenges and future prospects in the journey toward disease-modifying interventions that move beyond symptomatic relief.
