The heterogeneity and invasiveness of cancer cells pose serious challenges in cancer diagnosis and treatment.Advancements and innovations in metal-based nanomedicines provide novel avenues for addressing these challen...The heterogeneity and invasiveness of cancer cells pose serious challenges in cancer diagnosis and treatment.Advancements and innovations in metal-based nanomedicines provide novel avenues for addressing these challenges.Metal-based nanomedicines possess unique physicochemical properties that enable their interaction with living organisms,thereby inducing complex biological responses.These nanomaterials have been extensively used to enhance the contrast and sensitivity of cancer imaging and to amplify the distinction between cancerous and healthy tissues.Moreover,these nanomaterials can effectively combat a wide spectrum of cancers through various methods,including drug delivery,radiotherapy,photothermal therapy(PTT),photodynamic therapy(PDT),sonodynamic therapy(SDT),biocatalytic therapy,ion interference therapy(IIT),and immunotherapy.Currently,there is still a need for a comprehensive summary on the metal-based nanomaterials for cancer diagnosis and treatment.Herein,we present a systematic and complete overview of action mechanisms and the applications of metal-based nanomaterials in cancer theranostics.A summary of common strategies for synthesizing and modifying metal-based nanomedicines is presented,and their biosafety is analyzed.Then,the latest developments in their applications for cancer imaging and anticancer treatment are provided.Finally,the key technical challenges and reasonable perspectives of metal-based nanomedicines for cancer theranostics in clinical applications are discussed.展开更多
Background:Although sepsis is known to be the leading cause of morbidity and mortality in adult burn patients,its epidemiology and impact are poorly understood.This study aims to address these gaps by further characte...Background:Although sepsis is known to be the leading cause of morbidity and mortality in adult burn patients,its epidemiology and impact are poorly understood.This study aims to address these gaps by further characterizing predictors of sepsis and comparing outcomes between septic and non-septic burn patients in different age groups.Methods:We included patients(≥18 years)with thermal burn injuries≥5%total body surface area(TBSA)admitted to two burn centers between 1 January 2006 and 30 June 2021,and 1 January 2023 and 6 April 2025.Patients were stratified by age into adults(18-59 years)and older adults(≥60 years),and by diagnosis of sepsis during hospitalization(sepsis vs.control).Demographics,injury characteristics,mortality,and in-hospital complications were assessed.Multivariate logistic regression models were used to identify predictors of sepsis and mortality among septic patients.Results:This study included a total of 1465 patients,including 1094 adults and 371 older adults.Sepsis was diagnosed in 20.1%of adult burn patients,with a median onset at 10 d following injury.Increasing age,greater TBSA,and inhalation injury were identified as significant risk factors for sepsis.Among patients who developed sepsis,earlier onset and female sex were associated with an elevated risk of mortality.In older adults,the incidence of sepsis was 22.9%,with a median onset at 11 d post-burn.The odds of sepsis diagnosis increased with higher TBSA and the presence of inhalation injury.Earlier sepsis onset was associated with increased mortality in older adults.Conclusions:Sepsis represents a significant clinical challenge in burn patients,with age,TBSA,inhalation injury,and comorbidities significantly influencing its incidence and outcomes.Notably,early sepsis onset and female sex are associated with increased mortality,highlighting the need for advanced monitoring,prompt interventions,and the exploration of innovative sex-specific strategies to optimize outcomes in this high-risk population.展开更多
Acute exposure to high altitude can cause acute altitude illnesses and is associated with impaired cognitive and physical performance.The most effective preventive strategies currently recommended include environmenta...Acute exposure to high altitude can cause acute altitude illnesses and is associated with impaired cognitive and physical performance.The most effective preventive strategies currently recommended include environmental acclimatization(slow ascent and/or pre-acclimatization)or pharmacological support of acclimatization using acetazolamide.However,these strategies are not practical for high-altitude exposures that require rapid and unplanned ascent,high physical and mental performance,such as rescue missions or military operations.Dexamethasone and other modulators of the glucocorticoid system take effect quickly and are effective alternatives for preventing acute altitude illnesses when rapidly ascending to high altitudes.As the efficacy of dexamethasone in preventing acute mountain illnesses remains controversial,a review of existing studies on the use of dexamethasone for the prevention of acute mountain sickness was conducted,aiming to determine the best strategy.Possible mechanisms of protection against acute altitude illnesses are discussed based on the results of clinical trials.The data indicate that dexamethasone is most effective at altitudes above 4000 m at doses of 8–16 mg/d.Appropriately designed and powered trials are needed to obtain more evidence-based results on the dosage and timing of dexamethasone administration,and to provide optimized recommendations for the application of this powerful pharmacological tool.展开更多
Background:Cartilage repair remains a considerable challenge in regenerative medicine.Despite extensive research on biomaterials for cartilage repair in recent years,issues such as prolonged repair cycles and suboptim...Background:Cartilage repair remains a considerable challenge in regenerative medicine.Despite extensive research on biomaterials for cartilage repair in recent years,issues such as prolonged repair cycles and suboptimal outcomes persist.Organoids,miniature three-dimensional(3D)tissue structures derived from the directed differentiation of stem or progenitor cells,mimic the structure and function of natural organs.Therefore,the construction of cartilage organoids(COs)holds great promise as a novel strategy for cartilage repair.Methods:This study employed a digital light processing system to perform 3D bioprinting of a DNA-silk fibroin(DNA-SF)hydrogel sustained-release system(DSRGT)with bone-marrow mesenchymal stem cells(BMSCs)to construct millimeter-scale CO.COs at different developmental stages were characterized,and the COs with the best cartilage phenotype were selected for in vivo cartilage repair in a rat articular cartilage defect model.Results:This study developed a DSRGT by covalently grafting glucosamine(which promotes cartilage matrix synthesis)and TD-198946(which promotes chondrogenic differentiation)onto a hydrogel using acrylic acid-polyethylene glycolN-hydroxysuccinimide(AC-PEG-NHS).In vitro,4-week COs exhibited higher SRY-box transcription factor 9(SOX9),typeⅡcollagen(ColⅡ),and aggrecan(ACAN)expression and lower typeⅠcollagen(ColⅠ)and typeⅩcollagen(ColⅩ)expression,indicating that 4 weeks is the optimal culture duration for hyaline cartilage development.In vivo,the mitogen-activated protein kinase(MAPK)signaling pathway was upregulated in 4-week COs,enabling cartilage repair within 8 weeks.Transcriptomic analysis revealed that cartilage regenerated with 4-week COs presented gene expression profiles resembling those of healthy cartilage.Conclusion:This study employs DSRGT to construct COs,providing an innovative strategy for the regeneration of cartilage defects.展开更多
Background:Lumbar disc degeneration(LDD)displays considerable heterogeneity in terms of clinical features and pathological changes.However,researchers have not clearly determined whether the transcriptome variations i...Background:Lumbar disc degeneration(LDD)displays considerable heterogeneity in terms of clinical features and pathological changes.However,researchers have not clearly determined whether the transcriptome variations in LDD could be used to identify or interpret the causes of heterogeneity in clinical features.This study aimed to identify the transcriptomic classification of degenerated discs in LDD patients and whether the molecular subtypes of LDD could be accurately predicted using clinical features.Methods:One hundred and twenty-two nucleus pulposus(NP)tissues from 108 patients were consecutively collected for bulk RNA sequencing(RNA-seq).An unsupervised clustering method was employed to analyze the bulk RNA matrix.Differential analysis was performed to characterize the transcriptional signatures and subtype-specific extracellular matrix(ECM)dysregulation.The cell subpopulation states of each subtype were inferred by integrating bulk and single-cell sequencing datasets.Transwell and dual-luciferase reporter gene assays were employed to investigate possible molecular mechanisms involved.Machine learning algorithm diagnostic prediction models were developed to correlate molecular classification with clinical features.Results:LDD was classified into 4 subtypes with distinct molecular signatures and ECM remodeling:C1 with collagenesis,C2 with ossification,C3 with low chondrogenesis,and C4 with fibrogenesis.Chond1-3 in C1 dominated disc collagenesis via the activation of the mechanosensors TRPV4 and PIEZO1;NP progenitor cells in C2 exhibited chondrogenic and osteogenic phenotypes;Chond1 in C3 was linked to a disrupted hypoxic microenvironment leading to reduced chondrogenesis;Macrophages in C4 played a crucial role in disc fibrogenesis via the secretion of tumor necrosis factor-α(TNF-α).Furthermore,the random forest diagnostic prediction model was proven to have a robust performance[area under the receiver operating characteristic(ROC)curve:0.9312;accuracy:0.84]in stratifying the molecular subtypes of LDD based on 12 clinical features.Conclusions:Our study delineates 4 distinct molecular subtypes of LDD that can be accurately stratified on the basis of clinical features.The identification of these subtypes would facilitate precise diagnostics and guide the development of personalized treatment strategies for LDD.展开更多
The rapid progress of human organoid toolkits presents unprecedented opportunities in disease modeling,drug discovery,and personalized therapy,alongside profound bioethical challenges and concerns.On April 29th,2025,C...The rapid progress of human organoid toolkits presents unprecedented opportunities in disease modeling,drug discovery,and personalized therapy,alongside profound bioethical challenges and concerns.On April 29th,2025,China’s National Science and Technology Ethics Committee(Life Science Ethics Subcommittee)issued the Human Organoid Research Ethical Guidelines[1],establishing the world’s first comprehensive governance framework,especially focusing on brain organoids,embryo models,and chimeric research.This Guidelines represent a pioneering governance model in emerging biotechnology.This commentary offers an in-depth analysis to examine the policy’s innovative three-tiered structure,contrast it with current global regulatory standards,evaluate its domestic impacts as well as potential implications for international biotechnology governance,and provide recommendations for future directions.展开更多
Background:Brain volume measurement serves as a critical approach for assessing brain health status.Considering the close biological connection between the eyes and brain,this study aims to investigate the feasibility...Background:Brain volume measurement serves as a critical approach for assessing brain health status.Considering the close biological connection between the eyes and brain,this study aims to investigate the feasibility of estimating brain volume through retinal fundus imaging integrated with clinical metadata,and to offer a cost-effective approach for assessing brain health.Methods:Based on clinical information,retinal fundus images,and neuroimaging data derived from a multicenter,population-based cohort study,the Kai Luan Study,we proposed a cross-modal correlation representation(CMCR)network to elucidate the intricate co-degenerative relationships between the eyes and brain for 755 subjects.Specifically,individual clinical information,which has been followed up for as long as 12 years,was encoded as a prompt to enhance the accuracy of brain volume estimation.Independent internal validation and external validation were performed to assess the robustness of the proposed model.Root mean square error(RMSE),peak signal-tonoise ratio(PSNR),and structural similarity index measure(SSIM)metrics were employed to quantitatively evaluate the quality of synthetic brain images derived from retinal imaging data.Results:The proposed framework yielded average RMSE,PSNR,and SSIM values of 98.23,35.78 d B,and 0.64,respectively,which significantly outperformed 5 other methods:multi-channel Variational Autoencoder(mcVAE),Pixelto-Pixel(Pixel2pixel),transformer-based U-Net(Trans UNet),multi-scale transformer network(MT-Net),and residual vision transformer(ResViT).The two-(2D)and three-dimensional(3D)visualization results showed that the shape and texture of the synthetic brain images generated by the proposed method most closely resembled those of actual brain images.Thus,the CMCR framework accurately captured the latent structural correlations between the fundus and the brain.The average difference between predicted and actual brain volumes was 61.36 cm~3,with a relative error of 4.54%.When all of the clinical information(including age and sex,daily habits,cardiovascular factors,metabolic factors,and inflammatory factors)was encoded,the difference was decreased to 53.89 cm~3,with a relative error of 3.98%.Based on the synthesized brain magnetic resonance images from retinal fundus images,the volumes of brain tissues could be estimated with high accuracy.Conclusion:This study provides an innovative,accurate,and cost-effective approach to characterize brain health status through readily accessible retinal fundus images.展开更多
Dear Editor,As space exploration transitions from short orbital missions to extended stays on the International Space Station(ISS)and,ultimately,interplanetary travel,astronaut health has emerged as a critical focus.I...Dear Editor,As space exploration transitions from short orbital missions to extended stays on the International Space Station(ISS)and,ultimately,interplanetary travel,astronaut health has emerged as a critical focus.In particular,safeguarding cardiovascular function has become an operational imperative.Yet beyond safeguarding those in orbit,the physiological adaptations observed in microgravity offer a compelling lens through which to examine persistent challenges in terrestrial medicine,from orthostatic intolerance in the elderly to deconditioning in critical care survivors.By studying how the human cardiovascular system functions in the absence of gravity.展开更多
Dear Editor,Systemic sclerosis(SSc)is an autoimmune connective tissue disease in which there are vascular abnormalities,inflammation,and fibrosis[1].These three characteristics primarily affect the skin and lungs.Of a...Dear Editor,Systemic sclerosis(SSc)is an autoimmune connective tissue disease in which there are vascular abnormalities,inflammation,and fibrosis[1].These three characteristics primarily affect the skin and lungs.Of all the autoimmune rheumatic diseases,SSc has the highest all-cause mortality rate,and the underlying pathogenic processes that mediate disease are still obscure,with wide diff erences in presentation and progression[2,3].展开更多
Background:The level of premature deaths(deaths among those aged 30-69 years)caused by cancer is an important indicator of evaluating the level of cancer prevention and control.However,the current burden and temporal ...Background:The level of premature deaths(deaths among those aged 30-69 years)caused by cancer is an important indicator of evaluating the level of cancer prevention and control.However,the current burden and temporal trends in cancer-related premature deaths,and their impact on life expectancy at the global,regional,and national levels are not clear.Methods:Cancer mortality data for 185 countries were obtained from the GLOBOCAN 2022 database.High-quality cancer mortality data and national population statistics for 47 countries were extracted from the United Nations and national cancer registry databases,covering the period 2003-2022.Countries were classified based on the human development index(HDI).The death probability,the year of life lost(YLL),and the potential gain in life expectancy(PGLE)attributable to premature deaths from site-specific and all-cancers combined were calculated.Results:Globally,the probability of premature cancer deaths was 6.49%(95%UI 6.49-6.50).The YLLs caused by cancer-related premature death were 163.86 million(95%UI 163.70-164.03),constituting 65.58%of the total cancer-related YLLs.The PGLEs were 1.16 years(95%UI 1.16-1.16).The premature death probability increased with higher HDI levels in men,but decreased in women.Cancer-related premature deaths as a proportion of total cancer deaths varied from 18.31%(95%UI 18.20-18.43)in Japan to 84.44%(95%UI 76.10-91.16)in São Toméand Príncipe.Lung cancer was the leading cause of cancer-related premature deaths in men,and breast cancer ranked first in women.By eradicating premature deaths attributable to lung,liver,colorectal,and stomach cancer in men,and to breast,cervical,and lung cancer in women,0.55 years(95%UI 0.55-0.55)and 0.49 years(95%UI 0.49-0.49)of PGLEs could be achieved,accounting for 48.67%and 42.24%of the total PGLEs,respectively.Cancer-related premature deaths decreased significantly in 38 countries during 2003-2022(P<0.05).The probability of premature cancer-related deaths decreased by more than 15.50%from 2015 to 2022 in 16 countries.Conclusions:Cancer-related premature deaths declined in many countries,with 16 of them having achieved the expected reduction by 2022.The current burden of cancer-related premature deaths is profound but varies around the world.Eliminating premature deaths from major cancer types could substantially increase life expectancy,underscoring the importance of prevention and treatment efforts for these cancers.展开更多
Background:Antipsychotic-induced movement disorders(AIMDs)are prevalent side effects of antipsychotics,particularly during the acute phase of treatment.This study aimed to elucidate the genetic mechanisms underlying A...Background:Antipsychotic-induced movement disorders(AIMDs)are prevalent side effects of antipsychotics,particularly during the acute phase of treatment.This study aimed to elucidate the genetic mechanisms underlying AIMDs using a genome-wide association study(GWAS).Methods:GWASs on AIMDs were conducted in three independent cohorts:a discovery cohort of 3067 patients(2016 subjects were reserved after quality control),a validation cohort of 277 patients,and a multi-ancestry validation cohort of 766 patients.Subsequent post-GWAS analyses included gene-based analyses,transcriptome-wide association studies(TWASs),and polygenic risk score(PRS)profiling.Results:Our study identified two loci located in RAB44 gene(rs116249243,P=5.98×10^(-9);rs117097482,P=1.17×10^(-8))associated with extrapyramidal symptoms(EPSs),1 locus(rs6826172,P=5.56×10^(-9))related to akathisia,and 76 loci linked to involuntary movements(11 genes were mapped).Risk loci located in CNTNAP2,LUZP2,TMEM167A,and RAB44 genes were successfully replicated in the validation cohort,whereas the locus located in RAB44 was also replicated in the multi-ancestry cohort.Gene-based analyses indicated that XRCC4 and PAIP2B reached significance at the genome-wide level in involuntary movements.Tissue expression analysis revealed that involuntary movement-related genes are predominantly expressed in the substantia nigra.Additionally,the TWAS suggested a causal relationship between XRCC4 and involuntary movement.The PRSs derived from the discovery cohort significantly predicted AIMDs in the validation cohort,with area under the receiver operating characteristic curve(AUC)values from 0.60 to 0.80.Conclusions:Our findings highlight the role of substantia nigra related gene polymorphisms in AIMDs.This study provides novel insights into the pathogenesis of AIMDs and supports the potential for personalized treatment approaches for schizophrenia.展开更多
Despite having multiple treatment options,the overall outcomes,including the survival rates of non-small cell lung cancer(NSCLC)patients,remain relatively low,indicating the need to explore new approaches to achieve i...Despite having multiple treatment options,the overall outcomes,including the survival rates of non-small cell lung cancer(NSCLC)patients,remain relatively low,indicating the need to explore new approaches to achieve improved therapeutic responses.To that end,repurposed drugs such as metformin have been evaluated against many cancer types,including NSCLC.Metformin,a widely used oral hypoglycemic drug for type 2 diabetes,exhibits anticancer properties and synergy with several standards of care agents.In this review,we provide a comprehensive overview of the role and anticancer mechanisms of metformin-based combination approaches for the treatment of NSCLC.We logically discussed the experimental evidence from the in vitro and in vivo studies utilizing metformin alone,and then its combination with chemotherapeutic agents,targeted therapy,and immunotherapy.We also present clinical trials that underscore the beneficial and adverse outcomes of metformin use in combination with targeted therapy and chemotherapeutic agents,and emphasize the limitations and challenges for the treatment of diabetic and nondiabetic NSCLC patients.It appears that,regardless of the diverse anticancer mechanisms of this biguanide,the benefits may be confined to a specific patient subgroup,which opens new avenues to be explored for NSCLC treatment.展开更多
Tendon-related diseases(TRDs)are increasingly common in the current aging society and impose a significant burden on patients.Despite therapeutic advances,the pathophysiology of TRDs remains poorly understood,hinderin...Tendon-related diseases(TRDs)are increasingly common in the current aging society and impose a significant burden on patients.Despite therapeutic advances,the pathophysiology of TRDs remains poorly understood,hindering effective clinical management.The macrophages are highly plastic immune cells involved in the maintenance of in vivo homeostasis and the injury-healing process.Their dual role in TRDs has been widely investigated,either promoting tenogenic and chondrogenic differentiation or amplifying inflammatory response,underscoring their therapeutic potential for TRDs treatment.Therefore,the review aims to summarize the roles of macrophages in the healing of TRDs,characterized by limited regenerative capacity,and examine strategies for the modulation of macrophage phenotypes to accelerate the regeneration process.Finally,we review applications involving macrophage modulation within the context of tissue engineering of TRDs,providing novel insights for the design of biomaterials-based targeted delivery systems.展开更多
Immunotherapy for cardiovascular diseases(CVDs)holds great promise for precision management by modulating localized immune-inflammatory responses.The interplay between focal cardiovascular pathology and panvascular di...Immunotherapy for cardiovascular diseases(CVDs)holds great promise for precision management by modulating localized immune-inflammatory responses.The interplay between focal cardiovascular pathology and panvascular disease,necessitates highly integrated therapeutic strategies.Nano-technology-based theranostic platforms address this challenge by enabling both regulation and real-time imaging of immune cell activity within cardiovascular lesions.These functional nanotherapy systems not only halt disease progression at pathological sites but also reduce secondary cardiovascular events driven by shared inflammatory mechanisms.Additionally,nanoplatform-based dynamic visualization of immune cell responses facilitates adaptive,personalized interventions.This review introduces the role of immune cells in CVDs.It summarizes recent advances in nanomaterial-based immunomodulation strategies,including mechanisms of immune regulation,enhanced imaging,and therapeutic applications in atherosclerosis,myocardial infarction,ischemic stroke,abdominal aortic aneurysm,and myocarditis.Collectively,this integrated nanotheranostic paradigm establishes a robust foundation for the next generation of cardiovascular precision medicine.展开更多
Background:Most sepsis patients develop sepsis-associated acute kidney injury(SA-AKI),which poses a significant threat to survival and lacks specific treatment.To date,there are no published randomized controlled tria...Background:Most sepsis patients develop sepsis-associated acute kidney injury(SA-AKI),which poses a significant threat to survival and lacks specific treatment.To date,there are no published randomized controlled trials that have established a link between albumin use and SA-AKI development in sepsis.Therefore,it is unclear whether albumin use may influence the risk of SA-AKI.Methods:The present study employed a target trial emulation using observational data to track adult sepsis patients initially admitted to the intensive care unit at Beth Israel Deaconess Medical Center,Boston,Massachusetts,for a period of 7 d from 2008 to 2022.Immortal time bias was controlled using the clone-censor-weight(CCW)method,along with a new-user design to address current user bias.The exposure variable was the early administration of albumin following the onset of sepsis.Based on albumin use,patients were classified into two groups:the albumin group(n=27,088)and the no albumin group(n=27,088).The primary outcome was the development of SA-AKI,and the secondary outcome was 7-day all-cause mortality.The primary outcome was analyzed using competing risk analyses.Furthermore,sensitivity and subgroup analyses were also performed.Results:Among the 27,088 patients analyzed,albumin administration was associated with a significantly higher SA-AKI risk(relative difference=3.47%,95%CI 1.76-5.23)compared to non-administration.There was no clinically meaningful difference in 7-day survival(relative difference=0.05%,95%CI-2.30 to 2.45).Sensitivity analyses consistently supported these results.All these analyses were conducted on data that were collected after CCW.Conclusions:Early albumin administration may increase the risk of SA-AKI in sepsis patients without conferring a short-term survival benefit.These results underscore the need for a rigorous risk-benefit assessment when incorporating albumin into sepsis resuscitation protocols and highlight the need for further clinical validation.However,it is important to exercise caution when interpreting the conclusions of this study,given its exploratory and preliminary nature.展开更多
Antipsychotics,especially many second-generation antipsychotics(SGAs),remain central to schizophrenia treatment,are indispensable in acute mania and for bipolar maintenance(with selected roles in bipolar depression),a...Antipsychotics,especially many second-generation antipsychotics(SGAs),remain central to schizophrenia treatment,are indispensable in acute mania and for bipolar maintenance(with selected roles in bipolar depression),and serve as evidence-based augmenters in treatment-resistant depression.Nonetheless,acute antipsychotic-induced movement disorders(AIMDs)[extrapyramidal symptoms(EPS)]are common and clinically costly,impairing quality of life,adherence,and outcomes.The acute spectrum is dominated by dystonia(sustained,often painful contractions).展开更多
Background:Repetitive mild traumatic brain injury(rmTBI)is a significant risk factor for neurodegeneration,characterized by pathological protein deposition and persistent neuroinflammation.Research has observed increa...Background:Repetitive mild traumatic brain injury(rmTBI)is a significant risk factor for neurodegeneration,characterized by pathological protein deposition and persistent neuroinflammation.Research has observed increased interleukin-33(IL-33)levels in the peripheral blood of patients with rmTBI,suggesting IL-33 may participate in regulating the pathological development of rmTBI.The study aims to elucidate the impact and mechanism of IL-33 in the progression of neuropathology following rmTBI,and to explore its potential as a therapeutic target to improve the neurological outcome.Methods:The study employed an rmTBI mouse model using the wild-type(WT)and IL-33 knockout mice.Cognitive function was assessed via the Y-maze and Barnes tests.The main cell type expressing IL-33 and its receptor,suppression of tumorigenicity 2(ST2),was then investigated in the mouse brain through immunofluorescence colocalization.As the primary neural cell responsible for ST2 expression,microglia were studied in vitro using the BV2 cell line.The effects of lipid droplets(LDs)accumulation and amyloid-beta(Aβ)phagocytosis were measured to elucidate the impact of IL-33 on BV2 cells'phagocytosis.Additionally,HT22 neuronal apoptosis was assessed by flow cytometry.Finally,the cognitive effects of intranasal administration of IL-33 were evaluated in mice.Results:IL-33 KO mice exhibited pronounced cognitive impairment after rmTBI.In the mouse brain,astrocytes were identified as the primary source of IL-33 secretion,while microglia predominantly expressed ST2.Transcriptome sequencing revealed that IL-33 significantly influenced phagocytosis function.IL-33 mitigated LDs accumulation in BV2 cells and enhanced Aβphagocytosis in vitro.In addition,the culture medium of BV2 cells with activated IL-33/ST2 signaling reduced HT22 neuronal apoptosis and axonal damage.Furthermore,intranasal administration of IL-33 was observed to be effective in alleviating neurodegeneration and cognitive outcome of rmTBI mice.Conclusions:Dysfunction of the IL-33/ST2 axis following rmTBI leads to cognitive dysfunction via impairing microglial phagocytosis capacity and promoting neuronal damage.IL-33 would be a promising therapeutic target for alleviating neurodegeneration following rmTBI.展开更多
Background:Sudden cardiac death(SCD)accounts for more than half of all sudden death cases,posing a significant health burden in China.However,epidemiological data on SCD are scarce due to the lack of a central data re...Background:Sudden cardiac death(SCD)accounts for more than half of all sudden death cases,posing a significant health burden in China.However,epidemiological data on SCD are scarce due to the lack of a central data registry and the heterogeneity of case definitions.This study aims to provide reliable estimates of the incidence and risk factors of SCD in China at the national and regional levels from 2013 to 2021,as well as the current status of prevention.Methods:The multi-cause mortality data from 2013 to 2021 were obtained from the National Mortality Surveillance System of China.Deaths related to cardiac arrest were identified.Crude and age-standardized mortality rates(ASMR)were calculated by time,and region.Joint point regression was applied to identify significant changes during the study period.Subgroup analyses and multilevel negative binomial analysis were performed to understand the SCD risk factors.The first-line prevention measures and their current implementation in China and developed countries were also determined from published articles.Results:From 2013 to 2021,the crude mortality rate of sudden cardiac arrest increased markedly from 8.36 deaths per 100,000 population in 2013 to 18.59 deaths per 100,000 population in 2021.There were considerable differences among regions.Subgroup analysis and negative binomial regression results indicated that males and the elderly were at higher risk of SCD.SCD may be associated with poor medical conditions.More than half of SCDs occurred outside hospitals,and approximately 60%of SCDs were related to ischemic heart disease as the underlying cause.Currently,developed countries have widely adopted primary prevention and emergency treatment measures;however,the utilization rate of such measures in China is relatively low and should be improved.Conclusions:With the continuous rise in the prevalence of cardiovascular diseases and their related risk factors in China,the burden of SCD is expected to increase.In addition to strengthening the clinical pathways for sudden cardiac arrest cases in pre-hospital and hospital settings,it is also necessary to enhance public awareness,knowledge and first-line practical training through large-scale policies for governmental and community-based projects.展开更多
Aldehyde dehydrogenase 2(ALDH2),a mitochondrial enzyme,is the main acetaldehyde dehydrogenase involved in the scavenging of alcohol-derived acetaldehyde and endogenous aldehydes.The ALDH2^(rs671)mutation affects 560 m...Aldehyde dehydrogenase 2(ALDH2),a mitochondrial enzyme,is the main acetaldehyde dehydrogenase involved in the scavenging of alcohol-derived acetaldehyde and endogenous aldehydes.The ALDH2^(rs671)mutation affects 560 million East Asians and is closely related to an increased risk of various human diseases.In addition to its well-known function in detoxifying alcohol-derived acetaldehyde and endogenous aldehydes,ALDH2 is implicated in human health through its regulation of autophagic machinery and multiple cell death pathways(e.g.,apoptosis,necroptosis,pyroptosis,ferroptosis,and NETosis).This review summarizes the current knowledge of ALDH2 and the regulatory mechanism through which ALDH2 regulates autophagy and cell death.In addition,we outline the potential role of ALDH2 in the regulation of autophagy and cell death during the occurrence and progression of human diseases,aiming to provide a novel theoretical framework for human disease treatment.展开更多
Dear Editor,The National Health Commission(NHC)of China has championed the creation of weight management clinics to confront the growing crisis of overweight and obesity.Forecasts indicate that by 2030,the prevalence ...Dear Editor,The National Health Commission(NHC)of China has championed the creation of weight management clinics to confront the growing crisis of overweight and obesity.Forecasts indicate that by 2030,the prevalence of these conditions among Chinese adults and children could climb to 70.5%and 31.8%,respectively[1].This troubling trajectory,alongside an increasing burden of chronic illnesses such as diabetes,hypertension,and cardiovascular diseases,underscores the need for immediate action.Instead of focusing solely on weight management clinics,we propose that medical institutions prioritize the establishment of comprehensive chronic disease management clinics,building upon the foundation of weight management clinics to holistically address obesity,aging,and healthcare system challenges.展开更多
基金supported by the National Natural Science Foundation of China(82071981)the Program of Youth Science and Technology Innovation and Entrepreneurship Outstanding Talents(Team)of Jilin Province,China(20230508063RC)+3 种基金the Excellent Youth Training Foundation of Jilin University,China(419080520665)the Innovation and Entrepreneurship Talent Funding Program of Jilin Province,Chinathe Health Special Project of the Finance Department of Jilin Province,Chinathe Graduate Innovation Fund of Jilin University,China(2025CX297)。
文摘The heterogeneity and invasiveness of cancer cells pose serious challenges in cancer diagnosis and treatment.Advancements and innovations in metal-based nanomedicines provide novel avenues for addressing these challenges.Metal-based nanomedicines possess unique physicochemical properties that enable their interaction with living organisms,thereby inducing complex biological responses.These nanomaterials have been extensively used to enhance the contrast and sensitivity of cancer imaging and to amplify the distinction between cancerous and healthy tissues.Moreover,these nanomaterials can effectively combat a wide spectrum of cancers through various methods,including drug delivery,radiotherapy,photothermal therapy(PTT),photodynamic therapy(PDT),sonodynamic therapy(SDT),biocatalytic therapy,ion interference therapy(IIT),and immunotherapy.Currently,there is still a need for a comprehensive summary on the metal-based nanomaterials for cancer diagnosis and treatment.Herein,we present a systematic and complete overview of action mechanisms and the applications of metal-based nanomaterials in cancer theranostics.A summary of common strategies for synthesizing and modifying metal-based nanomedicines is presented,and their biosafety is analyzed.Then,the latest developments in their applications for cancer imaging and anticancer treatment are provided.Finally,the key technical challenges and reasonable perspectives of metal-based nanomedicines for cancer theranostics in clinical applications are discussed.
基金a grant from the National Institute of Health (R01AG080040-01A1).
文摘Background:Although sepsis is known to be the leading cause of morbidity and mortality in adult burn patients,its epidemiology and impact are poorly understood.This study aims to address these gaps by further characterizing predictors of sepsis and comparing outcomes between septic and non-septic burn patients in different age groups.Methods:We included patients(≥18 years)with thermal burn injuries≥5%total body surface area(TBSA)admitted to two burn centers between 1 January 2006 and 30 June 2021,and 1 January 2023 and 6 April 2025.Patients were stratified by age into adults(18-59 years)and older adults(≥60 years),and by diagnosis of sepsis during hospitalization(sepsis vs.control).Demographics,injury characteristics,mortality,and in-hospital complications were assessed.Multivariate logistic regression models were used to identify predictors of sepsis and mortality among septic patients.Results:This study included a total of 1465 patients,including 1094 adults and 371 older adults.Sepsis was diagnosed in 20.1%of adult burn patients,with a median onset at 10 d following injury.Increasing age,greater TBSA,and inhalation injury were identified as significant risk factors for sepsis.Among patients who developed sepsis,earlier onset and female sex were associated with an elevated risk of mortality.In older adults,the incidence of sepsis was 22.9%,with a median onset at 11 d post-burn.The odds of sepsis diagnosis increased with higher TBSA and the presence of inhalation injury.Earlier sepsis onset was associated with increased mortality in older adults.Conclusions:Sepsis represents a significant clinical challenge in burn patients,with age,TBSA,inhalation injury,and comorbidities significantly influencing its incidence and outcomes.Notably,early sepsis onset and female sex are associated with increased mortality,highlighting the need for advanced monitoring,prompt interventions,and the exploration of innovative sex-specific strategies to optimize outcomes in this high-risk population.
文摘Acute exposure to high altitude can cause acute altitude illnesses and is associated with impaired cognitive and physical performance.The most effective preventive strategies currently recommended include environmental acclimatization(slow ascent and/or pre-acclimatization)or pharmacological support of acclimatization using acetazolamide.However,these strategies are not practical for high-altitude exposures that require rapid and unplanned ascent,high physical and mental performance,such as rescue missions or military operations.Dexamethasone and other modulators of the glucocorticoid system take effect quickly and are effective alternatives for preventing acute altitude illnesses when rapidly ascending to high altitudes.As the efficacy of dexamethasone in preventing acute mountain illnesses remains controversial,a review of existing studies on the use of dexamethasone for the prevention of acute mountain sickness was conducted,aiming to determine the best strategy.Possible mechanisms of protection against acute altitude illnesses are discussed based on the results of clinical trials.The data indicate that dexamethasone is most effective at altitudes above 4000 m at doses of 8–16 mg/d.Appropriately designed and powered trials are needed to obtain more evidence-based results on the dosage and timing of dexamethasone administration,and to provide optimized recommendations for the application of this powerful pharmacological tool.
基金supported by the National Key Research and Development Program of China(2022YFB3804300)the National Natural Science Foundation of China(82230071,32471395,82427809,82472479)+2 种基金the Shanghai Science and Technology Innovation Action Plan(23141900600)the Research Physician Training Program of Shanghai Hospital Development Center(SHDC2023CRT013)the Shanghai Municipal Demonstration Project for Innovative Medical Device Applications(23SHS05700)。
文摘Background:Cartilage repair remains a considerable challenge in regenerative medicine.Despite extensive research on biomaterials for cartilage repair in recent years,issues such as prolonged repair cycles and suboptimal outcomes persist.Organoids,miniature three-dimensional(3D)tissue structures derived from the directed differentiation of stem or progenitor cells,mimic the structure and function of natural organs.Therefore,the construction of cartilage organoids(COs)holds great promise as a novel strategy for cartilage repair.Methods:This study employed a digital light processing system to perform 3D bioprinting of a DNA-silk fibroin(DNA-SF)hydrogel sustained-release system(DSRGT)with bone-marrow mesenchymal stem cells(BMSCs)to construct millimeter-scale CO.COs at different developmental stages were characterized,and the COs with the best cartilage phenotype were selected for in vivo cartilage repair in a rat articular cartilage defect model.Results:This study developed a DSRGT by covalently grafting glucosamine(which promotes cartilage matrix synthesis)and TD-198946(which promotes chondrogenic differentiation)onto a hydrogel using acrylic acid-polyethylene glycolN-hydroxysuccinimide(AC-PEG-NHS).In vitro,4-week COs exhibited higher SRY-box transcription factor 9(SOX9),typeⅡcollagen(ColⅡ),and aggrecan(ACAN)expression and lower typeⅠcollagen(ColⅠ)and typeⅩcollagen(ColⅩ)expression,indicating that 4 weeks is the optimal culture duration for hyaline cartilage development.In vivo,the mitogen-activated protein kinase(MAPK)signaling pathway was upregulated in 4-week COs,enabling cartilage repair within 8 weeks.Transcriptomic analysis revealed that cartilage regenerated with 4-week COs presented gene expression profiles resembling those of healthy cartilage.Conclusion:This study employs DSRGT to construct COs,providing an innovative strategy for the regeneration of cartilage defects.
基金supported by the National Natural Science Foundation of China(32270887,82272507,32200654,82430079,and 82472519)the National Key Research and Development Program of China(2022YFA1103202)+7 种基金the Chongqing High-End Medical Talents for Middle-aged and Young(YXGD202408)the Army Scientific and Technological Innovation Talents Prioritized Suppor t Program(2023-124)the Natural Science Foundation of Chongqing(CSTB2023NSCQ-ZDJO008)the Postdoctoral Innovative Talent Support Program(BX20220397)the Open Project of State Key Laboratory of TraumaBurns and Combined Injury(SFLKF202201)the Project for Enhancing Innovation of Army Medical University(2023XJS39)the Talent Innovation Training Program at the Army Medical Center(ZXZYTSYS09)。
文摘Background:Lumbar disc degeneration(LDD)displays considerable heterogeneity in terms of clinical features and pathological changes.However,researchers have not clearly determined whether the transcriptome variations in LDD could be used to identify or interpret the causes of heterogeneity in clinical features.This study aimed to identify the transcriptomic classification of degenerated discs in LDD patients and whether the molecular subtypes of LDD could be accurately predicted using clinical features.Methods:One hundred and twenty-two nucleus pulposus(NP)tissues from 108 patients were consecutively collected for bulk RNA sequencing(RNA-seq).An unsupervised clustering method was employed to analyze the bulk RNA matrix.Differential analysis was performed to characterize the transcriptional signatures and subtype-specific extracellular matrix(ECM)dysregulation.The cell subpopulation states of each subtype were inferred by integrating bulk and single-cell sequencing datasets.Transwell and dual-luciferase reporter gene assays were employed to investigate possible molecular mechanisms involved.Machine learning algorithm diagnostic prediction models were developed to correlate molecular classification with clinical features.Results:LDD was classified into 4 subtypes with distinct molecular signatures and ECM remodeling:C1 with collagenesis,C2 with ossification,C3 with low chondrogenesis,and C4 with fibrogenesis.Chond1-3 in C1 dominated disc collagenesis via the activation of the mechanosensors TRPV4 and PIEZO1;NP progenitor cells in C2 exhibited chondrogenic and osteogenic phenotypes;Chond1 in C3 was linked to a disrupted hypoxic microenvironment leading to reduced chondrogenesis;Macrophages in C4 played a crucial role in disc fibrogenesis via the secretion of tumor necrosis factor-α(TNF-α).Furthermore,the random forest diagnostic prediction model was proven to have a robust performance[area under the receiver operating characteristic(ROC)curve:0.9312;accuracy:0.84]in stratifying the molecular subtypes of LDD based on 12 clinical features.Conclusions:Our study delineates 4 distinct molecular subtypes of LDD that can be accurately stratified on the basis of clinical features.The identification of these subtypes would facilitate precise diagnostics and guide the development of personalized treatment strategies for LDD.
文摘The rapid progress of human organoid toolkits presents unprecedented opportunities in disease modeling,drug discovery,and personalized therapy,alongside profound bioethical challenges and concerns.On April 29th,2025,China’s National Science and Technology Ethics Committee(Life Science Ethics Subcommittee)issued the Human Organoid Research Ethical Guidelines[1],establishing the world’s first comprehensive governance framework,especially focusing on brain organoids,embryo models,and chimeric research.This Guidelines represent a pioneering governance model in emerging biotechnology.This commentary offers an in-depth analysis to examine the policy’s innovative three-tiered structure,contrast it with current global regulatory standards,evaluate its domestic impacts as well as potential implications for international biotechnology governance,and provide recommendations for future directions.
基金supported by the National Natural Science Foundation of China(62522119 and 62372358)the Beijing Natural Science Foundation(7242267)+2 种基金the Beijing Scholars Program([2015]160)the Natural Science Basic Research Program of Shaanxi(2023-JC-QN-0719)the Guangdong Basic and Applied Basic Research Foundation(2022A1515110453)。
文摘Background:Brain volume measurement serves as a critical approach for assessing brain health status.Considering the close biological connection between the eyes and brain,this study aims to investigate the feasibility of estimating brain volume through retinal fundus imaging integrated with clinical metadata,and to offer a cost-effective approach for assessing brain health.Methods:Based on clinical information,retinal fundus images,and neuroimaging data derived from a multicenter,population-based cohort study,the Kai Luan Study,we proposed a cross-modal correlation representation(CMCR)network to elucidate the intricate co-degenerative relationships between the eyes and brain for 755 subjects.Specifically,individual clinical information,which has been followed up for as long as 12 years,was encoded as a prompt to enhance the accuracy of brain volume estimation.Independent internal validation and external validation were performed to assess the robustness of the proposed model.Root mean square error(RMSE),peak signal-tonoise ratio(PSNR),and structural similarity index measure(SSIM)metrics were employed to quantitatively evaluate the quality of synthetic brain images derived from retinal imaging data.Results:The proposed framework yielded average RMSE,PSNR,and SSIM values of 98.23,35.78 d B,and 0.64,respectively,which significantly outperformed 5 other methods:multi-channel Variational Autoencoder(mcVAE),Pixelto-Pixel(Pixel2pixel),transformer-based U-Net(Trans UNet),multi-scale transformer network(MT-Net),and residual vision transformer(ResViT).The two-(2D)and three-dimensional(3D)visualization results showed that the shape and texture of the synthetic brain images generated by the proposed method most closely resembled those of actual brain images.Thus,the CMCR framework accurately captured the latent structural correlations between the fundus and the brain.The average difference between predicted and actual brain volumes was 61.36 cm~3,with a relative error of 4.54%.When all of the clinical information(including age and sex,daily habits,cardiovascular factors,metabolic factors,and inflammatory factors)was encoded,the difference was decreased to 53.89 cm~3,with a relative error of 3.98%.Based on the synthesized brain magnetic resonance images from retinal fundus images,the volumes of brain tissues could be estimated with high accuracy.Conclusion:This study provides an innovative,accurate,and cost-effective approach to characterize brain health status through readily accessible retinal fundus images.
文摘Dear Editor,As space exploration transitions from short orbital missions to extended stays on the International Space Station(ISS)and,ultimately,interplanetary travel,astronaut health has emerged as a critical focus.In particular,safeguarding cardiovascular function has become an operational imperative.Yet beyond safeguarding those in orbit,the physiological adaptations observed in microgravity offer a compelling lens through which to examine persistent challenges in terrestrial medicine,from orthostatic intolerance in the elderly to deconditioning in critical care survivors.By studying how the human cardiovascular system functions in the absence of gravity.
文摘Dear Editor,Systemic sclerosis(SSc)is an autoimmune connective tissue disease in which there are vascular abnormalities,inflammation,and fibrosis[1].These three characteristics primarily affect the skin and lungs.Of all the autoimmune rheumatic diseases,SSc has the highest all-cause mortality rate,and the underlying pathogenic processes that mediate disease are still obscure,with wide diff erences in presentation and progression[2,3].
基金supported by the Capital’s Funds for Health Improvement and Research(CFH2024-2G-40214)the CAMS Innovation Fund for Medical Sciences(2021-I2M-1-011,2021-I2M-1-061).
文摘Background:The level of premature deaths(deaths among those aged 30-69 years)caused by cancer is an important indicator of evaluating the level of cancer prevention and control.However,the current burden and temporal trends in cancer-related premature deaths,and their impact on life expectancy at the global,regional,and national levels are not clear.Methods:Cancer mortality data for 185 countries were obtained from the GLOBOCAN 2022 database.High-quality cancer mortality data and national population statistics for 47 countries were extracted from the United Nations and national cancer registry databases,covering the period 2003-2022.Countries were classified based on the human development index(HDI).The death probability,the year of life lost(YLL),and the potential gain in life expectancy(PGLE)attributable to premature deaths from site-specific and all-cancers combined were calculated.Results:Globally,the probability of premature cancer deaths was 6.49%(95%UI 6.49-6.50).The YLLs caused by cancer-related premature death were 163.86 million(95%UI 163.70-164.03),constituting 65.58%of the total cancer-related YLLs.The PGLEs were 1.16 years(95%UI 1.16-1.16).The premature death probability increased with higher HDI levels in men,but decreased in women.Cancer-related premature deaths as a proportion of total cancer deaths varied from 18.31%(95%UI 18.20-18.43)in Japan to 84.44%(95%UI 76.10-91.16)in São Toméand Príncipe.Lung cancer was the leading cause of cancer-related premature deaths in men,and breast cancer ranked first in women.By eradicating premature deaths attributable to lung,liver,colorectal,and stomach cancer in men,and to breast,cervical,and lung cancer in women,0.55 years(95%UI 0.55-0.55)and 0.49 years(95%UI 0.49-0.49)of PGLEs could be achieved,accounting for 48.67%and 42.24%of the total PGLEs,respectively.Cancer-related premature deaths decreased significantly in 38 countries during 2003-2022(P<0.05).The probability of premature cancer-related deaths decreased by more than 15.50%from 2015 to 2022 in 16 countries.Conclusions:Cancer-related premature deaths declined in many countries,with 16 of them having achieved the expected reduction by 2022.The current burden of cancer-related premature deaths is profound but varies around the world.Eliminating premature deaths from major cancer types could substantially increase life expectancy,underscoring the importance of prevention and treatment efforts for these cancers.
基金supported by the National Natural Science Foundation of China(82330042,82441005 and 82301687)the National Key R&D Program of China(2023YFE0119400)+9 种基金the Capital’s Funds for Health Improvement and Research(2024-1-4111)the STI2030-Major Projects-2021ZD0200702Fundamental Research Funds for the Central Universities(Peking University Medicine Fund for world’s leading discipline or discipline cluster development,BMU2022DJXK007)the Beijing Municipal Health Commission Research Ward Programme(3rd batch)Beijing Nova Program(20230484425)the Beijing Municipal Science&Technology Commission,Administrative Commission of Zhongguancun Science Park(Z221100003522010)the China Postdoctoral Science Foundation(2024M760141 and 2022M720302)the National Postdoctoral Program for Innovative Talents(BX20240029)the Beijing Natural Science Foundation(7254462)the Peking University Medicine Sailing Program for Young Scholars’Scientific&Technological Innovation,the Fundamental Research Funds for the Central Universities(BMU2025YFJHPY044 and BMU2025YFJHPY046).
文摘Background:Antipsychotic-induced movement disorders(AIMDs)are prevalent side effects of antipsychotics,particularly during the acute phase of treatment.This study aimed to elucidate the genetic mechanisms underlying AIMDs using a genome-wide association study(GWAS).Methods:GWASs on AIMDs were conducted in three independent cohorts:a discovery cohort of 3067 patients(2016 subjects were reserved after quality control),a validation cohort of 277 patients,and a multi-ancestry validation cohort of 766 patients.Subsequent post-GWAS analyses included gene-based analyses,transcriptome-wide association studies(TWASs),and polygenic risk score(PRS)profiling.Results:Our study identified two loci located in RAB44 gene(rs116249243,P=5.98×10^(-9);rs117097482,P=1.17×10^(-8))associated with extrapyramidal symptoms(EPSs),1 locus(rs6826172,P=5.56×10^(-9))related to akathisia,and 76 loci linked to involuntary movements(11 genes were mapped).Risk loci located in CNTNAP2,LUZP2,TMEM167A,and RAB44 genes were successfully replicated in the validation cohort,whereas the locus located in RAB44 was also replicated in the multi-ancestry cohort.Gene-based analyses indicated that XRCC4 and PAIP2B reached significance at the genome-wide level in involuntary movements.Tissue expression analysis revealed that involuntary movement-related genes are predominantly expressed in the substantia nigra.Additionally,the TWAS suggested a causal relationship between XRCC4 and involuntary movement.The PRSs derived from the discovery cohort significantly predicted AIMDs in the validation cohort,with area under the receiver operating characteristic curve(AUC)values from 0.60 to 0.80.Conclusions:Our findings highlight the role of substantia nigra related gene polymorphisms in AIMDs.This study provides novel insights into the pathogenesis of AIMDs and supports the potential for personalized treatment approaches for schizophrenia.
基金supported by the National Institutes of Health(RPS,R21 ES033806).
文摘Despite having multiple treatment options,the overall outcomes,including the survival rates of non-small cell lung cancer(NSCLC)patients,remain relatively low,indicating the need to explore new approaches to achieve improved therapeutic responses.To that end,repurposed drugs such as metformin have been evaluated against many cancer types,including NSCLC.Metformin,a widely used oral hypoglycemic drug for type 2 diabetes,exhibits anticancer properties and synergy with several standards of care agents.In this review,we provide a comprehensive overview of the role and anticancer mechanisms of metformin-based combination approaches for the treatment of NSCLC.We logically discussed the experimental evidence from the in vitro and in vivo studies utilizing metformin alone,and then its combination with chemotherapeutic agents,targeted therapy,and immunotherapy.We also present clinical trials that underscore the beneficial and adverse outcomes of metformin use in combination with targeted therapy and chemotherapeutic agents,and emphasize the limitations and challenges for the treatment of diabetic and nondiabetic NSCLC patients.It appears that,regardless of the diverse anticancer mechanisms of this biguanide,the benefits may be confined to a specific patient subgroup,which opens new avenues to be explored for NSCLC treatment.
基金supported by the Guangxi Natural Science Foundation(AD21220065 to JX)the National Natural Science Foundation of China(82102632 and 82160412 to JX)the Guangdong Basic and Applied Basic Research Foundation(2023A1515220072 to ZHD)。
文摘Tendon-related diseases(TRDs)are increasingly common in the current aging society and impose a significant burden on patients.Despite therapeutic advances,the pathophysiology of TRDs remains poorly understood,hindering effective clinical management.The macrophages are highly plastic immune cells involved in the maintenance of in vivo homeostasis and the injury-healing process.Their dual role in TRDs has been widely investigated,either promoting tenogenic and chondrogenic differentiation or amplifying inflammatory response,underscoring their therapeutic potential for TRDs treatment.Therefore,the review aims to summarize the roles of macrophages in the healing of TRDs,characterized by limited regenerative capacity,and examine strategies for the modulation of macrophage phenotypes to accelerate the regeneration process.Finally,we review applications involving macrophage modulation within the context of tissue engineering of TRDs,providing novel insights for the design of biomaterials-based targeted delivery systems.
基金supported by the National Natural Science Foundation of China(32371477,82090051,82301104,and 82300345)the National Key Research and Development Program of China(2021YFA1201000,2023YFC2605000)+2 种基金the National Natural Science Foundation of China Key Project(82430067,32030060)the Natural Science Foundation of Jiangsu Province(BK20230160)the Fundamental Research Funds for the Central Universities,Peking Union Medical College(3332025033).
文摘Immunotherapy for cardiovascular diseases(CVDs)holds great promise for precision management by modulating localized immune-inflammatory responses.The interplay between focal cardiovascular pathology and panvascular disease,necessitates highly integrated therapeutic strategies.Nano-technology-based theranostic platforms address this challenge by enabling both regulation and real-time imaging of immune cell activity within cardiovascular lesions.These functional nanotherapy systems not only halt disease progression at pathological sites but also reduce secondary cardiovascular events driven by shared inflammatory mechanisms.Additionally,nanoplatform-based dynamic visualization of immune cell responses facilitates adaptive,personalized interventions.This review introduces the role of immune cells in CVDs.It summarizes recent advances in nanomaterial-based immunomodulation strategies,including mechanisms of immune regulation,enhanced imaging,and therapeutic applications in atherosclerosis,myocardial infarction,ischemic stroke,abdominal aortic aneurysm,and myocarditis.Collectively,this integrated nanotheranostic paradigm establishes a robust foundation for the next generation of cardiovascular precision medicine.
基金supported by grants from the National Institute of Biomedical Imaging and Bioengineering(NIBIB)of the National Institutes of Health(NIH)under award numbers R01-EB001659(2003-2013)and R01-EB017205(2014-2018)approved by the Institutional Review Boards of Beth Israel Deaconess Medical Center(Boston,MA)and the Massachusetts Institute of Technology(Cambridge,MA).
文摘Background:Most sepsis patients develop sepsis-associated acute kidney injury(SA-AKI),which poses a significant threat to survival and lacks specific treatment.To date,there are no published randomized controlled trials that have established a link between albumin use and SA-AKI development in sepsis.Therefore,it is unclear whether albumin use may influence the risk of SA-AKI.Methods:The present study employed a target trial emulation using observational data to track adult sepsis patients initially admitted to the intensive care unit at Beth Israel Deaconess Medical Center,Boston,Massachusetts,for a period of 7 d from 2008 to 2022.Immortal time bias was controlled using the clone-censor-weight(CCW)method,along with a new-user design to address current user bias.The exposure variable was the early administration of albumin following the onset of sepsis.Based on albumin use,patients were classified into two groups:the albumin group(n=27,088)and the no albumin group(n=27,088).The primary outcome was the development of SA-AKI,and the secondary outcome was 7-day all-cause mortality.The primary outcome was analyzed using competing risk analyses.Furthermore,sensitivity and subgroup analyses were also performed.Results:Among the 27,088 patients analyzed,albumin administration was associated with a significantly higher SA-AKI risk(relative difference=3.47%,95%CI 1.76-5.23)compared to non-administration.There was no clinically meaningful difference in 7-day survival(relative difference=0.05%,95%CI-2.30 to 2.45).Sensitivity analyses consistently supported these results.All these analyses were conducted on data that were collected after CCW.Conclusions:Early albumin administration may increase the risk of SA-AKI in sepsis patients without conferring a short-term survival benefit.These results underscore the need for a rigorous risk-benefit assessment when incorporating albumin into sepsis resuscitation protocols and highlight the need for further clinical validation.However,it is important to exercise caution when interpreting the conclusions of this study,given its exploratory and preliminary nature.
文摘Antipsychotics,especially many second-generation antipsychotics(SGAs),remain central to schizophrenia treatment,are indispensable in acute mania and for bipolar maintenance(with selected roles in bipolar depression),and serve as evidence-based augmenters in treatment-resistant depression.Nonetheless,acute antipsychotic-induced movement disorders(AIMDs)[extrapyramidal symptoms(EPS)]are common and clinically costly,impairing quality of life,adherence,and outcomes.The acute spectrum is dominated by dystonia(sustained,often painful contractions).
基金supported by the National Natural Science Foundation of China(82271401,82071394)the Tianjin Health Research Project(TJWJ2024RC002)。
文摘Background:Repetitive mild traumatic brain injury(rmTBI)is a significant risk factor for neurodegeneration,characterized by pathological protein deposition and persistent neuroinflammation.Research has observed increased interleukin-33(IL-33)levels in the peripheral blood of patients with rmTBI,suggesting IL-33 may participate in regulating the pathological development of rmTBI.The study aims to elucidate the impact and mechanism of IL-33 in the progression of neuropathology following rmTBI,and to explore its potential as a therapeutic target to improve the neurological outcome.Methods:The study employed an rmTBI mouse model using the wild-type(WT)and IL-33 knockout mice.Cognitive function was assessed via the Y-maze and Barnes tests.The main cell type expressing IL-33 and its receptor,suppression of tumorigenicity 2(ST2),was then investigated in the mouse brain through immunofluorescence colocalization.As the primary neural cell responsible for ST2 expression,microglia were studied in vitro using the BV2 cell line.The effects of lipid droplets(LDs)accumulation and amyloid-beta(Aβ)phagocytosis were measured to elucidate the impact of IL-33 on BV2 cells'phagocytosis.Additionally,HT22 neuronal apoptosis was assessed by flow cytometry.Finally,the cognitive effects of intranasal administration of IL-33 were evaluated in mice.Results:IL-33 KO mice exhibited pronounced cognitive impairment after rmTBI.In the mouse brain,astrocytes were identified as the primary source of IL-33 secretion,while microglia predominantly expressed ST2.Transcriptome sequencing revealed that IL-33 significantly influenced phagocytosis function.IL-33 mitigated LDs accumulation in BV2 cells and enhanced Aβphagocytosis in vitro.In addition,the culture medium of BV2 cells with activated IL-33/ST2 signaling reduced HT22 neuronal apoptosis and axonal damage.Furthermore,intranasal administration of IL-33 was observed to be effective in alleviating neurodegeneration and cognitive outcome of rmTBI mice.Conclusions:Dysfunction of the IL-33/ST2 axis following rmTBI leads to cognitive dysfunction via impairing microglial phagocytosis capacity and promoting neuronal damage.IL-33 would be a promising therapeutic target for alleviating neurodegeneration following rmTBI.
基金supported by the Sci-Tech Innovation 2030 Agenda(2023ZD0503900,2023ZD0503901)the Provincial Natural Science Foundation of Hunan(2024JJ8118)the Central South University Innovation-Driven Research Program(2023CXQD007).
文摘Background:Sudden cardiac death(SCD)accounts for more than half of all sudden death cases,posing a significant health burden in China.However,epidemiological data on SCD are scarce due to the lack of a central data registry and the heterogeneity of case definitions.This study aims to provide reliable estimates of the incidence and risk factors of SCD in China at the national and regional levels from 2013 to 2021,as well as the current status of prevention.Methods:The multi-cause mortality data from 2013 to 2021 were obtained from the National Mortality Surveillance System of China.Deaths related to cardiac arrest were identified.Crude and age-standardized mortality rates(ASMR)were calculated by time,and region.Joint point regression was applied to identify significant changes during the study period.Subgroup analyses and multilevel negative binomial analysis were performed to understand the SCD risk factors.The first-line prevention measures and their current implementation in China and developed countries were also determined from published articles.Results:From 2013 to 2021,the crude mortality rate of sudden cardiac arrest increased markedly from 8.36 deaths per 100,000 population in 2013 to 18.59 deaths per 100,000 population in 2021.There were considerable differences among regions.Subgroup analysis and negative binomial regression results indicated that males and the elderly were at higher risk of SCD.SCD may be associated with poor medical conditions.More than half of SCDs occurred outside hospitals,and approximately 60%of SCDs were related to ischemic heart disease as the underlying cause.Currently,developed countries have widely adopted primary prevention and emergency treatment measures;however,the utilization rate of such measures in China is relatively low and should be improved.Conclusions:With the continuous rise in the prevalence of cardiovascular diseases and their related risk factors in China,the burden of SCD is expected to increase.In addition to strengthening the clinical pathways for sudden cardiac arrest cases in pre-hospital and hospital settings,it is also necessary to enhance public awareness,knowledge and first-line practical training through large-scale policies for governmental and community-based projects.
基金supported by the State Key Program of the National Natural Science Foundation of China(82030059)the National Science and Technology Major Project(2023ZD0505501)+2 种基金the National Natural Science Foundation of China(81701952 and 82172127)the National Key Research and Development Program of China(2020YFC1512700)the Key Research and Development Program of Shandong Province(2021SFGC0503 and 2022ZLGX03).
文摘Aldehyde dehydrogenase 2(ALDH2),a mitochondrial enzyme,is the main acetaldehyde dehydrogenase involved in the scavenging of alcohol-derived acetaldehyde and endogenous aldehydes.The ALDH2^(rs671)mutation affects 560 million East Asians and is closely related to an increased risk of various human diseases.In addition to its well-known function in detoxifying alcohol-derived acetaldehyde and endogenous aldehydes,ALDH2 is implicated in human health through its regulation of autophagic machinery and multiple cell death pathways(e.g.,apoptosis,necroptosis,pyroptosis,ferroptosis,and NETosis).This review summarizes the current knowledge of ALDH2 and the regulatory mechanism through which ALDH2 regulates autophagy and cell death.In addition,we outline the potential role of ALDH2 in the regulation of autophagy and cell death during the occurrence and progression of human diseases,aiming to provide a novel theoretical framework for human disease treatment.
基金supported by the Beijing Natural Science Foundation-Xiaomi Innovation Joint Fund(L233009).
文摘Dear Editor,The National Health Commission(NHC)of China has championed the creation of weight management clinics to confront the growing crisis of overweight and obesity.Forecasts indicate that by 2030,the prevalence of these conditions among Chinese adults and children could climb to 70.5%and 31.8%,respectively[1].This troubling trajectory,alongside an increasing burden of chronic illnesses such as diabetes,hypertension,and cardiovascular diseases,underscores the need for immediate action.Instead of focusing solely on weight management clinics,we propose that medical institutions prioritize the establishment of comprehensive chronic disease management clinics,building upon the foundation of weight management clinics to holistically address obesity,aging,and healthcare system challenges.
