Objective To investigate the prevalence and clinical significance of the centromere protein-F-like(CENP-F-like)immunofluorescence staining pattern in a large patient cohort and through literature review.Methods We ret...Objective To investigate the prevalence and clinical significance of the centromere protein-F-like(CENP-F-like)immunofluorescence staining pattern in a large patient cohort and through literature review.Methods We retrospectively analyzed antinuclear antibody(ANA)immunofluorescence assay results from 191274 patients at West China Hospital of Sichuan University between March 2018 and November 2020.Specific immunological markers were tested in sera with CENP-F-like patterns.Additionally,a narrative review of seven relevant studies was performed for comparison.Results In Southwest China,ANA positivity was found in 32.09%of patients,with the CENP-F-like pattern detected in 0.015%of all cases and 0.05%of ANA-positive individuals.The CENP-F-like pattern appeared predominantly at titers≥1∶320,most often in isolation(68.97%),but also mixed with cytoplasmic speckled patterns.Patients with cancers accounted for the highest proportion(31.03%),including solid tumors and hematologic malignancies.Metastasis was observed in patients with solid tumors,while graft-versus-host disease(GVHD)occurred in those with hematologic malignancies post-transplantation.Autoimmune diseases(AIDs)were diagnosed in 20.69%of cases,all showing disease-specific autoantibodies.These findings were broadly consistent with previous reports and suggest a possible association between the CENP-F-like pattern and malignancies.Conclusion The CENP-F-like pattern is rare in ANA tests but may be associated with clinically important conditions,particularly cancers and AIDs.The occurrence of metastasis and GVHD in patients with this pattern highlights its potential clinical relevance,and concurrent autoantibodies may assist in diagnosing AIDs.展开更多
This study makes an in-depth exploration of the core pathogenesis of chronic atrophic gastritis,Qi Deficiency with Stagnation,to systematically interpret it within the theoretical framework of Achieving Central Harmon...This study makes an in-depth exploration of the core pathogenesis of chronic atrophic gastritis,Qi Deficiency with Stagnation,to systematically interpret it within the theoretical framework of Achieving Central Harmony,and to provide a treatment plan.Professor Li Tingquan believes that the occurrence and development of chronic atrophic gastritis(CAG)is fundamentally a process of harmony imbalance of the spleen and stomach.Its specific manifestation lies in the interaction between qi deficiency and stagnation,namely,spleen deficiency as the root cause,and qi stagnation,phlegm-dampness,and blood stasis obstructing the middle energizer as the secondary manifestations.These factors are mutually causal and interact with one another.Based on this,he proposed a four-step method to treat the disease:eliminating pathogenic factors,harmonizing the spleen and stomach,activating blood circulation to resolve stasis,and tonifying the kidney to generate blood(metaphorically described as"closing the mountains to cultivate forests and thicken the soil,breeding seeds and irrigating for stomach recovery").This approach aims to restore the harmonious state of the middle energizer,providing a complete clinical framework of theory,principle,formula,and herbs for the prevention and treatment of CAG.展开更多
Objectives:The five-year survival rate for pancreatic cancer is notably low,posing a significant challenge to patient health.The primary treatments are radiotherapy and chemotherapy,sometimes combined with targeted th...Objectives:The five-year survival rate for pancreatic cancer is notably low,posing a significant challenge to patient health.The primary treatments are radiotherapy and chemotherapy,sometimes combined with targeted therapy;however,their clinical benefits are limited.Therefore,developing new models to evaluate the therapeutic potential of novel molecules is essential.Fingolimod and Dimethyl Fumarate(DMF),currently used to treat multiple sclerosis,have recently been shown to have anti-cancer effects in several preclinical tumor models.This study aims to evaluate the therapeutic potential of Fingolimod and DMF in pancreatic cancer by investigating their respective in vitro cytotoxicity and in vivo antitumor effects.Methods:In this study,we evaluated for the first time these two drugs in pancreatic preclinical models in vitro using 3D spheroid tumor models and in vivo,which are compared to two standard-of-care consisting of Gemcitabine and Erlotinib.Results:In vitro,both Fingolimod and DMF induced cytotoxicity in spheroids from two pancreatic cell lines.Additionally,Fingolimod and DMF displayed anticancer effects in two subcutaneous xenograft models using PANC-1 and CFPAC-1 cells.Conclusions:Although the responses observed with Fingolimod and DMF were similar to those of Gemcitabine and Erlotinib,these findings indicate a potential emerging interest in Fingolimod and DMF for the treatment of pancreatic cancer.However,further work is still necessary to fully characterize how these drugs affect tumor progression.展开更多
Introduction.Well-designed,strictly implemented,and fully standardized randomized controlled trials(RCTs)are a prerequisite for developing reliable scientific evidence,which can improve clinical practice,health outcom...Introduction.Well-designed,strictly implemented,and fully standardized randomized controlled trials(RCTs)are a prerequisite for developing reliable scientific evidence,which can improve clinical practice,health outcomes,and ultimately benefit patients.Suboptimal reporting is pervasive in medical research,resulting in biased research records and persistent uncertainty about the quality of available evidence.1,2,3,4 The standardization of research reports has attracted considerable attention.In 1996,the Consolidated Standards of Reporting Trials(CONSORT)was first published to improve the quality of RCTs and enhance the reproducibility of trial methods,results,and inferences.展开更多
The landscape of breast cancer treatment has undergone a transformative shift with the integration of immunotherapy.Historically considered a“cold”tumor with limited immunogenicity,breast cancer management was domin...The landscape of breast cancer treatment has undergone a transformative shift with the integration of immunotherapy.Historically considered a“cold”tumor with limited immunogenicity,breast cancer management was dominated by surgery,chemotherapy,radiotherapy,and targeted therapies1.However,the advent of immune checkpoint inhibitors(ICIs)has challenged this paradigm,opening a new frontier.The initial breakthrough in triple-negative breast cancer(TNBC)demonstrated that a subset of patients could derive profound and durable clinical benefit from pembrolizumab and atezolizumab2,3.Today,precision immunotherapy aims to identify the patients most likely to respond,to convert immunologically silent tumors into responsive tumors,and to strategically combine immunotherapies with other modalities to overcome resistance.This evolution from empirical application to biomarker-driven strategies marks the critical juncture at which we stand,transitioning promising clinical trial data into refined,effective,and accessible clinical practice4.Recent key clinical studies on breast cancer immunotherapy are summarized in Table 1.展开更多
Background:Artificial intelligence medical diagnostic devices(AIMDDs)show strong potential but face barriers to clinical use,emphasizing the need for rigorous clinical research.Objective:We assessed current AIMDD rese...Background:Artificial intelligence medical diagnostic devices(AIMDDs)show strong potential but face barriers to clinical use,emphasizing the need for rigorous clinical research.Objective:We assessed current AIMDD research,key challenges,and future directions.Methods:A scoping review followed Arksey and O'Malley's methodological framework and the Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews guidelines.PubMed,Web of Science Core Collection,and the Cochrane Database of Systematic Reviews(January 2020-December 2024)were searched on AIMDD design,implementation,and evaluation.Two independent researchers screened and extracted data from the literature using predefined criteria.Results:Ninety-seven articles met the inclusion criteria.Machine learning and deep learning approaches dominated across diverse disease fields,with oncology being the most frequent(41%).The key challenges identified include insufficient quantity,quality,representativeness,and diversity of data;research designs that do not adequately address clinical needs;poor patient selection;poorly defined gold standards;lack of external and prospective validation;and a disconnect between validation strategies and clinical practice.Additionally,issues such as the“black box”phenomenon,overfitting,and data privacy concerns hinder clinical translation.Completeness and standardization of reporting were also found to be lacking.Conclusions:Significant challenges remain in the development and clinical application of AIMDD.To facilitate their clinical translation,improvements are needed in dataset optimization,clinically driven research design,development of evaluation frameworks,enhanced interpretability,and standardized reporting and validation of algorithms.展开更多
The convergence of artificial intelligence(AI)and big data is reshaping contemporary oncology by enabling the integration of multimodal information across imaging,pathology,genomics,and clinical records.From a physici...The convergence of artificial intelligence(AI)and big data is reshaping contemporary oncology by enabling the integration of multimodal information across imaging,pathology,genomics,and clinical records.From a physician-centered perspective,these technologies can potentially be used to improve diagnostic precision,support individualized treatment planning,enhance longitudinal patient management,and accelerate both clinical and translational research.In this review,we synthesize the core AI methodologies most relevant to oncology-machine learning,deep learning,and large language models-and examine how they interact with established and emerging oncology data platforms.We further highlight practical use cases in clinical workflows and research pipelines,emphasizing opportunities for advancing precision cancer care while also addressing challenges associated with data heterogeneity,model generalizability,privacy protection,and real-world implementation.By underscoring the synergistic value of AI and big data,this review aims to inform the development of clinically meaningful,context-adapted strategies that promote translational innovation in both global and locally resourced healthcare environments.展开更多
Brain lesions,such as those caused by stroke or traumatic brain injury(TBI),frequently result in persistent motor and cognitive impairments that significantly affect the individual patient's quality of life.Despit...Brain lesions,such as those caused by stroke or traumatic brain injury(TBI),frequently result in persistent motor and cognitive impairments that significantly affect the individual patient's quality of life.Despite differences in the mechanisms of injury,both conditions share a high prevalence of motor and cognitive impairments.These deficits show only limited natural recovery.展开更多
Chronic pain represents a significant global health challenge,and the limitations of conventional analgesics have urged a search for alternative therapeutic strategies.Cannabinoids derived from Cannabis sativa have em...Chronic pain represents a significant global health challenge,and the limitations of conventional analgesics have urged a search for alternative therapeutic strategies.Cannabinoids derived from Cannabis sativa have emerged as prominent candidates.While psychotropic cannabinoids are known for their analgesic effects,their psychoactive properties often limit their clinical utility.Consequently,interest has shifted towards non-psychotropic cannabinoids that offer potential pain relief without inducing cognitive or euphoric effects.This comprehensive review investigates the pain-modulating mechanisms of cannabinoids,encompassing interactions with the endocannabinoid system and other non-traditional pathways,and summarizes the existing preclinical and clinical evidence supporting their use in various pain states.Furthermore,it discusses the therapeutic potential,clinical considerations,significant challenges,and the need for product standardization.This review also aims to evaluate the role and prospects of non-psychotropic cannabinoids as a therapeutic option for pain management.展开更多
Carbamazepine is an antiepileptic drug also used for neuropathic pain and mood stabilization.It is a strong enzyme inducer and autoinducer with multiple well-documented drug–drug interactions and adverse drug reactio...Carbamazepine is an antiepileptic drug also used for neuropathic pain and mood stabilization.It is a strong enzyme inducer and autoinducer with multiple well-documented drug–drug interactions and adverse drug reactions.Widely licensed and in use since the 1960s,carbamazepine has well-characterized pharmacological,pharmacogenetic,and safety profiles,and remains extensively used in neurology and psychiatry.In 2024,carbamazepine was recommended for inclusion in the World Health Organization list of essential medicines.Carbamazepine has a complex mode of action that includes neuronal stabilization,neuroprotection,neurotransmitter modulation,enhancement of autophagy,and anti-inflammatory effects.These make carbamazepine a good candidate for drug repurposing in oncology,genetic diseases,neurodegeneration,and systemic inflammation.Recent advances in precision medicine,genomics,and on/off-target drug repositioning have enabled the identification of new carbamazepinemolecular targets for novel applications in different therapeuticmodalities.This review highlights carbamazepine repurposing studies in cancers such as breast and colorectal,based on its mode of action.In addition,repurposing studies in genetic diseases such asmetaphyseal achondroplasia and Fragile-X,as well as in neurodegenerative conditions such as amyotrophic lateral sclerosis and Alzheimer's dementia,are discussed.The pharmacological mechanisms and drug repurposing pathways are critically summarized in order to provide insights into their therapeutic potential and proposed future directions.展开更多
The Chinese Society of Clinical Oncology Non-small Cell Lung Cancer(CSCO NSCLC)guidelines were first published in 2016,ranking among the earliest-released guidelines within the CSCO series.In 2020 the CSCO published s...The Chinese Society of Clinical Oncology Non-small Cell Lung Cancer(CSCO NSCLC)guidelines were first published in 2016,ranking among the earliest-released guidelines within the CSCO series.In 2020 the CSCO published separate guidelines for NSCLC and small cell lung cancer(SCLC)for the first time to improve clinical usability.展开更多
Tumor metabolic reprogramming is a core hallmark of cancer,characterized by pathways such as aerobic glycolysis,aberrant lipid metabolism,and glutaminolysis that support rapid proliferation and immunosuppressive micro...Tumor metabolic reprogramming is a core hallmark of cancer,characterized by pathways such as aerobic glycolysis,aberrant lipid metabolism,and glutaminolysis that support rapid proliferation and immunosuppressive microenvironments.Circular RNAs(circRNAs)are highly stable,evolutionarily conserved non-coding RNAs that have emerged as critical modulators of these metabolic shifts.This review aims to systematically elucidate the roles and mechanisms of circRNAs in reprogramming tumor metabolism,and to discuss their clinical potential as biomarkers and therapeutic targets.Through mechanisms including miRNA sponging,protein interactions,regulation of mitochondrial dynamics,and modulation of metabolic enzymes,circRNAs influence key metabolic pathways by targeting glycolytic enzymes,lipid synthesis regulators,and glutaminolysis-related molecules to either facilitate or inhibit their expression.This review systematically summarizes the unique contributions of circRNAs to tumor metabolic reprogramming,highlighting key mechanisms such as regulation of peptide-encoding protein translation,mitochondrial localization function,gene promoter-targeted transcriptional regulation,and cross-pathway metabolic mediation,which underscore their distinct biological advantages and regulatory roles in tumor metabolism.The stability and tissue specificity of circRNAs make them promising diagnostic biomarkers,while their role in drug resistance mediated by metabolic reprogramming highlights their potential as therapeutic targets.Strategies such as circRNA inhibitors,mimics,and nanoparticle-based delivery systems are being explored to modulate tumor metabolism.Despite challenges including complex regulatory networks and limited manipulation tools,advances in high-throughput technologies and clinical trials hold promise for translating circRNA research into novel cancer therapies.展开更多
Background:Large language models(LLMs)have shown considerable promise in supporting clinical decision-making.However,their adoption and evaluation in dermatology remains limited.This study aimed to explore the prefere...Background:Large language models(LLMs)have shown considerable promise in supporting clinical decision-making.However,their adoption and evaluation in dermatology remains limited.This study aimed to explore the preferences of Chinese dermatologists regarding LLM-generated responses in clinical psoriasis scenarios and to assess how they prioritize key quality dimensions,including accuracy,traceability,and logicality.Methods:A cross-sectional,web-based survey was conducted between December 25,2024,and January 22,2025,following the Checklist for Reporting Results of Internet E-Surveys guidelines.A total of 1247 valid responses were collected from practicing dermatologists across 33 of China's provincial-level administrative divisions.Participants evaluated responses to five categories of clinical questions(etiology,clinical presentation,differential diagnosis,treatment,and case study)generated by five LLMs:ChatGPT-4o,Kimi.ai,Doubao,ZuoYiGPT,and Lingyi-agent.Statistical associations between participant characteristics and model preferences were examined using chi-square tests.Results:ChatGPT-4o(Model 1)emerged as the most preferred model across all clinical tasks,consistently receiving the highest number of votes in case study(n=740),clinical presentation(n=666),differential diagnosis(n=707),etiology(n=602),and treatment(n=656).Significant variation in model preference by professional title was observed only for the differential diagnosis task(χ^(2)=21.13,df=12,p=0.0485),while no significant differences were found across hospital tiers(p>0.05).In terms of evaluation dimensions,accuracy was most frequently rated as“very important”(n=635).A significant association existed between hospital tier and the most valued dimension(χ^(2)=27.667,df=9,p=0.0011),with dermatologists in primary hospitals prioritizing traceability more than their peers in higher-tier hospitals.No significant associations were found across professional titles(p=0.127).Conclusions:Chinese dermatologists suggest a strong preference for ChatGPT-4o over domestic LLMs in psoriasis-related clinical tasks.While accuracy remains the primary criterion,traceability and logicality are also critical,particularly for clinicians in lower-tier hospitals.These findings suggest that future clinical LLMs should prioritize not only content accuracy but also source transparency and structural clarity to meet the diverse needs of different clinical settings.展开更多
Phrenic nerve stimulation(PNS)may preserve diaphragm activation and mitigate multiorgan injury during mechanical ventilation(MV);however,a minimal invasive rat model integrating PNS with MV is lacking.We established a...Phrenic nerve stimulation(PNS)may preserve diaphragm activation and mitigate multiorgan injury during mechanical ventilation(MV);however,a minimal invasive rat model integrating PNS with MV is lacking.We established an omohyoid muscle-based PNS rat model combined with MV.Bilateral nerves were exposed within 20±2 min by transection at the intermediate tendon of omohyoid muscle,minimizing trauma and bleeding.Threshold stimulation(0.6±0.2 mA)correlated with body weight.Ventilator-synchronized stimulation increased compound muscle action potentials by~30%,whereas histology confirmed intact nerve.Physiological parameters remained stable throughout ventilation.This model provides a safe and scalable platform for mechanistic and preclinical studies on PNS-mediated protection against MV-induced organ injury.展开更多
Retinal ganglion cells are the bridging neurons between the eye and the central nervous system,transmitting visual signals to the brain.The injury and loss of retinal ganglion cells are the primary pathological change...Retinal ganglion cells are the bridging neurons between the eye and the central nervous system,transmitting visual signals to the brain.The injury and loss of retinal ganglion cells are the primary pathological changes in several retinal degenerative diseases,including glaucoma,ischemic optic neuropathy,diabetic neuropathy,and optic neuritis.In mammals,injured retinal ganglion cells lack regenerative capacity and undergo apoptotic cell death within a few days of injury.Additionally,these cells exhibit limited regenerative ability,ultimately contributing to vision impairment and potentially leading to blindness.Currently,the only effective clinical treatment for glaucoma is to prevent vision loss by lowering intraocular pressure through medications or surgery;however,this approach cannot halt the effect of retinal ganglion cell loss on visual function.This review comprehensively investigates the mechanisms underlying retinal ganglion cell degeneration in retinal degenerative diseases and further explores the current status and potential of cell replacement therapy for regenerating retinal ganglion cells.As our understanding of the complex processes involved in retinal ganglion cell degeneration deepens,we can explore new treatment strategies,such as cell transplantation,which may offer more effective ways to mitigate the effect of retinal degenerative diseases on vision.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
Background:The Colorectal Cancer(CRC)pathogenesis and therapeutic efficacy are influenced by the gut microbiome,making it a promising biomarker for predicting treatment responses and adverse effects.This systematic re...Background:The Colorectal Cancer(CRC)pathogenesis and therapeutic efficacy are influenced by the gut microbiome,making it a promising biomarker for predicting treatment responses and adverse effects.This systematic review aims to outline the gut microbiome composition in individuals with CRC undergoing the same therapeutic regimen and evaluate interindividual microbiome profile variations to better understand how these differences may influence therapeutic outcomes.Methods:Key studies investigating the microbiome’s role in therapeutic approaches for CRC were searched in both PubMed and Cochrane databases on 12 and 22 March 2025,respectively.Eligible studies included free full-text English-language randomized clinical trials and human observational studies reporting on gut microbiome composition and treatment outcomes.RoB 2 and ROBINS-I were employed in the evaluation of bias for randomized trials and observational studies,respectively.Data extracted was narratively analyzed.Results:Six studies involving a total of 361 individuals were included.Therapeutic interventions,either standard treatments and/or those targeting the gut microbiome,generally increased probiotic taxa and reduced pro-carcinogenic bacteria.However,no consistent pattern of improved clinical outcomes was observed,suggesting that treatment mechanisms,the tumor’s nature,and individual characteristics play critical roles in microbiome modulation.Conclusion:The gut microbiome holds significant potential in clinical settings.Nonetheless,further research is needed to better understand its functional aspects and to consider the influence of treatment mechanisms,the tumor’s nature,and individual characteristics as modulators,in order to optimize clinical outcomes.展开更多
The growing recognition of the role of genetics in the development of amyotrophic lateral sclerosis is evident.However,there has yet to be a comprehensive analysis of the clinical characteristics and genetics of famil...The growing recognition of the role of genetics in the development of amyotrophic lateral sclerosis is evident.However,there has yet to be a comprehensive analysis of the clinical characteristics and genetics of familial amyotrophic lateral sclerosis in an Asian population.This study aimed to provide an in-depth analysis of the clinical features and genetic spectrum of familial amyotrophic lateral sclerosis over 15 years in a clinic-based cohort of patients from the Chinese mainland.Enrollment of 302 amyotrophic lateral sclerosis families from 28 provinces was undertaken from January 2008 to September 2023.A group-based trajectory model for disease progression based on amyotrophic lateral sclerosis Functional Rating Scale-Revised(ALSFRS-R)scores was validated using bootstrap internal validation in patients with familial amyotrophic lateral sclerosis,as well as patients with sporadic amyotrophic lateral sclerosis(matched at a 1:4 ratio,with replacement).DNA samples from 244 index patients were screened for variants in the pathogenic genes SOD1,FUS,TDP43,and C9ORF72,of which 146 were also subjected to genome-wide next-generation sequencing.Gene-level burden analysis was used to evaluate the distribution of rare variants in the cohort.We found that rapid dynamic disease progression was associated with an older age at onset,shorter diagnostic delay,lower body mass index,bulbar onset,and≥1 affected first-degree relative.Certain attributes,such as age at onset and time from onset to diagnosis,had comparable impacts on the clinical progression trajectories of both familial amyotrophic lateral sclerosis and sporadic amyotrophic lateral sclerosis.Harboring pathogenic/likely pathogenic variants in amyotrophic lateral sclerosis-causative genes reduced the age of onset of familial amyotrophic lateral sclerosis.Among the patients with familial amyotrophic lateral sclerosis,17.8%possessed≥2 pathogenic/likely pathogenic variants.Sequencing kernel association test analysis showed that the SOD1 rare variant burden(P=1.3e-15)was associated with a significant risk of familial amyotrophic lateral sclerosis.Our findings conclusively confirmed the clinical features and genetic spectrum of familial amyotrophic lateral sclerosis over 15 years in a clinical cohort from China,contributing to a deeper understanding of genotype-phenotype relationships in familial amyotrophic lateral sclerosis.This comprehensive evaluation of specific clinical characteristics,clinical prognosis,and genetic variants of amyotrophic lateral sclerosis based on detailed clinical and genetic information may lead to the development of genotype-specific treatment approaches.展开更多
Clear aligner treatment is a novel technique in current orthodontic practice.Distinct from traditional fixed orthodontic appliances,clear aligners have different material features and biomechanical characteristics and...Clear aligner treatment is a novel technique in current orthodontic practice.Distinct from traditional fixed orthodontic appliances,clear aligners have different material features and biomechanical characteristics and treatment efficiencies,presenting new clinical challenges.Therefore,a comprehensive and systematic description of the key clinical aspects of clear aligner treatment is essential to enhance treatment efficacy and facilitate the advancement and wide adoption of this new technique.This expert consensus discusses case selection and grading of treatment difficulty,principle of clear aligner therapy,clinical procedures and potential complications,which are crucial to the clinical success of clear aligner treatment.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
文摘Objective To investigate the prevalence and clinical significance of the centromere protein-F-like(CENP-F-like)immunofluorescence staining pattern in a large patient cohort and through literature review.Methods We retrospectively analyzed antinuclear antibody(ANA)immunofluorescence assay results from 191274 patients at West China Hospital of Sichuan University between March 2018 and November 2020.Specific immunological markers were tested in sera with CENP-F-like patterns.Additionally,a narrative review of seven relevant studies was performed for comparison.Results In Southwest China,ANA positivity was found in 32.09%of patients,with the CENP-F-like pattern detected in 0.015%of all cases and 0.05%of ANA-positive individuals.The CENP-F-like pattern appeared predominantly at titers≥1∶320,most often in isolation(68.97%),but also mixed with cytoplasmic speckled patterns.Patients with cancers accounted for the highest proportion(31.03%),including solid tumors and hematologic malignancies.Metastasis was observed in patients with solid tumors,while graft-versus-host disease(GVHD)occurred in those with hematologic malignancies post-transplantation.Autoimmune diseases(AIDs)were diagnosed in 20.69%of cases,all showing disease-specific autoantibodies.These findings were broadly consistent with previous reports and suggest a possible association between the CENP-F-like pattern and malignancies.Conclusion The CENP-F-like pattern is rare in ANA tests but may be associated with clinically important conditions,particularly cancers and AIDs.The occurrence of metastasis and GVHD in patients with this pattern highlights its potential clinical relevance,and concurrent autoantibodies may assist in diagnosing AIDs.
基金Supported by General Project of Shanxi Administration of Traditional Chinese Medicine(2023ZYYA007&2024ZYY2D009)Young Scientists Project of Shanxi Provincial Department of Science and Technology(202203021212026)Scientific and Technological Innovation Capacity Cultivation Program for Basic and Clinical Cooperative Research Project of Shanxi University of Chinese Medicine(2024PY-JL-23-01).
文摘This study makes an in-depth exploration of the core pathogenesis of chronic atrophic gastritis,Qi Deficiency with Stagnation,to systematically interpret it within the theoretical framework of Achieving Central Harmony,and to provide a treatment plan.Professor Li Tingquan believes that the occurrence and development of chronic atrophic gastritis(CAG)is fundamentally a process of harmony imbalance of the spleen and stomach.Its specific manifestation lies in the interaction between qi deficiency and stagnation,namely,spleen deficiency as the root cause,and qi stagnation,phlegm-dampness,and blood stasis obstructing the middle energizer as the secondary manifestations.These factors are mutually causal and interact with one another.Based on this,he proposed a four-step method to treat the disease:eliminating pathogenic factors,harmonizing the spleen and stomach,activating blood circulation to resolve stasis,and tonifying the kidney to generate blood(metaphorically described as"closing the mountains to cultivate forests and thicken the soil,breeding seeds and irrigating for stomach recovery").This approach aims to restore the harmonious state of the middle energizer,providing a complete clinical framework of theory,principle,formula,and herbs for the prevention and treatment of CAG.
基金supported by Porsolt SAS,https://www.porsolt.com/.
文摘Objectives:The five-year survival rate for pancreatic cancer is notably low,posing a significant challenge to patient health.The primary treatments are radiotherapy and chemotherapy,sometimes combined with targeted therapy;however,their clinical benefits are limited.Therefore,developing new models to evaluate the therapeutic potential of novel molecules is essential.Fingolimod and Dimethyl Fumarate(DMF),currently used to treat multiple sclerosis,have recently been shown to have anti-cancer effects in several preclinical tumor models.This study aims to evaluate the therapeutic potential of Fingolimod and DMF in pancreatic cancer by investigating their respective in vitro cytotoxicity and in vivo antitumor effects.Methods:In this study,we evaluated for the first time these two drugs in pancreatic preclinical models in vitro using 3D spheroid tumor models and in vivo,which are compared to two standard-of-care consisting of Gemcitabine and Erlotinib.Results:In vitro,both Fingolimod and DMF induced cytotoxicity in spheroids from two pancreatic cell lines.Additionally,Fingolimod and DMF displayed anticancer effects in two subcutaneous xenograft models using PANC-1 and CFPAC-1 cells.Conclusions:Although the responses observed with Fingolimod and DMF were similar to those of Gemcitabine and Erlotinib,these findings indicate a potential emerging interest in Fingolimod and DMF for the treatment of pancreatic cancer.However,further work is still necessary to fully characterize how these drugs affect tumor progression.
基金supported by the Talent Development Plan for High-level Public Health Technical Personnel Project in Beijing,Beijing Municipal Health Commission[No.XKGG-02-03].
文摘Introduction.Well-designed,strictly implemented,and fully standardized randomized controlled trials(RCTs)are a prerequisite for developing reliable scientific evidence,which can improve clinical practice,health outcomes,and ultimately benefit patients.Suboptimal reporting is pervasive in medical research,resulting in biased research records and persistent uncertainty about the quality of available evidence.1,2,3,4 The standardization of research reports has attracted considerable attention.In 1996,the Consolidated Standards of Reporting Trials(CONSORT)was first published to improve the quality of RCTs and enhance the reproducibility of trial methods,results,and inferences.
基金supported by the Non-communicable Chronic Diseases National Science and Technology Major Project(Grant No.2025ZD0544003).
文摘The landscape of breast cancer treatment has undergone a transformative shift with the integration of immunotherapy.Historically considered a“cold”tumor with limited immunogenicity,breast cancer management was dominated by surgery,chemotherapy,radiotherapy,and targeted therapies1.However,the advent of immune checkpoint inhibitors(ICIs)has challenged this paradigm,opening a new frontier.The initial breakthrough in triple-negative breast cancer(TNBC)demonstrated that a subset of patients could derive profound and durable clinical benefit from pembrolizumab and atezolizumab2,3.Today,precision immunotherapy aims to identify the patients most likely to respond,to convert immunologically silent tumors into responsive tumors,and to strategically combine immunotherapies with other modalities to overcome resistance.This evolution from empirical application to biomarker-driven strategies marks the critical juncture at which we stand,transitioning promising clinical trial data into refined,effective,and accessible clinical practice4.Recent key clinical studies on breast cancer immunotherapy are summarized in Table 1.
基金supported by the National Key R&D Program of China(2022YFC3501000,2022YFC3502300)National Natural Science Foundation of China(82374627)+2 种基金Fundamental Research Funds for the Central public welfare research institutes(Z0876)Fundamental Research Funds for the Central Universities(2024-JYB-KYPT-01)Beijing Municipal Science and Technology Commission(Z241100007724010).
文摘Background:Artificial intelligence medical diagnostic devices(AIMDDs)show strong potential but face barriers to clinical use,emphasizing the need for rigorous clinical research.Objective:We assessed current AIMDD research,key challenges,and future directions.Methods:A scoping review followed Arksey and O'Malley's methodological framework and the Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews guidelines.PubMed,Web of Science Core Collection,and the Cochrane Database of Systematic Reviews(January 2020-December 2024)were searched on AIMDD design,implementation,and evaluation.Two independent researchers screened and extracted data from the literature using predefined criteria.Results:Ninety-seven articles met the inclusion criteria.Machine learning and deep learning approaches dominated across diverse disease fields,with oncology being the most frequent(41%).The key challenges identified include insufficient quantity,quality,representativeness,and diversity of data;research designs that do not adequately address clinical needs;poor patient selection;poorly defined gold standards;lack of external and prospective validation;and a disconnect between validation strategies and clinical practice.Additionally,issues such as the“black box”phenomenon,overfitting,and data privacy concerns hinder clinical translation.Completeness and standardization of reporting were also found to be lacking.Conclusions:Significant challenges remain in the development and clinical application of AIMDD.To facilitate their clinical translation,improvements are needed in dataset optimization,clinically driven research design,development of evaluation frameworks,enhanced interpretability,and standardized reporting and validation of algorithms.
基金Hunan Provincial Natural Science Foundation of China,Grant/Award Numbers:2024JJ6289,2023JJ60464,2023JJ60334Changsha City Technology Program,Grant/Award Number:kq2403120+1 种基金Climb Plan of Hunan Cancer Hospital,Grant/Award Numbers:ZX2021005,QH2023006High-Level Talent Support Program of Hunan Cancer Hospital,Grant/Award Number:20250731-1050。
文摘The convergence of artificial intelligence(AI)and big data is reshaping contemporary oncology by enabling the integration of multimodal information across imaging,pathology,genomics,and clinical records.From a physician-centered perspective,these technologies can potentially be used to improve diagnostic precision,support individualized treatment planning,enhance longitudinal patient management,and accelerate both clinical and translational research.In this review,we synthesize the core AI methodologies most relevant to oncology-machine learning,deep learning,and large language models-and examine how they interact with established and emerging oncology data platforms.We further highlight practical use cases in clinical workflows and research pipelines,emphasizing opportunities for advancing precision cancer care while also addressing challenges associated with data heterogeneity,model generalizability,privacy protection,and real-world implementation.By underscoring the synergistic value of AI and big data,this review aims to inform the development of clinically meaningful,context-adapted strategies that promote translational innovation in both global and locally resourced healthcare environments.
基金supported by the Defitech Foundation(Morges,CH)to FCHthe Bertarelli Foundation-Catalyst program(Gstaad,CH)to FCH+2 种基金the Wyss Center for Bio and Neuroengineering the Lighthouse Partnership for AI-guided Neuromodulation to FCHthe Fonds de recherche du Quebec-Sante(FRQS#342969)to CEPthe Neuro X Postdoctoral Fellowship Program to CEP。
文摘Brain lesions,such as those caused by stroke or traumatic brain injury(TBI),frequently result in persistent motor and cognitive impairments that significantly affect the individual patient's quality of life.Despite differences in the mechanisms of injury,both conditions share a high prevalence of motor and cognitive impairments.These deficits show only limited natural recovery.
文摘Chronic pain represents a significant global health challenge,and the limitations of conventional analgesics have urged a search for alternative therapeutic strategies.Cannabinoids derived from Cannabis sativa have emerged as prominent candidates.While psychotropic cannabinoids are known for their analgesic effects,their psychoactive properties often limit their clinical utility.Consequently,interest has shifted towards non-psychotropic cannabinoids that offer potential pain relief without inducing cognitive or euphoric effects.This comprehensive review investigates the pain-modulating mechanisms of cannabinoids,encompassing interactions with the endocannabinoid system and other non-traditional pathways,and summarizes the existing preclinical and clinical evidence supporting their use in various pain states.Furthermore,it discusses the therapeutic potential,clinical considerations,significant challenges,and the need for product standardization.This review also aims to evaluate the role and prospects of non-psychotropic cannabinoids as a therapeutic option for pain management.
文摘Carbamazepine is an antiepileptic drug also used for neuropathic pain and mood stabilization.It is a strong enzyme inducer and autoinducer with multiple well-documented drug–drug interactions and adverse drug reactions.Widely licensed and in use since the 1960s,carbamazepine has well-characterized pharmacological,pharmacogenetic,and safety profiles,and remains extensively used in neurology and psychiatry.In 2024,carbamazepine was recommended for inclusion in the World Health Organization list of essential medicines.Carbamazepine has a complex mode of action that includes neuronal stabilization,neuroprotection,neurotransmitter modulation,enhancement of autophagy,and anti-inflammatory effects.These make carbamazepine a good candidate for drug repurposing in oncology,genetic diseases,neurodegeneration,and systemic inflammation.Recent advances in precision medicine,genomics,and on/off-target drug repositioning have enabled the identification of new carbamazepinemolecular targets for novel applications in different therapeuticmodalities.This review highlights carbamazepine repurposing studies in cancers such as breast and colorectal,based on its mode of action.In addition,repurposing studies in genetic diseases such asmetaphyseal achondroplasia and Fragile-X,as well as in neurodegenerative conditions such as amyotrophic lateral sclerosis and Alzheimer's dementia,are discussed.The pharmacological mechanisms and drug repurposing pathways are critically summarized in order to provide insights into their therapeutic potential and proposed future directions.
文摘The Chinese Society of Clinical Oncology Non-small Cell Lung Cancer(CSCO NSCLC)guidelines were first published in 2016,ranking among the earliest-released guidelines within the CSCO series.In 2020 the CSCO published separate guidelines for NSCLC and small cell lung cancer(SCLC)for the first time to improve clinical usability.
基金funded by National Natural Science Foundation of China(82360801).
文摘Tumor metabolic reprogramming is a core hallmark of cancer,characterized by pathways such as aerobic glycolysis,aberrant lipid metabolism,and glutaminolysis that support rapid proliferation and immunosuppressive microenvironments.Circular RNAs(circRNAs)are highly stable,evolutionarily conserved non-coding RNAs that have emerged as critical modulators of these metabolic shifts.This review aims to systematically elucidate the roles and mechanisms of circRNAs in reprogramming tumor metabolism,and to discuss their clinical potential as biomarkers and therapeutic targets.Through mechanisms including miRNA sponging,protein interactions,regulation of mitochondrial dynamics,and modulation of metabolic enzymes,circRNAs influence key metabolic pathways by targeting glycolytic enzymes,lipid synthesis regulators,and glutaminolysis-related molecules to either facilitate or inhibit their expression.This review systematically summarizes the unique contributions of circRNAs to tumor metabolic reprogramming,highlighting key mechanisms such as regulation of peptide-encoding protein translation,mitochondrial localization function,gene promoter-targeted transcriptional regulation,and cross-pathway metabolic mediation,which underscore their distinct biological advantages and regulatory roles in tumor metabolism.The stability and tissue specificity of circRNAs make them promising diagnostic biomarkers,while their role in drug resistance mediated by metabolic reprogramming highlights their potential as therapeutic targets.Strategies such as circRNA inhibitors,mimics,and nanoparticle-based delivery systems are being explored to modulate tumor metabolism.Despite challenges including complex regulatory networks and limited manipulation tools,advances in high-throughput technologies and clinical trials hold promise for translating circRNA research into novel cancer therapies.
基金National Key Research and Development Program of China,Grant/Award Number:2024YFF0507404Special Clinical Business Fund for High-Level Hospitals of China-Japan Friendship Hospital,Grant/Award Number:2024-NHLHCRF-TS-01。
文摘Background:Large language models(LLMs)have shown considerable promise in supporting clinical decision-making.However,their adoption and evaluation in dermatology remains limited.This study aimed to explore the preferences of Chinese dermatologists regarding LLM-generated responses in clinical psoriasis scenarios and to assess how they prioritize key quality dimensions,including accuracy,traceability,and logicality.Methods:A cross-sectional,web-based survey was conducted between December 25,2024,and January 22,2025,following the Checklist for Reporting Results of Internet E-Surveys guidelines.A total of 1247 valid responses were collected from practicing dermatologists across 33 of China's provincial-level administrative divisions.Participants evaluated responses to five categories of clinical questions(etiology,clinical presentation,differential diagnosis,treatment,and case study)generated by five LLMs:ChatGPT-4o,Kimi.ai,Doubao,ZuoYiGPT,and Lingyi-agent.Statistical associations between participant characteristics and model preferences were examined using chi-square tests.Results:ChatGPT-4o(Model 1)emerged as the most preferred model across all clinical tasks,consistently receiving the highest number of votes in case study(n=740),clinical presentation(n=666),differential diagnosis(n=707),etiology(n=602),and treatment(n=656).Significant variation in model preference by professional title was observed only for the differential diagnosis task(χ^(2)=21.13,df=12,p=0.0485),while no significant differences were found across hospital tiers(p>0.05).In terms of evaluation dimensions,accuracy was most frequently rated as“very important”(n=635).A significant association existed between hospital tier and the most valued dimension(χ^(2)=27.667,df=9,p=0.0011),with dermatologists in primary hospitals prioritizing traceability more than their peers in higher-tier hospitals.No significant associations were found across professional titles(p=0.127).Conclusions:Chinese dermatologists suggest a strong preference for ChatGPT-4o over domestic LLMs in psoriasis-related clinical tasks.While accuracy remains the primary criterion,traceability and logicality are also critical,particularly for clinicians in lower-tier hospitals.These findings suggest that future clinical LLMs should prioritize not only content accuracy but also source transparency and structural clarity to meet the diverse needs of different clinical settings.
基金Outstanding Young Investigator Program of Capital Medical University,Grant/Award Number:A2308。
文摘Phrenic nerve stimulation(PNS)may preserve diaphragm activation and mitigate multiorgan injury during mechanical ventilation(MV);however,a minimal invasive rat model integrating PNS with MV is lacking.We established an omohyoid muscle-based PNS rat model combined with MV.Bilateral nerves were exposed within 20±2 min by transection at the intermediate tendon of omohyoid muscle,minimizing trauma and bleeding.Threshold stimulation(0.6±0.2 mA)correlated with body weight.Ventilator-synchronized stimulation increased compound muscle action potentials by~30%,whereas histology confirmed intact nerve.Physiological parameters remained stable throughout ventilation.This model provides a safe and scalable platform for mechanistic and preclinical studies on PNS-mediated protection against MV-induced organ injury.
基金supported by the National Key Research and Development Program of China,No.2019YFA0111200the National Natural Science Foundation of China,Nos.U23A20436,82371047+3 种基金Key Research Project in Shanxi Province,No.202302130501008Shanxi Provincial Science Fund for Distinguished Young Scholars,No.202103021221008Key Research and Development Program in Shanxi Province,No.202204051001023Shanxi Medical University Doctor’s Startup Fund Project,No.SD22028(all to YG)。
文摘Retinal ganglion cells are the bridging neurons between the eye and the central nervous system,transmitting visual signals to the brain.The injury and loss of retinal ganglion cells are the primary pathological changes in several retinal degenerative diseases,including glaucoma,ischemic optic neuropathy,diabetic neuropathy,and optic neuritis.In mammals,injured retinal ganglion cells lack regenerative capacity and undergo apoptotic cell death within a few days of injury.Additionally,these cells exhibit limited regenerative ability,ultimately contributing to vision impairment and potentially leading to blindness.Currently,the only effective clinical treatment for glaucoma is to prevent vision loss by lowering intraocular pressure through medications or surgery;however,this approach cannot halt the effect of retinal ganglion cell loss on visual function.This review comprehensively investigates the mechanisms underlying retinal ganglion cell degeneration in retinal degenerative diseases and further explores the current status and potential of cell replacement therapy for regenerating retinal ganglion cells.As our understanding of the complex processes involved in retinal ganglion cell degeneration deepens,we can explore new treatment strategies,such as cell transplantation,which may offer more effective ways to mitigate the effect of retinal degenerative diseases on vision.
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.
基金supported by FCT/MCTES UIDP/05608/2020(https://doi.org/10.54499/UIDP/05608/2020)UIDB/05608/2020(https://doi.org/10.54499/UIDB/05608/2020).
文摘Background:The Colorectal Cancer(CRC)pathogenesis and therapeutic efficacy are influenced by the gut microbiome,making it a promising biomarker for predicting treatment responses and adverse effects.This systematic review aims to outline the gut microbiome composition in individuals with CRC undergoing the same therapeutic regimen and evaluate interindividual microbiome profile variations to better understand how these differences may influence therapeutic outcomes.Methods:Key studies investigating the microbiome’s role in therapeutic approaches for CRC were searched in both PubMed and Cochrane databases on 12 and 22 March 2025,respectively.Eligible studies included free full-text English-language randomized clinical trials and human observational studies reporting on gut microbiome composition and treatment outcomes.RoB 2 and ROBINS-I were employed in the evaluation of bias for randomized trials and observational studies,respectively.Data extracted was narratively analyzed.Results:Six studies involving a total of 361 individuals were included.Therapeutic interventions,either standard treatments and/or those targeting the gut microbiome,generally increased probiotic taxa and reduced pro-carcinogenic bacteria.However,no consistent pattern of improved clinical outcomes was observed,suggesting that treatment mechanisms,the tumor’s nature,and individual characteristics play critical roles in microbiome modulation.Conclusion:The gut microbiome holds significant potential in clinical settings.Nonetheless,further research is needed to better understand its functional aspects and to consider the influence of treatment mechanisms,the tumor’s nature,and individual characteristics as modulators,in order to optimize clinical outcomes.
基金supported by the Natural Science Foundation of Beijing,Nos.7244428(to WZ)and 7222215(to JH)the Peking University Medicine Sailing Program forYoung Scholars’Scientific and Technological Innovation,No.BMU2023YFJHPY034(to WZ)+4 种基金the National Natural Science Foundation of China,Nos.81873784,82071426(to DF),and81974197(to JH)the Clinical Cohort Construction Program of Peking University Third Hospital,No.BYSYDL2019002(to DF)Beijing Physician-Scientist TrainingProgram,No.BJPSTP-2024-03(to JH)the China Postdoctoral Science Foundation,Nos.2022TQ0014(to LX),2022M720284(to LX)the E-Town Cooperation&Development Foundation,No.YCXJ-JZ-2023-017(to LX).
文摘The growing recognition of the role of genetics in the development of amyotrophic lateral sclerosis is evident.However,there has yet to be a comprehensive analysis of the clinical characteristics and genetics of familial amyotrophic lateral sclerosis in an Asian population.This study aimed to provide an in-depth analysis of the clinical features and genetic spectrum of familial amyotrophic lateral sclerosis over 15 years in a clinic-based cohort of patients from the Chinese mainland.Enrollment of 302 amyotrophic lateral sclerosis families from 28 provinces was undertaken from January 2008 to September 2023.A group-based trajectory model for disease progression based on amyotrophic lateral sclerosis Functional Rating Scale-Revised(ALSFRS-R)scores was validated using bootstrap internal validation in patients with familial amyotrophic lateral sclerosis,as well as patients with sporadic amyotrophic lateral sclerosis(matched at a 1:4 ratio,with replacement).DNA samples from 244 index patients were screened for variants in the pathogenic genes SOD1,FUS,TDP43,and C9ORF72,of which 146 were also subjected to genome-wide next-generation sequencing.Gene-level burden analysis was used to evaluate the distribution of rare variants in the cohort.We found that rapid dynamic disease progression was associated with an older age at onset,shorter diagnostic delay,lower body mass index,bulbar onset,and≥1 affected first-degree relative.Certain attributes,such as age at onset and time from onset to diagnosis,had comparable impacts on the clinical progression trajectories of both familial amyotrophic lateral sclerosis and sporadic amyotrophic lateral sclerosis.Harboring pathogenic/likely pathogenic variants in amyotrophic lateral sclerosis-causative genes reduced the age of onset of familial amyotrophic lateral sclerosis.Among the patients with familial amyotrophic lateral sclerosis,17.8%possessed≥2 pathogenic/likely pathogenic variants.Sequencing kernel association test analysis showed that the SOD1 rare variant burden(P=1.3e-15)was associated with a significant risk of familial amyotrophic lateral sclerosis.Our findings conclusively confirmed the clinical features and genetic spectrum of familial amyotrophic lateral sclerosis over 15 years in a clinical cohort from China,contributing to a deeper understanding of genotype-phenotype relationships in familial amyotrophic lateral sclerosis.This comprehensive evaluation of specific clinical characteristics,clinical prognosis,and genetic variants of amyotrophic lateral sclerosis based on detailed clinical and genetic information may lead to the development of genotype-specific treatment approaches.
文摘Clear aligner treatment is a novel technique in current orthodontic practice.Distinct from traditional fixed orthodontic appliances,clear aligners have different material features and biomechanical characteristics and treatment efficiencies,presenting new clinical challenges.Therefore,a comprehensive and systematic description of the key clinical aspects of clear aligner treatment is essential to enhance treatment efficacy and facilitate the advancement and wide adoption of this new technique.This expert consensus discusses case selection and grading of treatment difficulty,principle of clear aligner therapy,clinical procedures and potential complications,which are crucial to the clinical success of clear aligner treatment.
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.
