Background:Glioblastoma(GBM)prognosis has seen little improvement over the past two decades.While immunotherapy has revolutionized cancer treatment,its impact on GBM remains limited.To characterize the evolving resear...Background:Glioblastoma(GBM)prognosis has seen little improvement over the past two decades.While immunotherapy has revolutionized cancer treatment,its impact on GBM remains limited.To characterize the evolving research landscape and identify future directions in GBM immunotherapy,we conducted a comprehensive bibliometric review.Methods:All literature related to immunotherapy in GBM from 1999 to 2024 was collected from the Web of Science Core Collection.CtieSpace and VOSviewer were used to conduct bibliometric analysis and visualize the data.Results:Bibliometric analysis identified 5038 publications authored by 23,335 researchers from 4699 institutions across 96 countries/regions,published in 945 journals.The United States produced the highest number of publications,while Switzerland achieved the highest average citation rate.Duke University led in institutional output and citations.John H Sampson was the most productive author,and Roger Stupp was the most cited.Frontiers in Immunology published the most papers,while Clinical Cancer Research was the most cited journal.Research focus centered on adoptive T cell therapy,particularly chimeric antigen receptor(CAR)-T cells with 572 dedicated publications.Within CAR-T research for GBM,the University of Pennsylvania was the leading institution,Frontiers in Immunology the predominant journal,and Christine E Brown(City of Hope National Medical Center)was the most prolific and cited author.Conclusions:There has been a growing interest in GBM immunotherapy over past decades.The United States is the dominant contributor.CAR-T therapy represents the primary research focus.Emerging strategies like chimeric antigen receptor-modified natural killer(CAR-NK)cells,chimeric antigen receptor-engineered macrophages(CAR-M),and cytomegalovirus-specific T cell receptor(CMV-TCR)T cells are gaining prominence,aiming to address limitations in antigen recognition inherent to CAR-T therapy for GBM.展开更多
Penetrance is a crucial indicator for accurately assessing disease risk and plays a vital role in disease research,gene therapy,and genetic counseling.However,with penetrance data dispersed across various sources,effi...Penetrance is a crucial indicator for accurately assessing disease risk and plays a vital role in disease research,gene therapy,and genetic counseling.However,with penetrance data dispersed across various sources,efficiently accessing and consolidating this information becomes a challenge.A comprehensive platform that integrates penetrance is urgently needed.Here,we present PenCards,a global,community-contributed public archive of variant penetrance,by first collecting penetrance data from all published literature and then using large international cohorts to specifically calculate the penetrance of autism-related variants.PenCards contains a total of 244,531 variants,including 239,244 single nucleotide variants,4994 insertions and deletions,and 293 copy number variants,covering approximately 300 phenotypes.We also provide a submission portal for the dynamic updating of penetrance.Additionally,to help users efficiently access genetic information,we comprehensively integrate over 150 variant-and gene-level resources.In summary,PenCards is a powerful platform designed to advance genetic research and diagnostics.PenCards is publicly available at https://genemed.tech/pencards/.展开更多
AIM:To conduct a genetic analysis of Han-Chinese patients with isolated congenital ptosis(ICP)and identify the genetic variants related to the condition.METHODS:Sixty-five unrelated patients with ICP were enrolled.Com...AIM:To conduct a genetic analysis of Han-Chinese patients with isolated congenital ptosis(ICP)and identify the genetic variants related to the condition.METHODS:Sixty-five unrelated patients with ICP were enrolled.Comprehensive clinical examinations,whole exome sequencing(WES),and Sanger sequencing were used to reveal the potential genetic causes.Combined with public and in-house control databases,multiple bioinformatics prediction tools,and conservation analysis,the potential variants were further analyzed.AlphaFold 3,an accurate modelling prediction tool,was utilized to generate three-dimensional structural models of both wild-type and mutated proteins.RESULTS:Three novel heterozygous variants in the zinc finger homeobox 4 gene(ZFHX4),c.5145C>A(p.N1715K),c.10382C>T(p.A3461V),and c.10795G>A(p.A3599T),were identified in three patients,respectively.Bioinformatics analyses suggested that these variants are likely to exert deleterious effects,supporting their potential involvement in the pathogenesis of ptosis.CONCLUSION:The novel heterozygous ZFHX4 variants are identified as disease-associated variants in three patients with ptosis,suggesting that ZFHX4 may be a disease-causing gene for autosomal dominant ICP with incomplete penetrance or a susceptibility gene.These findings expand the variant spectrum of ZFHX4,improve understanding of the pathogenesis of ZFHX4-related ptosis,and may contribute to the genetic counseling and disease management,as well as the development of experimental treatments.展开更多
Thrombosis is the pathological process resulting from the inappropriate and propagation of the hemostatic response. The principle determinants of thrombosis can be categorized in contemporary terms according to Vircho...Thrombosis is the pathological process resulting from the inappropriate and propagation of the hemostatic response. The principle determinants of thrombosis can be categorized in contemporary terms according to Virchow' s paradigm: abnormalities in endothelial function ( vessel function ), rheotogy ( blood flow ), or blood component,either alone or in combination, can promote thrombus formation.展开更多
Objective:Verrucous epidermal nevus(VEN),seborrheic keratosis(SK),verruca plana(VP),verruca vulgaris(VV),and nevus sebaceous(NS)are common verrucous proliferative skin diseases with similar clinical appearances,often ...Objective:Verrucous epidermal nevus(VEN),seborrheic keratosis(SK),verruca plana(VP),verruca vulgaris(VV),and nevus sebaceous(NS)are common verrucous proliferative skin diseases with similar clinical appearances,often posing diagnostic challenges.Dermoscopy and reflectance confocal microscopy(RCM)can aid in their differentiation,yet their specific features under these tools have not been systematically described.This study aims to summarize and analyze the dermoscopic and RCM features of VEN,SK,VP,VV,and NS.Methods:A total of 121 patients with histopathologically confirmed verrucous proliferative skin diseases were enrolled.Dermoscopy and RCM imaging was used to observe and analyze the microscopic features of these conditions.Results:Under dermoscopy,the 5 diseases displayed distinct characteristics:VEN typically showed gyriform structures;SK was characterized by gyriform structures,comedo-like openings,and milia-like cysts;VP and VV featured dotted vessels and frogspawn-like structures;NS presented as brownish-yellow globules.RCM revealed shared features such as hyperkeratosis and acanthosis across all 5 diseases.Specific features included gyriform structures and elongated rete ridges in VEN;pseudocysts and gyriform structures in SK;evenly distributed ring-like structures in VP;vacuolated cells and papillomatous proliferation in VV;and frogspawn-like structures in NS.Conclusion:These 5 verrucous proliferative skin conditions exhibit distinguishable features under both dermoscopy and RCM.The combination of these 2 noninvasive imaging modalities holds significant clinical value for the differential diagnosis of verrucous proliferative skin diseases.展开更多
BACKGROUND Uncertainty in illness(UI)and fear of progression(FoP)are significant psycho-logical challenges for lung cancer patients.Coping styles and social support are critical mediators,influencing patients'abil...BACKGROUND Uncertainty in illness(UI)and fear of progression(FoP)are significant psycho-logical challenges for lung cancer patients.Coping styles and social support are critical mediators,influencing patients'ability to manage the emotional and psy-chological burden of UI and FoP.However,limited research has explored the chain mediation effect of these factors on the relationship between UI and FoP,particularly among Chinese lung cancer patients.Convenience sampling was used to recruit inpatients diagnosed with lung cancer at a tertiary hospital in Changde City between November and December 2023.A total of 320 participants completed the Mishel Uncertainty in Illness Scale,Simp-lified Coping Style Questionnaire,Mandarin Chinese Version of the Medical Outcomes Study Social Support Survey,and Fear of Progression Questionnaire-Short Form.The chain mediation analysis was performed using the PROCESS macro to examine the relationships between the variables.RESULTS The results revealed that UI had a significant direct effect on FoP(effect=0.224,95%CI:0.136-0.408).Additionally,three indirect pathways were identified:(1)Social support(effect=0.128,95%CI:0.045-0.153);(2)Coping style(effect=0.115,95%CI:0.048-0.157);and(3)Chain mediators involving social support and coping style(effect=0.072,95%CI:0.045-0.120).The total indirect effect of the three mediation paths is 31.5%.These results confirm that social support and coping style significantly mediate the relationship between UI and FoP.CONCLUSION Based on cross-sectional data and a chain mediation model,this study explored the mechanisms between UI,social support,coping style,and FOP.Patients with lung cancer have higher levels of FOP,and the results of this study revealed a correlation between these four factors.Social support and coping style partially mediated the effects of UI on FOP,and there was a chain-mediating effect between UI and FOP.Programs designed to strengthen social support networks should also incorporate training to develop adaptive coping strategies,ultimately reducing FOP and improving overall quality of life.展开更多
Fast electron-hole recombination issues during titanium dioxide(TiO_(2))photocatalysis limit its application in preventing bacterial infection during bone defect repair.In this study,TiO_(2)@reduced graphene oxide(rGO...Fast electron-hole recombination issues during titanium dioxide(TiO_(2))photocatalysis limit its application in preventing bacterial infection during bone defect repair.In this study,TiO_(2)@reduced graphene oxide(rGO)composites were synthesized using a hydrothermal method in which rGO,which possesses very high electrical conductivity,promotes the separation of photoelectron-hole pairs of TiO_(2),thus improving the efficiency of photocatalytic production of reactive oxygen species(ROS).Subsequently,TiO_(2)@rGO composites were introduced into poly-L-lactic acid(PLLA)to prepare bone scaffolds with photocatalytic antibacterial function via selective laser sintering.The results showed that TiO_(2)grew on the surface of rGO and formed a covalent bond connection(Ti-O-C)with rGO.A decreased electrochemical impedance of TiO_(2)@rGO composites was observed,and the transient photocurrent intensity increased from 0.05 to 0.5μA/cm^(2).Analysis of electron spin resonance found that the photocatalytic products of TiO_(2)were·OH and·O^(2-),two kinds of ROS capable of killing bacteria via disrupting the structure of the bacterial membrane in vitro.Antibacterial experiments showed that the PLLA/TiO_(2)@rGO scaffolds had good antibacterial properties against Escherichia coli and Staphylococcus aureus.Finally,we report that these scaffolds exhibited both enhanced mechanical properties due to the addition of TiO_(2)@rGO as a reinforcement material and good biocompatibility during cell proliferation.展开更多
The first example of Nd@C_(3)N_(4)-photoredox/chlorine dual catalyzed alkylation with unactivated alkanes as the alkyl sources has been developed,which allows for the synthesis of various 4-alkylated cyclic sulfonyl k...The first example of Nd@C_(3)N_(4)-photoredox/chlorine dual catalyzed alkylation with unactivated alkanes as the alkyl sources has been developed,which allows for the synthesis of various 4-alkylated cyclic sulfonyl ketimines.In this process,chlorine functions as both a redox and hydrogen atom transfer catalyst.The synergism of the reversible Nd^(2+)/Nd^(3+)and Cl^(ˉ)/Cl˙redox pairs significantly enhances overall photocatalytic efficiency.The in vitro anticancer activity of 4-alkylated products was evaluated by using the CCK8assay against both human choroidal melanoma(MUM-2B)and lung cancer(A549)cell.Compound 3da showed approximately triple the potency of 5-fluorouracil.展开更多
Frozen shoulder(FS),also known as adhesive capsulitis,is a condition that causes contraction and stiffness of the shoulder joint capsule.The main symptoms are per-sistent shoulder pain and a limited range of motion in...Frozen shoulder(FS),also known as adhesive capsulitis,is a condition that causes contraction and stiffness of the shoulder joint capsule.The main symptoms are per-sistent shoulder pain and a limited range of motion in all directions.These symp-toms and poor prognosis affect people's physical health and quality of life.Currently,the specific mechanisms of FS remain unclear,and there is variability in treatment methods and their efficacy.Additionally,the early symptoms of FS are difficult to distinguish from those of other shoulder diseases,complicating early diagnosis and treatment.Therefore,it is necessary to develop and utilize animal models to under-stand the pathogenesis of FS and to explore treatment strategies,providing insights into the prevention and treatment of human FS.This paper reviews the rat models available for FS research,including external immobilization models,surgical internal immobilization models,injection modeling models,and endocrine modeling models.It introduces the basic procedures for these models and compares and analyzes the advantages,disadvantages,and applicability of each modeling method.Finally,our paper summarizes the common methods for evaluating FS rat models.展开更多
AIM:To assess the possibility of using different large language models(LLMs)in ocular surface diseases by selecting five different LLMS to test their accuracy in answering specialized questions related to ocular surfa...AIM:To assess the possibility of using different large language models(LLMs)in ocular surface diseases by selecting five different LLMS to test their accuracy in answering specialized questions related to ocular surface diseases:ChatGPT-4,ChatGPT-3.5,Claude 2,PaLM2,and SenseNova.METHODS:A group of experienced ophthalmology professors were asked to develop a 100-question singlechoice question on ocular surface diseases designed to assess the performance of LLMs and human participants in answering ophthalmology specialty exam questions.The exam includes questions on the following topics:keratitis disease(20 questions),keratoconus,keratomalaciac,corneal dystrophy,corneal degeneration,erosive corneal ulcers,and corneal lesions associated with systemic diseases(20 questions),conjunctivitis disease(20 questions),trachoma,pterygoid and conjunctival tumor diseases(20 questions),and dry eye disease(20 questions).Then the total score of each LLMs and compared their mean score,mean correlation,variance,and confidence were calculated.RESULTS:GPT-4 exhibited the highest performance in terms of LLMs.Comparing the average scores of the LLMs group with the four human groups,chief physician,attending physician,regular trainee,and graduate student,it was found that except for ChatGPT-4,the total score of the rest of the LLMs is lower than that of the graduate student group,which had the lowest score in the human group.Both ChatGPT-4 and PaLM2 were more likely to give exact and correct answers,giving very little chance of an incorrect answer.ChatGPT-4 showed higher credibility when answering questions,with a success rate of 59%,but gave the wrong answer to the question 28% of the time.CONCLUSION:GPT-4 model exhibits excellent performance in both answer relevance and confidence.PaLM2 shows a positive correlation(up to 0.8)in terms of answer accuracy during the exam.In terms of answer confidence,PaLM2 is second only to GPT4 and surpasses Claude 2,SenseNova,and GPT-3.5.Despite the fact that ocular surface disease is a highly specialized discipline,GPT-4 still exhibits superior performance,suggesting that its potential and ability to be applied in this field is enormous,perhaps with the potential to be a valuable resource for medical students and clinicians in the future.展开更多
In the past decade,immunotherapies targeting cytotoxic T-lymphocyte antigen-4(CTLA-4),programmed cell death 1(PD-1),and PD-1 ligand(PD-L1)have been approved for solid tumors.However,some patients demonstrate suboptima...In the past decade,immunotherapies targeting cytotoxic T-lymphocyte antigen-4(CTLA-4),programmed cell death 1(PD-1),and PD-1 ligand(PD-L1)have been approved for solid tumors.However,some patients demonstrate suboptimal clinical outcomes due to resistance.The tumor microenvironment(TME)significantly affects the efficiency of immunotherapy by mediating interactions between tumor and non-tumor cells,including dendritic cells,T cells,B cells,macrophages,neutrophils,NK cells,and myeloid-derived suppressor cells(MDSCs).These non-tumor cells often exhibit two phenotypes with altered functions,and tumor cells drives their transition towards tumor promotion through tumor-education.Tumor-educated cells(TECs)are cells influenced by tumor cells,which acquire immune-suppressive phenotypes and promote tumor progression through resistance to anticancer therapies.These cells undergo modifications in response to signals from the tumor,which can influence their roles in tumor progression.Their dynamic interactions with tumor cells contribute to the reshaping of the TME,facilitating cancer growth and immune modulation.This review summarizes research on TECs in TME,explores mechanisms related to tumor education,and discusses their role in tumor progression and immunotherapy resistance.Additionally,potential therapeutic approaches targeting these cells are also reviewed,which may complement current treatment strategies.展开更多
Recent research has demonstrated the impact of physical activity on the prognosis of glioma patients,with evidence suggesting exercise may reduce mortality risks and aid neural regeneration.The role of the small ubiqu...Recent research has demonstrated the impact of physical activity on the prognosis of glioma patients,with evidence suggesting exercise may reduce mortality risks and aid neural regeneration.The role of the small ubiquitin-like modifier(SUMO)protein,especially post-exercise,in cancer progression,is gaining attention,as are the potential anti-cancer effects of SUMOylation.We used machine learning to create the exercise and SUMO-related gene signature(ESLRS).This signature shows how physical activity might help improve the outlook for low-grade glioma and other cancers.We demonstrated the prognostic and immunotherapeutic significance of ESLRS markers,specifically highlighting how murine double minute 2(MDM2),a component of the ESLRS,can be targeted by nutlin-3.This underscores the intricate relationship between natural compounds such as nutlin-3 and immune regulation.Using comprehensive CRISPR screening,we validated the effects of specific ESLRS genes on low-grade glioma progression.We also revealed insights into the effectiveness of Nutlin-3a as a potent MDM2 inhibitor through molecular docking and dynamic simulation.Nutlin-3a inhibited glioma cell proliferation and activated the p53 pathway.Its efficacy decreased with MDM2 overexpression,and this was reversed by Nutlin-3a or exercise.Experiments using a low-grade glioma mouse model highlighted the effect of physical activity on oxidative stress and molecular pathway regulation.Notably,both physical exercise and Nutlin-3a administration improved physical function in mice bearing tumors derived from MDM2-overexpressing cells.These results suggest the potential for Nutlin-3a,an MDM2 inhibitor,with physical exercise as a therapeutic approach for glioma management.Our research also supports the use of natural products for therapy and sheds light on the interaction of exercise,natural products,and immune regulation in cancer treatment.展开更多
Objective:Near vision loss(NVL)is one of the leading causes of visual impairment worldwide,exerting a profound impact on individual quality of life and socio-economic development.This study aims to analyze the burden ...Objective:Near vision loss(NVL)is one of the leading causes of visual impairment worldwide,exerting a profound impact on individual quality of life and socio-economic development.This study aims to analyze the burden of NVL in China by sex and age groups from 1990 to 2021 and to project trends over the next 15 years.Methods:Using data from the Global Burden of Disease(GBD)2021 database,we conducted descriptive analyses of NVL prevalence in China,calculated age-standardized prevalence rates(ASPR)and age-standardized disability-adjusted life years rates(ASDR)to compare burden differences between sexes and age groups,and applied an autoregressive integrated moving average(ARIMA)model to predict NVL trends for the next 15 years.The model selection was based on best-fit criteria to ensure reliable projections.Results:From 1990 to 2021,China’s ASPR of NVL rose from 10096.24/100000 to 15624.54/100000,and ASDR increased from 101.75/100000 to 158.75/100000.In 2021,ASPR(16551.70/100000)and ASDR(167.69/100000)were higher among females than males(14686.21/100000 and 149.76/100000,respectively).China ranked highest globally in both NVL cases and disability-adjusted life years(DALYs),with female burden significantly exceeding male burden.Projections indicated this trend and sex gap will persist until 2036.Compared with 1990,the prevalence cases and DALYs increased by 239.20%and 238.82%,respectively in 2021,with the highest burden among females and the 55−59 age group.The ARIMA model predicted continued increases in prevalence and DALYs by 2036,with females maintaining a higher burden than males.Conclusion:This study reveals a marked increase in the NVL burden in China and predicts continued growth in the coming years.Public health policies should prioritize NVL prevention and control,with special attention to women and middle-aged populations to mitigate long-term societal and health impacts.展开更多
BACKGROUND Despite advances in the use of in vitro fertilization-embryo transfer(ET)in couples with infertility,recurrent implantation failure(RIF)after ET is still a major problem affecting women,with great psycholog...BACKGROUND Despite advances in the use of in vitro fertilization-embryo transfer(ET)in couples with infertility,recurrent implantation failure(RIF)after ET is still a major problem affecting women,with great psychological and economic burdens for the patient and his/her family.AIM To investigate the psychological burden(anxiety and depression)and evaluate the clinical benefits of endometrial receptivity testing(ERT)in patients experiencing RIF following frozen-thawed ET.METHODS A retrospective cohort study analyzed 371 patients experiencing RIF after assisted reproductive treatment at the First People’s Hospital of Changde City between January 2021 and June 2024.Demographic and clinical data were systematically collected through standardized questionnaires.Psychological assessment utilized validated instruments:The Self-Rating Depression Scale for depression evaluation and the Self-Rating Anxiety Scale for anxiety assessment.Participants were stratified by psychological status(anxiety/non-anxiety and depression/nondepression)to analyze influencing factors for anxiety and depression.The cohort was further categorized into the ERT and non-ERT groups based on ERT implementation to comparatively analyze their clinical outcomes.Additionally,they were divided into clinical and nonclinical pregnancy groups to identify factors affecting clinical pregnancy using univariate and multivariate logistic regression models.Compared with the non-ERT group,the 226 patients who underwent ERT-guided ET achieved a higher clinical pregnancy rate,thicker endometrium on transfer day,fewer embryos transferred,and a lower miscarriage rate.RESULTS The study identified a substantial psychological burden,with anxiety prevalence at 55.0%(mean Self-Rating Anxiety Scale score,50.89±9.34)and depression at 61.2%(mean Self-Rating Depression Scale score,55.55±9.48).Multivariate analysis identified annual household income>100000 yuan as protective factors against both anxiety and depression,whereas advanced maternal age(>35 years)and multiple implantation failures(≥3)served as risk factors.Additionally,anxiety-specific risk factors included prolonged infertility treatment(>5 years)and the spouse’s status as an only child.As to depression-specific risks,chronic infertility(>3 years)and higher educational attainment(college/bachelor’s degree or higher)were key determinants,whereas urban residence was a protective factor.Age>35 years was a risk factor for clinical pregnancy in patients experiencing RIF,whereas blastocyst-stage ET,a higher number of embryos transferred,and thicker endometrium were protective factors.CONCLUSION Patients experiencing RIF are particularly susceptible to anxiety and depression,and advanced maternal age and multiple implantation failures represent salient risk factors.Clinicians should implement proactive and evidencebased interventions to mitigate these psychological burdens.For patients experiencing RIF,ERT-guided ET demonstrates significant potential to improve assisted reproductive outcomes.展开更多
BACKGROUND Benign laryngotracheal stenosis(LTS)is a condition characterized by mucosal inflammation and fibrosis.It is difficult to treat with a high incidence rate.Respiratory distress and voice disorders of varying ...BACKGROUND Benign laryngotracheal stenosis(LTS)is a condition characterized by mucosal inflammation and fibrosis.It is difficult to treat with a high incidence rate.Respiratory distress and voice disorders of varying severity also affect patients'sleep quality and quality of life.AIM To investigate the association between anxiety and depression and sleep quality in patients with benign LTS and identify significant risk factors for sleep disorders.METHODS This retrospective cohort study enrolled 127 consecutive patients with benign LTS admitted to The First People's Hospital of Changde City between January 2021 and January 2024.Comprehensive assessments included demographic collection and Pittsburgh sleep quality index(PSQI),self-rating anxiety scale(SAS),and selfrating depression scale(SDS)scoring.Correlation analyses were conducted to examine relationships between psychological measures and sleep parameters,followed by multivariate logistic regression to determine independent risk factors.RESULTS The cohort demonstrated significantly impaired sleep quality(mean PSQI,7.79±2.47),with 48.0%(n=61)meeting the criteria for clinically significant sleep disturbance.The scores of all PSQI dimensions,as well as SAS and SDS scores of patients with LTS,significantly exceeded Chinese normative values.Strong positive correlations emerged between PSQI scores and both SAS and SDS measures.Multivariate logistic analysis identified middle age(41-50 years),multiple surgical interventions(≥3 procedures),lower socioeconomic status(monthly household income per capita≤5000 RMB),and concurrent anxiety/depression as independent predictors of sleep disturbance.CONCLUSION The results demonstrate a high prevalence of sleep disorders and comorbid anxiety or depressive moods among patients with LTS.These psychological factors both correlate with and independently predict sleep impairment.These results underscore the need for integrated and proactive approaches addressing both physical and mental health components in LTS management,focusing on high-risk subgroups stratified based on age,monthly household income per capita,anxiety/depression status,and number of prior surgeries.展开更多
BACKGROUND Mental disorders have become a major contributor to the Global Burden of Disease(GBD),a situation that has worsened with the onset of the coronavirus disease 2019(COVID-19)pandemic.Updated data on their imp...BACKGROUND Mental disorders have become a major contributor to the Global Burden of Disease(GBD),a situation that has worsened with the onset of the coronavirus disease 2019(COVID-19)pandemic.Updated data on their impact and a clear understanding of long-term trends are essential for global and national health authorities to implement effective prevention and intervention strategies for mental well-being.AIM To generate insights that will enhance global awareness of the burden of mental disorders and support the development of targeted,region-specific prevention and intervention strategies tailored to current global and local health challenges.METHODS We extracted data on incidence,disability-adjusted life years(DALYs),agestandardized incidence rate(ASIR),and age-standardized DALY rate(ASDR)for 12 categories of mental disorders from 1990 to 2021 across 204 countries and territories grouped into 21 regions.Trends in ASIR and ASDR were also analyzed during the COVID-19 period(2019-2021).RESULTS From 1990 to 2021,global ASIR rose by 15.23%(12.97%to 17.60%),while ASDR increased by 73.52%(70.24%to 76.71%).All 21 GBD regions saw a rise in cases and DALYs.In 2021,Central sub-Saharan Africa had the highest ASIR(8706.11),and East Asia reported the lowest(3340.99).Australasia recorded the highest ASDR(2787.87).On the national level,Greenland,Greece,United States,and Australia had the greatest ASDR values.During the pandemic years,ASIR and ASDR rose across all five socio-demographic index levels and GBD regions,with the exception of East Asia,where rates remained stable.Females experienced a higher ASDR than males in 2021.Major depressive disorder(557.87)and anxiety disorders(524.33)were the most burdensome among the 12 types,with depressive disorders ranking first in 13 out of the 21 regions.CONCLUSION The GBD study 2021 results highlight a continued and worsening global burden of mental disorders,further intensified by the COVID-19 crisis.This underscores the urgent need to reinforce mental health care systems.Special attention should be directed toward high-middle socio-demographic index areas and female populations.Expanding access to mental health services,enhancing public awareness,and delivering targeted interventions are essential to lessen the growing impact of mental disorders.展开更多
BACKGROUND Major depressive disorder(MDD)is a significant psychiatric condition that poses a serious threat to human life,primarily due to its association with suicidal behavior.The single nucleotide polymorphism rs37...BACKGROUND Major depressive disorder(MDD)is a significant psychiatric condition that poses a serious threat to human life,primarily due to its association with suicidal behavior.The single nucleotide polymorphism rs372369000 is a risk locus for MDD and is located within the B4GALT6 gene.However,the biological and pathological implications of B4GALT6 in the brain concerning MDD remain unclear.AIM To reveal the biological and pathological significance of B4GALT6 in the brain and MDD.METHODS An inflammation-associated depression mouse model was developed by treating mice with lipopolysaccharides.B4GALT6-like immunoreactivity distribution and expression level was examined throughout the brain.RESULTS B4GALT6-like immunoreactivity increased in the hippocampus,PrL,and the visual cortex V1 region of MDD mice.This elevation varied across different brain subregions and cell types.Specifically,pathological alterations in B4GALT6-like immunoreactivity were observed in CA1 microglia,CA2 neurons,CA3 microglia and neurons,as well as V1 microglia and astrocytes.These changes correlated with the pathology of depression.CONCLUSION Although the neuropathological role of B4GALT6 in the brain remains to be fully characterized,B4GALT6 may be a potential therapeutic target for MDD.展开更多
BACKGROUND Antenatal depression is a disabling mental disorder among pregnant women and may cause adverse outcomes for both the mother and the offspring.Early identification and intervention of antenatal depression ca...BACKGROUND Antenatal depression is a disabling mental disorder among pregnant women and may cause adverse outcomes for both the mother and the offspring.Early identification and intervention of antenatal depression can help to prevent adverse outcomes.However,there have been few population-based studies focusing on the association of social and obstetric risk factors with antenatal depression in China.AIM To assess the sociodemographic and obstetric factors of antenatal depression and compare the network structure of depressive symptoms across different risk levels based on a large Chinese population.METHODS The cross-sectional survey was conducted in Shenzhen,China from 2020 to 2024.Antenatal depression was assessed using the Chinese version of the Edinburgh Postnatal Depression Scale(EPDS),with a score of≥13 indicating the presence of probable antenatal depression.Theχ2 test and binary logistic regression were used to identify the factors associated with antenatal depression.Network analyses were conducted to investigate the structure of depressive symptoms across groups with different risk levels.RESULTS Among the 44220 pregnant women,the prevalence of probable antenatal depression was 4.4%.An age≤24 years,a lower level of education(≤12 years),low or moderate economic status,having a history of mental disorders,being in the first trimester,being a primipara,unplanned pregnancy,and pregnancy without pre-pregnancy screening were found to be associated with antenatal depression(all P<0.05).Depressive symptom networks across groups with different risk levels revealed robust interconnections between symptoms.EPDS8("sad or miserable")and EPDS4("anxious or worried")showed the highest nodal strength across groups with different risk levels.CONCLUSION This study suggested that the prevalence of antenatal depression was 4.4%.Several social and obstetric factors were identified as risk factors for antenatal depression.EPDS8("sad or miserable")and EPDS4("anxious or worried")are pivotal targets for clinical intervention to alleviate the burden of antenatal depression.Early identification of highrisk groups is crucial for the development and implementation of intervention strategies to improve the overall quality of life for pregnant women.展开更多
BACKGROUND The prognosis of patients with poorly differentiated gastric neuroendocrine neoplasms(PDGNENs)is dismal and related research is limited.AIM To investigate the prognostic factors,and validate a novel prognos...BACKGROUND The prognosis of patients with poorly differentiated gastric neuroendocrine neoplasms(PDGNENs)is dismal and related research is limited.AIM To investigate the prognostic factors,and validate a novel prognostic nomogram for PDGNEN patients.METHODS We conducted a retrospective study using clinical and pathological data from PDGNEN patients treated at the First Medical Center of the Chinese PLA General Hospital from January 2000 to June 2023.Overall survival(OS)differences were assessed with the Log-rank test and Kaplan-Meier survival curves.Cox regression analysis identified independent risk factors for prognosis.Model performance was evaluated using Harrell’s concordance index,receiver operating characteristic analysis,area under the curve,calibration curves,and decision curve analysis(UDC),including the area under the UDC.RESULTS The study included 336 patients(227 with neuroendocrine carcinoma and 109 with mixed adenoneuroendocrine carcinoma).The average age was 62.7 years.The cohort comprised 80(24.7%)patients in stage I,146(42.9%)in stage II,62(18.1%)in stage III,and 48(14.3%)in stage IV.Significant differences in OS were observed across tumor-node-metastasis stages(P<0.001).Multivariate analysis showed age,Ki-67 index,invasion depth,lymph node metastasis,distant metastasis,and platelet-to-lymphocyte ratio as independent risk factors.We developed a nomogram with a concordance index of 0.779(95%confidence interval:0.743-0.858).Receiver operating characteristic analysis showed area under the curves for 1-year,3-year,and 5-year OS predictions of 0.865,0.850,and 0.890,respectively.The calibration curve demonstrated good agreement with actual outcomes.The area under the UDC for the nomogram vs the 8th American Joint Committee on Cancer tumor-node-metastasis staging system were 0.047 vs 0.027,0.291 vs 0.179,and 0.376 vs 0.216 for 1-year,3-year,and 5-year OS,respectively.CONCLUSION PDGNENs are predominantly found in older men,often in advanced stages at diagnosis,resulting in poor prognosis.The established nomogram demonstrates strong predictive capability and clinical utility.展开更多
BACKGROUND Visceral adipose tissue(VAT)plays a role in the pathogenesis of Crohn's disease(CD)and is associated with treatment outcomes following infliximab(IFX)therapy.We developed and validated the first delta-r...BACKGROUND Visceral adipose tissue(VAT)plays a role in the pathogenesis of Crohn's disease(CD)and is associated with treatment outcomes following infliximab(IFX)therapy.We developed and validated the first delta-radiomics model to quantify VAT heterogeneity as a predictive biomarker for IFX response in patients with CD.AIM To develop a longitudinal computed tomography(CT)-based delta-radiomics model of VAT for predicting secondary loss of response(SLR)in patients with CD.METHODS This retrospective study included 161 patients with CD who achieved clinical remission following IFX induction therapy between 2015 and 2023.All patients underwent CT enterography before IFX initiation and after completing induction therapy.VAT volume was delineated by two radiologists in consensus.Radiomics features were extracted from pre-treatment and post-induction CT images,and delta-radiomics features were calculated as follows:Delta features=Feature-post-Feature-pre.A radiomics model was constructed using logistic regression.Model performance was assessed using discrimination,calibration,and decision curve analyses.RESULTS Nine significant delta-radiomics features were used to develop the delta-radiomics model,yielding an area under the receiver operating characteristic curve(AUC)of 0.816(95%CI:0.737-0.896)in the training cohort and 0.750(95%CI:0.605-0.895)in the validation cohort.Multivariable logistic regression identified platelet count,Montreal behavior classification,and the VAT/subcutaneous adipose tissue volume ratio prior to treatment as independent risk factors for SLR.The combined model integrating clinical predictors and delta-radiomics features achieved superior predictive performance,with an AUC of 0.853(95%CI:0.786-0.921)in the training cohort and 0.812(95%CI:0.677-0.948)in the validation cohort.CONCLUSION We developed a predictive model based on longitudinal changes in VAT,demonstrating significant potential for identifying patients with CD at high risk of SLR to IFX therapy.展开更多
基金supported by Key Research and Development Plan of Hunan Province(2024DK2006)the Fundamental Research Funds for the Central Universities of Central South University(1053320221769)+2 种基金Hunan Provincial Respiratory Disease Rehabilitation and Nursing Engineering Research Center Innovation Capacity Building Project(No.202012)the Zhangjiajie Science and Technology Development Key Special Project(No.202304)the National Key Clinical Specialty Major Scientific Research Project(No.20230382).
文摘Background:Glioblastoma(GBM)prognosis has seen little improvement over the past two decades.While immunotherapy has revolutionized cancer treatment,its impact on GBM remains limited.To characterize the evolving research landscape and identify future directions in GBM immunotherapy,we conducted a comprehensive bibliometric review.Methods:All literature related to immunotherapy in GBM from 1999 to 2024 was collected from the Web of Science Core Collection.CtieSpace and VOSviewer were used to conduct bibliometric analysis and visualize the data.Results:Bibliometric analysis identified 5038 publications authored by 23,335 researchers from 4699 institutions across 96 countries/regions,published in 945 journals.The United States produced the highest number of publications,while Switzerland achieved the highest average citation rate.Duke University led in institutional output and citations.John H Sampson was the most productive author,and Roger Stupp was the most cited.Frontiers in Immunology published the most papers,while Clinical Cancer Research was the most cited journal.Research focus centered on adoptive T cell therapy,particularly chimeric antigen receptor(CAR)-T cells with 572 dedicated publications.Within CAR-T research for GBM,the University of Pennsylvania was the leading institution,Frontiers in Immunology the predominant journal,and Christine E Brown(City of Hope National Medical Center)was the most prolific and cited author.Conclusions:There has been a growing interest in GBM immunotherapy over past decades.The United States is the dominant contributor.CAR-T therapy represents the primary research focus.Emerging strategies like chimeric antigen receptor-modified natural killer(CAR-NK)cells,chimeric antigen receptor-engineered macrophages(CAR-M),and cytomegalovirus-specific T cell receptor(CMV-TCR)T cells are gaining prominence,aiming to address limitations in antigen recognition inherent to CAR-T therapy for GBM.
基金supported by the National Natural Science Foundation of China(32070591,82371552,and W2512102)the Scientific Research Program of FuRong Laboratory(2023SK2093-1)+2 种基金the Central South University Research Programme of Advanced Interdisciplinary Study(2023QYJC010)the Natural Science Foundation of Hunan Province(2023JJ30975)the Fundamental Research Funds for the Central Universities of Central South University(2025ZZTS0834).
文摘Penetrance is a crucial indicator for accurately assessing disease risk and plays a vital role in disease research,gene therapy,and genetic counseling.However,with penetrance data dispersed across various sources,efficiently accessing and consolidating this information becomes a challenge.A comprehensive platform that integrates penetrance is urgently needed.Here,we present PenCards,a global,community-contributed public archive of variant penetrance,by first collecting penetrance data from all published literature and then using large international cohorts to specifically calculate the penetrance of autism-related variants.PenCards contains a total of 244,531 variants,including 239,244 single nucleotide variants,4994 insertions and deletions,and 293 copy number variants,covering approximately 300 phenotypes.We also provide a submission portal for the dynamic updating of penetrance.Additionally,to help users efficiently access genetic information,we comprehensively integrate over 150 variant-and gene-level resources.In summary,PenCards is a powerful platform designed to advance genetic research and diagnostics.PenCards is publicly available at https://genemed.tech/pencards/.
基金Supported by the National Natural Science Foundation of China(No.81873686)Natural Science Foundation of Hunan Province(No.2023JJ30715)+4 种基金Scientific Research Project of Hunan Provincial Health Commission(No.A202303018385)Health Research Project of Hunan Provincial Health Commission(No.W20243024)Distinguished Professor of the Lotus Scholars Award Program of Hunan ProvinceSublimation Scholars Project of Central South UniversityWisdom Accumulation and Talent Cultivation Project of the Third Xiangya Hospital of Central South University(No.YX202109).
文摘AIM:To conduct a genetic analysis of Han-Chinese patients with isolated congenital ptosis(ICP)and identify the genetic variants related to the condition.METHODS:Sixty-five unrelated patients with ICP were enrolled.Comprehensive clinical examinations,whole exome sequencing(WES),and Sanger sequencing were used to reveal the potential genetic causes.Combined with public and in-house control databases,multiple bioinformatics prediction tools,and conservation analysis,the potential variants were further analyzed.AlphaFold 3,an accurate modelling prediction tool,was utilized to generate three-dimensional structural models of both wild-type and mutated proteins.RESULTS:Three novel heterozygous variants in the zinc finger homeobox 4 gene(ZFHX4),c.5145C>A(p.N1715K),c.10382C>T(p.A3461V),and c.10795G>A(p.A3599T),were identified in three patients,respectively.Bioinformatics analyses suggested that these variants are likely to exert deleterious effects,supporting their potential involvement in the pathogenesis of ptosis.CONCLUSION:The novel heterozygous ZFHX4 variants are identified as disease-associated variants in three patients with ptosis,suggesting that ZFHX4 may be a disease-causing gene for autosomal dominant ICP with incomplete penetrance or a susceptibility gene.These findings expand the variant spectrum of ZFHX4,improve understanding of the pathogenesis of ZFHX4-related ptosis,and may contribute to the genetic counseling and disease management,as well as the development of experimental treatments.
文摘Thrombosis is the pathological process resulting from the inappropriate and propagation of the hemostatic response. The principle determinants of thrombosis can be categorized in contemporary terms according to Virchow' s paradigm: abnormalities in endothelial function ( vessel function ), rheotogy ( blood flow ), or blood component,either alone or in combination, can promote thrombus formation.
基金supported by the Project of Health Committee of Hunan Province(D202304128868),China.
文摘Objective:Verrucous epidermal nevus(VEN),seborrheic keratosis(SK),verruca plana(VP),verruca vulgaris(VV),and nevus sebaceous(NS)are common verrucous proliferative skin diseases with similar clinical appearances,often posing diagnostic challenges.Dermoscopy and reflectance confocal microscopy(RCM)can aid in their differentiation,yet their specific features under these tools have not been systematically described.This study aims to summarize and analyze the dermoscopic and RCM features of VEN,SK,VP,VV,and NS.Methods:A total of 121 patients with histopathologically confirmed verrucous proliferative skin diseases were enrolled.Dermoscopy and RCM imaging was used to observe and analyze the microscopic features of these conditions.Results:Under dermoscopy,the 5 diseases displayed distinct characteristics:VEN typically showed gyriform structures;SK was characterized by gyriform structures,comedo-like openings,and milia-like cysts;VP and VV featured dotted vessels and frogspawn-like structures;NS presented as brownish-yellow globules.RCM revealed shared features such as hyperkeratosis and acanthosis across all 5 diseases.Specific features included gyriform structures and elongated rete ridges in VEN;pseudocysts and gyriform structures in SK;evenly distributed ring-like structures in VP;vacuolated cells and papillomatous proliferation in VV;and frogspawn-like structures in NS.Conclusion:These 5 verrucous proliferative skin conditions exhibit distinguishable features under both dermoscopy and RCM.The combination of these 2 noninvasive imaging modalities holds significant clinical value for the differential diagnosis of verrucous proliferative skin diseases.
基金Supported by Hunan Provincial Natural Science Foundation of China,No.2024JJ9579 and No.2025JJ80410The Science and Technology Innovation Program of Changde City,No.2023YD23.
文摘BACKGROUND Uncertainty in illness(UI)and fear of progression(FoP)are significant psycho-logical challenges for lung cancer patients.Coping styles and social support are critical mediators,influencing patients'ability to manage the emotional and psy-chological burden of UI and FoP.However,limited research has explored the chain mediation effect of these factors on the relationship between UI and FoP,particularly among Chinese lung cancer patients.Convenience sampling was used to recruit inpatients diagnosed with lung cancer at a tertiary hospital in Changde City between November and December 2023.A total of 320 participants completed the Mishel Uncertainty in Illness Scale,Simp-lified Coping Style Questionnaire,Mandarin Chinese Version of the Medical Outcomes Study Social Support Survey,and Fear of Progression Questionnaire-Short Form.The chain mediation analysis was performed using the PROCESS macro to examine the relationships between the variables.RESULTS The results revealed that UI had a significant direct effect on FoP(effect=0.224,95%CI:0.136-0.408).Additionally,three indirect pathways were identified:(1)Social support(effect=0.128,95%CI:0.045-0.153);(2)Coping style(effect=0.115,95%CI:0.048-0.157);and(3)Chain mediators involving social support and coping style(effect=0.072,95%CI:0.045-0.120).The total indirect effect of the three mediation paths is 31.5%.These results confirm that social support and coping style significantly mediate the relationship between UI and FoP.CONCLUSION Based on cross-sectional data and a chain mediation model,this study explored the mechanisms between UI,social support,coping style,and FOP.Patients with lung cancer have higher levels of FOP,and the results of this study revealed a correlation between these four factors.Social support and coping style partially mediated the effects of UI on FOP,and there was a chain-mediating effect between UI and FOP.Programs designed to strengthen social support networks should also incorporate training to develop adaptive coping strategies,ultimately reducing FOP and improving overall quality of life.
基金supported by the following funds:The National Natural Science Foundation of China(Nos.52275393,51935014,and 82072084)Jiangxi Provincial Natural Science Foundation of China(No.20224ACB204013)+2 种基金The Project of State Key Laboratory of Precision Manufacturing for Extreme Service Performancethe National Key Research and Development Program of China(No.2023YFB4605800)the Independent Exploration and Innovation Project of Central South University(No.1053320221707).
文摘Fast electron-hole recombination issues during titanium dioxide(TiO_(2))photocatalysis limit its application in preventing bacterial infection during bone defect repair.In this study,TiO_(2)@reduced graphene oxide(rGO)composites were synthesized using a hydrothermal method in which rGO,which possesses very high electrical conductivity,promotes the separation of photoelectron-hole pairs of TiO_(2),thus improving the efficiency of photocatalytic production of reactive oxygen species(ROS).Subsequently,TiO_(2)@rGO composites were introduced into poly-L-lactic acid(PLLA)to prepare bone scaffolds with photocatalytic antibacterial function via selective laser sintering.The results showed that TiO_(2)grew on the surface of rGO and formed a covalent bond connection(Ti-O-C)with rGO.A decreased electrochemical impedance of TiO_(2)@rGO composites was observed,and the transient photocurrent intensity increased from 0.05 to 0.5μA/cm^(2).Analysis of electron spin resonance found that the photocatalytic products of TiO_(2)were·OH and·O^(2-),two kinds of ROS capable of killing bacteria via disrupting the structure of the bacterial membrane in vitro.Antibacterial experiments showed that the PLLA/TiO_(2)@rGO scaffolds had good antibacterial properties against Escherichia coli and Staphylococcus aureus.Finally,we report that these scaffolds exhibited both enhanced mechanical properties due to the addition of TiO_(2)@rGO as a reinforcement material and good biocompatibility during cell proliferation.
基金supported by grants from the Provincial Natural Science Foundation of Hunan(No.2023JJ60335)。
文摘The first example of Nd@C_(3)N_(4)-photoredox/chlorine dual catalyzed alkylation with unactivated alkanes as the alkyl sources has been developed,which allows for the synthesis of various 4-alkylated cyclic sulfonyl ketimines.In this process,chlorine functions as both a redox and hydrogen atom transfer catalyst.The synergism of the reversible Nd^(2+)/Nd^(3+)and Cl^(ˉ)/Cl˙redox pairs significantly enhances overall photocatalytic efficiency.The in vitro anticancer activity of 4-alkylated products was evaluated by using the CCK8assay against both human choroidal melanoma(MUM-2B)and lung cancer(A549)cell.Compound 3da showed approximately triple the potency of 5-fluorouracil.
基金National Key R&D Program of China,Grant/Award Number:2021YFC2502100,2023YFC3603404 and 2019YFA0111900The National Natural Science Foundation of China,Grant/Award Number:82072506,82272611 and 92268115+7 种基金The Hunan Provincial Science Fund for Distinguished Young Scholars,Grant/Award Number:2024JJ2089The Hunan Young Talents of Science and Technology,Grant/Award Number:2021RC3025The Provincial Clinical Medical Technology Innovation Project of Hunan,Grant/Award Number:2023SK2024 and 2020SK53709The Provincial Natural Science Foundation of Hunan,Grant/Award Number:2020JJ3060The National Natural Science Foundation of Hunan Province,Grant/Award Number:2023JJ30949The National Clinical Research Center for Geriatric Disorders,Xiangya Hospital,Grant/Award Number:2021KFJJ02 and 2021LNJJ05The Hunan Provincial Innovation Foundation for Postgraduate,Grant/Award Number:CX20230308 and CX20230312The Independent Exploration and Innovation Project for Postgraduate Students of Central South University,Grant/Award Number:2024ZZTS0163。
文摘Frozen shoulder(FS),also known as adhesive capsulitis,is a condition that causes contraction and stiffness of the shoulder joint capsule.The main symptoms are per-sistent shoulder pain and a limited range of motion in all directions.These symp-toms and poor prognosis affect people's physical health and quality of life.Currently,the specific mechanisms of FS remain unclear,and there is variability in treatment methods and their efficacy.Additionally,the early symptoms of FS are difficult to distinguish from those of other shoulder diseases,complicating early diagnosis and treatment.Therefore,it is necessary to develop and utilize animal models to under-stand the pathogenesis of FS and to explore treatment strategies,providing insights into the prevention and treatment of human FS.This paper reviews the rat models available for FS research,including external immobilization models,surgical internal immobilization models,injection modeling models,and endocrine modeling models.It introduces the basic procedures for these models and compares and analyzes the advantages,disadvantages,and applicability of each modeling method.Finally,our paper summarizes the common methods for evaluating FS rat models.
基金Supported by National Natural Science Foundation of China(No.82160195,No.82460203)Degree and Postgraduate Education Teaching Reform Project of Jiangxi Province(No.JXYJG-2020-026).
文摘AIM:To assess the possibility of using different large language models(LLMs)in ocular surface diseases by selecting five different LLMS to test their accuracy in answering specialized questions related to ocular surface diseases:ChatGPT-4,ChatGPT-3.5,Claude 2,PaLM2,and SenseNova.METHODS:A group of experienced ophthalmology professors were asked to develop a 100-question singlechoice question on ocular surface diseases designed to assess the performance of LLMs and human participants in answering ophthalmology specialty exam questions.The exam includes questions on the following topics:keratitis disease(20 questions),keratoconus,keratomalaciac,corneal dystrophy,corneal degeneration,erosive corneal ulcers,and corneal lesions associated with systemic diseases(20 questions),conjunctivitis disease(20 questions),trachoma,pterygoid and conjunctival tumor diseases(20 questions),and dry eye disease(20 questions).Then the total score of each LLMs and compared their mean score,mean correlation,variance,and confidence were calculated.RESULTS:GPT-4 exhibited the highest performance in terms of LLMs.Comparing the average scores of the LLMs group with the four human groups,chief physician,attending physician,regular trainee,and graduate student,it was found that except for ChatGPT-4,the total score of the rest of the LLMs is lower than that of the graduate student group,which had the lowest score in the human group.Both ChatGPT-4 and PaLM2 were more likely to give exact and correct answers,giving very little chance of an incorrect answer.ChatGPT-4 showed higher credibility when answering questions,with a success rate of 59%,but gave the wrong answer to the question 28% of the time.CONCLUSION:GPT-4 model exhibits excellent performance in both answer relevance and confidence.PaLM2 shows a positive correlation(up to 0.8)in terms of answer accuracy during the exam.In terms of answer confidence,PaLM2 is second only to GPT4 and surpasses Claude 2,SenseNova,and GPT-3.5.Despite the fact that ocular surface disease is a highly specialized discipline,GPT-4 still exhibits superior performance,suggesting that its potential and ability to be applied in this field is enormous,perhaps with the potential to be a valuable resource for medical students and clinicians in the future.
基金supported by the NIH/NCI grants(No.P01CA257907)the Educational Department of Hunan Province for Excellent Youth Scholars(No.23B0011)。
文摘In the past decade,immunotherapies targeting cytotoxic T-lymphocyte antigen-4(CTLA-4),programmed cell death 1(PD-1),and PD-1 ligand(PD-L1)have been approved for solid tumors.However,some patients demonstrate suboptimal clinical outcomes due to resistance.The tumor microenvironment(TME)significantly affects the efficiency of immunotherapy by mediating interactions between tumor and non-tumor cells,including dendritic cells,T cells,B cells,macrophages,neutrophils,NK cells,and myeloid-derived suppressor cells(MDSCs).These non-tumor cells often exhibit two phenotypes with altered functions,and tumor cells drives their transition towards tumor promotion through tumor-education.Tumor-educated cells(TECs)are cells influenced by tumor cells,which acquire immune-suppressive phenotypes and promote tumor progression through resistance to anticancer therapies.These cells undergo modifications in response to signals from the tumor,which can influence their roles in tumor progression.Their dynamic interactions with tumor cells contribute to the reshaping of the TME,facilitating cancer growth and immune modulation.This review summarizes research on TECs in TME,explores mechanisms related to tumor education,and discusses their role in tumor progression and immunotherapy resistance.Additionally,potential therapeutic approaches targeting these cells are also reviewed,which may complement current treatment strategies.
基金supported by Project of the Health Shanghai Initiative Special Fund(Medical-Sports Integration,Creating a New Model of Exercise for Health),No.JKSHZX-2022-02(to SC).
文摘Recent research has demonstrated the impact of physical activity on the prognosis of glioma patients,with evidence suggesting exercise may reduce mortality risks and aid neural regeneration.The role of the small ubiquitin-like modifier(SUMO)protein,especially post-exercise,in cancer progression,is gaining attention,as are the potential anti-cancer effects of SUMOylation.We used machine learning to create the exercise and SUMO-related gene signature(ESLRS).This signature shows how physical activity might help improve the outlook for low-grade glioma and other cancers.We demonstrated the prognostic and immunotherapeutic significance of ESLRS markers,specifically highlighting how murine double minute 2(MDM2),a component of the ESLRS,can be targeted by nutlin-3.This underscores the intricate relationship between natural compounds such as nutlin-3 and immune regulation.Using comprehensive CRISPR screening,we validated the effects of specific ESLRS genes on low-grade glioma progression.We also revealed insights into the effectiveness of Nutlin-3a as a potent MDM2 inhibitor through molecular docking and dynamic simulation.Nutlin-3a inhibited glioma cell proliferation and activated the p53 pathway.Its efficacy decreased with MDM2 overexpression,and this was reversed by Nutlin-3a or exercise.Experiments using a low-grade glioma mouse model highlighted the effect of physical activity on oxidative stress and molecular pathway regulation.Notably,both physical exercise and Nutlin-3a administration improved physical function in mice bearing tumors derived from MDM2-overexpressing cells.These results suggest the potential for Nutlin-3a,an MDM2 inhibitor,with physical exercise as a therapeutic approach for glioma management.Our research also supports the use of natural products for therapy and sheds light on the interaction of exercise,natural products,and immune regulation in cancer treatment.
基金supported by the Natural Science Foundation of Hunan Province(2023JJ30817)Hunan Provincial Natural Science Foundation-Hengyang City Joint Fund Project(2025JJ70129)+1 种基金Changsha Natural Science Foundation(kq2403057)China。
文摘Objective:Near vision loss(NVL)is one of the leading causes of visual impairment worldwide,exerting a profound impact on individual quality of life and socio-economic development.This study aims to analyze the burden of NVL in China by sex and age groups from 1990 to 2021 and to project trends over the next 15 years.Methods:Using data from the Global Burden of Disease(GBD)2021 database,we conducted descriptive analyses of NVL prevalence in China,calculated age-standardized prevalence rates(ASPR)and age-standardized disability-adjusted life years rates(ASDR)to compare burden differences between sexes and age groups,and applied an autoregressive integrated moving average(ARIMA)model to predict NVL trends for the next 15 years.The model selection was based on best-fit criteria to ensure reliable projections.Results:From 1990 to 2021,China’s ASPR of NVL rose from 10096.24/100000 to 15624.54/100000,and ASDR increased from 101.75/100000 to 158.75/100000.In 2021,ASPR(16551.70/100000)and ASDR(167.69/100000)were higher among females than males(14686.21/100000 and 149.76/100000,respectively).China ranked highest globally in both NVL cases and disability-adjusted life years(DALYs),with female burden significantly exceeding male burden.Projections indicated this trend and sex gap will persist until 2036.Compared with 1990,the prevalence cases and DALYs increased by 239.20%and 238.82%,respectively in 2021,with the highest burden among females and the 55−59 age group.The ARIMA model predicted continued increases in prevalence and DALYs by 2036,with females maintaining a higher burden than males.Conclusion:This study reveals a marked increase in the NVL burden in China and predicts continued growth in the coming years.Public health policies should prioritize NVL prevention and control,with special attention to women and middle-aged populations to mitigate long-term societal and health impacts.
文摘BACKGROUND Despite advances in the use of in vitro fertilization-embryo transfer(ET)in couples with infertility,recurrent implantation failure(RIF)after ET is still a major problem affecting women,with great psychological and economic burdens for the patient and his/her family.AIM To investigate the psychological burden(anxiety and depression)and evaluate the clinical benefits of endometrial receptivity testing(ERT)in patients experiencing RIF following frozen-thawed ET.METHODS A retrospective cohort study analyzed 371 patients experiencing RIF after assisted reproductive treatment at the First People’s Hospital of Changde City between January 2021 and June 2024.Demographic and clinical data were systematically collected through standardized questionnaires.Psychological assessment utilized validated instruments:The Self-Rating Depression Scale for depression evaluation and the Self-Rating Anxiety Scale for anxiety assessment.Participants were stratified by psychological status(anxiety/non-anxiety and depression/nondepression)to analyze influencing factors for anxiety and depression.The cohort was further categorized into the ERT and non-ERT groups based on ERT implementation to comparatively analyze their clinical outcomes.Additionally,they were divided into clinical and nonclinical pregnancy groups to identify factors affecting clinical pregnancy using univariate and multivariate logistic regression models.Compared with the non-ERT group,the 226 patients who underwent ERT-guided ET achieved a higher clinical pregnancy rate,thicker endometrium on transfer day,fewer embryos transferred,and a lower miscarriage rate.RESULTS The study identified a substantial psychological burden,with anxiety prevalence at 55.0%(mean Self-Rating Anxiety Scale score,50.89±9.34)and depression at 61.2%(mean Self-Rating Depression Scale score,55.55±9.48).Multivariate analysis identified annual household income>100000 yuan as protective factors against both anxiety and depression,whereas advanced maternal age(>35 years)and multiple implantation failures(≥3)served as risk factors.Additionally,anxiety-specific risk factors included prolonged infertility treatment(>5 years)and the spouse’s status as an only child.As to depression-specific risks,chronic infertility(>3 years)and higher educational attainment(college/bachelor’s degree or higher)were key determinants,whereas urban residence was a protective factor.Age>35 years was a risk factor for clinical pregnancy in patients experiencing RIF,whereas blastocyst-stage ET,a higher number of embryos transferred,and thicker endometrium were protective factors.CONCLUSION Patients experiencing RIF are particularly susceptible to anxiety and depression,and advanced maternal age and multiple implantation failures represent salient risk factors.Clinicians should implement proactive and evidencebased interventions to mitigate these psychological burdens.For patients experiencing RIF,ERT-guided ET demonstrates significant potential to improve assisted reproductive outcomes.
基金Supported by Science and Technology Innovation Program of Changde City,No.2024ZD165Hunan Provincial Natural Science Foundation of China,No.2025JJ80419.
文摘BACKGROUND Benign laryngotracheal stenosis(LTS)is a condition characterized by mucosal inflammation and fibrosis.It is difficult to treat with a high incidence rate.Respiratory distress and voice disorders of varying severity also affect patients'sleep quality and quality of life.AIM To investigate the association between anxiety and depression and sleep quality in patients with benign LTS and identify significant risk factors for sleep disorders.METHODS This retrospective cohort study enrolled 127 consecutive patients with benign LTS admitted to The First People's Hospital of Changde City between January 2021 and January 2024.Comprehensive assessments included demographic collection and Pittsburgh sleep quality index(PSQI),self-rating anxiety scale(SAS),and selfrating depression scale(SDS)scoring.Correlation analyses were conducted to examine relationships between psychological measures and sleep parameters,followed by multivariate logistic regression to determine independent risk factors.RESULTS The cohort demonstrated significantly impaired sleep quality(mean PSQI,7.79±2.47),with 48.0%(n=61)meeting the criteria for clinically significant sleep disturbance.The scores of all PSQI dimensions,as well as SAS and SDS scores of patients with LTS,significantly exceeded Chinese normative values.Strong positive correlations emerged between PSQI scores and both SAS and SDS measures.Multivariate logistic analysis identified middle age(41-50 years),multiple surgical interventions(≥3 procedures),lower socioeconomic status(monthly household income per capita≤5000 RMB),and concurrent anxiety/depression as independent predictors of sleep disturbance.CONCLUSION The results demonstrate a high prevalence of sleep disorders and comorbid anxiety or depressive moods among patients with LTS.These psychological factors both correlate with and independently predict sleep impairment.These results underscore the need for integrated and proactive approaches addressing both physical and mental health components in LTS management,focusing on high-risk subgroups stratified based on age,monthly household income per capita,anxiety/depression status,and number of prior surgeries.
文摘BACKGROUND Mental disorders have become a major contributor to the Global Burden of Disease(GBD),a situation that has worsened with the onset of the coronavirus disease 2019(COVID-19)pandemic.Updated data on their impact and a clear understanding of long-term trends are essential for global and national health authorities to implement effective prevention and intervention strategies for mental well-being.AIM To generate insights that will enhance global awareness of the burden of mental disorders and support the development of targeted,region-specific prevention and intervention strategies tailored to current global and local health challenges.METHODS We extracted data on incidence,disability-adjusted life years(DALYs),agestandardized incidence rate(ASIR),and age-standardized DALY rate(ASDR)for 12 categories of mental disorders from 1990 to 2021 across 204 countries and territories grouped into 21 regions.Trends in ASIR and ASDR were also analyzed during the COVID-19 period(2019-2021).RESULTS From 1990 to 2021,global ASIR rose by 15.23%(12.97%to 17.60%),while ASDR increased by 73.52%(70.24%to 76.71%).All 21 GBD regions saw a rise in cases and DALYs.In 2021,Central sub-Saharan Africa had the highest ASIR(8706.11),and East Asia reported the lowest(3340.99).Australasia recorded the highest ASDR(2787.87).On the national level,Greenland,Greece,United States,and Australia had the greatest ASDR values.During the pandemic years,ASIR and ASDR rose across all five socio-demographic index levels and GBD regions,with the exception of East Asia,where rates remained stable.Females experienced a higher ASDR than males in 2021.Major depressive disorder(557.87)and anxiety disorders(524.33)were the most burdensome among the 12 types,with depressive disorders ranking first in 13 out of the 21 regions.CONCLUSION The GBD study 2021 results highlight a continued and worsening global burden of mental disorders,further intensified by the COVID-19 crisis.This underscores the urgent need to reinforce mental health care systems.Special attention should be directed toward high-middle socio-demographic index areas and female populations.Expanding access to mental health services,enhancing public awareness,and delivering targeted interventions are essential to lessen the growing impact of mental disorders.
基金Supported by Hunan Provincial Natural Science Foundation of China,No.2025JJ80473 and No.2025JJ80484the Institute of Hospital Management,National Health Commission of China,Major Project,No.SZ2024HL021.
文摘BACKGROUND Major depressive disorder(MDD)is a significant psychiatric condition that poses a serious threat to human life,primarily due to its association with suicidal behavior.The single nucleotide polymorphism rs372369000 is a risk locus for MDD and is located within the B4GALT6 gene.However,the biological and pathological implications of B4GALT6 in the brain concerning MDD remain unclear.AIM To reveal the biological and pathological significance of B4GALT6 in the brain and MDD.METHODS An inflammation-associated depression mouse model was developed by treating mice with lipopolysaccharides.B4GALT6-like immunoreactivity distribution and expression level was examined throughout the brain.RESULTS B4GALT6-like immunoreactivity increased in the hippocampus,PrL,and the visual cortex V1 region of MDD mice.This elevation varied across different brain subregions and cell types.Specifically,pathological alterations in B4GALT6-like immunoreactivity were observed in CA1 microglia,CA2 neurons,CA3 microglia and neurons,as well as V1 microglia and astrocytes.These changes correlated with the pathology of depression.CONCLUSION Although the neuropathological role of B4GALT6 in the brain remains to be fully characterized,B4GALT6 may be a potential therapeutic target for MDD.
基金Supported by the Joint Funds of the National Natural Science Foundation of China,No.U23A20434National Natural Science Foundation of China,No.82301738,No.82371535,and No.82171518+1 种基金the National Key Research and Development Program of China,No.2021YFF1201204the Science and Technology Innovation Program of Hunan Province,No.2023RC3083.
文摘BACKGROUND Antenatal depression is a disabling mental disorder among pregnant women and may cause adverse outcomes for both the mother and the offspring.Early identification and intervention of antenatal depression can help to prevent adverse outcomes.However,there have been few population-based studies focusing on the association of social and obstetric risk factors with antenatal depression in China.AIM To assess the sociodemographic and obstetric factors of antenatal depression and compare the network structure of depressive symptoms across different risk levels based on a large Chinese population.METHODS The cross-sectional survey was conducted in Shenzhen,China from 2020 to 2024.Antenatal depression was assessed using the Chinese version of the Edinburgh Postnatal Depression Scale(EPDS),with a score of≥13 indicating the presence of probable antenatal depression.Theχ2 test and binary logistic regression were used to identify the factors associated with antenatal depression.Network analyses were conducted to investigate the structure of depressive symptoms across groups with different risk levels.RESULTS Among the 44220 pregnant women,the prevalence of probable antenatal depression was 4.4%.An age≤24 years,a lower level of education(≤12 years),low or moderate economic status,having a history of mental disorders,being in the first trimester,being a primipara,unplanned pregnancy,and pregnancy without pre-pregnancy screening were found to be associated with antenatal depression(all P<0.05).Depressive symptom networks across groups with different risk levels revealed robust interconnections between symptoms.EPDS8("sad or miserable")and EPDS4("anxious or worried")showed the highest nodal strength across groups with different risk levels.CONCLUSION This study suggested that the prevalence of antenatal depression was 4.4%.Several social and obstetric factors were identified as risk factors for antenatal depression.EPDS8("sad or miserable")and EPDS4("anxious or worried")are pivotal targets for clinical intervention to alleviate the burden of antenatal depression.Early identification of highrisk groups is crucial for the development and implementation of intervention strategies to improve the overall quality of life for pregnant women.
文摘BACKGROUND The prognosis of patients with poorly differentiated gastric neuroendocrine neoplasms(PDGNENs)is dismal and related research is limited.AIM To investigate the prognostic factors,and validate a novel prognostic nomogram for PDGNEN patients.METHODS We conducted a retrospective study using clinical and pathological data from PDGNEN patients treated at the First Medical Center of the Chinese PLA General Hospital from January 2000 to June 2023.Overall survival(OS)differences were assessed with the Log-rank test and Kaplan-Meier survival curves.Cox regression analysis identified independent risk factors for prognosis.Model performance was evaluated using Harrell’s concordance index,receiver operating characteristic analysis,area under the curve,calibration curves,and decision curve analysis(UDC),including the area under the UDC.RESULTS The study included 336 patients(227 with neuroendocrine carcinoma and 109 with mixed adenoneuroendocrine carcinoma).The average age was 62.7 years.The cohort comprised 80(24.7%)patients in stage I,146(42.9%)in stage II,62(18.1%)in stage III,and 48(14.3%)in stage IV.Significant differences in OS were observed across tumor-node-metastasis stages(P<0.001).Multivariate analysis showed age,Ki-67 index,invasion depth,lymph node metastasis,distant metastasis,and platelet-to-lymphocyte ratio as independent risk factors.We developed a nomogram with a concordance index of 0.779(95%confidence interval:0.743-0.858).Receiver operating characteristic analysis showed area under the curves for 1-year,3-year,and 5-year OS predictions of 0.865,0.850,and 0.890,respectively.The calibration curve demonstrated good agreement with actual outcomes.The area under the UDC for the nomogram vs the 8th American Joint Committee on Cancer tumor-node-metastasis staging system were 0.047 vs 0.027,0.291 vs 0.179,and 0.376 vs 0.216 for 1-year,3-year,and 5-year OS,respectively.CONCLUSION PDGNENs are predominantly found in older men,often in advanced stages at diagnosis,resulting in poor prognosis.The established nomogram demonstrates strong predictive capability and clinical utility.
基金Supported by the National Natural Science Foundation of China,No.82372072 and No.82071986.
文摘BACKGROUND Visceral adipose tissue(VAT)plays a role in the pathogenesis of Crohn's disease(CD)and is associated with treatment outcomes following infliximab(IFX)therapy.We developed and validated the first delta-radiomics model to quantify VAT heterogeneity as a predictive biomarker for IFX response in patients with CD.AIM To develop a longitudinal computed tomography(CT)-based delta-radiomics model of VAT for predicting secondary loss of response(SLR)in patients with CD.METHODS This retrospective study included 161 patients with CD who achieved clinical remission following IFX induction therapy between 2015 and 2023.All patients underwent CT enterography before IFX initiation and after completing induction therapy.VAT volume was delineated by two radiologists in consensus.Radiomics features were extracted from pre-treatment and post-induction CT images,and delta-radiomics features were calculated as follows:Delta features=Feature-post-Feature-pre.A radiomics model was constructed using logistic regression.Model performance was assessed using discrimination,calibration,and decision curve analyses.RESULTS Nine significant delta-radiomics features were used to develop the delta-radiomics model,yielding an area under the receiver operating characteristic curve(AUC)of 0.816(95%CI:0.737-0.896)in the training cohort and 0.750(95%CI:0.605-0.895)in the validation cohort.Multivariable logistic regression identified platelet count,Montreal behavior classification,and the VAT/subcutaneous adipose tissue volume ratio prior to treatment as independent risk factors for SLR.The combined model integrating clinical predictors and delta-radiomics features achieved superior predictive performance,with an AUC of 0.853(95%CI:0.786-0.921)in the training cohort and 0.812(95%CI:0.677-0.948)in the validation cohort.CONCLUSION We developed a predictive model based on longitudinal changes in VAT,demonstrating significant potential for identifying patients with CD at high risk of SLR to IFX therapy.
