Background:Continuous care for children with enterostomy and their families has been gaining popularity in China.Objective:To evaluate the feasibility of continuous care for children with enterostomy and their familie...Background:Continuous care for children with enterostomy and their families has been gaining popularity in China.Objective:To evaluate the feasibility of continuous care for children with enterostomy and their families in China.Methods:The PubMed,Web of Science,Embase,Cochrane Library,EBSCO,CNKI,CBM,VIP,and WanFang were searched for clinical trials until December 30,2025.Two reviewers independently searched articles,evaluated quality and extracted data.This review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses(PRISMA).Results:33 studies involving 2774 participants were included.The meta-analysis showed that continuous care strategy can significantly reduce the incidence of complications in children with enterostomy(OR=0.20,95%CI=0.16-0.26,p<0.001,I2=0%),effectively improve the family caregiver ability for enterostomy(MD=-10.34,95%CI=-13.82 to-6.85,p<0.001,I2=99%),shorten the time for family members to replace stoma bags(MD=-13.57,95%CI=-19.66 to-7.49,p<0.001,I2=100%),and alleviate negative emotions such as anxiety(SMD=-1.80,95%CI=-2.36 to-1.23,p<0.001,I2=92%)and depression(SMD=-1.54,95%CI=-2.04 to-1.04,p<0.001,I2=89%)in the families of the affected children.Conclusions:Continuous care can reduce complications of enterostomy in children,improve the family caregiver ability for enterostomy and alleviate negative emotions of family members such as anxiety and depression.展开更多
As a large family of RNA helicases,DEAD-box(DDX)RNA helicases play crucial roles in almost all cellular RNA processing activities.However,the role of the DDX gene family in cold tolerance of mei(Prunus mume)remains un...As a large family of RNA helicases,DEAD-box(DDX)RNA helicases play crucial roles in almost all cellular RNA processing activities.However,the role of the DDX gene family in cold tolerance of mei(Prunus mume)remains unclear.In this study,we identified 45 DDX genes through whole-genome analysis unevenly distributed across eight chromosomes and scaffolds of mei.Based on the phylogenetic tree and gene structure analysis,the DDX genes were classified into nine subfamilies based on their motif compositions and intron-exon structures.The results of synteny analysis showed that segmental duplication was considered a major factor contributing to the amplification of the PmDDX family.RNA-Seq and qRT-PCR results revealed differential expression of PmDDX genes under cold stress.Among these,PmDDX39 was significantly up-regulated under cold stress,suggesting its positive role in modulating mei cold tolerance.We found that silenced PmDDX39 under cold stress led to greater damage than the wild seedlings via virus-induced gene silencing(VIGS).Conversely,overexpression of PmDDX39 in Arabidopsis enhanced cold stress tolerance.Moreover,dual luciferase and yeast one-hybrid(Y1H)demonstrated that PmDDX39 directly activates the expression of the C-repeat binding factor(PmCBFf)by binding to its promoters.This study provides new insights into the structure,evolution,and functional role of the PmDDX gene family in mei responses to cold stress.展开更多
BACKGROUND Familial adenomatous polyposis(FAP)is a disorder of autosomal dominant inheritance that is responsible for around 1%of colorectal cancer(CRC)cases.AIM To determine the mutation profile of FAP-specific to th...BACKGROUND Familial adenomatous polyposis(FAP)is a disorder of autosomal dominant inheritance that is responsible for around 1%of colorectal cancer(CRC)cases.AIM To determine the mutation profile of FAP-specific to the Hungarian population.METHODS This prospective single-center study enrolled patients with clinically suspected FAP or attenuated FAP(aFAP).Whole-exome next-generation sequencing was performed to detect variants of 50 FAP priority genes and 173 CRC predisposing genes or other CRC disease-associated genes.To identify larger deletions and insertions,a multiplex amplifiable probe hybridization technique was used.The identified genes were then classified according to the American College of Medical Genetics and Genomics guidelines.RESULTS A total of 26 index patients with clinically suspected FAP(n=21)and aFAP(n=5)were enrolled.APC gene alterations were confirmed in 92.31%of the cases(region 1B deletion,n=2;whole-gene deletion,n=4;frameshift mutation,n=2;nonsense mutation,n=5,and splice mutation,n=1),with the remaining two cases having CHEK2 and MSH3 gene alterations.According to pathogenicity,21 cases had pathogenic mutations,6 cases had likely pathogenic mutations,and 16 cases had variants of unknown significance(VUS).The most frequent of the latter were the POLE(n=5)and PIEZO1(n=4)gene variants.CONCLUSION Germline mutations in the APC gene were confirmed in more than 90%of Hungarian patients with clinically suspected FAP.Although the role of VUS genes is unclear,they are highly likely to play a role in the development of CRC.展开更多
Objectives:In recent years,mental health has emerged as a pressing public health concern in China,driven by mounting societal pressures and fast-paced urban lifestyles.Physical activity,a well-established means of enh...Objectives:In recent years,mental health has emerged as a pressing public health concern in China,driven by mounting societal pressures and fast-paced urban lifestyles.Physical activity,a well-established means of enhancing psychological well-being,has received growing scholarly and policy attention.This study uses panel data from the 2020 and 2022 waves of the China Family Panel Studies(CFPS)to examine the impact of exercise frequency on mental health(with indicators such as CESD-8 depression scores)among college students and young employees,thereby providing empirical support for targeted mental health interventions.Methods:This study examines the relationship between individual exercise frequency and mental health among college students and young employees,using panel data from the 2020 and 2022 waves of the China Family Panel Studies(CFPS),with the Chinese version of the 8-item Center for Epidemiologic Studies Depression Scale(CESD-8)depression scores,self-rated health,and life satisfaction as outcome variables.Specifically,this study tests three hypotheses:(H1)increased exercise frequency significantly reduces depression symptoms and enhances well-being;(H2)the effects of exercise vary by social roles,with stronger mental health benefits among employed individuals and those with lower education;and(H3)lifestyle factors such as smoking amount,sleep duration,and Body Mass Index(BMI)partially mediate the relationship between exercise and mental health.Employing a two-way fixed effects model,baseline results indicate that a one-unit increase in exercise frequency significantly reduces the CESD-8 score by 0.183 points.To address potential endogeneity and spurious regression concerns,an instrumental variable(IV)approach is further applied.The heterogeneity analysis differentiates between students and employed individuals.Results:Among students,the effects of exercise on mental health are not statistically significant,regardless of education level.In contrast,for the employed,exercise demonstrates a significant positive impact on mental health,with particularly pronounced effects among those with lower educational attainment.These findings underscore the importance of promoting exercise as part of comprehensive mental health strategies.Mediation analysis indicates that the beneficial effect of exercise on mental health is partially transmitted through reductions in adverse health behaviors,especially smoking.Conclusions:Policymakers should integrate physical activity promotion into health interventions,prioritizing vulnerable groups to enhance psychological resilience and foster inclusive,health-oriented development.展开更多
新学期伊始,翻开鲁科版五四制小学英语的第七单元,《Family》的标题赫然在目,和所有英语老师一样,我对这个单元的内容、流程再熟悉不过了。按照以往的经验,我会带着孩子们认读图片、跟读录音、分组进行角色扮演,最后再进行一次基础小测...新学期伊始,翻开鲁科版五四制小学英语的第七单元,《Family》的标题赫然在目,和所有英语老师一样,我对这个单元的内容、流程再熟悉不过了。按照以往的经验,我会带着孩子们认读图片、跟读录音、分组进行角色扮演,最后再进行一次基础小测验。孩子们大多能流利地指着图片说出“This is my father.”但我总感觉缺了点什么,这些词汇对于他们而言,似乎只是一张需要死记硬背的单词表,与那个充满烟火气、承载着他们所有喜怒哀乐的“家”,隔着一层看不见的屏障。直到我看到坐在窗边的小雅,在课本“全家福”插图的旁边,用铅笔认真画了一个歪歪扭扭的小人,旁边工工整整地写着“me”。展开更多
Hodgkin lymphoma(HL)is a heterogenous lymphoproliferative disorder of B-cell origin and represents one of the most common malignancies in children and young adults.In addition to well-known underlying factors-such as ...Hodgkin lymphoma(HL)is a heterogenous lymphoproliferative disorder of B-cell origin and represents one of the most common malignancies in children and young adults.In addition to well-known underlying factors-such as Epstein-Barr virus infection-the familial aggregation demonstrated in large population studies suggested a genetic predisposition.First-degree relatives of patients with HL have an approximately threefold increased risk of developing the disease compared to the general population.These observations have recently prompted several whole-genome studies in affected families,identifying variants possibly implicated in lymphomagenesis,including alterations in DICER1(a member of the ribonuclease III family),POT1(protection of telomeres 1),KDR(kinase insert domain receptor),KLHDC8B(kelch domain-containing protein 8B),PAX5(paired box protein 5),GATA3(GATA binding protein 3),IRF7(interferon regulatory factor 7),EEF2KMT(eukaryotic elongation factor 2 lysine methyltransferase),and POLR1E(RNA polymerase I subunit E).In this article,we review current insights into the etiopathogenesis and risks of familial HL,and present case reports involving two sisters diagnosed with HL nearly 17 years apart.Recognizing the risk for first-degree relatives may potentially increase awareness of early symptoms among family members of HL patients,leading to earlier diagnosis and better outcomes.Conversely,understanding that the hereditary risk,though higher than in the general population,remains relatively low may provide reassurance for affected families.展开更多
This systematic review synthesizes empirical research on external risk factors for adolescent smartphone addiction.Scopus and Web of Science were searched for English peer-reviewed empirical articles from 2008 onward;...This systematic review synthesizes empirical research on external risk factors for adolescent smartphone addiction.Scopus and Web of Science were searched for English peer-reviewed empirical articles from 2008 onward;28 met inclusion criteria(excluding non-adolescents,generic internet addiction,non-empirical work,or non-English).Thematic synthesis organized findings into three external risk domains—family,school,and peers—considering cultural/contextual mechanisms.Family dynamics(parental phubbing,harsh parenting,dysfunction),school stressors,and adverse peer relationships were identified as accumulating,direct and indirect contributors to smartphone addiction.These operate within a techno-ecological framework,where digital technologies amplify vulnerabilities and create new pathways for maladaptive use.Evidence favors an ecological,multi-level perspective.Future research should use longitudinal designs,standardize measures across cultures,and examine understudied regions—especially Africa—to guide culturally sensitive interventions.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
From goldfish pampering to pet-friendly high-speed rail,China’s pet economy boom is reshaping lifestyles and sparking a multi-billion-dollar emotional economy where pets are family,not just animals.FOR Wu Ming,a busy...From goldfish pampering to pet-friendly high-speed rail,China’s pet economy boom is reshaping lifestyles and sparking a multi-billion-dollar emotional economy where pets are family,not just animals.FOR Wu Ming,a busy Beijing resident,unwinding after a long day involves watching his goldfish glide through a meticulously maintained home aquarium.展开更多
Background:Receptor-interacting protein kinases(RIPKs)regulate cell death,inflammation,and immune responses,yet their roles in cancer are not fully understood.This study investigates the expression,genomic alterations...Background:Receptor-interacting protein kinases(RIPKs)regulate cell death,inflammation,and immune responses,yet their roles in cancer are not fully understood.This study investigates the expression,genomic alterations,and functional implications of RIPK family members across various cancers.Methods:We collected multi-omics data from The Cancer Genome Atlas and other public databases,including gene expression,copy number variation(CNV),mutation,methylation,tumor mutation burden(TMB),and microsatellite instability(MSI).Differential expression and survival analyses were performed using DESeq2 and Cox proportional hazards models.CNV and mutation data were analyzed with GISTIC2 and Mutect2,and methylation data with the ChAMP package.Correlations with TMB and MSI were assessed using Pearson coefficients,and gene set enrichment analysis was conducted with the MSigDB Hallmark gene sets.Results:RIPK family members show significant differential expression in various cancers,with RIPK1 and RIPK4 frequently altered.Survival analysis reveals heterogeneous impacts on overall survival.CNV and mutation analyses identify high alteration frequencies for RIPK2 and RIPK7,affecting gene expression.RIPK1 and RIPK7 are hypermethylated in several cancers,inversely correlating with RIPK3 expression.RIPK1,RIPK2,RIPK5,RIPK6,and RIPK7 correlate positively with TMB,while RIPK3 shows negative correlations in some cancers.MSI analysis indicates associations with DNA mismatch repair.G ene set enrichment analysis highlights immune-related pathway enrichment for RIPK1,RIPK2,RIPK3,and RIPK6,and cell proliferation and DNA repair pathways for RIPK4 and RIPK5.RIPK family members showed heterogeneous alterations across cancers:for example,RIPK7 was mutated in up to~15%of u terine c orpus e ndometrial c arcinoma and l ung s quamous c ell c arcinoma cases,and RIPK1 and RIPK7 exhibited frequent promoter hypermethylation in multiple tumor types.Several genes displayed context-dependent associations with overall survival and with TMB/MSI.Conclusion:This pan-cancer analysis of the RIPK family reveals their diverse roles and potential as biomarkers and therapeutic targets.The findings emphasize the importance of RIPK genes in tumorigenesis and suggest context-dependent functions across cancer types.Further studies are needed to explore their mechanisms in cancer development and clinical applications.展开更多
The Changbai Mountains,in Northeast China's Jilin Province,are covered by vast,wild forests.The mountainous region has chilly,snowy weather for about nine months of the year.The lowest temperature is below-40 C in...The Changbai Mountains,in Northeast China's Jilin Province,are covered by vast,wild forests.The mountainous region has chilly,snowy weather for about nine months of the year.The lowest temperature is below-40 C in winter.In 2005,Huang Yi,a native of Southwest China's Sichuan Province,relocated to the Changbai Mountains,to work at the Mount Hengshan frontier inspection station.展开更多
Osmanthus fragrans is most famous for its strong aroma,and different varieties have different degrees of fragrance and color.Fragrance and color are important factors affecting the ornamental quality of O.fragrans.Ter...Osmanthus fragrans is most famous for its strong aroma,and different varieties have different degrees of fragrance and color.Fragrance and color are important factors affecting the ornamental quality of O.fragrans.Terpenoids are important secondary metabolites in plants,with β-carotene(C40)being the major pigment substance and linalool(C10)being the key aromatic component in O.fragrans.The geranylgeranyl pyrophosphate synthase genes(GGPPSs)play important roles in secondary metabolism in plants.However,the functions of the GGPPS family in floral color and fragrance formation has rarely been reported in O.fragrans.In this study,24 Of GGPPS genes were identified and classified into two subfamilies.The Of GGPPSs showed tissue-specific expression and Of GGPPS13 had highest expression in flowers.The Of GGPPS13 protein was localized to chloroplasts.The transcriptome data of Of GGPPS13 was verified by q RT-PCR and the expression level in‘Wanyingui'with strong aroma was higher than that in‘Zhuangyuanhong'with deep color at different flower development stages.Transient overexpression of Of GGPPS13 in O.fragrans petals showed that Of GGPPS13 increased the β-carotene content,the main color substance of O.fragrans,but decreased the linalool content,the main volatile organic compound(VOC)in the floral aroma of O.fragrans.Of GGPPS13 was indicated as the critical gene related to terpenoid synthesis in the floral aroma and color formation in O.fragrans.Our findings provide gene resources on the GGPPS gene family for further revealing the molecular regulation mechanism of the floral color and aroma formation in O.fragrans.展开更多
AIM:To investigate whether vaccinia-related kinase 1(VRK1)mediates transforming growth factor-beta2(TGF-β2)-caused epithelial-mesenchymal transition(EMT)and inflammatory responses in retinal pigment epithelial(RPE)ce...AIM:To investigate whether vaccinia-related kinase 1(VRK1)mediates transforming growth factor-beta2(TGF-β2)-caused epithelial-mesenchymal transition(EMT)and inflammatory responses in retinal pigment epithelial(RPE)cells through regulating snail family transcriptional repressor 1(SNAI1),and to validate its role in a proliferative vitreoretinopathy(PVR)mouse model.METHODS:Human RPE cell line ARPE-19 cells were treated with TGF-β2 to construct an EMT model.Western blot detected VRK1 level.The effects of VRK1 on SNAI1 expression and biological behavior of ARPE-19 cells were detected by immunofluorescence,ELISA,Transwell,and scratch assay,and the interaction between VRK1 and SNAI1 was confirmed through immunoprecipitation.A PVR mouse model was constructed,and the effects of VRK1 or/and SNAI1 on retinal damage were assessed by pathologic staining.Inflammatory factors and EMT-related proteins were assessed with ELISA and Western blot.RESULTS:VRK1 was upregulated in ARPE-19 cells after TGF-β2 treatment.Overexpression of VRK1 increased cell viability,promoted cell migration and EMT,and the levels of inflammatory factors.Silencing of VRK1 reversed the above indexes.There was a direct interaction between VRK1 and SNAI1,and overexpresssion SNAI1 weakened the impacts of silencing of VRK1.In PVR mice,silencing of VRK1 ameliorated retinal structural damage,decreased proinflammatory factor levels,and suppressed SNAI1 and mesenchymal marker expression.SNAI1 overexpression antagonized the protective effects of silencing VRK1 and exacerbated EMT and inflammatory responses.CONCLUSION:VRK1 plays a key role in retinal structural and inflammatory damage in PVR mice by regulating SNAI1 and mediating TGF-β2-caused EMT and inflammatory responses in RPE cells.展开更多
Dear Editor,We reported a Chinese family carrying a novel Crumbs homologue 1(CRB1)variant(c.1737_1755del).Consanguineous marriage resulted in a homozygous mutation,leading to the onset of Leber congenital amaurosis(LC...Dear Editor,We reported a Chinese family carrying a novel Crumbs homologue 1(CRB1)variant(c.1737_1755del).Consanguineous marriage resulted in a homozygous mutation,leading to the onset of Leber congenital amaurosis(LCA)in their offspring.展开更多
Voltage-gated sodium channels are essential ionic-conductance pathways in the nervous system,which play an irreplaceable role in modulating neuronal excitability and signal transduction.This review comprehensively ana...Voltage-gated sodium channels are essential ionic-conductance pathways in the nervous system,which play an irreplaceable role in modulating neuronal excitability and signal transduction.This review comprehensively analyzes the molecular mechanisms and pathophysiological significance of voltage-gated sodium channels,with particular emphasis on elucidating the molecular-action mechanisms of the distinct subtypes of these channels,including Nav1.1,Nav1.2,and Nav1.6,across various neurological disorders such as familial hemiplegic migraine,epilepsy,autism spectrum disorder,and retinal dysfunction.This review also provides a comprehensive overview of the pathogenic mechanisms associated with voltage-gated sodium channels,and systematically clarifies the evolutionary pathway of treatment strategies from conventional to innovative approaches.It analyzes two major categories of conventional sodium channel blockers and their applications:antiepileptic drugs(such as carbamazepine,lamotrigine,and phenytoin)and antiarrhythmic drugs(such as lidocaine,flecainide,and quinidine).However,these conventional blockers show limitations because of the lack of selectivity,driving research toward more precise therapeutic directions.Additionally,this review evaluates gabapentin,cannabidiol,and calcium channel blockers with different mechanisms of action.These drugs modulate neuronal excitability from multiple perspectives,providing diverse options for symptom relief.This review also highlights advances in gene therapy for specific diseases,such as STK-001,which promotes effective splicing of the sodium channel voltage-gated type 1 alpha subunit(SCN1A)gene,and ETX101,which utilizes adeno-associated virus 9 vectors to deliver engineered transcription factors.These two agents provide targeted therapeutic solutions for Dravet syndrome.Furthermore,this review summarizes some innovative therapeutic agents in clinical trials,including PRAX-222(for SCN2A gain-offunction mutation-related epilepsy),which has received Food and Drug Administration orphan drug designation,and the selective Nav1.6 inhibitor NBI-921352(for SCN8A-related epilepsy).Collectively,this review comprehensively compares the advantages and disadvantages of conventional drugs and gene therapy and envisions future treatment strategies that integrate the strengths of both approaches,facilitating personalized precision medicine to provide more accurate and effective treatment options for patients with ion channel diseases.展开更多
Progressive photoreceptor cell death is one of the main pathological features of age-related macular degeneration and eventually leads to vision loss.Ferroptosis has been demonstrated to be associated with retinal deg...Progressive photoreceptor cell death is one of the main pathological features of age-related macular degeneration and eventually leads to vision loss.Ferroptosis has been demonstrated to be associated with retinal degenerative diseases.However,the molecular mechanisms underlying ferroptosis and photoreceptor cell death in age-related macular degeneration remain largely unexplored.Bioinformatics and biochemical analyses in this study revealed xC^(–),solute carrier family 7 member 11-regulated ferroptosis as the predominant pathological process of photoreceptor cell degeneration in a light-induced dry age-related macular degeneration mouse model.This process involves the nuclear factor-erythroid factor 2-related factor 2-solute carrier family 7 member 11-glutathione peroxidase 4 signaling pathway,through which cystine depletion,iron ion accumulation,and enhanced lipid peroxidation ultimately lead to photoreceptor cell death and subsequent visual function impairment.We demonstrated that solute carrier family 7 member 11 overexpression blocked this process by inhibiting oxidative stress in vitro and in vivo.Conversely,solute carrier family 7 member 11 knockdown or the solute carrier family 7 member 11 inhibitor sulfasalazine and ferroptosis-inducing agent erastin aggravated H_(2)O_(2)-induced ferroptosis of 661W cells.These findings indicate solute carrier family 7 member 11 may be a potential therapeutic target for patients with retinal degenerative diseases including age-related macular degeneration.展开更多
Objectives:The current treatment options and therapeutic targets for triple-negative breast cancer(TNBC),an aggressive subtype of breast cancer(BrCA),are limited.This study aimed to identify novel biomarkers and trans...Objectives:The current treatment options and therapeutic targets for triple-negative breast cancer(TNBC),an aggressive subtype of breast cancer(BrCA),are limited.This study aimed to identify novel biomarkers and transcriptional regulatory networks(TRN)inherent in TNBC samples.Methods:We analyzed pan-cancer BrCA datasets from The Cancer Genome Atlas(TCGA)to compare triple-positive breast cancer(TPBC)with TNBC.TRN algorithms and virtual inference of protein-enriched regulon(VIPER)were used to identify master regulators and their target genes.Utilizing TNBC cells(MDA-MB-231 and MDA-MB-468),we validated the relationship of nuclear factor erythroid 2-like 3(NFE2L3)and basic helix-loop-helix family member E 40(BHLHE40)by performing a luciferase assay.The expression levels of these targets were measured after transfections with plasmid and siRNA via qRT-PCR and western blots.The effect of these genes on cell proliferation and migration was studied using phenotypic assays.Results:Using computational approaches,we identified NFE2L3 as a master regulator with BHLHE40 as its target gene.NFE2L3 protein binds to the promoter region of BHLHE40 and regulates its transcriptional activity.Additionally,silencing and overexpressing NFE2L3 and BHLHE40 in TNBC cell lines MDA-MB-231 and MDA-MB-468 showed that NFE2L3 directly regulates BHLHE40 at both transcriptional and translational levels.We found that BHLHE40 requires NFE2L3 for cell proliferation and migration in TNBC.Conclusion:These findings underscore the significance of NFE2L3 and BHLHE40 in TNBC,highlighting NFE2L3’s role in regulating the oncogenic activity of BHLHE40 in TNBC cells.展开更多
BACKGROUND Return to work(RTW)serves as an indication for young and middle-aged colorectal cancer(CRC)survivors to resume their normal social lives.However,these survivors encounter significant challenges during their...BACKGROUND Return to work(RTW)serves as an indication for young and middle-aged colorectal cancer(CRC)survivors to resume their normal social lives.However,these survivors encounter significant challenges during their RTW process.Hence,scientific research is necessary to explore the barriers and facilitating factors of returning to work for young and middle-aged CRC survivors.AIM To examine the current RTW status among young and middle-aged CRC survivors and to analyze the impact of RTW self-efficacy(RTW-SE),fear of progression(FoP),eHealth literacy(eHL),family resilience(FR),and financial toxicity(FT)on their RTW outcomes.METHODS A cross-sectional investigation was adopted in this study.From September 2022 to February 2023,a total of 209 participants were recruited through a convenience sampling method from the gastrointestinal surgery department of a class A tertiary hospital in Chongqing.The investigation utilized a general information questionnaire alongside scales assessing RTW-SE,FoP,eHL,FR,and FT.To analyze the factors that influence RTW outcomes among young and middle-aged CRC survivors,Cox regression modeling and Kaplan-Meier survival analysis were used.RESULTS A total of 43.54%of the participants successfully returned to work,with an average RTW time of 100 days.Cox regression univariate analysis revealed that RTW-SE,FoP,eHL,FR,and FT were significantly different between the non-RTW and RTW groups(P<0.05).Furthermore,Cox regression multivariate analysis identified per capita family monthly income,job type,RTW-SE,and FR as independent influencing factors for RTW(P<0.05).CONCLUSION The RTW rate requires further improvement.Elevated levels of RTW-SE and FR were found to significantly increase RTW among young and middle-aged CRC survivors.Health professionals should focus on modifiable factors,such as RTW-SE and FR,to design targeted RTW support programs,thereby facilitating their timely reintegration into mainstream society.展开更多
The kidneys play a critical role in maintaining glucose homeostasis.Under normal renal tubular function,most of the glucose filtered from the glomeruli is re-absorbed in the proximal tubules,leaving only trace amounts...The kidneys play a critical role in maintaining glucose homeostasis.Under normal renal tubular function,most of the glucose filtered from the glomeruli is re-absorbed in the proximal tubules,leaving only trace amounts in the urine.Glycosuria can occur as a symptom of generalized proximal tubular dysfunction or when the reabsorption threshold is exceeded or the glucose threshold is reduced,as seen in familial renal glycosuria(FRG).FRG is characterized by persistent glycosuria despite normal blood glucose levels and tubular function and is primarily associated with mutations in the sodium/glucose cotransporter 5A2 gene,which encodes the sodium-glucose cotransporter(SGLT)2.Inhibiting SGLTs has been proposed as a novel treatment strategy for diabetes,and since FRG is often considered an asymptomatic and benign condition,it has inspired preclinical and clinical studies using SGLT2 inhibitors in type 2 diabetes.However,patients with FRG may exhibit clinical features such as lower body weight or height,altered systemic blood pressure,diaper dermatitis,amino-aciduria,decreased serum uric acid levels,and hypercalciuria.Further research is needed to fully understand the pathophysiology,molecular genetics,and clinical manifestations of renal glucosuria.展开更多
文摘Background:Continuous care for children with enterostomy and their families has been gaining popularity in China.Objective:To evaluate the feasibility of continuous care for children with enterostomy and their families in China.Methods:The PubMed,Web of Science,Embase,Cochrane Library,EBSCO,CNKI,CBM,VIP,and WanFang were searched for clinical trials until December 30,2025.Two reviewers independently searched articles,evaluated quality and extracted data.This review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses(PRISMA).Results:33 studies involving 2774 participants were included.The meta-analysis showed that continuous care strategy can significantly reduce the incidence of complications in children with enterostomy(OR=0.20,95%CI=0.16-0.26,p<0.001,I2=0%),effectively improve the family caregiver ability for enterostomy(MD=-10.34,95%CI=-13.82 to-6.85,p<0.001,I2=99%),shorten the time for family members to replace stoma bags(MD=-13.57,95%CI=-19.66 to-7.49,p<0.001,I2=100%),and alleviate negative emotions such as anxiety(SMD=-1.80,95%CI=-2.36 to-1.23,p<0.001,I2=92%)and depression(SMD=-1.54,95%CI=-2.04 to-1.04,p<0.001,I2=89%)in the families of the affected children.Conclusions:Continuous care can reduce complications of enterostomy in children,improve the family caregiver ability for enterostomy and alleviate negative emotions of family members such as anxiety and depression.
基金supported by the Fundamental Research Funds for the Central Universities(Grant No.QNTD202503)Forestry and Grassland Science and Technology Innovation Youth Top Talent Project of China(Grant No.2020132608)Beijing High-Precision Discipline Project,Discipline of Ecological Environment of Urban and Rural Human Settlements.
文摘As a large family of RNA helicases,DEAD-box(DDX)RNA helicases play crucial roles in almost all cellular RNA processing activities.However,the role of the DDX gene family in cold tolerance of mei(Prunus mume)remains unclear.In this study,we identified 45 DDX genes through whole-genome analysis unevenly distributed across eight chromosomes and scaffolds of mei.Based on the phylogenetic tree and gene structure analysis,the DDX genes were classified into nine subfamilies based on their motif compositions and intron-exon structures.The results of synteny analysis showed that segmental duplication was considered a major factor contributing to the amplification of the PmDDX family.RNA-Seq and qRT-PCR results revealed differential expression of PmDDX genes under cold stress.Among these,PmDDX39 was significantly up-regulated under cold stress,suggesting its positive role in modulating mei cold tolerance.We found that silenced PmDDX39 under cold stress led to greater damage than the wild seedlings via virus-induced gene silencing(VIGS).Conversely,overexpression of PmDDX39 in Arabidopsis enhanced cold stress tolerance.Moreover,dual luciferase and yeast one-hybrid(Y1H)demonstrated that PmDDX39 directly activates the expression of the C-repeat binding factor(PmCBFf)by binding to its promoters.This study provides new insights into the structure,evolution,and functional role of the PmDDX gene family in mei responses to cold stress.
基金Supported by the Research Grants of the National Research,Development and Innovation Office,No.K125377,No.K134863 and No.K143549New National Excellence Program of the Ministry of Human Capacities,No.UNKP-20-5-SZTE-161,No.UNKP-22-3-SZTE-233,No.UNKP-23-5-SZTE-719,No.UNKP-22-4-SZTE-296 and No.UNKP-22-3-SZTE-278+1 种基金Janos Bolyai Research Grant,No.BO/00723/22the Géza Hetényi Research Grant by Albert Szent-Györgyi Medical School,University of Szeged.
文摘BACKGROUND Familial adenomatous polyposis(FAP)is a disorder of autosomal dominant inheritance that is responsible for around 1%of colorectal cancer(CRC)cases.AIM To determine the mutation profile of FAP-specific to the Hungarian population.METHODS This prospective single-center study enrolled patients with clinically suspected FAP or attenuated FAP(aFAP).Whole-exome next-generation sequencing was performed to detect variants of 50 FAP priority genes and 173 CRC predisposing genes or other CRC disease-associated genes.To identify larger deletions and insertions,a multiplex amplifiable probe hybridization technique was used.The identified genes were then classified according to the American College of Medical Genetics and Genomics guidelines.RESULTS A total of 26 index patients with clinically suspected FAP(n=21)and aFAP(n=5)were enrolled.APC gene alterations were confirmed in 92.31%of the cases(region 1B deletion,n=2;whole-gene deletion,n=4;frameshift mutation,n=2;nonsense mutation,n=5,and splice mutation,n=1),with the remaining two cases having CHEK2 and MSH3 gene alterations.According to pathogenicity,21 cases had pathogenic mutations,6 cases had likely pathogenic mutations,and 16 cases had variants of unknown significance(VUS).The most frequent of the latter were the POLE(n=5)and PIEZO1(n=4)gene variants.CONCLUSION Germline mutations in the APC gene were confirmed in more than 90%of Hungarian patients with clinically suspected FAP.Although the role of VUS genes is unclear,they are highly likely to play a role in the development of CRC.
文摘Objectives:In recent years,mental health has emerged as a pressing public health concern in China,driven by mounting societal pressures and fast-paced urban lifestyles.Physical activity,a well-established means of enhancing psychological well-being,has received growing scholarly and policy attention.This study uses panel data from the 2020 and 2022 waves of the China Family Panel Studies(CFPS)to examine the impact of exercise frequency on mental health(with indicators such as CESD-8 depression scores)among college students and young employees,thereby providing empirical support for targeted mental health interventions.Methods:This study examines the relationship between individual exercise frequency and mental health among college students and young employees,using panel data from the 2020 and 2022 waves of the China Family Panel Studies(CFPS),with the Chinese version of the 8-item Center for Epidemiologic Studies Depression Scale(CESD-8)depression scores,self-rated health,and life satisfaction as outcome variables.Specifically,this study tests three hypotheses:(H1)increased exercise frequency significantly reduces depression symptoms and enhances well-being;(H2)the effects of exercise vary by social roles,with stronger mental health benefits among employed individuals and those with lower education;and(H3)lifestyle factors such as smoking amount,sleep duration,and Body Mass Index(BMI)partially mediate the relationship between exercise and mental health.Employing a two-way fixed effects model,baseline results indicate that a one-unit increase in exercise frequency significantly reduces the CESD-8 score by 0.183 points.To address potential endogeneity and spurious regression concerns,an instrumental variable(IV)approach is further applied.The heterogeneity analysis differentiates between students and employed individuals.Results:Among students,the effects of exercise on mental health are not statistically significant,regardless of education level.In contrast,for the employed,exercise demonstrates a significant positive impact on mental health,with particularly pronounced effects among those with lower educational attainment.These findings underscore the importance of promoting exercise as part of comprehensive mental health strategies.Mediation analysis indicates that the beneficial effect of exercise on mental health is partially transmitted through reductions in adverse health behaviors,especially smoking.Conclusions:Policymakers should integrate physical activity promotion into health interventions,prioritizing vulnerable groups to enhance psychological resilience and foster inclusive,health-oriented development.
文摘新学期伊始,翻开鲁科版五四制小学英语的第七单元,《Family》的标题赫然在目,和所有英语老师一样,我对这个单元的内容、流程再熟悉不过了。按照以往的经验,我会带着孩子们认读图片、跟读录音、分组进行角色扮演,最后再进行一次基础小测验。孩子们大多能流利地指着图片说出“This is my father.”但我总感觉缺了点什么,这些词汇对于他们而言,似乎只是一张需要死记硬背的单词表,与那个充满烟火气、承载着他们所有喜怒哀乐的“家”,隔着一层看不见的屏障。直到我看到坐在窗边的小雅,在课本“全家福”插图的旁边,用铅笔认真画了一个歪歪扭扭的小人,旁边工工整整地写着“me”。
文摘Hodgkin lymphoma(HL)is a heterogenous lymphoproliferative disorder of B-cell origin and represents one of the most common malignancies in children and young adults.In addition to well-known underlying factors-such as Epstein-Barr virus infection-the familial aggregation demonstrated in large population studies suggested a genetic predisposition.First-degree relatives of patients with HL have an approximately threefold increased risk of developing the disease compared to the general population.These observations have recently prompted several whole-genome studies in affected families,identifying variants possibly implicated in lymphomagenesis,including alterations in DICER1(a member of the ribonuclease III family),POT1(protection of telomeres 1),KDR(kinase insert domain receptor),KLHDC8B(kelch domain-containing protein 8B),PAX5(paired box protein 5),GATA3(GATA binding protein 3),IRF7(interferon regulatory factor 7),EEF2KMT(eukaryotic elongation factor 2 lysine methyltransferase),and POLR1E(RNA polymerase I subunit E).In this article,we review current insights into the etiopathogenesis and risks of familial HL,and present case reports involving two sisters diagnosed with HL nearly 17 years apart.Recognizing the risk for first-degree relatives may potentially increase awareness of early symptoms among family members of HL patients,leading to earlier diagnosis and better outcomes.Conversely,understanding that the hereditary risk,though higher than in the general population,remains relatively low may provide reassurance for affected families.
基金supported by the 2025 Fujian Provincial Social Science Foundation Project(FJ2025C074).
文摘This systematic review synthesizes empirical research on external risk factors for adolescent smartphone addiction.Scopus and Web of Science were searched for English peer-reviewed empirical articles from 2008 onward;28 met inclusion criteria(excluding non-adolescents,generic internet addiction,non-empirical work,or non-English).Thematic synthesis organized findings into three external risk domains—family,school,and peers—considering cultural/contextual mechanisms.Family dynamics(parental phubbing,harsh parenting,dysfunction),school stressors,and adverse peer relationships were identified as accumulating,direct and indirect contributors to smartphone addiction.These operate within a techno-ecological framework,where digital technologies amplify vulnerabilities and create new pathways for maladaptive use.Evidence favors an ecological,multi-level perspective.Future research should use longitudinal designs,standardize measures across cultures,and examine understudied regions—especially Africa—to guide culturally sensitive interventions.
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From goldfish pampering to pet-friendly high-speed rail,China’s pet economy boom is reshaping lifestyles and sparking a multi-billion-dollar emotional economy where pets are family,not just animals.FOR Wu Ming,a busy Beijing resident,unwinding after a long day involves watching his goldfish glide through a meticulously maintained home aquarium.
基金supported by grants from the Tianjin Health Technology Project(Grant no.2022QN106).
文摘Background:Receptor-interacting protein kinases(RIPKs)regulate cell death,inflammation,and immune responses,yet their roles in cancer are not fully understood.This study investigates the expression,genomic alterations,and functional implications of RIPK family members across various cancers.Methods:We collected multi-omics data from The Cancer Genome Atlas and other public databases,including gene expression,copy number variation(CNV),mutation,methylation,tumor mutation burden(TMB),and microsatellite instability(MSI).Differential expression and survival analyses were performed using DESeq2 and Cox proportional hazards models.CNV and mutation data were analyzed with GISTIC2 and Mutect2,and methylation data with the ChAMP package.Correlations with TMB and MSI were assessed using Pearson coefficients,and gene set enrichment analysis was conducted with the MSigDB Hallmark gene sets.Results:RIPK family members show significant differential expression in various cancers,with RIPK1 and RIPK4 frequently altered.Survival analysis reveals heterogeneous impacts on overall survival.CNV and mutation analyses identify high alteration frequencies for RIPK2 and RIPK7,affecting gene expression.RIPK1 and RIPK7 are hypermethylated in several cancers,inversely correlating with RIPK3 expression.RIPK1,RIPK2,RIPK5,RIPK6,and RIPK7 correlate positively with TMB,while RIPK3 shows negative correlations in some cancers.MSI analysis indicates associations with DNA mismatch repair.G ene set enrichment analysis highlights immune-related pathway enrichment for RIPK1,RIPK2,RIPK3,and RIPK6,and cell proliferation and DNA repair pathways for RIPK4 and RIPK5.RIPK family members showed heterogeneous alterations across cancers:for example,RIPK7 was mutated in up to~15%of u terine c orpus e ndometrial c arcinoma and l ung s quamous c ell c arcinoma cases,and RIPK1 and RIPK7 exhibited frequent promoter hypermethylation in multiple tumor types.Several genes displayed context-dependent associations with overall survival and with TMB/MSI.Conclusion:This pan-cancer analysis of the RIPK family reveals their diverse roles and potential as biomarkers and therapeutic targets.The findings emphasize the importance of RIPK genes in tumorigenesis and suggest context-dependent functions across cancer types.Further studies are needed to explore their mechanisms in cancer development and clinical applications.
文摘The Changbai Mountains,in Northeast China's Jilin Province,are covered by vast,wild forests.The mountainous region has chilly,snowy weather for about nine months of the year.The lowest temperature is below-40 C in winter.In 2005,Huang Yi,a native of Southwest China's Sichuan Province,relocated to the Changbai Mountains,to work at the Mount Hengshan frontier inspection station.
基金funded by the National Natural Science Foundation of China(32071828 and 32471943)the Central Finance Forestry Science and Technology Promotion Demonstration Project,China(Su2024TG04)+1 种基金the Priority Academic Program Development of Jiangsu Higher Education Institutions(PAPD),Chinapartly supported by the open funds of the National Key Laboratory for Germplasm Innovation&Utilization of Horticultural Crops,China。
文摘Osmanthus fragrans is most famous for its strong aroma,and different varieties have different degrees of fragrance and color.Fragrance and color are important factors affecting the ornamental quality of O.fragrans.Terpenoids are important secondary metabolites in plants,with β-carotene(C40)being the major pigment substance and linalool(C10)being the key aromatic component in O.fragrans.The geranylgeranyl pyrophosphate synthase genes(GGPPSs)play important roles in secondary metabolism in plants.However,the functions of the GGPPS family in floral color and fragrance formation has rarely been reported in O.fragrans.In this study,24 Of GGPPS genes were identified and classified into two subfamilies.The Of GGPPSs showed tissue-specific expression and Of GGPPS13 had highest expression in flowers.The Of GGPPS13 protein was localized to chloroplasts.The transcriptome data of Of GGPPS13 was verified by q RT-PCR and the expression level in‘Wanyingui'with strong aroma was higher than that in‘Zhuangyuanhong'with deep color at different flower development stages.Transient overexpression of Of GGPPS13 in O.fragrans petals showed that Of GGPPS13 increased the β-carotene content,the main color substance of O.fragrans,but decreased the linalool content,the main volatile organic compound(VOC)in the floral aroma of O.fragrans.Of GGPPS13 was indicated as the critical gene related to terpenoid synthesis in the floral aroma and color formation in O.fragrans.Our findings provide gene resources on the GGPPS gene family for further revealing the molecular regulation mechanism of the floral color and aroma formation in O.fragrans.
文摘AIM:To investigate whether vaccinia-related kinase 1(VRK1)mediates transforming growth factor-beta2(TGF-β2)-caused epithelial-mesenchymal transition(EMT)and inflammatory responses in retinal pigment epithelial(RPE)cells through regulating snail family transcriptional repressor 1(SNAI1),and to validate its role in a proliferative vitreoretinopathy(PVR)mouse model.METHODS:Human RPE cell line ARPE-19 cells were treated with TGF-β2 to construct an EMT model.Western blot detected VRK1 level.The effects of VRK1 on SNAI1 expression and biological behavior of ARPE-19 cells were detected by immunofluorescence,ELISA,Transwell,and scratch assay,and the interaction between VRK1 and SNAI1 was confirmed through immunoprecipitation.A PVR mouse model was constructed,and the effects of VRK1 or/and SNAI1 on retinal damage were assessed by pathologic staining.Inflammatory factors and EMT-related proteins were assessed with ELISA and Western blot.RESULTS:VRK1 was upregulated in ARPE-19 cells after TGF-β2 treatment.Overexpression of VRK1 increased cell viability,promoted cell migration and EMT,and the levels of inflammatory factors.Silencing of VRK1 reversed the above indexes.There was a direct interaction between VRK1 and SNAI1,and overexpresssion SNAI1 weakened the impacts of silencing of VRK1.In PVR mice,silencing of VRK1 ameliorated retinal structural damage,decreased proinflammatory factor levels,and suppressed SNAI1 and mesenchymal marker expression.SNAI1 overexpression antagonized the protective effects of silencing VRK1 and exacerbated EMT and inflammatory responses.CONCLUSION:VRK1 plays a key role in retinal structural and inflammatory damage in PVR mice by regulating SNAI1 and mediating TGF-β2-caused EMT and inflammatory responses in RPE cells.
基金Supported by the National Natural Science Foundation of China(No.81970804)Natural Science Foundation of Hunan Province(No.2021JJ30949).
文摘Dear Editor,We reported a Chinese family carrying a novel Crumbs homologue 1(CRB1)variant(c.1737_1755del).Consanguineous marriage resulted in a homozygous mutation,leading to the onset of Leber congenital amaurosis(LCA)in their offspring.
基金supported by the National Natural Science Foundation of China,Nos.82471107,31970930(both to KY)the National Key Research and Development Program of China,No.2024YFA1108701(to KY)+1 种基金the Natural Science Foundation of Hubei Province,Nos.2020CFA069(to KY),2018CFB434(to KY),2025AFB042(to HQ)the Neuroscience Team Development Project of Wuhan University of Science and Technology,Nos.1180002,1180030(both to KY)。
文摘Voltage-gated sodium channels are essential ionic-conductance pathways in the nervous system,which play an irreplaceable role in modulating neuronal excitability and signal transduction.This review comprehensively analyzes the molecular mechanisms and pathophysiological significance of voltage-gated sodium channels,with particular emphasis on elucidating the molecular-action mechanisms of the distinct subtypes of these channels,including Nav1.1,Nav1.2,and Nav1.6,across various neurological disorders such as familial hemiplegic migraine,epilepsy,autism spectrum disorder,and retinal dysfunction.This review also provides a comprehensive overview of the pathogenic mechanisms associated with voltage-gated sodium channels,and systematically clarifies the evolutionary pathway of treatment strategies from conventional to innovative approaches.It analyzes two major categories of conventional sodium channel blockers and their applications:antiepileptic drugs(such as carbamazepine,lamotrigine,and phenytoin)and antiarrhythmic drugs(such as lidocaine,flecainide,and quinidine).However,these conventional blockers show limitations because of the lack of selectivity,driving research toward more precise therapeutic directions.Additionally,this review evaluates gabapentin,cannabidiol,and calcium channel blockers with different mechanisms of action.These drugs modulate neuronal excitability from multiple perspectives,providing diverse options for symptom relief.This review also highlights advances in gene therapy for specific diseases,such as STK-001,which promotes effective splicing of the sodium channel voltage-gated type 1 alpha subunit(SCN1A)gene,and ETX101,which utilizes adeno-associated virus 9 vectors to deliver engineered transcription factors.These two agents provide targeted therapeutic solutions for Dravet syndrome.Furthermore,this review summarizes some innovative therapeutic agents in clinical trials,including PRAX-222(for SCN2A gain-offunction mutation-related epilepsy),which has received Food and Drug Administration orphan drug designation,and the selective Nav1.6 inhibitor NBI-921352(for SCN8A-related epilepsy).Collectively,this review comprehensively compares the advantages and disadvantages of conventional drugs and gene therapy and envisions future treatment strategies that integrate the strengths of both approaches,facilitating personalized precision medicine to provide more accurate and effective treatment options for patients with ion channel diseases.
基金supported by the National Natural Science Foundation of China,Nos.82171076(to XS)and U22A20311(to XS),82101168(to TL)Shanghai Science and technology Innovation Action Plan,No.23Y11901300(to JS)+1 种基金Science and Technology Commission of Shanghai Municipality,No.21ZR1451500(to TL)Shanghai Pujiang Program,No.22PJ1412200(to BY)。
文摘Progressive photoreceptor cell death is one of the main pathological features of age-related macular degeneration and eventually leads to vision loss.Ferroptosis has been demonstrated to be associated with retinal degenerative diseases.However,the molecular mechanisms underlying ferroptosis and photoreceptor cell death in age-related macular degeneration remain largely unexplored.Bioinformatics and biochemical analyses in this study revealed xC^(–),solute carrier family 7 member 11-regulated ferroptosis as the predominant pathological process of photoreceptor cell degeneration in a light-induced dry age-related macular degeneration mouse model.This process involves the nuclear factor-erythroid factor 2-related factor 2-solute carrier family 7 member 11-glutathione peroxidase 4 signaling pathway,through which cystine depletion,iron ion accumulation,and enhanced lipid peroxidation ultimately lead to photoreceptor cell death and subsequent visual function impairment.We demonstrated that solute carrier family 7 member 11 overexpression blocked this process by inhibiting oxidative stress in vitro and in vivo.Conversely,solute carrier family 7 member 11 knockdown or the solute carrier family 7 member 11 inhibitor sulfasalazine and ferroptosis-inducing agent erastin aggravated H_(2)O_(2)-induced ferroptosis of 661W cells.These findings indicate solute carrier family 7 member 11 may be a potential therapeutic target for patients with retinal degenerative diseases including age-related macular degeneration.
文摘Objectives:The current treatment options and therapeutic targets for triple-negative breast cancer(TNBC),an aggressive subtype of breast cancer(BrCA),are limited.This study aimed to identify novel biomarkers and transcriptional regulatory networks(TRN)inherent in TNBC samples.Methods:We analyzed pan-cancer BrCA datasets from The Cancer Genome Atlas(TCGA)to compare triple-positive breast cancer(TPBC)with TNBC.TRN algorithms and virtual inference of protein-enriched regulon(VIPER)were used to identify master regulators and their target genes.Utilizing TNBC cells(MDA-MB-231 and MDA-MB-468),we validated the relationship of nuclear factor erythroid 2-like 3(NFE2L3)and basic helix-loop-helix family member E 40(BHLHE40)by performing a luciferase assay.The expression levels of these targets were measured after transfections with plasmid and siRNA via qRT-PCR and western blots.The effect of these genes on cell proliferation and migration was studied using phenotypic assays.Results:Using computational approaches,we identified NFE2L3 as a master regulator with BHLHE40 as its target gene.NFE2L3 protein binds to the promoter region of BHLHE40 and regulates its transcriptional activity.Additionally,silencing and overexpressing NFE2L3 and BHLHE40 in TNBC cell lines MDA-MB-231 and MDA-MB-468 showed that NFE2L3 directly regulates BHLHE40 at both transcriptional and translational levels.We found that BHLHE40 requires NFE2L3 for cell proliferation and migration in TNBC.Conclusion:These findings underscore the significance of NFE2L3 and BHLHE40 in TNBC,highlighting NFE2L3’s role in regulating the oncogenic activity of BHLHE40 in TNBC cells.
基金Supported by the Chongqing Medical University Program for Youth Innovation in Future Medicine,No.W0019Chongqing Municipal Education Commission’s 14th Five-Year Key Discipline Support Project,No.20240101 and No.20240102。
文摘BACKGROUND Return to work(RTW)serves as an indication for young and middle-aged colorectal cancer(CRC)survivors to resume their normal social lives.However,these survivors encounter significant challenges during their RTW process.Hence,scientific research is necessary to explore the barriers and facilitating factors of returning to work for young and middle-aged CRC survivors.AIM To examine the current RTW status among young and middle-aged CRC survivors and to analyze the impact of RTW self-efficacy(RTW-SE),fear of progression(FoP),eHealth literacy(eHL),family resilience(FR),and financial toxicity(FT)on their RTW outcomes.METHODS A cross-sectional investigation was adopted in this study.From September 2022 to February 2023,a total of 209 participants were recruited through a convenience sampling method from the gastrointestinal surgery department of a class A tertiary hospital in Chongqing.The investigation utilized a general information questionnaire alongside scales assessing RTW-SE,FoP,eHL,FR,and FT.To analyze the factors that influence RTW outcomes among young and middle-aged CRC survivors,Cox regression modeling and Kaplan-Meier survival analysis were used.RESULTS A total of 43.54%of the participants successfully returned to work,with an average RTW time of 100 days.Cox regression univariate analysis revealed that RTW-SE,FoP,eHL,FR,and FT were significantly different between the non-RTW and RTW groups(P<0.05).Furthermore,Cox regression multivariate analysis identified per capita family monthly income,job type,RTW-SE,and FR as independent influencing factors for RTW(P<0.05).CONCLUSION The RTW rate requires further improvement.Elevated levels of RTW-SE and FR were found to significantly increase RTW among young and middle-aged CRC survivors.Health professionals should focus on modifiable factors,such as RTW-SE and FR,to design targeted RTW support programs,thereby facilitating their timely reintegration into mainstream society.
文摘The kidneys play a critical role in maintaining glucose homeostasis.Under normal renal tubular function,most of the glucose filtered from the glomeruli is re-absorbed in the proximal tubules,leaving only trace amounts in the urine.Glycosuria can occur as a symptom of generalized proximal tubular dysfunction or when the reabsorption threshold is exceeded or the glucose threshold is reduced,as seen in familial renal glycosuria(FRG).FRG is characterized by persistent glycosuria despite normal blood glucose levels and tubular function and is primarily associated with mutations in the sodium/glucose cotransporter 5A2 gene,which encodes the sodium-glucose cotransporter(SGLT)2.Inhibiting SGLTs has been proposed as a novel treatment strategy for diabetes,and since FRG is often considered an asymptomatic and benign condition,it has inspired preclinical and clinical studies using SGLT2 inhibitors in type 2 diabetes.However,patients with FRG may exhibit clinical features such as lower body weight or height,altered systemic blood pressure,diaper dermatitis,amino-aciduria,decreased serum uric acid levels,and hypercalciuria.Further research is needed to fully understand the pathophysiology,molecular genetics,and clinical manifestations of renal glucosuria.
