AIM:To identify early biomarkers associated with glaucomatous visual field(VF)progression in patients with normal-tension glaucoma(NTG).METHODS:This study included patients were divided into two groups based on diseas...AIM:To identify early biomarkers associated with glaucomatous visual field(VF)progression in patients with normal-tension glaucoma(NTG).METHODS:This study included patients were divided into two groups based on disease progression status.Tear samples were collected for proteomic analysis.Dataindependent acquisition(DIA)mass spectrometry combined with bioinformatic analyses was performed to identify and validate potential protein biomarkers for NTG progression.Additionally,differentially expressed proteins(DEPs)were evaluated using mediating effect models and receiver operating characteristic(ROC)curve analysis.RESULTS:A total of 19 patients(20 eyes)with NTG participated in this study,including 10 patients(4 males and 6 females;10 eyes)in the progression group with mean age of 67.70±9.03y and 10 patients(4 males and 6 females;10 eyes)in the non-progression group with mean age of 68.60±7.58y.A total of 158 significantly differentially expressed proteins were detected.UniProt database annotation identified 3 upregulated proteins and 12 downregulated proteins.Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway analysis showed that these DEPs were mainly enriched in pathways such as oocyte meiosis.Gene Ontology(GO)enrichment analysis revealed functional clusters related to cellular processes.Weighted gene coexpression network analysis(WGCNA)indicated that the core proteins were primarily involved in the neurodegenerationmultiple diseases pathway and cellular processes.Mediating effect analysis identified PRDX4(L)as a potential protein biomarker.ROC curve analysis showed that GNAI1 had the largest area under the curve(AUC=0.889).CONCLUSION:This study identifies 15 differentially expressed proteins in the tear fluid of NTG patients,including PRDX4(L).PRDX4(L)plays a key role in oxidative stress.展开更多
Colorectal cancer remains one of the leading causes of morbidity and mortality worldwide.Despite notable advances in early detection and therapeutic strategies,the molecular mechanisms underlying tumor survival,chemot...Colorectal cancer remains one of the leading causes of morbidity and mortality worldwide.Despite notable advances in early detection and therapeutic strategies,the molecular mechanisms underlying tumor survival,chemotherapy resistance,and metastasis are not yet fully understood.MicroRNAs(miRNAs)have emerged as pivotal regulators of cancer development,as they modulate gene expression and orchestrate key signaling pathways.However,the epigenetic mechanisms that control miRNA expression and their downstream gene targets remain largely unclear.In this review,we highlight the critical role of the colorectal cancer microenvironment in influencing miRNA expression and discuss how this regulation contributes to tumorigenesis.A better understanding of these processes may lead to the identification of novel therapeutic targets and strategies to prevent recurrence.展开更多
Objectives:Pancreatic cancer(PC)is characterized by poor prognosis due to its limited treatment choices and delayed detection.S100A14 has been implicated in tumor progression,yet its regulatory hierarchy and functiona...Objectives:Pancreatic cancer(PC)is characterized by poor prognosis due to its limited treatment choices and delayed detection.S100A14 has been implicated in tumor progression,yet its regulatory hierarchy and functional interplay in PC remain unclear.This study aimed to define the role of S100A14 in PC progression.Methods:Integrated bioinformatic analyses of TCGA-PAAD and GSE22780 datasets identified candidate hub genes.Prognostic relevance was assessed via Kaplan-Meier and ROC analyses.Functional experiments were performed in PANC-1 and BxPC-3 cells,including qRT-PCR,CCK-8 assay,Western blotting,Transwell assay,and apoptosis assay.Co-immunoprecipitation(Co-IP)was used to verify S100A14-S100A16 interaction.CHX chase and dual-luciferase assays were employed to assess protein stability and transcriptional activity.Results:S100A14 was markedly upregulated in PC tissues and cell lines and identified as a key prognostic gene.Silencing S100A14 suppressed EMT,proliferation,invasion,and migration,while reversing S100A16-mediated p53 inhibition and enhancing apoptosis.Mechanistically,Co-IP assay confirmed the protein interaction between S100A14 and S100A16;S100A14 stabilized S100A16 protein through post-translational modification without transcriptional regulation;the S100A14/S100A16 axis reduced p53 protein stability and inhibited its transcriptional activity as well as the downstream p21 expression.Critically,knockdown of S100A14 abrogated the pro-metastatic phenotype of cancer cells.Conclusion:This study identifies S100A14 promotes PC progression by stabilizing S100A16 and suppressing the tumor-suppressive p53/p21 pathway;knockdown of S100A14 can reverse the above effects,restore p53 function,and enhance cancer cell apoptosis.Targeting the S100A14/S100A16/p53 regulatory axis could represent a promising therapeutic approach for PC.展开更多
AIM:To build a functional generalized estimating equation(GEE)model to detect glaucomatous visual field progression and compare the performance of the proposed method with that of commonly employed algorithms.METHODS:...AIM:To build a functional generalized estimating equation(GEE)model to detect glaucomatous visual field progression and compare the performance of the proposed method with that of commonly employed algorithms.METHODS:Totally 716 eyes of 716 patients with primary open angle glaucoma(POAG)with at least 5 reliable 24-2 test results and 2y of follow-up were selected.The functional GEE model was used to detect perimetric progression in the training dataset(501 eyes).In the testing dataset(215 eyes),progression was evaluated the functional GEE model,mean deviation(MD)and visual field index(VFI)rates of change,Advanced Glaucoma Intervention Study(AGIS)and Collaborative Initial Glaucoma Treatment Study(CIGTS)scores,and pointwise linear regression(PLR).RESULTS:The proposed method showed the highest proportion of eyes detected as progression(54.4%),followed by the VFI rate(34.4%),PLR(23.3%),and MD rate(21.4%).The CIGTS and AGIS scores had a lower proportion of eyes detected as progression(7.9%and 5.1%,respectively).The time to detection of progression was significantly shorter for the proposed method than that of other algorithms(adjusted P≤0.019).The VFI rate displayed moderate pairwise agreement with the proposed method(k=0.47).CONCLUSION:The functional GEE model shows the highest proportion of eyes detected as perimetric progression and the shortest time to detect perimetric progression in patients with POAG.展开更多
BACKGROUND Gastric cancer is one of the most common cancers worldwide,especially in East Asia.AIM To explore the clinical outcomes and progression-related factors of low-grade intraepithelial neoplasia(LGIN)in the gas...BACKGROUND Gastric cancer is one of the most common cancers worldwide,especially in East Asia.AIM To explore the clinical outcomes and progression-related factors of low-grade intraepithelial neoplasia(LGIN)in the gastric mucosa and provide valuable guidance for improving treatment efficacy.METHODS A total of 357 patients diagnosed with LGIN based on initial pathological examination in Anhui Provincial Hospital or three other medical consortium units between January 2022 and June 2024 were included.Among them,296 patients were followed up with endoscopic and biopsy pathology.Logistic regression was utilized to analyze the relevant risk factors for LGIN progression in the gastric mucosa.RESULTS The distribution sites of LGIN among the 357 patients were as follows:Gastric antrum(54.6%),gastric cardia(24.1%),gastric angulus(8.7%),gastric body(4.8%),gastric fundus(4.8%),and multiple sites(3.1%).Additionally,of the 357 patients with LGIN,112(31.4%)developed ulceration and 59(16.5%)experienced gastric polyps.Furthermore,231 of the 357(64.71%)patients with LGIN tested positive for Helicobacter pylori(H.pylori)infection.The H.pylori infection rates of the patients with LGIN with accompanying atrophy,intestinal metaplasia,and gastric ulcer were 51.95%,59.31%,and 28.57%,respectively.Multivariate logistic regression analysis showed that age≥60 years[odds ratio(OR)=3.063,95%confidence interval(CI):1.351-6.945,P=0.007],H.pylori infection(OR=3.560,95%CI:1.158-10.949,P=0.027),multiple locations(OR=10.136,95%CI:2.045-50.237,P=0.005),lesion size≥2 cm(OR=3.921,95%CI:1.664-9.237,P=0.002),and gastric ulcer(OR=2.730,95%CI:1.197-6.223,P=0.017)were predictive factors for LGIN progression.CONCLUSION LGIN progression is closely related to age,H.pylori positivity,multiple locations,lesion size≥2 cm,and gastric ulcer.Thus,actively identifying these risk factors in patients with LGIN may have certain clinical significance in preventing further tumor progression.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
Lipocalin-2(LCN2)is a member of the lipocalin superfamily with multiple functions and can participate in the transport of a variety of small lipophilic ligands in vivo.LCN2 is significantly expressed in various tumors...Lipocalin-2(LCN2)is a member of the lipocalin superfamily with multiple functions and can participate in the transport of a variety of small lipophilic ligands in vivo.LCN2 is significantly expressed in various tumors and plays an important role in regulating tumor cell proliferation,invasion,and metastasis.The specific actions of LCN2 in tumors may vary depending on the particular type of cancer involved.In this review,we provide an extensive overview of the transcriptional and post-transcriptional regulation of LCN2 in health and disease.Furthermore,we summarize the impact of LCN2 dysregulation in a broad range of tumors.Lastly,we examine the mechanisms of action of LCN2 during tumorigenesis,progression,and metastasis.Understanding the complex relationships between LCN2 and tumor development,progression,and metastasis is vital for advancing our knowledge of cancer biology,developing biomarkers for diagnosis and clinical decision-making,and creating therapeutic strategies to improve the management of patients with cancer.展开更多
Let a_(1),a_(2),a_(3)be nonzero integers with gcd(a_(1),a_(2),a_(3))=1,and let k be any positive integer,K=max[3,|a_(1)|,|a_(2)|,|a_(3)|,k].Suppose that l_(1),l_(2),l_(3)are integers each coprime to k.Suppose further ...Let a_(1),a_(2),a_(3)be nonzero integers with gcd(a_(1),a_(2),a_(3))=1,and let k be any positive integer,K=max[3,|a_(1)|,|a_(2)|,|a_(3)|,k].Suppose that l_(1),l_(2),l_(3)are integers each coprime to k.Suppose further that b is any integer satisfying some necessary congruent conditions.The solvability of linear equation a_(1)p_(1)+a_(2)p_(2)+a_(3)p_(3)=b(p_(j)=l_(j)(mod k),1≤j≤3)with prime variables pi,p_(2),ps is investigated.It is proved that if ai,a_(2),a_(3)are all positive,then the above equation is solvable whenever b≥K^(25);if a,a_(2),a_(3)are not all of the same sign,then the above equation has a solution p_(1),p_(2),p_(3)satisfying max(p_(1),p_(2),p_(3))≤3|b|+K^(25).展开更多
Epidermal growth factor receptor(EGFR)mutations are among the most prevalent driver gene alterations in non-small cell lung cancer(NSCLC).Osimertinib,with or without chemotherapy,the first-line standard treatment for ...Epidermal growth factor receptor(EGFR)mutations are among the most prevalent driver gene alterations in non-small cell lung cancer(NSCLC).Osimertinib,with or without chemotherapy,the first-line standard treatment for patients with advanced NSCLC bearing sensitive EGFR mutations,significantly prolongs the progression-free survival(PFS)to 25.5 months1.Despite great breakthroughs in survival data,patients inevitably experience disease progression.A large meta-analysis has indicated that,compared with chemother-apy,immuno-based therapies achieve longer PFS in patients with EGFR mutation who progressed on third-generation epidermal growth factor receptor tyrosine kinase inhibitors(EGFR-TKIs)2.Therefore,immunotherapies are often used after EGFR-TKI resistance is observed.展开更多
In the article“LncRNA PCGEM1 facilitates cervical cancer progression via miR-642a-5p/KIF5B axis”(Oncology Research,2024,Vol 32,No.7,pp.1221-1229.doi:10.32604/or.2024.047454),there were some errors in the content.In ...In the article“LncRNA PCGEM1 facilitates cervical cancer progression via miR-642a-5p/KIF5B axis”(Oncology Research,2024,Vol 32,No.7,pp.1221-1229.doi:10.32604/or.2024.047454),there were some errors in the content.In order to ensure the scientific and rigorous nature of our academic publications,we deleted the incorrect content that is not related to this study,supplemented the details of the method.展开更多
Ovarian cancer(OC),a highly lethal gynaecological malignancy,is often diagnosed at advanced stages,resulting in a poor prognosis.Sialylation,an important form of glycosylation,significantly contributes to the progress...Ovarian cancer(OC),a highly lethal gynaecological malignancy,is often diagnosed at advanced stages,resulting in a poor prognosis.Sialylation,an important form of glycosylation,significantly contributes to the progression of various solid tumours,including OC.Aberrant sialylation promotes tumour progression and metastasis by altering the structure and function of glycoproteins.Although its role in several solid tumours is well documented,the role of abnormal sialylation in OC and its potential as a therapeutic target remain poorly understood.This review highlights sialylation as a key regulator of the progression,metastasis,and drug resistance of OC.A deeper understanding of altered sialylation can contribute to the identification of novel therapeutic strategies for OC.展开更多
Objective We examined the associations between obesity-related indices and the risk of diabetes progression from prediabetes in older adults,comparing the differences in using the American Diabetes Association(ADA)and...Objective We examined the associations between obesity-related indices and the risk of diabetes progression from prediabetes in older adults,comparing the differences in using the American Diabetes Association(ADA)and World Health Organization(WHO)criteria.Methods Data were obtained from the Healthy Aging Evaluation Longitudinal Study conducted in China.At baseline,prediabetes(in participants without diabetes)was classified based on fasting plasma glucose(FPG)levels using both criteria.Body mass index(BMI)and waist circumference(WC)were categorized according to data distribution and diagnostic cut-off values,respectively.Cox proportional hazards regression models were used to estimate the adjusted hazard ratios(aHRs)with 95%confidence intervals(CIs)for obesity-related indices and diabetes progression from prediabetes.Results Among the 1,127 participants classified as prediabetic according to the ADA criteria,474 met the WHO criteria.Under ADA-defined prediabetes,the highest WC quartile(≥93 cm)was significantly associated with an increased diabetes risk(aHR 1.93[1.06,3.53,P<0.05]),whereas BMI-related and cut-off-based abdominal obesity demonstrated no significant associations(P>0.05).Under WHOdefined prediabetes,both the high tertile of WC(≥90 cm)and general obesity(BMI≥28.0 kg/m^(2))were significantly associated with progression to diabetes(P<0.05),with aHR 2.13(1.06,4.27)and 2.44(1.19,5.01),respectively.However,cut-off-based abdominal obesity and the high BMI tertile(≥25.75 kg/m^(2))were not significantly associated with diabetes progression(P>0.05).Conclusion Elevated WC,rather than BMI-based indices or cut-off-based abdominal obesity,was significantly associated with diabetes progression according to the ADA-defined prediabetes criteria.However,both the evaluated WC and general obesity predicted progression to diabetes according to the WHO criteria.展开更多
The published article titled“MicroRNA-92a Promotes Cell Proliferation in Cervical Cancer via Inhibiting p21 Expression and Promoting Cell Cycle Progression”has been retracted from Oncology Research,Vol.25,No.1,2017,...The published article titled“MicroRNA-92a Promotes Cell Proliferation in Cervical Cancer via Inhibiting p21 Expression and Promoting Cell Cycle Progression”has been retracted from Oncology Research,Vol.25,No.1,2017,pp.137–145.展开更多
This study analyzes whether the tax progression proviso’s calculation method for foreign income exemptions under a tax treaty breaches EU law.This research question has not yet been examined in the literature.In such...This study analyzes whether the tax progression proviso’s calculation method for foreign income exemptions under a tax treaty breaches EU law.This research question has not yet been examined in the literature.In such a case,a violation of the EU fundamental freedoms may result in taxpayers partially losing the tax-reducing effect of the basic allowance deduction due to the tax progression proviso’s calculation method in their EU or EEA state of residence.Theoretical,quantitative,and formal–analytical research methods were used to examine this issue.Moreover,the analysis uses Germany and Austria as examples.However,the findings can be replicated in all EU and EEA countries applying the same type of taxation.The study’s main contribution is demonstrating that the current progression proviso’s calculation method in Germany and Austria for income from other EU Member States and EEA states,exempt under DTAs,breaches EU law and is,therefore,prohibited.The fiscal policy implications of such unlawful taxation are highlighted.EU and EEA Member States must amend their tax laws if they violate EU law.Therefore,a new calculation method for taxation with a progression proviso is developed to bring the EU Member States’tax legislation in line with EU law.The study expands the literature on taxation and public finance,since it has not yet dealt with this issue.Moreover,the economic policy implications of the research findings are outlined.This study belongs to the field of taxation and fiscal policy and is of fundamental relevance.展开更多
Splenic histiocytic sarcoma(SHS)is a rare,aggressive hematological malignancy with unclear progression and management.Our case illustrates the progression and pathophysiological processes of SHS and provides key data ...Splenic histiocytic sarcoma(SHS)is a rare,aggressive hematological malignancy with unclear progression and management.Our case illustrates the progression and pathophysiological processes of SHS and provides key data for the diagnosis,treatment and management of SHS.A 60-year-old female with incidentally detected splenic mass(6.0 cm×5.7 cm)underwent splenectomy,confirmed as SHS in 2020.Post-op imatinib therapy was given.In 2022,hepatic metastases(2.4 cm×2.9 cm)with pancytopenia led to supportive care.Lesions enlarged to 4.3 cm×2.7 cm,leading to multi-organ failure and death at 33 months.The case was categorized into three distinct stages based on the pathophysiology of SHS:Early-stage splenic tumor growth,mid-stage liver metastasis with hematological abnormalities,and late-stage tumor infiltration leading to multiorgan failure.For SHS,this case highlights the pivotal role of early intervention and the value of personalized treatment strategies.展开更多
Candida albicans(C.albicans)represents one of the most prevalent opportunistic fungal pathogens in cancer patients.Although the association between C.albicans and cancer has been recognized for decades,the causal rela...Candida albicans(C.albicans)represents one of the most prevalent opportunistic fungal pathogens in cancer patients.Although the association between C.albicans and cancer has been recognized for decades,the causal relationship,whether C.albicans infection is a consequence of cancer or a direct contributor to cancer development-remains a subject of intensive investigation.Recently,the complex interplay between microbes and cancer has garnered significant attention within the scientific community,with growing interest in elucidating the underlying molecular mechanisms.This review systematically examines the biological characteristics of C.albicans,its multifaceted interactions with the host,and its relationship with the intestinal microbiota.Additionally,it provides a comprehensive analysis of the association between C.albicans and the development of various malignancies,with particular emphasis on digestive tract cancers.The review also identifies critical knowledge gaps and apparent contradictions in existing research,highlighting potential avenues for breakthroughs that will advance the efficient and accurate screening,diagnosis,and treatment of cancer.展开更多
Alzheimer’s disease(AD)is a slow,progressive neurodegenerative disease with clinical symptoms that typically emerge in the elderly,leading to deterioration of cognitive functions over time.Memory loss is the primary ...Alzheimer’s disease(AD)is a slow,progressive neurodegenerative disease with clinical symptoms that typically emerge in the elderly,leading to deterioration of cognitive functions over time.Memory loss is the primary symptom,eventually leading to significant declines in executive and cognitive functions,along with psychiatric and behavioral changes,and alterations in personality.展开更多
BACKGROUNDColorectal cancer(CRC)typically progresses from benign colorectal polyps,whichrepresent a precursor to malignancy.Identifying the factors influencing thisprogression is crucial for early intervention and pre...BACKGROUNDColorectal cancer(CRC)typically progresses from benign colorectal polyps,whichrepresent a precursor to malignancy.Identifying the factors influencing thisprogression is crucial for early intervention and prevention.Although genetic andenvironmental factors have been widely studied,the role of lifestyle factors suchas physical activity,diet,smoking,sleep,and stress remains underexplored,especially in patients with early stage CRC or polyps.Recent evidence suggeststhat lifestyle behaviors may influence cancer progression by modulating inflammatorypathways,metabolic health,and immune function.For instance,highlevels of physical activity are linked to a reduced risk of CRC development,whereas poor dietary habits,smoking,and inadequate sleep have all beenimplicated in increased cancer risk and progression.Moreover,early-stage CRCpatients,who are often asymptomatic or have minimal symptoms,may particularlybenefit from lifestyle modifications to slow disease progression andimprove overall prognosis.The gap in understanding the specific influence ofthese lifestyle factors on colorectal polyps and early stage cancer progressionunderscores the need for comprehensive studies.By assessing several modifiablelifestyle factors and their association with disease progression,clinicians canidentify practical intervention points.These interventions could ultimately reducethe need for more aggressive treatments and improve the long-term outcomes inaffected patients.AIMTo investigate the association between lifestyle factors and disease progression inpatients with colorectal polyps and early stage cancer.METHODSIn this observational study conducted from January 2022 to December 2023,werecruited 120 patients with colorectal polyps or early stage cancer from Jiangshan People's Hospital.Lifestyle factors,including physical activity,dietary patterns,smoking status,sleep quality,andstress levels,were assessed using validated questionnaires.Disease progression was evaluated using standardizedfollow-up colonoscopies and pathological examinations.Cox proportional hazards models were used to analyzethe association between lifestyle factors and disease progression after adjusting for potential confounders.RESULTSDuring the median follow-up of 18.4 months,42(35.0%)patients experienced disease progression.High levels ofphysical activity were associated with reduced progression risk[adjusted hazard ratio(HR)0.55,95%confidenceinterval(CI):0.38-0.80,P=0.002]compared to low activity levels.High adherence to a healthy dietary patternshowed similar protective effects(adjusted HR 0.62,95%CI:0.43-0.89,P=0.009).Current smoking(adjusted HR1.92,95%CI:1.35-2.73,P<0.001)and poor sleep quality(adjusted HR 1.38,95%CI:1.05-1.82,P=0.021)wereassociated with increased progression risk.The impact of lifestyle factors was particularly pronounced in patientsyounger than 60 years and those with multiple polyps at baseline.CONCLUSIONThis study demonstrated significant associations between lifestyle factors and disease progression in colorectalpolyps and early stage cancer.Physical activity,dietary patterns,smoking status,and sleep quality have emergedas key modifiable factors influencing disease progression.These findings support the integration of lifestyleassessments and modifications in the clinical management of patients with colorectal neoplasia.展开更多
Objective Glioma is a highly heterogeneous and malignant intracranial tumor that presents challenges for clinical treatment.ELMO domain containing 2(ELMOD2)is a GTPase-activating protein that regulates a range of cell...Objective Glioma is a highly heterogeneous and malignant intracranial tumor that presents challenges for clinical treatment.ELMO domain containing 2(ELMOD2)is a GTPase-activating protein that regulates a range of cellular biological processes.However,its specific role and prognostic value in tumorigenesis are still unknown.This study aimed to assess the prognostic relevance and signaling function of ELMOD2 in gliomas.Methods The Chinese Glioma Genome Atlas(CGGA)and The Cancer Genome Atlas(TCGA)databases were utilized to conduct a comprehensive analysis of the expression profile of ELMOD2 in gliomas,elucidating its associations with clinicopathological parameters and patient prognosis.Single-cell analysis was performed to characterize ELMOD2 expression across distinct glioma cell subpopulations.Gene Ontology(GO),Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analyses,and Gene Set Variation Analysis(GSVA)were employed to evaluate the potential biological functions of ELMOD2 in gliomagenesis.Specific small interfering RNAs(siRNAs)were used to knock down ELMOD2 in the glioma cell lines U251 and A172 to assess their cellular behaviors and examine the levels of multiple key signaling molecules associated with the occurrence of gliomas.Results ELMOD2 was overexpressed in gliomas,and this upregulation was correlated with tumor grade,isocitrate dehydrogenase mutation,and 1p/19q codeletion status.Notably,ELMOD2 expression was elevated in classical and mesenchymal subtypes,and single-cell resolution analysis revealed predominant enrichment within malignant cells.Functionally,ELMOD2 regulated cell cycle progression,and its overexpression was related to independent adverse outcomes.In vitro experiments revealed that ELMOD2 was located in the cytoplasm and nucleoplasm.Furthermore,ELMOD2 knockdown reduced proliferation,migration,and invasion and increased apoptosis in U251 and A172 cell lines.Finally,ELMOD2 knockdown significantly decreased p-Erk1/2.Conclusions ELMOD2 expression in glioma is positively correlated with tumorigenesis and is a crucial independent prognostic marker.Thus,ELMOD2 is a promising biomarker and therapeutic target for glioma treatment.展开更多
BACKGROUND Cholangiocarcinoma(CCA)is a highly aggressive malignancy with limited therapeutic options.Dysregulation of the Hippo-yes-associated protein(YAP)signaling pathway plays a key role in tumor progression,but th...BACKGROUND Cholangiocarcinoma(CCA)is a highly aggressive malignancy with limited therapeutic options.Dysregulation of the Hippo-yes-associated protein(YAP)signaling pathway plays a key role in tumor progression,but the effects of distinct bile acids on this pathway remain unclear.AIM To investigate the roles of glycochenodeoxycholic acid(GDCA)and deoxycholic acid(DCA)in CCA progression through Hippo-YAP signaling and to evaluate the effects of YAP-targeted interventions.METHODS The in vitro experiments were performed using HuCCT1 CCA cells treated with GDCA,DCA,and combinations with a YAP inhibitor(verteporfin)or agonist(GA-017).Key molecular changes in the Hippo-YAP pathway were assessed by western blot,immunofluorescence,and reverse transcription quantitative realtime polymerase chain reaction.Functional assays,including Cell Counting Kit-8,5-ethynyl-2’-deoxyuridine,Transwell,and terminal deoxynucleotidyl transferasemediated deoxyuridine triphosphate-nick end labelling,were conducted to evaluate cell proliferation,migration,invasion,and apoptosis.In vivo,nude mice bearing subcutaneous HuCCT1 tumors were treated with GDCA,DCA,or combined YAP modulators.Tumor growth was monitored,and molecular analyses of tumor tissues were performed using western blot.RESULTS The GDCA significantly activated YAP by reducing mammalian STE20-like protein kinase 1 and large tumor suppressor 1 phosphorylation,promoting YAP nuclear translocation,and enhancing tumor cell proliferation,migration,and invasion.In contrast,DCA inhibited YAP activation,suppressed tumor cell functions,and increased apoptosis.GDCA combined with YAP inhibitors attenuated its tumor-promoting effects,while DCA combined with YAP agonists reversed its inhibitory effects.In vivo,GDCA accelerated tumor growth,while DCA reduced tumor size and weight,with molecular changes consistent with in vitro findings.CONCLUSION The GDCA and DCA exert opposing effects on CCA progression through Hippo-YAP signaling.GDCA promotes tumor growth via YAP activation,while DCA inhibits these processes.YAP-targeted interventions demonstrate therapeutic potential,providing insights into new treatment strategies for CCA.展开更多
基金Supported by The Eye Hospital of Wenzhou Medical University(No.KYQD20220304)The Fifth Batch of Provincial Ten Thousand Personnel Program Outstanding Talents Funding(No.474092204)+1 种基金Innovative Talents and Teams(2024)-The Fifth Batch of Funding Funds for Scientific and Technological Innovation Leading Talents Under the Provincial Ten Thousand Personnel Program(No.4240924003G)The Key R&D Program of Zhejiang(No.2022C03112).
文摘AIM:To identify early biomarkers associated with glaucomatous visual field(VF)progression in patients with normal-tension glaucoma(NTG).METHODS:This study included patients were divided into two groups based on disease progression status.Tear samples were collected for proteomic analysis.Dataindependent acquisition(DIA)mass spectrometry combined with bioinformatic analyses was performed to identify and validate potential protein biomarkers for NTG progression.Additionally,differentially expressed proteins(DEPs)were evaluated using mediating effect models and receiver operating characteristic(ROC)curve analysis.RESULTS:A total of 19 patients(20 eyes)with NTG participated in this study,including 10 patients(4 males and 6 females;10 eyes)in the progression group with mean age of 67.70±9.03y and 10 patients(4 males and 6 females;10 eyes)in the non-progression group with mean age of 68.60±7.58y.A total of 158 significantly differentially expressed proteins were detected.UniProt database annotation identified 3 upregulated proteins and 12 downregulated proteins.Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway analysis showed that these DEPs were mainly enriched in pathways such as oocyte meiosis.Gene Ontology(GO)enrichment analysis revealed functional clusters related to cellular processes.Weighted gene coexpression network analysis(WGCNA)indicated that the core proteins were primarily involved in the neurodegenerationmultiple diseases pathway and cellular processes.Mediating effect analysis identified PRDX4(L)as a potential protein biomarker.ROC curve analysis showed that GNAI1 had the largest area under the curve(AUC=0.889).CONCLUSION:This study identifies 15 differentially expressed proteins in the tear fluid of NTG patients,including PRDX4(L).PRDX4(L)plays a key role in oxidative stress.
文摘Colorectal cancer remains one of the leading causes of morbidity and mortality worldwide.Despite notable advances in early detection and therapeutic strategies,the molecular mechanisms underlying tumor survival,chemotherapy resistance,and metastasis are not yet fully understood.MicroRNAs(miRNAs)have emerged as pivotal regulators of cancer development,as they modulate gene expression and orchestrate key signaling pathways.However,the epigenetic mechanisms that control miRNA expression and their downstream gene targets remain largely unclear.In this review,we highlight the critical role of the colorectal cancer microenvironment in influencing miRNA expression and discuss how this regulation contributes to tumorigenesis.A better understanding of these processes may lead to the identification of novel therapeutic targets and strategies to prevent recurrence.
基金supported by the Yunnan Province Liu Liang Expert Workstation(No.202305AF150148)Famous Doctor Projects of Yunnan Province(No.XDYC-MY-2022-0032)+1 种基金Yunnan Health Training Project of High Level Talents(No.L-2024029)Innovation Team Special Program of Yunnan(No.202505AS350004).
文摘Objectives:Pancreatic cancer(PC)is characterized by poor prognosis due to its limited treatment choices and delayed detection.S100A14 has been implicated in tumor progression,yet its regulatory hierarchy and functional interplay in PC remain unclear.This study aimed to define the role of S100A14 in PC progression.Methods:Integrated bioinformatic analyses of TCGA-PAAD and GSE22780 datasets identified candidate hub genes.Prognostic relevance was assessed via Kaplan-Meier and ROC analyses.Functional experiments were performed in PANC-1 and BxPC-3 cells,including qRT-PCR,CCK-8 assay,Western blotting,Transwell assay,and apoptosis assay.Co-immunoprecipitation(Co-IP)was used to verify S100A14-S100A16 interaction.CHX chase and dual-luciferase assays were employed to assess protein stability and transcriptional activity.Results:S100A14 was markedly upregulated in PC tissues and cell lines and identified as a key prognostic gene.Silencing S100A14 suppressed EMT,proliferation,invasion,and migration,while reversing S100A16-mediated p53 inhibition and enhancing apoptosis.Mechanistically,Co-IP assay confirmed the protein interaction between S100A14 and S100A16;S100A14 stabilized S100A16 protein through post-translational modification without transcriptional regulation;the S100A14/S100A16 axis reduced p53 protein stability and inhibited its transcriptional activity as well as the downstream p21 expression.Critically,knockdown of S100A14 abrogated the pro-metastatic phenotype of cancer cells.Conclusion:This study identifies S100A14 promotes PC progression by stabilizing S100A16 and suppressing the tumor-suppressive p53/p21 pathway;knockdown of S100A14 can reverse the above effects,restore p53 function,and enhance cancer cell apoptosis.Targeting the S100A14/S100A16/p53 regulatory axis could represent a promising therapeutic approach for PC.
基金Supported by the Korea Health Technology R&D Project through the Korea Health Industry Development Institute(KHIDI),funded by the Ministry of Health&Welfare,Republic of Korea(No.HR20C0026)the National Research Foundation of Korea(NRF)(No.RS-2023-00247504)the Patient-Centered Clinical Research Coordinating Center,funded by the Ministry of Health&Welfare,Republic of Korea(No.HC19C0276).
文摘AIM:To build a functional generalized estimating equation(GEE)model to detect glaucomatous visual field progression and compare the performance of the proposed method with that of commonly employed algorithms.METHODS:Totally 716 eyes of 716 patients with primary open angle glaucoma(POAG)with at least 5 reliable 24-2 test results and 2y of follow-up were selected.The functional GEE model was used to detect perimetric progression in the training dataset(501 eyes).In the testing dataset(215 eyes),progression was evaluated the functional GEE model,mean deviation(MD)and visual field index(VFI)rates of change,Advanced Glaucoma Intervention Study(AGIS)and Collaborative Initial Glaucoma Treatment Study(CIGTS)scores,and pointwise linear regression(PLR).RESULTS:The proposed method showed the highest proportion of eyes detected as progression(54.4%),followed by the VFI rate(34.4%),PLR(23.3%),and MD rate(21.4%).The CIGTS and AGIS scores had a lower proportion of eyes detected as progression(7.9%and 5.1%,respectively).The time to detection of progression was significantly shorter for the proposed method than that of other algorithms(adjusted P≤0.019).The VFI rate displayed moderate pairwise agreement with the proposed method(k=0.47).CONCLUSION:The functional GEE model shows the highest proportion of eyes detected as perimetric progression and the shortest time to detect perimetric progression in patients with POAG.
基金the Research Project of the Chinese Digestive Early Cancer Physicians’Joint Growth Program,No.GTCZ-2021-AH-34-0012.
文摘BACKGROUND Gastric cancer is one of the most common cancers worldwide,especially in East Asia.AIM To explore the clinical outcomes and progression-related factors of low-grade intraepithelial neoplasia(LGIN)in the gastric mucosa and provide valuable guidance for improving treatment efficacy.METHODS A total of 357 patients diagnosed with LGIN based on initial pathological examination in Anhui Provincial Hospital or three other medical consortium units between January 2022 and June 2024 were included.Among them,296 patients were followed up with endoscopic and biopsy pathology.Logistic regression was utilized to analyze the relevant risk factors for LGIN progression in the gastric mucosa.RESULTS The distribution sites of LGIN among the 357 patients were as follows:Gastric antrum(54.6%),gastric cardia(24.1%),gastric angulus(8.7%),gastric body(4.8%),gastric fundus(4.8%),and multiple sites(3.1%).Additionally,of the 357 patients with LGIN,112(31.4%)developed ulceration and 59(16.5%)experienced gastric polyps.Furthermore,231 of the 357(64.71%)patients with LGIN tested positive for Helicobacter pylori(H.pylori)infection.The H.pylori infection rates of the patients with LGIN with accompanying atrophy,intestinal metaplasia,and gastric ulcer were 51.95%,59.31%,and 28.57%,respectively.Multivariate logistic regression analysis showed that age≥60 years[odds ratio(OR)=3.063,95%confidence interval(CI):1.351-6.945,P=0.007],H.pylori infection(OR=3.560,95%CI:1.158-10.949,P=0.027),multiple locations(OR=10.136,95%CI:2.045-50.237,P=0.005),lesion size≥2 cm(OR=3.921,95%CI:1.664-9.237,P=0.002),and gastric ulcer(OR=2.730,95%CI:1.197-6.223,P=0.017)were predictive factors for LGIN progression.CONCLUSION LGIN progression is closely related to age,H.pylori positivity,multiple locations,lesion size≥2 cm,and gastric ulcer.Thus,actively identifying these risk factors in patients with LGIN may have certain clinical significance in preventing further tumor progression.
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 Program for Science Technology and Innovation Committee of Shenzhen(2021N062-JCYJ20210324115408023)Guangdong High-Level Hospital Construction Fund,Shenzhen High-Level Hospital Construction Fund。
文摘Lipocalin-2(LCN2)is a member of the lipocalin superfamily with multiple functions and can participate in the transport of a variety of small lipophilic ligands in vivo.LCN2 is significantly expressed in various tumors and plays an important role in regulating tumor cell proliferation,invasion,and metastasis.The specific actions of LCN2 in tumors may vary depending on the particular type of cancer involved.In this review,we provide an extensive overview of the transcriptional and post-transcriptional regulation of LCN2 in health and disease.Furthermore,we summarize the impact of LCN2 dysregulation in a broad range of tumors.Lastly,we examine the mechanisms of action of LCN2 during tumorigenesis,progression,and metastasis.Understanding the complex relationships between LCN2 and tumor development,progression,and metastasis is vital for advancing our knowledge of cancer biology,developing biomarkers for diagnosis and clinical decision-making,and creating therapeutic strategies to improve the management of patients with cancer.
文摘Let a_(1),a_(2),a_(3)be nonzero integers with gcd(a_(1),a_(2),a_(3))=1,and let k be any positive integer,K=max[3,|a_(1)|,|a_(2)|,|a_(3)|,k].Suppose that l_(1),l_(2),l_(3)are integers each coprime to k.Suppose further that b is any integer satisfying some necessary congruent conditions.The solvability of linear equation a_(1)p_(1)+a_(2)p_(2)+a_(3)p_(3)=b(p_(j)=l_(j)(mod k),1≤j≤3)with prime variables pi,p_(2),ps is investigated.It is proved that if ai,a_(2),a_(3)are all positive,then the above equation is solvable whenever b≥K^(25);if a,a_(2),a_(3)are not all of the same sign,then the above equation has a solution p_(1),p_(2),p_(3)satisfying max(p_(1),p_(2),p_(3))≤3|b|+K^(25).
基金supported by grants from the National Natural Science Foundation of China(Grant No.82273162)Jiangsu Cancer Hospital Science and Technology Development Fund Project(Grant No.YSZD202409).
文摘Epidermal growth factor receptor(EGFR)mutations are among the most prevalent driver gene alterations in non-small cell lung cancer(NSCLC).Osimertinib,with or without chemotherapy,the first-line standard treatment for patients with advanced NSCLC bearing sensitive EGFR mutations,significantly prolongs the progression-free survival(PFS)to 25.5 months1.Despite great breakthroughs in survival data,patients inevitably experience disease progression.A large meta-analysis has indicated that,compared with chemother-apy,immuno-based therapies achieve longer PFS in patients with EGFR mutation who progressed on third-generation epidermal growth factor receptor tyrosine kinase inhibitors(EGFR-TKIs)2.Therefore,immunotherapies are often used after EGFR-TKI resistance is observed.
文摘In the article“LncRNA PCGEM1 facilitates cervical cancer progression via miR-642a-5p/KIF5B axis”(Oncology Research,2024,Vol 32,No.7,pp.1221-1229.doi:10.32604/or.2024.047454),there were some errors in the content.In order to ensure the scientific and rigorous nature of our academic publications,we deleted the incorrect content that is not related to this study,supplemented the details of the method.
基金supported by Hubei Provincial Natural Science Foundation of China(No.2023AFB670).
文摘Ovarian cancer(OC),a highly lethal gynaecological malignancy,is often diagnosed at advanced stages,resulting in a poor prognosis.Sialylation,an important form of glycosylation,significantly contributes to the progression of various solid tumours,including OC.Aberrant sialylation promotes tumour progression and metastasis by altering the structure and function of glycoproteins.Although its role in several solid tumours is well documented,the role of abnormal sialylation in OC and its potential as a therapeutic target remain poorly understood.This review highlights sialylation as a key regulator of the progression,metastasis,and drug resistance of OC.A deeper understanding of altered sialylation can contribute to the identification of novel therapeutic strategies for OC.
文摘Objective We examined the associations between obesity-related indices and the risk of diabetes progression from prediabetes in older adults,comparing the differences in using the American Diabetes Association(ADA)and World Health Organization(WHO)criteria.Methods Data were obtained from the Healthy Aging Evaluation Longitudinal Study conducted in China.At baseline,prediabetes(in participants without diabetes)was classified based on fasting plasma glucose(FPG)levels using both criteria.Body mass index(BMI)and waist circumference(WC)were categorized according to data distribution and diagnostic cut-off values,respectively.Cox proportional hazards regression models were used to estimate the adjusted hazard ratios(aHRs)with 95%confidence intervals(CIs)for obesity-related indices and diabetes progression from prediabetes.Results Among the 1,127 participants classified as prediabetic according to the ADA criteria,474 met the WHO criteria.Under ADA-defined prediabetes,the highest WC quartile(≥93 cm)was significantly associated with an increased diabetes risk(aHR 1.93[1.06,3.53,P<0.05]),whereas BMI-related and cut-off-based abdominal obesity demonstrated no significant associations(P>0.05).Under WHOdefined prediabetes,both the high tertile of WC(≥90 cm)and general obesity(BMI≥28.0 kg/m^(2))were significantly associated with progression to diabetes(P<0.05),with aHR 2.13(1.06,4.27)and 2.44(1.19,5.01),respectively.However,cut-off-based abdominal obesity and the high BMI tertile(≥25.75 kg/m^(2))were not significantly associated with diabetes progression(P>0.05).Conclusion Elevated WC,rather than BMI-based indices or cut-off-based abdominal obesity,was significantly associated with diabetes progression according to the ADA-defined prediabetes criteria.However,both the evaluated WC and general obesity predicted progression to diabetes according to the WHO criteria.
文摘The published article titled“MicroRNA-92a Promotes Cell Proliferation in Cervical Cancer via Inhibiting p21 Expression and Promoting Cell Cycle Progression”has been retracted from Oncology Research,Vol.25,No.1,2017,pp.137–145.
文摘This study analyzes whether the tax progression proviso’s calculation method for foreign income exemptions under a tax treaty breaches EU law.This research question has not yet been examined in the literature.In such a case,a violation of the EU fundamental freedoms may result in taxpayers partially losing the tax-reducing effect of the basic allowance deduction due to the tax progression proviso’s calculation method in their EU or EEA state of residence.Theoretical,quantitative,and formal–analytical research methods were used to examine this issue.Moreover,the analysis uses Germany and Austria as examples.However,the findings can be replicated in all EU and EEA countries applying the same type of taxation.The study’s main contribution is demonstrating that the current progression proviso’s calculation method in Germany and Austria for income from other EU Member States and EEA states,exempt under DTAs,breaches EU law and is,therefore,prohibited.The fiscal policy implications of such unlawful taxation are highlighted.EU and EEA Member States must amend their tax laws if they violate EU law.Therefore,a new calculation method for taxation with a progression proviso is developed to bring the EU Member States’tax legislation in line with EU law.The study expands the literature on taxation and public finance,since it has not yet dealt with this issue.Moreover,the economic policy implications of the research findings are outlined.This study belongs to the field of taxation and fiscal policy and is of fundamental relevance.
基金Supported by the Program of General Hospital of Western Theater,No.2021-XZYG-C33.
文摘Splenic histiocytic sarcoma(SHS)is a rare,aggressive hematological malignancy with unclear progression and management.Our case illustrates the progression and pathophysiological processes of SHS and provides key data for the diagnosis,treatment and management of SHS.A 60-year-old female with incidentally detected splenic mass(6.0 cm×5.7 cm)underwent splenectomy,confirmed as SHS in 2020.Post-op imatinib therapy was given.In 2022,hepatic metastases(2.4 cm×2.9 cm)with pancytopenia led to supportive care.Lesions enlarged to 4.3 cm×2.7 cm,leading to multi-organ failure and death at 33 months.The case was categorized into three distinct stages based on the pathophysiology of SHS:Early-stage splenic tumor growth,mid-stage liver metastasis with hematological abnormalities,and late-stage tumor infiltration leading to multiorgan failure.For SHS,this case highlights the pivotal role of early intervention and the value of personalized treatment strategies.
文摘Candida albicans(C.albicans)represents one of the most prevalent opportunistic fungal pathogens in cancer patients.Although the association between C.albicans and cancer has been recognized for decades,the causal relationship,whether C.albicans infection is a consequence of cancer or a direct contributor to cancer development-remains a subject of intensive investigation.Recently,the complex interplay between microbes and cancer has garnered significant attention within the scientific community,with growing interest in elucidating the underlying molecular mechanisms.This review systematically examines the biological characteristics of C.albicans,its multifaceted interactions with the host,and its relationship with the intestinal microbiota.Additionally,it provides a comprehensive analysis of the association between C.albicans and the development of various malignancies,with particular emphasis on digestive tract cancers.The review also identifies critical knowledge gaps and apparent contradictions in existing research,highlighting potential avenues for breakthroughs that will advance the efficient and accurate screening,diagnosis,and treatment of cancer.
基金supported by the National Natural Science Foundation of China(82120108010 and 81930028).
文摘Alzheimer’s disease(AD)is a slow,progressive neurodegenerative disease with clinical symptoms that typically emerge in the elderly,leading to deterioration of cognitive functions over time.Memory loss is the primary symptom,eventually leading to significant declines in executive and cognitive functions,along with psychiatric and behavioral changes,and alterations in personality.
文摘BACKGROUNDColorectal cancer(CRC)typically progresses from benign colorectal polyps,whichrepresent a precursor to malignancy.Identifying the factors influencing thisprogression is crucial for early intervention and prevention.Although genetic andenvironmental factors have been widely studied,the role of lifestyle factors suchas physical activity,diet,smoking,sleep,and stress remains underexplored,especially in patients with early stage CRC or polyps.Recent evidence suggeststhat lifestyle behaviors may influence cancer progression by modulating inflammatorypathways,metabolic health,and immune function.For instance,highlevels of physical activity are linked to a reduced risk of CRC development,whereas poor dietary habits,smoking,and inadequate sleep have all beenimplicated in increased cancer risk and progression.Moreover,early-stage CRCpatients,who are often asymptomatic or have minimal symptoms,may particularlybenefit from lifestyle modifications to slow disease progression andimprove overall prognosis.The gap in understanding the specific influence ofthese lifestyle factors on colorectal polyps and early stage cancer progressionunderscores the need for comprehensive studies.By assessing several modifiablelifestyle factors and their association with disease progression,clinicians canidentify practical intervention points.These interventions could ultimately reducethe need for more aggressive treatments and improve the long-term outcomes inaffected patients.AIMTo investigate the association between lifestyle factors and disease progression inpatients with colorectal polyps and early stage cancer.METHODSIn this observational study conducted from January 2022 to December 2023,werecruited 120 patients with colorectal polyps or early stage cancer from Jiangshan People's Hospital.Lifestyle factors,including physical activity,dietary patterns,smoking status,sleep quality,andstress levels,were assessed using validated questionnaires.Disease progression was evaluated using standardizedfollow-up colonoscopies and pathological examinations.Cox proportional hazards models were used to analyzethe association between lifestyle factors and disease progression after adjusting for potential confounders.RESULTSDuring the median follow-up of 18.4 months,42(35.0%)patients experienced disease progression.High levels ofphysical activity were associated with reduced progression risk[adjusted hazard ratio(HR)0.55,95%confidenceinterval(CI):0.38-0.80,P=0.002]compared to low activity levels.High adherence to a healthy dietary patternshowed similar protective effects(adjusted HR 0.62,95%CI:0.43-0.89,P=0.009).Current smoking(adjusted HR1.92,95%CI:1.35-2.73,P<0.001)and poor sleep quality(adjusted HR 1.38,95%CI:1.05-1.82,P=0.021)wereassociated with increased progression risk.The impact of lifestyle factors was particularly pronounced in patientsyounger than 60 years and those with multiple polyps at baseline.CONCLUSIONThis study demonstrated significant associations between lifestyle factors and disease progression in colorectalpolyps and early stage cancer.Physical activity,dietary patterns,smoking status,and sleep quality have emergedas key modifiable factors influencing disease progression.These findings support the integration of lifestyleassessments and modifications in the clinical management of patients with colorectal neoplasia.
基金supported by grants from the Natural Science Foundation of Guangxi Province(Grant No:2022GXNSFAA035639 and 2023GXNSFBA026092)the National Natural Science Foundation of China(Grant No:81860445 and 82260554)the Innovation Project of Guangxi Graduate Education(Grant No:YCBZ2024118)。
文摘Objective Glioma is a highly heterogeneous and malignant intracranial tumor that presents challenges for clinical treatment.ELMO domain containing 2(ELMOD2)is a GTPase-activating protein that regulates a range of cellular biological processes.However,its specific role and prognostic value in tumorigenesis are still unknown.This study aimed to assess the prognostic relevance and signaling function of ELMOD2 in gliomas.Methods The Chinese Glioma Genome Atlas(CGGA)and The Cancer Genome Atlas(TCGA)databases were utilized to conduct a comprehensive analysis of the expression profile of ELMOD2 in gliomas,elucidating its associations with clinicopathological parameters and patient prognosis.Single-cell analysis was performed to characterize ELMOD2 expression across distinct glioma cell subpopulations.Gene Ontology(GO),Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analyses,and Gene Set Variation Analysis(GSVA)were employed to evaluate the potential biological functions of ELMOD2 in gliomagenesis.Specific small interfering RNAs(siRNAs)were used to knock down ELMOD2 in the glioma cell lines U251 and A172 to assess their cellular behaviors and examine the levels of multiple key signaling molecules associated with the occurrence of gliomas.Results ELMOD2 was overexpressed in gliomas,and this upregulation was correlated with tumor grade,isocitrate dehydrogenase mutation,and 1p/19q codeletion status.Notably,ELMOD2 expression was elevated in classical and mesenchymal subtypes,and single-cell resolution analysis revealed predominant enrichment within malignant cells.Functionally,ELMOD2 regulated cell cycle progression,and its overexpression was related to independent adverse outcomes.In vitro experiments revealed that ELMOD2 was located in the cytoplasm and nucleoplasm.Furthermore,ELMOD2 knockdown reduced proliferation,migration,and invasion and increased apoptosis in U251 and A172 cell lines.Finally,ELMOD2 knockdown significantly decreased p-Erk1/2.Conclusions ELMOD2 expression in glioma is positively correlated with tumorigenesis and is a crucial independent prognostic marker.Thus,ELMOD2 is a promising biomarker and therapeutic target for glioma treatment.
文摘BACKGROUND Cholangiocarcinoma(CCA)is a highly aggressive malignancy with limited therapeutic options.Dysregulation of the Hippo-yes-associated protein(YAP)signaling pathway plays a key role in tumor progression,but the effects of distinct bile acids on this pathway remain unclear.AIM To investigate the roles of glycochenodeoxycholic acid(GDCA)and deoxycholic acid(DCA)in CCA progression through Hippo-YAP signaling and to evaluate the effects of YAP-targeted interventions.METHODS The in vitro experiments were performed using HuCCT1 CCA cells treated with GDCA,DCA,and combinations with a YAP inhibitor(verteporfin)or agonist(GA-017).Key molecular changes in the Hippo-YAP pathway were assessed by western blot,immunofluorescence,and reverse transcription quantitative realtime polymerase chain reaction.Functional assays,including Cell Counting Kit-8,5-ethynyl-2’-deoxyuridine,Transwell,and terminal deoxynucleotidyl transferasemediated deoxyuridine triphosphate-nick end labelling,were conducted to evaluate cell proliferation,migration,invasion,and apoptosis.In vivo,nude mice bearing subcutaneous HuCCT1 tumors were treated with GDCA,DCA,or combined YAP modulators.Tumor growth was monitored,and molecular analyses of tumor tissues were performed using western blot.RESULTS The GDCA significantly activated YAP by reducing mammalian STE20-like protein kinase 1 and large tumor suppressor 1 phosphorylation,promoting YAP nuclear translocation,and enhancing tumor cell proliferation,migration,and invasion.In contrast,DCA inhibited YAP activation,suppressed tumor cell functions,and increased apoptosis.GDCA combined with YAP inhibitors attenuated its tumor-promoting effects,while DCA combined with YAP agonists reversed its inhibitory effects.In vivo,GDCA accelerated tumor growth,while DCA reduced tumor size and weight,with molecular changes consistent with in vitro findings.CONCLUSION The GDCA and DCA exert opposing effects on CCA progression through Hippo-YAP signaling.GDCA promotes tumor growth via YAP activation,while DCA inhibits these processes.YAP-targeted interventions demonstrate therapeutic potential,providing insights into new treatment strategies for CCA.
