Rheumatoid arthritis(RA)is a chronic systemic autoimmune disease that extends beyond joint inflammation,affecting pulmonary and metabolic pathways.Interstitial lung disease(ILD)is one of its most serious extra-articul...Rheumatoid arthritis(RA)is a chronic systemic autoimmune disease that extends beyond joint inflammation,affecting pulmonary and metabolic pathways.Interstitial lung disease(ILD)is one of its most serious extra-articular complications,while type 2 diabetes mellitus(T2DM)frequently coexists with RA and may exacerbate inflammatory and fibrotic processes.This editorial discusses the study by Sutton et al,the largest population-based analysis to date exploring the link between T2DM and ILD in patients with RA,and reflects on its mechanistic and clinical implications.In a nationwide cohort of more than 120000 hospitalized RA patients,Sutton et al demonstrated that the coexistence of T2DM nearly doubles the odds of developing ILD(odds ratio=2.02;95%confidence interval:1.84-2.22),with additional increases in pulmonary hypertension,pneumothorax,and length of stay.These findings reinforce the concept of a metabolic-pulmonary-autoimmune axis,in which chronic inflammation promotes insulin resistance and metabolic dysfunction,while hyperglycaemia and advanced glycation end-products amplify oxidative stress and fibrogenesis.This reciprocal interaction may induce a self-perpetuating cycle of“metaflammation”,fibrosis,and organ damage.Conclusion:Recognizing diabetes as a silent amplifier of RA-associated ILD redefines the interface between rheumatology,pulmonology,and endocrinology.Early detection and integrated management of metabolic and pulmonary comorbidities should be prioritized,while future studies must determine whether optimizing glycemic control can attenuate pulmonary fibrosis and improve longterm outcomes.展开更多
Honeycombing Lung(HCL)is a chronic lung condition marked by advanced fibrosis,resulting in enlarged air spaces with thick fibrotic walls,which are visible on Computed Tomography(CT)scans.Differentiating between normal...Honeycombing Lung(HCL)is a chronic lung condition marked by advanced fibrosis,resulting in enlarged air spaces with thick fibrotic walls,which are visible on Computed Tomography(CT)scans.Differentiating between normal lung tissue,honeycombing lungs,and Ground Glass Opacity(GGO)in CT images is often challenging for radiologists and may lead to misinterpretations.Although earlier studies have proposed models to detect and classify HCL,many faced limitations such as high computational demands,lower accuracy,and difficulty distinguishing between HCL and GGO.CT images are highly effective for lung classification due to their high resolution,3D visualization,and sensitivity to tissue density variations.This study introduces Honeycombing Lungs Network(HCL Net),a novel classification algorithm inspired by ResNet50V2 and enhanced to overcome the shortcomings of previous approaches.HCL Net incorporates additional residual blocks,refined preprocessing techniques,and selective parameter tuning to improve classification performance.The dataset,sourced from the University Malaya Medical Centre(UMMC)and verified by expert radiologists,consists of CT images of normal,honeycombing,and GGO lungs.Experimental evaluations across five assessments demonstrated that HCL Net achieved an outstanding classification accuracy of approximately 99.97%.It also recorded strong performance in other metrics,achieving 93%precision,100%sensitivity,89%specificity,and an AUC-ROC score of 97%.Comparative analysis with baseline feature engineering methods confirmed the superior efficacy of HCL Net.The model significantly reduces misclassification,particularly between honeycombing and GGO lungs,enhancing diagnostic precision and reliability in lung image analysis.展开更多
Colorectal cancer(CRC)with lung oligometastases,particularly in the presence of extrapulmonary disease,poses considerable therapeutic challenges in clinical practice.We have carefully studied the multicenter study by ...Colorectal cancer(CRC)with lung oligometastases,particularly in the presence of extrapulmonary disease,poses considerable therapeutic challenges in clinical practice.We have carefully studied the multicenter study by Hu et al,which evaluated the survival outcomes of patients with metastatic CRC who received image-guided thermal ablation(IGTA).These findings provide valuable clinical evidence supporting IGTA as a feasible,minimally invasive approach and underscore the prognostic significance of metastatic distribution.However,the study by Hu et al has several limitations,including that not all pulmonary lesions were pathologically confirmed,postoperative follow-up mainly relied on dynamic contrast-enhanced computed tomography,no comparative analysis was performed with other local treatments,and the impact of other imaging features on efficacy and prognosis was not evaluated.Future studies should include complete pathological confirmation,integrate functional imaging and radiomics,and use prospective multicenter collaboration to optimize patient selection standards for IGTA treatment,strengthen its clinical evidence base,and ultimately promote individualized decision-making for patients with metastatic CRC.展开更多
Background:A significant proportion of patients still cannot benefit from existing targeted therapies and immunotherapies,making the search for new treatment strategies extremely urgent.In this study,we combined integ...Background:A significant proportion of patients still cannot benefit from existing targeted therapies and immunotherapies,making the search for new treatment strategies extremely urgent.In this study,we combined integrate public data analysis with experimental validation to identify novel prognostic biomarkers and therapeutic targets for lung adenocarcinoma(LUAD).Methods:We analyzed RNA and protein databases to assess the expression levels of cytochrome C oxidase 5B(COX5B)in LUAD.Several computational algorithms were employed to investigate the relationship between COX5B and immune infiltration in LUAD.To further elucidate the role of COX5B in LUAD,we utilized multiple experimental approaches,including quantitative reverse transcription PCR assays,western blot,immunohistochemistry,electron microscopy,flow cytometry,and EdU proliferation assays.Results:We revealed that COX5B was significantly elevated in LUAD and positively correlated with poor prognosis of LUAD patients.Analysis of co-expression network indicated that COX5B may take part in the intracellular adenosine triphosphate(ATP)synthesis through the oxidative phosphorylation pathway.There was a negative correlation between COX5B expression and immune infiltration in LUAD.Furthermore,we validated that COX5B levels were significantly elevated in both LUAD tissues and cell lines.Specifically,immunohistochemistry(IHC)assays revealed a 2.32-fold increase of COX5B in tumor tissues compared to that in adjacent normal tissues(p=0.0044).Additionally,COX5B knockdown disrupted the redox homeostasis,ultimately suppressed the proliferation of LUAD cells.Subsequent investigations demonstrated that berberine effectively targeted COX5B,diminishing its protein expression and consequently inhibiting cell proliferation and tumor growth in LUAD.Conclusions:This study established that upregulated COX5B was positive associated with poor patient prognosis in LUAD,elucidating the mechanisms by which berberine targets COX5B to inhibit tumor growth,thereby providing a novel therapeutic target and strategy for the clinical management of LUAD.展开更多
Sepsis is a life-threatening condition caused by a dysregulated response of the body in response to an infection that harms its tissues and organs.Interleukin-6(IL-6)is a significant component of the inflammatory resp...Sepsis is a life-threatening condition caused by a dysregulated response of the body in response to an infection that harms its tissues and organs.Interleukin-6(IL-6)is a significant component of the inflammatory response as part of the pa-thogenesis of sepsis.It aids in the development of Acute lung injury and,subse-quently,multiple organ dysfunction syndrome.This letter probes into the corre-lation between plasma IL-6 levels and the risk of developing acute lung injury and multiple organ dysfunction syndrome in critically ill patients with sepsis.While it shows promising results,limitations like its observational study design,a limited sample size,a single center involvement,single-time-point measurement,and a lack of a control group restrain its cogency.The study is a big step in identifying IL-6 as a biomarker to improve patient care.展开更多
Background:To investigate SCL/TAL 1 interrupting locus(STIL)’s role and prognostic significance in lung adenocarcinoma(LUAD)progression,we examined STIL and E2 promoter binding factor 1(E2F1)expression and their impa...Background:To investigate SCL/TAL 1 interrupting locus(STIL)’s role and prognostic significance in lung adenocarcinoma(LUAD)progression,we examined STIL and E2 promoter binding factor 1(E2F1)expression and their impacts on LUAD prognosis using Gene Expression Profiling Interactive Analysis(GEPIA).Methods:Functional assays including CCK-8,wound-healing,5-ethynyl-2-deoxyuridine(EdU),Transwell assays,and flow cytometry,elucidated STIL and E2F1’s effects on cell viability,proliferation,apoptosis,and migration.Gene set enrichment analysis(GSEA)identified potential pathways,while metabolic assays assessed glucose metabolism.Results:Our findings reveal that STIL and E2F1 are overexpressed in LUAD,correlating with adverse outcomes.It enhances cell proliferation,migration,and invasion,and suppresses apoptosis,activating downstream of E2F1.Silencing E2F1 reversed the promotion effect of the STIL overexpression on cell viability and invasiveness.Importantly,STIL modulates glycolysis,influencing glucose consumption,lactate production,and energy balance in LUAD cells.Conclusion:Our model,incorporating STIL,age,and disease stage,robustly predicts patient prognosis,underscored STIL’s pivotal role in LUAD pathogenesis through metabolic reprogramming.This comprehensive approach not only confirms STIL’s prognostic value but also highlights its potential as a therapeutic target in LUAD.展开更多
Dear Editor,Lung cancer is a major global health concern,with 2.2 million patients diagnosed in 2020.Non-small cell lung cancer(NSCLC)accounts for 80%of these cases,primarily comprising two subtypes:lung adenocarcinom...Dear Editor,Lung cancer is a major global health concern,with 2.2 million patients diagnosed in 2020.Non-small cell lung cancer(NSCLC)accounts for 80%of these cases,primarily comprising two subtypes:lung adenocarcinoma(LUAD)and squamous cell carcinoma(LUSC)[1].Researchers use immunohisto-chemistry,next-generation sequencing,and single-cell RNA sequencing to study genetic alterations,tumor heterogeneity,and tumor microenvironments,aiming to identify potential therapeutic options for specific NSCLC subtypes[2].展开更多
Non-small cell lung cancer (NSCLC), as the leading cause of cancer-related deaths, poses a serious health issue worldwide1,according to the Global Cancer Statistics 2022. Approximately 30% of NSCLC patients are diagno...Non-small cell lung cancer (NSCLC), as the leading cause of cancer-related deaths, poses a serious health issue worldwide1,according to the Global Cancer Statistics 2022. Approximately 30% of NSCLC patients are diagnosed at an advanced or metastatic stage with a 5-year overall survival (OS) rate ranging from 7%-18%^(2). Unlike localized NSCLC, which can be treated with curative intent, patients with metastatic NSCLC typically undergo systemic treatment to delay progression and prolong survival.展开更多
Background:Lung cancer is one of the deadliest cancers worldwide,creating a pressing need to develop novel drugs that inhibit oncogenic signaling pathways.Numerous studies have shown that berberine(BBR)has anti–lung ...Background:Lung cancer is one of the deadliest cancers worldwide,creating a pressing need to develop novel drugs that inhibit oncogenic signaling pathways.Numerous studies have shown that berberine(BBR)has anti–lung cancer potential.We aimed to explore the anti–lung cancer effect of BBR and related mechanisms by targeting the glycogen synthase kinase 3β(GSK3β)/β-catenin pathway.Methods:Lung adenocarcinoma(LUAD)cells A549 and NCI-H1975 were treated with BBR.Results:Our results showed that BBR inhibited cell proliferation by decreasing c-Myc levels and induced cel cycle arrest in the G0/G1 phase by lowering cyclin D1 levels.BBR induced apoptosis by upregulating cleaved caspase 3 levels.BBR inhibited cell migration and invasion by decreasing N-cadherin levels.Furthermore,BBR upregulated the expression of GSK3βprotein and phospho-β-catenin proteins in the cytoplasm,while decreasing the expression ofβ-catenin protein.Next,LUAD cel s were exposed to CHIR-99021(a GSK3βinhibitor).This treatment led to an increase in c-Myc,cyclin D1,andβ-catenin levels at specific concentrations.BBR partially reversed the effects of CHIR-99021.Finally,LUAD cells were treated with CHIR-99021(4μmoL/L)combined with BBR(30 and 60μmoL/L)for 24 h.The expression of programmed death ligand 1(PD-L1)was assessed by Western blot analysis.Jurkat T cells and A549 cel s were cocultured for 24 h to examine the lactate dehydrogenase release rate.Results suggested that BBR suppressed the expression of PD-L1 and heightened the immune lethality of T cells.Conclusions:BBR suppressed the proliferative activity of LUAD cell lines A549 and NCI-H1975 in vitro,induced cell cycle arrest and cancer cel apoptosis in the G0/G1 stage,and repressed the migration and invasion of cancer cells.BBR reduced the PD-L1 protein expression and enhanced T-cell–mediated cytotoxicity.These effects appear to be related to BBR's regulation of the GSK3β/β-catenin pathway.展开更多
As the leading cause of cancer-related deaths,lung cancer remains a noteworthy threat to human health.Although immunotherapies,such as immune checkpoint inhibitors(ICIs),have significantly increased the efficacy of lu...As the leading cause of cancer-related deaths,lung cancer remains a noteworthy threat to human health.Although immunotherapies,such as immune checkpoint inhibitors(ICIs),have significantly increased the efficacy of lung cancer treatment,a significant percentage of patients are not sensitive to immunotherapies and patients who initially respond to treatment can quickly develop acquired drug resistance.Bispecific antibodies(bs Abs)bind two different antigens or epitopes simultaneously and have been shown to enhance antitumor efficacy with suitable safety profiles,thus attracting increasing attention as novel antitumor therapies.At present,in addition to the approved bs Ab,amivantamab,three novel bs Abs(KN046,AK112,and SHR-1701)are being evaluated in phase 3 clinical trials and many bs Abs are being evaluated in phase 1/2 clinical trials for patients with non-small cell lung cancer(NSCLC).Herein we present the structure,classification,and mechanism of action underlying bs Abs in NSCLC and introduce related clinical trials.Finally,we discuss challenges,potential solutions,and future prospects in the context of cancer treatment with bsAbs.展开更多
Lung cancer is the most frequent cause of cancer-related mortality worldwide.Nitric oxide(NO),prostaglandins(PGs),thromboxanes(TXs),and endothelins(ETs)participate in numerous physiological processes.These agents play...Lung cancer is the most frequent cause of cancer-related mortality worldwide.Nitric oxide(NO),prostaglandins(PGs),thromboxanes(TXs),and endothelins(ETs)participate in numerous physiological processes.These agents play an important role in lung carcinogenesis by regulating cancer cell proliferation,apoptosis,invasion,and angiogenesis.NO is a gaseous free radical with tumo-ricidal and tumorigenic activities in lung cancer.Arachidonic acid-derived PGs,including PGD2,PGE2,8-iso-PGF2α,and PGI2,are related to the development of lung cancer.PGD2 and PGI2 act as tumor suppressors,while PGE2 and 8-iso-PGF2αpromote tumor progression.TXA2 catalyzed by cyclooxygenase induces prolif-eration as well as angiogenesis.Elevated levels of TXB2,an inactive metabolite of TXA2,are positively correlated with lung carcinoma stages.ET-1 and ET-2 are 21 amino acid polypeptides;their silencing hinders lung cancer cell proliferation and invasion.ET-2 depletion also triggers apoptotic death.This chapter review aims to provide a comprehensive overview of the role of NO,PGs,TXs,and ETs in lung cancer.展开更多
Lung cancer, the leading cause of cancer deaths worldwide and in China, has a 19.7% five-year survival rate due to terminal-stage diagnosis^([1-3]).Although low-dose computed tomography(CT) screening can reduce mortal...Lung cancer, the leading cause of cancer deaths worldwide and in China, has a 19.7% five-year survival rate due to terminal-stage diagnosis^([1-3]).Although low-dose computed tomography(CT) screening can reduce mortality, high false positive rates can create economic and psychological burdens.展开更多
Objective:Erianin has potential anticancer activities,especially against lung cancer.The specific mechanisms underlying the anticancer effects,including the molecular targets and signaling pathways in lung cancer,rema...Objective:Erianin has potential anticancer activities,especially against lung cancer.The specific mechanisms underlying the anticancer effects,including the molecular targets and signaling pathways in lung cancer,remain poorly understood and necessitate further investigation.Methods:Lung cancer cell viability was evaluated using the CCK-8 assay.Flow cytometry was used to examine the effects of erianin on apoptosis and cell cycle progression.m RNA sequencing and metabolomics analysis were utilized to explore erianin-induced biological changes.Potential targets were identified and validated through molecular docking and Western blot analysis.The roles of mammalian target of rapamycin(m TOR)and carbamoyl-phosphate synthetase/aspartate transcarbamylase/dihydroorotase(CAD)in erianin-induced growth inhibition were studied using gene overexpression/knockdown techniques with uridine and aspartate supplementation confirming pyrimidine metabolism involvement.Additionally,lung cancer-bearing nude mouse models were established to evaluate the anti-lung cancer effects of erianin in vivo.Results:Erianin significantly inhibits the proliferation of lung cancer cells,induces apoptosis,and causes G2/M phase cell cycle arrest.Integrative analysis of m RNA sequencing and metabolomics data demonstrated that erianin disrupts pyrimidine metabolism in lung cancer cells.Notably,uridine supplementation mitigated the inhibitory effects of erianin,establishing a connection between pyrimidine metabolism and anticancer activity.Network pharmacology analyses identified m TOR as a key target of erianin.Erianin inhibited m TOR phosphorylation,thereby blocking downstream effectors(S6K and CAD),which are essential regulators of pyrimidine metabolism.Conclusions:Erianin is a promising therapeutic candidate for lung cancer.Erianin likely inhibits lung cancer cell growth by disrupting pyrimidine metabolism by suppressing m TOR activation.展开更多
In the present study,we aimed to investigate whether anlotinib reverses osimertinib resistance by inhibiting the formation of epithelial-mesenchymal transition(EMT)and angiogenesis.In a clinical case,anlotinib reverse...In the present study,we aimed to investigate whether anlotinib reverses osimertinib resistance by inhibiting the formation of epithelial-mesenchymal transition(EMT)and angiogenesis.In a clinical case,anlotinib reversed osimertinib resistance in non-small cell lung cancer(NSCLC).Therefore,we performed immunohistochemical analyses on tumor tissues from three NSCLC patients with osimertinib resistance to analyze alterations in the expression levels of EMT markers and vascular endothelial growth factor A(VEGFA)before and after the development of osimertinib resistance.The results revealed the downregulation of E-cadherin,coupled with the upregulation of vimentin and VEGFA in tumor tissues of patients exhibiting osimertinib resistance,compared with those in tissues from patients before receiving osimertinib.Subsequently,we established osimertinib-resistant(Osi-R)cell lines and found that the Osi-R cells acquired EMT features.Next,we analyzed the synergistic effects of the combination therapy to verify whether anlotinib could reverse osimertinib resistance by inhibiting EMT.The expression levels of VEGFA and tube formation were analyzed in the combination group in vitro.Finally,we determined the reversal of osimertinib resistance by the combination of osimertinib and anlotinib in vivo using 20 nude mice.The combined treatment of osimertinib and anlotinib effectively prevented the metastasis of Osi-R cells,inhibited tumor growth,exerted antitumor activity,and ultimately reversed osimertinib resistance in mice.The co-administration of osimertinib and anlotinib demonstrated synergistic efficacy in inhibiting EMT and angiogenesis in three NSCLC patients,ultimately reversing osimertinib resistance.展开更多
Background:Long noncoding RNA,LINC01106 exhibits high expression in lung adenocarcinoma(LUAD)tumor tissues,but its functional role and regulatory mechanism in LUAD cells remain unclear.Methods:LINC01106 expression was...Background:Long noncoding RNA,LINC01106 exhibits high expression in lung adenocarcinoma(LUAD)tumor tissues,but its functional role and regulatory mechanism in LUAD cells remain unclear.Methods:LINC01106 expression was analyzed in LUAD tissues and its functional impact on LUAD cells was assessed.LUAD cells were silenced with sh-LINC01106 and injected into nude mice to investigate tumor growth.The downstream transcription factors and molecular mechanism were determined using the Human transcription factor database(TFDB)database and Gene Expression Profiling Interactive Analysis(GEPIA)database.Additionally,the impact of linc01106 on autophagy was analyzed by determining the expression of autophagy-related genes(ATGs)in LUAD cells.Results:Our results showed that LINC01106 exhibited upregulation in both LUAD tissues and cell lines.The silencing of LINC01106 demonstrated a suppressive effect on tumorigenesis in a xenograft mouse model of LUAD.Additionally,LINC01106 was found to recruit TATA-binding protein-associated factor 15(TAF15),an RNA-binding protein,thereby enhancing the mRNA stability of TEA domain transcription factor 4(TEAD4).In turn,TEAD4 served as a transcription factor that bound to the LINC01106 promoter and regulated its expression.Further assays indicated that LINC01106 promoted autophagy in LUAD cells by upregulating the expression of autophagy-related genes(ATGs).The silencing of LINC01106 in LUAD cells inhibited autophagy,and cell proliferation,and promoted apoptosis,which all were effectively reversed by ATG5 overexpression.Conclusions:Overall,LINC01106,transcriptionally activated by TEAD4,interacts with TAF15 to promote the stability of TEAD4 and upregulates the expression of ATGs,promoting malignancy of LUAD cells.展开更多
Objective Chemoresistance,such as paclitaxel(PTX)resistance,has become a great obstacle in non-small cell lung cancer(NSCLC)treatment.The natural agent salidroside(SAL)has been shown to exert an antitumor effect on NS...Objective Chemoresistance,such as paclitaxel(PTX)resistance,has become a great obstacle in non-small cell lung cancer(NSCLC)treatment.The natural agent salidroside(SAL)has been shown to exert an antitumor effect on NSCLC.Nonethe-less,it is unclear whether SAL can decrease the resistance of NSCLC to PTX.Methods PTX-resistant NSCLC cells(H1299/PTX and A549/PTX)were generated.Cell Counting Kit-8(CCK-8)assay was used to detect cell viability.Colony formation assay and flow cytometry were utilized to assess cell proliferation and apop-tosis,respectively.Immunofluorescence staining and TOP/FOP flash luciferase assay were employed to estimateβ-catenin activation.Western blotting was implemented to estimate the protein levels of apoptosis-,proliferation-,and Wnt/β-catenin signaling-associated markers.A xenograft mouse model was established to investigate the impact of SAL on PTX resist-ance in vivo.Results SAL increased PTX-induced suppression of proliferation and promoted apoptosis in PTX-resistant NSCLC cells.SAL blocked the Wnt/β-catenin signaling in A549/PTX cells and in tumor-bearing mice.Activating Wnt/β-catenin signaling reversed the SAL-mediated increase in the sensitivity of NSCLC cells to PTX.SAL attenuated PTX resistance in NSCLC in the xenograft mouse model.Conclusion SAL enhances the sensitivity of NSCLC cells to PTX by blocking the Wnt/β-catenin signal transduction.展开更多
Objective:The neglect of occult lymph nodes metastasis(OLNM)is one of the pivotal causes of early non-small cell lung cancer(NSCLC)recurrence after local treatments such as stereotactic body radiotherapy(SBRT)or surge...Objective:The neglect of occult lymph nodes metastasis(OLNM)is one of the pivotal causes of early non-small cell lung cancer(NSCLC)recurrence after local treatments such as stereotactic body radiotherapy(SBRT)or surgery.This study aimed to develop and validate a computed tomography(CT)-based radiomics and deep learning(DL)fusion model for predicting non-invasive OLNM.Methods:Patients with radiologically node-negative lung adenocarcinoma from two centers were retrospectively analyzed.We developed clinical,radiomics,and radiomics-clinical models using logistic regression.A DL model was established using a three-dimensional squeeze-and-excitation residual network-34(3D SE-ResNet34)and a fusion model was created by integrating seleted clinical,radiomics features and DL features.Model performance was assessed using the area under the curve(AUC)of the receiver operating characteristic(ROC)curve,calibration curves,and decision curve analysis(DCA).Five predictive models were compared;SHapley Additive exPlanations(SHAP)and Gradient-weighted Class Activation Mapping(Grad-CAM)were employed for visualization and interpretation.Results:Overall,358 patients were included:186 in the training cohort,48 in the internal validation cohort,and 124 in the external testing cohort.The DL fusion model incorporating 3D SE-Resnet34 achieved the highest AUC of 0.947 in the training dataset,with strong performance in internal and external cohorts(AUCs of 0.903 and 0.907,respectively),outperforming single-modal DL models,clinical models,radiomics models,and radiomicsclinical combined models(DeLong test:P<0.05).DCA confirmed its clinical utility,and calibration curves demonstrated excellent agreement between predicted and observed OLNM probabilities.Features interpretation highlighted the importance of textural characteristics and the surrounding tumor regions in stratifying OLNM risk.Conclusions:The DL fusion model reliably and accurately predicts OLNM in early-stage lung adenocarcinoma,offering a non-invasive tool to refine staging and guide personalized treatment decisions.These results may aid clinicians in optimizing surgical and radiotherapy strategies.展开更多
BACKGROUND Lung cancer(LC)is one of the most prevalent cancers globally,with a high incidence among the elderly population.Elderly patients,particularly those with diabetes mellitus,are at an increased risk of postope...BACKGROUND Lung cancer(LC)is one of the most prevalent cancers globally,with a high incidence among the elderly population.Elderly patients,particularly those with diabetes mellitus,are at an increased risk of postoperative complications,in-cluding pulmonary infections,due to weakened immune function and metabolic abnormalities.Postoperative pulmonary infection(PPI)is a predominant com-plication after thoracoscopic radical resection of LC,significantly affecting patient outcomes and increasing healthcare burdens.Determining risk factors for PPI in this vulnerable population is crucial for improving surgical outcomes and redu-cing infection rates.AIM To develop and validate a predictive model for PPI in elderly patients with dia-betes undergoing thoracoscopic radical resection for LC and to assess its reliability and validity.METHODS This retrospective study included 212 patients with LC who received treatment at our hospital from March 2015 to March 2022.General clinical information,sur-gical treatment details,and laboratory test results were collected and analyzed.Patients were grouped according to infection occurrence during the postoperative hospitalization period.Risk factors for PPIs were determined through logistic regression analysis,and a nomogram prediction model was established using R software to assess its predictive accuracy and performance.RESULTS Among the 212 patients[median age:72 years(interquartile range:60-82 years)],41 developed PPI(19.34%),with Gram-negative bacteria being the predominant pathogens(64.14%).Factors,such as age of≥70 years,presence of respiratory diseases,maximum tumor diameter of≥4 cm,stages II-III,receiving neoadjuvant chemotherapy of≥2 times preoperatively,surgery duration of≥3 hours,chest drainage tube placement duration of≥3.5 days,preoperative fasting blood glucose levels,hemoglobin A1c(HbA1c)levels,and multi-leaf resection,were markedly higher in the infection group than in the non-infection group.Conversely,forced expiratory volume in 1 second(FEV1)of≥80%and albumin(Alb)levels were lower in the infection group.Multivariate logistic regression analysis revealed that receiving neoadjuvant chemotherapy of≥2 times[odds ratio(OR)=2.987;P=0.036],maximum tumor diameter of≥4 cm(OR=3.959;P=0.013),multi-leaf resection(OR=3.18;P=0.036),preoperative FEV1 of≤80%(OR=3.305;P=0.029),and high HbA1c levels(OR=2.39;P=0.003)as key risk factors for PPI,whereas high Alb levels(OR=0.507;P<0.001)was protective.The nomogram model demonstrated excellent diagnostic ability(area under the curve=0.901,0.915),and calibration curves and decision curve analysis revealed good predictive performance and clinical applicability of the model.CONCLUSION The primary pathogens of PPI in elderly patients with diabetes and LC undergoing thoracoscopic radical resection are Gram-negative bacteria.The nomogram model,based on preoperative neoadjuvant chemotherapy cycles,maximum tumor diameter,range of resection,and preoperative FEV1,Alb,and HbA1c levels,shows high clinical value in predicting the risk of PPI in this patient population.展开更多
文摘Rheumatoid arthritis(RA)is a chronic systemic autoimmune disease that extends beyond joint inflammation,affecting pulmonary and metabolic pathways.Interstitial lung disease(ILD)is one of its most serious extra-articular complications,while type 2 diabetes mellitus(T2DM)frequently coexists with RA and may exacerbate inflammatory and fibrotic processes.This editorial discusses the study by Sutton et al,the largest population-based analysis to date exploring the link between T2DM and ILD in patients with RA,and reflects on its mechanistic and clinical implications.In a nationwide cohort of more than 120000 hospitalized RA patients,Sutton et al demonstrated that the coexistence of T2DM nearly doubles the odds of developing ILD(odds ratio=2.02;95%confidence interval:1.84-2.22),with additional increases in pulmonary hypertension,pneumothorax,and length of stay.These findings reinforce the concept of a metabolic-pulmonary-autoimmune axis,in which chronic inflammation promotes insulin resistance and metabolic dysfunction,while hyperglycaemia and advanced glycation end-products amplify oxidative stress and fibrogenesis.This reciprocal interaction may induce a self-perpetuating cycle of“metaflammation”,fibrosis,and organ damage.Conclusion:Recognizing diabetes as a silent amplifier of RA-associated ILD redefines the interface between rheumatology,pulmonology,and endocrinology.Early detection and integrated management of metabolic and pulmonary comorbidities should be prioritized,while future studies must determine whether optimizing glycemic control can attenuate pulmonary fibrosis and improve longterm outcomes.
文摘Honeycombing Lung(HCL)is a chronic lung condition marked by advanced fibrosis,resulting in enlarged air spaces with thick fibrotic walls,which are visible on Computed Tomography(CT)scans.Differentiating between normal lung tissue,honeycombing lungs,and Ground Glass Opacity(GGO)in CT images is often challenging for radiologists and may lead to misinterpretations.Although earlier studies have proposed models to detect and classify HCL,many faced limitations such as high computational demands,lower accuracy,and difficulty distinguishing between HCL and GGO.CT images are highly effective for lung classification due to their high resolution,3D visualization,and sensitivity to tissue density variations.This study introduces Honeycombing Lungs Network(HCL Net),a novel classification algorithm inspired by ResNet50V2 and enhanced to overcome the shortcomings of previous approaches.HCL Net incorporates additional residual blocks,refined preprocessing techniques,and selective parameter tuning to improve classification performance.The dataset,sourced from the University Malaya Medical Centre(UMMC)and verified by expert radiologists,consists of CT images of normal,honeycombing,and GGO lungs.Experimental evaluations across five assessments demonstrated that HCL Net achieved an outstanding classification accuracy of approximately 99.97%.It also recorded strong performance in other metrics,achieving 93%precision,100%sensitivity,89%specificity,and an AUC-ROC score of 97%.Comparative analysis with baseline feature engineering methods confirmed the superior efficacy of HCL Net.The model significantly reduces misclassification,particularly between honeycombing and GGO lungs,enhancing diagnostic precision and reliability in lung image analysis.
文摘Colorectal cancer(CRC)with lung oligometastases,particularly in the presence of extrapulmonary disease,poses considerable therapeutic challenges in clinical practice.We have carefully studied the multicenter study by Hu et al,which evaluated the survival outcomes of patients with metastatic CRC who received image-guided thermal ablation(IGTA).These findings provide valuable clinical evidence supporting IGTA as a feasible,minimally invasive approach and underscore the prognostic significance of metastatic distribution.However,the study by Hu et al has several limitations,including that not all pulmonary lesions were pathologically confirmed,postoperative follow-up mainly relied on dynamic contrast-enhanced computed tomography,no comparative analysis was performed with other local treatments,and the impact of other imaging features on efficacy and prognosis was not evaluated.Future studies should include complete pathological confirmation,integrate functional imaging and radiomics,and use prospective multicenter collaboration to optimize patient selection standards for IGTA treatment,strengthen its clinical evidence base,and ultimately promote individualized decision-making for patients with metastatic CRC.
基金supported by grants from the Guangxi Natural Science Foundation(2024GXNSFAA010150)the Guangdong Basic and Applied Basic Research Foundation(2022A1515111167).
文摘Background:A significant proportion of patients still cannot benefit from existing targeted therapies and immunotherapies,making the search for new treatment strategies extremely urgent.In this study,we combined integrate public data analysis with experimental validation to identify novel prognostic biomarkers and therapeutic targets for lung adenocarcinoma(LUAD).Methods:We analyzed RNA and protein databases to assess the expression levels of cytochrome C oxidase 5B(COX5B)in LUAD.Several computational algorithms were employed to investigate the relationship between COX5B and immune infiltration in LUAD.To further elucidate the role of COX5B in LUAD,we utilized multiple experimental approaches,including quantitative reverse transcription PCR assays,western blot,immunohistochemistry,electron microscopy,flow cytometry,and EdU proliferation assays.Results:We revealed that COX5B was significantly elevated in LUAD and positively correlated with poor prognosis of LUAD patients.Analysis of co-expression network indicated that COX5B may take part in the intracellular adenosine triphosphate(ATP)synthesis through the oxidative phosphorylation pathway.There was a negative correlation between COX5B expression and immune infiltration in LUAD.Furthermore,we validated that COX5B levels were significantly elevated in both LUAD tissues and cell lines.Specifically,immunohistochemistry(IHC)assays revealed a 2.32-fold increase of COX5B in tumor tissues compared to that in adjacent normal tissues(p=0.0044).Additionally,COX5B knockdown disrupted the redox homeostasis,ultimately suppressed the proliferation of LUAD cells.Subsequent investigations demonstrated that berberine effectively targeted COX5B,diminishing its protein expression and consequently inhibiting cell proliferation and tumor growth in LUAD.Conclusions:This study established that upregulated COX5B was positive associated with poor patient prognosis in LUAD,elucidating the mechanisms by which berberine targets COX5B to inhibit tumor growth,thereby providing a novel therapeutic target and strategy for the clinical management of LUAD.
文摘Sepsis is a life-threatening condition caused by a dysregulated response of the body in response to an infection that harms its tissues and organs.Interleukin-6(IL-6)is a significant component of the inflammatory response as part of the pa-thogenesis of sepsis.It aids in the development of Acute lung injury and,subse-quently,multiple organ dysfunction syndrome.This letter probes into the corre-lation between plasma IL-6 levels and the risk of developing acute lung injury and multiple organ dysfunction syndrome in critically ill patients with sepsis.While it shows promising results,limitations like its observational study design,a limited sample size,a single center involvement,single-time-point measurement,and a lack of a control group restrain its cogency.The study is a big step in identifying IL-6 as a biomarker to improve patient care.
文摘Background:To investigate SCL/TAL 1 interrupting locus(STIL)’s role and prognostic significance in lung adenocarcinoma(LUAD)progression,we examined STIL and E2 promoter binding factor 1(E2F1)expression and their impacts on LUAD prognosis using Gene Expression Profiling Interactive Analysis(GEPIA).Methods:Functional assays including CCK-8,wound-healing,5-ethynyl-2-deoxyuridine(EdU),Transwell assays,and flow cytometry,elucidated STIL and E2F1’s effects on cell viability,proliferation,apoptosis,and migration.Gene set enrichment analysis(GSEA)identified potential pathways,while metabolic assays assessed glucose metabolism.Results:Our findings reveal that STIL and E2F1 are overexpressed in LUAD,correlating with adverse outcomes.It enhances cell proliferation,migration,and invasion,and suppresses apoptosis,activating downstream of E2F1.Silencing E2F1 reversed the promotion effect of the STIL overexpression on cell viability and invasiveness.Importantly,STIL modulates glycolysis,influencing glucose consumption,lactate production,and energy balance in LUAD cells.Conclusion:Our model,incorporating STIL,age,and disease stage,robustly predicts patient prognosis,underscored STIL’s pivotal role in LUAD pathogenesis through metabolic reprogramming.This comprehensive approach not only confirms STIL’s prognostic value but also highlights its potential as a therapeutic target in LUAD.
基金support through Manipal University Jaipur for the Enhanced Seed Grant under the Endowment Fund(Grant No.E3/2023-24/QE-04-05).
文摘Dear Editor,Lung cancer is a major global health concern,with 2.2 million patients diagnosed in 2020.Non-small cell lung cancer(NSCLC)accounts for 80%of these cases,primarily comprising two subtypes:lung adenocarcinoma(LUAD)and squamous cell carcinoma(LUSC)[1].Researchers use immunohisto-chemistry,next-generation sequencing,and single-cell RNA sequencing to study genetic alterations,tumor heterogeneity,and tumor microenvironments,aiming to identify potential therapeutic options for specific NSCLC subtypes[2].
基金supported by grants from the Noncommunicable Chronic Diseases-National Science and Technology Major Project (Grant No. 2023ZD0501700)the National Natural Science Foundation of China (Grant No. 82373349)the MOE Changjiang Distinguished Professor Supporting Project (Grant No. KY0120240205)。
文摘Non-small cell lung cancer (NSCLC), as the leading cause of cancer-related deaths, poses a serious health issue worldwide1,according to the Global Cancer Statistics 2022. Approximately 30% of NSCLC patients are diagnosed at an advanced or metastatic stage with a 5-year overall survival (OS) rate ranging from 7%-18%^(2). Unlike localized NSCLC, which can be treated with curative intent, patients with metastatic NSCLC typically undergo systemic treatment to delay progression and prolong survival.
基金Supported by a grant from the National Natural Science Foundation of China(no.82174457)。
文摘Background:Lung cancer is one of the deadliest cancers worldwide,creating a pressing need to develop novel drugs that inhibit oncogenic signaling pathways.Numerous studies have shown that berberine(BBR)has anti–lung cancer potential.We aimed to explore the anti–lung cancer effect of BBR and related mechanisms by targeting the glycogen synthase kinase 3β(GSK3β)/β-catenin pathway.Methods:Lung adenocarcinoma(LUAD)cells A549 and NCI-H1975 were treated with BBR.Results:Our results showed that BBR inhibited cell proliferation by decreasing c-Myc levels and induced cel cycle arrest in the G0/G1 phase by lowering cyclin D1 levels.BBR induced apoptosis by upregulating cleaved caspase 3 levels.BBR inhibited cell migration and invasion by decreasing N-cadherin levels.Furthermore,BBR upregulated the expression of GSK3βprotein and phospho-β-catenin proteins in the cytoplasm,while decreasing the expression ofβ-catenin protein.Next,LUAD cel s were exposed to CHIR-99021(a GSK3βinhibitor).This treatment led to an increase in c-Myc,cyclin D1,andβ-catenin levels at specific concentrations.BBR partially reversed the effects of CHIR-99021.Finally,LUAD cells were treated with CHIR-99021(4μmoL/L)combined with BBR(30 and 60μmoL/L)for 24 h.The expression of programmed death ligand 1(PD-L1)was assessed by Western blot analysis.Jurkat T cells and A549 cel s were cocultured for 24 h to examine the lactate dehydrogenase release rate.Results suggested that BBR suppressed the expression of PD-L1 and heightened the immune lethality of T cells.Conclusions:BBR suppressed the proliferative activity of LUAD cell lines A549 and NCI-H1975 in vitro,induced cell cycle arrest and cancer cel apoptosis in the G0/G1 stage,and repressed the migration and invasion of cancer cells.BBR reduced the PD-L1 protein expression and enhanced T-cell–mediated cytotoxicity.These effects appear to be related to BBR's regulation of the GSK3β/β-catenin pathway.
基金supported by the National Natural Science Foundation of China(Grant No.82272845)the Natural Science Foundation of Shandong(Grant No.ZR2023LZL001)。
文摘As the leading cause of cancer-related deaths,lung cancer remains a noteworthy threat to human health.Although immunotherapies,such as immune checkpoint inhibitors(ICIs),have significantly increased the efficacy of lung cancer treatment,a significant percentage of patients are not sensitive to immunotherapies and patients who initially respond to treatment can quickly develop acquired drug resistance.Bispecific antibodies(bs Abs)bind two different antigens or epitopes simultaneously and have been shown to enhance antitumor efficacy with suitable safety profiles,thus attracting increasing attention as novel antitumor therapies.At present,in addition to the approved bs Ab,amivantamab,three novel bs Abs(KN046,AK112,and SHR-1701)are being evaluated in phase 3 clinical trials and many bs Abs are being evaluated in phase 1/2 clinical trials for patients with non-small cell lung cancer(NSCLC).Herein we present the structure,classification,and mechanism of action underlying bs Abs in NSCLC and introduce related clinical trials.Finally,we discuss challenges,potential solutions,and future prospects in the context of cancer treatment with bsAbs.
文摘Lung cancer is the most frequent cause of cancer-related mortality worldwide.Nitric oxide(NO),prostaglandins(PGs),thromboxanes(TXs),and endothelins(ETs)participate in numerous physiological processes.These agents play an important role in lung carcinogenesis by regulating cancer cell proliferation,apoptosis,invasion,and angiogenesis.NO is a gaseous free radical with tumo-ricidal and tumorigenic activities in lung cancer.Arachidonic acid-derived PGs,including PGD2,PGE2,8-iso-PGF2α,and PGI2,are related to the development of lung cancer.PGD2 and PGI2 act as tumor suppressors,while PGE2 and 8-iso-PGF2αpromote tumor progression.TXA2 catalyzed by cyclooxygenase induces prolif-eration as well as angiogenesis.Elevated levels of TXB2,an inactive metabolite of TXA2,are positively correlated with lung carcinoma stages.ET-1 and ET-2 are 21 amino acid polypeptides;their silencing hinders lung cancer cell proliferation and invasion.ET-2 depletion also triggers apoptotic death.This chapter review aims to provide a comprehensive overview of the role of NO,PGs,TXs,and ETs in lung cancer.
基金supported by the National Natural Science Foundation of China(grant numbers 82204127 and 72204172)。
文摘Lung cancer, the leading cause of cancer deaths worldwide and in China, has a 19.7% five-year survival rate due to terminal-stage diagnosis^([1-3]).Although low-dose computed tomography(CT) screening can reduce mortality, high false positive rates can create economic and psychological burdens.
基金supported by the National Natural Science Foundation of China(82104207)Natural Science Foundation of Zhejiang Province(LQ22H280001)。
文摘Objective:Erianin has potential anticancer activities,especially against lung cancer.The specific mechanisms underlying the anticancer effects,including the molecular targets and signaling pathways in lung cancer,remain poorly understood and necessitate further investigation.Methods:Lung cancer cell viability was evaluated using the CCK-8 assay.Flow cytometry was used to examine the effects of erianin on apoptosis and cell cycle progression.m RNA sequencing and metabolomics analysis were utilized to explore erianin-induced biological changes.Potential targets were identified and validated through molecular docking and Western blot analysis.The roles of mammalian target of rapamycin(m TOR)and carbamoyl-phosphate synthetase/aspartate transcarbamylase/dihydroorotase(CAD)in erianin-induced growth inhibition were studied using gene overexpression/knockdown techniques with uridine and aspartate supplementation confirming pyrimidine metabolism involvement.Additionally,lung cancer-bearing nude mouse models were established to evaluate the anti-lung cancer effects of erianin in vivo.Results:Erianin significantly inhibits the proliferation of lung cancer cells,induces apoptosis,and causes G2/M phase cell cycle arrest.Integrative analysis of m RNA sequencing and metabolomics data demonstrated that erianin disrupts pyrimidine metabolism in lung cancer cells.Notably,uridine supplementation mitigated the inhibitory effects of erianin,establishing a connection between pyrimidine metabolism and anticancer activity.Network pharmacology analyses identified m TOR as a key target of erianin.Erianin inhibited m TOR phosphorylation,thereby blocking downstream effectors(S6K and CAD),which are essential regulators of pyrimidine metabolism.Conclusions:Erianin is a promising therapeutic candidate for lung cancer.Erianin likely inhibits lung cancer cell growth by disrupting pyrimidine metabolism by suppressing m TOR activation.
基金supported by the National Natural Science Foundation of China(Grant Nos.82172728,82370096).
文摘In the present study,we aimed to investigate whether anlotinib reverses osimertinib resistance by inhibiting the formation of epithelial-mesenchymal transition(EMT)and angiogenesis.In a clinical case,anlotinib reversed osimertinib resistance in non-small cell lung cancer(NSCLC).Therefore,we performed immunohistochemical analyses on tumor tissues from three NSCLC patients with osimertinib resistance to analyze alterations in the expression levels of EMT markers and vascular endothelial growth factor A(VEGFA)before and after the development of osimertinib resistance.The results revealed the downregulation of E-cadherin,coupled with the upregulation of vimentin and VEGFA in tumor tissues of patients exhibiting osimertinib resistance,compared with those in tissues from patients before receiving osimertinib.Subsequently,we established osimertinib-resistant(Osi-R)cell lines and found that the Osi-R cells acquired EMT features.Next,we analyzed the synergistic effects of the combination therapy to verify whether anlotinib could reverse osimertinib resistance by inhibiting EMT.The expression levels of VEGFA and tube formation were analyzed in the combination group in vitro.Finally,we determined the reversal of osimertinib resistance by the combination of osimertinib and anlotinib in vivo using 20 nude mice.The combined treatment of osimertinib and anlotinib effectively prevented the metastasis of Osi-R cells,inhibited tumor growth,exerted antitumor activity,and ultimately reversed osimertinib resistance in mice.The co-administration of osimertinib and anlotinib demonstrated synergistic efficacy in inhibiting EMT and angiogenesis in three NSCLC patients,ultimately reversing osimertinib resistance.
基金supported by the 2022 Natural Science Foundation of Fujian Province(No.2022J011486).
文摘Background:Long noncoding RNA,LINC01106 exhibits high expression in lung adenocarcinoma(LUAD)tumor tissues,but its functional role and regulatory mechanism in LUAD cells remain unclear.Methods:LINC01106 expression was analyzed in LUAD tissues and its functional impact on LUAD cells was assessed.LUAD cells were silenced with sh-LINC01106 and injected into nude mice to investigate tumor growth.The downstream transcription factors and molecular mechanism were determined using the Human transcription factor database(TFDB)database and Gene Expression Profiling Interactive Analysis(GEPIA)database.Additionally,the impact of linc01106 on autophagy was analyzed by determining the expression of autophagy-related genes(ATGs)in LUAD cells.Results:Our results showed that LINC01106 exhibited upregulation in both LUAD tissues and cell lines.The silencing of LINC01106 demonstrated a suppressive effect on tumorigenesis in a xenograft mouse model of LUAD.Additionally,LINC01106 was found to recruit TATA-binding protein-associated factor 15(TAF15),an RNA-binding protein,thereby enhancing the mRNA stability of TEA domain transcription factor 4(TEAD4).In turn,TEAD4 served as a transcription factor that bound to the LINC01106 promoter and regulated its expression.Further assays indicated that LINC01106 promoted autophagy in LUAD cells by upregulating the expression of autophagy-related genes(ATGs).The silencing of LINC01106 in LUAD cells inhibited autophagy,and cell proliferation,and promoted apoptosis,which all were effectively reversed by ATG5 overexpression.Conclusions:Overall,LINC01106,transcriptionally activated by TEAD4,interacts with TAF15 to promote the stability of TEAD4 and upregulates the expression of ATGs,promoting malignancy of LUAD cells.
基金supported by the Scientific Research Project of Hubei Cancer Hospital(No.2024HBCHYN08)the Natural Science Foundation of Hubei Province(No.2023AFB988)+1 种基金the Scientific Research Project in the Field of Oncology(No.FB2024025225)the Talent Project of Hubei Cancer Hospital(No.2025HBCHHHRC007).
文摘Objective Chemoresistance,such as paclitaxel(PTX)resistance,has become a great obstacle in non-small cell lung cancer(NSCLC)treatment.The natural agent salidroside(SAL)has been shown to exert an antitumor effect on NSCLC.Nonethe-less,it is unclear whether SAL can decrease the resistance of NSCLC to PTX.Methods PTX-resistant NSCLC cells(H1299/PTX and A549/PTX)were generated.Cell Counting Kit-8(CCK-8)assay was used to detect cell viability.Colony formation assay and flow cytometry were utilized to assess cell proliferation and apop-tosis,respectively.Immunofluorescence staining and TOP/FOP flash luciferase assay were employed to estimateβ-catenin activation.Western blotting was implemented to estimate the protein levels of apoptosis-,proliferation-,and Wnt/β-catenin signaling-associated markers.A xenograft mouse model was established to investigate the impact of SAL on PTX resist-ance in vivo.Results SAL increased PTX-induced suppression of proliferation and promoted apoptosis in PTX-resistant NSCLC cells.SAL blocked the Wnt/β-catenin signaling in A549/PTX cells and in tumor-bearing mice.Activating Wnt/β-catenin signaling reversed the SAL-mediated increase in the sensitivity of NSCLC cells to PTX.SAL attenuated PTX resistance in NSCLC in the xenograft mouse model.Conclusion SAL enhances the sensitivity of NSCLC cells to PTX by blocking the Wnt/β-catenin signal transduction.
基金supported by the National Natural Science Foundation of China(No.82272845)the Natural Science Foundation of Shandong(No.ZR2023ZD26).
文摘Objective:The neglect of occult lymph nodes metastasis(OLNM)is one of the pivotal causes of early non-small cell lung cancer(NSCLC)recurrence after local treatments such as stereotactic body radiotherapy(SBRT)or surgery.This study aimed to develop and validate a computed tomography(CT)-based radiomics and deep learning(DL)fusion model for predicting non-invasive OLNM.Methods:Patients with radiologically node-negative lung adenocarcinoma from two centers were retrospectively analyzed.We developed clinical,radiomics,and radiomics-clinical models using logistic regression.A DL model was established using a three-dimensional squeeze-and-excitation residual network-34(3D SE-ResNet34)and a fusion model was created by integrating seleted clinical,radiomics features and DL features.Model performance was assessed using the area under the curve(AUC)of the receiver operating characteristic(ROC)curve,calibration curves,and decision curve analysis(DCA).Five predictive models were compared;SHapley Additive exPlanations(SHAP)and Gradient-weighted Class Activation Mapping(Grad-CAM)were employed for visualization and interpretation.Results:Overall,358 patients were included:186 in the training cohort,48 in the internal validation cohort,and 124 in the external testing cohort.The DL fusion model incorporating 3D SE-Resnet34 achieved the highest AUC of 0.947 in the training dataset,with strong performance in internal and external cohorts(AUCs of 0.903 and 0.907,respectively),outperforming single-modal DL models,clinical models,radiomics models,and radiomicsclinical combined models(DeLong test:P<0.05).DCA confirmed its clinical utility,and calibration curves demonstrated excellent agreement between predicted and observed OLNM probabilities.Features interpretation highlighted the importance of textural characteristics and the surrounding tumor regions in stratifying OLNM risk.Conclusions:The DL fusion model reliably and accurately predicts OLNM in early-stage lung adenocarcinoma,offering a non-invasive tool to refine staging and guide personalized treatment decisions.These results may aid clinicians in optimizing surgical and radiotherapy strategies.
文摘BACKGROUND Lung cancer(LC)is one of the most prevalent cancers globally,with a high incidence among the elderly population.Elderly patients,particularly those with diabetes mellitus,are at an increased risk of postoperative complications,in-cluding pulmonary infections,due to weakened immune function and metabolic abnormalities.Postoperative pulmonary infection(PPI)is a predominant com-plication after thoracoscopic radical resection of LC,significantly affecting patient outcomes and increasing healthcare burdens.Determining risk factors for PPI in this vulnerable population is crucial for improving surgical outcomes and redu-cing infection rates.AIM To develop and validate a predictive model for PPI in elderly patients with dia-betes undergoing thoracoscopic radical resection for LC and to assess its reliability and validity.METHODS This retrospective study included 212 patients with LC who received treatment at our hospital from March 2015 to March 2022.General clinical information,sur-gical treatment details,and laboratory test results were collected and analyzed.Patients were grouped according to infection occurrence during the postoperative hospitalization period.Risk factors for PPIs were determined through logistic regression analysis,and a nomogram prediction model was established using R software to assess its predictive accuracy and performance.RESULTS Among the 212 patients[median age:72 years(interquartile range:60-82 years)],41 developed PPI(19.34%),with Gram-negative bacteria being the predominant pathogens(64.14%).Factors,such as age of≥70 years,presence of respiratory diseases,maximum tumor diameter of≥4 cm,stages II-III,receiving neoadjuvant chemotherapy of≥2 times preoperatively,surgery duration of≥3 hours,chest drainage tube placement duration of≥3.5 days,preoperative fasting blood glucose levels,hemoglobin A1c(HbA1c)levels,and multi-leaf resection,were markedly higher in the infection group than in the non-infection group.Conversely,forced expiratory volume in 1 second(FEV1)of≥80%and albumin(Alb)levels were lower in the infection group.Multivariate logistic regression analysis revealed that receiving neoadjuvant chemotherapy of≥2 times[odds ratio(OR)=2.987;P=0.036],maximum tumor diameter of≥4 cm(OR=3.959;P=0.013),multi-leaf resection(OR=3.18;P=0.036),preoperative FEV1 of≤80%(OR=3.305;P=0.029),and high HbA1c levels(OR=2.39;P=0.003)as key risk factors for PPI,whereas high Alb levels(OR=0.507;P<0.001)was protective.The nomogram model demonstrated excellent diagnostic ability(area under the curve=0.901,0.915),and calibration curves and decision curve analysis revealed good predictive performance and clinical applicability of the model.CONCLUSION The primary pathogens of PPI in elderly patients with diabetes and LC undergoing thoracoscopic radical resection are Gram-negative bacteria.The nomogram model,based on preoperative neoadjuvant chemotherapy cycles,maximum tumor diameter,range of resection,and preoperative FEV1,Alb,and HbA1c levels,shows high clinical value in predicting the risk of PPI in this patient population.
