Background:Ex vivo lung perfusion(EVLP)has emerged as a critical technique for lung preservation and evaluation prior to transplantation.While conventional rat EVLP systems utilize closed-loop dual cannulation of pulm...Background:Ex vivo lung perfusion(EVLP)has emerged as a critical technique for lung preservation and evaluation prior to transplantation.While conventional rat EVLP systems utilize closed-loop dual cannulation of pulmonary artery(PA)and vein,the effect of the simplified model using single PA cannulation with passive venous drainage is unknown.Methods:We developed two EVLP models in rats:a semi-closed circuit with PA-only cannulation and left atrial incision for passive venous drainage(SC-EVLP),and a closed circuit employing both arterial and venous cannulation(C-EVLP).Donor lungs were perfused for a defined duration and subsequently orthotopically transplanted.We evaluated pulmonary function parameters,histopathological injury scores,inflammatory cytokine levels,and apoptotic marker expression at the end of perfusion and posttransplantation.Results:Compared to the conventional EVLP,the SC-EVLP group exhibited significantly lower PA pressure and improved dynamic lung compliance throughout perfusion.Although the levels of tumor necrosis factor-αin the perfusate were higher in the SC-EVLP group,other cytokine levels in the perfusate and bronchoalveolar lavage fluid exhibited no significant differences.Pulmonary edema was reduced in the SC-EVLP group,as indicated by a lower lung wet-to-dry ratio.After transplantation,lungs from the SC-EVLP group exhibited lower histological injury scores,reduced apoptosis,and decreased serum cytokine levels,suggesting attenuated inflammation and tissue damage.Conclusions:In a rat model,single PA cannulation with passive venous drainage reduced pulmonary edema during EVLP and reduced lung injury and systemic inflammation after transplantation.展开更多
Background:Triptolide(TP)exhibits various pharmacological activities.Our previous studies have confirmed the efficacy of TP against lung adenocarcinoma(LUAD).However,the potent pharmacological activity of TP is underp...Background:Triptolide(TP)exhibits various pharmacological activities.Our previous studies have confirmed the efficacy of TP against lung adenocarcinoma(LUAD).However,the potent pharmacological activity of TP is underpinned by its complex mechanisms.Exploring its potential mechanisms is of great value for promoting the clinical application of TP and extending its clinical use.Methods:Differentially expressed genes(DEGs)associated with LUAD were analyzed and acquired from the TCGA database,while DEGs related to TP were obtained through RNA sequencing.Hub genes were identified through LASSO and random forest models.The efficacy of TP against LUAD was validated using tumor-bearing mouse models and A549 cells.The validation of hub genes was conducted using RT-qPCR.The regulatory effect of hub genes on TP efficacy was validated through overexpression cell models.Furthermore,the potential mechanisms by which TP improves gemcitabine(GEM)resistance were explored using a GEM-resistant cell line in combination with the overexpression model.Results:This study validated the therapeutic effect of TP against LUAD in vivo and in vitro.Bioinformatics revealed that the mechanism of TP's effect against LUAD might be associated with amino acid-related biological processes.Five hub genes were screened and identified by combining bioinformatics methods and experiments.The overexpression model validated that PSAT1 plays an effective role in the efficacy of TP and in alleviating GEM resistance.Conclusion:This study preliminarily demonstrated that the anti-LUAD effect of TP was associated with the PSAT1-regulated serine biosynthesis pathway,and that TP effectively improves GEM resistance by inhibiting PSAT1 expression.展开更多
Lung cancer is the most common but fatal malignant tumor worldwide.Patients with lung cancer experienced a relatively low 5-year overall survival rate,and issues such as metastasis and drug resistance remain prominent...Lung cancer is the most common but fatal malignant tumor worldwide.Patients with lung cancer experienced a relatively low 5-year overall survival rate,and issues such as metastasis and drug resistance remain prominent challenges in its clinical management.Neddylation,a novel type of post-translational modification,was overactivated in lung cancer and was closely associated with its occurrence,development,metastasis,and drug resistance.This review systematically summarizes the biological process of neddylation and deeply explores the latest research progress on how neddylation affects lung cancer cell proliferation,metastasis,and drug resistance mechanisms,with a focus on its regulation of key molecules such as Cullin-RING E3 ligases and the SCCRO family.Meanwhile,it concludes the current advances in potential therapeutic agents targeting neddylation-related targets,including small-molecule compounds(such as Pevonedistat)and natural extracts(such as arctigenin).Finally,the review prospectively evaluates the application potential and questions requiring further exploration of neddylation in lung cancer treatment.In conclusion,we aim to systematically summarize the biological process of neddylation,critically explore its roles in lung cancer proliferation,metastasis,and drug resistance,and evaluate the therapeutic potential of neddylation-targeting agents.展开更多
Acute lung injury(ALl)is characterized by a sudden decline in pulmonary gas exchange function due to various pathological factors,with severe cases progressing to acute respiratory distress syndrome(ARDS).ARDS affects...Acute lung injury(ALl)is characterized by a sudden decline in pulmonary gas exchange function due to various pathological factors,with severe cases progressing to acute respiratory distress syndrome(ARDS).ARDS affects approximately 3million patients annually,accounting for 10% of intensive care unit admissions[1].展开更多
Radiation-induced lung injury(RILI)is a common complication of radiotherapy.Although berberine(BBR)has been suggested to be associated with reduced RILI incidence,the underlying mechanisms remain unknown.Here,we inves...Radiation-induced lung injury(RILI)is a common complication of radiotherapy.Although berberine(BBR)has been suggested to be associated with reduced RILI incidence,the underlying mechanisms remain unknown.Here,we investigated whether the gut microbiota mediates the radioprotective effects of BBR using a C57BL/6 RILI mouse model with 20 Gy thoracic irradiation(n=6 per group).BBR(100 mg/kg)and inosine(INO,300 mg/kg)were administered orally in vivo.Antibiotic depletion and fecal microbiota transplantation were performed to assess microbiota dependence.Lung injury was assessed by histology,pulmonary function,and cytokine levels.Gut microbiota was analyzed by 16S rRNA sequencing,and metabolites were profiled using LC-MS/MS.Transcriptomic and epigenomic alterations were assessed by RNA sequencing,ATAC sequencing,and CUT&Tag analysis.Molecular docking and surface plasmon resonance were used to assess metabolite-protein interactions.We demonstrated that BBR alleviated RILI in a microbiota-dependent manner.BBR increased Akkermansia muciniphila abundance and metabolite INO levels.Mechanistically,INO was associated with reduced neuron navigator 3(NAV3)expression,accompanied by decreased chromatin accessibility and increased histone H3 lysine 27 trimethylation(H3K27me3)at the NAV3 locus.Together,these findings reveal a gut microbiota-mediated mechanism underlying BBR-mediated protection against RILI,and suggest microbiota-informed biomarkers for risk stratification.展开更多
Objective Post tuberculosis lung disease(PTLD)manifests in various forms,including tuberculosisassociated chronic obstructive pulmonary disease(TB-COPD),yet the clinical features of PTLD remain undercharacterized.This...Objective Post tuberculosis lung disease(PTLD)manifests in various forms,including tuberculosisassociated chronic obstructive pulmonary disease(TB-COPD),yet the clinical features of PTLD remain undercharacterized.This study aimed to assess longitudinal changes in lung function over a 5-year period and to identify predictors of airflow obstruction in a cohort of patients treated for active pulmonary TB.Methods Patients with active pulmonary TB were enrolled in this study and were followed during treatment,at treatment completion and five years post-treatment.Assessments included lung function and chest CT,analyzing longitudinal trends and airflow obstruction risk factors.Results Among 53 patients(mean age 36.9±13.9 years;64.2%male),7 patients(13.2%)exhibited airflow obstruction.At the 5-year follow-up,the mean FEV_(1)/FVC declined significantly(76.27%±12.04%vs.80.23%±11.02%,P<0.001)and 9 patients(17.0%)exhibited airflow obstruction.Seven of these patients predominantly showed air trapping consistent with small airway disease on chest CT,aligning with TB-COPD phenotype.Notably,four young-to-middle-aged patients(<60 years old)had persistent obstruction over the five years.Conclusion The initial test revealed that 13.2%of patients presented with airflow obstruction.By the 5-year follow-up,this proportion had increased to 17.0%,with most cases demonstrating imaging findings aligning with TB-COPD,even among younger,non-smoking individuals.These findings emphasize the importance of long-term follow-up and routine lung function assessments in TB survivors.展开更多
Down syndrome(DS)is caused by an extra copy of chromosome 21(Hsa21).Children with DS have an increased frequency of respiratory tract infections,impaired alveolar and vascular development,and pulmonary hypertension.Ho...Down syndrome(DS)is caused by an extra copy of chromosome 21(Hsa21).Children with DS have an increased frequency of respiratory tract infections,impaired alveolar and vascular development,and pulmonary hypertension.How trisomy 21 causes lung diseases remains poorly understood.In this study,we use the Dp16 mouse model,which contains a segmental chromosomal duplication of the entire Hsa21 syntenic region on mouse chromosome 16,to explore the gene dosage effects on DS-related lung diseases.The Dp16 mice present impaired alveolar development and inflammatory-like pathological changes.Single-cell RNA sequencing(scRNA-seq)analysis highlights increased APP-related interactions among male Dp16 lung cells.Specifically,altered antigen processing and presentation with increased MHC-II signaling are found in Dp16 immune cells.Reduced angiogenesis and altered inflammatory responses of Dp16 endothelial cells are also suggested.Moreover,scRNA-seq indicates hyperplasia of Dp16 vascular smooth muscle cells,which is validated by tissue immunofluorescence assessment.Transthoracic echocardiography further shows the existence of pulmonary hypertension in young Dp16 mice.Independent scRNA-seq analysis of the female lung cells recapitulates the majority of key findings identified in male mice,confirming the reproducibility of the results.Collectively,our results provide important clues for the further development of therapeutic approaches for DS-related lung diseases.展开更多
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
Pulmonary diseases have long posed a severe threat to human life and health.The incidence and mortality rates of pulmonary diseases have shown a rising trend year by year,highlighting the urgency of developing safe an...Pulmonary diseases have long posed a severe threat to human life and health.The incidence and mortality rates of pulmonary diseases have shown a rising trend year by year,highlighting the urgency of developing safe and effective therapeutic approaches.In recent years,to address the challenges faced by traditional treatment strategies for pulmonary diseases,the interdisciplinary integration has greatly promoted the rapid development of biomedical polymer materials in the field of pulmonary disease treatment.This review provides a detailed description of the structural characteristics of lung tissue,types of pulmonary diseases,traditional treatment methods,the categories and properties of biomedical polymer materials applied to pulmonary diseases.We systematically elaborate on the applications of biomedical polymer materials in the treatment of different pulmonary diseases and thoroughly discuss their functional roles in pulmonary diseases,particularly in the delivery of therapeutic agents to diseased sites,the formation of pulmonary aerosol formulations,and the facilitation of the effective accumulation of therapeutic agents.The latest research progresses of biomedical polymer materials are also introduced in pulmonary disease treatment.We have highlighted the current challenges and development opportunities of biomedical polymer materials in the treatment of pulmonary diseases,and provide future research directions for biomedical polymer materials in this field.This review will provide valuable reference for the basic research and clinical application of biomedical polymer materials in pulmonary disease treatment.展开更多
The published article titled“MicroRNA-138 Inhibits Cell Growth,Invasion,and EMT of Non-Small Cell Lung Cancer via SOX4/p53 Feedback Loop”has been retracted fromOncology Research,Vol.26,No.3,2018,pp.385–400.DOI:10.3...The published article titled“MicroRNA-138 Inhibits Cell Growth,Invasion,and EMT of Non-Small Cell Lung Cancer via SOX4/p53 Feedback Loop”has been retracted fromOncology Research,Vol.26,No.3,2018,pp.385–400.DOI:10.3727/096504017X14973124850905 URL:https://www.techscience.com/or/v26n3/56651 Following the publication,concerns have been raised about a number of figures in this article.An unexpected area of similarity was identified in terms of the cellular data,where the results from differently performed experiments were intended to have been shown,although the areas immediately surrounding this area featured comparatively different distributions of cells.In addition,the western blots in this article were presented with atypical,unusually shaped and possibly anomalous protein bands in many cases.展开更多
The published article titled“Long Noncoding RNA(lncRNA)HOTAIR Affects Tumorigenesis andMetastasis of Non-Small Cell Lung Cancer by Upregulating miR-613”has been retracted from Oncology Research,Vol.26,No.5,2018,pp....The published article titled“Long Noncoding RNA(lncRNA)HOTAIR Affects Tumorigenesis andMetastasis of Non-Small Cell Lung Cancer by Upregulating miR-613”has been retracted from Oncology Research,Vol.26,No.5,2018,pp.725–734.DOI:10.3727/096504017X15119467381615 URL:https://www.techscience.com/or/v26n5/56685 Following the publication,concerns have been raised about a number of figures in this article.An unexpected area of similarity was identified in terms of the cellular data,where the results from differently performed experiments were intended to have been shown,although the areas immediately surrounding this area featured comparatively different distributions of cells.In addition,the western blots in this article were presented with atypical,unusually shaped and possibly anomalous protein bands in many cases.展开更多
Objective:To determine whether immunotherapy can bring new hope for patients with limited-stage small-cell lung cancer(LS-SCLC).We conducted this retrospective study to evaluate whether immunotherapy can achieve bette...Objective:To determine whether immunotherapy can bring new hope for patients with limited-stage small-cell lung cancer(LS-SCLC).We conducted this retrospective study to evaluate whether immunotherapy can achieve better efficacy in LS-SCLC patients.Methods:We evaluated 122 LS-SCLC patients who received concurrent chemoradiotherapy(CCRT)or sequential chemoradiotherapy(SCRT)(Group A)and immunotherapy combined with CCRT/SCRT followed by immunotherapy(Group B),to assess the objective response rate(ORR),disease control rate(DCR),and progression-free survival(PFS).Factors affecting prognosis were also explored using Cox analysis.The prognosis of patients with type 2 diabetes and patients with different TNM stages was compared to guide the selection of clinical regimens.Results:The overall ORR was 55.93%.The overall DCR was 98.31%.The DCR was 100%in Group A and 96.61%in Group B.There was no statistical difference in ORR and DCR.The overall median PFS was 9.86 months(95%CI,8.62-11.10),and the difference in median PFS between the two groups was statistically significant(8.94 vs.11.89 months,p=0.03).The Cox regression analysis showed type 2 diabetes was associated with the survival prognosis.Patients with type 2 diabetes tended to choose immunotherapy combined with CCRT/SCRT.Patients in TNM stage IIIB had a significantly worse prognosis than those in stage I+II+IIIA.Conclusion:We suggest that LS-SCLC patients who receive immunotherapy combined with CCRT/SCRT can achieve longer PFS than those with CCRT/SCRT.Type 2 diabetes and TNM stage affect the survival prognosis.Patients with type 2 diabetes may benefit from immunotherapy combination treatments.展开更多
Conventional treatments for non-small cell lung cancer(NSCLC)suffer from low remission rates,high drug resistance,and severe adverse effects.To leverage the therapeutic potential of reactive oxygen species(ROS),nanoca...Conventional treatments for non-small cell lung cancer(NSCLC)suffer from low remission rates,high drug resistance,and severe adverse effects.To leverage the therapeutic potential of reactive oxygen species(ROS),nanocatalytic medicine utilizes nanomaterials to generate ROS specifically within tumor sites,enabling efficient and targeted cancer treatment.In this study,hyaluronic acid(HA)-modified copper-N,N-dimethyl-Nphenylsulfonylbisamine(DMSA)-assembled nanoparticles(Cu-DMSA-HA NPs)are developed with tumor-targeting capability and efficiently catalyze ROS production via coordination chemistry.Targeted delivery is facilitated by HA surface modification through recognition of overexpressed cluster of differentiation 44 receptors on cancer cells,which enhances nanoparticle uptake.Once internalized,intracellular glutathione is depleted by the NPs,followed by a Fenton-like reaction that sustains ROS production.Both in vitro and in vivo studies demonstrate that this catalytic strategy effectively inhibits DNA replication,prevents cell cycle progression,downregulates glutathione peroxidase 4 expression,induces ferroptosis,and ultimately suppresses NSCLC progression.Overall,the readily prepared Cu-DMSA-HA NPs exhibit robust catalytic activity and tumor specificity,highlighting their strong potential for clinical translation in nanocatalytic cancer therapy.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
Objectives:Although immune checkpoint inhibitors(ICIs)and targeted therapies have reshaped treatment non-small cell lung cancer(NSCLC)paradigms,prognosis remains poor for many patients due to delayed diagnosis and res...Objectives:Although immune checkpoint inhibitors(ICIs)and targeted therapies have reshaped treatment non-small cell lung cancer(NSCLC)paradigms,prognosis remains poor for many patients due to delayed diagnosis and resistance mechanisms.Liquid biopsy offers a minimally invasive approach to monitoring tumor evolution.Among circulating biomarkers,circulating tumor cells(CTCs)and cancer-associated macrophage-like cells(CAM-Ls)may provide complementary prognostic insights.The study aimed to evaluate the prognostic role of CTC and CAM-Ls dynamic in metastatic NSCLC patients.Methods:We retrospectively analyzed 77 patients with metastatic NSCLC who underwent CTC and CAM-L evaluation via the CellSearch^(R)system at baseline(T0)and after three months of first-line treatment(T1)including chemotherapy,targeted therapy,or ICIs.Survival outcomes were analyzed using Kaplan-Meier and Cox regression analyses.Results:Conversion to CTC-negative status at T1 was associated with improved outcomes,with median overall survival(OS)and progression-free survival(PFS)of 33 and 18 months,respectively,vs.10 and 6 months in persistently positive patients(both p<0.001).CTC negativity at T1 remained an independent prognostic factor for OS(HR:6.68)and PFS(HR:5.91,both p<0.0001).CAM-L positivity at T1 also correlated with longer OS(30 vs.12 months)and PFS(13 vs.6 months,both p<0.0001),particularly among ICI-treated patients.Combined CTC and CAM-L assessment further refined risk stratification.Conclusions:Dynamic monitoring of CTCs and CAM-Ls provides actionable prognostic information in metastatic NSCLC.CTC-negative status predicted longer OS and PFS,while CAM-L positivity at T1 was associated with improved outcomes,particularly in ICI-treated patients.Combined assessment of both biomarkers may directly inform therapeutic decision-making,through early detection of outcomes.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
Objectives:The PACIFIC trial established the benefit of durvalumab following chemo-radiotherapy for stage III non-small cell lung cancer(NSCLC).However,the concurrent use of radiotherapy(RT)and durvalumab(PACIFIC-2 tr...Objectives:The PACIFIC trial established the benefit of durvalumab following chemo-radiotherapy for stage III non-small cell lung cancer(NSCLC).However,the concurrent use of radiotherapy(RT)and durvalumab(PACIFIC-2 trial)showed no additional advantage.The PD-RAD study was set up to understand the immunological effects of RT on the tumor microenvironment(TME)to aid in optimizing sequencing of combination therapies.Methods:The PD-RAD trial(ClinicalTrials.gov identifier:NCT03258788)aimed to enroll thirty NSCLC patients receiving radical-intent RT.Tumor biopsies and blood samples were collected pre-RT and at week 2 during RT and analyzed using multiplex immunohistochemistry(mIHC)and high-dimensional mass cytometry(CyTOF),respectively.Results:Paired biopsies were collected from only three patients(Pts 1,3&4)and blood from four patients(Pts 1-4)before the study was closed early during the COVID-19 pandemic.Programmed Death-Ligand 1(PD-L1)expression in the TME was raised in Patient 1,who responded well to treatment,and unaltered in two patients with progressive disease.CyTOF analysis revealed elevated circulating classical monocytes,highest in the patient with a good response.Conclusions:This study underscores the challenges of integrating advanced immune monitoring during RT delivery and did not meet its primary endpoint.The hypothesis-generating findings highlight PD-L1+macrophages in the TME and classical monocytes in the blood as potential immune biomarkers of RT response,but larger studies are needed to validate these observations and characterize the immune changes following curative-intent RT in patients with NSCLC.展开更多
Dear Editor,Systemic sclerosis(SSc)is an autoimmune connective tissue disease in which there are vascular abnormalities,inflammation,and fibrosis[1].These three characteristics primarily affect the skin and lungs.Of a...Dear Editor,Systemic sclerosis(SSc)is an autoimmune connective tissue disease in which there are vascular abnormalities,inflammation,and fibrosis[1].These three characteristics primarily affect the skin and lungs.Of all the autoimmune rheumatic diseases,SSc has the highest all-cause mortality rate,and the underlying pathogenic processes that mediate disease are still obscure,with wide diff erences in presentation and progression[2,3].展开更多
The metastatic pattern of colon cancer is typically well characterized,with initial dissemination occurring through regional lymphatics,followed by hematogenous spread.The most frequent sites of metastasis in colorect...The metastatic pattern of colon cancer is typically well characterized,with initial dissemination occurring through regional lymphatics,followed by hematogenous spread.The most frequent sites of metastasis in colorectal cancer(CRC)include regional lymph nodes(50%–70%),liver(35%–50%),lungs(21%),peritoneum(15%),and ovaries(13%).1 Isolated distant lymph node metastasis,particularly in the absence of concurrent systemic disease,is exceedingly rare in CRC.To date,only six cases of isolated axillary lymph node metastasis(ALNM)from colorectal primaries have been documented in the literature.1–6 Even more uncommon is the incidental discovery of malignant cells in anastomotic doughnuts following stoma reversal procedures.Herein,we report a rare case involving both the incidental histopathological detection of tumor cells within doughnuts during stoma closure and the subsequent development of isolated ALNM after curative resection of sigmoid colon carcinoma.展开更多
基金Key Science and Technology Program of Shaanxi Province,Grant/Award Number:2024SF2-GJHX-45National Natural Science Foundation of China,Grant/Award Number:82472191The Natural Science Foundation of Shaanxi Province,Grant/Award Number:2024JC-ZDXM-49。
文摘Background:Ex vivo lung perfusion(EVLP)has emerged as a critical technique for lung preservation and evaluation prior to transplantation.While conventional rat EVLP systems utilize closed-loop dual cannulation of pulmonary artery(PA)and vein,the effect of the simplified model using single PA cannulation with passive venous drainage is unknown.Methods:We developed two EVLP models in rats:a semi-closed circuit with PA-only cannulation and left atrial incision for passive venous drainage(SC-EVLP),and a closed circuit employing both arterial and venous cannulation(C-EVLP).Donor lungs were perfused for a defined duration and subsequently orthotopically transplanted.We evaluated pulmonary function parameters,histopathological injury scores,inflammatory cytokine levels,and apoptotic marker expression at the end of perfusion and posttransplantation.Results:Compared to the conventional EVLP,the SC-EVLP group exhibited significantly lower PA pressure and improved dynamic lung compliance throughout perfusion.Although the levels of tumor necrosis factor-αin the perfusate were higher in the SC-EVLP group,other cytokine levels in the perfusate and bronchoalveolar lavage fluid exhibited no significant differences.Pulmonary edema was reduced in the SC-EVLP group,as indicated by a lower lung wet-to-dry ratio.After transplantation,lungs from the SC-EVLP group exhibited lower histological injury scores,reduced apoptosis,and decreased serum cytokine levels,suggesting attenuated inflammation and tissue damage.Conclusions:In a rat model,single PA cannulation with passive venous drainage reduced pulmonary edema during EVLP and reduced lung injury and systemic inflammation after transplantation.
基金National Natural Science Foundation of China,Grant/Award Number:No.82560858Beijing Science and Technology New Star Program Cross-cooperation Project,Grant/Award Number:No.20240484711Jiangxi Provincial Natural Science Foundation,Grant/Award Number:20252BAC200586。
文摘Background:Triptolide(TP)exhibits various pharmacological activities.Our previous studies have confirmed the efficacy of TP against lung adenocarcinoma(LUAD).However,the potent pharmacological activity of TP is underpinned by its complex mechanisms.Exploring its potential mechanisms is of great value for promoting the clinical application of TP and extending its clinical use.Methods:Differentially expressed genes(DEGs)associated with LUAD were analyzed and acquired from the TCGA database,while DEGs related to TP were obtained through RNA sequencing.Hub genes were identified through LASSO and random forest models.The efficacy of TP against LUAD was validated using tumor-bearing mouse models and A549 cells.The validation of hub genes was conducted using RT-qPCR.The regulatory effect of hub genes on TP efficacy was validated through overexpression cell models.Furthermore,the potential mechanisms by which TP improves gemcitabine(GEM)resistance were explored using a GEM-resistant cell line in combination with the overexpression model.Results:This study validated the therapeutic effect of TP against LUAD in vivo and in vitro.Bioinformatics revealed that the mechanism of TP's effect against LUAD might be associated with amino acid-related biological processes.Five hub genes were screened and identified by combining bioinformatics methods and experiments.The overexpression model validated that PSAT1 plays an effective role in the efficacy of TP and in alleviating GEM resistance.Conclusion:This study preliminarily demonstrated that the anti-LUAD effect of TP was associated with the PSAT1-regulated serine biosynthesis pathway,and that TP effectively improves GEM resistance by inhibiting PSAT1 expression.
基金supported by the National Natural Science Foundation of China(No.82574683)the National Natural Science Foundation of Science and Technology Department of Sichuan Province(Nos.2023NSFSC1928 and 2023NSFSC1992)+2 种基金Project of State Administration of Traditional Chinese Medicine of China(No.ZYYCXTD-D-202209)Project of Sichuan Provincial Administration of Traditional Chinese Medicine(No.2022C001)Fundamental Research Funds for the Central Universities(No.YJ201880).
文摘Lung cancer is the most common but fatal malignant tumor worldwide.Patients with lung cancer experienced a relatively low 5-year overall survival rate,and issues such as metastasis and drug resistance remain prominent challenges in its clinical management.Neddylation,a novel type of post-translational modification,was overactivated in lung cancer and was closely associated with its occurrence,development,metastasis,and drug resistance.This review systematically summarizes the biological process of neddylation and deeply explores the latest research progress on how neddylation affects lung cancer cell proliferation,metastasis,and drug resistance mechanisms,with a focus on its regulation of key molecules such as Cullin-RING E3 ligases and the SCCRO family.Meanwhile,it concludes the current advances in potential therapeutic agents targeting neddylation-related targets,including small-molecule compounds(such as Pevonedistat)and natural extracts(such as arctigenin).Finally,the review prospectively evaluates the application potential and questions requiring further exploration of neddylation in lung cancer treatment.In conclusion,we aim to systematically summarize the biological process of neddylation,critically explore its roles in lung cancer proliferation,metastasis,and drug resistance,and evaluate the therapeutic potential of neddylation-targeting agents.
基金supported by the National Natural Science Foun-dation of China(81970011,81970070,82100086,and 82270390)the Natural Science Foundation of Hubei Province(2025AFC006)+2 种基金the research fund from Medical Sci-Tech Innovation Platform of Zhongnan Hospital,Wuhan University(PTXM2025032)the Basic Medicine-Clinical Medicine Transformation Collaborative Fund of Zhongnan Hospital of Wuhan University,the Hubei Province Inno-vation Platform Construction Project(20204201117303072238)the Hubei Provincial Engineering Research Center of Model Animal.
文摘Acute lung injury(ALl)is characterized by a sudden decline in pulmonary gas exchange function due to various pathological factors,with severe cases progressing to acute respiratory distress syndrome(ARDS).ARDS affects approximately 3million patients annually,accounting for 10% of intensive care unit admissions[1].
基金supported by the National Natural Science Foundation of China(grant number 82373515 to J.L.).
文摘Radiation-induced lung injury(RILI)is a common complication of radiotherapy.Although berberine(BBR)has been suggested to be associated with reduced RILI incidence,the underlying mechanisms remain unknown.Here,we investigated whether the gut microbiota mediates the radioprotective effects of BBR using a C57BL/6 RILI mouse model with 20 Gy thoracic irradiation(n=6 per group).BBR(100 mg/kg)and inosine(INO,300 mg/kg)were administered orally in vivo.Antibiotic depletion and fecal microbiota transplantation were performed to assess microbiota dependence.Lung injury was assessed by histology,pulmonary function,and cytokine levels.Gut microbiota was analyzed by 16S rRNA sequencing,and metabolites were profiled using LC-MS/MS.Transcriptomic and epigenomic alterations were assessed by RNA sequencing,ATAC sequencing,and CUT&Tag analysis.Molecular docking and surface plasmon resonance were used to assess metabolite-protein interactions.We demonstrated that BBR alleviated RILI in a microbiota-dependent manner.BBR increased Akkermansia muciniphila abundance and metabolite INO levels.Mechanistically,INO was associated with reduced neuron navigator 3(NAV3)expression,accompanied by decreased chromatin accessibility and increased histone H3 lysine 27 trimethylation(H3K27me3)at the NAV3 locus.Together,these findings reveal a gut microbiota-mediated mechanism underlying BBR-mediated protection against RILI,and suggest microbiota-informed biomarkers for risk stratification.
基金supported by the National Science and Technology Major Project for the Prevention and Control of Emerging and Major Infectious Diseases[2025ZD01908702]Peking University Medicine Fund of Fostering Young Scholars’Scientific&Technological innovation[BMU2024YFJHP014]supported by Fundamental Research Funds for the Central Universities+1 种基金Key Clinical Projects of Peking University Third Hospital[BYSYZD2022014]Peking University Third Hospital[2025024].
文摘Objective Post tuberculosis lung disease(PTLD)manifests in various forms,including tuberculosisassociated chronic obstructive pulmonary disease(TB-COPD),yet the clinical features of PTLD remain undercharacterized.This study aimed to assess longitudinal changes in lung function over a 5-year period and to identify predictors of airflow obstruction in a cohort of patients treated for active pulmonary TB.Methods Patients with active pulmonary TB were enrolled in this study and were followed during treatment,at treatment completion and five years post-treatment.Assessments included lung function and chest CT,analyzing longitudinal trends and airflow obstruction risk factors.Results Among 53 patients(mean age 36.9±13.9 years;64.2%male),7 patients(13.2%)exhibited airflow obstruction.At the 5-year follow-up,the mean FEV_(1)/FVC declined significantly(76.27%±12.04%vs.80.23%±11.02%,P<0.001)and 9 patients(17.0%)exhibited airflow obstruction.Seven of these patients predominantly showed air trapping consistent with small airway disease on chest CT,aligning with TB-COPD phenotype.Notably,four young-to-middle-aged patients(<60 years old)had persistent obstruction over the five years.Conclusion The initial test revealed that 13.2%of patients presented with airflow obstruction.By the 5-year follow-up,this proportion had increased to 17.0%,with most cases demonstrating imaging findings aligning with TB-COPD,even among younger,non-smoking individuals.These findings emphasize the importance of long-term follow-up and routine lung function assessments in TB survivors.
基金supported by the Fundamental Research Funds for the Central Universities(226-2022-00035)the National Natural Science Foundation of China(81600986).
文摘Down syndrome(DS)is caused by an extra copy of chromosome 21(Hsa21).Children with DS have an increased frequency of respiratory tract infections,impaired alveolar and vascular development,and pulmonary hypertension.How trisomy 21 causes lung diseases remains poorly understood.In this study,we use the Dp16 mouse model,which contains a segmental chromosomal duplication of the entire Hsa21 syntenic region on mouse chromosome 16,to explore the gene dosage effects on DS-related lung diseases.The Dp16 mice present impaired alveolar development and inflammatory-like pathological changes.Single-cell RNA sequencing(scRNA-seq)analysis highlights increased APP-related interactions among male Dp16 lung cells.Specifically,altered antigen processing and presentation with increased MHC-II signaling are found in Dp16 immune cells.Reduced angiogenesis and altered inflammatory responses of Dp16 endothelial cells are also suggested.Moreover,scRNA-seq indicates hyperplasia of Dp16 vascular smooth muscle cells,which is validated by tissue immunofluorescence assessment.Transthoracic echocardiography further shows the existence of pulmonary hypertension in young Dp16 mice.Independent scRNA-seq analysis of the female lung cells recapitulates the majority of key findings identified in male mice,confirming the reproducibility of the results.Collectively,our results provide important clues for the further development of therapeutic approaches for DS-related lung diseases.
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.
基金the National Key Research and Development Program of China(No.2021YFB3800900)Natural Science Foundation of Xiamen,China(No.3502Z202371004)+2 种基金National Natural Science Foundation of China(Nos.52473150,51925305,52173115,51873208,51833010,and 52203183)Fundamental Research Funds for the Central Universities(No.20720230004)the Talent Cultivation Project Funds for the Innovation Laboratory for Sciences and Technologies of Energy Materials of Fujian Province(No.HRTP-[2022]52).
文摘Pulmonary diseases have long posed a severe threat to human life and health.The incidence and mortality rates of pulmonary diseases have shown a rising trend year by year,highlighting the urgency of developing safe and effective therapeutic approaches.In recent years,to address the challenges faced by traditional treatment strategies for pulmonary diseases,the interdisciplinary integration has greatly promoted the rapid development of biomedical polymer materials in the field of pulmonary disease treatment.This review provides a detailed description of the structural characteristics of lung tissue,types of pulmonary diseases,traditional treatment methods,the categories and properties of biomedical polymer materials applied to pulmonary diseases.We systematically elaborate on the applications of biomedical polymer materials in the treatment of different pulmonary diseases and thoroughly discuss their functional roles in pulmonary diseases,particularly in the delivery of therapeutic agents to diseased sites,the formation of pulmonary aerosol formulations,and the facilitation of the effective accumulation of therapeutic agents.The latest research progresses of biomedical polymer materials are also introduced in pulmonary disease treatment.We have highlighted the current challenges and development opportunities of biomedical polymer materials in the treatment of pulmonary diseases,and provide future research directions for biomedical polymer materials in this field.This review will provide valuable reference for the basic research and clinical application of biomedical polymer materials in pulmonary disease treatment.
文摘The published article titled“MicroRNA-138 Inhibits Cell Growth,Invasion,and EMT of Non-Small Cell Lung Cancer via SOX4/p53 Feedback Loop”has been retracted fromOncology Research,Vol.26,No.3,2018,pp.385–400.DOI:10.3727/096504017X14973124850905 URL:https://www.techscience.com/or/v26n3/56651 Following the publication,concerns have been raised about a number of figures in this article.An unexpected area of similarity was identified in terms of the cellular data,where the results from differently performed experiments were intended to have been shown,although the areas immediately surrounding this area featured comparatively different distributions of cells.In addition,the western blots in this article were presented with atypical,unusually shaped and possibly anomalous protein bands in many cases.
文摘The published article titled“Long Noncoding RNA(lncRNA)HOTAIR Affects Tumorigenesis andMetastasis of Non-Small Cell Lung Cancer by Upregulating miR-613”has been retracted from Oncology Research,Vol.26,No.5,2018,pp.725–734.DOI:10.3727/096504017X15119467381615 URL:https://www.techscience.com/or/v26n5/56685 Following the publication,concerns have been raised about a number of figures in this article.An unexpected area of similarity was identified in terms of the cellular data,where the results from differently performed experiments were intended to have been shown,although the areas immediately surrounding this area featured comparatively different distributions of cells.In addition,the western blots in this article were presented with atypical,unusually shaped and possibly anomalous protein bands in many cases.
基金funded by the National Natural Science Foundation of China(grant no.82273162)the National Natural Science Foundation of China(grant no.82203272)the Science and Technology Development Foundation of Nanjing Medical University(grant NMUB20240119)。
文摘Objective:To determine whether immunotherapy can bring new hope for patients with limited-stage small-cell lung cancer(LS-SCLC).We conducted this retrospective study to evaluate whether immunotherapy can achieve better efficacy in LS-SCLC patients.Methods:We evaluated 122 LS-SCLC patients who received concurrent chemoradiotherapy(CCRT)or sequential chemoradiotherapy(SCRT)(Group A)and immunotherapy combined with CCRT/SCRT followed by immunotherapy(Group B),to assess the objective response rate(ORR),disease control rate(DCR),and progression-free survival(PFS).Factors affecting prognosis were also explored using Cox analysis.The prognosis of patients with type 2 diabetes and patients with different TNM stages was compared to guide the selection of clinical regimens.Results:The overall ORR was 55.93%.The overall DCR was 98.31%.The DCR was 100%in Group A and 96.61%in Group B.There was no statistical difference in ORR and DCR.The overall median PFS was 9.86 months(95%CI,8.62-11.10),and the difference in median PFS between the two groups was statistically significant(8.94 vs.11.89 months,p=0.03).The Cox regression analysis showed type 2 diabetes was associated with the survival prognosis.Patients with type 2 diabetes tended to choose immunotherapy combined with CCRT/SCRT.Patients in TNM stage IIIB had a significantly worse prognosis than those in stage I+II+IIIA.Conclusion:We suggest that LS-SCLC patients who receive immunotherapy combined with CCRT/SCRT can achieve longer PFS than those with CCRT/SCRT.Type 2 diabetes and TNM stage affect the survival prognosis.Patients with type 2 diabetes may benefit from immunotherapy combination treatments.
基金supported by National Natural Science Foundation of China(82272943)Shanghai Municipal Science and Technology Commission(21Y11913400)Fundamental Research Funds for the Central Universities and National Key Research and Development Program of China(2022YFC2407405).
文摘Conventional treatments for non-small cell lung cancer(NSCLC)suffer from low remission rates,high drug resistance,and severe adverse effects.To leverage the therapeutic potential of reactive oxygen species(ROS),nanocatalytic medicine utilizes nanomaterials to generate ROS specifically within tumor sites,enabling efficient and targeted cancer treatment.In this study,hyaluronic acid(HA)-modified copper-N,N-dimethyl-Nphenylsulfonylbisamine(DMSA)-assembled nanoparticles(Cu-DMSA-HA NPs)are developed with tumor-targeting capability and efficiently catalyze ROS production via coordination chemistry.Targeted delivery is facilitated by HA surface modification through recognition of overexpressed cluster of differentiation 44 receptors on cancer cells,which enhances nanoparticle uptake.Once internalized,intracellular glutathione is depleted by the NPs,followed by a Fenton-like reaction that sustains ROS production.Both in vitro and in vivo studies demonstrate that this catalytic strategy effectively inhibits DNA replication,prevents cell cycle progression,downregulates glutathione peroxidase 4 expression,induces ferroptosis,and ultimately suppresses NSCLC progression.Overall,the readily prepared Cu-DMSA-HA NPs exhibit robust catalytic activity and tumor specificity,highlighting their strong potential for clinical translation in nanocatalytic cancer therapy.
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funded by Sapienza University PNRR-RT_SPOKE_1—ROME TECHNOPOLE—Spoke 1—B83C22002820006—ECS00000024 and FO R.O.onlus.
文摘Objectives:Although immune checkpoint inhibitors(ICIs)and targeted therapies have reshaped treatment non-small cell lung cancer(NSCLC)paradigms,prognosis remains poor for many patients due to delayed diagnosis and resistance mechanisms.Liquid biopsy offers a minimally invasive approach to monitoring tumor evolution.Among circulating biomarkers,circulating tumor cells(CTCs)and cancer-associated macrophage-like cells(CAM-Ls)may provide complementary prognostic insights.The study aimed to evaluate the prognostic role of CTC and CAM-Ls dynamic in metastatic NSCLC patients.Methods:We retrospectively analyzed 77 patients with metastatic NSCLC who underwent CTC and CAM-L evaluation via the CellSearch^(R)system at baseline(T0)and after three months of first-line treatment(T1)including chemotherapy,targeted therapy,or ICIs.Survival outcomes were analyzed using Kaplan-Meier and Cox regression analyses.Results:Conversion to CTC-negative status at T1 was associated with improved outcomes,with median overall survival(OS)and progression-free survival(PFS)of 33 and 18 months,respectively,vs.10 and 6 months in persistently positive patients(both p<0.001).CTC negativity at T1 remained an independent prognostic factor for OS(HR:6.68)and PFS(HR:5.91,both p<0.0001).CAM-L positivity at T1 also correlated with longer OS(30 vs.12 months)and PFS(13 vs.6 months,both p<0.0001),particularly among ICI-treated patients.Combined CTC and CAM-L assessment further refined risk stratification.Conclusions:Dynamic monitoring of CTCs and CAM-Ls provides actionable prognostic information in metastatic NSCLC.CTC-negative status predicted longer OS and PFS,while CAM-L positivity at T1 was associated with improved outcomes,particularly in ICI-treated patients.Combined assessment of both biomarkers may directly inform therapeutic decision-making,through early detection of outcomes.
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.
基金the National Institute for Health and Care Research(NHR)Manchester Biomedical Research Centre(BRC)(NIHR203308,NIHR-BRC-1215-20007)Astra-Zeneca(ESR-14-10711)+2 种基金CRUK RadNet(C19941/A27801)TMI and CFF are the recipient of an NIHR Senior Investigator Award(NIHR205054 and NIHR205061)CTH is supported by the NIHR University College London Hospitals NHS Foundation Trust BRC,the City of London CRUK RadNet and the CRUK Lung Cancer Centre of Excellence.
文摘Objectives:The PACIFIC trial established the benefit of durvalumab following chemo-radiotherapy for stage III non-small cell lung cancer(NSCLC).However,the concurrent use of radiotherapy(RT)and durvalumab(PACIFIC-2 trial)showed no additional advantage.The PD-RAD study was set up to understand the immunological effects of RT on the tumor microenvironment(TME)to aid in optimizing sequencing of combination therapies.Methods:The PD-RAD trial(ClinicalTrials.gov identifier:NCT03258788)aimed to enroll thirty NSCLC patients receiving radical-intent RT.Tumor biopsies and blood samples were collected pre-RT and at week 2 during RT and analyzed using multiplex immunohistochemistry(mIHC)and high-dimensional mass cytometry(CyTOF),respectively.Results:Paired biopsies were collected from only three patients(Pts 1,3&4)and blood from four patients(Pts 1-4)before the study was closed early during the COVID-19 pandemic.Programmed Death-Ligand 1(PD-L1)expression in the TME was raised in Patient 1,who responded well to treatment,and unaltered in two patients with progressive disease.CyTOF analysis revealed elevated circulating classical monocytes,highest in the patient with a good response.Conclusions:This study underscores the challenges of integrating advanced immune monitoring during RT delivery and did not meet its primary endpoint.The hypothesis-generating findings highlight PD-L1+macrophages in the TME and classical monocytes in the blood as potential immune biomarkers of RT response,but larger studies are needed to validate these observations and characterize the immune changes following curative-intent RT in patients with NSCLC.
文摘Dear Editor,Systemic sclerosis(SSc)is an autoimmune connective tissue disease in which there are vascular abnormalities,inflammation,and fibrosis[1].These three characteristics primarily affect the skin and lungs.Of all the autoimmune rheumatic diseases,SSc has the highest all-cause mortality rate,and the underlying pathogenic processes that mediate disease are still obscure,with wide diff erences in presentation and progression[2,3].
文摘The metastatic pattern of colon cancer is typically well characterized,with initial dissemination occurring through regional lymphatics,followed by hematogenous spread.The most frequent sites of metastasis in colorectal cancer(CRC)include regional lymph nodes(50%–70%),liver(35%–50%),lungs(21%),peritoneum(15%),and ovaries(13%).1 Isolated distant lymph node metastasis,particularly in the absence of concurrent systemic disease,is exceedingly rare in CRC.To date,only six cases of isolated axillary lymph node metastasis(ALNM)from colorectal primaries have been documented in the literature.1–6 Even more uncommon is the incidental discovery of malignant cells in anastomotic doughnuts following stoma reversal procedures.Herein,we report a rare case involving both the incidental histopathological detection of tumor cells within doughnuts during stoma closure and the subsequent development of isolated ALNM after curative resection of sigmoid colon carcinoma.
