Polycystic kidney disease (PKD) is an autosomal dominant genetic disorder that causes the formation of multiple cysts in the kidneys, leading to kidney failure. PKD is a common condition affecting approximately 1 in 5...Polycystic kidney disease (PKD) is an autosomal dominant genetic disorder that causes the formation of multiple cysts in the kidneys, leading to kidney failure. PKD is a common condition affecting approximately 1 in 500 individuals worldwide. The most prevalent type of PKD is autosomal dominant PKD (ADPKD). ADPKD is caused by mutations in either the PKD1 or PKD2 genes, which encode for proteins involved in cell growth and differentiation. These mutations lead to the formation of fluid-filled cysts in the kidneys, which can eventually lead to kidney failure. In addition to affecting the kidneys, PKD can also cause cysts in other organs, such as the liver, pancreas, and spleen. PKD can also lead to various complications, including high blood pressure, heart valve abnormalities, and brain aneurysms. This review focuses on the inheritance, pathophysiology, and treatment of PKD, with a specific emphasis on its effects on the cardiovascular system. Currently, there is no cure for PKD. However, several treatments are available to manage the symptoms and complications of the disease. These treatments include medications to control blood pressure, pain relievers, antibiotics for infections, and dialysis or kidney transplantation for kidney failure. Tolvaptan is the only FDA-approved drug specifically for ADPKD and has been shown to slow disease progression. In addition to summarizing current treatment options, this review will discuss promising future treatments, such as gene therapy and stem cell therapy.展开更多
This editorial discusses Thompson et al's original article,which is published in the most recent edition of the World Journal of Clinical Oncology and sheds critical light on the intertwined issues of health anxie...This editorial discusses Thompson et al's original article,which is published in the most recent edition of the World Journal of Clinical Oncology and sheds critical light on the intertwined issues of health anxiety and work loss in individuals diagnosed with serrated polyposis syndrome(SPS).SPS is rare,characterized by the development of multiple serrated colorectal polyps.This editorial provides an overview of SPS,including its pathophysiology,clinical presentation,diagnostic criteria,management strategies,and the psychosocial impact.SPS is linked to molecular alterations,which drive carcinogenesis.Colonoscopy and histological analysis are used for diagnosis.Genetic testing is also considered where there is a family history.Quality of life can be greatly impacted by the psychosocial effects of SPS,especially health anxiety.Further understanding of the molecular mechanisms and creating individualized surveillance are required.展开更多
This editorial underscores the importance of Maranhão et al’s study,which investigates pleural adenosine deaminase(P-ADA)as a biomarker for inflammatory pleural effusions.Despite advances in imaging,distinguishi...This editorial underscores the importance of Maranhão et al’s study,which investigates pleural adenosine deaminase(P-ADA)as a biomarker for inflammatory pleural effusions.Despite advances in imaging,distinguishing between inflammatory and non-inflammatory causes of pleural effusion remains a diagnostic challenge.The authors conducted a rigorous retrospective cohort analysis of 157 patients(124 with inflammatory exudates and 33 with non-inflammatory transudates),establishing a robust cutoff value of P-ADA≥9.00 U/L for diagnosing inflammatory diseases using receiver operating characteristic curve analysis and internal statistical calibration.This is the first study to define a standardized PADA threshold in a Brazilian cohort,addressing previous inconsistencies in cutoff values.Furthermore,the authors delved into the pathophysiological mechanisms underlying elevated P-ADA,linking it to purinergic signaling pathways and immune cell activation,particularly emphasizing the role of ADA2 isoforms in macrophages and lymphocytes.Their findings support P-ADA as a non-invasive,cost-effective biomarker for early diagnosis,treatment stratification,and minimizing the need for invasive procedures such as thoracentesis.This has particular relevance in resource-limited settings,where streamlined diagnostics can reduce healthcare costs and improve patient outcomes.Future studies must prioritize global validation,explore the integration of adenosine deaminase with additional biomarkers(e.g.,interleukin 6,C-reactive protein),and support the development of point-of-care technologies.展开更多
Splenic histiocytic sarcoma(SHS)is a rare,aggressive hematological malignancy with unclear progression and management.Our case illustrates the progression and pathophysiological processes of SHS and provides key data ...Splenic histiocytic sarcoma(SHS)is a rare,aggressive hematological malignancy with unclear progression and management.Our case illustrates the progression and pathophysiological processes of SHS and provides key data for the diagnosis,treatment and management of SHS.A 60-year-old female with incidentally detected splenic mass(6.0 cm×5.7 cm)underwent splenectomy,confirmed as SHS in 2020.Post-op imatinib therapy was given.In 2022,hepatic metastases(2.4 cm×2.9 cm)with pancytopenia led to supportive care.Lesions enlarged to 4.3 cm×2.7 cm,leading to multi-organ failure and death at 33 months.The case was categorized into three distinct stages based on the pathophysiology of SHS:Early-stage splenic tumor growth,mid-stage liver metastasis with hematological abnormalities,and late-stage tumor infiltration leading to multiorgan failure.For SHS,this case highlights the pivotal role of early intervention and the value of personalized treatment strategies.展开更多
Diabetic foot ulcers(DFUs)are a serious complication of diabetes mellitus and are associated with high morbidity,risk of amputation,and increasedmortality.AlthoughDFUs typically remain a chronic,non-healing wound,a sm...Diabetic foot ulcers(DFUs)are a serious complication of diabetes mellitus and are associated with high morbidity,risk of amputation,and increasedmortality.AlthoughDFUs typically remain a chronic,non-healing wound,a small portion of DFUsmay undergomalignant transformation.The subsequentmalignancies are skin cancers such as squamous cell carcinoma(SCC),basal cell carcinoma,or melanoma.Understanding the pathophysiology of DFUs and themolecular and clinical determinants that contribute to theirpotentialmalignant transformationif crucial for clinical management.Chronic inflammation,dysregulation of cytokine signaling,faulty immune surveillance,and impaired wound healing all play a role in creating a tumor-permissive environment for the diabetic foot.This review highlights molecularmechanisms driving this transformation,including,vascular endothelial growth factor(VEGF)and plateletderived growth factor(PDGF)pathway dysregulation,hypoxia-inducible factor 1-alpha(HIF-1α)mediated angiogenic signaling,chronic osteomyelitis,and oxidative stress,which can collectively promote progression to malignancies,most notably cutaneous squamous cell carcinoma.Classic examples like Marjolin’s ulcer demonstrate how chronic injury can drive carcinogenesis,reinforcing the importance of vigilant DFU management.Connecting findings across clinical reports and mechanistic studies reveals that understandingDFUcarcinogenesis is essential for earlier detection,informed targeted treatment,and improved patient outcomes.展开更多
Autotaxin(ATX or ENPP2) is a secreted glycoprotein widely present in biological fluids. ATX primarily functions as a plasma lysophospholipase D and is largely responsible for the bulk of lysophosphatidic acid(LPA) pro...Autotaxin(ATX or ENPP2) is a secreted glycoprotein widely present in biological fluids. ATX primarily functions as a plasma lysophospholipase D and is largely responsible for the bulk of lysophosphatidic acid(LPA) production in the plasma and at inflamed and/or malignant sites. LPA is a phospholipid mediator produced in various conditions both in cells and in biological fluids, and it evokes growth-factor-like responses, including cell growth, survival, differentiation and motility, in almost all cell types. The large variety of LPA effector functions is attributed to at least six G-protein coupled LPA receptors(LPARs) with overlapping specificities and widespread distribution. Increased ATX/LPA/LPAR levels have been detected in a large variety of cancers and transformed cell lines, as well as in non-malignant inflamed tissues, suggesting a possible involvement of ATX in chronic inflammatory disorders and cancer. In this review, we focus exclusively on the role of the ATX/LPA axis in pulmonary pathophysiology, analysing the effects of ATX/LPA on pulmonary cells and leukocytes in vitro and in the context of pulmonary pathophysi-ological situations in vivo and in human diseases.展开更多
Cirrhosis represents the end stage of chronic liver disease,significantly reducing life expectancy as it progresses from a compensated to a decompensated state,leading to serious complications.Recent improvements in m...Cirrhosis represents the end stage of chronic liver disease,significantly reducing life expectancy as it progresses from a compensated to a decompensated state,leading to serious complications.Recent improvements in medical treatment have created a shift in cirrhosis management.Various causes,including hepatitis viruses,alcohol consumption,and fatty liver disease,contribute to cirrhosis and are closely linked to liver cancer.The disease develops through hepatocyte necrosis and regeneration,resulting in fibrosis and sinusoidal capillarization,leading to portal hypertension and complications such as ascites,hepatic encephalopathy,and organ dysfunction.Cirrhosis also holds an increased risk of hepatocellular carcinoma.Diagnosing cirrhosis involves assessing fibrosis scores through blood tests and measuring liver stiffness through elastography.Liver transplantation is the definitive treatment for endstage liver disease and acute liver failure.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
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
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
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
Coronavirus disease 2019(COVID-19)pandemic,caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),have posed a big threat to human life.The human lung takes the primary hit,characterized by the process ...Coronavirus disease 2019(COVID-19)pandemic,caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),have posed a big threat to human life.The human lung takes the primary hit,characterized by the process ranging from mild syndrome to severe lung injury.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
Objectives:Non-small cell lung cancer(NSCLC)remains a leading cause of cancer-related mortality,with limited understanding of lncRNA-driven mechanisms in tumor progression.This study aimed to identify differentially e...Objectives:Non-small cell lung cancer(NSCLC)remains a leading cause of cancer-related mortality,with limited understanding of lncRNA-driven mechanisms in tumor progression.This study aimed to identify differentially expressed lncRNAs in NSCLC tissues and elucidate the functional role of the significantly upregulated RP3-340N1.2 in promoting malignancy.Methods:RNA sequencing was used to screen dysregulated lncRNAs.RP3-340N1.2 was functionally characterized via gain/loss-of-function assays in NSCLC cells,assessing proliferation,migration,and macrophage polarization.Mechanisms of interleukin 6(IL-6)regulation were explored using cytokine profiling,Actinomycin D assays,and RNA Immunoprecipitation(RIP)assays to study RP3-340N1.2 interactions with zinc finger CCCH-type containing 12A(ZC3H12A)and IL-6 mRNA.Results:RP3-340N1.2 was upregulated in NSCLC tissues and cells.Functional assays demonstrated that RP3-340N1.2 knockdown suppressed NSCLC cell proliferation/migration and reduced macrophage polarization toward tumor-associated phenotypes.Mechanistically,RP3-340N1.2 knockdown promoted IL-6 mRNA degradation,as supported by reduced IL-6 levels and accelerated mRNA decay.Further RIP assays revealed that RP3-340N1.2 interacts with ZC3H12A,an RNA-binding protein previously reported to degrade IL-6 mRNA,and that RP3-340N1.2 knockdown enhanced ZC3H12A binding to IL-6 mRNA.Consequently,RP3-340N1.2 knockdown in carcinoma cells attenuated IL-6-mediated tumor-promoting effects,including tumor cell proliferation and migration.Importantly,these effectswere observed not only in a direct carcinoma cell culturing system but also when carcinoma cells were exposed to conditioned medium from co-culturing RP3-340N1.2-knockdown tumor cells andmacrophages.Conclusion:RP3-340N1.2 drivesNSCLC malignancy by stabilizing IL-6 mRNA;its inhibition offers a potential therapeutic strategy to disrupt tumor-promoting interactions.展开更多
Irritable bowel syndrome(IBS)is one of the most common gastrointestinal disorders,characterized by abdominal pain,bloating,and changes in bowel habits.These symptoms cannot be explained by structural abnormalities and...Irritable bowel syndrome(IBS)is one of the most common gastrointestinal disorders,characterized by abdominal pain,bloating,and changes in bowel habits.These symptoms cannot be explained by structural abnormalities and there is no specific laboratory test or biomarker for IBS.Therefore,IBS is classified as a functional disorder with diagnosis dependent on the history taking about manifested symptoms and careful physical examination.Although a great deal of research has been carried out in this area,the pathophysiology of IBS is complex and not completely understood.Multiple factors are thought to contribute to the symptoms in IBS patients;altered gastrointestinal motility,visceral hypersensitivity,and the brain-gut interaction are important classical concepts in IBS pathophysiology.New areas of research in this arena include inflammation,postinfectious low-grade inflammation,genetic and immunologic factors,an altered microbiota,dietary factors,and enteroendocrine cells.These emerging studies have not shown consistent results,provoking controversy in the IBS field.However,certain lines of evidence suggest that these mechanisms are important at least a subset of IBS patients,confirming that IBS symptoms cannot be explained by a single etiological mechanism.Therefore,it is important to keep in mind that IBS requires a more holistic approach to determining effective treatment and understanding the underlying mechanisms.展开更多
Acute respiratory distress syndrome(ARDS) is a syndrome with heterogeneous underlying pathological processes. It represents a common clinical problem in intensive care unit patients and it is characterized by high mor...Acute respiratory distress syndrome(ARDS) is a syndrome with heterogeneous underlying pathological processes. It represents a common clinical problem in intensive care unit patients and it is characterized by high mortality. The mainstay of treatment for ARDS is lung protective ventilation with low tidal volumes and positive end-expiratory pressure sufficient for alveolar recruitment. Prone positioning is a supplementary strategy available in managing patients with ARDS. It was first described 40 years ago and it proves to be in alignment with two major ARDS pathophysiological lung models; the "sponge lung"- and the "shape matching"-model. Current evidence strongly supports that prone positioning has beneficial effects on gas exchange, respiratory mechanics, lung protection and hemodynamics as it redistributes transpulmonary pressure, stress and strain throughout the lung and unloads the right ventricle. The factors that individually influence the time course of alveolar recruitment and the improvement in oxygenation during prone positioning have not been well characterized. Although patients' response to prone positioning is quite variable and hard to predict, large randomized trials and recent meta-analyses show that prone position in conjunction with a lung-protective strategy, when performed early and in sufficient duration, may improve survival in patients with ARDS. This pathophysiology-based review and recent clinical evidence strongly support the use of prone positioning in the early management of severe ARDS systematically and not as a rescue maneuver or a last-ditch effort.展开更多
文摘Polycystic kidney disease (PKD) is an autosomal dominant genetic disorder that causes the formation of multiple cysts in the kidneys, leading to kidney failure. PKD is a common condition affecting approximately 1 in 500 individuals worldwide. The most prevalent type of PKD is autosomal dominant PKD (ADPKD). ADPKD is caused by mutations in either the PKD1 or PKD2 genes, which encode for proteins involved in cell growth and differentiation. These mutations lead to the formation of fluid-filled cysts in the kidneys, which can eventually lead to kidney failure. In addition to affecting the kidneys, PKD can also cause cysts in other organs, such as the liver, pancreas, and spleen. PKD can also lead to various complications, including high blood pressure, heart valve abnormalities, and brain aneurysms. This review focuses on the inheritance, pathophysiology, and treatment of PKD, with a specific emphasis on its effects on the cardiovascular system. Currently, there is no cure for PKD. However, several treatments are available to manage the symptoms and complications of the disease. These treatments include medications to control blood pressure, pain relievers, antibiotics for infections, and dialysis or kidney transplantation for kidney failure. Tolvaptan is the only FDA-approved drug specifically for ADPKD and has been shown to slow disease progression. In addition to summarizing current treatment options, this review will discuss promising future treatments, such as gene therapy and stem cell therapy.
文摘This editorial discusses Thompson et al's original article,which is published in the most recent edition of the World Journal of Clinical Oncology and sheds critical light on the intertwined issues of health anxiety and work loss in individuals diagnosed with serrated polyposis syndrome(SPS).SPS is rare,characterized by the development of multiple serrated colorectal polyps.This editorial provides an overview of SPS,including its pathophysiology,clinical presentation,diagnostic criteria,management strategies,and the psychosocial impact.SPS is linked to molecular alterations,which drive carcinogenesis.Colonoscopy and histological analysis are used for diagnosis.Genetic testing is also considered where there is a family history.Quality of life can be greatly impacted by the psychosocial effects of SPS,especially health anxiety.Further understanding of the molecular mechanisms and creating individualized surveillance are required.
文摘This editorial underscores the importance of Maranhão et al’s study,which investigates pleural adenosine deaminase(P-ADA)as a biomarker for inflammatory pleural effusions.Despite advances in imaging,distinguishing between inflammatory and non-inflammatory causes of pleural effusion remains a diagnostic challenge.The authors conducted a rigorous retrospective cohort analysis of 157 patients(124 with inflammatory exudates and 33 with non-inflammatory transudates),establishing a robust cutoff value of P-ADA≥9.00 U/L for diagnosing inflammatory diseases using receiver operating characteristic curve analysis and internal statistical calibration.This is the first study to define a standardized PADA threshold in a Brazilian cohort,addressing previous inconsistencies in cutoff values.Furthermore,the authors delved into the pathophysiological mechanisms underlying elevated P-ADA,linking it to purinergic signaling pathways and immune cell activation,particularly emphasizing the role of ADA2 isoforms in macrophages and lymphocytes.Their findings support P-ADA as a non-invasive,cost-effective biomarker for early diagnosis,treatment stratification,and minimizing the need for invasive procedures such as thoracentesis.This has particular relevance in resource-limited settings,where streamlined diagnostics can reduce healthcare costs and improve patient outcomes.Future studies must prioritize global validation,explore the integration of adenosine deaminase with additional biomarkers(e.g.,interleukin 6,C-reactive protein),and support the development of point-of-care technologies.
基金Supported by the Program of General Hospital of Western Theater,No.2021-XZYG-C33.
文摘Splenic histiocytic sarcoma(SHS)is a rare,aggressive hematological malignancy with unclear progression and management.Our case illustrates the progression and pathophysiological processes of SHS and provides key data for the diagnosis,treatment and management of SHS.A 60-year-old female with incidentally detected splenic mass(6.0 cm×5.7 cm)underwent splenectomy,confirmed as SHS in 2020.Post-op imatinib therapy was given.In 2022,hepatic metastases(2.4 cm×2.9 cm)with pancytopenia led to supportive care.Lesions enlarged to 4.3 cm×2.7 cm,leading to multi-organ failure and death at 33 months.The case was categorized into three distinct stages based on the pathophysiology of SHS:Early-stage splenic tumor growth,mid-stage liver metastasis with hematological abnormalities,and late-stage tumor infiltration leading to multiorgan failure.For SHS,this case highlights the pivotal role of early intervention and the value of personalized treatment strategies.
文摘Diabetic foot ulcers(DFUs)are a serious complication of diabetes mellitus and are associated with high morbidity,risk of amputation,and increasedmortality.AlthoughDFUs typically remain a chronic,non-healing wound,a small portion of DFUsmay undergomalignant transformation.The subsequentmalignancies are skin cancers such as squamous cell carcinoma(SCC),basal cell carcinoma,or melanoma.Understanding the pathophysiology of DFUs and themolecular and clinical determinants that contribute to theirpotentialmalignant transformationif crucial for clinical management.Chronic inflammation,dysregulation of cytokine signaling,faulty immune surveillance,and impaired wound healing all play a role in creating a tumor-permissive environment for the diabetic foot.This review highlights molecularmechanisms driving this transformation,including,vascular endothelial growth factor(VEGF)and plateletderived growth factor(PDGF)pathway dysregulation,hypoxia-inducible factor 1-alpha(HIF-1α)mediated angiogenic signaling,chronic osteomyelitis,and oxidative stress,which can collectively promote progression to malignancies,most notably cutaneous squamous cell carcinoma.Classic examples like Marjolin’s ulcer demonstrate how chronic injury can drive carcinogenesis,reinforcing the importance of vigilant DFU management.Connecting findings across clinical reports and mechanistic studies reveals that understandingDFUcarcinogenesis is essential for earlier detection,informed targeted treatment,and improved patient outcomes.
基金Supported by National Grants from the Hellenic Ministry of Education,Lifelong Learning and Religious Affairs,No.09SYN-12-679/680
文摘Autotaxin(ATX or ENPP2) is a secreted glycoprotein widely present in biological fluids. ATX primarily functions as a plasma lysophospholipase D and is largely responsible for the bulk of lysophosphatidic acid(LPA) production in the plasma and at inflamed and/or malignant sites. LPA is a phospholipid mediator produced in various conditions both in cells and in biological fluids, and it evokes growth-factor-like responses, including cell growth, survival, differentiation and motility, in almost all cell types. The large variety of LPA effector functions is attributed to at least six G-protein coupled LPA receptors(LPARs) with overlapping specificities and widespread distribution. Increased ATX/LPA/LPAR levels have been detected in a large variety of cancers and transformed cell lines, as well as in non-malignant inflamed tissues, suggesting a possible involvement of ATX in chronic inflammatory disorders and cancer. In this review, we focus exclusively on the role of the ATX/LPA axis in pulmonary pathophysiology, analysing the effects of ATX/LPA on pulmonary cells and leukocytes in vitro and in the context of pulmonary pathophysi-ological situations in vivo and in human diseases.
文摘Cirrhosis represents the end stage of chronic liver disease,significantly reducing life expectancy as it progresses from a compensated to a decompensated state,leading to serious complications.Recent improvements in medical treatment have created a shift in cirrhosis management.Various causes,including hepatitis viruses,alcohol consumption,and fatty liver disease,contribute to cirrhosis and are closely linked to liver cancer.The disease develops through hepatocyte necrosis and regeneration,resulting in fibrosis and sinusoidal capillarization,leading to portal hypertension and complications such as ascites,hepatic encephalopathy,and organ dysfunction.Cirrhosis also holds an increased risk of hepatocellular carcinoma.Diagnosing cirrhosis involves assessing fibrosis scores through blood tests and measuring liver stiffness through elastography.Liver transplantation is the definitive treatment for endstage liver disease and acute liver failure.
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 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.
基金supported by National Natural Science Foundation of China (82272943)Shanghai Municipal Science and Technology Commission (21Y11913400)+1 种基金Fundamental Research Funds for the Central UniversitiesNational 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Coronavirus disease 2019(COVID-19)pandemic,caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),have posed a big threat to human life.The human lung takes the primary hit,characterized by the process ranging from mild syndrome to severe lung injury.
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.
基金supported by the National Natural Science Foundation of China(No.81702296).
文摘Objectives:Non-small cell lung cancer(NSCLC)remains a leading cause of cancer-related mortality,with limited understanding of lncRNA-driven mechanisms in tumor progression.This study aimed to identify differentially expressed lncRNAs in NSCLC tissues and elucidate the functional role of the significantly upregulated RP3-340N1.2 in promoting malignancy.Methods:RNA sequencing was used to screen dysregulated lncRNAs.RP3-340N1.2 was functionally characterized via gain/loss-of-function assays in NSCLC cells,assessing proliferation,migration,and macrophage polarization.Mechanisms of interleukin 6(IL-6)regulation were explored using cytokine profiling,Actinomycin D assays,and RNA Immunoprecipitation(RIP)assays to study RP3-340N1.2 interactions with zinc finger CCCH-type containing 12A(ZC3H12A)and IL-6 mRNA.Results:RP3-340N1.2 was upregulated in NSCLC tissues and cells.Functional assays demonstrated that RP3-340N1.2 knockdown suppressed NSCLC cell proliferation/migration and reduced macrophage polarization toward tumor-associated phenotypes.Mechanistically,RP3-340N1.2 knockdown promoted IL-6 mRNA degradation,as supported by reduced IL-6 levels and accelerated mRNA decay.Further RIP assays revealed that RP3-340N1.2 interacts with ZC3H12A,an RNA-binding protein previously reported to degrade IL-6 mRNA,and that RP3-340N1.2 knockdown enhanced ZC3H12A binding to IL-6 mRNA.Consequently,RP3-340N1.2 knockdown in carcinoma cells attenuated IL-6-mediated tumor-promoting effects,including tumor cell proliferation and migration.Importantly,these effectswere observed not only in a direct carcinoma cell culturing system but also when carcinoma cells were exposed to conditioned medium from co-culturing RP3-340N1.2-knockdown tumor cells andmacrophages.Conclusion:RP3-340N1.2 drivesNSCLC malignancy by stabilizing IL-6 mRNA;its inhibition offers a potential therapeutic strategy to disrupt tumor-promoting interactions.
文摘Irritable bowel syndrome(IBS)is one of the most common gastrointestinal disorders,characterized by abdominal pain,bloating,and changes in bowel habits.These symptoms cannot be explained by structural abnormalities and there is no specific laboratory test or biomarker for IBS.Therefore,IBS is classified as a functional disorder with diagnosis dependent on the history taking about manifested symptoms and careful physical examination.Although a great deal of research has been carried out in this area,the pathophysiology of IBS is complex and not completely understood.Multiple factors are thought to contribute to the symptoms in IBS patients;altered gastrointestinal motility,visceral hypersensitivity,and the brain-gut interaction are important classical concepts in IBS pathophysiology.New areas of research in this arena include inflammation,postinfectious low-grade inflammation,genetic and immunologic factors,an altered microbiota,dietary factors,and enteroendocrine cells.These emerging studies have not shown consistent results,provoking controversy in the IBS field.However,certain lines of evidence suggest that these mechanisms are important at least a subset of IBS patients,confirming that IBS symptoms cannot be explained by a single etiological mechanism.Therefore,it is important to keep in mind that IBS requires a more holistic approach to determining effective treatment and understanding the underlying mechanisms.
文摘Acute respiratory distress syndrome(ARDS) is a syndrome with heterogeneous underlying pathological processes. It represents a common clinical problem in intensive care unit patients and it is characterized by high mortality. The mainstay of treatment for ARDS is lung protective ventilation with low tidal volumes and positive end-expiratory pressure sufficient for alveolar recruitment. Prone positioning is a supplementary strategy available in managing patients with ARDS. It was first described 40 years ago and it proves to be in alignment with two major ARDS pathophysiological lung models; the "sponge lung"- and the "shape matching"-model. Current evidence strongly supports that prone positioning has beneficial effects on gas exchange, respiratory mechanics, lung protection and hemodynamics as it redistributes transpulmonary pressure, stress and strain throughout the lung and unloads the right ventricle. The factors that individually influence the time course of alveolar recruitment and the improvement in oxygenation during prone positioning have not been well characterized. Although patients' response to prone positioning is quite variable and hard to predict, large randomized trials and recent meta-analyses show that prone position in conjunction with a lung-protective strategy, when performed early and in sufficient duration, may improve survival in patients with ARDS. This pathophysiology-based review and recent clinical evidence strongly support the use of prone positioning in the early management of severe ARDS systematically and not as a rescue maneuver or a last-ditch effort.
