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The effects of co-occurrent pollutants on antibiotic resistance genes (ARGs) in wastewater treatment plants (WWTPs) have raised attentions. However, how the different realistic exposure scenarios determining the effects of nanomaterials (NMs) on ARGs, was still unknown. Herein, the effects of NMs on ARGs under two realistic scenarios was investigated by short-term and long-term exposure modes. The presence of NMs with two different exposure modes could both promote the dissemination of ARGs, and the results were dose-, type- and duration-dependent. Compared to short-term exposure, the long-term exposure increased the abundances of ARGs with a greater extent except nano-ZnO. The long-term exposure increased the overall abundances of target ARGs by 2.9%-20.4%, while shot-term exposure caused the 3.4%-10.5% increment. The mechanisms of ARGs fates driven by NMs exposure were further investigated from the levels of microbial community shift, intracellular oxidative stress, and gene abundance. The variations of several potential bacterial hosts did not contribute to the difference in the ARGs transmission with different exposure modes because NMs types played more vital roles in the shift of microbial community compared to the exposure modes. For the short-term exposure, NMs were capable of triggering the QS by upregulating relevant genes, and further activated the production of surfactin and increased membrane permeability, resulting in the facilitation of ARGs transfer. However, NMs under long-term exposure scenario preferentially stimulated oxidative stress by generating more ROS, which then enhanced ARGs dissemination. Therefore, the exposure mode of NMs was one of the pivotal factors determining the ARGs fates by different triggering mechanisms. This study highlighted the importance of exposure scenario of co-occurrent pollutants on ARGs spread, which will benefit the comprehensive understanding of the actual environmental fates of ARGs.
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BACKGROUND: Distant metastatic parathyroid carcinoma (DM-PC) is a rare but often lethal entity with limited data about prognostic indicators. We sought to investigate the risk factors, patterns, and outcomes of DM-PC. METHODS: In this observational cohort study, 126 patients who underwent surgery for PC at a tertiary referral center from 2010 to 2023 were enrolled, among whom 38 had DMs. Univariate and multivariate Cox regression analyses were used to assess the effects of prognostic factors on DM. RESULTS: The cumulative incidence of DM was 14.1%, 33.8%, and 66.9% at 5, 10, and 20 years in the duration of disease course, respectively. DM-PC patients suffered a worse 5-year overall survival of 37.1% compared with 89.8% in the non-DM patients (p < 0.001). DM-PC patients also suffered more previous operations (p < 0.001), higher preoperative serum calcium (p<0.001) and parathyroid hormone (PTH) levels (p < 0.001), lower frequencies of R0 resection (p < 0.001), higher rates of pathological vascular invasion (p = 0.020), thyroid infiltration (p = 0.027), extraglandular extension (p = 0.001), upper aerodigestive tract (UAT) invasion (p < 0.001), and lymph node metastasis (p < 0.001). Multivariate Cox regression revealed that non-R0 resection (HR 6.144, 95% CI 2.881-13.106, p < 0.001), UAT invasion (HR 3.718, 95% CI 1.782-7.756, p < 0.001), and higher preoperative PTH levels (HR 1.001, 95% CI 1.000-1.001, p = 0.012) were independent risk factors of DM. CONCLUSIONS: Upper aerodigestive tract invasion and higher preoperative PTH levels might be risk factors for possible metastatic involvement of PC. R0 resection and closer surveillance should be considered in such cases to minimize the risk of DM and to optimize patient care.
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Sludge is one of the primary reservoirs of microplastics (MPs), and the effects of MPs on subsequent sludge treatment raised attention. Given the entry pathways, MPs would exhibit different properties, but the entry pathway-dependent effect of MPs on sludge treatment performance and the fates of antibiotic resistance genes (ARGs), another high-risk emerging contaminant, were seldom documented. Herein, MPs with two predominant entry pathways, including wastewater-derived (WW-derived) and anaerobic digestion-introduced (AD-introduced), were used to investigate the effects on AD performance and ARGs abundances. The results indicated that WW-derived MPs, namely the MPs accumulated in sludge during the wastewater treatment process, exhibited significant inhibition on methane production by 22.8%-71.6%, while the AD-introduced MPs, being introduced in the sludge AD process, slightly increased the methane yield by 4.7%-17.1%. Meanwhile, MPs were responsible for promoting transmission of target ARGs, and polyethylene terephthalate MPs (PET-MPs) showed a greater promotion effect (0.0154-0.0936) than polyamide MPs (PA-MPs) (0.0013-0.0724). Compared to size, entry pathways and types played more vital roles on MPs influences. Investigation on mechanisms based on microbial community structure revealed characteristics (aging degree and types) of MPs determined the differences of AD performance and ARGs fates. WW-derived MPs with longer aging period and higher aging degree would release toxics and decrease the activities of microorganisms, resulting in the negative impact on AD performance. However, AD-introduced MPs with short aging period exhibited marginal impacts on AD performance. Furthermore, the co-occurrent network analysis suggested that the variations of potential host bacteria induced by MPs with different types and aging degree attributed to the dissemination of ARGs. Distinctively from most previous studies, the MPs with different sizes did not show remarkable effects on AD performance and ARGs fates. Our findings benefited the understanding of realistic environmental behavior and effect of MPs with different sources.
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Metano , Microplásticos , Aguas del Alcantarillado , Metano/metabolismo , Aguas del Alcantarillado/microbiología , Anaerobiosis , Microplásticos/toxicidad , Eliminación de Residuos Líquidos , Farmacorresistencia Microbiana/genética , Contaminantes Químicos del Agua/análisis , Contaminantes Químicos del Agua/toxicidadRESUMEN
Chronic obstructive pulmonary disease (COPD) is a chronic inflammatory airway disease characterized by progressive respiratory difficulties. It has a high incidence and disability rate worldwide. However, currently there is still a lack of highly effective treatment methods for COPD, only symptom relief is possible. Therefore, there is an urgent need to explore new treatment options. Almost all cells can secrete extracellular vesicles (EVs), which participate in many physiological activities by transporting cargoes and are associated with the pathogenesis of various diseases. Recently, many scholars have extensively studied the relationship between COPD and EVs, which has strongly demonstrated the significant impact of EVs from different sources on the occurrence and development of COPD. Therefore, EVs are a good starting point and new opportunity for the diagnosis and treatment of COPD. In this review, we mainly describe the current mechanisms of EVs in the pathogenesis of COPD, also the relationship between diagnosis, prognosis, and treatment. At the same time, we also introduce some new methods for COPD therapy based on EVs. It is hoped that this article can provide new ideas for future research and contribute to the development of precision medicine.
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Vesículas Extracelulares , Medicina de Precisión , Enfermedad Pulmonar Obstructiva Crónica , Enfermedad Pulmonar Obstructiva Crónica/metabolismo , Enfermedad Pulmonar Obstructiva Crónica/terapia , Humanos , Vesículas Extracelulares/metabolismo , Medicina de Precisión/métodos , Animales , PronósticoRESUMEN
OBJECTIVES: To evaluate the safety and feasibility of removing drainage tubes at larger size of air leak in patients with prolonged air leak after pulmonary surgery. METHODS: Ninety-five patients who underwent pulmonary surgery with prolonged air leak in our centre were enrolled in this randomized controlled, single-centre, non-inferiority study. The drainage tube was clamped with a stable size of air leak observed over the last 6 h, which was quantified by gas flow rate using the digital drainage system. The control group (n = 48) and the study group (n = 46) had their drainage tube clamped at 0-20 ml/min and 60-80 ml/min, respectively. We continuously monitored clinical symptoms, conducted imaging and laboratory examinations, and decided whether to reopen the drainage tube. RESULTS: The reopening rate in the study group was not lower than that in the control group (2.08% vs 6.52%, P > 0.05). The absolute difference in reopening rate was 4.44% (95% confidence interval -0.038 to 0.126), with an upper limit of 12.6% below the non-inferiority margin (15%). There were significant differences in the length of stay [16.5 (13-24.75) vs 13.5 (12-19.25), P = 0.017] and the duration of drainage [12 (9.25-18.50) vs 10 (8-12.25), P = 0.007] between the control and study groups. No notable differences were observed in chest X-ray results 14 days after discharge or in the readmission rate. CONCLUSIONS: For patients with prolonged air leak, removing drainage tubes at larger size of air leak demonstrated similar safety compared to smaller size of air leak, and can shorten both length of stay and drainage duration. CLINICAL TRIAL REGISTRATION NUMBER: Name of registry: Gas flow threshold for safe removal of chest drainage in patients with alveolar-pleural fistula prolonged air leak after pulmonary surgery. Registration number: ChiCTR2200067120. URL: https://www.chictr.org.cn/.
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Tubos Torácicos , Remoción de Dispositivos , Humanos , Drenaje/métodos , Tiempo de Internación , Enfermedades Pleurales , Neumonectomía/métodos , Neumotórax/etiología , Neumotórax/diagnóstico , Remoción de Dispositivos/efectos adversosRESUMEN
INTRODUCTION AND IMPORTANCE: The elbow is one of the most mobile joints, and its movement is very important. Bony ankylosed elbow is an uncommon condition leading to complete loss of activity of elbow, and then lead to severe disability and limitation in activities of daily living. CASE PRESENTATION: A 63-year-old woman sustained comminuted fracture of left distal humerus. She underwent open reduction and internal fixation by plates. After the plates were removed in 2016ï¼stiffness developed.The elbow was stable but fixed at 90°ï¼there was no vascular injury or deficit in sensory and motor function of the ulnar nerve. She hopes to eliminate pain and restore normal mobility compatible with ADL. CLINICAL DISCUSSION: Complete bony ankylosis of the elbow joint may be caused by trauma, rheumatic disease, burns, congenital stiffness and other conditions. Even with the compensation of shoulder and wrist, it will still have a great impact on upper limb function. Whether to treat mainly depends on whether the patient has the require to improve the functionality and return to daily activities. Treatment methods are very limited, including interposition arthroplasty and TEA. Defect of soft tissue appeared was seen in our case, Hernia Patch was innovatively applied to reconstruct the defect of soft tissue and maintain continuity of elbow extension mechanism. CONCLUSION: Patients with post-traumatic elbow joint ankylosis were suffered from severe bony abnormalities, but also soft tissue contracture or defects due to multiple operations and trauma. We present a case of complete bony ankylosed elbow treated with total elbow arthroplasty and Hernia Patch.
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The continuously increased production of various chemicals and their release into environments have raised potential negative effects on ecological health. However, traditional labor-intensive assessment methods cannot effectively and rapidly evaluate these hazards, especially for chronic risk. In this study, machine learning (ML) was employed to construct quantitative structure-activity relationship (QSAR) models, enabling the prediction of chronic toxicity to aquatic organisms by leveraging the molecular characteristics of pollutants, namely, the molecular descriptors, fingerprints, and graphs. The limited dataset size hindered the notable advantages of the graph attention network (GAT) model for the molecular graphs. Considering computational efficiency and performance (R2 = 0.78; RMSE = 0.77), XGBoost (XGB) was used for reliable QSAR-ML models predicting chronic toxicity using small- or medium-sized tabular data and the molecular descriptors. Further kernel density estimation analysis confirmed the high accuracy of the model for pollutant concentrations ranging from 10-3 to 102 mg/L, effectively aligning with most environmental scenarios. Model interpretation showed SlogP and exposure duration as the primary influential factors. SlogP, representing the distribution coefficient of a molecule between lipophilic and hydrophilic environments, had a negative effect on the toxicity outcomes. Additionally, the exposure duration played a crucial role in determining the chronic toxicity. Finally, the chronic toxicity data of bisphenol A validated the robustness and reliability of the model established in this research. Our study provided a robust and feasible methodology for chronic ecological risk evaluation of various types of pollutants and could facilitate and increase the use of ML applications in environmental fields.
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Contaminantes Ambientales , Aprendizaje Automático , Reproducibilidad de los Resultados , Medición de Riesgo , Relación Estructura-Actividad CuantitativaRESUMEN
Osteoarthritis seriously affects the health of elderly individuals. In this study, hyaluronic acid-gold nano-optical probes (HA-GNPs) were prepared, and their effect on osteoarthritis and its underlying mechanism were explored. The HA-GNPs were synthesised via a one-step synthesis method and characterised and detected via ultraviolet-visible spectrophotometry, dynamic light scattering (particle size analysis), zeta potential analysis, and scanning and transmission electron microscopy. The cytotoxicity of the probes was determined using CCK-8 detection, fluorescent staining of dead and living cells, and an in vivo animal model, and related staining methods were established to identify the potential therapeutic capabilities of the probes. Our study showed that the synthesised HA-GNPs were more stable and suitable for probe construction than traditional sodium citrate-gold nanoparticles. The HA-GNPs were also found to be biocompatible and suitable for in vitro and in vivo experiments and clinical applications. These findings showed that HA-GNPs exert a substantial inhibitory effect on osteoarticular chondrocytes and offer a promising method for improving healing from osteoarthritis in the clinical setting in the future.
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Nanopartículas del Metal , Osteoartritis , Animales , Oro/uso terapéutico , Nanopartículas del Metal/uso terapéutico , Ácido Hialurónico , Osteoartritis/tratamiento farmacológico , Microscopía Electrónica de TransmisiónRESUMEN
Osteosarcoma (OS) is the most common malignant tumor of the bone tissue with the lowest survival rate among all pediatric cancers. OS cells grow vigorously under malnutrition; however, the mechanism by which they adapt to metabolic stress via metabolic reprogramming remains undefined. Here, we demonstrated that USP33, a member of the DUBs family, was significantly upregulated in the tissues of patients with OS compared to normal tissues. Moreover, high USP33 expression was significantly associated with poor survival. Functional assays suggested that USP33 promoted OS cell growth through the induction of aerobic glycolysis. Additionally, we confirmed that 6-phosphofructo-2-kinase/fructose-2, 6-biphosphatase 3 (PFKFB3) was critical for USP33-induced proliferation and aerobic glycolysis in OS cells, and the protein expression levels of PFKFB3 and USP33 were positively correlated in the OS tissues. Mechanistically, USP33 stabilized the expression of PFKFB3 by suppressing the ubiquitin mediated PFKFB3 degradation. Collectively, these findings reveal a mechanism by which OS cells survive in a dystrophic tumor microenvironment, with the USP33-PFKFB3 axis as a critical driver of aerobic glycolysis and OS proliferation. Furthermore, these findings reveal novel insights into the adaptation of cancer cells to metabolic stress in OS.
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BACKGROUND: To investigate the effect of continuous oral aspirin in perioperative period on bleeding in pneumonectomy. METHODS: A total of 170 patients who underwent pneumonectomy in our hospital from March 2021 to March 2022 were selected as the study objects. All patients took oral aspirin before surgery and did not take other antiplatelet agent or anticoagulants at the same time. The continuation group included 85 cases and continued to take aspirin 100 mg/day during the perioperative period, and the interruption group included 85 cases who stopped aspirin for 7 days before surgery and 3 days after surgery, without bridging therapy. The intraoperative blood loss, operation time, conversion to thoracotomy rate, postoperative bleeding rate, blood transfusion rate, thrombotic events, postoperative drainage volume, length of hospital stay, and total hospital cost of the two groups were compared. RESULTS: There were no statistically significant differences in intraoperative blood loss, operative time, rate of conversion to open, postoperative drainage, hospital stay, and cost between the two groups (p > 0.05), and there were no reoperations due to bleeding between the two groups. CONCLUSIONS: Aspirin should be continued throughout the perioperative period in all high-risk patients requiring pneumonectomy after balancing ischemic-bleeding risks.
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Aspirina , Pérdida de Sangre Quirúrgica , Humanos , Neumonectomía , Estudios Retrospectivos , Inhibidores de Agregación PlaquetariaRESUMEN
Background: Postoperative cerebral infarction (PCI) is serious complication for thoracic surgery patients, however, the risk factors still unclear. This study sought to investigate the incidence risk factors of postoperative cerebral infarction after thoracic surgery. Methods: Patients who underwent thoracic surgery from 2011 to 2022 at Beijing Chaoyang Hospital were identified and followed-up for 30 days postoperatively to determine the primary outcome of PCI. Patients with PCI were identified as the PCI cohort, and those without PCI were identified as the non-PCI cohort. The clinical data of all the patients were collected. The Mann-Whitney U test and chi-square test were used to analyze the baseline differences. Propensity-score matching (PSM) at a ratio of 1:4 was used to match the variables between the 2 cohorts, and a stepwise univariate conditional logistic regression was used to analyze the risk factors of PCI. Results: We enrolled 8,448 consecutive patients who underwent thoracic surgeries, including 21 with PCI and 8,827 without PCI. Among the 21 PCI patients, 6 patients died. A history of cerebral infarction [odds ratio (OR) = 4.38, P=0.037], perioperative blood transfusion (OR =6.22, P=0.013), a history of deep vein thrombosis (DVT) (OR =5.25, P=0.022), and hyperlipidemia (OR =13.76, P<0.01) were identified as independent risk factors among all the factors by the univariate logistical analysis after the PSM of the other covariates at a ratio of 1:4. Conclusions: PCI patients who undergo thoracic surgery have a poor prognosis. A history of cerebral infarction, perioperative blood transfusion, a history of DVT, and hyperlipidemia are risk factors of PCI. Patients with risk factors may need prevention measure and assist clinician for early diagnosis of PCI.
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BACKGROUND: Increasing evidence has demonstrated the clinical importance of hypoxia and its related factors in lung adenocarcinoma (LUAD). METHODS: RNA-seq datasets from The Cancer Genome Atlas (TCGA) were analyzed using the differentially expressed genes in hypoxia pathway by the Least Absolute Shrinkage and Selection Operator (LASSO) model. Applying gene ontology (GO) and gene set enrichment analysis (GSEA), a risk signature associated with the survival of LUAD patients was constructed between LUAD and normal tissue. RESULTS: In total, 166 hypoxia-related genes were identified. Based on the LASSO Cox regression, 12 genes were selected for the development of the risk signature. Then, we designed an OS-associated nomogram that included the risk score and clinical factors. The concordance index of the nomogram was 0.724. ROC curve showed better predictive ability using the nomogram (AUC = 0.811 for 5-year OS). Finally, the expressions of the 12 genes were validated in two external datasets and EXO1 was recognized as a potential biomarker in the progression of LUAD patients. CONCLUSIONS: Overall, our data suggested that hypoxia is associated with the prognosis, and EXO1 acted as a promising biomarker in LUAD.
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Adenocarcinoma del Pulmón , Neoplasias Pulmonares , Humanos , Pronóstico , Adenocarcinoma del Pulmón/genética , Hipoxia/genética , Relevancia Clínica , Neoplasias Pulmonares/genética , Exodesoxirribonucleasas , Enzimas Reparadoras del ADNRESUMEN
Due to the shortage of defect samples and the high cost of labelling during the process of hot-rolled strip production in the metallurgical industry, it is difficult to obtain a large quantity of defect data with diversity, which seriously affects the identification accuracy of different types of defects on the steel surface. To address the problem of insufficient defect sample data in the task of strip steel defect identification and classification, this paper proposes the Strip Steel Surface Defect-ConSinGAN (SDE-ConSinGAN) model for strip steel defect identification which is based on a single-image model trained by the generative adversarial network (GAN) and which builds a framework of image-feature cutting and splicing. The model aims to reduce training time by dynamically adjusting the number of iterations for different training stages. The detailed defect features of training samples are highlighted by introducing a new size-adjustment function and increasing the channel attention mechanism. In addition, real image features will be cut and synthesized to obtain new images with multiple defect features for training. The emergence of new images is able to richen generated samples. Eventually, the generated simulated samples can be directly used in deep-learning-based automatic classification of surface defects in cold-rolled thin strips. The experimental results show that, when SDE-ConSinGAN is used to enrich the image dataset, the generated defect images have higher quality and more diversity than the current methods do.
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BACKGROUND: Venous thromboembolism (VTE) is a common postoperative complication in patients with lung cancer that seriously affects prognosis and quality of life. At present, the detection rate of patients with early-stage lung cancer is increasing, but there are few studies on the risk factors for postoperative venous thromboembolism (VTE) in patients with stage IA non-small cell lung cancer (NSCLC). This study aimed to establish a nomogram for predicting the probability of postoperative VTE risk in patients with stage IA NSCLC. METHODS: The clinical data of 452 patients with stage IA NSCLC from January 2017 to January 2022 in our center were retrospectively analyzed and randomly divided into a training set and a validation set at a ratio of 7:3. Independent risk factors were identified by univariate and multivariate logistic regression analyses, and a nomogram was established based on the results and internally validated. The predictive power of the nomogram was evaluated by receiver operating characteristic curve (ROC), calibration curve, and decision curve analysis (DCA). RESULTS: The nomogram prediction model included three risk factors: age, preoperative D-dimer, and intermuscular vein dilatation. The areas under the ROC curve of this predictive model were 0.832 (95% CI: 0.732-0.924) and 0.791 (95% CI: 0.668-0.930) in the training and validation sets, respectively, showing good discriminative power. In addition, the probability of postoperative VTE occurrence predicted by the nomogram was consistent with the actual occurrence probability. In the decision curve, the nomogram model had a better net clinical benefit at a threshold probability of 5%-90%. CONCLUSION: This study is the first to develop a nomogram for predicting the risk of postoperative VTE in patients with stage IA NSCLC; this nomogram can accurately and intuitively evaluate the probability of VTE in these patients and help clinicians make decisions on prevention and treatment.
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Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Tromboembolia Venosa , Humanos , Carcinoma de Pulmón de Células no Pequeñas/cirugía , Carcinoma de Pulmón de Células no Pequeñas/complicaciones , Neoplasias Pulmonares/cirugía , Neoplasias Pulmonares/complicaciones , Nomogramas , Calidad de Vida , Estudios Retrospectivos , Factores de Riesgo , Tromboembolia Venosa/diagnóstico , Tromboembolia Venosa/epidemiología , Tromboembolia Venosa/etiologíaRESUMEN
The survival benefit of icotinib (an oral epidermal growth factor receptor [EGFR] tyrosine kinase inhibitor) in patients with advanced lung cancer has been confirmed in several studies. This study (ICAPE) evaluated the efficacy of icotinib as adjuvant therapy for patients with stage IIA-IIIA EGFR-mutant non-small-cell lung adenocarcinoma. Patients with stage IIA-IIIA EGFR-mutant non-small-cell lung adenocarcinoma were enrolled in the multicenter, open-label, single-arm, phase II study. Eligible patients received oral icotinib 125 mg thrice daily for 1.5 years after complete surgical resection. The primary endpoint was disease-free survival (DFS). Between March 2014 and January 2018, 79 patients were enrolled. The median follow-up time was 39.7 months with a median DFS and overall survival (OS) of 41.4 months (95% CI: 33.6-51.8) and 67.0 months (95% CI: 21.2-not reached [NR]), respectively. The 1-year, 3-year, and 5-year OS rates were 100%, 83.3%, and 61.7%, respectively. No significant difference was found in the median DFS between patients with Bcl-2 interacting mediator of cell death (BIM) mutant-type and wild-type (NR vs. 41.7 months; p = 0.75). No significant difference was found in the median DFS according to EGFR mutation types. Icotinib as adjuvant therapy demonstrated a favorable survival benefit in patients with stage IIA-IIIA EGFR-mutant non-small-cell lung adenocarcinoma, indicating that icotinib might be a promising treatment option for this patient population. The optimal adjuvant duration of icotinib is still not clear and needs more incoming data to answer.
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Adenocarcinoma del Pulmón , Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Humanos , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/genética , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Pulmón de Células no Pequeñas/patología , Adenocarcinoma del Pulmón/tratamiento farmacológico , Adenocarcinoma del Pulmón/genética , Receptores ErbB/genéticaRESUMEN
BACKGROUND: Circular RNAs (circRNAs) play a key role in regulating the drug resistance of numerous human tumors. However, whether circKRT17 involves in the osimertinib resistance of lung adenocarcinoma (LUAD) remains undetermined. METHODS: Relative mRNA/circRNA and protein levels were detected by qRT-PCR and western blotting. Localization of circKRT17 and YAP1 was determined by FISH and immunofluorescence staining. Cell growth and apoptosis were evaluated using colony formation, EdU assays, and flow cytometry. The N6-methyladenosine (m6A) modification was analyzed by MeRIP. The interplay between EIF4A3 and circKRT17 or YAP1 was verified by RNA pull-down or/and RIP assays. Subcutaneous tumor growth was monitored in nude mice, and Ki-67 and TUNEL staining were carried out to evaluate cell proliferation and apoptosis, respectively. RESULTS: CircKRT17 and METTL3 were elevated in osimertinib-insensitive LUAD tissues and cells. Knockdown of circKRT 17 and METTL3 increased the sensitivity of LUAD cells to osimertinib. Knockdown of METTL3 decreased the expression of circKRT17 by inhibiting m6A modification. CircKRT17 promoted the stability and nuclear transportation of YAP1 by recruiting EIF4A3 in LUAD cells. Overexpression of YAP1 abolished the impacts of circKRT17 knockdown on the osimertinib sensitivity of LUAD cells. CircKRT17 knockdown increased the repressive effects of osimertinib on tumor growth in vivo by inhibiting YAP1 signaling. CONCLUSION: METTL3 initiated the m6A modification of circKRT17, thus promoting osimertinib resistance of LUAD by enhancing YAP1 stability through EIF4A4 recruitment.
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Background: Recently, the new World Health Organization (WHO) tumor classification removed adenocarcinoma in situ (AIS) from the diagnosis of lung cancer. However, it remains unclear whether the "malignancy" item should be assessed when the modified Caprini Risk Assessment Model (RAM) is used to assess venous thromboembolism (VTE) risk in AIS. The purpose of our study is to assess differences between AIS and stage IA adenocarcinoma (AD) from a VTE perspective. Methods: A retrospective study was performed on AIS and IA adenocarcinoma in our hospital from January 2018 to December 2021, and divided into AIS group and AD group. Propensity score matching (PSM) was used to compare the incidence of VTE and coagulation function, and to analyze whether the RAM is more effective when the "malignancy" item is not evaluated in AIS. Results: 491 patients were included after screening, including 104 patients in the AIS group and 387 patients in the AD group. After PSM, 83 patients were matched. The incidence of VTE and D-dimer in the AIS group was significantly lower than that in the AD group (P<0.05).When using the RAM to score AIS, compared with retaining the "malignancy" item, the incidence of VTE in the intermediate-high-risk group was significantly higher after removing the item (7.9% vs. 36.4%, P=0.018), which significantly improved the stratification effect of the model. Conclusions: The incidence of postoperative VTE in AIS was significantly lower than that in stage IA adenocarcinoma. The stratification effect was more favorable when the "malignancy" item was not evaluated in AIS using the RAM.