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BACKGROUND: Circular RNAs (circRNA) are pivotal in hematological diseases. Previous study showed that circ_0014614 (circDAP3) was significantly underexpressed in bone marrow-derived exosomes from essential thrombocythemia (ET) patients, affecting the differentiation of bone marrow lineage cells into megakaryocytes. METHODS: Fluorescence in situ hybridization (FISH) was used to display circ_0014614's primary cytoplasmic location in K562 cells. Cytoscape software was used to predict the circRNA-miRNA-mRNA networks, and their expression at the cellular level was detected by Quantitative reverse transcription-polymerase chain reaction (qRT-PCR). qRT-PCR was utilized to detect the expression levels of circ_0014614ï¼miR-138-5p and caspase3 mRNA. Western blot was used to determine the protein levels of GATA-1, RUNX-1, NF-E2, CD41 and caspase3. The proliferation of K562 cells was assessed using the Cell Counting Kit-8 (CCK-8) Assay. Furthermore, the interplay between miR-138-5p and circ_0014614 or caspase3 was elucidated through a Dual-luciferase reporter assay. RESULTS: FISH assay indicated circ_0014614's primary cytoplasmic location in K562 cells. In ET bone marrow and K562 cells, circ_0014614 and caspase3 were down-regulated, whereas miR-138-5p saw a significant surge. Overexpressing circ_0014614 curtailed K562 cells' proliferation and differentiation. Further, circ_0014614 targeted miR-138-5p, with heightened miR-138-5p levels counteracting circ_0014614's inhibition. MiR-138-5p further targeted caspase3, and caspase3 silencing neutralized suppressed miR-138-5p's effects on K562 cell differentiation. CONCLUSION: Circ_0014614 was down-regulated in ET bone marrow and bone marrow lineage cells, and upregulating circ_0014614 can inhibit bone marrow lineage cells' proliferation and differentiation into megakaryocytes. Mechanistically, circ_0014614 functioned as ceRNA via sponging miR-138-5p and alleviated the inhibitory effect of miR-138-5p on its target caspase3, which potentially deters tumor activity in ET.
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Caspase 3 , Diferenciação Celular , Megacariócitos , MicroRNAs , RNA Circular , Trombocitemia Essencial , Humanos , MicroRNAs/genética , MicroRNAs/metabolismo , Megacariócitos/metabolismo , Megacariócitos/patologia , RNA Circular/genética , Caspase 3/metabolismo , Trombocitemia Essencial/genética , Trombocitemia Essencial/patologia , Trombocitemia Essencial/metabolismo , Células K562 , Células da Medula Óssea/metabolismo , Células da Medula Óssea/patologia , Feminino , Masculino , Pessoa de Meia-IdadeRESUMO
BACKGROUND Nonintubated video-assisted thoracic surgery (NIVATS) has been demonstrated to be safe and effective in patients. However, the risk factors for intraoperative hypoxia are unclear. This retrospective study aimed to identify the risk factors for the development of intraoperative hypoxia in patients undergoing NIVATS. MATERIAL AND METHODS The study included patients who underwent NIVATS between January 2011 and December 2018. Intraoperative hypoxia was defined as SpO2 ≤93%. Risk factors for hypoxia were identified by binary logistic regression analysis, and the characteristic distribution of patients with and without hypoxia was elaborated. RESULTS Of 2742 included patients, age, anesthesia method, the technical level of surgeons, stair-climbing ability, and type of thoracic procedure were associated with intraoperative hypoxia (P<0.05). The characteristics of patients with hypoxia were older age (P=0.011), higher body mass index and revised cardiac risk index level (P=0.033 and P=0.031), and lower composition of stair-climbing ≥22 m (P<0.001). These patients also had more anatomical lung surgery and mediastinal mass resection (P=0.033) and more epidural anesthesia (P=0.005). The surgeries were more likely to be performed by surgeons with less than 10 years of VATS training (P=0.009) and to have increased intraoperative maximum end-expiratory carbon dioxide partial pressure (P<0.001). These patients had a longer Intensive Care Unit stay (P<0.001), duration of chest-tube drainage (P=0.019), and postoperative hospitalization (P=0.003). CONCLUSIONS The current study suggests that old age and stair-climbing ability of patients, anesthesia method, thoracic procedures, and surgeon experience are risk factors for intraoperative hypoxia in patients undergoing NIVATS.
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Hipóxia/etiologia , Complicações Intraoperatórias/etiologia , Cirurgia Torácica Vídeoassistida/efeitos adversos , Adolescente , Adulto , Idoso , Anestesia Epidural/métodos , Tubos Torácicos , Feminino , Humanos , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Duração da Cirurgia , Período Pós-Operatório , Estudos Retrospectivos , Fatores de Risco , Adulto JovemAssuntos
Infecções por Coronavirus , Neoplasias , Pneumonia Viral , Índice de Gravidade de Doença , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Betacoronavirus , COVID-19 , China/epidemiologia , Infecções por Coronavirus/complicações , Infecções por Coronavirus/epidemiologia , Humanos , Anamnese , Pessoa de Meia-Idade , Neoplasias/complicações , Neoplasias/epidemiologia , Neoplasias/terapia , Pneumonia Viral/complicações , Pneumonia Viral/epidemiologia , Prognóstico , Estudos Prospectivos , Respiração Artificial , Fatores de Risco , SARS-CoV-2RESUMO
To efficiently capture feature information in tasks of fine-grained image classification, this study introduces a new network model for fine-grained image classification, which utilizes a hybrid attention approach. The model is built upon a hybrid attention module (MA), and with the assistance of the attention erasure module (EA), it can adaptively enhance the prominent areas in the image and capture more detailed image information. Specifically, for tasks involving fine-grained image classification, this study designs an attention module capable of applying the attention mechanism to both the channel and spatial dimensions. This highlights the important regions and key feature channels in the image, allowing for the extraction of distinct local features. Furthermore, this study presents an attention erasure module (EA) that can remove significant areas in the image based on the features identified; thus, shifting focus to additional feature details within the image and improving the diversity and completeness of the features. Moreover, this study enhances the pooling layer of ResNet50 to augment the perceptual region and the capability to extract features from the network's less deep layers. For the objective of fine-grained image classification, this study extracts a variety of features and merges them effectively to create the final feature representation. To assess the effectiveness of the proposed model, experiments were conducted on three publicly available fine-grained image classification datasets: Stanford Cars, FGVC-Aircraft, and CUB-200-2011. The method achieved classification accuracies of 92.8, 94.0, and 88.2% on these datasets, respectively. In comparison with existing approaches, the efficiency of this method has significantly improved, demonstrating higher accuracy and robustness.
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BACKGROUND: Stage III non-small cell lung cancer is a heterogeneous disease. Several international guidelines recommend neoadjuvant treatment before surgery; however, upfront surgery is the preferred approach for technically resectable non-small cell lung cancer in East Asia. The aim of this retrospective study was to evaluate the long-term outcomes of curative-intent upfront surgery in stage IIIA/B non-small cell lung cancer. METHODS: Patients who underwent curative-intent upfront surgery with stage cIIIA/B non-small cell lung cancer were identified. The clinical and pathological variables and survival outcomes were evaluated. RESULTS: Overall, 664 patients were identified, of whom 320 (48.8%) had N2 disease, 66.7% were males, 49.4% had a smoking history, and 61.2% had lung adenocarcinoma. Lobectomy was the most performed surgical procedure (84.9%). A total of 40 patients (6.02%) had positive margins (R1/R2). The grade III adverse event rate was 2.0% (13 of 664). The median follow-up was 30.6 (range 1.9-97.7) months. At follow-up, the mortality rate was 13.3% (88 of 664) and 37.2% of patients (247 of 664) had recurrence. Lung (101 of 247 (40.9%)) and brain (53 of 247 (21.5%)) were the most common sites of recurrence. The median overall survival was 60.0 (95% c.i. 51.5 to 67.6) months, with overall survival probability at 1, 2, 3, and 5 years being 89.6%, 77.8%, 67.2%, and 49.0% respectively. The R0 cohort showed an improved median overall survival compared with the R1/R2 cohort (67.4 versus 26.5 months respectively; P = greater than 0.001). The multivariable analysis revealed that age greater than or equal to 65 years (HR 1.51, 95% c.i. 1.08 to 2.12; reference = age less than 65 years), tumour size (greater than or equal to 5â cm (HR 2.13, 95% c.i. 1.41 to 3.21) and greater than or equal to 3 cm but less than 5â cm (HR 1.15, 95% c.i. 0.78 to 1.71); reference = less than 3â cm), and adjuvant treatment (chemotherapy (HR 0.69, 95% c.i. 0.49 to 0.96) and targeted therapy (HR 0.30, 95% c.i. 0.12 to 0.76); reference = none) significantly predicted overall survival. CONCLUSION: Upfront surgery is an option for the management of stage IIIA/B non-small cell lung cancer.
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Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Masculino , Humanos , Idoso , Feminino , Carcinoma Pulmonar de Células não Pequenas/cirurgia , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Estudos Retrospectivos , Neoplasias Pulmonares/cirurgia , Resultado do Tratamento , Estadiamento de NeoplasiasRESUMO
Background: Lung adenocarcinoma (LUAD) exhibits high fatality rates, and effective treatments are lacking. The expression of the N6-methyladenosine (m6A) regulatory protein ALKBH5 is associated with lung cancer. To identify new therapeutic targets for LUAD, we screened target genes of ALKBH5 and analyzed their potential mechanisms of action. Methods: LUAD samples from The Cancer Genome Atlas (TCGA) were used to analyze the expression of ALKBH5 and screen for genes with correlated expression. Intersection of the genes upregulated in cells with ALKBH5 silencing with the genes significantly associated with ALKBH5 were defined as ALKBH5 target genes. STRING was used to evaluate interactions between the target genes, and the relationship between ALKBH5 target gene expression and LUAD patient prognosis was analyzed using the R package Survminer. Target genes were evaluated by functional enrichment analyses. Results: ALKBH5 was highly expressed in LUAD tissues and was significantly associated with a poor prognosis. Fifteen ALKBH5 target genes were identified, primarily enriched in protein processing in the endoplasmic reticulum, transcriptional coregulator activity, and cell activation involved in the immune response. Upregulation of ZNF777, TCOF1, CPLX2, and ABL1 was associated with a poor prognosis, whereas upregulation of ZER1, VPS53, and RRBP1 was associated with a good prognosis. Conclusions: This study provides potential therapeutic targets for LUAD and a basis for further studies on the mechanism underlying the effects of ALKBH5.
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The immune cells of tumor microenvironment (TME) constitute a vital element of the tumor tissue. There is increasing evidence for their clinical significance in predicting prognosis and therapeutic outcomes. However, the TME immune cell infiltrating pattern of the bone marrow in acute myeloid leukemia (AML) patients remains unclear. Here, RNA-sequencing results of AML patients from TCGA database were used to quantify the abundance of 28 types of immune cells in the TME using the single-sample gene set enrichment analysis algorithm. We comprehensively evaluated the immune infiltration status in the TCGA-LAML cohort and defined two immunophenotypes: the immune hot and immune cold subtypes. Additionally, we constructed a TME score reflecting the immune infiltrating pattern of the patients using Cox regression algorithm. Subtypes with high TME score were characterized by over-activation of immune inflammation-related pathways, release of inflammatory factors, T-cell dysfunction, and poor prognosis. Subtypes with a low TME score were characterized by relatively low immune infiltration and immune exclusion. Our analysis indicated that patients in the low TME score group were more sensitive to chemotherapeutic drugs, and those in high TME score were more likely to respond to immunotherapy. Our study provides a new direction to evaluate anti-tumor therapy from immune infiltration of the TME, and the individualized scoring system in this study has important clinical significance in identifying patients who respond to immunotherapy.
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Leucemia Mieloide Aguda , Humanos , Prognóstico , Leucemia Mieloide Aguda/diagnóstico , Imunofenotipagem , Imunoterapia , Biomarcadores , Microambiente TumoralRESUMO
The increased use of low-dose computed tomography screening has led to more frequent detection of early stage lung tumors, including minimally invasive adenocarcinoma (MIA). To unravel the intricacies of tumor cells and the immune microenvironment in MIA, this study performs a comprehensive single-cell transcriptomic analysis and profiles the transcriptomes of 156,447 cells from fresh paired MIA and invasive adenocarcinoma (IA) tumor samples, peripheral blood mononuclear cells, and adjacent normal tissue samples from three patients with synchronous multiple primary lung adenocarcinoma. This study highlights a connection and heterogeneity between the tumor ecosystem of MIA and IA. MIA tumor cells exhibited high expression of aquaporin-1 and angiotensin II receptor type 2 and a basal-like molecular character. Furthermore, it identifies that cathepsin B+ tumor-associated macrophages may over-activate CD8+ T cells in MIA, leading to an enrichment of granzyme K+ senescent CD8+ T cells, indicating the possibility of malignant progression behind the indolent appearance of MIA. These findings are further validated in 34 MIA and 35 IA samples by multiplexed immunofluorescence. These findings provide valuable insights into the mechanisms that maintain the indolent nature and prompt tumor progression of MIA and can be used to develop more effective therapeutic targets and strategies for MIA patients.
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Adenocarcinoma de Pulmão , Adenocarcinoma , Neoplasias Pulmonares , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Linfócitos T CD8-Positivos , Ecossistema , Leucócitos Mononucleares , Adenocarcinoma de Pulmão/genética , Adenocarcinoma de Pulmão/patologia , Adenocarcinoma/genética , Pulmão/patologia , Perfilação da Expressão Gênica , Microambiente Tumoral/genéticaRESUMO
Reproduction and flight are two major adaptive strategies to cope with environmental stress in migratory insects. However, research on density-mediated flight and reproduction in the global migratory agricultural pest Spodoptera frugiperda is lacking. In this study, flight and reproductive performances in response to larval crowding were investigated in S. frugiperda. We found that larval crowding significantly reduced the pupal and body weights of S. frugiperda. Adults reared under the highest density of 30 larvae/jar had the minimum wing expansion, which was significantly smaller than that of larvae reared under solitary conditions. Larval crowding also significantly increased the pre-oviposition period (POP) and period of first oviposition (PFO) but decreased the lifetime fecundity, flight duration and flight distance. Our results showed that S. frugiperda reared under solitary conditions exhibited higher pupal and body weights and stronger reproductive and flight capacities than those reared under high-density conditions. Larval crowding did not enhance the migration propensity in S. frugiperda adults. In conclusion, larval crowding may not be a major factor affecting FAW migration due to high levels of cannibalism. These findings provide new insights into the population dynamics of S. frugiperda under larval crowding conditions.
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This study was to explore the role of NK cell subsets and gene expression in maintaining TFR status. We identified six types of NK cells in the PBMCs over both groups (healthy controls and patients with TFR). Gene Oncology analysis showed that up regulated genes were enriched in the categories of "immune response," "reaction to tumor cells," and "cytolysis." In addition, we found that the three NK cell subsets, mature and terminal NK cells, CD56 bright NK cells, and transitional NK cells, contained many significantly up regulated genes in both groups, and that CD56 bright NK cells and transitional NK cells in patients with CML-TFR were in a proliferating and activated state. Through single-cell RNA sequencing analysis, we confirmed that the mature and terminal, CD56 bright, and transitional subsets of NK cells play an indispensable role in maintaining TFR in patients with CML.
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Leucemia Mielogênica Crônica BCR-ABL Positiva , Humanos , Leucemia Mielogênica Crônica BCR-ABL Positiva/genética , Leucemia Mielogênica Crônica BCR-ABL Positiva/terapia , Células Matadoras Naturais/metabolismo , Indução de Remissão , Análise de Sequência de RNA , Antígeno CD56/metabolismoRESUMO
BACKGROUND: The risk factors for postoperative complications in non-intubated video-assisted thoracoscopic surgery (VATS) have not been observed before. Here to develop a simple risk score to predict the risk of postoperative complications for patients who scheduling non-intubated VATS, which is beneficial to guide the clinical interventions. METHODS: A total of 1,837 patients who underwent non-intubated VATS were included from January 2011 to December 2018. A development data set and a validation data set were allocated according to an approximate 3:2 ratio of total cases. The stepwise logistic regression was used to establish a risk score model, and the methods of bootstrap and split-sample were used for validation. RESULTS: Multivariable analysis revealed that the forced expiratory volume in the first second in percent of predicted, the anesthesia method, blood loss, surgical time, and preoperative neutrophil ratio were risk factors for postoperative complications. The risk score was established with these 5 factors, varied from 0 to 53, with the corresponding predicted probability of postoperative complications occurrence ranged from 1% to 92% and was calibrated (Hosmer-Lemeshow χ2 =6.261; P=0.618). Good discrimination was acquired in the development and validation data sets (C-statistic 0.705 and 0.700). A positive correlation was between the risk score and postoperative complications (P for trend <0.01). Three levels of low-risk (0-15 points], moderate-risk (15-30 points], and high-risk (>30 points] were established based on the score distribution of postoperative complications. CONCLUSIONS: This simple risk score model based on risk factors of postoperative complications can validly identify the high-risk patients with postoperative complications in the non-intubated VATS, and allow for early interventions.
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BACKGROUND: Early endotracheal extubation in operating room (E-OR) after lung transplantation is rarely reported worldwide. Herein, we aim to explore the feasibility and safety of E-OR after lung transplantation and demonstrate its potential benefits. METHODS: This study is a single-center retrospective database analysis of 18 patients. All lung transplantation patients with E-OR attempted between June 2018 and September 2019 were included retrospectively. Perioperative variables, including ischemia time, total blood loss, blood lactic acid, the partial pressure of oxygen, partial pressure of oxygen/fraction of inspiration oxygen ratio, time of semi-open pulmonary artery occlusion clamp, extubation rate, and complications after E-OR, were analyzed. Data were compared using non-parametric tests and expressed as the median or number (percentage). RESULTS: Clinical data of 18 patients with E-OR attempted were collected. Overall, 15/18 (83.33%) patients successfully underwent E-OR without reintubation. Reintubation occurred in 3/18 (16.67%) patients; one patient presented with decreased blood oxygen saturation and unconsciousness, while two patients developed hypoxemia and respiratory failure after E-OR. Extracorporeal membrane oxygenation (ECMO) was not used postoperatively. No grade 3 primary graft dysfunction was observed and all eighteen patients were alive 1 year after the transplant. No postoperative hemodialysis and tracheotomy occurred. The median length of stay in the intensive care unit (ICU) for E-OR patients was 120 hours, the median length of postoperative hospital stay was 19 days, and the median hospitalization cost was 35,577 USD. CONCLUSIONS: Early endotracheal extubation in operating room was feasible and did not delay postoperative recovery in these 18 lung transplantation recipients.
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Extubação , Transplante de Pulmão , Humanos , Tempo de Internação , Salas Cirúrgicas , Estudos RetrospectivosRESUMO
Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) are treatments commonly used for lung cancer. The toxicity profile including toxicity incidence, severity, and spectrum (involving various specific adverse events) of each EGFR-TKI are of particular clinical interest and importance. Data from phase II and III randomized controlled trials comparing treatments among EGFR-TKIs (osimertinib, dacomitinib, afatinib, erlotinib, gefitinib, and icotinib) and chemotherapy for lung cancer were synthesized with Bayesian network meta-analysis. The primary outcome was systemic all-grade and grade ≥3 adverse events. The secondary outcome was specific all-grade adverse events including those of the skin, gastrointestinal tract, lung, etc. 40 trials randomizing 13,352 patients were included. Generally greater toxicity for dacomitinib and afatinib, and safety for icotinib were suggested. Furthermore, we found individual EGFR-TKIs had different toxicity spectrums. These findings provide a compelling safety reference for the individualized use of EGFR-TKIs for patients with lung cancer.
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Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Teorema de Bayes , Receptores ErbB/genética , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Mutação , Metanálise em Rede , Inibidores de Proteínas Quinases/efeitos adversosRESUMO
Physiological management of migration-reproduction trade-offs in energy allocation often includes a package of adaptions referred to as the oogenesis-flight syndrome. In some species, this trade-off may be overestimated, because factors like flight behavior and environmental conditions may mitigate it. In this study, we examined the reproductive consequences induced by different flight scenarios in an economically-important Asian migrant insect, Cnaphalocrocis medinalis. We found that the influences of flight on reproduction are not absolutely positive or negative, but instead depend on the age at which the moth begins flight, flight duration, and how many consecutive nights they are flown. Adult flight on the 1st or 2nd night after emergence, flight for 6 h or 12 h nightly, and flight on the first two consecutive nights after emergence significantly accelerated onset of oviposition or enhanced synchrony of egg-laying. The latter can contribute to subsequent larval outbreaks. However, flight after the 3rd night, flight for 18 h at any age, or flight on more than 3 consecutive nights after adult emergence did not promote reproductive development, and in some scenarios even constrained adult reproduction. These results indicate that there is a migration/reproduction trade-off in C.medinalis, but that it is mitigated or eliminated by flight under appropriate conditions. The strategy of advanced and synchronized oviposition triggered by migratory flight of young females may be common in other migratory insect pests.
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Voo Animal/fisiologia , Mariposas/anatomia & histologia , Oviposição , Migração Animal , Animais , Feminino , Larva/anatomia & histologiaRESUMO
Spatial distribution of biogenic silica (BSi) and factors influencing BSi preservation and dissolution in sediments were discussed based on the investigation in the Changjiang Estuary adjacent sea. The results showed that the contents of BSi were higher in nearshore sediments than those in offshore sediments. Terrestrial input, sediment accumulation rate and hydrodynamic conditions were the dominant factors affecting BSi preservation in sediments. BSi dissolution rate constant showed no obvious change with stations and sediment depth. BSi dissolution mainly depended on the following factors including undersaturation of silicic acid in pore water compared with BSi solubility, organic coating in BSi surface and aluminum concentration in pore water. And these factors can influence BSi preservation and the build-up of silicic acid in sediments.