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The aim of this study was to develop a medical imaging and comprehensive stacked learning-based method for predicting high- and low-risk thymoma. A total of 126 patients with thymomas and 5 patients with thymic carcinoma treated at our institution, including 65 low-risk patients and 66 high-risk patients, were retrospectively recruited. Among them, 78 patients composed the training cohort, while the remaining 53 patients formed the validation cohort. We extracted 1702 features each from the patients' arterial-, venous-, and plain-phase images. Pairwise subtraction of these features yielded 1702 arterial-venous, arterial-plain, and venous-plain difference features each. The MannâWhitney U test and least absolute shrinkage and selection operator (LASSO) and SelectKBest methods were employed to select the best features from the training set. Six models were built with a stacked learning algorithm. By applying stacked ensemble learning, three machine learning algorithms (XGBoost, multilayer perceptron (MLP), and random forest) were combined by XGBoost to produce the the six basic imaging models. Then, the XGBoost algorithm was applied to the six basic imaging models to construct a combined radiomic model. Finally, the radiomic model was combined with clinical information to create a nomogram that could easily be used in clinical practice to predict the thymoma risk category. The areas under the curve (AUCs) of the combined radiomic model in the training and validation cohorts were 0.999 (95% CI 0.988-1.000) and 0.967 (95% CI 0.916-1.000), respectively, while those of the nomogram were 0.999 (95% CI 0.996-1.000) and 0.983 (95% CI 0.990-1.000). This study describes the application of CT-based radiomics in thymoma patients and proposes a nomogram for predicting the risk category for this disease, which could be advantageous for clinical decision-making for affected patients.
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Aprendizaje Automático , Timoma , Neoplasias del Timo , Tomografía Computarizada por Rayos X , Humanos , Timoma/diagnóstico por imagen , Timoma/patología , Masculino , Femenino , Persona de Mediana Edad , Tomografía Computarizada por Rayos X/métodos , Neoplasias del Timo/diagnóstico por imagen , Neoplasias del Timo/patología , Adulto , Estudios Retrospectivos , Anciano , Medición de Riesgo/métodos , Algoritmos , Nomogramas , RadiómicaRESUMEN
In bronchial ultrasound elastography, accurately segmenting mediastinal lymph nodes is of great significance for diagnosing whether lung cancer has metastasized. However, due to the ill-defined margin of ultrasound images and the complexity of lymph node structure, accurate segmentation of fine contours is still challenging. Therefore, we propose a dual-stream feature-fusion attention U-Net (DFA-UNet). Firstly, a dual-stream encoder (DSE) is designed by combining ConvNext with a lightweight vision transformer (ViT) to extract the local information and global information of images; Secondly, we propose a hybrid attention module (HAM) at the bottleneck, which incorporates spatial and channel attention to optimize the features transmission process by optimizing high-dimensional features at the bottom of the network. Finally, the feature-enhanced residual decoder (FRD) is developed to improve the fusion of features obtained from the encoder and decoder, ensuring a more comprehensive integration. Extensive experiments on the ultrasound elasticity image dataset show the superiority of our DFA-UNet over 9 state-of-the-art image segmentation models. Additionally, visual analysis, ablation studies, and generalization assessments highlight the significant enhancement effects of DFA-UNet. Comprehensive experiments confirm the excellent segmentation effectiveness of the DFA-UNet combined attention mechanism for ultrasound images, underscoring its important significance for future research on medical images.
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BACKGROUND: Salt stress severely inhibits plant growth, and the WRKY family transcription factors play important roles in salt stress resistance. In this study, we aimed to characterize the role of tobacco (Nicotiana tabacum) NtWRKY65 transcription factor gene in salinity tolerance. RESULTS: This study characterized the role of tobacco (Nicotiana tabacum) NtWRKY65 transcription factor gene in salinity tolerance using four NtWRKY65 overexpression lines. NtWRKY65 is localized to the nucleus, has transactivation activity, and is upregulated by NaCl treatment. Salinity treatment resulted in the overexpressing transgenic tobacco lines generating significantly longer roots, with larger leaf area, higher fresh weight, and greater chlorophyll content than those of wild type (WT) plants. Moreover, the overexpressing lines showed elevated antioxidant enzyme activity, reduced malondialdehyde content, and leaf electrolyte leakage. In addition, the Na+ content significantly decreased, and the K+/Na+ ratio was increased in the NtWRKY65 overexpression lines compared to those in the WT. These results suggest that NtWRKY65 overexpression enhances salinity tolerance in transgenic plants. RNA-Seq analysis of the NtWRKY65 overexpressing and WT plants revealed that NtWRKY65 might regulate the expression of genes involved in the salt stress response, including cell wall component metabolism, osmotic stress response, cellular oxidant detoxification, protein phosphorylation, and the auxin signaling pathway. These results were consistent with the morphological and physiological data. These findings indicate that NtWRKY65 overexpression confers enhanced salinity tolerance. CONCLUSIONS: Our results indicated that NtWRKY65 is a critical regulator of salinity tolerance in tobacco plants.
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Regulación de la Expresión Génica de las Plantas , Nicotiana , Proteínas de Plantas , Plantas Modificadas Genéticamente , Tolerancia a la Sal , Factores de Transcripción , Nicotiana/genética , Nicotiana/fisiología , Tolerancia a la Sal/genética , Plantas Modificadas Genéticamente/genética , Factores de Transcripción/genética , Factores de Transcripción/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismoRESUMEN
Macrophages play multiple roles in innate immunity including phagocytosing pathogens, modulating the inflammatory response, presenting antigens, and recruiting other immune cells. Tissue-resident macrophages (TRMs) adapt to the local microenvironment and can exhibit different immune responses upon encountering distinct pathogens. In this study, we generated induced macrophages (iMACs) derived from human pluripotent stem cells (hPSCs) to investigate the interactions between the macrophages and various human pathogens, including the hepatitis C virus (HCV), severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and Streptococcus pneumoniae. iMACs can engulf all three pathogens. A comparison of the RNA-seq data of the iMACs encountering these pathogens revealed that the pathogens activated distinct gene networks related to viral response and inflammation in iMACs. Interestingly, in the presence of both HCV and host cells, iMACs upregulated different sets of genes involved in immune cell migration and chemotaxis. Finally, we constructed an image-based high-content analysis system consisting of iMACs, recombinant GFP-HCV, and hepatic cells to evaluate the effect of a chemical inhibitor on HCV infection. In summary, we developed a human cell-based in vitro model to study the macrophage response to human viral and bacterial infections; the results of the transcriptome analysis indicated that the iMACs were a useful resource for modeling pathogen-macrophage-tissue microenvironment interactions.
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Hepacivirus , Macrófagos , Células Madre Pluripotentes , SARS-CoV-2 , Humanos , Macrófagos/inmunología , Macrófagos/virología , Hepacivirus/inmunología , Hepacivirus/fisiología , SARS-CoV-2/inmunología , Células Madre Pluripotentes/inmunología , Streptococcus pneumoniae/inmunología , COVID-19/inmunología , COVID-19/virología , Hepatitis C/inmunología , Hepatitis C/virología , Fagocitosis , Virosis/inmunología , Inmunidad InnataRESUMEN
BACKGROUND: Cervical cancer (CC) is the second most common malignancy in women, and identifying biomarkers of CC is crucial for prognosis prediction. Here, we investigated the expression of AF4/FMR2 Family Member 3 (AFF3) in CC and its association with clinicopathological features and prognosis. METHODS: Tumour and adjacent tissues, along with clinicopathological features and follow-up information, were collected from 78 patients. AFF3 expression was assessed using quantitative real-time polymerase chain reaction and Western blotting. The correlation between AFF3 expression and CC symptoms was using chi-square test. The 5-year overall survival (OS) was analysed using the Kaplan-Meier method. The Univariate analysis of prognostic risk factors was conducted using the COX proportional hazards model, followed by multivariate COX regression analysis including variables with p < 0.01. RESULTS: AFF3 expression was downregulated in CC, and its levels were correlated with lymph node metastasis (LNM) and International Federation of Gynaecology and Obstetrics (FIGO) stage. Patients with low AFF3 expression had a lower 5-year OS rate (52.78%, 19/36). Postoperative survival was reduced in patients with histological grade 3 (G3), myometrial invasion (depth ≥ 1/2), lymphovascular space invasion, LNM, and advanced FIGO stage. Low expression of AFF3 (HR: 2.848, 95% CI: 1.144-7.090) and histological grade G3 (HR: 4.393, 95% CI: 1.663-11.607) were identified as independent prognostic risk factors in CC patients. CONCLUSION: Low expression of AFF3 and histological G3 are independent predictors of poor prognosis in CC patients, suggesting that AFF3 could serve as a potential biomarker for prognostic assessment in CC.
Cervical cancer is a significant health concern worldwide, responsible for over 300,000 deaths annually and ranking as the fourth most common cancer in women. Existing screening methods have limitations, highlighting the need for innovative therapies. In our research, we identified a specific genetic material that varied significantly among cervical cancer patients with varying survival outcomes, detected in tissue samples obtained post-surgery. Our study demonstrates the considerable potential of this marker for accurately predicting outcomes in our study population. By analysing differences in the expression of this genetic marker, we can forecast the prognosis and progression of cervical cancer. These findings offer valuable insights for advancing cervical cancer treatment strategies, potentially improving outcomes for patients. Early detection and targeted treatment based on this genetic marker could extend patients' lives and prevent fatalities by enabling timely medical intervention and management.
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Neoplasias del Cuello Uterino , Humanos , Femenino , Neoplasias del Cuello Uterino/patología , Estadificación de Neoplasias , Pronóstico , Modelos de Riesgos Proporcionales , Reacción en Cadena en Tiempo Real de la Polimerasa , Metástasis Linfática , Proteínas NuclearesRESUMEN
BACKGROUND: Inflammatory response has been recognized as a pivotal pathophysiological process during cerebral ischemia. ChemR23 signaling is involved in the pathophysiology of various inflammatory diseases. Nevertheless, the role of ChemR23 signaling in ischemic stroke remains largely unknown. METHODS: Permanent ischemic stroke mouse model was accomplished by middle cerebral artery occlusion (MCAO). Resolvin E1 (RvE1) or chemerin-9 (C-9), the agonists of ChemR23, were administered by intracerebroventricular (i.c.v) injection before MCAO induction. Then, analysis of neurobehavioral deficits and brain sampling were done at Day 1 after MCAO. The brain samples were further analyzed by histological staining, immunofluorescence, RNA sequencing, ELISA, transmission electron microscope, and western blots. Furthermore, oxygen-glucose deprivation (OGD) was employed in SH-SY5Y to mimic MCAO in vitro, and ChemR23 signaling pathway was further studied by overexpression of ChemR23 or administration of related agonists or antagonists. Analysis of cell death and related pathway markers were performed. RESULTS: ChemR23 expression was upregulated following MCAO. Under in vitro and in vivo ischemic conditions, ChemR23 deficiency or inhibition contributed to excessive NLRP3-mediated maturation and release of IL-1ß and IL-18, as well as enhanced cleavage of GSDMD-N and neuronal pyroptosis. These influences ultimately aggravated brain injury and neuronal damage. On the other hand, ChemR23 activation by RvE1 or C-9 mitigated the above pathophysiological abnormalities in vivo and in vitro, and overexpression of ChemR23 in SH-SY5Y cells also rescued OGD-induced neuronal pyroptosis. Blockade of NLRP3 mimics the protective effects of ChemR23 activation in vitro. CONCLUSION: Our data indicated that ChemR23 modulates NLRP3 inflammasome-mediated neuronal pyroptosis in ischemic stroke. Activation of ChemR23 may serve as a promising potential target for neuroprotection in cerebral ischemia.
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Isquemia Encefálica , Accidente Cerebrovascular Isquémico , Neuroblastoma , Receptores de Quimiocina , Daño por Reperfusión , Animales , Humanos , Ratones , Isquemia Encefálica/complicaciones , Isquemia Encefálica/tratamiento farmacológico , Isquemia Encefálica/metabolismo , Quimiocinas , Infarto de la Arteria Cerebral Media/complicaciones , Inflamasomas/metabolismo , Péptidos y Proteínas de Señalización Intercelular , Accidente Cerebrovascular Isquémico/tratamiento farmacológico , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Piroptosis , Daño por Reperfusión/patología , Transducción de Señal , Receptores de Quimiocina/metabolismoRESUMEN
Neuroinflammation plays critical roles in vascular dementia (VaD), the second leading cause of dementia, which can be induced by chronic cerebral hypoperfusion (CCH). NLRP3 inflammasome-induced pyroptosis, the inflammatory programmed cell death, has been reported to contribute to the development of VaD. ChemR23 is a G protein-coupled receptor that has emerging roles in regulating inflammation. However, the role of ChemR23 signalling in NLRP3 inflammasome-induced pyroptosis in CCH remains elusive. In this study, a CCH rat model was established by permanent bilateral common carotid artery occlusion (BCCAO) surgery. Eight weeks after the surgery, the rats were intraperitoneally injected with the ChemR23 agonist Resolvin E1 (RvE1) or chemerin-9 (C-9). Additionally, primary rat hippocampal neurons and SH-SY5Y cells were adopted to mimic CCH injury in vitro. Our results showed that the levels of ChemR23 expression were decreased from the 8th week after BCCAO, accompanied by significant cognitive impairment. Further analysis revealed that CCH induced neuronal damage, synaptic injury and NLRP3-related pyroptosis activation in hippocampal neurons. However, pharmacologic activation of ChemR23 with RvE1 or C-9 counteracted these changes. In vitro experiments also showed that ChemR23 activation prevented primary neuron pyroptosis induced by chronic hypoxia. In addition, manipulating ChemR23 expression markedly regulated NLRP3 inflammasome-induced neuronal pyroptosis through PI3K/AKT/Nrf2 signalling in SH-SY5Y cells under hypoglycaemic and hypoxic conditions. Collectively, our data demonstrated that ChemR23 activation inhibits NLRP3 inflammasome-induced neuronal pyroptosis and improves cognitive function via the PI3K/AKT/Nrf2 signalling pathway in CCH models. ChemR23 may serve as a potential novel therapeutic target to treat CCH-induced cognitive impairment.
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Isquemia Encefálica , Disfunción Cognitiva , Neuroblastoma , Receptores Acoplados a Proteínas G , Animales , Humanos , Ratas , Hipoxia , Inflamasomas , Neuronas/metabolismo , Factor 2 Relacionado con NF-E2 , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Fosfatidilinositol 3-Quinasas , Proteínas Proto-Oncogénicas c-akt , Piroptosis , Receptores Acoplados a Proteínas G/metabolismoRESUMEN
Background: Combined small cell lung cancer (CSCLC) is rarely reported, which accounting for only 2% to 5% of all lung cancers. And enteric adenocarcinoma is also a rare subtype of non-small cell lung cancer (NSCLC) whose histomorphology is very similar to lung metastatic colorectal cancer. Case Description: We report a case with both small cell lung cancer (SCLC) and enteric adenocarcinoma for the first time. The patient was admitted to our hospital due to the left lung mass after a routine examination. She underwent computed tomography scan and needle biopsy, which showed the tumor consisted of two different components (70% SCLC and 30% enteric adenocarcinoma). The mixed density nodules were also observed in the right lung's lower lobe, and positron emission tomography-computed tomography (PET-CT) showed an increase of standard uptake value (SUV) greater than 2.5 in the right lung. Imaging and pathology experts agreed that the nodules of right lung were metastatic lesions after multi-disciplinary treatment (MDT). Considering the epidermal growth factor receptor (EGFR) p.L861Q mutation, the patient received gefitinib and EP chemotherapy, and she responded well to the combination therapy. At last follow-up, the progression-free survival (PFS) reached 11 months, and the adverse effects were clinically acceptable and tolerable. Conclusions: This case report provides direct evidence for EGFR-tyrosine kinase inhibitor (TKI) and EP chemotherapy is effective and useful in the treatment of CSCLC patients with enteric adenocarcinoma.
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Background: Inflammatory myofibroblastic tumor (IMT) is a rare disease that mainly involves the lung and the abdomen. The gold standard of the IMT treatment is radical surgery, while chemotherapy and radiotherapy are represented usually for unresectable lesions. Anaplastic lymphoma kinase (ALK) rearrangements are present in approximately 50% of IMT patients, and several clinical trials of ALK tyrosine kinase inhibitors (TKIs) in the treatment of ALK-positive IMT patients are underway. Case Description: We reported a case of IMT in the right pelvic cavity. Initially, the patient underwent resection of multiple lesions. Unfortunately, the patient's tumor recurred half a year later, and enhanced computerized tomography (CT) of the whole abdomen revealed multiple low-density masses. Then the patient underwent resection of the recurrent tumors. Immunohistochemical staining exhibited the expression of ALK in the tumor cells, and next-generation sequencing (NGS) technology revealed two novel ALK fusions, ALK-ribosome binding protein 1 (RRBP1) and hydroxyacid oxidase 1 (HAO1)-ALK fusions. These fusions were able to be transcribed and captured by RNA level. And the two fusions have not been reported in the IMTs. Conclusions: This case expanded the range of ALK fusion types and provided a promising molecular-targeted treatment strategy. In addition, the two novel ALK fusions may be the recurrent oncogenic mechanism in clinically aggressive IMT.
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Human pluripotent stem cell differentiation towards hematopoietic progenitor cell can serve as an in vitro model for human embryonic hematopoiesis, but the dynamic change of epigenome and transcriptome remains elusive. Here, we systematically profile the chromatin accessibility, H3K4me3 and H3K27me3 modifications, and the transcriptome of intermediate progenitors during hematopoietic progenitor cell differentiation in vitro. The integrative analyses reveal sequential opening-up of regions for the binding of hematopoietic transcription factors and stepwise epigenetic reprogramming of bivalent genes. Single-cell analysis of cells undergoing the endothelial-to-hematopoietic transition and comparison with in vivo hemogenic endothelial cells reveal important features of in vitro and in vivo hematopoiesis. We find that JUNB is an essential regulator for hemogenic endothelium specialization and endothelial-to-hematopoietic transition. These studies depict an epigenomic roadmap from human pluripotent stem cells to hematopoietic progenitor cells, which may pave the way to generate hematopoietic progenitor cells with improved developmental potentials.
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Hemangioblastos , Transcriptoma , Diferenciación Celular/genética , Epigenómica , Hematopoyesis/genética , Células Madre Hematopoyéticas/metabolismo , Humanos , Factores de Transcripción/metabolismoRESUMEN
Vascular cognitive impairment (VCI) is the second most common form of dementia. Andrographolide (Andro) shows potential effects in anti-inflammation, anti-oxidative stress, and anti-apoptosis. We have obtained 48 potential genes related to the effect of Andro on VCI through network pharmacology analysis. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were used to reveal significant enriched pathway of potential genes, and the mitogen-activated protein kinase (MAPK) pathway was screened out. To verify the results of network pharmacology, we tested the effects of Andro in VCI model induced by bilateral common carotid artery occlusion (BCCAO) surgery. The results showed that Andro treatment ameliorated the cognitive impairment induced by BCCAO. Immunohistochemistry study revealed that Andro could reduce neuronal damage and activation of microglia in the cortex and hippocampus in BCCAO rats. To test the MAPK pathway changes, we analyzed the expression of JNK, p38 and ERK and found that Andro reduced the levels of phosphorylated-ERK (p-ERK) and phosphorylated-p38 (p-p38) in BCCAO rats. In conclusion, Andro could improve neuronal survival, reduce neuroinflammation and ameliorate cognitive impairment in VCI. The underlying mechanisms of Andro treatment may be through the inhibition of MAPK pathway.
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Disfunción Cognitiva , Diterpenos , Animales , Disfunción Cognitiva/tratamiento farmacológico , Disfunción Cognitiva/metabolismo , Diterpenos/farmacología , Diterpenos/uso terapéutico , Microglía , Proteínas Quinasas Activadas por Mitógenos/metabolismo , Farmacología en Red , RatasRESUMEN
Our previous studies indicate that long noncoding RNA (lncRNA) LINC00467 can act as an oncogene to participate in the malignant progression of glioma, but the underlying molecular mechanism remains to be studied further. This study aimed to explore the biological role of the LINC00467/miR-339-3p/ inositol hexakisphosphate kinase 2 (IP6K2) regulatory axis in glioma. The Cancer Genome Atlas (TCGA), Oncomine databases and reverse transcriptionquantitative PCR (RTqPCR) were used to analyze IP6K2 expression in glioma. RT-PCR, EdU and transwell assays were conducted to observe the effect of IP6K2 on glioma cell proliferation, migration and invasion. Using bioinformatics analysis, RT-PCR, and dual luciferase reporter gene assay, the potential role of the LINC00467/miR-339-3p/IP6K2 regulatory axis in glioma was verified. The results showed that IP6K2 was up-regulated in glioma tissues and cell lines. Moreover, the expression level of IP6K2 was correlated with the clinical features of glioma patients. In vitro and in vivo experiments indicated that IP6K2 overexpression could promote the proliferation, migration, and invasion of glioma cells. Further bioinformatics analysis and in vitro assays revealed that LINC00467 could promote IP6K2 expression by binding to miR-339-3p and promote the malignant progression of glioma. Overall, LINC00467 could upregulate IP6K2 by binding to miR-339-3p and promote the proliferation, migration, and invasion of glioma cells. The LINC00467/miR-339-3p/IP6K2 regulatory axis might be a potential therapeutic target for glioma.
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Glioma , MicroARNs , Línea Celular Tumoral , Movimiento Celular/genética , Proliferación Celular/genética , Regulación Neoplásica de la Expresión Génica , Glioma/metabolismo , Humanos , MicroARNs/genética , MicroARNs/metabolismo , Fosfotransferasas (Aceptor del Grupo Fosfato)RESUMEN
BACKGROUND: Primary neuroendocrine tumors of the gallbladder (GB-NETs) are rare, accounting for 2% of all gallbladder cancers. Among GB-NETs, mixed neuroendocrine non-neuroendocrine neoplasms of the gallbladder (GB-MiNENs) are sporadic. CASE PRESENTATION: A 56-year-old woman admitted to our hospital due to right upper abdominal pain of 3 days duration. She underwent positron emission tomography/computed tomography, which showed multiple metastatic tumors and was unsuitable for operation. Initially, the patient was diagnosed with gallbladder adenocarcinoma. She underwent PD-1 inhibitor or combined with chemotherapy considering the PD-L1 high positive score. In the latter, the patient has the opportunity of surgery, and the new diagnosis was MiNENs. She achieved long-term disease control and has been alive from the first diagnosis. CONCLUSION: This case might support the strategy that PD-1 inhibitor could provide a feasible treatment option for MiNENs of gallbladder patients with the positive expression of PD-L1 in the future.
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Aging of hematopoietic stem cells (HSCs) directly contributes to dysfunction of hematopoietic and immune systems due to aging-associated alterations in HSC features. How the function of adult HSCs is regulated during aging so that relevant pathologic abnormalities may occur, however, remains incompletely understood. Here, we report that ATF4 deficiency provokes severe HSC defects with multifaceted aging-like phenotype via cell-autonomous mechanisms. ATF4 deletion caused expansion of phenotypical HSCs with functional attrition, characterized by defective repopulating and self-renewal capacities and myeloid bias. Moreover, the ATF4−/− HSC defects were associated with elevated mitochondrial ROS production by targeting HIF1α. In addition, loss of ATF4 significantly delayed leukemogenesis in the MLL-AF9induced leukemia model. Mechanistically, ATF4 deficiency impaired HSC function with aging-like phenotype and alleviated leukemogenesis by regulating HIF1α and p16Ink4a. Together, our findings suggest a possibility of developing new strategies for the prevention and management of HSC aging and related pathological conditions.
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BACKGROUND: Although physical activity (PA) and sedentary time in cancer survivors (CSs) were associated with health-related quality of life (HRQOL), it was not clear whether their associations were similar among CSs with different number of comorbid chronic diseases (CCDs). This study aimed to investigate the associations between PA, sedentary time and HRQOL in CSs with different number of CCDs. METHODS: A cross-sectional study was conducted among 1546 CSs between June and September 2018 in Shanghai, China. Data were collected with a self-reported questionnaire including sociodemographic characteristics, CCDs, PA, sedentary time and HRQOL. International Physical Activity Questionnaire and Cancer Quality of Life Questionnaire-Core30 were respectively used to measure PA and HRQOL of CSs. Associations of PA and sedentary time with HRQOL among CSs with different number of CCDs were evaluated by using logistic regression, adjusted for confounding factors. RESULTS: About seventy-five percent CSs had at least one CCD. Approximately three fifths CSs had high PA level and < 4 h/day sedentary time. Moderate PA level and high PA level were shown to be associated with better HRQOL among all participants. In CSs with ≤ 2 CCDs, high PA level was significantly associated with higher scores of physical function and lower scores of nausea and vomiting, appetite loss. However, there was a positive association between high PA level and constipation score among CSs with ≥ 3 CCDs. CSs with shorter sedentary time had better HRQOL in those with CCDs. CONCLUSIONS: High PA level and long sedentary time have significant association with worse HRQOL of CSs with ≥ 3 CCDs, while high PA level is positively associated with HRQOL in CSs with ≤ 2 CCDs. Our findings may support further studies of the causal association between PA, sedentary times and HRQOL to provide targeted proposal to improve the HRQOL of CSs according to their number of CCDs.
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Supervivientes de Cáncer/psicología , Ejercicio Físico/fisiología , Neoplasias/mortalidad , Calidad de Vida/psicología , Conducta Sedentaria , Adulto , Anciano , Anciano de 80 o más Años , China/epidemiología , Estudios Transversales , Ejercicio Físico/psicología , Femenino , Conductas Relacionadas con la Salud , Humanos , Masculino , Persona de Mediana Edad , Neoplasias/terapia , Encuestas y Cuestionarios , TerapéuticaRESUMEN
RATIONALE: Anaplastic thyroid carcinoma (ATC) is an aggressive malignancy that is almost always fatal and lacks effective systemic treatment options. Current treatments of ATC include surgery, radiation, and chemotherapy, used in combination when possible. In the aspect of immunotherapy, the biomarker of TMB-H and MSI-H may suggest that patients benefit from pembrolizumab. Programmed cell death-ligand 1 (PD-L1) is highly expressed in ATC but has not been written into the guidelines or approved by the FDA as a biomarker for thyroid cancer immunotherapy. PATIENT CONCERNS: A 55-year-old woman was admitted to our hospital because of a slight right-sided neck enlargement in November 2019. DIAGNOSES: The clinical diagnosis was ATC, pT3bN0M0, and stage IVB. INTERVENTIONS: Oral administration of apatinib (250âmg 3 times daily) was initiated after surgery, but some unpleasant side effects emerged after 1 month of treatment. Next-generation sequencing revealed that the tumor harbored 2 mutations, HRAS p.Q61R and TP53 p.P278S, and PD-L1 staining was positive with a high expression. Thus, camrelizumab (programmed cell death protein 1 inhibitor) was combined with apatinib, and apatinib was changed to 250âmg once a day from March 2020. OUTCOMES: No adverse reactions were observed after the treatment immunotherapy combined with antiangiogenic drugs. Currently, the survival time of patients is more than 11 months, and the quality of life is not affected. CONCLUSION: This case suggests that immunotherapy in patients with ATC based upon PD-L1 evaluation provides a therapeutic option. Targeting programmed cell death protein 1/PD-L1 may provide a much-needed treatment option for patients with advanced ATC.
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Inmunoterapia/métodos , Piridinas/administración & dosificación , Carcinoma Anaplásico de Tiroides/terapia , Neoplasias de la Tiroides/terapia , Administración Oral , Antineoplásicos/administración & dosificación , Antígeno B7-H1/metabolismo , Biomarcadores de Tumor , Femenino , Humanos , Persona de Mediana Edad , Carcinoma Anaplásico de Tiroides/diagnóstico , Carcinoma Anaplásico de Tiroides/metabolismo , Neoplasias de la Tiroides/diagnósticoRESUMEN
Glioma is a common life-threatening tumor with high malignancy and high invasiveness. LncRNA ZFPM2 antisense RNA 1 (ZFPM2-AS1) was confirmed to be implicated in numerous tumors, while its biological function and mechanism have not been thoroughly understood in glioma. The gene expression was measured by RT-qPCR. Cell proliferation, cell cycle, and cell apoptosis of glioma cells were validated by CCK-8, colony formation, flow cytometry and TUNEL assays. The effect of ZFPM2-AS1 on tumor growth was verified by in vivo assay. The exploration on ZFPM2-AS1-mediated mechanism was carried out via ChIP, luciferase reporter, and RIP assays. In the present study, ZFPM2-AS1 was demonstrated as a highly-expressed lncRNA in glioma tissues and cells. ZFPM2-AS1 silencing suppressed cell proliferation and cell cycle, but facilitated cell apoptosis. In addition, the inhibitive effect of silenced ZFPM2-AS1 was also observed in tumor growth. Furthermore, we found that SP1 interacted with ZFPM2-AS1 promoter to transcriptionally activate ZFPM2-AS1 expression. Moreover, ZFPM2-AS1 was identified as a competing endogenous RNA (ceRNA) for miR-515-5p to target SOD2. Rescue assays verified that SOD2 overexpression partially abolished the suppressive impact of ZFPM2-AS1 silencing on glioma cell growth. In conclusion, this study corroborated the regulatory mechanism of SP1/ZFPM2-AS1/miR-515-5p/SOD2 axis in glioma, indicating that targeting ZFPM2-AS1 might be an effective way to treat glioma.
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Neoplasias Encefálicas , Glioma , MicroARNs/metabolismo , ARN Largo no Codificante/metabolismo , Factor de Transcripción Sp1/metabolismo , Animales , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/patología , Línea Celular Tumoral , Progresión de la Enfermedad , Glioma/genética , Glioma/metabolismo , Glioma/patología , Humanos , Masculino , Ratones , Ratones Desnudos , MicroARNs/genética , ARN Largo no Codificante/genética , Factor de Transcripción Sp1/genética , Superóxido Dismutasa/genética , Superóxido Dismutasa/metabolismoRESUMEN
Uroplakin 1A (UPK1A) has recently been found dysregulation in many cancers. However, the functions of UPK1A and its underlying mechanisms in hepatocellular carcinoma (HCC) remain poorly understand. In the present study, we found that UPK1A was highly expressed in HCC tumor tissues compared with adjacent non-tumor tissues. Datasets from the Cancer Genome Atlas project (TCGA) and Gene expression Omnibus confirmed that UPK1A was highly expressed in HCC. High expression of UPK1A predicted poor overall survival (OS) in patients with HCC. Univariate and multivariate analysis showed that UPK1A was a significant and independent prognostic predictor for OS of patients with HCC. Functionally, silencing UPK1A suppressed HCC cell glycolysis and proliferation. Mechanistically, hypoxia-inducible factor 1α (HIF-1α) directly bound to the hypoxia response elements (HRE) of UPK1A promoter region, which led to the up-regulation of UPK1A under hypoxia. Furthermore, downregulation of UPK1A reduced key enzyme of glycolysis via regulating HIF-1α. Taken together, these data indicates the existence of a positive feedback loop between HIF-1α and UPK1A that modulates glycolysis and proliferation under hypoxia in HCC cells.
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The aim of this study was to investigate the effect of bioactive peptides (BAPT) from animal sources on the development of mouse preantral follicles in vitro. Preantral follicles were isolated and randomly divided into the following groups: an untreated group (control) and three groups supplemented with 20, 40 and 60 µg/mL BAPT, respectively. After establishing the in vitro follicle culture, the gene expression levels and hormone levels were quantified. After in vitro maturation, the developmental rates, reactive oxygen species (ROS) production levels and mitochondrial distributions of MII oocytes were investigated, followed by the analyses of embryonic developmental rates after in vitro fertilization.The results showed that BAPT promoted the growth of mouse preantral follicles. Notably, after 14 d of in vitro culture, the levels of 17 ß-estradiol and progesterone were up-regulated with BAPT treatments. Moreover, the expression levels of Oct4, Bmp15, GDF9, FOXO3, Zp3, FOXL2, Inhibin alpha, SOD2, Catalase, GPx and Bcl-2 in the developing follicles were significantly up-regulated after BAPT treatments (P < 0.05), while BAPT significantly inhibited the expression levels of BAX (P < 0.05). Following BAPT treatments, the ROS production levels of MII oocytes were decreased while the mitochondrial distributions were significantly enhanced. Furthermore, increased maturation rates, fertilization and embryonic developmental rates were found in these BAPT-treated groups (P < 0.05).These results demonstrated that BAPT significantly improved the development of preantral follicles in vitro by reducing ROS-dependent cellular damages and by enhancing mitochondrial distributions, thereby promoting the further applications of animal-derived BAPT in biomedical research.
Asunto(s)
Antioxidantes/farmacología , Factores Biológicos/farmacología , Redes Reguladoras de Genes/efectos de los fármacos , Folículo Ovárico/citología , Animales , Supervivencia Celular/efectos de los fármacos , Estradiol/metabolismo , Femenino , Fertilización In Vitro , Regulación de la Expresión Génica/efectos de los fármacos , Ratones , Folículo Ovárico/efectos de los fármacos , Folículo Ovárico/metabolismo , Progesterona/metabolismo , Distribución Aleatoria , Especies Reactivas de Oxígeno/metabolismo , Regulación hacia ArribaRESUMEN
PURPOSE: Less is known about sexual attitudes of breast cancer survivors (BCSs) and its association with sexual activity and sexual dissatisfaction. METHODS: We investigated the proportion of sexual activity and sexual dissatisfaction in a cross-sectional study among 341 Chinese BCSs aged 30-75 years old, and we described their association with sexual attitudes, as well as socio-demographic characteristics, physical health conditions, and mental health problems. RESULTS: Only 83 (24.3%) individuals reported sexual activity in the past year. More than 50% of BCSs considered that sexual activity had adverse impact on their disease recovery. The sexual attitudes such as "sexual activity may impede disease recovery" (adjusted odds ratio [AOR] = 0.51; 95% confidence interval, 95% CI: 0.30-0.88), "sexual activity may cause cancer recurrence or metastasizes" (AOR = 0.51; 95% CI: 0.30-0.87), and "their partner fear contracting cancer by sexuality" (AOR = 0.47; 95% CI: 0.23-0.98) were significantly associated with decreased likelihood of reporting sexual activity in the past year. Although 201 (58.9%) BCSs reported that breast cancer decreased the frequency of their sexual activity, only 37 (10.9%) had ever discussed sexuality with a doctor to seek advice. CONCLUSIONS: Most Chinese BCSs were sexually inactive. The sexual misconceptions about cancer were great barriers of sexual activity. Professional sexual education and consultation may be regarded as easy and effective intervention measures to correct BCSs' misguided sexual attitudes, and finally improving the overall sexual health for BCSs.