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Craft beer brewers need to learn process control strategies from traditional industrial production to ensure the consistent quality of the finished product. In this study, FT-IR combined with deep learning was used for the first time to model and analyze the Plato degree and total flavonoid content of Qingke beer during the mashing and boiling stages and to compare the effectiveness with traditional chemometrics methods. Two deep learning neural networks were designed, the effect of variable input methods on the effectiveness of the models was discussed. The experimental results showed that the CARS-LSTM model had the best predictive performance, not only as the best quantitative model for Plato in the mashing (R2p = 0.9368) and boiling (R2p = 0.9398) phases but also as the best model for TFC in the boiling phase (R2p = 0.9154). This study demonstrates the great potential of deep learning and provides a new approach to quality control analysis in beer brewing.
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Dipines are a type of important antihypertensive drug as L-calcium channel blockers, whose core skeleton is the 1,4-dihydropyridine structure. Since the dihydropyridine ring is a key structural factor for biological activity, the thermodynamics of the aromatization dihydropyridine ring is a significant feature parameter for understanding the mechanism and pathways of dipine metabolism in vivo. Herein, 4-substituted-phenyl-2,6-dimethyl-3,5-diethyl-formate-1,4-dihydropyridines are refined as the structurally closest dipine models to investigate the thermodynamic potential of dipine oxidative metabolism. In this work, the thermodynamic cards of dipine models' aromatization on 21 potential elementary steps in acetonitrile have been established. Based on the thermodynamic cards, the thermodynamic properties of dipine models and related intermediates acting as electrons, hydrides, hydrogen atoms, protons, and two hydrogen ions (atoms) donors are discussed. Moreover, the thermodynamic cards are applied to evaluate the redox properties, and judge or reveal the possible oxidative mechanism of dipine models.
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Oxidación-Reducción , Termodinámica , Dihidropiridinas/química , Dihidropiridinas/metabolismo , Antihipertensivos/química , Antihipertensivos/farmacología , Bloqueadores de los Canales de Calcio/química , Bloqueadores de los Canales de Calcio/farmacología , Estructura Molecular , Modelos MolecularesRESUMEN
Atmospheric and room temperature plasma (ARTP) mutagenesis technology has been developed rapidly in recent years because of its simple operation, safety, environmental friendliness, high mutation rate, and large mutation library capacity. It has been widely used in traditional fields such as food, agriculture, and medicine, and has been gradually applied in emerging fields such as environmental remediation, bioenergy, and microalgae utilization. In this paper, the Web of Science Core Collection (WOSCC) was used as the data source, and the keywords and core literature of ARTP mutagenesis technology were plotted by citespace software, and the research progress and research hotspots of ARTP mutagenesis technology were analyzed. Through citespace visualization analysis, it is concluded that the country with the largest number of studies is China, the institution with the largest number of studies is Jiangnan University, and the author of the most published papers is Jiangnan University. Through keyword analysis, it is concluded that the most widely used ARTP mutagenesis technology is fermentation-related majors, mainly for biosynthesis and microbial research at the molecular level. Among them, the most widely used microorganisms are Escherichia coli and Saccharomyces cerevisiae.
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Triadica sebifera (T. sebifera) has attracted much attention because of the high oil content in its seeds, but there are few systematic studies on the phenolic compounds of T. sebifera leaves (TSP). In this study, the extraction process of TSP was optimized by response surface methodology. The phenolic components of these extracts were analyzed by high-performance liquid chromatography (HPLC). Moreover, the effects of hot air drying (HD), vacuum drying (VD) and freeze drying (FD) on the antioxidant activity and characterization of T. sebifera leaf extract (TSLE) were evaluated. Under the conditions of ethanol concentration 39.8%, liquid-solid ratio (LSR) 52.1, extraction time 20.2 min and extraction temperature 50.6 °C, the maximum TSP yield was 111.46 mg GAE/g dw. The quantitative analysis and correlation analysis of eight compounds in TSP showed that the type and content of phenolic compounds had significant correlations with antioxidant activity, indicating that tannic acid, isoquercitrin and ellagic acid were the main components of antioxidant activities. In addition, through DPPH and ABTS determination, VD-TSLE and FD-TSLE showed strong scavenging ability, with IC50 values of 138.2 µg/mL and 135.5 µg/mL and 73.5 µg/mL and 74.3 µg/mL, respectively. Fourier transform infrared spectroscopy (FTIR) and scanning electron microscopy (SEM) infrared spectroscopy revealed small differences in the extracts of the three drying methods. This study lays a foundation for the effective extraction process and drying methods of phenolic antioxidants from T. sebifera leaves, and is of great significance for the utilization of T. sebifera leaves.
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Antioxidantes , Fenoles , Extractos Vegetales , Hojas de la Planta , Hojas de la Planta/química , Fenoles/química , Fenoles/aislamiento & purificación , Antioxidantes/química , Antioxidantes/farmacología , Antioxidantes/aislamiento & purificación , Extractos Vegetales/química , Extractos Vegetales/farmacología , Cromatografía Líquida de Alta PresiónRESUMEN
Lonicera similis Hemsl. (L. similis) is a promising industrial crop with flowers rich in phenolic compounds. In this study, an ultrasound-assisted extraction (UAE) was designed to extract phenolic compounds from L. similis flowers (LSFs). A contrastive analysis on the phenolic compounds' yield and characterization and the antioxidant activity of the extracts at three harvest stages (PGS I, PGS II, and PGS III) are reported. The results indicate that the optimal conditions are a sonication intensity of 205.9 W, ethanol concentration of 46.4%, SLR of 1 g: 31.7 mL, and sonication time of 20.1 min. Under these optimized conditions, the TPC values at PGS I, PGS II, and PGS III were 117.22 ± 0.55, 112.73 ± 1.68, and 107.33 ± 1.39 mg GAE/g, respectively, whereas the extract of PGS I had the highest TFC (68.48 ± 2.01 mg RE/g). The HPLC analysis showed that chlorogenic acid, rutin, quercetin, isoquercitrin, and ferulic acid are the main components in the phenolic compounds from LSFs, and their contents are closely corrected with the harvest periods. LSF extracts exhibited a better antioxidant activity, and the activity at PGS I was significantly higher than those at PGS II and PGS III. The correlation analysis showed that kaempferol and ferulic acid, among the eight phenolic compounds, have a significant positive correlation with the antioxidant activity, while the remaining compounds have a negative correlation. Minor differences in extracts at the three harvest stages were found through SEM and FTIR. These findings may provide useful references for the optimal extraction method of phenolic compounds from LSFs at three different harvest periods, which will help to achieve a higher phytochemical yield at the optimal harvest stage (PGS I).
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Antioxidantes , Flores , Lonicera , Fenoles , Extractos Vegetales , Antioxidantes/química , Antioxidantes/farmacología , Antioxidantes/aislamiento & purificación , Flores/química , Fenoles/química , Fenoles/aislamiento & purificación , Extractos Vegetales/química , Extractos Vegetales/farmacología , Lonicera/química , Cromatografía Líquida de Alta Presión , Ondas Ultrasónicas , SonicaciónRESUMEN
PURPOSE: Awake extubation and deep extubation are commonly used anesthesia techniques. In this study, the safety of propofol-assisted deep extubation in the dental treatment of children was assessed. MATERIALS AND METHODS: Children with severe caries who received dental treatment under general anesthesia and deep extubation between January 2017 and June 2023 were included in this study. Data were collected on the following variables: details and time of anesthesia, perioperative vital signs, and incidence of postoperative complications. The incidence of laryngeal spasm (LS) was considered to be the primary observation indicator. RESULTS: The perioperative data obtained from 195 children undergoing dental treatment was reviewed. The median age was 4.2 years (range: 2.3 to 9.6 years), and the average duration of anesthesia was 2.56 h (range 1 to 4.5 h). During intubation with a videoscope, purulent mucus was found in the pharyngeal cavity of seven children (3.6%); LS occurred in five of them (2.6%), and one child developed a fever (T = 37.8 °C) after discharge. Five children (2.6%) experienced emergence agitation (EA) in the recovery room. Also, 13 children (6.7%) experienced epistaxis; 10 had a mild experience and three had a moderate experience. No cases of airway obstruction (AO) and hypoxemia were recorded. The time to open eyes (TOE) was 16.3 ± 7.2 min. The incidence rate of complications was 23/195 (11.8%). Emergency tracheal reintubation was not required. Patients with mild upper respiratory tract infections showed a significantly higher incidence of complications (P < 0.001). CONCLUSIONS: Propofol-assisted deep extubation is a suitable technique that can be used for pediatric patients who exhibited non-cooperation in the outpatient setting. Epistaxis represents the most frequently encountered complication. Preoperative upper respiratory tract infection significantly increases the risk of complications. The occurrence of EA was notably lower than reported in other studies.
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Extubación Traqueal , Propofol , Humanos , Extubación Traqueal/métodos , Preescolar , Estudios Retrospectivos , Propofol/administración & dosificación , Propofol/efectos adversos , Niño , Masculino , Femenino , Anestésicos Intravenosos , Anestesia General/métodos , Complicaciones Posoperatorias/epidemiología , Laringismo/epidemiología , Intubación Intratraqueal/métodos , Anestesia Dental/métodosRESUMEN
The speed of evolution on structured populations is crucial for biological and social systems. The likelihood of invasion is key for evolutionary stability. But it makes little sense if it takes long. It is far from known what population structure slows down evolution. We investigate the absorption time of a single neutral mutant for all the 112 non-isomorphic undirected graphs of size 6. We find that about three-quarters of the graphs have an absorption time close to that of the complete graph, less than one-third are accelerators, and more than two-thirds are decelerators. Surprisingly, determining whether a graph has a long absorption time is too complicated to be captured by the joint degree distribution. Via the largest sojourn time, we find that echo-chamber-like graphs, which consist of two homogeneous graphs connected by few sparse links, are likely to slow down absorption. These results are robust for large graphs, mutation patterns as well as evolutionary processes. This work serves as a benchmark for timing evolution with complex interactions, and fosters the understanding of polarization in opinion formation.
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Evolución Biológica , Mutación , Modelos GenéticosRESUMEN
INTRODUCTION: Pseudomyxoma peritonei (PMP) is a condition characterised by the presence of gelatinous tumour-like growth within the peritoneal cavity. Combined cytoreductive surgery and intraperitoneal chemotherapy have shown to improve the survival rate in PMP patients. However, post-operative complications such as cognitive dysfunction, respiratory insufficiency and acute renal failure are still observed. This retrospective study aims to explore the risk factors associated with major post-operative complications and specifically investigate the correlation with intraoperative hypotension. PATIENTS AND METHODS: This retrospective cohort study included PMP patients treated at Beijing Aerospace Center Hospital from 1 June, 2014 to 30 December, 2020. The primary outcome measures were major post-operative complications, including neurological, pulmonary, cardiovascular, surgical complications, acute hepatic injury and acute kidney injuries. The secondary outcome measures included infection, fever and deep venous thrombosis. Statistical analysis was conducted using EmpowerStats and R software. RESULTS: A total of 782 patients were screened, and 668 patients were included in the statistical analysis. Amongst them, 234 (35.03%) individuals experienced major post-operative complications. Factors such as pre-operative American Society of Anaesthesiologists grading, age, haemoglobin and albumin levels, intraoperative mean arterial pressure, blood loss, fluid replacement volume, method of intraperitoneal hyperthermic perfusion and post-operative requirement for intensive care unit mechanical ventilation were found to be correlated with major complications. CONCLUSION: The identified risk factors provide valuable insights for improving clinical pathways in the management of PMP. Further prospective studies are warranted to establish the association between these factors and patient outcomes.
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In this study, we have synthesised a chiral l-hyp-Ni/Fe@SiO2 composite as a chiral stationary phase (CSP) for high-performance liquid chromatography (HPLC) for the first time. This was achieved by coating two-dimensional (2D) chiral metal-organic framework nanosheets (MONs) l-hyp-Ni/Fe onto the surface of activated SiO2 microspheres using the "wrapped in net" method. The separation efficiency of the l-hyp-Ni/Fe chromatographic column was systematically evaluated in normal-phase HPLC (NP-HPLC) and reversed-phase HPLC (RP-HPLC) configurations, employing various racemates as analytes. The findings revealed that 16 chiral compounds were separated using NP-HPLC, and five were separated using RP-HPLC, encompassing alcohols, amines, ketones, esters, alkanes, ethers, amino acids and sulfoxides. Notably, the resolution (Rs) of nine chiral compounds exceeded 1.5, indicating baseline separation. Furthermore, the resolution performance of the l-hyp-Ni/Fe@SiO2-packed column was compared with that of Chiralpak AD-H. It was observed that certain enantiomers, which either could not be resolved or were inadequately separated on the Chiralpak AD-H column, attained separation on the 2D chiral MONs column. These findings suggest a complementary relationship between the two columns in racemate separation, with their combined application facilitating the resolution of a broader spectrum of chiral compounds. In addition, baseline separation was achieved for five positional isomers on the l-hyp-Ni/Fe@SiO2-packed column. The effects of the analyte mass and column temperature on the resolution were also examined. Moreover, during HPLC analysis, the l-hyp-Ni/Fe columns demonstrated commendable repeatability, stability and reproducibility in enantiomer separation. This research not only advances the utilisation of 2D chiral MONs as CSPs but also expands their applications in the separation sciences.
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Estructuras Metalorgánicas , Dióxido de Silicio , Cromatografía Líquida de Alta Presión/métodos , Dióxido de Silicio/química , Estructuras Metalorgánicas/química , Estereoisomerismo , Nanoestructuras/química , Hierro/química , Níquel/químicaRESUMEN
Background: Head and neck squamous cell carcinoma (HNSCC) is the sixth most prevalent malignant cancer worldwide. The cysteine X cysteine (CXC) chemokine family contains 17 members, which are reportedly crucial for the growth, invasion, metastasis, and microenvironment of tumor cells. Although the precise functions of CXC ligands (CXCLs) in HNSCC are unclear, these proteins may play important roles in controlling tumor growth and forming the tumor immune environment. Methods: We downloaded the RNA sequencing and matched clinicopathological data of 379 patients with HNSCC as the training set from The Cancer Genome Atlas and two datasets from the Gene Expression Omnibus for use as validation sets. Results: Through consensus clustering, we identified two subtypes of HNSCC associated with the CXCL family, named cluster1 and cluster2. Patients with the cluster1 subtype showed favourable clinical outcomes, significant immune cell infiltration, and improved immune response signalling pathway modulation. We also developed a nomogram of CXCL family scores for therapeutic use and for predicting the overall survival (OS) of patients with HNSCC. Patients with lower scores showed longer OS and higher immune cell infiltration in their tissues. Conclusions: We developed a new classification method for HNSCC using the CXCL gene family, which can be used clinically to evaluate the prognosis and response to immunotherapy in patients with HNSCC.
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Tamoxifen (TAM) is the primary drug for treating estrogen receptor alpha-positive (ER+) breast cancer (BC). However, resistance to TAM can develop in some patients, limiting its therapeutic efficacy. The ubiquitin-specific protease (USP) family has been associated with the development, progression, and drug resistance of various cancers. To explore the role of USPs in TAM resistance in BC, we used qRT-PCR to compare USP expression between TAM-sensitive (MCF-7 and T47D) and TAM-resistant cells (MCF-7R and T47DR). We then modulated USP46 expression and examined its impact on cell proliferation, drug resistance (via CCK-8 and EdU experiments), glycolysis levels (using a glycolysis detection assay), protein interactions (confirmed by co-IP), and protein changes (analyzed through Western blotting). Our findings revealed that USP46 was significantly overexpressed in TAM-resistant BC cells, leading to the inhibition of the ubiquitin degradation of polypyrimidine tract-binding protein 1 (PTBP1). Overexpression of PTBP1 increased the PKM2/PKM1 ratio, promoted glycolysis, and intensified TAM resistance in BC cells. Knockdown of USP46 induced downregulation of PTBP1 protein by promoting its K48-linked ubiquitination, resulting in a decreased PKM2/PKM1 ratio, reduced glycolysis, and heightened TAM sensitivity in BC cells. In conclusion, this study highlights the critical role of the USP46/PTBP1/PKM2 axis in TAM resistance in BC. Targeted therapy against USP46 may represent a promising strategy to improve the prognosis of TAM-resistant patients.
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Neoplasias de la Mama , Tamoxifeno , Humanos , Femenino , Tamoxifeno/farmacología , Tamoxifeno/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/genética , Neoplasias de la Mama/metabolismo , Células MCF-7 , Resistencia a Antineoplásicos/genética , Glucólisis , Ribonucleoproteínas Nucleares Heterogéneas/genética , Ribonucleoproteínas Nucleares Heterogéneas/metabolismo , Proteína de Unión al Tracto de Polipirimidina/genética , Proteína de Unión al Tracto de Polipirimidina/metabolismoRESUMEN
BACKGROUND: Breast cancer is a common malignant tumor in women and most patients with breast cancer experience fatigue. Numerous studies have investigated the relationship between yoga and cancer-related fatigue (CRF) in patients with breast cancer. However, these studies drew their conclusions from small sample sizes and lacked sufficient evidence to demonstrate that yoga can effectively alleviate CRF. Therefore, this meta-analysis aims to systematically examine the effects of yoga on cancer fatigue in patients with breast cancer and establish a scientific basis for enhancing their quality of life. OBJECTIVE: To assess the effect of yoga on CRF in patients with breast cancer. METHODS: Computer searches were conducted on PubMed, Embase, Web of Science, CKNI, and Wanfang databases to retrieve articles related to yoga and CRF in patients with breast cancer from the hospital establishment date to July 2023. The literature was independently screened, and the information was extracted by the researchers. A meta-analysis was conducted using Review Manager Software (version 5.3). RESULTS: The findings from the meta-analysis of 18 studies indicate that yoga can effectively enhance CFR (standardized mean difference (SMD)â =â -0.51, 95% confidence interval [CI]â =â -0.92 to -0.10), improve sleep quality (MDâ =â -3.86, 95%CIâ =â -4.03 to -3.70) in patients with breast cancer, alleviate anxiety and depression (SMDâ =â -0.93, 95%CIâ =â -1.68, -0.18, SMDâ =â -1.23, 95%CIâ =â -2.02 to -0.44), and enhance quality of life (MDâ =â -11.20, 95%CIâ =â -14.16 to -8.24). CONCLUSION: Our study offers evidence for the subsequent reduction of CFR in patients with breast cancer. Yoga can alleviate fatigue, improve sleep quality and negative emotions, and improve the quality of life of patients with breast cancer.
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Neoplasias de la Mama , Yoga , Humanos , Femenino , Neoplasias de la Mama/complicaciones , Calidad de Vida , Mama , Fatiga/etiología , Fatiga/terapiaRESUMEN
BACKGROUND: Vascular tortuosity is a prevalent morphological change that frequently occurs in arteries across different parts of the body. OBJECTIVE: To analyze the relationship between the tortuosities of the extracranial internal carotid artery (EICA) and extracranial vertebral artery (EVA) with mild cognitive impairment. METHODS: The tortuosity index (TI), vascular deviation degree, tortuosity degree, and angle number of the EICA and EVA were retrospectively analyzed and calculated in 160 patients who underwent computed tomography angiography (CTA) in this study's department, and the Montreal cognitive assessment was adopted to evaluate the cognitive function of the patients. RESULTS: The differences in age, gender, arterial hypertension (AH), and diabetes mellitus (DM) between the normal group and the mild cognitive impairment group were statistically significant (p< 0.01). The TI was negatively correlated with the score of cognitive function. The tortuosities of the EICA and EVA were correlated with mild cognitive impairment (p< 0.05). The reduction in visual-spatial ability was correlated with the right EICA tortuosity, and the reduction in memory was correlated with the EVA tortuosity. Age, gender, HP, DM, and coronary heart disease (CHD) were potential risk factors for carotid tortuosity (p< 0.05). CONCLUSION: There was a significant correlation observed between the TIs of both the EICA and EVA and the presence of mild cognitive impairment. Advanced age, female, HP, DM, and CHD were independent risk factors for EICA and EVA tortuosities.
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Arteria Carótida Interna , Disfunción Cognitiva , Humanos , Femenino , Arteria Carótida Interna/diagnóstico por imagen , Estudios Retrospectivos , Arteria Vertebral/diagnóstico por imagenRESUMEN
Lung adenocarcinoma, the most frequent type of lung cancer, is the leading cause of cancer-related deaths worldwide. Ferroptosis, controlled cell death that involves a high degree of iron-dependent lipid peroxidation, has been linked to tumor therapy sensitivity, patient prognosis, and cancer development. The solute carrier superfamily has over 400 members and comprises the largest class of transporters in the human genome. Solute carrier proteins can facilitate the movement of different substrates across biological membranes, which is crucial for physiological activities, including ferroptosis. Here, we developed a new model to further explore the role of the solute carrier family in ferroptosis in the lung adenocarcinoma immunological milieu. We used consensus clustering to classify patients with lung cancer into two subgroups (cluster1 and cluster2). Patients in the cluster1 subtype had a better prognosis and higher immune cell infiltration ratios than those in the cluster2 subtype. Furthermore, to evaluate the prognosis, the immune cell infiltration ratio, and the medication sensitivity of patients with lung adenocarcinoma, we developed gene scores related to the solute carrier family. In conclusion, we successfully developed a model incorporating the solute carrier family and ferroptosis to predict survival and the impact of immunotherapy on patients with lung cancer.
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Adenocarcinoma del Pulmón , Ferroptosis , Neoplasias Pulmonares , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/terapia , Ferroptosis/genética , Adenocarcinoma del Pulmón/genética , Adenocarcinoma del Pulmón/terapia , Pronóstico , InmunoterapiaRESUMEN
BACKGROUND: To investigate the association between CT signs and clinicopathological features and disease recurrence in patients with hepatoid adenocarcinoma of stomach (HAS). METHODS: Forty nine HAS patients undergoing radical surgery were retrospectively collected. Association between CT and clinicopathological features and disease recurrence was analyzed. Multivariate logistic model was constructed and evaluated for predicting recurrence by using receiver operating characteristic (ROC) curve. Survival curves between model-defined risk groups was compared using Kaplan-Meier method. RESULTS: 24(49.0%) patients developed disease recurrence. Multivariate logistic analysis results showed elevated serum CEA level, peritumoral fatty space invasion and positive pathological vascular tumor thrombus were independent factors for disease recurrence. Odds ratios were 10.87 (95%CI, 1.14-103.66), 6.83 (95%CI, 1.08-43.08) and 42.67 (95%CI, 3.66-496.85), respectively. The constructed model showed an area under ROC of 0.912 (95%CI,0.825-0.999). The model-defined high-risk group showed poorer overall survival and recurrence-free survival than the low-risk group (both P < 0.001). CONCLUSIONS: Preoperative CT appearance of peritumoral fatty space invasion, elevated serum CEA level, and pathological vascular tumor thrombus indicated poor prognosis of HAS patients.
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Adenocarcinoma , Neoplasias Gástricas , Trombosis , Neoplasias Vasculares , Humanos , Estudios Retrospectivos , Pronóstico , Neoplasias Vasculares/patología , Recurrencia Local de Neoplasia/diagnóstico por imagen , Recurrencia Local de Neoplasia/patología , Adenocarcinoma/diagnóstico por imagen , Adenocarcinoma/cirugía , Neoplasias Gástricas/diagnóstico por imagen , Neoplasias Gástricas/cirugía , Tomografía Computarizada por Rayos X , Estadificación de NeoplasiasRESUMEN
OBJECTIVE: Anaplastic lymphoma kinase-tyrosine kinase inhibitors (ALK-TKIs) are new treatment for advanced non-small cell lung cancer. Here, we quantified the toxicity profiles of different ALK-TKIs to guide clinical decision making. MATERIALS AND METHODS: We searched PubMed, Embase, and the Cochrane Central Register of Controlled Trials. Data were analyzed using random effects and consistency models under the frequency framework. RESULTS: Of 865 relevant studies, 13 RCTs (encompassing 3,353 patients) were finally included. A network meta-analysis of all-grade AEs, fatal AEs, and treatment discontinuation due to AEs revealed no significant differences among the six ALK-TKIs. The rates of grade 3-4 AEs were: alectinib (16.2%), crizotinib (46.4%), brigatinib (63.7%), ensartinib (75.6%), ceritinib (78.3%), and lorlatinib (91.6%). The toxicity spectra of ALK-TKIs were different. The most frequent AEs associated with crizotinib were gastrointestinal reactions, visual disorders, neutropenia, edema, fatigue, and elevated alanine aminotransferase (ALT) or aspartate aminotransferase (AST) levels, while those in the alectinib group were anemia and constipation. Diarrhea, hepatotoxicity, and increased serum creatinine were most common with ceritinib. The most frequent AEs in the brigatinib group were gastrointestinal reactions, hypertension, cough, headache, and elevated ALT or AST levels. The most significant toxicities of ensartinib were skin disorders, including pruritus and rash. Changes in lipid levels were the most frequent AEs associated with lorlatinib; weight gain, cognitive effects, and mood effects were lorlatinib-specific AEs. CONCLUSIONS: The toxicity spectra of ALK-TKIs differed. Alectinib might be the safest ALK-TKI drug according to the combined evidence of grades 3-4 AEs and the combined incidence.
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Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Humanos , Quinasa de Linfoma Anaplásico/genética , Proteínas Tirosina Quinasas , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/genética , Crizotinib , Metaanálisis en Red , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/genética , Inhibidores de Proteínas Quinasas/efectos adversosRESUMEN
Breast cancer (BRCA) cells typically exist in nutrient-deficient microenvironments and quickly adapt to states with fluctuating nutrient levels. The tumor microenvironment of starvation is intensely related to metabolism and the malignant progression of BRCA. However, the potential molecular mechanism has not been thoroughly scrutinized. As a result, this study aimed to dissect the prognostic implications of mRNAs involved in the starvation response and construct a signature for forecasting the outcomes of BRCA. In this research, we investigated how starvation could affect BRCA cells' propensities for invasion and migration. The effects of autophagy and glucose metabolism mediated by starved stimulation were examined through transwell assays, western blot, and the detection of glucose concentration. A starvation response-related gene (SRRG) signature was ultimately generated by integrated analysis. The risk score was recognized as an independent risk indicator. The nomogram and calibration curves revealed that the model had excellent prediction accuracy. Functional enrichment analysis indicated this signature was significantly enriched in metabolic-related pathways and energy stress-related biological processes. Furthermore, phosphorylated protein expression of the model core gene EIF2AK3 increased after the stimulus of starvation, and EIF2AK3 may play an essential role in the progression of BRCA in the starved microenvironment. To sum up, we constructed and validated a novel SRRG signature that could accurately predict outcomes and may be developed as a therapeutic target for the precise treatment of BRCA.
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Neoplasias de la Mama , Humanos , Femenino , Neoplasias de la Mama/genética , Pronóstico , Nomogramas , Autofagia/genética , Western Blotting , Microambiente Tumoral/genéticaRESUMEN
BACKGROUND: The impact of marijuana on the general population is largely unknown. The present study aimed to assess the association between marijuana use and liver steatosis and fibrosis in the general United States population utilizing data from the National Health and Nutrition Examination Survey (NHANES). METHODS: This cross-sectional study was performed with data from the 2017-2018 cycle of NHANES. The target population comprised adults in the NHANES database with reliable vibration controlled transient elastography (VCTE) results. The median values of the controlled attenuation parameter (CAP) and liver stiffness measurement (LSM) were used to evaluate liver steatosis and fibrosis, respectively. After adjusting for relevant confounders, a logistic regression analysis was used to assess the association between marijuana use and liver steatosis and fibrosis. RESULTS: A total of 2622 participants were included in this study. The proportions of never marijuana users, past users, and current users were 45.9%, 35.0%, and 19.1%, respectively. Compared to never marijuana users, past and current users had a lower prevalence of liver steatosis (P = 0.184 and P = 0.048, respectively). In the alcohol intake-adjusted model, current marijuana use was an independent predictor of a low prevalence of liver steatosis in people with non-heavy alcohol intake. The association between marijuana use and liver fibrosis was not significant in univariate and multivariate regression. CONCLUSION: In this nationally representative sample, current marijuana use is inversely associated with steatosis. The pathophysiology is unclear and needs further study. No significant association was established between marijuana use and liver fibrosis, irrespective of past or current use.
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Diagnóstico por Imagen de Elasticidad , Hígado Graso , Uso de la Marihuana , Enfermedad del Hígado Graso no Alcohólico , Trastornos Relacionados con Sustancias , Adulto , Humanos , Estados Unidos/epidemiología , Diagnóstico por Imagen de Elasticidad/métodos , Estudios Transversales , Encuestas Nutricionales , Hígado Graso/diagnóstico por imagen , Hígado Graso/epidemiología , Hígado Graso/complicaciones , Cirrosis Hepática/diagnóstico por imagen , Cirrosis Hepática/epidemiología , Cirrosis Hepática/etiología , Trastornos Relacionados con Sustancias/complicaciones , Enfermedad del Hígado Graso no Alcohólico/diagnóstico por imagen , Enfermedad del Hígado Graso no Alcohólico/epidemiología , Enfermedad del Hígado Graso no Alcohólico/complicaciones , Hígado/patologíaRESUMEN
Intervertebral disc (IVD) degeneration and its inflammatory microenvironment can result in discogenic pain, which has been shown to stem from the nucleus pulposus (NP). Increasing evidence suggests that mitochondrial related genes are strictly connected to cell functionality and, importantly, it can regulate cell immune activity in response to damaged associated signals. Therefore, identification of mitochondria related genes might offer new diagnostic markers and therapeutic targets for IVD degeneration. In this study, we identified key genes involved in NP tissue immune cell infiltration during IVD degeneration by bioinformatic analysis. The key modules were screened by weighted gene co-expression network analysis (WCGNA). Characteristic genes were identified by random forest analysis. Then gene set enrichment analysis (GSEA) was used to explore the signaling pathways associated with the signature genes. Subsequently, CIBERSORT was used to classify the infiltration of immune cells. Function of the hub gene was confirmed by PCR, Western blotting and ELISA. Finally, we identified MFN2 as a crucial molecule in the process of NP cell pyroptosis and NLRP3 inflammasome activation. We speculate that the increased MFN2 expression in NP tissue along with the infiltration of CD8+ T cells, NK cell and neutrophils play important roles in the pathogenesis of IVD degeneration.
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Angiogenesis is crucial in the development and progression of tumors. This study examined the relationship between angiogenesis-related lncRNAs (AR-lncRNAs) and breast cancer (BC) immunity and prognosis. We used univariate Cox regression analysis to obtain AR-lncRNAs closely related to BC prognosis. Cluster analysis of BC patients was performed using non-negative matrix factorization (NMF) analysis according to the expression of AR-lncRNAs that were prognostically relevant. An AR-lncRNA risk model (AR-lncM) was created using LASSO regression analysis to predict the prognosis and survival of BC patients. Subsequently, the effect of LINC01614 on cell migration and invasion was verified by Transwell and Western blot assays, and the CCK-8 assay detected its impact on cell sensitivity to tamoxifen. Finally, we obtained 17 AR-lncRNAs from the TCGA database that were closely associated with the prognosis of BC patients. Based on the expression of these AR-lncRNAs, BC patients were divided into five clusters using NMF analysis. Cluster 1 was found to have a better prognosis, higher expression of immune checkpoints, and higher levels of immune cell infiltration. Furthermore, an AR-LncM model was created using ten prognostic-related AR-lncRNAs. The model's risk predictive performance was validated using survival analysis, timeROC curves, and univariate and multivariate Cox analysis. The most interesting gene in the model, LINC01614, was found to regulate epithelial-mesenchymal transition (EMT) and tamoxifen sensitivity in BC cells, implying that LINC01614 could be a potential therapeutic target for BC patients.