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To study the effect of polycrystalline 3C-SiC rough friction surface on the mechanism of subsurface brittleness during nanocrystalline grinding. Initial grinding models of polycrystalline 3C-SiC and diamond abrasive grains on rough friction surfaces are developed using molecular dynamics methods and the Voronoi method for constructing polycrystalline abrasive grains. The processing mechanism of 3C-SiC is analyzed by post-processing methods such as dislocation defect analysis, atomic arrangement analysis and stress analysis. At 2.6 nm, "stress concentration" occurs between the abrasive particles and the workpiece, forming irregular force shapes. The larger the grain size, the smaller the crystal hardness, the greater the possibility of crystal fracture, and it is obvious in the crystal of larger grains. At 8 nm, the crystal breaks and creates vacancies. The roughness of the polycrystalline 3C-SiC friction surface and the cross-cutting mechanism between grains with grain boundaries are found to be effective in ameliorating the damage in the subsurface layer.
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BACKGROUND: To evaluate the efficacy and safety of nab-paclitaxel plus cisplatin as the regimen of conversional chemoradiotherapy (cCRT) in locally advanced borderline resectable or unresectable esophageal squamous cell carcinoma (ESCC). METHODS: Patients with locally advanced ESCC (cT34, Nany, M01, M1 was limited to lymph node metastasis in the supraclavicular area) were enrolled. All the patients received the cCRT of nab-paclitaxel plus cisplatin. After the cCRT, those resectable patients received esophagectomy; those unresectable patients continued to receive the definitive chemoradiotherapy (dCRT). The locoregional control (LRC), overall survival (OS), event-free survival (EFS), distant metastasis free survival (DMFS), pathological complete response (pCR), R0 resection rate, adverse events (AEs) and postoperative complications were calculated. RESULTS: 45 patients with ESCC treated from October 2019 to May 2021 were finally included. The median follow-up time was 30.3 months. The LRC, OS, EFS, DMFS at 1 and 2 years were 81.5%, 86.6%, 64.3%, 73.2 and 72.4%, 68.8%, 44.8%, 52.7% respectively. 21 patients (46.7%) received conversional chemoradiotherapy plus surgery (cCRT+S). The pCR rate and R0 resection rate were 47.6 and 84.0%. The LRC rate at 1 and 2 years were 95.0%, 87.1% in cCRT+S patitents and 69.3%, 58.7% in dCRT patients respectively (HR, 5.14; 95%CI, 1.10-23.94; Pâ¯= 0.021). The toxicities during chemoradiotherapy were tolerated, and the most common grade 3-4 toxicitiy was radiation esophagitis (15.6%). The most common postoperative complication was pleural effusion (38.1%) and no gradeâ¯≥ IIIb complications were observed. CONCLUSION: nab-paclitaxel plus cisplatin are safe as the regimen of conversional chemoradiotherapy of ESCC.
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Biochar application is an effective strategy to address Agro-climatic challenges. However, the agro-environmental impacts of different biochar technology models are lacking of systematic summaries and reviews. Therefore, this paper comprehensively reviews recent developments derived from published literature, delving into the economic implications and environmental benefits of three distinct process namely technologies-pyrolysis, gasification, and hydrothermal carbonization. This paper specifically focuses on the agricultural life cycle assessment (LCA) methodology, and the influence of biochar preparation technologies and products on energy consumption and agricultural carbon emissions. LCA analysis shows that process and feedstock pose a predominant role on the properties and production rate of biochar, while gasification technology exhibits excellent economic attributes compared to the other two technologies. Biochar applications in agricultural has the beneficial effect of sequestering carbon and reducing emissions, especially in the area of mitigating the carbon footprint of farmland. However, the complexity of the composition of the prepared feedstock and the mismatch between the biochar properties and the application scenarios are considered as potential sources of risks. Notably, mechanism of carbon sequestration and emission reduction by soil microorganisms and agro-environmental sequestration by biochar application remains unclear, calling for in-depth studies. We review novel aspects that have not been covered by previous reviews by comparing the technical, economic, and environmental benefits of pyrolysis, gasification, and hydrothermal carbonization systematically. Overall, this study will provide a valuable framework to environmental implications of biochar preparation, application, and life cycle assessments.
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BACKGROUND: Overexpression of receptor tyrosine kinase-like orphan receptor 1 (ROR1) contributes to cancer cell proliferation, survival and migration, playing crucial roles in tumor development. ROR1 has been proposed as a potential therapeutic target for cancer treatment. This study aimed to develop novel humanized ROR1 monoclonal antibodies and investigate their anti-tumor effects. METHODS: ROR1 expression in tumor tissues and cell lines was analyzed by immunohistochemistry and flow cytometry. Antibodies from mouse hybridomas were humanized by the complementarity-determining region (CDR) grafting technique. Surface plasmon resonance spectroscopy, ELISA assay and flow cytometry were employed to characterize humanized antibodies. In vitro cellular assay and in vivo mouse experiment were conducted to comprehensively evaluate anti-tumor activity of these antibodies. RESULTS: ROR1 exhibited dramatically higher expression in lung adenocarcinoma, liver cancer and breast cancer, and targeting ROR1 by short-hairpin RNAs significantly inhibited proliferation and migration of cancer cells. Two humanized ROR1 monoclonal antibodies were successfully developed, named h1B8 and h6D4, with high specificity and affinity to ROR1 protein. Moreover, these two antibodies effectively suppressed tumor growth in the lung cancer xenograft mouse model, c-Myc/Alb-cre liver cancer transgenic mouse model and MMTV-PyMT breast cancer mouse model. CONCLUSIONS: Two humanized monoclonal antibodies targeting ROR1, h1B8 and h6D4, were successfully developed and exhibited remarkable anti-tumor activity in vivo.
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Anticuerpos Monoclonales Humanizados , Proliferación Celular , Receptores Huérfanos Similares al Receptor Tirosina Quinasa , Ensayos Antitumor por Modelo de Xenoinjerto , Receptores Huérfanos Similares al Receptor Tirosina Quinasa/metabolismo , Receptores Huérfanos Similares al Receptor Tirosina Quinasa/antagonistas & inhibidores , Receptores Huérfanos Similares al Receptor Tirosina Quinasa/inmunología , Animales , Humanos , Ratones , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Anticuerpos Monoclonales Humanizados/farmacología , Anticuerpos Monoclonales Humanizados/uso terapéutico , Femenino , Movimiento Celular/efectos de los fármacos , Neoplasias/tratamiento farmacológico , Neoplasias/inmunología , Neoplasias/patología , Neoplasias/terapia , Neoplasias/metabolismo , Ratones Transgénicos , Modelos Animales de Enfermedad , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/inmunologíaRESUMEN
Plant non-structural carbohydrates (NSCs), which largely comprise starch and soluble sugars, are essential energy reserves to support plant growth and physiological functions. While it is known that increasing global deposition of nitrogen (N) affects plant concentration of NSCs, quantification of seasonal responses and drivers of woody species leaf and root NSCs to N addition at larger spatial scales remains lacking. Here, we systematically analyzed data from 53 field experiments distributed across China, comprising 1202 observations, to test for effects of N addition on woody plant leaf and root NSCs across and within growing and non-growing seasons. We found (1) no overall effects of N addition on the concentrations of leaf and root NSCs, soluble sugars or starch during the growing season or the non-growing season for leaves. However, N addition decreased root NSC and starch concentrations by 13.8 % and 39.0 %, respectively, and increased soluble sugars concentration by 15.0 % during the non-growing season. (2) Shifts in leaf NSC concentration under N addition were driven by responses by soluble sugars in both seasons, while shifts in root NSC were driven by soluble sugars in the non-growing season and starch and soluble sugars in the growing season. (3) Relationships between N, carbon, and phosphorus stoichiometry with leaf and root NSCs indicated effects of N addition on woody plant NSCs allocation through impacts on plant photosynthesis, respiration, and growth. (4) Effects of N addition on leaf and root NSCs varied with plant functional types, where effects were more pronounced in roots than in leaves during the non-growing season. Overall, our results reveal divergent responses of woody plant leaf and root NSCs to N addition within non-growing season and highlight the role of ecological stoichiometry and plant functional types in woody plant allocation patterns of NSCs in response to ongoing N deposition under global change.
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OBJECTIVE: To introduce a novel approach for predicting the personalized probability of success of DPC treatment in carious mature permanent teeth using explainable machine learning (ML) models. METHODS: Clinical data were obtained from our previous single-center retrospective study, comprising 393 carious mature permanent teeth from 372 patients who underwent DPC and attended 1-year follow-up between January 2015 and February 2021. Six ML models were derived based on 80 % cases of the cohort, with the remaining 20 % cases used for validation. Shapley additive explanation (SHAP) values were utilized to assess feature importance and the clinical relevance of prediction models. RESULTS: Within the cohort, 9.67 % (38 out of 393) of teeth experienced failure at the 1-year follow-up after DPC treatment. Among the six evaluated ML models, the XGBoost model exhibited the highest discriminative ability. By prioritizing features based on their importance, streamlined and interpretable XGBoost model with 11 features were developed for 1-year prognostication post-DPC. The model demonstrated predictive accuracy with area under the curve (AUC) scores of 0.86 for the 1-year prediction. The final model has been translated into a web application to facilitate clinical decision-making. CONCLUSION: By incorporating demographic and clinical examination data, the XGBoost model offered a user-friendly tool for dentists to predict personalized probability of success, thereby improving personalized dental care and patient counseling. The utilization of SHAP for model interpretation provided transparent insights into the decision-making process.
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Purpose: This two-center study aimed to explore the main prognostic factors affecting the final disease status in children and adolescents with differentiated thyroid cancer (caDTC) following total thyroidectomy and radioiodine therapy (RAIT). Materials and methods: All caDTC patients from two centers in the period from 2004-2022 were retrospectively included. At the last follow-up, the patients' disease status was assessed and classified as an incomplete response (IR) or as an excellent or indeterminate response (EIDR). Then, the difference in preablation stimulated thyroglobulin (ps-Tg) levels between the two groups was compared, and the threshold for predicting IR was determined using receiver operating characteristic (ROC) analysis. Moreover, univariate and multivariate analyses were conducted to identify the factors influencing the patients' ultimate disease outcomes. Results: A total of 143 patients (98 females, 45 males; median age 16 years) were recruited. After a median follow-up of 42.9 months, 80 patients (55.9%) exhibited an EIDR, whereas 63 patients (44.1%) exhibited an IR. Patients with an IR had significantly greater ps-Tg levels than did those with an EIDR (median ps-Tg 79.2 ng/mL vs. 9.3 ng/mL, p<0.001). The ROC curve showed that ps-Tg ≥20 ng/mL was the most accurate for predicting IR at the last follow-up. According to multivariate analysis, only ps-Tg, T stage and the therapeutic response to initial RAIT were significantly associated with IR. Conclusion: In caDTC patients, the ps-Tg level, T stage, and response to initial RAIT are critical final outcome indicators.
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Radioisótopos de Yodo , Neoplasias de la Tiroides , Tiroidectomía , Humanos , Femenino , Masculino , Radioisótopos de Yodo/uso terapéutico , Adolescente , Neoplasias de la Tiroides/radioterapia , Neoplasias de la Tiroides/cirugía , Neoplasias de la Tiroides/patología , Neoplasias de la Tiroides/terapia , Estudios Retrospectivos , Pronóstico , Niño , China/epidemiología , Estudios de Seguimiento , Resultado del Tratamiento , Tiroglobulina/sangre , Terapia CombinadaRESUMEN
In light of the escalating industrial and environmental pollution, there is a pressing need for the development of novel materials capable of swiftly detecting pollutants. Here, we report the synthesis of five lanthanide metal-organic frameworks sharing a common structure, prepared via a hydrothermal method and denoted as [Ln2(H2DHBDC)2(phen)(H2O)6]n (where CUST-888 corresponds to Tb, CUST-889 corresponds to Eu, CUST-890 corresponds to Gd, CUST-891 corresponds to Dy, and CUST-892 corresponds to Nd). Notably, CUST-888 and CUST-889 exhibit discernible visual alterations in response to acidic and alkaline conditions. To assess their practical utility, luminescent test strips and light-emitting diode lights based on CUST-888 and CUST-889 were devised, enabling the visual detection of luminescence color changes induced by Hg2+, Cr2O72-, tetracycline, and 2,4,6-trinitrophenol. Furthermore, highlighters derived from CUST-888 and CUST-889 were designed, showcasing robust stability, adjustable color, and substantial potential for application in the realm of anticounterfeiting.
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Helicobacter pylori has been recognized not only as a causative agent of a spectrum of gastroduodenal diseases including chronic gastritis, peptic ulcer, mucosa-associated lymphoid tissue lymphoma, and gastric cancer, but also as the culprit in several extra-gastric diseases. However, the association of H. pylori infection with extra-gastric diseases remains elusive, prompting a reevaluation of the role of H. pylori-derived outer membrane vesicles (OMVs). Like other gram-negative bacteria, H. pylori constitutively sheds biologically active OMVs for long-distance delivery of bacterial virulence factors in a concentrated and protected form, averting the need of direct bacterial contact with distant host cells to induce extra-gastric diseases associated with this gastric pathogen. Additionally, H. pylori-derived OMVs contribute to bacterial survival and chronic gastric pathogenesis. Moreover, the immunogenic activity, non-replicable nature, and anti-bacterial adhesion effect of H. pylori OMVs make them a desirable vaccine candidate against infection. The immunogenic potency and safety concerns of the OMV contents are challenges in the development of H. pylori OMV-based vaccines. In this review, we discuss recent advances regarding H. pylori OMVs, focusing on new insights into their biogenesis mechanisms and biological functions.
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Infecciones por Helicobacter , Helicobacter pylori , Humanos , Animales , Factores de Virulencia/metabolismo , Membrana Externa Bacteriana/metabolismo , Proteínas de la Membrana Bacteriana Externa/metabolismoRESUMEN
In crowdsourcing scenarios, we can obtain each instance's multiple noisy labels from different crowd workers and then infer its unknown ground truth via a ground truth inference method. However, to the best of our knowledge, the existing ground truth inference methods always attempt to aggregate multiple noisy labels into a single consensus label as the ground truth. In this article, we aim to explore a new strategy, i.e., label selection, which directly selects the label of the highest quality worker as the ground truth. To this end, we propose a label consistency-based ground truth inference (LCGTI) method. In LCGTI, we argue that high-quality workers should have a low bias with other workers in labeling the same instances and a low variance with themselves in labeling similar instances. To estimate the bias, we calculate the label consistency of different workers on the same instances. To estimate the variance, we calculate the label consistency of the same worker on similar instances. Finally, we combine these two components to calculate the labeling quality of each worker on the inferred instance and perform label selection instead of label aggregation to achieve inference. The experimental results on 34 simulated and two real-world datasets show that LCGTI significantly outperforms all the other state-of-the-art label aggregation-based ground truth inference methods.
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RATIONALE AND OBJECTIVES: Research involving radiomics models based on magnetic resonance imaging (MRI) has mainly used radiomics features derived from a single MRI sequence at a single time point to develop predictive models. This study aimed to construct radiomics models based on before and after neoadjuvant chemotherapy (NAC) MRI for predicting the histological response to NAC in patients with high-grade osteosarcoma. MATERIALS AND METHODS: We included 109 patients with localized high-grade osteosarcomas of the extremities, who underwent pre- and post-NAC MRI examinations, from which radiomics features were extracted. According to the tumor necrosis rate, all patients were classified as good responders (GRs) or poor responders (PRs) and were randomly allocated into training and test sets at a 7:3 ratio. Radiomics features were extracted from T2-weighted (T2WI) and contrast-enhanced T1-weighted imaging (T1CE) of the two MRI scans to construct three models: pre-NAC, post-NAC, and combined pre-NAC and post-NAC (combined model). RESULTS: In total, 1175 radiomics features were extracted from each sequence. Following feature selection, nine radiomics features were selected for each model to construct radiomics signatures. The radiomics signatures of the pre-NAC, post-NAC, and combined models demonstrated good predictive performance for chemotherapy response in osteosarcoma. The combined model achieved the highest areas under the receiver operating curve (AUC) values of 0.999 and 0.915 in the training and test sets, respectively. The AUCs of the post-NAC model were higher than those of the pre-NAC model. CONCLUSION: MRI-based radiomics models demonstrate excellent performance in predicting the histological response to NAC in patients with high-grade osteosarcoma.
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BACKGROUND: The essential mineral elements play important roles in proper growth, development and maintenance of physiological homeostasis of an organism. Women are at greater risk of mineral deficiency during pregnancy. However, the predictors of mineral element levels in pregnant women remain unclear. This study was conducted to determine the urinary levels of calcium (Ca), iron (Fe), copper (Cu), manganese (Mn) and selenium (Se) in women during early pregnancy and to explore the predictors of urinary exposure to each mineral element and high co-exposure to mineral element mixture. METHODS: 298 pregnant women in first trimester were recruited when they attended antenatal care in a hospital in Jinan, Shandong Province, China. We collected their spot urine samples and questionnaire data on their sociodemographic characteristics, lifestyle habits, food and dietary supplement intake, and residential environment. The concentrations of Ca, Fe, Cu, Mn and Se in all urine samples were measured. LASSO regression, multiple linear regression and binary logistic regression were used to analyze the predictors affecting mineral element levels. RESULTS: The geometric means of creatinine-corrected Ca, Fe, Cu, Mn and Se concentrations were 99.37â¯mg/g, 1.75⯵g/g, 8.97⯵g/g, 0.16⯵g/g and 16.83⯵g/g creatinine, respectively. Factors that influenced the concentrations of individual mineral element were as follows: (1) Se and Ca concentrations increased with maternal age; (2) women taking tap water as family drinking water had higher Ca levels and those taking polyunsaturated fatty acids intermittently had higher Cu levels; (3) Fe was adversely related to consumption frequency of barbecued foods; (4) Pregnant women with more frequent consumption of shellfish/shrimp/crab and living near green spaces or parks had higher Mn exposure, and those with higher frequency of meat consumption had lower Mn exposure. In addition, maternal age and the frequency of egg consumption were associated with odds of exposure to a mixture of high Ca, Fe, Cu and Se. CONCLUSIONS: The pregnant women in this study had comparable concentrations of urinary Cu and Se but lower concentrations of Ca, Fe and Mn compared with those in other areas. Predictors of urinary mineral elements included maternal age (Se and Ca), type of domestic drinking water (Ca), consumption frequency of barbecued food (Fe), polyunsaturated fatty acid use (Cu), the presence of urban green spaces or parks near the home and frequency of meat and shellfish/shrimp/crab intake (Mn). Moreover, maternal age and egg consumption frequency were significant predictors of high-level co-exposure to urinary Ca, Fe, Cu and Se.
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Oligoelementos , Humanos , Femenino , China , Embarazo , Adulto , Oligoelementos/orina , Minerales/orina , Adulto Joven , Calcio/orina , Manganeso/orina , Cobre/orina , Hierro/orina , Selenio/orinaRESUMEN
Tendinopathy leads to low-grade tissue inflammation and chronic damage, which progresses due to pathological imbalance in angiogenesis. Reducing early pathological vascularization may be a new approach in helping to regenerate tendon tissue. Conventional stem cell therapy and tissue engineering scaffolds have not been highly effective at treating tendinopathy. In this study, tissue engineered stem cells (TSCs) generated using human umbilical cord mesenchymal stem cells (hUC-MSCs) were combined with microcarrier scaffolds to limit excessive vascularization in tendinopathy. By preventing VEGF receptor activation through their paracrine function, TSCs reduced in vitro angiogenesis and the proliferation of vascular endothelial cells. TSCs also decreased the inflammatory expression of tenocytes while promoting their anabolic and tenogenic characteristics. Furthermore, local injection of TSCs into rats with collagenase-induced tendinopathy substantially reduced early inflammation and vascularization. Mechanistically, transcriptome sequencing revealed that TSCs could reduce the progression of pathological angiogenesis in tendon tissue, attributed to Rap1-mediated vascular inhibition. TSCs may serve as a novel and practical approach for suppressing tendon vascularization, and provide a promising therapeutic agent for early-stage clinical tendinopathy.
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The application of organic fertilisers and biochar has become widespread in agroforestry ecosystems to enhance the yield and quality of crops and medicinal plants. However, their specific impact on both the yield and quality of Paris polyphylla (P. polyphylla), along with the underlying mechanisms, remains unclear. In this study, we investigated the distinct effects of organic fertiliser (at concentrations of 5% and 10%) and biochar application (at levels of 2% and 4%) on P. polyphylla saponin content. This content is intricately regulated by available soil nutrients, enzyme activities, and microbial community compositions and activities. Our results clearly demonstrated a significant increase in the saponin content, including total saponin, polyphyllin I (PPI), polyphyllin II (PPII), polyphyllin VI (PPVI), and polyphyllin VII (PPVII), in P. polyphylla following the application of both biochar and organic fertiliser. Moreover, in comparison to the control group, the addition of biochar and organic fertiliser led to a considerable rise in the activity of glycosyltransferase enzyme (GTS) and cycloartenol synthase (CAS) in P. polyphylla. Additionally, it increased soil available potassium (AK) and soil organic matter (SOM) concentration, along with the activity of urease, acid phosphatase, and catalase, although biochar amendment resulted in a decrease in nitrate nitrogen (NO3--N) concentration. Crucially, our findings revealed a positive correlation between total saponin content and the activity of CAS in P. polyphylla, soil AK, SOM concentration, and the activities of urease, acid phosphatase, and catalase. Conversely, there was a negative correlation with NO3--N content. Furthermore, the application of organic fertiliser and biochar significantly influenced microbial community structures and specific microbial taxa. Notably, total saponin content exhibited a positive relationship with the relative abundances of Dehalococcoidia, Saccharomycetes, and Agaricomycetes taxa while showing a negative correlation with the abundance of Verrucomicrobiae. In conclusion, the observed increase in saponin content can be attributed to the modulation of specific microbial taxa in soils, as well as alterations in soil nutrients and enzyme activities resulting from the application of biochar and organic fertiliser. This study identifies a potential mechanism for enhancing saponin content in the artificial cultivation of P. polyphylla.
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BACKGROUND: Artificial intelligence has been proposed for brain metastasis (BM) segmentation but it has not been fully clinically validated. The aim of this study was to develop and evaluate a system for BM segmentation. METHODS: A deep-learning-based BM segmentation system (BMSS) was developed using contrast-enhanced MR images from 488 patients with 10,338 brain metastases. A randomized crossover, multi-reader study was then conducted to evaluate the performance of the BMSS for BM segmentation using data prospectively collected from 50 patients with 203 metastases at five centers. Five radiology residents and five attending radiologists were randomly assigned to contour the same prospective set in assisted and unassisted modes. Aided and unaided Dice similarity coefficients (DSCs) and contouring times per lesion were compared. RESULTS: The BMSS alone yielded a median DSC of 0.91 (95% confidence interval, 0.90-0.92) in the multi-center set and showed comparable performance between the internal and external sets (p = 0.67). With BMSS assistance, the readers increased the median DSC from 0.87 (0.87-0.88) to 0.92 (0.92-0.92) (p < 0.001) with a median time saving of 42% (40-45%) per lesion. Resident readers showed a greater improvement than attending readers in contouring accuracy (improved median DSC, 0.05 [0.05-0.05] vs. 0.03 [0.03-0.03]; p < 0.001), but a similar time reduction (reduced median time, 44% [40-47%] vs. 40% [37-44%]; p = 0.92) with BMSS assistance. CONCLUSIONS: The BMSS can be optimally applied to improve the efficiency of brain metastasis delineation in clinical practice.
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AIM: The present study was conducted to measure the expression of early growth response factor 3 (Egr3), inflammatory cytokines (IL-1ß, IL-6), vascular endothelial growth factor (VEGF) and NF-κB in patients with coronary artery disease (CAD) to investigate the relationships of these molecules and Egr3 gene expression. METHODS: We recruited 132 CAD patients and 63 healthy individuals. The expression levels of Egr3, VEGF, p50 and p65 were measured by reverse transcription quantitative polymerase chain reaction and the levels of Egr3, IL-1ß and IL-6 in patients serum and in human coronary artery endothelial cells (HCAECs) were measured by enzyme-linked immunosorbent assay (ELISAs) in CAD patients. HCAECs were treated with ox-LDL to establish an in vitro atherosclerosis model. An oil red O staining assay was used to assess the lipid droplet formation. A colloidal external lumen formed by Matrigel was used to test the migration of HCAECs. The expression of Egr3, VEGF and NF-κB was determined by Western blotting. RESULTS: The levels of serum Egr3 and IL-6 in the severe stenosis group were greater than those in the mild stenosis group and controls (p < 0.05). The level of serum IL-1ß in the severe stenosis group was greater than that in the control group (p < 0.05). Moreover, Egr3 expression was positively associated with IL-6 levels (r= 0.55, p < 0.001), IL-1ß levels (r=0.21, p=0.004) and the Gensini score (r=0.20, p=0.02). We also found that Egr3 expression was significantly greater in CAD patients than that in controls. And its expression was highest in the mild patients. The expression of VEGF, P50 and P65 was also greater in CAD patients. In the in vitro experiment, we found that the inhibition of Egr3 expression significantly reduced the expression levels of p50, p65, IL-6 and CRP. Moreover, the inhibition of Egr3 expression significantly reduced the lipid droplet formation and decreased capability of lumen formation. CONCLUSIONS: In the pathogenesis of atherosclerosis, Egr3 gene expression may induce the expression of inflammatory factors and lipid droplet formation and lumen formation, which could promote the atherosclerosis development.
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Biological characteristics of pregnant women during early pregnancy make them susceptible to both poor sleep quality and metal/metalloid exposure. However, the effects of metal(loid) exposure on sleep quality in pregnant women remain unknown and unexplored. We aimed to examine the relationship between exposure to a mixture of metal(loid)s and pregnant women's sleep quality during early pregnancy. We recruited 493 pregnant women in the first trimester from prenatal clinics in Jinan, Shandong Province, China, and collected their spot urine samples. All urine specimens were assessed for eight metal(loid)s: arsenic (As), cadmium (Cd), iron (Fe), zinc (Zn), molybdenum (Mo), lead (Pb), selenium (Se), and mercury (Hg). We used the Pittsburgh Sleep Quality Index (PSQI) to assess sleep quality. Linear regression, logistic regression, generalized additive models (GAMs), quantile g-computation, and Bayesian kernel machine regression (BKMR) were applied to investigate the relationships between metal(loid) exposure and sleep quality. The results from single metal(loid) models, quantile g-computation models, and BKMR models consistently suggested that Fe was positively related to women's sleep quality. Moreover, in the quantile g-computation models, As was the most critical contributor to the negative effects of the metal(loid) mixture on sleep quality. In addition, we found significant As by Fe interaction for scores of PSQI and habitual sleep efficiency, Pb by Fe interaction for PSQI and sleep latency, and Hg by Fe interaction for PSQI, suggesting the interactive effects of As and Fe, Pb and Fe, Hg and Fe on sleep quality and specific sleep components. Our study provided the first-hand evidence of the effects of metal(loid) exposure on pregnant women's sleep quality. The underlying mechanisms need to be explored in the future.
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Calidad del Sueño , Humanos , Femenino , Embarazo , Estudios Transversales , Adulto , China , Contaminantes Ambientales/orina , Contaminantes Ambientales/toxicidad , Selenio/orina , Arsénico/orina , Arsénico/toxicidad , Metales/orina , Metales/toxicidad , Metales Pesados/orina , Metales Pesados/toxicidad , Mercurio/orina , Mercurio/toxicidad , Adulto Joven , Plomo/orina , Plomo/toxicidad , Exposición Materna , Cadmio/orina , Cadmio/toxicidad , Primer Trimestre del EmbarazoRESUMEN
Objective: Definitive chemoradiotherapy (dCRT) is the standard treatment for unresectable locally advanced esophageal cancer. However, this treatment is associated with substantial toxicity, and most malnourished or elderly patients are unable to complete this therapy. Therefore, there is a need for a more suitable radiotherapy combination regimen for this population. This study was aimed to evaluate the efficacy and safety of a combination regimen comprising chemotherapy with nimotuzumab and S-1 and concurrent radiotherapy for patients with fragile locally advanced esophageal cancer with a high Nutritional Risk Screening 2002 (NRS-2002) score. Methods: Eligible patients with unresectable esophageal carcinoma who had an NRS-2002 score of 2 or higher were enrolled. They were treated with S-1 and nimotuzumab with concurrent radiotherapy, followed by surgery or definitive radiotherapy. The primary endpoint was the locoregional control (LRC) rate. Results: A total of 55 patients who met the study criteria were enrolled. After completion of treatment, surgery was performed in 15 patients and radiotherapy was continued in 40 patients. The median follow-up period was 33.3 [95% confidence interval (95% CI), 31.4-35.1)] months. The LRC rate was 77.2% (95% CI, 66.6%-89.4%) at 1 year in the entire population. The overall survival (OS) rate and event-free survival (EFS) rate were 57.5% and 51.5% at 3 years, respectively. Surgery was associated with better LRC [hazard ratio (HR)=0.16; 95% CI, 0.04-0.70; P=0.015], OS (HR=0.19; 95% CI, 0.04-0.80; P=0.024), and EFS (HR=0.25; 95% CI, 0.08-0.75; P=0.013). Most adverse events were of grade 1 or 2, and no severe adverse events occurred. Conclusions: For malnourished or elderly patients with locally advanced esophageal cancer, radiotherapy combined with nimotuzumab and S-1 is effective and has a good safety profile.
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Osseointegration implant (OI) surgery is the latest rehabilitation technology for amputees, where a bone-anchored implant obviates the limitations of traditional socket prostheses. The bone mineral density (BMD) in the periprosthetic and other anatomical regions can be used to assess bone remodelling following OI surgery. Currently, limited studies have used BMD measurements in reporting post-operative OI outcomes and the association between the maintenance of BMD and implant efficacy has remained elusive. This review captured and analysed all studies that have reported the BMD as an objective outcome measure in patients with trans-femoral or trans-tibial OI. The PubMed, Medline, Scopus and Web of Science databases were searched using the terms 'amputation', 'osseointegration' and 'bone mineral density'. A total of 6 studies involving human participants were included for analysis. All studies used dual X-ray absorptiometry and/or X-rays for measuring BMD. Rehabilitation of trans-femoral or trans-tibial amputation using OI may help restore healthy BMD by enabling physiological bone loading. However, there is a low correlation between the BMD around the OI and the success of OI surgery or the risk of periprosthetic fractures. This review summarises the current evidence on BMD assessment in OI for lower limb amputee rehabilitation. Despite the great variability in the results, the available evidence suggests that OI may help restore BMD following surgery. The limited evidence calls for further investigation, as well as the development of a standard BMD measurement protocol.