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BACKGROUND: Pathological axillary lymph node (pALN) burden is an important factor for treatment decision-making in clinical T1-T2 (cT1-T2) stage breast cancer. Preoperative assessment of the pALN burden and prognosis aids in the individualized selection of therapeutic approaches. PURPOSE: To develop and validate a machine learning (ML) model based on clinicopathological and MRI characteristics for assessing pALN burden and survival in patients with cT1-T2 stage breast cancer. STUDY TYPE: Retrospective. POPULATION: A total of 506 females (range: 24-83 years) with cT1-T2 stage breast cancer from two institutions, forming the training (N = 340), internal validation (N = 85), and external validation cohorts (N = 81), respectively. FIELD STRENGTH/SEQUENCE: This study used 1.5-T, axial fat-suppressed T2-weighted turbo spin-echo sequence and axial three-dimensional dynamic contrast-enhanced fat-suppressed T1-weighted gradient echo sequence. ASSESSMENT: Four ML methods (eXtreme Gradient Boosting [XGBoost], Support Vector Machine, k-Nearest Neighbor, Classification and Regression Tree) were employed to develop models based on clinicopathological and MRI characteristics. The performance of these models was evaluated by their discriminative ability. The best-performing model was further analyzed to establish interpretability and used to calculate the pALN score. The relationships between the pALN score and disease-free survival (DFS) were examined. STATISTICAL TESTS: Chi-squared test, Fisher's exact test, univariable logistic regression, area under the curve (AUC), Delong test, net reclassification improvement, integrated discrimination improvement, Hosmer-Lemeshow test, log-rank, Cox regression analyses, and intraclass correlation coefficient were performed. A P-value <0.05 was considered statistically significant. RESULTS: The XGB II model, developed based on the XGBoost algorithm, outperformed the other models with AUCs of 0.805, 0.803, and 0.818 in the three cohorts. The Shapley additive explanation plot indicated that the top variable in the XGB II model was the Node Reporting and Data System score. In multivariable Cox regression analysis, the pALN score was significantly associated with DFS (hazard ratio: 4.013, 95% confidence interval: 1.059-15.207). DATA CONCLUSION: The XGB II model may allow to evaluate pALN burden and could provide prognostic information in cT1-T2 stage breast cancer patients. LEVEL OF EVIDENCE: 3 TECHNICAL EFFICACY: Stage 2.
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Biodegradable stents are the most promising alternatives for the treatment of cardiovascular disease nowadays, and the strategy of preparing functional coatings on the surface is highly anticipated for addressing adverse effects such as in-stent restenosis and stent thrombosis. Yet, inadequate mechanical stability and biomultifunctionality limit their clinical application. In this study, we developed a multicross-linking hydrogel on the polylactic acid substrates by dip coating that boasts impressive antithrombotic ability, antibacterial capability, mechanical stability, and self-healing ability. Gelatin methacryloyl, carboxymethyl chitosan, and oxidized sodium alginate construct a double-cross-linking hydrogel through the dynamic Schiff base chemical and in situ blue initiation reaction. Inspired by the adhesion mechanism employed by mussels, a triple-cross-linked hydrogel is formed with the addition of tannic acid to increase the adhesion and antibiofouling properties. The strength and hydrophilicity of hydrogel coating are regulated by changing the composition ratio and cross-linking degree. It has been demonstrated in tests in vitro that the hydrogel coating significantly reduces the adhesion of proteins, MC3T3-E1 cells, platelets, and bacteria by 85% and minimizes the formation of blood clots. The hydrogel coating also exhibits excellent antimicrobial in vitro and antiinflammatory properties in vivo, indicating its potential value in vascular intervention and other biomedical fields.
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Anti-Inflamatórios , Anticoagulantes , Bivalves , Poliésteres , Stents , Animais , Bivalves/química , Camundongos , Poliésteres/química , Poliésteres/farmacologia , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/química , Stents/efeitos adversos , Anticoagulantes/química , Anticoagulantes/farmacologia , Gelatina/química , Hidrogéis/química , Hidrogéis/farmacologia , Quitosana/química , Quitosana/análogos & derivados , Quitosana/farmacologia , Alginatos/química , Alginatos/farmacologia , Materiais Revestidos Biocompatíveis/química , Materiais Revestidos Biocompatíveis/farmacologia , Antibacterianos/farmacologia , Antibacterianos/química , Taninos/química , Taninos/farmacologia , Humanos , MetacrilatosRESUMO
BACKGROUND: No trial of supramolecular salicylic acid (SSA) for chloasma is available yet. OBJECTIVE: The purpose of this study was to assess the efficacy and safety of Bole DA 30% supramolecular salicylic acid (SSA) combined with 10% niacinamide in treating chloasma. METHODS: This multicenter (n=15), randomized, double-blind, parallel placebo-controlled trial randomized the subjects (1:1) to Bole DA 30% SSA or placebo. The primary endpoint was the effective rate after 16 weeks using the modified melasma area severity index (mMASI) [(pretreatment-posttreatment)/pretreatment×100%]. RESULTS: This study randomized 300 subjects (150/group in the full analysis set, 144 and 147 in the per-protocol set). The total mMASI score, overall Griffiths 10 score, left Griffiths 10 score, and right Griffiths 10 score were significantly lower in the Bole DA 30% SSA group than in the placebo group (all P<0.001). One study drug-related AE and one study drug-unrelated adverse events (AE) were reported in the Bole DA 30% SSA group. No AE was reported in the placebo group. CONCLUSION: Bole DA 30% SSA combined with 10% niacinamide is effective and safe for treating chloasma. CLINICAL TRIAL REGISTRATION NUMBER: ChiCTR2200065346.
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Importance: For patients with non-small cell lung cancer whose disease progressed while receiving EGFR tyrosine kinase inhibitor (EGFR-TKI) therapy, particularly third-generation TKIs, optimal treatment options remain limited. Objective: To compare the efficacy of ivonescimab plus chemotherapy with chemotherapy alone for patients with relapsed advanced or metastatic non-small cell lung cancer with the epidermal growth factor receptor (EGFR) variant. Design, Setting, and Participants: Double-blind, placebo-controlled, randomized, phase 3 trial at 55 sites in China enrolled participants from January 2022 to November 2022; a total of 322 eligible patients were enrolled. Interventions: Participants received ivonescimab (n = 161) or placebo (n = 161) plus pemetrexed and carboplatin once every 3 weeks for 4 cycles, followed by maintenance therapy of ivonescimab plus pemetrexed or placebo plus pemetrexed. Main Outcomes and Measures: The primary end point was progression-free survival in the intention-to-treat population assessed by an independent radiographic review committee (IRRC) per Response Evaluation Criteria in Solid Tumors version 1.1. The results of the first planned interim analysis are reported. Results: Among 322 enrolled patients in the ivonescimab and placebo groups, the median age was 59.6 vs 59.4 years and 52.2% vs 50.9% of patients were female. As of March 10, 2023, median follow-up time was 7.89 months. Median progression-free survival was 7.1 (95% CI, 5.9-8.7) months in the ivonescimab group vs 4.8 (95% CI, 4.2-5.6) months for placebo (difference, 2.3 months; hazard ratio [HR], 0.46 [95% CI, 0.34-0.62]; P < .001). The prespecified subgroup analysis showed progression-free survival benefit favoring patients receiving ivonescimab over placebo across almost all subgroups, including patients whose disease progressed while receiving third-generation EGFR-TKI therapy (HR, 0.48 [95% CI 0.35-0.66]) and those with brain metastases (HR, 0.40 [95% CI, 0.22-0.73]). The objective response rate was 50.6% (95% CI, 42.6%-58.6%) with ivonescimab and 35.4% (95% CI, 28.0%-43.3%) with placebo (difference, 15.6% [95% CI, 5.3%-26.0%]; P = .006). The median overall survival data were not mature; at data cutoff, 69 patients (21.4%) had died. Grade 3 or higher treatment-emergent adverse events occurred in 99 patients (61.5%) in the ivonescimab group vs 79 patients (49.1%) in the placebo group, the most common of which were chemotherapy-related. Grade 3 or higher immune-related adverse events occurred in 10 patients (6.2%) in the ivonescimab group vs 4 (2.5%) in the placebo group. Grade 3 or higher vascular endothelial growth factor-related adverse events occurred in 5 patients (3.1%) in the ivonescimab group vs 4 (2.5%) in the placebo group. Conclusions: Ivonescimab plus chemotherapy significantly improved progression-free survival with tolerable safety profile in TKI-treated non-small cell lung cancer. Trial Registration: ClinicalTrials.gov Identifier: NCT05184712.
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Protocolos de Quimioterapia Combinada Antineoplásica , Carboplatina , Carcinoma Pulmonar de Células não Pequenas , Receptores ErbB , Neoplasias Pulmonares , Pemetrexede , Intervalo Livre de Progressão , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Anticorpos Monoclonais Humanizados/administração & dosagem , Anticorpos Monoclonais Humanizados/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Carboplatina/administração & dosagem , Carboplatina/efeitos adversos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Método Duplo-Cego , Receptores ErbB/genética , Análise de Intenção de Tratamento , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/mortalidade , Mutação , Pemetrexede/administração & dosagem , Pemetrexede/efeitos adversos , Anticorpos Biespecíficos/administração & dosagem , Anticorpos Biespecíficos/efeitos adversosRESUMO
BACKGROUND: In the classification of bruxism patients based on electroencephalogram (EEG), feature extraction is essential. The method of using multi-channel EEG fusing electrocardiogram (ECG) and Electromyography (EMG) signal features has been proved to have good performance in bruxism classification, but the classification performance based on single channel EEG signal is still understudied. We investigate the efficacy of single EEG channel in bruxism classification. METHODS: We have extracted time-domain, frequency-domain, and nonlinear features from single EEG channel to classify bruxism. Five common bipolar EEG recordings from 2 bruxism patients and 4 healthy controls during REM sleep were analyzed. The time domain (mean, standard deviation, root mean squared value), frequency domain (absolute, relative and ratios power spectral density (PSD)), and non-linear features (sample entropy) of different EEG frequency bands were analyzed from five EEG channels of each participant. Fine tree algorithm was trained and tested for classifying sleep bruxism with healthy controls using five-fold cross-validation. RESULTS: Our results demonstrate that the C4P4 EEG channel was most effective for classification of sleep bruxism that yielded 95.59% sensitivity, 98.44% specificity, 97.84% accuracy, and 94.20% positive predictive value (PPV). CONCLUSIONS: Our results illustrate the feasibility of sleep bruxism classification using single EEG channel and provides an experimental foundation for the development of a future portable automatic sleep bruxism detection system.
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Bruxismo do Sono , Fases do Sono , Humanos , Bruxismo do Sono/diagnóstico , Valor Preditivo dos Testes , Eletroencefalografia/métodos , AlgoritmosRESUMO
OBJECTIVES: This study aimed to determine whether post-neoadjuvant therapy (NAT) axillary ultrasound (AUS) could reduce the false-negative rate (FNR) of sentinel lymph node biopsy (SLNB). We also performed subgroup analyses to identify the appropriate patient for SLNB. METHODS: A total of 220 patients with cytologically proven axillary node-positive breast cancer who underwent both SLNB and axillary lymph node dissection (ALND) after NAT were included. We calculated the FNR of SLNB. In the case of post-NAT AUS results available, AUS was classified as negative or positive. Then the FNR of post-NAT AUS combined with SLNB was evaluated. Subgroup analyses based on the number of sentinel lymph nodes removed, molecular subtypes, and the clinical N stage were also performed. RESULTS: The overall axillary lymph node pathological complete response rate was 45.5% (100/220). The FNR of SLNB alone was 15.8% (95%CI: 9.2 to 22.5%). Post-NAT AUS results were available for 181 patients. When combined negative post-NAT AUS results and SLNB, the FNR was reduced to 7.5% (95%CI: 2.4 to 12.7%). Subgroup analyses of the FNR for SLNB alone and negative post-NAT AUS combined with SLNB were shown as follows: in cases patients with less than three sentinel lymph nodes (SLNs) and at least three SLNs removed, the FNR was decreased from 24.5 to 13.2%, and 9.0 to 5.0%, respectively. The FNR was decreased from 20.8 to 10.5% in HR+/HER2+subgroup, 21.4 to 16.7% in HR-/HER2+subgroup, 15.9 to 7.0% in HR+/HER2- subgroup, and 0% in HR-/HER2- subgroup, respectively. For cN1 patients, the FNR was decreased from 18.1 to 12.1% while 17.1 to 3.6% for cN2 patients and 0% for cN3 patients. CONCLUSION: Using negative post-NAT AUS may help to decrease the FNR and improve patient selection for SLNB.
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Neoplasias da Mama , Linfonodo Sentinela , Humanos , Feminino , Biópsia de Linfonodo Sentinela/métodos , Neoplasias da Mama/patologia , Terapia Neoadjuvante/métodos , Metástase Linfática/patologia , Linfonodos/diagnóstico por imagem , Linfonodos/cirurgia , Linfonodos/patologia , Excisão de Linfonodo/métodos , Linfonodo Sentinela/diagnóstico por imagem , Linfonodo Sentinela/patologia , Axila/patologia , Estadiamento de NeoplasiasRESUMO
Background Breast cancer is highly heterogeneous, resulting in different treatment responses to neoadjuvant chemotherapy (NAC) among patients. A noninvasive quantitative measure of intratumoral heterogeneity (ITH) may be valuable for predicting treatment response. Purpose To develop a quantitative measure of ITH on pretreatment MRI scans and test its performance for predicting pathologic complete response (pCR) after NAC in patients with breast cancer. Materials and Methods Pretreatment MRI scans were retrospectively acquired in patients with breast cancer who received NAC followed by surgery at multiple centers from January 2000 to September 2020. Conventional radiomics (hereafter, C-radiomics) and intratumoral ecological diversity features were extracted from the MRI scans, and output probabilities of imaging-based decision tree models were used to generate a C-radiomics score and ITH index. Multivariable logistic regression analysis was used to identify variables associated with pCR, and significant variables, including clinicopathologic variables, C-radiomics score, and ITH index, were combined into a predictive model for which performance was assessed using the area under the receiver operating characteristic curve (AUC). Results The training data set was comprised of 335 patients (median age, 48 years [IQR, 42-54 years]) from centers A and B, and 590, 280, and 384 patients (median age, 48 years [IQR, 41-55 years]) were included in the three external test data sets. Molecular subtype (odds ratio [OR] range, 4.76-8.39 [95% CI: 1.79, 24.21]; all P < .01), ITH index (OR, 30.05 [95% CI: 8.43, 122.64]; P < .001), and C-radiomics score (OR, 29.90 [95% CI: 12.04, 81.70]; P < .001) were independently associated with the odds of achieving pCR. The combined model showed good performance for predicting pCR to NAC in the training data set (AUC, 0.90) and external test data sets (AUC range, 0.83-0.87). Conclusion A model that combined an index created from pretreatment MRI-based imaging features quantitating ITH, C-radiomics score, and clinicopathologic variables showed good performance for predicting pCR to NAC in patients with breast cancer. © RSNA, 2023 Supplemental material is available for this article. See also the editorial by Rauch in this issue.
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Neoplasias da Mama , Terapia Neoadjuvante , Humanos , Pessoa de Meia-Idade , Feminino , Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/tratamento farmacológico , Estudos Retrospectivos , Imageamento por Ressonância Magnética , Razão de ChancesRESUMO
BACKGROUND: Iruplinalkib (WX-0593) is an anaplastic lymphoma kinase (ALK)/c-ros oncogene 1 (ROS1) tyrosine kinase inhibitor. Here we reported the single-arm, phase II study (INTELLECT) results of the efficacy and safety of iruplinalkib for ALK-positive crizotinib-resistant advanced non-small cell lung cancer (NSCLC) patients. METHODS: ALK-positive crizotinib-resistant advanced NSCLC patients aged ≥18 years, with Eastern Cooperative Oncology Group performance status of 0-2 were eligible. Patients received iruplinalkib 180 mg orally once daily for a 21-day cycle with a 7-day lead-in phase at 60 mg orally once daily. The primary endpoint was the independent review committee (IRC)-assessed objective response rate (ORR). RESULTS: From August 7, 2019, to October 30, 2020, 146 patients were included. As of the data cut-off date on November 30, 2021, the median follow-up time was 18.2 months (95% confidence interval [CI] 16.8-18.8). IRC-assessed ORR and disease control rate (DCR) were 69.9% (95% CI 61.7-77.2%) and 96.6% (95% CI 92.2-98.9%), respectively. Investigator-assessed ORR and DCR were 63.0% (95% CI 54.6-70.8%) and 94.5% (95% CI 89.5-97.6%), respectively. Investigator-assessed median duration of response and progression-free survival (the same as median time to progression) were 13.2 months (95% CI 10.4-17.7) and 14.5 months (95% CI 11.7-20.0), respectively. Corresponding IRC-assessed results were 14.4 months (95% CI 13.1-not evaluable [NE]), 19.8 months (95% CI 14.5-NE), and NE (95% CI 14.5-NE), respectively. Investigator-assessed intracranial ORRs were 46% (41/90, 95% CI 35-56%) in patients with central nervous system metastases and 64% (27/42, 95% CI 48-78%) in patients with measurable intracranial lesions. Overall survival data were immature. Treatment-related adverse events (TRAEs) occurred in 136/146 (93.2%) patients. The most common TRAEs were aspartate aminotransferase increased (63 [43.2%]), alanine aminotransferase increased (54 [37.0%]), and blood creatine phosphokinase increased (51 [34.9%]). Dose interruption, reduction, and discontinuation due to TRAEs occurred in 21 (14.4%), 16 (11.0%), and four (2.7%) patients, respectively. CONCLUSIONS: In this study, iruplinalkib (WX-0593) demonstrated favorable efficacy and manageable safety profiles in patients with ALK-positive crizotinib-resistant advanced NSCLC. Iruplinalkib could be a new treatment option for this patient population. TRIAL REGISTRATION: Center for Drug Evaluation of National Medical Products Administration of China: CTR20190789, registered on April 28, 2019; ClinicalTrials.gov: NCT04641754, registered on November 24, 2020.
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Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Adolescente , Adulto , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Crizotinibe/uso terapêutico , Neoplasias Pulmonares/tratamento farmacológico , Proteínas Tirosina Quinases/uso terapêutico , Quinase do Linfoma Anaplásico/uso terapêutico , Proteínas Proto-Oncogênicas/uso terapêutico , Inibidores de Proteínas Quinases/uso terapêuticoRESUMO
BACKGROUND: Furmonertinib (AST2818) is a brain penetrant pan-epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) targeting both EGFR sensitizing mutations and T790M mutation. We report the pooled central nervous system (CNS) efficacy data of furmonertinib in patients with EGFR T790M mutated non-small cell lung cancer (NSCLC) from two phase 2 studies. METHODS: This was a pooled, post-hoc analysis of two phase 2 studies (NCT03127449 [phase 2a study of furmonertinib], NCT03452592 [phase 2b study of furmonertinib]). In the phase 2a study, patients received furmonertinib 40 mg, 80 mg, 160 mg, or 240 mg orally once daily. In the phase 2b study, all patients received furmonertinib 80 mg orally once daily. CNS efficacy of furmonertinib was analyzed in patients with baseline CNS lesions by an independent review center per Response Evaluation Criteria in Solid Tumors version 1.1. RESULTS: A total of 132 patients with baseline CNS metastases were included in this analysis. In 52 patients with measurable CNS lesions, CNS objective response rates were zero (0/1), 65% (22/34), 85% (11/13), and 25% (1/4), and CNS disease control rates were zero (0/1), 97% (33/34), 100% (13/13), and 100% (4/4) in the 40 mg, 80 mg, 160 mg, and 240 mg orally once daily group, respectively. In patients with measurable or non-measurable CNS lesions, median CNS progression-free survival was 2.8 months (95% confidence interval [CI] 1.4-8.3), 11.6 months (95% CI 8.3-13.8), 19.3 months (95% CI 5.5-not available [NA]), and not reached (95% CI 2.8 months-NA) in the 40 mg, 80 mg, 160 mg, and 240 mg orally once daily group, respectively. CONCLUSIONS: Furmonertinib showed promising CNS efficacy in doses of 80 mg orally once daily or higher in patients with EGFR T790M mutated NSCLC. TRIAL REGISTRATION: Both studies were registered on ClinicalTrial.gov. The phase 2a study was registered with NCT03127449 on April 25, 2017; The phase 2b study was registered with NCT03452592 on March 2, 2018.
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Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Receptores ErbB/genética , Inibidores de Proteínas Quinases/efeitos adversos , Mutação , Sistema Nervoso Central/patologia , Ensaios Clínicos Fase II como AssuntoRESUMO
BACKGROUND: Image-guided system (IGS) has been gradually applied in the field of rhinology, making functional endoscopic sinus surgery (FESS) a truly minimally invasive and precise surgery. This study was based on real-world data from China hospitals and aimed to evaluate the clinical and economic benefits of the IGS navigation system in FESS. METHODS: This was a two-center retrospective chart review of patients with chronic rhinosinusitis who underwent FESS, including open frontal sinus between July 1, 2018 and December 31, 2019 in China. The intervention group consisted of 100 patients who underwent FESS with the IGS navigation system (IGS group), and the control group consisted of 100 patients who underwent conventional FESS (Non-IGS group). Data were collected from surgical notes and hospital medical records. The primary endpoints for clinical effectiveness and safety were avoid rehospitalization due to bleeding, avoid reoperation due to bleeding, and avoid reoperation due to recurrence. RESULTS: There were no cases of rehospitalization due to bleeding, reoperation due to bleeding, and reoperation due to recurrence in the IGS group, with an avoidance rate of 100%. In the non-IGS group, there were four cases of rehospitalization and reoperation due to bleeding, with an avoidance rate 96.00% (P = 0.121). No cases of reoperation due to recurrence were in the non-IGS group. The total hospitalization cost was 17,391.51 CNY in the IGS group and 17,742.41 CNY in the non-IGS group per patient, with no statistical difference between the two groups (P = 0.715). Compared with the non-IGS group, the IGS group had an overall cost saving of 350.90 CNY per patient. Although the procedure-related medical costs of IGS group were increased by 1,286.12 CNY compared with the non-IGS group, this was more than offset by other costs. CONCLUSION: The results of the study indicated that the IGS may avoid occurrence of rehospitalization and reoperation due to postoperative bleeding. Although the use of navigation technology increased the cost of surgery, its clinical effectiveness brought other medical cost savings, resulting in no significant difference in the overall cost of navigation surgery compared to conventional surgery. The IGS should be considered cost-effectiveness in the treatment of FESS.
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Previous studies have determined that magnesium (Mg) in appropriate concentrations prevents plants from suffering from abiotic stress. To better understand the mechanism of Mg alleviation of aluminum (Al) stress in apple, we investigated the effect of Mg on plant growth, photosynthetic fluorescence, antioxidant system, and carbon (C) and nitrogen (N) metabolism of apple seedlings under Al toxicity (1.5 mmol/L) via a hydroponic experiment. Al stress induced the production of reactive oxygen in the leaves and roots and reduced the total dry weight (DW) by 52.37 % after 20 days of treatment relative to plants grown without Al, due to hindered photosynthesis and alterations in C and N metabolism. By contrast, total DW decreased by only 11.07 % in the Mg-treated plants under Al stress. Supplementation with 3.0 mmol/L Mg in the Al treatment decreased Al accumulation in the apple plants and reduced Al-induced oxidative damage by enhancing the activity of antioxidant enzymes (superoxide dismutase, catalase, and peroxidase) and reducing the production of H2O2 and malondialdehyde (MDA). Under Al stress, the Mg-treated plants showed a 46.17 % higher photosynthetic rate than the non-treated plants. Supplementation with Mg significantly increased the sucrose content by increasing sucrose synthase (SS) and sucrose-phosphate synthase (SPS) activities. Moreover, Mg facilitated the transport of 13C-carbohydrates from the leaves to roots. Regarding N metabolism, the nitrate reductase (NR), glutamine synthase (GS), and glutamate synthase (GOGAT) activities in the roots and leaves of the Mg-treated plants were significantly higher than those of the non-treated plants under Al stress. Compared with the non-treated plants under Al stress, the Mg-treated plants exhibited a significantly high level of NO3- and soluble protein content in the leaves, roots, and stems, but a low level of free amino acids. Furthermore, Mg significantly improved nitrogen accumulation and enhanced the transport of 15N from the roots to leaves. Overall, our results revealed that Mg alleviates Al-induced growth inhibition by enhancing antioxidant capacity and C-N metabolism in apple seedlings.
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Antioxidantes , Malus , Antioxidantes/farmacologia , Antioxidantes/metabolismo , Plântula , Alumínio/toxicidade , Alumínio/metabolismo , Magnésio/farmacologia , Magnésio/metabolismo , Malus/metabolismo , Carbono/metabolismo , Peróxido de Hidrogênio/metabolismo , Nitrogênio/metabolismo , Folhas de Planta/metabolismo , Raízes de Plantas/metabolismoRESUMO
Non-small cell lung cancer (NSCLC) has high rates of morbidity and mortality. E3 ubiquitin ligase usually has antitumor effects. This study evaluated the mechanism of E3 ligase FBXW7 (F-box and WD repeat domain containing 7) in the radiosensitivity of NSCLC. NCI-H1299 and NCI-H1299R cells were irradiated by 0, 2, 4, and 6 Gy doses of X-ray, respectively. In addition to the measurement of cell proliferation, apoptosis, and γ-H2AX, FBXW7 expression was measured and the interaction between FBXW7 and SOX9 (SRY-box transcription factor 9) was evaluated. Ubiquitination level and protein stability of SOX9 were examined after FBXW7 overexpression. The binding relationship between SOX9 and CDKN1A (cyclin-dependent kinase inhibitor 1A) was verified. Xenograft tumor model was established to evaluate the effect of FBXW7 on radiosensitivity in vivo. FBXW7 was under-expressed in radioresistant cells. Overexpression of FBXW7 repressed NCI-H1299 and NCI-H1299R cell proliferation and colony formation and increased γ-H2AX-positive foci. Overexpression of FBXW7 increased the ubiquitination level and reduced the protein stability of SOX9. SOX9 bound to the CDKN1A promoter to inhibit CDKN1A expression. FBXW7 inhibited tumorigenesis and apoptosis and enhanced radiosensitivity of NSCLC cells in vivo via the SOX9/CDKN1A axis. Overall, FBXW7 inhibited SOX9 expression by promoting SOX9 ubiquitination and proteasome degradation, suppressing the binding of SOX9 to CDKN1A, and upregulating CDKN1A, thereby improving the radiosensitivity of NSCLC cells.
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Carcinoma Pulmonar de Células não Pequenas , Proteínas F-Box , Neoplasias Pulmonares , Humanos , Proteína 7 com Repetições F-Box-WD/genética , Proteína 7 com Repetições F-Box-WD/metabolismo , Ubiquitina-Proteína Ligases/genética , Ubiquitina-Proteína Ligases/metabolismo , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/radioterapia , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Proteínas F-Box/genética , Proteínas F-Box/metabolismo , Complexo de Endopeptidases do Proteassoma/metabolismo , Proteínas de Ciclo Celular/genética , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/radioterapia , Neoplasias Pulmonares/metabolismo , Ubiquitinação , Tolerância a Radiação/genética , Quinases Ciclina-Dependentes/metabolismo , Fatores de Transcrição/metabolismo , Inibidor de Quinase Dependente de Ciclina p21/metabolismoRESUMO
OBJECTIVES: To investigate whether breast edema characteristics at preoperative T2-weighted imaging (T2WI) could help evaluate axillary lymph node (ALN) burden in patients with early-stage breast cancer. METHODS: This retrospective study included women with clinical T1 and T2 stage breast cancer and preoperative MRI examination in two independent cohorts from May 2014 to December 2020. Low (< 3 LNs+) and high (≥ 3 LNs+) pathological ALN (pALN) burden were recorded as endpoint. Breast edema score (BES) was evaluated at T2WI. Univariable and multivariable analyses were performed by the logistic regression model. The added predictive value of BES was examined utilizing the area under the curve (AUC), net reclassification improvement (NRI), and integrated discrimination improvement (IDI). RESULTS: A total of 1092 patients were included in this study. BES was identified as the independent predictor of pALN burden in primary (n = 677) and validation (n = 415) cohorts. The analysis using MRI-ALN status showed that BES significantly improved the predictive performance of pALN burden (AUC: 0.65 vs 0.71, p < 0.001; IDI = 0.045, p < 0.001; continuous NRI = 0.159, p = 0.050). These results were confirmed in the validation cohort (AUC: 0.64 vs 0.69, p = 0.009; IDI = 0.050, p < 0.001; continuous NRI = 0.213, p = 0.047). Furthermore, BES was positively correlated with biologically invasive clinicopathological factors (p < 0.05). CONCLUSIONS: In individuals with early-stage breast cancer, preoperative MRI characteristics of breast edema could be a promising predictor for pALN burden, which may aid in treatment planning. KEY POINTS: ⢠In this retrospective study of 1092 patients with early-stage breast cancer from two cohorts, the MRI characteristic of breast edema has independent and additive predictive value for assessing axillary lymph node burden. ⢠Breast edema characteristics at T2WI positively correlated with biologically invasive clinicopathological factors, which may be useful for preoperative diagnosis and treatment planning for individual patients with breast cancer.
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Doenças Mamárias , Neoplasias da Mama , Humanos , Feminino , Estudos Retrospectivos , Neoplasias da Mama/complicações , Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/patologia , Metástase Linfática/patologia , Axila/patologia , Linfonodos/diagnóstico por imagem , Linfonodos/patologia , Doenças Mamárias/patologia , Imageamento por Ressonância Magnética/métodos , Edema/diagnóstico por imagem , Edema/patologiaRESUMO
PURPOSE: This paper firstly reported the exact function of circ_0008797 on non-small cell lung cancer (NSCLC) progression. METHODS: NSCLC tissues/matched normal tissues were harvested from 88 NSCLC patients. RNA fluorescence in situ hybridization experiment was applied to detect circ_0008797 localization in NSCLC cells. circ_0008797 effect on NSCLC cells proliferation, migration, invasion, glucolysis, and apoptosis was researched by cell counting kit-8 assay, 5-ethynyl-2'deoxyuridine assay, Transwell experiment, glycolysis assay, and TUNEL assay. Dual luciferase reporter gene assay, RNA pull-down assay and RNA immunoprecipitation assay were used to verify the binding relationship between two genes. In vivo tumorigenesis and lung metastasis was performed using nude mice. Quantitative reverse transcription-polymerase chain reaction, immunohistochemistry and western blot were applied for genes expression detection. Hematoxylin and eosin staining was performed on lung tissues. RESULTS: circ_0008797 was low expressed in NSCLC tissues and cell lines, associating with poor outcome (p <.05). circ_0008797 was mainly expressed in NSCLC cells cytoplasm. circ_0008797 inhibited proliferation, migration, invasion, and glycolysis, but enhanced apoptosis of NSCLC cells (p <.05). circ_0008797 attenuated malignant phenotype of NSCLC cells by sponging miR-301a-3p. circ_0008797 facilitated SOCS2 expression by sponging miR-301a-3p. SOCS2 knockdown partially reversed the inhibitory effect of miR-301a-3p inhibition on NSCLC cells malignant phenotype (p <.05). circ_0008797 attenuated NSCLC prolifearion and metastasis in vivo (p <.05). CONCLUSION: circ_0008797 attenuates NSCLC proliferation, metastasis and aerobic glycolysis by sponging miR-301a-3p/SOCS2.
Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , MicroRNAs , RNA Circular , Proteínas Supressoras da Sinalização de Citocina , Animais , Carcinoma Pulmonar de Células não Pequenas/patologia , Linhagem Celular Tumoral , Proliferação de Células/genética , Glicólise/genética , Humanos , Hibridização in Situ Fluorescente , Neoplasias Pulmonares/patologia , Camundongos , Camundongos Nus , MicroRNAs/genética , RNA Circular/genética , Proteínas Supressoras da Sinalização de Citocina/genéticaRESUMO
To assess the relationship between the neutrophil-to-lymphocyte ratio (NLR) and related parameters to the severity of coronavirus disease 2019 (COVID-19) symptoms. Clinical data from 38 COVID-19 patients who were diagnosed, treated and discharged from the Qishan Hospital in Yantai over the period from January to February 2020 were analysed. NLR and procalcitonin (PCT) were determined in the first and fourth weeks after their admission, along with the clinical characteristics and laboratory test results of these patients. Based on results as obtained on the first and fourth weeks after admission, five indices consisting of NLR, white blood cells, neutrophils, lymphocytes (LY) and monocytes (MON) were selected to generate receiver operating characteristic curves, while optimal cutoff values, sensitivities and specificities were obtained according to the Yuden index. Statistically significant differences in neutrophils, LY and the NLR were present in the severe vs. moderate COVID-19 group from the first to the fourth week of their hospitalisation. The cut-off value of NLR for predicting the severity of COVID-19 was 4.425, with a sensitivity of 0.855 and a specificity of 0.979. A statistically significant positive correlation was present between PCT and NLR in the severe group as determined within the first week of admission. NLR can serve as a predictor of COVID-19 disease severity as patients' progress from the first to the fourth week of their hospitalisation. The statistically significant positive correlation between levels of NLR and PCT in severe patients indicated that increases in NLR were accompanied with gradual increases in PCT.
Assuntos
COVID-19/virologia , Linfócitos/fisiologia , Neutrófilos/fisiologia , Pró-Calcitonina/sangue , Adulto , Idoso , China , Feminino , Humanos , Contagem de Linfócitos , Masculino , Pessoa de Meia-Idade , Curva ROC , Estudos Retrospectivos , Índice de Gravidade de DoençaRESUMO
PURPOSE: Analyzing sleep quality and sleep structure in patients with patent foramen ovale (PFO) complicated with obstructive sleep apnea (OSA) and the interaction between OSA and PFO in sleep. METHODS: We compared patients with PFO complicated with OSA, patients with simple PFO, and controls. Pittsburgh Sleep Quality Index was used to compare sleep quality and polysomnography was used to compare sleep structure of the three groups. RESULTS: Compared with the control group (n = 62), PFO with OSA (n = 48) and simple PFO (n = 61) groups had more frequent occurrence of poor sleep quality (χ2 = 89.901; p < 0.001). These two groups also showed decreased sleep efficiency (p < 0.010), lower percentages of REM sleep, and reduced N3 sleep (p < 0.050). The N2 sleep was prolonged (p < 0.010). The nocturnal lowest SpO2 was lower and the oxygen desaturation index was higher (p < 0.50). Compared with the simple PFO group, the poor sleep quality was more frequent in the PFO with OSA group; sleep latency (p < 0.001) was prolonged; wake after sleep onset (p < 0.001) and arousal times (p = 0.031) were increased; and sleep micro-arousal index (p = 0.037), periodic leg movement index (p = 0.024), and apnea hypopnea index (p < 0.001) were higher in the PFO with OSA group. CONCLUSION: Patients with PFO and OSA have poor sleep quality with changes in sleep stage and high occurrence rate of sleep disorders. OSA further deteriorates sleep quality and alters sleep structure in patients with PFO.
Assuntos
Forame Oval Patente/fisiopatologia , Apneia Obstrutiva do Sono/fisiopatologia , Fases do Sono/fisiologia , Idoso , Comorbidade , Feminino , Forame Oval Patente/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Polissonografia , Apneia Obstrutiva do Sono/epidemiologiaRESUMO
Verruca plana is a kind of benign proliferative skin disease that generally occurs in exposed parts, but the treatment of warts poses a therapeutic challenge for physicians, as there is no method, among numerous approaches, that has been proven effective for completely curing this disease. We report a case of verruca plana cured by narrow-band ultraviolet B (NB-UVB), which provides a new treatment of verruca plana.
Assuntos
Dermatopatias , Terapia Ultravioleta , Verrugas , Humanos , Verrugas/radioterapiaRESUMO
BACKGROUND: The lacrimal ductal cyst (dacryops) is an uncommon clinical entity. It occurs anywhere that lacrimal gland tissue is present but most often appears as an expanding mass in the region of the lacrimal gland. The presence involving the medial part of the orbit is rare, ectopic location can be misleading in the differential diagnosis of orbital masses. The authors report a 53-year-old man who presented with dacryops occurred in an unusual location with significant clinical presentations. CASE PRESENTATION: A 53-year-old man had a painless mass located in the right superomedial orbit accompanied with foreign body sensation and lachrymation for two months, which had rapidly grown within 10 days. Decrease of visual acuity, high intraocular pressure (IOP) and limitation of extraocular movements in the right eye were present. The result of visual evoked potential (VEP) test suggested the impaired function of the optic nerve. Magnetic resonance imaging (MRI) studies revealed the presence of an isolated cystic lesion. The mass was completely removed via a transcutaneous approach, histopathologic findings were consistent with the lacrimal ductal cyst. The ocular motility and high IOP returned to normal. There had been no post-operative complications or signs of recurrence over five months follow-up. CONCLUSION: Lacrimal ductal cysts can present in the medial orbit, clinicians should include this entity in the differential diagnosis of orbital masses and be aware of its variable presentations such as high IOP in this case. We comment on the fact that many reported cases of ectopic dacryops may be an extension of normal lacrimal gland tissue.
Assuntos
Cistos , Doenças do Aparelho Lacrimal , Aparelho Lacrimal , Cistos/diagnóstico , Potenciais Evocados Visuais , Humanos , Doenças do Aparelho Lacrimal/diagnóstico , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , ÓrbitaRESUMO
PURPOSE: To study and analyze the sleep quality and sleep structure of patients with vestibular migraine (VM). METHODS: In this cross-sectional case-control study, the Pittsburgh Sleep Quality Index (PSQI) questionnaire and polysomnography (PSG) were used to compare the clinical characteristics of sleep disorders in 49 patients with VM, 52 patients with migraine, and 54 controls. RESULTS: The VM, migraine, and control groups did not significantly differ in terms of age or sex. Compared with the migraine and control groups, the VM group had a higher incidence of poor sleep quality (χ2 = 36.618, p < 0.01) and greater severity of poor sleep quality (p < 0.01). Furthermore, the VM group showed reduced sleep efficiency (p < 0.01) and reduced proportions of REM and slow wave (N3) sleep (p ≤ 0.01). Conversely, sleep latency (p = 0.01) and REM latency (p = 0.04) were prolonged, and proportions of light sleep phases (N1, p < 0.05, and N2, p < 0.01) and the micro-arousal index (p = 0.03) were increased. The migraine group had significantly higher apnea hypopnea (AHI) and periodic leg movement (PLMI) indices than the VM group. CONCLUSION: We report an effect of VM on sleep structure and an association with migraine. Similar to migraine, VM affects the sleep regulation centers and causes structural sleep disorders.
Assuntos
Transtornos de Enxaqueca/fisiopatologia , Transtornos do Sono-Vigília/fisiopatologia , Doenças Vestibulares/fisiopatologia , Adulto , Estudos de Casos e Controles , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Transtornos de Enxaqueca/complicações , Transtornos de Enxaqueca/epidemiologia , Polissonografia , Transtornos do Sono-Vigília/complicações , Transtornos do Sono-Vigília/epidemiologia , Inquéritos e Questionários , Doenças Vestibulares/complicações , Doenças Vestibulares/epidemiologiaRESUMO
PURPOSE: Radiomics allows for powerful data-mining and feature extraction techniques to guide clinical decision making. Image segmentation is a necessary step in such pipelines and different techniques can significantly affect results. We demonstrate that a convolutional neural network (CNN) segmentation method performs comparably to expert manual segmentations in an established radiomics pipeline. METHODS: Using the manual regions of interest (ROIs) of an expert radiologist (R1), a CNN was trained to segment breast lesions from dynamic contrast-enhanced MRI (DCE-MRI). Following network training, we segmented lesions for the testing set of a previously established radiomics pipeline for predicting lymph node metastases using DCE-MRI of breast cancer. Prediction accuracy of CNN segmentations relative to manual segmentations by R1 from the original study, a resident (R2), and another expert radiologist (R3) were determined. We then retrained the CNN and radiomics model using R3's manual segmentations to determine the effects of different expert observers on end-to-end prediction. RESULTS: Using R1's ROIs, the CNN achieved a mean Dice coefficient of 0.71 ± 0.16 in the testing set. When input to our previously published radiomics pipeline, these CNN segmentations achieved comparable prediction performance to R1's manual ROIs, and superior performance to those of the other radiologists. Similar results were seen when training the CNN and radiomics model using R3's ROIs. CONCLUSION: A CNN architecture is able to provide DCE-MRI breast lesion segmentations which are suitable for input to our radiomics model. Moreover, the previously established radiomics model and CNN can be accurately trained end-to-end using ground truth data provided by distinct experts.