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1.
BMC Cancer ; 20(1): 144, 2020 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-32087687

RESUMO

BACKGROUND: Information on the optimal salvage regimen for recurrent esophageal cancer is scarce. We aimed to assess the patterns of locoregional failure, and evaluate the therapeutic efficacy of salvage therapy along with the prognostic factors in recurrent thoracic esophageal squamous cell carcinoma (TESCC) after radical esophagectomy. METHODS: A total of 193 TESCC patients who were diagnosed with recurrence after radical surgery and received salvage treatment at our hospital were retrospectively reviewed from 2004 to 2014. The patterns of the first failure were assessed. The post-recurrence survival rate was determined using the Kaplan-Meier method and analyzed using the log-rank test. Multivariate prognostic analysis was performed using the Cox proportional hazard model. RESULTS: The median time of failure was 7.0 months. Among the 193 patients, 163 exhibited isolated locoregional lymph node (LN) recurrence and 30 experienced locoregional LN relapse with hematogenous metastasis. Among the 193 patients, LN recurrence was noted at 302 sites; the most common sites included the supraclavicular (25.8%; 78/302) and mediastinal LNs (44.4%; 134/302), particularly stations 1 to 6 for the mediastinal LNs (36.4%; 110/302). The median overall survival (OS) was 13.1 months after recurrence. In those treated with salvage chemoradiotherapy, with radiotherapy, and without radiotherapy, the 1-year OS rates were 68.5, 55.0, and 28.6%; the 3-year OS rates were 35.4, 23.8, and 2.9%; and the 5-year OS rates were 31.8, 17.2, 2.9%, respectively (P < 0.001). Furthermore, patient survival in those who received salvage chemoradiotherapy was significantly better than those treated with salvage radiotherapy alone (P = 0.044). Multivariate analysis showed that the pathological TNM stage and salvage treatment regimen were independent prognostic factors. CONCLUSIONS: Supraclavicular and mediastinal LN failure were the most common types of recurrence after R0 surgery in TESCC patients. Salvage chemoradiotherapy or radiotherapy could significantly improve survival in esophageal cancer with locoregional LN recurrence.

2.
Oncologist ; 2020 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-32083766

RESUMO

BACKGROUND: The role of postoperative radiotherapy in pathological T2-3N0M0 esophageal squamous cell carcinoma is unknown. We aimed to evaluate the efficacy and safety of postoperative radiotherapy in patients with pathological T2-3N0M0 thoracic esophageal squamous cell carcinoma. MATERIALS AND METHODS: Patients aged 18-72 years with pathological stage T2-3N0M0 esophageal squamous cell carcinoma after radical surgery and without neoadjuvant therapy were eligible. Patients were randomly assigned to surgery alone or to receive postoperative radiotherapy of 50.4 Gy in supraclavicular field and 56 Gy in mediastinal field in 28 fractions over 6 weeks. The primary endpoint was disease-free survival. The secondary endpoints were local-regional recurrence rate, overall survival, and radiation-related toxicities. RESULTS: From October 2012 to February 2018, 167 patients were enrolled in this study. We analyzed 157 patients whose follow-up time was more than 1 year or who had died. The median follow-up time was 45.6 months. The 3-year disease-free survival rates were 75.1% (95% confidence interval [CI] 65.9-85.5) in the postoperative radiotherapy group and 58.7% (95% CI 48.2-71.5) in the surgery group (hazard ratio 0.53, 95% CI 0.30-0.94, p = .030). Local-regional recurrence rate decreased significantly in the radiotherapy group (10.0% vs. 32.5% in the surgery group, p = .001). The overall survival and distant metastasis rates were not significantly different between two groups. Grade 3 toxicity rate related to radiotherapy was 12.5%. CONCLUSION: Postoperative radiotherapy significantly increased disease-free survival and decreased local regional recurrence rate in patients with pathological T2-3N0M0 thoracic esophageal squamous cell carcinoma with acceptable toxicities in this interim analysis. Further enrollment and follow-up are warranted to validate these findings in this ongoing trial. IMPLICATIONS FOR PRACTICE: The value of adjuvant radiotherapy for patients with node-negative esophageal cancer is not clear. The interim results of this phase III study indicated that postoperative radiotherapy significantly improved disease-free survival and decreased local-regional recurrence rate in patients with pathological T2-3N0M0 thoracic esophageal squamous cell carcinoma compared with surgery alone with acceptable toxicities. The distant metastasis rates and overall survival rates were not different between the two groups. Adjuvant radiotherapy should be considered for pathologic T2-3N0M0 thoracic esophageal squamous cell carcinoma. Prospective trials to identify high-risk subgroups are needed.

3.
Immunobiology ; 224(6): 765-773, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31515081

RESUMO

Otitis media with effusion (OME) often occurs in infants and young children, which is related to allergic reactions. Notch signaling pathway plays an important role in allergic responses. In this study, we aimed to investigate the role of Notch signaling pathway in the ovalbumin (OVA)-mediated allergic OME in vivo. OVA-induced OME rats were treated with a control vehicle or a γ-secretase inhibitor, N-[N-(3,5-difluorophenacetyl)-L-alanyl]-S-phenylglycine t-butyl ester (DAPT) suppressing the Notch signaling. We studied the effect of Notch signaling pathway in OME model, including histopathological assessment, the expression of Th1 cytokines (IFN-γ), Th2 cytokines (IL-4, IL-5), key transcription factors (T-bet, GATA-3) by quantitative real-time polymerase chain reaction (qRT-PCR). In addition, the level of Notch ligand (Jagged1) and the downstream target gene Hes1 were also evaluated by qRT-PCR and immunofluorescent staining. We observed that the production of Th2 cytokines was increased, the level of Th1 cytokines was decreased in OME experimental model. Likewise, Th2-cytokine(IL-4)level was reduced, but the level of Th1 cytokines(IFN-γ) was no changes. Additionally, administration of DAPT induced a decrease in the expression of GATA-3 mRNA, however, no influence on T-bet mRNA production. These results suggest that there is an imbalance with Th1/Th2 in OVA-mediated allergic OME. DAPT treatment can block the Notch signaling pathway and relieve the middle ear inflammation through modulating the level of Th2 responses in OVA-induced allergic OME.

4.
Sci Rep ; 9(1): 11243, 2019 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-31375715

RESUMO

In order to explore the important factors in the diagnosis of breast cancer in China, meta-analysis of previous studies was performed to understand the association between STAT3/p-STAT3 and breast cancer. Information about STAT3/p-STAT3 expression and clinical data about breast cancer in China in particular were gathered from PubMed, Web of Science, CNKI and WanFang databases. RevMan 5.3 and STATA 14.0 were used to analyze the occurrence, development and metastasis of breast cancer for 2818 patients in 18 studies. STAT3/p-STAT3 expression was higher in breast cancer tissue than in normal ones (OR = 7.48, 95% CI = 5.64-9.94), in highly differentiated breast cancer tissue than in lowly differentiated cancer tissues (OR = 2.13, 95% CI = 1.53-2.98), in III/IV stage breast cancer than in I/II stage breast cancer (OR = 3.58, 95% CI = 2.44-5.25), and in tissue with lymphatic metastasis than in normal tissues (OR = 3.72, 95% CI = 2.59-5.35), respectively. Thus, the expression of STAT3/p-STAT3 plays a clinicopathological and prognostic role in the diagnosis and treatment of Chinese breast cancer patients.

5.
Ann Surg Oncol ; 26(9): 2890-2898, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31183641

RESUMO

BACKGROUND: Effective tools evaluating the prognosis for patients with esophageal cancer undergoing surgery is lacking. The current study aimed to develop a nomogram to predict overall survival (OS) and provide evidence for adjuvant therapy for patients with esophageal carcinoma after esophagectomy. METHODS: The study retrospectively reviewed patients with pathologic T1N +/T2-4aN0-3, M0 thoracic esophageal squamous cell carcinoma after radical esophagectomy, with or without adjuvant therapy, in one institution as the training cohort (n = 2281). A nomogram was established using Cox proportional hazard regression to identify prognostic factors for OS, which were validated in an independent validation cohort (n = 1437). Area under curve (AUC) values of receiver operating characteristic curves were calculated to evaluate prognostic efficacy. RESULTS: In the training cohort, the median OS was 50.46 months, and the 5-year OS rate was 47.08%. Adjuvant therapy, sex, tumor location, grade, lymphovascular invasion, removed lymph nodes, and T and N categories were identified as predictive factors for OS. The nomogram showed favorable prognostic efficacy in the training and validation cohorts (5-year OS AUC: 0.685 and 0.744, respectively), which was significantly higher than that of the American Joint Committee on Cancer (AJCC) staging system. The nomogram distinguished OS rates among six risk groups, whereas AJCC could not separate the OS of 2A and 1B, 3C and 3B, or 3A and 2B. Patients with a nomogram score of 72 to 227 were predicted to achieve a 5-year OS increase of 10% or more from adjuvant therapy. CONCLUSION: The nomogram could effectively predict OS and aided decision making in adjuvant therapy for patients with thoracic esophageal squamous cell carcinoma after esophagectomy.


Assuntos
Neoplasias Esofágicas/mortalidade , Carcinoma de Células Escamosas do Esôfago/mortalidade , Esofagectomia/mortalidade , Nomogramas , Neoplasias Torácicas/mortalidade , Idoso , Neoplasias Esofágicas/patologia , Neoplasias Esofágicas/cirurgia , Carcinoma de Células Escamosas do Esôfago/patologia , Carcinoma de Células Escamosas do Esôfago/cirurgia , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Curva ROC , Estudos Retrospectivos , Taxa de Sobrevida , Neoplasias Torácicas/patologia , Neoplasias Torácicas/cirurgia
7.
Chemosphere ; 220: 539-545, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30597361

RESUMO

Historical records of heavy metals from remote areas are important for assessing temporal pollution trends of the regional atmosphere. Based on comparison analyses of heavy metals, Pb isotopes, and total carbon in sediment cores from two relatively remote lakes on the southeast Mongolian Plateau, atmospheric heavy metal pollution trends during ∼1900-2016 were reconstructed. The current anthropogenic fluxes of Zn, Cd and Pb in the region are 11.7, 0.104 and 2.44 mg m-2 yr-1, respectively, close to those in Lake Sayram in West China, but lower than most other records in China. Anthropogenic metal fluxes and 206Pb/207Pb ratios suggest that (1) before ∼1950 atmospheric metal pollution was negligible in the region; (2) since ∼1950, the pollution became detectable but was relatively slight until ∼1980, corresponded with the beginning of socio-economic development after the foundation of China in 1949 and the rapid development after the Reform and Opening-up in 1978; and (3) since ∼2000, atmospheric Pb stopped increasing because of the phasing out of leaded gasoline. Based on comparison and fitting analyses with other sediment records, a similar four-stage evolution picture of atmospheric heavy metals in China over the last century was uncovered. This study indicates rapid increase trends of atmospheric heavy metals in China since ∼1980 associated with economic development.


Assuntos
Poluição do Ar/análise , Monitoramento Ambiental/métodos , Poluição Ambiental/análise , Sedimentos Geológicos/análise , Metais Pesados/análise , Atmosfera , China , Registros
8.
Sci Total Environ ; 649: 929-937, 2019 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-30179821

RESUMO

Owing to rapid socio-economic development and climate warming, lakes even in remote areas have experienced marked changes in the last century. However, there are few studies revealing the multi-faceted biogeochemical changes and disentangling impacts of human and climate in relatively remote lakes in China. In this study we reconstructed historical changes of geochemistry, nutrition, primary production, ecology, and pollution in an alpine lake (Gonghai) in central North China, and revealed coherent changes and drivers in relatively remote Chinese lakes by compiling other records. Results show that Lake Gonghai has experienced considerably biogeochemical changes since the 1980s induced mainly by increased regional human activities, with detected human-related changes occurring in the 1950s-70s. The most important change is a shift of diatom primary producers in the 1980s, caused mainly by an increase of regional atmospheric N and P deposition associated with rapid socio-economic development. Another remarkable change is the increase of pollution levels since the 1980s, represented by heavy metals, also caused by atmospheric deposition. Compiled sediment records demonstrate similar biogeochemical changes in most lakes from relatively remote areas of China since the 1970s-80s, associated closely with increased inputs of human-induced atmospheric N, P and pollutants, whereas the influence of climate warming is likely limited. This study highlights markedly human-related biogeochemical changes in relatively remote Chinese lakes during the Anthropocene epoch.


Assuntos
Monitoramento Ambiental , Sedimentos Geológicos/análise , Lagos/química , Poluentes Químicos da Água/análise , China , Aquecimento Global
9.
Chem Asian J ; 14(3): 454-461, 2019 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-30516348

RESUMO

A convenient and divergent approach was developed to prepare diverse bacterial 3-deoxy-d-manno-oct-2-ulosonic acid (Kdo) oligosaccharides containing a Kdo-α-(2→4)-Kdo fragment. The orthogonal protected α-(2→4) linked Kdo-Kdo disaccharide 3, serving as a common precursor, was divergently transformed into the corresponding 8-, 8'-, and 4'-hydroxy disaccharides 5, 7, and 14, respectively. Then, these alcohols were glycosylated, respectively, with the 5,7-O-di-tert-butylsilylene (DTBS) protected Kdo thioglycoside donors 1 or 2 in an α-stereoselective and high-yielding manner to afford a range of Kdo oligosaccharides. Finally, removal of all protecting groups of the newly formed glycosides resulted in the desired free Kdo oligomer.

10.
Medicine (Baltimore) ; 97(51): e13192, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30572427

RESUMO

RATIONALE: Although lung cancer is the leading cause of cancer-related death in the world, targeted therapy plays an essential role in improving the survival of lung cancer. Next-generation sequencing (NGS) technology can dynamically monitor the genomic profiles of tumors and assist cancer diagnosis and treatment. PATIENT CONCERNS: We reported on a 55-year-old man who presented with chest tightness and wheezing for 1 month. DIAGNOSES: The patient was diagnosed with stage cT4N2M1a non-small cell lung cancer (NSCLC) and was found to have wild-type EGFR by pleural effusion cytology. INTERVENTIONS: The patient received systemic treatments, including chemotherapy, targeted therapy, and radiotherapy. During the cancer development, sequential DNA sequencing data that used circulating cell-free tumor DNA, and NGS revealed EGFR L858R and T790M mutations, MYC amplification, and other gene variations. OUTCOMES: The patient died of brain and lung metastases, and had an overall survival as long as 37 months. LESSONS: The dynamic monitoring of tumor genomic profiles has important implications for NSCLC diagnosis, treatment, and prognosis.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/genética , Sequenciamento de Nucleotídeos em Larga Escala , Neoplasias Pulmonares/genética , Monitorização Fisiológica/métodos , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/secundário , Neoplasias Encefálicas/terapia , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma Pulmonar de Células não Pequenas/terapia , Progressão da Doença , Evolução Fatal , Humanos , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/terapia , Masculino , Pessoa de Meia-Idade
11.
Carbohydr Res ; 465: 10-15, 2018 07 30.
Artigo em Inglês | MEDLINE | ID: mdl-29879545

RESUMO

The efficient synthesis of a linear pentasaccharide with the structure 1, ß-D-Araf-(1 → 2)-α-D-Araf-(1 → 5)-α-D-Araf-(1 → 5)-α-D-Araf-(1 → 5)-α-D-Araf-(1 â†’ 5), as its octyl glycoside has been achieved through a convergent [3 + 2] coupling strategy. The difficult-to-obtain 1,2-cis-ß-arabinofuranosidic bond at the non-reducing end of the target molecule was stereoselectively constructed by the use of a 2-quinolinecarbonyl-directed 1,2-cis glycosylation method.


Assuntos
Arabinose/síntese química , Proteínas de Bactérias/química , Mycobacterium leprae/química , Mycobacterium tuberculosis/química , Arabinose/análogos & derivados , Arabinose/química , Estrutura Molecular , Especificidade por Substrato
12.
Mol Cancer ; 17(1): 92, 2018 05 24.
Artigo em Inglês | MEDLINE | ID: mdl-29793547

RESUMO

BACKGROUND: Mounting evidence indicates that long noncoding RNAs (lncRNAs) could play a pivotal role in cancer biology. However, the role and molecular mechanism and global genes that were mediated by lncRNA AFAP1-AS1 in non-small cell lung cancer (NSCLC) remain largely unknown. METHODS: Expression of AFAP1-AS1 was analyzed in 92 NSCLC tissues and cell lines by Quantitative real time polymerase chain reaction (qRT-PCR). The effect of AFAP1-AS1 on proliferation was evaluated by function assays both in in vitro and in vivo. RNA-seq assays were performed after knockdown AFAP1-AS1. RNA immunoprecipitation (RIP) was performed to confirm the interaction between AFAP1-AS1 and EZH2. Chromatin immunoprecipitation (ChIP) was used to study the promoter region of p21. RESULTS: AFAP1-AS1 expression was increased in NSCLC tissues and was correlated with clinical outcomes of NSCLC. Further experiments revealed that inhibition of its expression in NSCLC cells resulted in diminished cell growth in vitro and in vivo. RNA-seq revealed that knockdown of AFAP1-AS1 could induce the expression of p21. Mechanistic investigations found that AFAP1-AS1 could interact with EZH2 and recruit EZH2 to the promoter regions of p21, thus epigenetically repressing p21 expression. CONCLUSIONS: Together, these results suggest that lncRNA AFAP1-AS1 may serve as a candidate prognostic biomarker and target for new therapies in human NSCLC.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/patologia , Inibidor de Quinase Dependente de Ciclina p21/genética , Proteína Potenciadora do Homólogo 2 de Zeste/genética , Neoplasias Pulmonares/patologia , RNA Longo não Codificante/genética , Animais , Carcinoma Pulmonar de Células não Pequenas/genética , Linhagem Celular Tumoral , Proliferação de Células , Regulação para Baixo , Epigênese Genética , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Pulmonares/genética , Masculino , Camundongos , Estadiamento de Neoplasias , Transplante de Neoplasias , Prognóstico , Análise de Sequência de RNA
13.
Oncol Lett ; 15(2): 2695-2699, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29434994

RESUMO

The imbalance between cell proliferation and apoptosis was implicated to serve key roles in cancer pathogenesis. The characteristics of microRNAs (miRNAs/miRs) have attracted much attention in research focusing on cancer pathogenesis in recent years. miR-122-3p has been reported to be associated with a number of disease processes and pathogenesis, including lung cancer. The present study aimed to investigate the association of miR-122-3p expression level with cell proliferation and apoptosis in a lung cancer cell line. A549 cells were transfected with miR-122-3p to interrupt the expression of miR-122-3p. Subsequently, MTT and BrdU assay, and western blot were used to analyze the influence of miR-122-3p on lung cancer cell proliferation, cell viability and its underlying mechanism. The present study revealed that, by targeting p27, overexpression of miR-122-3p inhibited cell proliferation in lung cancer. Furthermore, the cell apoptosis analysis suggested that overexpression of miR-122-3p was able to inhibit cell apoptosis by targeting Forkhead box O. These findings suggest that miR-122-3p may be associated with the pathology and progression of lung cancer and be a new therapeutic target for this disease.

14.
J Am Chem Soc ; 140(10): 3574-3582, 2018 03 14.
Artigo em Inglês | MEDLINE | ID: mdl-29481074

RESUMO

The stereodirecting effect of C5-ester functions on the glycosylation stereoselectivity of 3-deoxy-d- manno-oct-2-ulosonic acid (Kdo) ethyl thioglycoside donors is presented. The coupling of 5- O-arylcarbonyl or acetyl protected Kdo thioglycosides with acceptors proceeds in an α-selective and high-yielding manner, leading to formation of α-linked Kdo glycosides products. On the other hand, the glycosylation stereoselectivity of the 5- O-2-quinolinecarbonyl (Quin) or 4-nitropicoloyl substituted Kdo thioglycoside donors is switchable: (1) The glycosylation of the 5- O-Quin carrying Kdo donors with primary glycosyl acceptors shows complete ß-stereoselectivity, furnishing the corresponding ß-glycosides in good-to-excellent yield. (2) The stereochemical outcome of the secondary acceptors with these Kdo donors is determined mainly by the stereoelectronic nature of the acceptor. Only or predominant α anomeric products are obtained when the Kdo donors couple with the disarmed or highly crowded secondary carbohydrate acceptors, while the selectivity may switch to predominant ß in the glycosylation of the 5- O-4-nitropicoloyl carrying donor with more reactive secondary alcohols. The synthetic use of the newly developed Kdo donors 1c and 7b has been demonstrated by facile preparation of a structurally unique trisaccharide motif 19 which possesses both α- and ß-Kdo glycosidic bonds.


Assuntos
Ácidos Carboxílicos/química , Glicosídeos/síntese química , Açúcares Ácidos/síntese química , Compostos de Sulfidrila/síntese química , Glicosídeos/química , Glicosilação , Estrutura Molecular , Estereoisomerismo , Açúcares Ácidos/química , Compostos de Sulfidrila/química
15.
Ultrasonics ; 84: 319-328, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29207332

RESUMO

This paper presents a study on model assessment for predicting structural fatigue life using Lamb waves. Lamb wave coupon testing is performed for model development. Three damage sensitive features, namely normalized energy, phase change, and correlation coefficient are extracted from Lamb wave data and are used to quantify the crack size. Four data-driven models are proposed. The average relative error and the probability of detection (POD) are proposed as two measures to evaluate the performance of the four models. To study the influence of model choice on the probabilistic fatigue life prediction, probability density functions of the actual crack size are obtained from the POD models given the Lamb wave data. Crack growth model parameters are statistically identified using Bayesian parameter estimation with Markov chain Monte Carlo simulations. The model assessment and the influence of model choice on fatigue life prediction are made using both coupon testing data with artificial cracks and realistic lap joint testing data with naturally developed cracks.

16.
Bioanalysis ; 9(20): 1603-1615, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-29072493

RESUMO

AIM: Development of drug-related surrogate positive controls for isotype anti-drug antibodies assay remains challenging. Efforts on antibody engineering or chemical crosslinking have been made. However, multiple epitope recognition, purity and stability are often of concern. To tackle these challenges, we used LC-SPDP/SMPB crosslinking to conjugate polyclonal anti-drug IgG and human immunoglobulin isotype (hIgE, hIgA, hIgM or hIgG4) with optimized conditions. RESULTS: The final product was a hybrid of anti-drug IgG cross-linked to human isotype immunoglobulin through stable thioether bond. The characteristics of the hybrids and their performance as assay positive controls were further evaluated. CONCLUSION: The results demonstrate that LC-SPDP/SMPB chemical crosslinking method is suitable for generating stable hybrids to be used as assay positive controls in isotype anti-drug antibodies assay.


Assuntos
Anticorpos/análise , Cromatografia em Gel , Isotipos de Imunoglobulinas/análise , Anticorpos/química , Anticorpos/metabolismo , Complexo Antígeno-Anticorpo/análise , Ensaio de Imunoadsorção Enzimática , Humanos , Isotipos de Imunoglobulinas/química , Maleimidas/química , Preparações Farmacêuticas/química , Preparações Farmacêuticas/metabolismo , Sulfetos/química
17.
Sensors (Basel) ; 17(9)2017 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-28902148

RESUMO

This paper presents a systematic and general method for Lamb wave-based crack size quantification using finite element simulations and Bayesian updating. The method consists of construction of a baseline quantification model using finite element simulation data and Bayesian updating with limited Lamb wave data from target structure. The baseline model correlates two proposed damage sensitive features, namely the normalized amplitude and phase change, with the crack length through a response surface model. The two damage sensitive features are extracted from the first received S0 mode wave package. The model parameters of the baseline model are estimated using finite element simulation data. To account for uncertainties from numerical modeling, geometry, material and manufacturing between the baseline model and the target model, Bayesian method is employed to update the baseline model with a few measurements acquired from the actual target structure. A rigorous validation is made using in-situ fatigue testing and Lamb wave data from coupon specimens and realistic lap-joint components. The effectiveness and accuracy of the proposed method is demonstrated under different loading and damage conditions.

18.
Materials (Basel) ; 10(6)2017 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-28773003

RESUMO

Lamb waves have been reported to be an efficient tool for non-destructive evaluations (NDE) for various application scenarios. However, accurate and reliable damage quantification using the Lamb wave method is still a practical challenge, due to the complex underlying mechanism of Lamb wave propagation and damage detection. This paper presents a Lamb wave damage quantification method using a least square support vector machine (LS-SVM) and a genetic algorithm (GA). Three damage sensitive features, namely, normalized amplitude, phase change, and correlation coefficient, were proposed to describe changes of Lamb wave characteristics caused by damage. In view of commonly used data-driven methods, the GA-based LS-SVM model using the proposed three damage sensitive features was implemented to evaluate the crack size. The GA method was adopted to optimize the model parameters. The results of GA-based LS-SVM were validated using coupon test data and lap joint component test data with naturally developed fatigue cracks. Cases of different loading and manufacturer were also included to further verify the robustness of the proposed method for crack quantification.

19.
Inflammopharmacology ; 25(4): 471-484, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28577132

RESUMO

Our aim was to investigate whether tangeretin, a citrus flavonoid, was able to prevent neuroinflammation and improve dementia in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced rodent model of Parkinson's disease (PD). MPTP-HCl was infused into the substantia nigra pars compacta of male Sprague-Dawley rats. Tangeretin (50, 100 or 200 mg/kg body weight) was administered orally starting 3 days prior to MPTP injection and was continued for 20 days following injection. MPTP-lesioned rats revealed motor dysfunction in bar test and rota rod tests. Deficits in working memory and object recognition function were also observed following MPTP induction. Tangeretin treatment significantly attenuated the memory deficits and improved motor functions and cognition. Immunohistochemical analysis reveals the protective effects of tangeretin against MPTP lesion-induced dopaminergic degeneration and hippocampal neuronal loss. Tangeretin reduced expression of inflammatory mediators-COX-2, iNOS-as well reduced the levels of cytokines-interleukins (IL)-IL-1ß, IL-6 and IL-2. The experimental data suggest tangeretin as an effective candidate drug with potential for prevention and treatment of neuroinflammation and dementia associated with PD.


Assuntos
Demência/tratamento farmacológico , Flavonas/uso terapêutico , Mediadores da Inflamação/antagonistas & inibidores , Intoxicação por MPTP/tratamento farmacológico , Aprendizagem em Labirinto/efeitos dos fármacos , Animais , Cognição/efeitos dos fármacos , Cognição/fisiologia , Demência/metabolismo , Demência/psicologia , Relação Dose-Resposta a Droga , Flavonas/farmacologia , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Inflamação/psicologia , Mediadores da Inflamação/metabolismo , Intoxicação por MPTP/metabolismo , Intoxicação por MPTP/psicologia , Masculino , Aprendizagem em Labirinto/fisiologia , Doenças Neurodegenerativas/tratamento farmacológico , Doenças Neurodegenerativas/metabolismo , Doenças Neurodegenerativas/psicologia , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Ratos , Ratos Sprague-Dawley
20.
J Thorac Oncol ; 12(7): 1143-1151, 2017 07.
Artigo em Inglês | MEDLINE | ID: mdl-28411098

RESUMO

INTRODUCTION: The role of conformal radiotherapy (cRT) in thoracic esophageal squamous cell carcinoma (TESCC) has not been addressed in adjuvant settings. The aim of this study was to investigate whether postoperative radiotherapy using cRT after an R0 resection improves outcomes in pT3N0M0 TESCC compared with resection alone. METHODS: This study included 678 patients with pT3N0M0 TESCC who were treated at the Cancer Hospital, Chinese Academy of Medical Sciences, from January 2004 to December 2011. The patients were divided into two groups: a surgery plus cRT group (S+cRT group) comprising patients who underwent cRT after an R0 resection and a surgery group (S group), comprising a control group of patients who underwent an R0 resection alone. Propensity score matching was used to create patient groups that were balanced across several covariates (n = 83 in each group). Outcome measures included overall survival (OS), disease-free survival (DFS), and recurrence. RESULTS: In the overall study cohort, 5-year OS (75.2% versus 58.5%, p = 0.004) and DFS (71.8% versus 49.2%, p = 0.001) rates were significantly higher in the S+cRT group than in the S group. These data were confirmed in the matched samples (5-year OS, 75.7% versus 58.8% [p = 0.017]; DFS, 71.7% versus 50.3% [p = 0.009]). The overall (p = 0.001) and locoregional (p = 0.004) recurrence rates in the S+cRT group were significantly lower than in the S group. Multivariate Cox analyses in the matched samples revealed that surgery and postoperative cRT were independently associated with longer OS (hazard ratio = 0.505, 95% confidence interval: 0.291-0.876, p = 0.015) and longer DFS (hazard ratio = 0.513, 95% confidence interval: 0.309-0.854, p = 0.010) than resection alone. CONCLUSIONS: Postoperative radiotherapy using cRT is strongly associated with improved OS and DFS in patients with pT3N0M0 TESCC. A multicenter, randomized phase III clinical trial is warranted to confirm these findings.


Assuntos
Neoplasias Esofágicas/radioterapia , Neoplasias Esofágicas/cirurgia , Cuidados Pós-Operatórios/métodos , Neoplasias Esofágicas/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Prognóstico , Análise de Sobrevida
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