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1.
Materials (Basel) ; 17(10)2024 May 08.
Article in English | MEDLINE | ID: mdl-38793268

ABSTRACT

Commercial oxygen-free copper sheets were cold-rolled with reduction rates ranging from 20% to 87% and annealed at 400, 500 and 600 °C. The microstructure and texture evolution during the cold-rolling and annealing processes were studied using optical microscopy (OM), scanning electron microscopy (SEM) and electron back-scattered diffraction (EBSD). The results show that the deformation textures of {123}<634> (S), {112}<111> (Copper) and {110}<112> (Brass) were continuously enhanced with the increase in cold-rolling reduction. The orientations along the α-oriented fiber converged towards Brass, and the orientation density of ß fiber obviously increased when the rolling reduction exceeded 60%. The recrystallization texture was significantly affected by the cold-rolling reduction. After 60% cold-rolling reduction, Copper and S texture components gradually decreased, and the {011}<511> recrystallization texture component formed with the increase in annealing temperature. After 87% cold-rolling reduction, a strong Cube texture formed, and other textures were inhibited with the increase in annealing temperature. The strong Brass and S deformation texture was conducive to the formation of a strong Cube annealing texture. The density of the annealing twin boundary decreased with the increase in annealing temperature, and more annealing twin boundaries formed in the oxygen-free copper sheets with the increase in cold-rolling reduction.

2.
Heliyon ; 10(10): e30763, 2024 May 30.
Article in English | MEDLINE | ID: mdl-38770315

ABSTRACT

Accurate delineation of Gross Tumor Volume (GTV) is crucial for radiotherapy. Deep learning-driven GTV segmentation technologies excel in rapidly and accurately delineating GTV, providing a basis for radiologists in formulating radiation plans. The existing 2D and 3D segmentation models of GTV based on deep learning are limited by the loss of spatial features and anisotropy respectively, and are both affected by the variability of tumor characteristics, blurred boundaries, and background interference. All these factors seriously affect the segmentation performance. To address the above issues, a Layer-Volume Parallel Attention (LVPA)-UNet model based on 2D-3D architecture has been proposed in this study, in which three strategies are introduced. Firstly, 2D and 3D workflows are introduced in the LVPA-UNet. They work in parallel and can guide each other. Both the fine features of each slice of 2D MRI and the 3D anatomical structure and spatial features of the tumor can be extracted by them. Secondly, parallel multi-branch depth-wise strip convolutions adapt the model to tumors of varying shapes and sizes within slices and volumetric spaces, and achieve refined processing of blurred boundaries. Lastly, a Layer-Channel Attention mechanism is proposed to adaptively adjust the weights of slices and channels according to their different tumor information, and then to highlight slices and channels with tumor. The experiments by LVPA-UNet on 1010 nasopharyngeal carcinoma (NPC) MRI datasets from three centers show a DSC of 0.7907, precision of 0.7929, recall of 0.8025, and HD95 of 1.8702 mm, outperforming eight typical models. Compared to the baseline model, it improves DSC by 2.14 %, precision by 2.96 %, and recall by 1.01 %, while reducing HD95 by 0.5434 mm. Consequently, while ensuring the efficiency of segmentation through deep learning, LVPA-UNet is able to provide superior GTV delineation results for radiotherapy and offer technical support for precision medicine.

3.
Cell Death Differ ; 31(5): 683-696, 2024 May.
Article in English | MEDLINE | ID: mdl-38589496

ABSTRACT

Protein phosphatase 1 catalytic subunit gamma (PPP1CC) promotes DNA repair and tumor development and progression, however, its underlying mechanisms remain unclear. This study investigated the molecular mechanism of PPP1CC's involvement in DNA repair and the potential clinical implications. High expression of PPP1CC was significantly correlated with radioresistance and poor prognosis in human nasopharyngeal carcinoma (NPC) patients. The mechanistic study revealed that PPP1CC bound to Ku70/Ku80 heterodimers and activated DNA-PKcs by promoting DNA-PK holoenzyme formation, which enhanced nonhomologous end junction (NHEJ) -mediated DNA repair and led to radioresistance. Importantly, BRCA1-BRCA2-containing complex subunit 3 (BRCC3) interacted with PPP1CC to enhance its stability by removing the K48-linked polyubiquitin chain at Lys234 to prevent PPP1CC degradation. Therefore, BRCC3 helped the overexpressed PPP1CC to maintain its high protein level, thereby sustaining the elevation of DNA repair capacity and radioresistance. Our study identified the molecular mechanism by which PPP1CC promotes NHEJ-mediated DNA repair and radioresistance, suggesting that the BRCC3-PPP1CC-Ku70 axis is a potential therapeutic target to improve the efficacy of radiotherapy.


Subject(s)
DNA End-Joining Repair , Nasopharyngeal Carcinoma , Nasopharyngeal Neoplasms , Protein Phosphatase 1 , Radiation Tolerance , Humans , Nasopharyngeal Carcinoma/radiotherapy , Nasopharyngeal Carcinoma/pathology , Nasopharyngeal Carcinoma/genetics , Nasopharyngeal Carcinoma/metabolism , Protein Phosphatase 1/metabolism , Protein Phosphatase 1/genetics , Nasopharyngeal Neoplasms/radiotherapy , Nasopharyngeal Neoplasms/genetics , Nasopharyngeal Neoplasms/pathology , Nasopharyngeal Neoplasms/metabolism , Radiation Tolerance/genetics , Prognosis , Cell Line, Tumor , Ku Autoantigen/metabolism , Ku Autoantigen/genetics , Animals , DNA-Activated Protein Kinase/metabolism , DNA-Activated Protein Kinase/genetics , Mice, Nude , Female , Male , DNA Repair , Mice
4.
Cancer Med ; 12(24): 22091-22102, 2023 12.
Article in English | MEDLINE | ID: mdl-38073447

ABSTRACT

BACKGROUND AND PURPOSE: To identify anatomic prognostic factors and their potential roles in refining M1 classification for de novo metastatic nasopharyngeal carcinoma (M1-NPC). MATERIALS AND METHODS: All M1-NPC treated with chemotherapy and/or radiotherapy between 2010 and 2019 from two centers (training and validation cohort) were included. The prognostic value of metastatic disease extent and involved organs for overall survival (OS) were assessed by several multivariable analyses (MVA) models. A new M1 classification was proposed and validated in a separate cohort who received immuno-chemotherapy. RESULTS: A total of 197 M1-NPC in the training and 307 in the validation cohorts were included for M1 subdivision study with median follow-up of 46 and 57 months. MVA model with "≤2 organs/≤5 lesions" as the definition of oligometastasis had the highest C-index (0.623) versus others (0.606-0.621). Patients with oligometastasis had better OS versus polymetastasis (hazard ratio [HR] 0.47/0.63) while liver metastases carried worse OS (HR 1.57/1.45) in MVA in the training/validation cohorts, respectively. We proposed to divide M1-NPC into M1a (oligometastasis without liver metastases) and M1b (liver metastases or polymetastasis) with 3-year OS of 66.5%/31.7% and 64.9%/35.0% in the training/validation cohorts, respectively. M1a subset had a better median progress-free survival (not reach vs. 17 months, p < 0.001) in the immuno-chemotherapy cohort (n = 163). CONCLUSION: Oligometastasis (≤2 organs/≤5 lesions) and liver metastasis are prognostic for M1-NPC. Subdivision of M1-NPC into M1a (oligometastasis without liver metastasis) and M1b (liver metastasis or polymetastasis) depicts the prognosis well in M1-NPC patients who received immuno-chemotherapy.


Subject(s)
Liver Neoplasms , Nasopharyngeal Neoplasms , Humans , Nasopharyngeal Carcinoma/therapy , Nasopharyngeal Carcinoma/pathology , Prognosis , Neoplasm Staging , Nasopharyngeal Neoplasms/pathology , Liver Neoplasms/pathology , Retrospective Studies
5.
Int J Mol Sci ; 24(19)2023 Sep 28.
Article in English | MEDLINE | ID: mdl-37834154

ABSTRACT

Glioblastoma multiforme (GBM) is a highly aggressive malignancy and represents the most common brain tumor in adults. To better understand its biology for new and effective therapies, we examined the role of GDP-mannose pyrophosphorylase B (GMPPB), a key unit of the GDP-mannose pyrophosphorylase (GDP-MP) that catalyzes the formation of GDP-mannose. Impaired GMPPB function will reduce the amount of GDP-mannose available for O-mannosylation. Abnormal O-mannosylation of alpha dystroglycan (α-DG) has been reported to be involved in cancer metastasis and arenavirus entry. Here, we found that GMPPB is highly expressed in a panel of GBM cell lines and clinical samples and that expression of GMPPB is positively correlated with the WHO grade of gliomas. Additionally, expression of GMPPB was negatively correlated with the prognosis of GBM patients. We demonstrate that silencing GMPPB inhibits the proliferation, migration, and invasion of GBM cells both in vitro and in vivo and that overexpression of GMPPB exhibits the opposite effects. Consequently, targeting GMPPB in GBM cells results in impaired GBM tumor growth and invasion. Finally, we identify that the Hippo/MMP3 axis is essential for GMPPB-promoted GBM aggressiveness. These findings indicate that GMPPB represents a potential novel target for GBM treatment.


Subject(s)
Brain Neoplasms , Gene Silencing , Glioblastoma , Adult , Humans , Brain Neoplasms/genetics , Brain Neoplasms/metabolism , Cell Line, Tumor , Cell Proliferation , Gene Expression Regulation, Neoplastic , Glioblastoma/genetics , Glioblastoma/metabolism , Mannose , Matrix Metalloproteinase 3/metabolism
6.
Materials (Basel) ; 16(17)2023 Aug 29.
Article in English | MEDLINE | ID: mdl-37687597

ABSTRACT

To improve the mechanical properties and wear resistance of QAl9-4 aluminum bronze alloy parts of high-speed rail brake calipers, the solid aluminum bronze alloy was treated with a pulsed magnetic field in which the magnetic induction intensity was 3T at room temperature. After that, a tensile test and a friction and wear test were carried out on the alloy. The results indicate that the magnetic field promotes the movement of low-angle grain boundaries less than 2° and splices to form subcrystals or fine crystals, which reduces the mean grain size of the alloy. The disordered dislocation changed into a locally ordered dislocation line, the dislocation distribution became uniform, and the dislocation density increased, which simultaneously improved the alloy's tensile strength and elongation. The elongation increased by 10.2% compared with that without the magnetic field. The increase in strength can provide strong support for the wear-resistant hard phase, and the enhancement of plasticity can increase the alloy's ability to absorb frictional vibration. Therefore, it was hard for cracks to form and extend, and the specimen's average friction coefficient was reduced by 22.05%. The grinding crack width and depth decreased, the wear debris became more uniform and fine, and the alloy's wear resistance increased.

7.
iScience ; 26(6): 106932, 2023 Jun 16.
Article in English | MEDLINE | ID: mdl-37378335

ABSTRACT

Chemotherapy remains controversial for stage II nasopharyngeal carcinoma because of its considerable prognostic heterogeneity. We aimed to develop an MRI-based deep learning model for predicting distant metastasis and assessing chemotherapy efficacy in stage II nasopharyngeal carcinoma. This multicenter retrospective study enrolled 1072 patients from three Chinese centers for training (Center 1, n = 575) and external validation (Centers 2 and 3, n = 497). The deep learning model significantly predicted the risk of distant metastases for stage II nasopharyngeal carcinoma and was validated in the external validation cohort. In addition, the deep learning model outperformed the clinical and radiomics models in terms of predictive performance. Furthermore, the deep learning model facilitates the identification of high-risk patients who could benefit from chemotherapy, providing useful additional information for individualized treatment decisions.

8.
Psychol Res Behav Manag ; 16: 1471-1483, 2023.
Article in English | MEDLINE | ID: mdl-37131956

ABSTRACT

Purpose: Social support is a valid predictor of individuals' learning motivation, but the specific mechanism of the two is still unclear. In order to explore the specific mechanism between them, we examined the mediating role of belief in a just world (BJW) and the moderating role of gender in the relationship between social support and learning motivation. Methods: A total of 1320 students enrolled in three higher vocational colleges in eastern China were surveyed using the adolescent Social Support Scale, the college students' Motivation to Learn questionnaire, and the College Students' Belief in a Just World Scale. Descriptive statistics and correlation analyses were performed for all study variables, and finally, mediating and moderating effects were tested using the process developed by Hayes. Results: In China, the relationship between social support, BJW, and learning motivation of higher vocational college students shows a two-by-two positive correlation. Social support can directly influence learning motivation and function through the mediation of BJW. Gender moderates the first half of the pathway of the mediating effect of social support - BJW - learning motivation and the direct pathway of social support - learning motivation, ie, the positive effect of social support received on BJW and is more remarkable for boys when compared to girls. In addition, among the mediating effects played by BJW, the intrinsic justice dimension contributed the most, the ultimate justice dimension the second, and the intrinsic injustice dimension the least. Conclusion: This study adds to and extends the relevant research on the influence of social support on individuals. It confirms the moderating effect of gender and provides a new idea for enhancing the learning motivation of disadvantaged student groups. The results of the study can provide a reference for researchers and educators to further explore how to enhance the learning motivation of higher education students.

9.
Eur J Pharmacol ; 946: 175642, 2023 May 05.
Article in English | MEDLINE | ID: mdl-36871664

ABSTRACT

Cognitive impairment has become a major public health problem. Growing evidence suggests that high-fat diet (HFD) can cause cognitive dysfunction and increase the risk of dementia. However, effective treatment for cognitive impairment is not available. Ferulic acid (FA) is a single phenolic compound with anti-inflammatory and antioxidant properties. Nevertheless, its role in regulating learning and memory in HFD-fed mice and the underlying mechanism remains unclear. In this study, we aimed to identify the neuroprotective mechanisms of FA in HFD induced cognitive impairment. We found that FA improved the survival rate of HT22 cells treated with palmitic acid (PA), inhibited cell apoptosis, and reduced oxidative stress via the IRS1/PI3K/AKT/GSK3ß signaling pathway; Furthermore, FA treatment for 24 weeks improved the learning and memory of HFD-fed mice and decreased hyperlipidemia. Moreover, the expression of Nrf2 and Gpx4 proteins were decreased in HFD-fed mice. After FA treatment, the decline of these proteins was reversed. Our study showed that the neuroprotective effect of FA on cognitive impairment was related to the inhibition of oxidative stress and apoptosis and regulation of glucose and lipid metabolism. These findings suggested that FA can be developed as a potential agent for the treatment of HFD-induced cognitive impairment.


Subject(s)
Cognitive Dysfunction , Diet, High-Fat , Mice , Animals , Diet, High-Fat/adverse effects , Phosphatidylinositol 3-Kinases , Cognitive Dysfunction/drug therapy , Cognitive Dysfunction/etiology , Oxidative Stress , Apoptosis , Mice, Inbred C57BL
10.
Sensors (Basel) ; 23(6)2023 Mar 10.
Article in English | MEDLINE | ID: mdl-36991724

ABSTRACT

Singing-voice separation is a separation task that involves a singing voice and musical accompaniment. In this paper, we propose a novel, unsupervised methodology for extracting a singing voice from the background in a musical mixture. This method is a modification of robust principal component analysis (RPCA) that separates a singing voice by using weighting based on gammatone filterbank and vocal activity detection. Although RPCA is a helpful method for separating voices from the music mixture, it fails when one single value, such as drums, is much larger than others (e.g., the accompanying instruments). As a result, the proposed approach takes advantage of varying values between low-rank (background) and sparse matrices (singing voice). Additionally, we propose an expanded RPCA on the cochleagram by utilizing coalescent masking on the gammatone. Finally, we utilize vocal activity detection to enhance the separation outcomes by eliminating the lingering music signal. Evaluation results reveal that the proposed approach provides superior separation outcomes than RPCA on ccMixter and DSD100 datasets.


Subject(s)
Music , Singing , Voice Quality , Principal Component Analysis
11.
Radiother Oncol ; 178: 109436, 2023 01.
Article in English | MEDLINE | ID: mdl-36464180

ABSTRACT

BACKGROUND AND PURPOSE: This multicenter retrospective study aimed to investigated the prognostic value of unequivocal radiologic extranodal extension (rENE) and the efficacy of chemotherapy for stage T1-2 N1 nasopharyngeal carcinoma (NPC) in the IMRT era. MATERIALS AND METHODS: We included 1,082 patients treated in 2005-2017 from three centers. rENE was recorded as G1 (coalescent nodal mass comprising ≥ 2 inseparable nodes) or G2 (invading beyond perinodal fat to frankly infiltrate adjacent structures). Multivariable analysis (MVA) evaluated the prognostic value of rENE. The value of chemotherapy was assessed in rENE-positive (rENE + ) and rENE-negative (rENE - ) subset separately. RESULTS: Centers 1, 2, and 3 had 139/515 (27.0 %), 100/365 (27.4 %), and 43/202 (21.3 %) cN + patients with rENE, respectively. Compared to rENE-, rENE + patients had a worse distant metastasis-free survival (DMFS) and overall survival (OS) (all p < 0.001). MVA confirmed the prognostic of both G1-rENE and G2-rENE for distant metastasis [G1: hazard ratio (HR): 2.933, G2: HR: 6.942, all p < 0.001] and death (G1: HR: 1.587, p = 0.040; G2: HR: 6.162, p < 0.001). There was no significant difference for DMFS and OS between chemo-radiotherapy and radiotherapy alone in rENE + and rENE - groups (all p > 0.1). However, rENE + patients with a cumulative cisplatin/nedaplatin dose (CCND) of > 160 mg/m2 had an improved DMFS (p = 0.033) but no OS (p = 0.197). CONCLUSION: Unequivocal rENE is prognostic in patients with T1-2 N1 NPC. Addition of chemotherapy to radiotherapy did not affect DMFS and OS in rENE - patients. Chemotherapy with a CCND of > 160 mg/m2 improved DMFS in rENE + patients.


Subject(s)
Nasopharyngeal Neoplasms , Radiotherapy, Intensity-Modulated , Humans , Nasopharyngeal Carcinoma/pathology , Retrospective Studies , Extranodal Extension/pathology , Nasopharyngeal Neoplasms/drug therapy , Nasopharyngeal Neoplasms/pathology , Neoplasm Staging , Prognosis , Cisplatin/therapeutic use
12.
Front Immunol ; 14: 1309055, 2023.
Article in English | MEDLINE | ID: mdl-38283354

ABSTRACT

Treatment of non-small-cell lung cancer (NSCLC) has entered the immunotherapy era, marked by significant survival improvements due to the use of immune checkpoint inhibitors (ICIs). However, owing to factors, such as disease progression, long-term use, and side effects, some patients discontinue immunotherapy, resulting in limited subsequent treatment option and a negative impact on their survival and quality of life. We have collected relevant data which reveal that ICI rechallenge may be an effective clinical strategy. However, many factors affect the efficacy of rechallenge, including patient characteristics, initial treatment drugs, treatment duration, efficacy, toxicity, and side effects. Additionally, the side effects of rechallenge and mechanisms of reversing drug resistance play crucial roles. Identifying suitable candidates, optimizing treatment plans and duration, enhancing treatment efficacy, and minimizing toxicity and adverse effects in rechallenges are pressing clinical needs. Addressing these issues can provide guidance for the clinical use of immunotherapy rechallenges to better serve patients. This review focuses on the clinical considerations and strategies for immune therapy rechallenges in NSCLC.


Subject(s)
Carcinoma, Non-Small-Cell Lung , Lung Neoplasms , Humans , Immune Checkpoint Inhibitors/adverse effects , Quality of Life , Radioimmunotherapy
13.
Materials (Basel) ; 15(23)2022 Nov 23.
Article in English | MEDLINE | ID: mdl-36499825

ABSTRACT

The effect of a pulsed magnetic field on the microstructure of a QAl9-4 aluminium bronze alloy was studied in this work. It was found that the dislocation density, grain boundary angle, and microhardness of the alloy significantly changed after the magnetic field treatment with a peak magnetic induction intensity of 3T, pulse duration of about 100 us, pulse interval of 10 s, and pulse time of 360. EBSD was used to test the KAM maps of the alloy microzone. It was found that the alloy's dislocation density decreased by 10.88% after the pulsed magnetic field treatment; in particular, the dislocation in the deformed grains decreased significantly. The quantity of dislocation pile-up and the degree of distortion around the dislocation were reduced, which decreased the residual compressive stress on the alloy. Dislocation motion caused LAGB rotation, which reduced the misorientation of adjacent points inside the grain. The magnetic field induced the disappearance of deformation twins and weakened the strengthening effect of twins. The microhardness test results show that the alloy's microhardness decreased by 8.06% after pulsed magnetic field treatment. The possible reasons for the magnetic field effect on dislocation were briefly discussed. The pulsed magnetic field might have caused the transition to the electronic energy state at the site of dislocation pinning, which led to free movement of the vacancy or impurity atom. The dislocation was easier to depin under the action of internal stress in the alloy, changing the dislocation distribution and alloy microstructure.

14.
EBioMedicine ; 81: 104100, 2022 Jul.
Article in English | MEDLINE | ID: mdl-35689852

ABSTRACT

BACKGROUND: Distant metastasis remains the leading cause of treatment failure in patients with nasopharyngeal carcinoma (NPC), making it critical to identify efficient therapeutic targets for metastatic NPC. Previous studies have demonstrated that deoxynucleotidyltransferase terminal-interacting protein 1 (DNTTIP1) is associated with the development of various types of cancer. However, its role and mechanism in NPC have not been explored. METHODS: RNA-seq profiling was performed for three pairs of NPC and normal nasopharynx tissues. DNTTIP1 expression in NPC specimens was detected by immunohistochemistry. In vitro and in vivo assays were used to investigate the function of DNTTIP1. The molecular mechanism was determined using RT-qPCR, western blotting, RNA-seq, luciferase reporter assays, ChIP assays, and co-IP assays. FINDINGS: DNTTIP1 was found to be significantly upregulated in NPC tissues. Furthermore, DNTTIP1 promoted NPC growth and metastasis in vitro and in vivo. Upregulation of DNTTIP1 in NPC indicated poor clinical outcomes. Mechanistically, DNTTIP1 suppressed DUSP2 gene expression via recruiting HDAC1 to its promoter and maintaining a deacetylated state of histone H3K27. The downregulation of DUSP2 resulted in aberrant activation of the ERK signaling and elevated MMP2 levels, promoting NPC metastasis. Chidamide, an HDAC inhibitor, was shown to suppress NPC metastasis by regulating the DNTTIP1/HDAC1-DUSP2 axis. INTERPRETATION: Our findings demonstrate that DNTTIP1 not only regulates NPC metastasis but also independently predicts NPC prognosis. Furthermore, targeting DNTTIP1/HDAC1 by Chidamide may benefit NPC patients with metastasis. FUNDING: This work was supported by the National Natural Science Foundation of China (No. 81872464, 82073243).


Subject(s)
Nasopharyngeal Carcinoma , Nasopharyngeal Neoplasms , Cell Line, Tumor , Cell Movement/physiology , Cell Proliferation , DNA-Binding Proteins/genetics , DNA-Binding Proteins/metabolism , Dual Specificity Phosphatase 2/genetics , Dual Specificity Phosphatase 2/metabolism , Histone Deacetylase 1/genetics , Histone Deacetylase 1/metabolism , Humans , Nasopharyngeal Carcinoma/genetics , Nasopharyngeal Carcinoma/metabolism , Nasopharyngeal Carcinoma/pathology , Nasopharyngeal Neoplasms/genetics , Nasopharyngeal Neoplasms/metabolism , Nasopharyngeal Neoplasms/pathology , Neoplasm Invasiveness , Neoplasm Metastasis , Signal Transduction , Transcription Factors/genetics , Transcription Factors/metabolism
15.
Oral Oncol ; 99: 104438, 2019 12.
Article in English | MEDLINE | ID: mdl-31654937

ABSTRACT

PURPOSE: We evaluated the prognostic value of various grades of radiologic extranodal extension (rENE) and their potential roles in N-classification refinement for nasopharyngeal carcinoma (NPC). METHODS AND MATERIALS: All NPC patients treated with IMRT in our institution between 2005 and 2011 were included. Pre-treatment MR of cN+ cases were reviewed and rENE was recorded asG0: lymph nodes (LNs) without rENE; G1: tumor infiltrating beyond individual nodal capsule(s) into the surrounding fat plane; G2: coalescent nodal mass with unequivocal evidence of rENE; G3: tumor infiltrating beyond nodal capsule into adjacent structures. Multivariable analysis (MVA) assessed prognostic value of rENE for distant metastasis (DM) and death adjusted for age, gender, LDH, T-classification, N-classification, and chemotherapy cycles. RESULTS: A total of 1390 of 1616 (86%) NPC were cN+, and rENE was detected in 826/1390 (59%) patients: 256 (18.4%) G1-rENE, 487 (35%) G2-rENE, and 83 (6%) G3-rENE. MVA confirmed that G2-/G3-rENE had increased risk of DM (HR: 2.05/3.18, both p < 0.001) and death (HR: 1.62/2.39, p = 0.002/p < 0.001), while G1-rENE was non-prognostic (DM: p = 0.172; death: p = 0.320). We propose a refined N: New-N1: N1/N2 without G2-/G3-rENE; New-N2: N1_G2-rENE; New-N3: N2_G2-rENE, N1/N2_G3-rENE, or N3. The New-N classification had a lower AIC and higher c-index for DM (AIC: 3809.6 vs 3830.9; c-index: 0.700 vs. 0.677) and death (AIC: 3693.8 vs. 3705.9; c-index: 0.735 vs. 0.725) versus TNM-8 N. CONCLUSIONS: G2- and G3-rENE are independently prognostic for DM and death in NPC. Compared to the TNM8 N-classification, a refined N-classification incorporating G2- and G3-rENE improves prognostication of DM and mortality risk.


Subject(s)
Nasopharyngeal Carcinoma/classification , Female , Humans , Male , Middle Aged , Nasopharyngeal Carcinoma/radiotherapy , Prognosis
16.
Head Neck ; 41(9): 3317-3327, 2019 09.
Article in English | MEDLINE | ID: mdl-31206864

ABSTRACT

BACKGROUND: To investigate the prognostic value of radiologic extra-nodal extension (rENE) in stage II nasopharyngeal carcinoma (NPC). METHODS: Stage II NPC patients with N1 category (n = 365) were enrolled and divided into three groups according to the situation of rENE: without rENE, suspected rENE, and confirmed rENE (grades: A, infiltration into surrounding fat; B, matted nodes; C, infiltration into adjacent structures). RESULTS: Only high-grade rENE (including matted nodes and infiltration into adjacent structures) could significantly influence the survival outcomes, patients with high-grade rENE had significantly poorer survival than those without, with the 7-year distant metastasis-free survival and overall survival demonstrated to be 78.5% vs 93.0% (P < .001) and 81.9% vs 89.9% (P = .05), respectively. High-grade rENE, as defined in our study, is a stable criterion, with high intra-rater and inter-rater consistency. CONCLUSION: High-grade rENE was an evaluable predictor that could help with the selection of stage II patients with high risk of distant metastasis.


Subject(s)
Nasopharyngeal Carcinoma/diagnostic imaging , Nasopharyngeal Carcinoma/secondary , Nasopharyngeal Neoplasms/diagnostic imaging , Nasopharyngeal Neoplasms/pathology , Adult , Aged , Aged, 80 and over , Female , Humans , Magnetic Resonance Imaging , Male , Middle Aged , Nasopharyngeal Carcinoma/mortality , Nasopharyngeal Neoplasms/mortality , Neoplasm Grading , Neoplasm Staging , Observer Variation , Predictive Value of Tests , Reproducibility of Results , Retrospective Studies , Survival Rate , Young Adult
17.
Biomol NMR Assign ; 9(2): 309-11, 2015 Oct.
Article in English | MEDLINE | ID: mdl-25673506

ABSTRACT

A cDNA encoding a cysteine protease inhibitor, cystatin was cloned from sesame (Sesamum indicum L.) seed. This clone was constructed into an expression vector and expressed in E. coli and purified to homogeneous. The recombinant sesame cystatin (SiCYS) showed effectively inhibitory activity toward C1 cysteine proteases. In order to unravel its inhibitory action from structural point of view, multidimensional heteronuclear NMR techniques were used to characterize the structure of SiCYS. The full (1)H, (15)N, and (13)C resonances of SiCYS were assigned. The secondary structure of SiCYS was identified by using the assigned chemical shifts of (1)H(α), (13)C(α), (13)C(ß), and (13)CO through the consensus chemical shift index (CSI). The results of CSI analysis of SiCYS suggest eight ß-strands (residues 33-46, 51-61, 63-75, 80-87, 150-155, 157-169, 172-183, and 192-195) and two α-helices (residues 16-30, and 120-135).


Subject(s)
Cystatins/chemistry , Nuclear Magnetic Resonance, Biomolecular , Plant Proteins/chemistry , Sesamum/metabolism , Protein Structure, Secondary , Proton Magnetic Resonance Spectroscopy
18.
Int Orthop ; 35(12): 1875-82, 2011 Dec.
Article in English | MEDLINE | ID: mdl-21404022

ABSTRACT

PURPOSE: The purpose of this study was to determine the effect of exposure to pulsed electromagnetic fields (PEMF) on modulation of the cartilage apoptosis signalling pathway in ovariectomised rats by monitoring the expression of mRNA of X-linked inhibitor of apoptosis protein (XIAP) and Bax. METHODS: Forty-eight female Sprague-Dawley rats (250 ± 50 g) were randomly assigned to one of four groups: ovariectomy with PEMF treatment (PEMF group), ovariectomy with oestradiol (E2) treatment (oestrogen group), ovariectomy control (OVX group) and sham group. The ovariectomy model was prepared by surgical resection of the ovaries. After a three-month intermission, animals in the PEMF and oestrogen groups received treatment for 30 days; then serum 17ß-oestradiol levels, chondrocyte morphology, and XIAP and Bax mRNA expression in knee joint cartilage were analysed. RESULTS: The results showed different chondrocyte formation in each group. Serum E2 content in the PEMF and oestrogen groups was significantly higher than in the OVX group (p < 0.05). The expression of XIAP mRNA in the PEMF and oestrogen groups was significantly up-regulated compared to the OVX group, while that of Bax mRNA was significantly down-regulated (p < 0.05). The correlation between E2 level and expression of Bax mRNA was positive (0.506) and statistically significant (p < 0.001). CONCLUSION: These data demonstrate that PEMF can up-regulate XIAP mRNA expression and down-regulate Bax mRNA expression in ovariectomised rats. Changes in XIAP and Bax mRNA expression may be the mechanism by which PEMF therapy affects postmenopausal osteoarthritis.


Subject(s)
Apoptosis/radiation effects , Cartilage, Articular/radiation effects , Electromagnetic Fields/adverse effects , Ovariectomy , Animals , Cartilage, Articular/metabolism , Cartilage, Articular/pathology , Disease Models, Animal , Estrogens/pharmacology , Female , Gene Expression Regulation/radiation effects , RNA, Messenger/metabolism , Rats , Rats, Sprague-Dawley , Signal Transduction/radiation effects , Stifle/metabolism , Stifle/radiation effects , Up-Regulation/radiation effects , X-Linked Inhibitor of Apoptosis Protein/genetics , X-Linked Inhibitor of Apoptosis Protein/metabolism , bcl-2-Associated X Protein/genetics , bcl-2-Associated X Protein/metabolism
19.
Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi ; 25(12): 1455-8, 2011 Dec.
Article in Chinese | MEDLINE | ID: mdl-22242344

ABSTRACT

OBJECTIVE: To investigate the changes of lumbar bone histomorphometry after exposure to low frequency pulsed electromagnetic fields (PEMFs), and to further understand the effect of PEMFs on osteoporosis (OP) in ovariectomized OP rats. METHODS: Sixty-six 3-month-old Sprague Dawley rats were randomly divided into 4 groups: group A (n = 12), group B (n = 12), group C (n = 12), and group D (n = 30). In group A, the ovaries were not resected as sham-ovariectomy; in groups B, C, and D, the ovaries were resected. At 12 weeks after ovariectomy, the rats were exposed to PEMFs at 8 Hz, 3.8 mT, and 40 minutes/day for 30 days in group B; the rats were administered with premarin [0.065 mg/(kg x d) by gavage for 30 days] in group C; in group D, the rats were housed as ovariectomy control. The hair and activity of rats were observed; the levels of serum estradiol were determined. At 30 days after intervention, all rats were sacrificed to harvest the L4 vertebrae for bone histomorphometry. RESULTS: General observation showed hair loss and decreased activity in group D, and no abnormal appearances in groups A, B, and C. The level of serum estradiol in group A was significantly higher than that in group D [(54.93 +/- 23.52) pg/mL vs. (31.99 +/- 23.45) pg/mL] (t = 2.345, P = 0.029). Histological observation showed thinness of sclerotin, bigger medullary cavity, and sparse and thinner bone trabecula in group D; uniform bone trabecula with no breakage in groups A, B, and C at 30 days after intervention. The ratio of trabecular bone area in group B was significantly higher than that in group D (P < 0.05); it was higher than that in groups A and C, showing no significant difference (P > 0.05). The trabecular thickness in group B was significantly higher than that in group D (P < 0.05), but it was lower than that in groups A and C, showing no significant difference (P > 0.05). The trabecular number in group B was significantly lower than that in group D (P < 0.05), but it was higher than that in groups A and C, showing no significant difference (P > 0.05). The trabecular separation in group B was higher than that in group D and lower than that in groups A and C, showing no significant difference (P > 0.05). CONCLUSION: PEMFs at 8 Hz and 3.8 mT can significantly improve the character of bone microstructure in ovariectomized OP rats, increase the ratio of bone trabecular area and trabecular thickness, and decrease the trabecular number.


Subject(s)
Bone Density , Electromagnetic Fields , Lumbar Vertebrae/pathology , Osteoporosis/pathology , Animals , Disease Models, Animal , Female , Osteoporosis/etiology , Ovariectomy , Rats , Rats, Sprague-Dawley
20.
Connect Tissue Res ; 51(1): 1-7, 2010.
Article in English | MEDLINE | ID: mdl-20067410

ABSTRACT

This study was designed to determine the effects of pulsed electromagnetic fields (PEMF) on the mRNA expression of the receptor activator of NF-kappa-B (RANK) and carbonic anhydrase II (CA II) in ovariectomized rat osteoclast-like cells. Marrow cells were harvested from femora and tibiae of rats, from which the ovaries had been totally excised, and cultured in 6-well chamber slides. After 1 day of incubation, the marrow cells were exposed to PEMF for 3 days with 3.8 mT, 8 Hz, and 40 min per day. Osteoclast-like cells were confirmed by both tartrate resistant acid phosphatase (TRAP) stain and bone resorption assay. The expression of RANK and CA II mRNA was determined with real-time fluorescent-nested quantitative polymerase chain reaction. Compared with the sham group, the level of serum estradiol in the ovariectomized group was significantly decreased ( p < 0.05). The numbers of multinucleated, TRAP-positive osteoclast-like cells and resorption pits formed were observed. In invitro study, the expression of RANK and CA II were measured in sham, ovariectomized without PEMF, and ovariectomized with PEMF treatment. Compared with the ovariectomized (PEMF) experimental group and sham group, CA II mRNA expression was significantly increased in the ovariectomized control group ( p < 0.05, 0.01, respectively). Compared with the sham group, RANK mRNA expression was significantly increased in the ovariectomized control group ( p < 0.05). These data suggest that PEMF could regulate the expression of RANK and CA II mRNA in the marrow culture system.


Subject(s)
Bone and Bones/radiation effects , Carbonic Anhydrase II/genetics , Electromagnetic Fields , Osteoclasts/radiation effects , RNA, Messenger/radiation effects , Receptor Activator of Nuclear Factor-kappa B/genetics , Acid Phosphatase , Animals , Biomarkers/analysis , Biomarkers/metabolism , Bone Marrow Cells/cytology , Bone Marrow Cells/metabolism , Bone Marrow Cells/radiation effects , Bone Resorption/physiopathology , Bone and Bones/cytology , Bone and Bones/metabolism , Cells, Cultured , Down-Regulation/physiology , Estrogens/blood , Estrogens/deficiency , Female , Gene Expression Regulation/genetics , Gene Expression Regulation/radiation effects , Humans , Osteoclasts/cytology , Osteoclasts/metabolism , Osteoporosis, Postmenopausal/genetics , Osteoporosis, Postmenopausal/metabolism , Osteoporosis, Postmenopausal/therapy , Ovariectomy , RNA, Messenger/metabolism , Rats , Rats, Sprague-Dawley , Reverse Transcriptase Polymerase Chain Reaction , Staining and Labeling
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