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The objective of this study is to explore the antiproliferative activity of the traditional Chinese medicine monomer vitexin on colon cancer HCT-116 cells and its underlying mechanism. The in vitro antiproliferative activity of vitexin on colon cancer HCT-116 cells was evaluated using the CCK-8 assay. Potential drug targets for colon cancer were identified through GEO chip data mining, and molecular docking using Schrödinger software was conducted. Molecular dynamics simulations were employed to deeply analyze the interaction between candidate compounds and target proteins. Flow cytometry was employed to examine the cell cycle. The impact of vitexin on the expression of CDK1/cyclinB proteins in HCT-116 cells was assessed through Western blot analysis, immunofluorescence, and CDK inhibition assay. Vitexin exhibited inhibitory effects on colon cancer HCT-116 cells, with a half inhibitory concentration (IC50) value of 203.27 ± 9.85 µmol/L. The analysis of differential gene expression in GEO and TCGA datasets, along with the GENECARD dataset of related disease genes, identified 91 disease targets, including "CDK1." Vitexin induced cell cycle arrest in the G2/M phase of HCT-116 cells. Molecular docking revealed a strong interaction between Vitexin and CDK1 (Docking score - 9.497), with molecular dynamics simulations confirming the stability of the Vitexin-CDK1 complex and comparable inhibitory effects to Flavopiridol. Vitexin can inhibit the expression of CDK1/cyclin B proteins in HCT-116 cells, with an IC50 of 58.06 ± 3.07 µmol/L. Vitexin may inhibit colon cancer HCT-116 cell proliferation by suppressing CDK1/cyclin B expression, leading to cell cycle arrest in the G2/M phase.
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OBJECTIVES: To develop an innovative magnetic resonance imaging (MRI)-based PUMCH (Peking Union Medical College Hospital) classification system aimed at standardising the diagnosis of congenital cervical malformations (CCMs) by identifying their distinctive MRI features. METHODS: Seventy-nine consecutive patients with CCM underwent pre-treatment pelvic MRI; three experienced gynaecological radiologists retrospectively analysed these images. Qualitative assessments included Rock et al's classification; PUMCH classification; haematometra; cervical signal features; ovarian endometriosis; haematosalpinx; and uterine, vaginal, urinary, and musculoskeletal malformations. Quantitative assessments involved the uterine volume, sagittal cervical length, and maximum ovarian cross-sectional area. The surgical treatment types were also recorded. Statistical methods were used to incorporate differences in clinical features and surgical methods into our classification. RESULTS: Morphologically, CCMs were categorised into three types: type I (53%) was characterised by the presence of a cervix with visible cervical canals; type II (23%) featured an existing cervix with concealed cervical canals; and type III (24%) indicated cervical aplasia, which involves a blind end in the lower part of the uterine corpus. Haematometra was significantly more prevalent in patients with type I CCM than in those with type II (p < 0.001). There were three cervical signal patterns: no signal (27%), no evident layer differentiation (21%), and multi-layer differentiation with haematocele (52%). Most patients (94%) had complete vaginal atresia. Type I CCM patients had a higher likelihood of regaining normal uterovaginal anatomy compared to types II and III. CONCLUSIONS: Our proposed PUMCH classification system has a high potential for enhancing the efficiency of clinical diagnosis among patients with CCM. CRITICAL RELEVANCE STATEMENT: The proposed new PUMCH classification promised to elevate the conventional diagnostic trajectory for congenital cervical malformations, offering a valuable framework to refine the selection and planning of surgical interventions, thereby enhancing overall clinical efficacy. KEY POINTS: Effective classification of congenital cervical malformations is desirable to optimise the diagnostic process. We presented a PUMCH classification of congenital cervical malformations using pelvic MRI. The new classification significantly aids clinical triage for congenital cervical malformations.
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Some citrus orchards in China often experience nitrogen (N) deficiency. For the first time, targeted metabolomics was used to examine N-deficient effects on hormones in sweet orange (Citrus sinensis (L.) Osbeck cv. Xuegan) leaves and roots. The purpose was to validate the hypothesis that hormones play a role in N deficiency tolerance by regulating root/shoot dry weight ratio (R/S), root system architecture (RSA), and leaf and root senescence. N deficiency-induced decreases in gibberellins and indole-3-acetic acid (IAA) levels and increases in cis(+)-12-oxophytodienoic acid (OPDA) levels, ethylene production, and salicylic acid (SA) biosynthesis might contribute to reduced growth and accelerated senescence in leaves. The increased ethylene formation in N-deficient leaves might be caused by increased 1-aminocyclopropanecarboxylic acid and OPDA and decreased abscisic acid (ABA). N deficiency increased R/S, altered RSA, and delayed root senescence by lowering cytokinins, jasmonic acid, OPDA, and ABA levels and ethylene and SA biosynthesis, increasing 5-deoxystrigol levels, and maintaining IAA and gibberellin homeostasis. The unchanged IAA concentration in N-deficient roots involved increased leaf-to-root IAA transport. The different responses of leaf and root hormones to N deficiency might be involved in the regulation of R/S, RSA, and leaf and root senescence, thus improving N use efficiency, N remobilization efficiency, and the ability to acquire N, and hence conferring N deficiency tolerance.
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OBJECTIVES: To evaluate the diagnostic performance of quantitative magnetic resonance (MR) imaging biomarkers in distinguishing between inflammatory pancreatic masses (IPM) and pancreatic cancer (PC). METHODS: A literature search was conducted using PubMed, Embase, the Cochrane Library, and Web of Science through August 2023. Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2) was used to evaluate the risk of bias and applicability of the studies. The pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, and diagnostic odds ratio were calculated using the DerSimonian-Laird method. Univariate meta-regression analysis was used to identify the potential factors of heterogeneity. RESULTS: Twenty-four studies were included in this meta-analysis. The two main types of IPM, mass-forming pancreatitis (MFP) and autoimmune pancreatitis (AIP), differ in their apparent diffusion coefficient (ADC) values. Compared with PC, the ADC value was higher in MFP but lower in AIP. The pooled sensitivity/specificity of ADC were 0.80/0.85 for distinguishing MFP from PC and 0.82/0.84 for distinguishing AIP from PC. The pooled sensitivity/specificity for the maximal diameter of the upstream main pancreatic duct (dMPD) was 0.86/0.74, with a cutoff of dMPD ≤ 4 mm, and 0.97/0.52, with a cutoff of dMPD ≤ 5 mm. The pooled sensitivity/specificity for perfusion fraction (f) was 0.82/0.68, and 0.82/0.77 for mass stiffness values. CONCLUSIONS: Quantitative MR imaging biomarkers are useful in distinguishing between IPM and PC. ADC values differ between MFP and AIP, and they should be separated for consideration in future studies. CLINICAL RELEVANCE STATEMENT: Quantitative MR parameters could serve as non-invasive imaging biomarkers for differentiating malignant pancreatic neoplasms from inflammatory masses of the pancreas, and hence help to avoid unnecessary surgery. KEY POINTS: ⢠Several quantitative MR imaging biomarkers performed well in differential diagnosis between inflammatory pancreatic mass and pancreatic cancer. ⢠The ADC value could discern pancreatic cancer from mass-forming pancreatitis or autoimmune pancreatitis, if the two inflammatory mass types are not combined. ⢠The diameter of main pancreatic duct had the highest specificity for differentiating autoimmune pancreatitis from pancreatic cancer.
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As the detection rate of pancreatic cystic lesions(PCL)increases,artificial intelligence(AI)has made breakthroughs in the imaging workflow of PCL,including image post-processing,lesion detection,segmentation,diagnosis and differential diagnosis.AI-based image post-processing can optimize the quality of medical images and AI-assisted models for lesion detection,segmentation,diagnosis and differential diagnosis significantly enhance the work efficiency of radiologists.This article reviews the application progress of AI in PCL imaging and provides prospects for future research directions.
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Inteligência Artificial , Cisto Pancreático , Humanos , Cisto Pancreático/diagnóstico por imagem , Diagnóstico Diferencial , Processamento de Imagem Assistida por Computador/métodos , Neoplasias Pancreáticas/diagnóstico por imagemRESUMO
PURPOSE: We aimed to systematically assess the methodological quality and clinical potential application of published magnetic resonance imaging (MRI)-based radiomics studies about endometrial cancer (EC). METHODS: Studies of EC radiomics analyses published between 1 January 2000 and 19 March 2023 were extracted, and their methodological quality was evaluated using the radiomics quality score (RQS) and Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2). Pairwise correlation analyses and separate meta-analyses of studies exploring differential diagnoses and risk prediction were also performed. RESULTS: Forty-five studies involving 3 aims were included. The mean RQS was 13.77 (range: 9-22.5); publication bias was observed in the areas of 'index test' and 'flow and timing'. A high RQS was significantly associated with therapy selection-aimed studies, low QUADAS-2 risk, recent publication year, and high-performance metrics. Raw data from 6 differential diagnosis and 34 risk prediction models were subjected to meta-analysis, revealing diagnostic odds ratios of 23.81 (95% confidence interval [CI] 8.48-66.83) and 18.23 (95% CI 13.68-24.29), respectively. CONCLUSION: The methodological quality of radiomics studies involving patients with EC is unsatisfactory. However, MRI-based radiomics analyses showed promising utility in terms of differential diagnosis and risk prediction.
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Neoplasias do Endométrio , Imageamento por Ressonância Magnética , Radiômica , Feminino , Humanos , Diagnóstico Diferencial , Neoplasias do Endométrio/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodosRESUMO
Little information is available on how boron (B) supplementation affects plant cell wall (CW) remodeling under copper (Cu) excess. 'Xuegan' (Citrus sinensis) seedlings were submitted to 0.5 or 350 µM Cu × 2.5 or 25 µM B for 24 weeks. Thereafter, we determined the concentrations of CW materials (CWMs) and CW components (CWCs), the degree of pectin methylation (DPM), and the pectin methylesterase (PME) activities and PME gene expression levels in leaves and roots, as well as the Cu concentrations in leaves and roots and their CWMs (CWCs). Additionally, we analyzed the Fourier transform infrared (FTIR) and X-ray diffraction (XRD) spectra of leaf and root CWMs. Our findings suggested that adding B reduced the impairment of Cu excess to CWs by reducing the Cu concentrations in leaves and roots and their CWMs and maintaining the stability of CWs, thereby improving leaf and root growth. Cu excess increased the Cu fractions in leaf and root pectin by decreasing DPM due to increased PME activities, thereby contributing to citrus Cu tolerance. FTIR and XRD indicated that the functional groups of the CW pectin, hemicellulose, cellulose, and lignin could bind and immobilize Cu, thereby reducing Cu cytotoxicity in leaves and roots.
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Citrus sinensis , Boro/toxicidade , Cobre/toxicidade , Plântula , Parede Celular , Folhas de Planta , Pectinas/farmacologiaRESUMO
To investigate the boiling characteristics of flow outside the R410A tube under swaying conditions, this article conducts numerical simulation and experimental research on the flow boiling heat transfer of R410A outside a horizontal tube. The results show that when the swing frequency increased from 0.2 to 2 Hz, the sway amplitude is 0.03 m, the heat flux on the inner wall of the runner remains unchanged, and the mass flow rate increases from 85 to 170 kg/(m2·s), which makes the heat transfer coefficient of the working fluid in the annular area increases significantly. Keeping the inlet mass flow rate unchanged, the heat flux on the inner wall of the flow channel increases from 25 to 35 kW/m2, the heat transfer coefficient of the working fluid in the annular area has also improved, but under high heat flux conditions, the working fluid is evaporated and dried, its heat transfer coefficient increases less than in low heat flux conditions. When the sway amplitude increases from 0.02 to 0.07 m, the sway frequency is 0.2 Hz and 2 Hz respectively, and the heat transfer coefficient of the working fluid shows a downward trend as a whole. The studies provide a reference for heat exchanger design suitable for offshore swaying conditions.
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AIMS: The serine/arginine-rich splicing factor (SRSF) protein family members are essential mediators of the alternative splicing (AS) regulatory network, which is tightly implicated in cancer progression. However, the expression, clinical correlation, immune infiltration, and prognostic value of SRSFs in gliomas remain unclear. MATERIALS AND METHODS: Glioma samples were extracted from The Cancer Genome Atlas (TCGA) and Chinese Glioma Genome Atlas (CGGA) datasets. Several databases, such as HPA, DAVID, UALCAN were used to comprehensively explore the roles of SRSFs. In addition, experimental validation of SRSF10 was also conducted. KEY FINDINGS: Here, we found the expression alterations of the SRSF family in glioma samples using data from the TCGA and CGGA_325 datasets. Among the 12 genes, most were found to be closely associated with glioma clinical features, which linked to poor prognosis in glioma patients. Interestingly, survival analysis identified only SRSF10 as a potential independent risk prognostic biomarker for glioma patients. Immune analysis indicated that glioma patients with high SRSF10 expression may respond well to immunotherapies targeting immune checkpoint (ICP) genes. Finally, knocking down SRSF10 reduced glioma cell viability, induced G1 cell cycle arrest, and induced the exclusion of bcl-2-associated transcription factor 1 (BCLAF1) exon 5a. SIGNIFICANCE: Overall, this study uncovers the oncogenic roles of most SRSF family members in glioma, with the exception of SRSF5, while highlighting SRSF10 as a potential novel independent prognostic biomarker for glioma.
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Glioma , Fatores de Processamento de Serina-Arginina , Humanos , Arginina , Biomarcadores , Proteínas de Ciclo Celular , Éxons , Glioma/diagnóstico , Glioma/genética , Prognóstico , Proteínas Repressoras , Fatores de Processamento de Serina-Arginina/genéticaRESUMO
RATIONALE AND OBJECTIVES: Magnetic resonance imaging (MRI) has good diagnostic performance and causes no radiation damage, making it an ideal tool for the autoimmune pancreatitis (AIP) surveillance. However, its time cost is high. This study aimed to evaluate (1) whether a simplified protocol (SP) of MRI for AIP surveillance provides information equivalent to the comprehensive protocol (CP) and (2) the time cost reductions associated with using an SP. MATERIALS AND METHODS: This retrospective single-institutional study included 40 patients with AIP with at least two contrast-enhanced MRI/magnetic resonance cholangiopancreatography studies. Two radiologists evaluated two imaging sets (CP/SP) per patient, independently. Intra- and inter-observer agreement in the evaluation of the pancreas and extrapancreatic organs involvement using the SP/CP in addition to the time cost differences between the SP and CP were assessed. Intra- and inter-rater reliability were assessed using Cohen's kappa test, intraclass correlations, or the weighted kappa test. The differences in time costs between the CP and SP were compared using the Mann-Whitney U test or Wilcoxon signed-rank test. RESULTS: The SP had strong intra- and inter-observer agreement with the CP in evaluating MRI parameters (κ ï¼ 0.60, moderate to excellent) and disease activity status (κ ï¼ 0.80, all excellent). The overall image acquisition time cost for the SP was 49.2% of the CP. For the two radiologists, the image interpretation time cost of the SP was reduced by approximately 35% and 27% compared to the CP. CONCLUSION: For AIP surveillance, SP MRI provides information consistent with the CP and is less time-consuming.
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BACKGROUND: Mindfulness-based stress reduction (MBSR) has been suggested as an effective mind-body approach for relieving stress in patients with chronic diseases. As of yet, there is no conclusive research on MBSR's role in reducing affective disorders among cancer patients. A systematic review and meta-analysis was conducted to determine whether MBSR has an impact on loneliness, anxiety, and depression in cancer patients. METHODS: Systematic searches were conducted in PubMed, Embase, and the Cochrane Library from the start of these databases to January 2nd, 2022 to identify relevant randomized controlled trials. Two authors independently conducted the literature search, collected the data, and performed the statistical analysis. In order to account for potential between-study heterogeneity, a random-effect model was used in the meta-analysis. RESULTS: The meta-analysis included 16 studies with 2072 cancer patients. Among the 16 studies, 13 included patients with breast cancer, and the follow-up duration ranged from 6 to 53 weeks. Compared to controls receiving standard cancer care, interventions of MBSR with sessions for 6 to 8 weeks significantly improved loneliness (standard mean difference [SMD]: -0.35, 95% confidence interval [CI]: -0.59 to -0.12, Pâ =â .003, I2â =â 46%), anxiety (SMD: -0.51, 95% CI: -0.73 to -0.30, Pâ <â .001, I2â =â 77%), and depression (SMD: -0.61, 95% CI: -1.02 to -0.20, Pâ =â .004, I2â =â 94%) in patients with cancer. CONCLUSION: According to recent research, MBSR may be beneficial to patients diagnosed with cancer who are feeling lonely, anxious, or depressed.
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Neoplasias da Mama , Atenção Plena , Humanos , Feminino , Solidão , Depressão/etiologia , Depressão/terapia , Ansiedade/etiologia , Ansiedade/terapiaRESUMO
OBJECTIVES: We aimed to present the state of the art of CT- and MRI-based radiomics in the context of ovarian cancer (OC), with a focus on the methodological quality of these studies and the clinical utility of these proposed radiomics models. METHODS: Original articles investigating radiomics in OC published in PubMed, Embase, Web of Science, and the Cochrane Library between January 1, 2002, and January 6, 2023, were extracted. The methodological quality was evaluated using the radiomics quality score (RQS) and Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2). Pairwise correlation analyses were performed to compare the methodological quality, baseline information, and performance metrics. Additional meta-analyses of studies exploring differential diagnoses and prognostic prediction in patients with OC were performed separately. RESULTS: Fifty-seven studies encompassing 11,693 patients were included. The mean RQS was 30.7% (range - 4 to 22); less than 25% of studies had a high risk of bias and applicability concerns in each domain of QUADAS-2. A high RQS was significantly associated with a low QUADAS-2 risk and recent publication year. Significantly higher performance metrics were observed in studies examining differential diagnosis; 16 such studies as well as 13 exploring prognostic prediction were included in a separate meta-analysis, which revealed diagnostic odds ratios of 25.76 (95% confidence interval (CI) 13.50-49.13) and 12.55 (95% CI 8.38-18.77), respectively. CONCLUSION: Current evidence suggests that the methodological quality of OC-related radiomics studies is unsatisfactory. Radiomics analysis based on CT and MRI showed promising results in terms of differential diagnosis and prognostic prediction. CRITICAL RELEVANCE STATEMENT: Radiomics analysis has potential clinical utility; however, shortcomings persist in existing studies in terms of reproducibility. We suggest that future radiomics studies should be more standardized to better bridge the gap between concepts and clinical applications.
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OBJECTIVE: To develop and validate a model that can preoperatively identify the ovarian clear cell carcinoma (OCCC) subtype in epithelial ovarian cancer (EOC) using CT imaging radiomics and clinical data. MATERIAL AND METHODS: We retrospectively analyzed data from 282 patients with EOC (training set = 225, testing set = 57) who underwent pre-surgery CT examinations. Patients were categorized into OCCC or other EOC subtypes based on postoperative pathology. Seven clinical characteristics (age, cancer antigen [CA]-125, CA-199, endometriosis, venous thromboembolism, hypercalcemia, stage) were collected. Primary tumors were manually delineated on portal venous-phase images, and 1218 radiomic features were extracted. The F-test-based feature selection method and logistic regression algorithm were used to build the radiomic signature, clinical model, and integrated model. To explore the effects of integrated model-assisted diagnosis, five radiologists independently interpreted images in the testing set and reevaluated cases two weeks later with knowledge of the integrated model's output. The diagnostic performances of the predictive models, radiologists, and radiologists aided by the integrated model were evaluated. RESULTS: The integrated model containing the radiomic signature (constructed by four wavelet radiomic features) and three clinical characteristics (CA-125, endometriosis, and hypercalcinemia), showed better diagnostic performance (AUC = 0.863 [0.762-0.964]) than the clinical model (AUC = 0.792 [0.630-0.953], p = 0.295) and the radiomic signature alone (AUC = 0.781 [0.636-0.926], p = 0.185). The diagnostic sensitivities of the radiologists were significantly improved when using the integrated model (p = 0.023-0.041), while the specificities and accuracies were maintained (p = 0.074-1.000). CONCLUSION: Our integrated model shows great potential to facilitate the early identification of the OCCC subtype in EOC, which may enhance subtype-specific therapy and clinical management.
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Endometriose , Neoplasias Ovarianas , Humanos , Feminino , Carcinoma Epitelial do Ovário/diagnóstico por imagem , Estudos Retrospectivos , Tomografia Computadorizada por Raios X/métodos , Neoplasias Ovarianas/diagnóstico por imagemRESUMO
Cinnamigones A-C, three undescribed highly oxidized guaiane-type sesquiterpenes were isolated from the fruits of Cinnamomum migao. Cinnamigone A (1), structurally artemisinin-like, is a natural 1,2,4-trioxane caged endoperoxide with an unprecedented tetracyclic 6/6/7/5 ring system. Compounds 2-3 are classic guaiane sesquiterpene featuring different epoxy units. Guaiol (4) is considered to be the precursor of 1-3 in the biosynthesis pathway hypothesis. The planar structures and configurations of cinnamigones A-C were elucidated by spectral analysis, HRESIMS, X-ray crystallography and ECD calculations. Evaluation of the neuroprotective activity of 1-3 on N-methyl-á´ aspartate (NMDA) toxicity was demonstrated that compounds 1-2 exhibited moderate neuroprotective activity against NMDA-induced neurotoxicity.
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Cinnamomum , Sesquiterpenos , Estrutura Molecular , N-Metilaspartato , Sesquiterpenos/farmacologia , Sesquiterpenos/química , Sesquiterpenos de Guaiano/farmacologiaRESUMO
Objective To compare the image quality of three high-resolution dynamic MRI methods for evaluating the motion of temporomandibular joint disc and condyle. Methods Twenty-five patients with suspected temporomandibular joint disorders were examined by single-shot fast spin-echo (SSFSE),fast imaging employing steady-state acquisition (FIESTA),and spoiled gradient echo (SPGR) on the oblique sagittal position.Two radiologists performed subjective and objective evaluation on the images with double-blind method.The subjective evaluation included the signal intensity of mandibular condyle,articular disc,soft tissue around articular disc,and lateral pterygoid muscle,the contrast between articular disc and condyle,the contrast between articular disc and surrounding soft tissue,condylar motion,and disc movement.The objective evaluation indexes included image signal intensity,signal-to-noise ratio (SNR),and contrast-to-noise ratio (CNR).The subjective and objective indexes of the image quality were compared between the three sequences. Results The SSFSE sequence had lower signal intensity of articular disc and higher signal intensity of condyle and surrounding soft tissue than FIESTA and SPGR sequences (all P<0.001).The SPGR sequence showed higher signal intensity of lateral pterygoid muscle than the SSFSE and FIESTA sequences (P=0.017,P<0.001).Among the three sequences,SSFSE sequence showed the clearest articular disc structure (χ2=41.952,P<0.001),the strongest contrast between articular disc and condyle (χ2=35.379,P<0.001),the strongest contrast between articular disc and surrounding soft tissue (χ2=27.324,P<0.001),and the clearest movement of articular disc (χ2=44.655,P<0.001).SSFSE and FIESTA sequences showed higher proportion of disc displacement and reduction than SPGR sequence (all P<0.001).The CNR (χ2=21.400,P<0.001),SNR (χ2=34.880,P<0.001),and condyle signal intensity (F=337.151,P<0.001) demonstrated differences among SSFSE,FIESTA,and SPGR sequences.The CNR of SSFSE sequence was higher than that of FIESTA sequence (P<0.001),while it had no significant difference between SSFSE and SPGR sequences (P=0.472).In addition,the SSFSE sequence had higher SNR and signal intensity than FIESTA and SPGR sequences (all P<0.001). Conclusion The best image quality can be observed from SSFSE sequence where both the structure and movement of temporomandibular joint are well displayed.Therefore,SSFSE is preferred for the examination of temporomandibular joint movement.
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Amplitude de Movimento Articular , Articulação Temporomandibular , Humanos , Articulação Temporomandibular/diagnóstico por imagem , Articulação Temporomandibular/fisiologia , Imageamento por Ressonância Magnética , Transtornos da Articulação Temporomandibular/diagnóstico , Transtornos da Articulação Temporomandibular/fisiopatologiaRESUMO
BACKGROUND: Emerging evidence has shown that miR-29 is a promising biomarker and therapeutic target for malignancies. The roles of miR-29a/b/c in glioma pathogenesis remain need further investigation. METHODS: The expression levels of miR-29a/b/c and CDC42 were systematically analysed, and prognostic significance was evaluated by Kaplan-Meier survival and Cox regression analyses. The roles of miR-29a/b/c in apoptosis and the underlying mechanisms were explored via an alkaline single-cell gel electrophoresis assay, caspase 3/7 activity assays and Western blotting. RESULTS: miR-29a/b/c expression decreased progressively with the elevation of the WHO grade in our 147 human glioma specimens, compared with 20 non-tumour control brain tissues, and decreased miR-29a/b/c expression was associated with more aggressive phenotypes. Kaplan-Meier and Cox regression analyses demonstrated that lower miR-29a/b/c expression was correlated with worse prognosis, which was confirmed by analysis of 198 glioma patients from the CGGA cohort. These all indicate that miR-29a/b/c were independent predictors of prognosis in glioma patients. miR-29a/b/c induced apoptosis in GBM cells by silencing CDC42. Further detailed mechanistic investigation revealed that miR-29a/b/c promoted apoptosis in a p53-dependent manner by suppressing the CDC42/PAK/AKT/MDM2 pathway. CONCLUSIONS: miR-29a/b/c are independent predictors of prognosis in glioma patients. They induce glioblastoma cell apoptosis via silencing of CDC42 and suppression of downstream PAK/AKT/MDM2 signalling in a p53-dependent manner.
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Glioblastoma , Glioma , MicroRNAs , Humanos , Glioblastoma/genética , Glioblastoma/metabolismo , Glioblastoma/patologia , MicroRNAs/genética , MicroRNAs/metabolismo , Proteína Supressora de Tumor p53 , Proteínas Proto-Oncogênicas c-akt/metabolismo , Linhagem Celular Tumoral , Proliferação de Células/genética , Glioma/genética , Glioma/metabolismo , Glioma/patologia , Apoptose/genética , Ciclo CelularRESUMO
OBJECTIVES: To investigate the feasibility of a deep learning-accelerated T2-weighted turbo spin echo (TSE) sequence (T2DL) applied to female pelvic MRI, using standard T2-weighted TSE (T2S) as reference. METHODS: In total, 24 volunteers and 48 consecutive patients with benign uterine diseases were enrolled. Patients in the menstrual phase were excluded. T2S and T2DL sequences in three planes were performed for each participant. Quantitative image evaluation was conducted by calculating the signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR). Image geometric distortion was evaluated by measuring the diameters in all three directions of the uterus and lesions. Qualitative image evaluation including overall image quality, artifacts, boundary sharpness of the uterine zonal layers, and lesion conspicuity were assessed by three radiologists using a 5-point Likert scale, with 5 indicating the best quality. Comparative analyses were conducted for the two sequences. RESULTS: T2DL resulted in a 62.7% timing reduction (1:54 min for T2DL and 5:06 min for T2S in axial, sagittal, and coronal imaging, respectively). Compared to T2S, T2DL had significantly higher SNR (p ≤ 0.001) and CNR (p ≤ 0.007), and without geometric distortion (p = 0.925-0.981). Inter-observer agreement regarding qualitative evaluation was excellent (Kendall's W > 0.75). T2DL provided superior image quality (all p < 0.001), boundary sharpness of the uterine zonal layers (all p < 0.001), lesion conspicuity (p = 0.002, p < 0.001, and p = 0.021), and fewer artifacts (all p < 0.001) in sagittal, axial, and coronal imaging. CONCLUSIONS: Compared with standard TSE, deep learning-accelerated T2-weighted TSE is feasible to reduce acquisition time of female pelvic MRI with significant improvement of image quality.
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Synergies of transcription factors, chromatin modifiers and their target genes are vital for cell fate determination in human cancer. Although the importance of numerous epigenetic machinery for regulating gliomagenesis has been previously recognized, how chromatin modifiers collaborate with specific transcription factors remains largely elusive. Herein we report that Pontin chromatin remodelling factor acts as a coactivator for LEF1 to activate TGFß/SMAD signalling, thereby contributing to gliomagenesis. Pontin is highly expressed in gliomas, and its overexpression paralleled the grade elevation and poor prognosis of patients. Functional studies verified its oncogenic roles in GBM cells by facilitating cell proliferation, survival and invasion both in vitro and in vivo. RNA sequencing results revealed that Pontin regulated multiple target genes involved in TGFß/SMAD signalling. Intriguingly, we found that Pontin amplified TGFßR2 gene transcription by recruiting LEF1, thereby activating TGFß/SMAD signalling and facilitating gliomagenesis. Furthermore, higher TGFßR2 expression conferred worse patient outcomes in glioma. To conclude, our study revealed that the Pontin-LEF1 module plays a crucial role in driving TGFßR2 gene transcription, which could be exploited to target TGFß/SMAD signalling for anti-glioma therapy.
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ATPases Associadas a Diversas Atividades Celulares , Proteínas de Transporte , DNA Helicases , Glioma , Fator 1 de Ligação ao Facilitador Linfoide , Fatores de Transcrição , ATPases Associadas a Diversas Atividades Celulares/metabolismo , Proteínas de Transporte/metabolismo , Proliferação de Células , Cromatina , DNA Helicases/metabolismo , Glioma/genética , Humanos , Fator 1 de Ligação ao Facilitador Linfoide/metabolismo , Receptor do Fator de Crescimento Transformador beta Tipo II/genética , Fatores de Transcrição/metabolismo , Fator de Crescimento Transformador beta/metabolismoRESUMO
OBJECTIVE: To evaluate and compare the diagnostic performance of apparent diffusion coefficient (ADC) values and MRI-based radiomics analysis for lymph node metastasis (LNM) detection in patients with cervical cancer (CC). METHODS: We searched relevant databases for studies on ADC values and MRI-based radiomics analysis for LNM detection in CC between January 2001 and December 2021. Methodological quality assessment of risk of bias using Quality Assessment of Diagnostic Accuracy Studies 2 and radiomics quality score (RQS) of the studies was conducted. The pooled sensitivity, specificity, positive likelihood ratio (LR+), negative likelihood ratio (LR-), diagnostic odds ratio (DOR), and area under the curve (AUC) were calculated. Diagnostic performance was compared between the two quantitative analyses using a two-sample Z-test. RESULTS: In total, 22 studies including 2314 patients were included. Unclear risk of bias was observed in 4.5-36.4% of the studies. The 8 radiomics studies exhibited a median (interquartile range) RQS of 13.5 (5.5-15.75). The pooled sensitivity, specificity, LR+, LR-, DOR, and AUC of the ADC values vs radiomics analysis were 0.86 vs 0.84, 0.85 vs 0.73, 5.7 vs 3.1, 0.17 vs 0.22, 34 vs 14, and 0.91 vs 0.86, respectively. There was no threshold effect or publication bias, but significant heterogeneity existed among the studies. No significant difference was detected in the diagnostic performance of the two quantitative analyses using the Z-test. CONCLUSION: ADC values are more clinically promising because they are more easily accessible and widely applied, and exhibit a non-statistically significant trend to outperform radiomics analysis.