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AIM: This study aimed to develop highly precise radiomics and deep learning models to accurately detect acute lymphoblastic leukemia (ALL) using a T1WI image. MATERIALS AND METHODS: A total of 604 brain magnetic resonance data of ALL group and normal children (NC) group. Two radiologists independently retrieved radiomics features after manually delineating the area of interest along the clivus at the median sagittal position of T1WI. According to the 9:1 ratio, all samples were randomly divided into the training cohort and the testing cohort. support vector machine was then used to classify the radiomics model using the features that had a correlation coefficient of greater than 0.99 in the training cohort. The Efficientnet-B3 network model received the training set images to create a deep learning model. The sensitivity, specificity, and area under the ROC curve were calculated in order to evaluate the diagnostic efficacy of the different models after the validation of two aforementioned models in the testing cohort. RESULTS: The deep learning model had a higher AUC value of 0.981 than the radiomics model's value of 0.962 in the testing cohort. Delong's test showed no statistical difference between the two models (P>0.05). The accuracy/sensitivity/specificity/negative predictive value/positive predictive value achieved 0.9180/0.9565/0.8947/0.9714/0.8462 for the radiomics model and 0.9344/0.8696/0.9737/0.9250/0.9524 for deep learning model. CONCLUSIONS: The deep learning and radiomics models showed high AUC values in the training and test cohorts. They also exhibited good diagnostic efficacy for predicting ALL.
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Aprendizaje Profundo , Imagen por Resonancia Magnética , Leucemia-Linfoma Linfoblástico de Células Precursoras , Sensibilidad y Especificidad , Humanos , Leucemia-Linfoma Linfoblástico de Células Precursoras/diagnóstico por imagen , Masculino , Femenino , Imagen por Resonancia Magnética/métodos , Niño , Preescolar , Adolescente , Estudios Retrospectivos , Interpretación de Imagen Asistida por Computador/métodos , RadiómicaRESUMEN
Reperfusion is considered as the cornerstone of the treatment of high-risk pulmonary embolism (PE). However, when thrombolysis is contraindicated and surgery or interventional therapy is not available, the treatment of high-risk PE becomes very difficult. To our knowledge, there are no reports of successful treatment of high-risk PE with low-dose anticoagulation. On November 30, 2021, a 56-year-old male patient with subarachnoid hemorrhage was admitted to the emergency department of the First Affiliated Hospital of Chongqing Medical University. On the second day of admission, the patient suddenly went into shock during aneurysm clipping. After implementing D-dimer, markers of myocardial injury, echocardiography and computed tomography pulmonary angiography, a high-risk PE was diagnosed. Due to the contraindication of thrombolysis and the refusal of endovascular treatment, he was eventually cured with low-dose anticoagulation combined with vasopressors.
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Anticoagulantes , Embolia Pulmonar , Humanos , Embolia Pulmonar/tratamiento farmacológico , Masculino , Persona de Mediana Edad , Anticoagulantes/administración & dosificación , Anticoagulantes/uso terapéutico , Productos de Degradación de Fibrina-Fibrinógeno/análisis , Angiografía por Tomografía Computarizada , Hemorragia SubaracnoideaRESUMEN
Objective: To evaluate the sensitivity of endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) puncture to obtain intrathoracic lymph node samples combined with Xpert MTB/RIF (Xpert) detection for the diagnosis of intrathoracic lymph node tuberculosis. Methods: From March 2018 to June 2021, 106 patients [55 males and 51 females, age (45.1±18.6) years] with suspected intrathoracic lymph node tuberculosis and EBUS-TBNA were collected in Zhejiang Hospital of Integrated Traditional Chinese and Western Medicine, including 64 patients with subsequent diagnosis of intrathoracic lymph node tuberculosis and 42 patients without tuberculosis. Xpert test and traditional etiology test were performed on the patients' intrathoracic lymph node puncture specimens. The positive results of different detection methods and different methods were analyzed, and the influencing factors of Xpert independent detection positive were analyzed by univariate and multivariate logistic regression. Results: The sensitivity of Xpert was 65.6% (95%CI: 52.7%-77.1%), the specificity was 97.6% (95%CI: 87.4%-99.9%), the positive predictive value was 97.7% (95%CI: 85.7%-99.7%), the negative predictive value was 65.1% (95%CI: 57.0%-72.4%). The positive rate of Xpert alone (65.6%, 42/64) was not significantly different from that of MGIT960, histopathology and Xpert combined detection (70.3%, 45/64) (P<0.05). Multivariate logistic regression analysis showed that the location of the diseased lymph nodes in the mediastinum (OR=5.84, 95%CI: 1.112-30.704, P=0.037), necrosis in the lymph nodes (OR=6.32, 95%CI: 1.460-27.384, P=0.014), and the axial depth of the lymph nodes≥17 mm (OR=6.61, 95%CI: 1.408-30.969, P=0.017) were the promoting factors for the positive Xpert test. Conclusions: EBUS-TBNA combined with Xpert detection has a high clinical diagnostic value for intrathoracic lymph node tuberculosis. When the number of puncture samples is small, Xpert detection can be preferred. The positive rate of Xpert detection can be improved by selecting lymph nodes with mediastinal lesions, lymph nodes necrosis, and axial lymph nodes depth≥17 mm for puncture.
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Biopsia por Aspiración con Aguja Fina Guiada por Ultrasonido Endoscópico , Ganglios Linfáticos , Sensibilidad y Especificidad , Tuberculosis Ganglionar , Humanos , Masculino , Femenino , Persona de Mediana Edad , Tuberculosis Ganglionar/diagnóstico , Ganglios Linfáticos/patología , Biopsia por Aspiración con Aguja Fina Guiada por Ultrasonido Endoscópico/métodos , AdultoRESUMEN
Objective: To explore the characteristics of adverse drug reactions during the 24-week therapy with delamanid-containing regimen for patients with multidrug-resistant and rifampicin-resistant pulmonary tuberculosis (MDR/RR-PTB). Methods: The prospective multicenter study was conducted from June 2020 to June 2023. A total of 608 eligible patients with MDR/RR-PTB were enrolled in 26 tuberculosis medical institutions in China including 364 males and 79 females, aged 39.6(19.0-68.0) years. Patients were treated with chemotherapy regimens containing delamanid. Patients were closely supervised during treatment of medication, and all adverse reactions occurring during treatment were monitored and recorded. The clinical characteristics of adverse reactions were evaluated by descriptive analysis. Chi-square test and multivariate logistic regression were used to analyze the related factors of QTcF interval prolongation (QT corrected with Fridericia's formula). Results: Of the 608 patients enrolled in this study, 325 patients (53.5%) reported 710 adverse events within 24 weeks of treatment. The top 6 most common complications were hematological abnormalities (143 patients, 23.5%), QT prolongation (114 patients, 18.8%), liver toxicity (85 patients, 14.0%), gastrointestinal reaction (41 patients, 6.7%), peripheral neuropathy (25 patients, 4.1%) and mental disorders (21 patients, 3.5%). The prolongation of QT interval mostly occurred in the 12th week after the first dose of medication. Serious adverse reactions occurred in 21 patients (3.5%). There were 7 patients (1.2%) with mental disorders, including 2 patients (0.3%) with severe mental disorders. Conclusions: The safety of dalamanid-based regimen in the staged treatment of MDR/RR-PTB patients was generally good, and the incidence of adverse reactions was similar to that reported in foreign studies. This study found that the incidence of QT interval prolongation in Chinese patients was higher than that reported overseas, suggesting that the monitoring of electrocardiogram should be strengthened when using drugs containing delamanid that may cause QT interval prolongation.
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Antituberculosos , Nitroimidazoles , Oxazoles , Rifampin , Tuberculosis Resistente a Múltiples Medicamentos , Tuberculosis Pulmonar , Humanos , Masculino , Femenino , Tuberculosis Resistente a Múltiples Medicamentos/tratamiento farmacológico , Adulto , Estudios Prospectivos , Rifampin/efectos adversos , Persona de Mediana Edad , Oxazoles/efectos adversos , Oxazoles/uso terapéutico , Oxazoles/administración & dosificación , Antituberculosos/efectos adversos , Tuberculosis Pulmonar/tratamiento farmacológico , Nitroimidazoles/efectos adversos , Nitroimidazoles/uso terapéutico , Nitroimidazoles/administración & dosificación , Anciano , China , Adulto Joven , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/etiologíaRESUMEN
Bone mineral density (BMD) is an independent risk factor of osteoporosis-related fractures. We performed gene-based burden tests to assess the association between rare variants and BMD, and identified several BMD candidate genes. PURPOSE: BMD is highly heritable and a major predictor of osteoporotic fractures, but its genetic basis remains unclear. We aimed to identify rare risk variants contributing to BMD. METHODS: Utilizing the newly released UK Biobank 200,643 exome dataset, we conducted a gene-based exome-wide association study in males and females, respectively. First, 100,639 males and 117,338 females with BMD values were included in the polygenic risk scores (PRS) analysis. Among individuals with lower 30% PRS, cases were individuals with top 10% BMD, and individuals with bottom 10% BMD were the controls. Considering the effects of vitamin D (VD), individuals with the highest 30% VD concentration were selected for VD-BMD analysis. After quality control, 741 males and 697 females were included in the BMD analysis, and 717 males and 708 females were included in the VD-BMD analysis. The variants were annotated by ANNOVAR software, then BMD and VD-BMD qualified variants were imported into the SKAT R-package to perform gene-based burden tests, respectively. RESULTS: The gene-based burden test of the exonic variants identified genome-wide candidate associations in ANKRD18A (P = 1.60 × 10-5, PBonferroni adjust = 2.11 × 10-3), C22orf31 (P = 3.49 × 10-4, PBonferroni adjust = 3.17 × 10-2), and SPATC1L (P = 1.09 × 10-5, PBonferroni adjust = 8.80 × 10-3). For VD-BMD analysis, three genes were associated with BMD, such as NIPAL1 (P = 1.06 × 10-3, PBonferroni adjust = 3.91 × 10-2). CONCLUSIONS: Our study suggested that rare variants contribute to BMD, providing new sights for broadening the genetic structure of BMD.
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Densidad Ósea , Fracturas Osteoporóticas , Masculino , Femenino , Humanos , Densidad Ósea/genética , Exoma/genética , Estudio de Asociación del Genoma Completo , Fracturas Osteoporóticas/genética , Estudios de Asociación Genética , Polimorfismo de Nucleótido SimpleRESUMEN
Objective: To investigate and analyze the clinical efficacy of salvage liver transplantation (SLT), rehepatectomy (RH), local ablation (LA), and prognostic risk factors in patients with postoperative recurrence of hepatocellular carcinoma. Methods: Clinical data of 145 patients with recurrent liver cancer in the 900th Hospital of the Joint Logistics Support Force of the People's Liberation Army from January 2005 to June 2018 were retrospectively collected. SLT group, RH group, and LA group included 25, 44, and 76 cases, respectively. Follow-up and statistics were recorded on the overall survival rate, relapse-free survival rate, and complications of the three groups of patients at 1, 2, and 3 years after surgery. Univariate and multivariate COX analyses were used to analyze the prognostic risk factors in patients with recurrent HCC. Results: The overall survival rates of 1, 2, and 3 years following surgery in the SLT, RH, and LA groups were 100.0%, 84.0%, 72.0%, 95.5%, 77.3%, 65.9%, 90.8%, 76.3%, and 63.2%, respectively, when the recurrence of liver cancer met the Milan criteria. The overall survival rate did not differ statistically between SLT and RH (P = 0.303) or between RH and LA (P = 0.152). There were statistically significant differences in recurrence-free survival between SLT and RH or RH and LA (P = 0.046). There was no statistically significant difference in the incidence of complications between SLT and RH or RH and LA (P > 0.017). Age > 65 years was an independent risk factor affecting the overall survival rate in patients with recurrent HCC. Age > 65 years and recurrence time < 24 months were independent risk factors affecting the recurrence-free survival rate in patients with recurrent HCC. Conclusion: SLT is the best treatment option when the recurrence of HCC meets Milan's criteria. RH and LA are the appropriate treatment plans for recurrent HCC when the liver source is limited.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Trasplante de Hígado , Humanos , Anciano , Carcinoma Hepatocelular/patología , Neoplasias Hepáticas/patología , Pronóstico , Estudios Retrospectivos , Trasplante de Hígado/efectos adversos , Terapia Recuperativa/efectos adversos , Recurrencia Local de Neoplasia/patología , Resultado del Tratamiento , Hepatectomía , Factores de RiesgoRESUMEN
PURPOSE: To assess the diagnostic value of SuperSonic shear imaging (SSI) for the differentiation between benign and malignant thyroid nodules through meta-analysis. METHODS: Online database searches were performed on PubMed, EMBASE, the Cochrane Library, and the Web of Science until 31 July 2021. The Quality Assessment of Diagnostic Accuracy Studies-2 tool was used to assess the quality of the included studies. Three measures of diagnostic test performance were used to examine the value of SSI, including the summary area under the receiver operating characteristic curve (AUROC), the summary diagnostic odds ratio (DOR), and the summary sensitivity and specificity. Heterogeneity was explored using meta-regression and subgroup analyses. RESULTS: Finally, 21 studies with 3376 patients were included in this study. There were a total of 4296 thyroid nodules, in which 1806 malignant nodules and 2490 benign ones were involved. Thyroid nodules exhibited a malignancy rate of 42.0% (range 5.6-79.8%), 95.1% of which were of papillary variant. SSI showed a summary sensitivity of 74% [95% confidence interval (CI) 67-79%], specificity of 82% (95% CI 77-87%) and AUROC of 0.85 (95% CI 0.82-0.88) for the differentiation between benign and malignant thyroid nodules. The summary positive likelihood ratio (LR), negative LR, and DOR were 4.2 (95% CI 3.3-5.3), 0.32 (95% CI 0.26-0.40), and 13 (95% CI 9-18), respectively. CONCLUSIONS: SSI showed high accuracy in the diagnostic differentiation between benign and malignant thyroid nodules and can be served as a noninvasive and important adjunct for thyroid nodule evaluation.
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Diagnóstico por Imagen de Elasticidad , Nódulo Tiroideo , Diagnóstico Diferencial , Diagnóstico por Imagen de Elasticidad/métodos , Humanos , Reproducibilidad de los Resultados , Sensibilidad y Especificidad , Nódulo Tiroideo/diagnóstico por imagen , Nódulo Tiroideo/patologíaRESUMEN
OBJECTIVE: To investigate the significance and distribution of oxidized low-density lipoprotein antibodies (ox-LDL-Ab) in patients with antiphospholipid syndrome (APS). METHODS: In this study, 334 patients who were hospitalized in the Department of Rheumatology and Immunology, Peking University People's Hospital were included. There were 162 APS patients, 122 patients with other autoimmune diseases without thrombosis or obstetric disease as disease control and 50 healthy controls. The clinical data and laboratory indicators were retrospectively collected. The ox-LDL-Ab, anticardiolipin (aCL) IgG/IgA/IgM, and anti-ß2-glycoprotein â (aß2GPI) IgG/IgA/IgM were detected by enzyme-linked immunosorbent assay (ELISA). The relationship between ox-LDL-Ab and clinical and laboratory parameters were analyzed by SPSS 27.0. RESULTS: In APS group, 60.5% of patients had thrombosis, 48.1% had pregnancy morbidity, 34.0% had thrombocytopenia. The positive rates of aCL, aß2GPI and lupus anticoagulant (LAC) were 17.9%, 34.6%, and 46.9%, respectively. The ox-LDL-Ab titers and positive rate in APS group were higher than that in healthy controls [titers: 40.8 (25.4-66.0) U/mL vs. 24.1 (12.3-36.5) U/mL, P=0.001; positive rate: 67.3% vs. 36.0%, P=0.001]. The diffe-rences in titers and positive rate of ox-LDL-Ab between APS patients and disease controls were not statistically significant [titers: 40.8 (25.4-66.0) U/mL vs. 35.9 (24.2-53.1) U/mL, P=0.118; positive rate: 67.3% vs. 61.5%, P=0.318]. The area under curve (AUC) for aß2GPI, aCL, and ox-LDL-Ab were 0.745 (95%CI: 0.692-0.797), 0.666 (95%CI: 0.608-0.724), 0.609 (95%CI: 0.549-0.669), respectively. The Youden's index was 0.388, 0.269, and 0.132, respectively. The AUC for ox-LDL-Ab in seronegative APS patients was 0.562 (95%CI: 0.480-0.645). The sensitivity and specificity of ox-LDL-Ab in seronegative APS patients were 63.9% and 47.0%, respectively, and the Youden's index was 0.109. The ox-LDL-Ab positive group had higher positive rate of aß2GPI (42.2% vs. 18.9%, P=0.003) and aCL (22.9% vs. 7.5%, P=0.017) than the ox-LDL-Ab negative group. There was no correlation between ox-LDL-Ab and thrombosis, coronary artery disease, pregnancy morbidity, hyperlipidemia, hypocomplementemia, and LAC positivity. CONCLUSION: Ox-LDL-Ab was correlated with aCL and aß2GPI, and no association were observed between ox-LDL-Ab and thrombosis, coronary artery disease, and pregnancy morbidity.
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Síndrome Antifosfolípido , Enfermedad de la Arteria Coronaria , Trombosis , Embarazo , Femenino , Humanos , Anticuerpos Anticardiolipina , Estudios Retrospectivos , Relevancia Clínica , beta 2 Glicoproteína I , Inhibidor de Coagulación del Lupus , Lipoproteínas LDL , Autoanticuerpos , Inmunoglobulina G , Inmunoglobulina A , Inmunoglobulina MRESUMEN
Background and Aim: Four premolars extractions are routine procedures for correction of malocclusion, but will inevitably lead to a reduction of tongue space, whether this will weaken the pharyngeal airway remains a controversy. Patients and Methods: Cone-beam computed tomography (CBCT) radiographs of 80 patients who completed four premolar extraction orthodontic treatments were collected and divided into three anteroposterior skeletal groups according to the ANB (angle subspinale to nasion to supramentale) value. Linear, angular, cross-sectional area, and volumetric dimensions of the pharyngeal airway were measured using Dolphin Imaging 11.9 software. One-way analysis of variance and Pearson's correlation coefficient test were performed to assess the intergroup comparisons. Treatment changes were evaluated with two-sample t-tests. Results: In intergroup comparisons, vertical linear and cross-sectional area differences were identified in S-Go/N-Me, VD1, VD1/N-Me, VD2/N-Me, AA, OAA and OMINI (p<0.05), while other measurements showed no significant differences. Angle2, the tilting degree of the pharyngeal airway, showed a positive correlation with ANB (p<0.05). As for the treatment changes, a significant increase was found in the pharyngeal airway in the Class I group (OUA p<0.05, VD1 p<0.001, VD2 p<0.05) and Class II group (VD1 p<0.001. VD2, p<0.05), and inversely, a significant decrease was found in the pharyngeal airway in the Class III group (OAA p<0.05, OMINI p<0.05, OUA p<0.05). No volumetric difference was identified. Interestingly, regarding the preoperative pharyngeal airway size, values trended to the mean value significantly. Conclusion: Four premolar extraction orthodontic treatments did not affect the pharyngeal airway volume except for the vertical liner and cross-sectional area dimensions. The trend of the gold standard suggested a positive influence of four premolar extraction orthodontic treatments.
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Maloclusión de Angle Clase III , Maloclusión , Tomografía Computarizada de Haz Cónico Espiral , Humanos , Diente Premolar/cirugía , Mandíbula , Faringe , Tomografía Computarizada de Haz Cónico/métodos , Cefalometría/métodos , Imagenología Tridimensional/métodosRESUMEN
In order to verify the correlation between Polygonum multiflorum-induced liver injury and HLA-B*35 : 01 alleles, six hospitalized patients diagnosed with Polygonum multiflorum-induced liver injury (PM-DILI) were selected, and their clinicopathological data were collected. Simultaneously, blood HLA-B* 35 : 01 allele detection was performed. Among the six PM-DILI cases, 4 were male, aged 38.83 ± 10.13 years old. The types of liver injury were hepatocellular injury types in all, and the severity of liver injury in five cases was grade 3. The histological presentations were acute hepatitis and acute cholestatic hepatitis. PM-DILI cases were all HLA-B*35:01 carriers, with a carrier rate of 100%. This finding indicates that PM-DILI is significantly correlated with HLA-B*35:01 alleles. Therefore, HLA-B*35 : 01 alleles can be used as an important predictive indicator for PM-DILI.
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Enfermedad Hepática Inducida por Sustancias y Drogas , Fallopia multiflora , Antígenos HLA-B , Preparaciones de Plantas/toxicidad , Adulto , Alelos , Enfermedad Hepática Inducida por Sustancias y Drogas/genética , Fallopia multiflora/toxicidad , Femenino , Antígenos HLA-B/genética , Humanos , Masculino , Persona de Mediana EdadRESUMEN
OBJECTIVES: HIV-1 genetic diversity is increasing among men who have sex with men (MSM) in China, but the association of HIV-1 genotype with disease progression remains to be elucidated. METHODS: We collected data in an observational longitudinal cohort study of 860 HIV-1-infected MSM in Guangzhou, China between January 2008 and March 2017. Kaplan-Meier analysis and Cox proportional hazard model were used to predict the time from HIV-1 diagnosis to immunodeficiency progression (CD4 cell count < 200 cells/µl) as well as adjusted hazard ratio (aHR). RESULTS: CRF01_AE and HIV-1 subtype B infection were associated with higher percentage of patients progressed to immunodeficiency and higher incidence of immunodeficiency than infection with CRF07_BC or CRF55_01B. Compared with CRF07_BC, the time from HIV-1 diagnosis to immunodeficiency were different among the major HIV-1 genotypes, which ranked as follows, in descending order: CRF07_BC (7.03 years) > CRF55_01B (5.71 years, P = 0.014; aHR 3.752, P = 0.0923) > CRF01_AE (5.18 years, P < 0.001; aHR 4.733, P = 0.0152). HIV-1 genotype, viral load and baseline CD4 T-cell count were three independent variables associated with disease progression. CONCLUSIONS: Our results confirm differential rates of immunodeficiency progression as a function of HIV-1 genotype. The impact of HIV-1 genotype on HIV epidemics, patient management and prevention should be further investigated.
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Técnicas de Genotipaje/métodos , Infecciones por VIH/inmunología , VIH-1/genética , ARN Viral/genética , Adulto , Recuento de Linfocito CD4 , China , Progresión de la Enfermedad , Genotipo , Infecciones por VIH/genética , Infecciones por VIH/virología , VIH-1/clasificación , Homosexualidad Masculina , Humanos , Estimación de Kaplan-Meier , Estudios Longitudinales , Masculino , Carga Viral , Adulto JovenRESUMEN
AIM: To evaluate whether cardiac muscle area and radiation attenuation, determined using pre-chemotherapy computed tomography (CT), are associated with therapeutic response and overall survival (OS) in chemotherapy-treated advanced pancreatic cancer (APC) patients. MATERIALS AND METHODS: Ninety-eight chemotherapy-treated APC patients who underwent pre-chemotherapy CT between 2009 and 2018 were considered. Left ventricular muscle area (LVMA) and left ventricular muscle radiation attenuation (LVMRA) were measured using pre-chemotherapy arterial-phase CT. OS and progression-free survival (PFS) were analysed using Kaplan-Meier curves. Univariate and multivariate Cox regression analyses were performed to analyse potential factors affecting OS and PFS. RESULTS: Patients with low LVMRA, low LVMA at baseline CT, and multiple metastases had a significantly shorter median OS than patients with high LVMRA, high LVMA, and without multiple metastases (8.8 versus 14 months, p=0.017; 12.2 versus 18.1 months, p=0.038; 7.3 versus 13.5 months, p<0.001, respectively). Patients with low LVMRA and distant metastasis had a shorter median PFS than patients with high LVMRA and those without distant metastasis (4.9 versus 8.3 months, p=0.032; 5.4 versus 9.9 months, p=0.002, respectively). Moreover, the mean LVMRA was the highest in the partial response group (p=0.028). CONCLUSION: LVMRA could well predict PFS and OS in chemotherapy-treated APC patients.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Caquexia/etiología , Ventrículos Cardíacos/diagnóstico por imagen , Ventrículos Cardíacos/patología , Neoplasias Pancreáticas/tratamiento farmacológico , Tomografía Computarizada por Rayos X/métodos , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Neoplasias Pancreáticas/mortalidad , Interpretación de Imagen Radiográfica Asistida por Computador , Estudios Retrospectivos , Tasa de SupervivenciaRESUMEN
This study aimed to investigate the effect of miR-671-5p on metastasis of clear cell renal cell carcinoma (ccRCC) and underlying mechanism involved. The migration and invasion of ccRCC cells were determined by transwell and boyden assays in vitro and in vivo. Genes mRNA and protein expression were detected by quantitative polymerase chain reaction (qPCR) and western blot analysis, respectively. The target gene of miRNA was confirmed by luciferase reporter assays. Transcriptional regulation of miRNA by transcription factor was detected by chromatin immunoprecipitation assay (ChIP). The expression of miRNA in clinical specimens were detected by in situ hybridization (ISH). miR-671-5p promoted migration and invasion of ccRCC in vivo and in vitro. Moreover, miR-671-5p directly targeted APC to activate Wnt signaling, thus inducing the epithelial-mesenchymal transition (EMT) in ccRCC. Intriguingly, miR-671-5p expression was transcriptionally enhanced by HMGA1. Consistently, bioinformatics analysis suggested that HMGA1 was positively correlated with miR-671 expression, however, miR-671 was negatively correlated with APC. In situ hybridization analysis showed that miR-671-5p was upregulated in ccRCC compared with paracarcinoma and correlated with poor prognosis of ccRCC patients. In addition, univariate and multivariate analysis indicated that miR-671-5p expression was an independent prognostic factor for overall survival in ccRCC patients. Our data suggest that miR-671-5p is a tumor enhancer in regulating of ccRCC metastasis, and miR-671-5p may be utilized as a factor for the clinical diagnosis and prognosis of ccRCC.
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Proteína de la Poliposis Adenomatosa del Colon/genética , Carcinoma de Células Renales/patología , Proteína HMGA1a/genética , Neoplasias Renales/patología , MicroARNs/genética , Vía de Señalización Wnt , Carcinoma de Células Renales/genética , Línea Celular Tumoral , Movimiento Celular , Proliferación Celular , Regulación Neoplásica de la Expresión Génica , Humanos , Neoplasias Renales/genéticaRESUMEN
BACKGROUND: Human papillomavirus type 16 (HPV16)-E6 antibodies are detectable in peripheral blood before diagnosis in the majority of HPV16-driven oropharyngeal squamous cell carcinoma (OPSCC), but the timing of seroconversion is unknown. PATIENTS AND METHODS: We formed the HPV Cancer Cohort Consortium which comprises nine population cohorts from Europe, North America and Australia. In total, 743 incident OPSCC cases and 5814 controls provided at least one pre-diagnostic blood sample, including 111 cases with multiple samples. Median time between first blood collection and OPSCC diagnosis was 11.4 years (IQR = 6-11 years, range = 0-40 years). Antibodies against HPV16-E6 were measured by multiplex serology (GST fusion protein based Luminex assay). RESULTS: HPV16-E6 seropositivity was present in 0.4% of controls (22/5814; 95% CI 0.2% to 0.6%) and 26.2% (195/743; 95% CI 23.1% to 29.6%) of OPSCC cases. HPV16-E6 seropositivity increased the odds of OPSCC 98.2-fold (95% CI 62.1-155.4) in whites and 17.2-fold (95% CI 1.7-170.5) in blacks. Seropositivity in cases was more frequent in recent calendar periods, ranging from 21.9% pre-1996 to 68.4% in 2005 onwards, in those with blood collection near diagnosis (lead time <5 years). HPV16-E6 seropositivity increased with lead time: 0.0%, 13.5%, 23.7%, and 38.9% with lead times of >30 years (N = 24), 20-30 years (N = 148), 10-20 years (N = 228), and <10 years (N = 301 cases) (p-trend < 0.001). Of the 47 HPV16-E6 seropositive cases with serially-collected blood samples, 17 cases seroconverted during follow-up, with timing ranging from 6 to 28 years before diagnosis. For the remaining 30 cases, robust seropositivity was observed up to 25 years before diagnosis. CONCLUSIONS: The immune response to HPV16-driven tumorigenesis is most often detectable several decades before OPSCC diagnosis. HPV16-E6 seropositive individuals face increased risk of OPSCC over several decades.
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Anticuerpos Antivirales/sangre , Papillomavirus Humano 16/inmunología , Neoplasias Orofaríngeas/diagnóstico , Infecciones por Papillomavirus/diagnóstico , Carcinoma de Células Escamosas de Cabeza y Cuello/diagnóstico , Adulto , Anciano , Carcinogénesis/inmunología , Estudios de Casos y Controles , Femenino , Estudios de Seguimiento , Papillomavirus Humano 16/aislamiento & purificación , Humanos , Masculino , Persona de Mediana Edad , Proteínas Oncogénicas Virales/inmunología , Neoplasias Orofaríngeas/sangre , Neoplasias Orofaríngeas/inmunología , Neoplasias Orofaríngeas/virología , Infecciones por Papillomavirus/sangre , Infecciones por Papillomavirus/inmunología , Infecciones por Papillomavirus/virología , Estudios Prospectivos , Proteínas Represoras/inmunología , Seroconversión , Carcinoma de Células Escamosas de Cabeza y Cuello/sangre , Carcinoma de Células Escamosas de Cabeza y Cuello/inmunología , Carcinoma de Células Escamosas de Cabeza y Cuello/virología , Factores de TiempoRESUMEN
BACKGROUND: Increased vitamin B6 catabolism related to inflammation, as measured by the PAr index (the ratio of 4-pyridoxic acid over the sum of pyridoxal and pyridoxal-5'-phosphate), has been positively associated with lung cancer risk in two prospective European studies. However, the extent to which this association translates to more diverse populations is not known. MATERIALS AND METHODS: For this study, we included 5323 incident lung cancer cases and 5323 controls individually matched by age, sex, and smoking status within each of 20 prospective cohorts from the Lung Cancer Cohort Consortium. Cohort-specific odds ratios (ORs) and 95% confidence intervals (CIs) for the association between PAr and lung cancer risk were calculated using conditional logistic regression and pooled using random-effects models. RESULTS: PAr was positively associated with lung cancer risk in a dose-response fashion. Comparing the fourth versus first quartiles of PAr resulted in an OR of 1.38 (95% CI: 1.19-1.59) for overall lung cancer risk. The association between PAr and lung cancer risk was most prominent in former smokers (OR: 1.69, 95% CI: 1.36-2.10), men (OR: 1.60, 95% CI: 1.28-2.00), and for cancers diagnosed within 3 years of blood draw (OR: 1.73, 95% CI: 1.34-2.23). CONCLUSION: Based on pre-diagnostic data from 20 cohorts across 4 continents, this study confirms that increased vitamin B6 catabolism related to inflammation and immune activation is associated with a higher risk of developing lung cancer. Moreover, PAr may be a pre-diagnostic marker of lung cancer rather than a causal factor.
Asunto(s)
Inflamación/sangre , Neoplasias Pulmonares/sangre , Metabolismo , Vitamina B 6/sangre , Adulto , Anciano , Femenino , Humanos , Inflamación/patología , Neoplasias Pulmonares/epidemiología , Neoplasias Pulmonares/patología , Masculino , Persona de Mediana Edad , Ácido Piridóxico/metabolismo , Factores de Riesgo , FumadoresRESUMEN
We performed a 1-year prospective study to see whether zoledronic acid infusion combined with percutaneous kyphoplasty could provide more benefits in the treatment of T12 or L1 osteoporotic vertebral compression fracture (OVCF). INTRODUCTION: To investigate and analyze the clinical effects of zoledronic acid (ZOL) in combination with percutaneous kyphoplasty (PKP) in the treatment of OVCF in postmenopausal women. METHODS: Included in this study were 101 postmenopausal women patients with T12 or L1 OVCF who received PKP in our hospital between August 2015 and July 2017. They were randomly assigned to a zoledronic acid (ZOL) group (n = 50) or a control group (n = 51). Patients in ZOL group were treated preoperatively with IV infusion of 5 mg ZOL in combination with 0.25µg/d calcitriol and D3 600 mg/d calcium carbonate for a year. Patients in the control group were treated with the same dose of calcitriol and calcium carbonate D3 without ZOL. RESULTS: There was no statistically significant difference in age, height, weight, body mass index (BMI), menopause age, and the fractured vertebral body between the two groups. At 6 and 12 months after treatment, bone mineral density (BMD) in ZOL group was higher than that in the control group (p < 0.01); bone markers (NMID, P1NP, and ß-CTX) and the VAS score in ZOL group were significantly lower than those in the control group. No new fracture occurred in ZOL group. The incidence of recompression vertebral fracture (RVF) in the control group was 11.7%, while no RVF was detected in any patient in ZOL group. Mild adverse reactions in ZOL group were significantly higher than those in the control group, but all of them were relieved after symptomatic treatment. CONCLUSIONS: ZOL IV infusion in combination with PKP is beneficial for the treatment of T12 or L1 OVCF.
Asunto(s)
Conservadores de la Densidad Ósea/uso terapéutico , Fracturas por Compresión/terapia , Cifoplastia/métodos , Fracturas Osteoporóticas/terapia , Fracturas de la Columna Vertebral/terapia , Ácido Zoledrónico/uso terapéutico , Anciano , Anciano de 80 o más Años , Terapia Combinada , Femenino , Humanos , Vértebras Lumbares/lesiones , Vértebras Lumbares/cirugía , Persona de Mediana Edad , Osteoporosis Posmenopáusica/tratamiento farmacológico , Estudios Prospectivos , Recurrencia , Vértebras Torácicas/lesiones , Vértebras Torácicas/cirugíaRESUMEN
In this article fully atomistic Molecular Dynamics simulations were employed to study the behaviour of electrolyte salts (NaPF6, NaBF4, and NaTFSI) and different organic solvents (PC, EC, and EMC) in cylindrical carbon nanotubes, in order to reveal the storage mechanism. Organic solutions at 1 M concentrations were considered in bulk reservoir solutions, at the operational condition of sodium ion batteries. The effects of the solvents, nanotube diameter, and different anions (PF6-, BF4-, and TFSI-) are quantified by calculating the number of ions inside the nanotubes, solvation number and radial distribution functions. The solvent, anion and cylindrical nanoconfinement can influence the organic electrolyte solution structure.
RESUMEN
Background: There is observational evidence suggesting that high vitamin D concentrations may protect against lung cancer. To investigate this hypothesis in detail, we measured circulating vitamin D concentrations in prediagnostic blood from 20 cohorts participating in the Lung Cancer Cohort Consortium (LC3). Patients and methods: The study included 5313 lung cancer cases and 5313 controls. Blood samples for the cases were collected, on average, 5 years before lung cancer diagnosis. Controls were individually matched to the cases by cohort, sex, age, race/ethnicity, date of blood collection, and smoking status in five categories. Liquid chromatography coupled with tandem mass spectrometry was used to separately analyze 25-hydroxyvitamin D2 [25(OH)D2] and 25-hydroxyvitamin D3 [25(OH)D3] and their concentrations were combined to give an overall measure of 25(OH)D. We used conditional logistic regression to calculate odds ratios (ORs) and 95% confidence intervals (CIs) for 25(OH)D as both continuous and categorical variables. Results: Overall, no apparent association between 25(OH)D and risk of lung cancer was observed (multivariable adjusted OR for a doubling in concentration: 0.98, 95% CI: 0.91, 1.06). Similarly, we found no clear evidence of interaction by cohort, sex, age, smoking status, or histology. Conclusion: This study did not support an association between vitamin D concentrations and lung cancer risk.