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1.
Int J Rheum Dis ; 27(6): e15204, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38831528

RESUMEN

BACKGROUND: Previous studies have reported low serum 25-hydroxyvitamin D [25(OH)D] levels in dermatomyositis (DM) patients, but the exact causal relationship between them remains elusive. Our aim is to confirm the causal relationship between 25(OH)D and DM risk through a Mendelian randomization study. METHODS: Retrieve genome-wide association study (GWAS) data on 25(OH)D (n = 441 291) and DM (n cases = 201, n controls = 172 834) from the GWAS database (https://gwas.mrcieu.ac.uk/). Select single-nucleotide polymorphisms (SNPs) strongly correlated with 25(OH)D as instrumental variables (IVs). The primary analytical approach involves the use of the inverse-variance weighted method (IVW), supplemented by MR-Egger regression and weighted median methods to enhance the reliability of the results. Heterogeneity and sensitivity analyses were conducted using Cochran's Q and leave-one-out approaches, respectively. RESULTS: The IVW analysis confirmed a positive causal relationship between genetic variation in 25(OH)D levels and DM (OR = 2.36, 95% CI = 1.01-5.52, p = .048). Although not statistically significant (all p > .05), the other methods also suggested a protective effect of 25(OH)D on DM. Based on MR-Egger intercepts and Cochran's Q analysis, the selected SNPs showed no horizontal pleiotropy and heterogeneity. Sensitivity analysis demonstrated the robustness of the results against individual SNPs. CONCLUSION: We provide the first evidence of a causal relationship between 25(OH)D levels and DM. Our findings support the importance of measuring serum 25(OH)D levels and considering vitamin D supplementation in clinical practice for patients with DM.


Asunto(s)
Dermatomiositis , Estudio de Asociación del Genoma Completo , Análisis de la Aleatorización Mendeliana , Polimorfismo de Nucleótido Simple , Vitamina D , Humanos , Vitamina D/análogos & derivados , Vitamina D/sangre , Dermatomiositis/genética , Dermatomiositis/sangre , Dermatomiositis/diagnóstico , Dermatomiositis/epidemiología , Factores de Riesgo , Predisposición Genética a la Enfermedad , Biomarcadores/sangre , Medición de Riesgo , Deficiencia de Vitamina D/sangre , Deficiencia de Vitamina D/genética , Deficiencia de Vitamina D/diagnóstico , Deficiencia de Vitamina D/epidemiología , Estudios de Casos y Controles , Fenotipo , Bases de Datos Genéticas
2.
Front Pharmacol ; 15: 1370661, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38881871

RESUMEN

Objective: To compare the effects of tofacitinib and adalimumab on the risk of adverse lipidaemia outcomes in patients with newly diagnosed rheumatoid arthritis (RA). Methods: Data of adult patients newly diagnosed with RA who were treated with tofacitinib or adalimumab at least twice during a 3-year period from 1 January 2018 to 31 December 2020, were enrolled in the TriNetX US Collaborative Network. Patient demographics, comorbidities, medications, and laboratory data were matched by propensity score at baseline. Outcome measurements include incidental risk of dyslipidemia, major adverse cardiac events (MACE) and all-cause mortality. Results: A total of 7,580 newly diagnosed patients with RA (1998 receiving tofacitinib, 5,582 receiving adalimumab) were screened. After propensity score matching, the risk of dyslipidaemia outcomes were higher in the tofacitinib cohort, compared with adalimumab cohort (hazard ratio [HR] with 95% confidence interval [CI], 1.250 [1.076-1.453]). However, there is no statistically significant differences between two cohorts on MACE (HR, 0.995 [0.760-1.303]) and all-cause mortality (HR, 1.402 [0.887-2.215]). Conclusion: Tofacitinib use in patients with RA may increase the risk of dyslipidaemia to some extent compared to adalimumab. However, there is no differences on MACE and all-cause mortality.

3.
Neurol Ther ; 13(3): 715-725, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38592337

RESUMEN

INTRODUCTION: Recent studies have suggested a potential association between methotrexate use and an increased risk of dementia. However, the causal relationship between methotrexate and dementia remains unclear. This study aims to investigate the potential causal effect of methotrexate use on the risk of dementia using a two-sample Mendelian randomization (TSMR) approach. METHODS: We conducted a TSMR study using summary statistics from genome-wide association studies (GWAS) of methotrexate use and dementia. We obtained genetic instruments for methotrexate use from a large-scale GWAS meta-analysis and genetic instruments for dementia from a separate GWAS meta-analysis. We performed several statistical analyses, including inverse-variance weighted (IVW), weighted median (WM1), weighted mode (WM2), and MR-Egger regression methods, to estimate the causal effect of methotrexate on dementia risk. RESULTS: Our TSMR analysis showed a significant positive association between genetic predisposition to methotrexate use and dementia risk. The IVW method estimated a causal odds ratio (OR) of 0.476 [95% confidence interval (CI) 0.362-0.626] per unit increase in the log odds ratio of methotrexate use. WM1, WM2, and MR-Egger methods provided consistent results. CONCLUSION: The findings of this mendelian randomization (MR) study suggest a potential causal effect of methotrexate use on the risk of dementia. However, further research is needed to validate these findings and explore the underlying mechanisms. Since methotrexate is widely prescribed for various autoimmune diseases, a better understanding of its potential impact on dementia risk is crucial for optimizing treatment strategies and addressing potential adverse effects.

4.
Immun Inflamm Dis ; 12(2): e1190, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38376948

RESUMEN

BACKGROUND: The main subtypes of idiopathic inflammatory myopathies (IIMs)-polymyositis (PM) and dermatomyositis (DM)-are often presented as interstitial lung disease (ILD) in clinical practice; therefore, many researchers have combined the three studies into PM/DM with ILD. METHODS: Using bibliometrics, the research status, progress, and hotspots of PM/DM with ILD between 2000 and 2022 were studied. Literature data on PM/DM with ILD were retrieved from the Web of Science (WoS) database for the research period. Visualization software, including VOSviewer, Pajek, CiteSpace, and Scimago Graphica were used for bibliometric analysis. RESULTS: A total of 1555 relevant articles were obtained, and the overall research in this field showed an increasing trend. Regarding contributing countries and venues, Japan published the most articles while Rheumatology was the most prolific journal. Regarding authors, the most published article was by Wang Guochun from Changchun University of Technology in China. Keyword analysis and cocited literature cluster analysis showed that diagnosis, classification, autoantibodies, antibodies, prognosis, complications, and treatment of PM/DM with ILD have been hot topics in this field recently. Moreover, our study shows that anti-mda5 antibody, mortality, gene 5 antibody, IIMs, double-blind, and prognostic factors, among others, may be new hot topics. CONCLUSION: This study found that research on PM/DM with ILD has increased over time, and scholars are paying more attention to this field. The development of new drugs for the management, treatment, and prevention of PM/DM with ILD is the primary task of researchers and a direction for future research in this field.


Asunto(s)
Dermatomiositis , Enfermedades Pulmonares Intersticiales , Polimiositis , Humanos , Dermatomiositis/epidemiología , Dermatomiositis/complicaciones , Estudios Retrospectivos , Polimiositis/complicaciones , Enfermedades Pulmonares Intersticiales/complicaciones , Pronóstico , Ensayos Clínicos Controlados Aleatorios como Asunto
5.
Cancer Immunol Immunother ; 73(1): 14, 2024 Jan 18.
Artículo en Inglés | MEDLINE | ID: mdl-38236288

RESUMEN

Blood-based biomarkers of immune checkpoint inhibitors (ICIs) response in patients with nasopharyngeal carcinoma (NPC) are lacking, so it is necessary to identify biomarkers to select NPC patients who will benefit most or least from ICIs. The absolute values of lymphocyte subpopulations, biochemical indexes, and blood routine tests were determined before ICIs-based treatments in the training cohort (n = 130). Then, the least absolute shrinkage and selection operator (Lasso) Cox regression analysis was developed to construct a prediction model. The performances of the prediction model were compared to TNM stage, treatment, and Epstein-Barr virus (EBV) DNA using the concordance index (C-index). Progression-free survival (PFS) was estimated by Kaplan-Meier (K-M) survival curve. Other 63 patients were used for validation cohort. The novel model composed of histologic subtypes, CD19+ B cells, natural killer (NK) cells, regulatory T cells, red blood cells (RBC), AST/ALT ratio (SLR), apolipoprotein B (Apo B), and lactic dehydrogenase (LDH). The C-index of this model was 0.784 in the training cohort and 0.735 in the validation cohort. K-M survival curve showed patients with high-risk scores had shorter PFS compared to the low-risk groups. For predicting immune therapy responses, the receiver operating characteristic (ROC), decision curve analysis (DCA), net reclassifcation improvement index (NRI) and integrated discrimination improvement index (IDI) of this model showed better predictive ability compared to EBV DNA. In this study, we constructed a novel model for prognostic prediction and immunotherapeutic response prediction in NPC patients, which may provide clinical assistance in selecting those patients who are likely to gain long-lasting clinical benefits to anti-PD-1 therapy.


Asunto(s)
Infecciones por Virus de Epstein-Barr , Neoplasias Nasofaríngeas , Humanos , Infecciones por Virus de Epstein-Barr/complicaciones , Carcinoma Nasofaríngeo/terapia , Herpesvirus Humano 4 , Inmunoterapia , Pronóstico , Antígenos CD19 , Neoplasias Nasofaríngeas/terapia , ADN
6.
Phytomedicine ; 123: 155243, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38056147

RESUMEN

BACKGROUND: Rheumatoid arthritis (RA) is a chronic autoimmune disease that can cause joint inflammation and damage. Leonurine (LE) is an alkaloid found in Leonurus heterophyllus. It has anti-inflammatory effects. HYPOTHESIS/PURPOSE: The molecular mechanisms by which LE acts in RA are unclear and further investigation is required. METHODS: Mice with collagen-induced arthritis (CIA), and RA-fibroblast-like synoviocytes (FLSs) isolated from them were used as in vivo and in vitro models of RA, respectively. The therapeutic effects of LE on CIA-induced joint injury were investigated by micro-computed tomography, and staining with hematoxylin and eosin and Safranin-O/Fast Green. Cell Counting Kit-8, a Transwell® chamber, enzyme-linked immunosorbent assays, RT-qPCR, and western blotting were used to investigate the effects of LE on RA-FLS viability, migratory capacity, inflammation, microRNA-21 (miR-21) levels, the Hippo signaling pathway, and the effects and intrinsic mechanisms of related proteins. Dual luciferase was used to investigate the binding of miR-21 to YOD1 deubiquitinase (YOD1) and yes-associated protein (YAP). Immunofluorescence was used to investigate the localization of YAP within the nucleus and cytoplasm. RESULTS: Treatment with LE significantly inhibited joint swelling, bone damage, synovial inflammation, and proteoglycan loss in the CIA mice. It also reduced the proliferation, cell colonization, migration/invasion, and inflammation levels of RA-FLSs, and promoted miR-21 expression in vitro. The effects of LE on RA-FLSs were enhanced by an miR-21 mimic and reversed by an miR-21 inhibitor. The dual luciferase investigation confirmed that both YOD1 and YAP are direct targets of miR-21. Treatment with LE activated the Hippo signaling pathway, and promoted the downregulation and dephosphorylation of MST1 and LATS1 in RA, while inhibiting the activation of YOD1 and YAP. Regulation of the therapeutic effects of LE by miR-21 was counteracted by YOD1 overexpression, which caused the phosphorylation of YAP and prevented its nuclear ectopic position, thereby reducing LE effect on pro-proliferation-inhibiting apoptosis target genes. CONCLUSION: LE regulates the Hippo signaling pathway through the miR-21/YOD1/YAP axis to reduce joint inflammation and bone destruction in CIA mice, thereby inhibiting the growth and inflammation of RA-FLSs. LE has potential for the treatment of RA.


Asunto(s)
Artritis Experimental , Artritis Reumatoide , Ácido Gálico/análogos & derivados , MicroARNs , Animales , Ratones , Vía de Señalización Hippo , Microtomografía por Rayos X , Artritis Reumatoide/metabolismo , Artritis Experimental/inducido químicamente , MicroARNs/genética , Inflamación/metabolismo , Luciferasas/metabolismo , Luciferasas/farmacología , Luciferasas/uso terapéutico , Proliferación Celular , Fibroblastos , Células Cultivadas
7.
J Nurs Res ; 31(6): e304, 2023 Dec 01.
Artículo en Inglés | MEDLINE | ID: mdl-38036492

RESUMEN

BACKGROUND: Workplace violence (WPV) is a well-known and serious issue in most countries, and WPV against healthcare providers is of particular concern, especially among nurses working in emergency rooms (ERs). PURPOSE: We aimed to develop a deeper understanding of nurses' perceptions and coping strategies related to WPV that took place over a 1-year period from the perspective of nursing victims still working in ERs in southern Taiwan. METHODS: This is a qualitative study with in-depth and semistructured interviews. Nineteen ER nurse victims were recruited from six hospitals in southern Taiwan from June 2015 to April 2016. All of the interview recordings were analyzed using content analysis. RESULTS: The content analysis identified two themes of perceptions and two themes of coping strategies toward WPV. The two themes of perceptions were "adversity" and "dilemma," with the former covering the three subthemes of "misunderstanding of health policy," "unsafe environment," and "nursing shortage" and the latter covering the two subthemes of "burnout" and "keeping or quitting the job." The two themes of coping strategies were "adjustment" and "resilience," with the former covering the three subthemes of "acceptance of the reality of WPV," "self-regulation," and "culture and belief" and the latter covering the two subthemes of "living with WPV" and "problem solving." CONCLUSIONS/IMPLICATIONS FOR PRACTICE: The findings revealed that ER nurse victims of WPV experienced a complicated journey after encountering WPV. Their coping strategies may be referenced by other ER nurses to better prevent and manage violent events in ERs. To prevent and manage violence in ERs, hospital managers should create a safe working environment through, for example, assigning sufficient security personnel and staff; provide relevant training to ER nurses in communications and other skills; and implement support systems to strengthen nurse resilience.


Asunto(s)
Enfermeras y Enfermeros , Violencia Laboral , Humanos , Estudios Transversales , Encuestas y Cuestionarios , Adaptación Psicológica , Servicio de Urgencia en Hospital , Lugar de Trabajo
8.
J Immunother Cancer ; 11(8)2023 08.
Artículo en Inglés | MEDLINE | ID: mdl-37536937

RESUMEN

BACKGROUND: Immune checkpoint inhibitors (ICIs)-based treatments have been recommended as the first line for refractory recurrent and/or metastatic nasopharyngeal carcinoma (NPC) patients, yet responses vary, and predictive biomarkers are urgently needed. We selected serum interleukin-15 (sIL-15) out of four interleukins as a candidate biomarker, while most patients' sIL-15 levels were too low to be detected by conventional methods, so it was necessary to construct a highly sensitive method to detect sIL-15 in order to select NPC patients who would benefit most or least from ICIs. METHODS: Combining a primer exchange reaction (PER), transcription-mediated amplification (TMA), and a immuno-PER-TMA-CRISPR/Cas13a system, we developed a novel multiple signal amplification platform with a detection limit of 32 fg/mL, making it 153-fold more sensitive than ELISA. RESULTS: This platform demonstrated high specificity, repeatability, and versatility. When applied to two independent cohorts of 130 NPC sera, the predictive value of sIL-15 was accurate in both cohorts (area under the curve: training, 0.882; validation, 0.898). Additionally, lower sIL-15 levels were correlated with poorer progression-free survival (training, HR: 0.080, p<0.0001; validation, HR: 0.053, p<0.0001). CONCLUSION: This work proposes a simple and sensitive approach for sIL-15 detection to provide insights for personalized immunotherapy of NPC patients.


Asunto(s)
Interleucina-15 , Neoplasias Nasofaríngeas , Humanos , Carcinoma Nasofaríngeo/terapia , Interleucina-15/genética , Neoplasias Nasofaríngeas/terapia , Neoplasias Nasofaríngeas/genética , Repeticiones Palindrómicas Cortas Agrupadas y Regularmente Espaciadas , Ensayo de Inmunoadsorción Enzimática
9.
Inflammopharmacology ; 31(5): 2383-2392, 2023 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-37493915

RESUMEN

BACKGROUND: Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease characterized by joint swelling, pain, and deformation. RA patients have an increased risk of thyroid dysfunction, and drugs of RA treatment may have potential effects on thyroid function. METHODS: This is a single-center cross-sectional study including 281 inpatients with RA in the First Affiliated Hospital of Guangzhou University of Chinese Medicine. The purpose of this study is to explore the correlation between RA therapeutic drugs and thyroid function. The medical records of 281 inpatients with RA were collected, including general data, laboratory examination, complications, and RA treatment. Spearman correlation analysis was used to explore the association of independent variables with thyroid function and antibodies in RA patients. Multinomial logistics and binary logistic regression were used for multivariate analysis. The statistically significance level was set as P < 0.05. SPSS 22.0 was used for statistical analysis. RESULTS: Patients taking methotrexate (OR = 0.067, 95%CI: 0.008-0.588, P = 0.015) had lower levels of total thyroxine (TT4) (TT4 < 78.38 nmol/L). There was a negative correlation between glucocorticoids (r = - 0.153, P = 0.010) and total triiodothyronine (TT3) level (TT3 ≥ 1.34 nmol/L), but it was not significant in the multivariate regression model of TT3, although the regression model was statistically significant (P = 0.001). CONCLUSION: Methotrexate is associated with decreased TT4 levels in RA patients, and glucocorticoids is associated with decreased TT3 levels. Drugs of RA treatment may affect the thyroid function of patients while treating RA, which may be one of the causes of secondary thyroid diseases in RA patients.


Asunto(s)
Artritis Reumatoide , Tiroxina , Humanos , Metotrexato/efectos adversos , Estudios Transversales , Glucocorticoides , Artritis Reumatoide/tratamiento farmacológico
10.
PeerJ ; 11: e15419, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37304887

RESUMEN

Backgrounds: Early detection might help in reducing the burden and promoting the survival rate of gastric cancers. Herein, we tried to explore the diagnostic value of insulin-like growth factor binding protein 7 (IGFBP7) in gastric cancers. Methods: In this study, we first analyzed the expression levels and prognostic value of IGFBP7 mRNA in gastric cancers from The Cancer Genome Atlas (TCGA) database. Then, we recruited 169 gastric cancer patients and 100 normal controls as training cohort, and 55 gastric cancer patients and 55 normal controls as independent validation cohort. Enzyme-linked immunosorbent assay was applied to test the serum levels of IGFBP7. The receiver operating characteristic curve (ROC) and the area under the curve (AUC) were applied to evaluation the diagnostic value. Results: TCGA showed that IGFBP7 mRNA was dysregulated and associated with prognosis in gastric cancer patients. Then, we examined the expression of serum IGFBP7 and found that serum IGFBP7 expressed lower in gastric cancer patients than normal controls both in training and independent validation cohorts (p < 0.0001). In training cohort, with the cutoff value of 1.515 ng/ml, the AUC for distinguishing gastric cancer patients was 0.774 (95% CI [0.713-0.836]) with sensitivity of 36.7% (95% CI [29.5-44.5]) and specificity of 90.0% (95% CI [82.0-94.8]). As for early-stage EJA, the AUC was 0.773 (95% CI [0.701-0.845]) with the sensitivity of 33.3% (95% CI [14.4-58.8]). In independent validation cohort, with the same cutoff value, the AUC reached to 0.758 (95% CI [0.664-0.852]). Similarly, for early-stage gastric cancer diagnosis in the independent validation cohort, the AUC value was 0.778 (95% CI [0.673-0.882]). Conclusions: This study indicated that serum IGFBP7 might act as a potential early diagnostic marker for gastric cancers.


Asunto(s)
Neoplasias Gástricas , Humanos , Área Bajo la Curva , Proteínas de Unión a Factor de Crecimiento Similar a la Insulina/genética , ARN Mensajero/genética , Neoplasias Gástricas/diagnóstico
11.
Immun Inflamm Dis ; 10(10): e717, 2022 10.
Artículo en Inglés | MEDLINE | ID: mdl-36169251

RESUMEN

OBJECTIVE: Typically, Jaccoud arthropathy (JA) is characterized by joint deformation without bone erosion. However, some recent studies have shown that bone erosion also occurs in JA; however, this remains controversial. To date, there have been no unified diagnostic standards for JA. Herein, we report a case of systemic lupus erythematosus complicated with JA without bone erosion. METHODS: A 27-year-old woman was admitted to our department with a 2-year history of pain, swelling, and progressive deformities of her hands and feet. She was diagnosed with systemic lupus erythematosus and class V lupus nephritis 5 years prior. Upon examination, her erythrocyte sedimentation rate and C-reactive protein levels were found to be increased. She was positive for antinuclear antibodies, antidouble stranded DNA antibodies, and antiextractable nuclear antigen antibodies, with a decreased complement C3 and C4. Radiography and magnetic resonance imaging revealed no bone erosion. The patient was diagnosed with JA. She was treated with oral prednisone (10 mg daily), tofacitinib (5 mg twice daily), methotrexate (10 mg weekly), and celecoxib (0.2 g twice daily). RESULTS: The patient's joint symptoms improved after treatment. No further progress was observed during the 4-month follow-up period. CONCLUSION: We believe that bone erosion is the key to distinguish rhupus syndrome from JA. However, this needs to be confirmed with further long-term follow-up studies. We found that the use tofacitinib, MTX, and celecoxib in combination with prednisone may be an effective regimen for the treatment of JA.


Asunto(s)
Artritis Reumatoide , Lupus Eritematoso Sistémico , Adulto , Anticuerpos Antinucleares , Antígenos Nucleares , Artritis Reumatoide/complicaciones , Artritis Reumatoide/patología , Proteína C-Reactiva , Celecoxib , Complemento C3 , ADN , Femenino , Humanos , Lupus Eritematoso Sistémico/complicaciones , Lupus Eritematoso Sistémico/diagnóstico , Lupus Eritematoso Sistémico/tratamiento farmacológico , Metotrexato , Prednisona
12.
Cancer Cell Int ; 21(1): 643, 2021 Dec 03.
Artículo en Inglés | MEDLINE | ID: mdl-34861873

RESUMEN

BACKGROUND: Human papillomavirus (HPV) E6/E7 mRNA in situ hybridization (HPV E6/E7 RNAscope) appears to be a sensitive and specific technique in detecting transcriptionally active HPV. We aimed to examine the diagnostic utility of this technique in endocervical adenocarcinoma (ECA), to explore the prognostic factors for ECA patients and develop a clinically useful nomogram based on clinicopathological parameters to predict it. METHODS: We retrospectively analyzed 200 patients with ECA who had undergone surgery at Sun Yat-sen University Cancer Center from 2010 and 2014. The diagnostic performance of HPV E6/E7 RNAscope were evaluated by receiver operating characteristic (ROC) curve. A prognostic nomogram model including HPV E6/E7 RNAscope was generated based on multivariate Cox regression analysis, then we compared the predictive accuracy of the prognostic model with FIGO staging and treatment using concordance index (C-index), time-dependent ROC (tdROC), and decision curve analysis (DCA). RESULTS: The sensitivity and specificity of HPV E6/E7 RNAscope for distinguishing HPV-associated adenocarcinoma (HPVA) from non-HPV-associated adenocarcinoma (NHPVA) in the whole cohort were 75.8% and 80%, respectively. According the univariate analysis and multivariate logistic regression analysis, age, lymphovascular invasion (LVI), lymph node involvement (LNI), and HPV E6/E7 RNAscope were valuable predictive factors for OS. These parameters were incorporated into the nomogram model (nomogram A) compared with FIGO stage and treatment. The C-index of nomogram A for predicting OS was 0.825, which was significantly higher than FIGO stage (C-index = 0.653, p = 0.002) and treatment (C-index = 0.578, p < 0.001). CONCLUSIONS:  HPV E6/E7 RNAscope is highly specific for ECA, and the 4-variable nomogram showed more accurate prognostic outcomes in patients with ECA.

13.
EBioMedicine ; 51: 102566, 2020 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-31901863

RESUMEN

BACKGROUND: Early detection would improve upper gastrointestinal cancer prognosis. We aimed to identify serum protein biomarker for the detection of early-stage upper gastrointestinal cancer. METHODS: We performed a three-tiered study including 2028 participants from three medical centres. First, we applied two different antibody arrays to screen candidate serum proteins that increased in 20 patients with oesophageal squamous cell carcinoma (ESCC) compared with 20 normal controls. We then evaluated the selected protein by enzyme-linked immunosorbent assay in 1064 participants including 731 upper gastrointestinal cancer patients (287 ESCCs, 237 oesophagogastric junction adenocarcinomas (EJAs), and 207 stomach cancers) and 333 normal controls. The diagnostic value of the selected protein was finally validated in two independent cohorts of ESCC patients and controls (n=472 and 452, respectively). The receiver operating characteristic was used to calculate diagnostic accuracy. FINDINGS: Serum insulin-like growth factor binding protein-1 (IGFBP-1) identified in both antibody arrays showed significantly elevated levels in upper gastrointestinal cancers, compared with normal controls. Serum IGFBP-1 provided high diagnostic accuracy of early-stage ESCC, EJA, stomach and cancer (areas under the curve: 0·898, 0·936 and 0·864, respectively). This protein maintained diagnostic performance for early-stage ESCC in independent cohorts 1 and 2 (0·849 and 0·911, respectively). Additionally, serum levels of IGFBP-1 dropped significantly after surgical resection of primary tumours, compared with the corresponding pre-operative ESCC samples (p < 0·05). INTERPRETATION: Serum IGFBP-1 represents a promising diagnostic biomarker to detect early-stage upper gastrointestinal cancer.


Asunto(s)
Biomarcadores de Tumor/sangre , Detección Precoz del Cáncer , Carcinoma de Células Escamosas de Esófago/sangre , Carcinoma de Células Escamosas de Esófago/diagnóstico , Proteína 1 de Unión a Factor de Crecimiento Similar a la Insulina/sangre , Anticuerpos Antineoplásicos/inmunología , Carcinoma de Células Escamosas de Esófago/inmunología , Carcinoma de Células Escamosas de Esófago/patología , Humanos , Estadificación de Neoplasias , Curva ROC , Reproducibilidad de los Resultados
14.
Int J Biol Sci ; 15(9): 1977-1992, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31523198

RESUMEN

Background: Currently, there are no molecular biomarkers for the early detection of non-small-cell lung cancer (NSCLC). This study focused on identifying RNAs found on tumor-educated blood platelets (TEPs) for detecting stage I NSCLC. Methods: Platelet RNAs, isolated from the blood of 9 patients with NSCLC (stages I and II) and 8 healthy controls, were analyzed using RNA-seq. ITGA2B was selected as a candidate marker. Two different Polymerase Chain Reactions (PCR) were used to measure ITGA2B in platelet samples from healthy controls (n = 150), patients with NSCLC (n = 243), and patients with benign pulmonary nodules (n = 141) in two cohorts. Results: Platelet ITGA2B levels were significantly higher (p < 0.001) in patients with NSCLC than in all controls. The diagnostic accuracy of ITGA2B was area under the curve (AUC) of 0.922 [95% confidence interval (CI), 0.892-0.952], sensitivity of 92.8%, and specificity of 78.6% in the test cohort and 0.888, 91.2%, and 56.5% in the validation cohort for NSCLC by quantitative real time PCR (q-PCR). Furthermore, ITGA2B maintained diagnostic accuracy for patients with NSCLC using Droplet Digital PCR (ddPCR) and the other type of internal control, Ribosomal Protein L32 (RPL32) [ddPCR: 0.967 (0.929-1.000) and RPL32: 0.847(0.773-0.920)]. A nomogram incorporating ITGA2B, carcinoembryonic antigen (CEA) and stage could predict the overall survival (C-index = 0.756). Conclusions: TEP ITGA2B is a promising marker to improve identification of patients with stage I NSCLC and differentiate malignant from benign lung nodules.


Asunto(s)
Biomarcadores de Tumor/metabolismo , Plaquetas/metabolismo , Carcinoma de Pulmón de Células no Pequeñas/metabolismo , Carcinoma de Pulmón de Células no Pequeñas/patología , Integrina alfa2/metabolismo , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patología , Femenino , Humanos , Integrina alfa2/genética , Masculino , Persona de Mediana Edad , Selectina-P/genética , Selectina-P/metabolismo , Reacción en Cadena en Tiempo Real de la Polimerasa , Análisis de Secuencia de ARN
15.
BMC Cancer ; 19(1): 538, 2019 Jun 04.
Artículo en Inglés | MEDLINE | ID: mdl-31164099

RESUMEN

BACKGROUND: Despite recent advances in the treatments of hepatocellular carcinoma (HCC), the prognosis of HCC patients remains controversial. The purpose of this study was to investigate the prognostic performance of pretreatment albumin to C-reactive protein ratio (ACR) in patients with HCC. METHODS: This study included 409 initially diagnosed HCC patients retrospectively. The optimal cut-off points for distinguishing high and low ACR value was determined by the X-tile software. The chi-squared test was used for comparing the baseline clinicopathologic parameters in different groups and subgroups. The Cox regression with log-rank tests was used to analyze OS and DFS, and Kaplan-Meier curves was used to estimate the prognosis of HCC patients. RESULTS: Patients with lower ACR were significantly correlated with advanced clinical parameters, using a cut-off points of 5.4 (high ACR, n = 236 vs. low ACR, n = 173). Multivariate analysis demonstrated that ACR was associated with OS (HR = 0.544, 95% CI: 0.385-0.769, p = 0.001), with DFS (HR = 0.550, 95% CI: 0.392-0.772, p = 0.001). Treatment exposure (HR = 2.191; 95% CI: 1.533-3.132; p <  0.001), tumor size (HR = 1.973; 95% CI: 1.230-3.164; p = 0.005), serum AFP level (HR = 1.752; 95% CI: 1.277-2.403; p = 0.001), and TNM stage (HR = 0.470; 95% CI: 0.319-2.504; p <  0.001), were independent factors for OS in HCC patients. Treatment exposure (HR = 2.244; 95% CI: 1.590-3.166; p <  0.001), TNM stage (HR = 2.075; 95% CI: 1.436-3.000; p <  0.001), serum AFP level (HR = 1.819; 95% CI: 1.340-2.469; p = 0.001), tumor size (HR = 1.730; 95% CI: 1.113-2.689; p = 0.015), and ACR (HR = 0.550; 95% CI: 0.392-0.772; p = 0.001) were independent factors for DFS in HCC patients. CONCLUSIONS: Pretreatment ACR is a convenient and useful parameter for HCC patients predicting OS and DFS. Lower ACR was associated with advanced TNM stage, larger tumor size, and a high concentration of AFP. These results may help to design strategies to personalize management approaches among HCC patients.


Asunto(s)
Proteína C-Reactiva/análisis , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/mortalidad , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/mortalidad , Albúmina Sérica Humana/análisis , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores de Tumor/análisis , Distribución de Chi-Cuadrado , Supervivencia sin Enfermedad , Femenino , Estudios de Seguimiento , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Pronóstico , Modelos de Riesgos Proporcionales , Estudios Retrospectivos , Carga Tumoral , Adulto Joven , alfa-Fetoproteínas/análisis
16.
J Cancer ; 9(10): 1877-1884, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-29805715

RESUMEN

Background: Many studies have shown the prognostic value of inflammation based factors in different cancers. This work aimed to explore the prognostic value of pretreatment C-reactive protein/albumin (CRP/Alb) ratio in patients with cervical cancer, and compared to other inflammatory prognostic factors, such as neutrophil/lymphocyte ratio(NLR), Glasgow prognostic score (mGPS), prognostic index (PI), platelet/lymphocyte ratio (PLR), prognostic nutritional index (PNI), clinicopathological parameter and squamous cell carcinoma antigen (SCC-Ag). Methods: This study was a retrospective analysis of the data related to 229 patients with newly diagnosed cervical cancer. The potential prognostic factors were evaluated by univariate and multivariate survival analysis. The correlation between CRP/Alb ratio and other prognostic factors were analyzed by Chi-Square or Fisher's exact test. Results: Multivariate analyses showed that CRP/Alb ratio was an independent predictor of overall survival (OS) in cervical squamous cell carcinoma (SCC) (HR, hazard ratio = 2.529; p = 0.045), but not in all cases of cervical cancer. However, NLR was a prognostic factor in the whole cervical cancer (HR = 2.47; p = 0.020) as well as in SCC subgroup (HR = 2.28; p = 0.038). Spearman's rank correlation analysis revealed that NLR showed a positive correlation with CRP/Alb ratio (p < 0.001). The combined index of NLR and CRP/Alb ratio could enhance the prognostic value compared to NLR or CRP/Alb ratio alone. Moreover, a high CRP/Alb ratio > 0.022 was associated with older patients (p < 0.001) and more advanced International Federation of Gynecology and Obstetrics (FIGO) stages (p < 0.001). In addition, NLR and CRP/Alb ratio were associated with SCC-Ag concentration in SCC. Furthermore, CRP/Alb ratio was a superior prognosis factor than mGPS, PI, PLR and PNI in SCC. Moreover, positive correlation was present among SCC-Ag, NLR and CRP/Alb ratio. Conclusions: CRP/Alb ratio might be considered as a novel prognosis factor and combined with NLR could improve the accuracy of OS prediction in patients with cervical cancer as well as its most common histological SCC subtypes.

17.
J Nurs Res ; 25(2): 99-111, 2017 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-28277390

RESUMEN

BACKGROUND: Practicing a health-promoting lifestyle is believed to be effective for delaying or preventing the onset of diabetes. However, although empowerment interventions have proven effective for encouraging the adoption of a health-promoting lifestyle in people with diabetes, these interventions are rarely promoted to people with prediabetes. PURPOSE: The aims of this study were to develop an empowerment program for people with prediabetes and to examine its efficacy in terms of the adoption of a health-promoting lifestyle and improvements in blood sugar, body mass index, and self-efficacy. METHODS: A randomized controlled trial was conducted between May and December 2013. A convenience sample of people with a fasting blood sugar level of 100-125 mg/dl during the previous 3 months was recruited from the health examination center of a hospital in Kaohsiung, Taiwan. Participants were assigned to either the experimental group or the control group using block randomization with a block size of 8. The experimental group (n = 38) participated in a 4-month empowerment program (the ABC empowerment program), which encouraged participants to practice a health-promoting lifestyle in three phases: awareness raising, behavior building, and results checking. The control group (n = 40) received routine clinical care. Statistical analyses included descriptive statistics, independent t test, paired t test, and generalized estimated equations. RESULTS: After controlling for the differences at baseline and considering the interaction between group and time from baseline to 1 week and 3 months after completing the intervention, the generalized estimating equation showed significantly larger improvements in a health-promoting lifestyle, blood sugar, and self-efficacy in the experimental group than in the control group (p < .01). Furthermore, the experimental group achieved a larger reduction in body mass index than the control group at 3 months after completing the intervention (p = .001). CONCLUSIONS/IMPLICATIONS FOR PRACTICE: The empowerment program was shown to have short-term, positive effects on behavioral, physical, and psychosocial outcomes in a Taiwan population with prediabetes. The results of this study provide a useful reference not only for healthcare personnel when implementing empowerment interventions in people with prediabetes but also for nursing educators and healthcare policymakers.


Asunto(s)
Estilo de Vida Saludable , Educación del Paciente como Asunto , Poder Psicológico , Estado Prediabético/terapia , Autocuidado/psicología , Autoeficacia , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Taiwán
18.
J Gerontol B Psychol Sci Soc Sci ; 72(1): 120-128, 2017 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-27013536

RESUMEN

OBJECTIVES: To examine the relationship between loneliness and cognitive function and to explore the mediating role of physical health on the loneliness-cognition relationship in Chinese older adults (OAs). METHOD: Data came from a nationally representative sample of 14,199 Chinese OAs (aged 65+) from 2002, 2005, 2008, and 2011 waves of the Chinese Longitudinal Healthy Longevity Survey. A latent variable cross-lagged panel model combined with mediation analysis was used to determine the relationship between loneliness and cognitive function and the mediating effect of increase in the number of chronic conditions (ΔNCCs) on the ascertained loneliness-cognition relationship. RESULTS: Severe loneliness at prior assessment points was significantly associated with poorer cognitive function at subsequent assessments, and vice versa. The ΔNCCs partially mediated this prospective reciprocal relationships, accounting for 2.58% of the total effect of loneliness on cognition and 4.44% of the total effect of cognition on loneliness, respectively. DISCUSSION: Loneliness may predict subsequent cognitive decline, and vice versa. This loneliness-cognition relationship is partially explained by their impact on physical health. Multidisciplinary interventions aimed at reducing loneliness and cognitive decline per se and their associated risk factors as well as improving chronic illness management would be beneficial for emotional well-being and cognitive health in OAs.


Asunto(s)
Pueblo Asiatico/psicología , Envejecimiento Cognitivo/psicología , Soledad/psicología , Longevidad , Psicometría/estadística & datos numéricos , Encuestas y Cuestionarios , Anciano , Anciano de 80 o más Años , Enfermedad Crónica/etnología , Enfermedad Crónica/psicología , Disfunción Cognitiva/etnología , Disfunción Cognitiva/psicología , Estudios de Cohortes , Femenino , Humanos , Estudios Longitudinales , Masculino , Escala del Estado Mental/estadística & datos numéricos , Calidad de Vida/psicología
19.
Int J Mol Sci ; 17(11)2016 Nov 15.
Artículo en Inglés | MEDLINE | ID: mdl-27854304

RESUMEN

Recent studies have indicated that inflammation-based prognostic scores, such as the Glasgow Prognostic Score (GPS), modified GPS (mGPS) and C-reactive protein/Albumin (CRP/Alb) ratio, platelet-lymphocyte ratio (PLR), and neutrophil-lymphocyte ratio (NLR), have been reported to have prognostic value in patients with many types of cancer, including nasopharyngeal carcinoma (NPC). In this study, we proposed a novel inflammation-based stage, named I stage, for patients with NPC. A retrospective study of 409 newly-diagnosed cases of NPC was conducted. The prognostic factors (GPS, mGPS, CRP/Alb ratios, PLR, and NLR) were evaluated using univariate and multivariate analyses. Then, according to the results of the multivariate analyses, we proposed a I stage combination of independent risk factors (CRP/Alb ratio and PLR). The I stage was calculated as follows: patients with high levels of CRP/Alb ratio (>0.03) and PLR (>146.2) were defined as I2; patients with one or no abnormal values were defined as I1 or I0, respectively. The relationships between the I stage and clinicopathological variables and overall survival (OS) were evaluated. In addition, the discriminatory ability of the I stage with other inflammation-based prognostic scores was assessed using the AUCs (areas under the curves) analyzed by receiver operating characteristics (ROC) curves. The p value of <0.05 was considered to be significant. A total of 409 patients with NPC were enrolled in this study. Multivariate analyses revealed that only the CRP/Alb ratio (Hazard ratio (HR) = 2.093; 95% Confidence interval (CI): 1.222-3.587; p = 0.007) and PLR (HR: 2.003; 95% CI: 1.177-3.410; p = 0.010) were independent prognostic factors in patients with NPC. The five-year overall survival rates for patients with I0, I1, and I2 were 92.1% ± 2.9%, 83.3% ± 2.6%, and 63.1% ± 4.6%, respectively (p < 0.001). The I stage had a higher area under the curve value (0.670) compared with other systemic inflammation-based prognostic scores (p < 0.001). The I stage is a novel and useful predictive factor for OS in patients with NPC.


Asunto(s)
Plaquetas/patología , Proteína C-Reactiva/metabolismo , Neoplasias Nasofaríngeas/diagnóstico , Neoplasias Nasofaríngeas/mortalidad , Neutrófilos/patología , Albúmina Sérica/metabolismo , Adulto , Anciano , Área Bajo la Curva , Biomarcadores/sangre , Carcinoma , Recuento de Células , Femenino , Escala de Consecuencias de Glasgow , Humanos , Inflamación , Masculino , Persona de Mediana Edad , Análisis Multivariante , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas/sangre , Neoplasias Nasofaríngeas/patología , Estadificación de Neoplasias , Pronóstico , Curva ROC , Estudios Retrospectivos , Factores de Riesgo , Análisis de Supervivencia
20.
Int J Mol Sci ; 17(9)2016 Sep 03.
Artículo en Inglés | MEDLINE | ID: mdl-27598151

RESUMEN

The purpose of this work is to analyze preoperative serum aspartate aminotransferase (AST) levels and their effect on the prognosis of patients with non-small cell lung cancer (NSCLC) after surgical operation. These analyses were performed retrospectively in patients with NSCLC followed by surgery; participants were recruited between January 2004 and January 2008. All clinical information and laboratory results were collected from medical records. We explored the association between preoperative serum AST and recurrence-free survival (RFS), and the overall survival (OS) of NSCLC patients. Kaplan-Meier analysis and Cox multivariate analysis, stratified by the AST median value, were used to evaluate the prognostic effect. A chi-squared test was performed to compare clinical characteristics in different subgroups. A p-value of ≤0.05 was considered to be statistically significant. A total of 231 patients were enrolled. The median RFS and OS were 22 and 59 months, respectively. The AST levels were divided into two groups, using a cut-off value of 19 U/L: High AST (>19 U/L), n = 113 vs. low AST (≤19 U/L), n = 118. Multivariate analysis indicated that preoperative serum AST > 19 U/L (hazard ratio (HR) = 0.685, 95% confidence interval (CI): 0.493-0.994, p = 0.046 for RFS, HR = 0.646, 95% CI: 0.438-0.954, p = 0.028 for OS) was an independent prognostic factor for both RFS and OS. High preoperative serum AST levels may serve as a valuable marker to predict the prognosis of NSCLC after operation.


Asunto(s)
Aspartato Aminotransferasas/sangre , Biomarcadores de Tumor/sangre , Carcinoma de Pulmón de Células no Pequeñas/sangre , Neoplasias Pulmonares/sangre , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma de Pulmón de Células no Pequeñas/cirugía , Femenino , Humanos , Neoplasias Pulmonares/cirugía , Masculino , Persona de Mediana Edad , Periodo Preoperatorio , Análisis de Supervivencia
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