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1.
J Cell Mol Med ; 28(18): e70096, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39289804

RESUMEN

Metabolic associated fatty liver disease (MAFLD) is the most common chronic liver disease worldwide, characterized by excess lipid deposition. Insulin resistance (IR) serves as a fundamental pathogenic factor in MAFLD. However, currently, there are no approved specific agents for its treatment. Farrerol, a novel compound with antioxidant and anti-inflammatory effects, has garnered significant attention in recent years due to its hepatoprotective properties. Despite this, the precise underlying mechanisms of action remain unclear. In this study, a network pharmacology approach predicted protein tyrosine phosphatase non-receptor type 1 (PTPN1) as a potential target for farrerol's action in the liver. Subsequently, the administration of farrerol improved insulin sensitivity and glucose tolerance in MAFLD mice. Furthermore, farrerol alleviated lipid accumulation by binding to PTPN1 and reducing the dephosphorylation of the insulin receptor (INSR) in HepG2 cells and MAFLD mice. Thus, the phosphoinositide 3-kinase/serine/threonine-protein kinases (PI3K/AKT) signalling pathway was active, leading to downstream protein reduction. Overall, the study demonstrates that farrerol alleviates insulin resistance and hepatic steatosis of MAFLD by targeting PTPN1.


Asunto(s)
Resistencia a la Insulina , Proteína Tirosina Fosfatasa no Receptora Tipo 1 , Animales , Proteína Tirosina Fosfatasa no Receptora Tipo 1/metabolismo , Humanos , Ratones , Células Hep G2 , Masculino , Transducción de Señal/efectos de los fármacos , Hígado Graso/metabolismo , Hígado Graso/tratamiento farmacológico , Hígado Graso/patología , Proteínas Proto-Oncogénicas c-akt/metabolismo , Ratones Endogámicos C57BL , Modelos Animales de Enfermedad , Hígado/metabolismo , Hígado/efectos de los fármacos , Hígado/patología , Fosfatidilinositol 3-Quinasas/metabolismo , Receptor de Insulina/metabolismo , Enfermedad del Hígado Graso no Alcohólico/metabolismo , Enfermedad del Hígado Graso no Alcohólico/tratamiento farmacológico , Enfermedad del Hígado Graso no Alcohólico/etiología , Enfermedad del Hígado Graso no Alcohólico/patología , Metabolismo de los Lípidos/efectos de los fármacos , Fosforilación/efectos de los fármacos
2.
BMC Cardiovasc Disord ; 24(1): 471, 2024 Sep 03.
Artículo en Inglés | MEDLINE | ID: mdl-39227771

RESUMEN

OBJECTIVE: The aim of this study was to investigate the relationship between circulating levels of B cell activating factor (BAFF) and the presence and severity of coronary artery disease (CAD) and acute myocardial infarction (AMI) in humans, as its biological functions in this context remain unclear. METHODS: Serum BAFF levels were measured in a cohort of 723 patients undergoing angiography, including 204 patients without CAD (control group), 220 patients with stable CAD (CAD group), and 299 patients with AMI (AMI group). Logistic regression analyses were used to assess the association between BAFF and CAD or AMI. RESULTS: Significantly elevated levels of BAFF were observed in patients with CAD and AMI compared to the control group. Furthermore, BAFF levels exhibited a positive correlation with the SYNTAX score (r = 0.3002, P < 0.0001) and the GRACE score (r = 0.5684, P < 0.0001). Logistic regression analysis demonstrated that increased BAFF levels were an independent risk factor for CAD (adjusted OR 1.305, 95% CI 1.078-1.580) and AMI (adjusted OR 2.874, 95% CI 1.708-4.838) after adjusting for confounding variables. Additionally, elevated BAFF levels were significantly associated with a high GRACE score (GRACE score 155 to 319, adjusted OR 4.297, 95% CI 1.841-10.030). BAFF exhibited a sensitivity of 75.0% and specificity of 71.4% in differentiating CAD patients with a high SYNTAX score, and a sensitivity of 75.5% and specificity of 72.8% in identifying AMI patients with a high GRACE score. CONCLUSION: Circulating BAFF levels serve as a valuable diagnostic marker for CAD and AMI. Elevated BAFF levels are associated with the presence and severity of these conditions, suggesting its potential as a clinically relevant biomarker in cardiovascular disease.


Asunto(s)
Factor Activador de Células B , Biomarcadores , Angiografía Coronaria , Enfermedad de la Arteria Coronaria , Infarto del Miocardio , Valor Predictivo de las Pruebas , Índice de Severidad de la Enfermedad , Regulación hacia Arriba , Humanos , Masculino , Factor Activador de Células B/sangre , Enfermedad de la Arteria Coronaria/sangre , Enfermedad de la Arteria Coronaria/diagnóstico por imagen , Enfermedad de la Arteria Coronaria/diagnóstico , Femenino , Persona de Mediana Edad , Biomarcadores/sangre , Anciano , Infarto del Miocardio/sangre , Infarto del Miocardio/diagnóstico , Estudios de Casos y Controles , Factores de Riesgo , Medición de Riesgo , Pronóstico
3.
Dig Dis Sci ; 69(9): 3450-3465, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39044014

RESUMEN

BACKGROUND: Early drain removal (EDR) has been widely accepted, but not been routinely used in patients after pancreaticoduodenectomy (PD) and distal pancreatectomy (DP). This study aimed to evaluate the safety and benefits of EDR versus routine drain removal (RDR) after PD or DP. METHODS: A systematic search was conducted on medical search engines from January 1, 2008 to November 1, 2023, for articles that compared EDR versus RDR after PD or DP. The primary outcome was clinically relevant postoperative pancreatic fistula (CR-POPF). Further analysis of studies including patients with low-drain fluid amylase (low-DFA) on postoperative day 1 and defining EDR timing as within 3 days was also performed. RESULTS: Four randomized controlled trials (RCTs) and eleven non-RCTs with a total of 9465 patients were included in this analysis. For the primary outcome, the EDR group had a significantly lower rate of CR-POPF (OR 0.23; p < 0.001). For the secondary outcomes, a lower incidence was observed in delayed gastric emptying (OR 0.63, p = 0.02), Clavien-Dindo III-V complications (OR 0.48, p < 0.001), postoperative hemorrhage (OR 0.55, p = 0.02), reoperation (OR 0.57, p < 0.001), readmission (OR 0.70, p = 0.003) and length of stay (MD -2.04, p < 0.001) in EDR. Consistent outcomes were observed in the subgroup analysis of low-DFA patients and definite EDR timing, except for postoperative hemorrhage in EDR. CONCLUSION: EDR after PD or DP is beneficial and safe, reducing the incidence of CR-POPF and other postoperative complications. Further prospective studies and RCTs are required to validate this finding.


Asunto(s)
Remoción de Dispositivos , Drenaje , Pancreatectomía , Fístula Pancreática , Pancreaticoduodenectomía , Complicaciones Posoperatorias , Humanos , Drenaje/instrumentación , Drenaje/métodos , Pancreatectomía/efectos adversos , Pancreatectomía/métodos , Fístula Pancreática/etiología , Fístula Pancreática/prevención & control , Fístula Pancreática/epidemiología , Pancreaticoduodenectomía/efectos adversos , Factores de Tiempo , Resultado del Tratamiento
4.
BMC Med Imaging ; 24(1): 50, 2024 Feb 27.
Artículo en Inglés | MEDLINE | ID: mdl-38413923

RESUMEN

BACKGROUND: Asymptomatic COVID-19 carriers with normal chest computed tomography (CT) scans have perpetuated the ongoing pandemic of this disease. This retrospective study aimed to use automated machine learning (AutoML) to develop a prediction model based on CT characteristics for the identification of asymptomatic carriers. METHODS: Asymptomatic carriers were from Yangzhou Third People's Hospital from August 1st, 2020, to March 31st, 2021, and the control group included a healthy population from a nonepizootic area with two negative RT‒PCR results within 48 h. All CT images were preprocessed using MATLAB. Model development and validation were conducted in R with the H2O package. The models were built based on six algorithms, e.g., random forest and deep neural network (DNN), and a training set (n = 691). The models were improved by automatically adjusting hyperparameters for an internal validation set (n = 306). The performance of the obtained models was evaluated based on a dataset from Suzhou (n = 178) using the area under the curve (AUC), accuracy, sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and F1 score. RESULTS: A total of 1,175 images were preprocessed with high stability. Six models were developed, and the performance of the DNN model ranked first, with an AUC value of 0.898 for the test set. The sensitivity, specificity, PPV, NPV, F1 score and accuracy of the DNN model were 0.820, 0.854, 0.849, 0.826, 0.834 and 0.837, respectively. A plot of a local interpretable model-agnostic explanation demonstrated how different variables worked in identifying asymptomatic carriers. CONCLUSIONS: Our study demonstrates that AutoML models based on CT images can be used to identify asymptomatic carriers. The most promising model for clinical implementation is the DNN-algorithm-based model.


Asunto(s)
COVID-19 , Aprendizaje Profundo , Humanos , COVID-19/diagnóstico por imagen , Estudios Retrospectivos , Tomografía Computarizada por Rayos X/métodos , Aprendizaje Automático
5.
BMC Biol ; 21(1): 151, 2023 07 10.
Artículo en Inglés | MEDLINE | ID: mdl-37424015

RESUMEN

BACKGROUND: Chronic kidney disease (CKD) accelerates atherosclerosis, but the mechanisms remain unclear. Tyrosine sulfation has been recognized as a key post-translational modification (PTM) in regulation of various cellular processes, and the sulfated adhesion molecules and chemokine receptors have been shown to participate in the pathogenesis of atherosclerosis via enhancement of monocyte/macrophage function. The levels of inorganic sulfate, the essential substrate for the sulfation reaction, are dramatically increased in patients with CKD, which indicates a change of sulfation status in CKD patients. Thus, in the present study, we detected the sulfation status in CKD patients and probed into the impact of sulfation on CKD-related atherosclerosis by targeting tyrosine sulfation function. RESULTS: PBMCs from individuals with CKD showed higher amounts of total sulfotyrosine and tyrosylprotein sulfotransferase (TPST) type 1 and 2 protein levels. The plasma level of O-sulfotyrosine, the metabolic end product of tyrosine sulfation, increased significantly in CKD patients. Statistically, O-sulfotyrosine and the coronary atherosclerosis severity SYNTAX score positively correlated. Mechanically, more sulfate-positive nucleated cells in peripheral blood and more abundant infiltration of sulfated macrophages in deteriorated vascular plaques in CKD ApoE null mice were noted. Knockout of TPST1 and TPST2 decreased atherosclerosis and peritoneal macrophage adherence and migration in CKD condition. The sulfation of the chemokine receptors, CCR2 and CCR5, was increased in PBMCs from CKD patients. CONCLUSIONS: CKD is associated with increased sulfation status. Increased sulfation contributes to monocyte/macrophage activation and might be involved in CKD-related atherosclerosis. Inhibition of sulfation may suppress CKD-related atherosclerosis and is worthy of further study.


Asunto(s)
Aterosclerosis , Sulfotransferasas , Ratones , Animales , Sulfotransferasas/química , Sulfotransferasas/genética , Sulfotransferasas/metabolismo , Proteínas/metabolismo , Tirosina/metabolismo , Ratones Noqueados , Receptores de Quimiocina/metabolismo , Aterosclerosis/complicaciones , Procesamiento Proteico-Postraduccional
6.
Mol Carcinog ; 62(10): 1572-1584, 2023 10.
Artículo en Inglés | MEDLINE | ID: mdl-37555764

RESUMEN

In recent years, one of the most promising advances in the treatment of acute myeloid leukemia (AML) is the combination of a hypomethylating agent (HMA) with the BCL2 inhibitor venetoclax (VEN). To better understand the key factors associated with the response of VEN plus HMA, 212 consecutive AML patients were retrospectively recruited to establish and validate a scoring system for predicting the primary resistance to VEN-based induced therapy. All AML patients were divided randomly into a training set (n = 155) and a validation set (n = 57). Factors were selected using a multivariate logistic regression model, including FAB-M5, myelodysplastic syndrome-secondary acute myeloid leukemia (MDS-sAML), RUNX1-RUNX1T1 and FLT3-ITD mutation (FLT3-ITDm). A nomogram was then constructed including all these four predictors. The nomogram both presented a good performance of discrimination and calibration, with a C-index of 0.770 and 0.733 in the training and validation set. Decision curve analysis also indicated that the nomogram was feasible to make beneficial decisions. Eventually a total scoring system of 8 points was developed, which was divided into three risk groups: low-risk (score 0-2), medium-risk (score 3-4), and high-risk (score 5-8). There was a significant difference in the nonremission (NR) rate of these three risk groups (22.8% vs. 60.0% vs. 77.8%, p < 0.001). After adjustment of the other variables, patients in medium- or high-risk groups also presented a worse event-free survival (EFS) than that in the low-risk group (hazard ratio [HR] = 1.62, p = 0.03). In conclusion, we highlighted the response determinants of AML patients receiving a combination therapy of VEN plus HMAs. The scoring system can be used to predict the resistance of VEN, providing better guidance for clinical treatment.


Asunto(s)
Antineoplásicos , Leucemia Mieloide Aguda , Humanos , Estudios Retrospectivos , Antineoplásicos/uso terapéutico , Compuestos Bicíclicos Heterocíclicos con Puentes/uso terapéutico , Compuestos Bicíclicos Heterocíclicos con Puentes/farmacología , Leucemia Mieloide Aguda/tratamiento farmacológico , Leucemia Mieloide Aguda/genética , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos
7.
Dig Dis Sci ; 68(7): 2866-2877, 2023 07.
Artículo en Inglés | MEDLINE | ID: mdl-37160541

RESUMEN

BACKGROUND: Recurrence of common bile duct stones (CBDs) commonly happens after endoscopic retrograde cholangiopancreatography (ERCP). The clinical prediction models for the recurrence of CBDs after ERCP are lacking. AIMS: We aim to develop high-performance prediction models for the recurrence of CBDS after ERCP treatment using automated machine learning (AutoML) and to assess the AutoML models versus the traditional regression models. METHODS: 473 patients with CBDs undergoing ERCP were recruited in the single-center retrospective cohort study. Samples were divided into Training Set (65%) and Validation Set (35%) randomly. Three modeling approaches, including fully automated machine learning (Fully automated), semi-automated machine learning (Semi-automated), and traditional regression were applied to fit prediction models. Models' discrimination, calibration, and clinical benefits were examined. The Shapley additive explanations (SHAP), partial dependence plot (PDP), and SHAP local explanation (SHAPLE) were proposed for the interpretation of the best model. RESULTS: The area under roc curve (AUROC) of semi-automated gradient boost machine (GBM) model was 0.749 in Validation Set, better than the other fully/semi-automated models and the traditional regression models (highest AUROC = 0.736). The calibration and clinical application of AutoML models were adequate. Through the SHAP-PDP-SHAPLE pipeline, the roles of key variables of the semi-automated GBM model were visualized. Lastly, the best model was deployed online for clinical practitioners. CONCLUSION: The GBM model based on semi-AutoML is an optimal model to predict the recurrence of CBDs after ERCP treatment. In comparison with traditional regressions, AutoML algorithms present significant strengths in modeling, which show promise in future clinical practices.


Asunto(s)
Colangiopancreatografia Retrógrada Endoscópica , Cálculos Biliares , Humanos , Estudios Retrospectivos , Cálculos Biliares/diagnóstico por imagen , Cálculos Biliares/cirugía , Esfinterotomía Endoscópica , Conducto Colédoco
8.
J Digit Imaging ; 36(6): 2578-2601, 2023 12.
Artículo en Inglés | MEDLINE | ID: mdl-37735308

RESUMEN

With the advances in endoscopic technologies and artificial intelligence, a large number of endoscopic imaging datasets have been made public to researchers around the world. This study aims to review and introduce these datasets. An extensive literature search was conducted to identify appropriate datasets in PubMed, and other targeted searches were conducted in GitHub, Kaggle, and Simula to identify datasets directly. We provided a brief introduction to each dataset and evaluated the characteristics of the datasets included. Moreover, two national datasets in progress were discussed. A total of 40 datasets of endoscopic images were included, of which 34 were accessible for use. Basic and detailed information on each dataset was reported. Of all the datasets, 16 focus on polyps, and 6 focus on small bowel lesions. Most datasets (n = 16) were constructed by colonoscopy only, followed by normal gastrointestinal endoscopy and capsule endoscopy (n = 9). This review may facilitate the usage of public dataset resources in endoscopic research.


Asunto(s)
Inteligencia Artificial , Endoscopía Capsular , Humanos , Colonoscopía/métodos , Endoscopía Capsular/métodos , Intestino Delgado , Diagnóstico por Imagen
9.
J Digit Imaging ; 36(3): 827-836, 2023 06.
Artículo en Inglés | MEDLINE | ID: mdl-36596937

RESUMEN

Novel coronavirus disease 2019 (COVID-19) has rapidly spread throughout the world; however, it is difficult for clinicians to make early diagnoses. This study is to evaluate the feasibility of using deep learning (DL) models to identify asymptomatic COVID-19 patients based on chest CT images. In this retrospective study, six DL models (Xception, NASNet, ResNet, EfficientNet, ViT, and Swin), based on convolutional neural networks (CNNs) or transformer architectures, were trained to identify asymptomatic patients with COVID-19 on chest CT images. Data from Yangzhou were randomly split into a training set (n = 2140) and an internal-validation set (n = 360). Data from Suzhou was the external-test set (n = 200). Model performance was assessed by the metrics accuracy, recall, and specificity and was compared with the assessments of two radiologists. A total of 2700 chest CT images were collected in this study. In the validation dataset, the Swin model achieved the highest accuracy of 0.994, followed by the EfficientNet model (0.954). The recall and the precision of the Swin model were 0.989 and 1.000, respectively. In the test dataset, the Swin model was still the best and achieved the highest accuracy (0.980). All the DL models performed remarkably better than the two experts. Last, the time on the test set diagnosis spent by two experts-42 min, 17 s (junior); and 29 min, 43 s (senior)-was significantly higher than those of the DL models (all below 2 min). This study evaluated the feasibility of multiple DL models in distinguishing asymptomatic patients with COVID-19 from healthy subjects on chest CT images. It found that a transformer-based model, the Swin model, performed best.


Asunto(s)
COVID-19 , Aprendizaje Profundo , Humanos , COVID-19/diagnóstico por imagen , Estudios Retrospectivos , Redes Neurales de la Computación , Tomografía Computarizada por Rayos X
10.
J Digit Imaging ; 36(1): 326-338, 2023 02.
Artículo en Inglés | MEDLINE | ID: mdl-36279027

RESUMEN

Esophageal variceal (EV) bleeding is a severe medical emergency related to cirrhosis. Early identification of cirrhotic patients with at a high risk of EV bleeding is key to improving outcomes and optimizing medical resources. This study aimed to evaluate the feasibility of automated multimodal machine learning (MMML) for predicting EV bleeding by integrating endoscopic images and clinical structured data. This study mainly includes three steps: step 1, developing deep learning (DL) models using EV images by 12-month bleeding on TensorFlow (backbones include ResNet, Xception, EfficientNet, ViT and ConvMixer); step 2, training and internally validating MMML models integrating clinical structured data and DL model outputs to predict 12-month EV bleeding on an H2O-automated machine learning platform (algorithms include DL, XGBoost, GLM, GBM, RF, and stacking); and step 3, externally testing MMML models. Furthermore, existing clinical indices, e.g., the MELD score, Child‒Pugh score, APRI, and FIB-4, were also examined. Five DL models were transfer learning to the binary classification of EV endoscopic images at admission based on the occurrence or absence of bleeding events during the 12-month follow-up. An EfficientNet model achieved the highest accuracy of 0.868 in the validation set. Then, a series of MMML models, integrating clinical structured data and the output of the EfficientNet model, were automatedly trained to predict 12-month EV bleeding. A stacking model showed the highest accuracy (0.932), sensitivity (0.952), and F1-score (0.879) in the test dataset, which was also better than the existing indices. This study is the first to evaluate the feasibility of automated MMML in predicting 12-month EV bleeding based on endoscopic images and clinical variables.


Asunto(s)
Várices Esofágicas y Gástricas , Humanos , Hemorragia Gastrointestinal , Endoscopía , Cirrosis Hepática , Aprendizaje Automático
11.
Biochem Biophys Res Commun ; 588: 15-22, 2022 01 15.
Artículo en Inglés | MEDLINE | ID: mdl-34942529

RESUMEN

Insulin resistance (IR) attributed by the deficiency of lipophagy, is an abnormal state of downregulation of insulin-mediated glucose uptake and use into the liver. Chromosome 9 open reading frame 72 (C9orf72) variously modulates autophagy. We investigated the role and the downstream pathway of C9orf72 in hepatic IR. We found that C9orf72 knockdown alleviated hepatic IR by lipophagy promotion in T2DM mice and in IR-challenged hepatocytes in vitro. C9orf72 interacted with and activated cell division cycle 42 (Cdc42) protein in IR-challenged hepatocytes, Which in turn, inhibits lipophagy by promoting neural Wiskott-Aldrich syndrome protein (N-WASP) expression and activation. C9orf72 inhibited lipophagy by activating the Cdc42/N-WASP axis to facilitate hepatic IR; therefore, the knockdown of C9orf72 may be potentially therapeutic for the treatment of IR.


Asunto(s)
Autofagia , Proteína C9orf72/metabolismo , Técnicas de Silenciamiento del Gen , Resistencia a la Insulina , Hígado/metabolismo , Hígado/patología , Animales , Diabetes Mellitus Tipo 2/patología , Hepatocitos/metabolismo , Hepatocitos/patología , Masculino , Ratones Endogámicos C57BL , Ratones Obesos , Unión Proteica , Proteína Neuronal del Síndrome de Wiskott-Aldrich/metabolismo , Proteína de Unión al GTP cdc42/metabolismo
12.
J Card Fail ; 28(4): 604-613, 2022 04.
Artículo en Inglés | MEDLINE | ID: mdl-35105522

RESUMEN

BACKGROUND: This is first-in-man investigation of an implantable Heartech left ventricular partitioning device (LVPD) therapy for chronic heart failure (HF) after a myocardial infarction. METHODS AND RESULTS: Initially, 16 patients were chosen from 3 cardiac centers within China. All patients were treated with percutaneous ventricular restoration involving the Heartech LVPD implantation. Major adverse cardiovascular and cerebrovascular events were documented. Functional status, echocardiograph evaluation, European five-dimensional health scale, 6-minute walk test before the procedure and at postoperative follow-ups were recorded. We demonstrated successful implantation and device function with a success rate of 93.75%. One patient suffered a fatal myocardial infarction within the 12 ± 1 month follow-up. However, other patients did not report any major adverse cardiovascular and cerebrovascular events at their 12 ± 1 month follow-ups. After the operation, the average left ventricular end-systolic volume index decreased dramatically (66.00 mL/m2, interquartile range [IQR] 63.00-89.00 mL/m2 vs 48.00 mL/m2, IQR 32.25-68.25 mL/m2, P = .001), along with the left ventricular end-diastolic volume index (105.00 mL/m2, IQR 90.00-130.00 mL/m2 vs 76.50 mL/m2, IQR 57.75-120.25 mL/m2, P = .002). The left ventricular ejection fraction (35.00%, IQR 27.00-38.00% vs 42.50%, IQR 34.75-50.25%, P = .003), 6-minute walk test (383.13 ± 108.70 m vs 491.17 ± 118.44 m, P = .01), and European five-dimensional health scale (65.93 ± 11.25 vs 82.50 ± 5.44, P < .001), in turn, improved significantly. CONCLUSIONS: In our study, the Heartech LVPD was demonstrated as both safe and effective in reducing LV volume, enhancing LV function after implantation. These results remain constant at least till the 12 month follow-up. (Trial Registration: NCT02938637.).


Asunto(s)
Insuficiencia Cardíaca , Infarto del Miocardio , Humanos , Infarto del Miocardio/diagnóstico , Infarto del Miocardio/cirugía , Volumen Sistólico , Resultado del Tratamiento , Función Ventricular Izquierda , Remodelación Ventricular
13.
BMC Nephrol ; 22(1): 66, 2021 02 23.
Artículo en Inglés | MEDLINE | ID: mdl-33622294

RESUMEN

BACKGROUND: Sulfation of tyrosine, yielding O-sulfotyrosine, is a common but fixed post-translational modification in eukaryotes. Patients with increased circulating O-sulfotyrosine levels experience a faster decline in renal function with progression to end-stage renal disease (ESRD). In the present study, we measured serum O-sulfotyrosine levels in individuals with chronic kidney disease (CKD) and acute kidney injury (AKI) to explore its ability to differentiate AKI from CKD. METHODS: A total of 135 patients (20 with AKI and 115 with CKD) were recruited prospectively for liquid chromatography-mass spectrometry assessment of circulating O-sulfotyrosine. We also studied C57BL/6 mice with CKD after 5/6 nephrectomy (Nx). Blood samples were drawn from the tail vein on Day 1, 3, 5, 7, 14, 30, 60, and 90 after CKD. Serum separation and characterization of creatinine, blood urea nitrogen (BUN), and O-sulfotyrosine was performed. Thus, the time-concentration curves of the O-sulfotyrosine level demonstrate the variation of kidney dysfunction. RESULTS: The serum levels of O-sulfotyrosine were markedly increased in patients with CKD compared with AKI. Median O-sulfotyrosine levels in CKD patients versus AKI, respectively, were as follows:243.61 ng/mL(interquartile range [IQR] = 171.90-553.86) versus 126.55 ng/mL (IQR = 48.19-185.03, P = 0.004). In patients with CKD, O-sulfotyrosine levels were positively correlated with creatinine, BUN, and Cystatin C (r = 0.63, P < 0.001; r = 0.49, P < 0.001; r = 0.61, P < 0.001, respectively) by the multivariate linear regression analysis (ß = 0.71, P < 0.001; ß = 0.40, P = 0.002; ß = 0.73, P < 0.001, respectively). However, this association was not statistically significant in patients with AKI (r = - 0.17, P = 0.472; r = 0.11, P = 0.655; r = 0.09, P = 0.716, respectively). The receiver operating characteristic (ROC) analysis illustrated that the area under the curve was 0.80 (95% confidence interval [CI] 0.71-0.89; P < 0.001) and the optimal cut-off value of serum O-sulfotyrosine suggesting AKI was < 147.40 ng/mL with a sensitivity and specificity of 80.90 and 70.00% respectively. In animal experiments, serum levels of O-sulfotyrosine in mice were elevated on Day 7 after 5/6 nephrectomy (14.89 ± 1.05 vs. 8.88 ± 2.62 ng/mL, P < 0.001) until Day 90 (32.65 ± 5.59 vs. 8.88 ± 2.62 ng/mL, P < 0.001). CONCLUSION: Serum O-sulfotyrosine levels were observed correlated with degrading renal function and in CKD patients substantially higher than those in AKI patients. Thus serum O-sulfotyrosine facilitated the differential diagnosis of AKI from CKD.


Asunto(s)
Lesión Renal Aguda/sangre , Lesión Renal Aguda/diagnóstico , Insuficiencia Renal Crónica/sangre , Insuficiencia Renal Crónica/diagnóstico , Tirosina/análogos & derivados , Anciano , Animales , Diagnóstico Diferencial , Femenino , Humanos , Masculino , Ratones , Ratones Endogámicos C57BL , Persona de Mediana Edad , Tirosina/sangre
14.
Ren Fail ; 43(1): 307-312, 2021 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-33538236

RESUMEN

BACKGROUND: Chronic kidney disease (CKD) is associated with an increased risk of the progression of coronary artery disease (CAD). However, there are few data on the relationship between CAD severity and the duration of CKD. This study assessed the predictive value of the duration of kidney dysfunction in CKD patients with CAD severity. METHODS: In 145 patients (63.4% male, n = 92; mean age, 68.8 ± 12.8 years) with CKD, severity of CAD was assessed by coronary angiography and quantified by SYNTAX scores, and duration of kidney dysfunction was either assessed by checking historical biochemical parameters of individuals or was based on enquiries. RESULTS: Patients with high SYNTAX scores (≥ 22) had a greater prevalence of cardiovascular risk factors including age, gender, history of heart failure and smoking. In CKD patients, SYNTAX scores were positively correlated to duration of CKD and serum uric acid (UA), and negatively correlated to high-density lipoprotein-cholesterol (HDL-C) and ApoA1 levels. Univariate binary logistic regression and multivariate logistic analyses showed that SYNTAX scores correlated significantly with CKD duration, UA, and HDL-C. Receiver-operating characteristic analysis was used to explore a time point when coronary angiography application was economical and effective and yielded a Youden index of 6.5 years. CONCLUSIONS: Together, our results demonstrated that the duration of kidney dysfunction was an independent correlate of the severity of CAD in patients with CKD. Our findings suggest that coronary angiography should be considered for CKD patients with renal insufficiency having lasted for more than 6.5 years.


Asunto(s)
Angiografía Coronaria/estadística & datos numéricos , Enfermedad de la Arteria Coronaria/diagnóstico , Insuficiencia Renal Crónica/complicaciones , Anciano , Anciano de 80 o más Años , Enfermedad de la Arteria Coronaria/etiología , Enfermedad de la Arteria Coronaria/patología , Vasos Coronarios/diagnóstico por imagen , Vasos Coronarios/patología , Progresión de la Enfermedad , Femenino , Tasa de Filtración Glomerular/fisiología , Factores de Riesgo de Enfermedad Cardiaca , Humanos , Masculino , Persona de Mediana Edad , Curva ROC , Insuficiencia Renal Crónica/diagnóstico , Insuficiencia Renal Crónica/fisiopatología , Estudios Retrospectivos , Índice de Severidad de la Enfermedad , Factores de Tiempo
15.
Esophagus ; 18(1): 144-151, 2021 01.
Artículo en Inglés | MEDLINE | ID: mdl-32519226

RESUMEN

BACKGROUND: Gastroesophageal reflux disease (GERD) is a common gastrointestinal disorder. Proton pump inhibitors (PPIs) are first-line drugs for GERD. For those who fail to respond to PPIs, adding prokinetics to PPIs is recommended and several trials have been conducted to evaluate the efficacy of prokinetic-PPI combination therapy. METHODS: A systematic literature search was performed using PubMed and the Cochrane Library databases before February 2019 for randomized controlled trials (RCTs), which compared the efficacy of prokinetics plus PPI treatment with that of PPI monotherapy. Relevant studies were examined and data were extracted independently by two investigators. The risk ratios (RRs) with 95% CIs were used to evaluate the responder rate, and standard mean differences (SMDs) or mean differences (MDs) with 95% CIs were used for symptom score changes. Statistical heterogeneity was evaluated by the I2 statistic. Either a fixed-effect or a random-effect model was established for calculating the pooled data. RESULTS: A total of 14 studies, comprising 1,437 patients were ultimately included in the meta-analysis. The pooled analysis showed that compared to PPI monotherapy, addition of prokinetics to PPI did not elevate the rate of endoscopic responders (RR = 0.996, 95% CI 0.929 - 1.068, p = 0.917), but improved symptom response (RR = 1.185, 95% CI 1.042 - 1.348, p = 0.010). Additionally, the combined therapy achieved a greater symptom relief than monotherapy both in FSSG and GERD-Q subgroups (MD = - 2.978, 95% CI - 3.319 to - 2.638, p < 0.001; MD = - 0.723, 95% CI - 0.968 to - 0.478, p < 0.001). CONCLUSIONS: Adding prokinetics to PPIs achieves symptomatic improvement compared to PPI monotherapy, thus can enhance life quality of GERD patients. However, the combined treatment seems to have no significant effect on mucosal healing.


Asunto(s)
Reflujo Gastroesofágico , Inhibidores de la Bomba de Protones , Reflujo Gastroesofágico/diagnóstico , Reflujo Gastroesofágico/tratamiento farmacológico , Fármacos Gastrointestinales/uso terapéutico , Antagonistas de los Receptores H2 de la Histamina/uso terapéutico , Humanos , Inhibidores de la Bomba de Protones/uso terapéutico , Resultado del Tratamiento
16.
World J Surg Oncol ; 18(1): 193, 2020 Aug 03.
Artículo en Inglés | MEDLINE | ID: mdl-32746835

RESUMEN

BACKGROUND: The impact of primary tumor resection (PTR) on the prognosis of unresectable metastatic colorectal cancer (mCRC) patients remains debatable. We aimed to develop several prognostic nomograms which could be useful in predicting whether patients might benefit from PTR or not. METHODS: Patients diagnosed as mCRC without resected metastasis were identified from the Surveillance Epidemiology and End Results database and randomly assigned into two groups: a training cohort (6369 patients) and a validation cohort (2774 patients). Univariate and multivariable Cox analyses were performed to identify the independent predictors and construct nomograms that could independently predict the overall survival (OS) of unresectable mCRC patients in PTR and non-PTR groups, respectively. The performance of these nomograms was assessed by the concordance index (C-index), calibration curves, and decision curve analysis (DCA). RESULTS: Based on the result of univariate and multivariable Cox analyses, two nomograms were respectively constructed to predict the 1-year OS rates of unresectable mCRC patients when receiving PTR and not. The first one included age, gender, tumor grade, proximal colon, N stage, CEA, chemotherapy, radiotherapy, histology type, brain metastasis, liver metastasis, lung metastasis, and bone metastasis. The second nomogram included age, race, tumor grade, primary site, CEA, chemotherapy, brain metastasis, and bone metastasis. These nomograms showed favorable sensitivity with the C-index range of 0.700-0.725. The calibration curves and DCAs also exhibited adequate fit and ideal net benefits in prognosis prediction and clinical application. CONCLUSIONS: These practical prognosis nomograms could assist clinicians in making appropriate treatment decisions to effectively manage the disease.


Asunto(s)
Neoplasias del Colon , Nomogramas , Humanos , Estadificación de Neoplasias , Pronóstico , Programa de VERF
17.
Dig Dis Sci ; 64(2): 532-543, 2019 02.
Artículo en Inglés | MEDLINE | ID: mdl-30350242

RESUMEN

BACKGROUND: In recent decades, the patterns and trends of gastrointestinal (GI) cancer epidemics in Chinese population have been changing. AIMS: To present the epidemiological trends and geographic distributions of four major GI cancers (esophageal cancer, stomach cancer, liver cancer and colorectal cancer) in China from 2010 to 2014. METHODS: It used standardized data extracted from the National Central Cancer Registry database. RESULTS: The age-standardized incidence rates (ASIR) of esophageal cancer decreased from 16.7 to 12.2 per 100,000 and the age-standardized mortality rates (ASMR) decreased from 12.0 to 8.8 per 100,000. The ASIR and the ASMR of stomach cancer dropped from 23.7 to 19.5 per 100,000 and from 16.6 to 13.3 per 100,000. The ASIR of liver cancer fell from 21.4 to 17.8 per 100,000 and its ASMR fell from 18.4 per 100,000 to 15.3 per 100,000. The ASIR of colorectal cancer increased from 16.1 to 17.5 per 100,000, whereas the ASMR fluctuated between 7.6 and 7.9 per 100,000. Moreover, the incidence and mortality of each cancer differed between males and females, urban and rural residence, as well as various regions. CONCLUSION: From 2010 to 2014, esophageal cancer, stomach cancer and liver cancer showed downward trend, while the ASIR of colorectal cancer slightly rose and its ASMR presented stable.


Asunto(s)
Adenocarcinoma/epidemiología , Carcinoma Hepatocelular/epidemiología , Carcinoma de Células Escamosas/epidemiología , Neoplasias Gastrointestinales/epidemiología , Neoplasias Hepáticas/epidemiología , Sistema de Registros , Adenocarcinoma/mortalidad , Adulto , Anciano , Carcinoma Hepatocelular/mortalidad , Carcinoma de Células Escamosas/mortalidad , China/epidemiología , Neoplasias Colorrectales/epidemiología , Neoplasias Colorrectales/mortalidad , Neoplasias Esofágicas/epidemiología , Neoplasias Esofágicas/mortalidad , Femenino , Neoplasias Gastrointestinales/mortalidad , Humanos , Incidencia , Neoplasias Hepáticas/mortalidad , Masculino , Persona de Mediana Edad , Población Rural , Factores Sexuales , Neoplasias Gástricas/epidemiología , Neoplasias Gástricas/mortalidad , Población Urbana
18.
World J Surg Oncol ; 17(1): 75, 2019 Apr 30.
Artículo en Inglés | MEDLINE | ID: mdl-31039803

RESUMEN

BACKGROUND: The Toronto hepatocellular carcinoma (HCC) risk index (THRI) was developed to predict HCC in patients with cirrhosis. This study aimed to validate the THRI in a 10-year Asian cohort. METHODS: A total of 2836 patients with cirrhosis at the First Affiliated Hospital of Soochow University between January 2008 and May 2018 were evaluated. Based on the THRI value at diagnosis, patients were divided into three groups (< 120, low-risk; 120-240, intermediate-risk; > 240, high-risk). Student's t test and Fisher's exact test were applied to compare parameters between the HCC group and the non-HCC group. The receiver operator characteristic (ROC) curve was drafted to identify the value of the THRI in predicting HCC. Logistic regression was utilized to assess the relationship between the development of HCC and THRI values. The incidence of HCC was calculated for the three groups using the Kaplan-Meier method, and curves were compared using the log-rank test. RESULTS: Of 520 patients enrolled in this study, 76 patients developed HCC. Patients who developed HCC had a higher THRI score than those who did not develop HCC (279.5 ± 57.1 vs. 232.3 ± 67.6, respectively, p < 0.001). The area under the ROC curve for the THRI to predict HCC was 0.707 ([95% CI 0.645-0.769], p < 0.001), with a sensitivity of 0.842 and a specificity of 0.486 when the cutoff THRI value was 226. Compared to the low-risk group, the high-risk group presented higher odds of developing HCC (adjusting odds ratio 1.026 [95% CI 1.002-1.051], p = 0.036). Differences existed in the cumulative incidence of HCC among the three risk groups (log-rank, p < 0.001). The 5-year cumulative HCC incidence of the low-risk group, intermediate-risk group, and high-risk group was 0%, 13%, and 34%, respectively. CONCLUSION: This study validated THRI values for predicting HCC in Asians with cirrhosis, which presented a fine sensitivity to identify the high-risk population of HCC for secondary prevention.


Asunto(s)
Carcinoma Hepatocelular/etiología , Cirrosis Hepática/complicaciones , Neoplasias Hepáticas/etiología , Adulto , Anciano , Anciano de 80 o más Años , Área Bajo la Curva , Carcinoma Hepatocelular/epidemiología , Carcinoma Hepatocelular/patología , China/epidemiología , Femenino , Estudios de Seguimiento , Humanos , Incidencia , Pruebas de Función Hepática , Neoplasias Hepáticas/epidemiología , Neoplasias Hepáticas/patología , Masculino , Persona de Mediana Edad , Pronóstico , Estudios Retrospectivos , Factores de Riesgo , Adulto Joven
19.
Dis Colon Rectum ; 61(2): 207-213, 2018 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-29337776

RESUMEN

BACKGROUND: Identifying patients with Crohn's disease with rapid disease progress or high risk of early surgery is crucial to clinical decision making. OBJECTIVE: The aim was to evaluate the correlation between the Lémann index at diagnosis and abdominal surgery in the first year after Crohn's disease diagnosis and to find the risk factors for early surgery. DESIGN: This was a retrospective cohort study. SETTINGS: The study was conducted at a single tertiary hospital. PATIENTS: Patients diagnosed with Crohn's disease between 2013 and 2015 in our center were included. MAIN OUTCOME MEASURES: The outcome of interest was the need for an abdominal surgery within 1 year after the Lémann index evaluation at diagnosis. RESULTS: Of 212 eligible patients, 48 patients underwent abdominal surgery during follow-up. Lémann index was much higher in the surgery group (5.3 vs 2.6; p < 0.001). On tertiles of the Lémann index, the frequency of surgery grew (2.8%, 9.9%, and 55.7%; p < 0.001) as the Lémann index increased. The receiver operating characteristic curve was constructed taking into account the Lémann index for selecting patients with a high risk of surgery. Specificity, sensitivity, and area under receiver operating characteristic curve were 84.8%, 81.3%, and 0.89 of the Lémann Index at a cutoff level of 3.7. Patients with Lémann index ≥3.7 carried a higher risk of abdominal surgery (OR = 18.6; p < 0.001). Stricturing and penetrating disease were predictors for abdominal surgery, whereas antitumor necrosis factor treatment was associated with a significant reduction of surgical requirements. LIMITATIONS: This study was limited by its retrospective design. The ability of the Lémann index to predict the long-term risk of surgery was unknown. CONCLUSIONS: Lémann index at diagnosis is a reliable index to predict the risk of abdominal surgery in the first year after diagnosis of Crohn's disease. Patients with a high Lémann index might need closer follow-up or aggressive medical therapy. See Video Abstract at http://links.lww.com/DCR/A518.


Asunto(s)
Constricción Patológica/patología , Enfermedad de Crohn/diagnóstico , Factor de Necrosis Tumoral alfa/antagonistas & inhibidores , Adulto , Constricción Patológica/cirugía , Enfermedad de Crohn/cirugía , Femenino , Humanos , Masculino , Valor Predictivo de las Pruebas , Estudios Retrospectivos , Factores de Riesgo , Prevención Secundaria , Índice de Severidad de la Enfermedad , Factor de Necrosis Tumoral alfa/uso terapéutico , Adulto Joven
20.
J Pathol ; 241(1): 80-90, 2017 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-27763657

RESUMEN

Renal fibrosis is a significant threat to public health globally. Diverse primary aetiologies eventually result in chronic kidney disease (CKD) and immune cells influence this process. The roles of monocytes/macrophages, T cells, and mast cells have been carefully examined, whilst only a few studies have focused on the effect of B cells. We investigated B-cell function in tubulointerstitial fibrosis induced by unilateral ureteral obstruction (UUO), using genetic B-cell-deficient µMT mice or CD20 antibody-mediated B-cell-depleted mice. Obstructed kidneys of µMT and anti-CD20-treated mice showed lower levels of monocyte/macrophage infiltration and collagen deposition compared to wild-type mice. Mechanistically, anti-CD20 attenuated UUO-induced alterations of renal tumour necrosis factor-α (TNF-α), vascular cell adhesion molecule 1 (VCAM-1) pro-inflammatory genes, and CC chemokine ligand-2 (CCL2) essential for monocyte recruitment; B cells were one of the main sources of CCL2 in post-UUO kidneys. Neutralization of CCL2 reduced monocyte/macrophage influx and fibrotic changes in obstructed kidneys. Therefore, early-stage accumulation of B cells in the kidney accelerated monocyte/macrophage mobilization and infiltration, aggravating the fibrosis resulting from acutely induced kidney nephropathy. © 2016 The Authors. Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.


Asunto(s)
Linfocitos B/inmunología , Enfermedades Renales/inmunología , Monocitos/inmunología , Obstrucción Ureteral/inmunología , Animales , Movimiento Celular/inmunología , Quimiocina CCL2/antagonistas & inhibidores , Quimiocina CCL2/inmunología , Quimiotaxis de Leucocito/inmunología , Fibrosis , Mediadores de Inflamación/metabolismo , Enfermedades Renales/etiología , Túbulos Renales/inmunología , Túbulos Renales/patología , Masculino , Ratones Endogámicos C57BL , Obstrucción Ureteral/complicaciones
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