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BACKGROUND: In AFP-negative hepatocellular carcinoma patients, markers for predicting tumor progression or prognosis are limited. Therefore, our objective is to establish an optimal predicet model for this subset of patients, utilizing interpretable methods to enhance the accuracy of HCC prognosis prediction. METHODS: We recruited a total of 508 AFP-negative HCC patients in this study, modeling with randomly divided training set and validated with validation set. At the same time, 86 patients treated in different time periods were used as internal validation. After comparing the cox model with the random forest model based on Lasso regression, we have chosen the former to build our model. This model has been interpreted with SHAP values and validated using ROC, DCA. Additionally, we have reconfirmed the model's effectiveness by employing an internal validation set of independent periods. Subsequently, we have established a risk stratification system. RESULTS: The AUC values of the Lasso-Cox model at 1, 2, and 3 years were 0.807, 0.846, and 0.803, and the AUC values of the Lasso-RSF model at 1, 2, and 3 years were 0.783, 0.829, and 0.776. Lasso-Cox model was finally used to predict the prognosis of AFP-negative HCC patients in this study. And BCLC stage, gamma-glutamyl transferase (GGT), diameter of tumor, lung metastases (LM), albumin (ALB), alkaline phosphatase (ALP), and the number of tumors were included in the model. The validation set and the separate internal validation set both indicate that the model is stable and accurate. Using risk factors to establish risk stratification, we observed that the survival time of the low-risk group, the middle-risk group, and the high-risk group decreased gradually, with significant differences among the three groups. CONCLUSION: The Lasso-Cox model based on AFP-negative HCC showed good predictive performance for liver cancer. SHAP explained the model for further clinical application.

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INTRODUCTION AND OBJECTIVES: We initiated this multicenter study to integrate important risk factors to create a nomogram for hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) for clinician decision-making. PATIENTS AND METHODS: Between April 2011 and March 2022, 2281 HCC patients with an HBV-related diagnosis were included. All patients were randomly divided into two groups in a ratio of 7:3 (training cohort, n = 1597; validation cohort, n = 684). The nomogram was built in the training cohort via Cox regression model and validated in the validation cohort. RESULTS: Multivariate Cox analyses revealed that the portal vein tumor thrombus, Child-Pugh class, tumor diameter, alanine aminotransferase level, tumor number, extrahepatic metastases, and therapy were independent predictive variables impacting overall survival. We constructed a new nomogram to predict 1-, 2-, and 3-year survival rates based on these factors. The nomogram-related receiver operating characteristics (ROC) curves indicated that the area under the curve (AUC) values were 0.809, 0.806, and 0.764 in predicting 1-, 2-, and 3-year survival rates, respectively. Furthermore, the calibration curves revealed good agreement between real measurements and nomogram predictions. The decision curve analyses (DCA) curves demonstrated excellent therapeutic application potential. In addition, stratified by risk scores, low-risk groups had longer median OS than medium-high-risk groups (p < 0.001). CONCLUSIONS: The nomogram we constructed showed good performance in predicting the 1-year survival rate for HBV- related HCC.

Assuntos

Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/etiologia , Vírus da Hepatite B , Nomogramas , Neoplasias Hepáticas/etiologia , Área Sob a Curva

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INTRODUCTION AND OBJECTIVES: Both external radiotherapy and sorafenib are promising treatments for hepatocellular carcinoma (HCC). Nevertheless, the combined treatment of external radiotherapy and sorafenib has not been widely applied clinically due to potentially adverse effects. This meta-analysis aimed to evaluate the clinical efficacy and safety of external radiotherapy combined with sorafenib in the treatment of HCC. METHODS: Pubmed, MEDLINE, EMBASE, Cochrane Library, and Web of Science databases were searched. The primary and secondary observation endpoints were the end of survival and incidence of adverse events, respectively. 11 studies involving 664 patients were included in this meta-analysis. RESULTS: The results demonstrated that median overall survival (mOS) and median progression-free survival (mPFS) of the external radiotherapy combined with sorafenib (RS) group were 19.45 months and 8.20 months. The one- and two-year survival rates were 0.65 (95%CI: 0.55-0.76) and 0.40 (95%CI: 0.24-0.56). The incidence of adverse events was 0.34 (95%CI: 0.25-0.44). CONCLUSIONS: The findings demonstrated that the survival of the RS group was significantly improved and few severe adverse events were observed. Hence, it can be concluded that external radiotherapy combined with sorafenib is a safe, effective, and promising therapeutic option for HCC.

Assuntos

Antineoplásicos , Carcinoma Hepatocelular , Quimioembolização Terapêutica , Neoplasias Hepáticas , Antineoplásicos/efeitos adversos , Carcinoma Hepatocelular/patologia , Quimioembolização Terapêutica/efeitos adversos , Humanos , Neoplasias Hepáticas/patologia , Sorafenibe/efeitos adversos , Resultado do Tratamento

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INTRODUCTION: Microvascular invasion (MVI) of is generally considered to be an important prognostic factor for hepatocellular carcinoma (HCC) after operation, An accurate prediction of MVI before operation is helpful for clinical decision-making before operation. MATERIAL AND METHODS: A retrospective analysis of 227 cases of hepatocellular carcinoma patients after hepatectomy has been confirmed the pathological result whether there was MVI, and has been determined the independent risk factors of MVI. Based on these independent risk factors, we constructed a clinical scoring risk model for predicting MVI. RESULTS: Among the 227 patients with HCC, 74 (34.6%) were MVI positive. Using receiver operating characteristic (ROC) curve and logistic regression model, we found that alpha-fetoprotein(AFP)≥158 ng/mL(odds ratio[OR] = 4.152,95% confidence interval [95%CI]:1.602∼10.760,p = 0.003), Des-γ-carboxy prothrombin (DCP)≥178mAU/mL(OR = 9.730,95%CI:3.392∼27.910,p < 0.001), circulating tumor cells (CTCs)≥3/3.2 ml(OR = 7.747,95%CI:3.019∼19.881,P < 0.001), maximum tumor diameter≥59 mm(OR = 3.467,95%CI:1.368∼8.669,p = 0.008) and tumor margin unsmoothness(OR = 0.235,95%CI:0.096∼0.573,p = 0.001) were independent risk factors for MVI, they predicted that the area under the curve of MVI was 0.752, 0.777, 0.857, 0.743 and 0.333, respectively. Based on these five independent risk factors, we constructed a clinical scoring risk model for predicting MVI. The model predicts that the area under the curve of MVI is 0.922, and its prevalence rate from 0 to 5 are 3.1%(1/32), 5.3%(4/76), 12.2%(5/41), 66.7%(20/30), 87.9%(29/33), 100%(15/15), respectively (P < 0.001). CONCLUSION: Based on AFP, DCP, CTC, maximum tumor diameter and tumor margin unsmoothness, we constructed a model to predict the risk of MVI clinical score, so as to make a more accurate individualized treatment plan before operation, which has important clinical significance and application prospect to improve the curative effect of HCC.

Assuntos

Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Hepatocelular/cirurgia , Feminino , Hepatectomia , Humanos , Neoplasias Hepáticas/cirurgia , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Cuidados Pré-Operatórios , Estudos Retrospectivos , Fatores de Risco , Sensibilidade e Especificidade , Tomografia Computadorizada por Raios X

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A Th2 immune response is central to allergic airway inflammation, which afflicts millions worldwide. However, the mechanisms that augment GATA3 expression in an antigen-primed developing Th2 cell are not well understood. Here, we describe an unexpected role for Blimp-1, a transcriptional repressor that constrains autoimmunity, as an upstream promoter of GATA3 expression that is critical for Th2 cell development in the lung to inhaled but not systemically delivered allergens but is dispensable for TFH function and IgE production. Mechanistically, Blimp-1 acts through Bcl6, leading to increased GATA3 expression in lung Th2 cells. Surprisingly, the anti-inflammatory cytokine IL-10, but not the pro-inflammatory cytokines IL-6 or IL-21, is required via STAT3 activation to up-regulate Blimp-1 and promote Th2 cell development. These data reveal a hitherto unappreciated role for an IL-10-STAT3-Blimp-1 circuit as an initiator of an inflammatory Th2 response in the lung to allergens. Thus, Blimp-1 in a context-dependent fashion can drive inflammation by promoting rather than terminating effector T cell responses.

Assuntos

Alérgenos/imunologia , Asma/imunologia , Pulmão/imunologia , Pulmão/patologia , Fator 1 de Ligação ao Domínio I Regulador Positivo/metabolismo , Células Th2/imunologia , Animais , Asma/complicações , Diferenciação Celular , Fator de Transcrição GATA3/metabolismo , Imunoglobulina E/metabolismo , Inflamação/patologia , Interleucina-6/metabolismo , Interleucinas/metabolismo , Linfonodos/metabolismo , Camundongos Endogâmicos C57BL , Especificidade de Órgãos , Proteínas Proto-Oncogênicas c-bcl-6/metabolismo , Pyroglyphidae/imunologia , Receptores de Interleucina-21/metabolismo , Fator de Transcrição STAT3/metabolismo , Transdução de Sinais , Linfócitos T Auxiliares-Indutores/metabolismo

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While titanium is the metal of choice for most prosthetics and inner body devices due to its superior biocompatibility, the discovery of Ti-containing species in the adjacent tissue as a result of wear and corrosion has been associated with autoimmune diseases and premature implant failures. Here, we utilize the in situ liquid cell transmission electron microscopy (TEM) in a liquid flow holder and graphene liquid cells (GLCs) to investigate, for the first time, the in situ nano-bio interactions between titanium dioxide nanoparticles and biological medium. This imaging and spectroscopy methodology showed the process of formation of an ionic and proteic bio-camouflage surrounding Ti dioxide (anatase) nanoparticles that facilitates their internalization by bone cells. The in situ understanding of the mechanisms of the formation of the bio-camouflage of anatase nanoparticles may contribute to the definition of strategies aimed at the manipulation of these NPs for bone regenerative purposes.