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2.
Clin Exp Med ; 23(5): 1515-1536, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-36342581

RESUMO

The value of the different types of HDACs (histone deacetylases) for HCC (hepatocellular carcinoma) prognosis and clinicopathological features is still controversial. Here, we performed a meta-analysis to investigate the possible role of different types of HDACs in HCC. Until October 28, 2021, we have searched the Embase, Cochrane, PubMed, Scopus, Web of Science (WOS), SinoMed, Chinese China National Knowledge Infrastructure (CNKI), Chinese WanFang, and Chinese Weipu databases and evaluated eligible studies according to the criteria. We used hazard ratio (HR) and 95% confidence interval (95% CI) to evaluate the prognostic effects of different types of HDACs on overall survival (OS), disease-free survival (DFS)/recurrence-free survival (RFS) and used odds ratio (OR) and corresponding 95% CI to evaluate the significance of HDACs on clinicopathological characteristics. The I2 statistic and chi-square-based Q test were used to assess the heterogeneity. When the heterogeneity was significant, we conducted a subgroup analysis. In addition, Egger's test and funnel chart were used to assess publication bias. The high expression of class I HDACs was associated with poorer OS, DFS/RFS and differentiation, intrahepatic metastasis, tumor-node-metastasis (TNM), tumor number, tumor size, vascular invasion, and other poor clinicopathological characteristics. The high expression of class II HDACs was related to poor OS and multiple and larger tumors. After subgroup analysis, class II HDACs may also be related to worse TNM and Edmondson grading. The high expression of class III HDACs was related to poor OS, hepatitis B, liver cirrhosis, serum AFP, and vascular invasion. But it was more common in women and was related to single, smaller tumors. Type I, II, and III HDACs are associated with poor prognosis, and there are also correlations with some clinicopathological features, suggesting that different types of HDACs may be valuable biomarkers for HCC.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Feminino , Humanos , Biomarcadores Tumorais/metabolismo , Carcinoma Hepatocelular/metabolismo , Histona Desacetilases , Neoplasias Hepáticas/patologia , Prognóstico , Masculino
5.
Neuroendocrinology ; 112(3): 263-275, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-33902058

RESUMO

INTRODUCTION: Although gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) with liver metastasis encompass a wide variety of clinical conditions with various prognosis, no statistical model for predicting the prognosis of these patients has been established. We sought to establish a more elaborative and individualized nomogram to predict survival of patients with liver-limited metastatic GEP-NENs. In addition, this nomogram was validated by both the Surveillance, Epidemiology, and End Results (SEER) database and a Chinese multicenter cohort. METHODS: Patients diagnosed with GEP-NENs with liver-limited metastasis between 2010 and 2016 were identified from the SEER database. Kaplan-Meier survival analysis was performed to analyze survival outcomes. A nomogram was established based on the independent prognostic variables identified from univariate and multivariate Cox regression analyses. The nomogram was evaluated in both an internal validation SEER dataset and an external validation dataset composed of patients from the Chinese multicenter cohort. RESULTS: A total of 1,474 patients from the SEER database and 192 patients from the multicenter cohort were included. Age, tumor size, differentiation, primary tumor resection, and liver metastasis resection were identified as independent prognostic factors by univariate and multivariate Cox analyses and were verified by Kaplan-Meier survival analysis (all p < 0.0001). A nomogram was developed and validated by calibration curves and areas under the curve of the external validation cohort, which showed good consistency and veracity in predicting overall survival. CONCLUSION: A nomogram was developed for the first time to predict the survival of patients with liver-limited metastases from GEP-NENs. Both internal and external validation demonstrated excellent discrimination and calibration of our nomogram. Based on this prognostic model, clinicians could develop more personalized treatment strategies and surveillance protocols.


Assuntos
Neoplasias Hepáticas , Nomogramas , China/epidemiologia , Estudos de Coortes , Humanos , Estadiamento de Neoplasias , Prognóstico , Modelos de Riscos Proporcionais , Programa de SEER
6.
Aging (Albany NY) ; 12(6): 5479-5499, 2020 03 25.
Artigo em Inglês | MEDLINE | ID: mdl-32213661

RESUMO

It is crucial to grasp the characteristics of tumour immune microenvironment to improve effects of immunotherapy. In this study, the immune and stromal scores of 371 cases were calculated for quantitative analysis of immune and stromal cell infiltration in the tumour microenvironment of hepatocellular carcinoma (HCC). The weighted gene co-expression network analysis and protein-protein interaction network were analysed to identify immune microenvironment-related genes. The results showed that patients with high immune scores had a higher 4-year recurrence-free rate. TP53, CTNNB1, and AXIN1 mutations significantly varied with immune scores. In immune score-related modules analysis, Kyoto encyclopaedia of genes and genomes pathways and gene ontology terms were closely related to immune processes, tumorigenesis, and metastasis. Twelve new immune microenvironment-related genes were identified and had significantly positive correlations with seven immune checkpoint genes. In prognostic analysis, eleven immune microenvironment-related genes exhibited high expression, nine of which were validated in the GSE62232 dataset and were significantly associated with a good prognosis. Our findings suggest that calculating immune score and stromal score could help to determine tumour purity and immune cell infiltration in the tumour microenvironment. Nine immune microenvironment-related genes identified in this study had potential as prognostic markers for HCC.


Assuntos
Biomarcadores Tumorais/imunologia , Carcinoma Hepatocelular/imunologia , Perfilação da Expressão Gênica/métodos , Neoplasias Hepáticas/imunologia , Fígado/citologia , Microambiente Tumoral/imunologia , Biomarcadores Tumorais/genética , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/genética , Biologia Computacional , Regulação Neoplásica da Expressão Gênica , Humanos , Estimativa de Kaplan-Meier , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/genética , Recidiva Local de Neoplasia/genética , Recidiva Local de Neoplasia/imunologia , Prognóstico , Mapas de Interação de Proteínas , Células Estromais , Microambiente Tumoral/genética
7.
Ann Med ; 51(7-8): 333-344, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31714153

RESUMO

Albumin is the most abundant plasma protein and albumin infusion is commonly used. Conventionally, the biologic and therapeutic effects of albumin have been thought to be due to its oncotic properties. However, albumin has a variety of biologic functions, including molecular transport, anti-oxidation, anti-inflammation, endothelial stabilisation, anti-thrombotic effects, and the adjustment of capillary permeability. Despite this, the functions of albumin have not been thoroughly investigated. Recent studies have shown non-alcoholic fatty liver disease (NAFLD), viral hepatitis, cirrhosis, and liver failure to be associated with impairments in albumin function, which are associated with impairments in liver function and disease prognosis. Post-translational modifications of albumin cause structural modifications that affect protein function. Recently, the concentration of albumin associated with normal function, the 'efficient albumin concentration', has been attracting more interest. In addition, although many biologic markers, including albumin concentration, are widely used for the assessment of early liver dysfunction in patients with liver diseases, the predictive values are unsatisfactory. However, clinical evidence has suggested that albumin function may represent a novel biomarker of early impairment in liver function. In this review, we summarise the factors affecting albumin function and discuss the clinical significance of impairments in albumin function in various liver diseases.Key messagesThe importance of albumin depends not only on its concentration, but also on its various physiological functions.Impaired albumin function has been reported in a variety of liver diseases, and is associated with disease severity and prognosis, thereby proposing the concept of 'effective albumin concentration'.Albumin dysfunction occurs earlier than other conventional indicators, and albumin dysfunction may be a new biomarker of early impairment in liver function.Many exogenous and endogenous factors lead to post-translational modifications of albumin, which alters the three-dimensional structure of albumin, resulting in a decrease in its biological activity.


Assuntos
Hepatopatias/sangue , Albumina Sérica Humana/fisiologia , Humanos , Testes de Função Hepática
8.
Biomed Pharmacother ; 118: 109228, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31351430

RESUMO

PURPOSE: tumor-infiltrating immune cells are highly relevant to the progression and prognosis of colorectal cancer (CRC). The aim of this study is to explore the immune cells and immune-related gene expression in tumor microenvironment of CRC. METHODS: CIBERSORT, a deconvolution algorithm, was used to analyze the infiltration of 22 immune cell types in the tumor microenvironment and immune-related gene expression in 404 CRC and 40 adjacent non-tumorous tissues. RESULTS: a wide heterogeneity of immune cells among different paired tissues and in tumor stages was uncovered. M0 macrophages, M1 macrophages and CD4 memory activated T cells were infiltrated significantly more in CRC compared with normal tissues in both TCGA and GEO cohorts. CRC with T1-2 tumor stage showed increased CD4 memory activated T cells compared with T3-4 tumors. M0 macrophages were the highest in stage N1 tumors. Significant immune-related genes were identified to build prognostic models by Cox regression analysis. The concordance index of the prognostic model for TNM stage I-II was 0.69, and 0.71 for stage III-IV. The AUC values for 1-, 3-, and 5-year survivals were 0.674, 0.773, 0.812 for TNM stage I-II, respectively, and 0.764, 0.782, 0.803 for stage III-IV, respectively. CONCLUSION: these results could assist clinicians in selecting targets for immunotherapies and individualize treatment strategies for patients with CRC.


Assuntos
Neoplasias Colorretais/genética , Neoplasias Colorretais/imunologia , Regulação Neoplásica da Expressão Gênica , Microambiente Tumoral/genética , Microambiente Tumoral/imunologia , Estudos de Coortes , Neoplasias Colorretais/patologia , Feminino , Ontologia Genética , Humanos , Linfonodos/patologia , Macrófagos/patologia , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Estadiamento de Neoplasias , Prognóstico , Modelos de Riscos Proporcionais , Reprodutibilidade dos Testes , Fatores de Risco
9.
J Cell Mol Med ; 23(3): 1714-1722, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30588757

RESUMO

Time-restricted feeding (TRF), that is, no caloric intake for 14-16 hours each day leads to favourable nutritional outcomes. This study is the first to investigate TRF through a surgical perspective verifying its efficacy against liver ischaemia reperfusion (I/R) injury. We randomly assigned 100 10-week-old wild-type male C57BL/6 mice into two feeding regimens: TRF and ad libitum access to food. Main outcomes were evaluated at 6, 12 and 24 hours post-I/R surgery after 12 weeks of intervention. TRF group demonstrated minor liver injury via histological study; lower serum levels of liver enzymes, glucose and lipids; higher concentrations of free fatty acid and ß-hydroxybutyrate; decreased oxidative stress and inflammatory biomarkers; as well as less severe cell apoptosis and proliferation. Further exploration indicated better gut microenvironment and intestinal epithelial tight junction function. TRF employed its positive influence on a wide spectrum of biochemical pathways and ultimately revealed protective effect against hepatic I/R injury possibly through adjusting the gut microbiota. The results referred to a strong indication of adopting better feeding pattern for surgical patients.


Assuntos
Modelos Animais de Doenças , Jejum , Privação de Alimentos , Microbioma Gastrointestinal , Hepatopatias/prevenção & controle , Traumatismo por Reperfusão/prevenção & controle , Animais , Hepatopatias/etiologia , Hepatopatias/patologia , Hepatopatias/cirurgia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Estresse Oxidativo , Traumatismo por Reperfusão/etiologia , Traumatismo por Reperfusão/patologia , Traumatismo por Reperfusão/cirurgia
10.
Cell Physiol Biochem ; 51(1): 301-314, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30453302

RESUMO

BACKGROUND/AIMS: This study aims to examine the effect of long noncoding RNA HOST2 (LncRNA HOST2) on epithelial-mesenchymal transition (EMT), proliferation, invasion and migration of hepatocellular carcinoma (HCC) cells via activation of the JAK2-STAT3 signaling pathway. METHODS: HCC and para-cancerous tissues were collected from 136 HCC patients. Immunohistochemistry was used to detect the expression of JAK2 and STAT3. HCC SMMC7721 cells were grouped into blank, negative control (NC), HOST2 mimic and HOST2 inhibitor groups. The mRNA and protein expression levels of HOST2, JAK2, STAT3, E-cadherin, vimentin, Snail, Slug, Twist and Zeb1 in tissues and cells were determined by reverse transcription -quantitative polymerase chain reaction (RT-qPCR) and Western blotting, respectively. An MTT assay, scratch test and Transwell assay were applied to measure cell proliferation, migration and invasion, respectively. RESULTS: The levels of JAK2, STAT3 and vimentin were higher in HCC tissues, while the expression of E-cadherin was lower in HCC tissues compared with para-cancerous tissues. The silencing of HOST2 significantly decreased cell proliferation, migration and invasion, reduced the levels of HOST2, JAK2, STAT3 and vimentin, and elevated the expression of E-cadherin. HOST2 silencing also decreased the levels of Snail, Slug and Twist but increased the level of Zeb1 protein, while the opposite findings were observed in the HOST2 mimic group. CONCLUSION: These results reveal a possible mechanism in HCC in which LncRNA HOST2 may increase EMT and enhance proliferation, invasion and metastasis of HCC cells via activation of the JAK2-STAT3 signaling pathway.


Assuntos
Proliferação de Células , Transição Epitelial-Mesenquimal , Janus Quinase 2/metabolismo , RNA Longo não Codificante/metabolismo , Fator de Transcrição STAT3/metabolismo , Adulto , Idoso , Caderinas/genética , Caderinas/metabolismo , Carcinoma Hepatocelular/patologia , Linhagem Celular Tumoral , Movimento Celular , Feminino , Humanos , Janus Quinase 2/genética , Neoplasias Hepáticas/patologia , Masculino , Pessoa de Meia-Idade , Interferência de RNA , RNA Longo não Codificante/antagonistas & inibidores , RNA Longo não Codificante/genética , RNA Interferente Pequeno/metabolismo , Fator de Transcrição STAT3/genética , Transdução de Sinais , Vimentina/genética , Vimentina/metabolismo
11.
Asia Pac J Clin Oncol ; 13(5): e321-e330, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-27519165

RESUMO

AIM: To investigate whether the use of continuous Pringle maneuver (PM) adversely impacts the outcome of patients with hepatocellular carcinoma (HCC). METHODS: From January 1989 to January 2011, 586 HCC patients who underwent curative resection in Peking Union Medical College Hospital were identified from the database. Continuous PM was performed in 290 patients (PM group), including 163 patients with a hepatic inflow occlusion time of <15 min (PM-1 group) and 127 with 15-30 min (PM-2 group). An additional 296 patients underwent partial hepatectomy without inflow occlusion (occlusion-free, OF group). RESULTS: The PM group showed less estimated blood loss during hepatectomy than the OF group (P = 0.005) and the two groups experienced similar incidence of perioperative complications. There were no significant differences in either overall survival or disease-free survival (DFS) between the PM and OF groups (P = 0.117 and 0.291, respectively), and between the PM-1 and PM-2 groups (P = 0.344 and 0.103, respectively). Hepatic inflow occlusion and occlusion time were not independent risk factors for OS or DFS. CONCLUSIONS: Continuous PM effectively reduces intraoperative bleeding and does not adversely impact the outcomes of HCC patients. It remains a valuable tool in hepatic resection, even difficult, complicated resections requiring prolonged clamping times.


Assuntos
Carcinoma Hepatocelular/cirurgia , Hepatectomia/métodos , Neoplasias Hepáticas/cirurgia , Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/patologia , Intervalo Livre de Doença , Feminino , Humanos , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/patologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco
12.
Asia Pac J Clin Oncol ; 13(5): e312-e320, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-27098441

RESUMO

AIM: Primary clear cell carcinoma of liver (PCCCL) is a specific and rare subtype of primary hepatocellular carcinoma (HCC). We performed a retrospective study with long-term follow-up to investigate predictive factors and prognosis of intrahepatic recurrences of PCCCL after radical resection. METHODS: We retrospectively analyzed records of 38 patients with PCCCL who were diagnosed at Peking Union Medical College Hospital between January 1989 and September 2010, with a long-term follow up to January 2015, to determine their clinical characteristics and postoperative survival. The data were compared with 400 patients received radical hepatectomy for common type hepatocellular carcinoma (CHCC) during the study period. RESULTS: PCCCL tumors were smaller than those of CHCC (P < 0.001) and the incidence of vascular invasion of tumors in PCCCL group was significantly lower than that in CHCC (P = 0.029). The 1-, 3-, and 5-year overall survival (OS) for PCCCL patients were 94.6%, 67.3%, and 58.5%, respectively; 1-, 3-, and 5-year disease-free survival (DFS) were 89.2%, 54.1%, and 48.6%, respectively. Both OS and DFS were significantly better for PCCCL patients than for CHCC (P = 0.039 and 0.044). Cox modeling showed high Edmondson grade to be the only independent predictive factor for survival of PCCCL patients, which were different from those of CHCC. CONCLUSIONS: PCCCL is a less malignant subtype of HCC than CHCC, patients with PCCCL likely have later intrahepatic recurrences and a better prognosis. Edmondson grade predicts survival of patients with PCCCL after curative resection; those with higher Edmondson grades may require more careful follow-up and aggressive post-hepatectomy therapy.


Assuntos
Adenocarcinoma de Células Claras/patologia , Carcinoma Hepatocelular/patologia , Hepatectomia/métodos , Neoplasias Hepáticas/patologia , Adenocarcinoma de Células Claras/mortalidade , Adenocarcinoma de Células Claras/cirurgia , Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/cirurgia , Intervalo Livre de Doença , Feminino , Seguimentos , Humanos , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/cirurgia , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/cirurgia , Prognóstico , Estudos Retrospectivos
13.
Oncotarget ; 7(26): 40481-40490, 2016 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-27248174

RESUMO

BACKGROUND: Detection of circulating cell-free DNA (cfDNA) has potential clinical value for assessing tumor biology in patients with hepatocellular carcinoma (HCC), yet many traditional assays lack robustness. This study was the first to apply a high-throughput sequencing platform to detect tumor-associated mutations in HCC from circulating tumor-derived DNA (ctDNA) and to evaluate the utility and feasibility of this approach. METHODS: Using the MiSeq™ system, plasma and matched tumor DNA samples were analyzed for hotspot mutations in the TERT, CTNNB1, and TP53 genes that had been verified as the most prevalent mutations in HCC. We compared tumor and plasma data and prospectively investigated the association between significant mutations detected in ctDNA and the patients' clinical outcomes. RESULTS: In 41 patients, we detected tumor-associated mutations for HCC in 8 (19.5%) plasma samples. Among them, one showed a tumor-associated mutation in ctDNA but not in the tumor tissue which we used to detect. We also found that ctDNA with mutations could be detected more easily in patients who suffered vascular invasion (P=0.041) and predicted a shorter recurrence-free survival time (P<0.001). There was no relationship between detectable mutations and concentration of cfDNA (P=0.818). CONCLUSIONS: The results of our study suggest that tumor-associated mutations detected in plasma are associated with vascular invasion and might be used to predict a shorter recurrence-free survival time for HCC patients. This kind of biomarker can overcome the limitations of tumor heterogeneity. Moreover, the diagnostic performance is improved if multiple mutations in different genes are combined.


Assuntos
Carcinoma Hepatocelular/genética , Ácidos Nucleicos Livres/genética , Sequenciamento de Nucleotídeos em Larga Escala , Neoplasias Hepáticas/genética , Mutação , Idoso , Biomarcadores Tumorais/genética , Ácidos Nucleicos Livres/sangue , Análise Mutacional de DNA , DNA de Neoplasias/genética , Intervalo Livre de Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Telomerase/genética , Proteína Supressora de Tumor p53/genética , beta Catenina/genética
14.
Medicine (Baltimore) ; 95(17): e3491, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-27124050

RESUMO

Multiple primary malignancies (MPMs) are defined as 2 or more malignancies without subordinate relationship detected in different organs of an individual patient. Reports addressing MPM patients with hepatocellular carcinoma (HCC) are rare. We perform a 26-year follow-up study to investigate characteristics and prognosis of MPM patients associated with HCC due to the scarcity of relative researches.We retrospectively analyzed records of 40 patients who were diagnosed with MPM including HCC at the Departments of Surgery at Peking Union Medical College Hospital during 1989 to 2010. Their clinical characteristics and postoperative survival were compared with those of 448 patients who had HCC only during the study period.Among the 40 MPM patients, 11 were diagnosed synchronously and 29 metachronously. The most common extra-hepatic malignancies were lung cancer (15%), colorectal (12.5%), and thyroid carcinoma (12.5%). MPM patients had a negative hepatitis B virus infection rate (P = 0.013) and lower median alfa-fetoprotein (AFP) level (P = 0.001). Post-operative 1-, 3-, and 5-year overall survival (OS) rates for MPM patients were 82.5%, 64.5%, and 38.6% respectively, and showed no significant difference with those of HCC-only patients (84.7%, 54.2%, and 38.3% P = 0.726). During follow-up, 24 MPM patients died, including 17 (70.8%) who died of HCC-related causes. In univariate analysis, synchronous diagnosis, higher gamma glutamyltransferase (GGT) and/or AFP levels, tumor >5 cm and vascular invasion were significantly associated with shorter OS, but only tumor size was an independent OS factor in Cox modeling analysis.HCC should be considered as a potential second primary for all cancer survivors. Most MPM patients died of HCC-related causes and showed no significant difference in OS compared with HCC-only patients. Tumor size of HCC, rather than MPMs itself, was the only independent OS predictor for the MPM patients.


Assuntos
Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/cirurgia , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/cirurgia , Neoplasias Primárias Múltiplas/diagnóstico , Neoplasias Primárias Múltiplas/cirurgia , Segunda Neoplasia Primária/diagnóstico , Segunda Neoplasia Primária/cirurgia , Adulto , Idoso , Carcinoma Hepatocelular/mortalidade , China , Feminino , Seguimentos , Hepatectomia , Humanos , Neoplasias Hepáticas/mortalidade , Masculino , Pessoa de Meia-Idade , Neoplasias Primárias Múltiplas/mortalidade , Segunda Neoplasia Primária/mortalidade , Prognóstico , Estudos Retrospectivos , Análise de Sobrevida
15.
Gastroenterol Res Pract ; 2016: 5120760, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-28101103

RESUMO

Background. Currently there is no indicator that can evaluate actual liver lesion for early stages of viral hepatitis, nonalcoholic fatty liver disease (NAFLD), and cirrhosis. Aim of this study was to investigate if albumin binding function could better reflect liver function in these liver diseases. Methods. An observational study was performed on 193 patients with early NAFLD, viral hepatitis, and cirrhosis. Cirrhosis patients were separated according to Child-Pugh score into A, B, and C subgroup. Albumin metal ion binding capacity (Ischemia-modified albumin transformed, IMAT) and fatty acid binding capacity (total binding sites, TBS) were detected. Results. Both IMAT and TBS were significantly decreased in patients with NAFLD and early hepatitis. In hepatitis group, they declined prior to changes of liver enzymes. IMAT was significantly higher in cirrhosis Child-Pugh class A group than hepatitis patients and decreased in Child-Pugh class B and class C patients. Both IMAT/albumin and TBS/albumin decreased significantly in hepatitis and NAFLD group patients. Conclusions. This is the first study to discover changes of albumin metal ion and fatty acid binding capacities prior to conventional biomarkers for liver damage in early stage of liver diseases. They may become potential earliest sensitive indicators for liver function evaluation.

16.
Medicine (Baltimore) ; 94(14): e722, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25860220

RESUMO

Qualitative and quantitative analyses of circulating cell-free DNA (cfDNA) are potential methods for the detection of hepatocellular carcinoma (HCC). Many studies have evaluated these approaches, but the results have been variable. This meta-analysis is the first to synthesize these published results and evaluate the use of circulating cfDNA values for HCC diagnosis. All articles that met our inclusion criteria were assessed using QUADAS guidelines after the literature research. We also investigated 3 subgroups in this meta-analysis: qualitative analysis of abnormal concentrations of circulating cfDNA; qualitative analysis of single-gene methylation alterations; and multiple analyses combined with alpha-fetoprotein (AFP). Statistical analyses were performed using the software Stata 12.0. We synthesized these published results and calculated accuracy measures (pooled sensitivity and specificity, positive/negative likelihood ratios [PLRs/NLRs], diagnostic odds ratios [DORs], and corresponding 95% confidence intervals [95% CIs]). Data were pooled using bivariate generalized linear mixed model. Furthermore, summary receiver operating characteristic curves and area under the curve (AUC) were used to summarize overall test performance. Heterogeneity and publication bias were also examined. A total of 2424 subjects included 1280 HCC patients in 22 studies were recruited in this meta-analysis. Pooled sensitivity and specificity, PLR, NLR, DOR, AUC, and CIs of quantitative analysis were 0.741 (95% CI: 0.610-0.840), 0.851 (95% CI: 0.718-0.927), 4.970 (95% CI: 2.694-9.169), 0.304 (95% CI: 0.205-0.451), 16.347 (95% CI: 8.250-32.388), and 0.86 (95% CI: 0.83-0.89), respectively. For qualitative analysis, the values were 0.538 (95% CI: 0.401-0.669), 0.944 (95% CI: 0.889-0.972), 9.545 (95% CI: 5.298-17.196), 0.490 (95% CI: 0.372-0.646), 19.491 (95% CI: 10.458-36.329), and 0.87 (95% CI: 0.84-0.90), respectively. After combining with AFP assay, the values were 0.818 (95% CI: 0.676-0.906), 0.960 (95% CI: 0.873-0.988), 20.195 (95% CI: 5.973-68.282), 0.190 (95% CI: 0.100-0.359), 106.270 (95% CI: 22.317-506.055), and 0.96 (95% CI: 0.94-0.97), respectively. The results in this meta-analysis suggest that circulating cfDNA have potential value for HCC diagnosis. However, it would not be recommended for using independently, which is based on the nonrobust results. After combining with AFP, the diagnostic performance will be improved. Further investigation with more data is needed.


Assuntos
Carcinoma Hepatocelular/diagnóstico , DNA/sangue , Neoplasias Hepáticas/diagnóstico , Carcinoma Hepatocelular/sangue , Humanos , Neoplasias Hepáticas/sangue
17.
Hepatobiliary Pancreat Dis Int ; 13(4): 361-70, 2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-25100120

RESUMO

BACKGROUND: Postoperative liver failure remains a life-threatening complication. Preoperative evaluation of liver function is essential in reducing the complications after hepatectomy. However, it is difficult to accurately evaluate liver function before surgery because of the limitations of the liver function tests available. Recent advances in liver function tests improved the ability to assess liver function. The present review was to analyze these methods and their advantages. DATA SOURCES: MEDLINE was searched using the terms of "liver function test", "liver function evaluation" and "galactosyl serum albumin". Relevant articles published in English and Chinese from 1961 to 2014 were reviewed. RESULTS: Although serological tests are used frequently in practice, they reflect the degree of total liver damage or function, not the remnant of liver function. Child-Pugh score and model for end-stage liver disease (MELD) score assess whole liver function, and are particularly useful in determining whether patients with hepatocellular carcinoma and cirrhosis are candidates for resection or transplantation, but cannot determine the safe extent or removal. The indocyanine green and other metabolic quantitative liver function tests can evaluate functional hepatocytes, making them more accurate in predicting liver function. Computed tomography (CT) volumetry can provide anatomic information on the remnant liver volume but not on functional volume. 99mTc-galactosyl serum albumin scintigraphy, combined with single photon emission computed tomography, CT and three-dimensional reconstruction, may be a better quantitative measure of liver function, especially of remnant liver function. CONCLUSIONS: Tests used to evaluate liver functional reserve and to predict surgical risk have limitations. 99mTc-galactosyl serum albumin scintigraphy, which can more accurately evaluate the whole and regional liver function, may be promising in predicting resection margins and risks of liver failure.


Assuntos
Hepatectomia , Hepatopatias/diagnóstico , Hepatopatias/cirurgia , Falência Hepática/prevenção & controle , Testes de Função Hepática , Cuidados Pré-Operatórios/métodos , Biomarcadores/metabolismo , Hepatectomia/efeitos adversos , Humanos , Hepatopatias/diagnóstico por imagem , Hepatopatias/metabolismo , Falência Hepática/etiologia , Valor Preditivo dos Testes , Compostos Radiofarmacêuticos , Medição de Risco , Fatores de Risco , Índice de Gravidade de Doença , Agregado de Albumina Marcado com Tecnécio Tc 99m , Pentetato de Tecnécio Tc 99m , Tomografia Computadorizada de Emissão de Fóton Único , Tomografia Computadorizada por Raios X , Resultado do Tratamento
18.
World J Gastroenterol ; 20(20): 6314-21, 2014 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-24876753

RESUMO

AIM: To analyze the expression profiles of long non-coding RNAs (lncRNAs) in hepatocellular carcinoma. METHODS: Hepatocellular carcinoma (HCC) tissues and matched adjacent non-tumor (NT) liver tissues were collected from 29 patients with HCC, immediately after liver resection, between March 2011 and July 2013. The diagnosis of HCC was made based on histological examination. Differentially expressed lncRNAs between HCC and NT tissues were revealed through microarray-based lncRNAs expression profiling. Further, quantification of selected lncRNAs was performed using quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR). RESULTS: Six hundred and fifty-nine lncRNAs were differentially expressed between HCC and NT tissues, of which five [TCONS_00018278, AK093543, D16366, ENST00000501583, NR_002819 (MALAT1)] were selected for validation. Four of them were significantly downregulated in HCC tissues compared with NT tissues (P = 0.012, 0.045, 0.000 and 0.000, respectively), and the expression level of MALAT1 showed no significant difference (P = 0.114). CONCLUSION: This study identified a set of lncRNAs differentially expressed in HCC tissues and provided useful information for exploring potential therapeutic targets and diagnostic biomarkers of this cancer.


Assuntos
Carcinoma Hepatocelular/genética , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Neoplasias Hepáticas/genética , Análise de Sequência com Séries de Oligonucleotídeos/métodos , RNA Longo não Codificante/genética , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Reação em Cadeia da Polimerase em Tempo Real , Reação em Cadeia da Polimerase Via Transcriptase Reversa
19.
World J Gastroenterol ; 19(46): 8752-7, 2013 Dec 14.
Artigo em Inglês | MEDLINE | ID: mdl-24379596

RESUMO

AIM: To investigate effects of perirenal space blocking (PSB) on gastrointestinal function in patients with severe acute pancreatitis (SAP). METHODS: Forty patients with SAP were randomly allocated to receive PSB or no PSB (NPSB). All the SAP patients received specialized medical therapy (SMT). Patients in the PSB group received PSB + SMT when hospitalized and after diagnosis, whereas patients in the NPSB group only received SMT. A modified gastrointestinal failure (GIF) scoring system was used to assess the gastrointestinal function in SAP patients after admission. Pain severity (visual analog scale, 0 to 100) was monitored every 24 h for 72 h. RESULTS: Modified GIF score decreased in both groups during the 10-d study period. The median score decrease was initially significantly greater in the PSB group than in the NPSB group after PSB was performed. During the 72-h study period, pain intensity decreased in both groups. The median pain decrease was significantly greater in the PSB group than in the NPSB group at single time points. Patients in the PSB group had significantly lower incidences of hospital mortality, multiple organ dysfunction syndrome, systemic inflammatory response syndrome, and pancreatic infection, and stayed in the intensive care unit for a shorter duration. However, no difference in terms of operation incidence was found between the two groups. CONCLUSION: PSB could ameliorate gastrointestinal dysfunction or failure during the early stage of SAP. Moreover, PSB administration could improve prognosis and decrease the mortality of SAP patients.


Assuntos
Anestésicos Locais/administração & dosagem , Plexo Celíaco/fisiopatologia , Gastroenteropatias/terapia , Motilidade Gastrointestinal , Lidocaína/administração & dosagem , Bloqueio Nervoso/métodos , Pancreatite/terapia , Dor Abdominal/etiologia , Dor Abdominal/terapia , Doença Aguda , Adulto , China , Feminino , Gastroenteropatias/diagnóstico , Gastroenteropatias/etiologia , Gastroenteropatias/mortalidade , Gastroenteropatias/fisiopatologia , Mortalidade Hospitalar , Humanos , Masculino , Pessoa de Meia-Idade , Pancreatite/complicações , Pancreatite/diagnóstico , Pancreatite/mortalidade , Pancreatite/fisiopatologia , Estudos Prospectivos , Recuperação de Função Fisiológica , Índice de Gravidade de Doença , Fatores de Tempo , Resultado do Tratamento
20.
Sichuan Da Xue Xue Bao Yi Xue Ban ; 41(3): 476-9, 2010 May.
Artigo em Chinês | MEDLINE | ID: mdl-20629325

RESUMO

OBJECTIVE: To investigate the effect of glucagon-like peptide-2 (GLP-2) on intestinal barrier function in bile duct ligated rats. METHODS: Seventy-two SD rats were randomly divided into three groups: GLP-2 treated group (T), obstructive jaundice control group (C) and sham operation group (SO). Proliferating cell nuclear antigen (PCNA) and caspase-3 expression in the intestinal mucosa were measured by immunohistochemistry staining equiped image analyzing systems (Image proplus Version 4.5), and the height of the intestinal villi was observed and measured with light microscope, in the rats 1, 3 and 7 days after operation. RESULTS: The expression of PCNA in the intestinal villi of rats in C group decreased significantly (P < 0.05), which was more serious than those in the SO and T groups especially on the third and seventh day after operation (P < 0.05). Compared with the SO and T groups, the expression of caspase-3 in the rats of C group increased significantly. The expression of caspase-3 increased with timeafter operation (P < 0.05). The height of the villi of the rats in C group was shorter than those of the rats in SO and T groups, and it became shorter and shorter day by day(P < 0.05). The height of the intestinal villi of the rats in SO group and T groups had no significant changes post operation. CONCLUSION: GLP-2 may stimulate the growth of intestinal mucosa, increase the intestinal mucosa cell proliferation, diminish the number of the apoptosis cells, and protect the intestinal barrier function in obstructive jaundice rats.


Assuntos
Peptídeo 2 Semelhante ao Glucagon/uso terapêutico , Mucosa Intestinal/fisiopatologia , Intestinos/fisiopatologia , Icterícia Obstrutiva/tratamento farmacológico , Icterícia Obstrutiva/fisiopatologia , Animais , Caspase 3/genética , Caspase 3/metabolismo , Feminino , Peptídeo 2 Semelhante ao Glucagon/farmacologia , Mucosa Intestinal/efeitos dos fármacos , Mucosa Intestinal/metabolismo , Intestinos/patologia , Masculino , Antígeno Nuclear de Célula em Proliferação/genética , Antígeno Nuclear de Célula em Proliferação/metabolismo , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley
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