Angiotensin receptor blockers retard the progression and fibrosis via inhibiting the viability of AGTR1+ CAFs in intrahepatic cholangiocarcinoma.

BACKGROUND: Intrahepatic cholangiocarcinoma (iCCA) is a highly lethal malignancy characterized by massive fibrosis and has ineffective adjuvant therapies. Here, we demonstrate the potential of angiotensin receptor blockers (ARBs) in targeting iCCA. METHODS: Masson's trichrome staining was used to assess the effect of ARBs in iCCA specimens, CCK8 and gel contraction assays in vitro and in xenograft models in vivo. RNA-seq and ATAC-seq were used for mechanistic investigations. RESULTS: Patients with iCCA who were administered ARBs had a better prognosis and a lower proportion of tumour stroma, indicating alleviated fibrosis. The presence of AGTR1, the ARBs receptor, is associated with a poor prognosis of iCCA and is highly expressed in tumour tissues and cancer-associated fibroblasts (CAFs). The ARBs strongly attenuated the viability of AGTR1+ CAFs in vitro and retarded tumour progression and fibrosis in xenograft models of co-cultured CAFs and iCCA cells. Still, they did not have a significant effect on AGTR1- CAFs. Moreover, ARBs decreased the secretion of AGTR1+ CAF-derived MFAP5 via the Hippo pathway, weakened the interaction between CAFs and iCCA cells, and impaired the aggressiveness of iCCA cells by attenuating the activation of the Notch1 pathway in iCCA cells. CONCLUSIONS: ARBs exhibit anti-fibrotic function by inhibiting the viability of AGTR1+ CAFs. These findings support using ARBs as a novel therapeutic option for targeting iCCA.

A fast online questionnaire for screening mental illness symptoms during the COVID-19 pandemic.

The COVID-19 pandemic has caused massive effects on the situation of public mental health. A fast online questionnaire for screening and evaluating mental symptoms is urgent. In this work, we developed a new 19-item self-assessment Fast Screen Questionnaire for Mental Illness Symptoms (FSQ-MIS) to quickly identify mental illness symptoms. The FSQ-MIS was validated on a total of 3828 young adult mental disorder patients and 984 healthy controls. We applied principal component analysis (PCA), receiver operating characteristic (ROC) curve, and general log-linear analysis (GLA) to evaluate the construct and parallel validity. Results demonstrate that the proposed FSQ-MIS shows high test-retest reliability (0.852) and split-half reliability (0.844). Six factors obtained using PCA explained 54.3% of the variance and showed high correlations with other widely used scales. The ROC results (0.716-0.983) revealed high criterion validity of FSQ-MIS. GLA demonstrated the advantage of FSQ-MIS in predicting anxiety and depression prevalence in COVID-19, supporting the efficiency of FSQ-MIS as a tool for research and clinical practice.

Right ventricular dysfunction in patients with diffuse large B-cell lymphoma undergoing anthracycline-based chemotherapy: a 2D strain and 3D echocardiography study.

To investigate whether 2D strain and 3D echocardiography could early identify the impaired right ventricular (RV) function after anthracycline exposure. Sixty-one patients with diffuse large B-cell lymphoma treated with anthracycline were studied. Echocardiography was conducted at baseline, after the third cycle of the chemotherapy, after the completion of the chemotherapy, and follow-up at 10 months after the initiation of chemotherapy. RV global longitudinal strain (RV GLS) and RV free wall longitudinal strain (RV FWLS) were calculated using speckle tracking echocardiography. RV ejection fraction (RVEF) was analyzed by 3D echocardiography. RV systolic dysfunction was defined by ≥ 2 RV parameters below the threshold value, and cardiotoxicity was defined as a reduction in left ventricular EF > 10 to < 53%. After the third cycle of chemotherapy, only RV GLS was significantly decreased, while after the completion of the chemotherapy, RV GLS, RV FWLS, and RVEF were all significantly decreased compared with baseline measurements. At the end of follow-up, 9 patients (14.8%) were diagnosed with RV systolic dysfunction, and 16 patients (26.2%) had at least 1 abnormal RV function parameter. The proportion of RV systolic dysfunction was significantly higher in patients with cardiotoxicity than in patients without cardiotoxicity, yielding an odds ratio of 5.143. A percentage decrease in RV FWLS and RVEF were independent predictors of RV systolic dysfunction. Two-dimensional strain and 3D echocardiography are valuable methods for evaluating anthracycline-related impairment of RV function in DLBCL patients receiving chemotherapy. RV FWLS and RVEF are reliable predictors of RV systolic dysfunction.

Altered Effective Brain Connectivity During Habituation in First Episode Schizophrenia With Auditory Verbal Hallucinations: A Dichotic Listening EEG Study.

Background: Habituation is considered to have protective and filtering mechanisms. The present study is aim to find the casual relationship and mechanisms of excitatory-inhibitory (E/I) dysfunctions in schizophrenia (SCZ) via habituation. Methods: A dichotic listening paradigm was performed with simultaneous EEG recording on 22 schizophrenia patients and 22 gender- and age-matched healthy controls. Source reconstruction and dynamic causal modeling (DCM) analysis were performed to estimate the effective connectivity and casual relationship between frontal and temporal regions before and after habituation. Results: The schizophrenia patients expressed later habituation onset (p < 0.01) and hyper-activity in both lateral frontal-temporal cortices than controls (p = 0.001). The patients also showed decreased top-down and bottom-up connectivity in bilateral frontal-temporal regions (p < 0.01). The contralateral frontal-frontal and temporal-temporal connectivity showed a left to right decreasing (p < 0.01) and right to left strengthening (p < 0.01). Conclusions: The results give causal evidence for E/I imbalance in schizophrenia during dichotic auditory processing. The altered effective connectivity in frontal-temporal circuit could represent the trait bio-marker of schizophrenia with auditory hallucinations.

Speckle tracking echocardiography in the early detection and prediction of anthracycline cardiotoxicity in diffuse large B-cell lymphoma treated with (R)-CHOP regimen.

BACKGROUND: Despite speckle tracking echocardiography (STE) has emerged as a sensitive technique for identifying myocardial dysfunction, there are little data available on the appropriate timing to perform STE in the serial assessment after anthracycline administration. Moreover, further uncertainty is increased in the context of STE application in diffuse large B-cell lymphoma (DLBCL) research, as most recommendations are inferred by studies conducted primarily in breast cancer. OBJECTIVE: This study aimed to determine whether early measurement of strain parameters derived by STE could predict the development of cardiotoxicity. METHODS: Sixty-five patients were included in the final analysis. The patients were evaluated at baseline, after the third cycle and sixth-eighth cycle, and during follow-up. Global longitudinal strain (GLS) was analyzed using STE, and left ventricular ejection fraction (LVEF) was calculated by real time 3D echocardiography (RT3DE). RESULTS: There was a significant decrease in GLS after the third cycle of chemotherapy and remained decreased during subsequent follow-up, whereas LVEF decreased only at follow-up. A percentage reduction in GLS of 13.8% between baseline and the third cycle of chemotherapy was the best predictor of further LVEF reduction. CONCLUSION: Earlier monitoring timing and more accurate assessment methods might be helpful in the prevention of irreversible heart failure.

EYA4 inhibits hepatocellular carcinoma growth and invasion by suppressing NF-κB-dependent RAP1 transactivation.

BACKGROUND: Our previous studies demonstrated that eyes absent homolog 4 (EYA4), a member of the eye development-related EYA family in Drosophila, is frequently methylated and silenced in hepatocellular carcinoma (HCC) specimens and associated with shorter survival. The current work aimed to explore the mechanisms through which EYA4 functions as a tumor suppressor in HCC. METHODS: Stable EYA4-expressing plasmid (pEYA4) transfectants of the human HCC cell lines Huh-7 and PLC/PRF/5 (PLC) were established. Xenografts tumors were established via subcutaneous injection of the stable transfectants into BALB/c nude mice. Tissue samples were obtained from 75 pathologically diagnosed HCC patients. Quantitative real-time polymerase chain reaction, Western blotting and immunohistochemistry were performed to determine the expression of EYA4 in cell lines, xenografts and clinical specimens. The cell proliferation, colony formation, invasiveness and tumor formation of stable transfectants were studied. A gene expression microarray was utilized to screen genes regulated by EYA4 expression. The effect of EYA4 on nuclear factor-κB (NF-κB)/RAS-related protein 1 (RAP1) signaling was demonstrated through the co-transfection of pEYA4 and Flag-tagged RAS-related protein 1A gene-expressing plasmid (Flag-RAP1A), functional studies, chromatin immunoprecipitation, immunofluorescence staining and cellular ubiquitination assay. RESULTS: The restoration of EYA4 expression in HCC cell lines suppressed cell proliferation, inhibited clonogenic outgrowth, reduced cell invasion and restrained xenograft tumor growth, and Flag-RAP1A reversed the suppressive effects of pEYA4 in vitro. Activation of NF-κB with tumor necrosis factor-α (TNF-α) increased the binding of p65 to the RAP1A gene promoter and up-regulated RAP1 protein expression. The inhibition of NF-κB with BAY 11-7085 and p65 siRNA successfully blocked TNF-α-induced RAP1 up-regulation. EYA4 antagonized the TNF-α-induced phosphorylation and ubiquitination of inhibitor of NF-κBα (IκBα) as well as the nuclear translocation and transactivation of p65, resulting in repressed NF-κB activity and RAP1 expression. Blocking the serine/threonine phosphatase activity of EYA4 with calyculin A notably abrogated its suppressive effect on NF-κB activity. In addition, EYA4 expression was inversely correlated with IκBα/RAP1 activity in clinical HCC specimens. CONCLUSION: Our findings provide a functional and mechanistic basis for identifying EYA4 as a bona fide tumor suppressor that disrupts aberrant activation of the NF-κB/RAP1 signaling pathway and thus orchestrates a physiological impediment to HCC growth and invasion.

In vitro inhibitory effects of pristimerin on human liver cytochrome P450 enzymes.

1.Pristimerin (PTM) is a biological component isolated from Chinese herbal plant Celastrus and Maytenus spp. and it possesses numerous pharmacological activities. However, whether PTM affects the activity of human liver cytochrome P450 (CYP) enzymes remains unclear. 2.In this study, the inhibitory effects of PTM on the eight human liver CYP isoforms (i.e. 1A2, 3A4, 2A6, 2E1, 2D6, 2C9, 2C19 and 2C8) were investigated in vitro using human liver microsomes (HLMs). 3.The results showed that PTM inhibited the activity of CYP1A2, 3A4 and 2C9, with IC 50 values of 21.74, 15.88 and 16.58 µM, respectively, but that other CYP isoforms were not affected. Enzyme kinetic studies showed that PTM was not only a non-competitive inhibitor of CYP3A4, but also a competitive inhibitor of CYP1A2 and 2C9, with Ki values of 7.33, 11.60 and 8.09 µM, respectively. In addition, PTM is a time-dependent inhibitor for CYP3A4 with Kinact /KI value of 0.049/11.62 µM-1 min-1. 4.The in vitro studies of PTM with CYP isoforms indicate that PTM has the potential to cause pharmacokinetic drug interactions with other co-administered drugs metabolized by CYP1A2, 3A4 and 2C9. Further clinical studies are needed to evaluate the significance of this interaction.

EYA4 gene functions as a prognostic marker and inhibits the growth of intrahepatic cholangiocarcinoma.

BACKGROUND: The molecular prognostic markers and carcinogenesis of intrahepatic cholangiocarcinoma (ICC) have not been well documented. The purpose of this study was to investigate the prognostic value of the eyes absent homolog 4 (EYA4) gene in ICC and its biological effects on ICC growth in vitro and in vivo. METHODS: One hundred twelve patients with ICC who underwent hepatectomy were enrolled in the study. EYA4 mRNA and EYA4 protein levels in ICC and adjacent non-tumoral tissues were evaluated using real-time quantitative polymerase chain reaction and immunohistochemical staining, respectively. EYA4 protein levels in ICC cells were determined using western blot analysis. The associations between EYA4 expression and clinicopathologic features of ICC were analyzed. To identify independent prognostic factors, univariate and multivariate analyses were performed. The biological effects of EYA4 on ICC cells were evaluated by establishing stable EYA4-overexpressing transfectants in vitro, and EYA4's effects on tumor growth were evaluated by intra-tumoral injection of EYA4-expressing plasmids in a NOD/SCID murine model of xenograft tumors. RESULTS: ICC tissues had significantly lower EYA4 mRNA and protein levels compared with adjacent non-tumoral tissues (both P < 0.001). Univariate and multivariate analyses showed that EYA4 protein level, tumor number, adjacent organ invasion, lymph node metastasis, and tumor differentiation were independent prognostic factors for disease-free survival and overall survival (all P < 0.05). In vitro, EYA4 overexpression inhibited tumor cell growth, foci formation, and cell invasiveness. In vivo, intra-tumoral injection of EYA4-expressing plasmids significantly inhibited ICC growth in the murine xenograft model compared with the control group (P < 0.05). CONCLUSION: EYA4 gene functioned as a molecular prognostic marker in ICC, and its overexpression inhibited tumor growth in vitro and in vivo.

EYA4 functions as tumor suppressor gene and prognostic marker in pancreatic ductal adenocarcinoma through ß-catenin/ID2 pathway.

Eye absent homolog 4 (EYA4) was initially found as key gene in controlling eye development in Drosophila. We recently found that EYA4 was an independent prognostic factor in hepatocellular carcinoma. Its biological functions in malignancies remained unknown. The present study aimed at investigating its biological functions, molecular mechanisms and prognostic values in pancreatic ductal adenocarcinoma (PDAC). Overexpression of EYA4 in PDAC cells inhibited proliferation and invasion in vitro and tumor growth in vivo. Depletion of EYA4 in PDAC cells enhanced proliferation and invasion in vitro and tumor growth in vivo. Mechanistically, armed with the serine/threonine-specific protein phosphatase activity, EYA4 dephosphorylated ß-catenin at Ser675, blocked ß-catenin nuclear translocation and inhibited ID2 transactivation. Consistently, EYA4 expression inversely correlated with the levels of p-Ser675-ß-catenin and ID2 in tissues. EYA4 expression in PDAC tissues was significantly reduced as compared with adjacent non-tumoral tissues. EYA4 expression was an independent prognostic factor in PDAC, with a lower EYA4 level in association with shorter long-term survival and disease-free time. We showed that EYA4 functioned as tumor suppressor gene in PDAC via repressing ß-catenin/ID2 activation, and was an independent prognostic factor in PDAC.

DNA methylation profiling identifies EYA4 gene as a prognostic molecular marker in hepatocellular carcinoma.

BACKGROUND: DNA hypermethylation plays important roles in carcinogenesis by silencing key genes. This study aims to identify pivotal genes in hepatocellular carcinoma (HCC) by DNA methylation microarray and to assess their prognostic values. MATERIALS AND METHODS: DNA methylation microarray was performed in 45 pairs of HCC and adjacent nontumorous tissues and six normal liver tissues to identify hypermethylated genes in HCC. Potential prognosis-related genes were selected among hypermethylated genes by analyzing influences of methylation levels on disease-free survival (DFS) and overall survival (OS) in 45 patients. Their prognostic values were validated in 154 patients with HCC (including the initial 45 patients) to determine the independent prognostic gene. RESULTS: Altogether, 54 CpG islands in 44 genes were hypermethylated in HCC compared with liver tissues. Among them, methylation levels of ERG and HOXA11 were inversely associated with DFS (both P < 0.050), and methylation levels of EYA4 were inversely related to DFS and OS (both P < 0.050). EYA4 expression was inversely related to tumor size (P < 0.050). Lower EYA4 expression and larger tumor size were independent predictors of both shorter DFS and OS, and higher Barcelona Clinic Liver Cancer (BCLC) staging was an independent predictor of shorter OS (all P < 0.050). CONCLUSIONS: EYA4 functions as a prognostic molecular marker in HCC. Its aberrant hypermethylation and subsequent down-regulation may promote tumor progression.

Simvastatin enhances the chemotherapeutic efficacy of S-1 against bile duct cancer: E2F-1/TS downregulation might be the mechanism.

Simvastatin has inhibitory effects on cancers. The present study aimed to investigate the interactive effects between simvastatin and S-1 against bile duct cancer and its mechanisms. The effects of simvastatin and 5-fluorouracil (5-FU) alone or in combination on the growth and apoptosis of the human cholangiocarcinoma cell line EGI-1 and the gallbladder carcinoma cell line Mz-ChA-1 cells were evaluated in vitro. Real-time PCR and western blot were used to determine E2F-1 and thymidylate synthase (TS) expressions in the treated cells. Tumoricidal efficacy of simvastatin and S-1 was further investigated in a subcutaneous bile duct cancer model in NOD/SCID mice. Simvastatin enhanced the cytotoxicity of 5-FU on bile duct cancer cells in vitro. IC50 of 5-FU alone was 4.34 µmol/l for EGI-1 and 13.9 µmol/l for MZ-ChA-1, whereas it decreased markedly to 0.90 and 2.95 µmol/l, respectively, when combined with simvastatin. The Chou and Talalay combination index of 5-FU and simvastatin was 0.41 and 0.40 at IC50 for EGI-1 and MZ-ChA-1, respectively. Simvastatin alone or plus 5-FU significantly suppressed E2F-1 and TS expressions in EGI-1 and MZ-ChA-1. Simvastatin plus 5-FU induced greater proportion of apoptotic cells on both EGI-1 and MZ-ChA-1, with an increase in cleaved caspase-3 levels, compared with simvastatin or 5-FU alone (all P < 0.05). Simvastatin plus S-1 induced greater tumor inhibition than simvastatin or S-1 alone with E2F-1/TS downregulation in vivo (all P < 0.05). Simvastatin and S-1 exerted synergistic effects against bile duct cancer, which might be mediated by E2F-1/TS downregulation. The combination could be a reasonable regimen in the management of bile duct cancer.

Analysis of the genome-wide DNA methylation profile of side population cells in hepatocellular carcinoma.

BACKGROUND: DNA methylation plays an important role in maintaining pluripotency and regulating the differentiation of stem cells, but the DNA methylation profile of stem cells in hepatocellular carcinoma (HCC) remains unclear. AIMS: To investigate the genome-wide DNA methylation profile of side population (SP) cells of HCC, a special subpopulation of cells enriched with cancer stem cells, by DNA methylation microarray analysis and to analyze the functions and signal pathways of the aberrantly methylated genes in SP cells. METHODS: Side population cells were isolated from HCC cell lines Huh7 and PLC/PRF/5 using flow cytometry, and the tumorigenicity of these SP cells was assessed in NOD/SCID mice. The genome-wide DNA methylation status of SP cells and non-SP (NSP) cells was detected and compared by DNA methylation microarray analysis. Genes with differential methylation between SP and NSP cells were further analyzed for their functions and roles in related signaling pathways. RESULTS: Subcutaneous inoculation of 1 × 10(3) SP cells yielded tumors in 60 % NOD/SCID mice, whereas no tumor was developed after the inoculation of 1 × 10(6) NSP cells. Genome-wide DNA methylation microarray analysis showed that 72 and 181 genes were hypermethylated and hypomethylated, respectively, in both Huh7 and PLC/PRF/5 SP cells as compared with their corresponding NSP cells. Analyses of signaling pathways revealed that hypermethylated and hypomethylated genes were related to four and eight pathways, respectively. CONCLUSIONS: Hepatocellular carcinoma SP cells possessed a differential DNA methylation status compared with NSP cells, and the differentially methylated genes in SP cells were involved in 12 signaling pathways. Our results provide valuable clues for further investigations in elucidating the importance of epigenetic regulation in sustaining HCC SP cells and tumorigenesis.

Sorafenib enhances the chemotherapeutic efficacy of S-1 against hepatocellular carcinoma through downregulation of transcription factor E2F-1.

PURPOSE: Sorafenib and S-1 (one mixed formulation containing 5-FU prodrug and dihydropyrimidine dehydrogenase inhibitor) were two effective agents against hepatocellular carcinoma (HCC), but whether they had synergistic effects remained unclear. The present study aimed at evaluating their synergistic effects against HCC and its mechanisms. METHODS: Inhibitory effects of sorafenib, 5-FU and their combination on HCC cells PLC/PRF/5 and SK-HEP-1 were evaluated. Expressions of transcription factor E2F-1 and its downstream thymidylate synthetase (TS) in the treated cells were determined using real-time PCR and Western blot. In vivo anti-tumoral efficacy of S-1 plus sorafenib on HCC was evaluated in NOD/SCID mice. E2F-1 and TS expressions in tumors were determined by immunohistochemical staining. RESULTS: Sorafenib inhibited growth of HCC cells in dose-dependent manner, with IC50 of 5.4 ± 0.3 µmol/L for PLC/PRF/5 and 5.3 ± 0.5 µmol/L for SK-HEP-1. Sorafenib (1 µmol/L) enhanced inhibitory efficacy of 5-FU on HCC cells in vitro, dropping IC50 of 5-FU from 167.7 ± 12.1 to 105.4 ± 8.4 µmol/L for PLC/PRF/5 and 115 ± 10.2 to 82 ± 7.4 µmol/L for SK-HEP-1 (both p < 0.01). Sorafenib downregulated E2F-1 and TS expressions on HCC cells, and its combination with 5-FU yielded a synergistic downregulation of TS expression on HCC cells. In NOD/SCID mice with subcutaneously inoculated HCC, sorafenib combined with S-1 yielded greater inhibition on tumor growth and remarkable TS suppression when compared with sorafenib or S-1 alone (all p < 0.05). CONCLUSIONS: Sorafenib enhanced therapeutic efficacy of 5-FU/S-1 against HCC through downregulation of E2F-1 and TS expressions. Sorafenib combined with S-1 might represent as valuable therapeutic regimen against HCC.

Are surgical indications of Barcelona Clinic Liver Cancer staging classification justified?

Liver resection is the most effective treatment for hepatocellular carcinoma (HCC). The Barcelona Clinic Liver Cancer (BCLC) staging system is commonly accepted as a guideline for HCC treatment, but it only recommends liver resection for the patients with HCC at stage 0 to A1. The surgical indications of the BCLC staging system need to be re-evaluated. 120 HCC patients undergoing curative liver resection were retrospectively stratified to the BCLC staging system, and the survival of the patients at stages A, B and C was analyzed. The justification of the BCLC staging system was re-evaluated. Fifty-two patients were classified at stage A, 51 at stage B and 17 at stage C respectively. The hospital mortality of this cohort was zero and the morbidity was 24.1%. The 1-, 2-, 3-year overall survival rate of this cohort was 81.6%, 68.3%, and 57.5% respectively. There was no significant difference in the survival rate between the patients at stage A and B (P>0.05). If the treatment guidelines of BCLC staging system were followed, the majority of the patients at stages A and B (77.7%, 80/103) would not have been treated surgically. Our data suggest that the surgical indications of the BCLC staging system are not justified for HCC treatment. More studies may be needed as for how to further broaden the surgical indications of the BCLC staging system in the future.

Outcomes of non-anatomic liver resection for hepatocellular carcinoma in the patients with liver cirrhosis and analysis of prognostic factors.

PURPOSE: In the east countries, patients with hepatocellular carcinoma (HCC) are usually associated with varied degrees of liver cirrhosis, and anatomic resection is therefore limited to use, especially in those with severe liver cirrhosis. This study aims to evaluate the clinical value of non-anatomic resection in HCC patients with cirrhosis. METHODS: Seventy-seven consecutive HCC patients with cirrhosis underwent non-anatomic liver resection in Tongji Hospital from January 2003 to December 2006. The clinical data, severity of liver cirrhosis, and survival rates of these patients were retrospectively evaluated, and the prognostic factors were analyzed. RESULTS: One-, 2-, and 3-year overall and disease-free survival rates of this cohort of patients were 78%, 68%, 56%, and 66%, 58%, 55%, respectively. The hospital mortality and morbidity were 0% and 24.7%, respectively. The 1-, 2-, and 3-year overall survival rates were 85.7%, 77.1%, and 74.3% in the patients with mild cirrhosis, 81.5%, 63%, and 48.1% in the patients with moderate cirrhosis, and 60.0%, 53.3%, and 26.7% in the patients with severe cirrhosis, respectively. There was a significant difference among the patients with different grades of cirrhosis (P = 0.001). Multivariate and univariate analyses revealed that severity of cirrhosis, tumor diameter larger than 5 cm, and vascular invasion were independent prognostic factors. CONCLUSIONS: Non-anatomic liver resection for HCC could yield comparable outcomes with anatomic resection in the patients with mild cirrhosis or tumors diameter smaller than 5 cm. Severity of cirrhosis is an independent factor worsening long-time survival. Non-anatomic resection is a safe and effective surgical modality in the treatment of HCC patients with cirrhosis.

Are Surgical Indications of Barcelona Clinic Liver Cancer Staging Classification justified? / 华中科技大学学报（医学）（英德文版）

Liver resection is the most effective treatment for hepatocellular carcinoma (HCC).The Barcelona Clinic Liver Cancer (BCLC) staging system is commonly accepted as a guideline for HCC treatment,but it only recommends liver resection for the patients with HCC at stage 0 to A1.The surgical indications of the BCLC staging system need to be re-evaluated.120 HCC patients undergoing curative liver resection were retrospectively stratified to the BCLC staging system,and the survival of the patients at stages A,B and C was analyzed.The justification of the BCLC staging system was re-evaluated.Fifty-two patients were classified at stage A,51 at stage B and 17 at stage C respectively.The hospital mortality of this cohort was zero and the morbidity was 24.1％.The 1-,2-,3-year overall survival rate of this cohort was 81.6％,68.3％,and 57.5％ respectively.There was no significant difference in the survival rate between the patients at stage A and B (P＞0.05).If the treatment guidelines of BCLC staging system were followed,the majority of the patients at stages A and B (77.7％,80/103) would not have been treated surgically.Our data suggest that the surgical indications of the BCLC staging system are not justified for HCC treatment.More studies may be needed as for how to further broaden the surgical indications of the BCLC staging system in the future.