Hepatectomy is the main option of treatment for liver cancer,and how to control the blood loss is an important issue for the recovery of patients.Continuous hepatic vascular occlusion(Pringle maneuver)is the oldest and simplest way for vascular occlusion and still used in clinical practice.But continuous hepatic vascular occlusion often gives rise to postischemic reperfusion injury due to clamping the portal vein and the hepatic artery in the hepatic pedicle.So intermittent clamping or hemihepatic vascular occlusion is recommended in complex liver resections or for patients with liver cirrhosis.Total hepatic vascular exclusion has the advantages of occlusion of vascular inflow and outflow of the liver,and is mainly used for patients with tumors invading the caval veins.Major hepatic veins and limited inferior vena cava reconstruction has been also achieved under inflow occlusion with extraparenchymal control of major hepatic veins.It is crucial to know how to select the optimal methods of hepatic vascular occlusion according to the specific conditions.Focusing on this issue,we have reviewed and evaluated various methods and relevant researches in this paper.

Liver transplantation is one of the most effective treatment of hepatocellular carcinoma.And rapamycin is a new class of immunosuppressors already in use after liver transplantation.Recently.more and more studies find that rapamyein not only can exert immunosuppressive effects but also has antitumor properties.Therefore,the research about rapamycin in hepatocellular carcinoma has become a focus.Herein,we review the progress of rapamycin in the treatment of hepatocelhlar carcinoma together with current results and future developments.

Objective To investigate the expressions of extracellular matrix protein 1 (ECM1)and matrix metalloproteinase-9 (MMP-9) in hepatocellular carcinoma (HCC) and to explore their correlations with metastasis and recurrence.Methods Immunohistochemisty was employed to determine the expressions of ECM1 and MMP-9 in 120 HCC and 17 normal liver tissues.Results The positive rates of ECM1 and MMP-9 expression in HCC tissues were 73.3％ (88/120) and 65.0％ (78/120),respectively.They were significantly higher than that in normal liver tissues.The expression of ECM1 in HCC tissues was significantly correlated with vascular invasion and TNM stage.The expression of MMP-9 in HCC tissues was significantly correlated with tumor size,number of tumor nodules,differentiation of tumor and degree of cirrhosis.They were not correlated with age,gender,serum AFP level,HBsAg,Child-Pugh class and capsulated tumor.Patients with ECM1 and MMP-9 positivity had significantly poorer overall and disease-free survival rates.There was a significant positive correlation between ECM1 and MMP-9 (r=0.585,P＜0.001).Conclusion Both ECM1 and MMP-9 were significantly related to invasion and metastasis.Over-expression of both ECM1 and MMP-9 had predictive values for prognosis and recurrence of HCC after surgery.

Objective To evaluate the role of nodal gene modulating malignancy of a hepatocellular carcinoma cell lines SMMC7721. Methods To silence the expression of nodal gene in human hepatocellular carcinoma cells by RNA interference ( RNAi),and to observe the effect on cells biological behaviour and vasculogenic mimicry.4 expression vectors of nodal gene targeting small interference RNA were constructed and transfected into SMMC-7721 cells.Real-time quantitive PCR and Western blot were used to examine nodal gene expression. The effects of nodal gene RNA interference on proliferation,apoptosis,infestation,migration and vasculogenic mimicry of SMMC-7721 were studed. Results The expression of nodal gene was suppressed in SMMC-7721 cells by RNA interference.In the first 4,5,6 days of proliferation experiment,the proliferation of interference group was significantly lower than the control group(separately F =17 098.922,18 135.107,32 641.075,all P ＜ 0.05 ); 48 h after transfection,the apoptosis rate of interference group was significantly higher than the control group (F =1136.452,P ＜0.05); In the infestation and migration experiments,the cells through the transwell chamber in the interference group were less than the control group( separately F =83.6,1126.857,all P ＜ 0.05 ) ; 24 h and 48 h after transfection,the vasculogenic mimicry in the interference group did not form which was significantly different from the control group. Conclusions Interfering the expression of nodal gene inhibits the malignant biological behaviour and the formation of vasculogenic mimicry in human hepatocellular carcinoma cells.

Objective To evaluate the prtognostic significance of preoperative serum extracellular matrix protein 1 ( ECM1 ) levels in patients with hepatocellular carcinoma (HCC).Methods Preoperative serum levels of ECM1 were detected by enzyme-linked immunosorbent assay (ELISA) in 117 HCC patients and 53 healthy volunteers.Corrrlations to the clinicopathological characteristics and patients survival were analyzed.Results ECM1 were detected in all the samples of 117 HCC patients and 53 healthy volunteers,the median serum ECM1 level in HCC patients was significantly higher than that in healthy volunteers ( 166.39 vs 108.06 pg/ml,Z =- 7.805,P ＜ 0.001 ).Median serum ECM 1 levels were significantly higher in patients with invasive phenotypes,such as larger tumor size (Z =- 3.454,P =0.001 ),multiple nodule ( Z =- 2.201,P =0.028 ),vascular invasion ( Z =- 4.685,P ＜ 0.001 ),and advanced TN M stage ( Z =-4.610,P ＜ 0.001 ).Patients with lower serum ECM1 level (≤ 180 pg/ml ) have significantly better overall and disease free survival thanthose with higher levels ( ＞ 180 pg/ml).By Cox proportional-hazard model multivariate analysis,high serum ECM1 level ( ＞ 180 pg/ml) was an independent factor for OS and DFS in HCC patients.Conclusions Serum ECM1 levels are significantly correhted to the invasive phenotypes and survival rate.Serum ECM1 level could be used as a predictive marker for HCC recurrence and prognostic factor of HCC patients after surgery.

Objective To examine the expression of extracellular matrix protein 1 ( ECM1 ) in hepatocellular carcinoma (HCC) and its correlation with prognosis and recurrence of HCC.Methods Immunohistochemistry was used to detect expression of ECM1 in cancerous tissues from 77 HCC patients. The correlation between ECM1 expression and clinicopathologic features and prognosis were analyzed. Results ECM1 is mainly expressed in the cytoplasm of liver cells. The positive rate of ECM1 expression in HCC tissues were 74. 0% (57/77), and the expression level was significantly correlated with vascular invasion (χ2 =6.523, P =0.011 ) and TNM stage (χ2 =6.989, P =0.030). No significant correlation was found between the expression of ECM1 and patient's gender, age, AFP level of plasm, tumor size, number of nodules, and tumor differentiation. Patients with positive ECM1 expression have significantly poorer overall survival (OS) and disease-free survival (DFS) after curative resection than those with negative ECM1 expression (P =0. 016). The Cox multivariate analysis demonstrated that among the factors analyzed, ECM1 expression is an independent prognostic factors for OS and DFS in HCC patients after a curative resection (RR=3.721, P=0.002; RR=2.323, P=0.031). Conclusions Positive ECM1 is correlated with postoperative metastasis and invasion of HCC and poor prognosis.

Objective To assess the effects of gonadectomy on carcinogenesis and development of hepatocellular carcinoma (HCC) induced by chemical substances in rat model. Methods Fifty male and 50 female Sprague-Dawley rats (age of 5-6 weeks) were equally divided into four groups: male experimental (surgical castration) and control groups and female experimental (surgical castration)and control groups. The HCC model was induced by diethylnitrosamine (DEN) and Nnitrosomorpholine (NMOR) in SD rats. The effects of gonadectomy on occurring and development of HCC were observed. Results The incidence of HCC in female experimental group was higher than that in female control group (11/11 vs 5/14, P=0. 001), while it was lower in male experimental group than that in male control group (3/10 vs 12/12, P=0. 001). It was demonstrated that gonadectomy could increase the growth of HCC (P=0. 013) and tumor metastasis (P=0. 036) in female rats, but not in male rats. The formation of liver cirrhosis and HCC was found at 8 and 16 weeks in male experimental group, at 12 and 20 weeks in male control group, at 16 and 20 weeks in female experimental group and at 12 and 16 weeks in female control group. These findings showed that gonadectomy could improve the development of carcinogenesis in female rats and delay the carcinogenesis in male rats. Conclusion Sex hormones, especially estrogens, may be involved in development and metastasis of rats HCC.

Objective To investigate the expression of patterned matrix vasculogenic mimicry in hepatocellular carcinoma (HCC) and its prognostic significance. Methods HCC tissues from 151 patients undergoing curative resection in Anhui Provincial Hospital from January 2003 to December 2008 were studied.Postoperative follow-up and clinicopathologic data were reviewed.Immunohistochemical staining of laminin,CD34 and transmission electron microscopy were used to identify patterned matrix VM in HCC.The relations between clinicopathologic features, prognosis and patterned matrix VM were analyzed.Results Patterned matrix VM was positive in 31 out of 151 cases (20.5％ ).The expression of patterned matrix VM was positively correlated with tumor size ( x2 =4.132,P =0.042),vascular invasion ( x2 =5.825,P=0.016),high Edmondson grade (x2 =5.256,P=0.022),and late pTNM stage (x2 =6.218,P =0.013).Kaplan-Meier survival analysis revealed that cases of the VM positive group had poor overall 1,3 and 5 year survival (OS) and disease-free survival (DFS) than that of the VM negative group (67.7％,34.6％,11.5％ and 86.7％,64.7％,40.3％,respectively,x2 =14.852,P ＜ 0.001 ; and 41.9％,19.4％,6.5％ and 63.3％,40.6％,19.6％,respectively,x2 =10.065,P =0.002).Univariate and multivariate analyses revealed that multiple tumor nodules,vascular invasion and VM were independent prognostic factors for overall survival,while vascular invasion and VM were independent prognostic factors for disease-free survival. Conclusions Patterned matrix VM exists in HCC. The expression of patternedmatrix VM is associated with tumor size,Edmondson grade,pTNM stage and vascular invasion,and it might serve as an unfavorable prognostic factor for HCC patients.

Objective: To investigate the influential factors for failure of enhanced recovery after surgery(ERAS) from hepatectomy for hepatocellular carcinoma(HCC) patients and then to establish a risk prediction model. Methods: The relevant clinical data of 180 patients with HCC undergoing hepatectomy at Department of Hepatic Surgery, Affiliated Provincial Hospital, Anhui Medical University from January 2016 to June 2017 were analyzed retrospectively.There were 149 male patients and 31 female patients aging of (56.5±11.0)years(from 33 to 84 years old). The factors affecting postoperative failure of ERAS of HCC patients were identified by univariate and multivariate analyses, and then, all the obtained factors and their statistical values were used to establish the risk prediction model. Results: A total of 23 patients failed in the ERAS protocol(12.8%). The preoperative total bilirubin (TBIL), alanine aminotransferase(ALT) and amount of intraoperative bleeding were independent risk factors for failure of ERAS from hepatectomy(all P<0.05). The obtained risk prediction model was presented as follows: risk coefficient(R)=0.114×(TBIL)+ 0.082×(ALT)+ 0.008×(amount of intraoperative bleeding). At the cut of value of R=7.90, the area under the ROC curve of this model for predicting failure of ERAS was 0.866(95%CI: 0.788-0.945, P<0.01), with the sensitivity and specificity of 69.6% and 91.1%, respectively.External validation results indicated that the scoring system had good differential ability(area under the ROC curve=0.889, 95%CI: 0.811-0.967, P<0.01). Conclusions Higher level of preoperative TBIL(>21 μmol/L) and ALT(>50 U/L) and the larger amount of intraoperative bleeding (more than 400 ml) are independent risk factors for failure of ERAS inpatients undergoing hepatectomy for HCC and the established prediction model may have certain value for risk assessment.

Objective:To analyze the inflammatory mechanism and potential intervention drugs related to angiotensin converting enzyme 2 (ACE2) inhibitory mutations in order to provide reference for the treatment of corona virus disease 2019 (COVID-19).Methods:The data of lung adenocarcinoma with ACE2 mutations were screened from the cancer genome atlas (TCGA) database. The data were analyzed by R program language edgeR package and cluster Profiler package, gene ontology (GO)functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. Using String online analysis website for protein-protein interaction (PPI) network analysis, screening out the core genes, and finally using the Epigenomic Precision Medicine Prediction Platform (EpiMed) for multi-group association analysis of key genes, and drug candidates prediction.Results:A total of 1 005 differential genes were obtained, of which 91 were up-regulated and 914 down-regulated. A total of 71 GO were enriched, including 45 items related to biological processes, 16 items related to cell components, and 10 items related to molecular function. A total of 13 KEGG pathways were enriched, mainly in inflammatory pathways, various viral infectious diseases, transcriptional regulation, drug metabolism and protein digestion and absorption pathways. The differentially expressed genes were introduced into String online analysis website for PPI network analysis, a total of 252 proteins were obtained, and 10 core genes were H2A clustered histone 16(HIST1H2AL), H3 clustered histone 2 (HIST1H3B), H3 clustered histone 7 (HIST1H3F), H3 clustered histone 11 (HIST1H3I), H3 clustered histone 3 (HIST1H3C), H2B clustered histone 3 (HIST1H2BB), H2B clustered histone 6 (HIST1H2BI), H4 clustered histone 2 (HIST1H4B), H1-4 linker histone (HIST1H1E), H2A clustered histone 4 (HIST1H2AB). Interferon-α, resveratrol, celecoxib, heartleaf houttuynia herb, weeping forsythia capsule, dexamethasone, Chinese pulsatilla root, tumor necrosis factor-α inhibitors, liquorice root and famciclovir might be drugs for the treatment of ACE2 mutation-related inflammation.Conclusions:Inflammation associated with ACE2 inhibitory mutations is similar to the pathogenesis of COVID-19, which could lead to disease by promoting the activation of inflammatory pathways such as mitogen-activated protein kinase (MAPK), the Janus kinase signal transducer and activator of transcription (JAK/STAT), mammalian target of rapamycin (mTOR). Celecoxib, interferon and resveratrol may have the potential therapeutic effects on COVID-19.