Hepatocellular carcinoma is one of the most common malignancies in the worldwide.Selected patients with hepatocellular carcinoma are candidates for curative resection,but nevertheless there is a high risk of tumor recurrence.Microvascular invasion (MVI) is an aggressive biological behavior and has repeatedly been identified as a risk factor for prognosis after curative treatment,meanwhile,it is now becoming increasingly concerned.It would be of great significance to distinguish MVI in an early stage and choose an appropriate treatment timely to get a definite improvement for the long-term survival in patients with hepatocellular carcinoma after curative treatment.This review focuses on some certain issues of MVI.

Objective To evaluate the effects of reduced glutathione (GSH) on contractile and diastolic functions of the thoracic aorta of rats with obstructive jaundice.Methods Twenty-four adult male Sprague-Dawley rats,weighing 200-250 g,were randomly divided into 4 groups (n =6 each) using a random number table:sham operation group (group S),GSH group,bile duct ligation group (group BDL),and GSH + bile duct ligation group (group GSH + BDL).In GSH and GSH + BDL groups,GSH 300 mg/kg was infused via stomach everyday for 7 consecutive days,while the equal volume of normal saline was given in the other two groups.The common bile duct was ligated in the animals on 1 d after the end of intragastric administration in GSH and GSH + BDL groups.In GSH and GSH + BDL groups,after the model was established,GSH 300 mg/kg was infused via stomach everyday for 7 consecutive days,while the equal volume of normal saline was given in the other two groups.On 7th day after the model was extablished,blood samples were collected for determination of the levels of serum total bilirubin (TB),alanine aminotransferase (ALT) and aspartate aminotransferase (AST),tumor necrosis factor-alpha (TNF-α),interleukin-lβ (IL-1β) and 3-nitrotyrosine (3-NT),malondialdehyde (MDA),nitric oxide (NO) and GSH.The thoracic aortic rings were obtained and perfused with different concentrations of norepinephrine (NE),acetylcholine (Ach) and sodium nitroprusside (SNP).The maximum contraction and dilatation of aortic rings were recorded and the percentage was calculated.Some thoracic aortic rings were obtained again and perfused with different concentrations of NE after removal of the endothelium or after being perfused with L-NAME (nitricoxide synthase inhibitor).The maximum contraction of aortic rings was recorded and the percentage was calculated.Results Compared with group S,the serum levels of TB,ALT,AST,TNF-α,IL-1β,MDA,3-NT,NO and GSH were significantly increased in group BDL,and the serum levels of TB,ALT,AST,MDA,GSH and NO were increased in group BDL + GSH,the percentage of the maximum contraction amplitude of aortic rings in response to NE was decreased,and the percentage of the maximum dilatation amplitude of aortic rings in response to Ach and SNP were decreased in groups BDL and BDL + GSH,and no significant changes were found in the parameters mentioned above in group GSH.Compared with group BDL,the serum levels of TB,ALT,AST,TNF-α,IL-1β,MDA,3-NT and NO were significantly decreased,the level of GSH was increased,the percentage of the maximum contraction amplitude of aortic rings in response to NE was increased,the percentage of the maximum dilatation amplitude of aortic rings in response to Ach was increased,and no significant change was found in the percentage of the maximum dilatation amplitude of aortic rings in response to SNP in group BDL + GSH.Compared with the aortic rings from which the endothelium was removed or which were perfused with L-NAME in group BDL,no significant change was found in the percentage of the maximum contraction amplitude of aortic rings after removal of the endothelium or after being perfused with L-NAME in response to NE in group BDL + GSH.Conclusion GSH can improve the contractile and diastolic functions of thoracic aorta of rats with obstructive jaundice and this effect depends on the vascular endothelium.

ObjectiveTo investigate the effect of XPG down-regulation gene expression towards the proliferation of epithelial ovarian cancer cells and its chemosensitivity to platinum.Methods The small interference RNA ( siRNA ) -XPG fragments were designed and tranfected into SKOV3/DDP cell lines by lipofectamine transiently for choosing the best siRNA-XPG fragment to silence XPG gene expression.The pGPU6/GFP/Neo vector was used to construct the siRNA-XPG vectors,which was transfected into SKOV3/DDP cell line with expression of XPG gene.Real-time PCR and western blot were employed to confirm the silencing efficacy of siRNA-XPG.The growth curve of cells,cell cycle,the drug-resistance index of cells and intracellular drug concentration were measured by 4-methyl-thiazolyl-tetrazolium (MTT),flow cytometer (FCM) and high performance liguid chromatograph respectively.Results( 1 ) Real-time PCR results showed that XPG mRNA expression copy number in SKOV3/DDP tranfected with siRNA-XPG-733 fragment was 1.050 ± 0.023,which was significantly lower than that in SKOV3/DDP tranfected with other siRNA-XPG fragments(P ＜ 0.05,respectively),and was chosed to construct the siRNA-XPG vectors.The XPG mRNA expression was down-regulated in short hairpin RNA (shRNA)-XPG-733-SKOV3/DDP cell lines that confirmed by western blot.( 2 ) The growth curve showed that growth velocity of shRNA-XPG-733-SKOV3/DDP cell lines was lower than that of shRNA-GAPDH and shRNA-NC cell lines( P ＜ 0.05,respectively).The results of FCM also showed that 34.0％ of cells in shRNA-XPG-733-SKOV3/DDP cell lines were in S + G2/M phase,while only 58.7％ and 51.3％ in shRNA-GAPDH and shRNA-NC cell lines respectively ( P ＜ 0.05,respectively).( 3 ) The drug-resistance index of shRNA-XPG-733-SKOV3/DDP cell lines [ 50％ inhibiting concertration( IC50 ):( 13.79 ± 0.06) μg/ml ] was lower than that in shRNA-GAPDH and shRNANC cell lines [ IC50:( 27.84 ± 0.34 ) μg/ml and ( 28.32 ± 0.42 ) μg/ml,respectively ] statistically significant (P ＜ 0.05,respectively) ; but there was not statistically significant difference in intracellular drug concentration between shRNA-XPG-733-SKOV3/DDP cell lines [ (0.026 ± 0.005 ) μg/ml ] and shRNAGAPDH [ (0.024 ± 0.003 ) μg/ml ] and shRNA-NC cell lines [ ( 0.025 ± 0.007 ) μg/ml ] after treated by cisplatin in vitro ( P ＞ 0.05,respectively ).Conclusion The down-regulating of XPG gene resulted in slowing growth velocity and descending the drug-resistance index of shRNA-XPG-733-SKOV3/DDP cell lines,which may be related with descending in capability of DNA excision repair in cells.

Objective To compare anatomic resection (AR) and non-anatomic resection (NAR)for hepatocellular carcinoma (HCC) as a factor in preventing intra-hepatic recurrence and local recurrence after the initial surgical procedure.Methods A systematic review and Meta-analysis of nonrandomized trials comparing anatomic resection with non-anatomic resection for HCC published from 1990to 2010 in PubMed and Medline,Coehrane Library,Embase,and Science Citation Index were searched.Intra-hepatic recurrence,including early and late recurrence,and local recurrence were primary outcomes.5-year survival and 5-year disease-free survival were secondary outcomes.Pooled effect was calculated by utilizing either fixed effects model or random effects model.Result Eleven nonrandomized studies including 1576 patients were identified and analyzed.810 patients were in the AR group and 766 were in the NAR group.Patients in the AR group were characterized by lower prevalence of cirrhosis,more favorable hepatic function,and larger tumor size and higher prevalence of macrovascular invasion compared with patients in the NAR group.Anatomic resection significantly reduced the risks of local recurrence (OR,0.27; 95％ CI,-0.17～0.43; P＜0.001) and achieved a better 5-year disease-free survival (OR,2.10; 95％ CI,-1.41 ～3.12; P=0.001) in HCC patients.Also,anatomic resection was marginally effective in decreasing early intra-hepatic recurrence.However,anatomic resection was not advantageous in preventing late intra-hepatic recurrence.No significant differences were found between the AR and NAR groups with respect to postoperative morbidity,mortality,and length of hospitalization.Conclusion Anatomic resection was recommended to be superior to non-anatomic resection in reducing the risks of local recurrence,early intra-hepatic recurrence and achieving a better 5-year disease-free survival in HCC patients.

Objective To develop a fluorescence signal activatable multifunctional molecular probe with theranostics function through combining ultrasmall gold nanorods(UGNRs) with fluorescein,and to evaluate its therapeutic effect on photothermal therapy (PTT) in breast cancer cells.Methods The UGNRs were synthesized by the one-pot seedless method,then the functionalized modification of UGNRs were conducted using cysteamine.Finally,the activatable ultrasmall gold nanorods (AUGNRs) were synthesized by amide condensation of —NH2 of cysteamine and —COOH of carboxylated fluorescein CyS.The cell uptake ability and GSH-mediated imaging ability of AUGNRs were studied using breast cancer 4T1 cells.4T1 cells co-cultured with AUGNRs were irradiated with 808 nm excitation light,and the PTT effects were assessed by MTT colorimetric staining and calcein-AM/PI staining.Results The AUGNRs were synthesized successfully,which could be uptaken by 4T1 cells quickly and efficiently,and could achieve intracellular glutathione (GSH) triggered fluorescence recovery.No obvious cytotoxicity of AUGNRs to 4T1 cells was observed in the co-cultivation.Moreover,obvious PTT effects could be induced by 808 nm laser,which could effectively kill 4T1 cancer cells.Conclusion The fluorescence signals of AUGNRs can be induced by intracellular GSH,and tumor cell destruction can be achieved by 808 laser-excitated PTT effects.

Objective To study the impact of two surgical techniques in the treatment of hepatocellular carcinoma (HCC) with portal vein tumor thrombus (PVTT).Methods A retrospective study was conducted on 143 patients with HCC with PVTT who underwent hepatectomy from January 1995 to December 2010 at the Affiliated Tumor Hospital of Guangxi Medical University.The patients were divided into two groups:group A,115 patients who underwent resection of HCC with PVTT; group B,28 patients who underwent HCC resection but the PVTT was extracted from the cut opening of the portal vein or the transected liver parenchyma.Results The median overall survival of group A was 18.0 months and the cumulative 1-,2-,3-year survival rates were 60.6％,41.0％,25.6 ％,respectively; the median overall survival of group B was 7.0 months and the cumulative 1-,2-,3-year survival rates were 35.1％,13.6％,9.1％,respectively.The differences between the 2 groups were statistically significant (P ＜ 0.001).Univariate analysis showed tumor number,PVTT types,prophylactic transcatheter arterial chemoembolization (TACE),and surgical technique to be significant risk factor of postoperative overall survival (P ＜ 0.05).Cox multivariate analysis indicated prophylactic TACE and surgical technique to be independent prognostic factor (P ＜ 0.05).Conclusions When compared with group B patients,group A patients had significantly better overall survival.Postoperative prophylactic TACE further improved survival of these patients.

Primary liver cancer is one of the most common malignant tumors in the world, and hepatocellular carcinoma accounts for the majority of liver cancer. Hepatectomy is one of the most important treatment methods, but the high postoperative recurrence rate is the leading cause of treatment failure, which seriously reduces the long-term survival rate and reduces quality of life. Therefore, preventing the recurrence of liver cancer is an important part of treatment. At present, there is no standard program for the treatment of hepatocellular carcinoma to prevent recurrence after surgery, most of the treatment programs include transarterial chemoembolization, antiviral therapy, traditional Chinese medicine treatment, targeted therapy, immunity therapy, etc., which has certain clinical significance in preventing recurrence. This paper reviewed the research progress on preventing recurrence of hepatocellular carcinoma after surgery, which may provide guidance for the clinical study.

BACKGROUND:Ideal osteochondral tissue-engineered scaffolds should be able to mimic the normal structure ofhuman articular cartilage. OBJECTIVE:To prepare a layered osteochondral composite scaffold based on the anatomical and physiological functions of osteochondral articular cartilage and to observe its repair effect on osteochondral defects in rabbits. METHODS:The poly (lactide-glycolide acid)/β-tricalcium phosphate organic solution was sprayed on the surface of cartilage scaffold using rapid prototyping technology. The layered osteochondral composite scaffold was formed by the“dissolving-adhesion”process. Sixty rabbits were enrol ed, modeled into left knee articular cartilage defects, and then randomly divided into three groups. The layered osteochondral composite scaffold and cartilage scaffold were implanted into experimental and control groups, respectively. Those without any treatment served as controls. Gross and histological observations of the defect region were performed at 12 and 24 weeks after implantation. RESULTS AND CONCLUSION:Gross observation:At 12 weeks after implantation, the defects in the control group were obvious and not repaired at al;the 24-week defect area was decreased, covered by newly formed tissues, but with rough surface. In the experimental group, the defect surface was flat after 12 weeks of implantation, the texture was soft, and the boundary with the surrounding tissues was unclear;at 24 weeks, the defect was covered with transparent cartilaginous tissues and the surface was smooth. Histological observation:At 12 weeks after implantation, the irregular cal us appeared in the control group, but the trabeculae were not formed;in the experimental group, the thickness of the new cartilage was similar with that of the normal cartilage and there was irregular trabecular bone under the cartilage. After 24 weeks of implantation, there were new tissues in the control group, but the thickness was irregular and uneven and the trabecular structure was irregular;while the cartilage surface was smooth and repaired wel in the experimental group. In contrast, repair effect in the control group was poor as assessed by gross and histological observations. These results show that the layered composite scaffold holds a similar structure with human articular cartilage and can promote the repair of articular cartilage defects.

Objective To explore the association between ratio index of gamma glutamyl transpeptidase/platelet (GPRI) and the prognosis of patients with hepatitis B virus (HBV) related hepatocellular carcinoma (HCC) before liver resection. Methods A total of 368 patients underwent liver resection for HBV-related HCC were retrospectively analyzed in this study. Patients were divided into high GPRI group (n=184, GPRI≥0.38) and low GPRI group (n=184, GPRI<0.38). Clinicopathologic characteristics including overall survival (OS) and disease-free survival (DFS) were compared between the two groups. Independent risk factors influencing DFS and OS were determined by Cox multivariate analysis. Results Compared to low GPRI group, there were higher levels of serum total bilirubin and alanine aminotransferase, higher proportions of tumor diameter larger than 10 cm, amount of tumou more than 3, and patients with macrovascular invasion and intermediate or advanced HCC in high GPRI group (all P<0.05). Values of DFS at 1, 3, and 5 years were significantly lower in high GPRI group (50.8%, 16.9%and 5.7%) than those in low GPRI group (69.0%, 33.3%, 10.7%;P=0.001). Values of OS at 1, 3, and 5 years were also significantly lower in high GPRI group (75.0%, 51.8%and 36.0%) than those in low GPRI group (89.8%, 72.8%and 63.2%;P<0.05). Cox multivariate analysis also demonstrated that GPRI ≥0.38 was an independent risk factor for DFS and OS in patients with HBV-related HCC after liver resection. Conclusion Preoperative GPRI can predict tumor recurrence and long-term survival in patients with HBV-related HCC after liver resection.

Objective To explore the effect of preoperative antiviral therapy on hepatitis B virus ( HBV ) reactivation and postoperative liver function in perioperative patients with HBV-DNA-negative hepatocellular carcinoma(HCC).Methods 74 patients with preoperative HBV-DNA-negative scheduled which were analyzed.Patients were divided into two groups according to antiviral therapy or not:20 cases in antiviral treatment group received antiviral therapy for three days, 54 cases in non-antiviral teatment group did not receive antiviral therapy, and both groups received antiviral therapy after post-operative resuming to diets.The indicators of liver function and HBV-DNA levels were detected on pre-operative, post-operative 3rd and 7th day in two groups, and HBV-DNA-positive ( HBV-DNA>500 IU/mL) was defined as reactivation, conversely as inactivation.The indicators of liver function on pre-operative, post-operative 3rd and 7th day were compared between reactivation group and inactivation group.Results The reactivative rate was 21.6%(16/74) in all patients;27.7%(15/54) in pre-operative non-antiviral teatment group, 5.0%(1/20) in antiviral teatment group, and there was significant differences in reactivative rate between two groups ( P=0.035 ).The results of Logistic regression showed that pre-operative nonantiviral therapy was an independent risk factor of post-operative HBV reactivation (OR=13.952,95% confidence interval[CI]:1.358-143.379,P=0.027).The recovery of albumin (ALB) on post-operative 3rd, 7th days in antiviral treatment group was faster than those in nonantiviral treatment group, respectively (P=0.035,0.043).The recovery of ALB and alanine aminotransferase (ALT) on post-operative 7th day in reactivation group were slower than those in inactivation group, respectively (P=0.016, 0.048).Conclusion The pre-operative nonantiviral therapy is an independent risk factor of post-operative HBV reactivation in patients with HBV-DNA-negative HCC.The pre-operative antiviral therapy could inhibit post-operative HBV reactivation effectively and accelerate the post-operative recovery of liver function.