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Objective:To explore the current status of surgery for portal hypertension to grasp current status and future development of surgery in China.Methods:This study is jointly sponsored by China Hepatobiliary & Pancreatic Specialist Alliance & Portal Hypertension Alliance in China (CHESS).Comprehensive surveying is conducted for basic domestic situations of surgery for portal hypertension, including case load, surgical approaches, management of postoperative complications, primary effects, existing confusion and obstacles, liver transplantation(LT), laparoscopic procedures and transjugular intrahepatic portosystemic shunt(TIPS), etc.Results:A total of 8 512 cases of portal hypertension surgery are performed at 378 hospitals nationwide in 2021.Splenectomy plus devascularization predominated(53.0%)and laparoscopy accounted for 76.1%.Primary goal is preventing rebleeding(67.0%) and 72.8% of hospitals used preventive anticoagulants after conventional surgery.And 80.7% of teams believe that the formation of postoperative portal vein thrombosis is a surgical dilemma and 65.3% of hospitals practiced both laparoscopy and TIPS.The major reasons for patients with portal hypertension not receiving LT are due to a lack of qualifications for LT(69.3%)and economic factors(69.0%).Conclusions:Surgery is an integral part of management of portal hypertension in China.However, it is imperative to further standardize the grasp of surgical indications, the handling of surgical operation and the management of postoperative complications.Moreover, prospective, multi-center randomized controlled clinical studies should be performed.
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Objective:To investigate the expressions and clinical significance of tetraspanin CO-029 and integrin αv in intrahepatic cholangiocarcinoma (ICC ).Methods:Tissue microarray (TMA) was used to detect the expression of CO-029 and αv in 254 cases of intrahepatic cholangiocarcinoma. The relationship between the two factors and clinicopathological features, recurrence, metastasis and prognosis was analyzed.Spearman method was used to analyze their correlation.Relationship between αv and CO-029 was studied by mass spectrometry and database search,immunoprecipitation and Western blot were used to detect the coexistence.Results:Tissue microarray analysis showed that the positive expression rate of CO-029 was 51.6% (131/254), and the positive expression rate of αv was 61.4% (156/254). The expression of CO-029 and αv were closely correlated with tumor envelope, size, number and TNM stage ( P<0.05). According to the time of recurrence (TTR), the expressions of CO-029 and αv in early postoperative recurrence group (TTR <1 year) were significantly higher than those in non recurrence group (TTR ≥ 1 year). The patients with high CO-029 expression were more likely to relapse ( HR=2.01, 95% CI=1.45-2.79; P<0.001) and had shorter survival time ( HR=2.03, 95% CI=1.46-2.81; P<0.001). The patients with high expression of αv had shorter recurrence time ( HR=1.85, 95% CI=1.38-2.47; P<0.001) and shorter survival time ( HR=1.95, 95% CI=1.40-2.71; P<0.001). Co immunoprecipitation and Western blot confirmed that αv and CO-029 formed a complex. There was a positive correlation between CO-029 and αv in intrahepatic cholangiocarcinoma ( r=0.401, P<0.01). Conclusions:The differential expression of CO-029 and αv were closely related to the recurrence, metastasis and prognosis of intrahepatic cholangiocarcinoma, and CO-029 may couple with αv to form a complex to promote the invasion and metastasis of intrahepatic cholangiocarcinoma.
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Objective:To investigate the correlations between CO-029 expression and cholangiocarcinoma invasion and metastasis, and the further explore the potential mechanism involved.Methods:The constructed lentiviral vector of vshRNA-CO-029 (LV/GFP/CO-029) was used to transfect and screen the stable transfected cholangiocarcinoma cell line HCCC-9810-vshRNA-CO-029 as the silence group, HCCC-9810 cells transfected with the mock plasmid were used as the mock group, and the untransfected cells were used as the control group. Cell scratch assay, Transwell assay and in vivo implantation assay were used to detect the migration, invasion and metastasis of the three groups of cells. Immunoprecipitation and tumor necrosis factor (TNF)-α stimulation assay were used to detect the effect of CO-029 on the expression of EMT-related genes.Results:The scratch healing rate of the silence group was (27.11±4.58)%, which was lower than that in mock group (92.84±6.24)%, the number of cells passing through Matrigel in silence group was (57.15±6.10), which was significantly lower than that in mock group (108.20±9.21) and control group (112.00±10.45), the differences were statistically significant ( all P<0.01). The volume of liver tumors in the silence group of orthotopic xenograft mouse model was (2.17±0.54) cm 3, while the volume of liver tumors in the transplanted simulation group was (0.74±0.15) cm 3, the differences were statistically significant ( P<0.05). The incidence of lung metastasis and the number of lung metastases in the simulated group was 100%(6/6) and (214.17±35.64), respectively, while that in the silence group was 16.7% (1/6) and (41.56±14.15), respectively, the differences were statistically significant (all P<0.05). Co-immunoprecipitation showed that CO-029 can form a complex with TNF-αR1. TNF-α induced the down-regulation of E-cadherin and up-regulation of vimentin and N-cadherin in the mock group, but no significant changes were observed in the silence group. Conclusion:CO-029 expression is positively correlated with tumor invasion and metastasis of cholangiocarcinoma, and could couple with TNF-α to induce EMT, which is a novel well-established potential prognostic and therapeutic target for cholangiocarcinoma metastasis and prognosis intervention.
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Objective:To investigate the effects of hepatitis B virus X (HBx) on hepatocellular carcinoma (HCC) proliferation, invasion, and sorafenib resistance.Methods:HepG2 cell line infected with HBx ORF lentivirus was set as the HBx high expression group and infected with empty vector was set as the negative control group. The interference group was infected with the HBx siRNA virus based on the HBx high expression group to reduce HBx expression. Interference control group as interference group but with infected empty vector virus. Western blotting was used to measure the protein level of HBx. Cell proliferation, invasion ability, and sorafenib semi-inhibitory concentration (IC50) of HCC cells under different HBx expression levels were respectively detected by cell proliferation assay kit, Transwell invasion assay, and cell titer-glo kit.Results:Western blotting showed that the stable cell lines were successfully established. Cell proliferation of the HBx high expression group was better than that of the blank control and negative control groups, and the cell proliferation of the interference group was lower than that of the interference control and HBx high expression groups, and the differences were all statistically significant ( P<0.05). The number of cells crossing Matrigel gel was (46.2±4.1), (50.7±5.1) and (48.2±5.2) in the blank control group, negative control group, and interference group, respectively. The number of cells crossing Matrigel gel in the HBx high expression group (124.2±8.3) and the interference control group (117.2±7.5) were higher than the above three groups, respectively, and the differences were all statistically significant ( P<0.05). The IC50 of cells in the HBx high expression group and the interference control group were (5.36±0.31) μmol/L and (5.48±0.20) μmol/L, respectively, which were higher than those in the blank control group, the negative control group, and the interference group (4.75±0.22) μmol/L, (4.60±0.14) μmol/L and (3.98±0.03) μmol/L. The differences were all statistically significant ( P<0.05). Conclusion:HBx promoted the tumor proliferation and invasion of HepG2 HCC cells, enhanced the ability to sorafenib resistance, and inhibited apoptosis.
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Objective To investigate the effect of occult HBV infection (OBI) on carcinogenesis of cryptogenic hepatocellular carcinoma.Methods Samples of hepatocellular carcinoma (HCC) and pericarcinomatous tissues obtained after hepatectomy from January 2011 to November 2013 at the Third Affiliated Hospital of Sun Yat-Sen University were collected.They were divided into two groups:the cryptogenic HCC group (the CH group,n =26) and the HBV related HCC group (the HH group,n =40).These samples were compared with the normal liver tissues obtained in 30 patients.HBV DNA was identified by the nested polymerase chain reaction and the immunohistochemical method was taken to examine the hepatitis B virus X protein (HBx) and Yes-associated protein (YAP) expressions.Results OBI was identified in 20 (77.8％) cryptogenic HCC patients and 8 (26.7％) in the control group.There was a significant difference between the two groups (x2 =14.072,P ＜ 0.05).HBV DNA was detected in all the HBV-related HCC patients.The HBx protein expression was mainly located in the cytoplasm of liver cells and liver cancer cells,but YAP was expressed in the nucleus.Both of them showed diffuse brown or tan particles.In the HH group and the CH group,the positive expression rates of HBx protein in the tumorous tissues were 80.0％ and 90.0％,respectively,and 85.0％ and 82.5％ in the nontumorous tissues,but only in 40.0％ in the control group.The positive expression rates of YAP in the tumorous tissues were 65.0％ and 67.5％,respectively,15.0％ and 20.0％ in the nontumorous tissues,respectively,but only in 12.5％ in the control group.The HBx expression in the cancerous tissues and para-cancerous tissues of the HH group and the CH group showed no significant difference (P ＞ 0.05),but the YAP expression in the tumor tissues was significantly higher than that in the nontumorous tissues (P ＜ 0.05).The HBx and YAP expressions in the HH group were comparable to the CH group (P ＞ 0.05).However,their expressions in the cancerous tissue of the HH group and the CH group were significantly higher than in the normal liver tissues (P ＜ 0.05).Conclusion A high prevalence of HBV infection was observed in HBsAg-negative HCC and the high expressions of HBx and YAP might be involved in the process of cryptogenic hepatocellular carcinoma.
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Objective To investigate the role of transmembrane protein C0-029 in epithelial mesenchymal transition (EMT) induced by tumor necrosis factor alpha (TNFα) of intrahepatic cholangiocarcinoma (ICC) cells.Methods RT-PCR and Western blot were conducted to detect the CO-029 expression in ICC cells and tissues.The effect of CO-029 silencing by lenti-virus on EMT induced by TNFα was investigated.Western blot and mass spectrometry after immunoprecipitation were used to confirm whether TNFαR1 can directly or indirectly bind with CO-029 to form complexes in ICC.Results Differential expression of CO-029 was observed in ICC cells and tissues.The expression of CO-029 was significantly reduced by lenti-viral interference in ICC cells,resulting in the failure of TNFα to induce EMT.TNFαR1 in ICC could directly or indirectly form complexes with CO-029.Conclusion CO-029 mediates TNFα/TNFαR1 induced EMT in ICC,which might play an important role in the invasion and metastasis.
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Objective To investigate the expressions of tetraspanin CO-029 in intrahepatic cholangiocarcinoma (ICC) and to find out their clinical significance.Methods RT-PCR and western blot were used to detect the expressions of CO-029 in ICC and their matched para-tumorous tissues from 20 patients with ICC,as well as in the HCCC-9810 cell lines.The expressions of CO-029 were further detected via tissue microarray (TMA) in the pathological specimens of 40 patients with ICC.Correlations between the expressions of CO-029 and the clinicopathologic features and prognosis were analyzed.Results A high level of CO-029 was detected in the 20 patients with ICC and the HCCC-9810 cell lines via western blot and RTPCR.Moreover,the expression levels of CO-029 in the ICC tissues were higher than the matched para-tumorous tissues (P ＜ 0.05).TMA detection revealed the positive expression rate of CO-029 to be 65％ (26/40).The expression level of CO-029 was much higher in the early recurrence group (Time to recurrence,TTR ＜ 1 year) than the non-recurrence group (TTR≥ 1 year).On analysis,the correlations were significant between the expressions of CO-029 and tumor encapsulation,hilar lymph node metastasis,TNM stage and prognosis (P ＜0.05).Conclusions CO-029 was highly expressed in ICC.It had close correlations with recurrence,metastasis and prognosis of patients with ICC.
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Objective To study the effect of Tspan 8 on metastasis and invasion of human hepatocellular carcinomas(HCC).Methods RT-PCR and western blot were used to detect the expressions of Tspan 8 in HCC cell lines,HCC and matched nontumorous tissues.The expression of Tspan 8 was then down-regulated by LV/GFP/Tspan 8 in HCC cells.The expressions of Tspan 8 mRNA and protein were determined by RT-PCR and Western blot assay,respectively.The proliferation was examined by MTT,the expression of AMDM12 was assessed by Western blot,and the invasion ability of HCC cells was evaluated by transwells.Results A high level of Tspan 8 was found in high metastatic potential HCC cells,and the expression of Tspan 8 in HCC tissues was much higher than that in the matched nontumorous tissues. Down-regulation of Tspan 8 had no influence on the proliferation of HCC cells (P＞0.05),while it inhibited the expression of ADAM12 and the invasive ability of HCC cells (P＜0.01,P＜0.01 respectively).Conclusion Tspan 8 played an important role in invasion and metastasis of human hepatocellular carcinomas and down-regulation by LV/GFP/Tspan 8 inhibited the invasiveness of human hepatocellular carcinoma cells.
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In previous study, the 150-ku oxygen-regulated protein(ORP150) was identified as a candidate glycoprotein related to hepatocellular carcinoma.In order to further validate the expression level of ORP150 in hepatocellular carcinoma, protein expression was determined by Western blot and cell immunochemistry, and messenger RNA(mRNA) expression was detected by quantitative real-time polymerase chain reaction.The effect of ORP150 on apoptosis and invasive potential of hepatocellular carcinoma cells was evaluated using the small interference RNA(siRNA) technique.Both the protein and mRNA expression levels of ORP150 were significantly upregulated in hepatocellular carcinoma cell lines compared with a non-tumor human liver cell line.After transfection with the specific siRNA of ORP150, significantly greater apoptosis of hepatocellular carcinoma cells was induced compared with untransfected cells.However, no significant effect on invasive potential was found.Overexpression of ORP150 was associated with hepatocellular carcinoma, and ORP150 might promote the proliferation of hepatocellular carcinoma cells by inhibiting apoptosis.ORP150 could be a potential therapeutic target for hepatocellular carcinoma.