Serum metabolomics study on benign liver lesions and hepatic malignancies by central carbon pathway metabolites / 药学实践与服务

Objective To screen potential metabolites and significantly altered metabolic pathways of liver lesions by central carbon pathway metabolites. Methods 32 healthy volunteers (HC), 23 patients with biliary cysts (CYST), 19 patients with biliary stones (Stone), 45 patients with hepatocellular carcinoma (HCC), and 50 patients with hilarcholangiocarcinoma (HCCA) were recruited. Their serum samples were collected for UPLC-QQQ-MS analysis and further MPP statistical analysis. Pattern recognition was further used to discovery the differences in metabolome between groups, and to explore the significantly altered metabolic pathway and possible pathogenic mechanism of liver diseases. Results A total of 15, 7, 7, and 3 metabolites and a total of 8, 4, 4, and 1 metabolic pathway that were significantly different in serum between CYST, Stone, HCC, HCCA and healthy controls were identified and enriched through serum metabolomics analysis, respectively. Conclusion According to the above identified differential metabolites and enriched metabolic pathway results, it is shown that liver lesions mainly involved in the energy metabolism and amino acid metabolism & transport, in addition, inositol phosphate metabolism were significantly changed both in CYST, Stone, HCC and HCCA.

Assay of eupatilin and arteanoflavone in Artemisia anomala by HPLC / 药学实践杂志

Objective To determine the concentration of eupatilin and arteanoflavone in A rtemisia anomala by high per-formance liquid chromatography (HPLC).Methods A rtemisia anomala was extracted by ultrasonic for 60 minutes with 10 times volume of methanol.The HPLC was performed on a SHISEIDO MG-C18 column (3.0 mm × 100 mm,3μm).The mobile phase was a mixture of acetonitrile (ACN) and 0.1% formic acid (40:60,V/V ).The detection wavelength was 350 nm,the column temperature was 25 ℃ and the injection volumn was 5μl.Results Eupatilin and arteanoflavone were separated at base-line within 15min with good linearity.The method validation results show that the precisions,repeatability and stability were all in the normal range.The low,medium and high level recoveries of eupatilin were 100.26%,99.58%,102.24%,and those of arteanoflavone were 99.09%,101.12%,101.43%,respectively.Conclusion The method was rapid,simple,reproductive and accurate.It can be used to control the quality of Artemisia anomala.

Establishment of adipocytokine CTRP4 transgenic mouse / 中国比较医学杂志

Objective To establish the CTRP4 transgenic mouse model and investigate the function of the novel adipocytokine CTRP4.Methods CTRP4 overexpressing vector in pCAGGS was firstly constructed and then microinjected into zygote to establish the founder transgenic mice .F1 heterozygotes were generated by founder mice mating with wildtype mice, and the CTRP4 transgenic homozygotes were generated by F 1 littermates.The genotype was confirmed by PCR and test cross method .The expression level of CTRP 4 in transgenic mice was detected by western blot .Result The human CTRP4 transgenic homozygote mice line was established , and the expression level of CTRP 4 was confirmed raletively high in detected tissues including heart , liver, brain and kidney . Conclusion The human CTRP4 transgenic mice was successfully established .

Risk factors for postoperative liver failure of patients with hepatocellular carcinoma and bile duct tumor thrombus / 中华消化外科杂志

Objective To investigate the risk factors for postoperative liver failure of patients with hepatocellular carcinoma (HCC) and bile duct tumor thrombus through a risk evaluation model.Methods The clinical data of 107 patients with HCC and bile duct tumor thrombus who received hepatic resection at the Eastern Hepatobiliary Surgery Hospital from March 2002 to February 2011 were retrospectively analyzed.All patients were divided into the non-liver failure group (98 patients) and liver failure group (9 patients).Risk factors associated with liver failure were analyzed and a risk evaluation model was established.All data were analyzed using the bivariate regression model,and factors with significance were further analyzed using the multivariate regression model.Results Of the 107 patients,105 received hepatic resection + choledochotomy + thrombectomy and 2 received hepatic resection + extrahepatic bile duct resection + cholangiojejunostomy.The operation time was 2.0-5.5 hours,and the intraoperative blood loss was 200-3500 ml.In the non-liver failure group,5 patients had pleural and peritoneal effusion,3 had biliary bleeding,2 had incisional infection,1 had biliary infection,1 had bile leakage,1 had stress-induced ulcer of upper digestive tract and 1 had thoracic epidural hematoma.The bleeding of the patients with thoracic epidural hematoma was stopped after thoracic spinal decompression,but subsequent paraplegia occurred.In the liver failure group,2 patients died of postoperative acute liver failure,and 7 patients died of postoperative subacute liver failure (death caused by tumor recurrence or medicine was excluded).The results of univariate analysis showed that preoperative total bilirubin,albumin,pre-albumin,albumin/globulin ratio,distribution of tumor thrombus,operative blood loss and ratio of postoperative residual liver volume to the total liver volume were correlated with the postoperative liver failure in patients with HCC and bile duct tumor thrombus (OR =3.017,0.191,0.248,2.681,9.048,4.759,13.714,P ＜ 0.05).The results of multivariate analysis showed that preoperative total bilirubin ＞ 256.5 μmol/L,albumin/globulin ratio ≤ 1.3 and postoperative residual liver volume ＜ 50％ were the independent risk factors of postoperative liver failure (OR =5.537,11.107,172.450,P ＜ 0.05).The risk evaluation model was Z =1.77 × preoperative total bilirubin + 2.408 × preoperative albumin/globulin ratio + 5.150 × ratio of postoperative residual liver volume to the total liver volume-17.288.The risk of postoperative liver failure increased as the increase of Z value.The risk of postoperative liver failure ＞ 50％ when the Z value ＞ 0.Conclusions Preoperative total bilirubin ＞ 256.5μmol/L,albumin/globulin ratio ≤ 1.3 and postoperative residual liver volume ＜ 50％ were the independent risk factors of postoperative liver failure.Risk evaluation model is helpful in screening the risk factors so as to decrease the incidence of postoperative liver failure.

Artemisinin inhibits in vitro and in vivo invasion and metastasis of human hepatocellular carcinoma cells.

Artemisinin (ART) is isolated from the medicinal plant Artemisia annua L. To determine its effects on the invasion and metastasis of tumors, the human hepatocellular carcinoma (HCC) cell lines HepG2 and SMMC-7721 were treated with different concentrations of ART. Starting at 12.5µM, ART had inhibitory effects in migration and invasion assays that increased at higher concentrations. The inhibitory effect also became stronger with time, from 24 to 72h. ART significantly inhibited the in vivo metastatic abilities of the HepG2 HCC cell line. ART inhibited the invasion and metastasis of HCC cells both in vitro and in vivo by reducing the level of the MMP2 metalloproteinase, and by inducing the TIMP2 protein. ART activated Cdc42, which enhanced E-cadherin activity, resulting in greater cell-cell adhesion, and significantly reduced metastasis.

Ten-year experience in surgical treatment of hilar cholangiocarcinoma / 中华消化外科杂志

Objective To summarize the experiences of a single treatment group in surgical treatment of hilar cholangiocarcinoma during the past 10 years. Methods From January 2000 to December 2009, 1572 patients with hilar cholangiocarcinoma were admitted to the Eastern Hepatobiliary Surgery Hospital, and the clini-cal data of 462 patients in our treatment group were retrospectively analyzed. Among the patients, 314 received surgical treatment, and the remaining 148 received conservative interventions or refused any therapy. Factors that may have influenced the prognosis were analyzed by the Kaplan-Meier method, Log-rank test and Cox proportional hazards model. The correlation of different factors was analyzed by the chi-square test. Results A total of 314 patients underwent surgical treatment and tumor resection was performed in 237 patients, including 174 with R0 resection, 17 with R1 resection, and 46 with R2 resection. There were 91 patients with postoperative complications and 10 in-hospital deaths. A total of 260 patients had been followed up for 5-113 months, and the overall 1-, 3-, and 5-year survival rates were 71.7% , 32.6% and 10.9% , respectively; the 1-, 3-, and 5-year survival rates of patients with R0 resection were 76. 9% , 48. 6% and 32. 7% , respectively, with a median survival time of 35 months. R0 resection, TNM staging, regional lymph node involvement and tumor differentiation were the independent prognostic factors (RR = 2. 1, 1.9,2.2, 1.7, P<0.05). Conclusions Curative resection is the treatment of choice for hilar cholangiocarcinoma. Preoperative systematic evaluation and preparation can improve the radical resection rate and reduce postoperative morbidity.

Comparative study on three methods of hepatic vascular occlusion in hepatectomy / 中华肝胆外科杂志

Objective To compare the safety and damage to liver function of 3 methods of hepatic infusive vascular occlusion in hepatectomy for hepatocellular carcinoma. Methods Retrospectively, the clinical data of patients undergoing curative liver resection with pan- (n=30) and hemi(n= 30) vascular occlusion or hemi-hepatic artery reservation (n= 30) method were analyzed. Results All patients in the 3 groups had similar surgical duration and blood loss. Two and one patients from group 2 suffered from portal vein impairment and hemorrhea, respectively. Patients from group 1 had higher serum alanine aminotransferase and total bilirubin on days 1 and 7 after surgery. Conclusion Hepatectomy with hemi-hepatic artery reservation, which was not closely related to hepatic hilum, is safe and convenient for the resection of tumor involving hemi-liver and is especially suitable for the patients with severe liver cirrhosis.

Long-term results of surgical treatment in 181 cases of advanced stage gallbladder carcinoma / 中华肝胆外科杂志

Objective To analyze the characteristics and prognostic factors of gallbladder carcinoma and investigate the measures of various modus operandi. Methods The clinicopathological data of 181 patients with advanced gallbladder carcinoma treated in our hospital from June 2002 to June 2008 were retrospectively analyzed. SPSS16. 0 software package was used for statistical analysis.Results The overall median survival rate of the 181 patients with gallbladder carcinoma was 6 months. The median survival rate after radical resection for gallbladder carcinoma was 19.5 months,which was remarkably higher than other R1 resection, R2 resection and palliative operation groups (P ＜0. 01) The RO resection rates were 95.5%, 62. 2%, 14.1% and 4.7%, respectively based on different pathological stages of Nevin( Ⅱ , Ⅲ, Ⅳ, and Ⅴ ). There were significant differences among all groups (P＜0.01). The Cox multivariate analysis revealed that pathological stages of Nevin, total bilirubin, CA-199 and therapeutic method had significantly higher risk ratios for gallbladder carcinoma.Conclusion Radical resection may help to improve the survival rate and prognosis of advanced gallbladder carcinoma.

Surgery of hepatocellular carcinoma complicated with cancer thrombi in bile duct: efficacy for criteria for different therapy modalities.

PURPOSE: This study retrospectively compared different therapy modalities in patients with hepatocellular carcinoma (HCC) complicated by bile duct thrombi (BDT). METHODS: A total of 184 patients with BDT were selected from a pool of 12,114 patients with HCC, and their cases were reviewed in this study. RESULTS: The occurrence rate of BDT was 1.84% (223/12,114) in our study. The radical resection rate in types I, II, III, and IV was 70% (7/10), 38.46% (10/26), 20.4% (29/142), 33.3% (2/6), respectively. The mean survival time in patients who underwent radical hepatic resection and BDT removal (group A), palliative hepatectomy and BDT removal (group B), palliative hepatectomy and BDT removal plus unilateral liver artery ligation or postoperative transcatheter arterial chemoembolization (TACE; group C), TACE (group D), drainage to relieve the jaundice by ERCP or PTCD (group E), and conservative treatment (group F) was 37, 6, 16, 11, 3.0, 3.0 months, respectively. The survival rate of patients in group A was significantly greater than in other group (P < 0.0001); the rate in groups C and D was significantly higher than that in groups B, E, and F (P < 0.001). In group A, 1-year recurrence rate was 20.8% (10/48). One patient with severe jaundice suffered chronic liver failure after right lobe resection and died 2 months after operation. In groups B, C, D, E, and F, in ten cases, cholangitis occurred, in eight cases, hemobilia occurred, and 72 of 136 patients suffered liver failure and died within 6 months. Five patients underwent orthotopic liver transplantation; at the time of writing, three patients are still alive, and the longest survivor has now survived for 37 months since undergoing transplantation. CONCLUSIONS: Radical hepatic resection and removal of BDT, combined with TACE, are the best approach for treating HCC patients with BDT. Biliary drainage to relieve the jaundice is critical.