Long Noncoding RNA HOST2 Promotes Epithelial-Mesenchymal Transition, Proliferation, Invasion and Migration of Hepatocellular Carcinoma Cells by Activating the JAK2-STAT3 Signaling Pathway.

BACKGROUND/AIMS: This study aims to examine the effect of long noncoding RNA HOST2 (LncRNA HOST2) on epithelial-mesenchymal transition (EMT), proliferation, invasion and migration of hepatocellular carcinoma (HCC) cells via activation of the JAK2-STAT3 signaling pathway. METHODS: HCC and para-cancerous tissues were collected from 136 HCC patients. Immunohistochemistry was used to detect the expression of JAK2 and STAT3. HCC SMMC7721 cells were grouped into blank, negative control (NC), HOST2 mimic and HOST2 inhibitor groups. The mRNA and protein expression levels of HOST2, JAK2, STAT3, E-cadherin, vimentin, Snail, Slug, Twist and Zeb1 in tissues and cells were determined by reverse transcription -quantitative polymerase chain reaction (RT-qPCR) and Western blotting, respectively. An MTT assay, scratch test and Transwell assay were applied to measure cell proliferation, migration and invasion, respectively. RESULTS: The levels of JAK2, STAT3 and vimentin were higher in HCC tissues, while the expression of E-cadherin was lower in HCC tissues compared with para-cancerous tissues. The silencing of HOST2 significantly decreased cell proliferation, migration and invasion, reduced the levels of HOST2, JAK2, STAT3 and vimentin, and elevated the expression of E-cadherin. HOST2 silencing also decreased the levels of Snail, Slug and Twist but increased the level of Zeb1 protein, while the opposite findings were observed in the HOST2 mimic group. CONCLUSION: These results reveal a possible mechanism in HCC in which LncRNA HOST2 may increase EMT and enhance proliferation, invasion and metastasis of HCC cells via activation of the JAK2-STAT3 signaling pathway.

[Clinical observation on high intensity focused ultrasound combined with transcatheter arterial chemoembolization in the treatment of hepatocellular carcinoma].

OBJECTIVE: To study on the efficacy, prognosis and security of high-intensity focused ultrasound (HIFU) combined with transcatheter arterial chemoembolization (TACE) in the treatment of hepatocellular carcinoma (HCC). METHODS: Totally 72 HCC patients treated by HIFU from December 2009 to January 2011 were divided into two groups according to treatment methods: 40 cases in HIFU group, 32 cases in TACE + HIFU treatment group (combined group). Then set up a control group include 40 cases treated by only TACE in the same period (TACE group). The improvement of clinical symptoms, AFP, reduce rate of tumor volume, survival rate of 1 year after operation and postoperative complications in front and behind the treatment were analyzed. RESULTS: There was no significant statistical difference on the improvement of clinical symptoms in all these three groups (P > 0.05) after treatment for HCC. There is no significant statistical difference also on reduce rate of tumor volume and decrease rate of AFP in both HIFU group (35.0%, 41.4%) and TACE group (37.5%, 41.9%) (χ² = 0.054, P = 0.816; χ² = 0.002, P = 0.965). Both reduce rate of tumor volume (62.5%) and decrease rate of AFP (72.0%) in combined group were better than HIFU group (χ² = 5.394, P = 0.020; χ² = 5.098, P = 0.024) and TACE group (37.5%, 41.9%) (χ² = 4.448, P = 0.035; χ² = 5.062, P = 0.024). Kaplan-Meier survival curve showed that there was no significant statistical difference on short-term survival rate in the 3 groups. But the long-term survival rate of combined group was better than TACE group and HIFU group. CONCLUSION: TACE combined with HIFU is a effective, safe and noninvasive treatment method to HCC.

SPC25 promotes hepatocellular carcinoma metastasis via activating the FAK/PI3K/AKT signaling pathway through ITGB4.

Hepatocellular carcinoma (HCC) is a malignant tumor with a high metastatic rate. Recent studies have shown that the mitosis­associated spindle­assembly checkpoint regulatory protein spindle pole body component 25 homolog (SPC25) promotes HCC progression, although the underlying mechanism has yet to be fully elucidated. The aim of the present study was to investigate the mechanism through which SPC25 may promote HCC progression in greater detail. First, the expression of SPC25 was analyzed in publicly available databases to explore the association between SPC25 and HCC metastasis. Western blotting was subsequently performed to examine the level of SPC25 expression in different HCC cell lines. SPC25 was then silenced in HCCLM3 and Huh7 cells, and the effects of SPC25 silencing were investigated using cell proliferation, wound­healing, Transwell migration assays and an in vivo mouse model. Finally, the mechanism of SPC25 action with respect to the promotion of HCC metastasis was explored using microarray analysis and rescue experiments. The results obtained demonstrated that SPC25 is highly expressed in HCC, and this high level of expression is associated with poor prognosis and metastasis. Moreover, SPC25 silencing led to a marked inhibition of the invasion and migration of HCC cells both in vitro and in vivo. The gene­expression profiling and mechanistic experiments suggest that SPC25 preferentially influences the expression of genes associated with extracellular matrix (ECM)­integrin interactions, including integrin subunit ß4 (ITGB4), an upstream element of the integrin pathway. ITGB4 upregulation partly reversed the decline in cell invasion and migration capacities that resulted from SPC25 silencing. Furthermore, deleting both SPC25 and ITGB4 caused a decrease in the phosphorylation of focal adhesion kinase (FAK), phosphoinositide 3­kinase (PI3K) and AKT, which are downstream elements of the integrin pathway. Taken together, the results of the present study demonstrated the important role of SPC25 as a prognostic indicator and as a promoter of metastasis in HCC, and the underlying mechanism of its action has been partially elucidated, suggesting that SPC25 could be used as a biomarker and as a target for therapeutic intervention in the treatment of HCC.

[Expression of EphA7 protein in primary hepatocellular carcinoma and its clinical significance].

OBJECTIVE: To investigate the expression and clinical significance of EphA7 protein in primary hepatocellular carcinoma. METHODS: Immunohistochemistry and Western blot were used to detect the expression of EphA7 protein in 40 cases of primary hepatocellular carcinoma, their corresponding adjacent liver tissues and 10 cases of normal liver tissues. The relations with its clinical pathological parameters were analyzed too. RESULTS: Expression of EphA7 protein was mainly located in the cytoplasm and the blood vessels of the septa, which was found in hepatocellular carcinoma tissues, their corresponding adjacent liver tissues and normal liver tissues. Western blot analysis showed that the expression level of EphA7 protein in hepatocellular carcinoma (0.58 +/- 0.26) was greater than that in corresponding adjacent liver tissues (0.40 +/- 0.22, P < 0.05) and normal liver tissues (0.32 +/- 0.16, P < 0.05). But it had no significant difference between corresponding adjacent liver tissues and normal liver tissues (P > 0.05). EphA7 protein expression was correlated with histological differentiation, tumor thrombi in portal vein, lymph node metastasis and high AFP level (P < 0.05). CONCLUSIONS: EphA7 protein expression is significantly correlated with the biological behavior of primary hepatocellular carcinoma. The high expression of EphA7 protein may play an important role in the malignancy transformation, invasion progression and metastasis of primary hepatocellular carcinoma.

[The application of intraoperative ultrasonography in the diagnosis and therapy of insulinoma].

OBJECTIVE: To analyze the value of intraoperative ultrasonography (IOUS) in the diagnosis and therapy of insulinoma. METHODS: From January 2000 to December 2007, the application of intraoperative ultrasonography used in 44 cases with insulinoma who came from department of general surgery, First Affiliated Hospital of Zhengzhou University were retrospectively analyzed. There were 19 males and 25 females in the group. Every case accepted operation and examination of IOUS. RESULTS: Tumor was accurately located and its adjacent structure was also clear by IOUS in 43 cases, the other one was islet cell hyperplasia, the detection rate of tumor was 100%. The complications: one case occurred pancreatic fistula, one occurred pancreatitis, and there was no biliary fistula and hemorrhage. CONCLUSIONS: Presently, IOUS is one simple and effective method to local insulinoma, and it could improve the success rate of operation and reduce complications.

Long non-coding RNA DILC suppresses bladder cancer cells progression.

Accumulative researches have demonstrated the critical functions of long non-coding RNAs (lncRNAs) in the progression of malignant tumors, including bladder cancer (BC). Our previous studies showed that lnc-DILC was an important tumor suppressor gene in both liver cancer and colorectal cancer. However, the role of lnc-DILC in BC remains to be elucidated. In the present study, we for first found that lnc-DILC was downregulated in human bladder cancer tissues. Lnc-DILC overexpression suppressed the proliferation, metastasis and expansion of bladder cancer stem cells (CSCs). Mechanically, lnc-DILC suppressed BC cells progression via STAT3 pathway. Special STAT3 inhibitor S3I-201 diminished the discrepancy of growth, metastasis and self-renewal ability between lnc-DILC-overexpression BC cells and their control cells, which further confirmed that STAT3 was acquired for lnc-DILC-disrupted BC cell growth, metastasis and self-renewal. Taken together, our results suggest that lnc-DILC is a novel bladder tumor suppressor and indicate that lnc-DILC inhibits BC progression via inactivating STAT3 signaling.

[Nedaplatin combined with tegafur in the treatment for advanced esophageal cancer].

OBJECTIVE: To investigate the efficacy and toxicity of nedaplatin combined with tegafur in the treatment for patients with advanced esophageal cancer. METHODS: Among the 65 patients with advanced esophageal cancer, 27 had no history of prior chemotherapy and the other 38 had ever received postoperative adjuvant chemotherapy before. The median age of those cases was 58.0 years. Nedaplatin was given daily by intravenous infusion at a dose of 20 mg/m(2) for 2 hours and tegafur at a dose of 500 mg/m(2) for 8 hours on D1 approximately D5, every 21 days as a cycle. RESULTS: 193 cycles of chemotherapy were accomplished in the 65 patients, and 63 patients were evaluable for response evaluation. Of 27 patients with no prior history of chemotherapy, 6 achieved complete response and 16 partial response, with a response rate (CR + PR) of 81.5%. Among the 36 patients who had ever received postoperative adjuvant chemotherapy, 6 obtained complete response and 10 partial response with a response rate (CR + PR) of 44.4%. The overall median time to tumor progression in this series was 5.6 months. The overall median actuarial survival was 9.3 months, and the one-year survival rate was 24.9%. Nausea and vomiting were the major toxicities, but were mild and well tolerable. Grade 3 to 4 neutropenia was only observed in two patients (3.2%). CONCLUSION: The regimen of nedaplatin combined with tegafur is effective and tolerable for the treatment of advanced esophageal cancer.

Breviscapine alleviates hepatic injury and inhibits PKC-mRNA and its protein expression in brain-dead BA-Ma mini pigs.

BACKGROUND: Brain-dead donors are the main sources for organ transplantation, but many studies show that brain-death affects the organ's function after transplantation. This study was undertaken to investigate liver injury after brain-death in BA-Ma mini pigs and the protective effects of breviscapine on hepatic function and on PKC-alpha mRNA and its protein expression. METHODS: Fifteen BA-Ma mini pigs were equally divided into 3 groups at random: brain-dead (group B), breviscapine pretreated (group P), and control (group C). The brain-dead model was established by increasing intracranial pressure in a modified, slow and intermittent way. At 3, 6, 12, 18 and 24 hours after the initial brain-death, the levels of serum AST, ALT, TNF-alpha, IL-1beta, and IL-6 were determined. The changes in hepatic tissues were assessed, and the expression of PKC-alpha and PKC-alpha mRNA was detected by immunohistochemistry and RT-PCR, respectively. RESULTS: The levels of AST and ALT in groups B and P began to increase 12 hours after brain-death, while the values in group P were lower than those in group B (P<0.05). The levels of IL-1beta, IL-6, and TNF-alpha in groups B and P at 3, 6, 12 and 18 hours were lower than those in group B (P<0.05). At 6, 12 and 24 hours, the expressions of PKC-alpha mRNA and PKC-alpha protein in group P were lower than those in group B (P<0.05). The degree of injury to hepatic cells in group P was milder than that in group B. CONCLUSIONS: Breviscapine inhibits the degree of PKC-alpha mRNA transcription and its protein translation, decreases the release of inflammatory factors, and thus alleviates hepatic injury during brain-death.

[Expression and clinical significance of Ephrin-A1 in primary hepatocellular carcinoma].

OBJECTIVE: To investigate the expression and clinical significance of Ephrin-A1 mRNA and protein expression level in hepatocellular carcinoma. METHODS: Reverse transcription polymerase chain reaction (RT-PCR) and immunohistochemistry technique were used to detect the expression of the Ephrin-A1 mRNA and protein of 40 cases of hepatocellular carcinoma and their corresponding para-cancerous tissues and 10 cases of normal liver tissues. The relationships with its clinical pathology characters were analyzed. RESULTS: The mRNA of Ephrin-A1 was expressed in all of the 40 cases of hepatocellular carcinoma and their corresponding para-cancerous tissues and 10 cases of normal liver tissues. Semiquantitative analysis showed that the mRNA expression level of Ephrin-A1 in hepatocellular carcinoma (0.5413 +/- 0.1527) was greater than that in corresponding para-cancerous tissues (0.3895 +/- 0.0549, P < 0.05) and normal liver tissues (0.3770 +/- 0.1055, P < 0.05); but between corresponding para-cancerous tissues (0.3895 +/- 0.0549) and normal liver tissues (0.3770 +/- 0.1055), the mRNA expression level had no significant difference (P > 0.05). The positive rates of Ephrin-A1 protein were 20% (2/10) in normal tissues, 35% (14/40) in para-cancerous tissues and 62% (25/40) in hepatocellular carcinoma tissues, respectively; the protein expression level of Ephrin-A1 was gradually rising (chi(2) = 14.762, P < 0.05). The overexpression of Ephrin-A1 protein was correlated with histological differentiation, tumor thrombi in portal vein and lymph node metastasis (P < 0.05). CONCLUSIONS: The overexpression of Ephrin-A1 protein is correlated with histological differentiation, the lymph node metastasis and tumor thrombi in portal vein. It indicates that Ephrin-A1 may play an important role in the malignancy transformation, invasion progression and metastasis of hepatocellular carcinoma.

[Binding fistulojejunostomy for the treatment of external pancreatic fistula].

OBJECTIVE: To evaluate the safety and feasibility of binding fistulojejunostomy, a new operative procedure, in the treatment of external pancreatic fistula. METHODS: Eight patients suffering from external pancreatic fistula, 4 males and 4 females, aged 49 (22 approximately 69), underwent binding fistulojejunostomy: 2 cm-length of fistula was isolated and a tube was inserted therein, the jejunum was transected and the distant cut end was everted for the length of 3 cm, the mucosa of the everted jejunum was destroyed with carbolic acid, the everted mucosa of jejunum and the fistula were brought together and sutured with silk, the everted jejunum was then turned back to wrap over the fistula, a silk tie was lopped around the entire circumference of the anastomosis, and lastly, the tube was led out of the abdominal wall. RESULTS: all 8 patients recovered smoothly without pancreatic leakage and other complications. CONCLUSION: Binding fistulojejunostomy is safe and effective for the treatment of external pancreatic fistula.

Development of immune-affinity 96 spots monolith array for multiple mycotoxins detection in food samples.

In this paper, a novel highly sensitive chemiluminescence immune-affinity 96 spots monolith array was developed to detect deoxynivalenol (DON), zearalenone (ZEN), T-2 toxin (T-2), and fumonisin B1 (FB1) in corn samples. Firstly, the monolith array was prepared through on suit UV-initiated copolymerization using polyethylene glycol diacrylate (PEGDA) as cross-linker, glycidyl methacrylate (GMA) as functional monomer and polyethylene glycol 200 (PEG 200) as the porogen. Subsequently, the four mycotoxins immune-affinity monolith array was prepared by immobilization of DON, ZEN, T-2, and FB1 antibody. The mole ratio of PEGDA/GMA, UV exposure time, and the volume ratio of PEG 200/PEGDA were optimized to improve the performances of the immune-affinity monolith array. For the mycotoxins immune-affinity monolith array based on chemiluminescence detection, the limit of detection was 0.0036ng/mL (DON), 0.0048ng/mL (ZEN), 0.0039ng/mL (T-2), and 0.0017ng/mL (FB1), respectively. The linear response in the range of 0.01-0.1ng/mL (R(2)=0.98). The results showed that the proposed four mycotoxins immune-affinity monolith array was a stable, accurate, and highly sensitive method to determine levels of DON, ZEN, T-2, and FB1 in real samples.

Protective effect of antioxidant on renal damage caused by doxorubicin chemotherapy in mice with hepatic cancer.

OBJECTIVES: To investigate the protective effects and mechanism of antioxidant TBHQ on renal damage caused by doxorubicin chemotherapy in mice with hepatic cancer. METHODS: Cell H22 of mice with hepatic cancer which was subcultured for three times was subcutaneously transplanted to the groin of right lower limb of 45 SPF Kunming mice to establish the transplanted tumor model. The doxorubicin chemotherapy group and antioxidant intervention group received intraperitoneal injection of ADM (1 mg/kg·0.2 mL/2 d). The model control group received normal saline (NS) of the same volume at the same time. 1% TBHQ was added into the diet of mice of the antioxidant intervention group. Seven weeks later, morning urines and peripheral blood were randomly collected to detect UAlb, UCr, BUN, Scr and UAlb/Cr levels. All mice were beheaded. The renal tissues were made into homogenate, and SOD, T-AOC and MDA content in tissues were detected followed by cell lysis. All data were processed using SPSS19.0. RESULTS: The UAlb/Cr, BUN, Scr and MDA of doxorubicin chemotherapy group were significantly higher those of model control group and the activities of SOD, T-AOC in doxorubicin chemotherapy group were lower than those of model control group (P < 0.01). The UAlb/Cr, BUN, Scr and MDA of antioxidant intervention group were lower than those of doxorubicin chemotherapy group and the activities of SOD, T-AOC of antioxidant intervention group were higher than those of doxorubicin chemotherapy group doxorubicin chemotherapy group (P < 0.05). The BUN of model control group was higher than that of blank group, and T-AOC was lower than that of blank group, and difference was statistically significant (P < 0.05). CONCLUSIONS: Doxorubicin chemotherapy could lead to abnormal antioxidant capacity and renal function of tumor-bearing mice with hepatic cancer. TBHQ antioxidant intervention could effectively improve the antioxidant capacity of renal tissue and reduce the renal damage caused by doxorubicin to some extent.

Protection effect of triptolide to liver injury in rats with severe acute pancreatitis.

BACKGROUND: The high mortality of patients with severe acute pancreatitis (SAP) is due to multiorgan dysfunction. The mechanisms of SAP are still obscure. The aim of this study was to investigate the role of nuclear factor-kappa B (NF-kappaB) activation in rats with SAP associated with liver injury and the protection effect of triptolide against liver injury in rats with SAP. METHODS: Ninety Wistar rats were randomly divided into three groups (n=30 each group): severe acute pancreatitis (group P), treatment with triptolide (group T), and sham operation (group S). SAP models were induced by retrograde injection of 5% sodium taurocholate to the pancreatic duct. After the model was successfully established, no treatment was given to group P. In group T, triptolide (0.05 mg/ml) was injected intraperitoneally (0.2 mg/kg). In group S, the abdominal walls of rats were opened, sutured, but not treated. The rats were sacrificed after operation at 2, 6, and 12 hours, respectively. The serum levels of amylase (AMY), alanine aminotransferase (ALT), tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) were determined at three time points (10 rats for each time point). Liver tissues were obtained to detect the activity of NF-kappaB and to observe their pathological changes with light and electron microscopes. RESULTS: The serum levels of AMY and ALT were higher in groups P and T than in group S. The serum AMY levels were significantly lower in group T than in group P at 12 hours after operation. The serum ALT levels were significantly lower in group T than in group P at 6, 12 hours after operation. At the three time points, the levels of TNF-alpha and IL-6 in groups P and T increased more significantly than in group S. In group T they were decreased more significantly than in group P at the three time points. In groups P and T, NF-kappaB activity in liver tissue increased more significantly than in group S at the three time points. The activity of NF-kappaB was higher in group P than in groups S and T at the three time points. Liver pathological damages were milder in group T than in group P under light and electron microscopes. CONCLUSIONS: NF-kappaB plays an important role in the pathogenesis of liver injury in rats with SAP. Triptolide can reduce pathological damage to the liver. Its mechanism is to inhibit the activity of NF-kappaB and to decrease the release of inflammatory mediators.

[Radiolytic Decomposition of Ciprofloxacin Hydrochloride in Aqueous Solution Using γ Irradiation].

Effects of initial concentrations, pH values, different additives and composite pollutants on ciprofloxacin hydrochloride removal using γ irradiation were investigated. The experiments results showed γ irradiation could effectively remove ciprofloxacin hydrochloride; low initial concentration and strongly acidic condition were favorable for CIP removal using γ irradiation; the degradation of CIP was inhibited upon the addition of CO3(2-) and methanol, which indicated that the degradation of CIP might be mainly ascribed to *OH oxidation and the direct decomposition of CIP molecules induced by irradiation. BrO3- showed a synergistic effect with CIP in degradation of the composite pollutants when mixed together with CIP for γ irradiation, and the removal rates of both pollutants were improved. At an absorbed dose of 400 Gy, the removal rates of CIP and BrO3- were increased by 18.74% and 1.81%, respectively. The removal rates of TOC and COD were 15.22% and 61.44%, respectively, when the 100 mg x L(-1) CIP was degraded by γ irradiation at the absorbed dose of 6 000 Gy.

Different ischemic preconditioning for rat liver graft: protection and mechanism.

OBJECTIVE: To investigate the protective mechanism of different ischemic preconditioning (IPC) to ischemia/reperfusion (I/R) injury of rat liver graft. METHODS: 192 Wistar rats were randomly divided into 4 groups (48 rats in each group): control group (group C), experimental group 1 (group E1), experimental group 2 (group E2), and experimental group 3 (group E3). IPC was not carried out in group C. In the experimental groups, IPC was carried out by blocking blood flow of the portal vein and hepatic artery and then reperfusion by removal of the clamp before donor liver was resected. Group E1: 5-minute ischemia and 10-minute reperfusion; Group E2: 5-minute ischemia and 5-minute reperfusion and one more the same procedure; Group E3: 10-minute ischemia and 15-minute reperfusion. Four hours after IPC, liver transplantations were performed. Recipient blood and graft samples were obtained to determine the levels of ALT, AST, TNF-alpha and apoptosis index at 0.5, 2, 6, 24 hours after portal vein reperfusion. RESULTS: At 0.5, 2 hours after portal vein reperfusion, the levels of TNF-alpha in the experimental groups E1, E2, and E3 were significantly lower than in the control group (P<0.05), and the levels in group E2 were significantly lower than in groups E1 and E3 (P<0.05). At 24 hours, the levels of TNF-alpha in group E2 were significantly lower than in groups C, E1 and E3 (P<0.05). At 2 and 6 hours, apoptosis index in the experimental groups E1, E2, and E3 was significantly less than in the control group (P<0.05). Apoptosis index in group E2 was significantly less than groups E1 and E3 (P<0.05). At 24 hours apoptosis index in the experimental groups E1, E2, and E3 was significantly less than in the control group (P<0.05). CONCLUSIONS: Ischemic preconditioning could attenuate liver graft injury by decreasing apoptosis of hepatocytes and production of TNF-alpha. The method of IPC with 5-minute ischemia, 5-minute reperfusion and one more the same procedure is a better way to protect liver graft from ischemia-reperfusion injury.

Management of severe Budd-Chiari syndrome: report of 147 cases.

BACKGROUND: Budd-Chiari syndrome (BCS) is an uncommon disorder caused by the obstruction of hepatic venous outflow and/or the inferior vena cava. Major therapeutic approaches include operation and radiological intervention. This study was conducted to investigate the treatment of severe BCS. METHODS: The clinical data of 147 patients with severe BCS who had been treated at our hospital from November 1994 to December 2003 were retrospectively analyzed. RESULTS: One hundred twenty-one patients with BCS underwent surgery, including mesocaval C type shunt with artificial graft (82 patients), splenojugular shunt (37), mesojugular shunt (2), percutaneous transhepatic recanalization and dilatation and/or stent placement of the main hepatic vein (MHV) (12), and combined percutaneous transhepatic angioplasty (PTA) and stent placement of the inferior vena cava and mesocaval shunt (14). Follow-up for 6-108 months showed excellent results in 102 patients (69.4%), good results in 40 (27.2%), and 5 deaths. CONCLUSION: Good results could be obtained in most of patients with BCS after different surgical treatments according to the pathological changes of the IVC and MHV.

Triplex operation for portal hypertension with esophageal variceal bleeding: report of 140 cases.

BACKGROUND: Portal hypertension is a common disease. The surgical therapy of this disease focuses on the resultant upper digestive tract bleeding, which can imperil patients' life directly. This study was to evaluate the effect of triplex operation (mesocaval C shunt with artificial graft, ligation of the coronary vein and splenic artery) on portal hypertension and its associated upper digestive tract bleeding. METHODS: A retrospective study was made on clinical data of 140 patients undergoing triplex operation, who had suffered from portal hypertension and upper digestive tract bleeding. RESULTS: Postoperative portal pressure was 25-43 cmH2O(preoperative portal pressure 27-45 cmH2O) with the average reduction of 10 cmH2O. One patient (0.7%) died of cerebrovascular disease. Five patients (3.5%) suffered from mild hepatic encephalopathy, which was ameliorated through conservative treatment. Lymphatic fistula occurred in 3 patients (2.1%) who recovered without treatment 5, 10 days and 3 months after operation respectively. One hundred patients were followed up for 1 month to 6 years without recurrent hemorrhage or hepatic encephalopathy. Hypersplenism and ascites disappeared in 70 patients (70%) and 80 patients (80%) respectively. A significant reduction of ascites was seen in 12 patients(12%). The artificial vessels remained unblocking detected by B type ultrasonography and Doppler sonography in 95 patients(95%). CONCLUSION: Triplex operation is suitable for patients with the following portal hypertensions: portal hypertension caused by simple occlusion of the hepatic vein (a pathological type of Budd-Chiari syndrome); thrombosis of the portal vein or prehepatic portal hypertension because of cavernous transformation; intrahepatic portal hypertension with rebleeding after splenectomy or non-operation, and those patients with liver function in grade A or B according to the Child-Pugh classification.

Diagnosis and treatment of insulinoma: report of 105 cases.

OBJECTIVE: To study the methods for diagnosis and treatment of insulinoma. METHODS: Clinical data from 105 patients with insulinoma who had been admitted to our hospital from July 1966 to December 1999 were retrospectively reviewed. RESULTS: Fasting blood glucose values were less than 2.75 mmol/L in all the patients. Fasting serum insulin values in 60 patients were higher than 25 mU/L, average 65 mU/L. Before operation, carcinoma was detected in 2 of 45 patients by ultrasound scan, and in 10 of 35 by CT. Enucleation of insulinoma was performed in 60 patients. Operations included insulinoma resection (35 patients), distal resection of the pancreas (8), and biopsy (2). CONCLUSION: Whipple's triad and the index of insulin release >0.3 are the major variables for diagnosis. Intraoperative exploration and ultrasound scan are the methods for the localization of insulinoma. Enucleation of benign insulinoma is preferred, but proximal or distal resections of the pancreas are required only for large, deep or multiple tumors.

Surgical treatment of 1360 cases of Budd-Chiari syndrome: 20-year experience.

BACKGROUND: Budd-Chiari syndrome (BCS) is a disease caused by blood flow obstruction of the main hepatic veins (MHVs) and/or the outlet of the inferior vena cava (IVC), characterized by retrohepatic portal hypertension (PHT) and/or IVC hypertension. In the past decade, over 3000 cases of BCS have been reported in China. This study was to sum up our 20-year experience in surgical treatment of BCS and to investigate its pathological classification and principles of surgery. METHODS: The data from 1360 BCS patients were analyzed retrospectively. RESULTS: Four types (6 subtypes) were classified according to IVC angiography and hepatovenography: type Ia (594 patients), type Ib (123), type II (292), type IIIa (237), type IIIb (112), and type IV (2). Surgical procedures included: improved splenopneumopexy (265 cases), finger or balloon membranotomy (407), radical resection of membrane and thrombus (275), IVC bypass (88: cavocaval transflow 71 cases, and cavoatrial transflow 17 cases), mesocaval C-shape shunt (192), splenocaval shunt (32), splenoatrial shunt (23), splenojugular shunt (57), mesoatrial shunt (8), and combined methods (6), including plenal-cavoatrial shunt (4), and mesocavoatrial shunt (2), splenorenal shunt (4), mesojugular shunt (2), and other methods (1). The perioperative death rate and the complication rate after operation was 3.09% (42/1360) and 14.8% (201/1360) respectively. 885 cases were followed up from 9 months to 15 years (average 6.8+/-1.2 years. The 791 (89.4%) of 885 patients were successfully treated, 61 patients (6.89%) had a recurrence, and 33 died. CONCLUSION: Surgical treatment of BCS is dependent on a correct diagnosis and classification of the disease.

Aurora kinase a suppresses metabolic stress-induced autophagic cell death by activating mTOR signaling in breast cancer cells.

Aberrant Aur-A signaling is associated with tumor malignant behaviors. However, its involvement in tumor metabolic stress is not fully elucidated. In the present study, prolonged nutrient deprivation was conducted into breast cancer cells to mimic metabolic stress in tumors. In these cells, autophagy was induced, leading to caspase-independent cell death, which was blocked by either targeted knockdown of autophagic gene ATG5 or autophagy inhibitor 3-Methyladenine (3-MA). Aur-A overexpression mediated resistance to autophagic cell death and promoted breast cancer cells survival when exposed to metabolic stress. Moreover, we provided evidence that Aur-A suppressed autophagy in a kinase-dependent manner. Furthermore, we revealed that Aur-A overexpression enhanced the mammalian target of rapamycin (mTOR) activity under metabolic stress by inhibiting glycogen synthase kinase 3ß (GSK3ß). Inhibition of mTOR activity by rapamycin sensitized Aur-A-overexpressed breast cancer cells to metabolic stress-induced cell death. Consistently, we presented an inverse correlation between Aur-A expression (high) and autophagic levels (low) in clinical breast cancer samples. In conclusion, our data provided a novel insight into the cyto-protective role of Aur-A against metabolic stress by suppressing autophagic cell death, which might help to develop alternative cell death avenues for breast cancer therapy.