As a nuclear transcription repressor,the functions of TGIF are complicated,not only represses target genes expression directly,but also takes part in the regulation of multiple important cellular signaling pathways,which are associated with the differentiation of cells and tissues,inflammation,metabolism and tumors.In past few years,more and more studies on the role of TGIF in tumors suggest TGIF may be a new therapy target in the diagnosis and treatment of tumours.This article mainly reviews the research progress of TGIF in some signaling pathways like TGF-β,MAPK,PI3K/AKT,and tumours like hepatocellular carcinoma,lung carcinoma and urinary tract urothelial carcinoma.

Objective:To investigate the mechanism of endoplasmic reticulum (ER) stress-induced chemoresistance to cisplatin in gastric cancer cells. Methods:ER stress models were established in both BGC823 and SGC7901 gastric cancer cells. The expression of GRP78, an ER stress marker, was examined by Western blot analysis. Moreover, whether ER stress can decrease the sensitivity of gastric cancer cells to cisplatin and activate P38 was explored by flow cytometry and Western blot analysis, respectively. Whether ER stress-induced chemoresistance to cisplatin can be abrogated by blocking P38 activity in gastric cancer was also elucidated using flow cytometry. Results:GRP78 protein expression markedly increased after treating BGC823 and SGC7901 gastric cancer cells with tunica-mycin (TM) or thapsigargin (TG) for 8, 16, and 24 h (P<0.05), compared with that in the group treated for 0 h. The apoptotic rates of TM-(or TG)-, cisplatin-, and TM (or TG) plus cisplatin-treated groups significantly increased (P<0.05) in both BGC823 and SGC7901 gastric cancer cells compared with the rate in the control group. The apoptotic rate of TM (or TG) plus cisplatin-treated group signifi-cantly decreased (P<0.05) in both BGC823 and SGC7901 gastric cancer cells compared with that of the cisplatin-treated group. Com-pared with the group treated for 0 h, phospho-P38 expression markedly increased after treating BGC823 and SGC7901 gastric cancer cells with TM (or TG) for 8, 16, and 24 h (P<0.05). No difference in P38 protein expression was observed between each group in both BGC823 and SGC7901 gastric cancer cells (P>0.05). Both P38 inhibitors, either SB203580 or PD169316, can inhibit the activation of P38. The inhibition of P38 activity can overcome ER stress-induced chemoresistance to cisplatin in gastric cancer cells (P<0.05). Con-clusion:ER stress can trigger the chemoresistance to cisplatin by activating P38 in gastric cancer cells.

Pancreatic tuberculosis (PTB) is a rare,chronic,specific and infectious disease which is generally secondary to tuberculosis at the common sites of pancreas,and it has a high misdiagnosis rate due to the hidden onset and nonspecific symptoms of PTB.A patient with PTB was admitted to the First Affiliated Hospital of Zhengzhou University in June 2014.Before operation,the space-occupying lesions of the head of pancreas were detected by preoperative imaging examination,and the patient was regarded as with pancreatic cancer.Intraoperative exploration showed cystic duct involvement,and the granulomatous inflammation was detected by rapid pathological examination using frozen section technique,after that the patient received granuloma resection+cholecystectomy according to suspected PTB.The diagnosis of PTB was confirmed by postoperative pathological examination,and the patient received liver-protective and anti-tuberculosis treatments after discharge.

Objective To summarize the diagnosis and therapeutic experience of insulinoma in order to improve the surgical success rate and prognosis. Methods The clinical data of 138 patients with insulinoma from 1966 to 2007 were retrospectively analyzed. Results In this group of patients, hypoglycemia of different levels and Whipple triad were detected. 64 patients expressed different psychic symptom, 12 patients' psychic symptom were still present after blood glucose normalized after operation. Fasting serum insulin values in 88 patients were measured, and the insulin release index was higher than 0. 3. Before operation, tumor was detected in 8 of 75 patients by B-ultrasound scan, and in 17 of 68 patients by CT, and in 5 of 10 patients by MRI. The intra-operative B-ultrasound (IOUS) examination was applied in 44 cases, and 43 cases were successfully detected. The operations included enucleation of insulinoma (n=88) , resection of the body and tail of pancreass (n = 44) , pancreaticoduodenectomy (n=2) , and biopsy (n=1). The blood glucose symptoms normalized postoperatively in 132 patients. The blood glucose rebound in 110 patients, but blood glucose normalized within 2 weeks. After operation, 20 patients developed pancreatic fistula, 32 patients developed acute pancreatitis. Conclusions Insulinoma could be qualitatively diagnosed according to Whipple triad and the insulin release index. Operations with IOUS were simple and effective methods to localize the tumors. The only way to cure insulinoma was operation, and IOUS guided operation could avoid main pancreatic duct and vessel injury, decrease post-operative complications.

Objective To study the expression and the clinical significance of hypoxia-induced factor-1α (HIF-1α) in gallbladder cancer tissues,and the role and mechanism of HIF-1α in metformin-suppressed metastasis in gallbladder carcinoma GBC-SD cells.Methods 24 specimens of gallbladder cancer tissues and 5 specimens of chronic cholecystitis were collected from the First Affiliated Hospital of Zhengzhou University between June 2016 and February 2017.Immunohistochemistry and qPCR were used to detect the expression of HIF-1α in gallbladder cancer tissues,in adjacent non-cancer tissues and in chronic cholecystitis,and the clinical significance was analyzed.The model of metastasis was induced by hypoxia;the wound healing assay and the Transwell assay were used to detect the ability of cell metastasis;the expressions of HIF-1α and VEGF in gallbladder carcinoma GBC-SD cells were detected by western blotting assay and immunofiuorescence.Results The expression of HIF-1α in gallbladder cancer tissues was higher than the adjacent non-cancer tissues and in chronic cholecystitis.The expression of HIF-1α was correlated with lymph node metastasis and TNM staging in gallbladder cancer tissues (P ＜ 0.05).The wound healing rate after 48 h in the negative control group and in the treatment with hypoxia group (1％ O2) in GBC-SD cells were (46.5 ± 4.8) ％ and (67.3 ± 4.0) ％,respectively.The Transwell data showed that the numbers of metastasis after 24 h in the negative control group and in the treatment with hypoxia group GBC-SD cells were (147.4 ± 11.7) and (234.4 ± 17.7),respectively.When compared with the negative control group,treatment with hypoxia significantly increased the ability of metastasis and up-regulated the expression of HIF-1α and VEGF in GBC-SD cells (P ＜ 0.05).The wound healing rate after 48 h in the negative control group,the metformin group,the hypoxia group and the metformin and hypoxia group in GBC-SD cells were (40.6 ± 7.1) ％,(16.4 ± 9.4) ％,(69.5 ± 4.0) ％ and (22.4 ± 7.4) ％,respectively.The Transwell data showed that the numbers of metastasis after 24 h in the negative control group,the metformin group,the hypoxia group and the metformin and hypoxia group in GBC-SD cells were (148.4 ± 6.9),(90.0 ± 8.4),(185.8 ± 10.2) and (113.4± 8.6),respectively.When comparcd with the hypoxia group,treatment with metformin and hypoxia significantly decreased the ability of metastasis and down-regulated the expression of HIF-1α and VEGF in GBC-SD cells (P ＜ 0.05).The wound healing rate after 48 h in the negative control group,the 2MeoE2 group,the hypoxia group,the 2MeoE2 and hypoxia group in GBC-SD cells were (43.4 ±4.4)％,(25.9 ±9.0)％,(63.3 ±2.2)％,(46.2 ±4.5)％,respectively.The Transwell data showed that the numbers of metastasis after 24 h in the negative control group,the 2MeoE2 group,the hypoxia group,the 2MeoE2 and hypoxia group in GBC-SD cells were (144.2 ± 12.6),(80.2 ±7.7),(203.8 ±7.0),(124.0 ± 5.2),respectively.When compared with the hypoxia group,treatment with HIF-1α inhibitor 2MeoE2 and hypoxia significantly decreased the ability of metastasis and down-regulated the expression of HIF-1α and VEGF in GBC-SD cells (P ＜ 0.05).Conclusions The expression of HIF-1 α was correlated with lymph node metastasis and TNM staging in gallbladder cancer tissues.Treatment with hypoxia significantly increased the expression of HIF-1α and VEGF and promoted metastasis of GBC-SD cells,while treatment with metformin decreased the ability of metastasis induced by hypoxia via inhibiting the HIF-1o/VEGF pathway in GBC-SD cells.

Objective To explore the effect of calreticulin (CRT) on cell proliferation and invasion of human hepatocellular carcinoma cell line SMMC-7721 and HepG2.Methods SMMC-7721 and HepG2 cells were transfected with small interfering RNA (siRNA).The transfection rate was detected by immunoflurescence and western blot.The cell proliferation,invasion and apoptosis of SMMC-7721 and HepG2 cells were determined by using cell counting kit-8 (CCK-8) assays,transwell assays and flow cytometry,respectively.The p-Akt and Akt levels were detected by western blot.Results The growth inhibition rate in the siRNA experimental group of SMMC-7721 and HepG2 cells for 24,36 and 48 h were (41.0 ±2.2) ％,(46.5 ±1.6)％,(59.7 ±2.2)％ and (36.8 ±2.7)％,(47.3 ± 1.8)％,(61.5 ±3.2)％,respectively.The apoptosis rate after down-regulating the expression of CRT in SMMC-7721 and HepG2 cells for 36h were (45.2 ± 9.1) ％ and (48.9 ± 8.0) ％,respectively.Compared with the blank group and the negative control group,the growth inhibition rate in the siRNA experimental group was lower (P ＜0.05),but the apoptosis rate was significantly higher (P ＜ 0.05).Transwell experiments confirmed that the numbers of invaded SMMC-7721 and HepG2 cells in the blank group and the negative control group and siRNA experimental group were (96.8±7.3),(95.6±5.4),(34.0±4.2) and (124.0 ±9.9),(121.6 ±7.0),(70.4±9.5),respectively,indicating that cell invasion in the siRNA experimental group was significantly suppressed (P ＜ 0.05).The expression of p-Akt was decreased (P ＜ 0.05) after down-regulating the expression of CRT for 36h.Conclusion CRT gene silencing by siRNA can inhibit the SMMC-7721 and HepG2 cell proliferation and invasion,but increase the cell apoptosis by regulating PI3K/Akt signal pathway.

Objective To observe how brain death affects the hepatic morphology and function of pigs and explore the roles of NF-κB. Methods Under general anaesthesia twelve healthy pigs were allocated randomly to two groups:control group(6 pigs),with non-inflacted Foley balloon catheter placed in the cerebral ventricle for 24 h,and brain death group,6 pigs,with estabhshment of brain death for 24 h.The serum and hepatic tissues in the same locus were taken at 6 h,12 h,and 24 h after the initial conformation of brain death.AST and ALT were determined by automatic biochemistry analyzer.IL-1βwas determined by ELISA.The NF-κB mRNA was determined by Real-time PCR and the NF-κB p65 by immunohistochemistry. Results The AST,ALT,IL-1β in serum,the NF-κB mRNA and the NF-κB p65 in hepatic tissues in brain death group were higher than those in control group and they all increased with the time(P<0.05).In brain death group,hepatocytes were edematous lightly after 12 hours,and the swelling progressively deteriorated after 24 hours,but there were no necrosis. Conclusion The activated NF-κB by brain death promoted the synthesis and release of inflammatory mediators,resulting in the hepatic dysfunction.

Objective To summarize the experience in the diagnosis and management of insulinoma. Methods From January 1966 to December 2007, the clinical data of 131 patients with insulinoma were retrospectively analyzed. Results All the 131 cases had Whipple triad syndrome and 64 eases suffered from psychoneurosis symptoms. The fasting blood glucose or insultus blood glucose concentration of all the cases was lower than 2.8 mmol/L. The ratios of serum insulin to glucose were all higher than 0.3. Before operation, tumor was detected in 8 of 75 patients by B-us scan, and in 17 of 68 by CT, and in 5 of 10 by MRI. The intraoperative ultrasonography(IOUS) was applied in 44 eases, and tumor was found in 43 cases. Surgery included enucleation of insulinoma (88 cases), resection of the corpus and eauda of the pancreas (40 cases), duodenopancreatectomy (2 cases), and biopsy (1 case). The low blood glucose symptoms disappeared postoperatively in 130 cases. Pancreatic fistulae occurred in 20 cases, acute pancreatitis occurred in 32 cases. Conclusions Insulinoma can be diagnosed based on symptoms of Whipple triad and the ratio of serum insulin to glucose. Exploration and IOUS are the simple and effective methods to localize insulinoma.

Objective To study the efficacy and the safe dosage of high intensity focused ultrasound (HIFU) ablation in pancreatic cancer.Methods From November 2010 to May 2013,21 patients with advanced pancreatic cancer were treated by HIFU at the First Affiliated Hospital of Zhengzhou University.These patients who were randomly divided into two groups (10 and 11 patients respectively),were given a low-power (100～249 W) treatment and a high power (250 ～350 W) treatment.These two groups of 21 patients received a total of 25 times of HIFU treatment (3 patients received twice of low-power treatment,while 1 patient received twice of high-power treatment).The two groups were compared by analyzing the treatment parameters (average power,total treatment time,treatment total energy,treatment volume,etc.) and volume of tumour response as shown on postoperative imaging (CT or MRI) examinations.Also,the complications,degree of pain relief and survival were compared.The energy efficiency factor (EEF) and the ablation ratio were calculated.A preliminary study was conducted on the relationship of the ultrasound dose and the ablation effect of HIFU treatment for pancreatic cancer.Results (1) The EEF of the high-power group (≥250 W) and the low-power group (＜ 250 W) were (10.39 ± 5.71) J/mm3 and (21.62 ± 9.81) J/mm3,the former group was significantly lower than the latter group (P ＜0.05) ; the ablation ratio of the high-power group was higher than the low-power group,(91.52 ± 4.18)％ versus (51.59 ± 7.66)％ respectively,the difference was statistically significant (P ＜ 0.001).(2) The efficiency factor and the ablation volume for the HIFU treatment showed a linear trend,and both were negatively correlated (Pearson correlation coefficient r =-0.485,P ＜ 0.05).(3) There was no serious complication after the HIFU treatment.In the low-power group,six of ten patients were alleviated of his pain (60％) ; the CA19-9 decreased in four of ten patients after HIFU treatment (40％).In the high-power group,nine of eleven patients were significantly relieved of pain after treatment (82％),the CA19-9 decreased in five of nine patients after HIFU treatment (56％).(4) On Kaplan-Meier survival analysis,HIFU treatment of patients with pancreatic cancer,the median survival was 8 months and 9 months in the low-power group and high power group,respectively (Log-rank test x2 =0.05,P =0.944).Conclusion During HIFU treatment of patients with pancreatic cancer,if the ultrasound power was between 250 W and 350 W,there was a higher proportion of tumor ablation,but with no serious complications.Thus,this dose was safe.

Objective To investigate the effects of RNA interference targeting EphA7 gene on the growth of SMMC-7721 cell xenograft in nude mice.Methods Recombinant plasmid of EphA7 gene-targeting siRNA was transfected into hepatic cancer SMMC-7721 cells by LipofectamineTM2000,comparing with the empty vector transfected group,untransfected group and control group.The nude mice tumor model was established by subcutaneous injection of hepatic cancer cells in the left upper limb of the mice.Control group was injected with PBS as blank.Real-time PCR,immunohistochemistry and Western blot were employed to detect the mRNA and protein expressions of EphA7 in tumor tissues.The tumor formation time,tumor mass and weight of tumor were also considered in the analysis.Results About 9 ～ 12 days after the injection of tumor cells,the xenograft tumor formation can be observed around the injection site except the control group.35 days after tumor formation,there were obvious decreases in the tumor growth rate,tumor mass,as well as tumor weight in transfected group,comparing with empty vector transfected group and untransfected group (P ＜0.05).Transfection of RNA interference can inhibit the growth of xenograft tumor by 55％.Immunohistochemistry tests showed that there were less cells with positive staining of EPHA7 protein in transfected group,and the staining was lighter as pale yellow,in contrast with the untransfected group and the empty vector transfected group.Real-time PCR and Western blot revealed that the expression of EphA7 mRNA and EPHA7 protein of transfected group were significantly lower than those of untransfected group and empty vector trausfected group with statistically significance (P ＜ 0.05).Conclusion Silencing EphA7 gene with RNA interference can effectively inhibit the growth of SMMC-7721 cell in nude mice,which is expected to become a new target for gene therapy of hepatic cancer.