Autophagy is a dynamic process which subcellular membranes undergo morphological changes that lead to the degradation of cellular cytoplasmic organelles and macromolecules.It is regulated by themammalian target of rapamycin ( mTOR ) -dependent or -independent signaling pathways.It has been demonstrated that autophagy is induced or inhibited in various tumor cells,and it is closely related with cell survival and drug resistance.Because of the complex relationships with cell death,the roles of autophagy in cancer developnent,treatment,and drug-resistance are not the same,and thus controlling autophagy properly may become one of new means of cancer therapy.

Recent studies show that tumor cells get rid of the connections between cells,and induce tumor invasion and metastasis through epithelial-mesenchymal transition (EMT).EMT becomes an important way to invasion,metastasis and chemotherapy resistance of epithelial cell carcinoma which accounting for more than 90％ of malignant carcinomas.Members of Snail family,especially Snail is regarded as important adjustment factor of EMT,which induce the transformation from epithelial cell to mesenchymal phenotype through competitive inhibition E-calcium protein gene expression.Many researches show that EMT exists widely in digestive system tumors,which is closly related to the invasion,metastasis and chemotherapy resistance of digestive system tumors.

STAT3 can be activated by various cytokines and participate in the process of tumor cells proliferation,angiogenesis,invasion and chemotherapy resistance.Epithelial-mesenchymal transition (EMT)also plays an important role in the process of tumor invasion and metastasis and chemotherapy resistance.Studies have shown that STAT3 can regulate the process of EMT so as to change the invasion and metastasis abilities of tumor cells,and to enhance their ability of chemotherapy resistance.Discussion of the role and relation of STAT3 and EMT in tumor cells will be helpful to provide reliable theory for tumor molecular targeted therapy.

Sphincter of Oddi dysfunction (SOD) refers to a series of clinical syndromes that occurs because of structural or functional disorders involving the biliary and/or pancreatic sphincters.It remains controversial whether endoscopic sphincter manometry (SOM) or sphincterotomy is needed in patients with type Ⅲ SOD.An important problem is that ERCP (with or without SOM) carries significant risks, especially the post-ERCP pancreatitis.The EPISOD trial has updated our knowledge on type Ⅲ SOD.The latest Rome Ⅳ consensus suggested that the classification term type Ⅲ biliary SOD should be abandoned and a new classification of biliary SOD was proposed;also, manometry and sphincterotomy were not recommended for patients with this type of SOD.The goal of this paper is to review recent literatures and elucidate the selected important questions regarding type Ⅲ SOD.

OBJECTIVE:To investigate the effect of thymosin α1 combined with chemotherapy on immune function in patients with advanced gastric cancer and quality of life. METHODS:90 patients with advanced gastric cancer were randomly divided into observation group and control group with 45 cases in each group. Control group was treated with FOLFOX4 chemotherapy plan(so-dium oxaliplatin+calcium folinate+fluorouracil),and observation group was additionally treated with thymosin α1 1.5 mg subcutane-ously,once a day,on the basis of control group. A treatment course lasted for 3 weeks,and both received 3 courses of treatment. The immune function and quality of life were evaluated in 2 groups. RESULTS:The effective rate of observation group was 57.8%,and that of control group was 53.3%;there was no significant difference between 2 groups (P>0.05). The incidence of leukopenia in observation group was 24.4%,which was significantly lower than control group (55.6%),with statistical signifi-cance(P<0.05). There was no statistical significance in CD4+,CD8+ and NK score between 2 groups before chemotherapy(P>0.05). After treatment,above index of observation were all higher than those of control group,with statistical significance (P<0.05). The total health QLQ-C30 EORTC score in observation group was higher than in control group after chemotherapy,with sta-tistical significance(P<0.05). CONCLUSIONS:Thymosin α1 combined with chemotherapy can significantly improve the immune function and quality of life.

Objective To analyze the clinical features of acute hyperlipidemic panereatitis,and to investigate the therapeutic strategies.Methods In this retrospective study,44 patients with hyperlipidemic pancreatitis admitted to our hospital from January 2003 to December 2007 were enrolled,60 patients with acute pancreatitis of other etiologies were enrolled as the control group.Results The proportions of patients with overweight or obesity,hyperglycemia,fatty liver and hypertension were 81.8%,59.1%,54.5% and 68.2%,respectively;these were significantly higher than those in control group,which were 16.7%,16.7 %,13.3 % and 23.3 %,respectively (P＜0.05 or＜0.01).The proportion of patients with lithiasis was lower in HLP group than that in control group (13.6% vs 60.0%,P＜0.05).There was no difference in the proportions of patients with chronic alcoholism between two groups.The Ranson score,CTSI,complications in HLP group were 3.15±0.07,4.46±2.58 and 3.2±1.7,respectively;these parameters were significantly higher than those in control group,which were 1.62±0.22,2.62±1.90 and 0.9±1.2 (P＜0.05 or ＜ 0.01 ).The level of serum amylase in HLP group was 580±222 mmol/L,which was significantly lower than that of control group (1361±472 mmol/L,P ＜ 0.01 ).The triglyceride (TG) level was linearly correlated with Ranson score in HLP group ( r = 0.77,P ＜ 0.05 ),but there was no linear correlation between TG level and Ranson score in the control group.Conclusions There was a close relationship between HLP and metabolic syndrome.Serum TG was positively correlated with the severity of HLP.

Objective To investigate the diagnostic value of tumor marker measurement in biliary juice obtained during endoscopic retrograde cholangiopancreatography (ERCP) in differential diagnosis of suspected biliary-pancrentic diseases.Methods ERCP was performed in patients with suspected biliarypancreatic lesions that could not be diagnosed by routine methods including ultrasonography,MRCP,blood biochemistry and serum tumor marker test,and biliary juice was obtained to measure tumor markers including CEA and CA199.A total of 29 patients with definitive diagnosis were recruited and divided into benign and malignant groups.Serum biochemical findings and tumor markers were compared between 2 groups.The diagnostic value of uhrasonography,EUS,MRCP,ERCP and ERCP combined with biliary tumor markers were also compared.Results There was no significant difference in serum biochemical findings,serum CEA,serum CA19-9 or biliary CA19-9 between 2 groups,while the average biliary CEA in malignant group was significandy higher than that in benign group (P＜0.001).The accuracy of ERCP combined with biliary tumor markers in diagnosing suspected biliary-pancreatic diseases was 69.0%,which was higher than that of ultrasonography (6.9%),MRCP (37.9%) and ERCP (41.4%),respectively.Conclusion The diagnostic accuracy of suspected biliary-pancreatic diseases can be improved through ERCP combined with biliary CEA test,which is helpful in differential diagnosis between benign and malignant lesions.

Objective To study the clinicopathologic features of giant cell carcinoma of the pancreas(GCCP). Methods The clinicopathologic features of 19 pathologically diagnosed as GCCP were retrospecti- vely analyzed in detail, compared with 96 cases of common pancreatic carcinoma (PC). Results Tumors that occurred in the head of pancreas were found in 8 patients(42.1%), and those in the body or tail of pancreas in 11 patients(57.9%). The initial symptom is mainly characterized by abdominal pain (57.9%). Abdominal pain (73.7%), dyspepsia(63.2%) and weight loss(36.8%) were common symptoms when patients were diagnosed. Jaundices is not a common symptom in these patients. The abnormal rates of routine laboratory tests were dramatically lower than those in common PC. The assay of tumor markers between GCCP and common PC were approximately same. The sensitivity and accuracy of diagnosis by ultrasonography, spiral computed tomography and magnetic resonance imaging were high. The carcinomas grew so large that 9 patients ( 47.4%)were in stage Ⅳ, the rate of which was higher than that in common PC. Osteoid formation was found under microscopy in some patients, and the tumor cells differentiated poorly in most of patients. The overall 1-year survival rate was 17.6%, which was lower than that in common PC. Conclusions The clinicopathologic features of GCCP are different from those of common PC. Imaging tests may be combined with the assay of tumor markers simultaneously so as to diagnose GCCP as early as possible and thus the prognosis of GCCP patients could be improved.

Background:Intrahepatic cholestasis is a commonly seen clinical manifestation, and often accompanied with jaundice.Study on clinical characteristics of patients with different degrees of jaundice is helpful for the acknowledge of intrahepatic cholestasis.Aims:To explore the clinical characteristics of intrahepatic cholestasis with jaundice.Methods:General data, biochemistry parameters, etiology and treatment of 703 patients with intrahepatic cholestasis were retrospectively analyzed.Results:Jaundice occurred in 168 patients (23.9%), including 149 mild jaundice, 15 moderate jaundice and 4 severe jaundice.Levels of ALT, AST, ALP, GGT, DBIL, TBIL, ratio of DBIL/TBIL, TBA were significantly increased in jaundice group than in non-jaundice group (P<0.05).Levels of ALT, AST, DBIL, TBIL, TBA were statistically different between groups with different degrees of jaundice (P<0.05), however, no significant differences in ALP, GGT, ratio of DBIL/TBIL were seen (P>0.05).The main etiology of intrahepatic cholestasis were digestive system tumors, cardiovascular diseases, shock, hematologic diseases and primary biliary cholangitis.Ursodeoxycholic acid and S-ademetionine were the main drugs for treatment of intrahepatic cholestasis.Conclusions:For patients with intrahepatic cholestasis, levels of ALT, AST, ALP, GGT are increased with the development of jaundice, and attention on damage of hepatocytes should be paid.The etiology of intrahepatic cholestasis with jaundice involves diseases of different organs and systems, most of them are malignant tumor, cardiovascular diseases, shock and primary biliary cholangitis.

Background:Recently,studies have shown that piperlongumine( PL)selectively killed cancer cells by elevating reactive oxygen species(ROS)in various cancers. However,the effect of PL on gastric cancer cells remained to be further studied. Aims:To investigate the effect of PL on proliferation and apoptosis of human gastric cancer cell line MKN45 and its underlying mechanism. Methods:MKN45 cells were treated with different doses of PL,caspase inhibitor,antioxidant, and their combinations,respectively. Cell viability was assessed by CCK-8 assay;cell cycle,apoptosis and intracellular ROS level were measured by flow cytometry;and Western blotting was employed to determine the expression of apoptosis-related proteins( XIAP,cleaved-caspase3,7,9 and cleaved-PARP),p53 and its downstream target genes( p21, GADD45α and PUMA). Results:PL inhibited the proliferation of MKN45 cells in a dose- and time-dependent manner. In MKN45 cells treated with PL,the proportion of cells in G1 phase,apoptotic rate and intracellular ROS level were significantly increased,the expression of inhibitor of apoptosis protein XIAP was down-regulated,and the caspase-dependent apoptosis pathway,p53 and its downstream target genes were activated. Pretreatment with antioxidant NAC or Z-VAD-FMK, a general caspase inhibitor could partially abolish the effect of PL on ROS production and its antitumor effect. Conclusions:PL can inhibit cell proliferation and induce cell cycle G1 phase arrest and apoptosis in MKN45 cells. Its antitumor effect may be associated with a ROS-mediated p53 activation and subsequent triggering of caspases cascade of cell apoptosis.