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 investigate the serum levels of procalcitomn (PCT) and high mobility group box chromosomal protein-1 ( HMGB1 ) in patients with acute pancreatitis (AP) ; and study the relationship between the serum levels of PCT,HMGB1 and the severity and prognosis of AP.Methods The blood samples were collected from 80 AP patients,including 38 severe acute pancreatitis (SAP) patients and 42 mild acute pancreatitis (MAP) patients.The serum levels of HMGB1 were measured by ELISA kit,and the levels of PCT were measured by immunoassay chemiluminescent technique,then their relationship with other biochemical parameters,the severity and prognosis of AP was analyzed.30 healthy adults were treated as the control group.Results The serum PCT and HMGB1 levels were ( 8.18 ± 3.24) μg/L and ( 11.79 ± 3.98 ) μg/L in SAP group,and the corresponding values were (5.67 ± 2.43) μg/L and ( 5.38 ± 2.06) μg/L in MAP group,and both were significantly higher than those in control group [ ( 1.85 ± 0.86) μg/L and ( 1.87 ± 1.47) μg/L,P ＜0.01 ].The serum level of PCT was positively correlated with serum 1evel of HMGB1 ( r =0.276,P =0.014),and both were positively correlated with Ranson score,APACHE Ⅱ score,Balthazar CT score (P＜0.05 or ＜0.01 ).The HMGB1 levels were significantly higher in patients with organ dysfunction than those in patients without organ dysfunction (P ＜0.05).Conclusions In AP patients,serum PCT and HMGB1 levels were significantly increased,and they were positively correlated with disease severity.These results suggest that PCT and HMGB1 may act as potential serum markers for AP severity evaluation.

Multidrug resistance (MDR) is the main obstacle for cancer to cure,failure of chemotherapy and relapse.Cancer stem cells (CSCs) are driven force for tumorigenesis,the evolution of metastasis and recurrence,and the most fundamental reason for cancer drug-resistance.The primary drug resistance mechanism includes:ABC transporters strengthening CSCs drug resistance,high level expression of the anti-apoptotic genes,DNA repair capacity enhancement and hypoxic niches,and so on.To study CSCs biological characteristics and clarify the resistance molecular mechanisms,and to develop a targeted therapy for CSCs,and then to overcome and reverse the multidrug resistance of CSC,will enhance cancer cure rate and reduce the relapse rate.

Objective To investigate the expression of Delta-like 4 (DLL4) in pancreatic cancer and its clinical significance.Methods The expression of DLL4 in pancreatic cancer was examined by immunohistochemistry method.The microvessel density (MVD) was calculated after CD34 staining specifically for microvessel endothelium; and their correlations and relationship between them and clinicopathological parameters as well as prognosis of pancreatic carcinoma was investigated.Results The expression of DLL4 in pancreatic cancer was significantly higher than that in normal pancreatic tissue (68.3％ vs 20％,P ＜ 0.01).The over-expression of DLL4 in pancreatic cancer was related to degree of differentiation,TNM staging,lymph node metastasis and invasion depth,while not related to the size,location and histological types.The MVD in pancreatic cancer tissues was notably higher than that in normal tissues (34.9 ± 13.2 vs 18.9 ± 2.2,P ＜0.01).MVD was correlated to degree of differentiation,lymph node metastasis,but not related to the size,location and histological types.DLL4 expression was closely associated with prognosis.COX model analysis showed that TNM staging and DLL4 expression were independent prognostic factors for pancreatic cancer.Conclusions The over-expressions of DLL4 may play an important role in metastasis and invasion of pancreatic cancer.Expression of DLL4 and TNM staging is useful for predicting the prognosis of patients with pancreatic cancer.

Abstract: Bruton’s tyrosine kinase (BTK), a cytoplasmic tyrosine kinase, plays a central role in the activation of B cells and granulocytes, operating downstream of B cell and Fcγ receptors, and is considered an attractive target for treating autoimmune diseases. Preclinical investigations have demonstrated that inhibition of BTK activity holds promise as a potential therapeutic strategy for inflammatory immune responses such as autoimmune diseases and allergies. This review provides an overview of the mechanisms by which BTK contributes to immune-related diseases and summarizes current research on the development of BTK inhibitors for treating these conditions, aiming to offer novel insights into non-oncology applications for BTK inhibitors.

Objectives To investigate the clinical and imaging features discriminating mass forming chronic pancreatitis (CP) from pancreatic carcinoma. Methods The clinical, radiologic, laboratory and pathologic profiles of eleven patients with mass forming CP were reviewed retrospectively. Results The patients with mass forming CP were predominantly older, male, and presented with obstructive jaundice or abdominal symptoms. Serum level of CA19-9 was slightly elevated, generally below 100 U/ml, which was lower than that of pancreatic carcinoma. The diagnostic accuracy of B-ultrasound for mass forming CP was only 18.2% and it could only be the screening method; the diagnostic accuracy of CT was 45.5%, and the main CT features included dilation of main pancreatic duct and the branches, as well as pancreatic pseudocysts or calcification. The findings of MRCP and EUS were irregular dilation of main pancreatic duct and common bile duct, which were similar to pancreatic carcinoma. ERCP could provide imaging characteristics of biliary and pancreatic duct, and the nature of obstruction, the stricture and dilation of biliary and pancreatic duct. When combined with CT scan, ERCP was useful for differentiation from pancreatic head cancer. According to histopathology, a few mass forming CP was autoimmune pancreatitis. Conclusions Mass forming CP is associated with clinical and radiologic features that are similar to those of pancreatic carcinoma. It is necessary to carefully evaluating clinical and imaging findings, laboratory findings and histopathological examinations.

Background:Recently,cancer stem cells( CSCs)has become a hot topic in cancer research. For this research topic,the primary problem is the isolation and identification of CSCs,and suspension culture is considered to be an important method for CSCs isolation. Aims:To study the isolation and identification of gastric cancer stem cells( GCSCs) and evaluate its stemness characteristics. Methods:GCSCs-like cells were enriched through spheroid formation by suspending the human gastric cancer cell lines MKN45,MGC803 and SGC7901 in serum-free medium containing epidermal growth factor( EGF)and basic fibroblast growth factor( bFGF). The third generation tumor spheres obtained were tested for the ability of colony forming;its stemness markers were identified by immunofluorescent staining,and migration and invasion capabilities were assessed by wound scratch test and Transwell assay,respectively. Growth inhibition of tumor spheres in response to cisplatin was assessed by CCK-8 assay. Results:High expressions of stem cell markers CD44 and CD54 were observed in the tumor spheres,but gastric parietal cell marker H+ /K+-ATPase was lowly expressed. Compared with parental gastric cancer cells,tumor spheres had stronger colony forming ability(P<0. 05);Furthermore,healing of wound scratch was accelerated(P<0. 05),and number of invasive cells in Transwell chamber was increased in tumor spheres(P<0. 05). The 50% inhibition concentration of cisplatin to tumor spheres increased significantly when compared with parental gastric cancer cells. Conclusions:GCSCs enriched tumor spheres can be obtained by suspension culture with serum-free medium. The tumor spheres possess enhanced capabilities of self-renewal,proliferation,migration,invasion and potential of multilineage differentiation;meanwhile,it is more resistant to chemotherapy.

Objective To investigate the diagnostic value of intraductal ultrasonography (IDUS) and bile tumor marker in differential diagnosis of suspected biliary stricture.Methods A total of 57 patients with biliary stricture (8 benign strictures,49 cases of malignant strictures),who underwent IDUS and tests of serum and bile tumor markers (CA19-9 and CEA),were analyzed.The sensitivity,specificity,positive predictive value,negative predictive value and accuracy were compared among the outcomes of B-ultrasonography,CT,MRCP,IDUS,as well as IDUS combined with bile tumor markers.Results The specificity of the IDUS and the combined group were 63.6％ (7/11) and 77.8％ (7/9) respectively (P ＞ 0.05).The positive predictive value of the IDUS and the combined group were 91.8％ (45/49) and 95.9％ (47/49) respectively (P ＞0.05).The diagnostic accuracy of the IDUS and the combined group were 91.2％ (52/57) and 94.7％ (54/57) respectively (P ＞0.05).Data of the two groups were significantly higher than conventional imaging like B-ultrasound,CT and MRCP.The accuracy of IDUS combined with bile CEA for the diagnosis of distal bile duct cancer was 97.9％ (46/47),significantly higher than that of IDUS.Conclusion IDUS combined with biliary tumor markers is of high value for distinguishing the bile benign from malignant stricture.IDUS combined with biliary CEA test can improve the diagnostic accuracy of distal malignant biliary stricture diseases.

Objective To detect the expression of delta-like ligand 4 (DLL4) and its relation with the angiogenesis in pancreatic cancer.Methods SP immunohistochemistry method was used to detect the expression of DLL4 in pancreatic cancer and para-cancerous tissue.The microvessel density (MVD) was calculated with CD34 staining for microvessel endothelium and the correlation between expression of DLL4,MVD and clinicopathological parameters of pancreatic carcinoma was investigated.Results The expression of DLL4 in pancreatic cancer was significantly higher than that in para-cancerous normal pancreatic tissue (68.3％ vs 20％,P ＜0.01 ).The over-expression of DLL4 in pancreatic cancer was positively related to the differentiation degree,TNM staging,metastasis and invasion (P ＜0.05),but not related to the location,tumor size and histological types.The MVD in pancreatic cancer tissues was significantly higher than that in para-cancerous normal tissues (34.9 ± 13.2 vs 18.9 ±2.2,P ＜0.01).MVD was correlated with the differentiation degree,TNM staging,metastasis and invasion (P ＜0.05 ),but not with the tumor size and location,histological types.MVD in pancreatic cancer expressing DLL4 was significantly higher than that in pancreatic cancer not expressing DLL4 ( 38.8± 10.7vs 29.0 ± 15.2,P =0.038 ),and the expression of DLL4 and MVD were positively correlated ( r =0.669,P ＜ 0.05 ).Conclusions DLL4 expression may play an important role in pancreatic carcinogenesis by promoting angiogenesis and may be associated with tumor invasion and metastasis.

Objective To investigate the clinical,pathologic and endoscopic ultrasound characteristics of pancreatic neuroendocrine tumors (PNETs).Methods Clinical data of 24 consecutive patients of PNETs who were admitted between January 2002 and January 2011 were reviewed.Results Among these 24 patients,19 were diagnosed to have insulinomas,1 was malignant insulinoma,2 were gastrinomas,and 2 were glucagonomas.Eighteen (75％) cases of PNETs were functional PNETs,and 6 (25％) were nonfunctional PNETs.The mean age of the patients was (42 ± 14) years old ranging from 19 ～ 64 years old,and the percentage of male patient was 33.3％.The main symptoms of insulinomas were intermittent abdominal pain or discomfort,and the main manifestations of glucagonomas were weight loss,skin migratory erythema; and the main symptoms of gastrinomas were diarrhea,vomiting with large amounts of water-like liquid.The detection rate of CT was 86.7％ (13/15),and the detection rate of EUS was 100％ (15/15),but PET-CT detected only 40％ of tumors (2/5).The endoscopic ultrasound characteristics of PNETs were circular or oval hypoechoic mass,and the volume was small with clear boundary and homogeneous echo.There was no enlarged lymph node,and liquid was detected in big tumor.Twenty-two patients received operation and 2 patients did not.PNETs expressed CgA and Syn protein.All patients of PNETs were alive with 7 to 80 months follow-up.Conclusions The clinical characteristics of PNETs were unique.EUS has a high accuracy for detecting and localizing PNETs.The surgical method is similar to that of pancreatic cancer,and the prognosis is relatively good.