Pancreatic neuroendocrine neoplasm (pNEN)is a kind of rare neoplasms with high heterogeneity.Surgery is the first choice to cure local resectable tumor.However,for patients with local advanced tumor or distant metastasis, medical treatment is the main option. Medical treatment mainly encompasses biotherapy, targeted therapy and chemotherapy.Clinicians should make therapeutic option for patients based on the functional status and somatostatin receptor status of the tumor,tumor grade,tumor stage and drug toxicity profile.

Objective Compared with corresponding monovalent vaccine and pure vaccine vector, live attenuated Salmonella typhimurium expressing bivalent antigens of Helicobacter pylori (H. pylori) , UreB/HpaA was constructed by introducing a flexible and tenacious linker into urease subunit B (UreB) and HpaA of H. pylori and its protection against H. pylori infection in mice was then investigated. Methods UreB/hpaA fusion gene was amplified form H. pylori genomic DNA using sequence overlap extension PCR (SOE-PCR). UreB/HpaA bivalent live vaccine was constructed using attenuated Salmonella typhimurium vaccine vector SL3261, and its stability in vivo was observed in C57BL/6 mice. Evaluation of protection against H. pylori infection was performed in native female C57BL/6 mice by oral immunization with a single dose of the live SL3261 vaccine strain expressing UreB/HpaA (10 8 CFU). Results Sequencing results showed that encoding sequence (GGTGGAGGC) of three glycine residues was inserted into the position between ureB and hpaA fusion gene as an adapter. Bivalent live vaccine strain could be recovered from spleen and Peyer's patches for a longer time (at least 10 days). Bivalent live vaccine induced marked elevation of the levels of serum specific IgG1 and IgG2A in mouse. The immune protection rate of UreB and HpaA bivalent live vaccine was 77.3% (17/22). However only 50.0% (12/24) of the mice immunized with SL3261 vaccine strain expressing UreB and 43.5% (10/23) of the mice immunized with SL3261 vaccine strain expressing HpaA were completely protected against H. pylori challenge. Conclusions Oral immunization of mice with bivalent UreB/HpaA live vaccine could induce protective immunity against H. pylori , and the protection rate of bivalent vaccine appears to be higher than that of monovalent vaccine.

The etiology and pathogenesis of irritable bowel syndrome (IBS) are not fully understood, and intestinal microbiota had been assumed as a possible factor in the pathogenesis of IBS.Increasing evidences have shown that alterations of gut microbiota were found in IBS patients and modulation of intestinal microbiota might be effective in the treatment of IBS.This article reviewed the mechanism of involvement of intestinal microbiota in pathogenesis of IBS by altering mucosal permeability, activating immune reaction, disturbing gastrointestinal motility and affecting brain-gut axis.

Objective To evaluate the diagnostic potential of capsule endoscopies (CE) for suspected small bowel diseases. Methods From September 2002 to June 2003, 23 patients (12 males, 11 females ) , age ranged 10 to 75 years old, with suspected small bowel diseases, were referred to our department to perform CE using Given M2A Video Capsule System. All patients had undergone previous negative endo-scopic evaluation at least once with esophago-gastro-duodenoscopy and total colonoscopy. Additional diagnostic work-up including small bowel enteroclysis, selective angiography, scintigraphy and puch enteroscopy, were performed, totally 36 procedures. Two endoscopists independently reviewed capsule images to arrive a consensus diagnosis. The initial diagnostic yield was quantified, and the value of CE was assessed. Of the 23 patients, 18 suffered from obscure gastrointestinal bleeding, 3 abdominal pain, and 2 chronic diarrhea. Results Twenty-four studies in 23 patients were evaluated. During CE patients have not complained of any uncomfortable feeling, only one patient had repeated the procedure because the capsule lodged at the inferior segment of esophagus near the Z line. Of the 23 patients, 20 had positive findings with a diagnostic yield of 86. 8% . The positive findings included inflammatory lesions in 10 patients (Crohns disease 7 , aphthous ulcer 3 ) , vascular abnormalities 9 ( phlebectasis 6, angioma 2, angiodysplasia 1) , submucosal nodulation 2 , diverticula 2, jejunal stromal tumor 1. Four of 23 patients had more than one lesion. Diagnosis of 6 patients was confirmed by surgery and /or pathology. Nineteen capsules passed in the direction with the camera facing forward, while the other 4 backward. Generally, it delayed in passing through the pylorus and ileocecal valves. Capsules reached cecum in 17 patients (73. 9% ) . Conclusion CE provided clearly the small intestinal images, and is an efficient tool in diagnosing small bowel diseases with a high diagnostic yield.

Objective To investigate the effects of oral recombinant attenuated Salmonella ophimurium urease B subunit and catalase in the treatmeat of H.pylori infection in a H.pylori infected mouse model. Methods Thirty C57BL/6 mice were randomized into three groups and challenged twice by oral administration of H.pylori in three days. Four weeks after the second challenge, the mice were immunized by oral administration of recombinant attenuated Salmonella typhimurium urease B subunit (group A), recombinant attenuated Salmonella typhimurium catalase (group B), or saline (group C) respectively, and all mice were sacrificed 4 weeks after the immunization. The stomachs were collected for rapid urease test, modified Giemsa stain and quantitative culture to observe the gastric H.pylori densities, and HE stain was performed to assess the presence of inflammation. Lymph cells from the spleens were served for lymphoproliferation assay. Results Gastric H.pylori densities of group A, B and C were 1.58?10 5 CFU/g, 4.88?10 5 CFU/g and 1.92?10 6CFU/g respectively. H.pylori densities of therapeutic groups were significantly decreased ( P

Objective To characterize the clinical features and outcome of massive lower gastrointestinal hemorrhage in patients with Crohn's disease.Methods The clinical data form 13 patients Who identified as Crohn's disease accompanied by massive lower gastrointestinal hemorrhage between 1998 and 2007 were retrospectively analyzed.Results The ratio of men to women was 3.3 : 1.Bleeding was the first symptom of disease in foor patients.The lesion was involved in small howel in 10 cases.The origin of bleeding was identified in 8 cases.Four patients received surgical operation and none of them died,while 9 patients received medical treatment and 3 of them died.Totally 10 patients were followed up for 6 to 94 months.Eight patients had recurrent massive hemorrhage,and two of them subsequently required surgery.One patient died after surgery.All patients who had recurrent massive bleeding and still survival were characterized by recurrent bleeding as only or major clinical feature,and they were all with small bowel involvement.Conclusions Diagnostic and therapeutic approach of massive lower gastrointestinal hemorrhage in Crohn's disease is very challenging.It is possible that there exists a particular phenotype of Crohn's disease that presents a tendency of bleeding recurrence,whose bleeding probably related to small bowel lesions.

Objective To analyze the clinical features,clinical prognosis and predictive factors of ulcerative colitis (UC) complicated with cytomegalovirus (CMV) infection.Methods From May 2004 to November 2014,120 hospitalized patients diagnosed as UC and screened for CMV infection were enrolled.A total of 31 patients with moderate to severe UC accompanied by CMV infection were screened out.Demographics,clinical features,endoscopic appearance and treatment of patients with UC complicated with CMV infection were analyzed,and compared with 60 moderate to severe UC patients without CMV infection at the same period of hospitalization.Mann Whitney U test was performed for statistical analysis.Logistic regression analysis was used to analyze risk factors of UC complicated with CMV infection.Results Among 120 patients with UC,29 were mild or in remission period,whose CMV screening tests were all negative.Ninety-one were moderate to severe,31 patients (34.1 ％) of them had CMV infection,and 20 of 31 patients were steroid-refractory.Among the 31 patients with UC complicated with CMV infection,median age was 39 years (22 years,51 years),median disease duration was 24.0 months (6.0 months,42.0 months) which was shorter than that of patients without CMV infection (36.0 months (13.5 months,84.0 months)),and the difference was statistically significant (U=639.5,P=0.015).A total of 23 patients (74.2％) had extensive colitis and 26 patients (83.9％) had history of severe colitis.A total of 29 patients (93.5％) had history of corticosteroids treatment,12 patients (38.7％) had history of immunosuppressive agents treatment,and six patients (19.4 ％) had history of infliximab treatment.Compared with UC patients without CMV infection,fever,abdominal pain and weight loss were more common in UC patients with CMV infection.Five CMV-infected patients had mild liver dysfunction.Endoscopic appearance was longitudinal ulceration,irregular ulceration,large deep ulceration,punchedout ulceration and worm-like ulceration.Among the 25 CMV-infected patients who were treated with corticosteroids,11 patients (44.0％) had no response.Among the 39 CMV-negative patients who were treated with corticosteroids,eight patients (20.5％) had no response.The rate of patients who needed rescue therapy of the former was higher than that of the latter,and the difference was statistically significant (x2 =4.026,P=0.045).The results of multivariate Logistic regression analysis showed that hemoglobin over 100 g/L(OR=0.144,95％ confidence interval (CI) 0.040 to 0.516,P=0.003) was a protective factor of CMV infection,however corticosteroids use within a month before the onset (OR=8.946,95％oCI 2.459 to 32.541,P=0.001) was a risk factor.Conclusions UC patients treated with corticosteroids and immunomodulator therapy may predispose UC patients to CMV infection,on the other hand,CMV infection can exacerbate the severity of UC.CMV infection should be screened and monitored in UC patients,and anti viral therapy should be taken in time in case of CMV infection.

Objective To study the protective immune response induced by Helicobacter pylori (H. pylori) vaccine in mice. Methods Mice were orally immunized with cholera toxin(CT) plus H. pylori whole cell sonicate antigen, CT or normal saline(NS) respectively. Four weeks after immunization mice were challenged with H. pylori. Mice were sacrificed at different time points before and after challenge. Gastric H. pylori colonization, serum anti H. pylori IgG1, IgG2a and IgA antibodies, mRNA expressions of Th1 type cytokines including interferon(IFN) ?, interleukin(IL) 2, IL 12 and Th2 type cytokines including IL 4, IL 6, IL 10 in gastric mucosa and spleen, and gastric inflammation at different time points were all compared in different groups. Results (1) H. pylori colonization in CT plus sonicate antigen group was decreased significantly compared with CT group and NS group both 5 and 26 weeks after challenge. (2)The serum levels of anti H. pylori IgG1, IgG2a and IgA of CT plus sonicate antigen group were significantly higher than those of CT group and NS group at all time points. (3)The mRNA expression levels of Th1 type cytokines in the gastric mucosa of CT plus sonicate antigen group and CT group were higher than that of NS group both before and 5 weeks after H. pylori challenge. 26 weeks after the challenge, Th1 type cytokines in the gastric mucosa of NS group were increased, but those in the gastric mucosa of CT plus sonicate antigen group and CT group were decreased except for IL 12. (4)Before the challenge, Th2 type cytokines were expressed similarly in the gastric mucosae of both CT plus sonicate antigen group and CT group. 5 weeks after the challenge, IL 4 and IL 10 expressions were not detected in CT plus sonicate antigen group and CT group and the expression of IL 6 was lower than that of NS group. 26 weeks after the challenge, both IL 4 and IL 10 expressed again in CT plus sonicate antigen group, but only IL 10 expressed again in CT group. The expressions of IL 6 were similar in all groups. (5) Both Th1 and Th2 type cytokines were expressed in the spleen of all groups at different time points without significant difference. (6) Significant gastritis characterized by marked infiltration of lymphocyte, neutrocyte and mononuclear cells was found in CT plus sonicate antigen group 5 weeks after challenge. In CT group mild inflammation was also found. 26 weeks after the challenge, gastritis in NS group was exacerbated but gastritis in the other two groups was alleviated.Conclusions (1)Vaccine consisting of both H. pylori whole cell sonicate antigen and CT may induce both Th1 and Th2 type immune response at early stage. (2)The increased early Th1 response after H. pylori challenge may contribute to both the protective immunity and post immnization gastritis. Later, the Th2 response after the challenge increases, as Th1 response and post immnization gastritis both abated.

Objective To evaluate the effect of csomeprazole with different dosage and usage regimes on intragastric pH of healthy volunteers. Methods It was a randomized, open-label, three-way crossover study. Fifteen healthy volunteers received esomeprazole with 3 different dosages (20 mg or 40 mg once daily or 20 mg twice daily) with 5 days each. Twenty-four continuous ambulatory intragastric pH was recorded at day 5 of each regime. Results The mean time of intragastric pH above 4 was higher in regime of 20 mg twice daily [(21.16 ±2.45) hours ] than that in regimes of 20 mg once daily [(18. 70±4.19) hours] and 40 mg once daily [(19.27±2.68 ) hours] (P<0.05). The percentages of the sleeping and active period that pH remained above 3,4,5 were significantly higher in regime of 20 mg twice daily(day time:95.0%±7.5% ,92.0%±10.6% ,86.7% ± 14.5% ;night time:93.2%± 13.1% ,87.8%±20.3% ,78.6%±28. 9 % )compared with regimes of 40 mg once daily(day time:87.9%±9.5% ,83.5%±11.7%,75.6%±15.50%, night time:75. 7%±20. 8%,66. 9%±23. 8%,53. 3%±30. 3%) and 20 mg once daily(day time: 85.1 % ± 16.3 %, 81.1 %± 18. 1%, 71.5 % ± 20.3 % ; night time: 72.9 % ± 30.5 %,67.2 % ± 31.9 %, 55.7 % ± 31.8 % ) (P< 0.05 ). Esomeprazole maintained intragastric pH above these pH thresholds for a similar propotion of sleeping and active periods with 40 mg once daily and 20 mg once daily.Conclusions Esomeprazole has strong inhibitory effect on intragastric acid. The regime of 20 mg twice daily is superior to 40 mg once daily and 20 mg once daily in both day and night time acid inhibition.There is no difference between esomeprazole 40 mg once daily and 20 mg once daily.

Objective To evaluate the value of endoscopic profile in an adult population with typical heartburn. Methods Clinical and endoscopic data were collected from 5042 consecutive outpatients who underwent routine upper endoscopy without any alarm features between March 2006 and Feb. 2007. Results Three hundred and thirteen (6.2%) patients were diagnosed as having typical heartburn. Of these, erosive esophagitis (EE) was found in 99 (31.6%) patients, Barrett's esophagus (BE) in 10 (3. 2%) patients, peptic ulcer disease (PUD) in 21 (6. 7%) patients and carcinoma in three (0.9 %) patients (1 with esophageal carcinoma and 2 with gastric adenocarcinoma).Multivariate analysis revealed that age＞50, male, overweight and alcohol use were independent risk factors for positive endoscopy findings (P＜0.05) and EE (P＜0.05) in heartburn patients. Male and Helicobacter pylori infection were independent risk factors for PUD (P＜ 0.05). Conclusions In China, patients with typical heartburn but without alarm features, early endoscopic examination may be helpful in avoiding missing diagnosis of tumor.