Differences in the perceptions of patients with primary biliary cholangitis and physicians from various hospital departments: An online survey.

OBJECTIVES: Primary biliary cholangitis (PBC) is a chronic autoimmune liver disease that affects the quality of life (QoL) of patients. This study aimed to evaluate the differences in perceptions of PBC among physicians from different hospital departments and patients with PBC. METHODS: An online survey regarding the general knowledge, diagnosis, and management of PBC was completed by physicians and patients. RESULTS: A total of 239 patients with PBC and 239 physicians from eight hospital departments (gastroenterology, infectious diseases, rheumatology, hepatobiliary surgery, pathology, clinical laboratory, ultrasound, and radiology) completed the survey. The results showed that physicians from departments other than gastroenterologists and rheumatologists lacked knowledge of PBC, and that junior gastroenterologists were uncertain about the diagnostic and treatment pathways of PBC. Importantly, the lack of knowledge significantly impacted the QoL of patients, especially the emotional scores of PBC-40 (odds ratio -2.556, 95% confidence interval -3.852 to -1.260, P < 0.001). In addition, there was a perceived knowledge gap between patients and gastroenterologists. CONCLUSIONS: Physicians must improve their awareness of PBC. Patient education and patient-physician communication are important for improving the patient's QoL.

Population-specific genome-wide mapping of expression quantitative trait loci in the colon of Han Chinese.

OBJECTIVE: To establish the colonic expression quantitative trait locus map in Han Chinese population and provide a functional reference for interpreting genetic associations of diseases such as inflammatory bowel disease (IBD). METHODS: Colonic mucosal biopsies and peripheral blood samples were obtained from 48 Chinese Han individuals (24 ulcerative colitis patients and 24 healthy controls). Transcription profiling was performed using human whole genome expression array. Genotyping was done using a population-specific genotype array. Imputation was performed using IMPUTE2. Association between genotypes and gene expression was analyzed using a Matrix Expression Quantitative Trait Loci (eQTL) R package to identify eQTL. We used ChIPpeakAnno R package for annotation of the eQTL. Linkage disequilibrium between the eQTL and IBD risk loci was also investigated. RESULTS: We identified 6 377 single nucleotide polymorphism-transcript interactions (cis-eQTL) in the colon of the Chinese participants. Most of the eQTL located near the transcription starting sites and overlapped with histone modification marks on the genome. A significant proportion of the eQTL were found to be within transcription factor-binding sites. Two IBD risk loci were found to be colon cis-eQTL in Chinese individuals, and 51 cis-eQTL were identified in another 18 IBD risk loci. CONCLUSIONS: This study defined a population-specific catalogue of colon eQTL in the Chinese population. Potential functional variants of IBD association signals were identified. We provided a useful reference dataset for fine mapping IBD risk loci and identifying causal variants in the Chinese Han population.

Screening of specific binding peptide targeting blood vessel of human esophageal cancer in vivo in mice.

BACKGROUND: Cancer of the esophagus and gastroesophageal junction remains a virulent malignancy with poor prognosis. Rapid progresses were made in chemotherapeutic agents and the development of molecular markers allowed better identification of candidates for targeted therapy. This study aimed to identify the candidate peptides used for anti-angiogenic therapy of esophageal cancer by in vivo screening C7C peptide library for peptides binding specifically to blood vessels of human esophageal cancer. METHODS: The phage displayed C7C peptide library was injected intravenously into mice bearing human esophageal tumor xenografts under renal capsule. After 5 rounds of screening, 13 clones were picked up individually and sequenced. During each round of screening, titers of phage recovery were calculated from tumor xenograft and control tissues. Homing of these 9 peptides to tumor vessel was detected by calculating phage titers in the tumor xenograft and control tissues (lung and spleen) after each phage was injected into mice model, and compared with the distribution of phage M13 and VIII-related antigen in tumor xenograft by immunohistochemical staining. Comparisons among groups of data were made using one-way analysis of variance (ANOVA), followed by the Bonferroni multiple comparisons test. RESULTS: The number of phage recovered from tumor tissue of each round increased gradually in tumor group while decreased in control groups (P < 0.01 in tumor and spleen, P < 0.05 in lung). Immunohistochemical staining showed similar staining pattern with M13 antibody or VIII-related antigen antibody, suggesting that phages displaying the selected peptides could home to blood vessel of human esophageal cancer. According to their DNA, 9 corresponding peptide sequences were deduced. And the homing ability to blood vessel of phages displaying the selected peptides was confirmed by comparing with their recovery in tumor and control tissues. Two motifs, YSXNXW and PXNXXN, were also obtained by analyzing the homology of these peptide sequences. The staining distribution of phage with the sequence of PNPNNST was similar to that of the blood vessel marker factor VIII-related antigen staining. After sequencing, each phage with the selected peptide of PNPNNST with 1.0 × 10(11) pfu/ml was injected intravenously into mice. The homing ability to tumor vessel of these 9 kinds of peptides in the xenograft was higher than control tissues (lung and spleen). CONCLUSION: Nine peptides obtained from in vivo screening homed to the blood vessel of human esophageal cancer, and the two motifs of YSXNXW and PXNXXN are the possible biochemical recognition units binding to vascular endothelial cells of esophageal cancer.

OCTN and CARD15 gene polymorphism in Chinese patients with inflammatory bowel disease.

AIM: To investigate the single nucleotide polymorphism (SNPs) distribution of NOD2/CARD15 (R702W, G908R), OCTN1 1672C/T and OCTN2-207G/C in Chinese patients with inflammatory bowel disease (IBD). METHODS: A total of 61 patients with Crohn's disease (CD), 151 patients with ulcerative colitis (UC), and 200 unrelated healthy controls were genotyped. Genotyping was performed by sequence specific primer polymerase chain reaction (PCR-SSP) or by restriction fragment length polymorphism (PCR-RFLP) analysis. RESULTS: Among the subjects in our study groups, including patients with CD, UC and healthy controls, none had OCTN and CARD15 variants and very rare IBD family history was found in our patients with the percentage of 0 (0/61 with CD) and 1.3% (2/151 with UC). CONCLUSION: Our results indicate that although OCTN or CARD15 variation is associated with susceptibility to IBD in Western populations, these might be rare and may not be associated with susceptibility to IBD in Chinese patients.

Oral attenuated Salmonella typhimurium vaccine against MG7-Ag mimotope of gastric cancer.

AIM: To develop an oral attenuated Salmonella typhimurium vaccine against gastric cancer and to evaluate its efficacy in mice. METHODS: A complementary sequence of Nco I site and a sequence coding for MG7-Ag mimotope were designed at the 5' terminus of forward primer. Using p1.2 II-HBCAg plasmid as template, PCR was performed to get a fusion gene of the mimotope and a HBcAg gene. The fusion gene was then subcloned into the plasmid pYA3341 complementary to Salmonella typhimurium X4550, and the recombinant plasmid was then transformed into attenuated Salmonella typhimurium X4550. Balb/c mice were orally immunized with the recombinant Salmonella typhimurium X4550. The mice were immunized every 2 wk to reinforce the immunity. At the 6th wk, serum titer of antibody was detected by ELISA, and at the 8th wk, cellular immunity was detected by (51)Cr release test. Ehrlich ascites carcinoma cells expressing MG7-Ag were used in tumor challenge assay as a model to evaluate the protective effect of the vaccine. RESULTS: Serum titer of antibody against MG7-Ag was significantly higher in mice immunized with the vaccine than in control groups (0.9538+/-0.043 vs 0.6531+/-0.018, P<0.01; 0.9538+/-0.043 vs 0.6915+/-0.012, P<0.01), while in vitro (51)Cr release assay of the splenocytes showed no statistical difference in the three groups. Two weeks after tumor challenge, 1 in 5 immunized mice was tumor free, while all the mice in the control group presented tumor. CONCLUSION: Oral attenuated Salmonella typhimurium vaccine against the MG7-Ag mimotope of gastric cancer is immunogenic. It can induce significant humoral immunity against tumors in mice, and has some protective effects.

[Expression and significance of DARPP-32 in gastric carcinoma].

OBJECTIVE: To investigate the significance of DARPP-32 protein expression in gastric carcinoma tissue and cell lines. METHODS: The expression of DARPP-32 protein in normal gastric mucosa and gastric carcinoma tissue was evaluated by immunohistochemical staining using streptavidin-biotin complex technique. The expression in gastric carcinoma tissue and cell lines was evaluated by Western blotting. RESULTS: The expression rate of DARPP-32 protein in gastric adenocarcinoma tissue (92.7%) was significantly higher than that in normal gastric mucosa (52.6%, P < 0.05). There was no significant association between DARPP-32 protein expression and degree of tumor differentiation, local invasion and distant metastasis. As compared with adjacent non-carcinomatous gastric mucosa, both DARPP-32 and its truncated isoform t-DARPP were overexpressed in gastric adenocarcinoma tissue (t = 2.45, P = 0.015); and t-DARPP overexpression was more frequently seen. Expression of DARPP-32 and t-DARPP could also be detected in human gastric cancer cell lines. The expression of DARPP-32 protein was obviously reduced in SGC7901 drug-resistant cell strains. CONCLUSIONS: DARPP-32 is overexpressed in gastric carcinoma. It may play an important role in gastric carcinogenesis. The underlying signal pathways in neoplastic gastric epithelium may also be related to the multi-drug resistance property of gastric cancer cells.

Development of an oral DNA vaccine against MG7-Ag of gastric cancer using attenuated salmonella typhimurium as carrier.

AIM: To develop an oral DNA vaccine against gastric cancer and evaluate its efficacy in mice. METHODS: The genes of the MG7-Ag mimotope and a universal Th epitope (Pan-DR epitope, PADRE) were included in the PCR primers. By PCR, the fusion gene of the two epitopes was amplified. The fusion gene was confirmed by sequencing and was then cloned into pcDNA3.1(+) plasmid. The pcDNA3.1 (+)-MG7/PADRE was used to transfect an attenuated Salmonella typhimurium. C57BL/6 mice were orally immunized with 1X10(8) cfu Salmonella transfectants. Salmonella harboring the empty pcDNA3.1(+) plasmid and phosphate buffer saline (PBS) were used as negative controls. At the 6th week, serum titer of MG7-Ag specific antibody was detected by ELISA. At the 8th week cellular immunity was detected by an unprimed proliferation test of the spleenocytes by using a ((3)H)-thymidine incorporation assay. Ehrlich ascites carcinoma cells expressing MG7-Ag were used as a model in tumor challenge assay to evaluate the protective effect of the vaccine. RESULTS: Serum titer of antibody against MG7-Ag was significantly higher in mice immunized with the vaccine than that in control groups (0.841 vs 0.347, P<0.01; 0.841 vs 0.298, P<0.01), while in vitro unprimed proliferation assay of the spleenocytes showed no statistical difference between those three groups. Two weeks after tumor challenge, 2 in 7 immunized mice were tumor free, while all the mice in the control groups showed tumor formation. CONCLUSION: Oral DNA vaccine against the MG7-Ag momitope of gastric cancer is immunogenic. It can induce significant humoral immunity against tumor in mice, and the vaccine has partially protective effects.

Postoperative endoscopic surveillance of human living-donor small bowel transplantations.

AIM: To determine the significance of endoscopic surveillance in the diagnosis of acute rejection after human living-donor small bowel transplantations. METHODS: Endoscopic surveillance was performed through the ileostomy after human living-donor small bowel transplantations. The intestinal mucosa was observed and biopsies were performed for pathological observations. RESULTS: Acute rejection was diagnosed in time by endoscopic surveillance. The endoscopic and pathological manifestations of acute rejection were described. CONCLUSION: Endoscopic surveillance and biopsy are reliable methods to diagnose the acute rejection after human living-donor small bowel transplantations.