Multispecies probiotics complex improves bile acids and gut microbiota metabolism status in an in vitro fermentation model.

The consumption of probiotics has been extensively employed for the management or prevention of gastrointestinal disorders by modifying the gut microbiota and changing metabolites. Nevertheless, the probiotic-mediated regulation of host metabolism through the metabolism of bile acids (BAs) remains inadequately comprehended. The gut-liver axis has received more attention in recent years due to its association with BA metabolism. The objective of this research was to examine the changes in BAs and gut microbiota using an in vitro fermentation model. The metabolism and regulation of gut microbiota by commercial probiotics complex containing various species such as Lactobacillus, Bifidobacterium, and Streptococcus were investigated. The findings indicated that the probiotic strains had produced diverse metabolic profiles of BAs. The probiotics mixture demonstrated the greatest capacity for Bile salt hydrolase (BSH) deconjugation and 7α-dehydroxylation, leading to a significant elevation in the concentrations of Chenodeoxycholic acid, Deoxycholic acidcholic acid, and hyocholic acid in humans. In addition, the probiotic mixtures have the potential to regulate the microbiome of the human intestines, resulting in a reduction of isobutyric acid, isovaleric acid, hydrogen sulfide, and ammonia. The probiotics complex intervention group showed a significant increase in the quantities of Lactobacillus and Bifidobacterium strains, in comparison to the control group. Hence, the use of probiotics complex to alter gut bacteria and enhance the conversion of BAs could be a promising approach to mitigate metabolic disorders in individuals.

Association between Helicobacter pylori infection and growth outcomes in children: A meta-analysis.

BACKGROUND: Multiple studies have reported the association between Helicobacter pylori (H. pylori) infection and children's growth. The results of these studies are controversial. Our meta-analysis aimed to evaluate the association between H. pylori infection and growth outcomes in children. METHODS: We searched PubMed, Embase, Web of Science, and Cochrane Library, as well as two Chinese databases, Wanfang, and CNKI from inception to September 2019. Odds ratios (ORs) and standardized mean differences (SMDs) with their 95% confidence interval (95% CI) were selected as the effect size. We assessed pooled data using a random-effects model. Subgroup and sensitivity analyses were conducted. RESULTS: In total, 29 studies provided data from 9384 subjects. The meta-analysis results indicated a significant association of H. pylori infection with ponderal growth disorders (OR: 2.47; 95% CI: 1.13, 5.37; p = 0.02) and linear growth disorders (OR =1.76; 95% CI: 1.15, 2.69, p = 0.01). H. pylori infection has an adverse impact on children's height-for-age Z (HAZ) scores (SMD = -0.41; 95% CI: -0.69, -0.13; p < 0.01). Pooling SMDs by other outcomes (height, weight, BMI, weight-for-age and BMI-for-age Z scores, weight-for-age percentile scores, and linear and ponderal growth velocity with/without infection and eradication/non-eradication) all indicated no significant association. CONCLUSION: The current evidence supports the hypothesis that H. pylori infection is associated with growth outcomes in children, mainly HAZ scores. Clinicians might consider H. pylori infection in investigating linear growth disorders in children.

Histopathological Characteristics and Therapeutic Outcomes of Endoscopic Submucosal Dissection for Gastric High-Grade Intraepithelial Neoplasia.

Background: The endoscopic resection of suspected gastric high-grade intraepithelial neoplasia (HGIN) may incidentally cause the patient to suffer from early gastric cancer (EGC), complicating the subsequent clinical management. Identifying the risk factors for such misstaging may help guide the clinical management. Methods: The information obtained from 123,460 patients, who underwent conventional upper gastrointestinal endoscopy at the First Affiliated Hospital of Nanjing Medical University from January 2010 to December 2015, were retrospectively reviewed. Patients with an initial diagnosis of HGIN underwent endoscopic submucosal dissection (ESD), and received a final diagnosis of EGC. The risk factors for the upgraded pathology and noncurative resection were analyzed. Results: Among the 134 patients initially diagnosed with HGIN, 35 (26.12%) patients were finally diagnosed with EGC after ESD. A lesion size of ≥2 cm (odds ratio [OR] = 5.16, 95% confidence interval [CI] = 2.04-13.05; P < .01), ≤4 biopsies taken (OR = 2.73, 95% CI = 1.15-6.48; P < .05), and the presence of upper gastrointestinal bleeding (UGIB; OR = 15.64, 95% CI = 1.29-189.75; P < .05) were the independent risk factors for upgraded pathology. In addition, patients >65 years old (OR = 0.022, 95% CI = 0.901-6.549; P < .05) or with a lesion size of ≥2 cm (OR = 4.237, 95% CI = 1.650-10.878; P < .01) were more likely to endure the noncurative resection. Conclusion: For suspected gastric HGIN patients, age, lesion size, the number of biopsies, and UGIB should be taken into account before deciding on the ESD.

New genotypes of Helicobacter Pylori VacA d-region identified from global strains.

BACKGROUND: Pathogenesis of Helicobacter Pylori (HP) vacuolating toxin A (vacA) depends on polymorphic diversity within the signal (s), middle (m), intermediate (i), deletion (d) and c-regions. These regions show distinct allelic diversity. The s-region, m-region and the c-region (a 15 bp deletion at the 3'-end region of the p55 domain of the vacA gene) exist as 2 types (s1, s2, m1, m2, c1 and c2), while the i-region has 3 allelic types (i1, i2 and i3). The locus of d-region of the vacA gene has also been classified into 2 genotypes, namely d1 and d2. We investigated the "d-region"/"loop region" through bioinformatics, to predict its properties and relation to disease. One thousand two hundred fifty-nine strains from the NCBI nucleotide database and the dryad database with complete vacA sequences were included in the study. The sequences were aligned using BioEdit and analyzed using Lasergene and BLAST. The secondary structure and physicochemical properties of the region were predicted using PredictProtein. RESULTS: We identified 31 highly polymorphic genotypes in the "d-region", with a mean length of 34 amino acids (9 ~ 55 amino acids). We further classified the 31 genotypes into 3 main types, namely K-type (strains starting with the KDKP motif in the "d-region"), Q-type (strains starting with the KNQT motif), and E-type (strains starting with the ESKT motif) respectively. The most common type, K-type, is more prevalent in cancer patients (80.87%) and is associated with the s1i1m1c1 genotypes (P < .01). Incidentally, a new region expressing sequence diversity (2 aa deletion) at the C-terminus of the p55 domain of vacA was identified during bioinformatics analysis. CONCLUSIONS: Prediction of secondary structures shows that the "d-region" adopts a loop conformation and is a disordered region.

Virulence of Helicobacter pylori outer membrane proteins: an updated review.

Helicobacter pylori (H. pylori) infection is associated with some gastric diseases, such as gastritis, peptic ulcer, and gastric cancer. CagA and VacA are known virulence factors of H. pylori, which play a vital role in severe clinical outcomes. Additionally, the expression of outer membrane proteins (OMPs) helps H. pylori attach to gastric epithelial cells at the primary stage and increases the virulence of H. pylori. In this review, we have summarized the paralogs of H. pylori OMPs, their genomic loci, and the different receptors of OMPs identified so far. We focused on five OMPs, BabA (HopS), SabA (HopP), OipA (HopH), HopQ, and HopZ, and one family of OMPs: Hom. We highlight the coexpression of OMPs with other virulence factors and their relationship with clinical outcomes. In conclusion, OMPs are closely related to the pathogenic processes of adhesion, colonization, persistent infection, and severe clinical consequences. They are potential targets for the prevention and treatment of H. pylori-related diseases.

Endoscopic and Histopathology Characteristics in Patients with Esophageal High-Grade Intraepithelial Neoplasia.

BACKGROUND/AIMS: To correlate the endoscopic characteristics with the histopathology of specimens of esophageal high-grade intraepithelial neoplasia obtained by endoscopic submucosal dissection (ESD). METHODS: This was a retrospective study developed from January 2010 to December 2015. The study included 169 patients who underwent ESD and were diagnosed with esophageal high-grade intraepithelial neoplasia according to endoscopic forceps biopsy, Lugol staining, endoscopic ultrasonography, computed tomography, and Narrow-Band Imaging. The demographic, endoscopic, and histopathologic characteristics were analyzed. RESULTS: A total of 19 cases (11.2%) had a change in diagnosis after histopathology exam and 16 (9.5%) needed a change in established treatment. An increase in the severity of disease was correlated with a lesion size > 2 cm, less than 4 samples in biopsy, and depressed or excavated patterns (p < 0.05). One hundred forty patients (82.8%) underwent curative resection. Lesions with leukoplakia (p < 0.001) and negative Lugol staining (p = 0.028) were independent risk factor for non-curative resection. CONCLUSION: This study confirms that lesion size > 2 cm, depressed and excavated patterns, and ≤4 biopsy samples are independent risk factors for histological grade changes compared to pre-endoscopic treatment diagnosis. Similarly, leukoplakia and no Lugol staining of lesions are independent risk factors for non-curative resection.

Hiwi overexpression does not affect proliferation, migration or apoptosis of liver cancer cells in vitro or in vivo.

Piwi like RNA-mediated gene silencing 1 (Hiwi) is a human homolog of the Piwi gene family that has been reported to be upregulated in hepatocellular carcinoma (HCC). The present study aimed to investigate the role of Hiwi in the initiation and development of HCC in vitro and in vivo. Adenovirus-mediated Hiwi overexpression was established in primary murine hepatocytes and SMMC7721 HCC cells. Cell viability and proliferation were assessed using MTT and EdU assays, respectively. Cell migration was measured using a scratch migration assay. The cell cycle was assessed using flow cytometry, and the expression of genes associated with the epithelial mesenchymal transition (EMT) was assessed using reverse transcription-quantitative polymerase chain reaction. SMMC7721 cells that stably express Hiwi were also generated and injected subcutaneously into the nude mice, and tumor growth was examined. Recombinant adenovirus encoding green fluorescent protein or Hiwi was delivered by injection into the tail vein, and its effect on murine hepatocyte gene expression was studied. The present study revealed that the overexpression of Hiwi did not affect the proliferation or migration of liver cancer cells and failed to suppress perifosine- or doxorubicin-induced apoptosis in vitro. The tumors of mice that were injected with Hiwi-expressing SMMC7721 cells were not significantly larger compared with mice that were injected with control SMMC7721 cells. Hiwi overexpression did not noticeably alter the expression of genes involved in EMT, either in vitro or in vivo. The results of the present study indicate that although expression of Hiwi is associated with HCC development and progression in the clinic, it does not act as an oncogene in liver cancer cells.

Effect of Xiaochuanping powder on the inflammatory response and airway remodeling in asthmatic rats.

OBJECTIVE: To observe the effect of Xiaochuanping powder (XP), a traditional Chinese prescription for the treatment of cough and asthma, on serum concentrations of eosinophil cationic protein (ECP), αtumor necrosis factor (TNF)-α;, and interleukin (IL)-4, eosinophil counts, as well as expression of matrix metalloproteinase (MMP)-9, tissue inhibitor of metalloproteinase (TIMP)-1 in the lung tissues of asthmatic rats. METHODS: Sixty clean-grade Sprague-Dawley rats were divided randomly into six groups: normal control (NC), asthma model, Guilong Kechuanning (GK) group, as well as high-, intermediate-, and low- dose XP groups. Rats were sensitized with ovalbumin (OVA) to trigger asthma. Serum concentrations of ECP, TNF-α; and IL-4, eosinophil counts, as well as expression of MMP-9 and TIMP-1 in lung tissues were evaluated using an immunofluorescence method. mRNA expression of MMP-9 and TIMP-1 was determined using real-time quantitative polymerase chain reaction. RESULTS: Compared with the asthma-model group, serum concentrations of ECP, TNF-α, and IL-4, and eosinophil counts decreased significantly in the high- and intermediate-dose XP groups and GK group (all P < 0.01). Protein expression of MMP-9 and TIMP-1 decreased significantly in the high- and intermediate-dose XP groups and GK group (all P < 0.01). Transcription of MMP-9 and TIMP-1 mRNA and the ratio of expression of MMP-9: TIMP-1 in lung tissue were significantly lower (P < 0.01). CONCLUSION: XP can reduce TNF-α secretion, suppress the infiltration / activation of eosinophils, reduce serum concentrations of ECP and IL-4, reduce the protein and mRNA expression of MMP-9 and TIMP-1 in lung tissue, and regulate the balance between expression of MMP-9 and TIMP-1. In these ways, XP alleviated the inflammation and remodeling of the airways.

Manometric Measurement of the Sphincter of Oddi in Patients with Common Bile Duct Stones: A Consecutive Study of the Han Population of China.

Objective. Role of dysfunction of the sphincter of Oddi (SO) in choledocholithiasis is controversial. This study was to evaluate SO motor activity in patients with common bile duct (CBD) stones in the Han population of China. Patients and Methods. In this study, 76 patients with CBD stones were enrolled in a single tertiary endoscopy center. Data of SO motor activities was prospectively evaluated by endoscopic manometry. Mean basal SO pressure, amplitude, and frequency were collected and analyzed. Results. The mean basal SO pressure, amplitude, and frequency were 52.7 ± 40.0 (1.60-171.1) mmHg, 39.9 ± 19.7 (14.9-115.5) mmHg, and 5.7 ± 3.2 (1.3-13.8)/min, respectively. The basal SO pressure was higher in patients with CBD stones < 10 mm in diameter than that in those with CBD stones larger than 10 mm in diameter (60.7 ± 41.0 mmHg versus 36.8 ± 29.4 mmHg, P = 0.043). There was no significant difference in the basal SO pressure, amplitude, and frequency when compared with the CBD diameter, CBD stone number, prior cholecystectomy, periampullary diverticula, and symptoms. Levels of alanine aminotransferase, aspartate transaminase, γ-glutamyl transpeptidase, and alkaline phosphatase showed no significant difference in patients with normal or elevated basal SO pressure. Conclusion. These results identify that, in Chinese Han population, abnormalities of SO motor activity are associated with CBD stones.

Risk factors for intestinal metaplasia in a southeastern Chinese population: an analysis of 28,745 cases.

PURPOSE: To identify risk factors for intestinal metaplasia in a southeastern Chinese population. METHODS: Subjects who underwent upper GI endoscopy and endoscopic biopsy in the First Affiliated Hospital of Nanjing Medical University from 2008 to 2013 were included into this study. Various demographic, geographic, clinical and pathological data were analyzed separately to identify risk factors for intestinal metaplasia. RESULTS: The incidence of intestinal metaplasia differed significantly in 17 municipal areas ranging from 16.79 to 38.56% and was positively correlated with the age range of 40-70 years, male gender, gastric ulcer, bile reflux, Helicobacter pylori infection, atrophic gastritis, dysplasia, gastric cancer, degree of chronic and acute inflammation, and gross domestic product per capita (P < 0.01). Multivariate linear regression analysis indicated that only gross domestic product per capita revealed a significant difference in the incidence of intestinal metaplasia among all factors mentioned. CONCLUSION: This study confirms age, male gender, gastric ulcer, bile reflux, H. pylori infection, severe degree of chronic and acute inflammation to be the risk factors for intestinal metaplasia. We speculate that the gross domestic product per capita of different areas may be a potential independent risk factor impacting the incidence of intestinal metaplasia.

Downward trend in the prevalence of Helicobacter pylori infections and corresponding frequent upper gastrointestinal diseases profile changes in Southeastern China between 2003 and 2012.

This present study aims to determine trends in the prevalence of H. pylori infections in Southeastern China between 2003 and 2012, and investigate corresponding changes in the prevalence of upper gastrointestinal diseases. This retrospective study screened 196,442 patients with a mean age of 47.49 ± 14.47 years (age range 5-100 years) in Southeastern China, and a total of 134,812 cases of an endoscopy-referral patient population with digestive symptoms between 2003 and 2012 were enrolled. Based on esophago-gastro-duodenoscopy and pathology, patients diagnosed with chronic gastritis, peptic ulcer, gastric cancer or reflux esophagitis were included in this study. Basic demographic and clinical characteristics such as H. pylori infection status and endoscopic findings were collected and analyzed. Among the 134,812 subjects, mean prevalence of H. pylori infection was 31.97 %; which demonstrated a linear downward trend from 42.40 to 23.82 % (P < 0.001) at an annual rate of 2 % from 2003 to 2012. Similarly, the prevalence of duodenal and gastric ulcer rapidly decreased from 12.65 to 6.57 % and from 7.51 to 3.78 %, respectively; while the prevalence of gastric cancer (from 3.76 to 2.34 %) did not significantly change in the same time period. In contrast, the prevalence of reflux esophagitis increased from 6.19 to 12.80 %. The progressively decreasing prevalence of H. pylori infections from 2003 to 2012 in Southeastern China appears to be linked with the decline of related upper gastrointestinal diseases and increase of some gastrointestinal motility diseases.

Anatomical predilection of intestinal metaplasia based on 78,335 endoscopic cases.

BACKGROUND/AIMS: Gastric intestinal metaplasia (IM) is an important risk factor for intestinal-type gastric carcinoma, and successful treatment critically depends on its timely detection. In order to guide appropriate endoscopic surveillance, objective knowledge on the anatomical predilection of intestinal metaplasia development is urgently needed. MATERIALS AND METHODS: A total of 78,335 cases who underwent gastroduodenoscopy from 2008 to 2013 in Jiangsu and Anhui provinces in China, were studied. Demographic and clinical characteristics, as well as biopsy location and histological results, were analyzed. RESULTS: This study revealed that intestinal metaplasia incidence was 28.5% in angulus, 20.24% in lesser curvature of the antrum, and 25.48% in corpus; and all these were significantly higher than those observed in other sites (P < 0.01). Histological grading of intestinal metaplasia in the lesser curvature of the antrum and angulus was generally worse than the grading observed in the greater curvature of the antrum. For Helicobacter pylori-positive patients, acute inflammation was more severe in the lesser curvature of the antrum compared with the greater curvature. In the H. Pylori-negative group, both acute and chronic inflammations were more severe in the lesser curvature of the antrum. CONCLUSIONS: The angulus, lesser curvature in the antrum, and corpus are most prone to the development of intestinal metaplasia. Inflammation is most severe in the lesser curvature of the antrum, which corresponds to a higher predilection to develop intestinal metaplasia at this site. The lesser curvature of the antrum and corpus require the most attention during endoscopic biopsy surveillance.

Risk assessment of gastric cancer caused by Helicobacter pylori using CagA sequence markers.

BACKGROUND: As a marker of Helicobacter pylori, Cytotoxin-associated gene A (cagA) has been revealed to be the major virulence factor causing gastroduodenal diseases. However, the molecular mechanisms that underlie the development of different gastroduodenal diseases caused by cagA-positive H. pylori infection remain unknown. Current studies are limited to the evaluation of the correlation between diseases and the number of Glu-Pro-Ile-Tyr-Ala (EPIYA) motifs in the CagA strain. To further understand the relationship between CagA sequence and its virulence to gastric cancer, we proposed a systematic entropy-based approach to identify the cancer-related residues in the intervening regions of CagA and employed a supervised machine learning method for cancer and non-cancer cases classification. METHODOLOGY: An entropy-based calculation was used to detect key residues of CagA intervening sequences as the gastric cancer biomarker. For each residue, both combinatorial entropy and background entropy were calculated, and the entropy difference was used as the criterion for feature residue selection. The feature values were then fed into Support Vector Machines (SVM) with the Radial Basis Function (RBF) kernel, and two parameters were tuned to obtain the optimal F value by using grid search. Two other popular sequence classification methods, the BLAST and HMMER, were also applied to the same data for comparison. CONCLUSION: Our method achieved 76% and 71% classification accuracy for Western and East Asian subtypes, respectively, which performed significantly better than BLAST and HMMER. This research indicates that small variations of amino acids in those important residues might lead to the virulence variance of CagA strains resulting in different gastroduodenal diseases. This study provides not only a useful tool to predict the correlation between the novel CagA strain and diseases, but also a general new framework for detecting biological sequence biomarkers in population studies.

Comparison of endoscopic papillary large balloon dilation and endoscopic sphincterotomy for retrieval of choledocholithiasis: a meta-analysis of randomized controlled trials.

BACKGROUND: Endoscopic sphincterotomy (EST) is the most frequently used technique for removal of stones from the bile duct. In recent years, endoscopic papillary large balloon dilation (EPLBD) has been shown to be a safe and effective technique for the removal of large or difficult common bile duct stones. However, comparison of EPLBD and EST for effectiveness in bile duct stone removal has given inconsistent results. The present meta-analysis was carried out to compare the effect of EPLBD and EST in retrieval of choledocholithiasis. METHODS: A literature search was performed using Medline, PubMed, EMBase and the Cochrane Central Register of Controlled Trials (CENTRAL) for relevant articles published in English. A meta-analysis was performed on the retrieved studies. RESULTS: Seven randomized controlled trials and 790 patients were involved. EPLBD compared with EST resulted in similar outcomes for overall successful clearance rates of bile duct stones (97.35 vs. 96.35%, OR 1.28, 95% CI 0.58-2.82, P = 0.54), stone clearance in the first ERCP session (87.87 vs. 84.15%, OR 1.31, 95% CI 0.81-2.11, P = 0.21) and removal of large sized stones (OR 1.08, 95% CI 0.21-5.64, P = 0.49). EPLBD performed with either a short or a long ballooning time did not increase the bile duct stone clearance rate. EPLBD decreased overall usage of mechanical lithotripsy in the bile duct stone removal process (OR 0.51, 95% CI 0.30-0.86, P = 0.01). However, no significant difference was found between EPLBD and EST in the use of mechanical lithotripsy for the removal of large sized stones (OR 0.67, 95% CI 0.34-1.28, P = 0.22). Compared with EST, EPLBD did not show a short ERCP duration (WMD -0.75, 95% CI -1.57 to 0.08, P = 0.08). EPLBD was associated with fewer overall complications than EST (5.8 vs. 13.1%, OR 0.41, 95% CI 0.24-0.68, P = 0.0007). Hemorrhage occurred less frequently with EPLBD than with EST (OR 0.15, 95% CI 0.04-0.50, P = 0.002). There was no significant difference in post-ERCP pancreatitis, perforation and cholangitis. CONCLUSIONS: EPLBD is an effective and safe method for the removal of large or difficult common bile stones. EPLBD should be considered as an alternative to EST for patients in whom EST could not be routinely performed. Based on EPLBD causing fewer cases of hemorrhaging, EPLBD is also recommended for removal of large or difficult common bile duct stones in patients with an underlying coagulopathy or need for anticoagulation following ERCP. The long-term prognosis of EPLBD need to be further investigated.

[Prevention of restenosis with a new modified fully-covered retrievable esophageal stent].

OBJECTIVE: To observe and evaluate the effectiveness of a new modified fully-covered retrievable esophageal stent in preventing restenosis at the proximal end of the stent. METHODS: From January 2008 to October 2011, 380 consecutive patients who underwent placement of a conventional stent or a new modified stent for benign or malignant dysphagia were divided into two groups: conventional stent group 193 patients (male 137, female 56) and modified stent group 187 patients (male 125, female 62). The granulation formation and restenosis rate one month after stenting were evaluated. Data such as patient demographics, outcomes and complications were collected. The results were statistically analyzed by Student t test, chi-squared test, Fisher's exact probability or rank sum test. A P-value less than 0.05 was considered statistically significant. RESULTS: All stents were successfully implanted. They were highly effective in palliating dysphagia. The dysphagia score decreased from 3 (1) to 0 (1) in conventional stent group (P < 0.01), and that from 4 (1) to 0 (1) in modified stent group (P < 0.01). The modified stent group were superior to the conventional stent group in severe granulation formation rate (0 vs 4.7% (9/193), P = 0.004) and restenosis rate (2.7% (5/187) vs 7.3% (14/193), P = 0.041) within one month after stenting, and the modified stent was easier to retrieve. Postoperative remission rate of dysphagia, and complications such as chest pain, bleeding, perforation, stent migration had no statistical differences between the two groups (all P > 0.05). CONCLUSIONS: The new modified fully-covered retrievable esophageal stent can significantly reduce granulation formation at the proximal end of the stent. Using of this stent seems to be a better choice in treating patient of dysphagia, with lower restenosis rate and easier to retrieve.

Effector prediction in host-pathogen interaction based on a Markov model of a ubiquitous EPIYA motif.

BACKGROUND: Effector secretion is a common strategy of pathogen in mediating host-pathogen interaction. Eight EPIYA-motif containing effectors have recently been discovered in six pathogens. Once these effectors enter host cells through type III/IV secretion systems (T3SS/T4SS), tyrosine in the EPIYA motif is phosphorylated, which triggers effectors binding other proteins to manipulate host-cell functions. The objectives of this study are to evaluate the distribution pattern of EPIYA motif in broad biological species, to predict potential effectors with EPIYA motif, and to suggest roles and biological functions of potential effectors in host-pathogen interactions. RESULTS: A hidden Markov model (HMM) of five amino acids was built for the EPIYA-motif based on the eight known effectors. Using this HMM to search the non-redundant protein database containing 9,216,047 sequences, we obtained 107,231 sequences with at least one EPIYA motif occurrence and 3115 sequences with multiple repeats of the EPIYA motif. Although the EPIYA motif exists among broad species, it is significantly over-represented in some particular groups of species. For those proteins containing at least four copies of EPIYA motif, most of them are from intracellular bacteria, extracellular bacteria with T3SS or T4SS or intracellular protozoan parasites. By combining the EPIYA motif and the adjacent SH2 binding motifs (KK, R4, Tarp and Tir), we built HMMs of nine amino acids and predicted many potential effectors in bacteria and protista by the HMMs. Some potential effectors for pathogens (such as Lawsonia intracellularis, Plasmodium falciparum and Leishmania major) are suggested. CONCLUSIONS: Our study indicates that the EPIYA motif may be a ubiquitous functional site for effectors that play an important pathogenicity role in mediating host-pathogen interactions. We suggest that some intracellular protozoan parasites could secrete EPIYA-motif containing effectors through secretion systems similar to the T3SS/T4SS in bacteria. Our predicted effectors provide useful hypotheses for further studies.

Prevalence and risk factors for Helicobacter pylori infection in Chinese populations.

BACKGROUND: The prevalence of Helicobacter pylori is higher in developing countries. The aim of this study was to investigate the prevalence and risk factors of H. pylori infection in areas with high prevalence of gastric cancer in Jiangsu Province, China. METHODS: A prospective epidemiologic survey of H. pylori infection was accomplished in a natural population of 1457 individuals in Xiangshui and Gaoyou counties, Jiangsu Province, China. Questionnaires and laboratory tests for H. pylori infection ((13)C-urea breath test and serum IgG antibodies to H. pylori) were used and performed, respectively. RESULT: Among 1371 subjects who completed questionnaires and H. pylori detection, 851 (62%) were H. pylori positive. The prevalence reached a peak at the age of 30-40 years (67%). There was no sex difference. The annual family income level was shown to be positively correlated with the risk of H. pylori infection. The prevalence of H. pylori infection was also associated with family size, education level, and several diet-related factors, such as the number of times cooked rice and potatoes eaten per week, and a family history of stomach diseases. Compared to nonsymptomatic individuals, people with dyspeptic symptoms (nausea, vomiting, and belching) presented a low prevalence of H. pylori infection. No association between H. pylori prevalence and smoking or drinking was found. Using multivariate logistic regression analysis, annual family income and education level were the independent predictors for H. pylori infection. CONCLUSION: High prevalence of H. pylori infection was found in areas with a high risk of gastric cancer and was related to several risk factors. The underlying mechanisms need to be further investigated.

Coordinate increase of telomerase activity and c-Myc expression in Helicobacter pylori-associated gastric diseases.

AIM: To detect the telomerase activity and c-Myc expression in gastric diseases and to examine the relation between these values and Helicobacter pylori (H pylori) as a risk factor for gastric cancer. METHODS: One hundred and seventy-one gastric samples were studied to detect telomerase activity using a telomerase polymerase chain reaction enzyme linked immunosorbent assay (PCR-ELISA), and c-Myc expression using immunohistochemistry. RESULTS: The telomerase activity and c-Myc expression were higher in cancers (87.69% and 61.54%) than in noncancerous tissues. They were higher in chronic atrophic gastritis with severe intestinal metaplasia (52.38% and 47.62%) than in chronic atrophic gastritis with mild intestinal metaplasia (13.33% and 16.67%). In chronic atrophic gastritis with severe intestinal metaplasia, the telomerase activity and c-Myc expression were higher in cases with H pylori infection (67.86% and 67.86%) than in those without infection (21.43% and 7.14%). c-Myc expression was higher in gastric cancer with H pylori infection (77.27%) than in that without infection (28.57%). The telomerase activity and c-Myc expression were coordinately up-regulated in H pylori infected gastric cancer and chronic atrophic gastritis with severe intestinal metaplasia. CONCLUSION: H pylori infection may influence both telomerase activity and c-Myc expression in gastric diseases, especially in chronic atrophic gastritis.

[Coordinated expression of c-Myc and telomerase activity in Helicobacter pylori infected gastric diseases].

OBJECTIVE: To detect the telomerase activity and c-Myc expression in gastric diseases and to examine the relation between these values and Helicobacter pylori (Hp) as a risk factor for gastric cancer. METHODS: 171 gastric samples were studied to detect telomerase activity with telomerase polymerase chain reaction enzyme linked immunosorbent assay and c-Myc expression using immunohistochemistry. RESULTS: Telomerase activity and c-Myc expression were higher in cancers (87.7% and 61.5%) than in noncancerous tissues. Telomerase activity and c-Myc expression were higher in chronic atrophic gastritis with moderate or severe intestinal metaplasia (52.4% and 47.6%) than in chronic atrophic gastritis with mild intestinal metaplasia (13.3% and 16.7%). In chronic atrophic gastritis with moderate or severe intestinal metaplasia, telomerase activity and c-Myc expression were higher in cases with Hp infection (67.9% and 67.9%) than in these without infection (21.4% and 7.1%). c-Myc expression was higher in gastric cancer with Hp infection (77.3%) than that without infection (28.6%). Telomerase activity and c-Myc expression were coordinately up-regulated in Hp infected gastric cancer and chronic atrophic gastritis with moderate or severe intestinal metaplasia. CONCLUSIONS: Hp infection may influence both c-Myc expression and telomerase activity in gastric diseases, especially in chronic atrophic gastritis. c-Myc and telomerase co-expressed in gastric cancer and chronic atrophic gastritis with moderate or severe intestinal metaplasia.