Antitumor mechanisms of bifidobacteria.

Cancer remains one of the most common causes of mortality globally. Chemotherapy, one of the major treatment strategies for cancer, primarily functions by targeting the cancer cells and affecting them physiologically, but also affects normal cells, which is a major concern at present. Therefore, adverse effects of chemotherapy drugs, including myelosuppression and liver and kidney damage, are of concern. Now, microbial products have attracted attention in cancer treatment research. Notably, carcinogenesis is considered to be associated with microbial dysbiosis, particularly the positive antitumor effects of bifidobacteria. Although there remains a substantial amount to be understood about the regulation of bifidobacteria, bifidobacteria remain an attractive and novel source of cancer therapeutics. The present review focuses on introducing the latest information on the antitumor effects of bifidobacteria and to propose future strategies for using bifidobacteria in the development of cancer therapeutics.

Polaprezinc combined with clarithromycin-based triple therapy for Helicobacter pylori-associated gastritis: A prospective, multicenter, randomized clinical trial.

The efficacy and safety of polaprezinc combined with triple therapy was compared with triple therapy alone in the eradication of Helicobacter pylori. A randomized, parallel-group, open-label, controlled, prospective multicenter study was conducted in 11 cities in China. Treatment-naive patients with H. pylori-associated gastritis were randomly assigned to one of three arms for a 14-day treatment: Arm A triple therapy (omeprazole 20 mg, amoxicillin 1 g, and clarithromycin 500 mg, each twice daily) plus polaprezinc 75 mg twice daily; Arm B triple therapy plus polaprezinc 150 mg twice daily, or Arm C triple therapy alone. The rate of H. pylori eradication was the primary endpoint. Secondary endpoints were symptom improvement and lower incidence of adverse events. 303 patients completed the study- 106, 96, and 101 patients in Arms A, B, and C, respectively. Intention-to-treat (ITT) analysis showed that the rate of H. pylori eradication was significantly higher for Arms A (77.0%) and B (75.9%) compared to Arm C (58.6%) (P < 0.01), whereas there was no difference between Arms A and B (P = 0.90). Per-protocol (PP) analysis showed that the rate of H. pylori eradication was significantly higher for Arms A (81.1%) and B (83.3%) compared to Arm C (61.4%) (P < 0.01), whereas there was no significant difference between Arms A and B (P = 0.62). All three groups reported significant symptom improvement at 7, 14, and 28 days after treatment, compared to baseline (P < 0.0001). The adverse event rate for Arm B (5.1%) was higher than for Arms A (2.8%) (P = 0.04) and C (1.9%) (P = 0.02). There were no serious adverse events in any group. It appears that standard dose polaprezinc combined with triple therapy can significantly improve the H. pylori eradication rate, without an increase in toxicity.

Effects of different diets on intestinal microbiota and nonalcoholic fatty liver disease development.

AIM: To study the effects of different diets on intestinal microbiota and nonalcoholic fatty liver disease (NAFLD) development at the same caloric intake. METHODS: Thirty male Sprague-Dawley rats were randomized into five groups (six rats each). The control diet (CON) group and free high-fat diet (FFAT) group were allowed ad libitum access to a normal chow diet and a high-fat diet, respectively. The restrictive high-fat diet (RFAT) group, restrictive high-sugar diet (RSUG) group, and high-protein diet (PRO) group were fed a high-fat diet, a high-sugar diet, and a high-protein diet, respectively, in an isocaloric way. All rats were killed at 12 wk. Body weight, visceral fat index (visceral fat/body weight), liver index (liver/body weight), insulin resistance, portal lipopolysaccharide (LPS), serum alanine aminotransferase (ALT), serum aspartate aminotransferase (AST), and liver triglycerides were measured. The intestinal microbiota in the different groups of rats was sequenced using high-throughput sequencing technology. RESULTS: The FFAT group had higher body weight, visceral fat index, liver index, peripheral insulin resistance, portal LPS, serum ALT, serum AST, and liver triglycerides compared with all other groups (P < 0.05). Taking the same calories, the RFAT and RSUG groups demonstrated increased body weight, visceral fat index, peripheral insulin resistance and liver triglycerides compared with the PRO group (P < 0.05). The RFAT group also showed increased portal LPS compared with the PRO group (P < 0.05). Unweighted UniFrac principal coordinates analysis of the sequencing data revealed that the intestinal microbiota structures of the CON, FFAT, RSUG and PRO groups were roughly separated away from each other. Taxon-based analysis showed that, compared with the CON group, the FFAT group had an increased abundance of Firmicutes, Roseburia and Oscillospira bacteria, a higher ratio of Firmicutes to Bacteroidetes, and a decreased abundance of Bacteroidetes, Bacteroides and Parabacteroides bacteria (P < 0.05). The RFAT group showed an increased abundance of Firmicutes and decreased abundance of Parabacteroides bacteria (P < 0.05). The RSUG group showed an increased abundance of Bacteroidetes and Sutterella bacteria, higher ratio of Bacteroidetes to Firmicutes, and a decreased abundance of Firmicutes (P < 0.05). The PRO group showed an increased abundance of Bacteroidetes, Prevotella, Oscillospira and Sutterella bacteria, and a decreased abundance of Firmicutes (P < 0.05). Compared with the FFAT group, the RFAT group had an increased abundance of Bacteroidetes, higher ratio of Bacteroidetes to Firmicutes, and decreased abundance of Firmicutes and Oscillospira bacteria (P < 0.05). CONCLUSION: Compared with the high-protein diet, the NAFLD-inducing effects of high-fat and high-sugar diets are independent from calories, and may be associated with changed intestinal microbiota.

[Novaferon ameliorates dextran sulfate sodium-induced colitis and downregulates expression of TNF-α in mice].

OBJECTIVE: To explore the effects of novaferon on dextran sulfate sodium (DSS)-induced colitis and expression of TNF-α in mice and to evaluate the efficacy of novaferon on ulcerative colitis and the possible mechanisms. METHODS: A total of 70 BALB/C mice [weight (20.0±2.0) g, 8-week years old, female, pathogen free] were randomly divided into 7 groups: a normal group, a model group, a mesalazine treatment group, a prednisone treatment group, a low-dose novaferon group, a middle-dose novaferon group and a high-dose novaferon group (10 mice per group). The normal group-mice were given distilled water. The ulcerative colitis model was established by treated the mice with 4% DSS for 7 continuous days. At the 8th day, the mice in the all of drug treatment groups were injected corresponding drugs (i.p.). During the experiment, the general situation, daily weight, stool trait and occult blood were recorded, and the mice were killed on the 14th day. The disease activity index (DAI), colon length, histological scores were assessed. Immunohistochemistry was used to measure the expression of TNF-α in colonic mucosa. RESULTS: 1) The mice treated with DSS solution showed diarrhea, mucous stool and bloody stool, and the DAI score increased gradually. The mesalazine, predinison and nofaferon could ameliorate the general situation of the mice, reduce the DAI and histological scores, and reverse the decrease in the colon length. 2) Compared with the model group, the DAI scores were significantly decreased in the novaferon groups (at low, middle or high dose), the mesalazine group or the prednisone group (all P<0.01), but there was no difference among the mesalazine group, the prednisone group and the low-dose novaferon group (all P>0.05). The efficacy of novaferon in the middle-dose group and the high-dose group are better than that in the mesalazine group, the prednisone group and the low-dose novaferon group (all P<0.01). The efficacy of novaferon showed a dose-dependent manner. 3) The injury of colonic mucosa was relatively mild in the novaferon groups (at low-dose, middle-dose or high-dose), the mesalazine group and the prednisone group, and there were partial glands and less inflammatory cells. Compared with the model group, there was statistics difference (all P<0.05). The tissue injury was significantly alleviated, and the DAI score was decreased in the high-dose novaferon group compared the middle-dose novaferon group (P<0.05), but there was no significant difference between the low-dose novaferon group and the middle-dose novaferon group or between the mesalazine group and the prednisone group (both P>0.05). 4) The TNF-α expression was significantly down-regulated in the novaferon groups (at low-dose, middle-dose or high-dose), the mesalazine group and the prednisone group compared with model group (all P<0.01); but there was no significant difference between the mesalazine group and the prednisone group (P>0.05); the decrease of TNF-α expression by novaferon displayed a dose-dependent manner. Compared with the mesalazine group or the prednisone group, the TNF-α expression in novaferon groups at all dosages was dramatically reduced (all P<0.01). CONCLUSION: Novaferon can improve the DAI scores and colonic tissue injury in ulcerative colitis induced by DSS in mice, and down-regulate the TNF-α expression in dose-dependent manner.

Lactobacillus acidophilus suppresses colitis-associated activation of the IL-23/Th17 axis.

The aim of this paper is to determine the modulatory effects of Lactobacillus acidophilus on the IL-23/Th17 immune axis in experimental colitis. DSS-induced mouse models of UC were to be saline, hormones, and different concentrations of Lactobacillus acidophilus intervention. The expression of interleukin- (IL-) 17, tumor necrosis factor α (TNFα), IL-23, transforming growth factor ß1 (TGFß1), signal transducer and activator of transcription 3 (STAT3), and phosphorylated (p)-STAT3 was examined by RT-PCR, Western blotting, and immunohistochemical analysis. And the results showed that administration of L. acidophilus suppressed Th17 cell-mediated secretion of proinflammatory cytokine IL-17 through downregulation of IL-23 and TGFß1 expression and downstream phosphorylation of p-STAT3.

Chronic gastritis in China: a national multi-center survey.

BACKGROUND: Chronic gastritis is one of the most common findings at upper endoscopy in the general population, and chronic atrophic gastritis is epidemiologically associated with the occurrence of gastric cancer. However, the current status of diagnosis and treatment of chronic gastritis in China is unclear. METHODS: A multi-center national study was performed; all patients who underwent diagnostic upper endoscopy for evaluation of gastrointestinal symptoms from 33 centers were enrolled. Data including sex, age, symptoms and endoscopic findings were prospectively recorded. RESULTS: Totally 8892 patients were included. At endoscopy, 4389, 3760 and 1573 patients were diagnosed to have superficial gastritis, erosive gastritis, and atrophic gastritis, respectively. After pathologic examination, it is found that atrophic gastritis, intestinal metaplasia and dysplasia were prevalent, which accounted for 25.8%, 23.6% and 7.3% of this patient population. Endoscopic features were useful for predicting pathologic atrophy (PLR = 4.78), but it was not useful for predicting erosive gastritis. Mucosal-protective agents and PPI were most commonly used medications for chronic gastritis. CONCLUSIONS: The present study suggests non-atrophic gastritis is the most common endoscopic finding in Chinese patients with upper GI symptoms. Precancerous lesions, including atrophy, intestinal metaplasia and dysplasia are prevalent in Chinese patients with chronic gastritis, and endoscopic features are useful for predicting pathologic atrophy.

Efficacy profiles for different concentrations of Lactobacillus acidophilus in experimental colitis.

AIM: To determine the efficacy profiles of different concentrations of Lactobacillus acidophilus (L. acidophilus) for treating colitis using an experimental murine model. METHODS: Colitis was established in 64 BALB/c mice by adding 5% dextran sodium sulfate (DSS) to the drinking water and allowing ad libitum access for 7 d. The mice were then randomly divided into the following control and experimental model groups (n = 8 each; day 0): untreated model control; negative-treatment model control (administered gavage of 1 mL/10 g normal saline); experimental-treatment models C4-C8 (administered gavage of 10(4), 10(5), 10(6), 10(7), or 10(8) CFU/10 g L. acidophilus, respectively); positive-treatment model control (administration of the anti-inflammatory agent prednisone acetate at 45 µg/10 g). Eight mice given regular water (no DSS) and no subsequent treatments served as the normal control group. Body weight, fecal traits, and presence of fecal occult blood were assessed daily. All animals were sacrificed on post-treatment day 7 to measure colonic length, perform histological scoring, and quantify the major bacteria in the proximal and distal colon. Intergroup differences were determined by one-way ANOVA and post-hoc Student-Newman-Keuls comparison. RESULTS: All treatments (L. acidophilus and prednisone acetate) protected against colitis-induced weight loss (P < 0.05 vs model and normal control groups). The extent of colitis-induced colonic shortening was significantly reduced by all treatments (prednisone acetate > C4 > C5 > C7 > C8 > C6; P < 0.05 vs untreated model group), and the C6 group showed colonic length similar to that of the normal control group (P > 0.05). The C6 group also had the lowest disease activity index scores among the model groups. The bacterial profiles in the proximal colon were similar between all of the experimental-treatment model groups (all P > 0.05). In contrast, the bacterial profile in the distal colon of the C6 group showed the distinctive features (P < 0.05 vs all other experimental-treatment model groups) of Lactobacillus sp. and Bifidobacterium sp. being the most abundant bacteria and Staphylococcus aureus being the least abundant bacteria. CONCLUSION: The most therapeutically efficacious concentration of L. acidophilus (10(6) CFU/10 g) may exert its effects by modulating the bacterial profile in the distal colon.

[Mechanism of Novaferon on production of TNF-α by monocytes isolated from normal human peripheral blood].

OBJECTIVE: To study the role of Novaferon on TNF-α production and expression of NF-κB mRNA in monocytes isolated from normal human peripheral blood and to provide theoretical basis for treatment of immunological diseases with Novaferon. METHODS: Monocytes were isolated from the peripheral blood in 30 healthy volunteers and divided into 5 groups: group A was blank control, group B was stimulated by LPS without Novaferon intervention, group C by LPS together with Novaferon intervention, group D by LPS before Novaferon intervention, which group E by LPS after Novaferon intervention. We detected the concentration of TNF-α after LPS stimulation and Novaferon intervention in the supernatant by ELISA and expression of NF-κB mRNA by RT-PCR. RESULTS: Novaferon inhibited TNF-α production by monocytes isolated from healthy volunteers induced by LPS in vitro in group D compared with group B [(1446.76±72.36) pg/mL vs (946.46±46.12) pg/mL, P<0.01], and the rate was 29.7%. There was no significant change in TNF-α concentration in group C and E compared with group B [(1446.76±72.36) pg/mL vs (1275.62±87.75) pg/mL, P>0.05; (1446.76±72.36) pg/mL vs (1383.62±86.96) pg/mL, P>0.05]. There was significant change in NF-κB mRNA expression in group D compared with group B (0.2829±0.0365 vs 0.4994±0.0604, P<0.01). There was no significant change in NF-κB mRNA expression in group C and group E compared with group B (0.4716±0.0616 vs 0.4994±0.0604, P>0.05; 0.4767±0.0600 vs 0.4994±0.0604, P>0.05). CONCLUSION: Novaferon can suppress TNF-α secretion by monocytes induced by LPS in vitro, and it can affect the immunity function of monocytes, which may be associated with the downregulation of NF-κB mRNA expression in monocytes.

Gastroesophageal Reflux Disease Questionnaire (GerdQ) in real-world practice: a national multicenter survey on 8065 patients.

BACKGROUND AND AIM: Recently, Gastroesophageal Reflux Disease Questionnaire (GerdQ) has been developed for diagnosis of GERD. However, no study investigated its value in real-world practice. This study aimed to investigate whether GerdQ can be used for diagnosis of GERD in China. METHODS: A national multicenter survey was undertaken; all patients who underwent first diagnostic upper endoscopy for upper gastrointestinal (GI) symptoms were included. Data including the gender, age, symptoms, and endoscopic findings were prospectively recorded. The GerdQ score was measured before endoscopic procedure. RESULTS: Totally, 8065 patients were included. One thousand four hundred and thirty-five patients (17.8%) had reflux esophagitis. Among them, 620 (43.2%) patients' GerdQ score was ≥ 8. For 2025 patients with GerdQ ≥ 8, 620 (30.6%) were found to have reflux esophagitis, but the remaining 69.4% (1405/2025) were normal. Proportions of patients with reflux esophagitis increased in cut-off range from 3-18 for GerdQ. However, 22.2% of the patients with a GerdQ score ≤ 2 also had reflux esophagitis. Twenty-eight (0.3%) patients were diagnosed to have upper GI malignancies, and 10 out of these 28 (35.7%) patients' GerdQ score was ≥ 8. CONCLUSIONS: The study suggests the proportions of Chinese patients with reflux esophagitis rise up with the increase of GerdQ score, and GerdQ may be used for diagnosis of GERD. However, low GerdQ score cannot exclude the possibility of reflux esophagitis. A minority of Chinese patients has high GerdQ score but is diagnosed with malignancies, even in the absence of alarm features.

Calcitonin gene-related peptide is a promising marker in ulcerative colitis.

BACKGROUND: Assessment of the severity and extent of disease activity continues to present challenges for physicians in the treatment of ulcerative colitis. Standard markers that can objectively reflect disease activity are useful for physicians to both evaluate the course of ulcerative colitis and monitor the effectiveness of therapy for any given patient. AIMS: We hypothesize that calcitonin gene-related peptide (CGRP) can reflect the activity and severity of ulcerative colitis and be used as a marker to assess the effectiveness of various therapies. METHODS: We examined the expression levels of CGRP by reverse transcription polymerase chain reaction (RT-PCR) and semi-quantitative immunohistochemisty in mucosal biopsies from 38 patients with UC and 18 controls. Levels of CGRP mRNA and protein expression were compared between patients and controls with the clinical activity index (CAI) and the endoscopic activity index (EAI) for various levels of UC severity. RESULTS: Our results showed that the levels of CGRP mRNA and protein expression were significantly reduced in UC patients compared to controls. This effect was more pronounced in patients with more severe cases of UC. There is a statistically significant negative correlation between levels of CGRP mRNA expression and CAI/EAI scores. A statistically significant negative correlation was also found between levels of CGRP protein expression and CAI/EAI scores. Overall, high CAI and EAI scores were accompanied by low CGRP mRNA and protein expression levels. CONCLUSION: Levels of CGRP protein and mRNA expression in the colonic mucosa of patients are closely associated with UC severity and corroborate traditional indices used to assess the disease.

Asymmetric dimethylarginine: a novel biomarker of gastric mucosal injury?

Nitric oxide (NO), a multifunctional endogenous gas molecule, is metabolized from L-arginine by enzymatic reaction in the presence of nitric oxide synthase. NO, an important gas signaling molecule, is a gastric mucosa protective factor that contributes significantly to maintain normal gastric mucosa integrity. NO increases gastric mucosa blood flow, regulates the secretion of mucus and bicarbonate, and inhibits the secretion of gastric juice. Asymmetric dimethylarginine (ADMA) has been identified as the major endogenous inhibitor of nitric oxide synthase. The function of ADMA is to decrease NO production via inhibiting nitric oxide synthase activity. Besides inhibiting NO synthesis, ADMA also directly induces oxidative stress and cell apoptosis, and participates in inflammation reaction. Its systemic accumulation was observed in conjunction with several cardiovascular and metabolic diseases. ADMA also mediates gastric ulcer injury induced by ethanol, stress, helicobacter pylori and indomethacin. The mechanism of ADMA directly producing adverse effect in gastric mucosa is incompletely understood. It is widely accepted that NO bioavailability decrease is the majority reason. Promotion of apoptosis and aggravation of inflammation may be other important mechanisms of ADMA-induced gastric injury. ADMA might be a novel clinical and experimental biomarker related to gastric mucosa disorder. Although therapeutic tool targeting to ADMA is available in multiple cardiovascular diseases, it is unknown in gastrointestinal disease. The strategy to inhibit ADMA is beneficial to gastric ulcer induced by ethanol in rats. Thus, ADMA might be a candidate of therapeutic target in gastric mucosa damage.

Predictors of clinical and endoscopic findings in differentiating Crohn's disease from intestinal tuberculosis.

BACKGROUND: There are many similarities and overlaps in clinical manifestations and ileocolonoscopic features between Crohn's disease (CD) and intestinal tuberculosis (ITB). Differentiation between CD and ITB is of great importance. AIM: To investigate the values of clinical and endoscopic findings in differential diagnosis between CD and ITB. METHODS: Clinical and endoscopic features of a cohort of 130 cases of CD and 122 cases of ITB from June 2003 to February 2009 were retrospectively reviewed following predetermined criteria. Parameters were screened by logistic regression analysis. Furthermore, the diagnostic efficacy of screened parameters was analyzed by regression equation (mathematical model) and receiver operating characteristic curve (ROC curve). RESULTS: The clinical features helpful in differentiating CD from ITB are hematochezia, intestinal surgery, perianal diseases, pulmonary tuberculosis, ascites, and positive of PPD skin test; the sensitivity, specificity, accuracy, positive predictive value, and negative predictive value of regression mathematical model established by clinical features were 90.3, 76.8, 83.8, 80.7, and 88.0%, respectively. The endoscopic features helpful in differentiating CD from ITB were rectum involved lesions, longitudinal ulcer, cobblestone appearance, fixed-open ileocecal valve, transverse ulcer, and rodent ulcer; the sensitivity, specificity, accuracy, positive predictive value, and negative predictive value of regression mathematical model established by endoscopic features were 82.9, 82.0, 82.5, 82.9, and 82.0%, respectively. CONCLUSIONS: It was proposed that a diagnostic algorithm based on available clinical and endoscopic regression equation could improve the current sensitivity, specificity, and accuracy in differentiating between CD from ITB.

Up-regulation of signal transducer and activator of transcription-3 is associated with aggravation of ulcerative colitis.

OBJECTIVE: The signal transducers and activators of transcription (STAT) family of proteins are intracellular signal transduction molecules involved in the expression of numerous proinflammatory genes in inflammatory cells. This study was executed to determine the association between the expression pattern of STAT-3 in the colonic mucosa of patients with ulcerative colitis (UC) and the progression of this disease. METHODS: We carried out the real-time reverse transcription-polymerase chain reaction (RT-PCR), Western-blot analysis and immunohistochemical staining to examine the expression of STAT-3 at both mRNA and protein levels in 25 patients with UC and 10 normal controls. The association between STAT-3 expression pattern and the severity of the disease was also analyzed. RESULTS: The expression of STAT-3 mRNA and protein in the ulcerated and inflamed colonic mucosa was significantly higher than that in the non-inflamed colonic mucosa (for mRNA: P = 0.001, 0.02 and for protein: P = 0.003, 0.03, respectively), but there was no statistically significant difference in the non-inflamed colonic mucosa of UC patients and normal controls (for mRNA: P = 0.062 and for protein: P = 0.063). Furthermore, immunohistochemical analysis showed that among the inactive, mild approximately moderate, and severe colonic mucosae of UC patients, the positive rates of STAT-3 expression were 60.0%, 66.7%, and 88.9%, respectively. CONCLUSION: Our study provides convincing evidence for the first time that the up-regulation of STAT-3 in colonic mucosa may be associated with the progression of human UC and STAT-3 may be a potential therapeutic target for this disease.

[Analysis of clinical characteristics of 43 surgical patients with Crohn disease using the Montreal classification].

OBJECTIVE: To investigate the clinical features of Crohn disease according to the Montreal classification. METHODS: Clinical data of 43 surgical patients with Crohn disease (surgical group) and 125 non-surgical patients with Crohn disease (non-surgical group) were retrospectively analyzed and compared between two groups. The Montreal classification was used. RESULTS: In the surgical group, 28 patients (65.1%) were A2, 14 (32.6%) were A3 and only one was A1, which was not significantly different as compared to the non-surgery group. The proportions of L1, L2, L3, and L4 subtype in the surgical group were 41.9%, 25.6%, 30.2%, and 2.3%, respectively, which was not significantly different as compared to that in the non-surgery group. In the surgical group,B1 disease was found in 1 case (2.3%), B2 in 26 cases (60.5%), and B3 in 16 cases (37.2%), while in the non-surgical group, B1 was found in 79 cases (63.2%), B2 in 44 cases (35.2%) and B3 in 2 cases (1.6%). Differences were significant between two groups in disease behavior (P=0.001, P=0.004, P=0.001). CONCLUSIONS: Most surgical patients of Crohn disease are A2. L1 and L3 are the main lesion location. As disease behavior, B2 and B3 are the main reasons for operation.

Immunoreactivity and prognostic value of tumor-associated glycoprotein 72 in primary gallbladder carcinoma.

AIM: The purpose of this study was to investigate the expression of tumor-associated glycoprotein 72 (TAG-72) in primary gallbladder carcinoma (PGC) with an attempt to determine the potential usefulness of it in diagnostic and prognostic applications. METHODS: Tissue samples from 118 patients with PGC, 30 patients with chronic cholecystitis, and 20 normal gallbladders were stained with anti-TAG-72 antibodies for immunohistochemical analysis. Then, the clinical outcome of the patients after a maximum follow-up of 5 years was determined in 110 out of 118 patients. RESULTS: Clinicopathological characteristics of the carcinomas and clinical outcome of the patients were associated with the TAG-72 expression. TAG-72 was expressed more frequently in cancerous tissues of larger size, with lymph nodes metastasis, and with poor differentiation. Especially, a statistical association was found with more advanced UICC stages of the disease (55.77%, 65.38%, 92.86%, 93.75% and 100% in stages IA, IB, IIA, IIB, and III, respectively, p=0.02). Using a proportional hazard model, the survival rate of the patients with PGC expressing TAG-72 was significantly lower than the patients without TAG-72 expression (p<0.01), and including information of TAG-72 staining patterns within cancerous tissues along with clinical cancer staging may improve the accuracy of predicting patients' prognosis. CONCLUSION: These data suggest that TAG-72 expression is associated with clinicopathological parameters of aggressiveness in PGC. The detection of it combined with cancerous staging may increase the ability of investigators to predict the prognosis of patients with PGC.

Diagnosis and treatment of 81 patients with primary gastrointestinal lymphoma.

OBJECTIVE: To analyze the status quo of the diagnosis and treatments of primary gastrointestinal lymphoma (PGIL) in order to improve it. METHODS: Eighty-one patients with PGIL were analyzed retrospectively including clinical manifestations, endoscopic features, pathological features, HP infection, treatment, and prognosis. RESULTS: The age of patients with gastric lymphoma was (52.84+/-15.33) years. The age of patients with intestinal lymphoma was (42.09+/-15.28) years. Common symptoms included abdominal pain (76.5%), gastrointestinal bleeding (55.6%), anemia (54.3%), abdominal mass (25.9%), hypoproteinemia (40.7%), bowel obstruction (11.1%), abdominal distension, vomiting, and other non-specific gastrointestinal symptoms (32.1%), weight loss (33.3%); fever (8.6%), diarrhea (7.4%), digestive tract perforation (1.2%), constipation (1.2%), and dysphagia (1.2%). Endoscopic appearances were as follows: tumor type (67.7%), ulcer type (27.7%), and diffuse type (4.6%). Clinical diagnosis rate and endoscopic biopsy confirmation rate were 30.9% and 73.8%. MALT lymphoma accounted for 61.7% of the patients. HP detection rate was 39.5% and positive rate was 37.5%. A total of 69 patients received surgeries: 3 had preoperative chemotherapy, and 34 had postoperative chemotherapy. Twelve patients had non-surgical treatment, 6 patients of whom had simple chemotherapy and HP eradication therapy, and the other 6 gave up during the treatment. There was no significant difference in the survival rate of Stage I-II patients in the surgery alone group, surgery plus chemotherapy group, and chemotherapy and HP eradication therapy group(P>0.05). The survival rate of Stage III-IV patients in the surgery alone group was lower than that in the other 2 groups (P<0.05). The 5-year, 3-year, and 1-year survival rate was 55.87%, 70.96%, and 96.39%, respectively. CONCLUSION: There are no specific clinical and endoscopic features in PGIL, so the misdiagnosis rate is high. Multi-site biopsy or repeated biopsies and immunohistochemical methods can be used to raise the pathological diagnosis rate. Chemotherapy and HP eradication are recommended.

[Effect of prokinetic agents on the electrical activity of stomach and duodenum in rats].

OBJECTIVE: To determine the effect of prokinetic agents such as domperidone, mosapride, clarithromycin, and itopride on the electrical activity of the stomach and duodenum in SD rats,and also to explore the mechanism. METHODS: The organism functional experiment system BL-420E was used to record the myoelectrical activity in the stomach and duodenum of SD rats in all groups using domperidone, mosapride, itopride, clarithromycin, and physiological saline on the interdigestive phase. The effect of the prokinetic agents on the amplitude and frequency of gastric and duodenal electromyogram in the SD rats was compared. The antagonists such as atropine, phentolamine, and propranolol were added to investigate the mechanism of action with all prokinetic agents. RESULTS: All prokinetic agents increased the amplitude and frequency of gastric and duodenal fast waves in the SD rats(P<0.05). The effect of itopride was the most obvious among the 3 groups (P<0.05),and clarithromycin had the weakest effect(P<0.05). The amplitude and frequency of gastric and duodenal fast waves in the SD rats in the groups of clarithromycin,domperidone,mosapride, itopride, and physiological saline were inhibited by atropine(P<0.05),but not by phentolamine and propranolol. CONCLUSION: Itopride, mosapride, domperidone, and clarithromycin can increase the amplitude and frequency of gastric and duodenal fast waves in the SD rats. The mechanism may be related to cholinergic receptors, but not adrenergic receptors.

[The diagnostic value of double-balloon enteroscopy in 67 cases with obscure abdominal pain].

OBJECTIVE: To evaluate the diagnostic valve of double balloon enteroscopy in patients with obscure abdominal pain and analyze the etiology of chronic abdominal pain resulted from enteral diseases. METHODS: Sixty-seven cases with chronic abdominal pain underwent a previous negative gastroscopy, colonoscopy, gastrointestinal barium, B ultrasound and electrocardiogram were received double balloon enteroscopy during June 2005 to June 2008. RESULTS: Thirty-six of 67 patients was done by enteroscopy via anus, and 19 cases via oral, and 12 cases via both anus and oral. The lesions were found in 41 of the 67 patients, with overall diagnostic yield of 61.19%. Among 41 cases of abdominal pain resulted from small bowel diseases, Crohn's disease were found in 15 cases (36.59%), non-specific small enteritis in 10 cases (24.39%), tumors in 8 cases (19.51%), other enteral diseases in 8 cases (19.51%). CONCLUSIONS: Double balloon enteroscopy was a diagnostic modality with a high diagnostic value for obscure abdominal pain resulted from small bowel diseases. The most common causes of obscure abdominal pain were Crohn's disease, non-specific small enteritis and tumors.

The aggravatory effect of nicotine on Helicobacter pylori-induced gastric mucosa injury: role of asymmetric dimethylarginine.

BACKGROUND AND GOAL: Nitric oxide (NO) is a well-known gastric mucosa protection factor. Recently, it has been reported that methylated arginine compound such as asymmetric dimethylarginine (ADMA), which inhibits nitric oxide synthesis, may be related to the development of gastric mucosa injury in patients with Helicobacter pylori infection. In the present study, we tested the relationship between endogenous ADMA and gastric mucosa injury in H. pylor- infected patients and cultured gastric epithelial cells. METHODS: One hundred and fifty subjects with gastric diseases were entered in this study. The levels of ADMA in gastric juice and plasma were measured in both H. pylori+ and H. pylori- patients. We analyzed independent risk factors that contribute to ADMA levels by multiple linear regression analyses. Mucosal epithelium cells were treated with nicotine (10 microM) for 24 hours in the presence or absence of H. pylori. The concentrations of ADMA in the culture medium and the rate of cell apoptosis were determined. RESULTS: The ADMA level in gastric juice was significantly increased in H. pylori+ patients (P<0.05), whereas there were no differences in the content of ADMA in the plasma between H. pylori+ patients and H. pylori- patients. Smoking and H. pylori infection were 2 independent risk factors contributing to ADMA levels, and in the population of H. pylori+ patients, the level of ADMA in smokers was higher compared with nonsmokers. Incubation of nicotine (10 microM) with epithelial cells for 24 hours further increased the elevated level of ADMA and the rate of cell apoptosis owing to H. pylori infection. CONCLUSIONS: H. pylori infection caused an increase of ADMA levels in gastric juice, which was aggravated by smoking. Endogenous ADMA may be an important factor contributing to gastric mucosa injury.

Detrimental effects of nicotine on the acute gastric mucosal injury induced by ethanol: role of asymmetric dimethylarginine.

The aim of this study was to determine whether asymmetric dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide synthase (NOS), is responsible for the detrimental effects of nicotine on ethanol-induced gastric mucosal injury and its underlying mechanisms. Gastric mucosal injury was induced by an injection of ethanol in the stomach in rats. Animals were pretreated with nicotine for 28 days before ethanol injection. The gastric mucosal ulcer index (UI) and the levels of ADMA and NO in gastric juice were determined. In vitro, the cultured mucosal epithelial cells were treated with nicotine in the presence or absence of ethanol. The concentration of ADMA in the culture medium and the ratio of cell apoptosis were measured, and the effect of nicotine or ADMA alone on cell apoptosis was also examined. In rats treated with ethanol, the UI and ADMA levels were increased and the NO level was decreased, and these effects of ethanol were augmented by pretreatment with nicotine. Administration of nicotine alone did not show significant impact on UI, ADMA level, or NO level. In vitro, incubation of human epithelial cells with ethanol induced cell injury accompanied by increased ADMA levels in the culture medium, an effect which was amplified in the presence of nicotine. Similarly, ethanol was able to induce epithelial cell apoptosis that was exacerbated by nicotine. Incubation of epithelial cells with nicotine alone did not induce cell apoptosis, but administration of ADMA alone did induce cell apoptosis. The results suggest that the gastric mucosal injury induced by ethanol is augmented by nicotine, which is related to the increased ADMA level.