RATIONALE:IgG4-related disease (IgG4-RD) is a chronic fibro-inflammatory disorder which is characterized by elevated levels of serum IgG4 and infiltration of IgG4-bearing plasma cells in the involved organs. Primary biliary cirrhosis (PBC) and Primary Sjögren's syndrome (pSS) are both distinct from IgG4-related disease. We herein describe a Chinese patient with IgG4-related RPF overlapping with PBC and pSS. PATIENT CONCERNS:We report a case of 69-year-old male with recurrent lower abdominal pain for 10 months. Laboratory data showed elevated erythrocyte sedimentation rate and hepatobiliary enzymes, renal dysfunction, high titers of antinuclear antibody, anti-SS-A antibody and anti-mitochondrial type 2, high immunoglobulin (Ig) G levels and elevated serum IgG4 (9 g/L). Contrast-enhanced computed tomography and magnetic resonance imaging were suggestive of retroperitoneal fibrosis and unilateral ureteral occlusion. Immunohistochemical staining for IgG4 did not demonstrate infiltration of IgG4-positive plasma cells in the retroperitoneal mass, but revealed significant infiltration of lymphocytoplasma cells as well as fibrosis and fibrin accumulation. DIAGNOSES:The patient was diagnosed with IgG4-related retroperitoneal fibrosis based on the International Consensus Diagnostic Criteria. He was also diagnosed with primary biliary cirrhosis and primary Sjögren's syndrome. INTERVENTIONS:250 mg ursodeoxycholic acid was administered twice daily, and prednisolone was initiated at a dose of 40 mg/day and then tapered to 25 mg after 45 days. OUTCOMES:The size of the retroperitoneal soft tissue mass gradually reduced and the abnormal laboratory parameters were restored to normal. LESSONS:This rare clinical condition has seldom been reported in the literature, which suggests that common immunogenetic factors may be involved in the development of IgG-related RPF, PBC and pSS.

OBJECTIVE To study the phenotypic alteration of intestinal dendritic cells (DC) in a rat model of irritable bowel syndrome (IBS) and the change of mitogen-activated protein kinase (MAPK) signaling pathway, in order to explore the potential mechanism of ERK1/2 pathway mediation in abnormal DC immune response. METHODS IBS rat model was established by combining neonatal maternal separation and colorectal distension in 10 SD rats, and 10 healthy rats served as controls. Visceral sensitivity was evaluated with abdominal withdrawal reflex (AWR). Mesenteric lymph node DC (MLNDC) was isolated and purified by magnetic label-based technique after modeling. Expression of surface major histocompatibility complex (MHC)-Ⅱin control rats was determined by flow cytometric analyses. Western-blot was used to determine the expression of MHC-Ⅱ, p-p38, p38, phosphorylated extracellular regulated protein kinase (p-ERK1/2), ERK1/2, phosphorylated c-Jun N-terminal kinase (p-JNK), and JNK in MLNDC. RESULTS Visceral sensitivity was significantly higher in the IBS group than in the control group. The purity of the OX62 positivity MLNDC following magnetic sorting was about 85.57%±7.67%. MLNDC in the control group expressed high level of MHC-Ⅱ. The expression of MHC-Ⅱ and p-ERK1/2 in MLNDC in the IBS group were higher than those in the control group (1.05±0.13 vs 0.67±0.18, t=-2.973, P=0.041; 3.21±0.48 vs 2.34±0.85, t=-3.130, P=0.035); while there was no significant difference in the expressions of p-JNK and p-p38 compared with the control groups (0.95±0.17 vs 0.76±0.36, t=0.808, P=0.464; 1.07±1.13 vs 1.19±0.91, t=0.137, P=0.897). CONCLUSION The intestinal DC in IBS rats show a upregulated expression of MHC-Ⅱ, which may be related to the activation of intracellular ERK1/2 pathway.

Background: Colonoscopy is the procedure of choice for colon cancer screening, but is far from perfect, as lesions are missed due to lack of image contrast and due to their location behind haustral folds and at flexures.We have developed a novel dual-view optical probe that illuminates and images in the forward and omni-directional rear directions to provide a single registered video image.Objective: Evaluate the prototype dual-view probe in a standard colon model.Design: A colon model (Chamberlain Group, MA) was used for the study.Due to the stiffness of the model and the difficulty in advancing a colonoscope through it, the colon was cut into 3 sections (ascending, transverse, and descending colon)

OBJECTIVE:To study the effect of Weifuchun on inflammation of Helicobacter pylori (Hp)-infected gastric epithelial cells (GES-1) and its correlation with NF-kappaB signaling pathway. METHODS:Hp standard home-made strain (CagA +, VacA +) NCTCI 1637 infected GES-1 cells were used. Weifuchun was used as intervention. Weifuchun of different concentrations (5,10, and 20 microg/mL) were screened by MTT assay. A blank group and the model group were set up. Then the growth inhibition rate of drugs on gastric epithelial GES-1 cells was detected with MTT assay. Cell cycle was detected using flow cytometry. The supernatant liquid was separated to detect the contents of IL-8 and IL-4 by ELISA.The protein expression level of NF-kappaB was detected by Western blot analysis. RESULTS:MTT assay indicated significantly inhibitory effect of Weifuchun on GES-1 cells [5% inhibiting concentration (IC5)] was 10 microg/ml in the Weifuchun group. After GES-1 and Hp were cultured together,the contents of IL-8 in the supernatant were more obviously higher in the model group than in the blank group (P < 0.05), and then gradually decreased. After treatment with different concentrations of Weifuchun, the levels of IL-8 in the supernatant were less when compared with the model group at 12, 24, 48, and 72 h (P < 0.05). The decrement was the most significant in the high dose Weifuchun group. The IL-4 level in the supernatant was obviously lower in the model group than in the blank group. It obviously increased in the high concentration Weifuchun group (P < 0.05). There was no statistical difference in the IL-4 level between middle, low concentration Weifuchun group and the blank group (P > 0.05). The protein expression of intranuclear P65 increased and that of IkBalpha decreased 60 min after Hp infection. But the protein expression of intranuclear P65 decreased and the protein expression of IkBalpha increased after intervention of Weifuchun. CONCLUSIONS:Weifuchun adjusted H. pylori induced IL-8 and IL-4 production by gastric epithelial cells through blocking NF-kappaB pathways. Its mechanisms might possibly lie in inhibiting p65 from entry into nucleus and the degradation of IkBalpha. Weifuchun was an effective drug for treatment of Hp correlated chronic gastritis.

目的 研究浙江省医学和理工科大学生功能性肠病（FBD）流行病学特征，探讨FBD与心理因素的关系。方法 应用成人功能性胃肠病罗马Ⅲ诊断性问卷（ROMEⅢ-DQ）对浙江省两所医学和理工科高校大学生进行抽样调查（2010年11月至2011年3月），采用心理学症状自评量表（SCL-90）进行心理因素分析。结果 共纳入合格问卷1870份，按罗马Ⅲ标准诊断为FBD1033例，患病率55.24％；FBD各亚型患病率为：非特异性FBD26.58％（497/1870），功能性便秘16.95％（317/1870），肠易激综合征6.90％（129/1870），功能性腹胀4.12％（77/1870），功能性腹泻0.70％（13/1870）。不同性别、专业、年级的FBD患病率有差异，女性>男性，医学生>理工科生，总体上在校大学生FBD患病率随年级增高而增加，医学生尤其明显。44.05％（455/1033）的FBD重叠其他功能性胃肠病，9.00％（93/1033）的FBD合并嗳气症，8.23％（85/1033）合并功能性消化不良。患FBD大学生的SCL-90得分高于健康大学生。结论 FBD在大学生中有较高患病率，女性高于男性，不同专业患病率有差异，并且FBD与心理因素相关。

OBJECTIVE:To identify the expression and significance of protease-activated receptor-2 (PAR-2) and mast cell (MC) in the rat model of small intestinal mucosal damage by a short-term administration of diclofenac.METHODS:Twenty-four SD-rats were divided into 2 groups (control group and model group, 12 rats each) by random digit table. The rats in the control group were treated with 1 ml distilled water per 250 g, once a day while those in the model group diclofenac 7.5 mg/kg per day. Their terminal ileum was harvested at Day 5 after an intraperitoneal injection. Toluidine blue dyeing was employed to determine the distribution of MC and its count in intestinal mucous membrane. Immunohistochemistry, Western blot and real-time PCR (polymerase chain reaction) were employed analyze the location, expression and change of PAR-2 mRNA in intestinal mucous membrane.RESULTS:The count of MC was obviously higher in the model group than that in the control group (10.3 ± 2.2 vs 4.2 ± 1.2, P < 0.05). PAR-2 was expressed on the mucous surface, recesses epidermis and lamina propria inflammatory cells. And positive dyes were located within cytoplasm. As compared with the control group, the expression of PAR-2 mRNA was higher (2.63 ± 0.26 vs 1, P < 0.05) and its protein expression higher in the model group (24.3 ± 2.4 vs 17.5 ± 3.5, P < 0.05).CONCLUSION:Both PAR-2 and mast cell are involved in the pathogenesis of small intestinal mucosa injury induced by diclofenac in rats. PAR-2 may be activated by tryptase released from mast cells and participate in the pathogenesis of small intestinal injury as induced by non-steroidal anti-inflammatory drugs.

OBJECTIVE:To study the expression of Akt and MAPK in the stomach and colon of slow transit constipation (STC) in rats, as well as the effect of exogenous glial cell line-derived neurotrophic factor (GDNF) on it. METHODS:Forty-four SD rats were divided into control group and model group randomly. The STC model group was established by gastric irrigation of rhubarb for 3.5 months. The control group was received normal saline. After model building, each group was equally divided into 2 subgroup randomly, administrated with exogenous GDNF and normal saline by vein injection for one week respectively. The expression of Akt and MAPK in stomach and colon was detected by immunohistochemistry. RESULTS:(1) The expression of Akt in the stomach tended to weaker in STC rats comparing with the normal rats (P > 0.05), but it was stronger in STC plus GDNF group than in STC group (P < 0.05). (2) The expression of Akt and MAPK in the colon was weaker in STC group than in the normal group (all P < 0.05), and was stronger in STC plus GDNF group than in STC group (all P < 0.05). (3) The expression of MAPK in the stomach in STC group was weaker than in normal group (P < 0.05), and was stronger in STC plus GDNF group than in STC group (P < 0.01). There was no significant difference among STC plus GDNF group, normal group and GDNF group (P > 0.05). CONCLUSIONS:Long term consumption of rhubarb could induce STC by down-regulating the expression of Akt and MAPK in digestive tract. Exogenous GDNF may have a potential role on the etiology of STC.

OBJECTIVE To investigate the effect of milk and milk products on morphological structure and epidermal growth factor (EGF) of non-steroidal anti-inflammatory drugs (NSAIDs) induced small intestinal damage in animals. METHODS Eighty male SD rats were randomly divided into 5 groups: control group, diclofenac group, diclofenac with 10% low fat milk group, diclofenac with 10% colostrum group and diclofenac with yoghurt group. The animals with milk or colostrum or yoghurt were fed for 5 days before the administration of diclofenac with 15 mg/kg by gavage, once. Then they were observed the scores of anatomical lesion and the scores of tissue damage of mucous membrane and the height of villous at the 24(th) and 48(th) hour after making the models. Observation of the change of ultrastructural organization of mucous membrane was carried out with transmission and scanning electron microscope and immunohistochemistry of EGF. RESULTS The scores of anatomical lesion and tissue damage of mucous membrane of the colostrum group were lower than those of the diclofenac group (P < 0.05). The heights of the pile on small intestine of the 24(th) and 48(th)hour of the colostrum group were (145.7 ± 16.5) µm and (139.2 ± 19.0) µm, respectively. They were higher than those of the diclofenac group [(119.2 ± 19.2) µm and (105.4 ± 18.4) µm, P < 0.05]. However there was no difference of the scores and the height among diclofenac group, milk group and yoghurt group. TEM and SEM of tissues showed that the cytoplasmic membrane and other cellular components of villous epithelial cells were well preserved in colostrum group, and the microvilli in the milk group and yoghurt group were ablated more obviously. The positive area of EGF of small intestine [(6170.5 ± 1483.9) µm(2)] were higher 48 h after administration of diclofenac compared with the diclofenac group (P < 0.05). The expression of EGF in milk and yoghurt group were no significant statistical difference with the diclofenac group. CONCLUSION Bovine colostrum may have a beneficial effect in prevention of NSAIDs induced small intestinal injuries and preserve mechanical barrier of small intestinal mucosa which is probably relative to EGF.

OBJECTIVE:To pool the data of studies and evaluate the efficacy and safety of TNFα blocking agents in the treatment of ulcerative colitis (UC).METHODS:The randomized clinical trials (RCT) that compared the efficacy or safety of TNFα in the treatment of UC were researched from Pubmed, OVID, EMBASE, Cochrane library, CNKI, Wanfang data and VIP Chinese Scientific and Technologic Periodical Database. Statistical heterogeneity between trials was evaluated by Revman 5.0 and was considered to exist when P < 0.1. Heterogeneity of the included articles was tested, which was used to select proper effect model to calculate. Publication bias was investigated through visual inspection of funnel plots.RESULTS:Nine RCT including 1226 cases were analyzed. Eight hundred and six cases had received TNFα treatment and 420 cases had received placebo or glucocorticoid treatment. Compared with placebo or glucocorticoid groups, TNFα group achieved significantly higher rates of short-term clinical response, short-term clinical remission, long-term clinical response, long-term clinical remission and the total OR were 2.36 (95%CI 1.34 - 4.15), 2.42 (95%CI 1.22 - 4.81), 3.22 (95%CI 2.28 - 4.55) and 2.82 (95%CI 1.91 - 4.16) respectively. TNFα group was less likely to undergo colectomy than placebo group and the total OR was 0.31 (95%CI 0.20 - 0.48). TNFα could not improve the mucosal healing and quality of life. No significant difference was found in adverse effect between TNFα group and placebo or glucocorticoid group (OR = 1.07 (95%CI 0.55 - 2.09, P = 0.84)). The rate of serious adverse effect in TNFα group was less than placebo or glucocorticoid groups (OR = 0.65, 95%CI 0.48 - 0.89, P = 0.007). Inspection of the funnel plots for all dichotomous data measures had not revealed evidence of publication bias.CONCLUSIONS:Patients with moderately to severely active UC treated with TNFα have effective clinical response and clinical remission and are less likely to undergo colectomy than those receiving placebo or glucocorticoid. TNFα treatment is safe for UC but can not improve the mucosal healing and quality of life. Large-scale, high-quality RCTs are needed to confirm or refuse the available evidence.

This study was conducted to investigate the effect of tetramethylpyrazine (TMP) on CCl(4)-induced fibrosis in rats and the possible roles of leptin, TGF-beta1, Smad3, and Smad7 in this process. Liver fibrosis in rats was induced by the subcutaneous injection of 60% CCl(4) (0.3 mL /100 g body weight, biweekly ) for 12 weeks. Rats in TMP prevention and treatment groups were given TMP (10 mg /100 g body weight, daily) by gavage from days 1 and 31 after the start of CCl(4) injection, respectively. The mRNA expression of leptin, OB-Rb, TGF-beta1, and TGF-beta RII in the liver were detected by RT-PCR, whereas Smad3 and Smad7 protein were determined by Western blot. The results showed that hepatic cirrhosis was obviously alleviated in both TMP prevention and treatment groups. The mRNA expression of leptin, OB-Rb, TGF-beta1 and -beta RII, and Smad3 protein were higher in the cirrhotic models. In TMP prevention and treatment groups, these markers of expression were higher, compared with that of the normal control, but were lower when compared with that of the cirrhotic model group. Smad7 protein expression was lower in the cirrhotic model group than in the normal control. Smad7 expression in TMP prevention and treatment groups was higher, compared with that in the cirrhotic model group. Liver collagen in the TMP prevention group was the lowest among all CCl(4) injection groups. In conclusion, TMP can prevent and alleviate the development of liver fibrosis in rats. The possible mechanism could involve the downregulation of leptin, Ob-Rb, TGF-beta1, TGF-beta RII, and Samd3, and upregulation of Smad7.

OBJECTIVE:To investigate the distribution and expression of glial cell line-derived neutrophil factor(GDNF)in colon of slow transit constipation (STC) rats and the effect of exogenous GDNF on colon transit. METHODS:Forty-eight SD rats were divided randomly into controlled group and model group. The models were established by gastric irrigation of rhubarb for 3.5 months. The control group received normal saline. The models were successfully established and then the rats were divided randomly into four groups. They were a normal group, GDNF group, STC model group and a STC models plus GDNF group. Half of the rats in model and control group were administrated with exogenous GDNF intravenously for one week. The expression of GDNF and GDNF-mRNA in colon was detected with immunohistochemistry and RT-PCR. The colon transmit speed was measured with Chinese ink driving test. RESULTS:The colon transmit of the STC model group, the normal group, the STC models plus GDNF group and GDNF group were (60.00 +/- 5.62)%, (74.44 +/- 2.19)%, (74.67 +/- 7.07)% and (88.54 +/- 3.22)%. There was significant difference between the normal group and the STC model group (P < 0.01) as well as the STC models plus GDNF group and the STC model group (P < 0.01). The expression of GDNF with reverse transcriptase PCR in the STC model group, the normal group and the STC models plus GDNF group was 1.38, 2.29 and 2.21 respectively, with significant difference between the STC models and the normal group (P = 0.01) and between the STC models and the STC models plus GDNF group (P = 0.017). However, there was no significant difference between the normal group and the STC models plus GDNF group (P > 0.05). CONCLUSIONS:The down regulation of GDNF in colon may play an important role in pathogenesis of STC. Exogenous GDNF may improve the colon motor function by up-regulation of GDNF.

OBJECTIVE To approach the effect on mechanical barricade of the mucous membrane of small intestine caused by non-steroidal anti-inflammatory drugs (NSAIDs). METHODS Thirty-two male SD rats were randomly divided into control group and model group. The rats of the model group were given 7.5 mg/kg diclofenac by gavage, bid; the rats of the control group were given the same dose of saline. Then they were further randomly divided into two subgroups (n=8) at the first day and the fifth day after making the models to observe the scores of anatomical lesion on stomach and small intestine and the scores of tissue damage of mucous membrane and to quantitatively analyze the height of villi, as well as the thickness and the section area of mucous membrane with Carl Zeiss Imaging Systems. Observation of the change of ultrastructural organization of mucous membrane was carried out with transmission electron microscope. RESULTS The mucous membrane of stomach of the model groups was slightly edematous. There was no difference between the scores of the model groups and control groups. It was seen that the mucous membrane of small intestine of the first day model group presented with erythema, amaurosis and ulcer. The ulcer was distributed along mesentery. The mucous membrane of small intestine of the fifth day model group showed bleeding, perforation and sinus tract formation, and the scores of anatomical lesion was higher than that of the control group (P < 0.05). The scores of the lesions of the first and fifth day model groups were 3.5 and 5.0. The difference had statistical significance when compared with those of the control groups (the scores were 0) (P < 0.05). Cell degeneration and cellular necrosis of epithelial mucosa of small intestine was also seen in the first day model group. The top of villi was ablated. The height of the pile on jejunum was (126.9 +/- 32.0) microm and that on ileum was (118.6 +/- 22.9) microm. They were lower than those of the control group (P < 0.05). However there was no difference of the thickness and section area between them, but the thickness and section area showed a tendency of decrease. It was also seen that there were apomorphosis and sphacelism of epithelial cells in the fifth day model group. Some villi were ablated and laminae propria exposed. The height of villi on jejunum [(73.4 +/- 25.4) microm] and that on ileum [(109.3 +/- 17.6) microm] decreased significantly. The thickness of mucous membrane [(123.8 +/- 51.6) microm and (165.7 +/- 37.4) microm] decreased and the section area [(2.48 +/- 1.01) mm2 and (3.27 +/- 0.76) mm2] became smaller (P < 0.05 vs. control group). The mucous membrane of the villi on small intestine was continuous but arranged disorderly. Cytochondriome swelled, endocytoplasmic reticulin expanded with different degrees, intercellular junction widened partly. The microvilli in the fifth day model group were ablated more obviously and intercellular junctions were broken and destroyed gravely. CONCLUSIONS Diclofenac can cause damage to the function of mucous membrane barricade of small intestine. It could also lead to shortening of the villi, thinning of the mucous membrane, ablation of the microvilli, and widening of the tight intercellular junction as the characteristic morphological change.

OBJECTIVE:To compare the effectiveness and safety of radiofrequency ablation (RFA) with other therapeutic methods for patients with early hepatocellular carcinoma (HCC). METHODS:Randomized clinical trials (RCTs) which compared the efficacy or safety of RFA with other therapeutic methods for primary hepatocellular carcinoma in Cochrane library, EMBASE, PubMed, OVID and CBM were searched. Trials were considered of high quality if methodological quality score was 3 or more according to Jadad standard. Statistical heterogeneity between trials was evaluated by STATA 9.0 and considered to exist when P < 0.1. Heterogeneity of the included articles was tested and used to select proper effective model for calculation. Sensitivity analysis was performed and publication bias was investigated through visual inspection of funnel plots and Egger regression model. RESULTS:Six RCTs including 862 cases were analyzed. As compared with other therapeutic approaches, RFA significantly increased 3-year overall survival rate and reduced local recurrence rate of early hepatocellular carcinoma; the total OR were 2.06 (95% CI being 1.54-2.77, P = 0.000) and 0.40 (95% CI being 0.28-0.57, P = 0.000) respectively. As compared with other therapeutic approaches, the total OR of new HCC recurrence rates, extrahepatic metastasis rate and major complications in patients with HCC treated with RFA were 0.92 (95% CI being 0.68-1.24), 0.98 (95% CI being 0.30-3.22), 1.35 (95% CI being 0.49-3.77) respectively, showing no significant differences (P > 0.05). Inspection of the funnel plots for all outcome measures did not reveal evidence of publication bias (P = 0.670, 0.160, 0.884, 0.087, 0.317, respectively, by Egger regression model). CONCLUSIONS:RFA is superior to other treatment methods with respect to local recurrence and 3 year overall survival in early HCC and is the preferred therapeutic method for small HCC because it is minimally invasive, simple and convenient.