Functional bowel disorders (FBD) refer to a set of bowel symptoms related to the disorders of sensation, secretion and motility yet without a corresponding structural, histological, biochemical, or serological abnormalities.The pathogensesis of FBD is still not very clear.Whether these functional disorders reflect the inadequacy of our understanding of a disease or the limitation of our diagnostic testing is a question.With the development of the biomedical technology, some histological or biochemical changes were revealed, which supported the possibility that organic abnormality might exist in FBD.In this paper the progress of research on organic changes of irritable bowel syndrome and functional constipation was reviewed.

Objective To observe the role of brain-derived neurotrophic factor (BDNF) in the plasticity of enteric nervous-smooth muscle system,and to investigate the effects of BDNF induced plasticity on gastrointestinal motility in mice.Methods Male hybrid BDNF knockout (BDNF+/) mice and wild type (BDNF+/+) mice were selected,eight in each group.Gastrointestinal motility of BDNF+/+ mice and BDNF+/ mice were tested and compared.Longitudinal muscle strips of mice colon smooth muscle were prepared.The effects of carbachol (1 × 10 5 mol/L) and BDNF (1 × 10 7 mol/L) on contractile function of muscle strips were observed.And the effects of tetrodotoxin (TTX,1 × 10-6 mol/L) on BDNF induced contractile function of muscle strips were also studied.The changes of the density of mice intestinal myenteric plexus and the expression of smooth muscle α-actin (α-SMA) in colon smooth muscle were detected by immunohistochemical techniqne.The ultrastruetural alterations of myenteric plexus,neuromuscular junction (NMJ) and smooth muscle cells were detected by transmission electron microscope (TEM).T-test or Rank sum test was performed for comparison between groups.Results Number of feces particles and water content in feces of BDNF+/-mice ((3.80±0.75) and (39.60±1.47)％) were both lower than those of BDNF+/+ mice ((6.30± 1.03) and (51.00± 1.61) ％),and the differences were statistically significant (t=4.792,12.827;both P＜0.05).Carbachol (1 × 10-5 mol/L) could significantly increase contraction activity of smooth muscle of BDNF+/+ mice (R =3.26 ± 0.43) and BDNF+/-mice (R=2.15 ± 0.36),and the difference was statistically significant (t=15.754,9.632;both P＜0.05).The effects on contraction exciting of smooth muscle strips of BDNF+/+ mice were more significant than BDNF+/ mice,and the difference was statistically significant (t =5.972,P＜0.05).BDNF could significantly increase contraction of muscle strips of BDNF+/+ mice and R value increased from 1 to 1.41±0.09,and the differences were statistically significant (t=13.674,P＜0.05).TTX could obviously inhibit the excitatory effects of BDNF,R value decreased from 1.41 ± 0.09 to 1.03 ± 0.04 (t=11.692,P＜0.05).The density of myenteric plexus of BDNF+/ mice (median 5.8％,interquartile range 4.2％-7.0％) was significantly lower than that of BDNF+/+ mice (median 9.0％,interquartile range 7.1％-10.8％),and the difference was statistically significant (Z =3.730,P＜ 0.05).The expression of α-SMA of BDNF+/-mice (median 33.4％,interquartile range 28.8％-38.5％) was significantly lower than that of BDNF+/+ mice (median 44.6％,interquartile range 39.2％-48.8％),and the difference was statistically significant (Z=4.565,P＜0.05).The results of TEM indicated ultrastructural alterations of myenteric plexus,NMJ and smooth muscle in BDNF+/-mice.Conelusionss BDNF could induce the plasticity of morphology and function in enteric nervous-smooth muscle system,which may play an important role in mice gastrointestinal motility.

Objective To investigate the correlation between the expression changes of brain-derived neurotrophic factor (BDNF) in colon mucosa and abdominal pain in irritable bowel syndrome (IBS). The density of nerve fiber in colon mucosa and ultrastructural alterations of nerve fiber in IBS were also observed. Methods From September 2008 to January 2010,the IBS patients who visited the department of gastroenterology of our hospital and met the Rome Ⅲ diagnosis criteria were selected and divided into IBS with diarrhea (D-IBS) and IBS with constipation (C-IBS) according to their clinical features. The patients with colon polyps detected by colonoscopy in our hospital were selected as control group. All subjects were asked to fill in Self-Rating abdominal pain or abdominal uncomfortable Scale according to abdominal symptom in the last 2 weeks before visit and underwent colonoscopy. Four biopsy specimens were taken from the colon mucosa of rectosigmoid junction. Ofwhich,two specimens were for protein isolation and detection of BDNF expression level,one specimen was used for PGP 9. 5 immunohistochemistry staining in paraffin slices. Another specimen was used to observe the ultrastructure changes of nerve fiber in colon mucosa under transmission electron microscopy. Results Total 40 IBS patients were enrolled in this study,of those 21 were D-IBS patients,19 were C-IBS patients,and 21 were controls. The abdominal pain severity score and frequency score of IBS patients were (2. 3±0. 8) and (2. 1±0. 7),which were significantly higher than those of control group (0. 4±0. 7 and 0. 3±0. 5,P＜0. 001). Compared with the control group,the BDNF expression in colon mucosa was significantly elevated in IBS patients (P= 0. 003 ),and which correlated with the severity and frequency of abdominal pain/discomfort (r=0. 57,P＜0. 001and r=0. 46,P= 0. 003,respectively). The immunohistochemistry result indicated that the nerve fiber density in colon mucosa of IBS patients was significantly higher than that of controls,and there were ultrastructural changes of colon mucosal nerve fibers in IBS patients. Conclusion Increased colon mucosal BDNF expression may be associated with abdominal pain symptom in IBS patients. The impaired ultrastructural of mucosal nerve fibers may cause the increased BDNF expression in colon mucosa,and result in the increased mucosal nerve fiber density in IBS patients.

Objective To investigate possible disturbance of Th1/Th2 immunoregulation of large intestinal mucosa in patients with irritable bowel syndrome (IBS). Methods Mucosal specimens were harvested from ascending, descending colon and rectum by colonoscopy in 58 patients with IBS and 20 healthy controls. The expressions of Th1 and Th2 cytokines were determined by immunohistochemical staining. Results The large intestinal mucosa of patients with IBS were general normal both under colonoscopy and conventional histological assessment on hemotoxylin and eosin stained (H E) sections. Compared with controls, the expressions of Th1 cytokine (IFN ?) in the ascending, descending colon and rectum were significantly increased in diarrhea predominant IBS (D IBS) patients. The expression of interleukin 12 (IL 12) in the rectum was also significantly increased. However, the expressions of Th2 cytokines (IL 10)) in D IBS patients were decreased, but no significant difference compared with controls. The expressions of IFN ? in post infection IBS (pIBS) patients were increased significantly compared with controls among D IBS patients. Besides, IL 12 in the ascending colon and rectum were significantly increased. The expressions of IL 4 and IL 10 in pIBS patients were decreased, but no significant difference compared with controls. The expressions of Th1 and Th2 cytokines in non pIBS patients have no significant difference compared with controls. In constipation predominant IBS (C IBS) patients, the expressions of Th1 and Th2 cytokines had no statistical difference compared with controls. Conclusions The shift of Th1/Th2 balance of colon and rectal mucosa in D IBS patients was demonstrated along with the enhanced Th1 activity. Infection affected the shift of Th1/Th2 balance in D IBS patients. Th1/Th2 balance has been maintained in C IBS patients.

Objective To investigate the assessment methods and mechanisms of nonsteroidal antiinflammatory drugs (NSAID)-induced injury in rat small intestinal epithelial barrier,and to explore the protective effects of mucosal protective agents and antacids on it.Methods A total of 96 rats were evenly divided into the morphologic observation group and the mechanism research group,and 48 in each group.Then each group was evenly divided into eight subgroups:the healthy control group,the model group (model established with indomethacin),the teprenone prevention group,the rabeprazole prevention group,the treatment control group,the teprenone treatment group,the rabeprazole treatment group and the teprenone and rabeprazole combined group (combined group),six in each group.Exfoliated cells gap density of small intestine of each subgroup was determined by confocal laser endomicroscopy.Serum level of tumor necrosis factor-α (TNF-α)was measured with enzyme-linked immunosorbent assay (ELISA). The expression of nuclear factor-κB (NF-κB),caspase-3,zonula occludens-1 (ZO-1 )and occludin at protein level was detected by Western blotting.The LSD-t test or Hamhane′s T2 test was performed for statistical analysis.Results The exfoliated cells gap densities of the teprenone prevention group and the rabeprazole prevention group were (57.43 ± 24.55 )/1 000 and (59.80 ± 21 .14 )/1 000,respectively, which were both lower than that of the model group ((110.93±50.58)/1 000),and the differences were statistically significant (t= 53.50 and 54.13,both P < 0.01 ).The exfoliated cells gap density of the combined group was (40.53 ±15 .39)/1 000,which was lower than that of the treatment control group ((93.80±40.65 )/1 000 ),and the difference was statistically significant (t =44.27,P <0.01 ).The serum levels of TNF-α of the teprenone prevention group and the rabeprazole prevention group were (25 .80±8.97)ng/L and (22.74 ±7.15 )ng/L,repsectively,which were both lower than that of the model group ((44.48 ± 7.42 )ng/L),and the differences were statistically significant (t = 18.68 and 21 .74,both P <0.01 ).The serum level of TNF-αof the combined group ((13.66 ±4.98)ng/L)was lower than that of the treatment control group ((24.67±6.70)ng/L),and the difference was statistically significant (t = 9.02,P < 0.01 ).The caspase-3 levels of teprenone prevention group and rabeprazole prevention group were 1 .47 ±0.35 and 1 .58 ±0.34,and the NF-κB levels of these two groups were 1 .27±0.14 and 1 .21 ± 0.10,respectively.Compared with those of model group (2.44 ± 0.45 and 1 .69±0.13),the differences were statistically significant (t =0.97,0.86,0.42 and 0.48,respectively, all P <0.01 ).The levels of caspase-3 and NF-κB of the combined group were 0.66±0.06 and 0.44 ± 0.21 ,respectively,which were lower than those of the treatment control group,and the differences were statistically significant (t=0.34 and 0.56,both P <0.01).The expressions of occludin at protein level of the teprenone prevention group and the rabeprazole prevention group were 0.69 ±0.16 and 0.74 ±0.11 , and the levels of ZO-1 were 0.81 ± 0.08 and 0.84 ± 0.12.Compared with those of the model group (0.45 ±0.22 and 0.64±0.07 ),the differences were statistically significant (t =0.24,0.29,0.17 and 0.21 ,respectively,all P <0.01 ).The levels of occludin and ZO-1 of the combined group were 2.50 ± 0.46 and 1 .76±0.18,which were higher than those of the treatment control group,and the differences were statistically significant (t =1 .50 and 0.76,both P <0.01 ).Conclusions The exfoliated cells gap density may be a valuable indicator to predict the degree of inflammation response and permeability of epithelial barrier as well as to evaluate efficacy of medication.Teprenone and rabeprazole have prevention and treatment effects on NSAID-induced injury in rat small intestine.

Objective To study the efficacy and safety of oral calcium carbonate suspension and proton pump inhibitors (PPI) in symptoms relief of acid related diseases.Methods The multi-center,randomized and controlled study was carried out.A total of 400 acid-related diseases patients from 14 to 70 years old with at least one of moderate or severe symptoms such as acid regurgitation,epigastric pain,epigastric discomfort,upper abdominal burning or distension were equally divided into two groups and treated with oral calcium carbonate suspension or omeprazole enteric-coated tablets.The onset of symptoms relief of all patients of the first time after taking medicine was observed.The relief of clinical symptoms at the third day and seventh day after taking medicine was also observed.The adverse events were recorded.Analysis of variance was performed for statistical analysis.Results The onset of symptoms relief of oral calcium carbonate suspension group in acid regurgitation,epigastric pain,epigastric discomfort,upper abdominal burning or distension of the first time after taking medicine were significantly faster than those of PPI group (F=4.866,8.142,41.366,6.955,35.252; all P＜0.05).At the third day after taking medicine,the treatment efficiency of oral calcium carbonate suspension group and PPI group were 69.50％ and 72.50％,and at the seventh day the treatment efficiency of oral calcium carbonate suspension group and PPI group were 92.00％ and 96.50％.There was no significant difference in treatment efficiency and comprehensive efficacy between two groups at day three and seven after taking medicine (both P＞ 0.05).There were 14 cases of mild adverse events and two cases of moderate adverse events in oral calcium carbonate suspension group.There were 10 cases of mild adverse events in PPI group.There was no significant difference between two groups (P＞0.05).Conclusion Oral calcium carbonate suspension provides faster symptom relief than PPI and can effectively improve the symptoms of acid-related diseases.

Objective To study the feature of regional cerebral metabolism rate of glucose (rCMRglc) in patients with Alzheimer’s disease (AD) and the value of positron emission tomography (PET) scanning in diagnosis of AD. Methods 13 AD patients and 13 health controls ,Who matched in age,sex and education years,were scanned with PET. Results (1) Watching by naked eyes,there was mild decreasing of rCMRglc at parietal lobe in healthy elders. While in AD patients,there was widely decreasing of cerebral metabolism rate of glucose. The most significant region was parietal lobe, the next was temporal lobe,and the last was frontal lobe. (2) Detecting with PET and dealing with statistical parametric mapping (SPM) of 99 software,there was more significant decreasing of rCMRglc in regions 7,23,30,31 of cingulate gyrus,region 39 and 40 of pario-occipital lobe,region 20 of temporal lobe and region 6,8,9 of frontal lobe in AD group( P

Objective To investigate the value of fluorescin-aided confocal laser endomicroscopy (CLE) for diagnosis of helicobacter pylori (Hp) infection. Methods From June 2009 to November 2009, patients undergone gastric endoscope examination with upper gastrointestinal symptoms (upper abdominal discomfort, abdominal distension, satiation, acid reflux and eructation) or screened for gastric cancer were enrolled. The gastric mucosa CLE image data of twenty diagnosed Hp positive patients and 10 Hp negative patients was analyzed retrospectively. By comparing with histological image of targeted biopsy tissue, the CLE diagnostic criteria for Hp infection were established. In the prospective study, CLE diagnose result was compared with Hp tested result. The consistency of CLE diagnostic criteria in different observers was also analyzed. The CLE image data with histopathology result were compared accordingly. Results Total 72 patients were enrolled in the prospective study,of 34 Hp positive patients, 31 patients were correctly diagnosed by CLE. The accuracy, sensitivity and specificity of CLE diagnosis were 88.9%, 91.2 and 86.8% respectively. CLE image displaying fluorescin leakage and cell shedding was the highest specificity for Hp infection diagnosis, (97.4 %);fluorescin leakage plus gastric pits distortion and cell edema was the highest sensitivity (88. 2%). The consistency of CLE diagnostic criteria in different observers was high (Kappa value 0. 72, 0.87). The CLE image of Hp infection was highly correlated with inflammation activity (P＜0. 001). Conclusion CLE can accurately distinguish normal mucosa from Hp infected mucosa at the cellular level. The diagnostic value for Hp infection was reliable.

Objective To assess the value of confocal laser endomieroscopy (CLE) in diagnosis of early esophageal squamous cell carcinoma and precancerous lesions. Methods CLE examination was performed in 41 patients who needed further examination because of lesions in esophagus during July 2008 to April 2009. The diagnosis was made based on the features of esophageal squamous cells which was defined as low grade intraepithelial neoplasia(LGIN), high grade intraepithelial neoplasia (HGIN) and early esophageal squamous cell carcinoma (EC). Biopsy specimens were taken precisely matched to the CLE imaging sites. The result was compared with that of histopathology. Results There were 7281 eonfocal images obtained from 60 target lesions in 41 patients. The sensitivity, specificity and accuracy of CLE were 75.0%, 88.6% and 85.0% in diagnosis of LGIN, respectively, 85.7% ,92.3% and 90.0% in diagnosis of HGIN, respectively,and 88.9% ,96.1% and 95.0%, in diagnosis of EC,respectively. Conclusions It is an effective method for diagnosis of esophageal neoplastic lesions using CLE, which has high accuracy in diagnosis of HGIN and early esophageal cancer.

Objective To evaluate the feasibility of needle-based confocal laser endomicroscopy (nCLE) for imaging of intra-abdominal tissues and organs in rabbit models in vivo. Methods The nCLE miniprobe was inserted through the 19-gauge needle into various intra-abdominal tissues and organs[omentum majus, liver, pancreas and psoas major (skeletal muscle)]. The nCLE images were acquired and real-time sequences of respective locations were recorded. Finally, nCLE image characteristics were compared with histopathologic findings. Results nCLE was successfully performed in intra-abdominal tissues and organs of five rabbit models. The microscopic structures of cells, glands and microvessels in the omentum majus, liver, pancreas and psoas major ( skeletal muscle) were visualized clearly, respectively. Characteristics of various intra-abdominal tissues and organs were displayed on nCLE images, which were correlated well with histological findings. Conclusion Imaging of intra-abdominal tissues and organs with nCLE in vivo is feasible in future clinical practice.