Role of artificial intelligence in Crohn's disease intestinal strictures and fibrosis.

Crohn's disease (CD) is a chronic inflammatory disorder of the gastrointestinal tract. Intestinal fibrosis or stricture is one of the most prevalent complications in CD with a high recurrence rate. Manual examination of intestinal fibrosis or stricture by physicians may be biased or inefficient. A rapid development of artificial intelligence (AI) technique in recent years facilitates the detection of existing or possible intestinal fibrosis and stricture in CD through various modalities, including endoscopy, imaging examination, and serological biomarkers. We reviewed the articles on AI application in diagnosing intestinal fibrosis and stricture in CD during the past decade and categorized them into three aspects based on the detection methods, and found that AI helps accurate and expedient identification and prediction of intestinal fibrosis and stenosis in CD.

Clinical guideline on magnetically controlled capsule gastroscopy (2021 edition).

With the development and generalization of endoscopic technology and screening, clinical application of magnetically controlled capsule gastroscopy (MCCG) has been increasing. In recent years, various types of MCCG are used globally. Therefore, establishing relevant guidelines on MCCG is of great significance. The current guidelines containing 23 statements were established based on clinical evidence and expert opinions, mainly focus on aspects including definition and diagnostic accuracy, application population, technical optimization, inspection process, and quality control of MCCG. The level of evidence and strength of recommendations were evaluated. The guidelines are expected to guide the standardized application and scientific innovation of MCCG for the reference of clinicians.

[Effects of zhizhu tongbian decoction on the colon ink propelling rate, GDNF, and NOS mRNA expression in rats with slow transit constipation].

OBJECTIVE: To observe the effects of Zhizhu Tongbian Decoction (ZTD) on the enteric nervous system, mRNA expressions of glial cell line derived neurotrophic factor (GDNF) and nitric oxide synthase (NOS) in the slow transit constipation (STC) rats. METHODS: Thirty STC rat model was established by gastric irrigation of rhubarb. After the model building, they were randomly divided into three groups, i. e., the model group, the high dose ZTD group, and the low dose ZTD group, 10 in each. Another 10 rats were selected as the blank control group. Rats in the high dose ZTD group and the low dose ZTD group were administered with ZTD (at the daily dose of crude drug 4.8 g/kg and 2.4 g/kg respectively) by gastrogavage. Normal saline was given to rats in the blank control group and the model group. The ink propelling rate was determined using ink propelling test. Meantime, mRNA expressions of GDNF and NOS in the rat colon were measured using reverse transcriptional polymerase chain reaction (RT-PCR). RESULTS: Compared with the blank control group, the ink propelling rate and GDNF mRNA expression decreased, and NOS mRNA increased in the model group, showing statistical difference (P<0.01, P<0.05). Compared with the model group, the ink propelling rate increased in the high and low dose ZTD groups (P<0.01, P<0.05). The mRNA expressions of GDNF increased and the mRNA expressions of NOS decreased in the high dose ZTD group with statistical difference (P<0.01, P<0.05). But there was no difference in any index between the high and low dose ZTD groups. CONCLUSION: High dose ZTD could obviously improve the intestinal transmission function possibly through up-regulating the mRNA expressions of GDNF and down-regulating the mRNA expressions of NOS in STC rats.

[Treatment of functional dyspepsia by Chinese medical syndrome typing: a randomized control research].

OBJECTIVE: To assess the short- and long-term efficacy and safety of treating functional dyspepsia (FD) by Chinese medical syndrome typing (CMST). METHODS: A randomized, positive-drug parallel controlled study was conducted. Recruited were 170 FD patients who were randomly assigned to the test group (13 cases, treated by Chinese herbs) and the control group (34 cases, treated by Western medicine) in the ratio of 4:1. Different recipes were administered to patients in the test group according to CMST at the 1st, 2nd, and 4th week, respectively, while those in the control group took Domperidone or Esomeprazole Magnesium Enteric-coated Tablet according to Roma III Criteria. The therapeutic efficacy was observed at the 1st, 2nd, and 4th week of the treatment, including (1) clinical symptom score; (2) the score of SF-36 quality of life scale; (3) safety (4) compliance; (5) satisfaction; (6) the relapse rate; (7) cost-effectiveness ratio (C/E). The follow-up were performed at the 1st, 3rd, and 6th month. RESULTS: Sixteen patients fell off in the test group and 4 fell off i the control group, and the expulsion rate being 11.76% in the two groups, showing no statistical difference ( P > 0.05). The clinical symptom scores in the test group decreased from 5.62 +/- 2.30 before treatment to 1.41 +/- 1.22 after 4-week treatment, showing statistical difference (P < 0.01), but with no statistical difference when compared with the control group at the same time point (P>0.05). The healing rate and the total effective rate at week 4 were 38.24% and 86.76% respectively in the test group, and they were 60.00% and 65.00% at 6-month withdrawal. They were 41.18%, 79.41%, 46.67%, and 50.00%, respectively, in the control group. There was no statistical difference between the two groups (P>0.05). The scores of physical component-summary (PCS) and mental component-summary (MCS) both increased after 4-week treatment in the two groups, showing no statistical difference when compared with before treatment (P>0.05). There was statistical difference in the scores of PCS and MCS between at 6-month withdrawal and before treatment (P<0.05), but there was no statistical difference between the two groups (P>0.05). No obvious adverse reaction occurred in the two groups. The compliance and satisfaction after 4-week treatment were 95.59% and 91.91% in the test group, and 94.12% and 91.18% in the control group, showing no statistical difference between the two groups (P>0.05). The relapse rate in the test group was 10.29%, 19.12%, and 29.41%, respectively, after 1, 3, 6-month withdrawal, lower than that of the control group (17.65%, 23.53%, and 35.29%, respectively) at the same time point, but with no statistical difference. The C/E ratio of the test group/the control group was 15.59: 16. 53 at 4-week treatment and 22.27:28.28 after 6-month withdrawal respectively. The further analysis of incremental cost/incremental effectiveness showed that the ratio in the long-term decreased from 5.44 to 2.35 in the test group. CONCLUSIONS: The 4-week treatment of CMST had definite short- and long-term efficacy on FD patients, and improved their quality of life. It had better safety, compliance, and satisfaction. It was dominant in lower relapse rate and the cost/effectiveness. Therefore, it was worth spreading.

CD8-positive indolent T-Cell lymphoproliferative disorder of the gastrointestinal tract: A case report and review of literature.

BACKGROUND: Indolent T-cell lymphoproliferative disorder of the gastrointestinal tract (ITLPD-GI), a primary tumor forming in the gastrointestinal (GI) tract, represents a rarely diagnosed clonal T-cell disease with a protracted clinical course. CASE SUMMARY: This report presented a 45-year-old male patient with a 6-year history of anal fistula and a more than 10-year history of recurrent diarrhea who was not correctly diagnosed until the occurrence of complications such as intestinal perforation. Postsurgical histopathological analysis, combined with hematoxylin-eosin staining, immunohistochemistry and TCRß/γ clonal gene rearrangement test, confirmed the diagnosis of CD8+ ITLPD-GI. CONCLUSION: Individuals with this scarce lymphoma frequently show non-specific symptoms that are hard to recognize. So far, indolent CD8+ ITLPD-GI has not been comprehensively examined. The current mini-review focused on evaluating indolent CD8+ ITLPD-GI cases based on existing literature and discussing future directions for improved differential diagnosis, detection of genetic and epigenetic alterations, and therapeutic target identification.

Infliximab trough level combined with inflammatory biomarkers predict long-term endoscopic outcomes in Crohn's disease under infliximab therapy.

BACKGROUND: Infliximab trough level (ITL) severely affects therapeutic outcomes of Crohn's disease (CD) patients under infliximab (IFX). Recently, frontier research has focused on identifying ITL based on different therapeutic targets. Although previous studies have elaborated clinical value of ITL monitoring on short-term outcomes in CD patients during therapy, studies contraposing the predictive value of ITL on long-term endoscopic outcomes in CD patients are still scarce domestically and overseas. AIM: To explore the predictive value of ITL in combination with inflammatory biomarkers on long-term endoscopic outcomes in CD with clinical remission during IFX maintenance therapy. METHODS: CD patients with endoscopic remission under long-term IFX maintenance therapy in the First Affiliated Hospital of Zhejiang Chinese Medicine University from January 2012 to December 2020 were collected. ITL and inflammatory biomarkers were continuously monitored during the therapy. The Step I study was conducted from weeks 14 to 54 of IFX treatment. The Step II study was conducted from weeks 54 to 108 of IFX treatment. Endoscopic outcomes were defined as endoscopic activity (Crohn's disease endoscopic index of severity score > 2 points or Rutgeerts score > i1) and endoscopic remission (Crohn's disease endoscopic index of severity score ≤ 2 points or Rutgeerts ≤ i1). Endoscopic relapse free survival was defined as endoscopic remission at the beginning of the study stage and maintaining endoscopic remission during the study stage. RESULTS: At week 14, low ITL [odds ratio (OR) = 0.666, 95% confidence interval (CI): 0.514-0.862, P < 0.01] and high fecal calprotectin (FCP) level (OR = 1.002, 95%CI: 1.001-1.004, P < 0.01) increased the risk of endoscopic activity at week 54. At week 54, low ITL (OR = 0.466, 95%CI: 0.247-0.877, P < 0.01) and high C-reactive protein (CRP) level (OR = 1.590, 95%CI: 1.007-2.510, P < 0.01) increased the risk of endoscopic activity at week 108. At week 14, ITL ≤ 5.60 µg/mL [area under the curve (AUC) = 0.83, 95%CI: 0.73-0.90, P < 0.001] and FCP > 238 µg/g (AUC = 0.82, 95%CI: 0.72-0.89, P < 0.001) moderately predicted endoscopic activity at week 54. ITL ≤ 5.60 µg/mL in combination with FCP > 238 µg/g indicated 82.0% possibility of endoscopic activity. At week 54, ITL ≤ 2.10 µg/mL (AUC = 0.85, 95%CI: 0.72-0.93, P < 0.001) and CRP > 3.00 mg/L (AUC = 0.73, 95%CI: 0.60-0.84, P = 0.012) moderately predicted moderate endoscopic activity at week 108. ITL ≤ 2.10 µg/mL in combination with CRP > 3.00 mg/L indicated 100.0% possibility of endoscopic activity. From weeks 14 to 54 of IFX treatment, patients with ITL > 5.60 µg/mL had higher rate of endoscopic relapse free survival than those with ITL ≤ 5.60 µg/mL (95.83% vs 46.67%). From weeks 54 to 108 of IFX treatment, patients with ITL > 2.10 µg/mL had higher rate of endoscopic survival free relapsed rate than those with ITL ≤ 2.10 µg/mL (92.68% vs 30.77%). CONCLUSION: Combination of ITL, CRP, and FCP contribute to long-term endoscopic prognosis monitoring. During IFX maintenance treatment, low ITL, high CRP level, and high FCP level were independent risk factors of CD patients with clinical remission in adverse endoscopy outcomes within 1-year follow-up.

Efficacy and safety of vibrating capsule for functional constipation (VICONS): A randomised, double-blind, placebo-controlled, multicenter trial.

Background: Functional constipation (FC) is an intractable disease that carries large financial burden as well as emotional and physical stress. We aimed to assess the efficacy and safety of the newly developed smartphone-controlled vibrating capsule (VC) in patients with FC. Methods: From December 2018 to February 2020, we did a multicenter, blinded, placebo-controlled randomised trial in six top general hospitals in China focusing on patients aged 18 to 80 with FC. Patients were randomly assigned in a 1:1 ratio to receive VCs or placebo treatment for six weeks (two capsules per week) after a two-week baseline period. The primary outcome was the responder rate, defined as the proportion of patients with an increase of at least one complete spontaneous bowel movement (CSBM) per week during treatment compared to baseline in the full analysis set. This trial is registered with ClinicalTrials.gov, number NCT04671264, and is completed. Findings: 107 patients aged from 18 to 74 were randomly assigned to receive VC (n = 53) or placebo treatment (n = 54). The responder rate in the VC group was significantly higher than that in the placebo group (64·2% vs. 35·8%; difference, 27·7% [95% CI, 10·4-45·1]; P = 0·005). More patients in the VC group reported weekly CSBMs ≥ 1 for at least four weeks during treatment (difference, 22·7% [95% CI, 8-46]; P = 0·022) and follow-up period (difference, 17.3% [95% CI, 0-35]; P = 0·048). The mean Patient Assessment of Constipation-Symptoms score and Patient Assessment of Constipation-Quality of Life score differed significantly from the baseline in both groups (all P < 0·0001). The most common adverse event associated with VC was abdominal discomfort (3·7%). Interpretation: VCs can promote defecation, as well as ameliorating symptoms and improving the quality of life in patients with FC with sustained efficacy. VC appears to be a potential alternative physical treatment for FC with the exact mechanism and parameters warranting further investigation. Funding: The study was supported by "One hundred leading scientists for 21st century" of Health Department of Shanghai Municipal Government (to ZL, No.2017BR005).

[The effect of exogenous glial cell line-derived neurotrophic factor on expression of gastric and colonic Akt, MAPK in slow transit constipation rats].

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.

Clinical Value of Fecal Calprotectin in Predicting Mucosal Healing in Patients With Ulcerative Colitis.

Aim: This study aimed to evaluate the clinical significance of fecal calprotectin (FC) in assessment of ulcerative colitis (UC) patients' endoscopic patterns and clinical manifestation. Methods: A total of 143 UC patients who received colonoscopy and 108 controls were included. After providing stool samples, patients underwent total colonoscopy. FC was measured by an enzyme-linked immunosorbent assay (ELISA). Clinical activity was based on the Mayo score. Endoscopic findings was scored by the Ulcerative Colitis Endoscopic Index of Severity (UCEIS). Correlation analysis and receiver-operator characteristic (ROC) analysis were carried out to determine the significance of measurements. Results: The median (interquartile range, IQR) of FC levels was 211 (43-990) µg/g in UC and 87.5 (40.50~181) µg/g in the control group. Fecal calprotectin correlated significantly with both Mayo and UCEIS scores (Spearman's r 0.670 and 0.592, P < 0.01). With a cut-off value of 164 µg/g for fecal calprotectin concentration, the area under the curve (AUC) in receiver operator characteristic analysis was 0.830, sensitivity was 85.42%, specificity was 73.68%, positive predictive value (PPV) was 62.12%, and negative predictive value (NPV) was 9.10% in predicting clinical active disease. Similarly, the power of FC to predict mucosal healing (MH) was modest. With a cut-off value of 154.5 µg/g, the AUC was 0.839, sensitivity was 72.34%, and specificity was 85.71%. Conclusion: For evaluating the disease activity of UC, FC is a clinically relevant biomarker for both clinically active disease and MH in patients with UC. But the cut-off value still needs large and multicenter studies for confirmation.

Fatigue in patients with inflammatory bowel disease in Eastern China.

BACKGROUND: Fatigue is a very common but relatively neglected problem in patients with inflammatory bowel disease (IBD). The prevalence rate of IBD in China is the highest in Asia, but there is little research on fatigue in patients with IBD. Neither the relationship between fatigue and quality of life (QoL) nor the relationship between fatigue and work productivity (WP) in Chinese IBD patients has been reported. AIM: To investigate the prevalence of fatigue related to IBD in Eastern China, to identify the risk factors associated with fatigue, to assess the impact of fatigue on QoL, and to evaluate the relationship between fatigue and WP. METHODS: A cross-sectional study was conducted in a Regional Tertiary IBD Diagnostic and Treatment Center in Eastern China. Clinical data of patients were collected, and disease activity was evaluated. Blood samples were analyzed to assess anemia, albumin, and inflammation. Fatigue was assessed using the multidimensional fatigue inventory. QoL and WP were measured using the short inflammatory bowel disease questionnaire and the work productivity and activity impairment general health questionnaire, respectively. The patients also completed assessments of depression (Patient Health Questionnaire-9) and anxiety (Generalized Anxiety Disorder 7-item Scale). RESULTS: A total of 311 IBD patients, comprising 168 Crohn's disease patients and 143 ulcerative colitis patients, were enrolled. The prevalence of fatigue in patients with IBD was 60.77%. In a univariate logistic regression analysis, factors such as disease activity, depression, anxiety, anemia, and IBD-related surgery were individually related to a significantly increased risk of fatigue in IBD patients. Multivariate logistic regression analysis indicated that depression [odds ratio (OR) = 8.078, 95% confidence interval (CI): 4.113-15.865], anxiety (OR = 2.373, 95%CI: 1.100-5.119), anemia (OR = 2.498, 95%CI: 1.290-4.834), and IBD-related surgery (OR = 2.035, 95%CI: 1.084-3.819) were related to fatigue in IBD patients. There was a negative correlation between fatigue and QoL (r = -0.831; P < 0.0001) but a positive correlation between fatigue and WP loss. CONCLUSION: The prevalence of fatigue in IBD patients in Eastern China is remarkably high even in clinical remission. Factors such as depression, anxiety, anemia, and IBD-related surgery are major risk factors for fatigue in IBD patients. In addition, fatigue has a negative impact on QoL and is positively correlated with WP loss.

Predictive value of blood concentration of biologics on endoscopic inactivity in inflammatory bowel disease: A systematic review.

BACKGROUND: Although blood concentration of biologics is an important composition of disease management in inflammatory bowel disease (IBD) patients, complexity and uncertainty of biological management encourage many disputes in predicting the outcome of IBD patients through blood concentration of biologics. AIM: To verify the predictive value of blood concentration of biologics on endoscopic inactivity in IBD patients under different situations. METHODS: We searched PubMed/MEDLINE, Embase, and Web of Science up to May 2020 and identified IBD patients as the research cohort as well as the correlations between blood concentration of biologics and endoscopic inactivity in IBD patients as the research direction. RESULTS: A total of 23 articles with 30 clinical studies and 1939 IBD patients were included. The predictive cut-off value of blood concentration of infliximab on mucosal healing should be 2.7-10.6 µg/mL in IBD. Blood concentration of infliximab reaching 5.0-12.7 µg/mL or more increased the probability of fistula healing/closure in perianal fistulizing Crohn's disease. Blood concentration of adalimumab reaching 7.2-16.2 µg/mL or more could predict mucosal healing in IBD. The predictive cut-off value of blood concentration of adalimumab on fistula healing/closure should be 5.9-9.8 µg/mL in perianal fistulizing Crohn's disease. Blood concentration of vedolizumab surpassing 25.0 µg/mL indicated mucosal healing in ulcerative colitis patients under maintenance therapy and the predictive cut-off value of blood concentration on mucosal healing or endoscopic remission under induction therapy in IBD could be 8.0-28.9 µg/mL. CONCLUSION: Blood concentration of biologics should not be utilized to predict endoscopic inactivity of IBD independently due to discrepancies in clinical studies, whereas conducting therapeutic drug monitoring intensively contributes to precise therapy.

[Proteomic expression analysis of colonic mucosa in a rat model of irritable bowel syndrome].

OBJECTIVE: To explore the pathogenesis of irritable bowel syndrome (IBS) and the regulation of the network relationship between differential proteins. METHODS: Sixteen female SD rats of clean grade were randomly divided into IBS group (n = 8) and control group (n = 8). A rat model of IBS was established by a special odor of mothball as a conditional stimulation and colorectal distension plus the classic conditions of physical restraint as a non-conditional stimulation in turn. The total proteins were extracted from colon mucosa of two different rat groups. After preparation of total proteins, solubilized proteins were separated by two-dimensional differential gel electrophoresis. Those differential protein spots were identified by matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF MS). The identified proteins were classified through an online web gene ontology tool. Some of the valuable differently expressed proteins were chosen for further verification by Western blotting. RESULTS: Intensity changes of 19 spots were detected among 1396 protein spots. A total of 13 different proteins were identified by MALDI-TOF MS successfully; eight of these were up-regulated and five down-regulated in colon mucosa of IBS rat. The eight over-expressed proteins were cytokeratin 8, protein disulfide isomerase A3 (PDIA3), peroxiredoxin-6, cathepsin S, heterogeneous nuclear ribonucleoprotein F, eukaryotic translation initiation factor, carbonyl reductase 1, glyoxalase I; five under-expressed proteins were alpha-enolase, transgelin, serpinB5, cardiac alpha-actin 1 and 40S ribosomal protein SA. The results of Western blotting confirmed that PDIA3 was indeed over-expressed in colonic mucosa of IBS rat. CONCLUSIONS: Some proteins related to immunity of intestinal tract, inflammation and nerve are differently expressed in colonic mucosa of IBS rat. It is suggested that immunity, inflammation and neuro-endocrine network in gut are associated with the pathogenesis of IBS.

Insufficient awareness and vaccination practices for inflammatory bowel disease patients in China: A multi-center survey of Chinese gastroenterologists.

OBJECTIVE: The prevalence of inflammatory bowel disease (IBD) has been increasing worldwide, and the risk of infection has increased due to the use of immunosuppressive and biologic medications. Some of these infections can be prevented with vaccinations. The aim of this study was to evaluate the vaccination practices of Chinese gastroenterologists for patients with IBD. METHODS: Questionnaires based on quick response codes were sent using email and the WeChat platform to gastroenterologists at 20 hospitals in China. The vaccination practices of the gastroenterologists, including vaccinating for hepatitis B, hepatitis A, and varicella, were assessed. RESULTS: Of the 468 gastroenterologists who received the questionnaire, 307 (65.6%) completed it. Of the gastroenterologists who were most concerned about hepatitis B; 83.4% always or frequently asked about an infection history, 53.7% took an immunization history, and 73.6% tested patients for hepatitis B infection. However, few gastroenterologists did so for hepatitis A or varicella. The proportion of patients who were asked about an infection and immunization history and tested for varicella infection was 16.0%, 15.0%, and 9.4%, respectively. Only a few gastroenterologists recommended vaccination for patients without an infection before IBD medical treatment (26.7% for hepatitis A, 45.6% for hepatitis B, and 28% for varicella vaccination). CONCLUSION: Vaccination practices for patients with IBD used by Chinese gastroenterologists vary greatly, suggesting that education about immunization is needed.

[The expression of glial cell line-derived neutrophil factor and its effect on colonic transit function in slow transit constipation rats].

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.

Nested case-control study on risk factors for opportunistic infections in patients with inflammatory bowel disease.

BACKGROUND: When opportunistic infections occur, patients with inflammatory bowel disease (IBD) commonly display a significantly increased rate of morbidity and mortality. With increasing use of immunosuppressive agents and biological agents, opportunistic infections are becoming a hot topic in the perspective of drug safety in IBD patients. Despite the well-established role of opportunistic infections in the prognosis of IBD patients, there are few epidemiological data investigating the incidence of opportunis-tic infections in IBD patients in China. Besides, the risk factors for opportunistic infection in Chinese IBD patients remain unclear. AIM: To predict the incidence of opportunistic infections related to IBD in China, and explore the risk factors for opportunistic infections. METHODS: A single-center, prospective study of IBD patients was conducted. The patients were followed for up to 12 mo to calculate the incidence of infections. For each infected IBD patient, two non-infected IBD patients were selected as controls. A conditional logistic regression analysis was used to assess associations between putative risk factors and opportunistic infections, which are represented as odds ratios (OR) and 95% confidence intervals (CIs). RESULTS: Seventy (28.11%) out of 249 IBD patients developed opportunistic infections. Clostridium difficile infections and respiratory syncytial virus infections were found in 24 and 16 patients, respectively. In a univariate analysis, factors such as the severity of IBD, use of an immunosuppressant or immunosuppressants, high levels of fecal calprotectin, and C-reactive protein or erythrocyte sedimentation rate were individually related to a significantly increased risk of opportunistic infection. Multivariate analysis indicated that the use of any immunosuppressant yielded an OR of 3.247 (95%CI: 1.128-9.341), whereas the use of any two immunosuppressants yielded an OR of 6.457 (95%CI: 1.726-24.152) for opportunistic infection. Interestingly, when immunosuppressants were used in combination with infliximab (IFX) or 5-aminosalicylic acid, a significantly increased risk of opportunistic infection was also observed. The relative risk of opportunistic infection was greatest in IBD patients with severe disease activity (OR = 9.090; 95%CI: 1.532-53.941, relative to the remission stage). However, the use of IFX alone did not increase the risk of opportunistic infection. CONCLUSION: Factors such as severe IBD, elevated levels of fecal calprotectin, and the use of immunosuppressive medications, especially when used in combination, are major risk factors for opportunistic infections in IBD patients. The use of IFX alone does not increase the risk of opportunistic infection.

[Effects of teprenone on expression of heat shock protein 70 and c-fos in stomach following prednisolone ingestion: experiment with rats].

OBJECTIVE: To estimate the effect of teprenone on the expression of heat shock protein (HSP) 70 and c-fos in stomach following prednisolone ingestion. METHODS: Fifty male Sprague-Dawley rats were randomly into 5 equal groups: normal control group, undergoing gastric perfusion of normal saline (NS) for 7 days, and since the 4 th day undergoing fasting for 4 days; model control group, undergoing gastric perfusion of NS for 7 days, and since the 4 th day undergoing fasting and subcutaneous injection of prednisolone 40 mg/kg for 4 days; and 3 model therapy groups, undergoing gastric perfusion with low, middle, and high dose of teprenone (50 mg/kg, 100 mg/kg, and 200 mg/kg respectively) for 7 days and undergoing fasting and subcutaneous injection of prednisolone 40 mg/kg since the 4 th day. Twenty-four hours after the last administration of drugs, the rats were killed with their stomachs taken out. The gastric ulcer index (UI) was measured. HE staining was used to observe the injury index of the gastric mucosa. The mRNA expression of HSP70 in the gastric tissue was semi-quantitatively detected with reverse transcription-polymerase chain reaction. The protein expression of c-fos in the gastric tissue was detected with immunohistochemical staining. RESULTS: The injury index of the gastric mucosa of the model control group was 5.5, significantly higher than that of the normal control group (0, P = 0.000), and the injury indexes of the 3 teprenone groups were all significantly lower than that of the model control group dose-dependently (all P < 0.01). The UI of the model control group was 44.5, significantly higher than that of the normal control group (0, P = 0.000), and the UI values of the 3 teprenone groups were 32.5, 23.0, and 23.0 respectively, all significantly lower than that of the model control group dose-dependently (all P < 0.01). The expression value of c-fos of the model control group was 42 +/- 8, significantly higher than that of the normal control group (P < 0.01), and that expression values of c-fos of the 3 teprenone groups were all significantly lower than that of the model control groups dose-dependently (all P < 0.01). The expression value of HSP70 mRNA of the model control group was 0.22 +/- 0.03, significantly higher than that of the normal control group (0.04 +/- 0.02, P < 0.01), and the expression values of HSP70 mRNA of the 3 teprenone groups were 0.36 +/- 0.05, 0.41 +/- 0.09, and 0.49 +/- 0.05 respectively, all significantly higher than that of the model control group (all P < 0.01). CONCLUSION: Teprenone is Pretreatment with teprenone, beneficial cytoprotective agent of gastric mucosa, has a gastroprotective effect against steroid-induced mucosal damage to a certain extent with the mechanism related to c-fos and HSP70 l level in the gastric mucosa.

Mucosa repair mechanisms of Tong-Xie-Yao-Fang mediated by CRH-R2 in murine, dextran sulfate sodium-induced colitis.

AIM: To explore the significance of corticotropin-releasing hormone (CRH)-receptor (R)2 in mucosal healing of dextran sulfate sodium (DSS)-induced colitis and the effect of Tong-Xie-Yao-Fang (TXYF) on CRH-R2 expression and regulation. METHODS: Ulcerative colitis was induced in mice by administration of 3% (w/v) DSS for 7 d. Once the model was established, mice were administered urocortin-2 (30 µg/kg), a peptide which binds exclusively to CRH-R2, or various doses of aqueous TXYF extracts (2.8-11.2 g/kg), a CRH-R2 antagonist Astressin (Ast)2B (20 µg/kg), Ast2B + Ucn2, or Ast2B with various doses of aqueous TXYF extracts for 9 d. Colonic mucosal permeability was then evaluated by measuring the fluorescence intensity in serum. The colitis disease activity index (DAI), histology, body weight loss and colon length were assessed to evaluate the condition of colitis. Terminal deoxynucleotidyl transferase dUTP nick-end labeling was used to detect apoptosis of the intestinal epithelial cells. The expression level of Ki-67 represented the proliferation of colonic epithelial cells and was detected by immunohistochemistry. The expression levels of inflammation cytokines IL-6, TNF-α and CXCL-1 were examined in colon tissues using real-time PCR and ELISA kits. RESULTS: Compared with the DSS group, mice treated with the CRH-R2 antagonist Ast2B showed greater loss of body weight, shorter colon lengths (4.90 ± 0.32 vs 6.21 ± 0.34 cm, P < 0.05), and higher DAI (3.61 ± 0.53 vs 2.42 ± 0.32, P < 0.05) and histological scores (11.50 ± 1.05 vs 8.33 ± 1.03, P < 0.05). Additionally, the Ast2B group showed increased intestinal permeability (2.76 ± 0.11 µg/mL vs 1.47 ± 0.11 µg/mL, P < 0.001), improved secretion of inflammatory cytokines in colon tissue, and reduced colonic epithelial cell proliferation (4.97 ± 4.25 vs 22.51 ± 8.22, P < 0.05). Increased apoptosis (1422.39 ± 90.71 vs 983.01 ± 98.17, P < 0.001) was also demonstrated. The Ucn2 group demonstrated lower DAI (0.87 ± 0.55 vs 2.42 ± 0.32, P < 0.001) and histological scores (4.33 ± 1.50 vs 8.33 ± 1.03, P < 0.05). Diminished weight loss, longer colon length (9.58 ± 0.62 vs 6.21 ± 0.34 cm, P < 0.001), reduced intestinal permeability (0.75 ± 0.07 vs 1.47 ± 0.11 µg/mL, P < 0.001), inhibited secretion of inflammatory cytokines in colon tissue and increased colonic epithelial cell proliferation (90.04 ± 15.50 vs 22.51 ± 8.22, P < 0.01) were all observed. Reduced apoptosis (149.55 ± 21.68 vs 983.01 ± 98.17, P < 0.05) was also observed. However, significant statistical differences in the results of the Ast2B group and Ast2B + Ucn2 group were observed. TXYF was also found to ameliorate symptoms of DSS-induced colitis in mice and to promote mucosal repair like Ucn2. There were significant differences between the Ast2B + TXYF groups and the TXYF groups. CONCLUSION: CRH-R2 activates the intestinal mucosal antiinflammatory response by regulating migration, proliferation and apoptosis of intestinal epithelial cells in colitis-induced mice, and plays an important antiinflammatory role. TXYF promotes mucosal repair in colitis mice by regulating CRH-R2.

[Oesophageal acid exposure test in non-erosive gastroesophageal reflux disease and the diagnostic value of rabeprazole].

OBJECTIVE: To study the acid exposure characteristic of the subtypes of non-erosive gastroesophageal reflux disease (NERD) and discuss the value of rabeprazole in its diagnosis. METHODS: 32 cases of the NERD were subdivided into three groups--14 cases with abnormal acid reflux, 11 with acid hypersensitive oesophagus and the remaining 7 with functional heartburn. All the cases were treated with rabeprazole 10 mg bid for 2 weeks. RESULTS: (1) Acid exposure in each group: In the abnormal acid reflux group, the total degree of acid reflux, the degree of long reflux, the time of pH < 4 and the time percentage of pH < 4 were obviously increased as compared with the groups of acid hypersensitive oesophagus and functional heartburn; the symptom index of the group with acid hypersensitive oesophagus was apparently higher than that of the group of functional heartburn [(81.0 +/- 22.5)% vs (8.6 +/- 14.8)%, P < 0.01]. (2) Comparison of symptoms: There was no obvious difference in the score of typical symptoms and total score of symptoms before therapy among the groups; the score extraesophageal symptoms in the acid hypersensitive oesophagus group was much higher than that in the abnormal acid reflux group (4.0 +/- 3.8 vs 0.9 +/- 2.2, P < 0.05). (3) The curative effect: The score of oesophageal symptoms and the total score of symptoms in the abnormal acid reflux and the acid hypersensitive oesophagus groups after treatment with rabeprazole for 1 and 2 weeks showed obvious decrease, while in the functional heartburn group the scores showed only a declining trend, but with no statistical significance, and there was obvious distinction of the total score of symptoms in the abnormal acid reflux group as compared with the other two groups after 2 weeks of therapy. (4) The total effective rate was 56.3% and 68.8% after 1 week and 2 weeks of therapy. Rabeprazole test showed that the sensitivity and specificity for abnormal acid reflux and acid hypersensitive oesophagus were 64.0% and 71.4% after 1 week and 80.0% and 71.4% after 2 weeks of therapy. CONCLUSIONS: (1) The main manifestations shown by the acid exposure of abnormal acid reflux are the increase of total degree of acid reflux, the degree of long reflux and the time of pH < 4. (2) The patients with hypersensitive oesophagus may be much more likely to suffer from extraesophageal symptoms. (3) Rabeprazole diagnosis test is valuable in the diagnosis and subdivision of non-erosive gastroesophageal reflux disease.

Brain changes detected by functional magnetic resonance imaging and spectroscopy in patients with Crohn's disease.

Crohn's disease (CD) is a chronic, non-specific granulomatous inflammatory disorder that commonly affects the small intestine and is a phenotype of inflammatory bowel disease (IBD). CD is prone to relapse, and its incidence displays a persistent increase in developing countries. However, the pathogenesis of CD is poorly understood, with some studies emphasizing the link between CD and the intestinal microbiota. Specifically, studies point to the brain-gut-enteric microbiota axis as a key player in the occurrence and development of CD. Furthermore, investigations have shown white-matter lesions and neurologic deficits in patients with IBD. Based on these findings, brain activity changes in CD patients have been detected by blood oxygenation level dependent functional magnetic resonance imaging (BOLD-fMRI). BOLD-fMRI functions by detecting a local increase in relative blood oxygenation that results from neurotransmitter activity and thus reflects local neuronal firing rates. Therefore, biochemical concentrations of neurotransmitters or metabolites may change in corresponding brain regions of CD patients. To further study this phenomenon, brain changes of CD patients can be detected non-invasively, effectively and accurately by BOLD-fMRI combined with magnetic resonance spectroscopy (MRS). This approach can further shed light on the mechanisms of the occurrence and development of neurological CD. Overall, this paper reviews the current status and prospects on fMRI and MRS for evaluation of patients with CD based on the brain-gut-enteric microbiota axis.

Novel Anterior Brainstem Magnetic Resonance Imaging Findings in Non-Small Cell Lung Cancer with Leptomeningeal Carcinomatosis.

Leptomeningeal carcinomatosis (LC) is found in around 4% of patients with non-small cell lung cancer (NSCLC). The most common radiological finding of LC is diffuse leptomeningeal enhancement on contrast-enhanced brain magnetic resonance imaging (MRI). Herein, we report a novel brain MRI finding-non-enhanced, band-like, symmetric restricted diffusion along the anterior surface of the brainstem-of LC in four patients with NSCLC. We also identified three additional cases with similar MRI findings in a literature review. We hypothesized that the restricted diffusion along the anterior brainstem was caused by malignant cells concentrating in the cistern around the brainstem and infiltrating into the circumferential perforating arteries along the anterior brainstem surface, which then resulted in microinfarctions.