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.

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.

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.

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).

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.

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.

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.

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.

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.

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.

Case report of primary splenic angiosarcoma with hepatic metastases.

Primary splenic angiosarcoma (PSA) is the most unusual type of malignancy with early multifocal metastasis through hematogenous spread. PSA is generally believed to originate from splenic sinusoidal vascular endothelium with a high rate of metastasis and to have a poor prognosis. Its etiology and pathogenetic mechanisms have not yet been clearly described. Thus far, only approximately 200 cases have been reported. PSA has variable symptomatology with the potential to present with life-threatening complications. The diagnosis of PSA is challenging; and often late. PSA should be considered in the differential diagnosis of patients with splenomegaly and anemia of unknown etiology. Surgical treatment with splenectomy is considered the only curative intervention for potential long-term disease-free survival. Early diagnosis and treatment are very important. It is important that clinical doctors improve the understanding of PSA. Herein, we report one rare case of PSA with hepatic metastases, along with a review of the current literature.

Mechanism of aqueous fructus aurantii immaturus extracts in neuroplexus of cathartic colons.

AIM: To examine the effect of aqueous fructus aurantii immaturus (FAI) extracts on the intestinal plexus of cathartic colons. METHODS: Cathartic colons were induced in rats with dahuang, a laxative used in traditional Chinese medicine. Once the model was established (after approximately 12 wk), rats were administered mosapride (1.54 mg/kg) or various doses of aqueous FAI extracts (1-4 g/kg) for 14 d. Transit function was assessed using an ink propulsion test. Rats were then sacrificed, and the ultramicrostructure of colonic tissue was examined using transmission electron microscopy. The expression of the 5-hydroxytryptamine receptor 4 (5-HTR4) and neurofilament-H was assessed in colon tissues using real-time PCR, Western blot, and immunohistochemistry. RESULTS: Mosapride and high dose (4 g/kg) of aqueous FAI extracts significantly improved the bowel movement in cathartic colons compared to untreated model colons as measured by the intestinal transit rate (70.06 ± 7.25 and 72.02 ± 8.74, respectively, vs 64.12 ± 5.19; P < 0.05 for both). Compared to controls, the ultramicrostructure of cathartic colons showed signs of neural degeneration. Treatment with mosapride and aqueous FAI extracts resulted in recovery of ultrastructural pathology. Treatment with mosapride alone upregulated the gene and protein expression of 5-HTR4 compared to untreated controls (P < 0.05 for both). Treatment with aqueous FAI extracts (≥ 2 g/kg) increased 5-HTR4 mRNA levels (P < 0.05), but no change in protein level was observed by Western blot or immunohistochemistry. The mRNA and protein levels of neurofilament-H were significantly increased with mosapride and ≥ 2 g/kg aqueous FAI extracts compared to controls (P < 0.05 for all). CONCLUSION: Aqueous FAI extracts and mosapride strengthen bowel movement in cathartic colons via increasing the expression of 5-HTR4 and neurofilament-H.

Effects and mechanisms of transcutaneous electroacupuncture on chemotherapy-induced nausea and vomiting.

Nausea and vomiting are one of the major complications of chemotherapy for cancers. The aim of this study is to investigate the emetic effects and mechanisms involving serotonin and dopamine of needleless transcutaneous electroacupuncture (TEA) at Neiguan (PC6) and Jianshi (PC5) on chemotherapy-induced nausea and vomiting in patients with cancers. Seventy-two patients with chemotherapy were randomly divided into sham-TEA group (sham-TEA, n = 34) and TEA group (n = 38). TEA was performed at PC 6 and PC 5 (1 h, bid) in combination with granisetron. Sham-TEA was delivered at nonacupoints using the same parameters. We found the following. (1) In the acute phase, the conventional antiemetic therapy using Ondansetron effectively reduced nausea and vomiting; the addition of TEA did not show any additive effects. In the delayed phase, however, TEA significantly increased the rate of complete control (P < 0.01) and reduced the nausea score (P < 0.05), compared with sham-TEA. (2) TEA significantly reduced serum levels of 5-HT and dopamine in comparison with sham-TEA. Those results demonstrate that needleless transcutaneous electroacupuncture at PC6 using a watch-size digital stimulator improves emesis and reduces nausea in the delayed phase of chemotherapy in patients with cancers. This antiemetic effect is possibly mediated via mechanisms involving serotonin and dopamine.

Muscovite is protective against non-steroidal anti-inflammatory drug-induced small bowel injury.

AIM: To evaluate the effect of muscovite in preventing small bowel injury induced by nonsteroidal anti-inflammatory drugs (NSAIDs). METHODS: We recruited and screened thirty-two healthy volunteers who were randomly allocated equally into two groups: an NSAID control group, who received 75 mg slow-release diclofenac, twice daily for 14 d; and an NSAID-muscovite group, who received 3 g of muscovite in addition to the 75 mg of slow-release diclofenac, twice daily for 14 d. For gastroprotection, both groups were administered 20 mg/d of the proton pump inhibitor omeprazole. All eligible subjects underwent video capsule endoscopy (CE) prior to and 14 d after treatment. RESULTS: Thirty subjects (NSAID-muscovite group, n =16; NSAID control group, n =14) finally completed the whole trail. At the baseline CE examination, no statistically significant differences between the two groups have been observed. However, after 14 d of drug treatment, a significant difference was observed in the percentage of subjects with mucosal breaks when comparing the NSAID-muscovite group with the NSAID control group. While 71.4% (10/14) of subjects in the NSAID control group had at least one mucosal break, co-administration of muscovite in the NSAID-muscovite group reduced the rate to 31.3% (5/16) (P = 0.028). Moreover, higher number of mucosal breaks was found in the NSAID control group vs that in the NSAID-muscovite group (P < 0.05). CONCLUSION: Muscovite co-therapy reduced the incidence of small intestinal injury after 14 d of diclofenac administration.

[Effects of electroacupuncture on chemotherapy-induced nausea and vomiting and its mechanism].

OBJECTIVE: To observe the effects of electroacupuncture at Neiguan (PC 6) and Jianshi (PC 5) com- bined with granisetron on nausea and vomiting as well as serum levels of 5-hydroxy tryptamine (5-HT) and dopamine (DA) in chemotherapy patients. METHODS: Seventy-two chemotherapy patients who met the inclusive criteria were randomly divided into an observation group (38 cases) and a control group (34 cases). The patients in the observation group were treated with electroacupuncture at Neiguan (PC 6) and Jianshi (PC 5) combined with granisetron injection; the patients in the control group were treated with electroacupuncture at sham-point 1 and sham- point 2, and the rest treatment was identical to the observation group. After 3-day treatment, the clinical indices including times of vomiting and severity of nausea, etc. were observed in the two groups. RESULTS: (1) At the acute stage within 24 h, the times of vomiting in the two groups were not significantly different (P>0.05); at the delay stage, the severity of nausea was significantly higher in the control group (P<0.05). (2) As for the comprehensive efficacy and rate of complete control, there was no obvious difference between the two groups at the acute stage (P>0.05); while in the delay stage, the rate of complete control in the observation group was superior to that in the control group (P<0.01). (3) Compared before and after the treatment, serum levels of 5-HT and DA were evidently reduced in the observation group (both P<0.05), while those in the control group were not significantly changed after treatment (both P>0.05). CONCLUSION: Electroacupuncture at Neiguan (PC 6) and Jianshi (PC 5) combined with granisetron could obviously relieve the nausea in chemotherapy patients at the delay stage. The effect mechanism is possibly related to reducing the content of 5-HIT nndl nA

[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.

Itopride therapy for functional dyspepsia: a meta-analysis.

AIM: To evaluate the therapeutic effects of itopride vs other drugs (placebo, domperidone, mosapride) for functional dyspepsia (FD). METHODS: Randomized controlled trials (RCTs) of itopride for FD were retrieved from databases. Relevant information was extracted and analyzed, using the relative risk (RR) and weighted mean deviation, as appropriate. A random or fixed effect model was used, based on the heterogeneity of the included articles, and visual inspection of funnel plots was used to evaluate publication bias. RESULTS: Nine RCTs enrolling 2620 FD cases were included; 1372 cases received itopride treatment and 1248 cases received placebo or other drugs (control groups). Compared with control groups, itopride had superior RR values of 1.11 [95%CI: (1.03, 1.19), P = 0.006], 1.21 [95%CI: (1.03, 1.44), P = 0.02], and 1.24 [95%CI: (1.01, 1.53), P = 0.04] for global patient assessment, postprandial fullness, and early satiety, respectively. For the Leeds Dyspepsia Questionnaire score, the weighted mean deviation was -1.38 [95%CI: (-1.75, -1.01), P < 0.01]. The incidence of adverse effects was similar in the itopride and control groups. The funnel plots for all indicators showed no evidence of publication bias. CONCLUSION: Itopride has good efficacy in terms of global patients assessment, postprandial fullness, and early satiety in the treatment of patients with FD and shows a low rate of adverse reactions. Itopride can greatly improve FD syndromes-score.

[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.