Direct visualization of drug behaviors in the upper GI tract via magnetically controlled capsule endoscopy.

BACKGROUND AND AIMS: Actual behaviors of drugs in the upper GI tract are not well elucidated. We assess the feasibility of magnetically controlled capsule endoscopy (MCE) in direct and real-time visualization of oral drug behaviors in the stomach. METHODS: From November 2019 to December 2019, 9 patients with a recent history of upper GI symptoms and 10 healthy volunteers were enrolled in this study. Participants swallowed magnetically controlled capsules to examine the whole stomach. After baseline examination, participants ingested dyed sucralfate gel, and MCE recorded the adhesion time, retention time, and distribution area of sucralfate gel. Outcomes included behaviors of sucralfate gel, safety, and satisfaction assessment of the procedures. RESULTS: Adhesion time of sucralfate gel in the abdominal symptoms group was significantly shorter than in the healthy control group (23.76 ± 1.37 minutes vs 31.96 ± 3.09 minutes; P = .032), whereas retention time was longer (98.85 ± 13.94 minutes vs 63.93 ± 8.57 minutes; P = .043). The distribution area of sucralfate gel in the abdominal symptoms group was significantly larger than in healthy control group in cardia (24.29 ± 7.39 vs 9.18 ± 4.06; P < .0001), fundus (18.90 ± 7.08 vs 8.49 ± 4.10; P = .0015), and pylorus (4.64 ± 2.72 vs 0.94 ± 0.90; P = .0019). No adverse events were observed. All participants had a high degree of satisfaction. CONCLUSIONS: MCE is a feasible and noninvasive tool for direct and real-time visualization of drug behaviors (eg, sucralfate gel) in the stomach. (ClinicalTrials.gov. ID: NCT04327869.).

Cigarette Smoking and Mortality in Patients With Pancreatic Cancer: A Systematic Review and Meta-analysis.

Current evidence on cigarette smoking associated with pancreatic cancer mortality is limited. We searched MEDLINE, Web of Science, and Embase databases to identify relevant studies published through January 31, 2018. A random-effects model was used to estimate summary hazard ratios (HRs) and 95% confidence intervals (CIs). A total of 20 studies were retrieved, involving 2,517,623 participants. Of these, more than 15,341 patients with pancreatic cancer died. Compared with never smokers, current (summary HR, 1.56; 95% CI, 1.34-1.83) and former (summary HR, 1.15; 95% CI, 1.06-1.26) smokers had elevated risk of total mortality in patients diagnosed with pancreatic cancer. This effect of cigarette smoking is observed both in the Western regions and the Asia-Pacific regions. This effect of smoking is independent of alcohol use, body mass index, and history of diabetes but is modified by tumor stage and study settings. Dose-response associations between smoking and pancreatic cancer mortality were revealed for smoking intensity, cumulative amount of cigarettes smoked, and duration of smoking. Cigarette smoking was associated with an increase in total mortality for patients with pancreatic cancer. Future studies should further clarify the role of smoking as an effect modifier in treatment trials of pancreatic cancer.

Study of disease phenotype and its association with prognosis of paediatric inflammatory bowel disease in China.

BACKGROUND: To investigate the unique features of inflammatory bowel disease (IBD) in children, we wanted to identify whether there might be a strong correlation between the disease phenotype and its prognosis at various ages in paediatric patients. METHODS: We collected data from patients diagnosed with IBD (ulcerative colitis (UC) or Crohn's disease (CD)) from 2002 to 2016. The diagnosis was made according to the Porto criteria and Paris Classification. Patient characteristics, clinical manifestations and treatments were collected. Risk factors for surgery, mortality and relapse were analysed by Cox proportional hazard models. RESULTS: Of the 143 patients, 113 had CD, and 30 had UC; there were 89 males and 54 females with a median age of 9 years (y). Thirteen patients in the 0-2 y group were identified as having mutations in IL-10 receptor A, and this mutation was significantly more common in this age group than in 3-9 and 10-16 y patients. The risk factor for surgery was the B3 phenotype; risk factors for death were age 0-2 y and B3 phenotype; 0-2 y, B3 phenotype and steroid dependency were risk factors for early relapse. CONCLUSIONS: Clinical manifestations of the onset of IBD in infants and toddlers were extensive and aggressive and were closely associated with early relapse and death. It is of particular interest that some of these patients developed IBD due to monogenic disorders; thus, introduction of genetic testing is essential for these patients.

Adsorptive Granulocyte and Monocyte Apheresis in the Treatment of Ulcerative Colitis: The First Multicenter Study in China.

BACKGROUND/AIMS: Patients with active ulcerative colitis (UC) have elevated levels of activated myeloid-derived leukocytes as a source of inflammatory cytokines. The selective depletion of these leukocytes by adsorptive granulocyte/monocyte apheresis (GMA) with an Adacolumn should alleviate inflammation, promote remission and enhance drug efficacy. However, studies have reported contrasting efficacy outcomes based on patients' baseline demographic variables. This study was undertaken to understand the demographic features of GMA responders and nonresponders. METHODS: This was a multicenter study in China involving four institutions and 34 patients with active UC. Baseline conventional medications were continued without changing the dosage. The treatment efficacy was evaluated based on the endoscopic activity index and the Mayo score. RESULTS: Thirty of the 34 patients completed all 10 GMA treatment sessions. The overall efficacy rate was 70.59%. The receiver operating characteristic analysis showed that the area under the curve was approximately 0.766 for a Mayo score of ≤5.5 with 0.273 specificity and 0.857 sensitivity (Youden index, 0.584) for GMA responders. No GMA-related serious adverse events were observed. CONCLUSIONS: The overall efficacy of GMA in patients with active UC who were taking first-line medications or were corticosteroid refractory was encouraging. Additionally, GMA was well tolerated and had a good safety profile.

Alginate antacid (Gaviscon DA) chewable tablets reduce esophageal acid exposure in Chinese patients with gastroesophageal reflux disease and heartburn symptoms.

OBJECTIVE: To assess the efficacy of Gaviscon Double Action (DA) alginate antacid chewable tablets for reducing esophageal acid exposure in Chinese patients with gastroesophageal reflux disease (GERD). METHODS: Altogether 44 patients reporting moderate to severe heartburn symptoms underwent two pH monitoring visits. The treatment sequence was randomized to patients received DA alginate antacid or placebo at one visit and the alternate treatment 7 days later. After a standardized reflux-provoking meal, patients took four tablets of DA alginate antacid or placebo. Esophageal pH was measured for 4 h post-dosing using an electrode positioned 5 cm above the lower esophageal sphincter. The primary end-point was the percentage of 4-h post-dosing period with pH <4. Secondary end-points were number of acid reflux episodes (pH <4), longest reflux time and DeMeester scores. RESULTS: All 44 patients completed the study and provided data for analysis. With DA alginate antacid, the mean percentage time with pH <4 was 5.1%, significantly less (P = 0.0003) than with placebo (14.8%). DA alginate antacid was statistically significantly superior (P = 0.0290) to placebo (from at least twofold to threefold better) for all other end-points. Two patients reported two mild adverse events (AEs) that resolved within a month of completing the study. No patients had serious and/or severe AEs and none withdrew due to AEs. CONCLUSIONS: DA alginate antacid was statistically significantly superior to placebo in reducing post-prandial acid exposure without serious clinically relevant health risks. These findings suggest DA alginate antacid tablets are appropriate for treating acid reflux in Chinese GERD patients with heartburn symptoms.

Differences and Similarities in the Clinicopathological Features of Pancreatic Neuroendocrine Tumors in China and the United States: A Multicenter Study.

The presentation, pathology, and prognosis of pancreatic neuroendocrine tumors (PNETs) in Asian patients have not been studied in large cohorts. We hypothesized that the clinicopathological features of PNETs of Chinese patients might be different from those of US patients. The objectives of this study were to address whether PNETs in Chinese patients exhibit unique clinicopathological features and natural history, and can be graded and staged using the WHO/ENETS criteria. This is a retrospective review of medical records of patients with PNETs in multiple academic medical centers in China (7) and the United States (2). Tumor grading and staging were based on WHO/ENETS criteria. The clinicopathological features of PNETs of Chinese and US patients were compared. Univariate and multivariate analyses were performed to find associations between survival and patient demographics, tumor grade and stage, and other clinicopathological characteristics. A total of 977 (527 Chinese and 450 US) patients with PNETs were studied. In general, Chinese patients were younger than US patients (median age 46 vs 56 years). In Chinese patients, insulinomas were the most common (52.2%), followed by nonfunctional tumors (39.7%), whereas the order was reversed in US patients. Tumor grade distribution was similar in the 2 countries (G1: 57.5% vs 55.0%; G2: 38.5% vs 41.3%; and G3: 4.0% vs 3.7%). However, age, primary tumor size, primary tumor location, grade, and stage of subtypes of PNETs were significantly different between the 2 countries. The Chinese nonfunctional tumors were significantly larger than US ones (median size 4 vs 3 cm) and more frequently located in the head/neck region (54.9% vs 34.8%). The Chinese and US insulinomas were similar in size (median 1.5 cm) but the Chinese insulinomas relatively more frequently located in the head/neck region (48.3% vs 26.1%). Higher grade, advanced stage, metastasis, and larger primary tumor size were significantly associated with unfavorable survival in both countries. Several clinicopathological differences are found between Chinese and US PNETs but the PNETs of both countries follow a similar natural history. The WHO tumor grading and ENETS staging criteria are applicable to both Chinese and US patients.

Esomeprazole regimens for reflux symptoms in Chinese patients with chronic gastritis.

AIM: To compare symptom control with esomeprazole regimens for non-erosive reflux disease and chronic gastritis in patients with a negative endoscopy. METHODS: This randomized, open-label study was designed in line with clinical practice in China. Patients with typical reflux symptoms for ≥ 3 mo and a negative endoscopy who had a Gastroesophageal Reflux Disease Questionnaire score ≥ 8 were randomized to initial treatment with esomeprazole 20 mg once daily either for 8 wk or for 2 wk. Patients with symptom relief could enter another 24 wk of maintenance/on-demand treatment, where further courses of esomeprazole 20 mg once daily were given if symptoms recurred. The primary endpoint was the symptom control rate at week 24 of the maintenance/on-demand treatment period. Secondary endpoints were symptom relief rate, success rate (defined as patients who had symptom relief after initial treatment and after 24 wk of maintenance treatment), time-to-first-relapse and satisfaction rate. RESULTS: Based on the data collected in the modified intention-to-treat population (MITT; patients in the ITT population with symptom relief after initial esomeprazole treatment, n = 262), the symptom control rate showed a small but statistically significant difference in favor of the 8-wk regimen (94.9% vs 87.3%, P = 0.0473). Among the secondary endpoints, based on the data collected in the ITT population (n = 305), the 8-wk group presented marginally better results in symptom relief after initial esomeprazole treatment (88.3% vs 83.4%, P = 0.2513) and success rate over the whole study (83.8% vs 72.8%, P = 0.0258). The 8-wk regimen was found to provide a 46% reduction in risk of relapse vs the 2-wk regimen (HR = 0.543; 95%CI: 0.388-0.761). In addition, fewer unscheduled visits and higher patient satisfaction supported the therapeutic benefits of the 8-wk regimen over the 2-wk regimen. Safety was comparable between the two groups, with both regimens being well tolerated. CONCLUSION: Chinese patients diagnosed with chronic gastritis achieved marginally better control of reflux symptoms with an 8-wk vs a 2-wk esomeprazole regimen, with a similar safety profile.

Role of the potassium chloride cotransporter isoform 2-mediated spinal chloride homeostasis in a rat model of visceral hypersensitivity.

Visceral hypersensitivity represents an important hallmark in the pathophysiology of irritable bowel syndrome (IBS), of which the mechanisms remain elusive. The present study was designed to examine whether cation-chloride cotransporter (CCC)-mediated chloride (Cl(-)) homeostasis of the spinal cord is involved in chronic stress-induced visceral hypersensitivity. Chronic visceral hypersensitivity was induced by exposing male Wistar rats to water avoidance stress (WAS). RT-PCR, Western blotting, and immunohistochemistry were used to assess the expression of CCCs in the spinal cord. Patch-clamp recordings were performed on adult spinal cord slices to evaluate Cl(-) homeostasis and Cl(-) extrusion capacity of lamina I neurons. Visceral sensitivity was estimated by measuring the abdominal withdrawal reflex in response to colorectal distension (CRD). After 10 days of WAS exposure, levels of both total protein and the oligomeric form of the K(+)-Cl(-) cotransporter isoform 2 (KCC2), but not Na(+)-K(+)-2Cl(-) transporter isoform 1 (NKCC1), were significantly decreased in the dorsal horn of the lumbosacral spinal cord. The downregulation of KCC2 resulted in a depolarizing shifted equilibrium potential of GABAergic inhibitory postsynaptic current and impaired Cl(-) extrusion capacity in lamina I neurons of the lumbosacral spinal cord from WAS rats. Acute noxious CRD disrupted spinal KCC2 expression and function 2 h after the final distention in sham rats, but not in WAS rats. Pharmacological blockade of KCC2 activity by intrathecal injection of a KCC2 inhibitor [(dihydroindenyl)oxy] alkanoic acid enhanced visceral nociceptive sensitivity in sham rats, but not in WAS rats. These results suggest that KCC2 downregulation-mediated impairment of spinal cord Cl(-) homeostasis may play an important role in chronic stress-induced visceral hypersensitivity.

Emodin has a protective effect in cases of severe acute pancreatitis via inhibition of nuclear factor­κB activation resulting in antioxidation.

Severe acute pancreatitis (SAP) accounts for up to 20% of acute pancreatitis (AP) cases. The absence of effective treatment options has resulted in a high rate of morbidity and mortality. Emodin is a major component of the Chinese herb rhubarb, which has been widely used in the treatment of numerous diseases, including inflammation and cancer. There are a limited number of studies however, that have investigated the effectiveness of emodin in the treatment of SAP. The present study used a rat model of SAP, to investigate the effect and molecular mechanisms of emodin treatment. Administration of emodin was identified to significantly attenuate SAP, as determined by serum amylase analysis and histological assessment of edema, vacuolization, inflammation and necrosis (P<0.01). Furthermore, treatment with emodin markedly inhibited nuclear factor (NF)­κB DNA­binding activity (P<0.01) and the serum expression levels of tumor necrosis factor­α, interleukin (IL)­6 and IL­1ß (P<0.05). This attenuation was associated with decreased malondialdehyde and increased superoxide dismutase levels in the pancreatic tissues and serum (P<0.05). This study indicated that administration of exogenous emodin had therapeutic effects on the severity of SAP. The mechanism may be due to inhibition of NF­κB activation resulting in an antioxidation response, which can subsequently suppress the expression of cytokines.

Combined detection of serum UL16-binding protein 2 and macrophage inhibitory cytokine-1 improves early diagnosis and prognostic prediction of pancreatic cancer.

Pancreatic cancer (PC) is the fourth leading cause of cancer-related mortality in the United States. There is no effective serum biomarker for the early diagnosis of PC at present. Although serum UL16-binding protein 2 (ULBP2) and macrophage inhibitory cytokine-1 (MIC-1) levels are reported to be elevated in PC patients, the diagnostic and prognostic value of ULBP2 and MIC-1 alone or in combination remains unknown. The aim of the present case-control study was to compare the diagnostic value of ULBP2, MIC-1 and carbohydrate antigen 19-9 (CA19-9) in 359 serum samples, consisting of 152 cases of PC, 20 cases of pre-pancreatic cancer, 91 cases of chronic pancreatitis (CP) and 96 normal controls (NC). All patients were followed up for a median of 2 years. It was found that the serum levels of ULBP2, MIC-1 and CA19-9 were significantly higher in the PC patients compared with those in the NC group. In distinguishing PC from the CP, the highest sensitivity and specificity were ULBP2 (0.878) and CA19-9 (0.816), respectively. The area under the receiver operating characteristic curve of ULBP2 was 0.923, which was the highest of the three biomarkers. MIC-1 was the optimal choice for the diagnosis of early-stage PC (area under the curve, 0.831). Overall, MIC-1 in combination with ULBP2 improved the diagnostic accuracy in differentiating PC from CP and NC. In addition, a higher level of MIC-1 was correlated with a poorer prognosis, as calculated by the Kaplan-Meier test (P=0.039). Patients with serum MIC-1 levels of ≥1,932 ng/ml had a median survival time of 15.62±2.44 months (mean ± standard deviation) vs. 18.66±2.43 months in patients with a lower level of MIC-1. Overall, combined detection of serum MIC-1 and ULBP2 improved the diagnostic accuracy in differentiating PC from CP and NC, and serum MIC-1 level alone was a predictor of survival in the patients with PC.

Advances in pancreatic cancer research: moving towards early detection.

Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal forms of cancer. Substantial progress has been made in the understanding of the biology of pancreatic cancer, and advances in patient management have been significant. However, most patients (nearly 80%) who present with locally advanced or metastatic disease have an extremely poor prognosis. Survival is better for those with malignant disease localized to the pancreas, because surgical resection at present offers the only chance of cure. Therefore, the early detection of pancreatic cancer may benefit patients with PDAC. However, its low rate of incidence and the limitations of current screening strategies make early detection difficult. Recent advances in the understanding of the pathogenesis of PDAC suggest that it is possible to detect PDAC in early stages and even identify precursor lesions. The presence of new-onset diabetes mellitus in the early phase of pancreatic cancer may provide clues for its early diagnosis. Advances in the identification of novel circulating biomarkers including serological signatures, autoantibodies, epigenetic markers, circulating tumor cells and microRNAs suggest that they can be used as potential tools for the screening of precursors and early stage PDAC in the future. However, proper screening strategies based on effective screening methodologies need to be tested for clinical application.

Idiopathic mesenteric phlebosclerosis associated with long-term use of medical liquor: two case reports and literature review.

A 62-year-old woman was admitted to our hospital in 2011 because of recurrent abdominal pain, nausea and constipation for six months. Computed tomography enterography (CTE) showed tortuous thread-like calcifications in the ileocolic vein and right colic vein, while colonoscopy revealed purple-blue mucosa extending from the cecum to the splenic flexure. Based on the results of these tests, the patient was diagnosed with idiopathic mesenteric phlebosclerosis (IMP). She had a history of Chinese medical liquor intake for one and a half years and her symptoms subsided after conservative treatment. In 2013, a 63-year-old male patient who presented with recurrent lower right abdominal pain, bloating, melena and diarrhea for fifteen months was admitted to our institution. Colonoscopy and CTE led to the diagnosis of IMP. He also used Chinese medical liquor for approximately 12 years. The patient underwent total colectomy and the postoperative course was uneventful. We searched for previously published reports on similar cases and analyzed the clinical data of 50 cases identified in PubMed. As some of these patients admitted use of Chinese medicines, we hypothesize that Chinese medicines may play a role in the pathogenesis of IMP.

Neuron-glial communication mediated by TNF-α and glial activation in dorsal root ganglia in visceral inflammatory hypersensitivity.

Communication between neurons and glia in the dorsal root ganglia (DRG) and the central nervous system is critical for nociception. Both glial activation and proinflammatory cytokine induction underlie this communication. We investigated whether satellite glial cell (SGC) and tumor necrosis factor-α (TNF-α) activation in DRG participates in a 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced rat model of visceral hyperalgesia. In TNBS-treated rats, TNF-α expression increased in DRG and was colocalized to SGCs enveloping a given neuron. These SGCs were activated as visualized under electron microscopy: they had more elongated processes projecting into the connective tissue space and more gap junctions. When nerves attached to DRG (L6-S1) were stimulated with a series of electrical stimulations, TNF-α were released from DRG in TNBS-treated animals compared with controls. Using a current clamp, we noted that exogenous TNF-α (2.5 ng/ml) increased DRG neuron activity, and visceral pain behavioral responses were reversed by intrathecal administration of anti-TNF-α (10 µg·kg(-1)·day(-1)). Based on our findings, TNF-α and SGC activation in neuron-glial communication are critical in inflammatory visceral hyperalgesia.

Peptic ulcer bleeding in China: a multicenter endoscopic survey of 1006 patients.

OBJECTIVE: We aimed to describe the clinical picture, management and outcomes of Chinese patients with peptic ulcer bleeding (PUB), especially in those with high risks. METHODS: A multicenter endoscopic survey was conducted. All consecutive patients with endoscopy confirmed PUB from October 2010 to June 2011 were enrolled. Data including patients' gender, age, symptoms and endoscopic findings, Forrest classification, and endoscopic and medical treatment were documented. High-risk ulcer was defined as Forrest grades Ia to IIb upon endoscopy. Rates of rebleeding, surgery and mortality were recorded. RESULTS: In all, 1006 patients were included. Of these 437 (43.4%) were categorized with high-risk PUB, among whom 110 (25.2%) received endoscopic treatment, and the success rate was 99.1%. Rebleeding rates 1-3 days, 4-5 days and 6-30 days after treatment in high-risk patients who did and did not receive endoscopic treatment were 10.9% versus 10.4%, 3.6% versus 3.7% and 0.9% versus 1.5%, respectively. The surgery rates of high-risk patients with or without endoscopic treatment were 1.8% (2/110) versus 1.8% (6/327). During the 9-month study period, two patients with high-risk PUB died, therefore, the overall mortality rate of high-risk PUB was 0.5% (2/437). CONCLUSION: The study suggests that the proportions of high-risk PUB in China is 43.4%, while rebleeding and surgery rate after endoscopic treatment as well as the mortality rate of high-risk PUB in China are 15.6%, 1.8% and 0.5%, respectively.

Resolution of new-onset diabetes after radical pancreatic resection predicts long-term survival in patients with pancreatic ductal cell adenocarcinoma.

PURPOSE: To demonstrate the effect of diabetes mellitus (DM) (stratified by long-term/new-onset presurgical diabetes, resolved/unresolved postsurgical diabetes) on prognosis for pancreatic ductal cell adenocarcinoma (PDAC) after radical resection. METHODS: One hundred ninety-nine patients who underwent radical resection for PDAC between 2007 and 2011 at Ruijin Hospital (Shanghai, China) were retrospectively analyzed. Clinical and pathologic characteristics, surgical and adjuvant chemotherapy related outcomes, disease-free survival (DFS), and postoperative survival were compared among patients with long-term (≥2 years)/new-onset (<2 years) presurgical diabetes and resolved/unresolved postsurgical diabetes. Univariate and multivariable analysis was performed to determine factors associated with DFS and overall survival (OS). RESULTS: Of 199 patients, 90 (44.7%) had DM, 64 of which were new onset and 26 of which were long-standing. Resolution of DM after radical pancreatic resection was observed in 65% (42 of 64) in the new-onset group, but in none of the long-standing group. Resolved new-onset DM patients had larger, well-differentiated tumors compared to patients with unresolved new-onset DM. Patients with long-standing DM had shorter postoperative DFS and OS than nondiabetic/new-onset DM, whereas postoperative resolved new-onset DM is associated with longer DFS and OS than unresolved DM. Morbidity was higher and postoperative hospital stay was longer in patients with new-onset DM compared with patients with long-standing DM and patients without DM. There was no difference in the adjuvant chemotherapy toxicity rate among patients with long-standing or new-onset DM and those without DM. CONCLUSIONS: Different status of DM has different effects on outcome after resection for PDAC. Long-standing DM is related to progression of disease, whereas postsurgical resolved new-onset DM is a favorable prognostic factor.

Recovery from TNBS-induced colitis leads to the resistance to recurrent colitis and an increased ratio of FOXP3 to CD3 mRNA.

OBJECTIVE: The aim of our study was to investigate the effects of the recovery from acute colitis on recurrent colitis with 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced colitis in mice. METHODS: Acute colitis was induced via an intrarectal injection of TNBS. For recurrent colitis, mice were intrarectally treated with a repeated TNBS 14 days after the first TNBS administration. And another two groups (control and recovery groups) were added to the analysis. Disease activity index (DAI), macroscopic and histological assessments, mRNA expression of interleukin (IL)-1ß, IL-6, tumor necrosis factor (TNF), IL-10, forkhead box P3 (FOXP3) and the ratio of FOXP3 to CD3 in the colonic tissues were evaluated. RESULTS: Mice developed colitis after treated with TNBS. After the last TNBS administration, DAI in the recurrent colitis group was lower than that in the acute colitis group. In the recurrent colitis group, the mice exhibited longer colon length, reduced histological damage and lower IL-1ß, IL-6, TNF, IL-10 mRNA expression in the colon compared with the acute colitis group. The ratio of FOXP3 to CD3 mRNA expression in the colon of recurrent colitis was higher than that in the acute colitis. There was a significant negative correlation between the ratio of FOXP3 to CD3 mRNA expression and DAI in the acute and recurrent colitis groups (r= -0.808, P<0.05). CONCLUSIONS: Mice that recovered from TNBS-induced acute colitis with intestinal epithelial disruption are resistant to recurrent colitis, which is associated with an increased ratio of FOXP3 to CD3 mRNA expression.

The efficacy, safety and cost-effectiveness of hydrotalcite versus esomeprazole in on-demand therapy of NERD: A multicenter, randomized, open-label study in China.

OBJECTIVE: The aim of the study was to investigate whether hydrotalcite was comparable to esomeprazole, a proton pump inhibitor, in on-demand therapy for non-erosive reflux disease (NERD). METHODS: This was a multicenter, randomized, open-label clinical trial with initial and on-demand therapy. Patients who had complete symptom relief in the initial therapy were randomized to either hydrotalcite or esomeprazole in the on-demand therapy. The percentage of patients who quit on-demand therapy in the two groups and the cost-effectiveness of the treatment were evaluated as primary end points. The rate of symptom relief and the improvement of symptom score for initial therapy and the weekly average symptom score and weekly average number of days on treatment for on-demand therapy were evaluated as secondary end points. RESULTS: In total, 398 patients were recruited in the initial therapy group, among whom 253 were included in on-demand therapy, with 127 patients in the hydrotalcite group and the remaining 126 in the esomeprazole group. 14 (11.0%) patients in the hydrotalcite group and six (4.8%) in the esomeprazole group quit the on-demand therapy due to unsatisfactory symptom control (P = 0.065). Cost-effectiveness calculated as the ratio of the cost of hydrotalcite to that of esomeprazole (per person/day) was 35.3% in the on-demand therapy. Similar number of patients achieved symptom relief in both groups. CONCLUSION: Hydrotalcite is a good option of on-demand therapy for NERD patients due to its cost-effectiveness and speed of action.

Decreased dietary fiber intake and structural alteration of gut microbiota in patients with advanced colorectal adenoma.

BACKGROUND: Accumulating evidence indicates that diet is one of the most important environmental factors involved in the progression from advanced colorectal adenoma (A-CRA) to colorectal cancer. OBJECTIVE: We evaluated the possible effects of dietary fiber on the fecal microbiota of patients with A-CRA. DESIGN: Patients with a diagnosis of A-CRA by pathological examination were enrolled in the A-CRA group. Patients with no obvious abnormalities or histopathological changes were enrolled in the healthy control (HC) group. Dietary fiber intake was assessed in all patients. Short-chain fatty acids (SCFAs) in feces were detected by gas chromatography. The fecal microbiota community was analyzed by 454 pyrosequencing based on 16S ribosomal RNA. RESULTS: Lower dietary fiber patterns and consistently lower SCFA production were observed in the A-CRA group (n = 344). Principal component analysis showed distinct differences in the fecal microbiota communities of the 2 groups. Clostridium, Roseburia, and Eubacterium spp. were significantly less prevalent in the A-CRA group (n = 47) than in the HC group (n = 47), whereas Enterococcus and Streptococcus spp. were more prevalent in the A-CRA group (n = 47) (all P < 0.05). Butyrate and butyrate-producing bacteria were more prevalent in a subgroup of HC subjects with a high fiber intake than in those in both the low-fiber HC subgroup and the high-fiber A-CRA subgroup (all P < 0.05). CONCLUSION: A high-fiber dietary pattern and subsequent consistent production of SCFAs and healthy gut microbiota are associated with a reduced risk of A-CRA. This trial was registered at www.chictr.org as ChiCTR-TRC-00000123.

siRNA-based targeting of fractalkine overexpression suppresses inflammation development in a severe acute pancreatitis rat model.

Fractalkine (FKN), a chemokine that acts as both an adhesion molecule and a chemoattractant, is expressed in many inflammatory diseases. Chemokines play a crucial role in severe acute pancreatitis (SAP). This study used adenovirus-mediated siRNA to target FKN overexpression and assessed its ability to suppress inflammation development in a SAP rat model. Adenovirus-mediated FKN siRNA was transfected into cerulein-stimulated AR42J cells. The growth of cerulein-stimulated AR42J cells was determined by colony formation and MTT assays. The inhibitory effect of the FKN siRNA was studied in a SAP rat model in vivo and detected by ELISA, RT-PCR, western blot analysis and immunohistochemistry. FKN, IL-8 and TNF-α were found to be overexpressed in cerulein-stimulated AR42J cells by ELISA and western blot analysis (P<0.05). The animal experiments confirmed that FKN siRNA could inhibit inflammation development in SAP. The values of serum FKN, TNF-α and IL-8 levels were decreased after FKN siRNA treatment (P<0.05). Furthermore, western blotting and RT-PCR analysis showed that FKN protein and mRNA levels were decreased after injection with FKN siRNA (P<0.05). Immunohistochemistry also showed that inflammation was decreased after injection with FKN-siRNA in the SAP rat model. Treatment with siRNA can inhibit FKN overexpression and also suppresses inflammation development in a SAP rat model. More importantly, this study indicated that FKN, which is overexpressed in the SAP rat model, may serve as a novel and effective therapeutic target for SAP.

High dose glargine alters the expression profiles of microRNAs in pancreatic cancer cells.

AIM: To investigate the effect of high dose glargine on the expression profiles of microRNAs in human pancreatic cancer cells. METHODS: Real-time polymerase chain reaction array (RT-PCR) was applied to investigate miRNAs differentially expressed in Sw1990 cells treated with or without 100 IU/L glargine. Stem-loop RT-PCR was used to confirm the results of the array assay in Sw1990 and Panc-1 cells. The effects of miR-95 on cell growth, apoptosis, invasion and migration abilities were respectively examined by CCK8 assay, apoptosis assay, Matrigel invasion and migration assay in Sw1990 and Panc-1 cells. Nude mice xenograft models with Sw1990 cells were built to investigate pancreatic cancer growth in vivo after transfection by the lentivirus pGLV3-GFP- miR-95. RESULTS: Ten miRNAs were significantly up-regulated and 2 miRNAs down-regulated in glargine treated Sw1990 cells when compared with non-treated cells (2.48-fold changes on average, P < 0.01). miR-95, miR-134 and miR-34c-3p are the top three miRNAs regulated by glargine (3.65-fold, 2.67-fold and 2.60-fold changes respectively, P < 0.01) in Sw1990 cells. Stem-loop RT-PCR confirmed that high dose glargine up-regulated the expression of miR-95 and miR-134 in both Sw1990 and Panc-1 cells. The most obvious change is the apparent increase of miR-95. Forced expression of miR-95 significantly increased cell proliferation (Sw1990: 2.510 ± 0.129 vs 2.305 ± 0.187, P < 0.05; Panc-1: 2.439 ± 0.211 vs 2.264 ± 0.117, P < 0.05), invasion (Sw1990: 67.90 ± 12.33 vs 47.30 ± 5.89, P < 0.01; Panc-1: 37.80 ± 8.93 vs 30.20 ± 5.14, P < 0.01), migration (Sw1990: 101 ± 6.00 vs 51.20 ± 8.34, P < 0.01; Panc-1: 91.80 ± 9.22 vs 81.50 ± 7.47, P < 0.01) and inhibited cell apoptosis (Sw1990: 22.05% ± 1.92% vs 40.32% ± 1.93%, P < 0.05; Panc-1: 20.17% ± 0.85% vs 45.60% ± 1.43%, P < 0.05) when compared with paired negative controls, whereas knockdown of miR-95 obtained the opposite effect. Nude mice xenograft models confirmed that miR-95 promoted the growth of pancreatic cancer in vivo when compared with negative control (tumor volume: 373.82 ± 23.67 mL vs 219.69 ± 17.82 mL, P < 0.05). CONCLUSION: These observations suggested that modulation of miRNA expression may be an important mechanism underlying the biological effects of glargine.