Acute pancreatitis in intraductal papillary mucinous neoplasm: a single-center retrospective cohort study with systematic review and meta-analysis.

BACKGROUND: Intraductal papillary mucinous neoplasm (IPMN) is a cystic tumor of the pancreas arising from abnormal papillary proliferation of ductal epithelial cells, and is a precancerous lesion of pancreatic malignancy. This study aimed to evaluate associations between acute pancreatitis (AP) and histologic subtypes of IPMN. METHODS: In the clinical study, patients with IPMN confirmed by surgical resection specimens at our institute between 2009 and 2021 were eligible for inclusion. Associations and predictive accuracy of AP on the presence of HGD were determined by logistic regressions. In addition, a systematic review and meta-analysis was conducted through literatures upon search in PubMed, Embase, CENTRAL, China National Knowledge Infrastructure (CKNI), and Wanfang database, up to June, 2023. Pooled effects of the associations between AP and HGD and intestinal epithelial subtype subtype, shown as odds ratios (ORs) with 95% confidence intervals (CIs), were calculated using random effects model. RESULTS: The retrospective cohort study included 47 patients (32 males, 15 females) diagnosed with IPMN at our center between 2009 and 2021, including 11 cases with AP (median 62 years) and 36 cases (median 64.5 years) without. Accuracy, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of AP in predicting HGD were 78.7%, 57.1%, 82.5%, 36.4%, and 91.7%, respectively. Univariate logistic regression analysis showed that AP group had greater odds of presence of HGD (OR: 6.29,95% CI: 1.14-34.57) than non-AP group. Meta-analysis of five case-control studies in the literature included 930 patients and showed that AP-IPMN patients had higher odds for HGD (OR: 2.13, 95% CI 1.38-3.29) and intestinal epithelial subtype (OR: 5.38, 95% CI: 3.50-8.27) compared to non-AP IPMN. CONCLUSIONS: AP is predictive of malignancy in patients with IPMN.

Butyrate suppresses abnormal proliferation in colonic epithelial cells under diabetic state by targeting HMGB1.

Butyrate is widely accepted as a proliferation inhibitor in colon cancer but less thoroughly characterized in the colonic epithelium of objects with type 2 diabetes mellitus. The present study investigated the regulatory effect of butyrate on proliferation, the related molecule high-mobility group box 1 (HMGB1) and the receptor for advanced glycation end products (RAGE) in the colon of db/db type 2 diabetic model mice and non-cancerous NCM460 colon cells. Proliferation and the expression of HMGB1 and RAGE were increased and could be partially reversed by butyrate treatment in the colon of db/db mice, which were consistent in NCM460 cells under a high glucose state. In NCM460 cells, under the normal glucose state, proliferation increased by overexpression of HMGB1. Under a high glucose state, increased expression of HMGB1 was accompanied with a release from cell nuclei into the cytoplasm and extracellular matrix. Down-regulation of HMGB1 could lower the expression of RAGE and attenuate the abnormally increased proliferation. And overexpression of HMGB1 reversed the suppressing effect of butyrate on abnormally increased proliferation. Conclusively, butyrate suppressed the abnormally increased proliferation in colonic epithelial cells under diabetic state by targeting HMGB1.

Butyrate ameliorated-NLRC3 protects the intestinal barrier in a GPR43-dependent manner.

BACKGROUND: Intestinal barrier dysfunctions are related to dysbacteriosis and chronic gut inflammation in type 2 diabetes. Although there is emerging evidence that the chronic gut inflammatory response is stimulated by nucleotide-binding oligomerization domain-like receptors (NLRs), the relationship and precise mechanism between NLRC3 and the colonic epithelial barrier remains largely elusive. METHODS: We investigated the function and mechanism of NLRC3 in the colonic tissues of diabetic mice and colonic epithelial cell lines. The regulatory mechanism between NLRC3, butyrate and tight junctions was elucidated via a transepithelial electrical resistance measurement, transmission electron microscopy, RNA interference and western blotting. RESULTS: In this study, we found that NLRC3 expression was decreased in the colonic tissues of diabetic mice. NLRC3 over-expression ameliorated colonic epithelial barrier integrity and up-regulated tight junction proteins in colonic epithelial cells. Knockdown of TRAF6 diminished NLRC3-induced ZO-1/occludin expression. In addition, we demonstrated that butyrate could stimulate NLRC3 expression in both diabetic mice and colonic epithelial cells. GPR43 on colonic epithelial cells is involved in the activation of NLRC3 induced by butyrate. CONCLUSION: Our findings demonstrated that NLCR3 could ameliorate colonic epithelial barrier integrity in diabetes mellitus in a TRAF6-dependent manner, and NLCR3 was stimulated by butyrate via binding GPR43 on colonic epithelial cells.

Epigenetic modification of TLE1 induce abnormal differentiation in diabetic mice intestinal epithelium.

The intestinal epithelium cells (IECs) in diabetes mellitus (DM) patients have been proven to be abnormally differentiated. During the differentiation of IECs, epigenetic modification acts as an important regulator. In this study, we aimed to examine the epigenetic alteration of Transducin-like Enhancer of Split 1 (TLE1), a multitask transcriptional co-repressor, contributing to the differentiation homeostasis in IECs of DM mice. The IECs of type 2 diabetic mice model were isolated and collected. Methylation states of whole genomic DNA promoter regions were investigated by microarray. Methylated-specific PCR was used to detect the methylation state of TLE1 promoter in DM mice IECs. The expression of TLE1, Hes1, and differentiated cell markers were measured through real-time PCR, Western blots, and immunohistochemistry; by transfection assay, TLE1 or Hes1 was independently down-regulated in intestinal epithelium cell line, IEC-6. Subsequent modulation on TLE1, Hes1, and differentiated intestinal cell markers were detected. Global gene promoter regions in DM intestinal epithelium were less methylated comparing to normal control. The expression of TLE1 was significantly increased via hypomethylated activation in DM mice IECs. Hes1 was significantly suppressed and the terminal cell markers abnormally expressed in DM mice IECs (P < 0.05). Inhibition or induction on the abundance of TLE1 in IEC-6 cell line resulted in the corresponding dysregulation of Hes1 and intestinal epithelium differentiation (P < 0.05). Demethylation of TLE1 promoter region activates the self-expression in diabetic mice IECs. Subsequently, TLE1, through the transcriptional suppression on expression of Hes1, contributes to the aberrant differentiation of IECs in DM mice.

Certain Dietary Habits Contribute to the Functional Dyspepsia in South China Rural Area.

BACKGROUND Functional dyspepsia (FD) refers to a group of upper gastrointestinal syndromes, subdivided into two types: postprandial distress syndrome (PDS) and epigastric pain syndrome (EPS). The etiology of FD remains unclear; however, unhealthy dietary habit is one potential underlying cause. We aim to explore the association of poor dietary habits with FD and its subtypes. MATERIAL AND METHODS A validated epidemiological questionnaire was designed to investigate dietary habits and gastrointestinal syndromes. Citizens in the Baotun community of Dongguan were invited to complete the study questionnaire. All participants were asked to undergo a physical examination and a blinded physician interview. The study was conducted from June 2015 to June 2016. FD was diagnosed using ROME III criteria. The association between investigated dietary habits and dyspeptic symptoms were explored. RESULTS There were 1,304 adult residents recruited for the study survey; 165 residents had existing organic dyspepsia (OD), 203 residents were diagnosed with FD, and the other 936 participants, who were without dyspeptic symptoms or functional gastrointestinal diseases, were regarded as the control group. Subtype diagnosis indicated 61 participants had EPS, 66 participants had PDS, and 76 participants had coexisting EPS and PDS. Unhealthy dietary habits were more prevalent in the FD group than in the control groups (75.86% versus 37.50%; p<0.001). FD was found to be associated with irregular mealtime, dining out, fatty food, sweet food, and coffee (p<0.05). The impact of each dietary factor varied with FD subtypes. CONCLUSIONS Certain types of dietary habits were positively correlated with the prevalence of FD. FD subtypes showed relatively different associations with dietary factors.

Overexpression of miR-429 impairs intestinal barrier function in diabetic mice by down-regulating occludin expression.

Diabetes mellitus (DM) is a group of metabolic diseases characterised by insulin deficiency/resistance and hyperglycaemia. We previously reported the presence of an impaired tight junction and decreased expression of occludin (Ocln) and zonula occludens-1 (ZO-1) in the intestinal epithelial cells (IECs) of type 1 DM mice, but the exact mechanism remains unclear. In this study, we investigated the role of microRNAs (miRNAs) in impairing the tight junction in IECs of DM mice. Using an integrated comparative miRNA microarray, miR-429 was found to be up-regulated in IECs of type 1 DM mice. Then, miR-429 was confirmed to directly target the 3'-UTR of Ocln, although it did not target ZO-1. Moreover, miR-429 down-regulated the Ocln expression in IEC-6 cells in vitro. Finally, exogenous agomiRNA-429 was shown to down-regulate Ocln and induce intestinal barrier dysfunction in normal mice, while exogenous antagomiRNA-429 up-regulated Ocln in vivo and improved intestinal barrier function in DM mice. In conclusion, increased miR-429 could down-regulate the expression of Ocln by targeting the Ocln 3'-UTR, which impaired intestinal barrier function in DM mice.

Transgelin increases metastatic potential of colorectal cancer cells in vivo and alters expression of genes involved in cell motility.

BACKGROUND: Transgelin is an actin-binding protein that promotes motility in normal cells. Although the role of transgelin in cancer is controversial, a number of studies have shown that elevated levels correlate with aggressive tumor behavior, advanced stage, and poor prognosis. Here we sought to determine the role of transgelin more directly by determining whether experimental manipulation of transgelin levels in colorectal cancer (CRC) cells led to changes in metastatic potential in vivo. METHODS: Isogenic CRC cell lines that differ in transgelin expression were characterized using in vitro assays of growth and invasiveness and a mouse tail vein assay of experimental metastasis. Downstream effects of transgelin overexpression were investigated by gene expression profiling and quantitative PCR. RESULTS: Stable overexpression of transgelin in RKO cells, which have low endogenous levels, led to increased invasiveness, growth at low density, and growth in soft agar. Overexpression also led to an increase in the number and size of lung metastases in the mouse tail vein injection model. Similarly, attenuation of transgelin expression in HCT116 cells, which have high endogenous levels, decreased metastases in the same model. Investigation of mRNA expression patterns showed that transgelin overexpression altered the levels of approximately 250 other transcripts, with over-representation of genes that affect function of actin or other cytoskeletal proteins. Changes included increases in HOOK1, SDCCAG8, ENAH/Mena, and TNS1 and decreases in EMB, BCL11B, and PTPRD. CONCLUSIONS: Increases or decreases in transgelin levels have reciprocal effects on tumor cell behavior, with higher expression promoting metastasis. Chronic overexpression influences steady-state levels of mRNAs for metastasis-related genes.

MEK/ERK pathway activation by insulin receptor isoform alteration is associated with the abnormal proliferation and differentiation of intestinal epithelial cells in diabetic mice.

In previous studies, we have reported the abnormal proliferation and differentiation of intestinal epithelial cells (IECs) in diabetes mellitus (DM) mice. The insulin receptor (IR) and its downstream mitogen-activated protein kinase kinase (MAPKK also known as MEK)/extracellular-regulated protein kinase (ERK) pathway is a classic pathway associated with cell proliferation and differentiation. The purpose of the present study is to investigate the role of the MEK/ERK pathway in abnormal proliferation and differentiation of IECs in DM mice. DM mouse models were induced by intraperitoneal injection of streptozotocin. The expression levels of the IR and its isoforms in IECs of DM mice and in IEC-6 cells were investigated. To ensure that the downstream pathways were monitored, QPCR and Western blotting were performed to detect the expression levels of MEK1/2, ERK1/2, PI3K, and Akt. Moreover, siRNA for IR-A and U0126, a specific inhibitor of MEK, were used to further investigate the relationship between the IR/MEK/ERK pathway and abnormal proliferation and differentiation of IECs in DM mice. In DM mice, excessive proliferation, disturbed differentiation, and a high ratio of IR-A/IR-B were detected in IECs. The expression levels of MEK1, MEK2, and ERK1/2 and their phosphorylated proteins in DM mice were significantly higher than those in the control group (P < 0.05), which could be offset by using siRNA for IR-A. The abnormal proliferation and differentiation of IECs in DM mice were normalized after the in vivo administration of U0126. The abnormal proliferation and differentiation of IECs in DM mice are associated with high IR-A/IR-B ratio and increased IR/MEK/ERK pathway activity.

AKT and JNK Signaling Pathways Increase the Metastatic Potential of Colorectal Cancer Cells by Altering Transgelin Expression.

BACKGROUND: Transgelin (SM22) plays a crucial role in colorectal cancer (CRC) progression; nevertheless, its upstream regulatory mechanisms are poorly defined. AKT and JNK signaling pathways are strongly associated with tumor progression and metastasis, and there are some indications that these pathways might be involved in transgelin regulation. AIMS: To examine the role of AKT and JNK signaling in transgelin regulation in colorectal cancer progression. METHODS: Phospho-AKT (P-AKT), phospho-JNK (P-JNK), and transgelin expression were examined in one normal colon cell line (FHC) and three CRC cell lines (SW620, LoVo, and RKO) as well as in normal colon and CRC tissue samples by Western blot and qRT-PCR. Next, siRNA silencing of AKT or JNK pathways in SW620 cells was performed to examine their role in transgelin regulation. The effects of siRNA silencing on SW620 cell mobility and metastatic properties were examined by cell migration, invasion assays, and actin cytoskeleton. RESULTS: Transgelin, P-AKT, and P-JNK were increased in all examined cell lines. Moreover, transgelin mRNA and protein expression was especially elevated in SW620 cells. Furthermore, inhibition of Akt or JNK signaling resulted in transgelin downregulation. When transgelin, Akt, or JNK signaling was inhibited, SW620 cell migration and invasion were dramatically decreased with inhibition of actin cytoskeleton dynamics. CONCLUSION: This study demonstrates, for the first time, that activated AKT and JNK signaling pathways promote the overexpression of transgelin, which potentially contributes to CRC progression and metastasis.

Association of Bactericidal Dysfunction of Paneth Cells in Streptozocin-Induced Diabetic Mice with Insulin Deficiency.

BACKGROUND Type 1 diabetes mellitus (T1DM) is associated with increased risks of enteric infection. Paneth cells constitute the first line of the gut defense. Little is known about the impact of T1DM on the bactericidal function of intestinal Paneth cells. MATERIAL AND METHODS A T1DM mouse model was induced by intraperitoneal injection of streptozocin. The analysis of intestinal microbiota and the mucosal bactericidal assay were conducted to evaluate intestinal innate defense. Numbers of Paneth cells and their expression of related antimicrobial peptides were analyzed. Expression of total insulin receptor (IR) mRNA and relative levels of IR-A/IR-B were analyzed. The primary mouse small intestinal crypt culture was used to analyze the effect of insulin and glucose on the expression of related antimicrobial peptides of Paneth cells. RESULTS In T1DM mice, bacterial loads were increased and there was an alteration in the composition of the intestinal microflora. Exogenous bacteria had better survival in the small bowel of the T1DM mice. The expression of Paneth cell-derived antimicrobial peptides was significantly decreased in the T1DM mice, although the number of Paneth cells was increased. Relative levels of IR-A/IR-B in Paneth cells of diabetic mice were elevated, but the total IR mRNA did not change. Insulin treatment restored the expression of antimicrobial peptides and normalized the microbiota in the gut of T1DM mice. Subsequently, in vitro culture assay demonstrated that insulin rather than glucose was essential for the optimal expression of Paneth cell-derived antimicrobial peptides. CONCLUSIONS The bactericidal function of intestinal Paneth cells was impaired in STZ-induced diabetic mice, resulting in the altered intestinal flora, and insulin was essential for the optimal expression of Paneth cell-derived antimicrobial peptides.

High glucose-induced intestinal epithelial barrier damage is aggravated by syndecan-1 destruction and heparanase overexpression.

Syndecan-1 (Sdc1) and its endo-beta-D-glucuronidase heparanase (HPSE) are implicated in maintenance of intestinal epithelial barrier (IEB), but their alterations and roles in high-glucose/hyperglycaemia (HG) conditions have not been fully investigated. This study aimed to determine the expression pattern, the possible regulation mechanism of Sdc1 and HPSE in HG conditions, and their potential effects on IEB. Therefore, diabetic mice/cell models were developed, and tissue/serum samples, cell lysate and culture supernatants were harvested. The expression of Sdc1 and HPSE in control, HG and designated interventions groups were detected. Phosphorylations of mitogen-activated protein kinase signalling pathway (MAPK), the expressions of Occludin and ZO-1, and the levels of transepithelial electrical resistance (TEER) were measured and monitored. The results showed that in HG conditions, intestinal tissue and cellular Sdc1 were significantly decreased, but the expression of HPSE, and soluble Sdc1 in serum and culture supernatants were remarkably increased. Such alterations of Sdc1 and HPSE were associated with solely p38 MAPK activation, and were correlated with the reductions of Occludin, ZO-1 and TEER. Heparin (Sdc1 analogue) and SB203580 (a p38 MAPK inhibitor), instead of insulin, alleviated Sdc1 destruction and HPSE overexpression, and effectively prevented against the reductions of tight junctions and the abnormality of intestinal permeability in HG conditions. In conclusion, we confirm the unique alterations of Sdc1 and HPSE in HG conditions, and found their interactions with p38 MAPK activation and IEB. These indicate that Sdc1/HPSE modulation can be viewed as an important complementary treatment for relieving HG-induced gastrointestinal damage.

Lgr5 positive stem cells sorted from small intestines of diabetic mice differentiate into higher proportion of absorptive cells and Paneth cells in vitro.

Intestinal epithelial stem cells (IESCs) can differentiate into all types of intestinal epithelial cells (IECs) and Leucine-rich repeat-containing G protein-coupled receptor 5 (Lgr5) is a marker for IESC. Previous studies reported enhanced proliferation of IECs in diabetic mice. In this study, the in vitro differentiation of Lgr5 positive IESCs sorted from diabetic mice was further investigated. The diabetic mouse model was induced by streptozotocin (STZ), and crypt IECs were isolated from small intestines. Subsequently, Lgr5 positive IESCs were detected by flow cytometry (FCM) and sorted by magnetic activated cell sorting (MACS). Differentiation of the sorted IESCs was investigated by detecting the IEC markers in the diabetic mice using immunostaining, quantitative real-time reverse-transcription polymerase chain reaction (qRT-PCR), and Western blot analysis, which was compared with normal mice. We found that the proportion of Lgr5 positive cells in the crypt IECs of diabetic mice was higher than that of control mice (P < 0.05). Lgr5 positive IESCs could be significantly enriched in Lgr5 positive cell fraction sorted by MACS. Furthermore, the absorptive cell marker sucrase-isomaltase (SI) and the Paneth cell marker lysozyme 1 (Lyz1) were more highly expressed in the differentiated cells derived from Lgr5 positive IESCs of diabetic mice in vitro (P < 0.05). We demonstrate that the number of Lgr5 positive IESCs is significantly increased in the small intestines of STZ-induced diabetic mice. Lgr5 positive IESCs sorted from the diabetic mice can differentiate into a higher proportion of absorptive cells and Paneth cells in vitro. We characterized the expression of Lgr5 in the small intestine of diabetic mice, and sorted Lgr5 positive intestinal epithelial stem cells (IESCs) for investigating their differentiation in vitro. We proved that the quantity of Lgr5 positive IESCs was significantly increased in the small intestines of diabetic mice. IESCs sorted from the diabetic mice can differentiate into a higher proportion of absorptive cells and Paneth cells in vitro.

CXCR4 positive cell-derived Pdx1-high/Shh-low cells originated from embryonic stem cells improve the repair of pancreatic injury in mice.

Treatments for pancreatic injuries have been significantly improved recently, but full recovery of pancreatic function remains difficult. Embryonic stem cells have great potentialities for self-renewal and multiple differentiations. In this study, we explored an approach to induce the differentiation of pancreatic progenitor cells from embryonic stem cells in vitro. Male mouse embryonic stem cells were cultured by the hanging-drop method to form embryoid bodies. The definitive endoderm marked by CXCR4 in embryoid bodies was sorted by magnetic activated cell sorting and subsequently administrated with b-FGF, exendin-4, and cyclopamine to induce the differentiation of putative pancreatic progenitor cells, which was monitored by Pdx1, and Shh expressions. The putative pancreatic progenitor cells were transplanted into female BALB/c mice with pancreatitis induced by L-Arginine. Male donor cells were located by detecting sex-determining region of Y-chromosome DNA. Definitive endoderm cells (CXCR4(+) cells) were sorted from 5-day embryoid bodies. After 3-day administration with b-FGF, exendin-4, and cyclopamine, Pdx1-high/Shh-low cells were differentiated from CXCR4(+) cells. These cells developed into more amylase-secreted cells in vitro and could specifically reside in the damaged pancreas acinar area in mice with acute pancreatitis to enhance the regeneration. The putative pancreatic progenitor cells (Pdx1-high/Shh-low cells) derived from mouse embryonic stem cells through the administration of b-FGF, exendin-4, and cyclopamine on the CXCR4(+) cells in vitro could improve the regeneration of injured pancreatic acini in vivo.

Abnormal differentiation of intestinal epithelium and intestinal barrier dysfunction in diabetic mice associated with depressed Notch/NICD transduction in Notch/Hes1 signal pathway.

Proliferative change and intestinal barrier dysfunction in intestinal mucosa of diabetes have been described, but the differentiation characteristics of intestinal epithelial cells (IECs) and the mechanisms in the IECs development remain unclear. To explore the intestinal epithelial constitution patterns and barrier function, the diabetic mouse model was induced by streptozotocin. Tight junctions between IECs were significantly damaged and the serum level of D-lactate was raised in diabetic mice (P < 0.05). The expression of Zo1 and Ocln in the small intestine of diabetic mice were lower, while the markers for absorptive cell (SI) and Paneth cell (Lyz1) were significantly higher than in control mice (P < 0.05). The expression of Msi1, Notch1, and Dll1 in small intestine gradually increased throughout the course of hyperglycemia in diabetic mice (P < 0.05). However, the expression of NICD, RBP-jκ, Math1, and Hes1 had a reverse trend compared with Msi1 and Notch1. Intestinal absorptive cells and Paneth cells had a high proliferation rate in diabetic mice. However, the intestinal barrier dysfunction associated with the decreased expressions of Zo1 and Ocln was detected throughout hyperglycemia. In conclusion, downregulation of Notch/Hes1 signal pathway caused by depressed Notch/NICD transduction is associated with the abnormal differentiation of IECs and intestinal barrier dysfunction in diabetic mice.

Clinical features and expressions of Foxp3 and IL-17 in type 1 autoimmune pancreatitis in China.

BACKGROUND: Autoimmune pancreatitis (AIP) is a distinct type of pancreatitis associated with a presumed autoimmune mechanism. The aim of this study was to analyze the clinical features and expressions of forkhead box P3 (Foxp3) and interleukin-17 (IL-17) in type 1 AIP in China and to identify factors for differentiation of AIP from non-AIP chronic pancreatitis (CP). MATERIAL AND METHODS: We retrospectively reviewed pancreatic specimens with diagnosis of type 1 AIP and non-AIP CP at Sun Yat-Sen Memorial Hospital in China from January 2000 to December 2013. The clinical symptoms, serological data, imaging findings, histopathology, and immunohistochemical findings of Foxp3 and IL-17 in the 2 groups were analyzed. RESULTS: Twenty-nine patients with type 1 AIP and 20 patients with non-AIP CP were enrolled. Obstructive jaundice was more common in type 1 AIP than in non-AIP CP (62.1% vs. 30.0%, P=0.042). The diffuse or segmental enlargement of the pancreas was more frequent in type 1 AIP than in non-AIP CP (72.4% vs. 40.0%, P=0.038). Histopathology of type 1 AIP presented dense lymphoplasmacytic infiltration, "snowstorm-like" fibrosis and abundant immunoglobulin (Ig) G4+ cells. Foxp3+ cells were more frequently observed in type 1 AIP than in non-AIP CP. IL-17+ cell infiltration was similar between the 2 groups. Furthermore, a positive correlation was found between Foxp3+ and IgG4+ cell counts in the pancreas of patients with type 1 AIP. CONCLUSIONS: Type 1 AIP has distinctive symptoms, image, and pathological characteristics, which could be used for differentiation from non-AIP CP. Foxp3+ cells might be helpful to distinguish type 1 AIP from non-AIP CP.

Celiac plexus block for treatment of pain associated with pancreatic cancer: a meta-analysis.

Pancreatic ductal adenocarcinoma has a high rate of neural invasion (80 to 100%) and can be associated with moderate to severe pain in pancreatic cancer. Treatment of pain with celiac plexus blockage (CPB) combined with the three-step ladder utilization of pharmaceutical analgesics following WHO guidelines is used, but the evidence in randomized controlled trials is inconsistent. This meta-analysis identified and compared seven randomized control trials of pain relief from pancreatic cancer, by treatment with medical management alone to celiac plexus blockade with medical management. While no evidence of potential publication bias was detected, group size and statistical power may account for some of the inconsistent conclusions. The combined CPB groups had a significantly lower pain score at 4 weeks, but significance was not maintained at 8 weeks. The combined CPB groups required significantly less drug use compared to the combined control groups treated with pharmaceutical analgesics.

Gastroesophageal Reflux Disease Questionnaire (GerdQ) in real-world practice: a national multicenter survey on 8065 patients.

BACKGROUND AND AIM: Recently, Gastroesophageal Reflux Disease Questionnaire (GerdQ) has been developed for diagnosis of GERD. However, no study investigated its value in real-world practice. This study aimed to investigate whether GerdQ can be used for diagnosis of GERD in China. METHODS: A national multicenter survey was undertaken; all patients who underwent first diagnostic upper endoscopy for upper gastrointestinal (GI) symptoms were included. Data including the gender, age, symptoms, and endoscopic findings were prospectively recorded. The GerdQ score was measured before endoscopic procedure. RESULTS: Totally, 8065 patients were included. One thousand four hundred and thirty-five patients (17.8%) had reflux esophagitis. Among them, 620 (43.2%) patients' GerdQ score was ≥ 8. For 2025 patients with GerdQ ≥ 8, 620 (30.6%) were found to have reflux esophagitis, but the remaining 69.4% (1405/2025) were normal. Proportions of patients with reflux esophagitis increased in cut-off range from 3-18 for GerdQ. However, 22.2% of the patients with a GerdQ score ≤ 2 also had reflux esophagitis. Twenty-eight (0.3%) patients were diagnosed to have upper GI malignancies, and 10 out of these 28 (35.7%) patients' GerdQ score was ≥ 8. CONCLUSIONS: The study suggests the proportions of Chinese patients with reflux esophagitis rise up with the increase of GerdQ score, and GerdQ may be used for diagnosis of GERD. However, low GerdQ score cannot exclude the possibility of reflux esophagitis. A minority of Chinese patients has high GerdQ score but is diagnosed with malignancies, even in the absence of alarm features.

Rebamipide helps defend against nonsteroidal anti-inflammatory drugs induced gastroenteropathy: a systematic review and meta-analysis.

BACKGROUND: Gastrointestinal toxicity of nonsteroidal anti-inflammatory drugs (NSAIDs) has been perplexing most clinicians and users of NSAIDs. Rebamipide is increasingly advocated as a candidate option for the prevention of NSAIDs induced gastrointestinal mucosal injury. AIMS: To assess the efficacy and the safety of rebamipide for the prevention and treatment of NSAID-induced gastroenteropathy. METHODS: PubMed, Embase, Web of Science, Google Scholar, the Cochrane Library, Japan Science and Technology Information Aggregator, and China Biology Medicine Disc were searched up to December 2011. Randomized controlled trials (RCTs) recruiting subjects with co-prescriptions of NSAIDs and rebamipide were eligible. Efficacy and safety of rebamipide were reevaluated, and dichotomous data were pooled to obtain relative risk (RR) with a 95 % confidence interval. Heterogeneity and publication bias were assessed by the inconsistency index statistic and funnel plot analysis, respectively. RESULTS: The search identified 338 citations, and 15 RCTs including 965 individuals were eligible. In general, rebamipide acted better than placebo against short-term NSAID-induced gastroduodenal injury. Separate studies showed rebamipide was equal to or not superior to traditional strategies (including PPIs, H2RA and misoprostol treatment). Especially, rebamipide showed a beneficial effect against the small bowel damage (total RR = 2.70, 95 % confidence interval = 1.02-7.16, P = 0.045) when compared with placebo group. The average incidence of adverse events was about 36.1 % (0-70.0 %) but no serious event was recorded. CONCLUSIONS: Current evidences show rebamipide is effective and safe for defending against NSAID-induced gastroduodenal and lower-gastrointestinal injuries. However, more well-designed trials should be conducted to fully confirm the practical value of rebamipide.

Effects of hemicellulose on intestinal mucosal barrier integrity, gut microbiota, and metabolomics in a mouse model of type 2 diabetes mellitus.

Background and objective: Impaired gut barrier contributes to the progression of type 2 diabetes mellitus (T2DM), and the gut microbiota and metabolome play an important role in it. Hemicellulose, a potential prebiotics, how its supplementation impacted the glucose level, the impaired gut barrier, and the gut microbiota and metabolome in T2DM remained unclear. Methods: In this study, some mice were arranged randomly into four groups: db/db mice fed by a compositionally defined diet (CDD), db/db mice fed by a CDD with 10% and 20% hemicellulose supplementation, and control mice fed by a CDD. Body weight and fasting blood glucose levels were monitored weekly. The gut barrier was evaluated. Fresh stool samples were analyzed using metagenomic sequencing and liquid chromatography-mass spectrometry to detect gut microbiota and metabolome changes. Systemic and colonic inflammation were evaluated. Results: Better glycemic control, restoration of the impaired gut barrier, and lowered systemic inflammation levels were observed in db/db mice with the supplementation of 10 or 20% hemicellulose. The gut microbiota showed significant differences in beta diversity among the four groups. Fifteen genera with differential relative abundances and 59 significantly different metabolites were found. In the db/db group, hemicellulose eliminated the redundant Faecalibaculum and Enterorhabdus. The increased succinate and ursodeoxycholic acid (UDCA) after hemicellulose treatment were negatively correlated with Bifidobacterium, Erysipelatoclostridium, and Faecalibaculum. In addition, hemicellulose reduced the colonic expressions of TLR2/4 and TNF-α in db/db mice. Conclusion: Hemicellulose may serve as a potential therapeutic intervention for T2DM by improving impaired intestinal mucosal barrier integrity, modulating gut microbiota composition, and altering the metabolic profile.