Colchicine improves severe acute pancreatitis-induced acute lung injury by suppressing inflammation, apoptosis and oxidative stress in rats.

BACKGROUND: Inflammation, apoptosis and oxidative stress contribute to the development of severe acute pancreatitis-associated acute lung injury (SAP-ALI). Currently, there is no curative treatment for SAP-ALI in the clinic. This study investigated the potential therapeutic role and mechanisms of colchicine in a rat model of SAP-ALI. METHODS: Male Sprague-Dawley rats were randomized and administrated intragastrically with vehicle saline or colchicine (0.5 mg/kg/day) for seven days, followed by injecting sodium taurocholate to induce SAP-ALI. Together with a healthy control group of rats, their pancreatic and lung tissues and plasma samples were collected for histology, enzyme-linked immunosorbent assay (ELISA), immunoblot, immunohistochemistry, and immunofluorescence. RESULTS: Compared with the sham controls, the SAP group of rats with vehicle saline treatment displayed severe damages, inflammation with many neutrophil and macrophage infiltrates in pancreatic and lung tissues, accompanied by elevated levels of plasma interleukin-1ß (IL-1ß), IL-6 and tumor necrosis factor (TNF)-α, which were significantly mitigated in colchicine-treated SAP + COL group of rats. Furthermore, colchicine treatment significantly attenuated nuclear factor kappa-B (NF-κB)-p65, signal transducer and activator of transcription 3 (STAT3) and protein kinase B (AKT) phosphorylation, reduced inducible nitric oxide synthase (iNOS) and 4-Hydroxynonenal expression, ROS production and cell apoptosis by decreasing caspase-3 cleavage, Bax expression, but increasing Bcl-2, nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) expression in pancreatic and lung tissues, relative to the SAP group of rats. CONCLUSION: Colchicine treatment significantly mitigated the severity of SAP-ALI by inhibiting inflammation, oxidative stress and cell apoptosis in rats.

Endoscopic submucosal dissection for proximal duodenal subepithelial lesions: a retrospective cohort study.

BACKGROUND AND AIM: Endoscopic submucosal dissection (ESD) has been used to remove subepithelial lesions (SELs) in recent years; however, duodenal ESD is associated with high rates of immediate or delayed bleeding and perforation. Whether ESD can be recommended for the treatment of duodenal SELs remains controversial. Therefore, we evaluated the efficacy and safety of ESD for duodenal SELs. METHODS: We conducted a retrospective cohort study in 62 patients (62 lesions) who underwent ESD for duodenal SELs between January 2012 and December 2020. The therapeutic outcomes from ESD for duodenal SELs and procedure-related complications were analyzed. RESULTS: En bloc resection and complete resection rates associated with duodenal ESD were 90.3% and 100%, respectively; four patients had a positive microscopic margin on pathologic examination. The median procedure time was 45 min (range 20-106 min). During the procedure, two patients received emergency surgery for uncontrolled bleeding and perforation, respectively. After the procedure, delayed bleeding occurred in three patients (4.8%), which was successfully managed by clipping, and delayed perforation occurred in two patients (3.2%) and needed emergency surgery. Risk factors related to complications were analyzed. Lesion size was found to be significantly associated with the complications (P = 0.028). No recurrences were detected, and no distant metastasis was observed in any patient during a median follow-up period of 45.5 months (range, 6-103 months). CONCLUSION: Duodenal ESD is relatively safe and feasible for duodenal SELs, especially for lesions no more than 2 cm in size.

Radiocontrast agent and intraductal pressure promote the progression of post-ERCP pancreatitis by regulating inflammatory response, cellular apoptosis, and tight junction integrity.

OBJECTIVE: Post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (PEP) is the most common complication following ERCP and the mechanism is not fully understood. This study evaluated the changes in the inflammatory response, cellular apoptosis, and tight junction integrity in a rat model of pancreatitis to explore the underlying mechanism. METHODS: PEP was induced in rats by retrograde biliopancreatic ductal infusion of contrast agents or saline. Pancreatic tissues were harvested and evaluated by histopathologic, immunohistochemical, immunofluorescence, and Western blot analyses. In addition, amylase and proinflammatory cytokines in plasma were quantified by ELISA assay. RESULTS: PEP rats developed more severe acute pancreatitis than the sham group after injection of the contrast agent or isotonic saline. PEP rats exhibited increased tissue damage, plasma amylase, proinflammatory cytokines, necrosis, inflammatory infiltrates, apoptosis, and tight junction disruption. At the molecular level, contrast agent and isotonic saline-injected PEP rats demonstrated elevated NF-κB p65 and STAT3 pathways activation, altered expression and activation of apoptosis-related proteins, and suppressed expression of tight junction molecules. However, the contrast agent concentration had no effect on these changes. CONCLUSIONS: In models of acute pancreatitis induced using contrast agent and hydrostatic pressure, the contrast agent and high hydrostatic pressure easily induced the inflammatory response, apoptosis, and tight junction disruption. It is noteworthy that no significant difference in damaged pancreatic acinar cells was observed with different concentrations of the contrast agent.

Design of Phase-Changeable and Injectable Alginate Hydrogel for Imaging-Guided Tumor Hyperthermia and Chemotherapy.

The objective of the present study was to construct an alginate (AG)-based phase-changeable and injectable hydrogel for imaging-guided tumor hyperthermia and chemotherapy. Based on the binding between the α-l-guluronic blocks of AG and calcium ions, the AG/MoS2/Bi2S3-poly(ethylene glycol) (MBP)/doxorubicin (DOX) solution formed a cross-linked hydrogel to simultaneously encapsulate MBP nanosheets and DOX within the hydrogel matrix. The in situ formed hydrogel can act as a reservoir to control the release of entrapped drug molecules, and the doped MBP nanosheets and DOX can realize computed tomography/photoacoustic dual-modal imaging-guided in vivo tumor photothermal therapy and chemotherapy, respectively. The AG/MBP/DOX hydrogel exhibited excellent photothermal conversion properties with mass extinction coefficient of 45.1 L/g/cm and photothermal conversion efficiency of 42.7%. Besides, the heat from the photothermal transformation of MBP can promote drug diffusion from the hydrogel to realize on-demand drug release. Additionally, the hydrogel system can restrain MBP and DOX from entering into the blood stream during therapy, and therefore substantially decrease their side effects on normal organs. More importantly, the drug loading of the AG hydrogel was general and can be extended to the encapsulation of antibiotics, such as amoxicillin, for the prevention of postoperative infections.

Overexpression of YKL-40 Predicts Poor Prognosis in Patients Undergoing Curative Resection of Pancreatic Cancer.

OBJECTIVES: The aim of this study was to determine the prognostic value of YKL-40 expression in patients undergoing curative resection of pancreatic cancer. METHODS: This cohort study included 234 consecutive patients with pancreatic ductal adenocarcinoma who underwent curative resection. Surgical specimens were immunohistochemically assessed for YKL-40 expression. Kaplan-Meier method and Cox regression were used to evaluate the prognostic impact of YKL-40 expression. A multivariate logistic regression model was performed to examine the correlation between YKL-40 expression and tumor stage. RESULTS: Of the 234 patients, YKL-40 overexpression was detected in 149 (63.7%) patients. Survival curves showed that patients with YKL-40 overexpression had significantly shorter survival time than those with low YKL-40 expression (P < 0.001). Cox regression analysis indicated that YKL-40 expression was an independent prognostic factor for both overall survival (hazard ratio, 3.82; 95% confidence interval [CI], 2.38-6.13) and progression-free survival (hazard ratio, 3.73; 95% CI, 2.33-5.99). Multivariate logistic regression analysis demonstrated that YKL-40 overexpression was an independent predictor for advanced tumor stage (odds ratio 4.15; 95% CI, 1.35-12.71). CONCLUSIONS: YKL-40 overexpression predicts poor prognosis and advanced tumor stage in patients undergoing curative resection of pancreatic cancer. Application of adjuvant treatment targeting the YKL-40 pathway may improve prognosis.

Toll-like receptor 4 promotes angiogenesis in pancreatic cancer via PI3K/AKT signaling.

Deregulation of Toll-like receptor 4 (TLR4) is closely associated with the progression of various types of cancers, but its role in pancreatic carcinogenesis is unclear. This study aimed to investigate the role of TLR4 in the angiogenesis of pancreatic cancer and the underlying molecular mechanisms. The culture supernatant (conditioned medium) of PANC-1 cells after appropriate treatment was used for the treatment of HUVECs. The proliferation, migration and tube formation of HUVECs were assessed by MTT, Transwell and Matrigel, respectively. In pancreatic cancer tissues, TLR4, VEGF and CD31 were upregulated as determined by immunohistochemistry and the expression of TLR4 and VEGF was positively correlated with microvessel density as detected by CD31 staining. Activation of TLR4 signaling by LPS in PANC-1 cells resulted in increased VEGF and phosphorylation of AKT, which were abolished by TLR4 silencing with siRNA and PI3K/AKT signaling inhibitor LY294002. The conditioned medium from PANC-1 cells treated with LY294002 or transfected with TRL4 siRNA reduced the proliferation, migration and tube formation of HUVECs. In contrast, the conditioned medium from PANC-1 cells treated with LPS stimulated the proliferation, migration and tube formation of HUVECs, which was however significantly inhibited by pretreatment of PANC-1 cells with LY294002 or transfection with TRL4 siRNA. Our findings suggest TLR4 may promote angiogenesis in pancreatic cancer by activating the PI3K/AKT signaling pathway to induce VEGF expression.

[Liquid-based cytology diagnosis of endoscopic ultrasound-guided fine needle aspiration of pancreatic lesions].

OBJECTIVE: To investigate the diagnostic value of liquid-based cytology test (LCT) in pancreatic lesions sampled by ultrasound-guided fine needle aspiration (EUS-FNA). METHODS: A retrospective analysis of 556 cases of LCT smears sampled by EUS-FNA of pancreatic lesions was performed, and 164 cases had histologic diagnosis with subsequent surgical resection or biopsy and immunohistochemistry. The accuracy of the cytologic diagnosis was assessed using the histologic diagnosis as the gold standard. The discrepant cases were reviewed to identify sources of errors. RESULTS: The satisfactory rate for EUS-FNA was 96.0%(534/556). The sensitivity, specificity, positive predictive value, negative predictive value and diagnostic accuracy were 87.7%(128/146), 13/16, 97.7%(128/131), 41.9%(13/31) and 87.0%(141/162) respectively. The diagnostic accuracy was lower in cystic lesions than that in solid lesions. The LCT sensitivities of adenocarcinoma, lymphoma and neuroendocrine tumors were higher than those of cystic tumors and mesenchymal tumors. False positive diagnosis was mainly due to epithelial abnormalities in inflammatory reaction. False negative diagnosis was mainly due to scanty or lack of tumor cells in the smears, or mild atypia that was insufficient for diagnosis. CONCLUSIONS: EUS-FNA is a valuable tool for the diagnosis of pancreatic lesions. Standardized terminology and nomenclature are helpful to improve the diagnostic accuracy.

Bulk pancreatic cancer cells can convert into cancer stem cells(CSCs) in vitro and 2 compounds can target these CSCs.

Increasing evidence has confirmed the existence of cancer stem cells (CSCs) in both hematological malignancies and solid tumors. However, the origin of CSCs is still uncertain, and few agents have been capable of eliminating CSCs till now. The aim of this study was to investigate whether bulk pancreatic cancer cells could convert into CSCs under certain conditions and explore whether metformin and curcumin can kill pancreatic CSCs. Aspc1, Bxpc3 and Panc1 pancreatic cancer cells were cultured in stem cell culture medium (serum-free Dulbecco's modified Eagle medium/Nutrient Mixture F-12 containing basic fibroblast growth factor, epidermal growth factor, B27 and insulin) for 5 days and it was found that all the pancreatic cancer cells aggregated into spheres and expressed pancreatic cancer stem cell surface markers. Then characteristics of Panc1 sphere cells were analyzed and cytotoxicity assays were performed. The results show that Panc1 sphere cells exhibited CSC characteristics and were more resistant to conventional chemotherapy and more sensitive to metformin and curcumin than their parent cells. These findings suggested that bulk pancreatic cancer cells could acquire CSC characteristics under certain conditions, which may support the "yin-yang" model of CSCs (interconversion between bulk cancer cells and CSCs). These results also showed that metformin and curcumin could be candidate drugs for targeting pancreatic CSCs.

Adenovirus vector-mediated Gli1 siRNA induces growth inhibition and apoptosis in human pancreatic cancer with Smo-dependent or Smo-independent Hh pathway activation in vitro and in vivo.

Activation of Hedgehog (Hh) signaling pathway is a core molecular mechanism in pancreatic carcinogenesis. However, the inhibition of upstream Hh signals does not inhibit the growth of a subset of pancreatic cancer (PC). This study was to examine the effect of siRNA targeting Gli1, the downstream component of Hh pathway, on PC cells and to provide some insight into the underlying mechanisms. A Gli1siRNA-expressing adenovirus (Ad-U6-Gli1siRNA) was constructed, and its effect on PC cells was investigated in vitro and in vivo. Gli1 was expressed in 83.3% (20/24) PC tissues, whereas no expression was found in normal pancreatic ductal epithelium. Gli1 was expressed in SW1990 and CFPAC cells in which Smo was completely absent, as well as in PaTu8988, Panc-1 and BxPC-3 cells in which Smo was concomitantly present. Ad-U6-Gli1siRNA induced cell growth inhibition, strong G0/G1 cell cycle arrest and apoptosis in all five human PC cell lines. Meanwhile, Ad-U6-Gli1siRNA significantly suppressed the expression of Gli1, Ptch1 and two target genes, Cyclin D2 and Bcl-2, in all five lines. Furthermore, two tumor xenograft nude mice models were established by subcutaneously injecting Smo-positive Panc-1 cells or Smo-negative SW1990 cells. The in vivo experimental results demonstrated that Ad-U6-Gli1siRNA inhibited the growth of both Panc1-derived and SW1990-derived tumors and induced cell apoptosis. Our study indicates that Gli1-targeting siRNA could induce growth inhibition and apoptosis in PC through knockdown of Gli1 and its target genes; and this method may represent a more effective therapeutic strategy for PC with Smo-dependent or Smo-independent Hh pathway activation.

Aberrant DNA methyltransferase expression in pancreatic ductal adenocarcinoma development and progression.

BACKGROUND: Altered gene methylation, regulated by DNA methyltransferases (DNMT) 1, 3a and 3b, contributes to tumorigenesis. However, the role of DNMT in pancreatic ductal adenocarcinoma (PDAC) remains unknown. METHODS: Expression of DNMT 1, 3a and 3b was detected in 88 Pancreatic ductal adenocarcinoma (PDAC) and 10 normal tissue samples by immunohistochemistry. Changes in cell viability, cell cycle distribution, and apoptosis of PDAC cell lines (Panc-1 and SW1990) were assessed after transfection with DNMT1 and 3b siRNA. Levels of CDKN1A, Bcl-2 and Bax mRNA were assessed by qRT-PCR, and methylation of the Bax gene promoter was assayed by methylation-specific PCR (MSP). RESULTS: DNMT1, 3a and 3b proteins were expressed in 46.6%, 23.9%, and 77.3% of PDAC tissues, respectively, but were not expressed in normal pancreatic tissues. There was a co-presence of DNMT3a and DNMT3b expression and an association of DNMT1 expression with alcohol consumption and poor overall survival. Moreover, knockdown of DNMT1 and DNMT3b expression significantly inhibited PDAC cell viability, decreased S-phase but increased G1-phase of the cell cycle, and induced apoptosis. Molecularly, expression of CDKN1A and Bax mRNA was upregulated, and the Bax gene promoter was demethylated. However, a synergistic effect of combined DNMT1 and 3b knockdown was not observed. CONCLUSION: Expression of DNMT1, 3a and 3b proteins is increased in PDAC tissues, and DNMT1 expression is associated with poor prognosis of patients. Knockdown of DNMT1 and 3b expression arrests tumor cells at the G1 phase of the cell cycle and induces apoptosis. The data suggest that DNMT knockdown may be a novel treatment strategy for PDAC.

Prenylated phloroglucinol derivatives from Hypericum sampsonii.

Six new acylphloroglucinol derivatives, sampsonols A-F (1-6), were isolated from the petroleum ether extract of the aerial parts of Hypericum sampsonii. The structures and relative configurations of sampsonols A-F were elucidated by extensive spectroscopic analyses. All these compounds were tested for their in vitro cytotoxic and anti-inflammatory activities. Sampsonols A and B (1 and 2) showed significant cytotoxicity against four human tumor cell lines with IC(50) values in the range of 13-28µM, whereas sampsonols C and F (3 and 6) showed potent inhibitory activities against LPS-induced NO production in RAW 264.7 macrophages with IC(50) values of 27.3 and 29.3µM, respectively.

Gastro-protecting effect of gefarnate on chronic erosive gastritis with dyspeptic symptoms.

BACKGROUND: The role of gastro-protecting agents on symptomatic chronic gastritis is unclear. This multicenter, open, randomized trial was designed to compare the comprehensive effects of gefarnate with sucralfate on erosive gastritis with dyspeptic symptoms. METHODS: Totally 253 dyspepsia patients confirmed with erosive gastritis were enrolled from six centers in China. They randomly received either daily 300 mg gefarnate or 3 g sucralfate for six weeks. The primary endpoint was the effective rate of both treatments on endoscopic erosion at week six. RESULTS: Gefarnate showed an effective rate of 72% and 67% on endoscopic score and dyspeptic symptom release, which is statistically higher than sucralfate (40.1% and 39.3%, P < 0.001, intension-to-treat). For histological improvement, gefarnate showed both effective in decreasing mucosal chronic inflammation (57.7% vs. 24.8%, P < 0.001, intension-to-treat) and active inflammation (36.4% vs. 23.1%, P < 0.05, intension-to-treat) than the control. A significant increase of prostaglandins and decrease of myeloperoxidase in mucosa were observed in gefarnate group. Severity of erosion is non-relevant to symptoms but Helicobacter pylori (H. pylori) status does affect the outcome of therapy. CONCLUSIONS: Gefarnate demonstrates an effective outcome on the mucosal inflammation in patients with chronic erosive gastritis. Endoscopic and inflammation score should be the major indexes used in gastritis-related trials.

High expression of delta-like ligand 4 predicts poor prognosis after curative resection for pancreatic cancer.

BACKGROUND: Delta-like ligand 4 (DLL4)-Notch signaling plays a key role in tumor angiogenesis, but its prognostic value in patients with pancreatic ductal adenocarcinoma (PDAC) remains unclear. Our aim was to determine whether high DLL4 expression is correlated with poor prognosis after curative resection for PDAC. METHODS: Surgical specimens obtained from 89 patients with PDAC were immunohistochemically assessed for DLL4 and vascular endothelial growth factor receptor 2 (VEGFR-2) expression. Prognostic significance of DLL4 expression was evaluated by Kaplan-Meier method and Cox regression. The correlations of DLL4 expression with VEGFR-2 expression, tumor stage, and lymph node metastasis were examined by chi-square test and multivariate logistic regression. RESULTS: There were 38 (42.7%) and 51 patients who showed high and low DLL4 expression, respectively. Survival curves showed that patients with low DLL4 expression had a significantly better survival than those with high DLL4 expression (P < .001). Multivariate survival analysis demonstrated that high DLL4 expression was independently associated with both reduced overall survival (hazard ratio [HR] 2.24; 95% confidence interval [95% CI] 1.14-4.38) and reduced progression-free survival (HR 2.37; 95% CI 1.22-4.60). Multivariate logistic regression analyses showed that high DLL4 expression was independently associated with both advanced tumor stage (odds ratio [OR] 6.84; 95% CI 2.42-9.36) and lymph node metastasis (OR 3.27; 95% CI 1.04-10.34). We also found a positive correlation between DLL4 and VEGFR-2 expression (P < .001). CONCLUSIONS: High DLL4 expression is significantly associated with poor prognosis for surgically resected PDAC, advanced tumor stage, and lymph node metastasis. Application of adjuvant therapy targeting DLL4-Notch signaling may improve prognosis.

Comparison of antioxidative and antifibrotic effects of α-tocopherol with those of tocotrienol-rich fraction in a rat model of chronic pancreatitis.

OBJECTIVES: The α-tocopherol and tocotrienol-rich fraction (TRF) are considered effective antioxidants. This study aimed to compare the antioxidative and antifibrotic effects of α-tocopherol and TFR in dibutylin dichloride (DBTC)-induced chronic pancreatitis (CP) rats. METHODS: Oral administration of α-tocopherol and TFR (both 800 mg/kg per day) started the next day after DBTC (8 mg/kg) infusion into the tail vein for 4 weeks. Histological examination, Sirius red staining, and measurement of the contents of hydroxyproline and malondialdehyde of the pancreas were performed to evaluate pancreatic damage and fibrosis. Immunohistochemical analysis of α-smooth muscle actin and real-time reverse transcription polymerase chain reaction for transforming growth factor-ß1 (TGF-ß1) and collagen-α1(I) were performed to evaluate the activation of pancreatic stellate cells and the mRNA levels of fibrosis-related genes, respectively. RESULTS: Both α-tocopherol and TRF reduced oxidative stress, ameliorated inflammation and fibrosis, and down-regulated the mRNA expression of TGF-ß1 and collagen-α1(I) in DBTC-induced CP. The TRF was superior to α-tocopherol in alleviating inflammation and fibrosis and down-regulating TGF-ß1 mRNA expression. CONCLUSIONS: Oral administration of α-tocopherol and TRF improves pancreatic inflammation and fibrosis in DBTC-induced CP rats, with TRF being more effective than α-tocopherol. Therefore, TRF may be a novel option for alleviating inflammation and, particularly, the fibrotic process in CP.

Helicobacter pylori infection and gastritis: the Systematic Investigation of gastrointestinaL diseases in China (SILC).

BACKGROUND AND AIM: Helicobacter pylori infection remains common in East Asia, though its prevalence is decreasing in Western countries. H. pylori-related atrophic gastritis (AG) may reduce the likelihood of gastroesophageal reflux disease (GERD). We investigated the prevalence of H. pylori infection and AG and their association with endoscopic findings and symptom-defined GERD in Shanghai. METHODS: A representative random sample of 3600 Shanghai residents aged 18-80 years was invited to complete a general information questionnaire and a Chinese version of the Reflux Disease Questionnaire, to provide blood samples for H. pylori serology and pepsinogen (PG) I/II assay (to detect AG, defined as PGI < 70 µg/L and/or PGI/PGII < 7), and to undergo endoscopy. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated by multivariate logistic regression. RESULTS: A total of 1022 Shanghai residents underwent endoscopy and were valid for inclusion in the study. Of these, 71.7% tested positive for H. pylori, 63.8% had AG and 30.5% had moderate/severe AG (PGI < 50 µg/L and/or PGI/PGII < 5). Helicobacter pylori infection was equally common in all age groups. Severity of AG increased with age in women. Reflux esophagitis was inversely associated with AG (OR, 0.23 [CI, 0.09-0.55] for moderate/severe AG compared with no H. pylori or gastritis). However, symptom-defined GERD showed no clear association with AG. CONCLUSIONS: Helicobacter pylori infection and AG are very common in Shanghai, and the infection is acquired early in life. Atrophic gastritis is inversely associated with reflux esophagitis but is not significantly associated with symptom-defined GERD.

Epidemiology of symptom-defined gastroesophageal reflux disease and reflux esophagitis: the systematic investigation of gastrointestinal diseases in China (SILC).

OBJECTIVE: Gastroesophageal reflux disease (GERD) is thought to be less prevalent in China than in Western countries. However, essential population-based endoscopy data are lacking for this country. MATERIAL AND METHODS: As part of a wider study, 3600 individuals selected randomly from the Shanghai region were asked to undergo endoscopy. Participants completed a general information questionnaire and a Chinese version of the Reflux Disease Questionnaire. When sufficient numbers were available, associations were assessed using multiple logistic regression or the Wilcoxon rank-sum test. RESULTS: Of 3153 (87.6%) individuals who completed the survey, 1030 (32.7%) agreed to endoscopy and 1029 endoscopies were suitable for analysis. Symptom-defined GERD was more prevalent in the endoscopy group (4.7%) than in the non-endoscopy group (1.7%). Prevalence estimates were 6.4% for reflux esophagitis, 1.8% for endoscopically suspected esophageal metaplasia and 0.7% for hiatus hernia. Reflux esophagitis was more prevalent in patients with symptom-defined GERD than in those without (12.5% [6/48] vs. 6.1% [60/981]), and was significantly associated with reflux symptoms of any frequency or severity (OR = 2.10, 95% CI 1.13-3.89) and with negative Helicobacter pylori infection (OR = 0.44, 95% CI 0.25-0.80). Only 28.8% of participants with reflux esophagitis had heartburn and/or regurgitation symptoms. Epigastric burning was significantly more severe and frequent in participants with reflux esophagitis than in those without (p = 0.05). CONCLUSIONS: Reflux esophagitis is less prevalent in China than reported in Western countries. Further work is needed to establish why reflux esophagitis appears less symptomatic in China than in Western countries.

Plasma miR-216a as a potential marker of pancreatic injury in a rat model of acute pancreatitis.

AIM: To study the potential value and specificity of plasma miR-216a as a marker for pancreatic injury. METHODS: Two rat models were applied in this article: L-arginine-induced acute pancreatitis was used as one model to explore the potential value of plasma miR-216a for detection of pancreatic injury; nonlethal sepsis induced in rats by single puncture cecal ligation and puncture (CLP) was used as the other model to evaluate the specificity of plasma miR-216a compared with two commonly used markers (amylase and lipase) for acute pancreatitis. Plasmas were sampled from rats at indicated time points and total RNA was isolated. Real-Time Quantitative reverse transcriptase-polymerase chain reaction was used to quantify miR-216a in plasmas. RESULTS: In the acute pancreatitis model, among five time points at which plasmas were sampled, miR-216a concentrations were significantly elevated 24 h after arginine administration and remained significantly increased until 48 h after operation (compared with 0 h time point, P < 0.01, Kruskal-Wallis Test). In the CLP model, plasma amylase and lipase, two commonly used biomarkers for acute pancreatitis, were significantly elevated 24 h after operation (compared with 0 h time point, P < 0.01 and 0.05 respectively, Pairwise Bonferroni corrected t-tests), while miR-216a remained undetectable among four tested time points. CONCLUSION: Our article showed for the first time that plasma miR-216a might serve as a candidate marker of pancreatic injury with novel specificity.

Epidemiology of peptic ulcer disease: endoscopic results of the systematic investigation of gastrointestinal disease in China.

OBJECTIVES: Complications of peptic ulcer disease (PUD) are common in China. Population-based estimates of the prevalence of PUD are needed to quantify and characterize the population at risk of these complications. METHODS: As part of a large epidemiological study, 3,600 randomly selected residents of Shanghai (aged 18-80 years) were asked to undergo endoscopy and to provide blood samples for Helicobacter pylori serology. All participants also completed a general information questionnaire and Chinese versions of the reflux disease questionnaire (RDQ) and Rome II questionnaire. Associations between PUD and other factors were analyzed using a multiple logistic regression model. RESULTS: In total, 3,153 individuals (87.6%) completed the survey. All underwent blood tests, and 1,030 patients (32.7%) agreed to undergo endoscopy. Results from 1,022 patients were suitable for analysis. In all, 176 participants (17.2%) had PUD (62 with gastric ulcer; 136 with duodenal ulcer). The prevalence of H. pylori infection was 73.3% in the total population and 92.6% among those with PUD. H. pylori infection was associated with the presence of PUD (odds ratio (OR), 6.77; 95% confidence interval (CI), 2.85-16.10). The majority (72.2%) of individuals with PUD had none of the upper gastrointestinal symptoms assessed by the RDQ. PUD was not significantly associated with symptom-defined gastroesophageal reflux disease (GERD) (OR, 0.80; 95% CI, 0.32-2.03), reflux esophagitis (OR, 1.46; 95% CI, 0.76-2.79) or dyspepsia (OR, 1.69; 95% CI, 0.94-3.04). CONCLUSIONS: The prevalence of endoscopically confirmed PUD in this Shanghai population (17.2%) is substantially higher than in Western populations (4.1%). The majority of individuals with PUD were asymptomatic.

Upregulated histone deacetylase 1 expression in pancreatic ductal adenocarcinoma and specific siRNA inhibits the growth of cancer cells.

OBJECTIVES: So far, there are no investigations about the role of histone deacetylase 1 (HDAC1) in tumorigenesis of pancreatic ductal adenocarcinoma. This study was designed to elucidate the roles and mechanisms of HDAC1 in tumorigenesis of pancreatic ductal adenocarcinoma. METHODS: Real-time reverse transcription-polymerase chain reaction and immunohistochemistry techniques were adopted to detect the expression of HDAC1 in human pancreatic ductal adenocarcinoma tissues and paired paracancerous tissues. The roles of HDAC1 in human pancreatic cell line PaTu8988 were investigated using siRNA. RESULTS: Histone deacetylase 1 mRNA in pancreatic cancer tissues were significantly higher than in paracancerous tissues (P < 0.05). Immunohistochemistry showed that the indices of HDAC1 in pancreatic cancer tissues and paracancerous tissues were 56.4% (SD, 23.1%) and 6.7% (SD, 5.0%), respectively (P < 0.001). Knockdown of HDAC1 can generate a remarkable defect in proliferation and also can significantly induce apoptosis and S-phase arrest in PaTu8988 cells (P < 0.05). The Bcl-2 mRNA expression was significantly downregulated, whereas the p21 and Bax mRNA expression were significantly upregulated. CONCLUSIONS: The HDAC1 overexpression might play an important role in tumorigenesis of pancreatic cancer. Our data support the development of selective inhibitors targeting HDAC1 for the treatment of pancreatic ductal adenocarcinoma. Histone deacetylase 1 could be a new gene therapy target in pancreatic ductal adenocarcinoma.