Nicotine promotes tumor progression and epithelial-mesenchymal transition by regulating the miR-155-5p/NDFIP1 axis in pancreatic ductal adenocarcinoma.

BACKGROUND: Nicotine, the major component of cigarette smoke, has been reported to promote pancreatic ductal adenocarcinoma (PDAC) growth and invasion. Deregulation of microRNA (miRNA) expression is found in many cancers, including PDAC. The effects of nicotine on miRNAs change in PDAC progression remain unknown. METHODS: The effects of cigarette smoking/nicotine exposure on PDAC cell lines and tissues were evaluated. Quantitative real-time PCR and in situ hybridization assays were used to determine miR-155-5p expression in human PDAC tissue and cell lines upon cigarette smoking/nicotine exposure. Bioinformatics, loss-of-function experiments, luciferase reporter assay were performed to validate Nedd4 family interacting protein 1 (NDFIP1) as a direct target of miR-155-5p. The potentials of systemic miR-155-5p inhibitor-based therapy in overcoming nicotine exposure were evaluated in tumor xenograft model. RESULTS: Nicotine promoted PDAC cells proliferation, migration, invasion and epithelial-mesenchymal transition (EMT) in a dose-response manner. MiR-155-5p was found to be highly expressed in PDAC cell lines and tissues upon cigarette smoking/nicotine exposure. Functional studies showed that miR-155-5p knockdown could override the enhancement of oncogenic activity due to nicotine exposure in vitro and in vivo by directly interacting with the 3' untranslated regions (UTRs) of NDFIP1. CONCLUSIONS: These data demonstrate that nicotine-regulated miR-155-5p/NDFIP1 promotes tumor progression and EMT of PDAC.

IgA, albumin, and eosinopenia as early indicators of cytomegalovirus infection in patients with acute ulcerative colitis.

BACKGROUND: Cytomegalovirus (CMV) infection can significantly complicate and worsen the condition of acute severe ulcerative colitis (UC) patients. We aimed to explore the predictive risk factors to prevent and identify CMV infection at an early stage in acute UC patients. METHODS: A total of 115 moderate-to-severe active UC patients from 17 hospitals throughout China were enrolled. Active CMV infection was diagnosed by one of the following: CMV pp65 antigens, CMV IgM antibodies or CMV DNA. We identified the independent risk factors by multivariate analyses. RESULTS: A total of 64 of 115 active UC patients had active CMV infection. Compared to the non-CMV-infected patients, the CMV-infected patients had a tendency to be male and to exhibit abdominal pain; fever; oral ulcers; eosinopenia; low albumin, immunoglobulin (Ig) A, IgM, and IgG levels; increased high-sensitivity C-reactive protein (hsCRP) levels; hyponatremia; pancolonic lesions; initial onset type; severe activity; and glucocorticoid (high-dose) and immunosuppressive agent use (P < 0.05). In further multivariate analyses, the use of high-dose glucocorticoids (OR 13.55, 95% CI 2.49-73.61, P < 0.01) and immunosuppressive agents (OR 11.23, 95% CI 1.05-119.99, P = 0.04) were independent risk factors for CMV infection. A decrease eosinophil and albumin levels were risk factors for CMV infection. With every 0.1*10^9/L decrease in the peripheral blood eosinophil level or 1 g/L decrease in the serum albumin level, the risk for CMV infection in UC patients increased by 5.21-fold (1/0.192) or 1.19-fold (1/0.839), respectively. CONCLUSIONS: High-dose glucocorticoid and immunosuppressive agent treatment significantly increase the risk of CMV infection, and correcting eosinopenia and low albumin levels may help prevent CMV infection in UC patients.

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.

MicroRNA-193a-3p Reduces Intestinal Inflammation in Response to Microbiota via Down-regulation of Colonic PepT1.

Intestinal inflammation is characterized by epithelial disruption, leading to the loss of barrier function, recruitment of immune cells, and host immune responses to gut microbiota. PepT1, a di/tripeptide transporter that uptakes bacterial products, is up-regulated in inflamed colon tissue, which implies its role in bacterium-associated intestinal inflammation. Although microRNA (miRNA)-mediated gene regulation has been found to be involved in various processes of inflammatory bowel disease (IBD), the biological function of miRNAs in the pathogenesis of IBD remains to be explored. In this study we detected miRNA expression patterns in colon tissues during colitis and investigated the mechanism underlying the regulation of colonic PepT1 by miRNAs. We observed an inverse correlation between PepT1 and miR-193a-3p in inflamed colon tissues with active ulcerative colitis, and we further demonstrated that miR-193a-3p reduced PepT1 expression and activity as a target gene and subsequently suppressed the NF-κB pathway. Intracolonic delivery of miR-193a-3p significantly ameliorated dextran sodium sulfate-induced colitis, whereas the overexpression of colonic PepT1 via PepT1 3'-untranslated region mutant lentivirus vector abolished the anti-inflammatory effect of miR-193a-3p. Furthermore, antibiotic treatment eliminated the difference in the dextran sodium sulfate-induced inflammation between the presence and absence of miR-193a-3p. These findings suggest that miR-193a-3p regulation of PepT1 mediates the uptake of bacterial products and is a potent mechanism during the colonic inflammation process. Overall, we believe miR-193a-3p may be a potent regulator of colonic PepT1 for maintaining intestinal homeostasis.

Identification of Circulating MiR-25 as a Potential Biomarker for Pancreatic Cancer Diagnosis.

BACKGROUND: The aim of this study was to identify novel microRNAs for potential use in the diagnosis of pancreatic cancer (PaC). METHODS: A total of 1063 serum samples from 303 patients with PaC were collected, and the expression level of miR-25 was measured using quantitative real-time PCR (qRT-PCR). RESULTS: We found that miR-25 had significant diagnostic value for the differential diagnosis of PaC in normal controls with an AUC (the area under the ROC curve) of 0.915 (95% CI: 0.893-0.937) that was significantly higher compared with an AUC of 0.725 for serum tumor marker carcinoembryonic antigen (CEA) and an AUC of 0.844 for CA19-9. CONCLUSIONS: These data suggest that serum miR-25 has strong potential as a novel biomarker for the early detection of PaC.

Decreased MIZ1 Expression in Severe Experimental Acute Pancreatitis: A Rat Study.

AIM: We tested our hypothesis that Myc-interacting zinc finger protein 1 (MIZ1), a cell cycle regulator, suppressed inflammation, and therefore, represented a useful prognostic marker in patients with acute necrotizing pancreatitis (ANP) complicated by acute lung injury. METHODS: Sprague-Dawley rats were randomly divided into control and ANP groups at different time points. The MIZ1 protein expression was measured by Western blot and ELISA, and confirmed using immunohistochemistry. The severity of pancreatic and lung injury was evaluated by the injury score and wet/dry weight ratio. The severity of disease was evaluated by serum C-reactive protein (CRP). The MPO activity of lung tissue amylase levels and the degree of inflammation were evaluated by serum tumor necrosis factor (TNF)-α and interleukin (IL)-6 expression. The risk due to multiple factors was investigated by relationship analysis. RESULTS: The serum levels of CRP, amylase, TNF-α, and IL-6 were gradually increased at 6, 24, and 48 h in ANP when compared with the control rats. The MIZ1 expressions were greatly decreased in ANP rats, especially at 24 h. Statistical analysis showed that there were time-dependent differences in ANP rats when compared with control rats (6 vs. 24 or 48 h, P < 0.01). MIZ1 showed close negative correlation with the degree of pancreatic and lung injury, serum amylase, CRP, TNF-α, and IL-6 (P < 0.01, respectively). CONCLUSION: The decreasing MIZ1 expression was closely correlated with inflammatory response, and development of ANP. Decreasing MIZ1 levels indicate a risk for ANP.

Pancreatic cancer-secreted miR-155 implicates in the conversion from normal fibroblasts to cancer-associated fibroblasts.

Cancer-associated fibroblasts (CAF) are a major constituent of the pancreatic cancer microenvironment and that the meaning is as intended. Pancreatic cancer cells can induce normal fibroblasts to convert into CAF and, reciprocally, CAF promote tumor invasions and proliferations. The mechanism of the conversion from normal fibroblasts (NF) to CAF remains unclear. MicroRNA are short non-coding RNA involved in the post-transcription gene regulation, which have been defined as an imperative controller in tumor invasions, proliferations and colony formations. Microvesicles (MV) have been proved to be an important mediator of intercellular communication and can selectively transport secreted microRNA from a donor cell into a recipient cell. In this study, we isolated primary pancreatic fibroblasts from wild type C57 mice and co-cultured them with pancreatic cancer cell lines, BxPC-3 and SW1990, and observed the conversion from NF to CAF, or at least CAF-like cells. This phenomenon could also be replicated in primary fibroblasts treated with MV separated from a cancer cell media. We identified that miR-155 was upregulated in PaC-derived MV and we confirmed that normal fibroblasts could convert into CAF after MV containing miR-155 had been taken up. TP53INP1 is a target of miR-155 in fibroblasts and a downregulation of TP53INP1 protein levels could contribute to the fibroblasts' activation. These results indicated that pancreatic cancer cells might reprogram normal adjacent fibroblasts into CAF by means of secreted MV containing miR-155. Targeting the circulating microRNA might be a potential therapy for malignant tumors.

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.

Dietary fiber intake reduces risk for colorectal adenoma: a meta-analysis.

BACKGROUND & AIMS: Reports on the association between dietary fiber intake and risk of colorectal adenoma (CRA), the precursor of colorectal cancer, have been inconsistent. We conducted a meta-analysis of case-control and cohort studies to analyze this association. METHODS: We searched the MEDLINE and EMBASE databases to identify relevant studies published through July 2013. A random-effects model was used to estimate summary relative risks (SRRs) and 95% confidence intervals (CIs) for associations between fiber intake and CRA risk. Heterogeneity among studies was assessed using the Cochran Q and I(2) statistics. RESULTS: Our meta-analysis included 20 studies involving 10,948 subjects with CRA. The SRRs of CRA for total dietary fiber were 0.72 (95% CI, 0.63-0.83) in a high- vs low-intake analysis and 0.91 (95% CI, 0.87-0.95) per 10-g/day increase in fiber intake in a dose-response model. Subgroup analyses indicated a significant inverse association between total fiber intake and CRA risk in case-control studies (SRR, 0.66; 95% CI, 0.56-0.77), but not in cohort studies (SRR, 0.92; 95% CI, 0.76-1.10). The SRRs of CRA were 0.84 for fruit fiber (95% CI, 0.76-0.94; n = 6 studies), 0.93 for vegetable fiber (95% CI, 0.84-1.04; n = 6 studies), and 0.76 for cereal fiber (95% CI, 0.62-0.92; n = 9 studies) in high- vs low-intake analyses. CONCLUSIONS: Our findings support the hypothesis that high dietary fiber intake is associated inversely with CRA risk. Further studies with prospective designs that use validated questionnaires and control for important confounders are warranted.

Oridonin's therapeutic effect: suppressing Th1/Th17 simultaneously in a mouse model of Crohn's disease.

BACKGROUND AND AIM: Crohn's disease is a chronic inflammatory bowel disease. Oridonin is an effective component isolated from Rabdosia rubescens. It can inhibit the activation of transcription factor nuclear factor-kappa B and suppress the over expression of cytokines. We postulated that oridonin may be a potential therapeutic candidate for Crohn's disease. METHODS: To confirm the postulation, we investigated clinical and immunologic modulations of oridonin in a mouse model of trinitrobenzene sulfonic acid-induced colitis. RESULTS: It was found that oridonin attenuated trinitrobenzene sulfonic acid-induced colitis as represented by a reduction in colonic interferon-γ/inteleukin-17 secretion and a decrement in splenic Th1/Th17 cells and effector memory CD4(+) T cells. Oridonin treatment inhibited the proliferation of CD4(+) T cells and upregulated the apoptosis of lymphocytes by inhibiting nuclear translocation of transcription factor nuclear factor-kappa B. CONCLUSIONS: Oridonin is a potential modulator for trinitrobenzene sulfonic acid-induced colitis and other Th1/Th17 mediated inflammatory diseases.

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.

Characteristics, hotspots, and prospects of short video research: A review of papers published in China from 2012 to 2022.

In recent years, due to the increase in their global popularity, short video applications have become an important topic of research. The number of users has now exceeded one billion in China; accordingly, Chinese researchers have conducted many studies on short videos. Their findings can serve as important references for both theoretical research on and the practical development of short videos worldwide. In this study, we used bibliometrics method and the CiteSpace application to analyze the content of 2163 representative research papers on short videos published in China from 2012 to 2022. The number of such papers is increasing annually in China; moreover, several core groups of authors and research institutions focusing on short video research have already been formed. Some popular topics of research on these videos include the main characteristics of short videos, phenomenon of media convergence based on short videos, and application scenarios of short videos. Over the years, research on the popular short video application Douyin has been increasing, as well. The research results indicate that issues such as the marketing of short knowledge videos, standardized management of short video platforms, and impact of these videos on the education of college students are expected to become popular subjects of scholarly research in the near future.

Role of voltage gated Ca2+ channels in rat visceral hypersensitivity change induced by 2,4,6-trinitrobenzene sulfonic acid.

BACKGROUND: Visceral pain is common symptom involved in many gastrointestinal disorders such as inflammatory bowel disease. The underlying molecular mechanisms remain elusive. We investigated the molecular mechanisms and the role for voltage gated calcium channel (VGCC) in the pathogenesis in a rat model of 2,4,6-trinitrobenzenesulfonic acid (TNBS) induced visceral inflammatory hypersensitivity. RESULTS: Using Agilent cDNA arrays, we found 172 genes changed significantly in dorsal root ganglia (DRG) of TNBS treated rats. Among these changed genes, Cav1.2 and Cav2.3 were significantly up-regulated. Then the RT-PCR and Western blot further confirmed the up-regulation of Cav1.2 and Cav2.3. The whole cell patch clamp recording of acutely dissociated colonic specific DRG neurons showed that the peak IBa density was significantly increased in colonic neurons of TNBS treated rats compared with control rats (-127.82 ± 20.82 pA/pF Vs -91.67 ± 19.02 pA/pF, n = 9, *P < 0.05). To distinguish the different type of calcium currents with the corresponding selective channel blockers, we found that L-type (-38.56 ± 3.97 pA/pF Vs -25.75 ± 3.35 pA/pF, n = 9, * P < 0.05) and R-type (-13.31 ± 1.36 pA/pF Vs -8.60 ± 1.25 pA/pF, n = 9, * P < 0.05) calcium current density were significantly increased in colonic DRG neurons of TNBS treated rats compared with control rats. In addition, pharmacological blockade with L-type antagonist (nimodipine) and R-type antagonist (SNX-482) with intrathecal injection attenuates visceral pain in TNBS induced inflammatory visceral hypersensitivity. CONCLUSION: Cav1.2 and Cav2.3 in colonic primary sensory neurons play an important role in visceral inflammatory hyperalgesia, which maybe the potential therapeutic targets.

Upregulation of transgelin is an independent factor predictive of poor prognosis in patients with advanced pancreatic cancer.

Transgelin is a known actin-binding protein, which plays a role in regulating the functions of smooth muscle cells or fibroblasts. Recent evidence indicates that transgelin is involved in diverse human cancers, yet its role in pancreatic cancer remains unclear. We therefore evaluated the expression characteristics and function of transgelin in pancreatic cancer. Immunohistochemical analysis of benign (n = 30 patients) and malignant (n = 114 patients) pancreatic ductal cells showed significantly higher transgelin staining in malignant cells. Lymph node metastasis (P = 0.026) and diabetes (P = 0.041) were shown to significantly correlate with transgelin protein expression. Patients with high transgelin expression showed a shorter 5-year overall survival and a lower tumor-specific survival than those with low transgelin expression. Multivariate analysis revealed that transgelin was an independent factor affecting pancreatic tumor-specific survival (P = 0.025). In vitro, RNA interference-mediated transgelin knockdown resulted in inhibition of pancreatic cancer cell proliferation, migration and invasion. Depletion of transgelin expression could suppress pancreatic tumorigenicity and tumor growth in vivo, and produce enhanced cytotoxic effects of gemcitabine on pancreatic cancer cells both in vitro and in vivo. Our results indicate that transgelin plays a promoting role in tumor progression, and appears to be a novel prognostic marker for advanced pancreatic cancer.

Pharmacokinetic and Safety Study of Single and Multiple Oral Doses of Safinamide in Healthy Chinese Volunteers.

This randomized, parallel-group study evaluated the plasma pharmacokinetic profile of safinamide in 24 healthy Chinese men and women, randomly assigned to receive 50 or 100 mg of safinamide as a single dose, followed, after a 7-day washout, by multiple doses once daily for 7 days. Plasma safinamide was determined up to 96 h after the first single dose (day 1) and the last multiple dose (day 14), and up to 24 h after the first multiple dose (day 8). Following single- and multiple-dose administration, peak concentrations were achieved at a median time of 1.5-2 h. Plasma exposure increased in a dose-proportional manner. After single dose, mean half-life was 23-24 h. Area under the concentration-time curve (AUC) from time zero extrapolated to infinity was only slightly higher than AUC from time zero to the last quantifiable concentration, corresponding for the 2 parameters, respectively, to 12,380 and 11,560 ng • h/mL for the 50 mg and to 22,030 and 20,790 ng • h/mL for the 100-mg dose. AUC in the dosing interval at steady state was 13,150 and 23,100 ng • h/mL for 50 and 100 mg of safinamide. Steady state was reached in 6 days, accumulation was approximately twofold, and the pharmacokinetics were time independent. The plasma safinamide pharmacokinetic profile observed in this study is in line with the published results in both Chinese and non-Asian populations.

A model for predicting degree of malignancy in patients with intraductal papillary mucinous neoplasm.

Background/Objectives: There is no predictive model available to address early stage malignant intraductal papillary mucinous neoplasm (IPMN) including high grade dysplasia (HGD) and pT1a (invasive component≤0.5 cm). The aim of this study was to establish an objective and sufficient model to predict the degree of malignancy in patients with IPMN, which can be easily applied in daily practice and adopted for any type of lesion. Methods: A retrospective cohort study of 309 patients who underwent surgical resection for IPMN was performed. Members of the cohort were randomly allocated to the training or testing set. A detection tree model and random forest model were used for a 3-class classification to distinguish low grade dysplasia (LGD), HGD/pT1a IPMN, and invasive intraductal papillary mucinous cancer (I-IPMC) beyond pT1a. Results: Of the 309 patients, 54 (17.4%) had early stage malignancy (19 HGD, 35 pT1a), 49 (15.9%) had I-IPMC beyond pT1a, and 206 (66.7%) had LGD IPMN. We proposed a 3-class classification model using a random forest algorithm, and the model had an accuracy of 99.5% with the training set, and displayed an accuracy of 96.0% with the testing set. We used SHAP for interpretation of the model and showed the top five factors (mural nodule size, main pancreatic duct diameter, CA19-9 levels, lesion edge and common bile duct dilation) were most likely to influence the 3-class classification results in terms of interpretation of the random forest model. Conclusions: This predictive model will help assess an individual's risk for different stages of IPMN malignancy and may help identify patients with IPMN who require surgery.

DJ-1 promotes invasion and metastasis of pancreatic cancer cells by activating SRC/ERK/uPA.

A major hallmark of pancreatic ductal adenocarcinoma (PDAC) is extensive local tumor invasion and early systemic dissemination. DJ-1 has been shown to prevent cell death via the Akt pathway, thereby playing an important role in cancer progression and Parkinson's disease development. Here, we investigated the role of DJ-1 in tumor invasion and metastasis of pancreatic cancer and showed that DJ-1 is upregulated in 68.5% of pancreatic cancer specimens, correlated with tumor stage and predictive of short overall survival. Knockdown of DJ-1 expression in two PDAC cell lines reduced cell migration and invasion potential in vitro and inhibited metastasis in vivo. Knockdown of DJ-1 led to cytoskeleton disruption and diminished urokinase plasminogen activator (uPA) activity and expression, without affecting plasminogen activator inhibitor-1 and uPA receptor (uPAR) expression. All these effects were reversed by restoration of DJ-1 expression. In determining the pathway through which DJ-1 regulated cell migration and invasion, DJ-1 was found not to regulate Akt phosphorylation. Rather, it promoted extracellular signal-regulated kinase (ERK) and SRC phosphorylation. Inhibition of the ERK pathway in PDAC mimicked the effects of DJ-1 on cell migration, invasion, actin cytoskeleton and uPA/uPAR system and abolished the effects on promoting PDAC cell invasion and migration. These data represent the first identification of an important function of DJ-1, which is to regulate the invasion and metastasis properties of PDAC through the ERK/uPA cascade.

Serum microRNA expression profile as a biomarker in the diagnosis and prognosis of pancreatic cancer.

BACKGROUND: Detection of pancreatic cancer (PaC), particularly at early stages, remains a great challenge owing to lack of specific biomarkers. We sought to identify a PaC-specific serum microRNA (miRNA) expression profile and test its specificity and sensitivity as a biomarker in the diagnosis and prognosis of PaC. METHODS: We obtained serum samples from 197 PaC cases and 158 age- and sex-matched cancer-free controls. We screened the differentially expressed serum miRNAs with Illumina sequencing by synthesis technology using pooled serum samples followed by RT-qPCR validation of a large number of samples arranged in multiple stages. We used risk score analysis to evaluate the diagnostic value of the serum miRNA profiling system. To assess the serum miRNA-based biomarker accuracy in predicting PaC, we performed additional double-blind testing in 77 PaC cases and 52 controls and diagnostic classification in 55 cases with clinically suspected PaC. RESULTS: After the selection and validation process, 7 miRNAs displayed significantly different expression levels in PaC compared with controls. This 7 miRNA-based biomarker had high sensitivity and specificity for distinguishing various stages of PaC from cancer-free controls and also accurately discriminated PaC patients from chronic pancreatitis (CP) patients. Among the 7 miRNAs, miR-21 levels in serum were significantly associated with overall PaC survival. The diagnostic accuracy rate of the 7-miRNA profile was 83.6% in correctly classifying 55 cases with clinically suspected PaC. CONCLUSIONS: These data demonstrate that the 7 miRNA-based biomarker can serve as a novel noninvasive approach for PaC diagnosis and prognosis.

Clinical profiles and long-term outcomes of patients with pancreatic ductal adenocarcinoma and diabetes mellitus.

BACKGROUND: Diabetes mellitus (DM) is considered to be a possible risk factor and/or a manifestation of pancreatic ductal adenocarcinoma (PDAC). This study is aimed at analysing the potential association of diabetes mellitus with the development and pathogenic degrees of PDAC and post-surgical survival of Chinese Han PDAC patients. METHODS: A total of 1123 patients with PDAC were recruited and included 256 patients with diabetes mellitus within 2 years (new-onset) and 62 patients with diabetes mellitus ≥ 2 years (long-standing). Additional 466 patients with type 2 diabetes mellitus were included in this study. Their clinical characteristics and long-term outcomes were analysed. RESULTS: In comparison with patients with type 2 diabetes mellitus alone, PDAC patients with new-onset diabetes mellitus had an older onset age of diabetes mellitus and lower body mass index (BMI). Among PDAC cases, patients with new-onset diabetes mellitus were associated with neural invasion, poor tumour differentiation and shorter post-surgical survival. However, more than half of these patients became euglycemic after surgical resection of tumours. CONCLUSIONS: PDAC patients developed new-onset diabetes mellitus at an older age, and they had shorter post-surgical survival. The underlying mechanisms by which comorbid diabetes mellitus affect the clinical profiles and outcomes of PDAC patients deserve further researches.

Helicobacter pylori eradication with ecabet sodium, omeprazole, amoxicillin, and clarithromycin versus bismuth, omeprazole, amoxicillin, and clarithromycin quadruple therapy: a randomized, open-label, phase IV trial.

BACKGROUND: Helicobacter pylori infection is a substantial public health problem and plays etiological role in the pathogenesis of many gastroduodenal disorders. The addition of ecabet sodium is proven to improve the efficacy of the standard triple therapy. Our aim was to assess the efficacy and safety of ecabet sodium-containing quadruple therapy versus 10-day bismuth-containing quadruple therapy for H. pylori eradication. MATERIALS AND METHODS: We did a randomized, open-label, phase IV trial in four cities (eight sites) in China, comparing the efficacy and safety of 10-days ecabet sodium-containing versus bismuth-containing quadruple therapy in adults with H. pylori infection. Eligible patients were randomly assigned treatment and monitored H. pylori eradication by negative [13C]/[14C] urea breath test 28 days after the treatment as the primary outcome. Symptoms improvement and side effects were the secondary outcome. RESULTS: A total of 311 H. pylori-positive subjects were enrolled: 155 were assigned ecabet sodium quadruple therapy and 156 bismuth quadruple therapy. The eradication rates with ecabet sodium-containing and bismuth-containing quadruple regimens were 68.4% (106/155) and 68.0% (106/156) p = .9339 intention-to-treat (ITT) and 75.4% (104/138) and 77.0% (104/135) p = .7453 per-protocol (PP), respectively. The eradication rates for the ecabet sodium quadruple regimen differed significantly between cities (e.g., 81.2% ITT and 89.6% PP in Shanghai and 50% ITT and 53.5% PP in Xi'an). The symptom improvements and safety profiles were also similar for both treatments. CONCLUSIONS: Neither 10-day Ecabet sodium-containing quadruple therapy or 10-day bismuth-containing quadruple therapy can be recommended as empiric therapy in cities with high antibiotic resistance rate of China.