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Pancreatic cancer (PC) has been the fourth cancer‐related death worldwide, diagnosed at an unresectable stage due to its rapid progression and few symptoms of this disease at early stages. The aim of this study was to determine the association between the diversity of T‐cell receptor (TCR) repertoire and clinicopathological characteristics of patients with PC and other benign pancreatic diseases. In order to make a comprehensive analysis the TCR repertoire, high‐throughput sequencing was used to differentiate complementarity determining region 3 (CDR3) of the TCR β chain in peripheral blood samples from 3 PC, 3 chronic pancreatitis, 3 pancreatic cystic lesions and 3 pancreatic neuroendocrine tumour patients. We found that there were significant differences related to TCR repertoire between PC and other pancreatic diseases, and PC is a relatively immunosuppressive tumour. Changes of peripheral TCR repertoire may be used to predict the progression of PC and the response to immunotherapy. And there may exist novel‐specific antigens in PC patients which could be used to design targeting immunotherapy in the nearly future.

Pancreatitis is a significant risk factor for pancreatic ductal adenocarcinoma (PDAC). Previous studies in mice have demonstrated that pancreatitis contributes to oncogenic Kras-driven carcinogenesis, probably initiated in acinar cells; however, oncogenic Kras alone or in combination with caerulein-induced pancreatitis is not sufficient in initiating PDAC from the ductal compartment. We thus introduced ductal obstruction - which induces a more severe form of pancreatitis - by pancreatic ductal ligation in mice harbouring oncogenic Kras. This induced a particular phenotype with highly proliferative nonmucinous cells with nuclear atypia. Around these lesions, there was a significant proliferation of activated fibroblasts and infiltration of immune cells, corroborating the pathological features of preneoplastic lesions. Lineage-tracing experiments revealed that these preneoplastic cells derived from two distinctive cellular sources: acinar and ductal cells. Phenotypic characterisation revealed that the duct-derived preneoplastic lesions show a high proliferative potential with persistent activation of tumour-promoting inflammatory pathways while the acinar-derived ones were less proliferative with persistent p53 activation. Furthermore, the duct-derived preneoplastic cells have a particularly high nuclear-to-cytoplasmic ratio. These data demonstrate that ductal obstruction promotes preneoplastic lesion formation from the pancreatic ductal compartment.

Background Circular RNAs (circRNAs) are involved in various diseases and serve as biomarkers. The present study aimed to investigate unique expression profiles of circRNAs in colon tissues of Crohn's disease (CD) and search novel biomarkers for the diagnosis. Methods Differentially expressed (DE) circRNAs in biopsies from four CD patients, four ulcerative colitis (UC) patients, and four healthy controls (HC) were screened by microarray. Hsa_circ_0062142 and hsa_circ_0001666 were verified in another expanded validation cohort. Bioinformatics analysis was applied to predict the function of two DE circRNAs. Receiver operating characteristic (ROC) curves were constructed to evaluate the diagnostic value of CD. Results The top 10 upregulated circRNAs in CD compared with HC were hsa_circ_0000691, hsa_circ_0001666, hsa_circ_0004183, hsa_circ_0009024, hsa_circ RNA_405324, hsa_circ_0002003, hsa_circ_0085323, hsa_circ_0040994, hsa_circ_0062142, and hsa_circ_0048148; the top 10 downregulated circRNAs were hsa_circ_0049356, hsa_circ RNA_405443, hsa_circ RNA_403556, hsa_circ_0092328, hsa_circ_0003979, hsa_circ_0074491, hsa_circ_0023461, hsa_circ RNA_406237, hsa_circ_0034044, and hsa_circ RNA_400564 (fold change in descending order). The expression levels of hsa_circ_0001666 and hsa_circ_0062142 in CD were significantly higher than those in UC and HC (p, We explored the comprehensive circRNA expression profiles in colon tissues of Crohn's disease (CD) compared to tissues of ulcerative colitis (UC) and healthy controls. We showed that two circRNAs (hsa_circ_0062142 and hsa_circ_0001666) were significantly upregulated in colon tissues of CD than those in UC and healthy controls, presenting AUC of 0.803 and 0.858, respectively. Bioinformatics analysis indicated that the two differentially expressed circRNAs might be involved in the progression of CD. Our findings suggested that circRNAs might play a crucial role in the pathogenesis of CD and might provide potential diagnostic biomarkers and therapeutic targets for CD.

Esophageal cancer is one of the most common cancers and a leading cause of cancer‐related death worldwide. However, the mechanism of esophageal cancer pathogenesis remains poorly understood. Long noncoding RNAs (lncRNAs) dysregulation have been reported to involve in various human cancers, which highlights the potential of lncRNAs used as novel biomarkers for cancer diagnosis. Although more efforts have been made to identify novel lncRNAs signature in esophageal cancer, the expression pattern, prognostic value, and biological function of most lncRNAs in esophageal cancer still need to be systematically investigated. In this study, we comprehensively analyzed the expression profile of lncRNAs in more than 200 esophageal cancer patients tissue samples from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO). We identified thousands of lncRNAs are differentially expressed in esophageal cancer tissues, and many of those lncRNAs expression are associated with patients overall survival or recurrence‐free survival time. Moreover, copy number variation analyses revealed that genomic loci copy number amplification or deletion might contribute to these lncRNAs dysregulation. Among these lncRNAs, DUXAP8 and LINC00460 were significantly upregulated, and GO enrichment analyses indicated that the two lncRNAs associated protein‐coding genes involve with many known biological processes, such as cell cycle and cell‐cell adherens junction. Further experimental validation revealed that knockdown of DUXAP8 could impair esophageal cancer cells proliferation and invasion in vitro. Taken together, our findings identified more aberrantly expressed lncRNAs in esophageal cancer that may provide a useful resource for identifying novel esophageal cancer associated lncRNAs.

Background and aim Empirical proton pump inhibitor (PPI) treatment is recommended as a diagnostic indicator for gastroesophageal reflux disease (GERD) and as a therapy for symptomatic control, with responses generally seen within 4 weeks. However, there are no real-world data assessing the effectiveness of short-term empirical treatment with PPIs in patients with GERD in China. Methods The ENLIGHT study was a multicenter, prospective, observational study conducted in China. The primary outcome was the overall response rate after 4 weeks' empirical treatment with PPIs. Adult patients aged between 18 and 65 years of age, with a gastroesophageal reflux disease questionnaire score of ≥ 8, prescribed empirical PPI treatment by their physicians and with no planned endoscopy were eligible to participate. Statistical analyses were primarily descriptive. Results Overall, 987 patients were eligible to participate and were included in the full analysis set (FAS); 707 patients were included in the per protocol set. In the FAS, esomeprazole was received by 57.1% of patients and was the most commonly used PPI. After 4-week treatment, 71.1% (95% confidence interval [CI], 67.9% to 74.2%) of patients were considered responders to PPI. The response rate at the end of 2-week PPI treatment reached 57.0% (95% CI, 52.5% to 61.7%). The median time to response was 13 days (95% CI, 12 to 15). Response rates at 2 and 4 weeks of the per protocol set were similar to those of the FAS. Conclusions Short-term empirical PPI treatment can provide an effective relief of GERD symptoms in most Chinese patients in real-world practice.

Multidrug resistance (MDR) significantly restricts the clinical efficacy of gastric cancer (GC) chemotherapy, and it is critical to search novel targets to predict and overcome MDR. Leucine-rich repeats and immunoglobulin-like domains 1 (LRIG1) has been proved to be correlated with drug resistance in several cancers. The present study revealed that LRIG1 was overexpressed in chemosensitive GC tissues and decreased expression of LRIG1 predicted poor survival in GC patients. We observed that upregulation of LRIG1 enhanced chemosensitivity in GC cells. Interestingly, miR-20a, which was overexpressed in GC MDR cell lines and tissues, was identified to regulate LRIG1 expression by directly targeting its 3' untranslated region. We also found that inhibition of miR-20a suppressed GC MDR, and upregulation showed opposite effects. Moreover, we demonstrated that the miR-20a/LRIG1 axis regulated GC cell MDR through epidermal growth factor receptor (EGFR)-mediated PI3K/AKT and MAPK/ERK signaling pathways. Finally, LRIG1 expression in human GC tissues is inversely correlated with miR-20a and EGFR. Taken together, the newly identified miR-20a/LRIG1/EGFR link provides insight into the MDR process of GC, and targeting this axis represents a novel potential therapeutic strategy to block GC chemoresistance.

Gastric carcinoma is one of the most common malignancies worldwide and the second most frequent cause of cancer‐related death in China. Protein regulator of cytokinesis 1 (PRC1) is involved in cytokinesis and plays key roles in microtubule organization in eukaryotes. This study was aimed to analyse the expression and to investigate the functional role of PRC1 in gastric tumorigenesis. The expression of PRC1 was evaluated by qRT‐PCR, Western blot and immunohistochemistry. The biological function of PRC1 was determined by CCK‐8 proliferation assays, monolayer colony formation, xenografted nude mice and cell invasion assays by shRNA‐mediated knockdown in AGS and HGC27 cells. The regulation of PRC1 expression by piperlongumine was also investigated using dual‐luciferase reporter assay and ChIP‐qPCR analysis. PRC1 was up‐regulated in primary gastric cancers. Overexpression of PRC1 in gastric cancers was associated with poor disease‐specific survival and overall survival. PRC1 knockdown in AGS and HGC27 cell lines suppressed proliferation, reduced monolayer colony formation, inhibited cell invasion and migration ability and induced cell‐cycle arrest and apoptosis. Inhibition of PRC1 also suppressed tumour growth in vivo. We finally confirmed that PRC1 is a novel downstream target of piperlongumine in gastric cancer. Our findings supported the oncogenic role of PRC1 in gastric carcinogenesis. PRC1 might serve as a prognostic biomarker and potential therapeutic target for gastric carcinoma.

To detect the effects of tumor necrosis factor-like weak inducer of apoptosis (TWEAK) on SIRT1 expression and p53 deacetylation, involving cell senescence, in activated human hepatic stellate cell (HSC) in vitro, human HSC LX-2 was cultured with TWEAK for 24 h. The result showed that the expression of membrane receptor Fn14 was remarkably increased by TWEAK, which upregulated SIRT1 in LX-2 cells, detected by Western blotting and real-time PCR. The expression of p53 was not significantly altered; however, the ac-p53 was decreased. Furthermore, the viability of LX-2 cells was significantly enhanced by TWEAK. The activity of SA-β-Gal was notably inhibited, showing a suppressing effect of TWEAK on the senescence of activated HSC. Primary cultured HSC on days 7 and 11 was used to examine the expression of TWEAK, Fn14, SIRT1, and the activity of SA-β-Gal. The result indicated that the mRNA of TWEAK, SIRT1, and Fn14 was all decreased on day 11 compared to that on day 7, and the activity of SA-β-Gal was higher on day 11 than that on day 7. The present study suggested that TWEAK enhanced the expression of SIRT1 and decreased the acetylation of p53, probably inhibiting the senescence of activated HSC in vitro, which provides a molecular basis for TWEAK as a potential target in the therapy of liver fibrosis.

Background and aim Propranolol is widely used to prevent gastroesophageal variceal bleeding; however, some patients could not benefit from propranolol. This study is to evaluate the relationship between CYP2D6 and β2-adrenergic receptor (β2-AR) gene polymorphisms and the hemodynamic response to propranolol in Chinese Han patients. Methods The clinical data of patients with gastroesophageal varices undergoing hepatic venous pressure gradient (HVPG) measurement before and 7 days after oral propranolol administration in our department were collected. Four single nucleotide polymorphisms of CYP2D6 and β2-AR genes were detected. The relationship was identified by logistic regression model. Results Thirty patients were involved in the analysis. Sixty milligram propranolol twice each day was well tolerated by all the patients. The initial and secondary average of HVPG was 17.4 ± 5.8 mmHg vs. 13.2 ± 4.8 mmHg, respectively (t = 5.726, P T) genotype was an independent predicting factor for HVPG response to propranolol (P = 0.033). Conclusions CYP2D6 (188C>T) gene polymorphisms influence the hemodynamic response to propranolol in this population of Chinese Han patients with gastroesophageal varices. However, HVPG response cannot be completely predicted from CYP2D6 and β2-AR gene polymorphisms.

Background and Aim: Endoscopic ultrasonography (EUS) is a widely used imaging modality for detecting the depth of early gastric cancer (EGC) invasion. However, the studies pertaining to EUS for staging early gastric cancer have reported widely varied sensitivities and specificities. This study was conducted to estimate the overall diagnostic accuracy of EUS for staging the depth in EGCs. Methods: The literatures were identified by searching in PubMed, Embase, and Web of Knowledge databases. Two reviewers independently extracted the information from the literatures for constructing 2 × 2 table. A random-effect model or a fixed-effect model was used to estimate the sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, and diagnostic odds ratio. A summary receiver operating characteristic curve also was constructed. Meta-regression and subgroup analysis were used to explore the sources of heterogeneity. Results: The pooled sensitivity, specificity, positive likelihood ratio, and negative likelihood ratio of EUS for M staging were 76% (95% confidence interval [CI], 74–78%), 72% (95% CI, 69–75%), 3.67 (95% CI, 2.48–5.44), and 0.31 (95% CI, 0.24–0.40), respectively. For SM staging, these results were 62% (95% CI, 59–66%), 78% (95% CI, 76–80%), 2.99 (95% CI, 2.26–3.96), and 0.43 (95% CI, 0.32–0.57), respectively. For M/SM1 staging, they were 90% (95% CI, 88–92%), 67% (95% CI, 61–72%), 3.14 (95% CI, 2.08–4.73), and 0.12 (95% CI, 0.07–0.22), respectively. The area under the curve for mucosal, submucosal, and mucosal/minimal submucosal invasion staging were 0.85, 0.82, and 0.81, respectively. Conclusions: Endoscopic ultrasonography only has a relatively low accuracy for staging the depth of invasion in EGCs. Accordingly, EUS may be not indispensable in the staging of EGCs.

Background and Aim To investigate the effectiveness of peroral endoscopic myotomy (POEM) surgery in achalasia patients with failure of prior pneumatic dilation (PD). Methods Twenty-one patients with a history of failed PD were prospectively recruited as the case group, and 30 patients with no history of prior treatment for achalasia were included as the control group. Outcome of POEM procedures was evaluated through esophageal manometry, timed barium esophagogram and short form 36 (SF-36) questionnaires, which were performed before surgery, at 5 days after surgery and at the last follow-up, respectively. Relief of patients' symptoms was considered as the primary outcome. Secondary outcomes included lower esophageal sphincter pressure, esophageal emptying, quality of life of the patient, and procedure-related complications. Results The two groups were matched in terms of age, gender, body mass index, and results of preoperative examinations. For patients with failed PD, it was observed that Eckardt score, lower esophageal sphincter pressure, and height of the barium column were significantly decreased after POEM surgery. Besides, the mean physical component summary and mental component summary of patients at the final follow were significantly higher than those before surgery. Complications that occurred during the surgery included three cases of subcutaneous emphysema (14.3%) and one case of pneumothorax (4.8%). Patients with failed PD were found to have the significantly longer operation time than the control group. There was no significant difference between the two groups in terms of surgical outcome at the final follow-up. Conclusions POEM is a promising therapeutic modality for achalasia patients who have failed to respond to PD therapy. Previous dilation procedures might have no obvious influence on the efficacy of POEM surgery.

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.

Upregulation of proton extrusion is critical for tumor cell survival in an ischemic microenvironment with a lower extracellular pH (pHe). Lower pHe and higher intracellular pH (pHi) benefit cancer cells for invasion and growth. Vacuolar H(+)-ATPases (V-H(+)-ATPases) play a critical role in regulating the transmembrane pH gradient. Proton Pump Inhibitors (PPI), mainly treating acid-related diseases, could inhibit the expression of V-H(+)-ATPases. We have investigated whether PPI decreases the pHi of the human gastric adenocarcinoma cell line, SGC7901, by inhibiting V-H(+)-ATPases so as to enhance the cytotoxicity of anti-tumor drugs. We have assessed the optimal treatment time, pretreatment dosage of PPI and the possible mechanism of action. PPI exceeding 10 microg/ml inhibited protein expression of V-H(+)-ATPases in a dose-dependent manner, decreased the pHi value and reversed the transmembrane pH gradient, whereas PPI at final concentration of 1 microg/ml could not. Changes of the pH gradient were positively correlated with PPI concentration. The inhibitory effects of PPI on V-H(+)-ATPases primarily occurs from 12h to 24h after PPI pretreatment (P0.05). The pHi value of SGC7901 was lowest 24h after PPI pretreatment (P0.05). Administration of anti-tumor drugs 24h after PPI pretreatment produced the most cytotoxic effects on SGC7901 (P0.05) and significantly improved the early and total apoptosis rates (P0.01). PPI exceeding 20 microg/ml also significantly reduced the ADR-releasing index, thereby enhancing the intracellular ADR concentration (P0.01). Therefore, PPI could enhance the cytotoxic effects of anti-tumor drugs on the SGC7901 cells.

Microwave-assisted organic synthesis has been used for the cyclization of a monocyclic oxoamide to the corresponding bicyclic derivative via a Wittig-type coupling by means of phosphite reagents. The parameters influencing the reaction yields under microwave (dielectric heating) and classical conditions (convective heating) have been evaluated.