BACKGROUND:SERPINB2, a biomarker of Type-2 (T2) inflammatory processes, has been described in the context of asthma. Chronic rhinosinusitis with nasal polyps (CRSwNP) is also correlated with T2 inflammation and elevated 15LO1 induced by IL-4/13 in nasal epithelial cells. The aim of this study was to evaluate the expression and location of SERPINB2 in nasal epithelial cells (NECs) and determine whether SERPINB2 regulates 15LO1 and downstream T2 markers in NECs via STAT6 signalling.METHODS:SERPINB2 gene expression in bulk and single-cell RNAseq database was analysed by bioinformatics analysis. SERPINB2, 15LO1 and other T2 markers were evaluated from CRSwNP and HCs NECs. The colocalization of SERPINB2 and 15LO1 was evaluated by immunofluorescence. Fresh NECs were cultured at an air-liquid interface with or without IL-13, SERPINB2 Dicer-substrate short interfering RNAs (DsiRNAs) transfection, exogenous SERPINB2, 15-HETE recombinant protein and pSTAT6 inhibitors. 15LO1, 15-HETE and downstream T2 markers were analysed by qRT-PCR, western blot and ELISA.RESULTS:SERPINB2 expression was increased in eosinophilic nasal polyps compared with that in noneosinophilic nasal polyps and control tissues and positively correlated with 15LO1 and other downstream T2 markers. SERPINB2 was predominantly expressed by epithelial cells in NP tissue and was colocalized with 15LO1. In primary NECs in vitro, SERPINB2 expression was induced by IL-13. Knockdown or overexpression SERPINB2 decreased or enhanced expression of 15LO1 and 15-HETE in NECs, respectively, in a STAT6-dependent manner. SERPINB2 siRNA also inhibited the expression of the 15LO1 downstream genes, such as CCL26, POSTN and NOS2. STAT6 inhibition similarly decreased SERPINB2-induced 15LO1.CONCLUSIONS:SERPINB2 is increased in NP epithelial cells of eosinophilic CRSwNP (eCRSwNP) and contributes to T2 inflammation via STAT6 signalling. SERPINB2 could be considered a novel therapeutic target for eCRSwNP.

INTRODUCTION: The aim of this study was to explore the clinical characteristics and related factors of centrally mediated abdominal pain syndrome (CAPS). METHODS: Our study included 73 patients with CAPS and 132 age-matched and gender-matched healthy controls. The general information of the participants was collected, and the questionnaires were completed including the 7-item Generalized Anxiety Disorder Scale, 9-item Patient Health Questionnaire, Hamilton Anxiety Scale, Hamilton Depression Scale Pittsburgh Sleep Quality Index, Visual Analog Scale, and Short-Form 36. Univariate and forward stepwise regression analyses were performed to explore the influencing factors of CAPS. RESULTS: Nonexercise (adjusted odds ration [AOR] 4.53; confidence interval [CI] 1.602-12.809), mild-to-moderate depression (AOR 7.931; CI 3.236-19.438), married status (AOR 3.656; CI 1.317-10.418), and drinking coffee (AOR 0.199; CI 0.051-0.775) were found to be related with centrally mediated abdominal syndrome. The Hamilton Anxiety Scale score (7–13) was significantly related to moderate-to-severe abdominal pain (AOR 7.043; CI 1.319–37.593). Higher Hamilton Depression Scale score was related to lower mental component scale score (β = −0.726, P < 0.01) and physical component scale score (β = −0.706, P < 0.01). DISCUSSION: Depression, married status, and nonexercise were the independent risk factors of CAPS. Conversely, coffee intake was an independent protective factor of CAPS. Anxiety was related to the severity of abdominal pain, while depression was related to low health-related quality of life.

Background: Few studies have been conducted to explore the expression of tumor necrosis factor receptor-associated factor 6 in eosinophilic gastroenteritis patients. Therefore, the expression profile of tumor necrosis factor receptor-associated factor 6 in the gastrointestinal tract of eosinophilic gastroenteritis patients and its associations with clinical features were explored in this study. Methods: Thirty-four eosinophilic gastroenteritis patients who presented in Ruijin Hospital from December 2012 to May 2019 and had accepted gastrointestinal endoscopic examinations were recruited. Medical records and endoscopic biopsies were collected, and the prognosis was followed up by telephone. Healthy persons were selected as the control group. Hematoxylin and eosin and immunohistochemical staining were performed in both eosinophilic gastroenteritis patients and healthy persons. The final results were analyzed by skilled pathologists, and mean optical density values of tumor necrosis factor receptor-associated factor 6 were calculated by Image J software. Final results were analyzed by Statistical Package for the Social Sciences software 22.0. Results: Thirty-four patients (mean age: 25.56 ± 21.14 years, 61.76% males) were recruited for this study. There was no significant difference in tumor necrosis factor receptor-associated factor 6 mean optical density values of gastric tissues in eosinophilic gastroenteritis patients and healthy people (0.22 ± 0.16 vs. 0.14 ± 0.05, P > .05). Eosinophilic gastroenteritis patients had a significantly lower level of intestinal tumor necrosis factor receptor-associated factor 6 mean optical density values than that of healthy people (0.16 ± 0.05 vs. 0.23 ± 0.06, P < .05). Intestinal tumor necrosis factor receptor-associated factor 6 mean optical density values negatively linearly correlated with serum interleukin-10 level (r = −0.618, P = .043 < .05). There were no differences between eosinophilic gastroenteritis patients with or without relapse regarding the expression level of intestinal tumor necrosis factor receptor-associated factor 6 (P = .227 > .05). Conclusion: Patients with eosinophilic gastroenteritis might have a deficiency of intestinal tumor necrosis factor receptor-associated factor 6 compared to healthy controls.

Objectives:Acupuncture is therapeutic for refractory gastroesophageal reflux disease by an unclear mechanism. This study was aimed at investigating the effect of acupuncture on esophageal motility in patients with symptoms of refractory gastroesophageal reflux disease.Methods:Sixty-eight patients with refractory gastroesophageal reflux disease symptoms were prospectively enrolled from August 2014 to December 2018 and randomized into acupuncture and control groups (n = 33 and 35, respectively). The acupuncture group received acupuncture, and the control group received sham acupuncture. Pre- and post-acupuncture high-resolution manometry was performed to evaluate the effect of acupuncture on esophageal motility. The GerdQ questionnaire was used to evaluate the pre- and post-intervention symptoms.Results:After acupuncture, there was a significant increase in the length of lower esophageal sphincter (3.10 ± 1.08 cm vs. 3.78 ± 1.01 cm), length of intra-abdominal lower esophageal sphincter (2.14 ± 1.05 cm vs. 2.75 ± 1.16 cm), and mean basal pressure of lower esophageal sphincter (22.02 ± 10.03 mmHg vs. 25.06 ± 11.48 mmHg) in the acupuncture group (P = 0.014); moreover, the numbers of fragmented contraction and ineffective contraction decreased from 36 to 12 (P < 0.001) and 43 to 18 (P = 0.001), respectively, in the acupuncture group. However, no significant difference was observed in the control group. The GerdQ score decreased significantly from 9.45 ± 2.44 to 7.82 ± 2.21 points in the first week after acupuncture (P < 0.001).Conclusions:Acupuncture, which improves esophageal motility, has short-term efficacy in patients with symptoms of refractory gastroesophageal reflux disease. This trial is registered with Chinese Clinical Trial Registry (ChiCTR1800019646).

Introduction:Centrally mediated abdominal pain syndrome (CAPS) is characterized by severe abdominal pain. Diagnosis of CAPS is still an exclusionary diagnosis, there remain no effective diagnostic biomarkers so far. Duloxetine is the major pharmacotherapy of CAPS, while some CAPS patients do not respond to duloxetine treatment. However, there is a lack of molecular markers to predict the efficacy of duloxetine. In our pilot study, we have found differential expression profiles of serum miRNAs between CAPS patients and healthy controls. Our study aims to explore the clinical characteristics, specific miRNAs in serum as diagnostic biomarkers of CAPS and predictive biomarkers of the efficacy of duloxetine. Methods/design:In this prospective cohort study, we plan to enroll 430 participants including 215 CAPS patients and 215 healthy controls. The CAPS group takes duloxetine 30 mg per day as an initial dose. Patients will have 24-week medication period and follow up at week 0, 4, 12, 24 and 36. Blood samples will be obtained from patients at every visits and health controls at the initial visit and a series of questionnaires will be completed by the participants. The primary end points are: The differential expression of miRNAs between CAPS groups and healthy control groups at baseline. The changes in abdominal pain scores before and after duloxetine treatment in patients with CAPS and their relationship with the changes in miRNAs. The secondary end point is the changes in scores of depression, anxiety, sleep quality and quality of life before and after duloxetine treatment in patients with CAPS and their relationship with changes in miRNAs. Discussion:Findings of study will provide the reliable basis for diagnosis and the predictor of duloxetine efficacy of CAPS. Importantly, findings grant patients a chance to benefit from treatment.

Wnt1 inducible signaling pathway protein-1 (WISP1) may play an important role in promoting carcinogenesis. However, the biological function and underlying mechanism of WISP1 in pancreatic carcinogenesis still remains enigmatic. In this study, immunochemistry staining showed that protein levels of WISP1 were more significantly upregulated in pancreatic ductal adenocarcinoma (PDAC) tissues with Tp53 mutation than in PDAC tissues with Tp53 wild-type. In addition, a significant correlation was observed between increased malignant phenotype of tumors from well-differentiated adenocarcinoma tissues to moderately- or poorly-differentiated adenocarcinoma tissues shifting from cytoplasmic expression to nuclear accumulation of WISP1. Interestingly, WISP1 expression was correlated with the poor prognosis in PDAC patients with Tp53 mutation. Also, the biological function analysis showed that WISP1 may act as a potential oncogene in PDAC cells. In addition, immunofluorescence analysis showed that Tp53 mutation promoted WISP1 expression in PanIN and PDAC cells, while Siah E3 Ubiquitin Protein Ligase 1 (Siah1) inhibited WISP1 expression in PDAC cells. Moreover, through immunoprecipitation, immunoblotting analysis, in vitro binding assay, and ubiquitination assay, we found that Tp53 mutation inhibited ubiquitination and degradation of Siah1-dependent WISP1. Therefore, Tp53 mutation-Siah1-WISP1 is a new signaling pathway, playing an important role in pancreatic carcinogenesis.

Backgrounds and aims: This study aimed to compare the esophageal motility between gastroesophageal reflux disease (GERD) patients with typical symptoms but without globus sensation and GERD patients only with globus symptoms. Methods: A total of 57 consecutive GERD patients diagnosed by endoscopy or by 24-hour pH monitoring between May 2013 and September 2015 were included retrospectively into the study. The patients were grouped based on the presence or absence of globus. Thirty patients presented with typical reflux symptoms but without globus were assigned to the typical GERD group and 27 patients only with globus symptom were assigned to the globus GERD group. All patients underwent esophageal high resolution manometry (HRM) and the differences in esophageal motility between the two groups were analyzed. Results: The globus GERD group showed a significantly greater lower esophageal sphincter (LES) length, LES basal pressure and upper esophageal sphincter (UES) residual pressure than that of the typical GERD group (3.47 ± 0.76 vs 2.65 ± 0.62 cm, 21.71 ± 9.68 vs 16.04 ± 8.49 mmHg, 7.30 ± 4.42 vs 4.12 ± 2.92 mmHg, all p < 0.05). There was no significant difference between the two groups in terms of the distal wave amplitude, mean wave duration, distal contractile integral (DCI), contractile front velocity (CFV), distal latency (DL), integrated relaxation pressure (IRP) and UES basal pressure. The incidence of esophageal dysmotility in the globus GERD group (33.3%) was higher than in the typical GERD group (23.3%). There was no significant difference in esophageal acid exposure of the non-erosive gastroesophageal reflux disease (NERD) patients between the two groups. Conclusions: Globus GERD patients have a higher UES residual pressure, longer LES length, higher LES basal pressure and greater esophageal dysmotility than typical GERD patients. HRM is useful in evaluating esophageal motility of GERD patients.