Objectives: In this study we aimed to evaluate the nocebo response rate in patients with functional dyspepsia (FD) and to explore its influencing factors.

Methods: A literature search of the EMBASE, PubMed, and Cochrane Library databases was conducted for all articles published up to March 2021. Randomized, parallel-designed, placebo-controlled trials on pharmacological interventions for patients with FD were included. A meta-analysis that utilized random effects to analyze the incidence of adverse events (AEs) among participants who were given placebo was conducted, and the correlation between trial characteristics and the magnitude of the nocebo response rate was analyzed.

Results: Altogether, 27 studies including 1866 paitents were deemed eligible and included in the analysis. The total nocebo response rate was 26% (95% confidence interval [CI] 18%–33%). The most frequently reported AEs included nasopharyngitis (9%), constipation (6%), headache (5%), and diarrhea (3%). There were significant differences in nocebo response rates among studies conducted in different country or region, treatment duration, types of medication, sponsorship and different versions of the Rome criteria used for FD diagnosis. While number of centers engaged in the study, types of FD diagnosis and dosing frequency were not significantly associated with the nocebo response rate.

Conclusions: Patients with FD exhibit notable nocebo response strength in clinical trials. The researchers should adopt a more careful approach when analyzing the relationships between AEs and interventions in such trials.

Objectives: Autoimmune pancreatitis (AIP) is a rare and enigmatic immune-mediated inflammatory disease. We aimed to investigate the prevalence, characteristics, and associated factors of AIP-inflammatory bowel disease (IBD) in China.

Methods: A retrospective bidirectional case–control study was performed. The diagnoses of IBD and AIP were made based on the European Crohn’s and Colitis Organization guidelines and the International Consensus Diagnostic Criteria. IBD controls were matched by age, sex, and IBD type at a ratio of 1:4, while AIP controls were matched by AIP types.

Results: The age-standardized prevalence of AIP-IBD patients in the IBD and AIP population were 292.0 and 8151.93 per 100 000 population, respectively. IBD patients had a higher risk of AIP compared to non-IBD patients (odds ratio 8.4, 95% confidence interval 4.7–14.9,P < 0.0001), and AIP patients had a higher risk of developing IBD compared to the general population in China. The mean age at diagnosis of IBD and AIP was 34.83 years and 40.42 years. IBD was diagnosed before AIP in seven cases. The median total IBD and AIP duration was 43.5 months and 13.5 months. Use of mesalamine and tuberculosis were associated with AIP in IBD patients (P = 0.031). And fecal occult blood test was associated with IBD in AIP patients (P = 0.008).

Conclusions: Most AIP-IBD patients had ulcerative colitis and type 2 AIP. IBD patients are more likely to develop AIP compared to the general population, and vice versa. Use of mesalamine and tuberculosis infection were associated with AIP, and fecal occult blood test was associated with IBD.

Objective: To assess the clinical efficacy of fucoidan-assisted standard quadruple therapy (SQT) in Helicobacter pylori (H. pylori) eradication and the improvement of gut microbiota.

Methods: An open-label randomized controlled trial was conducted at the Affiliated Hospital of Qingdao University in Shandong Province, China. Ninety patients who tested positive for H. pylori were randomized to the standard quadruple therapy (SQT) group (SQ), SQT + fucoidan combination group (SF), and fucoidan + sequential SQT group (FS), respectively. Stool samples were collected for gut microbiota composition at baseline and after treatment.

Results: After H. pylori eradication, the relative abundances of most conditional pathogens in the SQ decreased, while those of several beneficial bacteria increased or decreased (P < 0.05). In FS, the abundances of most beneficial bacteria increased gradually from baseline to week 12, while those of the conditional pathogens decreased (P < 0.05). The abundance of Bifidobacterium had a decreasing trend in SQ, but remained unchanged in SF and increased in FS (P < 0.05). The abundances of most beneficial bacteria were significantly higher in FS than in SQ and SF (P < 0.05). Addition of fucoidan enhanced symptom improvement during H. pylori eradication compared with SQT alone.

Conclusions: Fucoidan considerably improved gut dysbiosis during SQT for H. pylori eradication. Gut microbiota can be maintained by the addition of fucoidan before eradication therapy with SQT rather than by concomitant addition with therapy. Fucoidan-assisted SQT could relieve gastrointestinal symptoms during H. pylori eradication.

Objectives: Esophageal neuroendocrine carcinoma (ENEC) is a rare cancer that is highly malignant and related to a poor prognosis. In this retrospective study we aimed to elucidate the clinical characteristics, diagnosis and management of patients with ENEC and to evaluate the potential prognostic factors.

Methods: Altogether 82 patients diagnosed with ENEC between January 2009 and December 2020 at the Fudan University Shanghai Cancer Center were retrospectively enrolled. Patients’ survival was analyzed using the Kaplan–Meier and log-rank methods. Univariate and multivariate analyses and a Cox regression model were used to identify the prognostic factors.

Results: The median overall survival (mOS) was 13 months in all patients. Multivariate analysis revealed that advanced tumor stage (hazard ratio [HR] 2.67, 95% confidence interval [CI] 1.07–6.66,P = 0.0353), liver (HR 3.36, 95% CI 1.53–7.41,P = 0.0026) and lung metastasis (HR 3.37, 95% CI 1.20–9.51,P = 0.0214) were associated with a poor prognosis. While positive chromogranin A (CgA) expression was related to a favorable outcome (HR 0.21, 95% CI 0.09–0.49,P < 0.001). Also, patients had adjustment of chemotherapy (dose reduction or less than three cycles) were prone to a worse prognosis compared with those did not (HR 4.36, 95% CI 2.10–9.08,P < 0.001).

Conclusion: In patients with ENEC, advanced cancer stage, adjustment of chemotherapy, liver and lung metastasis were associated with a poor survival, while CgA expression was related to a favorable prognosis.

Objectives: The interferon regulatory factor (IRF) family of proteins are involved in tumor progression. However, the role of IRF5 in tumorigenesis remains unknown. In this study we aimed to elucidate the functions of IRF5 in the progression of hepatocellular carcinoma (HCC).

Methods: IRF5 expression in HCC was analyzed through quantitative polymerase chain reaction (qPCR), western blot, and immunohistochemistry (IHC), etc. The Cell Counting Kit 8 (CCK8) assay, anchorage-independent assay, and EdU assay were used to evaluate the role of IRF5. The molecular mechanisms were studied by analyzing the metabolites with mass spectrum and immunoprecipitation.

Results: IRF5 was upregulated in HCC. Interfering with IRF5 inhibited the proliferation and tumorigenic potential of HCC cells. When studying the molecular mechanism, IRF5 was found to upregulate the expression of lactate dehydrogenase A (LDHA) and promoted glycolysis. Additionally, tripartite motif containing 35 (TRIM35) interacted with IRF5, promoting its ubiquitination and degradation. In the clinically obtained HCC samples, TRIM35 was negatively correlated with the expression of IRF5.

Conclusion: These findings reveal the oncogenic function of IRF5 in the progression of HCC by enhancing glycolysis, further supporting the potential of IRF5 as a viable target for HCC therapy.

Objectives: To compare the effectiveness and safety of transgastric and transrectal pure natural orifice transluminal endoscopic surgery (NOTES) for cholecystolithotomy.

Methods: This was a single-center retrospective comparative study of consecutive patients who underwent pure NOTES for either transrectal or transgastric gallbladder-preserving cholecystolithotomy between September 2017 and April 2020. Patients with symptomatic cholelithiasis were assigned for transrectal or transgastric NOTES based on the patients’ choice. Treatment success, postoperative pain, peritonitis, time to resume normal diet, and duration of hospitalization were compared.

Results: The technical success rate was 100%. Forty-eight patients underwent successful NOTES cholecystolithotomy via the transrectal (n = 26) or transgastric route (n = 22). One (3.8%) patient in the transrectal NOTES group experienced postoperative abdominal pain compared to 6 (27.3%) in the transgastric NOTES group (P = 0.04). Fever and bile peritonitis developed in one (3.8%) patient in the transrectal NOTES group versus 8 (36.4%) in the transgastric NOTES group (P = 0.005). A postoperative fluid diet was commenced at 6 h with the transrectal approach versus on day 3 for the transgastric NOTES group. The mean postoperative hospitalization for transrectal and transgastric NOTES groups was 4.5 days versus 7 days (P = 0.001). Three patients in the transgastric NOTES group developed postoperative gastric fistula.

Conclusions: Transrectal NOTES has advantages over transgastric NOTES, including preserved spatial orientation, relatively easier removal of specimens, early food intake, shorter hospitalization, fewer postoperative complications and less pain. Multicenter clinical trials with long-term follow-up are needed to confirm the safety and efficacy of both approaches.