Pyroptosis is a form of necrotic and inflammatory programmed cell death, which could be characterized by cell swelling, pore formation on plasma membranes, and release of proinflammatory cytokines (IL‐1β and IL‐18). The process of pyroptosis presents as dual effects: protecting multicellular organisms from microbial infection and endogenous dangers; leading to pathological inflammation if overactivated. Two pathways have been found to trigger pyroptosis: caspase‐1 mediated inflammasome pathway with the involvement of NLRP1‐, NLRP3‐, NLRC4‐, AIM2‐, pyrin‐inflammasome (canonical inflammasome pathway) and caspase‐4/5/11‐mediated inflammasome pathway (noncanonical inflammasome pathway). Gasdermin D (GSDMD) has been proved to be a substrate of inflammatory caspases (caspase‐1/4/5/11), and the cleaved N‐terminal domain of GSDMD oligomerizes to form cytotoxic pores on the plasma membrane. Here, we mainly reviewed the up to date mechanisms of pyroptosis, and began with the inflammasomes as the activator of caspase‐1/caspase‐11, 4, and 5. We further discussed these inflammasomes functions in diseases, including infectious diseases, sepsis, inflammatory autoimmune diseases, and neuroinflammatory diseases.
Introduction: Carbapenem-resistant Enterobacteriaceae (CRE) has emerged as a global threat to hospitalization patients. Infected pancreatic necrosis (IPN) leads to high risks of CRE infections with increasing mortality. Our study aims to determine the predictors related to 90-day overall mortality of CRE IPN. Methods: We retrospectively reviewed the drug resistance rates and clinical characteristics of CRE IPN patients from January 1, 2016, to January 1, 2021. Independent predictors of mortality were identified via univariate and multivariate analyses. Results: During the 5-year period, 75 IPN patients suffered from 135 episodes of CRE infections with mortality up to 50.7%. CRE strains were highly resistant ([ 50%) to nine of ten common antibiotics, except tigecycline (18%). The most common pathogen was carbapenem-resistant Klebsiella pneumoniae (84 of 135). Lung was the main site of extrapancreatic infections, followed by bloodstream and biliary tract. The independent predictors of mortality were Sequential Organ Failure Assessment (SOFA) score [ 2 (hazard ratio 3.746, 95% confidence interval 1.209-11.609, P = 0.022) and procalcitonin [ 6 ng/l (hazard ratio 2.428, 95% confidence interval 1.204-4.895, P = 0.013). Conclusion: CRE is widespread as a global challenge with a high mortality rate among IPN patients due to limited therapeutic options. Carbapenem-resistant K. pneumoniae is the leading category of CRE which requires more attention in clinical practice. High SOFA score and procalcitonin level represent two independent predictors of mortality in CRE IPN patients. Greater efforts are needed toward timely therapeutic intervention for CRE IPN.
Background The association of upper gastrointestinal endoscopic findings with sex, age, and Helicobacter pylori infection in asymptomatic healthy people is unclear. The aim of this study was to retrospectively determine the associations of upper gastrointestinal endoscopic findings in asymptomatic healthy people with sex, age, and H. pylori infection. Methods A retrospective study was conducted on 2923 patients from a health examination center in Xiangya Hospital between September 2015 and September 2019. Data on sex, age, H. pylori infection, and gastroscopy results were collected. Results Among 2923 asymptomatic patients who underwent gastroscopy, 2911 (99.59%) had abnormal results. The top three results were chronic gastritis (95.11%), peptic ulcer (17.45%), and duodenitis (9.17%). Inflammation of the gastric mucosa in chronic gastritis was more severe in the H. pylori-positive group. The incidence of peptic ulcer decreased with increasing age and was higher in men, patients aged < 30 years, and H. pylori-positive patients. The incidence of polyps was higher in women (9.54%) than in men (5.94%), and the incidence in individuals aged ≥60 years (11.63%) was higher than that in those aged < 60 years (6.83%). The pathological results of gastric polyps depended on the location of the lesion. Conclusion The incidence of abnormal upper gastrointestinal endoscopic results is high in asymptomatic healthy people undergoing a check-up and is associated with sex, age, and H. pylori infection. Gastroscopy should be considered part of a routine health check.
Acute pancreatitis (AP) is an acute inflammatory condition of the pancreas. Previous studies have shown that rutaecarpine (RUT), an important alkaloid component of Evodia rutaecarpa, exhibits certain protective effects against AP in rats by upregulating calcitonin gene-related peptide (CGRP). However, the molecular mechanism of RUT in AP remains unknown. This study aimed to investigate the effects of RUT on ceruleininduced AP in vivo and in vitro, and to explore the underlying molecular mechanisms.In cerulein/LPS-treated wild-type mice, but not CGRP gene knock-out mice, RUT significantly ameliorated pancreatic inflammation by alleviating histopathological changes, reducing IL-6 and TNF-α levels, and increasing in IL-10 levels. Moreover, RUT improved AP by suppressing the MAPK and NF-κB signaling pathways. These effects were mostly mediated through CGRP. Cell-based studies revealed that RUT significantly improved cell viability while suppressing the apoptosis of AR42J cells with cerulein-induced AP, downregulating IL-6 and TNF-α, stimulating IL-10 release, and inhibiting MAPK, NF-κB, and STAT3 signaling activation, all in a CGRP-dependent manner. RUT ameliorated cerulein/LPS-induced AP inflammatory responses in mice and AR42J cells in a CGRP-dependent manner and thus may represent a potential therapeutic option for AP patients. Our study provides valuable insights for AP drug development.
Background The association of upper gastrointestinal diseases with sex, age and Helicobacter pylori infection in asymptomatic healthy people is unclear.The aim of this study was to retrospectively determine the associations of upper gastrointestinal disease in asymptomatic healthy people with sex, age and H. pylori infection. Methods A retrospective study was conducted on 2923 patients from a health examination center in Xiangya Hospital between September 2015 and September 2019. Data on sex, age, H. pylori infection and gastroscopy results were collected. Results Among 2923 asymptomatic patients who underwent gastroscopy, 2911 patients (99.59%) had abnormal results. The top three results were chronic gastritis, peptic ulcer, and duodenitis. Inflammation of the gastric mucosa in chronic gastritis was more severe in the H. pylori-positive group. The incidence of peptic ulcer decreased with increasing age and was higher in males, patients aged < 30 years and H. pylori-positive patients.The incidence of polyps was higher in females than in males, and the incidence in individuals aged ≥ 60 years was higher than that in those aged < 60 years. Conclusion The incidence of upper gastrointestinal diseases is high in asymptomatic healthy people undergoing a check-up and is associated with sex, age and H. pylori infection.Gastroscopy should be considered part of a routine health check.
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