Our previous study showed that high levels of HMGB1 existed in rats following cardiopulmonary bypass (CPB)-induced acute lung injury (ALI) and neutralization of high-mobility group box 1(HMGB1) reduced CPB-induced ALI. However, the mechanism by which CPB increases HMGB1 secretion is unclear. Recent studies have shown that inflammasome-mediated cell pyroptosis promotes HMGB1 secretion. This study aimed to investigate the relationship between inflammasome-mediated pyroptosis and HMGB1 in CPB-related ALI. We employed oxygen-glucose deprivation (OGD)-induced alveolar macrophage (AM) NR8383 pyroptosis to measure HMGB1 secretion. We found that OGD significantly increased the levels of caspase-1 cleaved p10, IL-1β and ASC expression, caspase-1 activity and the frequency of pyroptotic AM, and promoted the cytoplasm transportation and secretion of HMGB1, which were significantly mitigated by ASC silencing or pre-treatment with glyburide (a Nlrp3 inhibitor) in AM. CPB also increased the expression levels of Nlrp3, ASC, caspase-1 P10, and IL-1β, and the percentages of AM pyroptosis in the lungs of experimental rats accompanied by increased levels of serum and bronchoalveolar lavage fluid (BALF) HMGB1. Treatment with glyburide significantly mitigated the CPB-increased ASC, caspase-1 p10 and IL-1β expression, and the percentages of AM pyroptosis in the lungs, as well as the levels of HMGB1 in serum and BALF in rats. Therefore, our data indicated that the Nlrp3/ASC-mediated AM pyroptosis increased HMGB1 secretion in ALI induced by CPB. These findings may provide a therapeutic strategy to reduce lung injury and inflammatory responses during CPB.

Background: Although sedation during gastrointestinal endoscopy is widely used in China, the characteristics of sedation use, including regional distribution, personnel composition, equipment used, and drug selection, remain unclear. The present study aimed to provide insights into the current practice and regional distribution of sedation for gastrointestinal endoscopy in China. Methods: A questionnaire consisting of 19 items was distributed to directors of anaesthesiology departments and anaesthesiologists in charge of endoscopic sedation units in mainland China through WeChat. Results: The results from 2758 participating hospitals (36.7% of the total) showed that 9 808 182 gastroscopies (69.3%) and 4 353 950 colonoscopies (30.7%), with a gastroscopy-to-colonoscopy ratio of 2.3, were conducted from January to December 2016. Sedation was used with 4 696 648 gastroscopies (47.9%) and 2 148 316 colonoscopies (49.3%), for a ratio of 2.2. The most commonly used sedative was propofol (61.0% for gastroscopies and 60.4% for colonoscopies). Haemoglobin oxygen saturation (SpO 2 ) was monitored in most patients (96.1%). Supplemental oxygen was routinely administered, but the availability of other equipment was variable (anaesthesia machine in 64.9%, physiological monitor in 84.4%, suction device in 72.3%, airway equipment in 75.5%, defibrillator in 32.7%, emergency kit in 57.0%, and difficult airway kit in 20.8% of centres responding). Conclusions: The sedation rate for gastrointestinal endoscopy is much lower in China than in the USA and in Europe. The most commonly used combination of sedatives was propofol plus an opioid (either fentanyl or sufentanil). Emergency support devices, such as difficult airway devices and defibrillators, were not usually available.

Inflammation has been correlated with intervertebral disc degeneration (IDD). Recent evidence suggests that TNF-α-stimulated gene 6 protein (TSG-6) secreted by bone marrow mesenchymal stem cells (BMSCs) displays a remarkable ability to inhibit inflammatory processes in a variety of diseases. However, it is unknown whether BMSCs exert their therapeutic effect against IDD by secreting TSG-6. Here we investigated the effects of BMSCs and TSG-6 on IDD and explored the possible underlying mechanisms in vitro and in vivo. We found that BMSCs and TSG-6 reduced the expression of MMP-3 and MMP-13, and increased the expression of collagen II and aggrecan in the IL-1β-treated nucleus pulposus cells (NPCs), but the protective effects of BMSCs and TSG-6 were attenuated when TSG-6 expression was silenced. We also found that the activation of the TLR2/NF-κB pathway was inhibited by BMSCs and TSG-6. The levels of IL-6 and TNF-α in the degenerated NPCs were reduced and the proliferation of IL-1β-treated NPCs was increased in the presence of BMSCs and TSG-6. Furthermore, in vivo experiments showed that BMSCs and TSG-6 restored the MRI T2-weighted signal intensity and increased collagen II and aggrecan expression in the degenerated nucleus pulposus (NP) tissues. Finally, our results showed that BMSCs and TSG-6 downregulated the TLR2/NF-κB signaling and reduced the expression of MMPs and inflammatory cytokines in the degenerated NP tissues. The present study is the first to demonstrate the involvement of TLR2/NF-κB pathway in the potential anti-IDD therapeutic effect of TSG-6, and the results provide new insight into the beneficial effect of BMSCs in the treatment of IDD.

No abstract

No abstract