Effect of Remimazolam Tosilate on Respiratory Depression in Elderly Patients Undergoing Gastroscopy: A Multicentered, Prospective, and Randomized Study.

Background: Remimazolam tosilate (RT) is a new type of γ-aminobutyric acid subtype A (GABAA) receptor agonist, having the possibility to be an ideal sedative drug for procedural sedation. At present, there are few studies on the effect of RT on respiratory depression in elderly patients. We aimed to evaluate the effect of RT on respiratory depression in elderly patients undergoing gastroscopy. Methods: This prospective, randomized, single-blinded trial recruited patients from eight centers in China between May 2022 and July 2022. A total of 346 elderly patients undergoing gastroscopy were randomly divided into RT group (0.2 mg/kg) or propofol group (1.5 mg/kg), respectively. The primary outcome was the incidence of respiratory depression. Secondary outcomes include the incidence of sedative-related adverse events, the success rate of sedation, time to fully alert, time to loss of consciousness (LOC), time to ready for discharge, as well as the the patients, endoscopists and anethetists' satisfaction. Results: The incidence of respiratory depression was significantly reduced in the RT group compared with the propofol group (9.8% vs 17.9%, P=0.042). The time of LOC and fully alert in the RT group were longer than that in the propofol group (P < 0.05). The incidences of hypotention (50.9% vs 32.4%, P=0.001) and hypotension requiring treatment (5.8% vs 1.7%, P=0.031) were significantly higher in the propofol group than that in the RT group. The incidence and severity of injection pain were more frequently recorded in the propofol group than that in the RT group (40.5% vs 12.1%, P<0.05). There were no statistically significant differences between the two groups in terms of sedation success rates, time to ready for discharge, endoscopists and anethetists' satisfaction and other sedative-related adverse events. Conclusion: RT may be a suitable alternative sedative agent for elderly patients undergoing gastroscopy due to its safety profile.

Activation of TREM-1 induces endoplasmic reticulum stress through IRE-1α/XBP-1s pathway in murine macrophages.

Increasing evidence suggests that endoplasmic reticulum (ER) stress activates several pro-inflammatory signaling pathways in many diseases, including acute lung injury (ALI). We have reported that blocking triggering receptor expressed on myeloid cells 1 (TREM-1) protects against ALI by suppressing pulmonary inflammation in mice with ALI induced by lipopolysaccharides (LPS). However, the molecular mechanism underlying the TREM-1-induced pro-inflammatory microenvironment in macrophages remains unclearly. Herein, we aimed to determine whether TREM-1 regulates the inflammatory responses induced by LPS associated with ER stress activation. We found that the activation of TREM-1 by a monoclonal agonist antibody (anti-TREM-1) increased the mRNA and protein levels of IL-1ß, TNF-α, and IL-6 in primary macrophages. Treatment of the anti-TREM-1 antibody increased the expression of ER stress markers (ATF6, PERK, IRE-1α, and XBP-1s) in primary macrophages. While pretreatment with 4-PBA, an inhibitor of ER stress, significantly inhibited the expression of ER stress markers and pro-inflammatory cytokines and reduced LDH release. Furthermore, inhibiting the activity of the IRE-1α/XBP-1s pathway by STF-083010 significantly mitigated the increased levels of IL-1ß, TNF-α, and IL-6 in macrophages treated by the anti-TREM-1 antibody. XBP-1 silencing attenuated pro-inflammatory microenvironment evoked by activation of TREM-1. Besides, we found that blockade of TREM-1 with LR12 ameliorated ER stress induced by LPS in vitro and in vivo. In conclusion, we conclude that TREM-1 activation induces ER stress through the IRE-1α/XBP-1s pathway in macrophages, contributing to the pro-inflammatory microenvironment.

An innovative experimental device for borehole ballooning.

The wrong judgment on borehole ballooning has a serious impact on safe and efficient drilling in the oil and gas drilling industries. In order to further investigate the characteristics of borehole ballooning, a new device is designed to research the effects of borehole ballooning under different conditions, such as different fracture opening pressures, rock types, and mud circulation pressures. The device consists of four units: a displacement unit, a triaxial clamping unit, a backpressure loading unit, and a control and data acquisition system. Based on this device, a series of experiments have been successfully carried out. The experimental results showed that the device can effectively simulate the typical characteristics of borehole ballooning, and it could provide theoretical support for further research of borehole ballooning.