Comparison of the efficacy and safety of ciprofol and propofol for ERCP anesthesia in older patients: A single-center randomized controlled clinical study.

STUDY OBJECTIVES: Ciprofol is a novel agonist at the gamma-aminobutyric acid-A (GABAA) receptor, exhibiting better cardiovascular stability and rapid recovery. The objective of this study was to compare the efficacy and safety of ciprofol and propofol for endoscopic retrograde cholangiopancreatography (ERCP) anesthesia in older patients. DESIGN: A single-center, randomized, parallel controlled clinical study. SETTING: General Hospital of Northern Theater Command. PATIENTS: We recruited 284 patients and intended to conduct ERCP from November 2021 to June 2022. INTERVENTIONS: Patients scheduled for ERCP were randomly assigned to two groups (n = 142 each): ciprofol group (anesthesia induction 0.3-0.4 mg/kg, anesthesia maintenance 0.8-1.2 mg/kg/h) and propofol group (anesthesia induction 1.5-2.0 mg/kg, anesthesia maintenance 4-12 mg/kg/h). MEASUREMENTS: The primary outcome was sedation success rate, defined as the proportion of patients with successful anesthesia induction. Secondary outcomes encompassed the time of successful induction, the time of complete recovery, the time of leaving the room and the incidence rate of adverse events (hypoxemia, hypotension and injection pain). MAIN RESULTS: The success rate of sedation in both groups was 100 %. The 95 % CI of the difference of sedation success rate was (- 2.63 %, 2.63 %), and the lower limit was greater than the non-inferiority limit of -8 %.The time of successful sedation induction in ciprofol group (38.4 ± 6.5 s) was longer than that in propofol group (30.6 ± 6.2 s, p < 0.05).The time of complete recovery in ciprofol group (12.8 ± 5.8 min) was shorter than that in propofol group (16.9 ± 5.0 min, p < 0.05). The time of leaving the room in ciprofol group (21.8 ± 5.8 min) was shorter than those in propofol group (25.9 ± 5.1 min, p < 0.05). The incidence of injection pain in ciprofol group (2 %) was lower than that in the propofol group (25 %, p < 0.05). Other outcomes didn't show statistical differences. CONCLUSIONS: Compared with propofol, ciprofol exhibited a comparable level of sedation in older patients undergoing ERCP, and recovery was safe and rapid with less injection pain. TRIAL REGISTRATION: www.chictr.org.cn (Registration number ChiCTR2100053386, Registration date November 20, 2021).

Efficient Tandem Electrocatalytic Nitrate Reduction to Ammonia on Bimodal Nanoporous Ag/Ag-Co across Broad Nitrate Concentrations.

Electrocatalytic nitrate (NO3-) reduction reaction (NO3-RR) represents a promising strategy for both wastewater treatment and ammonia (NH3) synthesis. However, it is difficult to achieve efficient NO3-RR on a single-component catalyst due to NO3-RR involving multiple reaction steps that rely on distinct catalyst properties. Here we report a facile alloying/dealloying-driven phase-separation strategy to construct a bimodal nanoporous Ag/Ag-Co tandem catalyst that exhibits a remarkable NO3-RR performance in a broad NO3- concentration range from 5 to 500 mM. In 10 and 50 mM NO3- electrolytes, the NH3 yield rates reach 3.4 and 25.1 mg h-1 mgcat.-1 with corresponding NH3 Faradaic efficiencies of 94.0% and 97.1%, respectively, outperforming most of the reported catalysts under the same NO3- concentration. The experimental results and density functional theory calculations demonstrate that Ag ligaments preferentially reduce NO3- to NO2-, while bimetallic Ag-Co ligaments catalyze the reduction of NO2- to NH3.

Heterostructured Co-Doped-Cu2O/Cu Synergistically Promotes Water Dissociation for Improved Electrochemical Nitrate Reduction to Ammonia.

Electrochemical nitrate reduction reaction (NO3RR) has recently emerged as a promising approach for sustainable ammonia synthesis and wastewater treatment, while the activity and selectivity for ammonia production have remained low. Herein, rational design and controllable synthesis of heterostructured Co-doped Cu2O/Cu nanoparticles embedded in carbon framework (Co-Cu2O/Cu@C) is reported for NO3RR. The Co-Cu2O/Cu@C exhibits a high ammonia yield rate of 37.86 mg h-1 mg-1 cat. with 98.1% Faraday efficiency, which is higher than those obtained for most of the Cu-based catalysts under similar conditions. Density functional theory calculations indicated that the strong electronic interactions at Cu/Co-Cu2O interface facilitate the N species deoxygenation process and doping of Co promotes water dissociation to generate *H for the N species hydrogenation process, leading to enhanced NO3RR performance. This work provides a new design strategy toward high-performance catalysts toward NO3RR for ammonia generation.

κ-Opioid Receptor Agonist Ameliorates Postoperative Neurocognitive Disorder by Activating the Ca2+/CaMKII/CREB Pathway.

Objective: Cardiopulmonary bypass (CPB) is an important cardiac operation and also a high-risk procedure, leading to postoperative neurocognitive disorder. However, there are few effective drugs to treat the aftermath of CPB. Therefore, we observe the effect of kappa opioid receptor (KOR) agonist on cognitive disorders of rats after cardiopulmonary bypass (CPB) and investigate the mechanism of the Ca2+/calmodulin-dependent protein kinase (CaMKII)/cAMP responsive element-binding protein (CREB) pathway. Methods: A total of 40 Sprague Dawley rats were randomly divided into the sham operation group (sham group, n = 10), CPB model group (CPB group, n = 10), CPB + KOR agonist U50488H group (UH group, n = 10), and CPB + specific CaMKII antagonist + U50488H group (CKU group, n = 10). The changes in the rats' cognitive function were evaluated using the Morris water maze, the hippocampal histopathological changes were observed via hematoxylin-eosin (H&E) staining, and the apoptosis rate of neuronal cells was detected through terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) staining. Moreover, enzyme-linked immunosorbent assay (ELISA) was applied to examine the changes in brain injury markers, inflammatory factors, and oxidative stress factors. The hippocampal variations in Ca2+ concentration and oxidative stress index (ROS) levels were measured by immunofluorescence staining, and western blotting was performed to determine the expression changes in the Ca2+/CaMKII/CREB pathway. Results: The KOR agonist could shorten latency, increase the swimming distance and residence time in the target quadrant, and ameliorate postoperative neurocognitive disorder (PND). Meanwhile, the KOR agonist relieved CPB-induced hippocampal and oxidative stress injuries, reduced NSE and S-100ß expression, decreased the apoptosis rate, and repressed the inflammatory response, which alleviated the brain injury. In addition, U50488H was able to decrease Ca2+ influx and glutamate (Glu) level, inhibit N-methyl-D-aspartate receptor (NMDAR) expression, upregulate CaMKII expression, promote CREB phosphorylation, and increase the brain-derived neurotrophic factor (BDNF) level in CPB rats. However, the protective effects of KORs against PND were suppressed following the application of the CaMKII-specific antagonist. Conclusion: The KOR agonist activates the Ca2+/CaMKII/CREB pathway, which improves the brain injury and relieves PND in CPB rats.

[The neuroglobin expression when retinal ganglion cells death in acute rats' retina ischemia].

OBJECTIVE: To investigate the intra-retinal expression of neuroglobin (Ngb) and death of retinal ganglion cells (RGCs) in acute retina ischemia rats. METHODS: It was an experimental study. The acute retina ischemia model was established by specific hypothesised left retina artery of Sprague-Dawley rats. Forty rats were divided into four groups (0, 15, 30, 60 min) by the time of retina ischemia. Every group has 10 rats, in one group random 3 rats were detected by Western blotting; 4 rats were detected by ganglion cell counted by hematoxylin and eosin stain and immunohistochemistry fluorescence intensity analysis. The rest 3 rats were detected by Western blotting. The difference among different data were analyzed statistically by One-factor analysis of variance and LSD-t analysis. RESULTS: The intra-retinal expression of Ngb reached maximum after acute ischemia 15 minute (P = 0.000). then the expression began decreasing. After 30 minute acute ischemia, the expression of Ngb had approached normal (P = 0.728), while, the cell number of RGCs began lower than 0 min group (P = 0.011); after 60 minute acute ischemia, the expression of Ngb had been obviously lower than 0 min group (P = 0.001), the cell number of RGCs had been further lower than 0 min group (P = 0.000). The expression of Ngb in RGCs layer was highest in rat retina. The expression in inner plexiform layer and external plexiform layer were lower than the former. The expression of Ngb RGCs was mostly intracytoplasm. After 30 minute acute ischemia, the expression of Ngb were detected in mitochondrial outer compartment and mitochondrial cristae, but in cytoplasm of inner nuclear layer and outer nuclear layer the Ngb was not found. CONCLUSION: Ngb quickly steps-up when RGCs die in acute retina ischemia, and mainly expresses intracytoplasm of RGCs. It has tense relationships with nerve cells' survival in hypoxia.