BACKGROUND HSK3486 (ciprofol) is a 2,6-disubstituted phenol derivative that acts like propofol as an agonist at the gamma-aminobutyric acid-A (GABA A ) receptor. OBJECTIVE To investigate the efficacy and safety of HSK3486 for general anaesthesia induction and maintenance. DESIGN A single-blinded, randomised, parallel-group, phase 3 trial. SETTING Involving 10 study centres, from November 24, 2020 to January 25, 2021. PATIENTS A total of 129 patients undergoing nonemergency, noncardiothoracic, and nonneurosurgical elective surgery. INTERVENTION Patients were randomly assigned at a 2:1 ratio into HSK3486 or propofol groups, to receive HSK3486 (0.4 mg kg −1 ) or propofol (2.0 mg kg −1 ) for induction before a maintenance infusion at initial rates of 0.8 and 5.0 mg kg −1 h −1 , and were adjusted to maintain a bispectral index (BIS) of 40–60 until the end of surgery. MAIN OUTCOME MEASURES Noninferiority between the drugs was evaluated as the lower limit of the 95% confidence interval (CI) for the between-group difference in the success rate of anesthetic maintenance (primary outcome) >−8%. Secondary outcomes included successful anaesthetic induction, full alertness and spontaneous breathing recovery, time until leaving the postanaesthesia care unit and changes in BIS. Safety profiles were also measured. RESULTS Of 129 enrolled patients, 128 completed the trial, with 86 in the HSK3486 group and 42 in the propofol group. The success rate for the maintenance of general anaesthesia was 100% for both groups, and noninferiority of HSK3486 was confirmed (95% CI −4.28% to 8.38%). No significant differences were found between the two groups of patients with regard to secondary outcomes (all P > 0.05). There appeared to be a comparable incidence of treatment for emergency adverse events (TEAEs) (80.2% vs. 81.0%, P = 1.000) and drug-related TEAEs (57.0% vs. 64.3%, P = 0.451) in the HSK3486 and propofol groups. CONCLUSION HSK3486 had a noninferior efficacy profile compared to propofol, exhibiting excellent tolerance. TRIAL REGISTRATION Clinicaltrials.gov, identifier: NCT04511728.

Chronic sinusitis (chronic rhinosinusitis, CRS) is a chronic inflammatory disease of the nasal cavity and paranasal sinuses, pathogenesis of which is not yet completely elucidated. MicroRNA has been shown to extensively be involved in immune response. To analyze the differential expression of miRNAs in chronic sinusitis, with or without nasal polyps (nasal polyps, NP), seven miRNAs (miR- 181b, miR-26b, miR-155, miR-146a, miR-125b, miR-124 and miR-92a) that are associated with inflammation were selected to be quantifying by RT-qPCR in 40 clinical samples and 5 controls. When compared to the normal control group, results showed that, in all patients with CRS, miR- 125b, miR-155 and miR-146a were up-regulated (P < 0.05), while miR-92a, miR-26b and miR- 181b were down-regulated (P < 0.05). MiR124 expression levels were not found to have significant changes. In relation to CRS without NP, miR-125b and miR-155 were significantly up-regulated while miR-92a, miR-26b, miR-181b were down-regulated in NP patients. Furthermore, the miR-92a and miR-26b expression levels were significantly reduced while miR-146a and miR124 expression levels had no significant changes in the NP samples. The RT-qPCR results indicate that the miRNAs were differentially expressed in CRS patients and various inflammation severities could lead to this difference. The results from this study may further reveal the relationship between miRNA expressions and inflammation. These results can also provide an important mechanism (primitive data) on the occurrence of chronic sinusitis and nasal polyps.

Background: Remimazolam tosilate (RT) is a new type of γ-aminobutyric acid subtype A (GABA A ) 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.

China is set to actively reduce its methane emissions in the coming decade. A comprehensive evaluation of the current situation can provide a reference point for tracking the country’s future progress. Here, using satellite and surface observations, we quantify China’s methane emissions during 2010–2017. Including newly available data from a surface network across China greatly improves our ability to constrain emissions at subnational and sectoral levels. Our results show that recent changes in China’s methane emissions are linked to energy, agricultural, and environmental policies. We find contrasting methane emission trends in different regions attributed to coal mining, reflecting region-dependent responses to China’s energy policy of closing small coal mines (decreases in Southwest) and consolidating large coal mines (increases in North). Coordinated production of coalbed methane and coal in southern Shanxi effectively decreases methane emissions, despite increased coal production there. We also detect unexpected increases from rice cultivation over East and Central China, which is contributed by enhanced rates of crop-residue application, a factor not accounted for in current inventories. Our work identifies policy drivers of recent changes in China’s methane emissions, providing input to formulating methane policy toward its climate goal.

We study a single removable server in an infinite and a finite queueing systems with Poisson arrivals and general distribution service times. The server may be turned on at arrival epochs or off at service completion epochs. We present a recursive method, using the supplementary variable technique and treating the supplementary variable as the remaining service time, to obtain the steady state probability distribution of the number of customers in a finite system. The method is illustrated analytically for three different service time distributions: exponential, 3-stage Erlang, and deterministic. Cost models for infinite and finite queueing systems are respectively developed to determine the optimal operating policy at minimum cost. (C) 2000 Elsevier Science Inc. All rights reserved

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Abstract-This paper examines the estimation comparison of two methods for Weibull parameters, one is the maximum likelihood method and the other is the least squares method. A numerical simulation study is carried out to understand performance of the two methods. Based on sample root mean square errors, we make a comparison between the two computation approaches. We find that the least squares method significantly outperforms the maximum likelihood when the sample size is small.