Objective:To determine the median effective dose (ED 50) and 95% effective dose (ED 95) of remimazolam for gastroscopy when combined with propofol in pediatric patients of different ages. Methods:This was a prospective study. American Society of Anesthesiologists Physical Status classification Ⅰ or Ⅱ pediatric patients, aged 3-12 yr, who underwent painless gastroscopy in Hainan Women and Children′s Medical Center from January to February 2024, were divided into the following groups: preschool group (3-6 yr) and school-age group (7-12 yr). Penehyclidine 0.01 mg/kg, afentanil 8 μg/kg and corresponding doses of remimazolam and propofol 1 mg/kg were intravenously injected, and gastroscopy was performed when the Modified Observer′s Assessment of Alertness/Sedation Scale score)≤1. Up-and-down sequential allocation was used. A positive response was defined as bucking, nausea, vomiting, body movement, and frowning occurred when the gastroscope entered the pharynx. The initial dose of remimazolam was 0.2 mg/kg, and the dose of remimazolam was increased/decreased by 0.02 mg/kg each time in the next patient. Probit regression method was applied to calculate the ED 50, ED 95 and 95% confidence interval ( CI) of remimazolam inhibiting responses to gastroscope placement when combined with propofol. The anesthesia-related adverse events were recorded. Results:A total of 27 pediatric patients completed the trial in preschool group and 26 cases in school-age group. The ED 50 of remimazolam was 0.266 mg/kg (95% CI 0.249-0.285 mg/kg) and the ED 95 was 0.302 mg/kg (95% CI 0.283-0.409 mg/kg) in preschool group. The ED 50 of remimazolam was 0.16 mg/kg (95% CI 0.147-0.170 mg/kg) and ED 95 was 0.183 mg/kg (95% CI 0.172-0.234 mg/kg) in school-age group. The ED 50 and ED 95 were significantly decreased in school-age group as compared with preschool group ( P<0.05). During anesthesia, 3 patients suffered hypotension (11%) in preschool group, and 3 patients suffered hypotension (12%), 2 patients suffered respiratory depression (8%), 2 patients suffered hiccup (8%), 1 patient suffered injection pain (4%) and 1 patient suffered muscle rigidity (4%) in school-age group. There was no significant difference in the incidence of adverse reactions between the two groups ( P>0.05). Conclusions:When combined with propofol, the ED 50 of remimazolam for gastroscopy in preschool and school-age pediatric patients is 0.266 mg/kg and 0.160 mg/kg, respectively, and the ED 95 is 0.302 mg/kg and 0.183 mg/kg, respectively, indicating a stronger anesthetic potency in school-age children. The probability of adverse reactions is low when the two are combined.

Objective:To explore the effects of magnanimous therapy on the magnanimous and enterprising traits of lung cancer patients and the analysis of related factors.Methods:Totally 197 patients with lung cancer were divided into individual group ( n=62), team group ( n=75) and control group ( n=60). Comparison and correlation analysis were applied to the data before and after the electroencephalogram and the magnanimous questionnaire, the cancer response questionnaire, the T-type psychological scale, the cancer heart state questionnaire and the cancer patient's life function index scale. t test, analysis of variance and Pearson correlation analysis were processed by SPSS 23.0. Results:After treatment, the " enterprising" dimension and " magnanimous" dimension of individual group and the " enterprising" dimension of the team group ((3.035±0.309), (3.041±0.265), (3.173±0.371)) were higher than that before treatment((2.934±0.326), (2.908±0.315), (3.130±0.387), all P<0.05). There was negative correlation between " magnanimous" dimension of the magnanimous questionnaire and " subconscious" dimension of the T-type psychological scale in individual group( r=-0.280, P<0.05). In team group, the " enterprising" dimension of the magnanimous questionnaire was negatively correlated with " Psychological" and " Yield" dimension of the cancer heart state questionnaire( r=-0.279, -0.285, P<0.05), and positively correlated with " Facing" of the cancer response questionnaire, " Good physical condition and ability" and " Psychological well-being" dimension of the cancer patient's life function index scale( r=0.367, 0.402, 0.379, P<0.05). There was a negative correlation between the " enterprising" dimension of the magnanimous questionnaire and the beta wave value in individual group. Conclusion:The magnanimous therapy can improve enterprising and magnanimous level of patients with lung cancer, and the effects are related with the above-mentioned psychosomatic factors.

Objective To explore the efficacy and safety of remimazolam combined with propofol for gastroscopy in school-age children.Methods A total of 106 children who underwent painless gastroscopy from january to february 2024 were selected,56 males and 50 females,aged 7-12 years,ASA physical status Ⅰ or Ⅱ.Children were randomly divided into two groups:propofol group(group P)and remimazolam combined with propofol group(group RP),53 children in each group.After intravenous injec-tion of alfentanil 8 μg/kg,group P was intravenously injected with propofol 2.5 mg/kg,and group RP was intravenously injected with remimazolam 0.183 mg/kg and propofol 1 mg/kg in turn.Gastroscopy was per-formed when the eyelash reflex disappeared and the modified observer's assessment alertness/sedation scale(MOAA/S)score≤1.The onset time of anesthesia,examination time,and recovery time were recorded.The number of add propofol and successful sedation cases were recorded.Adverse reactions such as respira-tory depression,hypotension,bradycardia,injection pain,hiccups,nausea and vomiting were recorded.Results Compared with group P,the onset time of anesthesia in group RP was significantly prolonged,and the recovery time was significantly shortened(P＜0.05).Compared with group P,the incidence of add propofol,hypotension,respiratory depression and injection pain in group RP were significantly decreased(P＜0.05).Conclusion Remazolam combined with propofol for gastroscopy in children can not only en-sure the sedative effect,but also reduce the incidence of adverse reactions,stabilize hemodynamic changes and shorten the recovery time.

The global COVID-19 coronavirus pandemic has infected over 109 million people, leading to over 2 million deaths up to date and still lacking of effective drugs for patient treatment. Here, we screened about 1.8 million small molecules against the main protease (M^pro) and papain like protease (PL^pro), two major proteases in severe acute respiratory syndrome-coronavirus 2 genome, and identified 1851M^pro inhibitors and 205 PL^pro inhibitors with low nmol/l activity of the best hits. Among these inhibitors, eight small molecules showed dual inhibition effects on both M^pro and PL^pro, exhibiting potential as better candidates for COVID-19 treatment. The best inhibitors of each protease were tested in antiviral assay, with over 40% of M^pro inhibitors and over 20% of PL^pro inhibitors showing high potency in viral inhibition with low cytotoxicity. The X-ray crystal structure of SARS-CoV-2 M^pro in complex with its potent inhibitor 4a was determined at 1.8 Å resolution. Together with docking assays, our results provide a comprehensive resource for future research on anti-SARS-CoV-2 drug development.
Humans ; Antiviral Agents/chemistry* ; COVID-19 ; COVID-19 Drug Treatment ; High-Throughput Screening Assays ; Molecular Docking Simulation ; Protease Inhibitors/chemistry* ; SARS-CoV-2/enzymology* ; Viral Nonstructural Proteins