Objective:To evaluate the effect of age on mood of patients during induction of general anesthesia with remimazolam.Methods:Eighty American Society of Anesthesiologists physical status Ⅰ or Ⅱpatients of both sexes, undergoing elective surgery with general anesthesia requiring tracheal intubation, aged 5-80 yr, with body mass index 18-30 kg/m 2, were divided into 4 groups ( n=20 each) according to different ages: juvenile group (R 1 group, 5-17 yr), youth group (R 2 group, 18-44 yr), middle-aged group (R 3 group, 45-59 yr) and elderly group (R 4 group, 60-80 yr). Remimazolam was intravenously injected in a loading dose of 0.1 mg/kg for induction of general anesthesia, followed by an infusion of 0.1 mg·kg -1·h -1 for maintenance of general anesthesia, and the other anesthetics for induction and maintenance of anesthesia were all the same in each group.The changes in emotion and brain wave within 3 min after remimazolam injection were recorded.The brain waves and Modified Observer′s Assessment of Alertness and Sedation (MOAA/S) scale score were recorded at 1, 2 and 3 min after administration.Adverse effects during anesthesia induction were also recorded. Results:Compared with group R 1, the incidence of happy mood was significantly decreased, the grade of mood was decreased, and the dream Likert score and MOAA/S score were decreased in R 3 and R 4 groups, and the dream Likert score and MOAA/S score were decreased in group R 2, and the incidence of hypoxemia during induction of general anesthesia was increased in group R 4( P<0.01). Compared with group R 2, the incidence of happy mood was significantly decreased in R 3 and R 4 groups, and MOAA/S score was significantly decreased in group R 4 ( P<0.05). Compared with R 1 and R 2 groups, the proportion of beta bands was significantly decreased, and the proportion of theta and delta bands was increased in R 3 and R 4 groups ( P<0.01). Compared with group R 3, the proportion of beta band was significantly decreased, and the proportion of delta band was increased in group R 4 ( P<0.01). Conclusion:Remimazolam 0.1 mg/kg used for induction of general anesthesia can cause happy mood, accompanied by enhanced brain electrical signal activity of beta band, especially in the patients under 45 yr of age.

Bacterial antitumor therapy has great application potential given its unique characteristics, including genetic manipulation, tumor targeting specificity and immune system modulation. However, the nonnegligible side effects and limited efficacy of clinical treatment limit their biomedical applications. Engineered bacteria for therapeutic applications ideally need to avoid their accumulation in normal organs and possess potent antitumor activity. Here, we show that macrophage-mediated tumor-targeted delivery of Salmonella typhimurium VNP20009 can effectively reduce the toxicity caused by administrating VNP20009 alone in a melanoma mouse model. This benefits from tumor-induced chemotaxis for macrophages combined with their slow release of loaded strains. Inspired by changes in the tumor microenvironment, including a decrease in intratumoral dysfunctional CD8⁺ T cells and an increase in PDL1 on the tumor cell surface, macrophages were loaded with the engineered strain VNP-PD1nb, which can express and secrete anti-PD1 nanoantibodies after they are released from macrophages. This novel triple-combined immunotherapy significantly inhibited melanoma tumors by reactivating the tumor microenvironment by increasing immune cell infiltration, inhibiting tumor cell proliferation, remodeling TAMs to an M1-like phenotype and prominently activating CD8⁺ T cells. These data suggest that novel combination immunotherapy is expected to be a breakthrough relative to single immunotherapy.