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Circadian rhythm involved with physiology has been reported to affect pharmacokinetics or pharmacodynamics. We hypothesized that circadian variations in physiology disturb anesthesia and eventually affect recovery after anesthesia. A retrospective cohort study initially included 107,406 patients (1 June 2016–6 June 2021). Patients were classified into morning or afternoon surgery groups. The primary outcome was daytime variation in PACU (post-anesthesia care unit) recovery time and Steward score. Inverse probability weighting (IPW) approach based on propensity score and univariable/multivariable linear regression were used to estimate this outcome. Of 28,074 patients, 13,418 (48%) patients underwent morning surgeries, and 14,656 (52%) patients underwent afternoon surgeries. LOWESS curves and IPW illustrated daytime variation in PACU recovery time and Steward score. Before adjustment, compared to morning surgery group, afternoon surgery group had less PACU recovery time (median [interquartile range], 57 [46, 70] vs. 54 [43, 66], p < 0.001) and a higher Steward score (5.62 [5.61, 5.63] vs. 5.66 [5.65, 5.67], p < 0.001). After adjustment, compared to morning surgery group, afternoon surgery group had less PACU recovery time (58 [46, 70] vs. 54 [43, 66], p < 0.001). In multivariable linear regression, morning surgery is statistically associated with an increased PACU recovery time (coefficient, −3.20; 95% confidence interval, −3.55 to −2.86). Among non-cardiac surgeries, daytime variation might affect recovery after general anesthesia. These findings indicate that the timing of surgery improves recovery after general anesthesia, with afternoon surgery providing protection. In this retrospective cohort study of 28,074 participants, the afternoon surgery group has a higher Steward score than the morning surgery group. In multivariable linear regression, morning surgery is statistically associated with an increased PACU recovery time. Among non-cardiac surgeries, daytime variation affects the recovery after general anesthesia, with afternoon surgery providing protection. [ABSTRACT FROM AUTHOR]

The efficient targeting of drugs to tumor cell and subsequent rapid drug release remain primary challenges in the development of nanomedicines for cancer therapy. Here, we constructed a glucose transporter 1 (GLUT1)-targeting and tumor cell microenvironment-sensitive drug release Glucose-PEG-PAMAM-s-s-Camptothecin-Cy7 (GPCC) conjugate to tackle the dilemma. The conjugate was characterized by a small particle size, spherical shape, and glutathione (GSH)-sensitive drug release. In vitro tumor targeting was explored in monolayer (2D) and multilayer tumor spheroid (3D) HepG2 cancer cell models (GLUT1+). The cellular uptake of GPCC was higher than that in the control groups and that in normal L02 cells (GLUT1−), likely due to the conjugated glucose moiety. Moreover, the GPCC conjugate exhibited stronger cytotoxicity, higher S arrest and enhanced apoptosis and necrosis rate in HepG2 cells than control groups but not L02 cells. However, the cytotoxicity of GPCC was lower than that of free CPT, which could be explained by the slower release of CPT from the GPCC compared with free CPT. Additional in vivo tumor targeting experiments demonstrated the superior tumor-targeting ability of the GPCC conjugate, which significantly accumulated in tumor meanwhile minimize in normal tissues compared with control groups. The GPCC conjugate showed better pharmacokinetic properties, enabling a prolonged circulation time and increased camptothecin area under the curve (AUC). These features contributed to better therapeutic efficacy and lower toxicity in H22 hepatocarcinoma tumor-bearing mice. The GLUT1-targeting, GSH-sensitive GPCC conjugate provides an efficient, safe and economic approach for tumor cell targeted drug delivery. [ABSTRACT FROM AUTHOR]