The study aimed to investigate the effects of intraoperative dexmedetomidine on postoperative sleep disturbance for different surgical patients and compare such effects between different dose of dexmedetomidine. Methods: A total of 7418 patients undergoing nine types of non-cardiac major surgeries were retrospectively studied. Patients were separated into DEX (dexmedetomidine) or Non-DEX (Non-dexmedetomidine) groups based on the use of dexmedetomidine during surgery. The patients who reported they could not fall asleep during the night or woke up repeatedly during the most of the night at the day of the surgery and whose NRS were >6 were defined as cases with severe sleep disturbance. Propensity score matched analysis based on all preoperative baseline data was performed along with logistic regression analysis including different surgery types and dosage of dexmedetomidine use. Results: In both of the unmatched cohort (OR, 0.49 [95% CI: 0.43-0.56]) and matched cohort (0.49 [95% CI: 0.42-0.58]), the DEX group had a significantly lower incidence of severe sleep disturbance than the Non-DEX group. In the subgroup analysis, for gynecological and urological surgery population, the ORs for DEX-group reached 0.21 (95% CI, 0.13-0.33; P<0.0001) and 0.30 (95% CI,0.19-0.47; P<0.0001), respectively. In addition, low-dose dexmedetomidine (0.2-0.4 μg•kg −1 •h −1) showed the greatest effect with an odds ratio of 0.38 (95% CI: 0.31-0.44; P<0.0001), and the incidence of severe sleep disturbance in the low-dose group was significantly lower (11.5% vs. 17.7% vs. 16.5%, P<0.0001) than that in the medium-(0.4-0.6 μg•kg −1 •h −1) and high-dose (0.6-0.8 μg•kg −1 •h −1) groups. Conclusion: Intraoperative dexmedetomidine use can significantly decrease the incidence of severe sleep disturbance on the day of surgery for patients undergoing non-cardiac major surgery, and the effects were most significant in patients receiving gynecological and urological surgery. Furthermore, low-dose dexmedetomidine (0.2-0.4 μg•kg −1 •h −1) is most effective for prevention of postoperative sleep disturbance.

Estrone-3-sulfate (E3S) uptake mediated by organic anion transporting polypeptide 1B3 (OATP1B3) can be activated by epigallocatechin gallate (EGCG). In this study, by using chimeric transporters and site-directed mutagenesis, we found that Val386 in transmembrane domain 8 (TM8) is essential for OATP1B3's activation by EGCG. Kinetic studies showed that the loss of activation of 1B3-TM8 and 1B3-V386F in the presence of EGCG is due to their decreased substrate binding affinity and reduced maximal transport rate. The overall transport efficiencies of OATP1B3, 1B3-TM8, and 1B3-V386F in the absence and presence of EGCG are 8.6 ± 0.7 vs 15.9 ± 1.4 (p < 0.05), 11.2 ± 2.1 vs 2.7 ± 0.3 (p < 0.05), and 10.2 ± 1.0 vs 2.5 ± 0.3 (p < 0.05), respectively. While 1B3-V386F cannot be activated by EGCG, its transport activity for EGCG is also diminished. OATP1B3's activation by EGCG is substrate-dependent as EGCG inhibits OATP1B3-mediated pravastatin uptake. Furthermore, the activation of OATP1B3-mediated E3S uptake by quercetin 3-O-α-L-arabinopyranosyl(1 → 2)-α-L-rhamnopyranoside is not affected by TM8 and V386F. Taken together, the activation of OATP1B3 by small molecules is substrate-and modulator-dependent, and V386 in TM8 plays a critical role in the activation of OATP1B3-mediated E3S uptake by EGCG.

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Human organic anion transporting polypeptide 2B1 (OATP2B1) is a crucial transporter for the absorption and disposition of many drugs. Its inhibition by small molecules may alter the pharmacokinetic profile of...