The acupoint herbal plaster for the prevention and treatment of postoperative nausea and vomiting after PLIF with general anesthesia: study protocol for a multicenter randomized controlled trial.

BACKGROUND: Postoperative nausea and vomiting (PONV) are common in posterior lumbar intervertebral fusion (PLIF) patients undergoing general anesthesia. The previous clinical observation has shown that a traditional acupoint herbal plaster (AHP) is beneficial to patients with PONV. This trial aims to assess the effect of the AHP for the prevention and treatment of PONV after PLIF in patients with general anesthesia. METHODS: A multicenter, parallel, randomized controlled trial (RCT) will be conducted. A total of 166 participants will be randomized to either a treatment group receiving an AHP or a control groups receiving an acupoint placebo plaster (APP) in a 1:1 ratio. The primary outcomes are the first occurrence and frequency of nausea and vomiting. The secondary outcomes include the severity grading of nausea and vomiting using a visual analog scale (VAS) measurement system, quality of life, and serological indicators. The safety evaluation is mainly about adverse events and skin reactions' observation. Assessments will be carried out at the baseline, day 1, and day 2 (the end of the intervention). The central randomization system in the clinical trial ( http://124.205.181.142:8082/xwtf/ ) will be used to conduct random allocation. DISCUSSION: This scientific methodology design of the trial is expected to provide clinical evidence to support the AHP for the prevention and treatment of PONV. TRIAL REGISTRATION: This study is retrospectively registered with the Chinese Clinical Trial Registry ( http://www.chictr.org.cn ) on 19 April 2018. ID: ChiCTR1800015768.

Recognition of LXXLL by ligand binding domain of the Farnesoid X receptor in molecular dynamics simulation.

The Farnesoid X receptor (FXR) has recently become a potential therapeutical target. The recruitment of coactivator protein (specified by LXXLL sequence) is the initial step in transcriptional activation of nuclear receptors (NRs). In this paper, the process of recognition of the LXXLL motif by the ligand binding domain (LBD) of FXR is observed in a 25 ns molecular dynamics simulation. The hydrophobic and hydrogen bonding interactions between the LBD and the coactivator are fully analyzed. This observation provides justification for the 'on deck' model proposed by Nettles and Greene. At last, insight to the protein-polypeptide interactions and protein conformational changes are discussed.

Fluoro-substitution effects in deoxyfluoro-D-glucose derivatives: random conformational search and quantum chemical calculation.

The effect of substitution by the fluorine atom at different positions of D-glucose was investigated by quantum chemical calculation of the low-energy conformers. These were obtained through the Random conformational search method. The geometries of conformers were optimized at the RHF/6-31(d) level, then reoptimization and vibrational analysis were performed at the B3LYP/6-31+G(d) level. Single-point energies were calculated at the B3LYP/6-311++G(2d,2p) level. The free energies of solvation in water were calculated utilizing the AM1-SM5.4 solvation model. For all substitution positions, the ring conformation does not change much, and the pyranoid 4C1 conformers are dominant, while variations in the substitution site result in different effects in the network of hydrogen bonds, anomeric effect, the solvation free energy, and the ratio of alpha- and beta-anomers.

3-deoxy-3,3-difluoro-D-arabinofuranose: first stereoselective synthesis and application in preparation of gem-difluorinated sugar nucleosides.

The design and synthesis of gem-difluorinated sugar nucleosides were described. The key intermediate, 3-deoxy-3,3-difluoro-d-arabinofuranose 9, was first stereoselectively prepared from the chiral gem-difluorohomoallyl alcohol 12. The kinetic formation of single anti-14 in the benzylation of 12 could be accomplished by controlling the amount of sodium hydride used. The dihydroxylation of 14 (a mixture of anti and syn isomers) followed by deprotection and oxidation stereoselectively afforded furanose 9 with the arabino configuration at the C2 position. N(1)-(3-Deoxy-3,3-difluoro-beta-D-arabinofuranosyl)cytosine 6 was prepared from 9 by the glycosylation reaction. 4'-Thiofuranose 25 was easily synthesized from 9. The oxidation of 25 followed by the condensation with silylated N(4)-benzoylcytosine (Pummerer reaction) failed to give our desired protected nucleoside l-3'-deoxy-3',3'-difluoro- 4'-thiocytidine 27', but the regioisomer 27 was obtained. The regiochemistry of the Pummerer reaction was determined by the kinetic acidity of the alpha-proton of 4'-thiofuranose 25.

On the 6-exo atom transfer radical cyclization reactions of 3-butenyl 2-iodoalkanoates.

Bis(tributyltin)-initiated atom transfer cyclization reactions of 3-butenyl iodoalkanoates in the presence of BF3.OEt2 as the catalyst afforded the 6-exo cyclization products as a mixture of 3,4-cis- and trans-substituted tetrahydro-2H-pyran-2-ones in 53-71% yield with the major isomers being the cis ones. Ab initio calculations at the B3LYP/6-31G level on the transition states of the radical cyclization and on the cyclized products revealed that the reactions are kinetically controlled and the transition states for the 6-exo radical cyclization are in boat conformations. Moreover, the cis-oriented transition states are of lower energy than the corresponding trans-oriented ones, which are in excellent agreement with experimental results.