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In view of the passenger travel demand changing from popularization to high quality and customization, a customized passenger route planning method with multi-departure point and multi-arrival point is proposed, and a customized passenger route optimization model with the minimum total cost for enterprise operation and passenger travel time is established. An improved genetic algorithm is proposed to solve the optimization model. Finally, the feasibility of the optimization method and the effectiveness of the improved genetic algorithm are verified by a practical case.

Low selenium status is associated with increased risk of Graves’ disease (GD). While several trials have discussed the efficacy of selenium supplementation for thyroid function, in GD patients, the effectiveness of selenium intake as adjuvant therapy remains unclear. In this systematic review and meta-analysis, we aimed to determine the efficacy of selenium supplementation on thyroid function in GD patients. Two reviewers searched PubMed, Web of Science, the Cochrane Central Register of Controlled Trials, and four Chinese databases for studies published up to October 31, 2017. RCTs comparing the effect of selenium supplementation on thyroid hyperfunction in GD patients on antithyroid medication to placebo were included. Serum free thyroxine (FT4), free triiodothyronine (FT3), thyrotrophic hormone receptor antibody (TRAb), and thyroid-stimulating hormone (TSH) levels were assessed. Ten trials involving 796 patients were included. Random-effects meta-analyses in weighted mean difference (WMD) were performed for 3, 6, and 9 months of supplementation and compared to placebo administration. Selenium supplementation significantly decreased FT4 (WMD=-0.86 [confidence interval (CI)-1.20 to -0.53]; p=0.756; I2=0.0%) and FT3 (WMD=-0.34 [CI-0.66 to -0.02]; p=0.719; I2=0.0%) levels at 3 months, compared to placebo administration; these findings were consistent at 6 but not 9 months. TSH levels were more elevated in the group of patients taking selenium than in the control group at 3 and 6, but not 9 months. TRAb levels decreased at 6 but not 9 months. At 6 months, patients on selenium supplementation were more likely than controls to show improved thyroid function; however, the effect disappeared at 9 months. Whether these effects correlate with clinically relevant measures remains to be demonstrated.

Carnosic acid (CA) is a phenolic terpenoid mainly existed in rosemary, sage and other Labiate herbs. It possesses powerful antioxidant, anti-inflammatory and other health-promoting activities for treating degenerative and chronic diseases. The low solubility and dissolution in aqueous environment of carnosic acid posed a challenge for its application in functional food and accessibility for intestine absorption. The target of my research is to enhance the bioavailability and evaluate bioactivities of carnosic acid by encapsulated in a lecithin based nanoemulsion system. The first part of the research is mainly about the investigation of the properties of carnosic acid and the development of the carnosic acid nanoemulsion (CA-NE). The CA-NE was formulated by medium chain triglycerides as oil phase, lecithin as the emulsifier and prepared by a two-step high speed-high pressure homogenization method. The produced nanoemulsion possess good stability under various pH and low ionic strength conditions. Storage under different temperatures showed good stability of formulated carnosic acid nanoemulsion (CA-NE). The second part of current research is focusing on the bioaccessibility and bioavailability evaluation by in vitro/in vivo models. The pH-stat lipolysis results revealed the nano-emulsified CA was much more bioaccessible than the unformulated CA with 2.8-fold improvement by nanoemulsion system compared with the MCT oil suspension and more than 12-fold compared with the water suspension based on the in vitro lipolysis study. The human gastrointestinal tract (TIM-1) model which simulated the physiological conditions of human upper GI tract revealed that the nanoemulsion greatly improved the oral bioaccessibility of CA by 5.8-fold and indicated a better bioavailability. The pharmacokinetics (PK) study using rats as model animal further showed that the oral bioavailability of carnosic acid enhanced almost 2.2-fold when encapsulated in the nanoemulsion compared with the unformulated CA suspension. Being the first thorough study on nanoemulsion formulation for carnosic acid, by applying two complementary simulation models and animal study, the present research elucidated the reason why nanoemulsion encapsulation would influence the bioavailability of carnosic acid and nanoemulsion proved to be a useful method for improving the oral bioavailability of CA. The third part of my research evaluated the bioactivities of carnosic acid after encapsulation by nanoemulsion system. The antioxidant activity of CA after encapsulation by nanoemulsion decreased from the result obtained by the cellular antioxidant assay (CAA) using HepG2 cells, which mainly attributed to the sustained release and longer endocytosis process as proved by the cellular uptake by confocal laser scanning microscopy. The efficacy on the inhibition on inflammation was conducted using lipopolysaccharide-stimulated RAW 264.7 macrophage cells. Results showed significantly enhanced anti-inflammatory ability of CA-NE with inhibiting the pro-inflammatory cytokines NO and TNF-α production (p< 0.05). The antiproliferative efficacy of carnosic acid nanoemulsion (CA-NE) on various carcinoma cells originated from different tissues or organs was evaluated and discussed by MTT assay. Results showed the inhibition was significantly improved by the use of the emulsion delivery system. We also evaluated how the nanoemulsion affected the anti-bacterial activities of four common food pathogens of carnosic acid, which showed the encapsulation would not affect the activity of carnosic acid as anti-bacterial agent. This result indicated a potential application of the nanoemulsion in food and beverages acting as food preservatives.The findings in the current research suggested encapsulation in lecithin based nanoemulsion delivery system opens new possibilities for the successful application of carnosic acid in functional food formulations with increased bioavailability and bioefficacies. This study also indicates the successful design and potential application of the lecithin-based nanoemulsion formulation to other hydrophobic nutraceuticals or drugs.