a Rosmarinic acid (RA), one of the main bioactive compounds of Rosmarinus officinalis L., exhibits diverse pharmacological effects. However, its oral absolute bioavailability and dose proportionality in vivo have not been comprehensively studied. In the present study, a validated LC-MS/MS method was developed for the determination of RA in rat plasma. Pharmacokinetic parameters were obtained following oral and intravenous dosing using DAS 3.0 software. Absolute bioavailability in rats was determined by comparing pharmacokinetic data after administration of single oral (12. 332.34 to 295.32 min, respectively. The power model showed RA lacked dose proportionality over the dose range from 12.5-50 mg kg À1 . Oral absolute bioavailability was calculated to range from 0.91% to 1.69%. All the results demonstrated that the pharmacokinetic properties of RA in rats after oral administration were characterized as rapid absorption, middle-speed elimination and poor absolute bioavailability. Systemic exposure exhibited lack of dose proportionality over the dose range from 12.5 to 50 mg kg À1 . These presented data could provide useful information for the rational clinical application and optimal dosage form design of RA.

Andrographolide (ADG) is a diterpenoid isolated from Andrographis paniculata with a wide spectrum of biological activities, including anti-inflammatory, anticancer and hepatoprotective effects. However, its poor water solubility and efflux by P-glycoprotein have resulted in lower bioavailability. In this study, ADG nanosuspensions (ADG-NS) were prepared using a wet media milling technique followed by freeze drying. d -α-Tocopheryl polyethylene glycol 1000 succinate (TPGS), a surfactant that inhibits P-glycoprotein function, and sodium lauryl sulfate were used as surface stabilizers. A Box–Behnken design was used to optimize the nanosuspension preparation. The products of these optimal preparation conditions were amorphous and possessed much faster dissolution in vitro than a coarse powder of ADG. The particle size and redispersibility index of the freeze-dried ADG-NS were 244.6±3.0 nm and 113%±1.14% (n=3), respectively. A short-term stability study indicated that the freeze-dried ADG-NS could remain highly stable as nanosuspensions during the testing period. A test of transport across a Caco-2 cell monolayer revealed that the membrane permeability ( P app ) of ADG-NS was significantly higher than the permeability of the ADG coarse powder or ADG-NS without TPGS ( P <0.01). Compared to the ADG coarse powder, a physical mixture, commercial dripping pills and ADG-NS without TPGS, ADG-NS exhibited significantly higher plasma exposure with significant enhancements in C max and area under the curve of plasma concentration versus time from zero to the last sampling time (AUC 0− t ) ( P <0.01). An evaluation of the anti-inflammatory effect on Carr-induced paw edema demonstrated that the ADG-NS were more effective in reducing the rate of paw swelling, producing a greater increase in the serum levels of nitric oxide (NO), Interleukin-1 (IL-1) and tumor necrosis factor-α (TNF-α) ( P <0.01) and an increase in superoxide dismutase activity ( P <0.05) compared to the ADG coarse powder. This study indicated that nanosuspensions could act as an effective delivery device for ADG to enhance its oral bioavailability and biological efficacy.

No abstract

The establishment of the Discipline Development Consortium for Medical Informatics has ushered in a new phase of medical informatics (MI) research in China. Consequently, Chinese government, healthcare providers, and scholars, have increased their attention on the topic with the aim of improving patient care and healthcare delivery. The purpose of this study was to examine the research progress of medical informatics in China over the past 20 years using Master’s theses. Descriptive analysis was completed to identify the temporal distribution, spatial distribution, institutional distribution, specialty distribution, and advisor distribution, of the theses. A structural topic modeling-based analysis was performed to determine topic prevalence, topic correlation, associations between prolific institutions and topics, and topic trend. Our results reveal that the majority of institutions publishing theses on MI include universities with medical departments, medical universities, engineering universities, and research institutes. Most theses advisors focus on the field of medical informatics, while the sub-fields studied include software engineering, computer science, and biomedical engineering. The themes of theses can be divided into seven categories, including: electronic medical records and hospital informatics, Internet + medicine, and health information management and analysis, while new technologies, such as mHealth, Internet+, cloud computing, and big data, are growing in interest. Medical informatics in China should be established as an independent discipline to enhance research focus and to promote cross-institutional, cross-disciplinary, and cross-national collaboration between authors and institutions.