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Purpose: Raw "Pinelliae Rhizoma" (RPR) is widely used in Chinese clinics to treat insomnia. This study investigated its underlying sedative and hypnotic mechanisms and main active components. Methods: A locomotor activity test was used to evaluate the sedative effects of RPR at three dosages (0.2 g/mL, 0.4 g/mL, and 0.8 g/mL) in mice. Polysomnography was used to assess its ability to improve sleep. Ultra-performance liquid chromatography/time of flight/mass spectrometry (UPLC-TOF–MS) analysis was used to identify the potential active components of RPR. Results: Mice in the RPR groups were less active than mice in the vehicle group; this difference was greatest in the 0.8 g/mL RPR group. Compared with the vehicle, 0.8 g/mL RPR increased the duration of rapid eye movement (REM) sleep in the dark phase. In addition, the duration of wakefulness in the 0.8 g/mL RPR group decreased with increasing durations of nonrapid eye movement (NREM) and REM sleep. Compared with diazepam, 0.8 g/mL RPR increased REM sleep duration in both the light and dark phases and increased the number of transitions both from NREM sleep to REM sleep and from REM sleep to wakefulness. A total of 33 RPR constituents, including 15 alkaloids, were identified. Conclusion: The results preliminarily indicated that RPR exerts sedative and hypnotic effects in mice, mainly leading to improvements in REM sleep. These effects are possibly due to the alkaloid constituents of RPR. [ABSTRACT FROM AUTHOR]

Adding nitrogen fertilizers to soils can induce short-term changes in soil N pools, and consequently cause extra release of nitrous oxide (N2O) emissions that are sourced directly from soils rather than from added N – a response termed the 'priming effect'. However, it is unknown how priming effects on nitrous oxide (N2O) emissions can be altered following a strong freeze–thaw cycle. A mesocosm (pot) experiment evaluated two soil managements: with and without history of manure applications. These soils were subjected to three moisture regimes: Low, Medium and High. Apart from the controls, which received no N, we banded 15 N-labelled urea into these soils representing a typical fall fertilization, and subsequently simulated a wide fall-freeze–thaw cycle, with temperatures from + 2, to − 18, and finally + 23 °C, respectively. The overall highest N2O production was observed 1 day after thawing. At that time, measurements of N2O site preference indicated that denitrification produced 83% of the N2O flux. Relative to the unamended controls (baseline), adding urea consistently triggered a 24% greater cumulative N2O production originated from soil N following thawing (245 vs. 305 μg N2O-N kg−1 soil, P = 0.022). This substantiates a positive priming of N2O that manifested shortly after the rapid, wet thawing of the soils. Soils having a manure history or higher moisture also exhibited an augmented production of N2O from soil N rather than from the added urea (Ps < 0.01). Although the overall N2O priming was positive, two weeks after thawing, negative priming of daily N2O fluxes also occurred, but only in soils under High moisture. Besides urea addition, the propensity for primed N2O emissions after soil thawing was enhanced under higher moisture conditions and in the soil with history of manure applications. [ABSTRACT FROM AUTHOR]

Allisartan isoproxil (AI) is a blocker of the angiotensin II type 1 receptor. We evaluated the safety and pharmacokinetics of single‐ and multiple‐dose AI in healthy Chinese individuals. Participants were assigned to receive AI or placebo. Plasma concentration of EXP3174 (carboxylic acid derivative) was measured using liquid chromatography‐tandem mass spectrometry. Pharmacokinetic parameters were determined by noncompartmental methods. Twelve subjects were enrolled, and the ratio of men to women was 5:1. Main pharmacokinetic parameters of EXP3174 after single and multiple doses of AI were a mean maximum concentration in plasma (Cmax) of 2242 ± 1037 ng/mL and median time to reach Cmax (Tmax) of 3.5 hours (2.5‐8 hours). The median Tmax, at steady state was 4.0 hours (1.5‐8 hours). The mean Cmax at steady state (Cmax, SS) was 2047 ± 1050 ng/mL. In terms of EXP3174, there was no significant difference in the Cmax, SS, area under the curve from time zero to 24 hours of quantifiable concentration at steady state (AUC0–24 SS), and AUC0‐72 after multiple doses of AI. Serious adverse events did not occur. These data suggest that AI is safe and well tolerated in healthy Chinese individuals at a single dose of 480 or 480 mg once daily for 7 days. [ABSTRACT FROM AUTHOR]

Meloxicam is an enolate nonsteroidal anti‐inflammatory agent. This trial investigated the pharmacokinetics, safety, and bioequivalence of single oral doses of Aomei meloxicam (15 mg) and Mobic meloxicam (15 mg) in healthy volunteers under fasting and fed conditions. A single‐site, single‐dose, randomized, open, 2‐period, 2‐sequence, crossover bioequivalence study was performed: 24 healthy volunteers were enrolled in each of the fasting and fed arms. Each HV was randomly assigned to receive the Aomei drug (test) in one period and the Mobic drug (reference) in the other period. The concentration of meloxicam in plasma was detected using liquid chromatography–tandem mass spectrometry. The primary pharmacokinetic parameters were calculated using a noncompartmental model. In the fasting arm, the 90% confidence interval of the geometric mean ratios of maximum plasma concentration, area under the concentration‐time curve from time 0 to the last measurable plasma concentration, and area under the concentration‐time curve from time 0 to infinity between the test and reference products were 99.5% to 111.7%, 101.2% to 106.8%, and 101.8% to 108.3%, respectively. In the fed arm, the 3 parameters were 94.1% to 102.4%, 97.6% to 103.0%, and 97.5% to 103.7%, respectively. These parameters were in the range of 80% to 125%, and the 2 products were considered bioequivalent in both the fasting and fed states and were well tolerated. The severity of all adverse events was mild. Aomei meloxicam tablets and Mobic meloxicam tablets were bioequivalent in healthy Chinese volunteers. [ABSTRACT FROM AUTHOR]