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ABSTRACTBackgroundRomiplostim and eltrombopag are thrombopoietin receptor agonists (TPORAs) that have been approved by the FDA on 22 August 2008 and 20 November 2008 for pediatric immune thrombocytopenia (ITP). However, postmarketing pharmacovigilance of TPORAs in children still attracts much attention. We aimed to evaluate the safety of the TPORAs romiplostim and eltrombopag using data from the Adverse Event Reporting System database of FDA (FAERS).Research design and methodsWe conducted a disproportionality analysis and analyzed data from the FAERS database to characterize the key features of adverse events (AEs) associated with TPO-RAs approved for children under 18 years of age.ResultsSince their approval in the market in 2008, 250 and 298 reports of romiplostim and eltrombopag use in children have been published in the FAERS database, respectively. The most frequent AE associated with romiplostim and eltrombopag was epistaxis. Neutralizing antibodies and vitreous opacities showed the strongest signals for romiplostim and eltrombopag, respectively.ConclusionsThe labeled AEs for romiplostim and eltrombopag in children were analyzed. Unlabeled AEs may reflect the potential of new clinical individuals. Early recognition and management of AEs that appear in children treated with romiplostim and eltrombopag are of key importance in clinical practice.

Effective therapies are urgently needed for the SARS-CoV-2 pandemic. Chloroquine has been proved to have antiviral effect against coronavirus in vitro. In this study, we aimed to assess the efficacy and safety of chloroquine with different doses in COVID-19. In this multicenter prospective observational study, we enrolled patients older than 18 years old with confirmed SARS-CoV-2 infection excluding critical cases from 12 hospitals in Guangdong and Hubei Provinces. Eligible patients received chloroquine phosphate 500 mg, orally, once (half dose) or twice (full dose) daily. Patients treated with non-chloroquine therapy were included as historical controls. The primary endpoint is the time to undetectable viral RNA. Secondary outcomes include the proportion of patients with undetectable viral RNA by day 10 and 14, hospitalization time, duration of fever, and adverse events. A total of 197 patients completed chloroquine treatment, and 176 patients were included as historical controls. The median time to achieve an undetectable viral RNA was shorter in chloroquine than in non-chloroquine (absolute difference in medians −6.0 days; 95% CI −6.0 to −4.0). The duration of fever is shorter in chloroquine (geometric mean ratio 0.6; 95% CI 0.5 to 0.8). No serious adverse events were observed in the chloroquine group. Patients treated with half dose experienced lower rate of adverse events than with full dose. Although randomized trials are needed for further evaluation, this study provides evidence for safety and efficacy of chloroquine in COVID-19 and suggests that chloroquine can be a cost-effective therapy for combating the COVID-19 pandemic.

Although cartilage tissue engineering has been developed for decades, it is still unclear whether angiogenesis was the accompaniment of chondrogenesis in cartilage regeneration. This study aimed to explore the process of anti-angiogenesis during cartilage regenerative progress in cartilage repair extracellular matrix (ECM) materials under Hypoxia. C3H10T1/2 cell line, seeded as pellet or in ECM materials, was added with chondrogenic medium or DMEM medium for 21 days under hypoxia or normoxia environment. Genes and miRNAs related with chondrogenesis and angiogenesis were detected by RT-qPCR technique on Days 7, 14, and 21. Dual-luciferase report system was used to explore the regulating roles of miRNAs on angiogenesis. Results showed that the chondrogenic medium promotes chondrogenesis both in pellet and ECM materials culture. HIF1α was up-regulated under hypoxia compared with normoxia (P < 0.05). Meanwhile, hypoxia enhanced chondrogenesis. miR-140-5p exhibited higher expression while miR-146b exhibited lower expression. The chondrogenic phenotype was more stabilized in the ECM materials in chondrogenic medium than DMEM medium, with lower VEGFα expression even under hypoxia. Dual-luciferase report assays demonstrated that miR-140-5p directly targets VEGFα by binding its 3′-UTR. Taken together, chondrogenic cytokines, ECM materials and hypoxia synergistically promoted chondrogenesis and inhibited angiogenesis. miR-140-5p played an important role in this process. [ABSTRACT FROM AUTHOR]

A selective and sensitive method employing high‐performance liquid chromatography–electrospray ionization mass spectrometry was developed and validated for the determination of mitiglinide in human plasma.With gliclazide as the internal standard, mitiglinide was extracted from plasma with n‐hexane: = 80 : 20 (v/v). The organic layer was evaporated and the residue was redissolved in methanol: water (10 mM CH3COONH4, pH = 3.0) = 65 : 35 (v/v). An aliquot of 10 µl was chromatographically analyzed on a prepacked Shimadzu VP‐ODS (5 µm, 150 × 2.0 mm i.d.) using the mobile phase comprising methanol: water (10 mM CH3COONH4) = 65 : 35 (v/v) by means of selected‐ion monitoring mode mass spectrometry. Standard curves were linear (r2 = 0.9972) over the concentration range of 2.84–11 300 pmol/ml and had good accuracy and precision. The within‐ and between‐batch precisions of the method were within 15% of standard deviation. The lower limit of detection was 1.42 pmol/ml. The validated HPLC/ESI‐MS method has been successfully applied in the pharmacokinetics of mitiglinide in 12 healthy Chinese volunteers. Copyright © 2006 John Wiley & Sons, Ltd.