The relationships between screen exposure, parent-child interactions and comprehension in 8-month-old infants: The mediating role of shared viewing and parent-child conversation.

OBJECTIVE: To explore the relationships between screen exposure, parent-child interactions and comprehension in 8-month-old infants, and to examine whether shared viewing and parent-child conversation during screen exposure may play mediating role in that relationships. METHODS: The sample included 437 infants aged 8 months from the Children's Health Department of Guiyang Maternal and Child Health Hospital during January 2022 to February 2023. The use of electronic screen devices was assessed using a screen exposure questionnaire. The Brigance Parent-child interactions Scale was used to assess parent-child interactions and the Putonghua Communicative Development Inventory (PCDI) scale was used to assess infants' word comprehension. RESULTS: 48.7% of infants were found to be using screens 1-2 days per week. There was a significant difference (p < 0.05) in the PCDI-comprehension scores of screen-exposed infants compared to non-screen-exposed infants. Shared viewing and parent-child conversation during screen exposure were positively associated with parent-child interactions (p < 0.05). Mediation analysis revealed that parent-child conversation fully mediated between screen exposure and PCDI-comprehension, but partially mediated between parent-child interactions and PCDI-comprehension. CONCLUSIONS: Shared viewing and parent-child conversation during screen exposure may mediate between screen exposure and comprehension development. Shared viewing, parent-child conversation and parent-child interactions may be protective factors for screen exposure in comprehension development. Suggests that parents should accompany and communicate with their children when they use electronic screen devices to reduce the negative impact of screen exposure on children's comprehension.

Comparison of pharmacokinetics and safety of albuvirtide in healthy subjects after intravenous drip and bolus injection.

Albuvirtide (ABT) is the first long-acting HIV fusion inhibitor developed in China, blocking the invasion of HIV-1 virus into target cells. This study aimed to compare the pharmacokinetics (PK), tolerability, and safety of ABT following a single intravenous (IV) bolus injection or intravenous drip in healthy Chinese subjects. A single-center, randomized, open-label, single-period, parallel phase I clinical trial was conducted. Thirty subjects were randomly divided into three groups in a ratio of 1:1:1. After an overnight fast, all subjects received a single dose of 320 mg ABT either by intravenous drip for 45 min (group A) or bolus injection for 0.5 min (group B), or bolus injection for 3 min (group C). ABT plasma concentrations were analyzed using a validated enzyme-linked immunosorbent assay (ELISA). Non-compartmental analysis was used to evaluate PK parameters. The median time to reach maximum concentration was 0.75 h in group A and 0.16 h in both groups B and C. Elimination half-life, mean residence time, apparent clearance, and apparent volume of distribution were similar among the three groups. The 90% confidence intervals (CI) of geometric mean ratios of PK parameters for groups B and C relative to group C were within 85-120%. All adverse events (AEs) reported in this study were mild, according to the CTCAE guidelines and the study investigator's judgement. ABT bolus injections for 0.5 min and 3 min are expected to be well tolerated and to exhibit similar PK characteristics as IV drip for 45 min, offering potential clinical benefits.

Safety, pharmacokinetics and pharmacodynamics of HRS-7535, a novel oral small molecule glucagon-like peptide-1 receptor agonist, in healthy participants: A phase 1, randomized, double-blind, placebo-controlled, single- and multiple-ascending dose, and food effect trial.

AIM: To assess the safety, tolerability, pharmacokinetics (PKs) and pharmacodynamics of HRS-7535, a novel glucagon-like peptide-1 receptor agonist (GLP-1RA), in healthy participants. MATERIALS AND METHODS: This phase 1 trial consisted of single-ascending dose (SAD), food effect (FE) and multiple-ascending dose (MAD) parts. In the SAD part, participants were randomized (6:2) to receive HRS-7535 (at doses of 15, 60 and 120 mg; administered orally once daily) or placebo. In the FE part, participants were randomized (8:2) to receive a single dose of 90-mg HRS-7535 or placebo, in both fed and fasted states. In the MAD part, participants were randomized (18:6) to receive daily HRS-7535 (120 mg [30/60/90/120-mg titration scheme]) or placebo for 28 days. The primary endpoints were safety and tolerability. RESULTS: Nausea and vomiting were the most frequently reported AEs across all three parts. In the SAD part, the median Tmax was 5.98-5.99 hours and the geometric mean t1/2 was 5.28-9.08 hours across the HRS-7535 dosing range. In the MAD part, the median Tmax was 5.98-10.98 hours and the geometric mean t1/2 was 6.48-8.42 hours on day 28 in participants on HRS-7535. PKs were approximately dose-proportional. On day 29 in the MAD part, the mean (percentage) reduction in body weight from baseline was 4.38 kg (6.63%) for participants who received HRS-7535, compared with 0.8 kg (1.18%) for those participants who received a placebo. CONCLUSIONS: HRS-7535 exhibited a safety and tolerability profile consistent with other GLP-1RAs and showed PKs suitable for once-daily dosing. These findings support further clinical development of HRS-7535 for type 2 diabetes.

Effect of High-Fat Food on the Pharmacokinetic Profile and Safety of SAF-189s, an ALK/ROS1 Inhibitor, in Healthy Chinese Adults.

BACKGROUND AND OBJECTIVES: This study was conducted to investigate the effect of high-fat meals on the pharmacokinetics (PK) and safety profile of SAF-189s, a novel ALK/ROS1 inhibitor. METHODS: This was a single-center, phase I, open-label, crossover study in which healthy adults (≥18 years) were randomized (1:1) to two sequences of SAF-189s administration (fasted-fed or fed-fasted) separated by a 14-day washout. After a ≥10-h overnight fast, volunteers received SAF-189s 160 mg orally in a fasted state or 30 min after a high-fat, high-calorie meal. Similarity of pharmacokinetic parameters was concluded if the 90% CI for the geometric mean ratio (GMR) between the fed and fasted group fell within the predefined range of 0.80-1.25. RESULTS: In total, 24 subjects were enrolled and 23 completed the study. SAF-189s maximum plasma concentration (Cmax; GMR: 109.1% [90% CI 103.1-115.4]) was comparable under fed (high-fat meal, n = 24) versus fasted (n = 23) conditions, with no effect on area under the plasma concentration-time curve from time 0 to t (AUC0-t; GMR: 105.1% [90% CI 100.3-110.2]) and AUC from time 0 to infinity (AUC0-∞; GMR: 105.5% [90% CI, 100.6-110.6]). In both groups, the median time to maximum plasma concentration (tmax) was around 6 h and mean plasma half-life (t½) was around 35 h. Fed administration led to a lower incidence of treatment-emergent adverse events (TEAEs; 29.2% vs 54.2%), including gastrointestinal disorders (4.2% vs 41.7%) and headache (0.0% vs 12.5%), versus fasted administration. CONCLUSIONS: A high-fat meal had minimal effect on the pharmacokinetic profile of SAF-189s compared with a fasted state following a single dose of 160 mg. Administration with a high-fat meal led to a lower incidence of TEAEs.

LC-MS/MS determination of HY072808, a novel candidate for treating atopic dermatitis, and its active metabolite: Application to a first-in-human pharmacokinetic study.

HY072808 is a novel phosphodiesterase 4 inhibitor currently under clinical development to treat atopic dermatitis. The first step is to address the pharmacokinetics and safety after topical administration of HY072808 ointments in healthy humans. In this study, we developed a highly sensitive liquid chromatography-tandem mass spectrometry method to determine plasma HY072808 and its active metabolite, ZZ24, in tiny amounts. The plasma samples were prepared using a simple liquid-liquid extraction method. Liquid chromatographic separation was achieved by gradient elution. The MS/MS quantification was performed in positive ion mode via multiple reaction monitoring. The method showed satisfactory linearity from 10 to 4,000 pg/ml for HY072808 and ZZ24. There was no significant interference from blank plasma. The method was validated for accuracy and precision, matrix effect and extraction recovery, dilution integrity, injection carryover and stability according to the related guidelines of the regulatory authorities. The HY072808 and ZZ24 concentrations in human plasma from a clinical trial were determined using this method. In conclusion, the validated method was robust and could be utilized to support the clinical development of HY072808.

Cross sectional, surveillance and longitudinal study of poor visual acuity in Gui an New Distinct of Guizhou Province / 中国学校卫生

Objective@#To understand the development trend of poor vision among primary students through cross sectional, surveillance and longitudinal analysis, so as to put forward some suggestions on adolescents growth and health.@*Methods@#Visual data of 3 753 pupils were inclucled for analysis from Gui an New Distinct, Guizhou Province in autumn semester 2021, and were compared with data collected during the year of 2016-2021. The curve, increment and contribution rate of poor vision from each grade of the three designs were contrasted.@*Results@#In 2021, poor vision rate among pupils in this town was 25.6%. The curve of poor vision rate in cross sectional data was U shaped with significant rise followed by decline which was different from monitoring and longitudinal tracking data, and the trend of poor vision rate of monitoring and longitudinal tracking data were linear with continued increases. The cross sectional data in 2021 showed that the highest contribution rate of poor vision rate of pupils was in grade 1(87.0% ), while other data showed that those were both in grade 4(45.0%, 33.9%).@*Conclusion@#The accuracy of the development trend of poor vision is lowest in cross sectional analysis and highest in longitudinal analysis. However, data acquisition and preservation is easy in cross sectional study and difficult in longitudinal study. It is necessary to improve the electronic information system based on cross sectional data to gradually form a complete monitoring and longitudinal tracking data, and combine different data to provide more accurate information.

Pharmacokinetics, safety and bioequivalence of two formulations of progesterone soft capsule in healthy Chinese postmenopausal females: Impacts of a high-fat meal.

Progesterone is an important natural hormone regulating ovulation and menstruation. The present study aimed to investigate the pharmacokinetics and safety of two formulations of progesterone in Chinese postmenopausal females under fasting and fed conditions. The study adopted a single-dose, open-label, randomized, three-period bioequivalence design. A total of 96 subjects were enrolled and randomly assigned to the fasting cohort or fed cohort. A high-fat meal (890 kcal) was used in the fed study. The reference-scaled average bioequivalence method was used for bioequivalence evaluation. A high-fat meal led to a 22-fold higher peak concentration (Cmax ) and a 7-fold higher area under the curve (AUC) while time to reach Cmax and half-life was not significantly affected. The concentration-time curve displayed double peaks suggesting the existence of enterohepatic circulation. The test/reference geometric mean ratios for Cmax and AUC under fasting and fed conditions are all within the range of 80% to 125%. All adverse events (AEs) that occurred during the trial were mild and did not cause drop-out, though these AEs occurred more frequently under fed state. In conclusion, the two formulations of progesterone are bioequivalent in Chinese subjects under fasting and fed conditions. Drug label modification regarding food effects needs further discussion.