Identification of the changes in the platelet proteomic profile of elderly individuals.

Background: Platelet hyperreactivity is a risk factor for thrombosis in elderly patients with cardiovascular diseases. However, the mechanism of platelet hyperactivation has not been elucidated. This study aims to investigate alterations in the proteomes of platelets and their correlation with platelet hyperreactivity among elderly individuals. Methods: This study included 10 young (28.1 ± 1.9 years), 10 middle-aged (60.4 ± 2.2 years), and 10 old (74.2 ± 3.0 years) subjects. Washed platelets were used in the present study. Platelet samples were analysed by using data-independent acquisition (DIA) quantitative mass spectrometry (MS). Results: The results showed that the platelet proteomic profile exhibited high similarity between the young and middle-aged groups. However, there were significant differences in protein expression profiles between the old group and the young group. By exploring the dynamic changes in the platelet proteome with ageing, clusters of proteins that changed significantly with ageing were selected for further investigation. These clusters were related to the initial triggering of complement, phagosome and haemostasis based on enrichment analysis. We found that platelet degranulation was the major characteristic of the differentially expressed proteins between the old and young populations. Moreover, complement activation, the calcium signalling pathway and the nuclear factor-κB (NF-κB) signalling pathway were enriched in differentially expressed proteins. Conclusions: The present study showed that there are obvious differences in the protein profiles of the elderly compared with young and middle-aged populations. The results provide novel evidence showing changes in platelet hyperactivity and susceptibility to thrombosis in the elderly population.

Colonic L-cell impairment in aged subjects with type 2 diabetes leads to diminished GLP-1 production.

AIMS: Glucagon-like peptide 1 (GLP-1) is produced by the L subtype of enteroendocrine cells (EECs). Patients with type 2 diabetes (T2D) exhibit reduced incretin effect, but the pathophysiology and functional change of the L-cells remain unclear. Deciphering the mechanisms of the biological changes in L-cells under T2D conditions may assist in the research of gut-based strategies for T2D therapy. METHODS: We investigated the fasting serum GLP-1 levels and the distribution of colonic L-cells in young and aged participants with and without T2D. Additionally, we established an aged male T2D Wistar rat model subjected to a long-term high-fat and high-fructose (HFHF) diet. Histological investigations and single-cell RNA sequencing (scRNA-seq) analyses were performed to explore the mechanisms underlying functional changes in the colonic EECs. RESULTS: We observed a decline in circulating GLP-1 levels and a reduced number of colonic L-cells in elderly patients with T2D. The mechanisms underlying impaired L-cell formation and disturbed GLP-1 production were revealed using aged T2D rats induced by a long-term HFHF diet. The scRNA-seq results showed that the transcription factors that regulate L-cell commitment, such as Foxa1, were downregulated, and the expression of genes that participate in encoding GLP-1, GLP-1 posttranslational processing, hormone secretion, and nutrient sensing was disturbed. CONCLUSIONS: Taken together, the reduced L-cell lineage commitment and disturbed L-cell functions might be the major cause of the reduced GLP-1 production in aged populations with T2D. Our study provides new insights for identifying novel targets in colonic L-cells for improving endogenous GLP-1 production.

Effect of Different Durations of Eye-Covering Pretreatment on Emergence Delirium after Ophthalmic Surgery in Preschool-Aged Children: A Randomized Controlled Study.

Background: Preoperative eye-covering training for 3 hours has been reported to effectively reduce the incidence of emergence delirium (ED) in preschool children. However, most children can only maintain the eye being covered for less than 60 min, and shortening eye-covering duration can also achieve similar clinical effects as long duration of eye-covering. This study was designed to compare the effects of 30-min and 60-min eye-covering pretreatment based on cartoon education only on preoperative anxiety, postoperative ED, and pain score after ophthalmic surgery with general anesthesia in preschool-aged children. Methods: Preschool-aged children (3-7 years) who were diagnosed with cataract, blepharoptosis, trichiasis, strabismus, eyelid tumor, and underwent ophthalmic surgery with general anesthesia from August 2021 to January 2022 were recruited. A total of 228 patients were randomly assigned at a 1 : 1:1 ratio to receive 30-min eye covering (30-min group), 60-min eye covering (60-min group) pretreatment, or programmed education only (C group). The preoperative anxiety, postoperative emergence delirium, and pain were compared between the groups. Results: The preoperative anxiety score, postoperative ED score, and incidence of ED in the 30-min group (n = 76) and 60-min group (n = 72) were significantly lower than those in the C group (n = 76), demonstrating a significant between-group difference (P < 0.001). However, the 30-min group and 60-min group had no significant difference in the abovementioned outcome measures (P > 0.05). Moreover, no significant difference was found in postoperative pain scores among the three groups (H = 0.274, P=0.872). Conclusion: Both 30-min and 60-min eye-covering pretreatments significantly reduce preoperative anxiety and postoperative ED after ophthalmic surgery with general anesthesia in preschool-aged children. The effects of the two groups show no intergroup difference, but the 30-min eye-covering pretreatment may be more convenient for practicing. Trial Registration. This study was registered with the No. NCT04973150.