Based on the neuroprotective and anti-inflammatory properties of semaglutide, this study aims to investigate whether semaglutide improves core symptoms in BTBR T (+) Itpr3 (tf)/J (BTBR) mice, a model of autism spectrum disorder (ASD), through modulation of inflammation-related targets and signaling pathways.

A total of 32 male C57 BL/6J (C57) and BTBR mice (7 weeks old) were randomly divided into 4 groups (n=8): The treatment group received intraperitoneal injection of 25 nmol/kg semaglutide, while the control group received normal saline, with continuous intervention for 7 d, and body weight was monitored continuously throughout the intervention period. Mouse behavioral indicators were evaluated using various behavioral tests, including the three-chamber sociability test, grooming test, marble-burying test, novel object recognition test, Y-maze test and open field test. After behavioral assessments, the brain tissues were collected, and network pharmacology, GO/KEGG enrichment analysis, protein-protein interaction analysis, molecular docking technology, and qRT-PCR were employed to explore the potential mechanisms of semaglutide.

Semaglutide intervention for 7 d significantly reduced the body weight of BTBR mice (P<0.05), increased the preference index from chamber time (P<0.01) and preference index from sniffing time (P<0.05), elevated the novel object recognition discrimination index (P<0.01), and reduced repetitive stereotyped behaviors such as self-grooming (P<0.001) and marble burying (P<0.01). However, no significant effects on the above mentioned behaviors were observed in C57 mice, and no obvious impact on locomotor activity was demonstrated in the open field test. Network pharmacology analysis identified 78 common targets which enriched in inflammation-related pathways. Semaglutide exhibited favorable binding affinity with potential targets in inflammation-related pathways including Serpine1, Mmp9, Pparg, Stat3, Ppara, and Nr1h3, with binding energies all ≤-4 kcal/mol. qRT-PCR further confirmed that semaglutide intervention significantly downregulated mRNA expression levels of Serpine1, Mmp9, Stat3, Il6, Tnfa, Il17a, and Il1b (P<0.05), and upregulated Pparg expression (P<0.05) in the hippocampus of BTBR mice.

Semaglutide alleviates ASD-like symptoms in BTBR mice by regulating inflammation-related pathways, thus offering a promising potential treatment and foundational research for the clinical management of ASD.

To investigate the relationship between platelet/hemoglobin ratio (PHR) and the severity of diabetic foot ulcer (DFU) and its predictive value for DFU progression.

A retrospective study was performed in 345 DFU patients treated in Department of Endocrinology, the First Affiliated Hospital of Army Medical University from March 2018 to March 2023. Their general demographic information was obtained, and the results of laboratory tests, including hemoglobin A1c (HbA1c), fasting plasma glucose (FPG), biochemical and related blood routine indicators were collected. According to Wanger grading, the patients were assigned into mild (n=145) and severe ulcer groups (n=200). The demographic data and clinical parameters were compared between the 2 groups. Multivariate logistic regression model was applied to identify the independent predictors for severe ulcer in DFU, and receiver operating characteristic (ROC) curve was plotted to evaluate the predictive performance of PHR for DFU progression.

The severe ulcer group presented remarkable increases in male proportion, HbA1c and FPG levels, platelet (PLT) count and PHR when compared with the mild ulcer group (P<0.05). Multivariate logistic regression analysis revealed that PHR and male were independent risk factors, while, HDL-C was a protective factor for progression to severe ulcer in DFU patients (P<0.05). ROC curve analysis showed that the area under the curve of PHR for predicting severe ulcer was 0.701 (95%CI: 0.646~0.756).

PHR is strongly associated with the severity of DFU, and shows certain predictive value for the progression to severe ulcer in DFU patients.