Background: Stroke-associated pneumonia (SAP) commonly complicates acute ischemic stroke (AIS) and significantly worsens outcomes. Type 2 diabetes mellitus (T2DM) may contribute to malnutrition, impair innate immunity function, and increase the probability of SAP occurrence in AIS patients. We aimed to determine early predictors of SAP in AIS patients with T2DM and to construct a nomogram specifically for predicting SAP in this population by combining the A²DS² score with available nutrition-related parameters.Methods: A total of 1,330 consecutive AIS patients with T2DM were retrospectively recruited. The patients were randomly allocated to the training (n = 887) and validation groups (n = 443). Univariate and multivariate binary logistic regression analyses were applied to determine the predictors of SAP in the training group. A nomogram was established according to the identified predictors. The areas under the receiver operating characteristic curve (AUROC) and calibration plots were performed to access the predictive values of the nomogram. The decision curve was applied to evaluate the net benefits of the nomogram.Results: The incidence of SAP was 9% and 9.7% in the training and validation groups, respectively. The results revealed that the A²DS² score, stroke classification, Geriatric Nutritional Risk Index, hemoglobin, and fast blood glucose were independent predictors for SAP. A novel nomogram, A²DS²-Nutrition, was constructed based on these five predictors. The AUROC for A²DS²-Nutrition (0.820, 95% CI: 0.794–0.845) was higher than the A²DS² score (0.691, 95% CI: 0.660–0.722) in the training group. Similarly, it showed a better predictive performance than the A²DS² score [AUROC = 0.864 (95% CI: 0.828–0.894) vs. AUROC = 0.763 (95% CI: 0.720–0.801)] in the validation group. These results were well calibrated in the two groups. Moreover, the decision curve revealed that the A²DS²-Nutrition provided an additional net benefit to the AIS patients with T2DM compared to the A²DS² score in both groups.Conclusion: The A²DS² score, stroke classification, Geriatric Nutritional Risk Index, hemoglobin, and fast blood glucose were independent predictors for SAP in AIS patients with T2DM. Thus, the proposed A²DS²-Nutrition may be a simple and reliable prediction model for SAP occurrence in AIS patients with T2DM.

Background: Stroke-associated infection (SAI) is a common complication after a stroke. The incidence of infection was higher in people with sarcopenia than in the general population. However, the relationship between pre-stroke sarcopenia risk and SAI in older patients has not been confirmed. This study aimed to investigate the association between pre-stroke sarcopenia risk and SAI in older patients with acute ischemic stroke (AIS).Methods: This retrospective study was conducted by the Peking University People’s Hospital. We evaluated the pre-stroke sarcopenia risk by applying the SARC-F questionnaire. Multivariate logistic regression was applied to explore the association between pre-stroke sarcopenia risk and SAI.Results: A total of 1,002 elder patients with AIS (592 men; 72.9 ± 8.6 years) were enrolled in our study. Pre-stroke sarcopenia risk was found in 29.1% of the cohort. The proportion of patients with pre-stroke sarcopenia risk was larger in the SAI group than in the non-SAI group (43.2 vs. 25.3%, p < 0.001). In multivariate logistic analysis, pre-stroke sarcopenia risk was shown to be independently associated with SAI (OR = 1.454, 95% CI: 1.008–2.097, p = 0.045) after adjusting for potential factors. This association remained consistent across the subgroups based on age, sex, body mass index, smoking status, drinking status, diabetes, hypertension, and dyslipidemia.Conclusion: Pre-stroke sarcopenia risk was independently associated with SAI in older patients with AIS. Our findings highlight the significance of pre-stroke sarcopenia identification in the prevention and management of SAI in this population.

Background and Aims: Activation of hepatic stellate cells (HSCs) and subsequent dysregulation of the TGF-β1 signaling pathway are central to the progression of hepatic fibrosis. Neuropilin-1 (NRP1) has been identified as a co-receptor involved in multiple signaling pathways, yet its role in modulating TGF-β receptor stability in HSCs remains to be fully elucidated. This study investigated the regulatory role of the NRP1/Src/Rab7 axis in TβRI lysosomal degradation during HSC activation. Methods: Hepatic fibrosis was induced in male C57BL/6 mice via intraperitoneal CCl ₄ injection for four weeks. HSC-specific knockdown of Nrp1 was achieved using an AAV8-pLrat-sh Nrp1 vector. TβRI stability and lysosomal degradation were evaluated through cycloheximide (CHX) chase assays and chloroquine treatment. The impact on the TGF-β1/Smad signaling pathway was assessed both in vitro and in vivo. Results: Nrp1 silencing in primary HSCs reduced TβRI protein levels and attenuated p-Smad2/3 signaling without affecting mRNA levels. Consistently, NRP1 deficiency accelerated lysosomal degradation of TβRI, accompanied by increased TβRI–LAMP1 colocalization and enhanced trafficking of TβRI into Rab7-positive late endosomes. Mechanistically, NRP1 loss diminished Src kinase activity and consequently reduced Src-dependent tyrosine phosphorylation of Rab7, leading to elevated Rab7-GTP levels and enhanced late endosomal sorting of TβRI. Rab7 knockdown or Src reactivation partially rescued TβRI stability and restored downstream signaling. In vivo, HSC-specific Nrp1 knockdown attenuated CCl ₄ -induced fibrosis and reduced TβRI levels, while Rab7 inhibition partially reversed these effects. Conclusions: These data suggest that the NRP1/Src/Rab7 axis contributes to TβRI stability by modulating its lysosomal degradation pathway. Targeting this axis may provide a potential approach for intervening in the progression of hepatic fibrosis.