Effect of MR-guided perfusion imaging mismatch profiles within 6 h on endovascular thrombectomy outcomes.

BACKGROUND: The treatment of acute ischemic stroke (AIS) aims to achieve early vascular recanalization and reperfusion of the penumbra. However, the effect of early penumbral imaging within 6 h on clinical outcomes remains unclear. The objective of this study was to determine the effect of magnetic resonance-guided (MR-guided) perfusion imaging within 6 h after symptom onset on endovascular thrombectomy outcomes in AIS patients. METHODS: We prospectively collected the clinical information of consecutive AIS patients undergoing endovascular thrombectomy based on MR-guided perfusion imaging within 6 h after symptom onset from AISRNA and EVTRNA studies. The primary outcome was defined as the poor outcome (mRS > 2 within 90 days). The perfusion-weighted imaging/diffusion-weighted imaging (PWI/DWI) mismatch was assessed by an automated software. RESULTS: We enrolled 84 patients (25 in the mismatch ≤ 1.8 group and 59 in the mismatch > 1.8 group). Significant difference was found between the mismatch > 1.8 group and the mismatch ≤ 1.8 group for the incidence of disabling stroke (mRS > 2) within 90 days (40.7% vs. 68.0%, OR: 3.099, 95% CI: 1.154-8.323, P = 0.025). Intracranial hemorrhage occurred in 8 patients (13.6%) in the mismatch > 1.8 group and 10 patients in the mismatch ≤ 1.8 group (40.0%) (P = 0.010). The risk of severe cerebral edema was 2/59 (3.4%) vs. 7/25 (28.0%) (P = 0.004). These findings remained stable after adjustment. CONCLUSIONS: MR-guided perfusion imaging mismatch profiles within 6 h after symptom onset may be feasible to predictclinical outcomes and reduce clinically ineffective reperfusion after endovascular thrombectomy.

Enhancement of oral bioavailability and anti-colitis effect of luteolin-loaded polymer micelles with RA (rosmarinic acid)-SS-mPEG as carrier.

OBJECTIVE: Polymer micelles were prepared (L-RSPMs) with luteolin and synthetic RA-SS-mPEG polymeric material before evaluation of their anti-inflammatory effect on 2, 4, 6-trinitro-benzene-sulfonic acid (TNBS)-induced ulcerative colitis (UC) model in rats. METHODS: The synthetic RA-SS-mPEG was characterized with NMR spectroscopy, before preparation of luteolin-coated RA-SS-mPEG polymer micelles. The in vitro characterization and evaluation of the formulation were accomplished, couple with its pharmacokinetic parameters. The levels of PEG2, MDA, CRP and GSH, as well as concentrations of TNF-α, IL1-ß, IL-6 and IL-10 in serum and colon tissue were detected via ELISA kit. The degree of colon injury and inflammation was evaluated via histopathologic examination. RESULTS: L-RSPMs displayed small average droplet size (133.40 ± 4.52 nm), uniformly dispersed (PDI: 0.163 ± 0.011), good stability, slow release and enhanced solubility. We observed 353.28% increase in the relative bioavailability of L-RSPMs compared to free luteolin, while the half-life of the micelle was extended by 6.16h. Compared to model (M) group, luteolin (low and high doses) and L-RSPMs (low and high doses) significantly reduced levels of MDA, PEG2, CRP, TNF-α, IL-6 and IL-1ß in colon tissue and serum of colitic rats but dose dependently increased IL-10 and SOD levels (p < 0.01). Histopathologic examination of colon showed that luteolin (low and high doses) and L-RSPMs (low and high doses) improved colonic inflammation in colitic rats to varying degrees compared to M group. CONCLUSION: L-RSPMs could improve TNBS-induced colon inflammation by enhancing bioavailability, promoting antioxidant effects and regulating cytokine release, which may become a potential agent for UC treatment in clinical settings.

Excess fatty acids induce pancreatic acinar cell pyroptosis through macrophage M1 polarization.

Free fatty acid derived from hyperlipidemia contributes to the development of inflammation in the pancreas. Here we explore the molecular mechanisms of fatty acid-induced pancreatitis through cellular experiments and the construction of a mouse model of hyperlipidemic pancreatitis. We found that palmitic acid stimulation leads to M1 polarization of macrophage, which secretes cathepsin S via exosomes to pancreatic acinar cells and leads to activation of the caspase1-mediated classical pyrolysis pathway, resulting in inflammation and pancreatic tissue damage. In vivo experiments have also demonstrated that the high levels of fatty acids induced by hyperlipidaemia exacerbate the development of pancreatitis, and that cathepsin S inhibitors significantly alleviate hyperlipidemic pancreatitis. Therefore, cathepsin S may be a new target for the clinical treatment of hyperlipidemic pancreatitis.

Development and validation of a nomogram for suicide attempts in patients with first-episode drug-naïve major depressive disorder.

Objective: The risk of suicide can be decreased by accurately identifying high-risk suicide groups and implementing the right interventions. The aim of this study was to develop a nomogram for suicide attempts (SA) in patients with first-episode drug-naïve (FEDN) major depressive disorder (MDD). Methods: This study undertook a cross-sectional analysis of 1,718 patients diagnosed with FEDN MDD, providing comprehensive clinical data from September 2016 to December 2018. Data on anthropometric and sociodemographic factors were gathered, and the severity of depression and anxiety was evaluated using the 17-item Hamilton Depression Scale (HAMD-17) and the Hamilton Anxiety Scale (HAMA), respectively. Additionally, thyroid hormone levels, lipid profile parameters, and fasting blood glucose (FBG) were measured. Suicide attempt (SA) history was verified based on an amalgamation of medical records, patient interviews, and family interviews. Participants were randomly divided into a training group (70%, n = 1,204) and a validation group (30%, n = 514). In the training group, LASSO analysis and multivariate regression were used to identify variables associated with SA. A nomogram was then constructed using the identified risk factors to estimate the likelihood of SA within the training group. To assess the accuracy, the area under the receiver operating characteristic curve (AUC) was utilized, and calibration plots were employed to evaluate calibration. Additionally, decision curve analysis (DCA) was performed to assess the precision of the model. Finally, internal validation was carried out using the validation group. Results: A practical nomogram has been successfully constructed, incorporating HAMD, HAMA, thyroid stimulating hormone (TSH), thyroid peroxidase antibody (TPOAb), and systolic blood pressure (SBP) parameters, to estimate the probability of SA in Chinese patients diagnosed with FEDN MDD. The pooled area under the ROC for SA risk in both the training and validation groups was found to be 0.802 (95% CI: 0.771 to 0.832) and 0.821 (95% CI: 0.774 to 0.868), respectively. Calibration analysis revealed a satisfactory correlation between the nomogram probabilities and the actual observed probabilities. The clinical applicability of the nomogram was confirmed through decision curve analysis. To enhance accessibility for clinicians and researchers, an online version of the nomogram can be accessed at https://doctorjunjunliu.shinyapps.io/dynnomapp/. Conclusions: We constructed and validated a nomogram for the early detection of FEDN MDD patients with a high risk of SA, thereby contributing to the implementation of effective suicide prevention programs.

Association between triglyceride glucose index (TyG) and psychotic symptoms in patients with first-episode drug-naïve major depressive disorder.

Objective: Major depressive disorder (MDD) sufferers frequently have psychotic symptoms, yet the underlying triggers remain elusive. Prior research suggests a link between insulin resistance (IR) and increased occurrence of psychotic symptoms. Hence, this study sought to investigate the potential association between psychotic symptoms in Chinese patients experiencing their first-episode drug-naïve (FEDN) MDD and the triglyceride glucose (TyG) index, an alternative measure of insulin resistance (IR). Methods: Between September 2016 and December 2018, 1,718 FEDN MDD patients with an average age of 34.9 ± 12.4 years were recruited for this cross-sectional study at the First Hospital of Shanxi Medical University in China. The study collected clinical and demographic data and included assessments of anxiety, depression, and psychotic symptoms using the 14-item Hamilton Anxiety Rating Scale (HAMA), the 17-item Hamilton Depression Rating Scale (HAMD-17), and the positive subscales of the Positive and Negative Syndrome Scale (PANSS), respectively. Measurements of metabolic parameters, fasting blood glucose (FBG), and thyroid hormones were also gathered. To assess the correlation between the TyG index and the likelihood of psychotic symptoms, the study used multivariable binary logistic regression analysis. Additionally, two-segmented linear regression models were employed to investigate possible threshold effects in case non-linearity relationships were identified. Results: Among the patients, 9.95% (171 out of 1,718) exhibited psychotic symptoms. Multivariable logistic regression analysis showed a positive correlation between the TyG index and the likelihood of psychotic symptoms (OR = 2.12, 95% CI: 1.21-3.74, P = 0.01) after adjusting for confounding variables. Moreover, smoothed plots revealed a nonlinear relationship with the TyG index, revealing an inflection point at 8.42. Interestingly, no significant link was observed to the left of the inflection point (OR = 0.50, 95% CI: 0.04-6.64, P = 0.60), whereas beyond this point, a positive correlation emerged between the TyG index and psychotic symptoms (OR = 2.42, 95% CI: 1.31-4.48, P = 0.01). Particularly, a considerable 142% rise in the probability of experiencing psychotic symptoms was found with each incremental elevation in the TyG index. Conclusions: Understanding the non-linear link between the TyG index and the risk of psychotic symptoms in Chinese patients with FEDN MDD highlights the potential for targeted therapeutic approaches. By acknowledging the threshold effect observed, there is an opportunity to mitigate risk factors associated with IR-related psychiatric comorbidities through tailored interventions. These preliminary results stress the need for further longitudinal research to solidify these insights and contribute to more effective therapeutic strategies.