Background and purpose: Soluble ST2 (sST2) is a promising biomarker in inflammation, atherosclerosis and cardiovascular diseases. We investigated the association between serum sST2 and poor outcome in patients with transient ischaemic attack (TIA)/ischaemic stroke. Methods: Patients within 24 h after onset and with measured serum sST2 were prospectively enrolled in this study. Poor outcome was a combination of a new stroke event (ischaemic or haemorrhagic) and all-cause death within 90 days and 1 year. The associations of serum sST2 with poor outcome were analysed by Cox proportional hazards. Results: Among the 430 patients included, the median (interquartile range) sST2 was 17.72 (9.31-28.84) ng/mL. A total of 19 (4.4%) and 38 (8.8%) patients experienced poor outcome within 90 days and 1 year, respectively. Compared with the lowest sST2 tertile, hazard ratios (HRs) [95% confidence intervals (CI)] for the highest tertile were 5.14 (1.43-18.51) for poor outcome within 90 days and 3.00 (1.29-6.97) at 1 year after multivariate adjustments. Adding sST2 to a prediction model significantly improved risk stratification of poor outcome in TIA/ischaemic stroke, as observed by the continuous net reclassification improvement of 60.98% (95% CI, 15.37-106.6%, P = 0.009) and integrated discrimination improvement of 2.63% (95% CI, 0.08-5.18%, P = 0.043) at 90 days and the continuous net reclassification improvement of 41.68% (95% CI, 8.74-74.61%, P = 0.013) at 1 year. Conclusions: Increased serum sST2 levels in TIA/ischaemic stroke were associated with increased risks of poor outcome within 90 days and 1 year, suggesting that serum sST2 may be a potential long-term prognostic biomarker for TIA/ischaemic stroke.

Numb, an endocytic protein, is involved in both neural differentiation and protein post-endocytic trafficking. Although negative Numb expression has been linked to human mammary carcinomas, little is known about its expression and functions in other diseases. In the present study, we observed that Numb is expressed in renal tubule epithelia and its expression is increased in the fibrotic kidney in vivo. We determined that in proximal tubular epithelial cells (NRK52E cells), TGF-β1 induces the expression of Numb and ectopic expression of Numb leads to dissolution of E-cadherin adhesion, reorganization of cytoskeleton, activation of Rac1 and Cdc42, and enhancement of migration. Either knockdown of α-adaptin or overexpression of Numb asparagine-proline-phenylalanine (NPF) mutant interferes with AP-2 dependent endocytosis and rescues Ecadherin level in NRK52E cells. Moreover, knockdown of integrin β1 or α-adaptin, and overexpression of a Numb dominant-negative form (Numb phosphotyrosine binding [PTB] domain) impair integrin endocytosis, and markedly inhibit Numb-induced cell migration and activation of Rac1 and Cdc42. Taken together, our work identifies Numb as an important player in renal fibrosis, by regulating epithelial-to-mesenchymal transition (EMT) process including E-cadherin adhesion dissolution, actin reorganization, and migration enhancement in NRK52E cells.

Background and purpose Several clinical trials have demonstrated that dual antiplatelet therapy (DAPT) benefited patients with transient ischaemic attack (TIA) with an ABCD2 score ≥4. The present study aimed to investigate whether the ABCD3‐I score could be a more appropriate tool for selection of patients with TIA to receive DAPT in real‐world settings. Methods We derived data from the TIA database of The First Affiliated Hospital of Zhengzhou University. The predictive outcome was ischaemic stroke at 90 days. The additive interaction effect was presented by the attributable proportion due to interaction. Kaplan–Meier curves were plotted to present cumulative stroke rates in different risk categories with monotherapy and DAPT. Cox proportional hazards regression was used to determine risk factors associated with stroke. Results Among 785 patients, the mean (SD) age was 56.95 (12.73) years and 77 patients (9.8%) had an ischaemic stroke at 90 days. A total of 55.8% of patients (attributable proportion due to interaction; 95% confidence interval, 20.8%–90.9%) were attributed to additive interaction of ABCD3‐I score and antiplatelet therapy. Kaplan–Meier curves showed a significant difference between patients receiving monotherapy and DAPT in high‐risk patients with TIA (P = 0.021). DAPT reduced 90‐day stroke risk in high‐risk patients with TIA as assessed independently by ABCD3‐I score (adjusted hazard ratio, 0.43; 95% confidence interval, 0.20–0.92, P = 0.031). The benefit did not exist in low‐ and medium‐risk patients by ABCD3‐I score (patients with ABCD2 score ≥ 4 or <4). Conclusions High‐risk patients with TIA assessed by ABCD3‐I score received the most pronounced clinical benefit from early use of DAPT in real‐world clinical experience.

Background and purpose Post‐stroke fatigue (PSF) is a common neuropsychiatric affective symptom occurring after stroke. Evidence indicates activated inflammatory pathways are involved in modulating the stroke and fatigue. High‐sensitivity C‐reactive protein (hs‐CRP) is one of the most sensitive indicators of inflammation. Our aim was to estimate the association between plasma hs‐CRP and PSF after acute ischaemic stroke. Methods In all, 212 acute ischaemic stroke patients were consecutively recruited within the first 14 days after stroke onset and followed up for 6 months. Plasma hs‐CRP levels were assayed by enzyme linked immunosorbent assay. Fatigue severity was assessed using the Fatigue Scale for Motor and Cognitive Functions. A score ≥ 43 is defined as PSF. Results Sixty‐eight stroke patients (32.1%) were diagnosed with PSF at 6 months’ follow‐up. In the patients with PSF, plasma hs‐CRP levels were significantly higher compared with those in non‐PSF patients (t = −8.524, P ≤ 0.001). In multivariate analyses, plasma levels of hs‐CRP were independently associated with PSF at 6 months (odds ratio 3.435, 95% confidence interval 2.222–5.309; P ≤ 0.001) after adjusting other recorded variables. Based on the receiver operating characteristic curve, the optimal cut‐off value of plasma hs‐CRP levels as an indicator for the prediction of PSF was projected to be 0.52 mg/dl, which yielded a sensitivity of 77.9% and a specificity of 74.3%, with the area under the curve 0.794 (95% confidence interval 0.725–0.864; P ≤ 0.001). Conclusion Elevated plasma hs‐CRP levels at admission were associated with PSF 6 months after stroke, suggesting that these alterations might predict the development of PSF in stroke patients.

rate at day 30 (CR and ORR) were 39% and 75%, respectively (28 evaluable patients), and 41% and 55% at day 100, respectively (27 evaluable patients). At day 180, 10 out of 14 evaluable patients (38.5%) showed CR. A total of 15 patients experienced relapse or progression. Biopsy of the accessible lesions was performed in 10