Investigate the effect of Alteplase and Aspirin on the functional outcomes of patients with acute ischemic stroke with mild non-disabling neurological deficit. In this single-center, randomized controlled study, we selected 60 patients with acute ischemic stroke with mild non-disabling neurological deficit admitted to our hospital from January 2021 to January 2022, and randomly divided them into the study group (n = 30) and the control group (n = 30), the control group was given the Aspirin treatment, the study group was given the Alteplase treatment, and the changes in neurological recovery, daily living ability, exercise ability, balance ability, cognitive function, and short-term prognosis outcomes were observed in these 2 groups. The factors influencing the short-term outcome of Alteplase therapy in patients with acute ischemic stroke were analyzed. The National Institutes of Health Neurological Deficit Score (NIHSS) scores at T1 and T2 of the study group were lower than those in the control group, but the scores of Barthel indicators (BI), Fugl-Meyer Motor Assessment Scale (FMA), Berg Balance Scale (BBS) and Montreal Cognitive Assessment Scale (MoCA) of the study group were higher than those in the control group, and the difference was statistically significant (P < .05). The short-term prognostic outcomes of these 2 groups were not significantly different (P > .05). The effect of the use of Alteplase or Aspirin on short-term functional outcomes in patients with acute ischemic stroke and mild non-disabling neurological deficit is not much different.

OBJECTIVE: Apart from its fibrinolytic activity, the tissue plasminogen activator (tPA)/plasmin system has been reported to cleave the peptide amyloid beta, attenuating brain amyloid deposition in Alzheimer\'s disease. As aggregation of human islet amyloid polypeptide (hIAPP) is toxic to beta cells, we sought to determine whether activation of the fibrinolytic system can also reduce islet amyloid deposition and its cytotoxic effects, which are both observed in type 2 diabetes.
METHODS: The expression of Plat (encoding tPA) and plasmin activity were measured in isolated islets from amyloid-prone hIAPP transgenic mice or non-transgenic control islets expressing non-amyloidogenic mouse islet amyloid polypeptide cultured in the absence or presence of the amyloid inhibitor Congo Red. Plat expression was also determined in hIAPP-treated primary islet endothelial cells, bone marrow-derived macrophages (BMDM) and INS-1 cells, in order to determine the islet cell type(s) producing tPA in response to hIAPP aggregation. Cell-free thioflavin-T assays and MS were used to respectively monitor hIAPP aggregation kinetics and investigate plasmin cleavage of hIAPP. Cell viability was assessed in INS-1 beta cells treated with hIAPP with or without plasmin. Finally, to confirm the findings in human samples, PLAT expression was measured in freshly isolated islets from donors with and without type 2 diabetes.
RESULTS: In isolated islets from transgenic mice, islet Plat expression and plasmin activity increased significantly with the process of amyloid deposition (p≤0.01, n=5); these effects were not observed in islets from non-transgenic mice and were blocked by Congo Red (p≤0.01, n=4). In response to hIAPP exposure, Plat expression increased in BMDM and INS-1 cells vs vehicle-treated cells (p≤0.05, n=4), but not in islet endothelial cells. Plasmin reduced hIAPP fibril formation in a dose-dependent manner in a cell-free system, and restored hIAPP-induced loss of cell viability in INS-1 beta cells (p≤0.01, n=5). Plasmin cleaved monomeric hIAPP, inducing a rapid decrease in the abundance of full-length hIAPP and the appearance of hIAPP 1-11 and 12-37 fragments. hIAPP 12-37, which contains the critical amyloidogenic region, was not toxic to INS-1 cells. Finally, PLAT expression was significantly increased by 2.4-fold in islets from donors with type 2 diabetes (n=4) vs islets from donors without type 2 diabetes (n=7) (p≤0.05).
CONCLUSIONS: The fibrinolytic system is upregulated in islets with hIAPP aggregation. Plasmin rapidly degrades hIAPP, limiting its aggregation into amyloid and thus protecting beta cells from hIAPP-induced toxicity. Thus, increasing islet plasmin activity might be a strategy to limit beta cell loss in type 2 diabetes.

Increasing evidence demonstrates that brain-derived neurotrophic factor (BDNF) can be regarded as a biomarker for major depression. Our previous work found that the ratio of mature BDNF (mBDNF) to precursor-BDNF (proBDNF) was a pivotal factor in the pathogenesis of major depressive disorder (MDD). But the mechanism behind the ratio is still obscure. Tissue plasminogen activator (tPA) and plasminogen activator inhibitor-1 (PAI-1) both play essential roles in depression by regulating the ratio of BDNF/proBDNF. In present study, we analyzed BDNF, proBDNF, tPA and PAI-1 in the peripheral blood in 57 MDD patients pre- and post-treatment and in 57 healthy controls. We verified that BDNF and tPA levels were significantly decreased, whereas proBDNF and PAI-1 levels elevated obviously in MDD group pre-treatment. And after 4 weeks SSRIs treatment, the BDNF and tPA levels increased while the proBDNF and PAI-1 levels reduced. The MDD pre-treatment group had the lowest ratio of BDNF to proBDNF compared to MDD post-treatment group and control group. Though the ratio of tPA/PAI-1 in MDD pre-treatment had not reached the significance, it was still the lowest one among the three groups. The combination of tPA+PAI+BDNF showed the best diagnostic value for MDD. In summary, our data suggested that the interaction between tPA and PAI-1 implicated to the MDD and the antidepressant treatment which might through regulating the BDNF/proBDNF ratio. The combination of tPA, PAI-1 and BDNF might offer a helpful way for MDD diagnosis.

BACKGROUND: Pars Plana Vitrectomy (PPV) combined with subretinal injection of low-dose recombinant tissue plasminogen activator (rt-PA) and intravitreal injection of Conbercept as a novel therapy for submacular hemorrhage (SMH) requires evaluation.
METHODS: In a retrospective interventional clinical study, 14 eyes of 14 patients with SMH underwent PPV along with rt-PA (subretinal) and Conbercept (intravitreal) injections. The main outcomes included best-corrected visual acuities (BCVAs), degrees of blood displacement, and adverse events. All patients completed at least 6-month follow-up visits.
RESULTS: Mean BCVAs significantly improved at 7 days (22.29 ± 15.35), 1 month (30.71 ± 16.42), 3 months (38.29 ± 13.72), 4 months (38.86 ± 14.15), and 6 months (41.21 ± 14.91) post-treatment compared to baseline (16.36 ± 13.97) (F = 12.89, P = 0.004). The peak improvement in BCVAs occurred at 6 months postoperatively. The procedure effectively eliminated subfoveal hemorrhages in all eyes, with clots removal and absorption occurring within one month and complete regression by 3-month follow-up visits. Postoperatively, two cases of AMD resulted in discoid scars on the fundus. No instances of rt-PA-related retinal toxicity were observed during the follow-up period.
CONCLUSIONS: The combined approach of PPV with low-dose rt-PA and anti-VEGF shows promise in enhancing both vision and anatomical structure in SMH therapy. Individualized treatment plans tailored to the primary disease should be developed to optimize visual prognoses.
BACKGROUND: Retrospectively registered No.ChiCTR2100053034. Registration date: 10/11/2021.

BACKGROUND: Tissue plasminogen activator (tPA) is an effective treatment for acute ischemic stroke. Although initial improvement is observed when administered for branch atheromatous disease (BAD), some cases subsequently worsen. Clinical data on the characteristics of these patients is lacking, and the benefits of tPA are unclear.
OBJECTIVE: To analyze rebound cases and elucidate the clinical characteristics and outcomes associated with tPA administration in BAD.
METHODS: This multicenter retrospective study was conducted in Japan. Worsening after initial improvement of a condition is termed as rebound, and such cases were compared with other types of ischemic stroke in patients with and without rebound. The characteristics of patients with BAD who rebounded were examined.
RESULTS: The study included 93 patients. Among the patients who were administered tPA, the NIHSS scores at 24 h and 7 days post-tPA were significantly higher in patients with BAD than in patients with other types of infarcts. The group with BAD exhibited a significantly higher rate of rebound than other groups (37.5 % vs. 0 %, P < 0.001). However, no differences were observed in outcomes between patients who experienced rebound after tPA administration and those who did not.
CONCLUSIONS: Reevaluation and changing the strategy of tPA use in patients with BAD may be necessary. However, this study does not totally discourage its use, as specific patients can benefit.

OBJECTIVE: To investigate the effect of hospital working hours on outcomes of patients with acute ischemic stroke 3 months after receiving alteplase intravenous thrombolysis.
METHODS: A retrospective analysis was performed on 254 individuals with acute ischemic stroke who received alteplase intravenous thrombolysis between January 2018 and December 2020 either during peak hospital working hours (08:00-17:59; Group A) or off-peak hours (18:00-07:59 the following day; Group B). Patients were also categorized according to which of four peak/off-peak-hour periods they received treatment in: Group 1 (08:00-11:59), Group 2 (12:00-17:59), Group 3 (18:00-21:59), Group 4 (22:00-07:59 the following day). Baseline data and 3-month prognosis were compared across groups. Logistic regression analysis was used to investigate the correlation between hospital working hours and 3-month prognosis.
RESULTS: There were no significant differences in door-to-needle time, onset-to-needle time, 24-hour National Institutes of Health Stroke Scale (NIHSS) score, 7-day NIHSS score or Modified Rankin Score between Groups 1 to 4 or between Groups A and B. Whether treatment was administered during peak or off-peak hours did not significantly affect 3-month prognosis.
CONCLUSIONS: At this hospital, differences in the time at which stroke patients were treated were not associated with outcomes.

Bleeding within the pleural space may result in persistent clot formation called retained hemothorax (RH). RH is prone to organization, which compromises effective drainage, leading to lung restriction and dyspnea. Intrapleural fibrinolytic therapy is used to clear the persistent organizing clot in lieu of surgery, but fibrinolysin selection, delivery strategies, and dosing have yet to be identified. We used a recently established rabbit model of RH to test whether intrapleural delivery of single-chain urokinase (scuPA) can most effectively clear RH. scuPA, or single-chain tissue plasminogen activator (sctPA), was delivered via thoracostomy tube on day 7 as either one or two doses 8 h apart. Pleural clot dissolution was assessed using transthoracic ultrasonography, chest computed tomography, two-dimensional and clot displacement measurements, and gross analysis. Two doses of scuPA (1 mg/kg) were more effective than a bolus dose of 2 mg/kg in resolving RH and facilitating drainage of pleural fluids (PF). Red blood cell counts in the PF of scuPA, or sctPA-treated rabbits were comparable, and no gross intrapleural hemorrhage was observed. Both fibrinolysins were equally effective in clearing clots and promoting pleural drainage. Biomarkers of inflammation and organization were likewise comparable in PF from both groups. The findings suggest that single-agent therapy may be effective in clearing RH; however, the clinical advantage of intrapleural scuPA remains to be established by future clinical trials.

Ischemic stroke represents a significant global health challenge, often resulting in death or long-term disability, particularly among the elderly, where advancing age stands as the most unmodifiable risk factor. Arising from the blockage of a brain-feeding artery, the only therapies available to date aim at removing the blood clot to restore cerebral blood flow and rescue neuronal cells from death. The prevailing treatment approach involves thrombolysis by administration of recombinant tissue plasminogen activator (tPA), albeit with a critical time constraint. Timely intervention is imperative, given that delayed thrombolysis increases tPA leakage into the brain parenchyma, causing harmful effects. Strategies to preserve tPA\'s vascular benefits while shielding brain cells from its toxicity have been explored. Notably, administering neuroserpin (Ns), a brain-specific tPA inhibitor, represents one such approach. Following ischemic stroke, Ns levels rise and correlate with favorable post-stroke outcomes. Studies in rodent models of focal cerebral ischemia have demonstrated the beneficial effects of Ns administration. Ns treatment maintains blood-brain barrier (BBB) integrity, reducing stroke volume. Conversely, Ns-deficient animals exhibit larger stroke injury, increased BBB permeability and enhanced microglia activation. Furthermore, Ns administration extends the therapeutic window for tPA intervention, underscoring its potential in stroke management. Remarkably, our investigation reveals the presence of Ns within extracellular vesicles (EVs), small membrane-surrounded particles released by all cells and critical for intercellular communication. EVs influence disease outcome following stroke through cargo transfer between cells. Clarifying the role of EVs containing NS could open up urgently needed novel therapeutic approaches to improve post-ischemic stroke outcome.

BACKGROUND: The objective of this study was to establish a predictive model utilizing machine learning techniques to anticipate the likelihood of thrombolysis resistance (TR) in acute ischaemic stroke (AIS) patients undergoing recombinant tissue plasminogen activator (rt-PA) intravenous thrombolysis, given that nearly half of such patients exhibit poor clinical outcomes.
METHODS: Retrospective clinical data were collected from AIS patients who underwent intravenous thrombolysis with rt-PA at the First Affiliated Hospital of Bengbu Medical University. Thrombolysis resistance was defined as ([National Institutes of Health Stroke Scale (NIHSS) at admission - 24-hour NIHSS] × 100％/ NIHSS at admission) ≤ 30%. In this study, we developed five machine learning models: logistic regression (LR), extreme gradient boosting (XGBoost), support vector machine (SVM), the least absolute shrinkage and selection operator (LASSO), and random forest (RF). We assessed the model\'s performance by using receiver operating characteristic (ROC) curve, calibration curve, and decision curve analysis (DCA), and presented the results through a nomogram.
RESULTS: This study included a total of 218 patients with AIS who were treated with intravenous thrombolysis, 88 patients experienced TR. Among the five machine learning models, the LASSO model performed the best. The area under the curve (AUC) on the testing group was 0.765 (sensitivity: 0.767, specificity: 0.694, accuracy: 0.727). The apparent curve in the calibration curve was similar to the ideal curve, and DCA showed a positive net benefit. Key features associated with TR included NIHSS at admission, blood glucose, white blood cell count, neutrophil count, and blood urea nitrogen.
CONCLUSIONS: Machine learning methods with multiple clinical variables can help in early screening of patients at high risk of thrombolysis resistance, particularly in contexts where healthcare resources are limited.

BACKGROUND: Differences of treatment outcome between full or reduced dose of tissue plasminogen activator (tPA) for bridge mechanical thrombectomy (MT) in the extended time window have not been clearly established. We aimed to present real-world results of bridge MT with different tPA dosages in the standard and extended windows.
METHODS: Patients with anterior circulation stroke treated with MT between 2017 and 2021 at two stroke referral centers were retrospectively reviewed. Bridge MT with tPA were categorized as full (0.9 mg/kg) or reduced (<0.9 mg/kg) dose. Standard window (SW) cohort was defined as MT performed within 6 h of acute ischemic stroke onset, while those beyond 6 h as the extended window (EW) cohort. 90 days Modified Rankin Scale (mRS) score, technical treatment success, in-hospital mortality, and post-treatment hemorrhage were analyzed.
RESULTS: A total of 423 patients met the inclusion criteria, 218 of which treated in the SW, while 205 treated in the EW. Within the SW cohort, the full-dose tPA group demonstrated a higher proportion of good functional outcome (GFO) at 90 days (mRS0-3) versus reduced (49% vs 21%, p = 0.0358). The overall GFO of SW was higher than that of the EW cohort (33% vs 20%, p = 0.0480). Within the EW cohort, GFO was similar between full and reduced dose groups. Successful reperfusion rate was lower in SW versus EW cohorts (39% vs 58%, p = 0.0199).
CONCLUSIONS: In real-world practice, the GFO of bridge MT is better than MT alone. The tPA dosage is not a determining factor of GFO in EW MT.