Pharmacological inhibition of RUNX1 reduces infarct size after acute myocardial infarction in rats and underlying mechanism revealed by proteomics implicates repressed cathepsin levels.

Myocardial infarction (MI) results in prolonged ischemia and the subsequent cell death leads to heart failure which is linked to increased deaths or hospitalizations. New therapeutic targets are urgently needed to prevent cell death and reduce infarct size among patients with MI. Runt-related transcription factor-1 (RUNX1) is a master-regulator transcription factor intensively studied in the hematopoietic field. Recent evidence showed that RUNX1 has a critical role in cardiomyocytes post-MI. The increased RUNX1 expression in the border zone of the infarct heart contributes to decreased cardiac contractile function and can be therapeutically targeted to protect against adverse cardiac remodelling. This study sought to investigate whether pharmacological inhibition of RUNX1 function has an impact on infarct size following MI. In this work we demonstrate that inhibiting RUNX1 with a small molecule inhibitor (Ro5-3335) reduces infarct size in an in vivo rat model of acute MI. Proteomics study using data-independent acquisition method identified increased cathepsin levels in the border zone myocardium following MI, whereas heart samples treated by RUNX1 inhibitor present decreased cathepsin levels. Cathepsins are lysosomal proteases which have been shown to orchestrate multiple cell death pathways. Our data illustrate that inhibition of RUNX1 leads to reduced infarct size which is associated with the suppression of cathepsin expression. This study demonstrates that pharmacologically antagonizing RUNX1 reduces infarct size in a rat model of acute MI and unveils a link between RUNX1 and cathepsin-mediated cell death, suggesting that RUNX1 is a novel therapeutic target that could be exploited clinically to limit infarct size after an acute MI.

Intravenous Alteplase Versus Best Medical Therapy for Patients With Minor Stroke: A Systematic Review and Meta-Analysis.

BACKGROUND: The efficacy of thrombolysis (IVT) in minor stroke (National Institutes of Health Stroke Scale score, 0-5) remains inconclusive. The aim of this study is to compare the effectiveness and safety of IVT with best medical therapy (BMT) by means of a systematic review and meta-analysis of randomized controlled trials and observational studies. METHODS: We searched the PubMed, Embase, Cochrane Library, and Web of Science databases to obtain articles related to IVT in minor stroke from inception until August 10, 2023. The primary outcome was an excellent functional outcome, defined as a modified Rankin Scale score of 0 or 1 at 90 days. The associations were calculated for the overall and preformulated subgroups by using the odds ratios (ORs). This study was registered with PROSPERO (CRD42023445856). RESULTS: A total of 20 high-quality studies, comprised of 13 397 patients with acute minor ischemic stroke, were included. There were no significant differences observed in the modified Rankin Scale scores of 0 to 1 (OR, 1.10 [95% CI, 0.89-1.37]) and 0 to 2 (OR, 1.16 [95% CI, 0.95-1.43]), mortality rates (OR, 0.67 [95% CI, 0.39-1.15]), recurrent stroke (OR, 0.89 [95% CI, 0.57-1.38]), and recurrent ischemic stroke (OR, 1.09 [95% CI, 0.68-1.73]) between the IVT and BMT group. There were differences between the IVT group and the BMT group in terms of early neurological deterioration (OR, 1.81 [95% CI, 1.17-2.80]), symptomatic intracranial hemorrhage (OR, 7.48 [95% CI, 3.55-15.76]), and hemorrhagic transformation (OR, 4.73 [95% CI, 2.40-9.34]). Comparison of modified Rankin Scale score of 0 to 1 remained unchanged in subgroup patients with nondisabling deficits or compared with those using antiplatelets. CONCLUSIONS: These findings indicate that IVT does not yield significant improvement in the functional prognosis of patients with acute minor ischemic stroke. Additionally, it is associated with an increased risk of symptomatic intracranial hemorrhage when compared with the BMT. Moreover, IVT may not have superiority over BMT in patients with nondisabling deficits or those using antiplatelets.

Nano­selenium functionalized chitosan gel beads for Hg(II) removal from apple juice.

The presence of potentially toxic elements and compounds poses threats to the quality and safety of fruit juices. Among these, Hg(II) is considered as one of the most poisonous heavy metals to human health. Traditional chitosan-based and selenide-based adsorbents face challenges such as poor adsorption capacity and inconvenient separation in juice applications. In this study, we prepared nano­selenium functionalized chitosan gel beads (nanoSe@CBs) and illustrated the synergistic promotions between chitosan and nanoSe in removing Hg(II) from apple juice. The preparation conditions, adsorption behaviors, and adsorption mechanism of nanoSe@CBs were systematically investigated. The results revealed that the adsorption process was primarily controlled by chemical adsorption. At the 0.1 % dosage, the adsorbent exhibited high uptake, and the maximum adsorption capacity from the Langmuir isotherm model could reach 376.5 mg/g at room temperature. The adsorbent maintained high adsorption efficiency (> 90 %) across a wide range of Hg(II) concentrations (0.01 to 10 mg/L) and was unaffected by organic acids present in apple juice. Additionally, nanoSe@CBs showed negligible effects on the quality of apple juice. Overall, nanoSe@CBs open up possibilities to be used as a safe, low-cost and highly-efficient adsorbent for the removal of Hg(II) from juices and other liquid foods.

Definition, prediction, prevention and management of patients with severe ischemic stroke and large infarction.

ABSTRACT: Severe ischemic stroke carries a high rate of disability and death. The severity of stroke is often assessed by the degree of neurological deficits or the extent of brain infarct, defined as severe stroke and large infarction, respectively. Critically severe stroke is a life-threatening condition that requires neurocritical care or neurosurgical intervention, which includes stroke with malignant brain edema, a leading cause of death during the acute phase, and stroke with severe complications of other vital systems. Early prediction of high-risk patients with critically severe stroke would inform early prevention and treatment to interrupt the malignant course to fatal status. Selected patients with severe stroke could benefit from intravenous thrombolysis and endovascular treatment in improving functional outcome. There is insufficient evidence to inform dual antiplatelet therapy and the timing of anticoagulation initiation after severe stroke. Decompressive hemicraniectomy (DHC) <48 h improves survival in patients aged <60 years with large hemispheric infarction. Studies are ongoing to provide evidence to inform more precise prediction of malignant brain edema, optimal indications for acute reperfusion therapies and neurosurgery, and the individualized management of complications and secondary prevention. We present an evidence-based review for severe ischemic stroke, with the aims of proposing operational definitions, emphasizing the importance of early prediction and prevention of the evolution to critically severe status, summarizing specialized treatment for severe stroke, and proposing directions for future research.

Systematic review: Pharmacological interventions for the treatment of post-stroke fatigue.

BACKGROUND: Post-stroke fatigue (PSF) affects around 50% of stroke survivors. Previous systematic reviews of randomized controlled trials found insufficient evidence to guide practice, but most excluded Chinese studies. Furthermore, their searches are now out-of-date. AIMS: To systematically review and perform a meta-analysis of randomized placebo-controlled trials of pharmacological interventions for treating PSF. METHODS: We screened Airitri, CNKI, VIP, CINAHL, ClinicalTrials.gov, CENTRAL, Cochrane Stroke Group Trial Register, EMBASE, EU Clinical Trial Register, ISRCTN, MEDLINE, PsycINFO, Wanfang, and WHO ICTRP up to 11 November 2022. Our primary outcome was fatigue severity. We conducted subgroup analysis by drug type and sensitivity analysis after excluding the trials at high risk of bias. Secondary outcomes included mood and quality of life. RESULTS: We screened 33,297 citations and identified 10 published completed trials, 6 unpublished completed trials, and 6 ongoing trials. Pharmacological treatments were associated with lower fatigue severity at the end of treatment (10 published completed trials, 600 participants, pooled standardized mean difference (SMD) = -0.80, 95% confidence interval (CI): -1.29 to -0.31; I2 = 86%, p < 0.00001), but not at follow-up (265 participants, pooled SMD = -0.14, 95% CI: -0.38 to 0.10; I2 = 0, p = 0.51). However, these trials were small and had considerable risk of bias. Beneficial effects were seen in trials with low risk of bias on randomization, missing outcome data, and reporting bias. There were insufficient data on secondary outcomes for meta-analysis, but six trials reported improved quality of life. CONCLUSION: There is insufficient evidence to support a particular pharmacological treatment for PSF, thus current clinical guidelines do not require amendment.

Prognostic value of day-of-event serum calcium and magnesium for predicting 1-year prognosis after intracerebral hemorrhage.

AIM: To investigate whether serum calcium and magnesium on the day of symptom onset contribute to prognosis at 1 year after intracerebral hemorrhage (ICH). METHODS: We prospectively enrolled patients admitted < 24 h after symptom onset of primary ICH to West China Hospital between January 2012 and October 2014. Blood samples were collected at admission to determine the concentration of serum calcium and magnesium. We analyzed associations of the serum concentration of calcium and magnesium with unfavorable outcome (defined as modified Rankin scale, mRS ≥ 3) at 1 year. RESULTS: We included 874 patients (mean age 59.1 ± 13.5 years, 67.6% males), of whom 470 patients had mRS ≥ 3 and 284 patients died at 1 year. Compared to patients with the highest tertile level of calcium concentration (≥ 2.29 mmol/L), patients in the lowest tertile (≤ 2.15 mmol/L) had higher odds of unfavorable outcome (odds ratio, OR 1.61, 95% confidence interval [CI] 1.04-2.50, P = 0.034). The Kaplan-Meier survival curve revealed a significant difference of cumulative survival rate across calcium tertiles (log-rank P value = 0.038). There was no significant association between serum concentration of magnesium and functional outcome at 1 year. CONCLUSION: A reduced serum concentration of calcium on the day-of-event was associated with unfavorable outcome at 1 year after ICH. Future studies are needed to illustrate the pathophysiological mechanism of calcium and whether calcium could be a treatment target for improving outcomes after ICH.

Predicting the emergence of malignant brain oedema in acute ischaemic stroke: a prospective multicentre study with development and validation of predictive modelling.

Background: We aimed to develop and validate a prognostic model for predicting malignant brain oedema in patients with acute ischaemic stroke in a real-world setting of practice. Methods: A prospective multicentre study enrolled adult patients with acute ischaemic stroke with brain CT < 24 h of onset of symptoms admitted to nine tertiary-level hospitals in China between September 2017 and December 2019. Malignant brain oedema was defined as any patient who had decompressive craniectomy, discharge in coma, or in-hospital death attributed to symptomatic brain swelling. The derivation cohort was a consecutive cohort of patients from one centre and the validation cohort was non-consecutive patients from the other centres. Multivariable logistic regression was used to define independent predictors from baseline clinical characteristics, imaging features, complications, and management. A web-based nomogram and a risk score were developed based on the final model. Model performance was assessed for discrimination and calibration in both derivation and validation cohorts. The study is registered, NCT03222024. Findings: Based on the derivation cohort (n = 1627), the model was developed with seven variables including large infarct (adjusted odds ratio [OR] 40.90, 95% CI 20.20-82.80), National Institutes of Health Stroke Scale (NIHSS) score (OR 1.09, 1.06-1.12), thrombolysis (OR 2.11, 1.18-3.78), endovascular treatment (OR 2.87, 1.47-5.59), pneumonia (OR 2.47, 1.53-3.97), brain atrophy (OR 0.57, 0.37-0.86), and recanalisation (OR 0.36, 0.17-0.75). The classification threshold of a predicted probability ≥0.14 showed good discrimination and calibration in both derivation cohort (area under the receiver-operating curve [AUC] 0.90, 0.87-0.92; sensitivity 0.95, 0.92-0.98) and validation cohort (n = 556, AUC 0.88, 0.82-0.95; sensitivity 0.84, 0.73-0.95). The risk score based on this model had a total point that ranged from -1 to 20, with an optimal score of ≥10 showing good discrimination and calibration in both derivation (AUC 0.89, 0.87-0.92; sensitivity 0.95, 0.92-0.98) and validation (AUC 0.88, 0.82-0.95; sensitivity 0.84, 0.73-0.95) cohorts. Interpretation: The INTEP-AR model (i.e. large Infarct, NIHSS score, Thrombolysis, Endovascular treatment, Pneumonia, brain Atrophy, and Recanalisation) incorporating multiple clinical and radiological characteristics has shown good prognostic value for predicting malignant brain oedema after acute ischaemic stroke. Funding: National Natural Science Foundation of China; Science and Technology Department of Sichuan Province; West China Hospital.

Adsorptive performance and mechanism exploration of l-lysine functionalized celluloses for enhanced removal of Pb(II) from aqueous medium.

In this study, two novel biosorbents of l-lysine grafted cellulose (L-PCM, L-TCF) were prepared for Pb(II) removal from aqueous solutions. Various adsorption parameters were surveyed, such as adsorbent dosages, initial concentration of Pb(II), temperature and pH, using adsorption techniques. At normal temperature, less adsorbent can achieve better adsorption capacity (89.71 ± 0.27 mg g-1 with 0.5 g L-1 of L-PCM, 16.84 ± 0.02 mg g-1 with 3.0 g L-1 of L-TCF). The pH range of application for L-PCM was 4-12 and that of L-TCF was 4-13. The adsorption of Pb(II) by biosorbents went through the boundary layer diffusion stage and void diffusion stage. The adsorption mechanism was chemisorption based on multilayer heterogeneous adsorption. The pseudo-second-order model fitted the adsorption kinetics perfectly. The Freundlich isotherm model adequately described Multimolecular equilibrium relationship between Pb(II) and biosorbents; the predicted maximum adsorption capacities of the two adsorbents were 904.12 and 46.74 mg g-1, respectively. The results showed that the adsorption mechanism was the electrostatic attraction between Pb(II) and -COOH and the complexation between Pb(II) and -NH2. This work demonstrated that l-lysine modified cellulose-based biosorbents have great potential in the field of Pb(II) removal from aqueous solutions.

Preparation and modification of nanocellulose and its application to heavy metal adsorption: A review.

Heavy metals are a notable pollutant in aquatic ecosystems that results in many deadly diseases of the human body after enrichment through the food chain. As an environmentally friendly renewable resource, nanocellulose can be competitive with other materials at removing heavy metal ions due to its large specific surface area, high mechanical strength, biocompatibility and low cost. In this review, the research status of modified nanocellulose for heavy metal adsorbents is primarily reviewed. Two primary forms of nanocellulose are cellulose nanocrystals (CNCs) and cellulose nanofibers (CNFs). The preparation process of nanocellulose was derived from natural plants, and the preparation process included noncellulosic constituent removal and extraction of nanocellulose. Focusing on heavy metal adsorption, the modification of nanocellulose was explored in depth, including direct modification methods, surface grafting modification methods based on free radical polymerization and physical activation. The adsorption principles of nanocellulose-based adsorbents when removing heavy metals are analyzed in detail. This review may further facilitate the application of the modified nanocellulose in the field of heavy metal removal.

A systematic review and synthesis of global stroke guidelines on behalf of the World Stroke Organization.

BACKGROUND: There are multiple stroke guidelines globally. To synthesize these and summarize what existing stroke guidelines recommend about the management of people with stroke, the World Stroke Organization (WSO) Guideline committee, under the auspices of the WSO, reviewed available guidelines. AIMS: To systematically review the literature to identify stroke guidelines (excluding primary stroke prevention and subarachnoid hemorrhage) since 1 January 2011, evaluate quality (The international Appraisal of Guidelines, Research and Evaluation (AGREE II)), tabulate strong recommendations, and judge applicability according to stroke care available (minimal, essential, advanced). SUMMARY OF REVIEW: Searches identified 15,400 titles; 911 texts were retrieved, 200 publications scrutinized by the three subgroups (acute, secondary prevention, rehabilitation), and recommendations extracted from most recent version of relevant guidelines. For acute treatment, there were more guidelines about ischemic stroke than intracerebral hemorrhage; recommendations addressed pre-hospital, emergency, and acute hospital care. Strong recommendations were made for reperfusion therapies for acute ischemic stroke. For secondary prevention, strong recommendations included establishing etiological diagnosis; management of hypertension, weight, diabetes, lipids, and lifestyle modification; and for ischemic stroke, management of atrial fibrillation, valvular heart disease, left ventricular and atrial thrombi, patent foramen ovale, atherosclerotic extracranial large vessel disease, intracranial atherosclerotic disease, and antithrombotics in non-cardioembolic stroke. For rehabilitation, there were strong recommendations for organized stroke unit care, multidisciplinary rehabilitation, task-specific training, fitness training, and specific interventions for post-stroke impairments. Most recommendations were from high-income countries, and most did not consider comorbidity, resource implications, and implementation. Patient and public involvement was limited. CONCLUSION: The review identified a number of areas of stroke care where there was strong consensus. However, there was extensive repetition and redundancy in guideline recommendations. Future guideline groups should consider closer collaboration to improve efficiency, include more people with lived experience in the development process, consider comorbidity, and advise on implementation.

Design and Synthesis of Highly Potent and Specific ABHD6 Inhibitors.

Fine-tuning than complete disruption of 2-arachidonoylglycerol (2-AG) metabolism in the brain represents a promising pharmacological approach to limit potential untoward effects associated with complete blockade of monoacylglycerol lipase (MGL), the primary hydrolase of 2-AG. This could be achieved through a/b-hydrolase domain containing 6 (ABHD6) inhibition, which will provide a smaller and safer contribution to 2-AG regulation in the brain. Pharmacological studies with ABHD6 inhibitors have recently been reported, where modulation of ABHD6 activity either through CB1R-dependent or CB1R-independent processes showed promise in preclinical models of epilepsy, neuropathic pain and inflammation. Furthermore in the periphery, ABHD6 modulates 2-AG and other fatty acid monoacylglycerols (MAGs) and is implicated in Type-2 diabetes, metabolic syndrome and potentially other diseases. Herein, we report the discovery of single-digit nanomolar potent and highly specific ABHD6 inhibitors with >1000-fold selectivity against MGL and FAAH. The new ABHD6 inhibitors provide early leads to develop therapeutics for neuroprotection and the treatment of inflammation and diabetes.

Lenticulostriate artery length and middle cerebral artery plaque as predictors of early neurological deterioration in single subcortical infarction.

BACKGROUND: Early neurological deterioration (END) is not a rare phenomenon in single subcortical infarction (SSI; traditionally known as lacunar infarction) patients. Predictors of END in SSI patients are uncertain. AIMS: We aimed to investigate the association between infarct lesion characteristics, penetrating artery morphology, carrier artery plaque features and END using whole-brain vessel-wall imaging. METHODS: We prospectively collected data from SSI patients without stenosis of the corresponding carrier artery. The infarct lesion size and location, lenticulostriate artery (LSA) morphological characteristics, and features of the middle cerebral artery (MCA) plaques involving M1 segment adjacent to LSA origin on the symptomatic side were compared between patients with or without END. RESULTS: A total of 74 participants were enrolled, of whom 23 cases (31.1%) showed END. Multivariable logistic regression analysis adjusted for baseline National Institutes of Health Stroke Scale score and axial maximal diameter of infarct lesion revealed that the patients with MCA plaques adjacent to the LSA origin were more likely to develop END (odds ratio (OR) = 3.87, 95% confidence interval (CI) = 1.21-12.33), while with longer average length of LSAs were less likely to occur END (OR = 0.21, 95% CI = 0.05-0.92). CONCLUSION: MCA plaques located adjacent to the LSA origin and average length of LSAs on the symptomatic side were independent predictors of END in SSI patients. This finding might provide new insights into the mechanisms of the neurological progression in SSI and facilitate therapeutic interventions.

Increasing burden of stroke in China: A systematic review and meta-analysis of prevalence, incidence, mortality, and case fatality.

BACKGROUND: The epidemiology of stroke is evolving in China as the population undergoes demographic, lifestyle, and economic transitions. An updated review is pertinent to providing feedback on current, and in planning future, prevention and management strategies. AIMS: To identify high-quality epidemiological studies for quantifying the prevalence, incidence, mortality, and case fatality for stroke in China. METHODS: A search was undertaken across a range of bibliographic databases on 30 November 2021 without time limitation. Assessments were made of the risk of bias of the included studies. The outcomes were synthesized using a random-effects model. Subgroup analysis and meta-regression models were used to define the source of heterogeneity. RESULTS: Of 9407 identified records, 26 population-based studies were included. Due to significant heterogeneity across the studies, the original range for crude rates of indices was wide. The pooled annual prevalence was 1329.5/100,000 (95% confidence interval (CI) 713.6-2131.9, p < 0.001), incidence 442.1/100,000 (327.6-573.8, p < 0.001), mortality 154.1/100,000 (52.6-308.8, I2 = 100%, p < 0.001), and case fatality 35.8% (26.1% to 46.1%, I2 = 97%, p < 0.001). The prevalence and incidence of stroke have increased, but stroke-related case fatality has declined in China over recent decades. There are significant regional and rural-urban differences in incidence rates. CONCLUSION: Despite improved public health policies and healthcare delivery, the burden of stroke remains high in China. Further coordinated efforts are required in prevention and community care to offset the likelihood of further expansion in the absolute number of stroke cases in this large population.

Adenomyosis-Associated Ischemic Stroke: Pathophysiology, Detection and Management.

Female-specific risk factors for stroke have gradually received attention. The relationship between ischemic stroke and adenomyosis, a benign uterine disorder commonly present in parous women, is underrecognized. We aimed to provide an overview of the epidemiology, pathophysiological mechanisms, clinical characteristics, diagnostic considerations, and potential therapeutic strategies of adenomyosis-associated ischemic stroke. We shared our experience with the diagnosis and management of a patient, and summarized current findings and knowledge gaps of this disease based on previous literature. The relevant studies were searched in English and Chinese databases up to April 2022 using the keywords "ischemic stroke", "cerebral infarction" and "adenomyosis". Then, we provided a narrative review of the retrieved articles. Finally, the data of 32 cases were analyzed. We found that increased levels of carbohydrate antigen 125 and D-dimer and decreased level of hemoglobin are biomarkers of adenomyosis-associated ischemic stroke. In addition, hypercoagulability might be a key mechanism leading to thromboembolism in the cerebrovascular system. Additional studies are needed to find optimal prevention strategies for the disease. A better understanding of this "rare" pathogenesis of ischemic stroke may inform a more precise diagnosis and effective prevention strategy in middle-aged women with embolic stroke of undetermined source.

Tuning oxygen vacancies in epitaxial LaInO3 films for ultraviolet photodetection.

LaInO3 (LIO) represents a new, to the best of knowledge, type of perovskite oxides for deep-ultraviolet (DUV) photodetection owing to the wide bandgap nature (∼5.0 eV) and the higher tolerance of defect engineering for tunable carrier transport. Here we fabricate fast-response DUV photodetectors based on epitaxial LIO thin films and demonstrate an effective strategy for balancing the photodetector performance using the oxygen growth pressure as a simple control parameter. Increasing the oxygen pressure is effective to suppress the oxygen vacancy formation in LIO, which is beneficial to suppress the dark current and enhance the response speed. The optimized LIO photodetector achieves a fast rise/fall time of 20 ms/73 ms, a low dark current of 2.0 × 10-12 A, a photo-to-dark current ratio of 1.2 × 103, and a detectivity of 6 × 1012 Jones.

The stress hyperglycemia ratio is associated with the development of cerebral edema and poor functional outcome in patients with acute cerebral infarction.

Background and purpose: Absolute hyperglycemia at admission has been shown to be associated with the development of cerebral edema (CED) after acute cerebral infarction. Stress hyperglycemia is a more objective reflection of hyperglycemic state than absolute hyperglycemia. However, studies on the associations between stress hyperglycemia and CED are limited. We aimed to explore the associations of stress hyperglycemia, measured by stress hyperglycemia ratio (SHR), with the development of CED and poor functional outcome of acute cerebral infarction. Methods: Patients with acute middle artery cerebral infarction admitted to the Department of Neurology, West China Hospital of Sichuan University, within 24 h of symptom onset from January 2017 to March 2021 were included. Stress hyperglycemia was assessed by the SHR: admission fasting plasma glucose (FPG)/hemoglobin A1c (HbA1c). The primary outcome was the degree of CED evaluated on brain image. The secondary outcomes were moderate-to-severe CED, poor functional outcome (modified Rankin Scale score > 2), and death at 90 days. The associations between the SHR and outcomes were assessed with multivariate logistic regression analyses. We further compared the predictive value of the SHR, admission random plasma glucose (RPG), and admission FPG for outcomes in the training dataset and validation dataset. Results: 638 patients were enrolled. Each 0.1-point increase in the SHR was independently associated with a 1.31-fold increased risk of a higher degree of CED [odds ratio (OR): 1.31 (95% confidence interval (CI): 1.20-1.42), P < 0.001]. The SHR was independently associated with moderate-to-severe CED [per 0.1-point increase: OR: 1.39 (95% CI: 1.24-1.57), P < 0.001], poor functional outcome [per 0.1-point increase: OR: 1.25 (95% CI: 1.12-1.40), P < 0.001], and death [per 0.1-point increase: OR: 1.13 (95% CI: 1.03-1.25), P < 0.05]. The predictive value of the SHR (as a continuous variable), exhibited by the area under the curve in receiver operating characteristic analysis, was higher than that of the RPG and FPG for moderate-to-severe CED and poor functional outcome (P < 0.05). Conclusion: The SHR is independently associated with the severity of CED, poor functional outcome, and death after acute cerebral infarction, and the SHR (as a continuous variable) has a better predictive value for moderate-to-severe CED and poor functional outcome than the RPG and FPG.

Acute iron overload aggravates blood-brain barrier disruption and hemorrhagic transformation after transient focal ischemia in rats with hyperglycemia.

Hemorrhagic transformation (HT) has been reported to be associated with a poor prognosis after acute ischemic stroke. Blood-brain barrier (BBB) damage is considered as the major pathophysiologic mechanism of HT. Our aim was to investigate the role of acute iron overload in BBB damage and HT after transient focal ischemia in rats with hyperglycemia. Transient middle cerebral artery occlusion (MCAO) was induced in rats with hyperglycemia. Animals were assigned to four groups: Sham, Vehicle, Iron overload and Iron chelator treatment groups. Brain samples were collected at 24 h after surgery to quantify the amount of hemorrhage, determine extravasation of Evans blue and detect the levels of following proteins: ferritin, matrix metalloproteinase-9 (MMP-9), zonula occludens-1 (ZO-1), Occludin and Claudin-5 by western blot analysis and immunohistochemistry. Compared to the Vehicle group, the Iron overload group had a significantly higher amount of hemorrhage and more extravasation of Evans blue. The Iron overload group had lower levels of ZO-1, Occludin and Claudin-5 and higher levels of ferritin and MMP-9 than the Vehicle group. Administering iron chelator reduced the extension of hemorrhage and extravasation of Evans blue, reversed the MCAO-induced reduction of ZO-1, Occludin and Claudin-5 and decreased the levels of ferritin and MMP-9. Our results suggest that acute iron overload aggravates BBB damage and HT after transient ischemia in rats with hyperglycemia, which provides basic evidence for iron overload as a potential factor associated with BBB damage and HT in ischemic stroke patients when accompanied with hyperglycemia.