During the coronavirus disease 2019 (COVID‑19) pandemic, some patients with severe COVID‑19 exhibited complications such as acute ischemic stroke (AIS), which was closely associated with a poor ...prognosis. These patients often had an abnormal coagulation, namely, elevated levels of D‑dimer and fibrinogen, and a low platelet count. Certain studies have suggested that COVID‑19 induces AIS by promoting hypercoagulability. Nevertheless, the exact mechanisms through which COVID‑19 leads to a hypercoagulable state in infected patients remain unclear. Understanding the underlying mechanisms of hypercoagulability is of utmost importance for the effective treatment of these patients. The present review aims to summarize the current status of research on COVID‑19, hypercoagulability and ischemic stroke. The present review also aimed to shed light into the underlying mechanisms through which COVID‑19 induces hypercoagulability, and to provide therapies for different mechanisms for the more effective treatment of patients with COVID‑19 with ischemic stroke and prevent AIS during the COVID‑19 pandemic.
In this study, clinical data including demographic characteristics, clinical manifestations, medication regimens, imaging reports, and laboratory tests were collected. All continuous data failed to ...pass the normality tests. ...the continuous data were described in the form of the median and interquartile range (median IQR), and Mann–Whitney U tests were applied to compare the difference between the two groups. There were no statistically significant differences in demographics, laboratory tests, comorbid complications, and treatment between these two groups Supplementary Table 3, http://links.lww.com/CM9/B917. Because mood disorders were the most common neuropsychiatric symptoms in this study and psychosis was found to be associated with outcomes in patients with NPSLE, we further analyzed the MRI risk factors for mood disorders and psychosis.
The role of neutrophil extracellular traps (NETs) in procoagulant activity (PCA) in stroke patients caused by thromboembolic occlusion of the internal carotid artery (ICA) remains unclear. Our ...objectives were to evaluate the critical role of NETs in the induction of hypercoagulability in stroke and to identify the functional significance of NETs during atherothrombosis.
The levels of NETs, activated platelets (PLTs), and PLT-derived microparticles (PMPs) were detected in the plasma of 55 stroke patients and 35 healthy controls. NET formation and thrombi were analysed using immunofluorescence. Exposed phosphatidylserine (PS) was evaluated with flow cytometry and confocal microscopy. PCA was analysed using purified coagulation complex, thrombin, and fibrin formation assays.
The plasma levels of NETs, activated PLTs, and PMP markers in the carotid lesion site (CLS) were significantly higher than those in the aortic blood. NETs were decorated with PS in thrombi and the CLS plasma of ICA occlusion patients. Notably, the complementary roles of CLS plasma and thrombin-activated PLTs were required for NET formation and subsequent PS exposure. PS-bearing NETs provided functional platforms for PMPs and coagulation factor deposition and thus increased thrombin and fibrin formation. DNase I and lactadherin markedly inhibited these effects. In addition, NETs were cytotoxic to endothelial cells, converting these cells to a procoagulant phenotype. Sivelestat, anti-MMP9 antibody, and activated protein C (APC) blocked this cytotoxicity by 25%, 39%, or 52%, respectively.
NETs played a pivotal role in the hypercoagulability of stroke patients. Strategies that prevent NET formation may offer a potential therapeutic strategy for thromboembolism interventions.
This study was supported by grants from the National Natural Science Foundation of China (61575058, 81873433 and 81670128) and Graduate Innovation Fund of Harbin Medical University (YJSKYCX2018-58HYD).
Abstract Background: Pulmonary embolism (PE) is a severe and acute cardiovascular syndrome with high mortality among patients with autoimmune inflammatory rheumatic diseases (AIIRDs). Accurate ...prediction and timely intervention play a pivotal role in enhancing survival rates. However, there is a notable scarcity of practical early prediction and risk assessment systems of PE in patients with AIIRD. Methods: In the training cohort, 60 AIIRD with PE cases and 180 age-, gender-, and disease-matched AIIRD non-PE cases were identified from 7254 AIIRD cases in Tongji Hospital from 2014 to 2022. Univariable logistic regression (LR) and least absolute shrinkage and selection operator (LASSO) were used to select the clinical features for further training with machine learning (ML) methods, including random forest (RF), support vector machines (SVM), neural network (NN), logistic regression (LR), gradient boosted decision tree (GBDT), classification and regression trees (CART), and C5.0 models. The performances of these models were subsequently validated using a multicenter validation cohort. Results: In the training cohort, 24 and 13 clinical features were selected by univariable LR and LASSO strategies, respectively. The five ML models (RF, SVM, NN, LR, and GBDT) showed promising performances, with an area under the receiver operating characteristic (ROC) curve (AUC) of 0.962–1.000 in the training cohort and 0.969–0.999 in the validation cohort. CART and C5.0 models achieved AUCs of 0.850 and 0.932, respectively, in the training cohort. Using D-dimer as a pre-screening index, the refined C5.0 model achieved an AUC exceeding 0.948 in the training cohort and an AUC above 0.925 in the validation cohort. These results markedly outperformed the use of D-dimer levels alone. Conclusion: ML-based models are proven to be precise for predicting the onset of PE in patients with AIIRD exhibiting clinical suspicion of PE. Trial Registration: Chictr.org.cn: ChiCTR2200059599
Treatment of antioxidants is necessary to protect ischemic stroke associated neuronal damage. Xanthohumol (XN), a natural flavonoid extracted from hops, has been reported to have potential function ...as an antioxidant and can be used for neuro protection. However, the role of XN in ischemic stroke remains unclear. Here, we studied the neuroprotective effects of XN through experimental stroke models. Middle cerebral artery occlusion (MCAO) and oxygen–glucose deprivation (OGD) was used as in vivo and in vitro model, respectively. We found that the treatment of XN improved MCAO-induced brain injury by reducing infarct size, improving neurological deficits, reversing neuronal damage, reducing oxidative stress injury and cell apoptosis. Further experimental studies showed that XN could revive neuronal apoptosis induced by OGD by preventing oxidative stress injury. In addition, our study suggested that these effects were related to the inhibition of phosphorylation of p38-MAPK and the mediation of nuclear Nrf2 activation. In conclusion, the neuroprotective effects of XN showed in this study make XN a promising supplement for ischemic stroke protection.
Abstract
Background
In December 2019, coronavirus 2019 (COVID-19) emerged in Wuhan and rapidly spread throughout China.
Methods
Demographic and clinical data of all confirmed cases with COVID-19 on ...admission at Tongji Hospital from 10 January to 12 February 2020 were collected and analyzed. The data on laboratory examinations, including peripheral lymphocyte subsets, were analyzed and compared between patients with severe and nonsevere infection.
Results
Of the 452 patients with COVID-19 recruited, 286 were diagnosed as having severe infection. The median age was 58 years and 235 were male. The most common symptoms were fever, shortness of breath, expectoration, fatigue, dry cough, and myalgia. Severe cases tend to have lower lymphocyte counts, higher leukocyte counts and neutrophil-lymphocyte ratio (NLR), as well as lower percentages of monocytes, eosinophils, and basophils. Most severe cases demonstrated elevated levels of infection-related biomarkers and inflammatory cytokines. The number of T cells significantly decreased, and were more impaired in severe cases. Both helper T (Th) cells and suppressor T cells in patients with COVID-19 were below normal levels, with lower levels of Th cells in the severe group. The percentage of naive Th cells increased and memory Th cells decreased in severe cases. Patients with COVID-19 also have lower levels of regulatory T cells, which are more obviously decreased in severe cases.
Conclusions
The novel coronavirus might mainly act on lymphocytes, especially T lymphocytes. Surveillance of NLR and lymphocyte subsets is helpful in the early screening of critical illness, diagnosis, and treatment of COVID-19.
Dysregulation of immune response, especially T lymphocytes, might be highly involved in the pathological process of COVID-19. Surveillance of neutrophil-to-lymphocyte ratio and lymphocyte subsets is helpful in the early screening of critical illness, diagnosis, and treatment of COVID-19.
Mechanistic study on the 1,3,2-diazaphospholene (1)-catalyzed reduction reaction of allyl 2-phenylacrylate 4 with HBpin or ammonia borane (AB) was systematically performed by the density functional ...theory (DFT) method. When HBpin is employed as the reductant, the reductive Ireland–Claisen (IC) rearrangement reaction occurs. First, the active species P-hydrido-1,3,2-diazaphospholene 3 is generated through the metathesis reaction of 1 with HBpin. Next, the terminal CC double bond of 4 is inserted into the P–H bond of 3 to produce 6a through the 1,2-addition (Markovnikov) step, which is followed by the pinB–H bond activation to afford key boron enolate 8. Then, 8 undergoes the 3,3 rearrangement that is followed by the alcoholysis reaction with methanol leading to the final product γ,δ-unsaturated carboxylic acid. The 3,3 rearrangement step is the rate-determining step with the Gibbs energy barrier (ΔG ≠) and Gibbs reaction energy (ΔG) of 23.9 and −27.5 kcal/mol, respectively. When AB is employed as the reductant, the transfer hydrogenation reaction occurs through two comparable pathways, 1,2- and 1,4-transfer hydrogenation pathways. The former pathway directly leads to the hydrogenation product with the ΔG ≠ and ΔG values of 22.4 and −27.7 kcal/mol, respectively. The latter pathway produces an enolate intermediate (rate-determining step, ΔG ≠/ΔG = 24.1/–0.3 kcal/mol) first, which then prefers to undergo the enol–keto tautomerism instead of the 3,3 rearrangement to afford the hydrogenation product. Obviously, the generation of the boron enolate plays a crucial role in the reductive IC rearrangement reaction because it prevents the enol–keto tautomerism.
BACKGROUND AND PURPOSE:Information on stroke survivors infected with coronavirus disease 2019 (COVID-19) is limited. The aim of this study was to describe specific clinical characteristics and ...outcomes of patients with COVID-19 with a history of stroke.
METHODS:All the confirmed cases of COVID-19 at Tongji Hospital from January 27 to March 5, 2020, were included in our cohort study. Clinical data were analyzed and compared between patients with and without a history of stroke.
RESULTS:Of the included 1875 patients with COVID-19, 50 patients had a history of stroke. The COVID-19 patients with medical history of stroke were older with more comorbidities, had higher neutrophil count, and lower lymphocyte and platelet counts than those without history of stroke. The levels of D-dimers, cardiac troponin I, NT pro-brain natriuretic peptide, and interleukin-6 were also markedly higher in patients with history of stroke. Stroke survivors who underwent COVID-19 developed more acute respiratory distress syndrome and received more noninvasive mechanical ventilation. Data from propensity-matched analysis indicated a higher proportion of patients with COVD-19 with a history of stroke were admitted to the intensive care unit requiring mechanical ventilation and were more likely to be held in the unit or die, compared with non-stroke history COVID-19 patients.
CONCLUSIONS:Patients with COVID-19 with a history of stroke had more severe clinical symptoms and poorer outcomes compared with those without a history of stroke.
The mechanism of the N–N cross-coupling of nitroarene and aniline catalyzed by 1,2,2,3,4,4-hexamethylphosphetane oxide (1PO) as well as the prediction of a better catalyst was theoretically ...investigated using DFT and DLPNO-CCSD(T) calculations. An active species 1P is generated through deoxygenation of 1PO by diphenylsilane. Then, 1P extracts one oxygen atom from nitroarene to produce nitrosoarene. In this deoxygenation step, the 3 + 1 cheletropic addition is a rate-determining step with the ΔG 0≠ and ΔG 0 values of 28.8 and −7.3 kcal/mol, respectively. Next, nitrosoarene exclusively undergoes a dehydrative condensation reaction with aniline to form an azo-cation intermediate, which is the origin of the high selectivity in this cross-coupling reaction. In this step, 2,4,6-trimethylbenzoic acid plays an essential role to significantly reduce the ΔG 0≠ value from 41.1 to 14.8 kcal/mol. Subsequently, 1P reacts with the azo cation to form a stable hydrazinylphosphonium species through the nucleophilic attack of the phosphorus atom to the cationic nitrogen atom. The phosphonium center preferably accepts a hydroxyl group from water to ensure the formation of hydrazine in the subsequent step. In the 3 + 1 cheletropic addition step, the highest occupied molecular orbital (HOMO) of 1P plays an important role. The small-ring scaffold of 1P raises the HOMO energy compared to acyclic phosphorus compounds to achieve high activity of 1P. Substitution of a dimethylamino group for the methyl group in 1P was theoretically predicted to improve the activity by further increasing the HOMO energy.
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