Individuals with T-786C and G894T genotypes of eNOS in Chinese Han population have an increased risk of developing rheumatoid arthritis.

Several genetic polymorphisms in endothelial nitric oxide synthase (eNOS) are associated with the pathogenesis of rheumatoid arthritis (RA). This study explored the effect of eNOS gene polymorphism on genetic susceptibility of RA in Chinese Han population. Patients with RA (n=236) and healthy volunteers (n=240) were enrolled in this study. Genotyping of eNOS T-786C and G894T polymorphisms was performed by polymerase chain reaction-restriction fragment length polymorphism. Genotyping and gene frequency distribution of eNOS T-786C and G894T polymorphisms were evaluated. RA patients showed higher frequencies of mutated TC and CC genotypes of eNOS T-786C polymorphism and mutated GT and TT genotypes of G894T polymorphism than healthy controls. More specifically, the genotype frequencies of eNOS T-786C polymorphism were significantly different between RA patients and controls. The expression of eNOS was enhanced in RA patients compared with controls. Further, eNOS expression was enhanced after C was replaced with T in T-786C polymorphism in the promoter. Overall, the individuals with mutations in T-786C and G894T of eNOS may have an increased risk of RA, and T-786C and G894T polymorphisms of eNOS are associated with genetic susceptibility of RA in Chinese Han population.

Predictors of functional dependence at one year in acute ischemic stroke with large vessel occlusion.

BACKGROUND: In China, the current status of clinical treatment of eLVO and the factors affecting its long-term prognosis are unclear. OBJECTIVE: This study aims to explore the predictive factors of functional outcomes at one year in patients of acute ischemic stroke with emergent large vessel occlusion (eLVO). METHODS: We retrospectively collected 536 patients who underwent treatments for eLVO. Primary outcomes included one-year functional outcomes and delayed functional independence (DFI). The logistic regression was performed to predict the primary outcome. RESULTS: 431 (85%) survivors participated in the one-year follow-up. In the multivariate logistic analysis adjusted for baseline characteristics, the following factors were found to be significant predictors of functional dependence at one year: old age (aOR = 1.042, 95% CI=1.01-1.076, p = 0.011), low Alberta stroke program early CT score (ASPECTS) (aOR = 0.791, 95% CI=0.671-0.933, p = 0.005), unsuccessful reperfusion (aOR = 0.168, 95% CI=0.048-0.586, p = 0.005), poor medication compliance (aOR = 0.022, 95% CI=0.007-0.072, p < 0.001), and complicated with stroke-associated pneumonia (SAP) (aOR = 2.269, 95% CI=1.103-4.670, p = 0.026). We also found that men (aOR = 3.947, 95% CI=1.15-13.549, p = 0.029) had better medication adherence (aOR = 14.077, 95% CI=1.736-114.157, p = 0.013), and going to rehabilitation centers (aOR = 5.197, 95% CI=1.474-18.327, p = 0.010) were independent predictors of DFI. CONCLUSION: The significant predictors of functional dependence at one year were: old age, low ASPECTS, unsuccessful reperfusion, poor medication adherence, and combination with SAP. Men, good medication adherence, and going to rehabilitation centers contributed to getting delayed functional independence.

Differential Influence of the COVID-19 Pandemic on Mechanical Thrombectomy and Bridging Therapy for Acute Ischemic Stroke.

Background: The coronavirus disease 2019 (COVID-19) pandemic is having a dramatic impact on acute stroke care. Its effects may accompany stroke care for a long time. We compared the treatment, short-term and long-term functional outcomes of patients with AIS from 2019 to 2020. Our objective was to evaluate the effect of COVID-19 epidemic on mechanical thrombectomy (MT) in patients in our hospital. Methods: We collected information on subjects treated with MT in 2019-2020, including age, sex, time from the onset to arterial sheath insertion, time from the onset to recanalization, the rate of lung infection and hemorrhagic transformation, modified Rankin scale (mRS), NHISS, and ASPECTS. Results: The number of patients with MT decreased significantly by 26.6% in 2020 (p = 0.025). The pretreatment ASPECTS score for 2020 was significantly higher than 2019 (p = 0.004). Besides, the patients were more likely to develop lung infection (65 vs. 54.1%, p = 0.042) and had a higher risk of hemorrhagic transformation (47.4% vs. 30.4%, p = 0.005) in 2019. The discharged mRS reflected the worse short-term functional prognosis of patients with MT in 2019 (66 vs. 44.9%, p = 0.046). In the subgroup analysis of bridging thrombolysis (BT), more patients with BT are expected to have a poor short-term functional prognosis in 2020, according to the discharged mRS (62.5 vs. 37.5%, p = 0.024). However, there was no difference in mRS at 180 days between the two groups (p = 0.094). Conclusion: For patients with MT, both short- and long-term functional outcomes were not significantly affected due to the mild condition of patients admitted to hospital in 2020. For patients with BT, the COVID-19 pandemic has prolonged the green channel time of stroke, leading to a poor short-term functional prognosis of patients with stroke in the pandemic period. There was no difference in the effectiveness of direct MT and BT during the COVID-19 pandemic.

Low serum transthyretin levels predict stroke-associated pneumonia.

BACKGROUND AND AIMS: Stroke-associated pneumonia (SAP) is commonly seen in ischemic stroke patients. Low transthyretin levels are found to be correlated with stroke. This study aims to investigate the potential relationship between transthyretin levels and SAP. METHODS AND RESULTS: In total, 920 patients were involved in our study. Serum transthyretin levels were measured within 24 h at admission. We defined SAP according to the modified Centers for Disease Control criteria. In the study population, 123 (13.4%, 77 men, 46 women) were diagnosed with SAP. In the multivariable analysis, we found that serum transthyretin levels were significantly lower in SAP compared with non-SAP patients (231 ± 80 vs. 279 ± 75; P < 0.001) after adjusting for confounders. Meanwhile, we discovered that low transthyretin levels (≤252 mg/L) were independently associated with the development of SAP (OR 3.370; 95% CI: 1.763-6.441; P < 0.001). Moreover, patients with SAP had a worse clinical outcome than those without SAP at discharge. In addition, dysphagia, leukocyte count and NLR (neutrophil-to-lymphocyte ratio) were also found to be associated with SAP. CONCLUSION: We found that low transthyretin levels significantly increased the risk of SAP. Patients with high risk of developing SAP could be early identified and prevented timely.

Leonurine protects against influenza A virus infection-induced pneumonia in mice.

Influenza A virus (H1N1), a swine-origin influenza A virus, causes seasonal epidemics that result in severe illnesses and deaths. Leonurine has been reported to function as an anti-inflammatory agent with protective effects on nervous, urinary and cardiovascular systems. However, the therapeutic effects of leonurine on the pneumonia caused by H1N1 infection remain unclear. Hematoxylin and eosin staining was performed to evaluate the lung injuries of mice infected by H1N1. The amount of immune cells was analyzed by flow cytometry. Enzyme-linked immunosorbent assay was used to evaluate the alteration of multiple cytokines in lung tissues. Real-time quantitative polymerase chain reaction assay was performed to investigate the ribonucleic acid (RNA) levels of certain genes. The protein levels in toll-like receptor 4/nuclear factor kappa-light-chain-enhancer of activated B cells (TLR4/NF-κB) signaling were estimated by western blot assay. Leonurine treatment significantly inhibited the mortality caused by H1N1 infection. Leonurine treatment (60 mg/kg) alleviated the lung injuries caused by virus infection. The inflammatory cell accumulation and cytokine expression were inhibited by the leonurine administration. Leonurine inhibited the mRNA expression of pro-inflammatory cytokines in the lung homogenates at day 5 postinfection. Leonurine regulated the TLR4/NF-κB signaling in the lung homogenates of H1N1-infected mice at day 5 postinfection. Leonurine protects against H1N1 infection-induced pneumonia in mice.

High Fibrinogen to Albumin Ratio: A Novel Marker for Risk of Stroke-Associated Pneumonia?

Background: Stroke-associated pneumonia (SAP) is associated with poor prognosis after acute ischemic stroke (AIS). Purpose: This study aimed to describe the parameters of coagulation function and evaluate the association between the fibrinogen-to-albumin ratio (FAR) and SAP in patients with AIS. Patients and methods: A total of 932 consecutive patients with AIS were included. Coagulation parameters were measured at admission. All patients were classified into two groups according to the optimal cutoff FAR point at which the sum of the specificity and sensitivity was highest. Propensity score matching (PSM) was performed to balance potential confounding factors. Univariate and multivariate logistic regression analyses were applied to identify predictors of SAP. Results: A total of 100 (10.7%) patients were diagnosed with SAP. The data showed that fibrinogen, FAR, and D-dimer, prothrombin time (PT), activated partial thromboplastin time (aPTT) were higher in patients with SAP, while albumin was much lower. Patients with SAP showed a significantly increased FAR when compared with non-SAP (P < 0.001). Patients were assigned to groups of high FAR (≥0.0977) and low FAR (<0.0977) based on the optimal cut-off value. Propensity score matching analysis further confirmed the association between FAR and SAP. After adjusting for confounding and risk factors, multivariate regression analysis showed that the high FAR (≥0.0977) was an independent variable predicting the occurrence of SAP (odds ratio =2.830, 95% CI = 1.654-4.840, P < 0.001). In addition, the FAR was higher in the severe pneumonia group when it was assessed by pneumonia severity index (P = 0.008). Conclusions: High FAR is an independent potential risk factor of SAP, which can help clinicians identify high-risk patients with SAP after AIS.

Quercetin attenuates mitochondrial dysfunction and biogenesis via upregulated AMPK/SIRT1 signaling pathway in OA rats.

Despite the severity of osteoarthritis (OA), current medical therapy strategies for OA aim at symptom control and pain reduction, as there is no ideal drug for effective OA treatment. OA rat model was used to explore the therapeutic function of quercetin on remission of OA, by determining the reactive oxygen species (ROS) levels, mitochondrial function and extracellular matrix integrity. Quercetin could attenuate ROS generation and augment the glutathione (GSH) and glutathione peroxidase (GPx) expression levels in OA rat. Quercetin not only enhanced mitochondrial membrane potential, oxygen consumption, adenosine triphosphate (ATP) levels in mitochondria, but also increased the mitochondrial copy number. Furthermore, the interlukin (IL)-1ß-induced accumulation of nitric oxide (NO), matrixmetalloproteinase (MMP)-3) and MMP-13 could be suppressed by quercetin. Finally, we confirmed that the therapeutic properties of quercetin on OA might function through the adenosine monophosphate-activated protein kinase/sirtuin 1 (AMPK/SIRT1) signaling pathway. In summary, quercetin could alleviate OA through attenuating the ROS levels, reversing the mitochondrial dysfunction and keeping the integrality of extracellular matrix of joint cartilage. The underlying mechanism might involve the regulation of AMPK/SIRT1 signaling pathway.