Aihua Fei

Prognostic Significance of Neutrophil-to-Lymphocyte Ratio in Patients with Sepsis: A Prospective Observational Study

Background. The neutrophil-to-lymphocyte ratio (NLR) is an easily accessible biological marker that has been reported to represent disease severity. The aim of this study is to investigate the association between NLR and mortality in patients with sepsis. Methods. A total of 333 consecutive adult patients with sepsis were screened for eligibility in this prospective, observational study cohort. Severity scores and leukocyte counts were prospectively recorded upon entry to the intensive care unit (ICU). Receiver operating characteristic (ROC) curves and binary logistic regression models were used to assess the performance of NLR in predicting unfavorable outcome. Correlations between variables and disease severity were analyzed through Spearman correlation tests. Results. Median NLR levels were significantly higher in patients who died than in survivors. NLR had a modest power for predicting poor outcome as suggested by area under the curve (AUC) of 0.695 ± 0.036. Multivariate linear regression indicated that increased NLR levels were related to unfavorable outcome independently of the effect of possible confounders. Spearman correlation tests showed that there was a positive correlation between NLR levels and disease severity. Conclusions. Increased NLR levels were independently associated with unfavorable clinical prognosis in patients with sepsis. Further investigation is required to increase understanding of the pathophysiology of this relationship.

Predictors of Outcome and Hemorrhage in Patients Undergoing Endovascular Therapy with Solitaire Stent for Acute Ischemic Stroke.

Background Endovascular mechanical thrombectomy is emerging as a promising therapeutic approach for acute ischemic stroke and show some advantages. However, the data of predicting clinical outcome after thrombectomy with Solitaire retriever were limited. We attempt to identify prognostic factors of clinical outcome in patients with acute ischemic stroke undergoing thrombectomy with Solitaire retriever. Methods We conducted a retrospective analysis of consecutive acute ischemic strokes cases treated between December 2010 and December2013 where the Solitaire stent retriever was used for acute ischemic stroke. We assessed the effect of selected demographic characteristics, clinical factors on poor outcome at 3 months (modified Rankin score 3–6), mortality at 3 months, and hemorrhage within 24 h (symptomatic and asymptomatic). Clinical, imaging and logistic variables were analyzed. A multivariate logistic regression analysis was used to identify variables influencing clinical outcome, based on discharge NIHSS score change and mRS at 3 months. Results Eighty nine consecutive patients with acute ischemic stroke underwent mechanical thrombectomy. Multivariate analysis revealed that admission NIHSS score, Serum glucose and endovascular procedure duration were independently associated with clinical outcome. Sex, NIHSS score at admission, diabetes and time of operation were associated with sICH in 1 day. NIHSS score ≥20 (OR 9.38; 95% CI 2.41–36.50), onset to reperfusion >5 hours (OR 5.23; 95% CI1.34,20.41) and symptomatic intracranial hemorrhage (OR 10.19; 95% CI1.80,57.83) were potential predictive factors of mortality at 3 months. Conclusion Multiple pre- and intra-procedural factors can be used to predict clinical outcome, symptomatic intracranial hemorrhage and mortality in acute ischemic stroke patients undergoing endovascular therapy. This knowledge is helpful for patients selection for endovascular mechanical thrombectomy.

Salvianolate inhibits reactive oxygen species production in H 2 O 2 -treated mouse cardiomyocytes in vitro via the TGFβ pathway

Aim:To investigate the effects of salvianolate, a water-soluble active compound from Salvia miltiorrhiza Bunge, on reactive oxygen species (ROS) production in mouse cardiomyocytes in vitro.Methods:Primary ventricular cardiomyocytes were prepared from neonatal mouse. The cell viability was determined using MTT assay. Culture medium for each treatment was collected for measuring the levels of NO, iNOS, total antioxidant capacity (TAOC) and transforming growth factor β1 (TGFβ1). TGFβ1 and Smad2/3 expression in the cells was detected with Western blotting.Results:H2O2 (1.25 mmol/L) did not significantly affect the cell viability, whereas the high concentration of salvianolate (5 g/L) alone dramatically suppressed the cell viability. Treatment of the cells with H2O2 (1.25 mmol/L) markedly increased ROS and iNOS production, and decreased the levels of NO, TAOC and TGFβ1 in the culture medium. Furthermore, the H2O2 treatment significantly increased TGFβ1 and Smad2/3 expression in the cells. Addition of salvianolate (0.05, 0.1, and 0.5 g/L) concentration-dependently reversed the H2O2-induced alterations in the culture medium; addition of salvianolate (0.05 g/L) reversed the H2O2-induced increases of TGFβ1 and Smad2/3 expression in the cells. Blockage of TGFβ1 with its antibody (1 mg/L) abolished the above mentioned effects of salvianolate.Conclusion:Salvianolate inhibits ROS and iNOS production and increases TAOC and NO levels in H2O2-treated cardiomyocytes in vitro via downregulation of Smad2/3 and TGFβ1 expression. High concentration of salvianolate causes cytotoxicity in mouse cardiomyocytes.

Isoquercetin activates the ERK1/2-Nrf2 pathway and protects against cerebral ischemia-reperfusion injury in vivo and in vitro

Isoquercetin has exhibited a wide range of therapeutic properties, including antioxidant, anti-inflammatory and anti-allergic activities. The aim of the present study was to investigate the effect of isoquercetin on rats with 2 h middle cerebral artery occlusion (MCAO) and evaluate the neuroprotective effect of isoquercetin on a primary culture of rat hippocampal neuronal cells subjected to oxygen-glucose deprivation followed by reoxygenation (OGD/R). In vivo, the rats treated with isoquercetin exhibited a lower degree of neurological dysfunction and smaller infarct volume than the vehicle-treated rats. In vitro, it was found that isoquercetin prevented the OGD/R-induced increase in apoptosis, lactate dehydrogenase release and reduction in cell viability. Additionally, isoquercetin induced the upregulation of nuclear factor erythroid 2-related factor 2 gene and protein expression, and increased extracellular signal-regulated kinase 1 and 2 (ERK1/2) phosphorylation. This indicates that the ERK1/2 pathway may contribute to the neuroprotective effect of isoquercetin against OGD/R-induced oxidative damage in rat hippocampal neurons. These findings suggest the potential importance of isoquercetin in the treatment of ischemia/reperfusion-related brain injury and associated diseases.

Comparison of Therapeutic Effect of Recombinant Tissue Plasminogen Activator by Treatment Time after Onset of Acute Ischemic Stroke

We aimed to compare the therapeutic effect of recombinant tissue plasminogen activator (rt-PA) administered at different time windows within the first 6 hours after onset of acute ischemic stroke (AIS). A retrospective analysis was performed of data collected from 194 patients who received rt-PA thrombolysis within 4.5 hours after AIS onset and from 29 patients who received rt-PA thrombolysis between 4.5–6 hours after AIS onset. The National Institutes of Health Stroke Scale (NIHSS) scores were statistically decreased in both groups (P < 0.05) at 24 hours and 7 days after onset. There was no statistical difference in the modified Rankin score or mortality at day 90 after treatment between the two groups (P > 0.05). In conclusion, AIS patients who received rt-PA treatment between 4.5–6 hours after onset were similar in therapeutic efficacy to those who received rt-PA within 4.5 hours after onset. Our results suggest that intravenous thrombolytic therapy for AIS within 4.5–6 hours after onset is effective and safe.

The role of charged multivesicular body protein 5 in programmed cell death in leukemic cells

The Homo sapiens charged multivesicular body protein 5 (CHMP5) is a member of the multivesicular body, which serves as an anti-apoptotic protein and is thought to participate in leukemogenesis. In this study, a short-hairpin RNA-based RNA interference approach was used to inhibit the expression of CHMP5 in the leukemic cell line U937. After CHMP5 was inhibited, antibody microarray and western blot analysis were used to study the changes in the programmed cell death (PCD) pathway. PCD can be classified into three types: apoptosis, necrosis, and autophagy. Results showed that caspase 3 was activated in CHMP5-deficient U937 cells, indicating that the apoptotic pathway was activated, although neither the intrinsic nor the extrinsic apoptotic pathways were activated. Our results also showed that the Granzyme B/Perforin apoptotic pathway was activated by CHMP5 silencing. Necrosis is activated by caspase-independent executioners. In this study, we showed that the apoptosis-inducing protein-mediated necrotic PCD pathway is activated after CHMP5 inhibition. It was found that autophagic PCD did not occur in CHMP5-deficient U937 cells. In conclusion, after CHMP5 inhibition, both Granzyme B/Perforin apoptotic pathway and apoptosis-inducing factor-mediated necrotic pathway were activated, while autophagic pathway was not activated.

Mechanical thrombectomy by Solitaire stent for treating acute ischemic stroke: A prospective cohort study

BACKGROUND Acute ischemic stroke (AIS) is a worldwide serious health problem. Intravenous (IV) thrombolysis with recombinant tissue plasminogen activator (rt-PA) is the standard treatment; however, only a small number of patients benefit from it due to the strict application restrictions. Recently, more and more evidence prove mechanical thrombectomy is an effective and safe therapy of AIS. PATIENTS AND METHODS From December 2010 to March 2015, 83 patients who underwent mechanical thrombectomy were collected as a sample pool. All patients met the following criteria: National Institutes of Health Stroke Scale (NIHSS) score ≥10, treatment performed within 6 h from the onset of symptoms, no large hypodensity on CT or multimodal MRI, and angiography revealed occlusion of a major cerebral artery. Recanalization rates were assessed immediately post-procedure by follow-up angiography according to the thrombolysis in cerebral infarction score criteria. Assessment of the modified Rankin Scale was performed 90 days after treatment. RESULTS The mean age of patients was 63.3 years, and NIHSS scores 19.12 ± 4.60 at presentation. The vessel occlusions occurred in the middle cerebral artery (68.7%), distal internal carotid artery (7.2%), internal carotid artery with tandem middle cerebral artery occlusion (14.5%), basilar artery (2.4%), and vertebral artery (7.2%). Successful recanalization (TICI 3/2b) was achieved in 56 of 83 patients (67.5%). At 90-day follow-up, good clinical outcome (mRS ≤ 2) was achieved in 33 of 83 patients (39.8%), while 20 patients died (24.1%). CONCLUSIONS This study revealed mechanical thrombectomy with Solitaire stent device was an effective and safe therapy, which achieved a high rate of angiographic recanalization and independent outcome accompanied by a low mortality rate.

The relationship between coagulation abnormality and mortality in ICU patients: a prospective, observational study

We conducted a prospective, observational study to assess the prognostic value of hemostasis-related parameters in unselected ICU patients. We collected baseline characteristics from 497 consecutive unselected medical and trauma patients during their ICU stay. Each hemostasis-related parameter was analyzed alone or combined with APACHE II scores for any association with ICU mortality by calculating the under the curve (AUC) of the ROC curve, the net reclassification improvement (NRI) and integrated discrimination improvement (IDI) indices. Of all hemostasis-related indicators examined, the AUC for fibrin degradation products (FDPs) was less than that for APACHE II scores, but larger than that for disseminated intravascular coagulation (DIC) scores. The prediction power of FDPs is relatively low. Multiple regression analysis revealed that FDPs and APACHE II scores significantly predicted primary outcome. The combined use of FDPs level and APACHE II scores generated an NRI of 9.94% and an IDI of 3.54%. In conclusion, FDP is the best independent indicator of ICU mortality among all hemostasis-related indicators examined. The use of FDP level and APACHE II scores in parallel significantly improves the ability to predict ICU mortality, suggesting the application of these parameters could be used to improve patient care and management in the ICU.

IGF-1 protects tubular epithelial cells during injury via activation of ERK/MAPK signaling pathway

Injury of renal tubular epithelial cells can induce acute renal failure and obstructive nephropathy. Previous studies have shown that administration of insulin-like growth factor-1 (IGF-1) ameliorates the renal injury in a mouse unilateral ureteral obstruction (UUO) model, whereas the underlying mechanisms are not completely understood. Here, we addressed this question. We found that the administration of IGF-1 significantly reduced the severity of the renal fibrosis in UUO. By analyzing purified renal epithelial cells, we found that IGF-1 significantly reduced the apoptotic cell death of renal epithelial cells, seemingly through upregulation of anti-apoptotic protein Bcl-2, at protein but not mRNA level. Bioinformatics analyses and luciferase-reporter assay showed that miR-429 targeted the 3′-UTR of Bcl-2 mRNA to inhibit its protein translation in renal epithelial cells. Moreover, IGF-1 suppressed miR-429 to increase Bcl-2 in renal epithelial cells to improve survival after UUO. Furthermore, inhibition of ERK/MAPK signaling pathway in renal epithelial cells abolished the suppressive effects of IGF-1 on miR-429 activation, and then the enhanced effects on Bcl-2 in UUO. Thus, our data suggest that IGF-1 may protect renal tubular epithelial cells via activation of ERK/MAPK signaling pathway during renal injury.

Protective effects of ethyl pyruvate on lipopolysaccharide‑induced acute lung injury through inhibition of autophagy in neutrophils

Among a number of clinical factors, bacterial infection is one of the most common causes of acute lung injury (ALI), a serious complication that carries a high risk of mortality (~40%). During the process of ALI, intense local and systemic inflammation is elicited, which exacerbates the injury. Neutrophil infiltration into airspace is observed in early stage of ALI, and is required for the full development of ALI through an array of mechanisms, including the release of granule contents and the production of pro-inflammatory cytokines, due to the overactivation of complement and cytokines. The present study noted that ethyl pyruvate alleviated ALI in lipopolysaccharide (LPS)-induced ALI mice. Increased autophagy in neutrophils from ALI mice was observed, while ethyl pyruvate diminished autophagy in neutrophils and constrained granule release, and therefore myeloperoxidase (MPO) in bronchoalveolar lavage fluid and the production of proinflammatory cytokines. Using neutrophil cells, it was identified that autophagy was required for neutrophil activation and granule release, and that ethyl pyruvate caused neutrophil autophagy, leading to the restriction of granule release, and thus contributing to the mitigation of ALI. If autophagy was obviated through knockdown of key regulator of autophagy Atg5, the effects of ethyl pyruvate on granule release by neutrophils disappeared. Taken together, the results demonstrated that ethyl pyruvate alleviates ALI through inhibition of autophagy-induced granule release by neutrophils, and this mechanism suggested a novel potential therapeutic target in autophagy regulation for ALI.