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Background and Purpose: Hemorrhagic transformation (HT) has an adverse effect on the prognosis of patients with acute ischemic stroke, and it is currently known associated with coagulation system. But the conclusion is not consistent and remains to be identified. The aim of this study was to investigate the association between coagulation function and spontaneous hemorrhagic transformation. Methods: Patients within 7 days from the onset of ischemic stroke who did not receive reperfusion therapy (thrombolysis or endovascular treatment) were included between January 2016 and October 2017. Coagulation function indicators, including prothrombin time (PT), activated partial thromboplastin time (APTT), international normalized ratio (INR), thrombin time (TT) and fibrinogen (FIB), were tested within 24 h after admission. HT was defined as hemorrhage presented on follow-up magnetic resonance imaging (MRI) or computed tomography (CT) but not on baseline CT. We performed binary logistic regression to examine the association between coagulation function and HT. The coagulation indicators were entered into logistic regression analysis as continuous variables (per 1-unit/L increase) and four-categorized variables (with data collapsed into quartiles), respectively. Results: A total of 1141 patients were included (mean age, 64 ± 15 years; 63.7% males). 102 patients experienced HT (8.9%), of whom 14 patients experienced symptomatic HT (sHT, 1.2%). After adjustment for confounders, TT in the highest quartile is inversely associated with risk of HT (as continuous variable, odds ratio [OR] 0.85; 95% confidence level [CI] 0.73-0.99, P = 0.042; as four-categorized variable, OR 0.36, 95% CI 0.18 - 0.7, P = 0.003). Whether as continuous variables or four-categorized variables, PT, INR, APTT and FIB had no association with HT. Conclusion: Not the whole process of coagulation function is associated with spontaneous HT. Prolonged TT, which may indicate an extension of the last step of the coagulation process, is independently and inversely associated with spontaneous HT in patients with acute ischemic stroke.

Background and Purpose: Hemorrhagic transformation (HT) is a potentially serious complication in patients with acute ischemic stroke (AIS). Whether the ratio of low-density lipoprotein cholesterol to high-density lipoprotein cholesterol (LDL-C/HDL-C) is associated with HT remains unclear. Methods: Ischemic stroke patients within 7 days of stroke onset from January 2016 to November 2017 were included in this study. Lipid profiles were measured within 24h after admission. HT was determined by a second computed tomography or magnetic resonance imaging within 7 days after admission. Univariate and multivariate logistic regression analysis was used to assess the association between LDL-C/HDL-C and HT. Results: We enrolled 1239 patients with AIS (788 males; mean age, 64 ± 15 years), of whom 129 (10.4%) developed HT. LDL-C/HDL-C was significantly lower on admission in patients with HT than those without HT (2.00 ± 0.89 vs. 2.25 ± 1.02, P=0.009). The unadjusted odds ratio (OR) of low LDL-C/HDL-C for HT was 2.07 (95% confidence interval [CI] 1.42-3.01, P#156;0.001). After adjustment for possible confounders, lower LDL-C/HDL-C (≤1.52) was significantly associated with HT (OR 1.53, 95% CI: 1.02-2.31, P=0.046). Similar results were observed between lower LDL-C (≤ 4 mmol/L) and HT (OR 4.17, 95% CI: 1.25-13.90, P=0.02). However, no significant association was found between HT and high HDL-C, low triglycerides or low total cholesterol. Conclusion: Lower LDL-C/HDL-C and LDL-C were significantly associated with increased risk of HT after AIS. Further investigations are warranted to confirm these findings and then optimize lipid management in stroke patients with lower LDL/HDL-C or LDL-C.

Background and Purpose: Leukocyte is currently known as a potential risk factor for symptomatic intracranial hemorrhage after reperfusion therapy, but there is little evidence on whether leukocyte is associated with the overall risk of Hemorrhagic Transformation (HT) after Acute Ischemic Stroke (AIS). Methods: Patients within seven days after stroke onset were included between January 2016 and October 2017. The laboratory data were collected within 24 hours after admission. HT was defined as hemorrhage presented on follow-up magnetic resonance imaging or Computed Tomography (CT) but not on baseline CT. The univariate analysis and multivariate logistic regression were performed to assess the association of white blood cell, neutrophil, lymphocyte, Neutrophil-To- Lymphocyte Ratio (NLR) with HT. Then the relationship between their levels and HT in different stroke subtypes was further studied. Results: We included 1233 Chinese AIS patients (mean age 64.10 ±14.53 years; 63.5% male). HT occurred in 145 patients (11.8%). After adjusting for confounders, NLR (odds ratio [OR] 1.295, 95% Confidence Interval [CI] 1.085-1.546, P=0.004) was independently associated with HT. In stroke subtypes, NLR was found to be significantly related to HT in cardio-embolic stroke (OR 1.366, 95% CI 1.019-1.830, P=0.037) but showed no significance in large-artery atherosclerosis, small-artery occlusion and undetermined etiology. Conclusions: Higher level of NLR is associated with greater risk of hemorrhagic transformation in patients with acute ischemic stroke, especially in cardio-embolic stroke. Moreover, the results suggest that therapeutic interventions that may increase the risk of bleeding should be undertaken carefully in the management of AIS patients with higher NLR.

Inhibitor of growth 4 is a member of the inhibitor of growth family proteins, which is involved in cell apoptosis, migration, invasion, and cell cycle progress. In this study, we investigated the inhibitor of growth 4 level in non-small cell lung cancer tissues and explored the antitumor activity of inhibitor of growth 4 in vitroand in vivousing non-small cell lung cancer cell line SPC-A1 and its underlying molecular mechanisms. We also explored its role on the radiosensitivity in SPC-A1 cells. The level of inhibitor of growth 4 protein was significantly decreased in 28 cases of non-small cell lung cancer tissues in comparison with corresponding noncancerous lung epithelial tissues. Upregulation of inhibitor of growth 4 by plasmid pcDNA3.1-ING4 delivery could suppress proliferation and increase apoptosis of SPC-A1 cells both in vitroand in vivo. Additionally, we found that overexpression of inhibitor of growth 4 in SPC-A1 cell line could lead to a higher Bcl-2/Bax ratio, which might be an important factor in the apoptosis regulation. Furthermore, overexpression of inhibitor of growth 4 enhanced the radiosensitivity of SPC-A1 cells to irradiation. Inhibitor of growth 4 upregulation plus radiotherapy induced synergistic tumor suppression in SPC-A1 xenografts implanted in athymic nude mice. Thus, the restoration of inhibitor of growth 4 function might provide a potential strategy for non-small cell lung cancer radiosensitization.

Background and Purpose: Cerebral microbleeds (CMBs) are known to be potential risk factors for intracerebral hemorrhage (ICH), but there is controversy on the relationship between CMBs and hemorrhagic transformation (HT) after ischemic stroke. Besides, the question regarding whether the relationship between CMBs and HT can be affected by antithrombotic drugs in acute stage of ischemic stroke has not yet reached a consensus. Methods: 174 acute ischemic stroke patients with atrial fibrillation (AF) and/or rheumatic heart disease (RHD) were prospectively and consecutively enrolled in the study, of which 160 patients (mean 68.09 ±12.59 years) were finally included in the final analysis (West China Hospital, Sichuan University, n=125; People’s Hospital of Deyang City, n=35).We assessed the presence, location and number of CMBs by using susceptibility-weighted imaging (SWI) within 7 days after admission, and the incidence of hemorrhagic transformation was evaluated by magnetic resonance imaging(MRI) during hospitalization. The univariate and multivariate analyses were used to analyze the relationship between CMBs and HT. Results: CMBs were detected in 90 patients (56.3%). HT was found in 62 (38.8%) patients, among which 43 were hemorrhagic infarction (HI) and 19 were parenchymal haemorrhage (PH). The presence of CMBs was not significantly different among different HT subtypes (no HT, HI and PH; 59.2%, 51.2%, versus 52.6%, P=0.64). There was no relationship between the number/location of CMBs and hemorrhagic transformation subtypes (P=0.38). In the 2 subgroups of patients treated with anticoagulants and antiplatelets after admission, the incidence of HT was not significantly different between patients with and without CMBs (anticoagulants, 13.3% versus 18.2%, P=0.71; antiplatelets, 29.2% versus 40.3%, P= 0.21). Conclusion: The present study suggests that CMBs do not predict the presence of hemorrhagic transformation in acute ischemic stroke patients with AF and/or RHD. The results were not affected by anticoagulant or antiplatelet agents used in acute stage of ischemic stroke.

Recently, the non-protein-coding functional elements in the human genome have been identified as key regulators in postgenomic biology, and a large number of pseudogenes as well as long non-coding RNAs (lncRNAs) have been found to be transcribed in multiple human cancers. However, only a small proportion of these pseudogenes has been functionally characterized. In this study, we screened for pseudogenes associated with human non-small-cell lung cancer (NSCLC) by comparative analysis of several independent datasets from the GEO. We identified a transcribed pseudogene named DUXAP8 that is upregulated in tumor tissues. Patients with higher DUXAP8 expression exhibited shorter survival, suggesting DUXAP8 as a new candidate prognostic marker for NSCLC patients. Knockdown of DUXAP8 impairs cell growth, migration, and invasion, and induces apoptosis both in vitro and in vivo. Mechanistically, DUXAP8 represses the tumor suppressors EGR1 and RHOB by recruiting histone demethylase LSD1 and histone methyltransferase EZH2, thereby promoting cell proliferation, migration, and invasion. These findings indicate that the pseudogene DUXAP8 may act as an oncogene in NSCLC by silencing EGR1 and RHOB transcription by binding with EZH2 and LSD1, which may offer a novel therapeutic target for this disease.

Elevated alkaline phosphatase (ALP) levels are associated with cerebral small vascular diseases, such as silent brain infarction and cerebral white matter hyperintensity (cWMH), but few prospective data are available for cerebral microbleeds (CMBs). The aim of the study was to investigate associations between serum ALP levels and CMBs in acute ischemic stroke patients with atrial fibrillation and/or rheumatic heart disease. This prospective study involved consecutively recruited acute ischemic stroke patients with atrial fibrillation and/or rheumatic heart disease treated at two large tertiary care hospitals in southwestern China. We used logistic regression to examine the relationships between ALP levels and CMBs. Of 128 patients (56 males; mean age, 68 years) included, 71 (55.5%) patients had CMBs. Compared with the first tertile of ALP concentration, participants in the third tertile were 3.59 times more likely to have multi-CMBs (≥2) [95% confidence interval (CI): 1.21-10.71; P = 0.02] after adjusting for age, gender, smoking habits, drinking habits, ALT (alanine transaminase) levels, AST (aspartate transaminase) levels, renal impairment and cWMH.