Insulin-like growth factor binding protein-1 regulates HIF-1α degradation to inhibit apoptosis in hypoxic cardiomyocytes.

Hypoxia is important in ischemic heart disease. Excessive Insulin-like growth factor binding protein-1 (IGFBP-1) amounts are considered to harm cardiomyocytes in acute myocardial infarction. However, the mechanisms by which IGFBP-1 affects cardiomyocytes remain undefined. The present study demonstrated that hypoxia up-regulates IGFBP-1 and HIF-1α protein expression in cardiomyocytes. Subsequent assays showed that IGFBP-1 suppression decreased HIF-1α expression and inhibited hypoxia-induced apoptosis in cardiomyocytes, which was reversed by HIF-1α overexpression, indicating that HIF-1α is essential to IGFBP-1 function in cellular apoptosis. In addition, we showed that IGFBP-1 regulated HIF-1α stabilization through interacting with VHL. The present findings suggest that IGFBP-1-HIF-1α could be targeted for treating ischemic heart disease.

[Construction of sepsis-associated competing endogenous RNA network based on Gene Expression Omnibus datasets and bioinformatic analysis].

OBJECTIVE: To analyze the sepsis related long non-coding RNA (lncRNA) and mRNA expression profiles based on Gene Expression Omnibus (GEO) datasets and bioinformatic analysis, and to analyze the sepsis-associated competing endogenous RNA (ceRNA) network based on microRNA (miRNA) database. METHODS: The sepsis-related lncRNA dataset was downloaded from the GEO database, and the differential expression analysis was conducted by Bioconductor on the sepsis dataset to obtain differentially expressed lncRNA (DElncRNA) and differentially expressed mRNA (DEmRNA), and cluster heat map was drawn. miRNA combined with DElncRNA were predicted by miRcode. mRNA targeted by miRNA was simultaneously met by three databases: TargetScan, miRDB, and mirTarBase. The interaction relationship of lncRNA-miRNA-mRNA was obtained. The regulatory network visualization software CytoScape was used to draw ceRNA networks. DEmRNA in the ceRNA networks were imported into the Search Tool for the Retrieval of Interacting Genes Database (STRING) online database to draw the protein-protein interaction (PPI) map. The gene ontology (GO) function annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis of DEmRNA were performed. RESULTS: Dataset GSE89376 and GSE145227 were found from GEO database. Difference analysis showed there were 14 DElncRNA and 359 DEmRNA in the elderly group of GSE89376; 8 DElncRNA and 153 DEmRNA in the adult group of GSE89376; 1 232 DElncRNA and 1 224 DEmRNA in the children group of GSE145227. Clustering heatmap showed that there were significant differences in the expression of lncRNA and mRNA between the sepsis group and the control group. The ceRNA networks were constructed with miRNA. Several DElncRNA and multiple DEmRNA participated in the ceRNA network of sepsis. The PPI diagram demonstrated that several genes encoding proteins interacted with each other and form a multi-node interaction network with multiple genes encoding proteins. Functional annotation and enrichment analysis demonstrated that there might be a crosstalk mechanism on functionally related genes such as nuclear receptor activity, ligand-activated transcription factor activity, and steroid hormone receptor activity, and played a role in the occurrence and development of diseases through forkhead box transcription factor O (FoxO) signaling pathway, Janus kinase/signal transducers and activators of transcription (JAK/STAT) signaling pathway, p53 signaling pathway, and phosphateidylinositol 3-kinase (PI3K)/Akt signaling pathway. CONCLUSIONS: Through sepsis-related lncRNA-miRNA-mRNA ceRNA network and combining with KEGG pathway analysis, there were several lncRNA and mRNA participating in the ceRNA network related sepsis, which played an important role in several signal pathways.

Derivation of a Prediction Rule for Unfavorable Outcome after Ischemic Stroke in the Chinese Population.

BACKGROUND: Efficient assessment of patients after ischemic stroke has important reference value for doctors to choose appropriate treatment for patients. Our study aimed to develop a new prognostic model for predicting outcomes 3 months after ischemic stroke among Chinese Population. METHODS: A prospective observational cohort study among ischemic stroke patients presenting to Emergency Department in the Second Affiliated Hospital of Guangzhou Medical University was conducted from May 2012 to June 2013. Demographic data of ischemic stroke patients, assessment of NIHSS and laboratory results were collected. Based on 3-month modified Rankin Scale (mRS) ischemic stroke patients were divided into either favorable outcome (mRS: 0-2) or unfavorable outcome groups (mRS: 3-6). The variables closely associated with prognosis of ischemic stroke were selected to develop the new prognostic model (NAAP) consisted of 4 parameters: NIHSS, age, atrial fibrillation, and prealbumin. The prognostic value of the modified prognostic model was then compared with NIHSS alone. RESULTS: A total of 454 patients with suspected stroke were recruited. One hundred eighty-six patients with ischemic stroke were included in the final analysis. A new prognostic model, NAAP was developed. The area under curve (AUC) of NAAP was .861 (95%confidence interval: .803-.907), whilst the AUC of NIHSS was .783 (95%CI: .717-.840), (P = .0048). Decision curve analysis showed that NAAP had a higher net benefit for threshold probabilities of 65% for predictive risk of poor outcomes. CONCLUSIONS: The modified prognostic model, NAAP may be a better prognostic tool for predicting 3-month unfavorable outcomes for ischemic stroke than NIHSS alone.

Comparison of outcomes in emergency department patients with suspected cardiac chest pain: two-centre prospective observational study in Southern China.

BACKGROUND: Hong Kong (HK) and Guangzhou (GZ) are cities in China with different healthcare systems. This study aimed to compare 30-day and 6-month mortality and characteristics of patients with suspected cardiac chest pain admitted to two emergency departments (ED) in HK and GZ. METHODS: A prospective observational study enrolled patients with suspected cardiac chest pain presenting to EDs in the Prince of Wales Hospital (PWH), HK and the Second Affiliated Hospital of Guangzhou Medical University (AHGZMU),GZ. The primary outcome was 30-day and 6-month mortality. RESULTS: In total, 996 patients were recruited, 407 cases from GZ and 589 cases from HK.The 30-day and 6-month mortality of chest patients were 3.7% and 4.7% in GZand 0.3% and 1.9% in HK, respectively. Serum creatinine level (Cr) was an independent factor for 30-day mortality whilst Cr and systolic blood pressure (SBP) were independent factors for 6-month mortality. In Cox regression analysis, unadjusted and adjusted hazard ratios for 30-day and 6-month mortality in GZ were significantly increased. CONCLUSION: The 30-day and 6-month mortality of patients with suspected cardiac chest pain in Guangzhou were higher than in Hong Kong due to due to different baseline clinical characteristics of patients and different distributions of diagnoses, which were associated with different healthcare systems. Serum creatinine and SBP were independent factors for 30-day and 6-month mortality.

Gestalt for shock and mortality in the emergency department: A prospective study.

OBJECTIVE: The diagnosis of shock in patients presenting to the emergency department (ED) is often challenging. We aimed to compare the accuracy of experienced emergency physician gestalt against Li's pragmatic shock (LiPS) tool for predicting the likelihood of shock in the emergency department, using 30-day mortality as an objective standard. METHOD: In a prospective observational study conducted in an urban, academic ED in Hong Kong, adult patients aged 18years or older admitted to the resuscitation room or high dependency unit were recruited. Eligible patients had a standard ED workup for shock. The emergency physician treating the patient was asked whether he or she considered shock to be probable, and this was compared with LiPS. The proxy 'gold' or reference standard was 30-day mortality. The area under the receiver operating curve (AUROC) was used to predict prognosis. The primary outcome measure was 30-day mortality. RESULTS: A total of 220 patients fulfilled the inclusion criteria and were included in the analysis. The AUROC for LiPS (0.722; sensitivity=0.733, specificity=0.711, P<0.0001) was greater than emergency physician gestalt (0.620, sensitivity=0.467, specificity=0.774, P=0.0137) for diagnosing shock using 30-day mortality as a proxy (difference P=0.0229). LiPS shock patients were 6.750 times (95%CI=2.834-16.076, P<0.0001) more likely to die within 30-days compared with non-shock patients. Patients diagnosed by emergency physicians were 2.991 times (95%CI=1.353-6.615, P=0.007) more likely to die compared with the same reference. CONCLUSIONS: LiPS has a higher diagnostic accuracy than emergency physician gestalt for shock when compared against an outcome of 30-day mortality.

Prognostic values of 4 risk scores in Chinese patients with chest pain: Prospective 2-centre cohort study.

Four risk scores for stratifying patients with chest pain presenting to emergency departments (EDs) (namely Thrombolysis in myocardial infarction [TIMI], Global registry for acute coronary events [GRACE], Banach and HEART) have been developed in Western settings but have never been compared and validated in Chinese patients. We aimed to find out to the number of MACE within 7 days, 30 days, and 6 months after initial ED presentation, and also to compare the prognostic performance of these scores in Chinese patients with suspected cardiac chest pain (CCP) to predict 7-day, 30-day, and 6-month major adverse cardiac events (MACE).A prospective 2-center observational cohort study of consecutive patients presenting with chest pain to the EDs of 2 university hospitals in Guangdong and Hong Kong from 17 March 2012 to 14 August 2013 was conducted. Patients aged ≥18 years with suspected CCP but without ST-segment elevation myocardial infarction (STEMI) were recruited.Of 833 enrolled patients (mean age 65.1 years, SD14.5; 55.6% males), 121 (14.5%) experienced MACE within 6 months (4.8% with safety outcomes and 10.3% with effectiveness outcomes). The HEART score had the largest area under the receiver operating characteristic (ROC) curve for predicting MACE at 7-day, 30-day, and 6-month follow-up [area under curve (AUC) = 0.731, 0.726, and 0.747, respectively. The HEART score also had the largest AUC for predicting effectiveness outcome (AUC = 0.715, 0.704, and 0.721, respectively). However, there was no significant difference in AUC between HEART and TIMI scores. Banach had the largest AUC for predicting safety outcome (AUC = 0.856, 0.837, and 0.850, respectively).The HEART score performed better than the GRACE and Banach scores to predict total MACE and effectiveness outcome in Chinese patients with suspected CCP, whereas the Banach score best predicted safety outcomes.

Development of a new stroke scale in an emergency setting.

BACKGROUND: Early identification of stroke is crucial to maximize early management benefits in emergency departments. This study aimed to develop and validate a new stroke recognition instrument for differentiating acute stroke from stroke mimics in an emergency setting. METHODS: A prospective observational cohort study among suspected stroke patients presenting to Emergency Department in the Second Affiliated Hospital of Guangzhou Medical University was conducted from May 2012 to March 2013. The symptoms and signs of suspected stroke patients were collected. Logistic regression analysis was used to identify the factors associated with acute stroke. The symptoms and signs closely associated with acute stroke were selected to develop the new stroke scale, Guangzhou Stroke Scale (GZSS). The diagnostic value of GZSS was then compared with ROSIER, FAST and LAPSS. The primary outcome was confirmed stroke by CT within 24 h. RESULTS: Four hundred and sixteen suspected stroke patients (247 ischemia, 107 hemorrhage, 4 transient ischemic attack, 58 non-stroke) were assessed. A new stroke scale, GZSS (total score from -1 to 8.5), was developed and consisted of nine parameters: vertigo (-1), GCS ≤ 8 (+2), facial paralysis (+1), asymmetric arm weakness (+1), asymmetric leg weakness (+1), speech disturbance (+0.5), visual field defect (+1), systolic blood pressure ≥145 mmHg (+1) and diastolic blood pressure ≥95 mmHg (+1). Among the four scales, the discriminatory value (C-statistic) of GZSS was the best (AUC: 0.871 (p < 0.001) when compared to ROSIER (0.772), LAPSS (0.722) and FAST (0.699). At an optimal cut-off score of >1.5 on a scale from -1 to 8.5, the sensitivity and specificity of GZSS were 83.2 and 74.1 %, whilst the sensitivities and specificities of ROSIER were 77.7 and 70.7 %, FAST were 76.0 and 63.8 %, LAPSS were 56.4 and 87.9 %. CONCLUSION: GZSS had better sensitivity than existing stroke scales in Chinese patients with suspected stroke. Further studies should be conducted to confirm its effectiveness in the initial differentiation of acute stroke from stroke mimics.

STEMI Outcomes in Guangzhou and Hong Kong: Two-Centre Retrospective Interregional Study.

BACKGROUND AND OBJECTIVES: Healthcare systems are organized very differently in Hong Kong (HK) and Guangzhou (GZ). This study compared managements of the emergency departments (ED) and one-year mortalities of ST-segment elevation myocardial infarction (STEMI) patients in two teaching hospitals in Guangzhou and Hong Kong. METHODS: Retrospective observational study of STEMI mortalities and treatments in the Prince of Wales Hospital (PWH) and the Second Affiliated Hospital of Guangzhou Medical University (AHGZMU), was conducted between January and December 2010. The primary outcome was one-year all cause mortality. RESULTS: Univariate analysis of 76 cases from PWH and 111 cases from AHGZMU showed similar clinical characteristics, except for lower proportions of males (74% vs 92%, P = 0.002), hyperlipidemia (5% vs 25%, P<0.001), and Killip class I (56% vs 91%; P<0.001) in AHGZMU. The onset-to-door time of STEMI patients in AHGZMU was longer than in PWH (median 205 min [(IQR: 95-432) vs 120 min (IQR: 55-225), P = 0.001]. In AHGZMU, 85 (77%) patients received primary percutaneous coronary intervention (PPCI) as the main reperfusion treatment, whereas 18 (24%) received PPCI and 51 (67%) patients received thrombolytic therapy in PWH. Overall the one-year mortality in AHGZMU was 20%, whilst in PWH it was 14% (P = 0.436). The standardized one-year all-cause mortality ratios for AHGZMU and PWH were comparable (18.7 vs. 18.2%, P = 0894). Independent predictors of one-year mortality included older age (>67 years) and hyperglycemia (>10 mmol/L). Aged over 65 years, presence of anterior wall infarct, body weight ≤65 kg, SBP <100 mmHg at ED and glucose level >10 mmol/L were the independent predictors of in-hospital MACE. CONCLUSION: There was no statistically significant difference between the standardized one-year all-cause mortalities of STEMI patients in the setting mainly using thrombolysis with shorter door-to-treatment time and the setting mainly using PCI with longer door-to-treatment time. Aged over 67 years and glucose level over 10 mmol/L were the independent predictors of one-year mortality. Older age, presence of anterior wall infarct, lower body weight, lower SBP at ED and hyperglycemia were the independent predictors of in-hospital MACE.

Extensive serum biomarker analysis in patients with ST segment elevation myocardial infarction (STEMI).

ST segment elevation myocardial infarction (STEMI) is one of the leading causes of morbidity and mortality and some characteristics of STEMI are poorly understood. The aim of the present study is to detect protein expression profiles in the serum of STEMI patients, and to identify biomarkers for this disease. Cytokine profiles of serum from STEMI patients and healthy controls were analyzed with a semi-quantitative human antibody array for 174 proteins, and the results showed blood serum concentrations of 21 cytokines differed considerably between STEMI patients and healthy subjects. In the next phase, a sandwich ELISA kit individually validated eight biomarker results from 21 of the microarray experiments. Clinical validation demonstrated a significant increase of BNDF, PDGF-AA and MMP-9 in patients with AMI. Meanwhile, BNDF, PDGF-AA and MMP-9 distinguished AMI patients from healthy controls with a mean area under the receiver operating characteristic (ROC) curves of 0.870, 0.885, and 0.81, respectively, with diagnostic cut-off points of 0.688 ng/mL, 297.86 ng/mL and 690.066 ng/mL. Our study indicated that these three cytokines were up-regulated in STEMI samples, and may hold promise for the assessment of STEMI.

Hemodynamic measurements for evaluating vasovagal syncope in the emergency department.

Syncope is a sudden and transient loss of consciousness and postural tone, with spontaneous recovery without medical intervention. It accounts for 1.0% to 1.5% of emergency department (ED) visits and up to 6% of hospital admissions. Vasovagal syncope may be the cause of syncope in 21% to 40% of cases. A 53-year-old Chinese woman was brought to the ED by ambulance after a near-syncope episode while performing gentle morning exercises. She was hypotensive and bradycardic in the ambulance. Upon arrival at the ED, her blood pressure was 89/61 mmHg. The use of a Doppler cardiac output monitor readily demonstrated that the patient's systemic vascular resistance was reduced, with cardiac output at the lower limit of the normal range. These hemodynamic data were useful in supporting the diagnosis of vasovagal syncope; they helped in the risk stratification of our patient with syncope, and guided the management and subsequent disposition decision.