Fibrinolytic therapy use for ST-segment elevation myocardial infarction and long-term outcomes in China: 2-year results from the China Acute Myocardial Infarction Registry.

BACKGROUND: Data on fibrinolytic therapy use for ST-segment elevation myocardial infarction (STEMI) and long-term clinical outcomes in developing countries are limited. We aimed to investigate the management and 2-year mortality of fibrinolytic-treated patients in China. METHODS: A total of 19,112 patients with STEMI from 108 hospitals participated in the China Acute Myocardial Infarction registry between January 2013 and September 2014. We investigated the 2-year all-cause mortality among patients treated with fibrinolysis. Non-invasive clinical indexes were used to diagnose successful fibrinolysis or not. RESULTS: Only 1823 patients (9.5%) enrolled in the registry underwent fibrinolysis and 679 (37.2%) could be treated within 3 h after symptom onset. The overall use of rescue percutaneous coronary intervention was 8.9%. Successful fibrinolysis, which could be achieved in 1428 patients (78.3%), was related to types of fibrinolytic agents, symptom to needle time, infarction site, and Killip class. Follow-up data were available for 1745 patients (95.7%). After multivariate adjustment, successful fibrinolysis was strongly associated with a decreased risk of death compared with failed fibrinolysis at 2 years (8.5% vs. 29.0%, hazard ratio: 0.27, 95% confidence interval: 0.20-0.35). CONCLUSION: Within a minority of STEMI patients in the CAMI registry underwent fibrinolysis, most of them could achieve successful clinical reperfusion, presenting a much benign 2-year survival outcome than those with failed fibrinolysis. Quality improvement initiatives focusing on fibrinolysis are warranted to achieve its promise fully. TRIAL REGISTRATION: URL: https// www. CLINICALTRIALS: gov . Unique identifier: NCT01874691. Registered 11/06/2013.

Orbital solitary fibrous tumours: clinicopathological characteristics and recurrence prediction.

BACKGROUND: SFTs are thought to have an unpredictable clinical course and currently have no recognized prognostic criterion. Our study aimed to determine the relationship between clinicopathological characteristics and the prognosis of patients with orbital SFTs. METHODS: The clinicopathological features of these patients were extracted from clinical records. The relationships between these features and prognosis were analysed. RESULTS: The positive rates of CD34, CD99, Blc2, and STAT6 expression were 90.3%, 90.3%, 83.9%, and 100%, respectively. The tumour recurrence rate was 38.7%. A higher recurrence rate was observed in patients with Ki67 index ≥ 5 (56.25% vs. 20%, P = 0.038). CONCLUSION: A Ki67 index ≥ 5 was an effective parameter for predicting tumour recurrence of orbital SFTs. Close follow-up is needed for these patients.

Number of standard modifiable risk factors and mortality in patients with first-presentation ST-segment elevation myocardial infarction: insights from China Acute Myocardial Infarction registry.

BACKGROUND: Recent publications reported a paradoxical finding that there was an inverse association between the number of standard modifiable risk factors (SMuRFs; smoking, hypertension, diabetes, and hyperlipidemia) and mortality in patients with myocardial infarction. However, the current evidence is only limited to those highly developed countries with advanced medical management systems. METHODS: The China Acute Myocardial Infarction registry is a prospective observational study including patients with acute myocardial infarction from three-level hospitals across 31 administrative regions throughout mainland China. A total of 16,228 patients with first-presentation ST-elevation myocardial infarction (STEMI) admitted to hospitals from January 2013 to September 2014 were enrolled in the current analysis. Cox proportional hazard models adjusting for baseline characteristics, clinical profiles at presentation, and in-hospital treatments were used to assess the association of the number of SMuRFs with all-cause mortality at 30 days after STEMI presentation. RESULTS: A total of 1918 (11.8%), 11,503 (70.9%), and 2807 (17.3%) patients had 0, 1-2, and 3-4 SMuRFs at presentation, respectively. Patients with fewer SMuRFs were older and more likely to be females, experienced longer pre-hospital delays, and were less likely to receive primary percutaneous coronary intervention and evidence-based medications. Compared with those without any SMuRF, patients with 1-2 SMuRFs and 3-4 SMuRFs were associated with an HR of 0.74 (95% CI, 0.63-0.87) and 0.63 (0.51-0.77) for all-cause mortality up to 30 days in the unadjusted model (Ptrend < 0.0001). However, after multivariate adjustment, the number of SMuRFs was positively associated with increased mortality risk (HR for 1-2 SMuRFs, 1.15 [0.95-1.39]; HR for 3-4 SMuRFs, 1.31 [1.02-1.68]; Ptrend = 0.03), and the association was only significant among patients admitted to hospitals beyond 12 h from onset (HR for 1-2 SMuRFs, 1.39 [1.03-1.87]; HR for 3-4 SMuRFs, 2.06 [1.41-3.01]) but not their counterparts (Pinteraction = 0.01). CONCLUSIONS: The increased crude mortality risk among patients without SMuRFs is explained by confounding factors related to their poor risk profiles (old age, longer pre-hospital delays, and poor clinical management). After multivariate adjustment, a higher risk-factor burden was associated with poor prognosis among patients with STEMI.

De-escalation of Dual Antiplatelet Therapy After Percutaneous Coronary Intervention in Patients With Acute Coronary Syndrome: An Updated Meta-analysis and Trial Sequential Analysis of 21 Studies and 38,741 Patients.

ABSTRACT: Dual antiplatelet therapy (DAPT) is recommended among patients with established acute coronary syndrome. In this meta-analysis, we sought to compare the clinical outcomes between de-escalation versus unchanged DAPT based on both randomized controlled trials (RCTs) and observational studies. The primary outcomes were major adverse cardiovascular events for observational studies and net clinical events for RCTs. Four RCTs and 17 observational studies with a total of 38,741 patients were included. Net clinical events were more common with unchanged DAPT than with de-escalation in RCTs [odd ratio (OR): 1.71; 95% confidence interval (CI), 1.21-2.43; I2 = 69.4%], which was mainly due to higher risks of any bleeding (OR: 1.81; 95% CI, 1.14-2.88; I2 = 75.5%) and major bleeding (OR: 1.58; 95% CI, 1.02-2.46; I2 = 0), without significant differences in ischaemic events. However, trial sequential analysis revealed that sufficient information was obtained just for net clinical events, not for respective ischaemic or bleeding events in RCTs. In the analysis based on real-world observational studies, the risks of myocardial infarction (OR: 0.77; 95% CI, 0.61-0.98; I2 = 0) and stroke (OR: 0.42; 95% CI, 0.22-0.81; I2 = 0) were lower with the unchanged DAPT group. Therefore, de-escalation of DAPT led to a marked reduction in net clinical events compared with unchanged DAPT in RCTs, which was mainly due to reduced bleeding events. However, sufficient information for ischaemic events was not obtained. In the analysis based on real-world observational studies, myocardial infarction and stroke were more common with de-escalation, which should arise our attention.

Beta-Blocker Use after Discharge in Patients with Acute Myocardial Infarction in the Contemporary Reperfusion Era.

Background and objectives: The effect of beta-blocker use after discharge on patients with acute myocardial infarction (AMI) in the contemporary reperfusion era remains ambiguous. By applying meta-analysis, we sought to assess the role of beta-blockers in the contemporary reperfusion era. Materials and Methods: Randomized controlled trials (RCT) and observational studies using propensity score matching, comparing use of beta-blockers with non-use of beta-blockers, in patients with AMI after discharge. The primary outcome was all-cause mortality. Odds ratios (OR) and associated 95% confidence intervals (CI) were calculated. Results: One RCT and eight observational studies, containing 47,339 patients with AMI, were included. Compared with non-use of beta-blockers, beta-blocker use after discharge may have reduced the risk of all-cause mortality (OR: 0.70, 95% CI: 0.61 to 0.80, I2 = 14.4%), cardiac death (OR: 0.63, 95% CI: 0.44 to 0.91, I2 = 22.8%), myocardial infarction (OR: 0.73, 95% CI: 0.62 to 0.86, I2 = 0), and revascularization (OR: 0.92, 95% CI: 0.85 to 0.99, I2 = 0). No significant differences were found in major adverse cardiovascular events (MACE, OR: 0.88, 95% CI: 0.66 to 1.17, I2 = 78.4%), heart failure (OR: 0.56, 95% CI: 0.29 to 1.08, I2 = 0) or stroke (OR: 1.13, 95% CI: 0.92 to 1.39, I2 = 0). For patients with preserved left ventricular function, beta-blocker use after discharge may have also reduced the risk of all-cause mortality (OR: 0.61, 95% CI: 0.44 to 0.84, I2 = 0). Conclusions: Use of beta-blockers after discharge may still be beneficial for AMI patients in the contemporary reperfusion era, with or without preserved left ventricular function.

China Tongxinluo Study for myocardial protection in patients with Acute Myocardial Infarction (CTS-AMI): Rationale and design of a randomized, double-blind, placebo-controlled, multicenter clinical trial.

Acute ST-segment elevation myocardial infarction (STEMI) remains a serious life-threatening event. Despite coronary revascularization, patients might still suffer from poor outcomes caused by myocardial no-reflow and ischemic/reperfusion injury. Tongxinluo (TXL), a traditional Chinese medicine, has been preliminarily demonstrated to reduce myocardial no-reflow and ischemic/reperfusion injury. We further hypothesize that TXL treatment is also effective in reducing clinical end points for the patients with STEMI. METHODS AND RESULTS: The CTS-AMI trial is a prospective, randomized, double-blind, placebo-controlled, multicenter clinical study in China. An estimated 3,796 eligible patients with STEMI from about 120 centers are randomized 1:1 ratio to TXL or placebo groups. All enrolled patients are orally administrated a loading dose of 8 capsules of TXL or placebo together with dual antiplatelet agents on admission followed by 4 capsules 3 times a day until 12 months. The primary end point is 30-day major adverse cardiovascular and cerebrovascular events, a composite of cardiac death, myocardial reinfarction, emergency coronary revascularization, and stroke. Secondary end points include each component of the primary end point, 1-year major adverse cardiovascular and cerebrovascular events, and other efficacy and safety parameters. CONCLUSIONS: Results of CTS-AMI trial will determine the clinical efficacy and safety of traditional Chinese medicine TXL capsule in the treatment of STEMI patients in the reperfusion era.

The relationship between ß1 -adrenergic and M2 -muscarinic receptor autoantibodies and hypertrophic cardiomyopathy.

NEW FINDINGS: What is the central question of this study? The concentrations of ß1 -adrenergic receptor and M2 -muscarinic receptor autoantibodies in hypertrophic cardiomyopathy (HCM) patients and the relationship between the cardiac autoantibodies and clinical manifestations of HCM have rarely been reported. What is the main finding and its importance? We found that the concentrations of the two autoantibodies in HCM patients were significantly higher than those in control subjects. Furthermore, we found that the concentrations of the two autoantibodies could reflect myocardial injury and diastolic dysfunction in HCM patients to some extent and might be involved in the occurrence of arrhythmia. These findings might be valuable in exploration of the mechanisms of occurrence and progression of HCM. ABSTRACT: Increasing attention is being given to the role of immunological mechanisms in the development of heart failure. The purpose of this study was to investigate the concentration of serum ß1 -adrenergic receptor autoantibody (ß1 -AAb) and M2 -muscarinic receptor autoantibody (M2 -AAb) in patients with hypertrophic cardiomyopathy (HCM), and the relationship between ß1 -AAb, M2 -AAb and clinical indices. One hundred and thirty-four patients with HCM were recruited consecutively into the HCM group. Forty healthy subjects were assigned as the normal controls (NCs). Serum samples were collected to measure the concentrations of ß1 -AAb and M2 -AAb by enzyme-linked immunosorbent assay. The clinical data of HCM patients were collected. The serum concentrations of ß1 -AAb and M2 -AAb of HCM patients were significantly higher than those of NCs. In HCM patients, those with a left atrial diameter ≥50 mm or moderate-to-severe mitral regurgitation had significantly higher concentrations of the two autoantibodies. Patients with a history of syncope had higher concentrations of ß1 -AAb. Female patients and patients with a family history of sudden cardiac death or atrial fibrillation had higher concentrations of M2 -AAb. Maximal wall thickness, interventricular septum thickness and resting left ventricular outflow tract gradient were positively correlated with log ß1 -AAb or log M2 -AAb in HCM patients. In conclusion, the serum concentrations of ß1 -AAb and M2 -AAb of HCM patients were significantly higher than those of NCs. Being female, syncope, a family history of sudden death, atrial fibrillation, left atrial diameter ≥50 mm, moderate-to-severe mitral regurgitation, maximal wall thickness, interventricular septum thickness and resting left ventricular outflow tract gradient may affect the concentrations of the two autoantibodies.

A Practical Risk Score to Predict 24-Month Post-Discharge Mortality Risk in Patients With Non-ST-Segment Elevation Myocardial Infarction.

BACKGROUND: Risk stratification of patients with non-ST-segment elevation myocardial infarction (NSTEMI) is important in terms of treatment strategy selection. Current efforts have focused on short-term risk prediction after discharge, but we aimed to establish a risk score to predict the 24-month mortality risk in survivors of NSTEMI.Methods and Results:A total of 5,509 patients diagnosed with NSTEMI between January 2013 and September 2014 were included. Primary endpoint was all-cause death at 24 months. A multivariable Cox regression model was used to establish a practical risk score based on independent risk factors of death. The risk score included 9 variables: age, body mass index, left ventricular ejection fraction, reperfusion therapy during hospitalization, Killip classification, prescription of diuretics at discharge, heart rate, and hemoglobin and creatinine levels. The C-statistics for the risk model were 0.83 (95% confidence interval [CI]: 0.81-0.85) and 0.83 (95% CI: 0.79-0.86) in the development and validation cohorts, respectively. Mortality risk increased significantly across groups: 1.34% in the low-risk group (score: 0-58), 5.40% in intermediate group (score: 59-93), and 23.87% in high-risk group (score: ≥94). CONCLUSIONS: The current study established and validated a practical risk score based on 9 variables to predict 24-month mortality risk in patients who survive NSTEMI. This score could help identify patients who are at high risk for future adverse events who may benefit from good adherence to guideline-recommended secondary prevention treatment.

Contemporary invasive management and in-hospital outcomes of patients with non-ST-segment elevation myocardial infarction in China: Findings from China Acute Myocardial Infarction (CAMI) Registry.

BACKGROUND: Few studies have investigated the use of invasive strategy for patients with non-ST-segment elevation myocardial infarction (NSTEMI) in China. We aimed to describe the contemporary pattern of management, medically and invasively, in patients with NSTEMI across China. METHODS: Using data of China Acute Myocardial Infarction Registry, we analyzed the baseline characteristics, in-hospital medication, index coronary angiography (CAG) and revascularization by stratification of gender, age, and risk assessment. Primary outcomes included in-hospital major adverse cardio-cerebral events (MACCE, a composite of all-cause death, myocardial (re)infarction, and stroke) and length of stay (LOS). RESULTS: A total of 10,266 NSTEMI patients were enrolled between January 2013 and November 2016. Dual antiplatelet therapy and statins were prescribed in 92.9% and 92.1% of overall patients respectively. CAG was performed in 45.6% of these patients, and 40.9% had an index revascularization. Female, older or higher risk patients were less likely to receive CAG or revascularization. The rates of CAG were 67.9% in the provincial-level, 46.2% in the prefectural, and 12.1% in the county-level hospitals. Of those patients undergoing revascularization, 77.0% (1,156/1,501) very-high-risk patients received urgent revascularization and 16.2% (440/2,699) high-risk patients underwent early revascularization as recommended. The overall in-hospital MACCE was 6.7%, and the median LOS was 10 (6) days. Revascularization was associated with reduction for in-hospital MACCE regardless of risk and age. CONCLUSION: Invasive management was underused and profoundly deferred among patients with NSTEMI in China. The risk-treatment paradox, procedure deferral and medical resources distribution imbalance may represent opportunities for improvement.

The association between body mass index and in-hospital outcome among patients with acute myocardial infarction-Insights from China Acute Myocardial Infarction (CAMI) registry.

BACKGROUND: The relationship between body mass index (BMI) and in-hospital mortality risk among patients with acute myocardial infarction (AMI) remains controversial. METHODS AND RESULTS: We included 35,964 patients diagnosed with AMI in China Acute Myocardial Infarction registry between January 2013 and December 2016. Patients were categorized into 4 groups according to BMI level: BMI <18.5, 18.5-24.9, 25-30, and ≥30 kg/m2 for underweight, normal, overweight, and obese groups, respectively. Clinical data were extracted for each patient, and multivariable logistic regression analysis was used to examine the association between BMI level and in-hospital mortality. Compared with normal-weight patients, obese patients were younger, more often current smokers, and more likely to have hypertension, hyperlipidemia, and diabetes. Multivariable regression analysis results demonstrated that compared with normal group, underweight group had significantly higher in-hospital mortality (odds ratio [OR]: 1.34; 95% confidence interval [CI]: 1.06-1.69; p = 0.016), while overweight group (OR: 0.86; 95% CI: 0.77-0.97; p = 0.011) and obese group (OR: 0.65; 95% CI: 0.46-0.91; p = 0.013) had lower mortality. All subgroups showed a trend toward lower in-hospital mortality risk as BMI increased. CONCLUSIONS: Our study provided robust evidence supporting "obesity paradox" in a contemporary large-scale cohort of patients with AMI and demonstrated that increased BMI was independently associated with lower in-hospital mortality.

CAMI-NSTEMI Score　- China Acute Myocardial Infarction Registry-Derived Novel Tool to Predict In-Hospital Death in Non-ST Segment Elevation Myocardial Infarction Patients.

BACKGROUND: Accurate risk stratification of non-ST segment elevation myocardial infarction (NSTEMI) patients is important due to great variability in mortality risk, but, to date, no prediction model has been available. The aim of this study was therefore to establish a risk score to predict in-hospital mortality risk in NSTEMI patients.Methods and Results:We enrolled 5,775 patients diagnosed with NSTEMI from the China Acute Myocardial Infarction (CAMI) registry and extracted relevant data. Patients were divided into a derivation cohort (n=4,332) to develop a multivariable logistic regression risk prediction model, and a validation cohort (n=1,443) to test the model. Eleven variables independently predicted in-hospital mortality and were included in the model: age, body mass index, systolic blood pressure, Killip classification, cardiac arrest, electrocardiogram ST-segment depression, serum creatinine, white blood cells, smoking status, previous angina, and previous percutaneous coronary intervention. In the derivation cohort, the area under curve (AUC) for the CAMI-NSTEMI risk model and score was 0.81 and 0.79, respectively. In the validation cohort, the score also showed good discrimination (AUC, 0.86). Diagnostic performance of CAMI-NSTEMI risk score was superior to that of the GRACE risk score (AUC, 0.81 vs. 0.72; P<0.01). CONCLUSIONS: The CAMI-NSTEMI score is able to accurately predict the risk of in-hospital mortality in NSTEMI patients.

Dual-time-point myocardial 18F-FDG imaging in the detection of coronary artery disease.

BACKGROUND: Myocardial 18F-deoxyglucose (18F-FDG) uptake has been observed to be enhanced in patients with coronary artery disease (CAD) under fasting conditions. However, whether the increased 18F-FDG is induced by myocardial ischemia and how to discriminate ischemic from physiological 18F-FDG uptake have rarely been investigated. METHODS: Under fasting conditions, 18F-FDG PET imaging was performed in 52 patients with suspected CAD. Two 18F-FDG imaging sessions were conducted within two hours after a single administration of 18F-FDG (dual-time-point imaging), and with an intervention of an exercise test after the first imaging. Abnormal 18F-FDG uptake was determined by the classification of the 18F-FDG distribution pattern, and the changes of the 18F-FDG distribution between the two PET imaging sessions were analyzed. 99mTc-sestamibi was injected at peak exercise and myocardial perfusion imaging (MPI) was conducted after 18F-FDG imaging. Coronary angiography was considered the reference for diagnosing CAD. RESULTS: Overall, 54.8% (17/31) of CAD patients and 36.2% (21/58) of stenotic coronaries showed exercise-induced abnormal uptake of 18F-FDG. Based on the classification of the 18F-FDG distribution pattern, the sensitivity and specificity of exercise 18F-FDG imaging to diagnose CAD was 80.6% and 95.2% by patient analysis, 56.9% and 98.0% by vascular analysis, respectively. Compared with MPI, 18F-FDG imaging had a tendency to have higher sensitivity (80.6% vs 64.5%, P = 0.06) on the patient level. CONCLUSION: Myocardial ischemia can induce 18F-FDG uptake. With the classification of the 18F-FDG distribution pattern, dual-time-point 18F-FDG imaging under fasting conditions is efficient in diagnosing CAD.

Atrial fibrillation in patients hospitalized with acute myocardial infarction: analysis of the china acute myocardial infarction (CAMI) registry.

BACKGROUND: The incidence, clinical outcomes and antithrombotic treatment spectrum of atrial fibrillation (AF) in patients hospitalized with acute myocardial infarction (AMI) have not been well studied in Chinese population. METHODS: Twenty-six thousand five hundred ninety-two consecutive patients diagnosed with AMI were enrolled in CAMI registry from January 2013 to September 2014. After excluding 343 patients with uncertain AF status and 1,591 patients transferred out during hospitalization, 24,658 patients were finally included in this study and involved in analysis. RESULTS: In the CAMI registry, 740 (3.0%) patients were recorded with AF prevalence during hospitalization. Higher-risk baseline clinical profile was observed in patients with AF. These patients were less likely to receive reperfusion/revascularization than those without AF. The in-hospital mortality (including death and treatment withdrawal) was significantly higher in patients with AF than that of without AF (25.2% vs. 7.2%, respectively; p < 0.01). The case of composite of adverse events was similar, which included death, treatment withdrawal, re-infarction, heart failure or stroke (42.1% vs. 16.0%, p <0.01). In multivariate logistic regression analysis, AF was an independent predictor for in-hospital mortality (odds ratio, 1.88; 95% confidence interval: 1.27-2.78) and the composite of adverse events (odds ratio, 2.11; 95% CI: 1.63-2.72). Only 5.1% of patients with AF were treated with warfarin, and 1.7% were treated with both warfarin and dual antiplatelet therapy. CONCLUSIONS: The analysis was based on the CAMI registry in China. The patients hospitalized for AMI who developed AF were at significantly higher risk for in-hospital mortality and other adverse events. However, the anticoagulants including warfarin have been largely underused post hospital discharge. TRIAL REGISTRATION: Clinical Trial Registration: Identifier: NCT01874691 .

Abnormalities of myocardial perfusion and glucose metabolism in patients with isolated left ventricular non-compaction.

BACKGROUND: The prevalence of myocardial perfusion and glucose metabolic abnormalities and their significance in patients with isolated left ventricular non-compaction (ILVNC) have not been well investigated. METHODS: Seventeen ILVNC patients who underwent cardiac magnetic resonance (CMR) and (99m)Tc-sestamibi SPECT/fluorine-18 deoxyglucose ((18)F-FDG) PET imaging were included. Left ventricular non-compaction, regional wall motion abnormalities, left ventricular ejection fraction (LVEF), and delayed enhancement (DE) were estimated using CMR. Myocardial perfusion and metabolism were evaluated with SPECT/PET. RESULTS: Ninety-five (32.9%) segments were considered non-compacted. DE was present in 52 (18.0%) segments and 10 (58.8%) patients. The rate of occurrence of DE was significantly higher in compacted segments than in non-compacted segments (22.7% vs 8.4%, P = .003). Myocardial perfusion abnormalities were present in 92 (31.8%) segments, of which 66 were perfusion/metabolism match and 26 were perfusion/metabolism mismatch. The rate of occurrence of perfusion abnormality was similar between compacted and non-compacted segments (32.0% vs 31.6%, P = .948), but it was significantly higher in segments with DE than in those without DE (51.9% vs 27.4%, P = .001). None of the imaging features alone (non-compaction, DE, perfusion abnormalities, match or mismatch) showed significant correlations with LVEF (all P > .05). CONCLUSION: In the current study, myocardial perfusion/metabolism mismatch and match were observed in both non-compacted and compacted myocardium in ILVNC patients. Further research is warranted to determine their pathologic and clinical significance.

The Correlation of Centromere Protein Q with Diagnosis and Prognosis in Hepatocellular Carcinoma.

Introduction: Hepatocellular carcinoma (HCC) is one of the major types of liver cancer. Previous studies have shown that the centromere protein family is associated with malignant biological behaviors such as HCC proliferation. As a member of the centromere protein family, centromere protein Q (CENPQ) is closely associated with immunotherapy and immune cell infiltration in various tumors. However, the role and mechanism of CENPQ in HCC remain unclear. Methods: Multiple public databases and RT-qPCR were used to study the expression of CENPQ in HCC. Based on TCGA data, the correlation between CENPQ and clinicopathological characteristics and prognosis of HCC patients was analyzed, and its diagnostic value was evaluated. The potential biological functions of CENPQ in HCC were explored by functional enrichment analysis of differentially expressed genes. The distribution of tumor-infiltrating immune cell types was assessed using single-sample GSEA, and immune checkpoint gene expression was analyzed using Spearman correlation. Subsequently, loss-of-function experiments were performed to determine the function of CENPQ on the cell cycle and proliferation of HCC cells in vitro. Results: CENPQ was found highly expressed in HCC and correlated with weight, BMI, age, AFP, T stage, pathologic stage, histologic grade, and prothrombin time (all p < 0.05). ROC and Kaplan-Meier analyses indicated that CENPQ may be potentially used as a diagnostic marker for HCC (AUC = 0.881), and its upregulation is associated with decreased OS (p = 0.002), DSS (p < 0.001), and PFI (p = 0.002). Functional enrichment analysis revealed an association of CENPQ with biological processes such as immune cell infiltration, cell cycle, and hippo-merlin signaling deregulation in HCC. Furthermore, knockdown of CENPQ manifested in HCC cells with G0/1 phase cycle arrest and decreased proliferative capacity. Conclusion: CENPQ expression was higher in HCC tissues than in normal liver tissues. It was significantly associated with poor prognosis, immune cell infiltration, cell cycle, and proliferation. Therefore, CENPQ may become a promising prognostic biomarker for HCC patients.

The prevalence and outcomes in STEMI patients aged ≥75 undergoing primary percutaneous coronary intervention in China.

Objective: To investigate the prevalence and outcomes of primary percutaneous coronary intervention (PCI) in Chinese patients with ST-segment elevation myocardial infarction (STEMI) aged ≥75 years. Methods: We identified STEMI patients aged ≥75 years between 2013 and 2014 from a multicenter registry. The primary outcome was all-cause mortality. The secondary outcome was major adverse cardiac and cerebrovascular event (MACCE) including a composite of all-cause mortality, cardiac death, recurrent MI, stroke, revascularization, and major bleeding. Hazard ratios (HR) and associated 95% confidence interval (CI) were calculated. Results: Approximately 32.9% (n = 999) patients received primary PCI. Primary PCI was associated with lower risks of two-year all-cause mortality (18.0% vs. 36.4%; adjusted HR: 0.54, 95% CI: 0.45 to 0.65, P < 0.0001), MACCE (28.7% vs. 43.5%; adjusted HR: 0.68, 95% CI: 0.59 to 0.80, P < 0.0001), and cardiac death (10.0% vs. 23.6%; adjusted HR: 0.49, 95% CI: 0.38 to 0.62, P < 0.0001) relative to no reperfusion (n = 2041) in patients aged ≥75 years. The better outcomes in two-year all-cause mortality, MACCE, and cardiac death were consistently observed in STEMI patients aged ≥85 years. No differences were observed in recurrent MI, stroke, revascularization, and major bleeding between the two groups. Additionally, in patients with relatively high-risk profiles such as cardiogenic shock or delaying hospital admission, primary PCI was also superior to no reperfusion. Conclusion: Primary PCI may decrease two-year all-cause mortality, MACCE, and cardiac death in STEMI patients aged ≥75 years, even in these with age ≥85 years, cardiogenic shock, or delaying hospital admission. However, primary PCI was underutilized in Chinese clinical practice.

CENPL accelerates cell proliferation, cell cycle, apoptosis, and glycolysis via the MEK1/2-ERK1/2 pathway in hepatocellular carcinoma.

Centromere protein L (CENPL) is involved in the mitotic process of eukaryotic cells and the development of various types of cancer. However, its role in hepatocellular carcinoma (HCC) remains unclear. This study aimed to investigate the expression and clinical significance of CENPL in HCC, and explore its involvement in regulating HCC cell proliferation, apoptosis, cell cycle, and glycolysis both in vivo and in vitro. CENPL expression was analyzed in HCC and normal liver tissues using The Cancer Genome Atlas, Gene Expression Omnibus mining, real-time quantitative polymerase chain reaction, and immunohistochemistry. Functional assays were used to assess the role of CENPL in HCC cell proliferation, apoptosis, cell cycle, and glycolysis. The potential pathways underlying the regulatory effects of CENPL, as well as the expression of mitogen-activated protein kinase (MAPK) signaling pathway-related molecules and markers of proliferation and glycolysis were investigated. CENPL was significantly upregulated in HCC tissue and associated with multiple clinicopathological features and poor patient prognosis. Univariate and multivariate analyses demonstrated that CENPL may serve as an independent prognostic factor for HCC. Upregulation of CENPL in HCC regulated tumor proliferation and glycolytic processes. Mechanistic studies revealed that differentially expressed genes between the CENPL-overexpressing and control groups were mainly concentrated in the MAPK signaling pathway. Pathway inhibition analysis indicated that CENPL activated the MEK1/2-ERK1/2 signaling pathway to promote proliferation and glycolysis in HCC cells. This study elucidated the role of CENPL in regulating cell proliferation, apoptosis, cell cycle, and glycolysis in HCC. CENPL may represent a therapeutic target and prognostic biomarker for HCC.

Association of the stress hyperglycemia ratio with coronary artery disease complexity as assessed by the SYNTAX score in patients with acute coronary syndrome.

BACKGROUND: Mounting evidence supports a significant correlation between the stress hyperglycemia ratio (SHR) and both short- and long-term prognoses in patients with acute coronary syndrome (ACS). Nevertheless, research examining the association between the SHR and the complexity of coronary artery disease (CAD) is scarce. Therefore, this study aimed to explore the association between the SHR and CAD complexity, as assessed by the SYNTAX score, in patients with ACS. METHODS: A total of 4715 patients diagnosed with ACS were enrolled and divided into five groups according to the quintiles of the SHR. CAD complexity was assessed using the SYNTAX score and categorized as low (≤ 22) or mid/high (> 22) levels. Logistic regression was utilized to examine the association between the SHR and CAD severity (mid-/high SYNTAX score). Restricted cubic spline (RCS) curves were generated to assess the association between the SHR and CAD severity. Subgroup analyses were conducted to stratify outcomes based on age, sex, diabetes mellitus (DM) status, and clinical presentation. RESULTS: Among the total ACS population, 503 (10.7%) patients had mid/high SYNTAX scores. Logistic regression analysis revealed that the SHR was an independent risk factor for mid/high SYNTAX scores in a U-shaped pattern. After adjusting for confounding variables, Q1 and Q5 demonstrated elevated odds ratios (ORs) relative to the reference category Q3, with ORs of 1.61 (95% CI: 1.19 ∼ 2.19) and 1.68 (95% CI: 1.24 ∼ 2.29), respectively. Moreover, the ORs for Q2 (1.02, 95% CI: 0.73 ∼ 1.42) and Q4 (1.18, 95% CI: 0.85 ∼ 1.63) resembled that of Q3. Compared with the merged Q2-4 group, the ORs were 1.52 (95% CI: 1.21 ∼ 1.92) for Q1 group and 1.58 (95% CI: 1.25 ∼ 2) for the Q5 group. Subgroup analysis revealed that the U-shaped association between the SHR and mid/high SYNTAX score was attenuated in DM patients (P for interaction = 0.045). CONCLUSIONS: There were U-shaped associations between the SHR and CAD complexity in ACS patients, with an SHR ranging from 0.68 to 0.875 indicating a relatively lower OR for mid/high SYNTAX scores. Further studies are necessary to both evaluate the predictive value of the SHR in ACS patients and explore the underlying mechanisms of the observed U-shaped associations.

Kaempferol mitigates sepsis-induced acute lung injury by modulating the SphK1/S1P/S1PR1/MLC2 signaling pathway to restore the integrity of the pulmonary endothelial cell barrier.

Sepsis-induced acute lung injury (SALI) is the common complication of sepsis, resulting in high incidence and mortality rates. The primary pathogenesis of SALI is the interplay between acute inflammation and endothelial barrier damage. Studies have shown that kaempferol (KPF) has anti-sepsis properties. Sphingosine kinase 1 (SphK1)/sphingosine-1-phosphate (S1P) signaling pathway's significance in acute lung damage and S1P receptor 1 (S1PR1) agonists potential in myosin light chain 2 (MLC2) phosphorylation are documented. Whether KPF can regulate the SphK1/S1P/S1PR1/MLC2 signaling pathway to protect the lung endothelial barrier remains unclear. This study investigates the KPF's therapeutic effects and molecular mechanisms in repairing endothelial cell barrier damage in both LPS-induced sepsis mice and human umbilical vein endothelial cells (HUVECs). KPF significantly reduced lung tissue damage and showed anti-inflammatory effects by decreasing IL-6 and TNF-α synthesis in the sepsis mice model. Further, KPF administration can reduce the high permeability of the LPS-induced endothelial cell barrier and alleviate lung endothelial cell barrier injury. Mechanistic studies showed that KPF pretreatment can suppress MLC2 hyperphosphorylation and decrease SphK1, S1P, and S1PR1 levels. The SphK1/S1P/S1PR1/MLC2 signaling pathway controls the downstream proteins linked to endothelial barrier damage, and the Western blot (WB) showed that KPF raised the protein levels. These proteins include zonula occludens (ZO)-1, vascular endothelial (VE)-cadherin and Occludin. The present work revealed that in mice exhibiting sepsis triggered by LPS, KPF strengthened the endothelial barrier and reduced the inflammatory response. The SphK1/S1P/S1PR1/MLC2 pathway's modulation is the mechanism underlying this impact.

Current status of emergency medical service use in ST-segment elevation myocardial infarction in China: Findings from China Acute Myocardial Infarction (CAMI) Registry.

BACKGROUND: The mortality rate of myocardial infarction in China has increased dramatically in the past three decades. Although emergency medical service (EMS) played a pivotal role for the management of patients with ST-segment elevation myocardial infarction (STEMI), the corresponding data in China are limited. METHODS: An observational analysis was performed in 26,305 STEMI patients, who were documented in China acute myocardial infarction (CAMI) Registry and treated in 162 hospitals from January 1st, 2013 to January 31th, 2016. We compared the differences such as demographic factors, social factors, medical history, risk factors, socioeconomic distribution and treatment strategies between EMS transport group and self-transport group. RESULTS: Only 4336 patients (16.5%) were transported by EMS. Patients with symptom onset outside, out-of-hospital cardiac arrest and presented to province-level hospital were more likely to use EMS. Besides those factors, low systolic blood pressure, severe dyspnea or syncope, and high Killip class were also positively related to EMS activation. Notably, compared to self-transport, use of EMS was associated with a shorter prehospital delay (median, 180 vs. 245 min, P < 0.0001) but similar door-to-needle time (median, 45 min vs. 52 min, P = 0.1400) and door-to-balloon time (median, 105 min vs. 103 min, P = 0.1834). CONCLUSIONS: EMS care for STEMI is greatly underused in China. EMS transport is associated with shorter onset-to-door time and higher rate of reperfusion, but not substantial reduction in treatment delays or mortality rate. Targeted efforts are needed to promote EMS use when chest pain occurs and to set up a unique regionalized STEMI network focusing on integration of prehospital care procedures in China. TRIAL REGISTRATION: ClinicalTrials.gov (NCT01874691), retrospectively registered June 11, 2013.