Long-term outcomes and independent predictors of mortality in patients presenting to emergency departments with acute heart failure in Beijing: a multicenter cohort study with a 5-year follow-up / 中华医学杂志(英文版)

BACKGROUND@#Acute heart failure (AHF) is the most common disease in emergency departments (EDs). However, clinical data exploring the outcomes of patients presenting AHF in EDs are limited, especially the long-term outcomes. The purposes of this study were to describe the long-term outcomes of patients with AHF in the EDs and further analyze their prognostic factors.@*METHODS@#This prospective, multicenter, cohort study consecutively enrolled 3335 patients with AHF who were admitted to EDs of 14 hospitals from Beijing between January 1, 2011 and September 23, 2012. Kaplan-Meier and Cox regression analysis were adopted to evaluate 5-year outcomes and associated predictors.@*RESULTS@#The 5-year mortality and cardiovascular death rates were 55.4% and 49.6%, respectively. The median overall survival was 34 months. Independent predictors of 5-year mortality were patient age (hazard ratio [HR]: 1.027, 95 confidence interval [CI]: 1.023-1.030), body mass index (BMI) (HR: 0.971, 95% CI: 0.958-0.983), fatigue (HR: 1.127, 95% CI: 1.009-1.258), ascites (HR: 1.190, 95% CI: 1.057-1.340), hepatic jugular reflux (HR: 1.339, 95% CI: 1.140-1.572), New York Heart Association (NYHA) class III to IV (HR: 1.511, 95% CI: 1.291-1.769), heart rate (HR: 1.003, 95% CI: 1.001-1.005), diastolic blood pressure (DBP) (HR: 0.996, 95% CI: 0.993-0.999), blood urea nitrogen (BUN) (HR: 1.014, 95% CI: 1.008-1.020), B-type natriuretic peptide (BNP)/N-terminal pro-B-type natriuretic peptide (NT-proBNP) level in the third (HR: 1.426, 95% CI: 1.220-1.668) or fourth quartile (HR: 1.437, 95% CI: 1.223-1.690), serum sodium (HR: 0.980, 95% CI: 0.972-0.988), serum albumin (HR: 0.981, 95% CI: 0.971-0.992), ischemic heart diseases (HR: 1.195, 95% CI: 1.073-1.331), primary cardiomyopathy (HR: 1.382, 95% CI: 1.183-1.614), diabetes (HR: 1.118, 95% CI: 1.010-1.237), stroke (HR: 1.252, 95% CI: 1.121-1.397), and the use of diuretics (HR: 0.714, 95% CI: 0.626-0.814), β-blockers (HR: 0.673, 95% CI: 0.588-0.769), angiotensin-converting enzyme inhibitors (ACEIs) (HR: 0.714, 95% CI: 0.604-0.845), angiotensin-II receptor blockers (ARBs) (HR: 0.790, 95% CI: 0.646-0.965), spironolactone (HR: 0.814, 95% CI: 0.663-0.999), calcium antagonists (HR: 0.624, 95% CI: 0.531-0.733), nitrates (HR: 0.715, 95% CI: 0.631-0.811), and digoxin (HR: 0.579, 95% CI: 0.465-0.721).@*CONCLUSIONS@#The results of our study demonstrate poor 5-year outcomes of patients presenting to EDs with AHF. Age, BMI, fatigue, ascites, hepatic jugular reflux, NYHA class III to IV, heart rate, DBP, BUN, BNP/NT-proBNP level in the third or fourth quartile, serum sodium, serum albumin, ischemic heart diseases, primary cardiomyopathy, diabetes, stroke, and the use of diuretics, β-blockers, ACEIs, ARBs, spironolactone, calcium antagonists, nitrates, and digoxin were independently associated with 5-year all-cause mortality.

Effects of Shenfu Injection () on Inflammatory Response during Post-Resuscitation Myocardial Dysfunction after Cardiac Arrest in Swine / 中国结合医学杂志

OBJECTIVE@#To investigate whether Shenfu Injection (SFI, ) can alleviate post-resuscitation myocardial dysfunction by inhibiting the inflammatory response.@*METHODS@#After 8 min of ventricular fibrillation and 2 min of basic life support, 24 pigs were randomly divided into 3 groups (n=8), which were given intravenous bolus injections of SFI (1.0 mL/kg), epinephrine (EP, 0.02 mg/kg) and normal saline (SA), respectively. The animals were sacrificed at 24 h after restoration of spontaneous circulation (ROSC), and serum interleuking-6 (IL-6) and tumor necrosis factor-α (TNF-α) levels were measured by enzyme-linked immunosorbent assay (ELISA); expressions of Toll-like receptor 4 (TLR4)/nuclear factor kappa B (NF-κB) mRNAs and proteins were determined by RT-PCR and Western blot, respectively.@*RESULTS@#Compared with the EP and the SA groups, the ultrastructure of myocardial cells were slightly damaged and the systolic function of the left ventricle was markedly improved in the SFI group at 24 h after ROSC (P<0.05). In addition, compared with the EP and SA groups, the SFI group also showed significantly reduced levels of serum IL-6 and TNF-α, protein and mRNA levels of myocardial NF- κB and TLR4 (P<0.05).@*CONCLUSIONS@#Activation of TLR4/NF-κB signaling pathway may be involved in the pathological mechanisms of post-resuscitation myocardial dysfunction. SFI may block NF-κB-mediated inflammatory response by reducing the activity of NF- κB and the level of TNF-α, thus playing a protective role in post-resuscitation myocardial dysfunction.

Effect of neutrophil CD64 for diagnosing sepsis in emergency department / 世界急诊医学杂志（英文）

@# BACKGROUND:The aim of this study is to investigate the diagnostic and prognostic value of neutrophil CD64 (nCD64) as a novel biomarker in sepsis patients. METHODS: One hundred fifty-one adult patients diagnosed with sepsis and 20 age-matched healthy controls were enrolled in the study. Patients with sepsis were further subdivided into a sepsis group and a septic shock group. nCD64 expression, serum procalcitonin (PCT) level, C-reactive protein (CRP) level, and white blood cell (WBC) count were obtained for each patient, and Sequential Organ Failure Assessment (SOFA) scores were calculated. RESULTS: nCD64 expression was higher in the sepsis group with confirmed infection than in the control group. The receiver operating characteristic (ROC) curve of nCD64 was higher than those of SOFA score, PCT, CRP and WBC for diagnosing infection. The area under the curve (AUC) of nCD64 combined with SOFA score was the highest for all parameters. The AUC of nCD64 for predicting 28-day mortality in sepsis was signifi cantly higher than those of PCT, CRP, and WBC, but slightly lower than that of SOFA score. The AUC of nCD64 or PCT combined with SOFA score was signifi cantly higher than that of any single parameter for predicting 28-day mortality. CONCLUSION: nCD64 expression and SOFA score are valuable parameters for early diagnosis of infection and prognostic evaluation of sepsis patients.

Risk factors for acute kidney injury in patients with acute myocardial infarction / 中华医学杂志(英文版)

Background@#Acute kidney injury (AKI) is a serious and fatal complication of acute myocardial infarction (AMI). It has high shortand long-term mortality rates and a poor prognosis but is potentially preventable. However, the current incidence, risk factors, and outcomes of AKI in the Chinese population are not well understood and would serve the first step to identify high-risk patients who could receive preventative care.@*Methods@#The medical data of 1124 hospitalized patients diagnosed with AMI from October 2013 to September 2015 were reviewed. AKI was defined according to the 2012 Kidney Disease Improving Global Outcomes criteria. All the patients were divided into either the AKI group or the non-AKI group. A univariate comparison analysis was performed to identify possible risk factors associated with AKI. A multiple logistic regression analysis was used to identify the independent risk factors for AKI in patients with AMI.@*Results@#Overall, the incidence of AKI was 26.0%. The mortality rate of the AKI group was 20.5%, and the mortality rate of the non-AKI group was 0.6% (P < 0.001). Logistic regression analysis showed that the independent risk factors for AKI in patients with AMI included: age (>60 years old) (odds ratio [OR] 1.04, 95% confidence interval [CI] 1.02–1.05, P = 0.000), hypertension (OR 2.51, 95% CI 1.62–3.87, P = 0.000), chronic kidney disease (OR 3.52, 95% CI 2.01–6.16, P = 0.000), Killip class ≥3 (OR 5.22, 95% CI 3.07–8.87, P = 0.000), extensive anterior myocardial infarction (OR 3.02, 95% CI 1.85–4.93, P = 0.000), use of furosemide (OR 1.02, 95% CI 1.02–1.03, P = 0.000), non-use of angiotensin-converting enzyme inhibitors/angiotensin receptor blocker (OR 1.58, 95% CI 1.04–2.40, P = 0.032). These factors provided an accurate tool to identify patients at high risk of developing AKI.@*Conclusions@#Approximately 26.0% of patients undergoing AMI developed AKI, and the development of AKI was strongly correlated with in-hospital mortality. The risk factors for AKI in patients with AMI were determined to help identify high-risk patients and make appropriate clinical decisions.

Risk factors for acute kidney injury in patients with acute myocardial infarction / 中华医学杂志(英文版)

BACKGROUND@#Acute kidney injury (AKI) is a serious and fatal complication of acute myocardial infarction (AMI). It has high short- and long-term mortality rates and a poor prognosis but is potentially preventable. However, the current incidence, risk factors, and outcomes of AKI in the Chinese population are not well understood and would serve the first step to identify high-risk patients who could receive preventative care.@*METHODS@#The medical data of 1124 hospitalized patients diagnosed with AMI from October 2013 to September 2015 were reviewed. AKI was defined according to the 2012 Kidney Disease Improving Global Outcomes criteria. All the patients were divided into either the AKI group or the non-AKI group. A univariate comparison analysis was performed to identify possible risk factors associated with AKI. A multiple logistic regression analysis was used to identify the independent risk factors for AKI in patients with AMI.@*RESULTS@#Overall, the incidence of AKI was 26.0%. The mortality rate of the AKI group was 20.5%, and the mortality rate of the non-AKI group was 0.6% (P 60 years old) (odds ratio [OR] 1.04, 95% confidence interval [CI] 1.02-1.05, P = 0.000), hypertension (OR 2.51, 95% CI 1.62-3.87, P = 0.000), chronic kidney disease (OR 3.52, 95% CI 2.01-6.16, P = 0.000), Killip class ≥3 (OR 5.22, 95% CI 3.07-8.87, P = 0.000), extensive anterior myocardial infarction (OR 3.02, 95% CI 1.85-4.93, P = 0.000), use of furosemide (OR 1.02, 95% CI 1.02-1.03, P = 0.000), non-use of angiotensin-converting enzyme inhibitors/angiotensin receptor blocker (OR 1.58, 95% CI 1.04-2.40, P = 0.032). These factors provided an accurate tool to identify patients at high risk of developing AKI.@*CONCLUSIONS@#Approximately 26.0% of patients undergoing AMI developed AKI, and the development of AKI was strongly correlated with in-hospital mortality. The risk factors for AKI in patients with AMI were determined to help identify high-risk patients and make appropriate clinical decisions.

Extracorporeal Membrane Oxygenation Improving Survival and Alleviating Kidney Injury in a Swine Model of Cardiac Arrest Compared to Conventional Cardiopulmonary Resuscitation / 中华医学杂志(英文版)

Background@#Acute kidney injury (AKI) frequently occurs in cardiopulmonary resuscitation patients. Studies comparing the effects of extracorporeal membrane oxygenation (ECMO) with conventional cardiopulmonary resuscitation (CCPR) on AKI were rare. This study aimed to compare the effects of ECMO with those of CCPR on survival rate and AKI and explore the underlying mechanisms in a swine model of cardiac arrest (CA).@*Methods@#Sixteen male pigs were treated with ventricular fibrillation to establish CA model and then underwent CCPR (CCPR group, n = 8) or ECMO during cardiopulmonary resuscitation (ECPR group, n = 8). The study endpoints were 6 h after return of spontaneous circulation (ROSC) or death. Serum and urine samples were collected at baseline and during the 6 h after ROSC. The biomarkers of AKI were detected by enzyme-linked immunosorbent assay. The apoptosis of renal tubular epithelial cells was discovered by transmission electron microscope (TEM) and terminal deoxynucleotidyl transferase dUTP nick end labeling assay. Apoptosis-related genes were detected by immune-staining and Western blotting. Data were compared by Student's t-test.@*Results@#All pigs in ECPR group were successfully resuscitated with a higher 6-h survival rate (8/8) compared to CCPR group (6/8). The expressions of AKI biomarkers including neutrophil gelatinase-associated lipocalin (NGAL), tissue inhibitor of metalloproteinase2 (TIMP2), insulin-like growth factor-binding protein 7 (IGFBP7), liver fatty acid-binding protein (LFABP), and kidney injury molecule1 (Kim-1) were all increased along with the time after ROSC in both groups and lower in ECPR group compared with CCPR group. Especially, products of urinary TIMP and IGFBP levels (TIMP*IGFBP) were significantly lower at ROSC4 (0.58 ± 0.10 ng/ml vs. 1.18 ± 0.38 ng/ml, t = 4.33, P = 0.003) and ROSC6 (1.79 ± 0.45 ng/ml vs. 3.00 ± 0.44 ng/ml, t = 5.49, P < 0.001); urinary LFABP was significantly lower at ROSC6 (0.74 ± 0.06 pg/ml vs. 0.85 ± 0.11 pg/ml, t = 2.41, P = 0.033); and urinary Kim-1 was significantly lower at ROSC4 (0.66 ± 0.09 pg/ml vs. 0.83 ± 0.06 pg/ml, t = 3.99, P = 0.002) and ROSC6 (0.73 ± 0.12 pg/ml vs. 0.89 ± 0.08 pg/ml, t = 2.82, P = 0.016). Under light microscope and TEM, the morphological injures in renal tissues were found to be improved in ECPR group. Moreover, apoptosis was also alleviated in ECPR group.@*Conclusions@#Compared with CCPR, ECMO improves survival rate and alleviates AKI in a swine model of CA. The mechanism of which might be via downregulating AKI biomarkers and apoptosis in kidney.

Early Changes in Circulatory T Helper Type 1, 2, and 17 Cells of Patients with Out-of-Hospital Cardiac Arrest after Successful Cardiopulmonary Resuscitation / 中华医学杂志(英文版)

Background@#Immune disorder is an important feature of patients with out-of-hospital cardiac arrest (OHCA) after the return of spontaneous circulation (ROSC). We investigated the expression of circulatory T helper type (Th) 1, Th2, and Th17 cells to explore the early immune alteration in OHCA patients after ROSC.@*Methods@#During July-September 2016 and March-September 2017, 65 consecutive OHCA patients with ROSC >12 h and 30 healthy individuals were enrolled in this study. Clinical and 28-day survival data were collected. Peripheral blood samples were analyzed to evaluate the expression of Th1/Th2/Th17 cells by flow cytometry from OHCA patients after ROSC on days 1 and 3 and from healthy individuals.@*Results@#Compared with healthy individuals, T lymphocyte counts and Th1 cell counts decreased on days 1 and 3 after ROSC (1464 [1198, 2152] vs. 779 [481, 1140] vs. 581 [324, 1118]/μl, χ = 30.342, P 3 days; patients were divided into survivors (n = 10) and nonsurvivors (n = 18) based on 28-day survival. No significant differences in Th1/Th2/Th17 cell counts, ratios in CD4+ lymphocytes, and Th1/Th2 cell ratio were seen between survivors and nonsurvivors on both days (all P > 0.05). There was no difference over time in both survivors and nonsurvivors (all P > 0.05).@*Conclusion@#Downregulated T lymphocyte counts, including Th1/Th2/Th17 subsets and Th1/Th2 cell ratio imbalance, occur in the early period after ROSC, that may be involved in immune dysfunction in OHCA patients.

Characteristics, Management, and Outcomes of Acute Heart Failure in the Emergency Department: A Multicenter Registry Study with 1-year Follow-up in a Chinese Cohort in Beijing / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>The emergency department (ED) has a pivotal influence on the management of acute heart failure (AHF), but data concerning current ED management are scarce. This Beijing AHF Registry Study investigated the characteristics, ED management, and short- and long-term clinical outcomes of AHF.</p><p><b>METHODS</b>This prospective, multicenter, observational study consecutively enrolled 3335 AHF patients who visited 14 EDs in Beijing from January 1, 2011, to September 23, 2012. Baseline data on characteristics and management were collected in the EDs. Follow-up data on death and readmissions were collected until November 31, 2013, with a response rate of 92.80%. The data were reported as median (interquartile range) for the continuous variables, or as number (percentage) for the categorical variables.</p><p><b>RESULTS</b>The median age of the enrolled patients was 71 (58-79) years, and 46.84% were women. In patients with AHF, coronary heart disease (43.27%) was the most common etiology, and myocardium ischemia (30.22%) was the main precipitant. Most of the patients in the ED received intravenous treatments, including diuretics (79.28%) and vasodilators (74.90%). Fewer patients in the ED received neurohormonal antagonists, and 25.94%, 31.12%, and 33.73% of patients received angiotensin converting enzyme inhibitors/angiotensin receptor blockers, beta-blockers, and spironolactone, respectively. The proportions of patients who were admitted, discharged, left against medical advice, and died were 55.53%, 33.58%, 7.08%, and 3.81%, respectively. All-cause mortalities at 30 days and 1 year were 15.30% and 32.27%, respectively.</p><p><b>CONCLUSIONS</b>Substantial details on characteristics and ED management of AHF were investigated. The clinical outcomes of AHF patients were dismal. Thus, further investigations of ED-based therapeutic approaches for AHF are needed.</p>

Epinephrine in Out-of-hospital Cardiac Arrest: Helpful or Harmful? / 中华医学杂志(英文版)

<p><b>OBJECTIVE</b>Epinephrine is the primary drug administered during cardiopulmonary resuscitation (CPR) to reverse cardiac arrest. The evidence for the use of adrenaline in out-of-hospital cardiac arrest (OHCA) and in-hospital resuscitation is inconclusive. We conducted a systematic review on the clinical efficacy of adrenaline in adult OHCA patients to evaluate whether epinephrine provides any overall benefit for patients.</p><p><b>DATA SOURCES</b>The EMBASE and PubMed databases were searched with the key words "epinephrine," "cardiac arrest," and variations of these terms.</p><p><b>STUDY SELECTION</b>Data from clinical randomized trials, meta-analyses, guidelines, and recent reviews were selected for review.</p><p><b>RESULTS</b>Sudden cardiac arrest causes 544,000 deaths in China each year, with survival occurring in <1% of cases (compared with 12% in the United States). The American Heart Association recommends the use of epinephrine in patients with cardiac arrest, as part of advanced cardiac life support. There is a clear evidence of an association between epinephrine and increased return of spontaneous circulation (ROSC). However, there are conflicting results regarding long-term survival and functional recovery, particularly neurological outcome, after CPR. There is currently insufficient evidence to support or reject epinephrine administration during resuscitation. We believe that epinephrine may have a role in resuscitation, as administration of epinephrine during CPR increases the probability of restoring cardiac activity with pulses, which is an essential intermediate step toward long-term survival.</p><p><b>CONCLUSIONS</b>The administration of adrenaline was associated with improved short-term survival (ROSC). However, it appears that the use of adrenaline is associated with no benefit on survival to hospital discharge or survival with favorable neurological outcome after OHCA, and it may have a harmful effect. Larger placebo-controlled, double-blind, randomized control trials are required to definitively establish the effect of epinephrine.</p>

Effects of Shenfu Injection () on cerebral metabolism in a porcine model of cardiac arrest / 中国结合医学杂志

<p><b>OBJECTIVE</b>To investigate the effects of Shenfu Injection (, SFI) on cerebral metabolism in a porcine model of cardiac arrest (CA).</p><p><b>METHODS</b>Thirty Wuzhishan minipigs were randomly assigned to the control group (n=6), epinephrine group (EP group, n=12) and Sfigroup (n=12). After 8 min of untreated ventricular fifibrillation (VF), pigs in the EP group or Sfigroup were administered with either EP (0.02 mg/kg) or Sfi(1.0 mL/kg), respectively. After successful resuscitation, cerebrospinal fluid (CSF) levels of glucose, pyruvate, lactate, glutamate and glycerol were measured at 1, 6, 12 and 24 h after recover from spontaneous circulation (ROSC). In addition, neurologic defificit score (NDS) was calculated at 24 h after ROSC. Surviving pigs were killed at 24 h after ROSC, and the brain tissue was obtained for ultra-microstructure examination.</p><p><b>RESULTS</b>Compared with the EP group, CSF glucose and pyruvate levels were higher (all P<0.01), and lactate levels were lower in the Sfigroup (P<0.01). Meanwhile, CSF glutamate and glycerol levels in the Sfigroup were lower in comparison to the EP group (all P<0.05). In addition, Sfidecreased NDS at 24 h after ROSC (P<0.01), and alleviated the histopathological damage of the brain.</p><p><b>CONCLUSIONS</b>Sficould alleviate brain injury after CA, which may be associated with improving cerebral metabolism.</p>

A Novel Porcine Model of Septic Shock Induced by Acute Respiratory Distress Syndrome due to Methicillin-resistant / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Sepsis is one of the main causes of mortality in critically ill patients following progression to septic shock. To investigate the pathophysiologic changes of sepsis, we developed a novel porcine model of septic shock induced by acute respiratory distress syndrome (ARDS) due to methicillin-resistant Staphylococcus aureus(MRSA) pneumonia.</p><p><b>METHODS</b>Twenty-six male Landraces (Lvyuanweiye, Beijing, China) weighing 30 ± 2 kg were divided into four groups: sham group (SH; n = 5); cotton smoke inhalation group (SM; n = 6); MRSA pneumonia group (MR; n = 6); and septic shock group with cotton smoke inhalation + MRSA pneumonia (SS; n = 9). Extensive hemodynamics, oxygen dynamics, and lung function were monitored for 24 h following the injury or until death. Tissues were collected, and histopathology evaluations were carried out.</p><p><b>RESULTS</b>Blood cultures from 6 of 9 animals in the SS group were positive for MRSA. Two hours following the injury, decreased mean arterial blood pressure (60-70 mmHg) and cardiac index (<2 L.min-1.m-2) were observed in the animals in the SS group, while systemic vascular resistance index was increased. The hemodynamic characteristics of septic shock were only observed in the SS group but not significant in the other groups. The PO2/FiO2in the SM and SS groups decreased to 300 and 100, respectively. In the SS group, extravascular lung water index increased to 20 ml/kg, whereas thoracopulmonary compliance decreased to 10 ml/H2O after injury. Deterioration of pulmonary function in the SS group was more serious than the SM and MR groups. Severe lung injury in the SS group was confirmed by the histopathology evaluations. The lung injury confirmed by high-resolution thin-section computed tomography and histopathology in the SS group was more serious than those of other groups.</p><p><b>CONCLUSIONS</b>In the present study, we developed a novel porcine model of septic shock induced by ARDS due to severe MRSA pneumonia with characteristic hyperdynamic and hypodynamic phases in 24 h, which mimicked the hemodynamic changing of septic shock in human.</p>

Variations of Postresuscitation Lung Function after Thrombolysis Therapy in a Cardiac Arrest Porcine Model Caused by Pulmonary Thromboembolism / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Study of lung function in survivor from cardiac arrest (CA) caused by pulmonary thromboembolism (PTE) was rare. The aim of this study was to investigate the variations of postresuscitation lung function after thrombolysis treatment in a CA porcine model caused by PTE.</p><p><b>METHODS</b>After 2 min of untreated CA, pigs of 10-12 weeks with a weight of 30 ± 2 kg (n = 24) were treated with recombinant human tissue plasminogen activator (50 mg). Cardiopulmonary resuscitation (CPR) and ventilation were initiated after drug administration. Pulmonary function and arterial blood gas parameters were measured at baseline, return of spontaneous circulation (ROSC) immediately, and 1 h, 2 h, 4 h, and 6 h after ROSC.</p><p><b>RESULTS</b>The dynamic lung compliance decreased significantly at ROSC immediately and 1 h after ROSC compared to baseline (21.86 ± 2.00 vs. 26.72 ± 2.20 ml/mmHg and 20.38 ± 1.31 vs. 26.72 ± 2.20 ml/mmHg, respectively; P < 0.05; 1 mmHg = 0.133 kPa). Compared with baseline, airway resistance increased significantly at ROSC immediately and 1 h after ROSC (P < 0.05). Respiratory index also increased after ROSC and showed significant differences among baseline, ROSC immediately, and 2 h after ROSC (P < 0.05). Oxygen delivery decreased at ROSC immediately compared to baseline (P < 0.05). The oxygenation index decreased significantly at any time after ROSC compared to baseline (P < 0.05). Extravascular lung water index and pulmonary vascular permeability index (PVPI) showed significant differences at ROSC immediately compared to baseline and 1 h after ROSC (P < 0.05); PVPI at ROSC immediately was also different from 6 h after ROSC (P < 0.05). Ventilation/perfusion ratios increased after ROSC (P < 0.05). Histopathology showed fibrin effusion, bleeding in alveoli, and hemagglutination in pulmonary artery.</p><p><b>CONCLUSIONS</b>Lung function remains abnormal even after CPR with thrombolysis therapy; it is essential to continue anticoagulation and symptomatic treatment after ROSC.</p>

Programmed Cell Death-1/Programmed Death-ligand 1 Pathway: A New Target for Sepsis / 中华医学杂志(英文版)

<p><b>OBJECTIVE</b>Sepsis remains a leading cause of death in many Intensive Care Units worldwide. Immunosuppression has been a primary focus of sepsis research as a key pathophysiological mechanism. Given the important role of the negative costimulatory molecules programmed cell death-1 (PD-1) and programmed death-ligand 1 (PD-L1) in the occurrence of immunosuppression during sepsis, we reviewed literatures related to the PD-1/PD-L1 pathway to examine its potential as a new target for sepsis treatment.</p><p><b>DATA SOURCES</b>Studies of the association between PD-1/PD-L1 and sepsis published up to January 31, 2017, were obtained by searching the PubMed database.</p><p><b>STUDY SELECTION</b>English language studies, including those based on animal models, clinical research, and reviews, with data related to PD-1/PD-L1 and sepsis, were evaluated.</p><p><b>RESULTS</b>Immunomodulatory therapeutics could reverse the deactivation of immune cells caused by sepsis and restore immune cell activation and function. Blockade of the PD-1/PD-L1 pathway could reduce the exhaustion of T-cells and enhance the proliferation and activation of T-cells.</p><p><b>CONCLUSIONS</b>The anti-PD-1/PD-L1 pathway shows promise as a new target for sepsis treatment. This review provides a basis for clinical trials and future studies aimed at revaluating the efficacy and safety of this targeted approach.</p>

Study of Cardiac Arrest Caused by Acute Pulmonary Thromboembolism and Thrombolytic Resuscitation in a Porcine Model / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>The success rate of resuscitation in cardiac arrest (CA) caused by pulmonary thromboembolism (PTE) is low. Furthermore, there are no large animal models that simulate clinical CA. The aim of this study was to establish a porcine CA model caused by PTE and to investigate the pathophysiology of CA and postresuscitation.</p><p><b>METHODS</b>This model was induced in castrated male pigs (30 ± 2 kg; n = 21) by injecting thrombi (10-15 ml) via the left external jugular vein. Computed tomographic pulmonary angiography (CTPA) was performed at baseline, CA, and return of spontaneous circulation (ROSC). After CTPA during CA, cardiopulmonary resuscitation (CPR) with thrombolysis (recombinant tissue plasminogen activator 50 mg) was initiated. Hemodynamic, respiratory, and blood gas data were monitored. Cardiac troponins T, cardiac troponin I, creatine kinase-MB, myoglobin, and brain natriuretic peptide (BNP) were measured by enzyme-linked immunosorbent assay. Data were compared between baseline and CA with paired-sample t-test and compared among different time points for survival animals with repeated measures analysis of variance.</p><p><b>RESULTS</b>Seventeen animals achieved CA after emboli injection, while four achieved CA after 5-8 ml more thrombi. Nine animals survived 6 h after CPR. CTPA showed obstruction of the pulmonary arteries. Mean aortic pressure data showed occurrence of CA caused by PTE (Z = -2.803, P = 0.002). The maximal rate of mean increase of left ventricular pressure (dp/dtmax) was statistically decreased (t = 6.315, P = 0.000, variation coefficient = 0.25), and end-tidal carbon dioxide partial pressure (PetCO2) decreased to the lowest value (t = 27.240, P = 0.000). After ROSC (n = 9), heart rate (HR) and mean right ventricular pressure (MRVP) remained different versus baseline until 2 h after ROSC (HR, P = 0.036; MRVP, P = 0.027). Myoglobin was statistically increased from CA to 1 h after ROSC (P = 0.036, 0.026, 0.009, respectively), and BNP was increased from 2 h to 6 h after ROSC (P = 0.012, 0.014, 0.039, respectively).</p><p><b>CONCLUSIONS</b>We established a porcine model of CA caused by PTE. The dp/dtmaxand PetCO2may be important for the occurrence of CA, while MRVP may be more important in postresuscitation.</p>

Effect of Splenic Regulatory T-cell Apoptosis on the Postresuscitation Immune Dysfunction in a Porcine Model / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Postresuscitation immune dysfunction contributes to the low survival rate after successful resuscitation, but its mechanism remains poorly understood. The purpose of this study was to investigate whether splenic regulatory T-cell (Treg) apoptosis was involved in the postresuscitation immune dysfunction.</p><p><b>METHODS</b>Thirty-eight pigs were randomly divided into sham-operated group (SHAM group, n = 8), 12 h post return of spontaneous circulation (ROSC) group, 24 h post-ROSC group, and 48 h post-ROSC group (n = 10 per group). A Wuzhishan miniature porcine model of 8-min ventricular fibrillation cardiac arrest (CA) was established. The apoptosis rates of Treg in the spleen were tested by flow cytometry; the expressions of forkhead/winged helix transcription factor (Foxp3) of Treg in the spleen were detected by real-time polymerase chain reaction; and the levels of interleukin-4 (IL-4), IL-10, and interferon gamma (IFN-γ) of Treg in the spleen were detected by enzyme-linked immunosorbent assay.</p><p><b>RESULTS</b>The apoptosis rates of Treg in all post-ROSC groups were significantly lower than that of SHAM group (7.7% ± 1.9%, 7.1% ± 1.8%, 6.2% ± 0.4% vs. 13.1% ± 1.6%; P < 0.05); the expression levels of Foxp3 and IL-10 were also decreased with the increase of apoptosis rates of Treg. Helper T-cells CD4+ lymphocyte subsets were significantly lower in the post-ROSC groups compared with SHAM group (29.1% ± 2.2%, 24.3% ± 2.2%, 24.1% ± 2.5% vs. 43.8% ± 4.5%; P < 0.01) at 12, 24, and 48 h after ROSC. Compared with SHAM group, the levels of IFN-γ (161.0 ± 12.9, 167.7 ± 10.5, 191.2 ± 7.7 vs. 7.6 ± 0.9 ng/L) and IL-4 (27.7 ± 6.2, 35.9 ± 3.5, 50.6 ± 6.1 vs. 13.3 ± 2.3 ng/L) and the ratio of IFN-γ/IL-4 (8.6 ± 2.3, 4.9 ± 0.4, 4.5 ± 0.9 vs. 0.8 ± 0.2) were all greatly elevated in all post-ROSC groups (P < 0.05).</p><p><b>CONCLUSIONS</b>Apoptosis rate of Treg was significantly decreased after CA, and thus the proportion of Treg was increased and the inhibitory effects were enhanced, which further led to the decrease of the amount of CD4+ T-cells. In addition, the T helper type 2/T helper type 1 (Th2/Th1) cell drift of Treg in the spleen caused postresuscitation immune dysfunction.</p>

Shen-Fu Injection () alleviates post-resuscitation myocardial dysfunction by up-regulating expression of sarcoplasmic reticulum Ca(2+)-ATPase / 中国结合医学杂志

<p><b>OBJECTIVE</b>To compare the effect of Shen-Fu Injection (SFI) and epinephrine on the expression of sarcoplasmic reticulum Ca(2+) ATPase 2a (SERCA2a) in a pig model with post-resuscitation myocardial dysfunction.</p><p><b>METHODS</b>Ventricular fibrillation (VF) was electrically induced in Wu-zhi-shan miniature pigs. After 8 min of untreated VF and 2 min of cardiopulmonary resuscitation (CPR), all animals were randomly administered a bolus injection of saline placebo (SA group, n=10), SFI (0.8 mg/kg, SFI group, n=10) or epinephrine (20 μg/kg, EPI group, n=10). After 4 min of CPR, a 100-J shock was delivered. If the defibrillation attempt failed to attain restoration of spontaneous circulation (ROSC), manual chest compressions were rapidly resumed for a further 2 min followed by a second defibrillation attempt. Hemodynamic variables were recorded, and plasma concentrations of catecholamines were measured. Adenylate cyclase (AC), cyclic adenosine monophosphate (cAMP) and the expressions of β1-adrenoceptor (AR) and SERCA 2a were determined.</p><p><b>RESULTS</b>Cardiac output, left ventricular dp/dtmax and negative dp/dtmax were significantly higher in the SFI group than in the SA and EPI groups at 4 and 6 h after ROSC. The expression of β1-AR and SERCA2a at 24 h after ROSC were significantly higher in the SFI group than in the SA and EPI groups (P<0.05 or P<0.01).</p><p><b>CONCLUSIONS</b>The administration of epinephrine during CPR decreased the expression of SERCA2a and aggravated postresuscitation myocardial function (P<0.01). SFI attenuated post-resuscitation myocardial dysfunction, and the mechanism might be related to the up-regulation of SERCA2a expression.</p>

Effects of Shen-Fu Injection () on apoptosis of regulatory T lymphocytes in spleen during post-resuscitation immune dysfunction in a porcine model of cardiac arrest / 中国结合医学杂志

<p><b>OBJECTIVE</b>To investigate whether Shen-Fu Injection (, SFI) reduces post-resuscitation immune dysfunction in a porcine model of cardiac arrest by modulating apoptosis of regulatory T lymphocytes (Treg) in the spleen.</p><p><b>METHODS</b>After 8-min untreated ventricular fibrillation and 2-min basic life support, 24 pigs were divided into 3 groups with a random number table, i.e. SFI group, epinephrine (EP) group, and saline (SA) group (8 in each group), which received central venous injection of SFI (1.0 mL/kg), EP (0.02 mg/kg) and SA, respectively. The same procedure without CA initiation was achieved in the sham-operated (sham) group (n=6). After successful return of spontaneous circulation (ROSC), apoptosis rate of splenic Treg was detected by flow cytometry; and the mRNA expression of forkhead/winged helix transcription factor (Foxp3) of splenic Treg was detected by real time-polymerase chain reaction; and the levels of interleukin-4 (IL-4) and interferon-γ (IFN-γ) in porcine splenic Treg were detected by using enzyme-linked immunosorbent assay (ELISA).</p><p><b>RESULTS</b>Compared with the sham group, the apoptosis rate of Treg was significantly decreased, and the levels of Foxp3 mRNA expression, IFN-γ, IL-4 and IFN-γ/IL-4 were increased in the SA group (P<0.05 or P<0.01). Compared with the EP and SA groups, SFI treatment increased the apoptosis rate of Treg and reduced the levels of Foxp3 mRNA expression, IFN-γ and IFN-γ/IL-4 (P<0.05).</p><p><b>CONCLUSIONS</b>SFI has signifificant effects in attenuating post-resuscitation immune dysfunction by modulating apoptosis of Treg in the spleen.</p>

Effects of Chinese medicine shen-fu injection on the expression of inflammatory cytokines and complements during post-resuscitation immune dysfunction in a porcine model / 中国结合医学杂志

<p><b>OBJECTIVE</b>To investigate the action of Shen-Fu Injection (SFI) in regulating the expression of the serum complements and inflammatory cytokines synthesized and released in response to the stress of global ischemia accompanying cardiac arrest (CA) and resuscitation.</p><p><b>METHODS</b>Thirty pigs were randomly divided into the sham (n=6) and 3 returns of spontaneous circulation (ROSC) groups (n=24). After 8-min untreated ventricular fibrillation and 2-min basic life support, 24 pigs of the ROSC groups were randomized into three groups (n=8 per group), which received central venous injection of SFI (SFI group), epinephrine (EP group), or saline (SA group). Hemodynamic status and blood samples were obtained at 0, 0.5, 1, 2, 4, 6, 12, and 24 h after ROSC.</p><p><b>RESULTS</b>Serum concentrations of specific activation markers of the complement system C3, C4 and C5b-9 were increased during cardiopulmonary resuscitation through 24 h after ROSC. There were intense changes of various pro-inflammatory cytokines and anti-inflammatory cytokines as early as 0.5 h after CA. Compared with the EP and SA groups, SFI treatment reduced the proinflammatory cytokines levels of interleukin (IL)-6, IL-8 and tumor necrosis factor α (TNF-α, P<0.05), and increased the anti-inflammatory cytokine levels of IL-4 and IL-10 (P<0.05). Further, SFI treatment decreased the values of C3, C4 and C5b-9 compared with the EP and SA groups.</p><p><b>CONCLUSIONS</b>SFI, derived from the ancient Chinese medicine, has significant effects in attenuating post-resuscitation immune dysfunction by modulating the expression of complements and cytokines levels. The current study provided an experimental basis for the clinical application of a potential pharmacologic target for post resuscitation immune dysfunction.</p>

Comparison of Shenfu Injection () and epinephrine on catecholamine levels in a porcine model of prolonged cardiac arrest / 中国结合医学杂志

<p><b>OBJECTIVE</b>To compare the effects of Shenfu Injection (SFI) and epinephrine (EPI) on catecholamine levels in a porcine model of prolonged cardiac arrest (CA).</p><p><b>METHODS</b>After 8 min of untreated ventricular fibrillation, 24 Wuzhishan miniature pigs were randomly assigned to one of the three groups (n=8 per group) and received central venous injection, respectively: SFI group (1 mL/kg), EPI group (20 μg/kg EPI), and normal saline (NS) group. Cardiac output (CO), maximum rate of increase/decrease in left ventricular pressure (±dp/dt), serum levels of EPI, norepinephrine (NE), and dopamine (DA) were determined at baseline and at 0.5, 1, 2, and 4 h after restoration of spontaneous circulation.</p><p><b>RESULTS</b>The duration of cardiopulmonary resuscitation was shorter in the EPI and SFI groups than in the NS group (P<0.05). The EPI level increased significantly after restoration of spontaneous circulation (ROSC) in all three groups, and was significantly different between the EPI group and the other two groups immediately after ROSC (both P<0.01), but these differences gradually disappeared over time. There were no significant differences in NE or DA levels among the three groups, and there were no correlations between catecholamine levels and CO or dp/dt (P>0.05).</p><p><b>CONCLUSIONS</b>SFI did not significantly affect endogenous catecholamine levels during cardiopulmonary resuscitation after prolonged ventricular fibrillation. However, SFI improved oxygen metabolism, and produced a better hemodynamic status compared with EPI. SFI might be a potentially vasopressor drug for the treatment of CA.</p>

Progress in research into the genes associated with venous thromboembolism / 世界急诊医学杂志（英文）

@#BACKGROUND: Venous thromboembolism (VTE), including both deep vein thrombosis (DVT) and pulmonary embolism (PE), is a common, lethal disorder that affects hospitalized and non-hospitalized patients. This study aimed to review the progress in the research into VTE. DATA SOURCES: We reviewed the studies about VTE and verified different genetic polymoriphisms of VTE. RESULTS: The pathogenesis of VTE involves hereditary and acquired factors. Many studies indicated that the disorder of coagulation and fibirnolytic system is of utmost importance to this disease. Genetic polymoriphism-related VTE demonstrated significant differences among geographies and ethnicities. CONCLUSION: VTE has many risk factors, but genetic factors play an important role.