Multifunctional Lipidated Protein Carrier with a Built-In Adjuvant as a Universal Vaccine Platform Potently Elevates Immunogenicity of Weak Antigens.

Weak antigens represented by MUC1 are poorly immunogenic, which greatly constrains the development of relevant vaccines. Herein, we developed a multifunctional lipidated protein as a carrier, in which the TLR1/2 agonist Pam3CSK4 was conjugated to the N-terminus of MUC1-loaded carrier protein BSA through pyridoxal 5'-phosphate-mediated transamination reaction. The resulting Pam3CSK4-BSA-MUC1 conjugate was subsequently incorporated into liposomes, which biomimics the membrane structure of tumor cells. The results indicated that this lipidated protein carrier significantly enhanced antigen uptake by APCs and obviously augmented the retention of the vaccine at the injection site. Compared with the BSA-MUC1 and BSA-MUC1 + Pam3CSK4 groups, Pam3CSK4-BSA-MUC1 evoked 22- and 11-fold increases in MUC1-specific IgG titers. Importantly, Pam3CSK4-BSA-MUC1 elicited robust cellular immunity and significantly inhibited tumor growth. This is the first time that lipidated protein was constructed to enhance antigen immunogenicity, and this universal carrier platform exhibits promise for utilization in various vaccines, holding the potential for further clinical application.

Feeding behavior explains the different effects of cabbage on MEAM1 and MED cryptic species of Bemisia tabaci.

MEAM1 (Middle East-Asia Minor 1, "B" biotype) and MED (Mediterranean, "Q" biotype) are the two most destructive cryptic species of the Bemisia tabaci complex on the planet. Our previous studies have shown that MEAM1 outcompetes MED on cabbage; the underlying mechanism is unknown. In the Brassicaceae family, the glucosinolate-myrosinase defense system plays a crucial role in deterring feeding, inhibiting growth, and causing acute toxicity against a wide range of generalist herbivores. In the present study, we first compared the survival of MEAM1 and MED exposed to sinigrin (a glucosinolate) and myrosinase (an enzyme that degrades glucosinolates); we found that survival of both species was high in response to sinigrin alone but was near zero in response to sinigrin + myrosinase. We then used electropenetrography (electrical penetration graphs, EPG) to assess the feeding behaviors of MEAM1 and MED whiteflies on cabbage. The EPG results revealed that the mean duration of each potential drop (pd, indicating an intracellular puncture) was substantially longer for MED than MEAM1 on cabbage, indicating that the exposure to the toxic hydrolysates of glucosinolate and myrosinase is greater for MED than for MEAM1. We therefore conclude that differences in penetrating behaviors may help explain the different effects of cabbage on MEAM1 and MED whitefly species.

Does Braun enteroenterostomy reduce delayed gastric emptying after pancreaticoduodenectomy?

Whether an additional Braun enteroenterostomy is necessary in reducing delayed gastric emptying (DGE) after pancreaticoduodenectomy (PD) has not yet been well investigated. Herein, in this retrospective study, 395 consecutive cases of patients undergoing classic PD from 2009 to 2013 were reviewed. Patients with and without Braun enteroenterostomy were compared in preoperative baseline characteristics, surgical procedure, postoperative diagnosis, and morbidity including DGE. The DGE was defined and classified by the International Study Group of Pancreatic Surgery recommendation. The incidence of DGE was similar in patients with or without Braun enteroenterostomy following PD (37/347, 10.7% vs 8/48, 16.7%, P = 0.220). The patients in the 2 groups were not different in patient characteristics, lesions, surgical procedure, or postoperative complications, although patients without Braun enteroenterostomy more frequently presented postoperative vomiting than those with Braun enteroenterostomy (33.3% vs 15.3%, P = 0.002). Bile leakage, pancreatic fistula, and intraperitoneal abscess were risk factors for postoperative DGE (all P < 0.05). Prokinetic agents and acupuncture were effective in symptom relief of DGE in 24 out of 45 patients and 12 out of 14 patients, respectively.The additional Braun enteroenterostomy following classic PD was not associated with a decreased rate of DGE. Postoperative abdominal complications were strongly correlated with the onset of DGE. Prokinetic agents and acupuncture could be utilized in some patients with DGE.

[Effect of temperature on hospital admission among patients with chronic systolic heart failure].

OBJECTIVE: To investigate the effect of temperature on hospital admission among patients with chronic systolic heart failure (CSHF). METHODS: Data regarding in-hospital patients with CSHF were gathered from 12 hospitals in Hubei province, between 2000 and 2010. Patients with a history of congenital heart disease and the history of cancer from this series, were excluded. Chi-square (χ(2)) tests and t tests were used for descriptive analysis. Univariate and multivariate logistic regression methods were performed to determinate the risk of hospital admission of every month to compare with the previous one. We used 2-tailed 95% confidence interval (CI), and tests with P < 0.01 to consider the significant levels, statistically. We also used the SPSS 13.0 for Windows, release 15, 2006 (SPSS Inc, Chicago, Ill) for data analyses. RESULTS: (1) 48 964 patients were enrolled in the present study. The numbers of admission increased 18.71%, 13.84%, -21.90%, -34.62%, -21.97%, -3.81%, -2.04%, 10.13%, -17.13%, -0.85%, 21.54% and 42.70% from January to December when compared to the average number of admission. (2) The odds ratios (ORs) (95% CI, P values) of hospital admission in January, February and December were 1.09 (0.96 - 1.23, 0.54), 0.98 (0.84 - 1.10, 0.46) and 0.96 (0.84 - 1.08, 0.59), respectively in females which did not show any significant differences when compared to the number in August. However the ratios were 0.61 (0.54 - 0.69, < 0.01), 0.80 (0.68 - 0.92, < 0.01) and 0.73 (0.64 - 0.83, < 0.01), respectively, in males that showed significant differences when, compared to the figures in August. (3) The OR of admission increased more when temperature got lower for patients with coronary artery disease, hypertension heart disease or rheumatic heart disease, but not with dilated cardiomyopathy. (4) The OR of admission showed a different impact on patients with different occupation, along with the change of temperature. Low or high temperature did not seem to have different effects on the OR of admission in patients who were free-lanced or unemployed. CONCLUSION: Temperature seemed to have significant effects on the risk of admission, which related to gender, etiology or occupation.

Effect of anxiety and depression on the recurrence of persistent atrial fibrillation after circumferential pulmonary vein ablation.

BACKGROUND: The effects of anxiety and depression on the recurrence of persistent atrial fibrillation (AF) after circumferential pulmonary vein ablation (CPVA) are not clear. Whether CPVA can alleviate the anxiety and depression symptoms of persistent AF patients is unknown. METHODS: One hundred and sixty-four patients with persistent AF, of which 43 treated with CPVA (CPVA group) and 103 treated with anti-arrhythmics drugs (medicine group), were enrolled. The Zung Self-Rating Anxiety Scale (SAS), and Zung Self-Rating Depression Scale (SDS) were assessed before and 12 months after treatment in all patients. RESULTS: The scores of SAS (40.33 ± 7.90 vs. 49.76 ± 9.52, P < 0.01) and SDS (42.33 ± 8.73 vs. 48.17 ± 8.77, P < 0.01) decreased 12 months after CPVA. Over 12 months follow-up, AF relapsed in 17 patients in CPVA group. Compared with the data in the recurrent group (17 patients), the scores of SAS and SDS were significantly lower in the non-recurrent group (26 patients) at baseline. The results of multivariate Logistic regression analysis showed normal scores of SAS and SDS were the independent risk factors of AF recurrence after CPVA. CONCLUSIONS: Anxiety and depression increase the recurrence risk of persistent AF after CPVA. CPVA can ameliorate the anxiety and depression symptoms in patients with persistent AF.

Serum uric acid levels correlate with atrial fibrillation in patients with chronic systolic heart failure.

BACKGROUND: Studies have shown that increased levels of serum uric acid (SUA) are associated with atrial fibrillation (AF). However, less is known about the prognostic value of SUA levels for AF in patients with chronic heart failure (CHF). The aim of the study was to examine the prognostic value of SUA levels for AF in patients with CHF. METHODS: Sixteen thousand six hundred and eighty-one patients diagnosed with CHF from 12 hospitals were analyzed. Patients were categorized into AF group and non-AF group, death group, and survival group according to the results of the patients' medical records and follow-up. Univariate and multivariate Cox proportional hazards analyses were performed to examine the risk of AF. The sensitivity and specificity of SUA level in predicting the prognosis were examined by multivariate Cox models and receiver operating characteristic (ROC) curves. RESULTS: The results of univariate predictors in overall patients showed that the higher SUA level was associated with AF. SUA level (HR, 1.084; 95%CI, 1.017 - 1.144; P < 0.001), diuretics (HR, 1.549; 95%CI, 1.246 - 1.854; P < 0.001), and New York Heart Association (NYHA) (HR, 1.237; 95%CI, 1.168 - 1.306; P < 0.001) function class were the independent risk factors for AF. The sensitivity and specificity of the models were 29.6% and 83.8% respectively for predicting AF. When SUA level was added to these models, it remained significant (Wald c(2), 1494.88; P < 0.001 for AF); 58.8% (95%CI, 57.7% - 60.0%) of the observed results were concordant with the separate model. CONCLUSION: Higher SUA level is associated strongly with AF in patients with CHF. SUA level can increase the sensitivity and specificity in predicting AF.

[Impact of red cell distribution width on outcome of 16 681 patients with chronic systolic heart failure].

OBJECTIVE: To determinate the prognostic value of red cell distribution width (RDW) and the relationships between RDW and clinical characteristics in patients with chronic heart failure (CHF). METHODS: A total of 16 681 in-hospital patients with chronic systolic HF and LVEF < 50% from 12 hospitals in Hubei province, China were enrolled. All patients were followed up with telephone call. Patients were divided into RDW ≤ 13.2% (n = 3981), 13.3% - 14.1% (n = 3996), 14.2% - 14.8% (n = 4319) and ≥ 14.9% (n = 4385) groups. Multivariate Cox regression analysis was performed to determine whether RDW is an independent risk factor of all-cause mortality in overall patients, patients with various etiologies. Multivariate Cox proportional hazard analysis was performed to determine the risk of all-cause mortality among various RDW groups. RESULTS: (1) Compared with RDW ≤ 13.2% group, adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) of all-cause mortality for RDW 13.3% - 14.1%, 14.2% - 14.8% and ≥ 14.9% were 0.892 (95%CI 0.818 - 0.973, P = 0.01), 0.859 (95%CI 0.793 - 0.931, P < 0.01) and 1.034 (95%CI 0.961 - 1.111, P = 0.373) respectively. (2) Compared with MCV normal group, the adjusted HRs of MCV elevation and MCV decline groups were 1.351 (95%CI 1.063 - 1.718, P < 0.01) and 1.316 (95%CI 1.034 - 1.675, P < 0.01), respectively. (3) Compared to patients with rheumatic heart diseases, the adjusted HR for all-cause mortality in patients with coronary heart disease, dilated cardiomyopathy and hypertensive heart disease with RDW > 16% were 1.437 (95%CI 1.141 - 1.810, P < 0.01), 1.651 (95%CI 1.276 - 2.138, P < 0.01) and 1.276 (95%CI 1.004 - 1.621, P < 0.01), respectively. (4) The RDW is independently correlated with BMI (r = -0.345, P < 0.01), diastolic blood pressure (r = -0.321, P < 0.01), albumin (r = -0.411, P < 0.01), blood urine nitrogen (r = 0.476, P < 0.01), right ventricular end-diastolic diameter (r = 0.383, P < 0.01), LVEF (r = -0.463, P < 0.01) and heart rate (r = 0.379, P < 0.01). CONCLUSIONS: There is a J shape relationship between all-cause mortality and RDW. The elevation or decline of MCV with increased RDW is linked with increased all-cause mortality in CHF patients.

[Investigation on the prevalence and related factors of medicinal therapy in patients with chronic systolic heart failure].

OBJECTIVE: To investigate the prevalence and related factors of medicinal therapy in patients with chronic systolic heart failure (CSHF). METHODS: Data on in-hospital patients with CSHF were studied from 12 hospitals in Hubei province, in 2000 and 2010. Differences on gender and age were calculated and Multivariate Cox regression analysis was performed to determinate the independent risk factors of all-cause mortality. RESULTS: (1) 16 681 patients were enrolled in this study. Among which, 6453 died during the 5.82 ± 1.63 years of follow-up. The annual medical expenditure was larger in the survival group than in the dead ones (3.19 ± 0.65 vs. 3.32 ± 0.57, P < 0.01). (2) The prevalence of Angiotensin II receptor blocker increased along with age which accounted as 7.73%, 7.35%, 12.26%, 14.29%, 17.19%, 19.87% and 20.49%, respectively, in the < 30, 30 - 39, 40 - 49, 50 - 59, 60 - 69, 70 - 79 and ≥ 80-year groups. The distribution of digitalis, diuretics, ß-receptor blocker, Angiotensin-converting enzyme inhibitors showed inversed U shape. (3) The annual medical expenditure increased as patients got older, with age groups < 30, 30 - 39, 40 - 49, 50 - 59, 60 - 69 and 70 - 79 years old as 2.96 ± 0.70, 3.09 ± 0.62, 3.15 ± 0.58, 3.30 ± 0.59 and 3.25 ± 0.58, respectively (P < 0.01). It reduced to the same level as in the 50 - 59 year-old group. The distribution of annual medical expenditure showed similar pattern in males. However, the trends were only found in patients at 50 - 59, 60 - 69, 70 - 79 and ≥ 80 years-old groups in female. CONCLUSION: More attention should be paid to medicinal therapy in patients with CSHF. Medicinal therapy shifted with age and gender, of which females had more adverse trend than in males.

Prognosis investigation in patients with chronic heart failure and pericardial effusion.

BACKGROUND: Researchers still do not reach the consensus on the incidence, characters and the prognostic value of pericardial effusion (PE) in patients with chronic heart failure (CHF). This study is to investigate the incidence, characters and the prognostic value of pericardial effusion (PE) in patients with CHF. METHODS: One thousand one hundred and eighty-nine patients, with a diagnosis of CHF consecutively admitted to three centers, were enrolled. M-mode echocardiography was used to determine the presence or absence of PE and to semi-quantify it. The 118 patients with PE and 472 without PE were followed up. The relationship between the PE and other parameters and the prognostic value of PE for CHF were analyzed by univariate and multivariate analyses. RESULTS: After following up, 550 patients were analyzed, of which 226 were dead. The incidence of PE was 9.92%. Moderate PE was the most common which account 90.68% (107/118). The 6.78% of the patients (8/118) had small while only 2.54% (3/118) had large one. The systolic blood pressure (OR=1.04, 95%CI (1.01-1.07), P=0.08), left ventricular ejection fraction (LVEF) (OR=1.09, 95%CI (1.02-1.15), P=0.06), and main pulmonary artery diameter (MPAD) (OR=1.51, 95%CI (1.24-1.85), P<0.001) were the independent predictors of PE. The glomerular filtration rate (GFR) (OR=1.013, 95%CI (1.005-1.026), P=0.02), systolic blood pressure (OR=1.02, 95%CI (1.00-1.03), P=0.015), LVEF (OR=1.08, 95%CI (1.04-1.12), P<0.001) and diabetes mellitus (OR=3.53, 95%CI (1.99-6.44), P<0.001) were determined as the independent predictors of CHF prognosis. CONCLUSIONS: The PE is not uncommon in CHF patients and most PE are small to moderate. PE is not related to the etiology of CHF while is strongly connected with higher systolic blood pressure, low LVEF and large MPAD. PE dose not increase the risk of death in patients with CHF.

[Characteristics of in-hospital patients with chronic heart failure in Hubei province from 2000 to 2010].

OBJECTIVE: To evaluate the current status of chronic heart failure (CHF) in Hubei province and analyze the epidemiology of CHF including the general condition, etiology and pharmacological therapy. METHODS: Data of in-hospital patients with CHF were investigated between 2000 and 2010 from 12 hospitals in Hubei Province. INCLUSION CRITERIA: over 18 years of age, organic heart disease and with the symptom of HF including dyspnea and fatigue. Patients with a history of myocardial infarction in the prior 12 months, congenital heart disease, pericardial disease and the history of cancer were excluded. RESULTS: (1) A total of 12 450 patients were enrolled (7166 male, 57.56%). The average age was (62.0 ± 14.5) years. Patients in the scale of age ≥ 80, 70 - 79, 60 - 69, 50 - 59, 40 - 49 and < 40 was 9.53% (1187/12 450), 30.80% (3835/12 450), 23.45% (2920/12 450), 18.81% (2342/12 450), 10.73% (1336/12 450) and 6.67% (830/12 450), respectively (P < 0.01). The NYHA class I, II, III and IV was 0.60%, 23.20%, 50.31% and 26.50%, respectively. (2) The age of patients was significant reduced from 2000 - 2003, 2004 - 2006 to 2007 - 2010 [(66.4 ± 14.1) years, (64.9 ± 14.4) years and (64.2 ± 14.8) years, P < 0.01]. (3) The major causes of CHF were hypertension (31.54%), coronary heart disease (28.24%), dilated cardiomyopathy (26.57%) and rheumatic valvular heart disease (17.49%). The most frequent etiology for CHF was rheumatic valvular heart disease in patients aged less than 40 years old, dilated cardiomyopathy in patients aged 40 - 49 and 50 - 59 years and hypertension in patients aged 60-69, 70-79 and ≥ 80 years. (4) Drug use was as follows: Digitalis (47.49%), diuretics (68.75%), ACEI (50.66%), ß-blocker (44.06%) and aldosterone antagonist (53.08%). Use of digitalis (Wald χ(2) = 903.41, P < 0.01;r = 0.271, P < 0.01), diuretics (Wald χ(2) = 818.05, P < 0.01; r = 0.249, P < 0.01), aldosterone antagonists (Wald χ(2) = 76.92, P < 0.01; r = 0.091, P < 0.01) increased while the ß-blocker (Wald χ(2) = 160.65, P < 0.01; r = -0.117, P < 0.01) declined in proportion to NYHA class increase. CONCLUSIONS: The age of in-hospital patients with CHF declined in the previous 10 years. The primary etiology was hypertension for aged CHF in-hospital patients with CHF. There was big gap between guideline recommended standard therapy and current drug use for in-hospital patients with CHF in Hubei province.

[The prognostic value of etiology in patients with chronic systolic heart failure].

OBJECTIVE: To determinate the prognostic value of etiology in patients with chronic systolic heart failure (CSHF). METHODS: Data of in-hospital patients with CSHF were investigated between 2000 and 2010 from 12 hospitals in Hubei province. All patients were followed up through telephone calls. Univariate and multivariate Cox proportional hazards analyses were then used to explore the differences in the all-cause mortality, heart failure (HF) mortality and sudden cardiac death (SCD) among patients caused by different etiologies. Kaplan-Meier curve were then constructed and Univariate and multivariate Cox regression analyses were used to select demographic and clinical variables in predicting the all-cause mortality, HF mortality and SCD in CSHF patients. Multivariate logistic models and ROC curve were developed with or without the confirmed etiology to assess the incremental additive information related to different etiologies. RESULTS: (1) Over the median 3 (2 - 4) years follow-up program, 6453 (38.69%) patients died, including 5505 (33.00%) due to HF prognosis and 717 (4.30%) died of SCD. All-cause mortality rates accounted for 34.50%, 54.30%, 41.48% and 15.76%, with HF mortality rates as 30.11%, 44.95%, 36.25% and 13.10%. SCDs accounted 8.46%, 8.45%, 9.84% and 1.05% in patients with CHD, DCM, HHD and RHD, respectively. (2) Compared with RHD patients, the adjusted HRs for all-cause mortality were 1.554 (1.240 to 1.947; P < 0.001), 1.405 (1.119 to 1.764; P = 0.003) and 1.315 (1.147 to 1.467; P = 0.005) while the adjusted HRs and 95%CIs for HF mortality were 1.458 (1.213 - 1.751; P < 0.001), 1.763 (1.448 - 2.147; P < 0.001) and 1.281 (1.067 - 1.537; P = 0.008), in patients with CHD, DCM and HHD, respectively. There were no significant differences in CHD (HR 3.345; 95%CI, 1.291 to 8.666; P = 0.013) or HHD (HR 2.062; 95%CI, 0.794 to 5.352; P = 0.137), while only DCM (HR 4.764; 95%CI, 1.799 to 12.618; P = 0.002) remained significant in SCD despite of the multivariate adjustment. (3) Etiology increased the sensitivity and specificity of predicting models for all-cause mortality (AUC 0.839, 95%CI, 0.832 to 0.845 vs. 0.776, 95%CI, 0.768 to 0.784) and HF mortality (AUC 0.814, 95%CI, 0.806 to 0.822 vs. 0.796, 95%CI, 0.788 to 0.804) but not with SCD (AUC 0.777, 95%CI, 0.749 to 0.809 vs. 0.747, 95%CI, 0.727 to 0.766). CONCLUSION: CSHF due to CHD, DCM and HHD carried a worse prognosis than that of RHD. Different etiologies provided significant incremental prognostic information beyond readily available clinical variables for all-cause mortality and HF mortality.

[Prevalence and prognostic value of liver function abnormalities in patients with chronic systolic heart failure].

OBJECTIVE: To evaluate systemically the prevalence and prognostic values of liver function abnormalities in patients with chronic systolic heart failure (HF) have not been systematically evaluated. METHODS: A total of 16 681 hospitalized patients with a diagnosis of chronic systolic HF and left ventricular ejection fraction (LVEF) < 50% were recruited from 12 hospitals in Hubei Province. All patients were followed up by telephone contacts. And they were divided into the death and survival groups according to the follow-up results. RESULTS: Over a median follow-up period of 3 years, 6453 (38.69%) patients died. The prevalence of liver function abnormality was 71.94% (12 001/16 681). The elevations of direct bilirubin, γ-glutamyl-transferase and alanine aminotransferase were the most common findings accounting for 33.37% (4863/14 574), 32.51% (4337/13 341) and 30.12% (5024/16 681) respectively. The abnormality of alkaline phosphatase was rare and its increase and decrease accounted for 3.82% (474/12 397) and 4.51% (559/12 397) respectively. The prevalence of low albumin and total bilirubin elevation was 23.24% (3408/14 664) and 19.37% (3231/16 681). And high direct bilirubin (HR 1.264, 95%CI 1.103 - 1.423; P = 0.02), high total bilirubin (HR 1.126, 95%CI 1.019 - 1.234; P = 0.02) and low albumin (HR 0.889, 95%CI 0.794 - 0.889; P < 0.01) were determined as the independent risk factors of total mortality. There were the correlations of LVEF with direct bilirubin (r = -0.235, P < 0.01), total bilirubin (r = -0.209, P < 0.01), albumin (r = 0.107, P < 0.01) and right ventricular end-diastolic diameter (RVDD) with direct bilirubin (r = 0.149, P < 0.01), total bilirubin (r = 0.154, P < 0.01) and albumin (r = -0.086, P < 0.01). CONCLUSION: The prevalence of liver function abnormalities is high in patients with chronic systolic HF. Low albumin, high direct bilirubin and high total bilirubin increase their total mortalities. Low LVEF and high RVDD are positively correlated with a high prevalence of liver function abnormalities.