Hydrogel-based co-delivery of CIK cells and oncolytic adenovirus armed with IL12 and IL15 for cancer immunotherapy.

Intratumoral injection of various effector cells combined with oncolytic adenovirus expressing antitumor cytokines exert an effective antitumor immune effect by oncolysis and altering the tumor microenvironment. However, this combination therapy had certain limitations. When used in high concentrations, effector cells and oncolytic viruses can spread rapidly to surrounding non-target tissues. And because both therapies used in combination are immunogenic and exhibit shorter biological activity, multiple injections were required to attain an adequate therapeutic index. To overcome these drawbacks, we encapsulated gelatin-based hydrogel capable of co-deliver oncolytic adenovirus armed with IL12 and IL15 (CRAd-IL12-IL15) and CIK cells for enhancing and prolonging the antitumor effects of both therapies after a single intratumoral injection. The injectable and biodegradable hydrogel reduced the dispersion of high-dose oncolytic adenovirus and CIK cells from the injection site to the liver and other non-target tissues. In this study, a novel oncolytic adenoviral vector CRAd-IL12-IL15 was constructed to verify the cytokine expression and oncolytic ability, which can upregulate the expression levels of Bcl-2, Cish and Gzmb in tumor cells. The CRAd-IL12-IL15 + CIKs/gelatin treatment maintained sustained release of CRAd-IL12-IL15 and active CIK cells over a longer period of time, attenuating the antiviral immune response against adenovirus. In conclusion, the results suggested that hydrogel-mediated co-delivery of CRAd-IL12-IL15 and CIK cells might be a an approach to overcome limitations. Both treatments could be effectively retained in tumor tissue and sustained to induce potent anti-tumor immune responses with a single administration.

Hemorrhagic pleural effusion related to acquired coagulation factor VIII deficiency: A case report.

A patient with acquired hemophilia A (AHA) with hemorrhagic pericardial effusions was admitted to Xiamen Chang Gung Hospital (Xiamen, China) in August 2015. The patient had been experiencing progressive dyspnea for 1 week. Bloody effusion (~6.3 l) was drained from the membrane surrounding the heart over a period of 20 days. Biochemical, cytological and radiological examinations were unable to elucidate the reason for the effusion. Coincidentally, it was discovered that activated partial thromboplastin time prolongation could not be corrected by plasma mixing. Furthermore, immunologic and functional assays identified that the patient had factor VIII-deficient plasma. Finally, the coagulopathy was treated by infusion of cryoagglutinin and steroids to eradicate the coagulation inhibitor. The production of cardiac bloody effusions did not recur. Notably, the patient was diagnosed with AHA accompanied by the rare complication of pericardial effusions. The present case was the first to report AHA with the complication of pericardial effusions.

Prompt bone marrow-derived mesenchymal stem cell therapy enables early porcine heart function recovery from acute myocardial infarction.

Impact of early bone marrow-derived mesenchymal stem cell (BMDMSC) implantation on left ventricular (LV) function after AMI was studied.Twelve mini-pigs were equally divided into placebo (AMI through left coronary artery ligation) and cell-treated groups [BMDMSCs (3.0 × 10(7)) implanted into infarct area (IA)] with myocardium harvested by post-AMI day 90. Six healthy animals served as controls.On post-AMI day 90, magnetic resonance imaging showed a lower LV ejection fraction but higher LV dimensions in the placebo group (P < 0.003) that also had increased IAs but reduced wall thickness (P < 0.005). Pro-apoptotic gene expressions (Bax, caspase-3) and apoptotic nucleus number in IAs and peri-IAs were highest in the placebo group (P < 0.001). Inflammatory biomarker expressions (MMP-9, oxidized protein, CD40+ cells) were highest, whereas those of angiogenesis (VEGF, CD31+ cells, SDF-1α, CXCR4) and myocardium-preservation (connexin43, troponin-I, cytochrome-C) were lowest in the placebo group (P < 0.01).BMDMSC implantation preserved LV function and alleviated remodeling at post-AMI day 90.

[Preliminary study on characteristics of volumetric oxygen transfer coefficient in granular sludge systems].

The volumetric oxygen transfer coefficient (k(L)a) was tested with mature aerobic granules in the same aeration measurement device and under the same aeration conditions. The k(L)a (min(-1)) was 0.586 1 +/- 0.009 5, 0.586 1 +/- 0.0272, 0.555 6 +/- 0.016 8, 0.5338 +/- 0.0268 for floc sludge, and 0.645 5 +/- 0.027 6, 0.632 0 +/- 0.0755, 0.618 5 +/- 0.062 5, 0.640 6 +/- 0.055 5 for aerobic granules, when the sludge concentration MLSS (mg x L(-1)) was controlled at 2 000, 4 000, 6 000, 8 000, respectively. This indicated that granular sludge exhibited higher k(L)a values than the flocs, and the k(L)a value of floc sludge decreased with the increase of the sludge concentration; however, insignificant decease was found for granular sludge. After screening of granules with different diameter, the k(L)a values of the aerobic granular sludge with different sizes which had the same MLSS, volume, surface area and particle number were compared, and insignificant difference was found, suggesting that the effects of these factors on the k(L)a of granular sludge were negligible. The findings of this work may have significance for the energy-saving operation of wastewater treatment plants.

Value and level of plasma homocysteine in patients with angina pectoris undergoing coronary angiographic study.

This study tested whether the plasma level of total homocysteine (tHcy) was predictive of obstructive coronary artery disease (CAD) and clinical outcome in patients undergoing coronary angiographic (CAG) study. From September 2002 to October 2004, 1,305 consecutive patients with angina pectoris undergoing CAG study were consecutively enrolled. Blood samples were prospectively collected to assess the plasma level of tHcy from each patient before catheterization. Of these 1305 patients, 676 (51.8%) had multivessel disease (group 1), 367 (28.1%) had single-vessel disease (group 2), and 262 (20.1%) had normal coronary artery or insignificant coronary artery disease (group 3). The plasma level of tHcy was notably higher in group 1 than in groups 2 and 3 (11.6 ± 4.4 versus 10.9 ± 4.0 versus 10.4 ± 3.8, P < 0.001). Univariate binary logistic regression analysis demonstrated that the plasma tHcy level was strongly associated with multiple-vessel disease (MVD) (defined as ≥ 2 vessel disease) (P < 0.001). Multivariate binary logistic regression analysis showed that tHcy level, fasting blood sugar, diabetes mellitus, and age were significantly and independently predictive of MVD (all P < 0.03). Univariate Cox regression analysis demonstrated that tHcy level was predictive of long-term mortality (P = 0.042). However, the tHcy level was not an independent predictor of long-term mortality on multivariate Cox regression analysis (P > 0.05). The results of our study support the hypothesis that tHcy level is an independent predictor of MVD in patients with chest pain undergoing CAG study. Conversely, our study did not support the tHcy level as an independent predictor of long-term mortality in this clinical setting.

Gender differences in patients undergoing coronary stenting in current stent era.

BACKGROUND: Prior studies have demonstrated worse results of women in both hospital and short-term outcomes post-percutaneous coronary intervention. However, with advanced devices like drug-eluting stents (DESs) available, there are no consistent data revealing gender impact in outcome. This study examined whether gender affected hospital outcome and showed one-year single-center patient results of coronary stenting. METHODS: The study group included 969 consecutive patients (250 women and 719 men) undergoing coronary stenting for stable or unstable angina. Clinical events were assessed for at least 1 year post-procedure. RESULTS: Compared to men, women were older, presented more often with diabetes, hypertension, dyslipidemia, and lower creatinine clearance rate (Ccr); they had less percutaneous transluminal coronary angioplasty (PTCA) history, smaller vessel size, and shorter lesions. The hospital major adverse cardiovascular event (MACE) rate was 2.8% of women and 0.97% of men (P = 0.037). The one-year MACE rate was 10.0% of women and 10.4% of men (P = 0.874). After adjusting other covariates, women still had significantly higher hospital MACE rates (P = 0.034) and odds ratios (0.18; 95% confidence interval: 0.036-0.874). In women (n = 250), there was no statistically significant difference in hospital or one-year MACE between bare metal stent (BMS) and DES groups. Meanwhile, in men (n = 719), DES had a significant one-year improvement of MACE compared to BMS (P = 0.004). The female hospital MACE rate was five times greater than male results. However, there were similar one-year outcomes between women and men. DES currently have an advantage in long-term outcome. CONCLUSIONS: Currently, with the use of BMS and DES, adverse hospital post-procedure cardiovascular event rate has occurred more often in women than in men. However, the MACE rate differences between women and men resolved with one year follow-up.

Dynamic aortic pouch: a rare etiology of aortic regurgitation.

The causes of aortic regurgitation (AR) include rheumatic heart disease, infective endocarditis, and various congenital and degenerative defects. We report an unusual case of AR in a 72-year-old man due to an aortic root pouch. The diagnosis AR was made by cardiac echocardiography, and the cause was revealed by cardiac catheterization and 64-slice cardiac computed tomography. During aortic valve replacement, a saccular pouch between the noncoronary cusp and the right coronary cusp of the aortic valve was noted.

Comparison of 30-day mortality between anterior-wall versus inferior-wall ST-segment elevation myocardial infarction complicated by cardiogenic shock in patients undergoing primary coronary angioplasty.

OBJECTIVES: In this study, 30-day mortality from cardiogenic shock caused by left anterior descending artery (LAD) occlusion was compared with that caused by left circumflex (LCX) or right coronary artery (RCA) occlusion after primary percutaneous coronary intervention (PCI). METHODS: Between May 2001 and December 2009, 212 consecutive patients with anterior-wall ST-elevation myocardial infarction complicated by cardiogenic shock due to LAD (n = 97) occlusion (group 1) and LCX or RCA (n = 115) occlusion (group 2) undergoing primary PCI were enrolled. RESULTS: The results showed a higher mean peak level of creatine phosphokinase and incidence of extracorporeal membrane oxygenation in group 1 than group 2 (all p < 0.01). However, no significant difference was noted in the achievement of normal blood flow in the infarct-related artery (p = 0.461) and 30-day morality (p = 0.338). Univariate analysis demonstrated a significant association of 30-day morality with age, lower left-ventricular ejection fraction, advanced congestive heart failure and unsuccessful reperfusion (all p < 0.02). Multivariate analysis revealed unsuccessful reperfusion as the most independent predictor of 30-day mortality (p = 0.002). CONCLUSION: No significant difference was noted in 30-day mortality between patients with acute myocardial infarction and cardiogenic shock caused by LAD occlusion and by either RCA or LCX occlusion undergoing primary PCI.