DC-CTL targeting carbonic anhydrase IX gene combined with iAPA therapy in the treatment of renal cell carcinoma.

INTRODUCTION: To deliver specific antigens in tumor immunotherapy, tumor cell lysates are commonly used to sensitize dendritic cells (DCs). However, the lysates possess low immunogenicity and contain many types of non-tumor-related antigens, which may induce autoimmune diseases. Tumor antigen peptides can provide high specificity but are expensive and their short half-lives limit their clinical application. METHODS: In this study, we used adenovirus to transfer the carbonic anhydrase IX (CA9) gene into DCs to generate specificity to renal cell carcinoma (RCC) which is the most common space-occupying lesion in humans. Inhibition of antigen presentation attenuators (iAPA) technology was also used to enhance the DC delivery capacity. Finally, DCs were co-cultured with cytotoxic T-lymphocytes (CTLs) and the anti-tumor effects were evaluated. RESULTS: The results showed that the CA9-DC-CTLs possessed a high specificity to CA9-positive cells and showed stronger anti-tumor activity than GFP-DC-CTLs both in vitro and in vivo. DISCUSSION: These findings may suggest a novel treatment option for RCC.

Simultaneous removal of NOx and SO2 with H2O2 over silica sulfuric acid catalyst synthesized from fly ash.

Considering that the utilization of fly ash in the removal of flue gas pollutants not only provide a way of high value-added utilization of fly ash, but also greatly reduce the cost of removing flue gas pollutant, the synthesis of silica sulfuric acid catalyst from fly ash and its application in simultaneous removal of NOx and SO2 with H2O2 were investigated in this work. Circulating fluidized bed boiler (CFB) fly ash and pulverized coal boiler (PC) fly ash were selected as raw material to prepare silica sulfuric acid catalyst by H2SO4 activation. PC fly ash was difficult to be activated by H2SO4 due to its dense structure, while CFB fly ash could be treated with H2SO4 to promote dealumination, thereby increasing the silica content. Moreover, the -SO3H withdrawing groups were detected on the silica surface by XPS and Py-FTIR technologies, indicating the formation of silica sulfuric acid. Silica sulfuric acid showed higher activity in catalyzing the NO oxidation by H2O2, and a possible reaction mechanism was proposed. Combined with alkali absorption, 99% SO2 and 92% NOx removal efficiencies can be achieved. The effects of activation conditions such as activation temperature, activation time and calcination temperature and removal experimental parameters such as H2O2 concentration, SO2 concentration and simulated flue gas temperature on the catalytic performance were studied. Finally, the catalyst was not found to be deactivated for ten hours in the stability test.

The roles of Brønsted acidity in low-temperature catalytic oxidation of NO over acidic zeolites with H2O2.

In this study, low-temperature catalytic NO oxidation with H2O2 over Na- and H-exchanged Y and ZSM-5 zeolites was investigated at 140 °C which is the average exhaust temperature of coal-fired power plant. Fast catalytic NO oxidation rates were observed over H-zeolites, and catalytic activity was proportional to the amount of Brønsted acid sites. HZSM-5 and HY zeolites show 65% and 95% NO removal efficiency, respectively, but the catalytic stability of HY was lower than HZM-5 due to partial dealumination during the reaction. In-situ DRIFTS analysis showed that NO+ species coordinated at framework sites played a direct role in the catalytic NO oxidation. Moreover, the possible reaction pathway was proposed to elucidate the mechanism of NO oxidation with H2O2 catalyzed over Brønsted acid sites. The effect of reaction temperature, H2O2 concentration, H2O2 flow and SO2 concentration on NO oxidation were investigated over H-zeolites. The experimental results indicated that the NO removal efficiency was increased with the increase of H2O2 concentration, but decreased with the increase of SO2 concentration. The NO removal efficiency first increased and then decreased with the increase of H2O2 flow and reaction temperature.

NO oxidation over Fe-based catalysts supported on montmorillonite K10, γ-alumina and ZSM-5 with gas-phase H2O2.

The catalytic gas-phase H2O2 oxidation of NO was achieved over Fe-based catalysts supported on montmorillonite K10, γ-alumina and ZSM-5. ESR tests illustrate that the three catalysts can catalyze decomposition of H2O2 yielding highly reactive hydroxyl radicals, of which Fe/K10 has the fastest rate, followed by Fe/γ-alumina. Fe3+ in Fe/K10 and Fe/γ-alumina show lower density of electron cloud due to a strong interaction between Fe3+ and the support, which benefits the electron transfer from the H2O2 to Fe3+, thus favoring the production of hydroxyl radicals. Fe species exist on the surface of Fe/K10 mainly in the form of Fe2O3, whereas Fe species of Fe/γ-alumina and Fe/ZSM-5 exist mainly in the form of Fe3O4, and it is found that Fe2O3 is more active than Fe3O4 in catalytic gas-phase H2O2 oxidation of NO. Interestingly, Fe/ZSM-5 has the lowest efficiency in generating hydroxyl radicals, its NO removal efficiency is 90%, which is much higher than 47.5% for Fe/γ-alumina and 62.3% for Fe/K10. In-situ IR results suggested that Fe/ZSM-5 are dual functional in oxidation of NO, that is, whether both Fe ion sites and Brønsted acid sites collectively provide the catalytic functionality. In the meantime, a possible reaction mechanism on catalytic gas-phase H2O2 oxidation of NO over Brønsted acid sites is proposed.

The DPP-4 inhibitor saxagliptin ameliorates ox-LDL-induced endothelial dysfunction by regulating AP-1 and NF-κB.

Diabetes-associated cardiovascular complications are the leading cause of death for diabetic patients. Dipeptidyl peptidase 4 (DPP-4) inhibitor agents, known as gliptins, are a class of potent anti-glycemic agents developed to treat diabetes. Recently, gliptins have been shown to have independent cardiovascular benefits. In this study, we revealed the protective role of saxagliptin in vascular endothelial cells. Our data show that saxagliptin suppresses oxidized low-density lipoprotein cholesterol (ox-LDL)-induced expression of its receptor lectin-like ox-LDL receptor-1 (LOX-1). Saxagliptin treatment reduces ox-LDL-induced production of cytokines and vascular adhesion molecules including tumor necrosis factor (TNF-α), interleukin-1ß (IL-1ß), vascular cell adhesion molecule 1 (VCAM-1), and intercellular cell adhesion molecule-1 (ICAM-1). The presence of saxagliptin suppressed ox-LDL-induced adhesion of monocytes to endothelial cells in co-culture adhesion experiments. Moreover, saxagliptin mitigated ox-LDL-induced production of reactive oxygen species and suppressed elevated expression of endothelial nicotinamide adenine dinucleotide phosphate oxidase subunit (NOX-4) induced by ox-LDL. Mechanistically, saxagliptin exerted inhibitory effects against ox-LDL-induced phosphorylation of JNK kinase, expression of the activator protein 1 (AP-1) subunits c-Jun/c-fos, and AP-1 promoter activity. Saxagliptin also suppressed nuclear factor κB (NF-κB) p65 accumulation and inhibited its promoter activity. Our data elaborate the molecular mechanism of saxagliptin-mediated endothelial protection and indicate that saxagliptin could have vascular benefits independent on its anti-glycemic function.

Effects of microrna-93 on mouse cardiac microvascular endothelial cells injury and inflammatory response by mediating SPP1 through the NF-ΚB pathway.

BACKGROUND: This study aims to investigate the regulative role of microRNA-93 (miR-93) in mouse cardiac microvascular endothelial cells (CMECs) injury and inflammatory response by negatively targeting SPP1 gene via the NF-κB signaling pathway. METHODS: Healthy Balb/c mice were recruited to establish a mouse model with myocarditis using the CVB3 virus. Mice were grouped into normal, blank, negative control (NC), miR-93 inhibitor, miR-93 mimic, SPP1 short hairpin RNA (shRNA), and miR-93 mimic+SPP1 shRNA groups. Reverse transcription quantitative polymerase chain reaction and Western blot analysis were applied to determine the expressions of miR-93, SPP1, VEGFA, p50, p65, Bax, and Bcl-2. MTT assay was conducted to evaluate cell viability, annexin V-fluorescein isothiocyanate/propidium iodide double staining was conducted to examine cell apoptosis, enzyme-linked immunosorbent assay was conducted to measure secretion of inflammatory factors, and chemical colorimetry was conducted to determine NO secretion. RESULTS: SPP1 was a target gene of miR-93. Compared with the normal group, other six groups showed increased expressions of SPP1, p50, p65, VEGFA, and Bax, as well as cell apoptosis rate and secretion of cell inflammatory factors, and decreased expression of Bcl-2, cell viability, and NO secretion. Compared with the blank group, the miR-93 inhibitor group showed elevated expressions of SPP1, p50, p65, VEGFA, and Bax, as well as cell apoptosis rate and secretion of cell inflammatory factors, and reduced Bcl-2, cell viability, and NO secretion. While the miR-93 mimic and SPP1 shRNA groups displayed opposite results. CONCLUSION: Taking our results together, we conclude that upregulation of miR-93 reduces CMECs injury and inflammatory response by negatively targeting SPP1 via inactivating the NF-κB signaling pathway.

[Ultrasonic monitoring of carotid blood flow in interposed abdominal pulling-pressing cardiopulmonary resuscitation].

OBJECTIVE: To explore the difference in ultrasonic monitoring in carotid blood flow, resuscitation effects and prognosis between interposed abdominal pulling-pressing cardiopulmonary resuscitation (IAPP-CPR) and standard cardiopulmonary resuscitation (STD-CPR). METHODS: Seventy-five cardiac arrest (CA) patients admitted to emergency department of Shijingshan Teaching Hospital of Capital Medical University from June 2015 to December 2017 were enrolled. The patients were divided into STD-CPR group and IAPP-CPR group according to the treatment orders of them and the desire of relatives. All patients were given persistent external compression, airway open, tube intubation, and mechanical ventilation, vasoactive drugs application, defibrillation if required. STD-CPR group was operated according to the 2015 American Heart Association (AHA) CPR guidelines. On the basis of the standard CPR, IAPP-CPR group was recovered using abdominal lifting and compressing CPR instrument to press down to lift the upper abdomen continuously, when the chest compressing relaxed (frequency 100 times/min, down and lift time ratio 1:1, compressing strength 50 kg, lifting strength 30 kg). The patients' gender, age and CA etiology were recorded in the two groups. The vital signs and blood flow of carotid artery were monitored with ultrasonic Doppler during the CPR. The return of spontaneous circulation (ROSC) rate and 48-hour survival rate were observed in patients. The influence factors of ROSC were screened by Logistic regression analysis. RESULTS: The data of 75 patients with CA were enrolled finally, with STD-CPR group of 38 patients and IAPP-CPR group of 37 patients. There were no significant differences in patients' gender, age or CA etiology between the two groups. Comparing with STD-CPR group, the peak blood flow velocity of carotid artery in IAPP-CPR group was speeded up significantly (cm/s: 107.16±13.75 vs. 78.99±14.77, P < 0.01), the overall blood flow volume of carotid artery was increased significantly (mL/min: 989.06±115.88 vs. 751.62±118.92, P < 0.01), but there was no significant difference in inner diameter of carotid artery between the two groups (mm: 4.55±0.25 vs. 4.61±0.21, P > 0.05). During the CPR, the mean arterial pressure (MAP) and the transcutaneous oxygen saturation (SpO2) in IAPP-CPR group were significantly higher than those of STD-CPR group, but no significant difference was found in heart rate between the two groups. Four patients in STD-CPR group got ROSC, and 3 survived over 48 hours (1 myocardial infarction patient died of ventricular fibrillation) while 6 patients in IAPP-CPR group got ROSC and survived over 48 hours. There was no significant difference in ROSC rate or 48-hour survival rate between the two groups, but data of IAPP-CPR group was slightly higher than that of STD-CPR group [ROSC rate: 16.22% (6/37) vs. 10.53% (4/38), 48-hour survival rate: 16.22% (6/37) vs. 7.89% (3/38), both P > 0.05]. Multivariate Logistic regression analysis showed that the higher the MAP during CPR, the greater the possibility of ROSC was [odds ratio (OR) = 1.361, 95% confidence interval (95%CI) = 1.182-1.669, P = 0.030]. CONCLUSIONS: IAPP-CPR was superior to traditional STD-CPR in improving arterial blood flow and resuscitation effect, but no superiority was found in ROSC rate and survival rate, which may be relate to the small number of patients that included in this study. More clinic trials are needed.

A scoring system for assessing the severity of acute diarrhea of adult patients.

BACKGROUND: Diarrhea is frequently seen in developed and developing countries, and severe diarrhea is characterized by the high risk of death. Thus, it is very important to assess the severity of diarrhea early. We conducted a multi-center study to identify risk factors for the severity of diarrhea in adult patients and formulate an adult diarrhea state score (ADSS) for out-patient clinicians. METHODS: A total of 219 adult patients with acute diarrhea were divided into two groups: 132 patients with mild diarrhea and 87 with severe diarrhea. Logistic regression was used to determine risk factors for the severity of diarrhea. The risk factors were assessed and an ADSS was formulated. Receiver operating characteristic (ROC) analysis was made to evaluate the diagnostic accuracy of ADSS, and the Kappa test was used to confirm the diagnostic reliability. RESULTS: Five risk factors for evaluating the severity of diarrhea in adults included age (P<0.05), axillary temperature (P<0.01), mean arterial pressure (P<0.01), white blood cell count (WBC; P<0.01), and WBC in stool (P<0.01). The area under the ROC curve for ADSS was 0.958 when the cut off value was 4 (a sensitivity of 0.909; a specificity of 0.874), and the Kappa value was 0.781 (P<0.05). CONCLUSION: The risk factors associated with the pathogenic condition of diarrhea were identified, quantified and formulated into an ADSS, which has high diagnostic accuracy and reliability for the early identification of patients with severe acute diarrhea.

The identification of risk factors for critically ill patients with acute fever and formulation of activation criteria to alert outpatient clinic doctors.

RATIONALE, AIMS AND OBJECTIVES: Acute fever is the most common early clinical symptom of many critical illnesses with a high mortality rate. It is necessary to identify patients with severe acute fever early and accurately. The aim of this study is to identify risk factors for critically ill outpatients with acute fever and formulate activation criteria of adult fever state score (AFSS) to alert outpatient clinic doctors. METHODS: Retrospectively, 357 adult patients with acute fever were divided into two groups: 180 patients with a severe state and 177 patients with a mild state. Logistic regression was used to determine risk factors for the severe state. Risk factors were weighted and an AFSS was formulated. A receiver operating characteristic (ROC) analysis of weighted cumulative scores was performed to evaluate the diagnostic accuracy of AFSS, and the kappa test was used to confirm diagnostic reliability. A χ(2) -test for trend was applied to determine the relevance between AFSS and admission rate and in-hospital mortality. A Kruskal-Wallis test was used to examine the relationship between AFSS and length of stay. RESULTS: Risk factors for state included: old age, long fever course, past medical history, abnormal temperature, abnormal respiratory rate, abnormal heart rate, abnormal mean arterial pressure and abnormal peripheral white blood cell count. The area under the ROC curve of AFSS was 0.964 and ≥8 points predicted severe state; the Kappa value was 0.801. With an increase in score, there was an increase in admission rate, mortality rate and length of stay. The forecast performance of AFSS was superior to the modified early warning score. CONCLUSIONS: The AFSS has high diagnostic accuracy and reliability for the early identification of patients with severe acute fever.

The identification of risk factors for infectious patients with acute fever and formulation of activation criteria to alert outpatient clinic doctors.

RATIONALE, AIMS AND OBJECTIVES: Acute fever is the most common clinical symptom for infectious diseases. It is necessary to identify risk factors for infectious patients with acute fever and formulate activation criteria of early warning infectiosity score system (EWIS) to alert outpatient clinic doctors. METHODS: Logistic regression analysis was used to determine risk factors for infectious diseases from the clinical data of 758 patients with acute fever. Risk factors were weighted and an EWIS was formulated. A receiver operator characteristic (ROC) analysis of weighted cumulative scores was performed to evaluate the diagnostic accuracy of EWIS, and the Kappa test used to confirm diagnostic reliability. A χ(2) -test for trend was applied to determine the relevance between EWIS and incidence of infectious diseases. RESULTS: Risk factors for infections included conjunctival hyperaemia, rash, diarrhoea, increased alanine aminotransferase, splenomegaly and abnormal percentage of peripheral neutrophils (NE%). Risk factors were weighted and tabulated. The areas under the ROC curves of the EWIS was 0.929 and ≥ 4 points predicted infectious diseases, and the Kappa values were 0.750. As the score increased, the incidence of infectious diseases increased. The areas under the ROC curves of the EWIS predicting on single viral and bacterial infectious diseases were 0.961 and 0.896, and the Kappa values were 0.807 and 0.701, respectively. CONCLUSIONS: Risk factors for infections have been identified, quantified and formulated into a table of EWIS that have high diagnostic accuracy and reliability for the early identification of contagious diseases.

An outbreak of angiostrongyliasis cantonensis in Beijing.

An outbreak of 81 cases of angiostrongyliasis cantonensis (AC) occurred in Beijing, China, during June through September 2006. Epidemiological characteristics, clinical signs and symptoms, laboratory tests, imaging, and treatment data from the 81 AC patients were collected and analyzed. All cases had a history of eating raw freshwater snails, and acquired Angiostrongylus cantonensis as a result. The incubation period ranged from 1 to 36 days. The main symptoms were fever, severe headache, neck stiffness, and skin paresthesia. A significant increase in eosinophilia occurred in the peripheral blood of 62 cases and in cerebrospinal fluid of 64 cases; 36 patients presented a linearly enhanced abnormal signal of the leptomeninges site during a cranial MRI examination, indicative of meningitis; 18 cases had a significant nodule shadow and spot flaky ground-glass shadow on chest computerized tomography. All patients were relieved of their illness with a 7-day treatment of albendazole.

[Epidemiological analysis on 141 cases of angiostrongyliasis cantonensis in Beijing].

OBJECTIVE: To provide scientific basis for angiostrongyliasis cantonensis control and prevention in Beijing. METHODS: Descriptive epidemiological method was used to analyze angiostrongyliasis cantonensis reported from June to September in 2006. RESULTS: 141 cases were treated at the Beijing Friendship Hospital with the peak in July (61 cases) and August (68 cases). All patients had dined at the same restaurant in Beijing city and they ate undercooked Pomacea canaliculata or related eatables. The source of Pomacea canaliculata was from Guilin in Guangxi. Major manifestations would include fever (56.79%), headache (93.83%), neck stiffness (100%), and skin paresthesia (77.78%). Some cases had significant eosinophil increase in peripheral blood picture and cerebrospinal fluid respectively. CONCLUSION: The source of infection related to angiostrongyliasis cantonensis was clear, suggesting that the improvement of restaurant sanitation and on awareness of personal hygiene were important preventive and control measures on angiostrongyliasis cantonensis.