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There are two serious obstacles to tumor immunotherapy. Firstly, the immune response of the tumor is seriously reduced due to immunosuppressive tumor microenvironment (ITM) and low immunogenicity of tumor. The second obstacle is the dense and complex heterogeneous structures, which seriously prevent the nanoparticles (NPs) from penetrating deeper into tumor tissue. Immunogenic cell death (ICD) induced by doxorubicin (DOX) is an effective method to enhance tumor immune activity. However, interferon-γ (IFN-γ) secreted by cytotoxic T lymphocytes (CTL) after ICD induction would increase the expression of indoleamine 2,3-dioxygenase 1 (IDO1) and enhance ITM. IDO1 siRNA would reduce the expression of IDO1 protein, regulate the tumor immunosuppressive microenvironment and regulate ITM, so as to enhance the ICD effect of DOX. In this paper, a novel charge conversional, particle size reduction and highly penetrable NPs based on a pH sensitive copolymer poly(ethylene glycol)-poly-L-lysine-2,3-dimethylmaleic anhydride (mPEG-PLL-DMA, PLD) and polyamidoamine (PAMAM) dendrimers to achieve deep delivery of tumor tissue. DOX and IDO1 siRNA were encapsulated to achieve efficient tumor immunotherapy. Preparation and cell level experiments showed that PLD material had significant pH sensitivity. Results of 3D tumor penetrable experiment in vitro showed that adding the pH sensitive material PLD significantly improved the permeability of the preparation. In addition, 4T1 tumor model was established for BALB/c mice and all animal experiments were displayed in according with the requirements of the Animal Experiment Ethics Committee of Shenyang Pharmaceutical University. The results of in vivo efficacy experiments and tissue experiments evaluated that IDO1 siRNA significantly improved the ICD effect owing to DOX, so as to significantly inhibit tumor growth.
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OBJECTIVE@#To investigate the correlation of intraplaque neovascularization (IPN) detected by carotid contrast-enhanced ultrasound (CEUS) with revascularization in patients following percutaneous coronary intervention (PCI).@*METHODS@#This study was conducted among 105 patients who were followed up for more than 12 months after PCI. All the patients received CEUS examination for assessment of carotid plaque formation and IPN, which were compared between patients with revascularization (REV group, n=27) and those without revascularization (N-REV group, n=78). ROC curve was used to analyze the diagnostic efficacy of CEUS for predicting revascularization. Univariate and multivariate logistic regression analyses were performed to identify the risk factors associated with revascularization.@*RESULTS@#In the REV group, the IPN score was 0 in 1 (3.7%) patient, 1 in 8 (29.6%) patients, 2 in 15 (55.6%) patients and 3 in 3 (11.1%) patients. Significant differences were noted between REV and N-REV groups in plaque length (15.70±6.93 vs 12.10±6.64, P < 0.05), maximum plaque thickness (3.69±1.12 vs 3.14±1.18, P < 0.05) and IPN (1.74±0.71 vs 0.87±0.63, P < 0.001). IPN score was identified as an independent risk factor for revascularization in patients following PCI, and at the cutoff value of 1.5, its sensitivity, specificity, positive predictive value, and negative predictive value for predicting the occurrence of revascularization were 74%, 89%, 69%, and 91%, respectively, with an AUC of 0.848 (95% CI: 0.703-0.905, P < 0.001).@*CONCLUSION@#CEUS allows noninvasive and semi-quantitative assessment of neovascularization in carotid artery plaques, and IPN detected by CEUS is correlated with the risk of revascularization in patients following PCI.
Subject(s)
Humans , Neovascularization, Pathologic , Percutaneous Coronary Intervention , ROC Curve , Risk Factors , Vascular Surgical ProceduresABSTRACT
A methodology of quantitative analysis on ginsenoside Re (G-Re) in rat plasma by ultra performance liquid chromatography-triple quadrupole mass spectrometry was developed for comparing the pharmacokinetic profiles between normal rats and Ultraviolet B (UVB) irradiation-induced damage rats after oral administration. The sample separation was carried out on an Ascentis?Express C18column (5.0 mm× 3.0 mm,2.7 μm) with 0.1% formic acid in water and acetonitrile as the mobile phase under gradient elution. MS analysis was operated in multiple-reaction monitoring (MRM) mode using electrospray ionization (ESI) with negative ion mode,and the ions for quantification were m/z 991.54/945.53/475.60. The limit of detection (LOD,S/N=3), limit of quantification (LOQ, S/N=10) were 4.0 ng/mL and 13.5 ng/mL, respectively. G-Re was in good linearity between 15 ng/mL and 20000 ng/mL(r=0.999),the intra-day and inter-day precisions, recovery, matrix effect and stability could meet the pharmacokinetic analysis requirement. The results indicated that the metabolic process of G-Re conformed to a two-compartment pharmacokinetic model after single oral administration in the normal and model groups. The t1/2αwere(0.21± 0.04) h and (0. 69 ± 0. 07) h, respectively; t1/2βwere (17. 08 ± 0. 53) and (21. 40 ± 16. 77) h, respectively;AUC(0-t)were (321.91±2.27) μg/(L·h) and (474.99±194.96) μg/(L·h), respectively;AUC(0-∞)were (332. 44 ± 1. 66) μg/(L·h) and (518. 64 ± 231. 39) μg/(L·h), respectively; the pharmacokinetic parameters were significantly different between normal and UVB irradiated rats (p<0.05), except for t1/2α. This UHPLC-QQQ-MS method showed excellent separation, accuracy, high sensitivity, specificity and good repeatability,and it was suitable for the pharmacokinetic study of G-Re in vivo.
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Objective To explore the effect of adenosine preconditioning on vascular endothelial growth factor(VEGF)and angiopoietin-1 (Ang-1) in oxygen-glucose deprivation and reoxygenation astrocytes.Methods Astrocytes of pallium in Sprague Dawley rats were cultured in vitro,and the third generation of astrocytes were passaged to 96 pore plate.The astrocytes were divided into normal control group,oxygen-glucose deprivation group and adenosine preconditioning group randomly when the astrocytes adhered to the wall and grew the evection.The cells in the normal control group did not received oxygen glucose deprivation;the cells in the oxygen-glucose deprivation group received oxygen-glucose deprivation 8 h and reoxygenation 24 h;the cells in the adenosine preconditioning group were given adenosine 100 μmol · L-1 at 24 hours before received oxygen-glucose deprivation 8 h and reoxygenation 24 h.The shape of astrocytes were observed after reoxygenation 24 h.The cytoactivity of astrocytes in each group was detected by methyl thiazolyl tetrazolium assay;the concentration of VEGF and Ang-1 in supernatant of astrocytes in each group was detected by enzyme linked immunosorbent assay.Results The astrocytes in the normal control group grew well.The edema of astrocytes in the oxygen-glucose deprivation group was obvious,and the cell body became round;the cell morphology changed from irregular to spindle shape;and the neurites became shorter or even disappeared.Compared with the oxygen-glucose deprivation group,the astrocytes in the adenosine preconditioning group had a mildly edema,and the cells were arranged orderly.The vitality of astrocytes in the normal control group,oxygen-glucose deprivation group and adenosine preconditioning group was 0.698 ± 0.059,0.196 ± 0.062,0.412 ± 0.009 respectively;the vitality of astrocytes in the oxygen-glucose deprivation group was obviously lower than that in the normal control group(q =3.561,P ＜0.05);the vitality of astrocytes in the adenosine preconditioning group was obviously higher than that in the oxygen-glucose deprivation group (q =2.102,P ＜ 0.05).The concentration of VEGF in supemate in the normal control group,oxygen-glucose deprivation group and adenosine preconditioning group was (0.038 ± 0.005),(0.053 ± 0.007),(0.084 ± 0.006) μg · L-1 respectively;the concentration of Ang-1 in supemate in the normal control group,oxygen-glucose deprivation group and adenosine preconditioning group was (0.030 ± 0.007),(0.049 ± 0.008),(0.080 ± 0.004) μg · L-1 respectively.The concentration of VEGF and Ang-1 in the oxygen-glucose deprivation group were obviously higher than those in the normal control group(q =1.394,1.633;P ＜ 0.05);the concentration of VEGF and Ang-1 in the adenosine preconditioning group were obviously higher than those in the oxygen-glucose deprivation group (q =1.584,1.632;P ＜ 0.05).Conclusion The adenosine preconditioning can increase the expression of VEGF and Ang-1 in astrocytes after oxygen-glucose deprivation.It can enhance the tolerance of brain to ischemia-reperfusion injury and produce neural protection effect.
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Endocardial fiborelastosis (EFE) is a common infantile myocardiosis. The pathogenesis of EFE may be associated with viral infection, genetic factors, immune factors and endocardial dysplasia. The fundamental pathological changes of EFE include hyperplasia of endocardium elastic fibers and collagen fibers. Acute EFE is a frequent type. Clinical manifestations of EFE are non-specific and children with EFE mainly present with congestive heart failure. Echocardiography is very helpful to the diagnosis of EFE. It is necessary to differentiate EFE from pneumonia complicated by acute congestive heart failure, viral myocarditis and anomalous origin of the left coronary artery. Treatment is meant to control symptoms of congestive heart failure. Patients who respond well to digitalis and have good medication compliance have a favorable prognosis.
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Humans , Diagnosis, Differential , Endocardial Fibroelastosis , Diagnosis , Therapeutics , PrognosisABSTRACT
<p><b>OBJECTIVE</b>To study the ECG features in children with dilated cardiomyopathy (DCM), and related factors for the occurrence of arrhythmia secondary to DCM.</p><p><b>METHODS</b>Data from 68 children with DCM from January 1998 to March 2011 were studied. The children were classified into three groups: severe arrhythmia (n=42), non-severe arrhythmia (n=20) and non-arrhythmia (n=6). Left ventricular end diastolic diameter (LVED), left ventricular ejection fraction (LVEF) and left ventricular fractional shortening (LVFS) were compared.</p><p><b>RESULTS</b>Abnormal ECG results were found in all of the 68 children with DCM. Sinus tachycardia (91%) and ectopic pulsatile (86%) were common. LVED in the severe arrhythmia group (74±6 mm) was greater than that in the non-severe arrhythmia group (65±4 mm; P<0.05) and non-arrhythmia group (61±3 mm; P<0.05). LVED in the non-severe arrhythmia group was also greater than that in the non-arrhythmia group (P<0.05). LVEF and LVFS in the severe arrhythmia group were (30±11)% and (22±4)%, respectively, which were lower than those in the non-severe arrhythmia group［(37±12)% and (28±5)%, respectively］and non-arrhythmia group［(45±9)% and (34±7)%, respectively］(P<0.05). There were also significant differences in the LVEF and LVFS between the non-severe arrhythmia and non-arrhythmia groups (P<0.05).</p><p><b>CONCLUSIONS</b>The common abnormal ECG findings are sinus tachycardia and ectopic pulsatile in children with DCM. Arrhythmia is one of the main clinical manifestations of DCM. The occurrence of arrhythmia is associated with the left ventricular size and heart function.</p>
Subject(s)
Adolescent , Child , Child, Preschool , Female , Humans , Infant , Male , Arrhythmias, Cardiac , Cardiomyopathy, Dilated , ElectrocardiographyABSTRACT
<p><b>OBJECTIVE</b>To investigate the status of voice fatigue and throat disease in the secondary school teachers in Urumqi.</p><p><b>METHODS</b>This study included 11 689 teachers from 109 secondary schools offered by Teaching and Researching Center of Urumqi as the second-stage random sampling. Among them, 3217 teachers were selected to carry out voice fatigue test and routine examination of throat. For those with abnormal routine inspection results, the stroboscopic laryngoscopy were added.</p><p><b>RESULTS</b>The failure rate difference of 3217 secondary school teachers voice fatigue tests during different periods had statistical significance (F = 202.653, P < 0.05). The failure rate difference of voice fatigue test among different throat diseases groups had statistical significance (F = 9.516, P < 0.05). There was statistical significance in failure rates of the voice fatigue tests between 908 cases of disease group and 2309 cases of normal group among different genders and periods (P < 0.05). Female teachers had higher failure rates than male teachers in voice fatigue tests. High failure rates appeared when high volume required for male and female teachers in voice fatigue tests. There was statistical significance in mean value sound pressure level (MVSPL) and mean value fundamental frequency (MVF0) of the voice fatigue tests between different gender and periods (P < 0.05). Male teachers had higher MVSPL than female teachers, female teachers had higher MVF0 than male teachers. There was statistical significance in failure rates of the voice fatigue tests among teachers from different tribes in different periods (P < 0.05). The Uighur had the highest failure rate, while Han had the lowest. Make further pairwise comparisons, failure rates difference of the Han and the Uighur in the voice fatigue tests during different periods had statistical significance. Comparison among other tribes had no statistical significance (P > 0.05).</p><p><b>CONCLUSIONS</b>Voice fatigue is common in secondary school teachers. Female teachers tend to get voice fatigue more easily, when required high volume, the voice fatigue is more serious. Uighurs teachers have highest degree of voice fatigue.</p>
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Adult , Female , Humans , Male , Middle Aged , Young Adult , Faculty , Occupational Diseases , Diagnosis , Epidemiology , Teaching , Voice Disorders , Diagnosis , EpidemiologyABSTRACT
<p><b>OBJECTIVE</b>To explore an effective therapy for treatment of infantile febrile convulsion.</p><p><b>METHODS</b>Seventy infants of febrile convulsion were randomly divided into two groups, a combined acupuncture and drug group (n = 36) were treated with Xingnao Kaiqiao needling method with Shuigou (GV 26) selected as main combined with intramuscular injection of luminal and intravenous perfusion of diazepam; and a drug group (n = 34) treated with simple intramuscular injection of luminal and intravenous perfusion of diazepam. Their therapeutic effects, the time of inducing the stopping convulsion, and the recurrence rate were investigated.</p><p><b>RESULTS</b>The total effective rate was 86.1% in the combined acupuncture and drug group, better than 79.4% in the drug group (P<0.05), and the time of inducing the stopping convulsion in the combined acupuncture and drug group was shorter than that in the drug group (P<0.01), and the recurrence rate in the combined group was lower than that in the drug group (P<0.05).</p><p><b>CONCLUSION</b>Acupuncture combined with intramuscular injection of luminal and intravenous perfusion of diazepam is an effective and safe method for febrile convulsion.</p>
Subject(s)
Humans , Acupuncture Points , Acupuncture Therapy , Fever , Seizures , Seizures, FebrileABSTRACT
Objective To explore the changes of serum nitric oxide(NO) and trace element Zinc in children with pneumonia and their clinical significance.Methods The observing group contained 48 patients with pneumonia in our hospital from Oct.2005 to May 2006,who were collected 3 mL of blood sample on empty stomach on the second day.Twenty-six of them had been collected serum during their convalescence stage.The control group contained 20 children,who were healthy in the same stage.The levels of NO of 48 pneumonia,26 convalescence stage(recovery group) and 20 healthy patients were determined by UV-2100 spectrophotometer.The Zinc in serum was determined by P-E503-mode atomic absorption spectrophotometric analysis antigenic in those patients.Blood viscosity was measured and analyzed with the statistic analysis SPSS 10.0 software.Results The levels of NO in pneumonia children[(57.76?19.41) ?mol/L] were significantly higher than that in control group [(25.09?5.51) ?mol/L] and recovery group[(30.08?8.05) ?mol/L](P_a