Herpes simplex viruses (HSV) are human pathogens responsible for a variety of diseases,including localized mucocutaneous lesions,encephalitis,and disseminated diseases.HSV infection leads to rapid induction of innate immune responses.A critical part of this host response is the type I IFN system including the induction of type I IFNs,IFN-mediated signaling and amplification of IFN response.This provides the host with immediate countermeasure during acute infection to limit initial viral replication and to facilitate an appropriate adaptive immune response.However,HSV has devised multiple strategies to evade and interfere with innate immunity.This review will focus on the induction of type I IFN response by HSV during acute infection and current knowledge of mechanisms by which HSV interferes with this induction process.

Adoptive cellular immunotherapy (ACI) achieves the elimination and control of tumor by mobilizing the body's immune function.It also has targeted efficacy and mild untoward effects.Cytokineinduced killer cells and tumor-infiltrating lymphocytes have been widely used in clinic and have obtained preliminary efficacy.With the development and clinical application of the specific gene transfer of T cell,it will further increase the efficacy of immunotherapy.At present,improving cell culture technology and cell function and using with other treatment are the key links to improve the efficacy of ACI.

Objective To investigate the effects of cefoprazone/sulbactam(CPZ/Sul)and dexamethasone(DXM) on serum IL-8,IL-10 in SD rats with severe pneumonia due to Klebsiella pneumoniae.Methods A rat model of severe pneumonia was induced by intratra- cheal instillation of Klebsiella pneumoniae with a dose of 3.6×108CFU(0.3ml).60 male SD rats were random divided into control group,model group,cefoprazone/sulbactam(CF-L/Sul)group and cefoprazone/sulbactam plus dexamethasone(DXM+CPZ/Sul)group.15 rats in each group were then divided into three subgroups and 5rats in each subgroup were examined at the 6th,8th and 10th day,respectively.Arterial gas analysis.total WBC and PMN cell counts in BALF were examined.ELISA method was used to detect the level of IL-8 and IL-10 in serum.RESULTSIn model group,PaO2 were progressively decreased while total WBC and PMN cell counts in BALF were markedly increased.In CPZ/Sul group,all parameters were alleviated,but there were no significant difference of serum IL-8 and IL-10 between model group and CPZ/Sul group.In DXM+CPZ/SUl group,all parameters were significantly alleviated including serum IL-8 and IL-10.Conclu sions Severe pneumonia of rat due to Klebsiella pneumoniae was characterized by significant elevation of serum IL-8 and IL-10,which suggested the imbalance of inflammatory/anti-inflammatory mediators during the course of severe pneumonia.DXM codd markedly decrease the production of inflammatory mediators and slightly decrease the production of anti-inflammatory mediators,which could restore the balance and contribute to the relief of severe pneumonia.

Objective:To investigate the correlation between low-density lipoprotein cholesterol (LDL-C) and hemorrhagic transformation (HT) after intravenous thrombolysis in patients with acute ischemic stroke (AIS).Methods:Patients with AIS received intravenous thrombolysis using standard dose alteplase in the First Hospital of Shanxi Medical University from January 2014 to December 2019 were enrolled retrospectively. Head CT scan was performed within 24 h after thrombolytic therapy to identify the occurrence of HT. The demographic and baseline clinical data were compared between the HT group and the non-HT group. Multivariate logistic regression analysis was used to determine the correlation between LDL-C and HT after thrombolysis. Results:A total of 323 patients with AIS who received intravenous thrombolytic therapy were enrolled, their age was 65±12 years (range, 54-78 years), and 219 were males (67.8%). The median baseline National Institutes of Health Stroke Scale (NIHSS) score was 4 (interquartile range, 3-9). Ninety one patients (28.17%) developed HT, of which 8 (2.48%) had symptomatic intracerebral hemorrhage. Univariate analysis showed that there were significant differences in LDL-C, age, baseline NIHSS score, baseline systolic and diastolic blood pressure, baseline fibrin degradation products, and the proportion of patients with atrial fibrillation and stroke etiology between the HT group and the non-HT group (all P<0.05). Multivariate logistic regression analysis showed that lower LDL-C (odds ratio [ OR] 0.531, 95% confidence interval [ CI] 0.358-0.788; P=0.002), higher baseline NIHSS score ( OR 1.063, 95% CI 1.010-1.120; P=0.020) and higher baseline systolic blood pressure ( OR 1.015, 95 CI 1.004-1.026; P=0.008) were the independent risk factors for HT after intravenous thrombolysis in patients with AIS. Conclusions:Low LDL-C is an independent risk factor for HT in patients with AIS after intravenous thrombolysis. The patients with lower LDL-C should be cautious in lipid-lowering therapy and be alert to the occurrence of HT.

Fucoidan has been reported to exhibit various beneficial activities ranging from to antivirus and anticancer properties. However, little information is available about the effects of fucoidan on cerebral ischemia-reperfusion injury (IRI). Our study aimed to explore the effects of fucoidan on cerebral IRI, as well as the underlying mechanisms. Sprague-Dawley (SD) rats were randomly subjected to four groups: Sham, IRI+saline (IRI+S), IRI+80 mg/kg fucoidan (IRI+F80), and IRI+160 mg/kg fucoidan (IRI+F160). Fucoidan (80 mg/kg or 160 mg/kg) was intraperitoneally injected from 7 days before the rats were induced to cerebral IRI model with middle cerebral artery occlusion (MCAO) method. At 24 h after reperfusion, neurological deficits and the total infarct volume were determined. The levels of inflammation-associated cytokines (interleukin (IL)-1β, IL-6, myeloperoxidase (MPO), and tumor necrosis factor (TNF)-α), oxidative stress-related proteins (malondialdehyde (MDA) and superoxide dismutase (SOD)) in the ischemic brain were measured by enzyme-linked immunosorbent assay (ELISA). Besides, the levels of apoptosis-related proteins (p-53, Bax, and B-cell lymphoma (Bcl)-2) and mitogen-activated protein kinase (MAPK) pathway (phosphorylation-extracellular signal-regulated kinase (p-ERK), p-c-Jun N-terminal kinase (JNK), and p-p38) were measured. Results showed that administration of fucoidan significantly reduced the neurological deficits and infarct volume compared to the IRI+S group in a dose-dependent manner. Also, fucoidan statistically decreased the levels of inflammation-associated cytokines, and oxidative stress-related proteins, inhibited apoptosis, and suppressed the MAPK pathway. So, Fucoidan plays a protective role in cerebral IRI might be by inhibition of MAPK pathway.
Animals ; Apoptosis ; Brain ; Cytokines ; Enzyme-Linked Immunosorbent Assay ; Infarction, Middle Cerebral Artery ; Interleukin-6 ; Lymphoma, B-Cell ; Methods ; Peroxidase ; Phosphotransferases ; Protein Kinases ; Rats ; Rats, Sprague-Dawley ; Reperfusion ; Reperfusion Injury* ; Superoxide Dismutase ; Tumor Necrosis Factor-alpha

Objective To explore the effects of renal denervation (RDN) on hypothalamus angiotensinⅡ(AngⅡ) and oxidative stress in myocardial infarction (MI) dogs. Methods Eighteen mongrel dogs were randomly divided into MI group (n=6), RDN group (n=6) and sham operation group (n=6). Myocardial infarction model was made in the former two groups by gelatin sponge embolization of the left anterior descending artery. One week after MI, RDN was given to dogs in RDN group. Levels of AngⅡ, malondialdehyde (MDA), superoxide dismutase (SOD) and expression of gp91phox protein were detected four weeks after MI. Results Compared with control group, hypothalamus AngⅡ, MDA and expression of gp91phox protein were increased in MI group (P<0.01), but SOD was decreased (P<0.01). There was a negative correlation between AngⅡand SOD activity in MI group (r=-0.849, P < 0.01). There was a positive correlation between AngⅡ and expression of gp91phox protein in MI group (r=0.950, P<0.01). Compared with MI group, hypothalamus AngⅡ, MDA and expression of gp91phox protein were decreased in RDN group (P<0.01), but SOD was increased (P<0.01). Conclusion RDN can de?crease the level of hypothalamus AngⅡand the level of hypothalamus oxidative stress, and improve heart function of MI dogs.

Objective To observe the effect of renal denervation (RDN) on the cardiac oxidative stress and sympathetic nerve remodeling after myocardial infarction (MI) in canine. Methods Canine (n=18) were randomly divided into three groups: Sham operation group (SHAM group, n=6), MI group (n=6), MI+RDN group (n=6). Anterior myocardial infarction was gained by gelatin sponge embolization of the left anterior descending artery. At four weeks post-MI, left ventricular end-diastolic volume (LVEDV), left ventricular end-systolic volume (LVESV) and left ventricular ejection fraction (LVEF) were examined using echocardiography. Immunohistochemical assay was used to analyze the distribution and density of tyrosine hydroxylase (TH) stained nerve fibers at peri-infarct zone. Myocardial superoxide dismutase (SOD) activity and malondialde?hyde (MDA) were also assessed. Results Compared with dogs in SHAM group, LVEF and SOD expression were decreased in MI group and MI+RDN group (P<0.05), but Left ventricular end diastolic pressure (LVEDP), LVEDV, LVESV, MDA and rate of TH positive staining nerve fibers were increased (P<0.05). There was a negative correlation between the rate of TH positive staining nerve fibers and SOD level (rs=-0.818,P<0.05) and a positive correlation between rate of TH positive stain?ing nerve fibers with MDA level (rs=0.900,P<0.05). By contract, compared with MI group, LVEF and SOD in MI +RDN group were increased (P<0.05), while LVEDV, LVESV, MDA and rate of TH positive staining nerve fibers were significant?ly lowered (P<0.05). Conclusion RDN is effective to decrease the level of cardiac oxidative stress and improve cardiac sympathetic nerve remodeling and heart function after myocardial infarction in canine.

Purpose To evaluate the diagnostic value of diffusion weighted imaging with high b value in acute cerebral microinfarcts.Materials and Methods Conventional MRI and diffusion weighted imaging with standard b value (b=1000 s/mm2) and high b value (b=3000 s/mm2) were performed in the 7 patients with acute cerebral infarction,and all the images were evaluated.The signal to noise ration (SNR) and contrast to noise ration (CNR) were measured.Results Five patients were detected much more microinfarcts in high b value as HB group than that in standard b value as SB group.The SNR and CNR were significantly higher in high b value group than that in standard b value group (P＜0.05),but the apparent diffusion coefficient value showed no significant difference between the two groups (P＞0.05).Conclusion DWI with high b value could sensitively detect acute cerebral microinfarcts with high clinical value.

BACKGROUND:It has been proved that miR-34a plays an inhibitory role in the growth of lung cancer stem cels, but the underlying mechanism remains unclear.
OBJECTIVE:To explore the inhibitory effect of miR-34a on lung cancer stem celsand the underlying mechanism.
METHODS:The CD133+lung cancer stem cels were separated from lung cancer A549 cel lines using magnetic activated cel sorting method. And miR-34a-overexpressing CD133+lung cancer stem cels were established by liposome transfection technology. Besides,the targeted relationship between miR-34a and Notch1 was analyzed by the dual-luciferase reporter. Afterwards, Notch1 silencing was performed by gene knockout, and its effect on lung cancer stem cels was determined.
RESULTS AND CONCLUSION:After sorted and detected by immunomagetic selection and flow cytometry assay respectively, a high rate of CD133+lung cancer stem cel was obtained. And qRT-PCR detected that the expression level of miR-34a in CD133+lung cancer stem cels was significantly lower than that in CD133-lung cancer stem cels. Moreover, miR-34a-overexpressing CD133+lung cancer stem cels were successfuly constructedandmiR-34a significantly inhibited proliferation and induced apoptosis of lung cancer stemcels. Dual-luciferase reporter assay indicated that Notch1 mRNA was a target of miR-34a. In addition, Notch1 silencing obviously inhibited proliferation and induced apoptosis of lung cancer stem cels. These findings suggest that miR-34a can inhibite lungcancer stem celsviathe Notch1 signaling pathway.

Objective To explore and compare the clinical efficacy of levetiracetam tablets and compound sodium valproate sustained release tablets in the treatment of children and adolescents with epilepsy.Methods From April 2017 to April 2018,80 children and adolescents with epilepsy treated in Chaonan Minsheng Hospital of Shantou were selected as study objects,and they were randomly divided into two groups by drawing lots,with 40 cases in each group.The observation group was given levetiracetam tablets,and the control group was treated with valproate.The improvement of EEG after therapy,the total effective rate,and the incidence of adverse reactions were observed and evaluated.Results The EEG improvement rates after treatment for 6 months in the observation group and control group were 41.17％,45.71％,respectively,the difference was not statistically significant(x2 =0.508,P ＞0.05).The EEG improvement rates after treatment for 9 months in the observation group and control group were 70.58％,74.28％,respectively,the difference was not statistically significant (x2 =0.225,P ＞ 0.05).The total effective rate in the observation group was 92.50％,which was 95.00％ in the control group,the difference was not statistically significant between the two groups (x2 =0.354,P ＞ 0.05).However,the incidence rate of adverse reactions of the observation group(22.50％) was significantly lower than that of the control group(45.00％)(x2 =6.864,P ＜ 0.05).Conclusion Both levetiracetam tablets and compound sodium valproate sustained release tablets have appreciable efficacy and safety in the treatment of epilepsy in children and adolescents,but levetiracetam therapy has less adverse reactions,which deserves further promotion in monotherapy of epilepsy in children and adolescents.