The epidermal growth factor receptor (EGFR) is overexpressed in many epithelial cancers,and is commonly caused by EGFR gene amplification and gene mutations. The most frequently occurring variant,the type III mutation (EGFRvIII) ,is characterized by an inframe deletion of exons 2-7 of the coding sequence. It is expressed only in tumors and not found in normal tissues, and therefore represents an attractive therapeutic target. The tumor therapy methods targeted for EGFRvIII include immu-notherapy, ribozyme, RNA interference, etc.

OBJECTIVETo investigate the effect of extracellular regulating kinase (ERK) signaling pathway on the secretion of gamma-aminobutyric acid (GABA) in cultured rat hippocampal neurons induced by stromal cell derived factor-1 (SDF-1).

METHODSThe hippocampal neurons of newborn SD rats were cultured and identified in vitro; the phosphorylation level of ERK1/2 was examined by Western blot; ELISA was used to detect the effect of PD98059, a ERK1/2 specific blocker on GABA secretion of cultured hippocampal neurons and Western blot were adopted to measure the protein expression levels of glutamate decarboxylase (GAD65/67) and gamma aminobutyric acid transporter (GAT); after blocking ERK1/2 signaling pathway with PD98059; RT-PCR was used to detect the mRNA expression levels of GAT-1 and GAD65 after treated with PD98059.

RESULTSThe levels of ERKl/2 phosphorylation were increased significantly by SDF1 acting on hippocampal neurons, and CX-CR4 receptor blocker AMD3100, could inhibit SDF-1 induced ERK1/2 activation; SDF-1 could inhibit the secretion of GABA in cultured hippocampal neurons, and ERK1/2 specific inhibitor PD98059, could partly reverse the inhibition of GABA secretion by SDF-1. The effects of SDF-1 on cultured hippocampal neurons was to decrease the mRNA genesis of glutamic acid decarboxylase GAD65 and GABA transporter GAT-1, besides, ERK inhibitor PD98059 could effectively flip the effect of SDF-1. The results of Western blot showed that SDF-1 could inhibit the protein expression of GAT-1 and GAD65/67 in hippocampal neurons and the inhibition of GAT-1 and GAD65/67 protein expression could be partially restored by ERK1/2 blocker.

CONCLUSIONSDF-1 acts on the CXCR4 of hippocampal neurons in vitro, and inhibits the expression of GAD by activating the ERK1/2 signaling pathway, and this may represent one possible pathway of GABA secretion inhibition.

Animals ; Blotting, Western ; Cells, Cultured ; Chemokine CXCL12 ; pharmacology ; Flavonoids ; pharmacology ; Glutamate Decarboxylase ; metabolism ; Hippocampus ; cytology ; MAP Kinase Signaling System ; Neurons ; metabolism ; Phosphorylation ; RNA, Messenger ; Rats ; Rats, Sprague-Dawley ; Receptors, CXCR4 ; metabolism ; gamma-Aminobutyric Acid ; secretion

Adult ; Dimethylformamide ; poisoning ; Female ; Humans ; Occupational Exposure ; Young Adult

Objective To explore the efficacy and safety of low-dose ketamine for prevention of shivering during cesarean section under subarachnoid space and epidural anesthesia.Methods Ninety pregnant women who scheduled cesarean delivery under subarachnoid space and epidural anesthesia were randomized divided into three groups:control group (30 patients) low-dose ketamine group (30 patients) and high-dose ketamine group (30 patients).0.9％ sodium chloride,0.25 mg/kg(3 ml),and 0.50 mg/kg (3 ml) ketamine were given in three groups before operation.The incidence of shivering and adverse effect were recorded respectively before anesthesia,after anesthesia 15 min and 30 min and after operation 1 h.Results The level of mean arterial pressure (MAP) in control group after anesthesia 15 main and 30 min and after operation 1 h[(62 ± 10),(58 ± 8),(61 ± 11) mm Hg(1 mm Hg =0.133 kPa)] were significantly lower than those in high-dose ketamine group [(78 ± 12),(82 ± 8),(76 ± 11)mm Hg] and low-dose ketamine group [(72 ± 10),(76 ± 6),(80 ± 7) mm Hg],there was significant difference (P ＜ 0.05).There was no shivering need treat in low-dose ketamine group and high-dose ketamine group.The rate of hallucinations and nystagmus in low-dose ketamine group [0,6.7％ (2/30)] was significantly lower than that in high-dose ketamine group [20.0％ (6/30),50.0％ (15/30)],there was significant difference (P ＜ 0.05).Conclusion The pretreatment with low-dose ketamine on shivering during cesarean section under subarachnoid space and epidural anesthesia has better preventive effectiveness,0.25 mg/kg of ketamine is more effective than 0.50mg/kg.

OBJECTIVE:To investigate the occurrence of ADR induced by Shuxuening injection in Beijing area,and to pro-vide reference for rational drug use in clinic. METHODS:ADR induced by Shuxuening injection in Beijing area during 2003-2013 was classified statistically in respects of population,organs/systems involved in ADR,clinical manifestations,occurrence time, drug combination and prognosis. RESULTS:Of 1648 ADR cases,the incidence of ADR in the elderly patients was higher than young patients,and that of female patients (60.92％) was higher than that of male patients (39.14％). Multiple organs/systems were involved in Shuxuening injection-induced ADR,and top 3 were nervous system (422 cases,21.33％),skin and its appen-dants (411 cases,20.78％) and others (305 cases,15.42％). Clinical manifestations were skin rash,itching,dizziness and ner-vousness,palpitation,arrhythmia,etc. ADR mostly occurred within 5-30 min after medication. In ADR reports,there were a vari-ety of drugs combined with Shuxuening injection. Shuxuening injection combined with Alprostadil injection was most common(61 cases,accounting for 23.46％ of drug combination). Among 1648 ADR cases,there were 622 cured cases and 1039 cases im-proved,4 cases were not improved,3 cases had sequelae and 1 case died. CONCLUSIONS:Clinical application of Shuxuening in-jection should strictly follow the indications of drug package inserts;differentiation of symptoms and signs is based on specific dos-age,solvent,route of administration,etc. It is necessary to strengthen the prescription check,and strengthen the observation after medication especially for the elderly and other special groups so as to reduce and avoid ADR.

The preventive effect of garlic against toxicity of dimethylnitrosamine (NDMA) in rats medicated with aminopyrine (AP) and NaNO2 was investigated. 28 rats were divided into three groups. The 6 rats of group C were set as control taking basal diet; the 10 rats of group B were given basal diet, AP, and NaNO2; the 12 rats of group A were given basal diet with an addition of 10% of garlic, AP and NaNO2. AP and NaNO2 in the dosage of 30 mg per kg of body weight were dissolved in 0.5% acetic acid and given by gavage to rats of groups A and B.During the experimental period of 35 days, 3 rats of group B died while all the rats of group A survived. At the end of the experiment, Hb, SGPT and SGOT were determined and all rats were killed for pathological studies. It was found Hb value of group A was higher than that of group B (P

Objective To investigate of the radiological manifestations in congenital cystic adenomatoid malformation (CCAM) of lung in adult and to improve the diagnostic accuracy of CCAM of lung in adult.Methods Five cases with pathologically proved CCAM of lung in adult were retrospectively analyzed.Chest X-ray was available in 5 cases and chest CT was performed in 2 cases.Results On plain chest radiography,thin wall air cystic lesions with air-fluid level were detected in 3 cases.Honeycomb like small cystic lesion was detected in 1 case.Multiple round cystic lesions were found in 1 case.CT scan of the chest demonstrated a round thin wall air cystic lesion in the lateral segment of right lung's middle lobe,and a thin wall air cystic lesion with the wall merged into the shadow of chest wall in the left apicoposterior segment in one case.Small cystic lesions just like honeycomb were found in bilateral basal segments of the inferior lobes,with a 0.8—1.0 cm sized round mass revealed in the right lung′s inferior lobe basal segment, and the mass was spiculated in another case.Conclusion The imaging signs of CCAM of lung in adult is cyst or cyst-solid and at the risk of developing carcinoma.

Objective To investigate whether CD4~+CD25~(high)regulatory T cells(tregs)were increased in the tumor tissue and peripheral blood of prostate cancer patients.Methods The prevalence of CD4~+CD25~(high)regulatory T cells inside the prostate tumor was detected compared with benign tissue from the same prostate.Furthermore,the frequency of CD4~+CD25~(high)regulatory T cells in peripheral blood was detected in prostate cancer patients compared with normal donors.Results Moreover,CD4~+CD25~(high)regulatory T cells from blood and supernatants from cultured prostate tumor tissue samples exhibited immunosuppressive function in vitro.CD4~+CD25~(high)T normal peripheral blood cells were found for the ratio was(0.5?0.1)%.Lower than the proportion of T cells in peripheral blood of patients with CD4~+CD25~(high)was(2.3?0.7)%,P

Objective: To investigate the effect of recombinant BCG secreting IL-2 (rBCG-IL-2) on peritoneal macrophages of mouse and inquire into the effect of rBCG-IL-2 on immunity of host. Methods: Gene engineering technology, electricity transfer- ence and inoculation tumor cell are adopted; MTT assay is used to determine tumoricidal effect of macrophages. Results: Tumo- ricidal effect of macrophages of rBCG-IL-2 groups was higher than those of the control coups and BCG groups, and the tumorici- dal effect of macrophages could reach a high state in a week. Conclusion: rBCG-IL-2 can raise tumoricidal effect of macrophages, improve immunity of host and is a prospect biological preparation.

Piroxicam has polymorphism. Different crystalline forms can exhibit different physicochemical properties and biological activities. Analysis of the intermolecular interactions is essential to reveal the formation mechanism and differences of polymorphs. In this paper, Hirshfeld surface analysis and semi-empirical methods were used to calculate and analyze the intermolecular interactions in seven polymorphic forms of piroxicam. The results show that the Hirshfeld surface analysis method can clearly and intuitively reveal the intermolecular interactions, among which H…H, O…H/H…O and N…H/H…N interactions account for 95% of the total energy. There are differences in the proportion and distribution of the forces of different crystal forms. The energy calculation shows that the lattice energy of the hydrate is significantly lower than that of the anhydrous forms, and in the specific energy distribution, the contribution of the dispersion force is the most prominent. Further interaction energy analysis was found that within the distance of 3.8 Å from the center of the piroxicam molecule, different crystalline forms of piroxicam molecule have different interaction energies with surrounding molecules.