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Objective To establish an experimental autoimmune encephalomyelitis (EAE) model in female C57BL / 6 mice aged 6-8 weeks and investigate its disease phenotype so as to build a better animal model of multiple sclerosis (MS) . Methods The EAE model was established in 50 female C57BL / 6 mice through intradermal injection of myelin oligodendrocyte glycoprotein 35-55 peptide. We assessed the disease progression daily according to a 15-point score for 90 days, and further observed the brain lesions in terms of pathology. Results There were three courses of disease in the EAE model: chronic course (3 mice), relapse and remission course (7 mice) and monophasic course (11 mice) . Interestingly, we identified some mice (28 mice) had changes in coat color, mental and motor activity, as well as inflammatory demyelinating lesions in the brain tissue although their neurological functions were scored as 0 point. Conclusion The EAE model in C57BL / 6 female mice shows disease phenotype similar to multiple sclerosis and can be used as a good animal model.
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Objective: To evaluate the ability of new injury severity score (NISS), acute physiology and chronic health evaluation II (APACHE II), Glasgow coma scale (GCS), a combination of NISS and GCS, a combination of APACHE II and GCS, a combination of NISS and APACHE II to predict all-cause mortality of patients with severe trauma in mainland China. Methods: This was a multicenter observational cohort study conducted in the ICU of the Chonggang General Hospital, Daping Hospital of the Army Medical University and Affiliated Hospital of Zunyi Medical College from January 2012 to August 2016. The score of NISS, APACHE II, GCS, a combination of NISS and GCS, a combination of APACHE II and GCS, a combination of NISS and APACHE II were calculated based on data from the first 24 hours of ICU admission. Data were processed with Student's t-test, chi-square test, and receiver operating characteristic (ROC) curve of six scoring systems. Calibration was assessed with the Hosmer-Lemeshow test. The primary endpoint was death from any cause during ICU stay. Results: A total of 852 and 238 patients with severe trauma were assigned to the derivation group and validation group, respectively. Area under the ROC curve (AUC) was 0.826 [95% confidence interval (CI)=0.794-0.855)] for NISS, 0.802 (95% CI=0.768-0.832) for APACHE II, 0.808 (95% CI=0.774-0.838) for NGCS, 0.859 (95% CI=0.829 -0.886) for NISS+NGCS, 0.864 (95% CI=0.835-0.890) for APACHE II +NGCS, 0.896 (95% CI=0.869-0.929) for NISS+APACHE II in the derivation cohort. Similarly, the score of NISS+APACHE II was also better than the other five scores in the validation cohort (AUC=0.782; 95% CI=0.725-0.833) and had a good calibration (P=0.41). Conclusions: Taking into account anatomical and physiological parameters completely, the combination of NISS and APACHE II performs better than NISS, APACHE II, NGCS, NISS+NGCS, APACHE II +NGCS for predicting mortality in ICU severe trauma patients. It is needful to develop models that contain various types of accessible predictors (demographic variables, injury cause/mechanism, physiological and anatomical variables, etc.) as comprehensive as possible.
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<p><b>OBJECTIVE</b>To investigate whether exogenous agmatine inhibits lipopolysaccharide (LPS)-induced activation and dysfunction of human umbilical vein endothelial cells (HUVECs) by modulating nuclear factor-κB (NF-κB) and MAPK signal pathways and the production of reactive oxygen species (ROS).</p><p><b>METHODS</b>Cultured HUVECs were treated with agmatine at the optimized concentration of 1.0 mmolγL, LPS (10 µgγmL), and LPS + agmatine, with or without pretreatment with the inhibitors of NF-κB (PDTC), p38 (SB203580), and ERK (PD98059) for 1 h. The levels of soluble vascular cell adhesion molecule 1 (VCAM-1), soluble intercellular adhesion molecule 1 (sICAM-1), soluble E-selectin and monocyte chemoattractant protein 1 (MCP-1) in the supernatant were determined using ELISA, and their mRNA expressions, along with heme oxygenase-1 (HO-1), and NAD(P)H: quinone oxidoreductase 1 (NQO-1), were assessed using real-time PCR. ROS production in the cells was determined using 2, 7-dichlorofluoresce in diacetate (DCFH-DA) as the fluorescence probe. The protein expressions of VCAM-1, ICAM-1, p65, phospho-p65 (p-p65), IκBα, p-IκBα, ERK, p-ERK, p38, p-p38, JNK, and p-JNK were detected using Western blotting.</p><p><b>RESULTS</b>LPS stimulation for 6 and 24 h significantly increased the levels of sVCAM-1, sICAM-1, sE-selectin and MCP-1 in the supernatant, intracellular ROS production, and the mRNA expressions of these molecules (P<0.05). Intervention with 1 mmolγL agmatine, similar with pretreatment with p38, ERK and NF-κB inhibitors, obviously inhibited such effects of LPS in HUVECs (P<0.05). Agmatine significantly up-regulated the mRNA expression of HO-1 (P<0.05), inhibited LPS-induced phosphorylation of p38, ERK, nuclear p65 and cytoplasmic IκBα, and up-regulated the protein expression of cytoplasmic IκBα.</p><p><b>CONCLUSION</b>Agmatine inhibits LPS-induced activation and dysfunction of HUVECs by modulating NF-κB and MAPK signal pathways to down-regulate the expressions of adhesion molecules and chemokines and by up-regulating the expression of HO-1 to reduce ROS production.</p>
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<p><b>OBJECTIVE</b>To study the effect of Platycarya strobilacea Sieb. et Zucc (PSZ) extract on methuosis of human nasopharyngeal carcinoma CNE1 and CNE2 cells and explore the underlying mechanism.</p><p><b>METHODS</b>CNE1 and CNE2 cells were treated with 1 mg/mL PSZ extract and the expressions of Rac1 mRNA and Rac1 protein were detected using RT-qPCR and Western blotting, respectively. Results CNE1 and CNE2 cells showed obvious morphological changes typical of methuosis following treatment with PSZ extract characterized by cell merging, accumulation of large cytoplasmic vacuoles, and membrane rupture without obvious changes in the nuclei. PSZ treatment resulted in up-regulated Rac1 mRNA and Rac1 protein expressions in the cells. Application of EHT 1864 obviously blocked the effect of PSZ extract in inducing methuosis in CNE1 and CNE2 cells.</p><p><b>CONCLUSION</b>PSZ extract can induce methuosis in CNE1 and CNE2 cells by inducing the overexpression of Rac1.</p>
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<p><b>OBJECTIVE</b>To study the efficacy and safety of sorafenib combined with low dose cytarabine for treating patients with FLT3(+) relapsed and refractory acute myeloid leukemia (FLT3(+) RR-AML).</p><p><b>METHODS</b>Seven patients with FLT3(+) RR-AML were treated with sorafenib and low dose cytarabine. The curative rate and adverse effects were observed in these patients.</p><p><b>RESULTS</b>Out of 7 RR-AML patients after treatment, 5 patients achieved complete remission (CR), 2 patients achieved partial remission (PR), and the overall response rate (ORR) after one course of therapy was 100%. No severe bleeding, nausea, vomiting and other side effects were found in these patients.</p><p><b>CONCLUSION</b>Sorafenib combined with low dose cytarabine can effectively induce the remission of FLT3(+) RR-AML patients, and is worth for further clinical trails to verify its safty and efficiency.</p>