AIM:To explore the therapeutic effect of a novel Rho kinase inhibitor WAR 5 on the experimental autoimmune encephalomyelitis (EAE) and its possible mechanism.METHODS: Female C57BL/6 mice were randomly divided into EAE group and WAR5 group.EAE model was induced by the application of MOG 35-55 peptide.WAR5 was in-jected intraperitoneally every other day from post-immunization (PI) day 3 to PI day 27.The clinical score and body weight were recorded every other day .On PI day 28, the animals were sacrificed and spinal cords were obtained for HE and mye-lin staining .The splenocytes were isolated and the expression of CD 16/32 and CD206 were analyzed by flow cytometry . The protein extracts from the brains and spinal cords were collected for the measurement of inducible nitric oxide synthase ( iNOS) by Western blotting .RESULTS:The administration of WAR 5 delayed the onset of EAE and attenuated the clini-cal symptoms .The results of the pathological examination revealed that WAR 5 inhibited the infiltration of inflammatory cells and improved myelination in spinal cords , accompanied with the poralization of M 1 macrophages to M2 phenotype in the spleen.WAR5 inhibited the expression of iNOS in the central nervous system , especially in the spinal cords .CON-CLUSION:The therapeutic effect of WAR5 on EAE may be related to the shift of M1 macrophages to M2 phenotype and inhibition of inflammation in the central nerve system .

Hot-melt extrusion technology was used to prepare solid dispersion of posaconazole for improving its dissolution. Solubility parameter, glass transition temperature and melting method were utilized to screen polymers. Using KollidonVA64, Soluplus, Eudragit L100 and combined carrier KollidonVA64-Eudragit L100 as polymer carrier, solid dispersion was prepared by hot-melt extrusion technology and characterized by drug dissolution. The formulation and process factor affecting dissolution were studied. The state of posaconazole in solid dispersion was characterized by differential scanning calorimetry and preliminary analysis of the stability was studied by influencing factors experiments. When using KollidonVA64-Eudragit L100(2 ∶8)as the carrier, 10 % triethyl citrate as the plasticizer and extrusion temperature of 150 °C, the dissolution of posaconazole was improved significantly. Drug was molecular or amorphous form in the carrier. Proportion of Eudragit L100 and KollidonVA64, temperature, drug loading and plasticizer influenced dissolution of posaconazole. Solid dispersion was stable for high temperature and strong light but sensitive to high humidity. Solid dispersion using hot-melt extrusion technology can significantly improve the dissolution of posaconazole.

Objective:To explore the role of arginine metabolism in the inflammatory response to influenza A virus (FluA) infection.Methods:Eighteen-month-old mice were infected with FluA via nasal drip, with samples collected on the 6th day post-infection. The concentration of cytokines was determined by the Luminex multifactor assay, while the metabolites in bronchoalveolar lavage fluid (BALF) were analyzed using targeted metabolomic method. Correlation analysis was employed to examine the correlation between cytokines and metabolites. Macrophages were infected with FluA at a multiplicity of infection (MOI) of 1 and cultured with different concentrations of arginine for 24 h. The mRNA and protein expression levels of interleukin (IL)-1β, IL-6, tumor necrosis factor α (TNF-α) and IL-10 were detected by real time fluorescence quantitative RT-PCR (qRT-PCR) and Cytometric Bead Array (CBA).Results:In comparison to the control group, the levels of surfactant protein D (SP-D), TNF-α, monocyte chemotactic protein-1 (MCP-1), IL-1α, IL-6, IL-10, recombinant S100 calcium binding protein (S100) A9, interferon inducible protein 10 (IP-10), macrophage inflammatory protein-1α (MIP-1α), matrix metalloprotein-9 (MMP-9), and Complement Factor D in BALF of FluA infection exhibited a significant elevation. The concentrations of arginine, aspartate, citrulline, glutamic acid, ornithine, proline, creatine, and sarcosine in arginine metabolism were up-regulated, which was correlated with most of elevated cytokine levels. The supplementation of arginine after FluA infection significantly decreased the levels of IL-1β, IL-6, and TNF-α, but increased the level of IL-10 in macrophages.Conclusions:Arginine reduces the inflammatory response induced by FluA infection in macrophages, suggesting that it may be a potential intervention target for severe pulmonary inflammation following FluA infection.

Objective To investigate human papillomavirus (HPV) genotypes in adult patients with plantar warts,and to explore their relationship with clinical features of adult plantar warts.Methods PCR,gene sequencing and TA-cloning technique were performed to detect HPV types in 221 patients with plantar warts.Meanwhile,clinical data were recorded,including patients' age,disease duration,symptoms and number of warts.Results Of 221 specimens,HPV DNA was detected in 215,with the HPV-positive rate being 97％.Single HPV infections were detected in 206 specimens (96％,206/215),among which,HPV types included HPV-27 (44.7％,92/206),-2 (12.1％,25/206),-57 (7.3％,15/206),-7 (Alpha genus;0.5％,1/206),-65 (Gamma genus;0.5％,1/206),-1 (33.5％,69/206) and-63 (Mu genus;1.5％,3/206).There were no significant differences in age,disease duration,number of warts,incidence of pain and gender among patients with HPV-27,-2 or-57 infections.Compared with patients with HPV-27 infection,patients with HPV-1 infection were more related to age ≤ 30 years,disease duration ≤ 1 year,number of warts ≤ 2 and high incidence of pain.Conclusion HPV-27,-2,-57 and-1 are the main types in adult patients with plantar warts,and HPV types are correlated with clinical features of adult plantar warts.