AIM:To investigate the therapeutic effect of mitochondrial fission inhibitor-1(Mdivi-1)on experi-mental autoimmune encephalomyelitis(EAE)in mice,and to explore its mechanism.METHODS:The mice immunized with myelin oligodendrocyte glycoprotein peptide fragment 35-55(MOG35-55)were randomly divided into DMSO model group and Mdivi-1 intervention group.All mice were sacrificed on the 28th day after the first immunization.The demyelination was analyzed by Luxol fast blue staining.The protective mechanism of Mdivi-1 in the spinal cord tissue was investigated by immunofluorescence staining,TUNEL staining and the in vitro experiment with MO3.13 oligodendrocytes treated with staurosporine.The mitochondrial depolarization was detected by JC-1 staining,the cell injury was checked by LDH leakage,and the viability of MO3.13 oligodendrocytes was determined by MTT assay.RESULTS:Compared with DMSO model group,the demyelinating injury was alleviated and the proportion of apoptotic CC1+ oligodendrocytes in Mdivi-1 group was decreased.The cleaved caspase-3,caspase-9,cytochrome C and Bax protein expression levels in the spinal cord of Mdivi-1-treated mice was also attenuated.The in vitro MO3.13 cell experiments suggested that Mdivi-1 inhibited MO3.13 cell mitochondrial depolarization,attenuated the cell damage and increased the cell viability.CONCLUSION:Mdivi-1 pro-tects against the myelin injury in EAE mice,which may be related to the suppression of oligodendrocyte apoptosis.

Similar to blood,interstitial fluid(ISF)contains exogenous drugs and biomarkers and may therefore substitute blood in drug analysis.However,current ISF extraction techniques require bulky instruments and are both time-consuming and complicated,which has inspired the development of viable alterna-tives such as those relying on skin or tissue puncturing with microneedles.Currently,microneedles are widely employed for transdermal drug delivery and have been successfully used for ISF extraction by different mechanisms to facilitate subsequent analysis.The integration of microneedles with sensors enables in situ ISF analysis and specific compound monitoring,while the integration of monitoring and delivery functions in wearable devices allows real-time dose modification.Herein,we review the progress in drug analysis based on microneedle-assisted ISF extraction and discuss the related future opportunities and challenges.

【Objective】 To explore the effect and mechanism of Fasudil in the treatment of experimental autoimmune myocarditis (EAM) in mice so as to provide a theoretical basis for the clinical use of Fasudil in treating myocarditis. 【Methods】 Balb/c male mice were used as the research objects, and the EAM mice model was constructed using MyHC-α614-629 polypeptide. Mononuclear cells were isolated and cultured to detect the number of mononuclear cells in mouse spleen. Inflammation infiltration, fibrosis and IL-6 expression in mouse myocardial tissue were detected by HE staining, Masson staining and immunohistochemistry, respectively. The protein expressions of Notch1 and IL-6 were detected by Western blotting. qRT-PCR was used to detect the expressions of pro-inflammatory factors (IL-1α, IL-1β and IL-6) as well as key genes of TLRs and NOTCH signaling pathway. 【Results】 EAM mice showed increased HW, decreased BW, increased HW/e-BW, and increased inflammatory infiltration and fibrosis in myocardial tissue. The above-mentioned symptoms or pathological features were improved in EAM mice treated with Fasudil. The analysis showed that the pro-inflammatory factors IL-1α, IL-1β and IL-6 in the myocardial tissue of EAM mice were significantly increased, but only the expression of IL-6 was statistically different after Fasudil treatment compared with the control group. In addition, TLRs signaling pathway might also play an important role in the EAM mice treated with Fasudil. The expressions of IL-6 and Notch1 were consistent, and the expressions of the key genes of NOTCH signaling pathway (Notch1, Hes1 and Jag2) were down-regulated after Fasudil treatment. 【Conclusion】 Fasudil exerts a protective effect on down-regulation of IL-6 expression by inhibiting the NOTCH signaling pathway in EAM mice.

Erythrocytes (red blood cells, RBCs) are the most abundant circulating cells in the blood and have been widely used in drug delivery systems (DDS) because of their features of biocompatibility, biodegradability, and long circulating half-life. Accordingly, a "camouflage" comprised of erythrocyte membranes renders nanoparticles as a platform that combines the advantages of native erythrocyte membranes with those of nanomaterials. Following injection into the blood of animal models, the coated nanoparticles imitate RBCs and interact with the surroundings to achieve long-term circulation. In this review, the biomimetic platform of erythrocyte membrane-coated nano-cores is described with regard to various aspects, with particular focus placed on the coating mechanism, preparation methods, verification methods, and the latest anti-tumor applications. Finally, further functional modifications of the erythrocyte membranes and attempts to fuse the surface properties of multiple cell membranes are discussed, providing a foundation to stimulate extensive research into multifunctional nano-biomimetic systems.

Objective To evaluate the application effect of"2+2"medicine-education cooperation talents training mode. Methods The nursing undergraduates of 2013 grade were divided into the experimental and control group. The"2+2"medicine-education cooperation talents training mode was adopted in the former and traditional training model was used in the latter. The final examination scores of the fifth and sixth semester, scores of graduation examination, scores of the Nurse Competence Scale were compared between the two groups. Results There was no difference of scores of theory examination between the two group except the Nursing Professional English whose scores were higher in the control group. The practical skills exam scores of Medical Nursing, Surgical Nursing, Paediatric Nursing, Nursing of Gynecology and Obstetrics, Emergency Nursing, Rehabilitation Nursing, Community Nursing in the experimental group were 89.32 ± 6.02, 89.46 ± 5.29, 88.06 ± 6.34, 89.32 ± 5.58, 83.99 ± 6.44, 82.58 ± 5.78, 83.56±6.12, the control group were 87.72±5.90, 87.85±6.32, 85.59±5.79, 87.45±5.65, 81.82±6.06, 80.34± 5.89, 81.28±5.42, and the differences were statistically significant (t=2.052-3.261, P<0.05). The total and practical skills scores of graduation examination in the experimental group were 82.86±4.92, 85.60±4.54, which were 81.07 ± 5.52, 84.07 ± 4.59 in the control group. There were significant differences between the two groups (t=2.060, 2.011, P<0.05). The total score of Nurse Competence Scale and scores of the four dimensions of Teaching-coaching, Managing situations, Ensuring quality, Work role were 74.95 ± 3.40, 76.38 ± 3.98, 75.49 ± 3.23, 75.42 ± 2.72, 77.49 ± 2.76 in the experimental group, the control group were 73.63 ± 4.39, 72.90 ± 4.23, 74.12 ± 4.19, 74.32 ± 3.36, 76.46 ± 3.24, respectively. The differences were statistically significant (t=2.021- 2.492, P<0.05). Conclusions The"2 + 2"medicine- education cooperation talents training mode is proved to be an effective way to train nursing applied talents to meet regional demands. It could improve the hospital′s synthetic strength including health care quality and teaching ability, promote the development and construction of the nursing specialty and train the double-certificate teachers.

Objective To evaluate the effect of dexmedetomidine on the postoperative pulmonary function in patients undergoing laparoscopic operation.Methods Eighty American Society of Anesthesiologists physical status Ⅰ or Ⅱ patients,aged 45-64 yr,weighing 45-70 kg,undergoing laparoscopic radical resection of rectal cancer,were divided into 2 groups (n =40 each) using a random number table:control group (group C) and dexmedetomidine group (group Dex).General anesthesia combined with epidural anesthesia was used.In group Dex,dexmedetonidine was intravenously infused as a bolus of 0.3 μg/kg over 10 min after epidural catheterization and before induction of general anesthesia,followed by an infusion of O.4 μg · kg-1 · h-1 starting from the end of tracheal intubation until 30 min before the end of operation.The equal volume of normal saline was given instead in group C.After epidural catheterization and before infusion of dexmedetomidine (T0),immediately before termination of pneumoperitoneum (T1) and at 1,6 and 24 h after operation (T2-4),blood samples were taken from the peripheral vein for determination of concentrations of serum interleukin-6 (IL-6),IL-10,tumor necrosis factor-alpha and malondialdehyde,and arterial blood gas analysis was performed simultaneously.Respiratory index and oxygenation index (OI) were calculated,and the occurrence of OI ≤ 300 mmHg was recorded.Results Compared with group C,the serum IL-6 and tumor necrosis factor-alpha concentrations and respiratory index were significantly decreased,and IL-1O concentrations and OI were increased at T1-4,and malondialdehyde concentrations were decreased at T1-3,and the incidence of OI ≤ 300 mmHg was decreased in group Dex (P＜0.05).Conclusion Dexmedetomidine can inhibit inflammatory responses and improve the postoperative pulmonary function in patients undergoing laparoscopic operation.

In recent years ,as a novel drug delivery system ,gold nanoparticles have attracted widespread attention .Be-cause of their special physicochemical properties ,such as quantum size effect ,unique optical phenomenon ,easily reacting with thiol compounds or disulfides and so on ,gold nanoparticles can delivery variety of types of drugs ,like proteins ,nucleic acid , small molecular drugs ,therefore they can be applied in tumor treatment and detection .In this paper the preparation of drug-loading gold nanoparticles ,their drug-loading ways and safety issues were reviewed .

OBJECTIVE: To explore the therapeutic effect of Fasudil-modified splenic mononuclear cells (MNCs) in experimental autoimmune encephalomyelitis (EAE) and the possible mechanisms.
 METHODS: C57BL/6 female mice were immunized with myelin oligodendrocyte glycoprotein peptide 35-55 to establish active immunity EAE model. Splenic MNCs were isolated on the 9th day after immunization and treated with or without Fasudil for 72 h in vitro. These cells were collected for analysis of the variance of T cell subtypes, the level of cytokines and the activity of Rho kinase (ROCK). MNCs (5×107 cells) were resuspended in 500 µL of phosphate buffer solution (PBS) and transferred into EAE model (intraperitoneal injection), which was divided into a PBS-MNCs group and a Fasudil-MNCs group. Changes of body weight and clinical symptom scores were observed.
 RESULTS: Splenic encephalitogenic MNCs from EAE mice on the 9th day after immunization could establish passive transfer EAE model. But Fasudil-treated MNCs did not trigger EAE development. Compared with the PBS-MNCs group, the loss of body weight was less in the Fasudil-MNCs group. The in vitro experiment indicated that Fasudil could suppress the activity of ROCK on MNCs (P<0.01), decrease the percentage of CD4+ T cells with the expression of interferon-γ (IFN-γ) and interleukin-17 (IL-17) (IFN-γ: P<0.01; IL-17: P<0.05), while increase the secretion of CD4+ T cells with the expression of transforming growth factor-β (TGF-β) and IL-10 (all P<0.001) . Furthermore, Fasudil could inhibit the release of IL-17 (P<0.001) and enhance the level of IL-10 (P<0.05).
 CONCLUSION Fasudil-modified cell therapy affects the occurrence and development of EAE by inhibiting the inflammatory reaction of helper T cell 1 (Th1) and Th17 while enhancing the immunoregulative effect of Th2.
1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine ; analogs & derivatives ; Animals ; Encephalomyelitis, Autoimmune, Experimental ; Female ; Interferon-gamma ; Interleukin-10 ; Interleukin-17 ; Mice ; Mice, Inbred C57BL ; Myelin-Oligodendrocyte Glycoprotein ; Spleen ; T-Lymphocytes ; Transforming Growth Factor beta ; rho-Associated Kinases

Objective To investigate the immunoregulatory effect of Fasudil-modified macrophages on cell transferred experimental autoimmune encephalomyelitis ( EAE) in a mouse model.Methods Fe-male C57BL/6 mice were immunized with MOG35-55 to establish the model of EAE.The encephalomyelitic mononuclear cells ( MNCs) were isolated from spleen of mice with EAE on day 9 after immunization and treated with or without Fasudil for 72 h in vitro.Several assays including the flow cytometry analysis, Griess reaction and ELISA were performed to analyze the M1 and M2 phenotypes of macrophages, the production of NO and the levels of cytokines, respectively.The cultured MNCs (5×107 cells) were resuspended in 500μl of PBS and transferred into na?ve C57BL/6 recipients via intraperitoneal injection.Two groups including the PBS-MNCs group and the Fasudil-MNCs group were set up.The body weights and clinical scores of the mice in each group were recorded in every other days after the induction of EAE in the recipients.Results The Fasudil treated MNCs affected the induction of EAE in adoptive cell transferred mice.The expression of CD16/32, iNOS and IL-12 on F4/80-macrophages were decreased, while the expression of CD206, CD23 and IL-10 on F4/80-macrophages were increased upon the treatment of Fasudil, indicating that Fasudil im-proved the differentiation of macrophages from M1 to M2 phenotypes.Moreover, Fasudil inhibited the pro-duction of NO and enhanced the expression of Arginase-1.Conclusion Fasudil ameliorated the clinical se-verity of EAE in mice by promoting the transformation of macrophages from M1 to M2 phenotype.

ObjectiveTo investigate the effect of dexmedetomidine on postoperative intracranial pressure (ICP) in patients with severe brain injury.MethodsNinety ASA Ⅱ or Ⅲ patients with severe brain injury,aged 19-64 yr,with Glasgow coma scale 3-7,undergoing emergency craniotomy,were randomly divided into 3 groups (n =30 each):control group (group C) and 2 different doses of dexmedetomidine groups (groups D1,D2 ).Anesthesia was induced with propofol 1.5-2.0 mg/kg,fentanyl 4 μg/kg and vecuronium 0.1 mg/kg and maintained with iv infusion of propofol and remifentanil and intermittent iv boluses of vecuronium.The patients were mechanically ventilated after tracheal intubation.Dexmedetomidine 0.3 and 0.7 μg· kg- 1· h- 1 were infused after tracheal intubation in groups D1 and D2 respectively and the infusion was maintained for 48 h.ICP was monitored after operation and maintained ＜ 30 mm Hg by iv injection of hexadecadrol,mannitol and glycerol fructose within 2 d after operation.Venous blood samples were obtained from peripheral vein after anesthesia induction and at 6,12 and 24 h after operation (T0-3) for determination of sertum IL-1β and TNF-α concentrations by ELISA.The clinical results were evaluated using Glasgow prognosis score at 3 months after operation.The amount of hexadecadrol,mannitol and glycerol fructose consumed during 2 d after operation was recorded.ResultsCompared with T0,serum IL-1βand TNF-α concentrations were significantly higher at T1-3 in the three groups ( P ＜ 0.05).The serum IL-1β and TNF-α concentrations at T1-3 and the amount of hexadecadrol,mannitol and glycerol fructose consumed were significantly lower,and the clinical results were significant better in groups D1 and D2 than in group C,and in group D2 than in group D1 ( P ＜ 0.05).ConclusionDexmedetomidine can reduce postoperative ICP in patients with severe brain injury in a dose-dependent manner which is helpful for improving prognosis.The decrease in IL-1β and TNF-α levels and inhibition of inflammatory response may be involved in the mechanism.