Objective To explore the effect of theta burst stimulation (TBS) paradigm of repetitive transcranial magnetic stimulation (rT-MS) on executive function in patients with chronic schizophrenia. Methods 60 patients meeting DSM-IV for chronic schizophrenia disor-ders criteria were enrolled. They were randomly divided into TBS group (n=30) and sham intervention group (n=30). They were assessed with digit span performance, space span performance and Wisconsin Card Sorting Test (WCST) before and 4 weeks after intervention. Re-sults After intervention, the forward score of digit span performance, the total score and forward score of space span performance increased (P<0.05), the error selection percentage, the error selection number and the percentage of error number of WCST decreased, the percentage of conceptual level of WCST increased (P<0.05) in the TBS group. However, there was no significant difference in the digit span perfor-mance, space span performance and WSCT in the sham intervention group (P>0.05). There was significant difference in all the items be-tween 2 groups after intervention (P<0.05). Conclusion TBS paradigm of rTMS could improve the executive function in schizophrenic pa-tients.

Objective To compare the efficacy of amisulpride and other SGAs in treating the negative symptoms of Schizophrenia.Methods The randomized controlled trials (RCTs) about Schizophrenia treated with amisulpride and other SGAs from Jan 1995 to Mar 2013 were searched in The Pubmed,EMbase,Cochrane Library,WanFang Data,CNKI and VIP.Two reviewers independently screened the literatures,extracted the data,and evaluated the methodological quality.Than meta-analyses were conducted by using RevMan 5.1 and Stata 12.0 software.Results The totall3 RCTs were included.Among the 1814 patients involved.The results of meta-analyses showed that the score of PANSS-N was no significant differences between two groups (MD =-0.33,95％ CI:(-0.87,0.21),Z =1.20,P =0.23) ; and the score of SANS was no significant differences between two groups (MD =-0.21,95％ CI:(-1.51,1.50),Z =0.31,P =0.76).The side effects were more in other SGAs group than those in amisulpride group.Conclusion Amisulpride is as effective as other SGAs for the treatment of schizophrenia with predominantly negative symptoms,and it has more advantage than other SGAs in safety.

Objective To evaluate the effect of theta burst stimulation( TBS) paradigm of repetitive tran?scranial magnetic stimulation ( rTMS ) on the treatment of schizophrenia through assessing executive function. Methods 60 patients met with DSM?4 and ICD?10 for schizophrenia disorders criteria were enrolled in this study. The group was divided into theta burst stimulation group(research group, n=30) and sham intervention group ( control group, n=30) . The research group and control group were assessed with the Wisconsin card sorting test (WCST) and the go/no?go task by event?related potential(ERPs) before and after 4 weeks treatment. Each test results of all groups before and after treatment were compared with each other respectively. Results Regarding the WCST test,compared with the baseline,the post?rTMS state of the TBS group showed a decrease in the error selec?tion percentage((59.8±14.7)%),the preservative error number(55.3±18.0) and the preservative error percentage (71.3±12.6)%,but the percentage of conceptual level(71.3±12.6)% increased in the TBS group(P<0.05). Re?garding the go/no?go task by ERPs,compared with the baseline,the post?rTMS statet of the TBS group showed an increase in the no?go P3 amplitude(P<0.05 or 0.01) . After intervention,the score of WCST test and the no?go P3 amplitude were significant differences in TBS group compared with same rTMS group(P>0.05).Conclusions The?ta burst stimulation paradigm of rTMS can improve the executive function in schizophrenic patients.

Objective To investigate the pathogens distribution in neonatal blood culture and their drug resistance to antibacteri‐al drugs in Dalian City .Methods The routine blood culture ,identification and drug sensitivity test were carried out in the hospital‐ized neonates from August 2014 to August 2015 .And the obtained data were analyzed .Results A total of 186 strains of pathogenic bacteria were detected from 1 570 cases of neonatal blood culture and the positive rate was 11 .8% .Gram positive bacteria accounted for 74 .2% (138/186) and were dominated by Staphylococcus epidermidis .Gram negative bacteria accounted for 25 .3% (47/186) , which were mainly onion burkholderia bacterium .One strain was fungus ,accounting for 0 .5% .The drug sensitivity test results showed that Gram positive bacteria had the higher resistance rate to penicillin and erythromycin (80 .0% -90 .0% ) ,100 .0% sensi‐tivity to vancomycin ,linezolid and teicoplanin ;E .coli and K .pneumoniae had the highest resistance rate to ampicillin (88 .2% -100 .0% ) ,100 .0% sensitivity to imipenem ,amikacin ,low resistance rate to piperacillin/tazobactam ,cefoperazone/sulbactam ,amoxi‐cillin/clavulanic acid ,cefepime and ceftazidime (0% -10 .0% ) .The resistance rate of onion burkholderia bacterium to ticarcillin/clavulanate and meropenem was higher than 80 .0% ,which had 100 .0% sensitivity to cefoperazone /sulbactam ,levofloxacin ,mino‐cycline and compound sulfamethoxazole .Conclusion The neonatal blood culture pathogen in Dalian City is dominated by Gram pos‐itive bacteria ,coagulase negative staphylococcus is the main pathogen .Due to the different regional environmental ,pathogens and drug resistance should be regularly monitored and analyzed to provide objective and accurate basis for clinical rational use of anti‐bacterial drugs .

The objective of this research was to fabricate a novel tissue inducible nerve guide conduit, and to evaluate its biologic property. The microspheres were prepared with chitosan that encapsulated ligustrazine. The drug release of the chitosan microspheres was detected with application of the controlled release method in vitro. Chitosan microspheres were mixed with collagen to fabricate the tissue inducible nerve conduit, which were crosslinked with 2% genipin for 24h. Mechanical properties of the nerve guide conduit samples, including maximum load and breaking load, were measured using an Instron Series IX Automated Materials Testing System. The flexibility of the nerve guide conduit was determined with the texture evaluation instrument. Different methods, such as scanning electron microscope (SEM), light microscope (LMS) and immunofluorescence were used to analyze the spatial structure of the nerve guide conduit, the distribution of the microspheres, the state of the nerve duct combined with mesenchymal stem cells (MSCs), and the effect of the ligustrazine that released from chitosan microsphere on MSCs differentiation into nerve cells, respectively. The results showed that the chitosan microspheres had better releasing effect. The mechanical properties resultant nerve guide conduit were determined. The maximum load and breaking load of the genipin crosslinked samples were significantly higher than that observed with the non-crosslinkers, increasing to (0.76 +/- 0.15) N and (0.69 +/- 0.17) N from (0.23 +/- 0.09) N and (0.20 +/- 0.12) N for the non-crosslinkers (P < 0.01). The degradation rates of non-crosslinked and crosslinked by genipin were(58.62 +/- 7.59) mg and (9.23 +/- 2.47) mg, respec- tively. This had a statistical significance (P < 0.01). The average linearities in dry and hygrometric state of the nerve guide conduit were (0.597 +/- 0.012) LC and (0.333 +/- 0.015) LC, respectively, which also had statistical significance (P < 0.01). The flexibility in the hygrometric state of the nerve guide conduit was better than that of the dry. SEM analysis of the samples demonstrated that the structures of the nerve guide conduit were significantly changed in crosslinking samples, the microspheres were uniformly distributed on the surface of scaffold, the ligustrazine that released from the chitosan microspheres could promote MSCs to express NSE and MAP2 that were the relevant marker molecule of nerve cells. The nerve guide conduit is combined with MSCs, which promote MSCs proliferation and NSE expression by the ligustrazine that released from the chitosan microspheres. The conduit has better biological compatibility and tissue inducible function.
Animals ; Cell Differentiation ; drug effects ; Cells, Cultured ; Chitosan ; chemistry ; Collagen ; chemistry ; Guided Tissue Regeneration ; methods ; Mesenchymal Stromal Cells ; cytology ; Microspheres ; Nerve Regeneration ; drug effects ; Pyrazines ; pharmacology ; Rats ; Tissue Engineering ; Tissue Scaffolds ; chemistry

Objective To explore the effect and mechanism of hesperidin in treating the lung injury in the mouse model of respiratory syncytial virus (RSV)-induced bronchiolitis. Methods A mouse model of RSV-induced bronchiolitis was established,and 60 BALB/c mice were assigned into a control group,a model group,a low-dose hesperidin (18 mg/kg) group,a high-dose hesperidin (36 mg/kg) group,and a high-dose hesperidin (36 mg/kg)+Jagged1(1 mg/kg) group by random number table method,with 12 mice in each group. Corresponding doses of drugs were administrated for intervention,and the control group and model group were administrated with the same amount of saline.The bronchoalveolar lavage fluid (BALF) samples were collected and alveolar macrophages were isolated.ELISA was employed to detect the levels of interleukin (IL)-4,IL-6,tumor necrosis factor-α (TNF-α),and IL-10 in BALF,and flow cytometry to detect the M1/M2 polarization of macrophages.qRT-PCR and Western blotting were respectively conducted to detect the mRNA and protein levels of inducible nitric oxide synthase (iNOS),arginase 1 (Arg-1),Jagged1,and Notch1 in the lung tissue. Results Compared with the control group,the modeling of RSV-induced bronchiolitis elevated the IL-4,IL-6,and TNF-α levels,increased the proportion of M1-type macrophages and the lung inflammation and mucus secretion scores,and up-regulated the mRNA and protein levels of iNOS,Jagged1,and Notch1 in BALF (all P<0.001).Meanwhile,the modeling lowered the IL-10 level,decreased the proportion of M2-type macrophages,and down-regulated the mRNA and protein levels of Arg-1 (all P<0.001).Compared with the model group,low- and high-dose hesperidin lowered the IL-4,IL-6,TNF-α levels,decreased the proportion of M1-type macrophages and the lung inflammation and mucus secretion scores,and down-regulated the mRNA and protein levels of iNOS,Jagged1,and Notch1 in BALF (all P<0.05).Moreover,hesperidin elevated the IL-10 level,increased the proportion of M2-type macrophages,and up-regulated the mRNA and protein levels of Arg-1 (all P<0.001).Using recombinant Jagged1 protein to activate Notch1 signaling pathway can significantly attenuate the promotion of high-dose hesperidin on M2 macrophage polarization and amelioration of lung inflammation damage (all P<0.01). Conclusion Hesperidin may alleviate the lung inflammation damage in mice with RSV-induced bronchiolitis by inhibiting the Jagged1/Notch1 signaling pathway and promoting the M2-type polarization of macrophages.
Animals ; Mice ; Bronchiolitis/metabolism* ; Hesperidin/metabolism* ; Interleukin-10/pharmacology* ; Interleukin-4/pharmacology* ; Interleukin-6/metabolism* ; Jagged-1 Protein/pharmacology* ; Lung Injury/metabolism* ; Macrophages ; Mice, Inbred BALB C ; RNA, Messenger/metabolism* ; Tumor Necrosis Factor-alpha/metabolism*

Objective: Taxifolin is a natural flavonoid compound that can be isolated from onions, grapes, oranges and grapefruit. It also acts as a medicine food homology with extraordinary antioxidant and anti-inflammatory activity. This study aims to explain the protective effects and potential mechanisms of taxifolin against inflammatory reaction. Methods: Levels of interleukin (IL)-6, IL-1β and intracellular reactive oxygen species (ROS) were assessed in different time after the treatment of taxifolin in RAW264.7 cells induced by lipopolysaccharide (LPS). Subsequently, the mRNA and protein levels of inducible nitric oxide synthase (iNOS), vascular endothelial growth factor (VEGF), cyclooxygenase (COX)-2, tumor necrosis factor (TNF)-α and the phosphorylation expression levels of the MAPK signal pathway were also evaluated. A silico analysis was used to explain the binding situation for the investigation of taxifolin and MAPK signal pathway. And then MAPK inhibitors were used to reveal the expression level of iNOS, VEGF, COX-2 and TNF-α in RAW264.7 cells. Results: It was demonstrated that cell inflammatory damage induced by LPS was significantly alleviated after the treatment of taxifolin. Then, the mRNA and protein levels of iNOS, VEGF, COX-2 and TNF-α were reduced and the phosphorylation expression levels of the MAPK signal pathway were down-regulated remarkably as well. In silico analysis, taxifolin could form a relatively stable combination with MAPK signal pathway. MAPK inhibitors showed increasing or decreasing effect in the mRNA levels of iNOS, VEGF, COX-2 and TNF-α, which suggesting that taxifolin down-regulated iNOS, VEGF, COX-2 and TNF-α expressions were not entirely through the MAPK pathway. Conclusion: This finding demonstrated that taxifolin improved the inflammatory responses that partly involved in the phosphorylation expression level of MAPK signal pathway in RAW264.7 cells exposed to acute stress.

Immune checkpoints are the crucial regulators of immune system and play essential roles in maintaining self-tolerance, preventing autoimmune responses, and minimizing tissue damage by regulating the duration and intensity of the immune response. Furthermore, immune checkpoints are usually overexpressed in cancer cells or noninvasive cells in tumor tissues and are capable of suppressing the antitumor response. Based on substantial physiological analyses as well as preclinical and clinical studies, checkpoint molecules have been evaluated as potential therapeutic targets for the treatment of multiple types of cancers. In the last few years, extensive evidence has supported the immunoregulatory effects of traditional Chinese medicines (TCMs). The main advantage of TCMs and natural medicine is that they usually contain multiple active components, which can act on multiple targets at the same time, resulting in additive or synergistic effects. The strong immune regulation function of traditional Chinese medicine on immune checkpoints has also been of great interest. For example,