Objective To study the pharmacokinetic parameters of riluzole tablets and commercial riluzole capsules in Beagle dogs,and evaluate the correlation between the release rate in vitro and the absorption in vivo, and calculate the relative bioavailability of riluzole tablets. Methods Six Beagle dogs were treated with 50 mg of riluzole tablets or capsules,and then cross-treated by the other drug after 14-days wash out period. Blood concentration of riluzole was measured by high performance liquid chromatography ( HPLC ) . The atrioventricular model was used to calculate the pharmacokinetic parameters and Wanger-Nelson method was applied to assess the correlation between the release rate in vitro and the absorption in vivo. Results The t1/2 ,tmax ,Cmax ,AUC0-72 and AUC0-∞ in the tablet and capsule groups were (12. 43±3. 87) and (12. 57±3. 25) h,(6. 00±2. 60) and (6. 23±2. 72) h,(56. 24±16. 51) and (60. 82±18. 13) ng·mL-1 ,(1 255. 83±311. 39) and (1 283. 50±313. 81) ng·mL-1 ·h, (1 282. 57±322. 64) and (1 297. 22±297. 39) ng·mL-1 ·h,respectively. The relative bioavailability of capsules versus tablets was (105. 9±30. 6 )%. Conclusion HPLC method can be applied to measure the concentration of blood riluzole with little interference and high levels of repeatability and accuracy. The absorption in Beagle dogs between riluzole tablets and capsules was equal,and a good correlation between the in vivo absorption and in vitro release has been found in this study.

AIM: To establish the determination method of chlorogenic acid and baicalin in Ganmaozhike Granules (Flos Lonicerae,Radix Scutellariae,etc.). METHODS : The contents of chlorogenic acid and baicalin in Ganmaozhike Granules were determined by HPLC. RESULTS : The linear velation was good. The average recovery of chlorogenic acid was 101.9%,RSD was 1.12%;The average recovery of baicalin was 99.2%,RSD was 1.31%. CONCLUSION : The method is simple,accurate and with a good reproducibility and can be used for the quality control of the granules.

Objective To investigate the effect of the administrative intervention on smoking cessation of medical personnel and demonstrate the feasibility and the validity of this approach.Methods Two comparable hospitals were selected,one hospital with 136 smoking medical staff members was used as the intervention group;the other hospital which had 127 smoking medical staff members was used as the control group.We applied administrative intervention and health education to the intervention group and health education only to the control group.The intervention time was 10 months,we used the questionnaire survey before and after intervening to evaluate the smoking rate,the intention to quit smoking,the willingmess to accept the help of quitting and the proportion of those who quitted smoking.Results The smoking rate of intervention group (37.4％) was lower than that of control group (77.2％),the difference was statistically significant (x2=40.99,P＜0.01).The proportion of control group smokers in planning(51.1％) is statistically significant as compared with intervention group (46.18％) (x2=46.18,P＜0.01).The proportion of people who were willing to accept the help from families and friends and smoking cessation counseling in intervention group was significanly higher than that in the control group.(x2=10.04,x2=7.73,x2=7.58;P＜ 0.01).But the proportion of accepting the medicine for quitting smoking was not significantly different (x2=0.16,P＞0.05).The proportion of smokers who wanted to quit smoking on their own willingness in control group was significantly higher than that in intervention group (x2=36.27,P＜0.01).After10 months,61 people (46.6％) in the intervention group succeeded in quitting smoking and 13 (10.6％) people in control group succeeded (x2=28.21,P＜0.01).Conclusion Administrative intervention has feasibility and validity when hospitals take activities for smoking cessation.

Obej ctive Abnormal proliferation of T cells plays an important role in the development of autoimmune diseases. The article aimed to study the inhibitory effect of small molecule compound BD691 on T cell proliferation and its mechanism. Methods Human peripheral blood T-lymphocytes were isolated and purified by the immunomagnetic microbeads,then T cells were ac-tivated with anti-CD3/CD28 mAbs or alloantigen.The inhibitory effect of BD691 on activated T cell proliferation, the cytotoxic effect BD891 on resting T cells and the expression of activated T cells marker CD25 were measured by flow cytometry.Furthermore, ELISA was used to detect the secretion of cytokines associated with T cell differentiation. Results BD691 significantly inhibited the prolif-eration of T cells being stimulated by anti-CD3/CD28 mAb or alloantigen in a dose-dependent manner, and IC50 values are (8.5 ± 1.5)μmol/L and (7.2 ±1.3)μmol/L, respectively.However, BD691 had no obvious cytotoxic effects on resting T cells and periph-eral blood mononuclear cells, even at a high concentration ( up to 100μmol/L) .In T cells which were not activated by anti-CD3/CD28 mAb, the percentage of CD25+T cells is only 1.6%of the total cells, while the number increased to 68% after activating treatment.Mean-while, in T cells which were activated by 0, 3.3, 10, 30μmol/L BD691, no obvious change of CD25 expression were observed, while immunosuppressant FK506 (0.1μmol/L) significantly decreased the expression of CD25 +T cells (14.9%).In unactivated T cells, 95.6%cells were at G0/G1 phase, while after activation, the percentage of cells at G0/G1 phase reduced to 57.7%.In addition, BD691 inhibited the secretion of IFN-γ, IL-6 and IL-17 in activated T cells, but had no effects on the secretion of IL-2, IL-4 and IL-10. Co nclusion BD691 exerts no effects on T cell activation, but it inhibits T cell proliferation by inducing T cell cycling arrest at G0/G1 phase.Moreover, BD691 inhibits the secretion of key cytokines (such as IFN-γ, IL-6, IL-17) closely related to the differ-entiation of Th1 and Th17 cells.The results suggest that BD 691 is a potential lead compound to develop a new immunosuppressant for the inhibition of abnormal proliferation and differentiation of T cells.

Objective Benzothiazole derivative BD960 has immunosuppressive activity after cell -based assays for high-throughput screening.The paper aimed to investigate the involved mechanism of BD960 on T cell proliferation. Methods Human peripheral blood T-lymphocytes were isolated and purified by the immunomagnetic microbeads.Then the T cells were activated by anti-CD3/anti-CD28 mAbs or alloantigen.The effect of BD960 on activa-ted T cell proliferation, the cytotoxic effect BD960 on resting T cells and the expression of activated T cells marker CD25 were measured by flow cytometer.Cytokine levels, including IL-2, IL-4, IL-6, IL-10, IL-17A and IFN-γ, were determined by ELISA. Results BD960 significantly inhibited the proliferation of T cells stimulated by anti-CD3/anti-CD28 mAb or alloantigen in a dose-dependent manner.The IC50 value is (2.3 ±0.3)μmol/L or (2.5 ±0.3)μmol/L, respectively.Moreover, BD960 had no obvious cytotoxic effects on rest-ing T cells and peripheral blood mononuclear cells, even at a high concentration ( up to 100μmol/L) .The ratio of CD25 expression on T cell was 69.7%after stimulated by Anti-CD3/CD28 mAbs with 72 h, the concentration (0.625、2.5、10)μmol/L of BD960 also had no potent effects on the ratio, but 0.1μmol/L FK506 could inhibit CD25 expression as low as 9.4%.The G0/G1 phase of activated T cells was 58.5%after stimulated by BD960 with 96 h.BD960 could induce cell cycle arrest at the G0/G1 phase in activated T cells with the increase of concentration and RAPA in the concentration of 0.1 μmol/L was 91.5%.In addition, BD960 (0.625、2.5、10)μmol/L could inhibit the secretion of IFN-γ, IL-6 and IL-17 in activated T cells with the increase of concentration, without any effects on the secretion of IL-2, IL-4 and IL-10. Conclusion BD960 not only exerts the inhibition on the late stage of T cell activation of cell proliferation but also inhibits the secretion of inflammatory cytokines, such as IL-6, IL-17 and IFN-γ, while the mechanism of BD960 on T cell proliferation was not the same as FK506.As a result, BD960 has the potential to be the lead compound to develop a new immunosuppressant.

Objective To compare the predictive effect of Charlison's weighted index of comorbidities (WIC), the diagnostic criteria for emergency sepsis (MEDS) and combination of the two scoring systems to predict the emergency pulmonary infection prognosis. Methods A total of 327 patients with pulmonary infection admitted from January 2016 to January 2017 were enrolled in this study whose WIC score,MEDS score and risk stratification were recorded at admission.They were divided into survival group and death group according to the 28 d treatment outcome,the optimal cutoff of WIC score and MEDS score to predict the prognosis were found by ROC curve, and the prediction effect of WIC score, MEDS score, the combined use of both and APACHEⅡto predict the prognosis were compared. Results The mortality of low,middle and high risk of WIC score were 13.7%(29/212),48.7%(38/78)and 78.4%(29/37)with significant difference(χ2=82.097,P=0.000),mortality of low,middle and high risk of MEDS score were 11.3%(23/203),50.6%(40/77)and 73.3%(33/45)with significant difference(χ2=145.526,P=0.000).The WIC scores in survival group and death group were 1.3 ± 0.9 and 2.7 ± 1.1 with significant difference(t=11.030,P=0.000).The MEDS score of live group(6.1 ± 4.0) was significantly lower than death group(12.6 ± 4.9)(t=11.502,P=0.000).the optimal cutoff values of WIC and MEDS to predict prognosis were 1.7 points, 11.6 points, the ROC curve area between WIC, MEDS score and combined application to predict prognosis were 0.632, 0.798, 0.897, and the sensitivity and accuracy of the combined prediction[93.8%(212/226)/89.9%(294/327)] were significantly higher than those of the individual WIC[72.7%(168/231)/75.2%(246/327)] and MEDS[67.5%(156/232)/72.2%(236/327)] (χ2=0.562-42.594, P < 0.05). The sensitivity and accuracy of the combined application and APACHE Ⅱto predict of prognosis had no statistical significant difference(P>0.05).Conclusions The sensitivity and accuracy of WIC score combined with MEDS score to predict the prognosis of patients with acute lung infection is higher than the individual WIC score and MEDS score,and its prediction effect is more better.

Objective To summary the clinical characteristics of acute necrotizing encephalopathy in childhood so as to estimate the prognosis and guide the therapy. Methods We collected and analyzed retro-spectively the data of 10 acute necrotizing encephalopathy cases hospitalized in the pediatric department of our hospital from January 2014 to April 2018. The clinical manifestations,laboratory examinations and imaging features were retrospectively analyzed. Results A total of 10 cases all had fever and convulsions (100％). There was no specific clinical manifestation in the early stage,always showing the symptoms of acute respira-tory infection or acute gastroenteritis. Mental malaise,lethargy,restlessness and frequent convulsions occured when the conditions aggravated. Nine patients had different degrees of consciousness disorder. It could be complicated by multiple organ dysfunction syndrome,hemophagocytic syndrome and so on. Eight patients un-derwent MRI. In acute phase, homogeneously prolonged T1 and T2 relaxation time of the brain lesions on MRI were found in most patients,and diffusion-weighted imaging ( DWI) and FLAIR showed high signal in-tensity. Six cases underwent head CT examination, hypodensities were seen on 4 cases. Cerebrospinal fluid (CSF) was detected in all patients,and the protein levels in CSF increased to varying degrees,while white blood cells did not increase. Of the 10 patients,3 died,1 was discharged normally,1 had hemophagocytic syn-drome,transferred to pediatric hematology department,and 5 patients were transferred to rehabilitation depart-ment. Conclusion Acute necrotizing encephalopathy in children always make progress rapidly, has high mortality,many survivors have severe neurological sequelae,which is worthy of being attention.

Objective To analyze the frequency of interleukin (IL)-22+CD161+CD4+ T cells in the peripheral blood mononuclear cells (PBMCs) in rheumatoid arthritis (RA) patients compared with healthy control subjects and investigate the relationship of IL-22+CD4+CD161+ T lymphocyte frequency changes with RA disease activity.In addition to explore the pathogenesis of RA,and to look for new treatment targets for RA.Methods Twenty-one RA cases were included in the Department of Rheumatology of Tangshan Gongren Hospital from 2017 to 2018.Fourteen patients were female and 7 were male with the age ranged from 36 to 74 years old.The average age of this group of patients was (55±10) years,the average disease course was (60±50) months.All patients fulfilled the classification criteria of American College of Rheumatology [American College of Rheumatology (ACR)].Twenty-one subjects were enrolled as the control group,all of them came to Tangshan Gongren Hospital for regular health check-up.Fifteen subjects in the control group were female and 6 were male.Their age ranged between 40-78 years old with the average age of (55±9) years.IL-22+CD4+CD161+ T cells in PBMCs were detected by flow cytometry.The frequency variation of different CD4+CD161 + T was compared between case and control groups.The correlation was studied between the frequency and RA disease activity score (DAS28),tender joints number,swollen joints number,red blood cell sedimentation rate,high sensitive C reactive protein and white blood cell counts,red blood cell counts,platelet counts,IgG,IgA,IgM,complement C3 level,complement C4 level.T-test or Mann-Whitney U test were used for single-factor analysis,Pearson's test was used for correlation analysis.Results The percentage of RA group secreted CD4+ T cells (0.33± 0.20)％ of INF-γand IL-22,CD4+ T cells (0.51±0.29)％ of IL-22,and CD4+CD161+ T cells of IL-22 simultaneously.The number (0.55 ±0.28)％ was.significantly higher than that of the healtby control group [(0.22±0.14)％,(0.25±0.18)％,(0.36±0.24)％],and the differences were statistically significant [P=0.002,P=-0.0.45,P=0.026].Conclusion The percentage of IL-22+CD4+CD161+ T lymphocytes in the peripheral blood monocytes in RA patients is significantly higher than that in the healthy controls.The results of this study suggest that IL-22+CD4+CD161+ T lymphocytes in RA patients maybe related to RA disease activity and joint lesions.