Objective To analyze the effect of inducible costmulator (ICOS)/inducible costmulator ligand (ICOSL) signaling pathway on hepatic fibrosis in mice infected with Schistosoma japonicum.Methods Seventy-eight ICOSL knockout (ICOSL-KO) mice and 77 wild type C57BL/6J mice were used as experimental schistosomiasis model infected with Schistosoma japonicum.The sera of mice were collected on the day before infection (0 week),and at 4,7,12,16 and 20 weeks post infection.Then,the concentrations of hyaluronic acid (HA) and hydroxyproline (HYP) in mice sera were measured by sandwich enzyme linked immunosorbent assay (ELISA) kits.The expressions of transforming growth factor β1 (TGF-β1),α-smooth muscle actin (a-SMA) and Collagen-Ⅰ in livers from ICOSL-KO/wild type mice were assessed by immunohistochemical staining.The granulomatous pathology and fibrosis level in mice liver were dynamically observed by hematoxylin and eosin (HE) staining and Masson's staining,respectively.The difference between groups was detected by t test or x2 test when appropriate.Results After infection with Schistosoma japonicum,the levels of HA and HYP were gradually increased.In ICOSL-KO mice,the levels of HA at 7,12,16 and 20 weeks post infection were all significantly lower than those in wild type mice [(161.32±15.44) vs (186.01±21.24) ng/mL,t=2.528 2,P＜0.05; (166.73±18.18) vs (231.39±20.12) ng/mL,t=4.342 4,P＜0.05; (193.58±21.06) vs (252.51±25.29) ng/mL,t=4.003 9,P＜0.05; (253.98±24.53) vs (310.88±23.86) ng/mL,t=3.718 0,P＜0.05].Similarly,HYP levels in ICOSL-KO mice at 12,16 and 20 weeks post infection were all significantly lower than those in wild type mice (all P＜0.05).Immunohistochemical staining showed that TGF-β1,α-SMA and Collagen-Ⅰ expressions in liver of ICOSL-KO mice from 7 to 20 weeks post infection were all significantly lower than those of wild type mice (all P＜0.05).HE staining showed,the volume of liver egg granulomas of ICOSL-KO mice was significantly smaller than that of wild type C57BL/6J mice (P＜0.01).Furthermore,Masson's staining showed that the level of hepatic fibrosis in ICOSL-KO mice was lower than that in wild type mice and the fibrosis scores were statistically different between two groups (all P＜0.05).The mortality rate of the wilde type C57BL/6J mice was higher than that of ICOSL-KO mice.After 20 weeks of infection,the difference was statistically significant (55.84 ％ vs 37.18 ％,x2 =5.427,P＜0.05).Conclusions The degree of hepatic fibrosis and related indicators are obviously down-regulated in ICOSL-KO mice infected with Schistosoma japonicum.These findings suggest that ICOS/ICOSL signaling pathway has an important impact on the process of hepatic fibrosis caused by Schistosoma japonicum.

Objective:To analyze effect on the CD154-CD40 signaling pathway and Th1/Th2 polariza-tion by deficient inducible co-stimulator ( ICOS)-ICOS ligand ( ICOSL) signaling in mice infected with Schistosoma japonicum. Methods:ICOSL knockout ( ICOSL-KO) mice and wild-type C57BL/6J mice were used as experimental Schistosomiasis model infected with Schistosoma japonicum. The expressions of CD154 and CD40 on splenocytes and on inflammatory cells around granulomatous infiltration of liver in mice infected with Schistosoma japonicum were analyzed by flow cytometry,immunohistochemical staining, respectively, on the day before infection (0 week) and at the end of 4, 7, 12, 16 and 20 weeks post-infection. The splenocytes of the mice were stimulated with soluble egg antigen( SEA) for 72 hours, then the concentrations of interferon gamma(IFN-γ) and interleukin-4 (IL-4) in the culture supernatants were measured by sandwich enzyme-linked immunosorbent assay ( ELISA) kits. The levels of SEA-specific an-tibodies of IgG and IgG1 and IgG2a were measured in the mice sera by ELISA. The granulomatous pa-thology in the mice liver was dynamically observed by hematoxylin and eosin ( HE ) staining. Results:Compared with the wild-type C57BL/6J mice, the expressions of CD154 on CD4 + T splenocytes [(18. 62 ± 4. 76)% vs. (27. 91 ± 3. 94)%, (22. 44 ± 4. 67)% vs. (40. 86 ± 5. 21)%, (25. 50 ± 6. 81)% vs. (43. 81 ± 8. 41)%, (20. 22 ± 5. 28)% vs. (40. 95 ± 7. 34)%, (17. 87 ± 4. 59)% vs. (33. 16 ± 6. 31)%, all P <0. 01] and of CD40 on CD19 + B splenocytes [(19. 43 ± 3. 26)% vs. (24.37 ±3.59)%, (23. 00 ± 4. 47)% vs. (31. 80 ± 5. 86)%, (24. 46 ± 5. 01)% vs. (35. 85 ± 5. 32)%, (23. 42 ± 4. 69)% vs. (33. 30 ± 6. 14)%, (22. 85 ± 3. 78)% vs. (30. 88 ± 5. 94)%, all P<0 . 05 ] in the ICOSL-KO mice significantly decreased at the end of 4 , 7 , 12 , 16 and 20 weeks post-infection. Moreover, the expressions of CD154[(0. 319 ± 0. 066) vs. (0. 488 ± 0. 086), (0. 389 ± 0. 067) vs.(0.596±0.082),(0.378±0.064) vs.(0.543±0.072),(0.348±0.069) vs.(0.523±0.076), all P<0. 01] and CD40[ (0. 398 ± 0. 066) vs. (0. 546 ± 0. 079), (0. 461 ± 0. 085) vs. (0. 618 ± 0. 076), (0. 453 ± 0. 087) vs. (0. 587 ± 0. 074), (0. 449 ± 0. 065) vs. (0. 565 ± 0. 082), all P <0 . 05 ] on inflammatory cells around granulomatous infiltration in liver from the ICOSL-KO mice were sig-nificantly lower than those of the wild-type C57 BL/6 J mice at the end of 7 , 12 , 16 and 20 weeks post-in-fection. The levels of IFN-γ of the ICOSL-KO mice were significantly higher than those of the wild-type C57BL/6J mice at the end of 4, 7, 12, 16 and 20 weeks post-infection (P <0. 05). However, the levels of IL-4 of the ICOSL-KO mice were significantly lower than those of the wild-type mice ( P <0. 05). Compared with the wild-type C57BL/6J mice, the levels of SEA-specific antibodies of IgG and IgG1 and IgG2a in the sera of the ICOSL-KO mice significantly decreased (P<0. 01). Moreover, The Th2 differentiation index of the ICOSL-KO mice was significantly lower than that of the wild-type mice in post-infection (P<0. 01). Also, the ratio of IgG1/IgG2a of the ICOSL-KO mice were significantly lower than that of the wild-type mice at the end of 7 , 12 and 16 weeks post-infection ( P<0 . 05 ) . And the vo-lume of liver egg granulomas of the ICOSL-KO mice was significantly smaller than that of the wild-type mice ( P <0 . 01 ) . Conclusion: These findings suggest that there is obvious down-regulation in the expressions of CD154 and CD40 and impairment of Th2 immune response in the ICOSL-KO mice infected with Schistosoma japonicum, accompanying with notedly reduced hepatic granulomatous pathology. The ICOS-ICOSL signaling has a regulatory effect on CD154-CD40 signaling pathway, and may play an impor-tant role in the hepatic egg granuloma formation of Schistosomiasis.

Nowadays,medical students have high pressure in hunting job.We analyzed the background of hunting job for medical students and discussed the corresponding psychological problems.Finally,we provided the countermeasures to solve these problems for medical students to find a job.

Age-related macular degeneration(AMD)is a kind of degenerative diseases with complex pathogenesis and stimulation of multiple factors.It has become one of the major diseases causing-blindness in the elderly population in China.Recently,some epidemiological findings demonstrated that diabetes mellitus possibly is one of risk factors for AMD,and this will offers a new approach for the prevention and treatment of AMD.Thus,it is very important for US to strengthen the research of mechanism of AMD impacted by diabetes mellitus,pay more attention to the progress of AMD,search for a scientific and rational therapeutic way of improving the prognosis and elevate the quality of life in the patients with diabetes mellitus.

Objective:To investigate efficacy of paroxetine in the treatment of diarrhea-predominant irritable bowel syndrome(D-IBS).Methods:In a self-controlled trial,45 patients with D-IBS symptoms according to the Rome Ⅱ criteria were treated with paroxetine 10mg Qd for 12 weeks.The efficacy measures included D-IBS gastroin- testinal symptoms,abnormal frequency or consistency of defecation,Hamilton Depression Scale(HAMD)and Hamil- ton Anxiety Scale(HAMA).Results:42 cases completed 12 week therapy.The overall IBS symptoms,the Bristol stool consistency,stool frequency and abdominal pain were relieved significantly at week 2(P

Objective:To investigate the efficacy of mirtazapine in patients with anorexia nervosa.Methods: A randomized,controlled study was undertaken in 42 patients with anorexia nervosa.Subjects were treated with mir- tazapine or selective serotonin reuptake inhibitor(SSRIs)for 12 weeks and followed up to 12 weeks.The clinical out- come measures included body weight,Hamilton Depression Scale(HAMD),Hamilton Anxiety Scale(HAMA)and the side effects of medications.Results:38 subjects completed the trial,20 in mirtazapine group,18 in SSRIs group. The weight gain in mirtazapine group was significantly more that that in SSRIs group at week 6 but the difference was not significant at week 12.The scores of HAMD and HAMA at endpoint were significantly lower than those at base- line(P0.05).No severe adverse events were observed in both groups.Common side effects of SSRIs were gastroenterological discomfort,while those of mir- tazapine included somnolence and weight gain.Conclusion:Mirtazapine can improve appetite and weight gain in pa- tients with anorexia nervosa in addition to relieve anxiety and depression.It is well tolerated and has ealier onset of effect than SSRIS.

Objective To investigate whether caspase-8 regulates Bcl-2 expression in Fas and Actinomycin D(AD) induced apoptosis in Bel-7402 cells.Methods Bel-7402 cells were divided into four groups randomly,that is:control,Fas group,Fas-AD group and Ac-IEFD-cho group,and treated with Fas-AD in the presence/absence of caspase-8 inhibitor Ac-IEFD-cho.The expressions of caspase-8 and Bcl-2 were determined with Western Blot and RT-PCR,respectively.Results Compared with control group and Fas group,after Bel-7402 cells were treated with Fas-AD,typical apoptosis morphology was clearly observed,the expression of activated caspase-8 increased significantly,and the Bcl-2 expression decreased apparently.However,after Bel-7402 cells were treated with Fas-AD in the presence of the caspase-8 inhibitor Ac-IEFD-cho,the expressions of activated caspase-8 decreased while the Bcl-2 expression increased.Conclusion Activated caspase-8 can regulate Bcl-2 in Fas-and AD-induced apoptosis in Bel-7402 cells.

Administration, Oral ; Anti-Inflammatory Agents, Non-Steroidal ; adverse effects ; therapeutic use ; Aspirin ; adverse effects ; therapeutic use ; Brain Edema ; chemically induced ; Child ; Coma ; chemically induced ; Female ; Humans ; Liver ; drug effects ; pathology ; physiopathology ; Reye Syndrome ; chemically induced ; Treatment Outcome

Objective To evaluate the relationship between pharmacodynamics of sufentanil-induced respiratory depression and age factors. Methods Forty ASA Ⅰ or Ⅱ patients scheduled for elective abdominal surgery were randomly divided into 2 groups according to the age: young and middle-aged group (25-64 yr, group M) and elderly group (65-80 yr, group E). EC50 was determined by up-and-down sequential trail. The initial target effect-site concentration (Ce) of sufentanil was set at 0.40 and 0.35 μg/ml in group M and E respectively.Each time Ce decreased/increased by 10% in the next patient depending on whether or not the respiratory depression occurred. Respiratory depression was defined as VT ≤ 5 ml/kg, RR ≤ 8 bpm/min, SpO2 ≤ 94%,PET CO2 ≥ 55 mm Hg, and/or apnea ≥ 15 s. Results The EC50 and 95 % confidence interval of sufentanil causing respiratory depression were 0.61 (0.54-0.70) μg/ml and 0.41 (0.38-0.45) μg/ml in group M and E respectively with the significant difference. Conclusion The efficacy of sufentanil-induced respiratory depression is related to age factors and the elderly patients are more sensitive to sufentanil-induced respiratory depression.

Under the condition of microgravity, human body will experience a series of cardiovascular deconditioning. The vascular endothelial cells are the most important component of the vessel wall, so the changes of biological characteristics of vascular endothelial cells are directly related to cardiovascular deconditioning. Therefore, it is important to prevent and treat the cardiovascular deconditioning in astronauts by studying the effect of microgravity on biological characteristics of vascular endothelial cells.