OBJECTIVE To assess the efficancy of Yangxue Qingnao granules on simvastatin-induced vascular injury model in zebrafish. METHODS Since statins can inhibit vascular development in zebrafish,in this study,we developed a novel animal model using 1 to 3 day post-fertilization larval zebrafish by optimizing the doses and duration of simvastatin exposure.Five pro-angiogenic drugs with a variety of mechanisms were tested to validate the newly developed zebrafish model. Zebrafish was treated with different concentration of Yangxue Qingnao granules( 62.5,125 and 250 μg·mL-1)for 2 d then tested for the area of subintestinal vein vessels. RESULTS Vascular regeneration promoting effect of five pro-angiogenic drugs (calycosin, astragaloside, chlorogenic acid, ferulic acid and Panax Notoginseng Saponins)were 8-48%,24-51%,35-58%,28-75% and 37-69%,respectively.In 62.5,125 and 250 μg·mL-1Yangxue Qingnao granules group,vascular regeneration promoting effect were 21% (P>0.05), 84%(P<0.01) and 53%(P<0.01). CONCLUSION Our results demonstrate that the zebrafish vascular injury model validated in this study could be used for in vivo angiogenesis studies and drug screening and for assessing pro-angiogenic drugs with different mechanisms.Yangxue Qingnao granules could promote the vascular regeneration in zebrafish.

Objective To study the influence of crosstalk phenomenon on the measurement of gross radioactivity in drinking water.Methods The gross activity in different standard materials with different thickness and area was measured using national standard method.Results There was no obvious change in crosstalk factor with the increase of 241Am powder amount in the measurement,whereas the larger amount of uranium used might lead to larger crosstalk factor.The different measurement channels resulted in different crosstalk factors.The influence of beta radioactivity on alpha radioactivity measurement was significant.On the contrary,the alpha-to-beta crosstalk factor was negligible.The area of sample plate imposed no significant influence on crosstalk factor.Conclusions The gross beta activity can be corrected to decrease the influence of alpha radioactivity using powder standard samples,when simultaneous alpha and beta counting mode is applied in measurement grass radioactivity in drinking water.

Objective To investigate the possible mechanism of aggregation and activation of neu-trophils(polymorphonuclear neutrophils,PMN)in mice with chlamydial pneumonitis. Methods C57BL/ 6 mice were inoculated intranasally with 3×103 inclusion-forming units(IFU)of Chlamydia muridarum(Cm) to induce the murine model of chlamydial pneumonitis. Samples of lung tissues collected at different time points after infection were stained by hematoxylin and eosin for histopathological assessment of inflammation. The levels of myelo-peroxidase(MPO)were detected for the evaluation of PMN aggregation. The mononu-clear cells were isolated from lung tissues. The inflammatory cells were counted with Giemsaˊs staining. CD11b+Gr1+ cell population and CD11b expression in lung mononuclear cells were analyzed by flow cytome-try. The expression of chemokines(MIP-2,LIX,KC and MCP-1)in lung tissues at mRNA level was meas-ured by RT-PCR. Results Chlamydial pneumonitis was induced in mice by intranasal inoculation of 3×103 IFU of Cm. Compared with the mice from control group,large amounts of inflammatory cells including PMN, monocytes and lymphocytes were induced in lung tissues of mice with Cm infection. PMN responded earlier than monocytes to the infection. The levels of MPO were significantly increased in mice with Cm infection and reached the highest level on the 7th day after infection. A decline in MPO levels was observed on the 14th day but the levels were still higher than those on day 0. The percentages and total numbers of CD11b+Gr1+ cells were significantly increased after Cm infection. Moreover,an increased expression of PMN CD11b was also detected by flow cytometry. The expression of chemokines(MIP-2,LIX,KC and MCP-1)was in-creased in lung tissues of mice after Cm infection. The results of the study indicated that Cm infection in-duced the expression of PMN chemoattractants,resulting in the recruitment of PMN. Conclusion The infil-tration and activation of PMN in lung tissues of mice were induced by Cm infection through increasing the ex-pression of chemokines. PMN played an important role in immune responses against Cm infection.

Objective:To investigate the effect of IL-17A on the differentiation and maturation of murine bone marrow-derived dendritic cells( BMDCs ) . Methods: Murine bone marrow cells were isolated and cultured in RPMI1640 complete medium in the presence of GM-CSF(20 ng/ml) for 8 days to induce differentiation of murine bone marrow cells to DC progenitors. Then these cells were treated with LPS(1 μg/ml) for 36 h which polarized immature DCs into mature DCs. Different concentrations of rmIL-17A(10 or 100 ng/ml) was added to the culture medium at different stages of BMDC differentiation and maturation. Co-stimulatory molecules expression on BMDC were analyzed by flow cytometry,and the culture supernatants were analyzed for IL-12p40 and IL-10 level by ELISA. Results:rmIL-17 could promote co-stimulatory molecules( CD40,CD80,CD86 and MHCⅡ) expression on BMDCs in a does-dependent manner,especially,the expression of CD40 and MHCⅡhad a significant increase in high concentration of rmIL-17A group;rmIL-17A was added while LPS induced maturation of BMDCs. CD40,CD80,CD86 and MHCⅡexpression on BMDC increased sharply in LPS plus rmIL-17A stimulation group,besides,CD86,MHCⅡ showed a higher level expression on BMDC with the increase of con-centration of rmIL-17A. Furthermore,secretion of IL-12p40 and IL-10 increased significantly in the group of DCs treated with LPS plus low concentration of rmIL-17 compared with the group without rmIL-17(P<0. 001). However,high concentration of rmIL-17A group showed significantly higher levels of IL-12p40(P<0. 001),but there was no difference in IL-10. Conclusion:IL-17A promotes the phe-notypic development of BMDC progenitors propagated in GM-CSF and cooperate with LPS to induce BMDC differentiation and matura-tion.

Cerebral small vessel disease (CSVD) is a series of clinical syndrome characterized by the damage of small blood vessels in the brain caused by a variety of causes. Although the pathophysiological mechanisms of CSVD are not fully understood, increasing evidence suggests that matrix metalloproteinase-9 plays an important role in the occurrence and development of CSVD.

In recent years, the incidence of cerebral small vessel disease (CSVD) has been increasing with the aging of the population, and the cognitive impairment caused by it has brought huge burden to patients and their families. As a novel inflammatory biomarker, lipoprotein-associated phospholipase A 2 (Lp-PLA 2) directly participates in the pathogenesis of cognitive impairment in patients with CSVD by regulating circulatory vascular injury and neuroinflammation, and is expected to become a predictive indicator and therapeutic target for CSVD.

OBJECTIVETo evaluate the efficacy of intraoperative magnetic resonance imaging (iMRI) and multimodal navigation in surgical resection of glioblastoma.

METHODSBetween February 2009 and July 2010, 76 glioblastoma patients underwent surgical resection guided by iMRI and multimodal navigation. The cohort consisted of 43 male and 33 female patients, with a mean age of 49 years (range: 14-79 years). Rates of gross total resection (GTR) and extent of resection (EoR) were calculated at first and final iMRI scans.Pearson χ(2) test was used to compare the rates of GTR.

RESULTSiMRI and multimodal navigation were successfully implemented in all cases. Rates of GTR were misestimated by neurosurgeons in 24 cases (31.6%), which were confirmed by first iMRI. Total tumor resection were achieved in 20 cases (26.3%) as a result of iMRI scan, increasing the rates of gross total resection from 52.6% to 78.9% (χ(2) = 11.692, P = 0.001). Extent of resection in 28 patients who underwent further tumor resection were increased from 81.5% to 98.1%, leading to the overall extent of resection improved from 92.3% to 98.4%. At 3-month follow-up, 3 cases (3.9%) developed permanent neurologic deficits. The mean clinical follow-up was 15.6 months (range 3.0-45.0 months). The 2-year overall survival rate was 19.7%. The median progression-free survival of gross total resection group was 12 months (95% CI: 10.1-13.9 months), compared with 9 months (95%CI: 7.9-10.1 months) of the subtotal resection group (χ(2) = 4.756, P = 0.029). The overall survival of gross total resection group was 16 months (95% CI: 13.7-18.3 months), compared with 12 months (95% CI: 9.7-14.3 months) of the subtotal resection group (χ(2) = 7.885, P = 0.005).

CONCLUSIONCombined with multimodal navigation, iMRI helps maximize surgical resection of glioblastoma, preserving neurological function while increasing progression-free survival and overall survival.

Adolescent ; Adult ; Aged ; Brain Neoplasms ; surgery ; Female ; Glioblastoma ; surgery ; Humans ; Magnetic Resonance Imaging ; Male ; Middle Aged ; Monitoring, Intraoperative ; methods ; Neuronavigation ; Young Adult

Objective:To investigate the protective effect of IL-22 on rat liver ischemia reperfusion injury (IRI) and the potential mechanisms.Methods:Eighteen male specific pathogen free SD rats (7-8 weeks, about 250g) were randomly divided into three groups: Sham group (Sham), hepatic ischemia reperfusion (IRI) and IL-22 preconditioning group (IL-22+ IRI), respectively. The liver IRI model of 70% rats was established. The IL-22+ IRI group was intraperitoneally injected with rcIL-22 (50 mg/kg) 1 hour before surgery, and the Sham group and IRI group were injected with the same dose of normal saline 1 hour before surgery. After 1 h ischemia and 6 h reperfusion, blood was collected from the abdominal aorta, then liver tissue, serum aspartate transaminase (AST) and alanine aminotransfease (ALT) levels were measured. The levels of superoxide dismutase (SOD) and malondialdehyde (MDA) in liver tissue were detected. The expression of signal transducer and activator of transcription 3 (STAT3), p-STAT3, nuclear factor erythorid-2 related factor 2 (Nrf2) and heme oxygenase 1 (HO-1) were detected by Western blot. Results:Compared with Sham group, serum AST [(1 923.50±92.63) U/L, (1 004.25±65.05) U/L)] and ALT [(1 172.51±180.31) U/L, (583.50±164.75) U/L] levels were increased in IRI group and IL-22+ IRI group (AST: F=293.62; ALT: F=30.33, P<0.05). The levels of MDA in IRI group and IL-22+ IRI group [(1.72±0.12) μmol/mg, (0.98±0.05) μmol/mg] in liver tissue were higher than those in Sham group (0.58±0.14) μmol/mg protein ( F=186.73, P<0.05), and the expression of p-STAT3, Nrf2 and HO-1 was increased. SOD level in IRI group (28.51±3.85) U/mg was lower than that in Sham group (70.25±5.64) U/mg protein ( F=203.41, P<0.05). Compared with IRI group, serum AST and ALT levels in IL-22+ IRI group were decreased, SOD activity in liver tissue was increased, MDA level was decreased, and p-STAT3, Nrf2 and HO-1 expression was increased (all P<0.05). Conclusion:IL-22 could alleviate liver IRI in rats, and the mechanism may be related to the activation of STAT3 and Nrf2/HO-1 signaling pathway and anti-oxidative stress.

Objective:To investigate the mechanism of excessive inflammation in the lung of C3H/HeN(C3H) mice following Chlamydia muridarum(Cm) airway infection.Methods:Chlamydial pneumonitis was induced in C3H and C57BL/6(C57) mice by intranasal inoculation with 1×103IFU (inclusion forming unites) of Cm strains.The expression of TLR2,TLR4 and MyD88 mRNA in the lung at different time point post-infection was measured by RT-PCR.Results:Cm infection induced Toll-like receptors expression in two strains of mice.The expression of TLR2 and TLR4 mRNA,especially TLR2 mRNA(P<0.001 or P<0.05),were significantly higher in highly susceptible C3H mice on day 7 and day 14 d post-infection compared with C57 mice.Further studies showed that the expression of MyD88 mRNA was also significantly higher in C3H mice on day 7 post-infection,and maintained high expression untill the day 14.Conclusion:Cm lung infection induced high level of TLR2,TLR4 and MyD88 mRNA expression in C3H mice,which may associate with excessive inflammation in C3H mice.

Based on the clinical characteristics of thromboembolic vasculitis， the diagnostic criteria in western medicine and the dialectical standard in traditional Chinese medicine （TCM） were analyzed and established by consulting relevant literature， and the modeling method， modeling objects as well as modeling advantages and disadvantages for the animal models of thromboembolic vasculitis were summarized in this paper. By analyzing its coincidence with the characteristics of clinical symptoms in traditional Chinese and western medicine， it was found that the animal model of thromboembolic vasculitis had a higher degree of coincidence with the clinical symptoms in western medicine， as well as cold and dampness blocking collaterals syndrome and heat toxin injury yin syndrome in TCM， but lower degree of coincidence with damp-heat toxin syndrome and Qi-blood deficiency syndrome. There is no animal model consistent with blood stasis syndrome. The pathological and hemorheological indexes （blood viscosity， erythrocyte sedimentation rate） were the most common indexes. Compared with a large number of cases reported in clinical treatment of thromboangiitis obliterans， the experimental research was relatively weak. It is the focus of future research to establish a reasonable model to judge the quantitative standard， and to establish the animal model with higher coincidence degree with TCM syndrome.