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AIM:To investigate the effect of gastrodin(GAS)on microglia-mediated inflammatory response after hypoxic-ischemic brain damage(HIBD)neonatal mice by regulating the expression of JAK1/STAT1 pathway through C-C chemokine recepeor 5(CCR5).METHODS:Forty-eight C57BL/6J mice at about 10 days after birth were randomly divided into sham group,HIBD model group and HIBD+GAS group.BV-2 microglia were divided into control(Con)group,oxygen glucose deprivation(OGD)group,oxygen glucose deprivation with gastrodin intervention(OGD+GAS)group,GAS group,Maraviroc(MVC)group,OGD+MVC group,and OGD+MVC+GAS group.The mRNA expression of CCL4 and CCR5 were detected by RT-qPCR.The protein expression of CCR5,p-JAK1,p-STAT1,tumor necrosis factor-α(TNF-α)and interleukin-1β(IL-1β)were detected by Western blot.The expression of CCR5,p-JAK1 and p-STAT1 in cells were observed by immunofluorescence staining.RESULTS:(1)Compared with sham group,the expression levels of CCL4 and CCR5 mRNA,and CCR5,p-JAK1 and p-STAT1 proteins were significantly higher in the ischemic side of the corpus callosum in HIBD group(P<0.05).(2)Compared with Con group,the protein levels of CCR5,p-JAK1 and p-STAT1 significantly increased in BV-2 cells of OGD group(P<0.05).The protein levels of CCR5,p-JAK1 and p-STAT1 in BV-2 cells of OGD+GAS group were significantly lower than those of OGD group(P<0.05).(3)Maraviroc did not cause significant BV-2 cell death in the 0~80 μmol/L range.The p-JAK1 and p-STAT1 protein levels in MVC+OGD group were significantly lowered compared with OGD group(P<0.05),but no significant difference was found between MVC+ OGD and OGD+MVC+GAS groups.CONCLUSION:Gastrodin can exert neuroprotective effects via CCR5/JAK1/STAT1 signaling pathway.
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Background Air pollution is related to the occurrence and development of mental diseases. Olfactory bulb damage might be the potential prodromal symptom and sign of these diseases. The toxicity of diesel exhaust (DE), one of the main sources of air pollution, on olfactory bulb and the underlying mechanisms remain to be elucidated. Objective To explore the toxicity of DE on mouse olfactory bulb and underlying mechanisms. Methods A total of 40 C57BL/6 mice were randomly divided into four groups for exposure to DE by systemic inhalation: control group (filtered air), low exposure group (750 μg·m−3 DE), medium exposure group (1500 μg·m−3 DE), and high exposure group (3000 μg·m−3 DE). The mouse inhalation exposure to DE was performed 1 h per day for 28 d. HE staining was performed to observe pathological changes in mouse olfactory bulb tissue. TUNEL assay was used to observe apop-tosis in olfactory bulb. Kyoto Encyclopedia of Genes and Genomes (KEGG) was exhibited to explore potential mechanisms of olfactory bulb damage associated with DE. Quantitative real-time PCR (qPCR) was used to determine mRNA expression levels of inflammatory factors including tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6). Immunofluorescence staining was conducted to observed the microglia and astrocyte activation in olfactory bulb. Results The HE staining results showed that the number of periglomerular cells in the glomerular layer of olfactory bulb decreased in a dose-dependent manner, and the cells in the granule cell layer of olfactory bulb became disordered after DE exposure. The TUNEL staining showed that TUNEL positive cells in olfactory bulb tissue and neuronal apoptosis increased in the exposed groups compared with the control group (P<0.05). The KEGG pathway analysis showed that DE associated with significant enrichment of TNF signaling pathway in olfactory bulb tissue. The qPCR results showed that the TNF-α relative expression level significantly increased by 67% and the IL-6 relative expression level by 340% in the DE high exposure dose group compared with the control group (P<0.05). According to the immunofluorescence staining results, the numbers of activated microglia and astrocytes in olfactory bulb tissue significantly increased in the DE high exposure group, the relative fluorescence intensity of ionized calcium binding adaptor molecule 1 (IBA-1) increased by 120%, the granule cell layer relative fluorescence intensity of glial fibrillary acidic protein (GFAP) increased by 400%, and the glomerular layer relative fluorescence intensity of GFAP increased by 240% than those in the control group (P<0.05). Conclusion Inhalation exposure to DE can lead to glial cell activation including microglia and astrocytes in olfactory bulb tissue by activating inflammatory pathways and releasing inflammatory factors TNF-α and IL-6, leading to neuronal apoptosis in olfactory bulb tissue.
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Objective: To examine the efficacy and safety of pemetrexed plus apatinib for the treatment of advanced non-squamous non-small cell lung cancer (NSCLC) in elderly patients. Methods: Between January 2016 and June 2017, 38 elderly patients with ad-vanced non-squamous NSCLC from Qingdao Municipal Hospital were examined. All patients received first-or second-line therapy. The inclusion criteria were an age of≥65 years, physical status score of 0-2, and expected survival time of>3 months. Eighteen patients were assigned to the test group, and the remaining 20 patients were assigned to the control group. The patients in the test group were treated with pemetrexed plus apatinib, pemetrexed 500 mg/m2 on day 1 and apatinib 250 mg/d on days 1-21. The control group re-ceived pemetrexed in a 21-day cycle until the disease progressed or intolerable adverse reactions developed. The study was reviewed and approved by the medical ethics committee of Qingdao Municipal Hospital. Results: The disease control rates in the test and con-trol groups were 72.2% and 35%, respectively, with a statistically significant difference (χ2=5.265, P=0.022). The median progression-free survival time (PFS) in the test and control groups were 5.7 months [95% confidence interval (CI): 2.8-8.6] and 3.1 months (95% CI:2.7-3.5), with a statistically significant difference (χ2=4.01, P=0.045). The difference in the incidence of hand-foot syndrome and hyper-tension between the two groups was statistically significant (P=0.007 and P=0.016, respectively), with side effects of 1 or 2 degree in most cases, which was acceptable. Conclusions: Pemetrexed plus apatinib has a definite curative effect on advanced NSCLC, with con-trollable adverse reactions.
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Objective To study the influence of the distance of displaced fragment on the union of diaphysis fracture. Methods A wedge-shaped bone fragment was taken from central radial of the right forelimb of 120 New Zealand white rabbits for estabhshment of experimental animal model. The bone fragment was fixed to the main bone with two Kirschner wires, with certain space between bone fragment and the main bone. Then, the rabbits were divided into five groups, ie, Group A (in situ fixation),Group B (the space was 1/5 diameter of the radial shaft), Group C (the space was 2/5 diameter of the radial shaft), Group D (the space was 3/5 diameter of the radial shaft), Group E (the space was 4/5 diameter of the radial shaft). The animals were killed at 2, 4, 6, 8 weeks after operation. X-ray photos were taken to observe the fracture healing and the improved Gary X-ray used for scoring. HE staining after tissue section was employed to observe the histomorphological changes of fracture healing. Immunohistochemical method was used to determine expression of BMP-2. Results X-ray findings showed insignificant statistical difference between Group A and Group B, delayed union in Groups C and D and nonunion of bone absorption in Group E. Morphological observation showed same change in fracture site in Groups A and B lout significant late in emergence, formation and remodeling of the callus in the other groups compared with Group A, mainly with delayed fracture union or nonunion. There was no statistical difference in expression of BMP-2 between Group B and Group A (P > 0. 05), but there was statistical significance in Groups C, D and E compared with Group A at 2 weeks (P <0.01). There was statistical difference between Group E and Group A at 4 weeks (P <0. 01) but no statistical difference at 6 and 8 weeks between either two groups (P > 0. 05). Conclusions The distance of displaced fragment will influence fracture healing. The larger distance of the displaced fragment will beget more obvious influence on fracture healing. When the distance is more than 2/5 diameter of the bone shaft, the fracture will present union disorder.
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BACKGROUND: With the development of n0eo-adjuvant chemotherapy, 5-year survival rate of bone tumors has significantly increased. Limb salvage has replaced amputation to become a major means of treating knee tumors and has achieved good results. OBJECTIVE: To investigate and compare the effect of knee joint reconstruction using hinge-knee system and rotating knee system. DESIGN, TIME AND SETTING: Comparative observation. The patients were selected from Department of Spine and Orthopedic Surgery, First Affiliated Hospital of Gaungxi Medical University between June 1999 and March 2006. PARTICIPANTS: A total of 72 patients with tumor round the knee were selected from the First Affiliated Hospital of Gaungxi Medical University, and 9 cases were lost in follow-up. Of the remaining 63 cases, there were 35 males and 28 females, aged 31 years (range, 15-58 years); 40 cases underwent knee joint reconstruction using hinge-knee system and 23 using rotating knee system. METHODS: The tumor excision of superior tibia was performed according to Ennecking principle. After joint reduction of hinge-knee prosthesis, the bolt was adjusted and locked; the high polymer polyethylene pad was placed in rotating knee system, and the joint rotation axis was assembled. The tumor excision of inferior tibia was performed from the medial thigh along medial vastus muscle posterior margin till medial patellar ligament of superior tibia. After joint reduction of hinge-knee prosthesis, the bolt was adjusted and locked; the high polymer polyethylene pad was placed in rotating knee system, and the joint rotation axis was assembled. MAIN OUTCOME MEASURES: The treatment effect was evaluated according to MSTS functional scores, ambulation scores, flexion-extension-angle, knee rotation and infection, relapse and operative time. RESULTS: The 63 patients were followed up for 9 months to 8 years. In hinge-knee system group, operative time was (2.663±0.336) hours; there were 5 cases of relapse, 3 cases of metastasis/death and 2 case of infection. In rotating knee system group, operative time was (2.572±0.288) hours; there were 3 cases of relapse, 2 cases of metastasis/death, and 2 case of infection. One case in rotating knee system group developed fracture and dislocation of the polyethylene bush of rotating axis and there was no syndrome after changing fittings. No prosthesis loosening was found in two groups. With exception of patients with relapse and metastasis/death, 50 cases were evaluated, and no significant difference was found in MSTS scores between two groups (P > 0.05); the total score and single item score of ambulation scores in rotating knee system group were significantly greater than hinge-knee system group (P < 0.05). The extension angle in two groups reached or was close to 0°, and the flexion-extension angle of hinge-knee system group (119.375±17.490)° was similar to rotating knee system group (125.000±15.340)° (P=0.260). CONCLUSION: The rotating knee system displays superior function than hinge-knee system in knee salvage after surgery. Ambulation scores revealed that the knee joint function of the rotating knee system is superior over hinge-knee system, while the MSTS scores did not. Therefore, ambulation scores is more sensitive and appropriate to evaluate the function after knee salvage. There were no significant differences in operative time and flexion-extension ability and syndrome between two methods.
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0.05).Ambulation scores revealed significant difference (P