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Objective:To investigate the expression changes at the transcriptional level in normal lung tissues of mice after exposure to heavy ion radiation for different durations at different doses, aiming to provide evidence for exploring sensitive genes of heavy ion radiation, heavy ion radiation effect and the damage mechanism.Methods:Experiments on the temporal kinetics: the whole thorax of mice was irradiated with 14.5Gy carbon-ions and the total RNA of lung tissue was extracted at 3days, 7days, 3 weeks and 24 weeks. In dose-dependent experiment, the total RNA of lung tissue was extracted at 1 week after irradiated with a growing thoracic dose of 0, 7.5, 10.5, 12.5, 14.5, 17.5 and 20Gy. Protein-to-protein interaction (PPI) analysis and gene-ontology biological process enrichment analysis were performed on significant differentially expressed genes (DEGs).Results:A clearly differential expression patterns were observed at 3-day (acute stage), 1-week (subacute stage), 3-week (inflammatory stage) and 24-week (fibrosis stage) following 14.5Gy carbon-ions irradiation. Among those, the 3-day time point was found to be the mostly different from the other time points, whereas the 7-day time point had the highest uniformity with the other time points. Cellular apoptosis was the main type of cell death in normal lung tissues following carbon-ions exposure. The interactive genes of Phlda3, GDF15, Mgmt and Bax were identified as the radiosensitive genes, and Phlda3 was the center ( R=0.76, P<0.001). Conclusion:The findings in this study provide transcriptional insights into the biological mechanism underlying normal lung tissue toxicity induced by carbon-ions.
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Objective@#To study dose-response relationships of fractionated irradiation induced pulmonary fibrosis in mice according to radiological imaging changes of lung.@*Methods@#A total of 8-10 week old-female C57BL6 mice were randomized into different groups for whole thoracic irradiation. The prescribed doses were 0, 2.0, 4.0, 6.0, 7.0, 8.5 Gy per fraction in a total of 5 fractions. CT imaging was performed at 24 weeks post irradiation. The averaged lung density and volume changes were obtained by the three-dimensional segmentation algorithm, and further analyzed in Boltzmann regression modeling.@*Results@#At the endpoint of 24 weeks, the dose-dependent pulmonary radiological alternations were revealed by coronal view of CT images. Translational analysis of fibrosis-related gene-signatures as well as histological collagen stainings further corroborated the radiological findings. According to Boltzmann modeling, the E50 of radiation-induced lung density changes was found to be (30.80±0.80)Gy (adjusted R2=0.97); whereas the E50 for radiation-induced lung volume reduction was determined as (31.31±7.07)Gy (adjusted R2=0.92). Both outcomes indicated a remarkable enhancement of tolerance to normal lung tissues after exposure with 5-fraction versus single fraction scheme.@*Conclusions@#The radiation-induced lung density and volume changes depend not only on total dose, but also the number and dose of fractions.
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Objective To investigate the radiation induced pulmonary fibrosis with a dose-response mouse model, based on the CT image changes of pulmonary fibrosis.Methods Female C57BL6 mice aged 8-10 weeks were randomly divided into 20 Gy or escalated doses of X-ray whole thoracic irradiation ( WTI) groups. CT scan was performed at different time points before and after radiation. The average lung density and lung volume changes were obtained by three-dimensional segmentation algorithm. After gene chip and pathological validation, the parameters of CT scan were subject to the establishment of logistic regression model. Results At the endpoint of 24 weeks post-irradiation, the lung density in the 20 Gy irradiation group was (-289.81± 12.06) HU, significantly increased compared with (-377.97± 6.24) HU in the control group ( P<0.001) . The lung volume was ( 0.66±0.01) cm3 in the control group, significantly larger than ( 0.44±0.03) cm3 in the irradiated mice ( P<0.001) . The results of quantitative imaging analysis were in accordance with the findings of HE and Mason staining, which were positively correlated with the fibrosis-related biomarkers at the transcriptional level ( all R2=0.75, all P<0.001) . The ED50 for increased lung density was found to be ( 13.64± 0.14) Gy ( R2=0.99, P<0.001) and ( 16.17± 4.36) Gy ( R2=0.89, P<0.001) for decreased lung volume according to the logistic regression model. Conclusions Quantitative CT measurement of lung density and volume are reliable imaging parameters to evaluate the degree of radiation-induced pulmonary fibrosis in mouse models. The dose-response mouse models with pulmonary fibrosis changes can provide experimental basis for comparative analysis of high-dose hypofractioned irradiation-and half-lung irradiation-induced pulmonary fibrosis.
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Objective To study dose-response relationships of fractionated irradiation induced pulmonary fibrosis in mice according to radiological imaging changes of lung. Methods A total of 8-10 week old-female C57BL6 mice were randomized into different groups for whole thoracic irradiation. The prescribed doses were 0, 2. 0, 4. 0, 6. 0, 7. 0, 8. 5 Gy per fraction in a total of 5 fractions. CT imaging was performed at 24 weeks post irradiation. The averaged lung density and volume changes were obtained by the three-dimensional segmentation algorithm, and further analyzed in Boltzmann regression modeling. Results At the endpoint of 24 weeks, the dose-dependent pulmonary radiological alternations were revealed by coronal view of CT images. Translational analysis of fibrosis-related gene-signatures as well as histological collagen stainings further corroborated the radiological findings. According to Boltzmann modeling, the E50 of radiation-induced lung density changes was found to be (30.80±0.80)Gy (adjusted R2 =0.97);whereas the E50 for radiation-induced lung volume reduction was determined as ( 31. 31 ± 7. 07 ) Gy(adjusted R2=0. 92). Both outcomes indicated a remarkable enhancement of tolerance to normal lung tissues after exposure with 5-fraction versus single fraction scheme. Conclusions The radiation-induced lung density and volume changes depend not only on total dose, but also the number and dose of fractions.
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Objective To study the changes of gastrointestinal movement function in rats with chronic unpredictable mild stress(CUMS) and explore the mechanisms underlying it.Methods The rats were divided into stress model group and control group.The stress model rats were induced by 21-day chronic unpredictable mild stress as well as social-isolated fed.The rate of ink propulsion of gastrointestinal tract and the contraction of intestinal canal in rats were observed.Immunohistochemistry was adopted to detect the expression of OT in rats.Results (1) After the models were induced,weight-gain and sucrose preference of model group ((69.97 ± 9.81) g,(49.05± 5.98) g) were lower than those in control group ((116.27 ± 13.60) g,(83.51 ± 3.08) g) (P ＜ 0.001),and both the crossing-score and rearing-score ((24.00 ± 13.52),(3.90 ± 2.51)) were lower than those in control group ((53.60 ± 27.98),(11.50 ± 8.85)) in the open-field test.(2) The rate of ink propulsion of model group ((67.33 ± 6.24) ％) was decreased when compared to the control group ((76.83 ± 10.00) ％) (P ＜ 0.05),and the intestinal canal contraction amplitude and contraction frequency ((1.37 ± 0.18) g,(0.58 ± 0.02) S-1) were lower than those in control group ((1.88 ± 0.13) g),(0.62 ± 0.04) S-1) (P ＜ 0.05).(3) Compared with the control group (6.07 ± 3.71),OT immunoreactive substance was increased in model group (59.17 ± 16.08) of rats (P＜0.001).Conclusion Chronic stress can cause the decrease in gastrointestinal movement function of rats.These changes may be related to the increased expression of OT in paraventricular nucleus.
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With the gradual perfection of the socialist market economy, the tempo of medical and health re- form is being increasingly accelerated. It is imperative for hospitals to seize opportunities available so as speed up reform in the system of commercialized hospital logistics. There should be clear guidelines for reform in this aspect. In Beijing the implementation of such reform is divided into 3 stages. In the first stage, each hospital should complete re- form in the responsibility system of comprehensive geals for hospital logistics. In the second stage, each hospital should complete reform in its systems of logistics management, properties, and labor employment. In the third stage, logistic service groups extending across hospitals and running on a large scale should be set up. Sound guarantee in or- ganization and support in policy are indispensable to reform in the system of commercialized hospital logistics. [