Objective: To investigate the effect of fractionated radiotherapy on the immune system of mice with subcutaneously transplanted hepatocellular carcinoma. Methods: Logarithmic growth of mouse hepatocellular carcinoma cells Hepa 1-6 were inoculated subcutaneously on the right side of C57BL/6 J mice (1×10⁷ cells /mice). The tumor-bearing mice were randomly divided into control group (Ctrl) and irradiation group (IR), 20 mice in each group. Additionally, 10 healthy mice were set as normal control group. Local fractionated X-ray irradiation of 8 Gy×3 fraction was given to the subcutaneous tumors, and the dose rate was 0.883 Gy/min. At 7 and 14 d after irradiation, the tumor organ index, spleen organ index, spleen pathological changes, and splenic T lymphocyte subsets, B lymphocyte subsets, and NK cells were detected. Results: Compared with Ctrl, at 7 and 14 d after irradiation, the tumor organ index decreased (t=4.649, 26.34, P<0.05), and the percentage of NK cells increased significantly (t=3.952, 3.633, P<0.05). The percentages of CD3+ , CD4+ , CD3+ CD4+ lymphocytes and the ratio of CD4+ /CD8+ lymphocyte decreased at 7 d after irradiation (t=3.193, 3.656, 3.219, 2.641, P<0.05), and the percentage of CD3+ lymphocyte decreased at 14 d after irradiation (t=3.031, P<0.05). But after irradiation, there were no significant changes in spleen organ index, B lymphocyte, CD3+ CD4+ lymphocyte and CD8+ lymphocyte. Conclusions Local hepatoma radiotherapy causes imbalance of lymphocytes in distal spleen of mice and hence reduces immunity, which provides a novel mechanism of radiological immunity damage.

Objective:To investigate the protective effect of cimetidine on mice with fractionated X-ray irradiation through right thorax.Methods:Thirty male C57BL/6 mice were randomly divided into control group, irradiation group and irradiation + cimetidine group (100 mg/kg), 10 mice in each group. Mice right thorax was locally irradiated with X-rays at a dose rate of 0.883 Gy/min to a cumulative dose of 24 Gy, 8 Gy per day in 3 d. After irradiation, the irradiation + cimetidine group was given cimetidine (100 mg·kg -1·d -1) for 7 d consecutively, and Ctrl and IR groups were given saline. Seven days after irradiation, the mice weight, spleen index and its T lymphocytes, B lymphocytes and NK cells were measured. Spleen tissue was stained with HE for pathological observation. Results:The fractionated irradiation lightly suppressed mice growth but obviously induced abscopal damage on spleen so that the spleen index were decreased. The irradiation group (0.369±0.011) had statistically significant difference compared with the control group(0.396±0.022)( t=2.978, P<0.05), the spleen pathological structure became disorder, and the percentages of CD3+ , CD4+ , CD3+ CD4+ , CD3+ CD8+ lymphocytes in spleen were decreased significantly( t=5.754, 3.570, 4.442, 5.281, 4.570, P<0.05). Cimetidine could partially restore the weight of irradiated mice, relieved spleen structure damage and effectively restored lymphocyte subsets, and partly recovered the levels of CD3+ , CD3+ CD4+ , CD3+ CD8+ lymphocytes in the spleen ( t=3.523, 2.706, 2.520, P<0.05). Conclusions:Cimetidine, as a potential radiation protection drug, could effectively reduce the mouse spleen injury induced by X-ray fractionated irradiation by improving mouse immune function.

Histone modification plays an important role in the process of cellular DNA damage repair. In recent years, a great number of studies have shown that histone modification affectsradiation responses including recruitment of DNA damage repair factors, creation of chromatin open structures and establishment of repressive histone marks.Regulation of histone modification may influence the process of DNA damage repair and thus affect radiation sensitivity. In this paper, the effects of histone modification on DNA damage repair, cellular radiosensitivity and the underlying mechanisms are reviewed.

Objective To investigate the changes of invasion and migration potential of residual hepatocarcinoma cells after fractionated X-ray irradiation and its underlying mechanism.Methods HepG2 cells were exposed to X-rays (2 Gy × 10) and recovered for 30 days after irradiation to generate residual cells.The changes of cellular invasion and migration potential were detected in the residual and its control cells using a Transwell assay.The expressions of epithelial-mesenchymal transition(EMT)-related proteins of N-cadherin and Snail were detected by Western blot.HepG2 subcutaneous tumor models were established using nude mice that were divided into control and radiation group.In radiation group,the tumors were locally irradiated with a dose of 2 Gy per fraction daily,5 days per week for 2 weeks until the cumulative dose reached to 20 Gy.The growth of the tumor was observed,and on the day 39 after cell implantation (i.e.day 14 after radiation),the liver metastasis and the expression of N-cadherin in tumor with or without radiation were detected.Results The invasions and migrations of the residual cells and xenograft tumor were significantly enhanced in comparison with the control group (t =5.126,7.714,P ＜0.05).The expressions of N-cadherin and Snail in the radiation group were significantly higher than that in the control group (t =7.509,7.184,P＜0.05).In the HepG2 subcutaneous tumor model,the weight and volume of tumor in nude mice of the radiation group was significantly smaller than that in the control group (t =2.396,3.170,P ＜0.05),and the number of liver metastases in nude mice and the expression of N-cadherin in tumor were significantly higher than those in the control group (t =2.994,5.695,P ＜0.05).Conclusions Fractionated irradiation enhances the abilities of invasion and migration by inducing EMT in hepatocarcinoma cells,which provides new insights of the recurrence and metastasis of hepatocarcinoma after radiotherapy.

Objective To establish an intestinal organoid-based assay to investigate the radiation mitigation effect of epiregulin in vitro. Methods Intestinal crypts were released from tissue incubated with EDTA. Intestinal crypts seeded in 3D matrigel were irradiated at 24 h after plating. The radiation mitigation effect of epiregulin was evaluated by measuring the survival rate, size and budding numbers of the organoid after irradiation, and the basic FGF was used as a positive control of epiregulin. Results Radiation-induced lethality and dose-dependent survival curve of the intestinal organoid were consistent with in vivo data. Treatment with epiregulin (400 ng/ml) at 24 h post-radiation significantly increased survival rate of 8 Gy X-ray irradiated intestinal organoid in comparison with non-treated group [(12.56 ± 1.02)％vs. (4.73 ± 0.38)％, t=12.43,P<0.05]. Conclusions Epiregulin has radiation mitigation effect on intestinal organoid and could serve as a potential medical countermeasure to mitigate gastrointestinal toxicity.

Objective To analyze the application of intraoperative neurophysiological monitoring combined with neuronavigation multi-modal fusion technology in the brainstem glioma resection. Methods One hundred twenty patients with brainstem glioma were divided into observation group and control group. The control group was treated by traditional operation, while the observation group was treated by intraoperative nerve electrophysiological monitoring combined with neuronavigation multimodal fusion technology. The general condition, clinical efficacy, KPS score, complications and survival rate of the two groups were compared. Results The effect was significantly better in the observation group(76.66%)than in control group(53.33%)( x2=11.962,P=0.001).KPS scores were significantly higher in the observation group (27.91 ±1.98) than in the control group (12.11 ±2.13)(t=32.669, P<0.001). Conclusions Intraoperative nerve electrophysiological monitoring plus neuronavigation multimodality fusion technology can improve clinical efficacy and quality of life in patients with brainstem glioma.

Objective To evaluate the ability of contrast-enhanced ultrasound (CEUS) as a prognostic indicator of renal function in chronic kidney disease (CKD) patients.Methods A total of 122 patients with CKD were collected,and patients with allergies to sulfur hexafluoride,pregnancy,cardiopulmonary insufficiency,urinary calculus and tumour were excluded.These patients were divided into estimated glomerular filtration rate [eGFR,ml·min1· (1.73 m2)-1] ≥60 group,eGFR 30-59 group and eGFR ＜ 30 group.CEUS was performed after an intravenous bolus injection of 1.5 ml SonoVue (BR1;Bracco Milan,Italy).Time-intensity curves (TICs) and quantitative indexes were created using QLAB quantification software.Followed up for 2 years,and patients with eGFR dropped 50％,double serum creatinine and end-stage renal disease (ESRD) were regarded as having kidney failure events.Risk factors related to kidney survival were investigated using a multivariate Cox regression model.Results One hundred patients were enrolled in the study,with 78％ patients in CKD 1-2 stages,16％ in CKD 3 stage and 6％ in CKD 4-5 stages.Patients were followed for a mean period of 14.1 months,ten (10％) patients exhibited composite kidney failure events.Among 3 groups,significant differences in the left kidney length derived peak intensity (DPI) were noted (P=0.014,P=0.010).Multivariate Cox regression analysis revealed that the DPI was an independent factor of progression of kidney disease.Multiple linear regression showed that age,basic eGFR,peak intensity were associated with eGFR decline rate.Patients with DPI ＜ 12.27 db were less to recover from kidney disease progression as compared with patients with DPI≥ 12.27 db (P=0.008).The area under the curve (AUC) for DPI was 0.778(95％ CI 0.612-0.944,P＜ 0.05),with a sensitivity of 64％ and a specificity of 88％.Conclusions The DPI might be the most valuable CEUS parameter for the evaluation of renal function.The DPI could serve as an independent predictor of the long-term prognosis of CKD patients.

If loosely defined,an abscopal effect occurs when localized irradiation affects the whole organism.In recent years,distant tumor regression and normal tissue damage after localized irradiation have been concerned by immuno-oncologists.However,the mechanisms of this effect are still far from clear.Mounting evidences suggest that the generation of abscopal effects is closely related to immune regulation.Radiotherapy might become a systemic tumor-treatment modality by enhancing immune function and played an important role in every stage of tumor development and prognosis.For the moment,targeting the immune checkpoint has become an attractive approach for malignant tumor therapy.Preclinical data have revealed that a strong abscopal effect could be effectively induced by the co-treatement of immune checkpoint inhibitors and irradiation,which could recruit antitumor T cells and achieve a powerful antitumor effect.This review discusses current progress and perspectives of abscopal effects in the combination of radiotherapy and immunotherapy.

Objective To explore the expressions of Bcl-2 and Bax proteins in the neurons of spinal cord after tibial nerve and common peroneal nerve injuries in rats.Methods A total of 90 male SD rats were randomly divided into three groups, the group A was as control group, group B as suture of tibial nerve cut group, and group C as suture of the common peroneal nerve cut group.The L4-6 segment spinal cord of the rats were removed for HE staining and immumohistochemical staining on 3, 7, 14, 28 days after the operation.The number of motor neurons in the spinal anterior horn were calculated.The expressions differences of Bcl-2 and Bax proteins were detected by immuno-histochemistry, and values of Bcl-2/Bax were calculated.Results The number of motor neurons in the anterior horn of spinal cord in group B were less than that in group C on 1, 3, 7, 14, 28 days after the operation (P< 0.01).The expression of Bcl-2 protein in group B and group C showed an upward and then declining trend.It decreased to the lowest on the postoperative 3 d in group B and 7 d in group C, respectively.The expressions of Bax protein in group B and C showed an upward and then declining trend, and it increased to the highest on the postoperative 3 d in groups B and C.The values of Bcl-2/Bax in groups B and C were showed an decreased and then increased trend and it was lower in group B than group C on the postoperative 3, 7, 14, 28 d(P< 0.01).Conclusion Injuries of tibial nerve and common peroneal nerve of the rats would lead the apoptosis of motor neurons in the spinal cord, but compared with the injury of common peroneal nerve, tibial nerve injury would lead less apoptosis of motor neurons.

Objective To explore the expressions of Bcl-2 and Bax proteins in the neurons of spinal cord after tibial nerve and common peroneal nerve injuries in rats.Methods A total of 90 male SD rats were randomly divided into three groups, the group A was as control group, group B as suture of tibial nerve cut group, and group C as suture of the common peroneal nerve cut group.The L4-6 segment spinal cord of the rats were removed for HE staining and immumohistochemical staining on 3, 7, 14, 28 days after the operation.The number of motor neurons in the spinal anterior horn were calculated.The expressions differences of Bcl-2 and Bax proteins were detected by immuno-histochemistry, and values of Bcl-2/Bax were calculated.Results The number of motor neurons in the anterior horn of spinal cord in group B were less than that in group C on 1, 3, 7, 14, 28 days after the operation (P< 0.01).The expression of Bcl-2 protein in group B and group C showed an upward and then declining trend.It decreased to the lowest on the postoperative 3 d in group B and 7 d in group C, respectively.The expressions of Bax protein in group B and C showed an upward and then declining trend, and it increased to the highest on the postoperative 3 d in groups B and C.The values of Bcl-2/Bax in groups B and C were showed an decreased and then increased trend and it was lower in group B than group C on the postoperative 3, 7, 14, 28 d(P< 0.01).Conclusion Injuries of tibial nerve and common peroneal nerve of the rats would lead the apoptosis of motor neurons in the spinal cord, but compared with the injury of common peroneal nerve, tibial nerve injury would lead less apoptosis of motor neurons.