TLD calibration and absorbed dose measurement in a radiation-induced liver injury model under a linear accelerator

The application of a thermoluminescent detector(TLD) for dose detection at the liver irradiation site in mice under linear accelerator precision radiotherapy and the use of a single high dose to irradiate the mouse liver to construct a biological model of a radiation-induced liver injury(RILD) in mice were to determine the feasibility of constructing a precision radiotherapy model in small animals under a linear accelerator. A 360° arc volumetric rotational intensity-modulated radiotherapy(VMAT) plan with a prescribed dose of 2 Gy was developed for the planned target volume(PTV) at the location of the TLD within solid water to compare the difference between the measured dose of TLD and the assessed parameters in the TPS system. The TLD was implanted in the livers of mice, and VMAT was planned based on TLD to compare the measured and prescribed doses. C57BL/6 J mice were randomly divided into control and 25-Gy radiation groups and were examined daily for changes in body weight. They were euthanized at 3 and 10 weeks after radiation, and the levels of liver serum enzymes such as alanine aminotransferase(ALT), aspartate aminotransferase(AST), and alkaline phosphatase(ALP) were measured to observe any pathological histological changes in the irradiated areas of the mouse liver. The measured values of solid underwater TLD were within ± 3% of the Dmean value of the evaluation parameter in the TPS system. The mice in the 25-Gy radiation group demonstrated pathological signs of radiation-induced liver injury at the site of liver irradiation. The deviation in the measured and prescribed doses of TLD in the mouse liver ranged from-1.5 to 6%;construction of an accurate model of RILD using the VMAT technique under a linear accelerator is feasible.

Treatment of radiation-induced brain injury with bisdemethoxycurcumin

Radiation therapy is considered the most effective non-surgical treatment for brain tumors.However,there are no available treatments for radiation-induced brain injury.Bisdemethoxycurcumin(BDMC)is a demethoxy derivative of curcumin that has anti-proliferative,anti-inflammatory,and anti-oxidant properties.To determine whether BDMC has the potential to treat radiation-induced brain injury,in this study,we established a rat model of radiation-induced brain injury by administe ring a single 30-Gy vertical dose of irradiation to the whole brain,followed by intraperitoneal injection of 500μL of a 100 mg/kg BDMC solution every day for 5 successive weeks.Our res ults showed that BDMC increased the body weight of rats with radiation-induced brain injury,improved lea rning and memory,attenuated brain edema,inhibited astrocyte activation,and reduced oxidative stress.These findings suggest that BDMC protects against radiationinduced brain injury.

Rabbit model of radiation-induced lung injury

Objective:To explore the feasibility of establishing an animal model of chronic radiationinduced lung injury.Methods:Twenty-eight New Zealand white rabbits were randomly divided into 3 groups(the right lung irradiation group,the whole lung irradiation group and the control group).Animal model of radiation-induced lung injury was established b) highdoes radiotherapy in the irradiation groups,then all rabbits underwent CT and pathological examinations at 1.2.4.8.12.16 weeks,respectively after radiation.Results:Within 4 weeks of irradiation,some rabbits in the right lung irradiation group and whole lung irradiation group died. CT and pathological examinations all showed acute radiation pneumonitis.At 8-12 weeks after irradiation,CT scanning showed ground glass samples signs,patchy shadows and fibrotic stripes. Pathological examination showed the fibrosis pulmonary alveolar wall thickened obviously. Conclusions:The clinical animal model of chronic radiation-induced lung injury which corresponds to practical conditions in clinic can be successfully established.

Correlation between miR-564, TGF-β1, and radiation-induced lung injury

Objective Our study aimed to analyze the expression of miR-564 and TGF-β1 in cancer tissues and the serum of patients with radiation-induced lung injury,and to investigate the relationship between them and radiation-induced lung injury.Methods In situ hybridization and real-time fluorescence quantitative method were used to detect the expression of miR-564.Additionally,immunohistochemistry and enzyme-linked immunosorbent assay(ELISA)were performed to detect the expression of TGF-β1.Results The overall incidence of acute radiation pneumonia was 55.9%(100/179).The incidence of≥grade 2 radioactive pneumonia was 24.0%(43/179)and that of grade 1 was 31.8%(57/179).The expression of miR-564 in grade≥2 was slightly higher than that in patients without or with grade 1,but there was no statistical difference(P=0.86).The serum level and ratio of miR-564 in patients with grade≥2 were significantly higher than those without or with grade 1(P=0.005,P=0.025,respectively).The expression of TGF-β1 in grade≥2 was significantly higher than that of patients without or with grade 1(P=0.017).The serum levels of TGF-β1 in grade≥2 were significantly higher than those in patients without or with grade 1(P=0.038).Although the ratio of TGF-β1 in radiation pneumonia of grade≥2 was significantly higher than that of without or with grade 1,there was no significant difference(P=0.24).Moreover,patients with higher expression of miR-564 and lower expression of TGF-β1 had better prognosis.Conclusion MiR-564 and TGF-β1 are predictors of radiation-induced lung injury.Monitoring its changing trend can improve the accuracy of predicting radiation-induced lung injury.The levels and ratio of serum miR-564 and TGF-β1 in patients with radiation-induced lung injury are related to the severity of radiationinduced lung injury.

Neuron-specific enolase expression in a rat model of radiation-induced brain injury following vascular endothelial growth factor-modified neural stem cell transplantation

BACKGROUND： Previous studies have shown that transplantation of vascular endothelial growth factor （VEGF）-modified neural stem cells （NSC） provides better outcomes, compared with neural stem cells, in the treatment of brain damage. OBJECTIVE： To compare the effects of VEGF-modified NSC transplantation and NSC transplantation on radiation-induced brain injury, and to determine neuron-specific enolase （NSE） expression in the brain. DESIGN, TIME, AND SETTING： The randomized, controlled study was performed at the Linbaixin Experimental Center, Second Affiliated Hospital, Sun Yat-sen University, China from November 2007 to October 2008. MATERIALS： VEGF-modified C17.2 NSCs were supplied by Harvard Medical School, USA. Streptavidin-biotin-peroxidase-complex kit （Boster, China） and 5, 6-carboxyfluorescein diacetate succinimidyl ester （Fluka, USA） were used in this study. METHODS： A total of 84 Sprague Dawley rats were randomly assigned to a blank control group （n = 20）, model group （n = 20）, NSC group （n = 20）, and a VEGF-modified NSC group （n = 24）. Rat models of radiation-induced brain injury were established in the model, NSC, and VEGF-modified NSC groups. At 1 week following model induction, 10 pL （5 ×10^4 cells/μL） VEGF-modified NSCs or NSCs were respectively infused into the striatum and cerebral cortex of rats from the VEGF-modified NSC and NSC groups. A total of 10μL saline was injected into rats from the blank control and model groups. MAIN OUTCOME MEASURES： NSE expression in the brain was detected by immunohistochemistry following VEGF-modified NSC transplantation. RESULTS： NSE expression was significantly decreased in the brains of radiation-induced brain injury rats （P 〈 0.05）. The number of NSE-positive neurons significantly increased in the NSC and VEGF-modified NSC groups, compared with the model group （P 〈 0.05）. NSE expression significantly increased in the VEGF-modified NSC group, compared with the NSC group, at 6 weeks following transplantation （P 〈 0.05）. CONCLUSION： VEGF-modified NSC transplantation increased NSE expression in rats with radiation-induced brain injury, and the outcomes were superior to NSC transplantation.

Radiation-induced brain injury after a conventional dose of intensity-modulated radiotherapy for nasopharyngeal carcinoma:a case report and literature review

A 61-year-old female nasopharyngeal carcinoma patient was admitted to the hospital with sudden cognitive dysfunction one month after Volumetric Intensity Modulated Arc Therapy(VMAT)conventional dose radiotherapy,and the initial diagnosis was radiation-induced brain injury(RBI).After comprehensive treatment with steroid hormones,the patient’s condition rapidly improved.Typically,in nasopharyngeal carcinoma patients treated with VMAT,the incidence of RBI is extremely low when the temporal lobe dose is less than 65 Gy or 1%of the volume is less than 65 Gy.When this limit is exceeded,RBI may occur in varying degrees.However,in this case,even though the temporal lobe dose was under the prescribed limit,the patient still experienced RBI.The rare observations in this case can be used as a reference,and clinicians should seriously consider the possibility of RBI in similar cases.

Time-dependent Changes in CT of Radiation-induced Liver Injury:A Preliminary Study in Gastric Cancer Patients

In this study, the time-dependent changes on dynamic computed tomograph (CT) of radiation-induced liver injury in gastric cancer patients was examined.The CT images of 52 gastric cancer patients who had received chemoradiotherapies were reviewed on the PACS system.Dynamic CT scan was performed in all the subjects.Our results showed that 18 patients were found to have radiation-induced liver injury.The CT findings of radiation-induced liver injury in gastric cancer patients tend to show up one month after radiation treatment.The damaged area was of low density on all three phases, and then it was enhanced on portal vein phase or delay phase.The focal radiation reaction of liver without basic disease vanished 9-11 months later after treatment.We are led to conclude that dynamic CT is of help in the diagnosis of CRT-induced liver injury, and it may be the method of choice for following up the whole course of the CRT-induced liver injury, i.e., form hepatic damage to healing.The classification of CT findings we recommend can avoid the influence of technological factors, and thereby serve as a better guide for treatment of CRT-induced liver injury.

Prevention and treatment of radiation-induced lung injury by hydroxypiperquin phosphate: a clinical and experimental study

Objective: To evaluate the hydroxypiperquin phosphate (HPQP) as a modifier of radiation-induced injury in human and rat lungs. Methods: Sixty-five patients with lung cancer treated with conventional radiotherapy were divided into 2 groups randomly: Thirty cases were treated with HPQP and the others were in a control group. The changes of X - ray manifestation before, after and during taking drug were compared. An animal model of radiation-induced fibrosis of lungs was also established. Hydroxyproling (HP) content in lung tissue and the pathological changes in rat lungs were checked with microscope and electron microscope after 4 months and 6 months respectively. Results: The changes of lung X-ray manifestation in treatment group were much lighter than that in control group. The HP content and the change of pathology in the lungs of those rats with HPQP treatment were obviously less than that in control group. Conclusion: HPQP plays an important role in prevention and treatment of radiation-induced injury in lungs.

Traumatic brain injury induced by exposure to blast overpressure via ear canal

Exposure to explosive shockwave often leads to blast-induced traumatic brain injury in military and civilian populations.Unprotected ears are most often damaged following exposure to blasts.Although there is an association between tympanic membrane perforation and TBI in blast exposure victims,little is known about how and to what extent blast energy is transmitted to the central nervous system via the external ear canal.The present study investigated whether exposure to blasts directed through the ear canal causes brain injury in LongEvans rats.Animals were exposed to a single blast(0–30 pounds per square inch(psi))through the ear canal,and brain injury was evaluated by histological and behavioral outcomes at multiple time-points.Blast exposure not only caused tympanic membrane perforation but also produced substantial neuropathological changes in the brain,including increased expression of c-Fos,induction of a profound chronic neuroinflammatory response,and apoptosis of neurons.The blast-induced injury was not limited only to the brainstem most proximal to the source of the blast,but also affected the forebrain including the hippocampus,amygdala and the habenula,which are all involved in cognitive functions.Indeed,the animals exhibited long-term neurological deficits,including signs of anxiety in open field tests 2 months following blast exposure,and impaired learning and memory in an 8-arm maze 12 months following blast exposure.These results suggest that the unprotected ear canal provides a locus for blast waves to cause TBI.This study was approved by the Institutional Animal Care and Use Committee at the University of Mississippi Medical Center(Animal protocol#0932 E,approval date:September 30,2016 and 0932 F,approval date:September 27,2019).

Experimental research of pulmonary injury on irradiation combined with pemetrexed

Objective: The aim of our study was to examine whether irradiation combined with pemetrexed can exacerbate pulmonary injury. Methods: Two groups of male Wister Rats were subjected to bilateral apex of lungs irradiation(a single dose of 12 Gy), with or without pemetrexed(20 mg/kg) by intraperitoneal injection at the same time; a third group of weightand age- matched animals were treated with pemetrexed alone, as the same dose scheme, time and root of injection. The fourth group served as control. The whole lung mounts were dissected to histological evaluation, while serum cytokine transforming growth factor-β1(TGF-β1) analysis were compared at 1, 7, 21, 35, 49 days post-irradiation after irradiation. Results: Histological examination showed a thickening of alveolar septal, accumulation of inflammatory cells. The irradiation treatment group and the radiation-chemo treatment group showed a statistically significant higher level of TGF-β1(P < 0.05) than other two groups, but there were no differences between these two irradiation groups. Conclusion: These results demonstrated that pemetrexed can not aggravate pulmonary injury and it could be safely used in concurrent or sequential radio-chemotherapy in lung adenocarcinoma.

中医外治单元疗法治疗胡蜂蜇伤的疗效观察

目的观察中医外治单元疗法对胡蜂蜇伤急诊患者的疗效。方法将2021年4月至2023年9月安徽中医药大学第一附属医院急诊科收治的70例胡蜂蜇伤患者采用随机数字表法分为观察组与对照组,各35例。对照组采用基础治疗方法,观察组在对照组基础上加用中医外治单元疗法,疗程为5 d。比较两组患者治疗前后疗效、数字疼痛评分(NRS)和毒效应指标[天门冬氨酸氨基转移酶/丙氨酸氨基转移酶(AST/ALT)、总胆红素(TBIL)、肌酐(SCr)、部分凝血酶原时间(APTT)、超敏C反应蛋白(hs-CRP)],并记录两组蜇伤处肿胀开始消退时间。结果观察组总有效率(85.71%)高于对照组(62.86%),肿胀消退时间短于对照组,差异有统计学意义(P<0.05)。两组患者治疗前后NRS评分、AST/ALT、TBIL、SCr、APTT、hs-CRP差值比较,差异均有统计学意义(P<0.05)。结论中医外治单元疗法能加速胡蜂蜇伤局部肿胀消退,缓解疼痛,降低毒效应指标,促进炎症吸收,加速患者康复。

不同针具在眼科耳尖放血疗法中的应用对比

目的探讨不同针具在眼科耳尖放血疗法中的应用对比。方法选择开展眼科耳尖放血疗法的15家医院的70名眼科门诊护士进行调查,分别调查对比护士使用不同针具为患者进行耳尖放血疗法过程中的感受、操作时护士发生针刺伤的风险性等情况。结果在五组不同针具护士使用感受比较中发现一次性末梢采血器(安全锁卡式)比其他四组针具在使用中操作方便简单性、使用后针具的处理及针刺深度把握最优,在使用针具完成治疗过程中发生针刺伤的比例最低。结论一次性末梢采血器(安全锁卡式)用于耳尖放血时在满足治疗需求的同时,操作更为简便,可更加有效地降低护士针刺伤的发生率,从而保障护士的职业安全。

基于自由场爆炸的小型猪内耳听觉损伤模型

建立真实爆炸环境下的小型猪内耳听觉爆炸伤模型,研究不同爆炸冲击波压力对小型猪内耳听觉损伤的影响。选取14头健康小型猪,在爆炸前进行听性脑干反应(auditory brainstem response,ABR)测试。搭建自由场爆炸实验平台,使用1.9和8.0 kg TNT炸药,爆源离地面1.8 m,身体固定于防护装置中,仅暴露头部。在不同距离布放小型猪,记录冲击波峰值压力,计算即刻死亡率。爆炸后再次进行ABR测试,并取耳蜗组织进行扫描电镜观察,分析毛细胞损伤情况。在1.8~3.8 m范围内,冲击波峰值压力从96.3 kPa升至628.3 kPa,随着距离的增大,峰值压力减小。8 kg TNT爆炸在2.6 m处(峰值压力628.3 kPa)导致小型猪即刻死亡率为50%。比较爆炸前后ABR阈值发现,短声(click)和各频率短纯音(2、4和8 kHz)诱发的ABR阈值均显著升高(P<0.05),其中以4 kHz阈值变化最显著。扫描电镜显示,随着冲击波压力的升高,内毛细胞的损伤程度高于外毛细胞。爆炸冲击波可引起小型猪听觉系统的明显损伤,表现为ABR阈值升高和耳蜗毛细胞结构破坏。内毛细胞对爆炸冲击波更敏感。所建立的小型猪爆炸性听觉损伤模型可为研究爆炸伤机制和防护措施提供了重要的实验基础。

Proteomic analysis of acute radiation-induced rectal injury in rats

Objective:To comprehensively elucidate overall protein alterations associated with acute radiation-induced rectal injury in rats.Methods:A rat model of acute radiation-induced rectal injury was established by irradiating rectal segments with a single dose of 17.5 Gy X-rays.These segments were then collected at 7 d and 10 d post-irradiation.Tandem mass tag-based quantitative proteomic analysis was then performed.Results:65,526 peptides were identified,corresponding to 8,088 proteins.Hematoxylin-eosin staining revealed characteristic epithelial cell degeneration and necrosis,intestinal gland atrophy and dilatation,and interstitial inflammatory cell infiltration.Inflammation was more pronounced in the 10 d irradiation group than in the 7 d irradiation group.Overall,127 up-and 108 downregulated proteins were identified at 7 d post-irradiation,and 122 up-and 44 downregulated proteins were identified at 10 d post-irradiation.Notably,17 up-and 6 downregulated proteins were consistently co-expressed at both time points.The expression of three of these proteins was validated via real-time quantitative PCR:polypeptide YY(Pyy),thymidylate synthase(Tyms),and tetraspanin(CD9).Tyms transcript levels were significantly higher in irradiated rectal tissues(P<0.05).Pyy transcript levels were significantly higher at both time points(P<0.05).Finally,CD9 mRNA expression was significantly lower in both the 7 d and 10 d irradiation groups(P<0.05).Conclusions:The potential targets were found to prevent and treat acute radiation-induced rectal injury in clinical practice.

Evaluating a novel protective agent against radiation-induced acute intestinal injury

Objective:To develop and synthesize a novel derivative of ethyl pyruvate,named TZC02,and investigate its radioprotective effects against ionizing radiation(IR)-induced intestinal injury in mice.Methods:Male C57BL/6J mice weighing(20±2)g in the survival experiment were randomly divided into five groups(n=10 in each):control group,IR group,IR+TZC02(50 mg/kg)group,IR+TZC02(100 mg/kg)group,and IR+TZC02(200 mg/kg)group.Mice's survival rates were monitored for 7 d.In other experiments,the male mice were randomly divided into three groups(n=5 per group):control group,IR group,and IR+TZC02(100 mg/kg)group.TZC02 was intragastrically administered 1 h before 12 Gy abdominalγ-ray irradiation(ABI)and 24 h,48 h after irradiation,respectively.Three days after IR exposure,small intestinal tissues were collected and the number of small intestinal crypts was determined using hematoxylin&eosin(H&E)staining.Immunohistochemical analysis was used to assess the regenerative capacity of the small intestine(SI)and radiation-induced damage,stemness markers or DNA repair surrogates,including Ki67,lysozyme,and villus.The expressions of histone H2AX phosphorylation(γH2AX)and caspase-3 were evaluated through immunofluorescence analyses.Additionally,in vitro cultured small intestinal organoids were employed to investigate the effects of TZC02 on SI regeneration after irradiation.Results:The administration of TZC02 significantly improved the 7 d-survival rate of mice exposed to 12 Gy ABI(P<0.05).Compared to the IR group,TZC02 treatment attenuated the decrease of SI Ki67-positive cells[(59.60±6.33)vs.(37.70±7.82),t=11.89,P<0.0001]and Paneth cells[(9.90±1.37)vs.(5.50±1.71),t=6.02,P<0.001]in five crypts,and reduced structural damage to the SI[villus height,(349.49±60.17)μm vs.(294.72±40.09)μm;t=3.39;P<0.05].TZC02 also significantly decreased the crypt apoptosis detected by caspase-3[(10.75±1.26)vs.(29.83±2.56),t=13.39,P<0.0001]and DNA damage detected by gH2AX[(10.40±1.14)vs.(29.60±2.70),t=10.13,P<0.0001].The organoid survival 7 d post-irradiation further confirmed the protective effects of TZC02(area of organoids,(0.119±0.081)mm^(2)vs.(0.080±0.037)mm^(2);t=2.30;P<0.05).Conclusions:This study demonstrate that TZC02 can offer effective protection against IR-induced intestinal injury,suggesting its potential as a promising protective compound for patients treated with radiotherapy.

Basic research of the relationship between irradiation dose and volume in radiation-induced pulmonary injury

Background Irradiation dose and volume are the major investigated the relationships between the irradiation dose model of graded volume irradiation of the rat lung. physical factors of radiation-induced lung injury. The study and volume in radiation-induced lung injury by setting up a Methods Animals were randomly assigned to three groups. The ELEKTA precise 2.03 treatment plan system was applied to calculate the irradiation dose and volume. The treatment plan for the three groups was： group I received a ＂high dose to a small volume＂ （25% volume group） with the mean irradiation volume being 1.748 cm^3 （25% lung volume）; the total dose and mean lung dose （MLD） were 4610 cGy and 2006 cGy, respectively （bilateral AP-PA fields, source to axis distance （SAD） = 100 cm, 6MVX, single irradiation）; Group 2 received a ＂low dose to a large volume＂ （100% volume group） with the mean irradiation volume being 6.99 cm^3 （100% lung volume）; the total dose was 1153 cGy. MLD was 2006 cGy, which was the same as that of group 1 （bilateral AP-PA fields, SAD = 100 cm, 6MVX, single irradiation）; Group 3 was a control group. With the exception of receiving no irradiation, group 3 had rest steps that were the same as those of the experimental groups. After irradiation, functional, histopathological, and CT changes were compared every two weeks till the 16th week. Results Functionally, after irradiation breath rate （BR） increases were observed in both group 1 and group 2, especially during the period of 6th-8th weeks. The changes of BR in the 100% volume group were earlier and faster. For the 25% volume group, although pathology was more severe, hardly any obvious increase in BR was observed. Radiographic changes were observed during the early period （the 4th week） and the most obvious changes manifested during the mediated period （the 8th week）. The extensiveness of high density and the decreased lung permeability were presented in the 100% volume group, and ground glass opacity and patchy consolidation were presented in the 25% volume group without pleural effusion, pleural thickening, and lung shrinking. Morphologically, the 100% volume group mainly presented signs of vascular damage, including signs of vascular wall edemas, hypertrophy, and sclerosis. The 25% volume group mainly presented with erythrocyte cell exudation, inflammation, and parenchymal damage. Conclusions The delivery of a small dose of radiation to a large volume is not safe. A low dose smeared out over large volumes, albeit reversible, may lead to fatal respiratory dysfunction. Damage to the lung may be more dependent on the volume of irradiation than on the radiation dose. Clinically, the safest approach is to limit both the volume of the irradiated normal lung and the amount of received radiation.

Neurotrophins differentially stimulate the growth of cochlear neurites on collagen surfaces and in gels

The electrodes of a cochlear implant are located far from the surviving neurons of the spiral ganglion, which results in decreased precision of neural activation compared to the normal ear. If the neurons could be induced to extend neurites toward the implant, it might be possible to stimulate more discrete subpopulations of neurons, and to increase the resolution of the device. However, a major barrier to neurite growth toward a cochlear implant is the fluid filling the scala tympani, which separates the neurons from the electrodes. The goal of this study was to evaluate the growth of cochlear neurites in three-dimensional extracellular matrix molecule gels, and to increase biocompatibility by using fibroblasts stably transfected to produce neurotrophin-3 and brain-derived neurotrophic factor. Spiral ganglion explants from neonatal rats were evaluated in cultures. They were exposed to soluble neurotrophins, cells transfected to secrete neurotrophins, and/or collagen gels. We found that cochlear neurites grew readily on collagen surfaces and in three-dimensional collagen gels. Co-culture with cells producing neurotrophin-3 resulted in increased numbers of neurites, and neurites that were longer than when explants were cultured with control fibroblasts stably transfected with green fluorescent protein. Brain-derived neurotrophic factor-producing cells resulted in a more dramatic increase in the number of neurites, but there was no significant effect on neurite length. It is suggested that extracellular matrix molecule gels and cells transfected to produce neurotrophins offer an opportunity to attract spiral ganglion neurites toward a cochlear implant.

An Appreciation for the Rabbit Ladderlike Modeling of Radiation-induced Lung Injury with High-energy X-Ray

Background：To evaluate the utility of rabbit ladderlike model of radiation-induced lung injury （RILI） for the future investigation of computed tomography perfusion.Methods：A total of 72 New Zealand rabbits were randomly divided into two groups：36 rabbits in the test group were administered 25 Gy of single fractionated radiation to the whole lung of unilateral lung;36 rabbits in the control group were sham-radiated.All rabbits were subsequently sacrificed at 1,6,12,24,48,72 h,and 1,2,4,8,1 6,24 weeks after radiation,and then six specimens were extracted from the upper,middle and lower fields of the bilateral lungs.The pathological changes in these specimens were observed with light and electron microscopy;the expression of tumor necrosis factor-α （TNF-a） and transforming growth factor-βl （TGF-β1） in local lung tissue was detected by immunohistochemistry.Results：（1） Radiation-induced lung injury occurred in all rabbits in the test group.（2） Expression of TNF-a and TGF-β1 at 1 h and 48 h after radiation,demonstrated a statistically significant difference between the test and control groups （each P 〈 0.05）.（3） Evaluation by light microscopy demonstrated statistically significant differences between the two groups in the following parameters （each P 〈 0.05）：thickness of alveolar wall,density of pulmonary interstitium area （1 h after radiation）,number offibroblasts and fibrocytes in interstitium （24 h after radiation）.The test group metrics also correlated well with the time ofpostradiation.（4） Evaluation by electron microscopy demonstrated statistically significant differences in the relative amounts of collagen fibers at various time points postradiation in the test group （P 〈 0.005）,with no significant differences in the control group （P 〉 0.05）.At greater than 48 h postradiation the relative amount of collagen fibers in the test groups significantly differ from the control groups （each P 〈 0.05）,correlating well with the time postradiation （r =0.99318）.Conclusions：A consistent and reliable rabbit model of RILI can be generated in gradient using 25 Gy of high-energy X-ray,which can simulate the development and evolution of RILI.

Transplantation of bone marrow stromal cells overexpressing humanvascular endothelial growth factor 165 enhances tissue repair in a ratmodel of radiation-induced injury

Background The multilineage differentiation potential ability of bone marrow stromal cells(BMSCs) showed great potential in tissue engineering, while vascular endothelial growth factor 165(VEGF165) promotes vasculogenesis and further promotes tissue regeneration. This study aimed to assess the ability of rat BMSCs expressing human VEGF A165(hVEGF165) to promote tissue repair in rat model of radiation-induced injury.Methods Rat BMSCs were isolated from the tibia. Plasmid DNA expressing hVEGF165 was stably transfected into BMSCs using liposomes. The right hindlimb muscle of 40 rats was irradiated using a 60 Co γ source(total dose 30 Gy). The animals were divided into four groups(n=10): not injected with BMSCs(control; group 1) or intramuscularly injected two times(once in 2 weeks) with pcDNATM3.1-transfected BMSCs(group 2), untransfected BMSCs(group 3), or hVEGF165-transfected BMSCs(group 4). Angiography was performed 1 week after the last injection of BMSCs; samples of the hindlimb muscle were subjected to transmission electron microscopy, ultrastructural analysis, reverse transcription-PCR(RT-PCR), Western blotting, and immunohistochemistry.Results Rat BMSCs with multipotent differentiation capacity were isolated. hVEGF165-transfected BMSCs overexpressed hVEGF165 mRNA and protein. Injection of BMSCs(groups 2–4) increased the average vessel number, density, diameter, and cross-sectional area; mRNA expression of the myogenic markers including myoblast determination protein, myogenin, and α-smooth muscle actin; and CD31 protein expression; and promoted the repair of blood vessels and myofibers after radiation-induced injury compared to group 1; each of these parameters and hVEGF165 mRNA or protein expression were markedly improved in rats injected with hVEGF165-transfected BMSCs compared to groups 2 and 3.Conclusions BMSCs expressing hVEGF165 enhanced the repair of radiation-induced tissue injury by promoting vasculogenesis and muscle fiber regeneration. BMSCs expressing hVEGF165 may have potential clinical applications.

Prevention and treatment for radiation-induced skin injury during radiotherapy

The skin tissue has the largest area in the human body and functions as both a barrier and a defender.As such,it tends to be the first tissue to be damaged.Advances in medical technology provide prospects as well as side effects,for example,radiation therapy for cancer.With increasing cancer morbidity and radiation widely applied for cancer therapy,radiation-induced skin injury(RSI)has become a serious concern.In recent decades,research efforts have focused on the mechanisms underlying RSI.This review summarizes the mainstream opinions on these mechanisms,including the pathological,molecular biological,and cytobiological alterations.Radiationinduced reactive oxygen species(ROS),cytokines and involved signaling pathways are evaluated.Other relevant aspects include radiation-induced skin fibrosis(RSF)and radiation-related skin cell senescence.Moreover,we review strategies for the prevention and treatment in clinical and pre-clinical studies to support the treatment of RSI during radiotherapy.The prevention strategies include dose control,pre-irradiation instructions,and RSI assessments,while the main treatments include physical therapy,external-use dressings or creams,biological therapy and surgical reconstruction.