DTI and pathological changes in a rabbit model of radiation injury to the spinal cord after ^(125)I radioactive seed implantation

Excessive radiation exposure may lead to edema of the spinal cord and deterioration of the nervous system. Magnetic resonance imaging can be used to judge and assess the extent of edema and to evaluate pathological changes and thus may be used for the evaluation of spinal cord injuries caused by radiation therapy. Radioactive ^125I seeds to irradiate 90% of the spinal cord tissue at doses of 40–100 Gy （D90） were implanted in rabbits at T10 to induce radiation injury, and we evaluated their safety for use in the spinal cord. Diffusion tensor imaging showed that with increased D90, the apparent diffusion coefficient and fractional anisotropy values were increased. Moreover, pathological damage of neurons and microvessels in the gray matter and white matter was aggravated. At 2 months after implantation, obvious pathological injury was visible in the spinal cords of each group. Magnetic resonance diffusion tensor imaging revealed the radiation injury to the spinal cord, and we quantified the degree of spinal cord injury through apparent diffusion coefficient and fractional anisotropy.

Effects of Ligustrazine on Bone Marrow Microvessel Systemin the Early Period of Acute Radiation Injury in Mice

Sublethally irradiated mice were immediately treated with 250 mg/kg Ligustrazine Phosphiatis intraperitoneally twice a day for seven days, and the bone marrow sections of ulna were observed. On the 5th day, the number of bone marrow microvessels of the Ligustrazine group was much greater than that of the control group. On the 7th day, the amount of the control group decreased to normal, while the ligustrazine group was still increasing, and the microvessel area was enlarged obviously. The percentage of the hematopoietic tissue volume in bone marrow between the two groups had no significant difference in the first 7days. On the 7th day after irradiation, the peripheral neutrophilic granulocytes increased in the Ligustrazine group- The results suggested that early use of Ligustrazine after acute radiation injury might improve the blood supply of bone marrow, and be helpful for recovery of hematopoiesis.

Effect of Ligustrazine on Expressions of Basic Fibroblast Growth Factor and Its Receptor in Bone Marrow of Mice with Acute Radiation Injury

Objective: To study the expressions of basic fibroblast growth factor (bFGF) and its receptor (bFGFR) in bone marrow of mice with acute radiation injury, and to evaluate the effect of Ligustrazine (Lt) on them. Methods: Fifty-six Kunming mice of clean grade were randomly divided into 3 groups, the normal group, the control group and the Lt group. Mice in the latter two groups were once homogeneously systemic irradiated with 6.0 Gy of 60 Co, with the absorption dose rate of 0. 56 Gy/min, then treated with saline (0.2 ml/ mice) or Lt (2 mg/mice) respectively, twice a day through gastrogavage for successive 13 days. Mice were sacrificed in batch on the 3rd, 7th and 14th day by cervical dislocation to collect the bilateral femoral bone marrow for preparing bone marrow mono-nuclear cell (BMMNC) suspension. The bFGFR expression on surface of BMMNC was determined by flow cytometry; and the bFGF expres-sion level in one side of femoral bone marrow tissue was detected by immunohistochemistry with SABC-AP assay. Results: The bFGF expression in bone marrow of mice on the 3rd, 7th and 14th day after acute radiation injury all were significantly lower than that of the normal mice (P<0.05 or P<0.01). The expressions of bFGF and bFGFR in the Lt group detected were significantly higher than that in the control group detected at the corresponding time points (P<0.05 or P < 0.01). Conclusion:By way of enhancing bFGF expression in bone marrow and bFGFR expression on surface of BMMNC to accelerate the repairing of hemopoietic micro-environment in bone marrow might be one of the mechanisms of Lt in promoting hemopoietic function reconstitution after acute radiation injury.Original article on CJITWM (Chin) 2004;24(5):439

Radioprotective effects of the expression of FLT3 ligand regulated by Egr-1 regulated element on radiation injury of SCID mice

Objective: In order to explore the radioprotective effects of the expression of hematopoietic growth factors regulated by radio-inducible promoter on radiation injury. Methods:The human FL (Flt3 ligand) cDNA and EGFP (enhanced green fluorescent protein) cDNA were linked together with IRES and then inserted into the eukaryotic expression vector pCI-Egr, which was constructed by substituting CMV promoter in pCIneo with the Egr-1 promoter (Egr-EF). The vector was transferred into human bone marrow stromal ...

Practical approaches to effective management of intestinal radiation injury:Benefit of resectional surgery

AIM:To study the outcome of patients undergoing surgical resection of the bowel for sustained radiation-induced damage intractable to conservative management.METHODS:During a 7-year period we operated on 17 cases (5 male,12 female) admitted to our surgical department with intestinal radiation injury (IRI).They were originally treated for a pelvic malignancy by surgical resection followed by postoperative radiotherapy.During follow-up,they developed radiation enteritis requiring surgical treatment due to failure of conservative management.RESULTS:IRI was located in the terminal ileum in 12 patients,in the rectum in 2 patients,in the descending colon in 2 patients,and in the cecum in one patient.All patients had resection of the affected region(s).There were no postoperative deaths,while 3 cases presented with postoperative complications (17.7%).All patients remained free of symptoms without evidence of recurrence of IRI for a median follow-up period of 42 mo (range,6-96 mo).CONCLUSION:We report a favorable outcome without IRI recurrence of 17 patients treated by resection of the diseased bowel segment.

Biomarkers Associated with Radiation-Induced Lung Injury in Cancer Patients

Radiotherapy (RT) is a common and effective non-surgical treatment for thoracic solid tumors, and radiation-induced lung injury (RILI) is the most common side effect of radiotherapy. Even if RT is effective in the treatment of cancer patients, severe radiation pneumonitis (RP) or pulmonary fibrosis (PF) can reduce the quality of life of patients and may even lead to serious consequences of death. Therefore, how to overcome the problem of accurate prediction and early diagnosis of RT for pulmonary toxicity is very important. This review summarizes the related factors of RILI and the related biomarkers for early prediction of RILI.

Expression of Angiotensin Ⅱ and Aldosterone in Radiation-induced Lung Injury

Objective Radiation-induced lung injury （RILl） is the most common, dose-limiting complication in thoracic malignancy radiotherapy. Considering its negative impact on patients and restrictions to efficacy, the mechanism of RILl was studied. Methods Wistar rats were locally irradiated with a single dose of 0, 16, and 20 Gy to the right half of the lung to establish a lung injury model. Two and six months after irradiation, the right half of the rat lung tissue was removed, and the concentrations of TGF-[31, angiotensin II, and aldosterone were determined via enzyme-linked immunosorbent assay. Results Statistical differences were observed in the expression levels of angiotensin II and aldosterone between the non-irradiation and irradiation groups. Moreover, the expression level of the angiotensin II-aldosterone system increased with increasing doses, and the difference was still observed as time progressed. Conclusions Angiotensin II-aldosterone system has an important pathophysiological function in the progression of RILI.

Catalytic PtPd bimetal nanocrystals with high-index facets for radiation injury repair

Radiotherapy is one of the most important clinical cancer treatments,which works mainly by delive ring a prescribed radiation dose to the tumor tissues.However,high doses of radiation may also lead many irreversible damages to the surrounding normal tissues.Thereby,how to effectively reduce these sideeffects has been a significant factor in influencing cancer therapeutic effect.In this work,we synthesized the hollow PtPd nanocubes with high-index facets,and investigated the radiation protection capability in vitro and in vivo.Our results showed the PtPd nanocrystals can decrease the ROS level and improve the survival rate of radiated cells.Meanwhile,survival rate of radiated mice can significantly increase from 0 to 30%after PtPd treatment.Consequently,the enzyme and ROS level in radiated mice can be recovered.

Clinical and Experimental Study on Prevention and Treatment of Acute Radiation Injury in Nasopharyngeal Carcinoma Patients by Yiqi Huoxue Yangyin Recipe (益气活血养阴方)

Objective: To observe the effect of Chinese herbal medicine in alleviating acute toxic adverse effect of radiotherapy and on growth of stromal cells in bone marrow. Methods: Seventy two patients with nasopharyngeal carcinoma (NPC) were randomly divided into two groups. Radical radiotherapy was applied to both groups. In the radiotherapeutic period, to the 36 patients in the treated group, Yiqi Huoxue Yangyin Recipe (YHYR) was given additionally by oral taking and compressing on radiation area, and to the 36 patients in the control group, vitamin B 12 solution was given for gargling or compressing. Experimental study was carried out in rats of two groups, irradiated with 5.0 Gy X ray and treated with YHYR or normal saline intraperitoneally, to observe the colony forming unit fibroblastoid (CFU F) in cultured bone marrow stromal cells (BMSC), taken from the rats at different time.Results: The oral mucomembranous radiation damage occurred in 47.2% of the treated group when the dose of radiation reached to 41.4±9.4 Gy, while in the control group, it was 91.7% when the dose reached to 30.9±8.9 Gy. The skin radiation damage occurrence rate in the two groups was 13.9% and 33.3% respectively when the dose of radiation reached to 50.2±5.6 Gy and 43.2±6.3 Gy respectively. Comparison of the two groups showed significant difference ( P <0.01), the radiation damage was significantly slighter in the treated group. Experimental study showed that the rats in the two groups were significantly different in occurrence and degree of bone marrow function inhibition, P <0.01. The numbers of CFU F in cultured BMSC of radiation damaged rats taken at respective different culture time were also significantly different between the two groups, P < 0.01 .Conclusion: YHYR could significantly reduce acute radiation damage of mucomembrane and skin, alleviate the inhibition on bone marrow function, and eliminate the injury of radiation on BMSC.

Effects of Zaizhang－I，A Traditional Chinese Herbal Medicine，on Hematopoietic Recovery from Radiation Injury In Mice

Effects of Zaizhang-I (ZZ-I)on the recovery of hemopoietic systems from radiation injury were investigated. Mice,irradiated with 6.0 Gy -rays,were injected i. p. once daily for 7 consecutive days with either ZZ-I or saline(0.01 ml/g body wt.). The experiments showed that ZZ-I significantly promoted the recovery of not only peripheral WBC, BMC, CFU-S and CFU-GM but also the abnormal femur micro-vessel system such as blood vessels and sinus ectasia, hyperemia and hemorrhage etc.These results suggest that ZZ-I could accelerate hemopoietic recovery from radiation injury in mice by stimulating hemopoietic stem cells and improving hemopoietic inductive microenvironment (HIM).

Development of radiation countermeasure agents for acute radiation syndromes

The risk of internal and external exposure to ionizing radiation(IR)has increased alongside the development and implementation of nuclear technology.Therefore,serious security issues have emerged globally,and there has been an increase in the number of studies focusing on radiological prevention and medical countermeasures.Radioprotective drugs are particularly important components of emergency medical preparedness strategies for the clinical management of IR-induced injuries.However,a few drugs have been approved to date to treat such injuries,and the related mechanisms are not entirely understood.Thus,the aim of the present review was to provide a brief overview of the World Health Organization's updated list of essential medicines for 2023 for the proper management of national stockpiles and the treatment of radiological emergencies.This review also discusses the types of radiation-induced health injuries and the related mechanisms,as well as the development of various radioprotective agents,including Chinese herbal medicines,for which significant survival benefits have been demonstrated in animal models of acute radiation syndrome.

Progress in the Pathogenesis and Treatment of Radiation-Induced Brain Injury

Malignant tumors are one of the serious public health problems that threaten the survival time of human beings.They are prone to metastasis to distant organs and the central nervous system is one of the common target organs.As it is difficult for chemotherapeutics,targeted drugs and other macromolecules to pass through the blood brain barrier(BBB),local radiation therapy is often used for treating intracranial primary or metastatic tumors.However,whether it is whole brain radiation therapy(WBRT)or stereotactic body radiation therapy(SBRT),the choice of radiation dose is limited by the side effects of radiation therapy on the surrounding normal brain tissues.Radiation-induced brain injury(RBI)can further develop into radiation necrosis(RN)in the late stage.Bevacizumab is often effective against RBI by antagonizing vascular endothelial growth factor(VEGF),but it still cannot completely reverse RN.Emerging treatment options such as human pluripotent stem-cell transplantation have made it possible to reverse the process of RN.

Differential Proteomics Reveals the Potential Injury Mechanism Induced by Heavy Ion Radiation in Mice Ovaries

In the present study, we used a proteomics approach based on a two-dimensional electrophoresis （2-DE） reference map to investigate protein expression in the ovarian tissues of pubertal Swiss-Webster mice subjected to carbon ion radiation （CIR）. Among the identified proteins, ubiquitin carboxy-terminal hydrolase L1 （UCH-L1） is associated with the cell cycle[1] and that it influences proliferation in ovarian tissues. We analyzed the expression of UCH-L1 and the proliferation marker proliferation cell nuclear antigen （PCNA） following CIR using immunoblotting and immunofluorescence. The proteomics and biochemical results provide insight into the underlying mechanisms of CIR toxicity in ovarian tissues.

Radiation dermatitis wet healing:a concept analysis

Objective:To explore the concept of radiation dermatitis wet healing through a literature review and provide references for future treatment of patients with radiation skin injury.Methods:Related ar ticles selected from China National Knowledge Infrastructure(CNKI),Wanfang Database,Pub Med,Web of Science,Medline,and EBSCO were analyzed with Rodger’s concept analysis.Results:We identified the application status of wet healing in domestic and foreign literature,defined explicit attributes of the procedure,and clarified concepts related to wet healing of radiation skin injury to provide a reference for the management of radiation dermatitis with wet healing.Conclusions:Treatment of radiation dermatitis with wet healing is a unique procedure.Analyzing this concept can contribute to its development in the future and can offer a theoretical basis for treatment of patients with radiation skin injury.

Combination of biodegradable hydrogel and antioxidant bioadhesive for treatment of breast cancer recurrence and radiation skin injury

Postoperative radiotherapy is the standard method for inhibition of breast cancer recurrence and metastasis,whereas radiation resistant and ineluctable skin radiation injury are still key problems encountered in the prognosis of breast cancer.Herein,we design an internally implantable biodegradable hydrogel and extracutaneously applicable antioxidant bioadhesive to concurrently prevent postoperative tumor recurrence and radioactive skin injury after adjuvant radiotherapy.The biodegradable silk fibroin/perfluorocarbon hydrogel loading doxorubicin(DOX)formed by consecutive ultrasonication-inducedβ-sheets-crosslinked amphiphilic silk fibroin/perfluorocarbon/DOX nanoemulsion,exhibits continuous release of oxygen in physiological environment to improve hypoxia and sensitivity of radiotherapy,as well as simultaneous release of DOX to finally achieve effective anti-cancer effect.A stretchable bioadhesive is fabricated by copolymerization ofα-thioctic acid and N,N-diacryloyl-L-lysine,and gold nanorods and gallic acid are loaded into the bioadhesive to afford gentle photothermal therapy and antioxidant functions.The near-infrared light-induced controlled release of gallic acid and mild photothermal therapy can efficiently eliminate excess free radicals generated by radiotherapy and promote radioactive wound healing.Ultimately,in vivo animal studies substantiate the efficacy of our methodology,wherein the post-tumor resection administration of hydrogel and concomitant application of an antioxidant bioadhesive patch effectively inhibit tumor recurrence and attenuate the progression of skin radiation damage.

Hyperbaric oxygen therapy as a complementary treatment for radiation proctitis:Useless or useful?-A literature review

Radiotherapy(RT)is the backbone of multimodality treatment of more than half of cancer cases.Despite new modern RT techniques,late complications may occur such as radiation proctitis(RP).The natural history of RP is unpredictable.Minor symptoms may resolve spontaneously or require conservative treatment.On the other hand,for similar and uncomplicated clinical contexts,symptoms may persist and can even be refractory to the progressive increase in treatment measures.Over the last decades,an enormous therapeutic armamentarium has been considered in RP,including hyperbaric oxygen therapy(HBOT).Currently,the evidence regarding the impact of HBOT on RP and its benefits is conflicting.Additional prospective and randomised studies are necessary to validate HBOT’s effectiveness in the‘real world’clinical practice.This article reviewed the relevant literature on pathophysiology,clinical presentation,different classifications and discuss RP management including a proposal for a therapeutic algorithm with a focus on HBOT.

Neuroprotective agents effective against radiation damage of central nervous system

Ionizing radiation caused by medical treatments,nuclear events or even space flights can irreversibly damage structure and function of brain cells.That can result in serious brain damage,with memory and behavior disorders,or even fatal oncologic or neurodegenerative illnesses.Currently used treatments and drugs are mostly targeting biochemical processes of cell apoptosis,radiation toxicity,neuroinflammation,and conditions such as cognitive-behavioral disturbances or others that result from the radiation insult.With most drugs,the side effects and potential toxicity are also to be considered.Therefore,many agents have not been approved for clinical use yet.In this review,we focus on the latest and most effective agents that have been used in animal and also in the human research,and clinical treatments.They could have the potential therapeutical use in cases of radiation damage of central nervous system,and also in prevention considering their radioprotecting effect of nervous tissue.

Mesenchymal stem cell therapy for acute radiation syndrome: Innovative medical approaches in military medicine

After a radiological or nuclear event, acute radiation syndrome(ARS) will present complex medical challenges that could involve the treatment of hundreds to thousands of patients. Current medical doctrine is based on limited clinical data and remains inadequate. Efforts to develop medical innovations that address ARS complications are unlikely to be generated by the industry because of market uncertainties specific to this type of injury. A prospective strategy could be the integration of cellular therapy to meet the medical demands of ARS. The most clinically advanced cellular therapy to date is the administration of mesenchymal stem cells(MSCs). Results of currently published investigations describing MSC safety and efficacy in a variety of injury and disease models demonstrate the unique qualities of this reparative cell population in adapting to the specific requirements of the damaged tissue in which the cells integrate. This report puts forward a rationale for the further evaluation of MSC therapy to address the current unmet medical needs of ARS. We propose that the exploration of this novel therapy for the treatment of the multivariate complications of ARS could be of invaluable benefit to military medicine.

Study on Oxygen Supply and Protection of Bone Marrow in Acute Radiation injured Mice

After irradiated by & Gy 60Co γ-ray, mice were intraperitoneally injected immediately with 0.2 ml 100 % compound blood-activating soup twice a day for 10 days. The in situ ulnar bone marrow partial pressure of oxygen (PbO2) was determined in vivo before, during and after irradiation respectively. The bone marrow sections in the same part were observed. Our results showed that the normal murine ulnar PbO2 was 12.72±1. 05kpa. During irradiation, the level of PbO2 decreased to 10. 78±1. 17 kpa (P＜0. 001). And 3 days after irradiation, PbO2 decreased to 9. 75±0. 52 kpa, suggesting that the commonly used 'blood-activating and stasis-eliminating' Chinese drugs could promote the rehabilitation and proliferation of bone marrow microvessels in the acute radiation injured mice, expand their areas, increase the oxygen supply of bone marrow microenviroment, thereby leading to PbO2 much higher increase than that of control group. It is also helpful in the proliferation and rehabilitation of hematopoietic cells.

Study on the Protective Effects of Compound Blood-activating Soup on Bone Marrow Hematopoietic Cells in Acute Radiation Injured Mice

After irradiation with 8 Gy 60Coγ-ray,mice were immediaterly given intraperitoneal injection of 200 mg 100 % compound blood-activating soup twice a day. On the 3rd and 7th day, the P53 gene expression of bone marrow hematopoietic cells in Chinese drug group was found to be higher than that in normal group, and it was also significantly higher than that in control group. The expression level of GADD153 gene which was not expressed in normal group was much lower in Chinese drug group than that in control group. On the 7th day after irradiation, the P53 and GADD153 gene expression levels of splenic mononuclear cells were consistent with those of bone marrow hematopoietic cells both in Chinese drug group and control group. On the 3rd and 7th day, the bone marrow hematopoietic tissue volume in Chinese drug group was higher than that in control group, with no difference found between the two groups. While on the 14th day, the difference became significant (P＜0. 01). The results showed that commonly used blood-activating and stasis-eliminating drugs may strengthen .the viability of hematopoietic cells and promote the rehabilitation of hematopoiesis by inducing wt-P53 expression to block the bone marrow hematopoietic cells in G1 phase, during which DNA could be repaired.