Unique brain injury patterns after proton vs photon radiotherapy for WHO grade 2-3 gliomas.

BACKGROUND: Central nervous system (CNS) injury following brain-directed radiotherapy remains a major challenge. Proton radiotherapy (PRT) minimizes radiation to healthy brain, potentially limiting sequelae. We characterized CNS radiotoxicity, including radiation-induced leukoencephalopathy (RIL), brain tissue necrosis (TN), and cerebral microbleeds (CMB), in glioma patients treated with PRT or photons (XRT). PATIENTS AND METHODS: Thirty-four patients (19 male; median age 39.6 years) with WHO grade 2-3 gliomas treated with partial cranial radiotherapy (XRT [n = 17] vs PRT[n = 17]) were identified and matched by demographic/clinical criteria. Radiotoxicity was assessed longitudinally for 3 years post-radiotherapy via serial analysis of T2/FLAIR- (for RIL), contrast-enhanced T1- (for TN), and susceptibility (for CMB)-weighted MRI sequences. RIL was rated at whole-brain and hemispheric levels using a novel Fazekas scale-informed scoring system. RESULTS: The scoring system proved reliable (ICC > 0.85). Both groups developed moderate-to-severe RIL (62%[XRT]; 71%[PRT]) within 3 years; however, XRT was associated with persistent RIL increases in the contralesional hemisphere, whereas contralesional hemispheric RIL plateaued with PRT at 1-year post-radiotherapy (t = 2.180; P = .037). TN rates were greater with PRT (6%[XRT] vs 18%[PRT]; P = ns). CMB prevalence (76%[XRT]; 71%[PRT]) and burden (mean #CMB: 4.0[XRT]; 4.2[PRT]) were similar; however, XRT correlated with greater contralesional hemispheric CMB burden (27%[XRT]; 17%[PRT]; X2 = 4.986; P = .026), whereas PRT-specific CMB clustered at the radiation field margin (X2 = 14.7; P = .002). CONCLUSIONS: CNS radiotoxicity is common and progressive in glioma patients. Injury patterns suggest radiation modality-specificity as RIL, TN, and CMB exhibit unique spatiotemporal differences following XRT vs PRT, likely reflecting underlying dosimetric and radiobiological differences. Familiarity with such injury patterns is essential to improve patient management. Prospective studies are needed to validate these findings and assess their impacts on neurocognitive function.

Balanced Duality: H2O2-Based Therapy in Cancer and Its Protective Effects on Non-Malignant Tissues.

Conventional cancer therapy strategies, although centered around killing tumor cells, often lead to severe side effects on surrounding normal tissues, thus compromising the chronic quality of life in cancer survivors. Hydrogen peroxide (H2O2) is a secondary signaling molecule that has an array of functions in both tumor and normal cells, including the promotion of cell survival pathways and immune cell modulation in the tumor microenvironment. H2O2 is a reactive oxygen species (ROS) crucial in cellular homeostasis and signaling (at concentrations maintained under nM levels), with increased steady-state levels in tumors relative to their normal tissue counterparts. Increased steady-state levels of H2O2 in tumor cells, make them vulnerable to oxidative stress and ultimately, cell death. Recently, H2O2-producing therapies-namely, pharmacological ascorbate and superoxide dismutase mimetics-have emerged as compelling complementary treatment strategies in cancer. Both pharmacological ascorbate and superoxide dismutase mimetics can generate excess H2O2 to overwhelm the impaired H2O2 removal capacity of cancer cells. This review presents an overview of H2O2 metabolism in the physiological and malignant states, in addition to discussing the anti-tumor and normal tissue-sparing mechanism(s) of, and clinical evidence for, two H2O2-based therapies, pharmacological ascorbate and superoxide dismutase mimetics.

Cell Therapies for Acute Radiation Syndrome.

The risks of severe ionizing radiation exposure are increasing due to the involvement of nuclear powers in combat operations, the increasing use of nuclear power, and the existence of terrorist threats. Exposure to a whole-body radiation dose above about 0.7 Gy results in H-ARS (hematopoietic acute radiation syndrome), which is characterized by damage to the hematopoietic system; higher doses result in further damage to the gastrointestinal and nervous systems. Only a few medical countermeasures for ARS are currently available and approved for use, although others are in development. Cell therapies (cells or products produced by cells) are complex therapeutics that show promise for the treatment of radiation injury and have been shown to reduce mortality and morbidity in animal models. Since clinical trials for ARS cannot be ethically conducted, animal testing is extremely important. Here, we describe cell therapies that have been tested in animal models. Both cells and cell products appear to promote survival and lessen tissue damage after whole-body irradiation, although the mechanisms are not clear. Because radiation exposure often occurs in conjunction with other traumatic injuries, animal models of combined injury involving radiation and future countermeasure testing for these complex medical problems are also discussed.

Pathology of acute sub-lethal or near-lethal irradiation of nonhuman primates prophylaxed with the nutraceutical, gamma tocotrienol.

Exposure to high, marginally lethal doses or higher of ionizing radiation, either intentional or accidental, results in injury to various organs. Currently, there is only a limited number of safe and effective radiation countermeasures approved by US Food and Drug Administration for such injuries. These approved agents are effective for only the hematopoietic component of the acute radiation syndrome and must be administered only after the exposure event: currently, there is no FDA-approved agent that can be used prophylactically. The nutraceutical, gamma-tocotrienol (GT3) has been found to be a promising radioprotector of such exposure-related injuries, especially those of a hematopoietic nature, when tested in either rodents or nonhuman primates. We investigated the nature of injuries and the possible protective effects of GT3 within select organ systems/tissues caused by both non-lethal level (4.0 Gy), as well as potentially lethal level (5.8 Gy) of ionizing radiation, delivered as total-body or partial-body exposure. Results indicated that the most severe, dose-dependent injuries occurred within those organ systems with strong self-renewing capacities (e.g., the lymphohematopoietic and gastrointestinal systems), while in other tissues (e.g., liver, kidney, lung) endowed with less self-renewal, the pathologies noted tended to be less pronounced and less dependent on the level of exposure dose or on the applied exposure regimen. The prophylactic use of the test nutraceutical, GT3, appeared to limit the extent of irradiation-associated pathology within blood forming tissues and, to some extent, within the small intestine of the gastrointestinal tract. No distinct, global pattern of bodily protection was noted with the agent's use, although a hint of a possible radioprotective benefit was suggested not only by a lessening of apparent injury within select organ systems, but also by way of noting the lack of early onset of moribundity within select GT3-treated animals.

Effects of radiation mitigating amino acid mixture on mice of different sexes.

To date, few FDA-approved medical countermeasures are available for addressing hematopoietic acute radiation syndrome (H-ARS). In this study, we present our latest research findings focusing on the evaluation of a novel radiation mitigator known as the mitigating amino acid mixture (MAAM). MAAM is composed of five amino acids as the recently reported amino acid-based oral rehydration solution for mitigating gastrointestinal (GI)-ARS. CD2F1 male and female mice were exposed to 60Co-γ total body irradiation (TBI) at 9.0 or 9.5 Gy. Following irradiation, mice were orally administered with MAAM or a saline vehicle control once daily for a duration of 14 days, commencing 24 h after TBI. Mouse survival and body weight change were monitored for 30 days after irradiation. Complete blood counts (CBCs), bone marrow (BM) stem and progenitor cell survival (clonogenicity), and a serum cytokine antibody array were analyzed using samples from day 30 surviving mice. Our data revealed that MAAM treatment significantly enhanced survival rates in irradiated male CD2F1 mice, and the survival rate increased from 25% in the vehicle control group to 60% in the MAAM-treated group (p < 0.05) after 9.0 Gy TBI. The number of BM colonies significantly increased from 41.8 ± 6.4 /104 cells (in the vehicle group) to 78.5 ± 17.0 /104 cells (in the MAAM group) following 9.0 Gy TBI. Furthermore, MAAM treatment led to a decrease in the levels of six cytokines/proteins [cluster of differentiation 40 (CD40), interleukin (IL)-17A, C-X-C motif chemokine 10 (CXCL10/CRG-2), cutaneous T cell-attracting chemokine (CTACK), macrophage inflammatory protein (MIP)-3ß, and IL-1ß] and an increase in the levels of five other cytokines/proteins [IL-3Rß, IL-5, leptin, IL-6, and stem cell factor (SCF)] in mouse serum compared to the vehicle group after 9.0 Gy TBI. However, similar alleviating effects of MAAM were not observed in the irradiated CD2F1 female mice. The serum cytokine profile in the irradiated female mice was different compared to the irradiated male mice. In summary, our data suggest that the beneficial effects of the mitigative amino acid combination treatment after radiation exposure may depend on sex.

Voice Changes of Patients With Nasopharyngeal Carcinoma in Eleven Years After Radiotherapy: A Cross-Sectional Study.

OBJECTIVES: The objective of this study was to assess voice changes in patients with nasopharyngeal carcinoma (NPC) using subjective and objective assessment tools and to make inferences regarding the underlying pathological causes for different phases of radiotherapy (RT). METHODS: A total of 187 (123 males and 64 females) patients with post-RT NPC with no recurrence of malignancy or other voice diseases and 17 (11 males and 6 females) healthy individuals were included in this study. The patients were equally divided into 11 groups according to the number of years after RT. The acoustic analyses, GRBAS (grade, roughness, breathiness, asthenia, and strain) scales, and Voice Handicap Index (VHI)-10 scores were collected and analyzed. RESULTS: The fundamental frequency (F0) parameters in years 1 and 2 and year 11 were significantly lower in patients with NPC than in healthy individuals. The maximum phonation times in years 1 and 11 were significantly shorter than those in healthy individuals. The jitter parameters were significantly different between year 1 and from years 8 to 11 and the healthy individuals. The shimmer parameters were significantly different between years 1, from years 9 to 11, and healthy individuals. Hoarseness was the most prominent problem compared to other items of the GRBAS. The VHI-10 scores were significantly different between years 1 and 2 and year 11 after RT in patients with NPC. CONCLUSIONS: Voice quality was worse in the first 2 years and from years 8 to 11 but remained relatively normal from years 3 to 7 after RT. Patient-reported voice handicaps began during year 3 after RT. The most prominent problem was perceived hoarseness, which was evident in the first 2 years and from years 9 to 11 after RT. The radiation-induced mucous edema, laryngeal intrinsic muscle fibrosis, nerve injuries, upper respiratory tract changes, and decreased lung capacity might be the pathological reasons for voice changes in post-RT patients with NPC.

Establishment of human hematopoietic organoids for evaluation of hematopoietic injury and regeneration effect.

BACKGROUND: Human hematopoietic organoids have a wide application value for modeling human bone marrow diseases, such as acute hematopoietic radiation injury. However, the manufacturing of human hematopoietic organoids is an unaddressed challenge because of the complexity of hematopoietic tissues. METHODS: To manufacture hematopoietic organoids, we obtained CD34+ hematopoietic stem and progenitor cells (HSPCs) from human embryonic stem cells (hESCs) using stepwise induction and immunomagnetic bead-sorting. We then mixed these CD34+ HSPCs with niche-related cells in Gelatin-methacryloyl (GelMA) to form a three-dimensional (3D) hematopoietic organoid. Additionally, we investigated the effects of radiation damage and response to granulocyte colony-stimulating factor (G-CSF) in hematopoietic organoids. RESULTS: The GelMA hydrogel maintained the undifferentiated state of hESCs-derived HSPCs by reducing intracellular reactive oxygen species (ROS) levels. The established hematopoietic organoids in GelMA with niche-related cells were composed of HSPCs and multilineage blood cells and demonstrated the adherence of hematopoietic cells to niche cells. Notably, these hematopoietic organoids exhibited radiation-induced hematopoietic cell injury effect, including increased intracellular ROS levels, γ-H2AX positive cell percentages, and hematopoietic cell apoptosis percentages. Moreover, G-CSF supplementation in the culture medium significantly improved the survival of HSPCs and enhanced myeloid cell regeneration in these hematopoietic organoids after radiation. CONCLUSIONS: These findings substantiate the successful manufacture of a preliminary 3D hematopoietic organoid from hESCs-derived HSPCs, which was utilized for modeling hematopoietic radiation injury and assessing the radiation-mitigating effects of G-CSF in vitro. Our study provides opportunities to further aid in the standard and scalable production of hematopoietic organoids for disease modeling and drug testing.

Genetic Upregulation of Activated Protein C Mitigates Delayed Effects of Acute Radiation Exposure in the Mouse Plasma.

Exposure to ionizing radiation, accidental or intentional, may lead to delayed effects of acute radiation exposure (DEARE) that manifest as injury to organ systems, including the kidney, heart, and brain. This study examines the role of activated protein C (APC), a known mitigator of radiation-induced early toxicity, in long-term plasma metabolite and lipid panels that may be associated with DEARE in APCHi mice. The APCHi mouse model used in the study was developed in a C57BL/6N background, expressing the D168F/N173K mouse analog of the hyper-activatable human D167F/D172K protein C variant. This modification enables increased circulating APC levels throughout the mouse's lifetime. Male and female cohorts of C57BL/6N wild-type and APCHi transgenic mice were exposed to 9.5 Gy γ-rays with their hind legs shielded to allow long-term survival that is necessary to monitor DEARE, and plasma was collected at 6 months for LC-MS-based metabolomics and lipidomics. We observed significant dyslipidemia, indicative of inflammatory phenotype, upon radiation exposure. Additionally, observance of several other metabolic dysregulations was suggestive of gut damage, perturbations in TriCarboxylic Acid (TCA) and urea cycles, and arginine metabolism. We also observed gender- and genotype-modulated metabolic perturbations post radiation exposure. The APCHi mice showed near-normal abundance for several lipids. Moreover, restoration of plasma levels of some metabolites, including amino acids, citric acid, and hypoxanthine, in APCHi mice is indicative of APC-mediated protection from radiation injuries. With the help of these findings, the role of APC in plasma molecular events after acute γ-radiation exposure in a gender-specific manner can be established for the first time.

Emerging role of mesenchymal stem cell-derived exosome microRNA in radiation injury.

PURPOSE: Radiation injury (RI) is a common occurrence in malignant tumors patients receiving radiation therapy. While killing tumor cells, normal tissue surrounding the target area is inevitably irradiated at a certain dose, which can cause varying results of radiation injury. Currently, there are limited clinical treatments available for radiation injuries. In recent years, the negative effects of stem cell therapy have been reported more clearly and non-cellular therapies such as exosomes have become a focus of attention for researchers. As a type of vesicle-like substances secreted by mesenchymal stem cells (MSC), MSC derived exosomes (MSC-exo) carry DNA, mRNA, microRNA (miRNAs), specific proteins, lipids, and other active substances involved in intercellular information exchange. miRNAs released by MSC-exo are capable of alleviating and repairing damaged tissues through anti-apoptosis, modulating immune response, regulating inflammatory response and promoting angiogenesis, which indicates that MSC-exo miRNAs have great potential for application in the prevention and treatment of radiation injury. Therefore, it is necessary to explore the underlying therapeutic mechanisms of MSC-exo miRNAs in this process, which may shed new lights on the treatment of radiation injury. CONCLUSIONS: Increasing evidence confirms that MSC-exo has shown encouraging applications in tissue repair due to the anti-apoptotic, immunoreactive, and pro-angiogenesis effects of the miRNAs it carries as intercellular communication carriers. However, miRNA-based therapeutics are still in their infancy and many practical issues remain to be addressed for clinical applications.

Patient-Reported Outcome Measures Following Hyperbaric Oxygen Therapy for Radiation Cystitis: Early Results From the Multicenter Registry for Hyperbaric Oxygen Therapy.

PURPOSE: Our purpose was to determine changes in patient-reported hematuria and urinary symptoms after hyperbaric oxygen (HBO2) treatment for radiation cystitis (RC). MATERIALS AND METHODS: We analyzed prospectively collected data from the Multicenter Registry for Hyperbaric Oxygen Therapy Consortium accumulated within a week of beginning and ending HBO2. Measures included the modified Radiation Therapy Oncology Group (RTOG) Hematuria Scale, Urinary Distress Inventory Short Form, and EuroQol Five Dimension Five Level instrument. RTOG hematuria and Urinary Distress Inventory Short Form scores were compared using the sign test. Logistic regression was used to evaluate characteristics associated with hematuria improvement. RESULTS: A total of 470 registry patients had RC. The median age, number of HBO2 sessions, and years after radiation were 73 (IQR 12) years, 39 (IQR 10) sessions, and 5 (IQR 8) years, respectively. Eighty-four percent of patients (393/470) had prostate cancer‒related radiation. EuroQol Five Dimension Five Level scores improved from 0.83 (IQR 0.14) to 0.85 (IQR 0.22; P < .001. Three hundred seventy patients had complete RTOG hematuria scores that improved from 2 (IQR 2) to 0 (IQR 2; P < .001. Two hundred forty-six patients had complete Urinary Distress Inventory Short Form ratings that decreased from 33.3 (IQR 44) to 22.2 (IQR 33; P < .001). Regression analysis of those with visible hematuria before HBO2 showed lower improvement odds associated with higher HBO2 hematuria scores (odds ratio [OR] 0.44, 95% CI 0.26-0.73; P < .01), a smoking history (OR 0.44, 95% CI 0.21-0.92; P = .03), or a nonprostate cancer history (OR 0.32, 95% CI 0.10-0.99; P = .05). CONCLUSIONS: HBO2 for RC improved reported hematuria, urinary function, and quality of life. Higher baseline hematuria scores, smoking, and nonprostate cancer history were associated with lower odds of hematuria improvement.

[Diagnostic value of whole blood cell parameters logistic regression model for radiation injury on radiation workers].

Objective: To explore the diagnostic value of whole blood cell parameters logistic regression model for radiation injury on radiation workers by comparing the differences of whole blood cell parameters between occupational radiation injury population and occupational health examination population. Methods: In February 2023, 184 radiation workers who received occupational health examinations in our hospital and occurrenced chromosome aberration from July 2021 to July 2022 were retrospectively selected as the radiation injury group. And other 184 radiation workers encountered in the same period without chromosome aberration occurrence were selected as the control group. Collected whole blood cell parameters from two groups of research subjects, conducted comparative analysis, constructed a logistic regression model, and evaluated the diagnostic value of the logistic regression model for radiation injury on radiation workers by receiver operating characteristic curve (ROC) and area under curve (AUC) . In addition, with the same standard, 60 radiation workers with chromosome aberration and 60 radiation workers without chromosome aberration from August 2022 to January 2023 were included in the validation queue to validate the logistic regression model. Results: Neu_X, Neu_Y, Neu_Z, Lym_X, Lym_Y, Lym_Z, Mon_X, Mon_Y, Mon_Z, Micro, MCHC in the radiation injury group were significantly higher than those in the control group, and the difference was statistically significant (P<0.05) . And MCV and Macro in the radiation injury group were lower than those in the control group, and the difference was statistically significant (P<0.05) . Moreover, logistic regression analysis showed that Lym_X, Lym_Y, Lym_Z, MCHC, Micro were all independent risk factors for diagnosing radiation injury on radiation workers (OR=1.08、1.02、0.99、1.06、51.32, P<0.05) . ROC curve analysis showed that the AUC, sensitivity, specificity, and accuracy of the logistic regression model based by Lym_X, Lym_Y, Lym_Z, MCHC and Micro in diagnosing radiation injury on radiation workers were 0.80, 85.9%, 65.8% and 75.9% respectively. The validation queue verified the logistic regression model and the AUC, sensitivity, specificity, and accuracy of the logistic regression model were 0.80, 81.7%, 71.7% and 76.7% respectively, the model fitted well. Conclusion: Radiation damage can cause changes in multiple whole blood cell parameters of radiation workers. The logistic regression model based by Lym_X, Lym_Y, Lym_Z, MCHC and Micro showed good diagnosis ability and can be used for the screening of radiation injury on radiation workers.

3D skin bioprinting as promising therapeutic strategy for radiation-associated skin injuries.

Both cutaneous radiation injury and radiation combined injury (RCI) could have serious skin traumas, which are collectively referred to as radiation-associated skin injuries in this paper. These two types of skin injuries require special managements of wounds, and the therapeutic effects still need to be further improved. Cutaneous radiation injuries are common in both radiotherapy patients and victims of radioactive source accidents, which could lead to skin necrosis and ulcers in serious conditions. At present, there are still many challenges in management of cutaneous radiation injuries including early diagnosis, lesion assessment, and treatment prognosis. Radiation combined injuries are special and important issues in severe nuclear accidents, which often accompanied by serious skin traumas. Mass victims of RCI would be the focus of public health concern. Three-dimensional (3D) bioprinting, as a versatile and favourable technique, offers effective approaches to fabricate biomimetic architectures with bioactivity, which provides potentials for resolve the challenges in treating radiation-associated skin injuries. Combining with the cutting-edge advances in 3D skin bioprinting, the authors analyse the damage characteristics of skin wounds in both cutaneous radiation injury and RCI and look forward to the potential value of 3D skin bioprinting for the treatments of radiation-associated skin injuries.

The scheme, and regulative mechanism of pyroptosis, ferroptosis, and necroptosis in radiation injury.

Radiotherapy (RT) stands as the primary treatment for tumors, but it inevitably causes damage to normal cells. Consequently, radiation injury is a crucial consideration for radiation oncologists during therapy planning. Cell death including apoptosis, autophagy, pyroptosis, ferroptosis, and necroptosis play significant roles in tumor treatment. While previous studies elucidated the induction of apoptosis and autophagy by ionizing radiation (IR), recent attention has shifted to pyroptosis, ferroptosis, and necroptosis, revealing their effects induced by IR. This review aims to summarize the strategies employed by IR, either alone or in combination therapy, to induce pyroptosis, ferroptosis, and necroptosis in radiation injury. Furthermore, we explore their effects and molecular pathways, shedding light on their roles in radiation injury. Finally, we summarize the regulative agents for these three types of cell death and their mechanisms. In summary, optimizing radiation dose, dose rate, and combined treatment plans to minimize radiation damage and enhance the killing effect of RT is a key focus.

Cutaneous Radiation Injuries: REAC/TS Clinical Experience.

The Radiation Emergency Assistance Center/Training Site (REAC/TS) is one of the US Department of Energy (DOE)/National Nuclear Security Administration (NNSA) Nuclear Emergency Response Team (NEST) assets and has been responding to radiological incidents since 1976. REAC/TS is in the Oak Ridge Institute for Science and Education (ORISE). A critical part of the REAC/TS mission is to provide emergency response, advice, and consultation on injuries and illnesses caused from ionizing radiation. Fortunately, radiation injuries are not frequent, but when they occur, they are more likely to be cutaneous radiation injuries (CRI) or internal contamination. In this paper, we will review selected cases from the REAC/TS experience in order to illustrate cutaneous patterns of injury and treatment options.

Genetic landscape of breast cancer subtypes following radiation therapy: insights from comprehensive profiling.

Background: In breast cancer, in the era of precision cancer therapy, different patterns of genetic mutations dictate different treatments options. However, it is not clear whether the genetic profiling of breast cancer patients undergoing breast-conserving surgery is related to the adverse reactions caused by radiotherapy. Methods: We collected formalin-fixed paraffin-embedded (FFPE) tumor tissue samples from 54 breast cancer patients treated with radiation after breast-conserving surgery and identified comprehensive molecular information in hundreds of cancer-associated genes by FoundationOne CDx (F1CDx), a next-generation sequencing (NGS)-based assay. Results: Among our cohort of 54 breast cancer patients, we found high-frequency mutations in cancer-related genes such as TP53 (56%), RAD21 (39%), PIK3CA (35%), ERBB2 (24%), and MYC (22%). Strikingly, we detected that the WNT pathway appears to be a signaling pathway with specific high-frequency mutations in the HER2 subtype. We also compared the mutation frequencies of the two groups of patients with and without cutaneous radiation injury (CRI) after radiotherapy and found that the mutation frequencies of two genes, FGFR1 and KLHL6, were significantly higher in patients with CRI : No subgroup than in those with CRI : Yes. Conclusion: Different breast cancer subtypes have their own type-specific mutation patterns. FGFR1 and KLHL6 mutations are protective factors for radiation-induced skin toxicity in breast cancer patients.

A Case of Local Radiation Injury in the Creation of Lichtenburg Art.

Despite the fact that there may be no immediate outward signs of tissue destruction, the ultimate damage caused by radiation exposure is immediate and may be predicted based on the source, length of exposure, and type of tissue to which the radiation is exposed. Although predictable, difficulty in caring for these patients stems from the multiple sources of radiation to which people may be exposed, the various parts of the body exposed, the dose involved, the rarity of the condition, and a general lack of knowledge on the part of treating physicians. Due to these factors, there is significant variation in treatment recommendations. Additionally, knowledge about how to treat these injuries is limited and often very difficult to access, even among healthcare professionals. This report highlights the first known case of localized radiation injury secondary to the utilization of a linear accelerator to generate Lichtenberg art. In this case, an accident occurred while working with a retired accelerator and led to severe local radiation injury to this patient's bilateral hands, prompting a series of searches and inquiries as to the next best step in management. From consulting clinicians at the Centers for Disease Control and Prevention (CDC) who are experts in managing radiation injury to the eventual need for digit amputation, this case highlights the profound lack of knowledge and accessible resources for clinicians and patients facing localized radiation injury. This is a noninterventional observation case report without the requirement of ethical approval.

Effect and mechanism of radiation combined with different decompression loads on acute injury of rat / 解放军医学杂志

Objective To investigate the effect of rats'injuries and its mechanism caused by specific dose of radiation combined with decompression exposure.Methods 81 male SD rats were randomly divided into control group(n=9),radiation group(n=18),radiation+low-load decompression group(n=18),radiation+medium-load decompression group(n=18),and radiation+high-load decompression group(n=18).In addition to control group,the rats were irradiated with 60Co γ rays at 4 Gy and then underwent rapid escape experiments.The high-pressure exposure schemes were to stay underwater 57 m for 30 min,45 min or 60 min and reduce to normal pressure within(30±5)s,respectively.The high-pressure exposure was not carried out in radiation group.The behavior and death of rats in each group were observed 0.5 h after leaving the cabin.Blood(abdominal aorta)and lung tissues were collected at 3 h and 72 h,respectively.The changes of lung wet-dry weight ratio(W/D),lung pathology and serum levels of interleukin(IL)-1β,IL-6,tumor necrosis factor-α(TNF-α),superoxide dismutase(SOD),malondialdehyde(MDA),nitric oxide(NO),intercellular adhesion molecule-1(ICAM-1)and thromboxane B2(TXB2)were analyzed.Results Compared with control group and radiation group,radiation+low-load decompression group showed no significant difference in the injury and death rate of rats(P＞0.05),while radiation+medium-load decompression group and radiation+high-load decompression group showed significantly increase of the injury and death rate of rats(P＜0.05).Compared with control group,other groups showed no significant change in pulmonary W/D at 3 h(P＞0.05),and increased at 72 h(P＜0.05).HE staining showed that compared with control group,radiation group showed mild lung interstitial edema,while radiation+low-load decompression group showed obvious pulmonary tissue edema and a small number of red blood cells exudated in the alveolar cavity.The edema,congestion and inflammatory cell infiltration of lung tissue were more serious in radiation+medium-load decompression group and radiation+high-load decompression group.Compared with control group and radiation group,all radiation+decompression groups showed an increase in serum levels of IL-1β,IL-6,TNF-α,MDA,NO,ICAM-1 and TXB2(P＜0.05),and a decrease in SOD activity(P＜0.05).Compared with radiation+low-load decompression group,radiation+medium-load decompression group and radiation+high-load decompression group showed increase in serum levels of IL-1β,IL-6,MDA,ICAM-1 and TXB2(P＜0.05),and decrease in activity of SOD(P＜0.05).Except for control group,serum levels of IL-1β,IL-6,TNF-α,MDA,NO,ICAM-1 and TXB2 were decreased at 72 h compared with 3 h(P＜0.05),and SOD activity was increased at 72 h in all groups(P＜0.05).Conclusions High-load decompression can increase the injury and death rate of rats exposed to radiation and high pressure.The potential mechanism of the combined injury effect of radiation and decompression was related to inflammation,immune stress,oxidative damage,vasomotor activity and coagulation mechanism.

Identification and diagnostic value of characteristic volatile organic compounds in exhaled breath of mice with early stage radiation injury / 军事医学

Objective To investigate the characteristic volatile organic compounds(VOCs)in exhaled breath and their diagnostic value in mice with early stage radiation injury.Methods The thermal desorption gas chromatography-mass spectrometry(TD-GC/MS)technique was used to analyze VOCs in exhaled breath of irradiated mice by 60Coγ-ray with 800 cGy.The characteristic VOCs in the early stage of radiation injury were identified,and a diagnostic model was established.Results The 30-day survival rate of mice was 4.2%.There were significant differences in characteristic VOCs at 7 hours after radiation injury,and thirty characteristic VOCs related to early-stage radiation injury were identified.The diagnostic value of differential metabolites in mice after irradiation was evaluated via the ROC curve,and the area under the ROC curve(AUC)of a single compound exceeded 0.8.The diagnostic model was constructed by screening 9 potential biomarkers of exhalation through Fisher discriminant analysis,and its sensitivity and specificity were close to 100%.Conclusion Analysis of VOCs in exhaled breath is expected to provide a non-invasive diagnostic method for early screening and diagnosis of radiation injury.

Dimethyl fumarate inhibits NLRP3/AIM2 inflammasomes to prevent spleen radiation injury ZHANG / 中国药理学通报

Aim To investigate the protective effect of dimethyl fumarate on spleen injury induced by gamma radiation in mice and the related mechanism. Methods C57BL/6 mice were randomly divided into the blank control group, radiation model group and DMF administration group, which were administered once at 12 h before irradiation and once at 0. 5 h, 12 h, 24 h and 48 h after irradiation. The 30-day survival rate, body weight and pathological injury of spleen were measured after a one-time total body irradiation of Co 7 rays (8 Gy). TUNEL staining was used to detect apoptosis of spleen cells. Enzyme-linked immunoassay ( ELISA) was applied to detect the contents of TNF-a, IL-1 p, IL-6, IL-18, NLRP3 and AIM2 in spleen. Western blot test and immunofluorescence staining test was employed to verify the changes of NLRP3 and AIM2 contents in spleen tissue after irradiation. Results DMF could obviously improve the survival rate of irradiated mice, improve the weight loss of irradiated mice, re-duce the pathological injury of spleen, and inhibit the apoptosis of spleen cells after irradiation. ELISA results showed that DMF could significantly inhibit the increase of spleen inflammatory cytokines TNF-a, IL-lp, IL-6, IL-18 and inflammasome components NL-RP3 and AIM2 induced by irradiation. Western blot and tissue immunofluorescence staining also confirmed that DMF could inhibit the increase of NLRP3 and AIM2 inflammasome protein levels caused by irradiation. Meanwhile, NLRP3 agonist and AIM2 agonist could antagonize the radiation protection effect of DMF on spleen cells. Conclusion DMF can ameliorate spleen injury of Co 7-ray injured mice, and its mechanism is closely related to NLRP3/AIM2 inflamma-somes, which can be used as a potential protective drug for radiation injury.