OBJECTIVE:This study was designed to explore the toxic effects of Transferrin a(tfa)-mediated uranium exposure on the hematopoietic system. METHODS:Zebrafish embryos were subjected to uranium nitrate solutions at concentrations of 50, 100, 250, and 500 μg/L for a defined period, followed by sample collection. The impact of uranium on hematopoietic system development in zebrafish was evaluated through hemoglobin staining, qRT-PCR, and in situ hybridization. RNA-Seq was utilized to detect differentially expressed genes (DEGs) in embryos exposed to 100 μg/L uranium, with subsequent bioinformatics analysis to confirm these DEGs. Furthermore, blood samples from patients with hematological disorders and impaired hematopoietic function were collected, and RNA-Seq was applied to identify DEGs. RESULTS:Uranium exposure in zebrafish embryos led to reduced hemoglobin expression, with key transcription factors for primitive and definitive hematopoiesis being significantly downregulated at 100 μg/L uranium exposure. Overexpression of tfa resulted in a marked increase in hemoglobin content and upregulation of GATA1, a key factor in primitive hematopoiesis. Patients with hematopoietic dysfunction exhibited abnormalities in the tfa signaling pathway. CONCLUSION:tfa plays a role in mediating the inhibitory effects of uranium on hematopoietic function.
As socioeconomic development progresses, nuclear energy and technology advance rapidly. Concurrently, nuclear accidents may result in the release of additional radioactive isotopes into the environment. Groundwater and oceans are key pathways for radioactive nuclides in the environmental cycle, with aquatic organisms being particularly vulnerable to radiation exposure. Aquatic model organisms are essential for studying radiation effects on non-human species in aquatic environments and for extrapolating dose-response relationships to humans. However, current models for calculating radiation doses in the aquatic model organism zebrafish remain underdeveloped. To better elucidate the mechanisms of radiation damage effects, integrating Micro-CT and 3D modeling techniques, a series of zebrafish mesh-type models (including adults and larvae, named zebrafish-mesh family: ZF-mesh family) with multiple internal organs are established in this study. The Monte Carlo software PHITS is used to simulate and calculate the Absorbed Fractions (AFs) and S-values for singleenergy electrons ranging from 0.001 to 10 MeV, single-energy photons from 0.001 to 5 MeV, and eight radioactive nuclides commonly found in nuclear power plant liquid effluents: 3H, 14C, 90Sr, 106Ru, 134Cs, 137Cs, 60Co, 131I, across various source-target organ configurations. The results indicate that the mesh-type models of zebrafish at multiple developmental stages can be used for radiation dosimetry calculations. Analysis of the dosimetry parameter database, established through Monte Carlo calculations with this series of mesh-type models, shows that the maximum difference in self-AFs between the geometric and curved models reaches 52.8%. Comparisons between models at different developmental stages show that the impact of radioactive nuclides on internal organs depends on both the decay properties of the nuclides and the organ volumes. For adult fish, the dose contribution from 90Sr is most significant, reaching up to 1.81 x10- 5 mGy center dot MBq- 1 center dot s- 1 in the heart of male fish. In larvae fish, 14C has the most notable impact, with a dose rate of 4.38 x10- 3 mGy center dot MBq- 1 center dot s- 1 in the heart at 48 h post-fertilization (hpf). Comparisons of yolk mass changes at various developmental stages in larvae fish reveal that organ location is a key factor influencing self-AFs. This influence is often more significant than the variations caused by changes in organ volume. Due to the small size of zebrafish organs, the increase in energy deposition caused by secondary electrons is not evident in adult fish. In the smallest larvae hearts, no increase in energy deposition is observed. In summary, detailed surface modeling of model organisms across multiple developmental stages and the establishment of a comprehensive dosimetric parameter database are crucial. This approach significantly improves the reliability of radiation impact assessments for non-human species.
The biological mechanisms triggered by low-dose exposure still need to be explored in depth. In this study, the potential mechanisms of low-dose radiation when irradiating the BEAS-2B cell lines with a Cs-137 gamma-ray source were investigated through simulations and experiments. Monolayer cell population models were constructed for simulating and analyzing distributions of nucleus-specific energy within cell populations combined with the Monte Carlo method and microdosimetric analysis. Furthermore, the 10 × Genomics single-cell sequencing technology was employed to capture the heterogeneity of individual cell responses to low-dose radiation in the same irradiated sample. The numerical uncertainties can be found both in the specific energy distribution in microdosimetry and in differential gene expressions in radiation cytogenetics. Subsequently, the distribution of nucleus-specific energy was compared with the distribution of differential gene expressions to guide the selection of differential genes bioinformatics analysis. Dose inhomogeneity is pronounced at low doses, where an increase in dose corresponds to a decrease in the dispersion of cellular-specific energy distribution. Multiple screening of differential genes by microdosimetric features and statistical analysis indicate a number of potential pathways induced by low-dose exposure. It also provides a novel perspective on the selection of sensitive biomarkers that respond to low-dose radiation.
To determine if hepatic and splenic perfusion parameters are useful in identifying severe portal hypertension (SPH). The study enrolled 52 patients who underwent perfusion CT scan within one week before the hepatic venous pressure gradient (HVPG) measurement. A commercial software package was used for post-processing to generate hepatic and splenic perfusion parameters. Correlations were assessed using Pearson and Spearman rank correlation coefficients. Logistic regression was used to screen predictive parameters of SPH. The cut-off values of parameters for severe portal hypertension were calculated, as well as the sensitivity and specificity. There was a significant difference between SPH and non-severe portal hypertension (NSPH) in blood volume of liver (BVLiver), hepatic arterial fraction (HAF), hepatic arterial perfusion (HAP), portal venous perfusion (PVP), mean slope of increase in spleen (MSISpleen), BVSpleen, blood flow of spleen (BFSpleen), BVSpleen/Liver, and BVSpleen/Liver(P) (p < 0.05). The Spearman correlation coefficient was − 0.541 (p < 0.001) between BVSpleen/Live and HVPG and − 0.568 (p < 0.001) between BVSpleen/Liver(P) and HVPG. Using a BVSpleen/Liver value of 0.780 or BVSpleen/Liver(P) value of 1.061 as the cut-off value for the detection of SPH, the sensitivity and specificity were 94.7
We aimed to investigate the predictive value of body compositions measured by CT, including skeletal muscle and adipose tissue, for hepatic encephalopathy (HE) in cirrhotic patients following transjugular intrahepatic portosystemic shunt (TIPS). Patients who underwent TIPS between November 2015 and April 2021 were included in this retrospective study. CT images taken at L3 were quantified for three body composition indexes (cm2/m2), visceral fat area index (VFAI), subcutaneous fat area index (SFAI), and skeletal muscle index (SMI) at baseline. Multivariable logistic regression models were conducted to assess associations between post-TIPS HE and body compositions. Nomograms based on the multivariable logistic regression models were developed and were evaluated from Calibration curves. Male patients had greater SMI, whereas SFAI and VFAI were higher in females (p < 0.001 for each). In sex stratified multivariate analyses after adjustment for other confounding variables, VFAI in males (p = 0.033) and SFAI in females (p = 0.003) were significant predictors of post-TIPS HE. Male patients with low VFAI (< 53.52 cm2/m2) (OR 6.44; 95
In the current international situation, there is the possibility of nuclear war and nuclear terrorism. The nuclear and radiological emergency in the event of an accident should be enhanced. The World Health Organization (WHO) issued a publication on January 27, 2023, updating the list of drugs recommended for stockpiling in response to radiation and nuclear emergencies, which was the first update since 2007. The list of recommended drug stocks in the publication includes drugs to prevent or reduce the effects of radiation, as well as drugs used to treat injuries after exposure. Based on the list of drugs, this article reviews the emergency response to nuclear and radiological accidents, the general situation of emergency drug stockpiles, drug reserves in some countries, and current considerations, with a view to providing references for emergency medical rescue in nuclear and radiological accidents in China.
Ionizing radiation can cause changes in nervous system function. However, the underlying mechanism remains unclear. In this study, Caenorhabditis elegans (C. elegans) was irradiated with 75 Gy of 60Co whole-body γ radiation. Behavioral indicators (head thrashes, touch avoidance, and foraging), and the development of dopaminergic neurons related to behavioral function, were evaluated to assess the effects of ionizing radiation on nervous system function in C. elegans. Various behaviors were impaired after whole-body irradiation and degeneration of dopamine neurons was observed. This suggests that 75 Gy of γ radiation is sufficient to induce nervous system dysfunction. The genes nhr-76 and crm-1, which are reported to be related to nervous system function in human and mouse, were screened by transcriptome sequencing and bioinformatics analysis after irradiation or sham irradiation. The expression levels of these two genes were increased after radiation. Next, RNAi technology was used to inhibit the expression of crm-1, a gene whose homologs are associated with motor neuron development in other species. Downregulation of crm-1 expression effectively alleviated the deleterious effects of ionizing radiation on head thrashes and touch avoidance. It was also found that the expression level of crm-1 was regulated by the nuclear receptor gene nhr-76. The results of this study suggest that knocking down the expression level of nhr-76 can reduce the expression level of crm-1, while down-regulating the expression level of crm-1 can alleviate behavioral disorders induced by ionizing radiation. Therefore, inhibition of crm-1 may be of interest as a potential therapeutic target for ionizing radiation-induced neurological dysfunction.
The health of radiation workers has always been our focus. Epidemiological investigation shows that long-term exposure to low-dose ionizing radiation can affect human health, especially cancer and cardiovascular disease, and there are many studies on it. However, up to now, there have been few reports on the research of blood and biological samples from radiation workers. In this study, radiation workers and healthy control groups were strictly screened, and the transcriptome of mRNA and circRNA was sequenced by extracting their peripheral venous blood. At the same time, appropriate data sets were selected in the GEO database for bioinformatics analysis, and circRNA-miRNA-mRNA network was constructed. We identified 9 different circular ribonucleic acids, 3 tiny ribonucleic acids, and 2 central genes (NOD 2 and IRF 7). These differentially expressed genes and non-coding RNA are closely related to ionizing radiation damage, and play an important role as biological markers. In conclusion, this study may provide new insights into the role of the circRNA-miRNA-mRNA regulatory network in the health of radiation workers, and provides a new strategy for the future study of radiation biology.
The reproductive system is vulnerable to ionizing radiation, which is a hot research topic at present. We tested the effect of polydatin on spermatocytes(GC-1 cells) after X-ray irradiation. The reproductive damage model of C.elegans was established by 60Coγ-ray, and the protective effect of polydatin on reproductive damage caused by ionizing radiation was evaluated. We quantified the ROS levels of GC-1 cells and C.elegans after irradiation with polydatin and evaluated the anti-apoptosis effect of polydatin at proper concentration. Differential genes of C.elegans reproductive damage were screened out from transcriptome sequencing results and comparable GEO datasets. It was proved that 100μM polydatin significantly reduced the apoptosis of GC-1 cells induced by 2 Gy X-ray. In addition, the longevity, reproductive capacity, germ cell apoptosis and spawning and hatching capacity of polydatin were tested. The results showed that 100 μM polydatin content significantly increased the influence of 50 Gy 60Coγ-ray on reproductive capacity of C.elegans. Quantitative analysis of mRNA and protein levels of apoptosis-related genes and reproductive-related genes by qRT-PCR and Western blotcon firmed that polydatin with appropriate dosage had good protective effects on reproductive damage caused by radiation, which laid a foundation for the application research of polydatin in radiation protection.
Non-coding RNAs (ncRNAs) have attracted wide attention in the field of ionizing radiation (IR). They have been found to be involved in cell development, proliferation, differentiation, and apoptosis in both clinical radiotherapy and radiation protection studies. Despite the production of an increasing number of relevant reports in recent years, the molecular mechanisms involved are yet to be clearly understood. In the last few years, ncRNAs have received a lot of research attention, especially microRNAs, long noncoding RNAs, and circular RNAs, which have a well-known association with the development of human disease and are closely related to the biological phenotypic changes caused by IR. With recent developments of research methods, these ncRNAs might play a significant regulatory role in future radiation protection and radiotherapy. This review will summarize the research progress of various types of ncRNAs as biomarkers of IR and potential new targets for radiotherapy, aiming to provide references for future research and the formulation of new strategies.
Microdosimetry is a tool for the investigation of microscopic energy deposition of ionizing radiation. This work used Caenorhabditis elegans as a model to estimate the microdosimetric deposition level at the 60Co gamma radiation. Monte Carlo software PHITS was employed to establish irradiated nematodes model. The dose deposition of the entire body and gonad irradiated to 100 Gy was calculated. The injury levels of radiation were evaluated by the detection of biological indicators. The result of microdosimetric experiment suggested that the dose of whole body of nematodes was estimated to be 99.9 ± 57.8 Gy, ranging from 19.6 to 332.2 Gy. The dose of gonad was predicted to be 129.4 ± 558.8 Gy (9.5-6597 Gy). The result of biological experiment suggested that there were little changes in the length of nematodes after irradiation. However, times of head thrash per minute and the spawning yield in 3 consecutive days decreased 27.1% and 94.7%, respectively. Nematodes in the irradiated group displayed heterogeneity. Through contour analysis, trends of behavior kinematics and reproductive capacity of irradiated nematodes proved to be consistent with the dose distribution levels estimated by microdosimetric model. Finally, C. elegans presented a suitable combined model of microdosimetry and biology for studying radiation.
Gastrointestinal (GI) tract graft-versus-host disease (GvHD) is a major cause of post-allo-HSCT (hematopoietic stem cell transplantation) morbidity and mortality. Patients with steroid-refractory GI-GvHD have a poor prognosis and limited therapeutic options. FMT2017002 trial (#NCT03148743) was a non-randomized, open-label, phase I/II clinical study of FMT for treating patients with grade IV steroid-refractory GI-GvHD. A total of 55 patients with steroid-refractory GI-GvHD were enrolled in this study. Forty-one patients with grade IV steroid-refractory GI-GvHD were included in the final statistical analysis. Of them, 23 patients and 18 patients were assigned to the FMT group and the control group, respectively. On days 14 and 21 after FMT, clinical remission was significantly greater in the FMT group than in the control group. Within a follow-up period of 90 days, the FMT group showed a better overall survival (OS). At the end of the study, the median survival time was >539 days in the FMT group and 107 days in the control group (HR=3.51; 95% CI, 1.21–10.17; p =0.021). Both the event-free survival time (EFS) (HR=2.3, 95% CI, 0.99–5.4; p =0.08) and OS (HR=4.4, 95% CI, 1.5–13.04; p =0.008) were higher in the FMT group during the follow-up period. Overall, the mortality rate was lower in the FMT group (HR=3.97; 95% CI, 1.34–11.75; p =0.013). No differences in the occurrence of any other side effects were observed. Our data suggest that the diversity of the intestinal microbiota could be affected by allo-HSCT. Although its effectiveness and safety need further evaluation, FMT may serve as a therapeutic option for grade IV steroid-refractory GI-GvHD. Clinical Trial Registration [ ClinicalTrials.gov ], identifier [NCT03148743].
目的 研究某医院粒籽源永久性植入治疗病房内的外照射剂量水平和分布情况,对其辐射风险进行评估,为加强粒籽源永久性植入治疗放射工作人员的放射防护与监督提供科学依据,同时提出合理化的辐射防护建议.方法 采用热释光剂量测量方法对粒籽源永久性植入治疗病房内10类区域的剂量水平进行为期1年的监测,并结合病人植入粒籽源数目和住院天数进行剂量分析.结果 该病区一年内共收住病人1232人次,其中行粒籽源永久性植入治疗病人432人次(190人),共植入粒籽源2.746843 × 101 Bq(7423.9 mCi),人均6.3566 x 108 Bq(17.18 mCi),粒籽源永久性植入治疗病人年度住院天数2478天,平均住院6天.热释光剂量监测结果表明,各监测点处的剂量范围为0.23~13.94 mSv,均值为3.37 mSv,中值为1.90 mSv.其中病床两侧和输液架处的剂量范围明显高于其他点位处,经剂量/活度和剂量/(活度·天)分析,其差异依旧存在,均存在统计学差异.结论 该粒籽源永久性植入病房内存在外照射剂量偏高的点位,医护人员和陪护人员应减少在此点位居留的时间或远离此点位.医护人员年度个人剂量监测结果远低于国家标准要求,亦低于本次实验点位剂量监测结果,与医护人员的实际工作和居留情况有关.工作人员在穿戴防护用品的情况下,在剂量安全范围内,可适当增加粒籽植入活度和住院天数.患者在术后穿戴防护,可明显降低其对医护人员的外照射剂量.
Objective: The present study aimed to analyze the mechanism by which long-term occupational exposure of workers to low-dose ionizing irradiation induces epithelial-mesenchymal transition (EMT) of the human bronchial epithelial cells using transcriptome profiling. Methods: RNA-seq transcriptomics was used to determine gene expression in blood samples from radiation-exposed workers followed by bioinformatics analysis. Normal bronchial epithelial cells (16HBE) were irradiated for different durations and subjected to immunofluorescence, Western blotting, scratch healing, and adhesion assays to detect the progression of EMT and its underlying molecular mechanisms. Results: Transcriptomics revealed that exposure to ionizing radiation led to changes in the expression of genes related to EMT, immune response, and migration. At increased cumulative doses, ionizing radiation-induced significant EMT, as evidenced by a gradual decrease in the expression of E-cadherin, increased vimentin, elevated migration ability, and decreased adhesion capability of 16HBE cells. The expression of fibronectin 1 (FN1) showed a gradual increase with the progression of EMT, and may be involved in EMT. Conclusion: Ionizing radiation induces EMT. FN1 may be involved in the progression of EMT and could serve as a potential biomarker for this process.
Background: Gastrointestinal (GI) tract graft-vs-host disease (GvHD) is a major cause of post-allo-HCT morbidity and mortality. Patients with steroid-refractory GI-GvHD face a poor prognosis and limited therapeutic options. Here, we report an interim analysis on the safety and efficacy of fecal microbiota transplantation (FMT) in treating steroid-refractory GI-GvHD.Methods: We did a non-randomized, open-label, phase 1 clinical study on patients with grade IV steroid-refractory GI-GvHD. FMT efficacy was evaluated using indexes of abdominal pain, diarrhea and bloody purulent stool at 14 and 21 days after the diagnosis of steroid-refractory GI-GvHD. The primary outcomes referred to clinical complete remission or partial remission. Secondary outcomes referred to EFS (event free survival) and OS (overall survival) at Day 90 and the end of the research. Safety was evaluated according to adverse events during FMT and the whole follow-up period. The study was registered with ClinicalTrials.gov as #NCT03148743.Results: A total of 56 patients with steroid-refractory GI-GvHD were enrolled. Of them, 24 patients with grade IV steroid-refractory GI-GvHD were assigned to FMT and 18 to the control group. The characteristics of the two group patients at baseline were similar. At Day 14 after FMT, 13 (54.2%) patients in FMT group and none (0%) of 18 control group achieved clinical remission (p<0.05), while 20(83%) patients in FMT group and 7(39%) in control group showed effective response (clinical remission+partial remission) (RR 7.86, 95% CI 1.88–32.9; p=0.005). At Day 21, the clinical remission was significantly greater in FMT group than in control group (14 (58.3%) of 24 vs 3(16%) of 18; RR 6.0, 95% CI 1.22–29.45; p=0.027). Within a follow up of 90 days, the FMT group showed better OS (HR, 7.0; 95% CI, 1.53-32.08; p=0.012). At the end of the research, the median survival time was >600 days in FMT group and 107 days in control group (HR, 4.73; 95% CI, 1.58-14.14; p=0.005). Both the EFS (HR, 0.24; 95% CI, 0.06-0.95; p=0.055) and OS (HR, 5.97; 95% CI, 1.52-23.43; p=0.01) kept increasing during the follow-up in FMT group. Overall, the mortality rate was lower in FMT group (HR, 5.97; 95% CI, 1.52-23.43; p=0.01). No difference was observed in the occurrence of other side effects, such as hemorrhagic cystitis, infection of bacteria & fungi, CMV&EBV, septicemia, TMA, cardiac events, thrombocytopenia and epilepsy.Conclusions: The diversity of intestinal microbiota can be affected by allo-HSCT. FMT is effective and safe in treating grade IV steroid refractory GI–GvHD.
采用职业健康体检资料和问卷形式,利用单因素和多因素logistic回归模型,分析探讨某企业内不同工种的放射工作人员暴露在低剂量电离辐射环境下发生甲状腺结节的风险.结果表明,放射工作人员中以混合射线组甲状腺结节发生风险最高,随着年龄和放射工龄的增加发生风险会增加;性别不同与甲状腺结节发生风险有关.
<span id="ChDivSummary" name="ChDivSummary" class="abstract-text">目的了解高血压家族史与超重/肥胖对高血压患病的交互作用,为高血压的防治提供参考依据。方法于2017年9—12月采用普查的方法对北京市某科研院所的1 250名在职职工进行问卷调查和体格检查;应用logistic回归模型分析高血压家族史和超重/肥胖与高血压发病风险的关联强度,并采用相加作用模型分析其交互作用。结果北京市某科研院所1 250名职工中,患高血压者273例,高血压患病率为21.84%;有60.80%(760/1 250)的职工有高血压家族史,有48.72%(609/1 250)的职工超重/肥胖。在调整了性别、年龄、文化程度、家庭月收入、吸烟、饮酒和睡眠时间等混杂因素后,多因素非条件logistic回归分析结果显示,有高血压家族史者患高血压的风险为无高血压家族史者的2.59倍(OR=2.59,95%CI=1.38~4.84),超重/肥胖者患高血压的风险为正常体重者的3.21倍(OR=3.21,95%CI=1.66~6.21),有高血压家族史且超重/肥胖者患高血压的风险为无高血压家族史且非超重/肥胖者的7.64倍(OR=7.64,95%CI=4.21~13.89)。交互作用分析结果显示,高血压家族史及超重/肥胖的交互作用超额相对危险度、交互作用归因比和交互作用指数分别为2.85(95%CI=0.35~5.35)、 0.37(95%CI=0.13~0.62)和1.75(95%CI=1.06~2.89),纯交互作用归因比为42.8%,即高血压家族史和超重/肥胖对高血压患病具有相加交互作用。结论有高血压家族史和超重/肥胖均可增加高血压的患病风险,且两者的交互作用增加了患高血压的风险。</span>
Low-dose ionizing radiation (LDIR) may increase the mortality of solid cancers in nuclear industry workers, but only few individual cohort studies exist, and the available reports have low statistical power. The aim of the present study was to focus on solid cancer mortality risk from LDIR in the nuclear industry using standard mortality ratios (SMRs) and 95% confidence intervals. A systematic literature search through the PubMed and Embase databases identified 27 studies relevant to this meta-analysis. There was statistical significance for total, solid and lung cancers, with meta-SMR values of 0.88, 0.80, and 0.89, respectively. There was evidence of stochastic effects by IR, but more definitive conclusions require additional analyses using standardized protocols to determine whether LDIR increases the risk of solid cancer-related mortality.
目的 探讨北京房山地区变应性鼻炎(AR)患者就诊情况与花粉浓度的相关性.方法 按月份比较2017年4月~9月北京市气象局所测得的花粉数据以及同期北京核工业医院房山院区AR患者就诊人次占耳鼻咽喉科门诊总就诊量的比例(门诊构成比).对每日AR患者的门诊构成比和对应的花粉浓度进行Pearson相关分析.结果 2017年4月~9月不同月份花粉浓度比较,χ2=121.9,P<0.01,差异有统计学意义.花粉播散时间存在4~5月、8~9月两个高峰期.2017年4~9月AR患者门诊构成比的 χ2=167.8,P<0.01,差异有统计学意义.AR患者门诊构成比存在2个高峰,分别为4~5月和8~9月.AR患者就诊比例的变化与花粉浓度变化的趋势在时间上表现出一致性.2017年4~9月的花粉浓度和同期AR患者门诊就诊的比例的r=0.561,P<0.0.1,呈正相关.结论 北京房山地区AR患者就诊情况与花粉浓度存在相关性.