2023 Vol. 47, No. 4

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2023, 47(4)
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Contents
2023, 47(4): 1-4.
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2023, 47(4): 199-200. doi: 10.3760/cma.j.cn121381-202303038-00298
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Clinical Investigation
Evaluation of plaque vulnerability and early warning value of the third-generation dual-source low-dose CT integrative cardio-cerebrovascular imaging
Rong Wang, Qingyu Ji, Jiao Du, Xiaolin Liu, Yaoqiang Mu, Lintao Li, Yongchun Zhang, Kai Sun
2023, 47(4): 201-210. doi: 10.3760/cma.j.cn121381-202104020-00286
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Objective To screen the high-risk population with cardiovascular and cerebrovascular risk factors using third-generation dual-source low-dose computed tomography (CT) integrative cardio-cerebrovascular imaging (i.e., simultaneous coronary artery and head and neck artery computed tomography angiography (CTA)), and to provide early warning of cardiovascular and cerebrovascular diseases by analyzing the risk factors for the occurrence of vulnerable plaques. Methods Patients requiring simultaneous coronary artery and head and neck artery CTA were prospectively selected from the Baotou Central Hospital from January 2016 to January 2019, and 614 cases were consecutively included. According to the inclusion and exclusion criteria, 500 patients were selected, including 245 males and 255 females. The age was (57.8±14.2) years. Based on CTA characteristics, the 500 patients were divided into the vulnerable plaque group (200 cases), the stable plaque group (97 cases), and the normal plaque group (203 cases). The stable plaque group and the normal plaque group were called the non-vulnerable plaque group. Through the follow-up of major cardiovascular and cerebrovascular adverse events (MACCE) in patients with vulnerable plaque, the multivariate logistic model was constructed to analyze the vulnerable plaque risk factors and evaluate the plaque block vulnerability. Chi-square test was used to compare the counting data groups. Analysis of variance was used to compare the measurement data with normal distribution between multiple groups. The comparison between two groups of econometric data with skewed distribution used a non parametric U-test, while the comparison between multiple groups used a non parametric Kruskal-Wallis test. Multivariate Logistic regression analysis was used to examine the correlation between vulnerable plaques, risk factors, and MACCE. Two-sample t test was used for the single-factor comparative analysis of indicators between the vulnerable plaque group and the non-vulnerable plaque group. Results (1) The levels of age, body mass index, blood glucose, homocysteine, triglyceride, low-density lipoprotein, apolipoprotein E, lipoprotein, cystatin C, C-reactive protein, erythrocyte sedimentation rate, and glycosylated hemoglobin c in the vulnerable plaque group were significantly higher than those in the non-vulnerable plaque group, and the differences were statistically significant (t=2.267−24.930, all P<0.05). The incidence of MACCE, hypertension, diabetes, coronary heart disease in the vulnerable plaque group were higher than those in the non-vulnerable plaque group, and the differences were statistically significant (χ2=10.349−102.667, all P<0.05). High-density lipoprotein, lactate dehydrogenase, and the level of creatine kinase were significantly lower in the vulnerable plaque group than those in the non-vulnerable plaque group, and the differences were statistically significant (t=4.062, 2.965, Z=−2.065; all P<0.05). (2) Age (OR=1.027, 95%CI: 1.004–1.052), hypertension (OR=1.654, 95%CI: 1.026–2.667), glycosuria (OR=2.488, 95%CI: 1.370–4.517), hyperglycemia (OR=1.227, 95%CI: 1.100–1.368), homocysteine (OR=1.078, 95%CI: 1.020–1.140), and C-reactive protein (OR=2.011, 95%CI: 1.022–3.958) were risk factors for vulnerable plaques. (3) Compared with the non-vulnerable plaque group, the onset of MACCE in the vulnerable plaque group was earlier ((1.1±0.3) years vs. (0.8±0.2) years), and the patients were younger ((59.9±13.7) years vs. (54.1±8.5) years). All the differences were statistically significant (t=7.775, P<0.001; t=2.059, P=0.043). (4) More patients with MACCE had multiple signs of vulnerable plaques. (5) The probability of MACCE in patients with vulnerable plaque was 7.637 times higher than that in patients without vulnerable plaque. Vulnerable plaque was an independent risk factor for MACCE (OR=7.637, 95%CI: 5.047–11.554). Conclusion The third-generation dual-source low-dose CT integrated cardio-cerebrovascular imaging is of great value for the early warning of cardiovascular and cerebrovascular diseases.
Basic Science Investigations
The effects of EGFR and NRF2 on DNA damage repair induced by ionizing radiation
Yu Gao, Chang Xu, Qiang Liu
2023, 47(4): 211-219. doi: 10.3760/cma.j.cn121381-202303015-00294
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Objective To investigate the effect of epidermal growth factor receptor (EGFR) and nuclear factor-E2-related factor 2(NRF2) on DNA damage response and repair in human cervical cancer HeLa cells after exposure to ionizing radiation. Methods Human cervical cancer HeLa cells were treated in two groups. (1) EGFR was knocked down in HeLa cells using a small interfering RNA, and the cells were irradiated using a 137Cs γ-ray irradiation source. HeLa cells were divided into control group (HeLa siCtrl), knockdown EGFR group (HeLa siEGFR), irradiation group (HeLa siCtrl+8 Gy), and knockdown EGFR+irradiation group (HeLa siEGFR+8 Gy). The number of phosphorylated histone 2A variant (γ-H2AX) foci in the cells was detected by immunofluorescence assay (6, 12, and 24 h after 8 Gy irradiation); the NRF2 downstream target genes were detected by real-time fluorescence quantitative polymerase chain reaction (RT-qPCR) assay; the expression levels of flow cytometry were used to detect the effect of EGFR on HeLa cell cycle; nucleoplasmic separation assay was used to isolate cytoplasmic and cytosolic proteins from HeLa cells; protein immunoblotting was used to detect the phosphorylation levels of NRF2, EGFR, HO-1, ataxia-telangiectasia mutated gene and Rad3-related kinase (ATR) Thr1989 locus, cell cycle checkpoint kinase 1 (p-CHK1), and Ser345 site phosphorylation level. (2) A small interfering RNA was used to knock down NRF2 in HeLa cells, and the cells were irradiated with a 137Cs γ-ray irradiation source. HeLa cells were divided into control group (HeLa siCtrl), knockdown NRF2 group (HeLa siNRF2), irradiation group (HeLa siCtrl+8 Gy), and knockdown NRF2+ irradiation group (HeLa siNRF2+8 Gy). An immunofluorescence assay was used to detect the number of γH2AX foci in HeLa cells. Inter-group comparisons of measures conforming to normal distribution were performed by two independent sample t-tests (chi-squared). Results (1) After 8 Gy irradiation for 6, 12, and 24 h, the number of γH2AX foci in HeLa siEGFR+8 Gy were more than that HeLa siCtrl ((94.00±1.00)% vs. (89.67±2.03)%, (72.33±1.76)% vs. (60.00±1.73)%, (43.00±2.31)% vs. (26.33±1.20)%), and the differences were statistically significant (t=3.919, 4.989, 6.402; all P<0.05). The HeLa siEGFR+8 Gy impaired radiation-induced G2/M phase cell cycle block compared with the HeLa siCtrl, ((46.53±3.06)% vs. (37.90±4.61)%), and the difference was statistically significant (t=4.384, P<0.05). Compared with the HeLa siCtrl, HeLa siEGFR+8 Gy inhibited the radiation induced decrease in HO-1 expression by 66.66%(1.35±0.10 vs. 0.45±0.02), and the difference was statistically significant (t=8.782, P<0.05). The level of NRF2 protein in the nucleus was reduced after knocking down EGFR, and the radiation-induced activation level of the ATR-CHK1 signaling pathway downstream of NRF2 and the level of HO-1 protein were reduced. (2) After 8 Gy irradiation for 6, 12, and 24 h, the number of γH2AX foci in HeLa siNRF2+8 Gy was more than that HeLa siCtrl ((96.67±0.88)% vs. (89.67±2.03)%, (77.33±1.20)% vs. (60.00±1.73)%, (54.33±2.19)% vs. (26.33±1.20)%), and all differences were statistically significant (t=3.166, 4.989, 11.220; all P<0.05). Conclusions Under ionizing radiation conditions, knocking down EGFR can reduce the nuclear translocation of NRF2 protein, inhibit the activation of the ATR-CHK1 signaling pathway and the downstream expression of the HO-1 gene, and decrease the DNA damage repair capacity of human cervical cancer HeLa cells.
Exosome-mediated T cell activation by mouse lung epithelial MLE-12 cells irradiated with 60Co γ ray
Zhixin Wang, Meiyu Wang, Haoxin Guo, Li Du, Yilong Wang, Zhihua Yang, Maoxiang Zhu
2023, 47(4): 220-228. doi: 10.3760/cma.j.cn121381-202304003-00296
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Objective To evaluate T cell activation driven by exosomes from mouse lung epithelial MLE-12 cells (MLE-12 cells) irradiated with 60Co γ ray. Methods MLE-12 cells were divided into a control group and a 60Co γ irradiation group (2, 4, 6, and 8 Gy), and exosomes were extracted from the supernatant of their culture medium by using ultracentrifugation. Nanoparticle tracking analysis and transmission electron microscope were used to determine the morphological structure and quantity of exosomes. The expression of lysosomal associated membrane protein (CD63), tetraspanin (CD81), tumor susceptibility gene (TSG101), and type Ⅰ endoplasmic reticulum protein (Calnexin) in exosomes were identified by Western blot (WB). Flow cytometry (FCM) was used to detect the expression of major histocompatibility complex class Ⅰ (MHC Ⅰ), major histocompatibility complex class Ⅱ (MHC Ⅱ), immune regulatory protein B7-1 (CD80), and immune regulatory protein B7-2 (CD86) on the surface of exosomes. Naive T cells isolated from mouse spleens were cocultured with exosomes (exo/NC MLE) secreted by MLE-12 cells in the control group (NC MLE-12) and exosomes (exo/IR MLE) secreted by MLE-12 cells in the 6 Gy 60Co γ irradiation group (IR MLE-12), respectively. FCM was used to detect the changes of T cell subsets CD3+, CD4+, and CD8+ and their activated proliferation indicators T cell specific surface glycoprotein CD28 and early activation antigen 1 (CD69). Naive T cells were incubated with NC MLE-12, IR MLE-12, and MLE-12 cells from exosome inhibitor GW4869-treated groups, respectively. FCM was used to detect the changes of T cell subsets CD3+, CD4+, and CD8+ and their activation indicators CD28 and CD69. Independent samples t-test was used for comparison between two groups. Analysis of variance was used to compare multiple groups. Bonferroni adjustment was applied for pairwise comparison between two groups. Results The exosomes produced from MLE-12 cells showed a typical saucer-like structure, with a particle size of 30–150 nm. WB results showed that the exosomes specific markers CD63, CD81, and TSG101 were highly expressed in exosomes, but the negative marker Calnexin was low in expression, compared with the MLE-12 cells. Compared with the control group, at different times after 6 Gy γ ray irradiation, the number of exosomes secreted by a single MLE-12 cell increased at 24 and 48 hours (t=5.36, 6.66, both P<0.05). The phenomenon of an increase in the number of exosomes secreted by a single MLE-12 cell 24 hours after irradiation with different doses of γ rays has a dose-effect relationship, and the difference is statistically significant at doses of 6 and 8 Gy (t=4.14, 5.67, both P<0.05) after the MLE-12 cells were irradiated with γ ray. The expression levels of MHC Ⅰ, MHC Ⅱ, CD81, and TSG101 increased in exo/IR-MLE compared with exo/NC-MLE. FCM results showed that the expression levels of MHC Ⅰ, MHC Ⅱ, CD80, and CD86 increased in exo/IR-MLE compared with exo/NC-MLE (t=4.04–6.47, all P<0.05). Compared with the exo/NC-MLE, in the T cells cocultured with exo/IR-MLE, the CD3+, CD4+, and CD8+ T cells all proliferated (t=3.08–5.88, all P<0.05), and the expression levels of CD28 and CD69 increased (t=3.02–8.65, all P<0.05). The exosome inhibitor GW4869 can suppress T cell activation induced by IR MLE-12 (t=3.64–23.03, all P<0.05). Conclusion Exosomes from MLE-12 cells irradiated with 60Co γ ray could activate T cells through antigen presentation.
Analysis of quality control test results of medical digital radiography in Liaoning Province from 2021 to 2022
Xin Zhao, Guangpeng Li, Hezheng Zhai, Xunming Cai
2023, 47(4): 229-235. doi: 10.3760/cma.j.cn121381-202208009-00278
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Objective To analyze the quality control test results of medical digital radiography (DR) equipment in Liaoning Province in 2021 to 2022 and understand the quality status of DR equipment to provide a reference for the hospitals to strengthen the quality management of DR equipment. Methods Using the convenient sampling method, 75 medical DR equipment in use in 59 hospitals in Liaoning Province from 2021 to 2022 were selected as the research objects. The relevant equipment was used in accordance with the WS76—2020 Specification for Testing of Quality Control in Medical X-ray Diagnostic Equipment to test the general and special items of DR equipment from different manufacturers, observe whether the DR equipment has automatic exposure control (AEC) function and damage, and whether the equipment can obtain preprocessed images and pixel values. An independent sample t-test was used to compare the detection indexes of general and special items on different brands of equipment. The Kruskal-Wallis H test was utilized to compare the detection indexes among different brands of equipment. Results Among the 75 DR equipment, Siemens AG, Germany, accounted for 11% (8/75), Shanghai United Imaging Healthcare Co., Ltd. accounted for 38% (29/75), Beijing Wandong Medical Technology Co., Ltd. accounted for 13% (10/75), Neusoft Medical Systems Co., Ltd., Shenyang, accounted for 7% (5/75), and other companies accounted for 31% (23/75). The qualification rate of tube voltage indication and four side deviations between the light and irradiation fields detected by DR general testing projects in other companies is 96% (22/23). A total of 55% (41/75) of the equipment failed to detect AEC repeatability, AEC response, and consistency between AEC ionization chambers. In specialized testing projects, the qualification rate of ranging error in other companies is 88% (15/17) and that of other testing items is 100%. Meanwhile, 51% (38/75) of equipment cannot detect detector dose indication, signal transmission characteristics, and response uniformity. A total of 15% (11/75) of the tested equipment has no measuring tools, resulting in measurement errors that cannot be calculated. A total of 40% (30/75) of the equipment have high and low contrast resolutions based on the survey results as the baseline value. Except for the undetected equipment, the remaining equipment accounted for 26% (10/38) of the baseline values for detector dose indication based on the survey results. In the special test items, the qualified rate of distance measuring error in other companies was 88% (15/17) and that of other test items was 100%. No significant difference was observed between the general and special test indexes among brands of equipment (H=0.34–9.38, all P>0.05). Conclusions The results suggested that the hospital should entrust qualified units to test the status of DR equipment annually to debug the equipment in time and ensure the accuracy of DR. At the same time, some DR equipment in hospitals lack detection functions and testing projects. The health administrative supervision department should provide standards for DR equipment testing in hospitals as soon as possible, and strengthen the supervision and inspection of DR equipment quality control.
Review Articles
Study on the application of 18F-FDG uptake assessment in PET/CT of lung cancer
Xinyue Tian, Yitong Luo, Tianqi Jiang, Xuemei Wang
2023, 47(4): 236-242. doi: 10.3760/cma.j.cn121381-202210020-00295
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18F-fluorodeoxyglucose (FDG) PET/CT is a non-invasive imaging modality that is widely used to assess lung cancer. This technique provides valuable insights into tumor heterogeneity and is thus a fundamental tool for the early diagnosis, accurate staging, early therapeutic response assessment, and prognostic evaluation of lung cancer. In PET/CT, semi-quantitative evaluation is commonly used to assess 18F-FDG uptake in tumors. The process utilizes objective parameters to depict tumor metabolic characteristics. However, in multi-center analyses of 18F-FDG PET/CT images, the standardization of uptake value proves challenging, thereby hindering the widespread implementation of semi-quantitative evaluation in clinical practice. Conversely, visual evaluation method is a simpler, more feasible, and highly repeatable alternative that is less susceptible to external factors. In this study, the author critically appraises the application and limitations of 18F-FDG uptake evaluation in PET/CT imaging of lung cancer.
Application value of PET/CT in preoperative localization of primary hyperparathyroidism and new advances in preoperative localization imaging
Yujia Zhao, Xia Bai
2023, 47(4): 243-248. doi: 10.3760/cma.j.cn121381-202301012-00291
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Primary hyperparathyroidism (PHPT) is a common endocrine disease, which is usually caused by hyperparathyroidism. Surgical resection of hyperfunctional lesions is the main treatment for PHPT, and correct location of the lesions is very important to guide the minimally invasive surgical treatment of PHPT patients. PET/CT has been used as the first-line imaging method for preoperative localization of parathyroid adenoma, and how to screen the patients suitable for PET/CT from the serum biochemistry has become the focus of clinical application, as well as the analysis of its relationship with PET related parameters from the level of pathology and immunohistochemistry is the focus of current research. This article mainly analyzes the relationship between biochemical level, pathological information, immunohistochemical analysis and PET/CT related parameters of PHPT, providing guidance for the clinical application of PET, and further introducing the new imaging progress of preoperative localization of PHPT.
Application of MRI and PET imaging in early diagnosis of Alzheimer disease
Lijie Bao, Zilong Zhao, Ning Su, Maorong Zhou
2023, 47(4): 249-253. doi: 10.3760/cma.j.cn121381-202211009-00288
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Alzheimer disease (AD) is one of the most common progressive neurodegenerative diseases, which seriously threatens the life and health of patients. Early diagnosis and intervention can slow down or even reverse the progression of the disease. At present, MRI and PET imaging have been applied in the diagnosis of AD, which have unique advantages in the early diagnosis of AD. The authors focus on the application of structural MRI, functional MRI and PET imaging in the early diagnosis of AD.
Mechanism and research progress of radiation bystander effect
Tianxing Ma, Jintian Li, Yi Zhang, Jianqing Liang
2023, 47(4): 254-260. doi: 10.3760/cma.j.cn121381-202210012-00297
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A deep understanding of radiobiology theory is essential for studying the effects of radiation. Radiation bystander effect (RIBE) has become a research hotspot in the field of radiobiology since its discovery. The direct and indirect effects of radiation on targeted and non-targeted cells, tissues, and organs profoundly affect the progress and outcome of radiotherapy for malignant tumors. Up to now, a large number of experimental studies have been conducted in vitro and in vivo to reveal the mechanism of RIBE. The exogenous mediators generated by radiation migrate into the adjacent tissues or cells, stimulating the activation of various signaling pathways, leading to immune and inflammatory responses, epigenetic regulation, and radiation-induced carcinogenic transformation. This paper reviews the research status and mechanism of RIBE in order to provide a theoretical basis for the development of new drugs for radiation protection and improvement of radiotherapy efficacy.
Case Report
Misdiagnosis of struma ovarii with peritoneal metastasis by 18F-FDG PET/CT imaging: a case report
Lijie Bao, Zilong Zhao, Ji Zhang, Hui Yang, Jianfei Wu, Maorong Zhou
2023, 47(4): 261-264. doi: 10.3760/cma.j.cn121381-202206014-00293
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Struma ovarii is a rare disease in which the tumor is composed entirely of thyroid tissue, or thyroid tissue accounts for more than 50% of the total tumor. The author reported a case of a patient with struma ovarii with peritoneal metastasis who received medical treatment due to persistent abdominal distension. The characteristics of the case were analyzed according to the clinical manifestations, laboratory examination and imaging findings of the patient. Combined with relevant literatures, the imaging manifestations and causes of misdiagnosis of struma ovarii were further reviewed, so as to provide clinical basis for early diagnosis.