2021 Vol. 45, No. 4

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2021, 45(4): 0-0.
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2021, 45(4): 1-4.
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Basic Science Investigation
Protective effects of N-oxalyl-D-phenylalanine on hematopoietic system injury induced by ionizing radiation in mice
Haikang Tang, Yuanyuan Meng, Xin Meng, Wei Long, Xiaoliang Zhou, Wenqing Xu
2021, 45(4): 205-213. doi: 10.3760/cma.j.cn121381-202103021-00048
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Objective To study the protective effects of N-oxalyl-D-phenylalanine (NOFD) on the radiation injury of hematopoietic system in mice. Methods Eighteen healthy C57BL/6J male mice aged 6−8 weeks were divided into three groups with six mice each according to randomized block design: a control group, a 4 Gy γ ray whole body irradiation group (TBI group), and a 4 Gy γ ray whole body irradiation + 5 mg/kg NOFD group (TBI+NOFD group). The mice in the TBI+NOFD group were intraperitoneally given with 5 mg/kg NOFD at 2, 16 h before irradiation, and 3 d after irradiation, respectively, while the control group and TBI group were intraperitoneally given with the same amount of normal saline at the same time as that in the TBI+NOFD group. The number of peripheral blood cells in each group of mice were analyzed using a blood cell counter. The percentage of B cells, T cells, and myeloid cells in peripheral blood were detected via flow cytometry. The number and percentage of hematopoietic stem cell (HSC) and hematopoietic progenitor cell (HPC) in bone marrow cells were detected via flow cytometry. Levels of phosphorylated histone H2AX (γ-H2AX) and mitochondrial reactive oxygen species in bone marrow cells were detected via flow cytometry. The proliferation ability of bone marrow cells was evaluated by counting colony-forming units-granulocyte-macrophage (CFU-GM) and colony-forming units-spleen(CFU-S). Student's t test was used for comparison between two groups. Results Compared with that in the TBI group, the number of peripheral blood erythrocytes in the TBI+NOFD group substantially increased ((9.05±0.16)×109/mL vs. (9.57±0.15)×109/mL). The percentage of T cells increased ((11.54±0.20)% vs. (15.31±1.88)%), whereas the percentage of myeloid cells decreased ((32.67±2.87)% vs. (24.90±2.19)%). The number of HSC increased ((2.24±0.54)×103/femur vs. (6.77±1.67)×103/femur), whereas the percentage of HSC and HPC in bone marrow cells significantly increased ((0.09±0.02)% vs. (0.59±0.13)%, (0.62±0.14)% vs. (1.82±0.43)%; t=1.998−3.633, all P<0.05). The median fluorescence intensity (MFI) of mitochondrial reactive oxygen species (MitoSOX) in bone marrow nucleated cells (BMNC) and HPC in the TBI+NOFD group was significantly lower than that in the TBI group ((6.66±0.56)×103 vs. (3.19±0.25)×103, (2.51±0.46)×103 vs. (1.20±0.35)×103; t=6.350, 2.282, both P<0.05). Moreover, the MFI of γ-H2AX in BMNC, HPC, and HSC in the TBI+NOFD group was significantly lower than that in the TBI group ((10.25±0.77)×103 vs. (7.22±0.15)×103, (18.37±2.52)×103 vs. (12.44±0.34)×103, (26.05±2.64)×103 vs. (17.16±1.20)×103; t=4.356, 2.577, 3.070, all P<0.05). Compared with those in the TBI group, CFU-GM (12.33±1.48 vs. 24.00±3.92) and CFU-S (6.00±1.07 vs. 10.83±1.01) in the TBI+NOFD group significantly increased (t=2.788, 3.288; both P<0.05). Conclusion NOFD exerts an obvious protective effect on the radiation injury of hematopoietic system in mice.
Effects of CRIM1 on radiosensitivity and metastasis of non-small cell lung cancer
Kejun Li, Wenyue Zhao, Na Li, Yan Wang, Qiang Liu, Liqing Du
2021, 45(4): 214-223. doi: 10.3760/cma.j.cn121381-202101046-00042
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Objective To investigate the effects of cysteine-rich motor neuron protein 1 (CRIM1) on radiosensitivity and metastasis of non-small cell lung cancer (NSCLC) and its possible mechanisms. Methods Short hairpin RNA (shRNA) was used to knock down the expression level of CRIM1 in NSCLC cells H460 and H358, and H460 and H358 cells were divided into three groups respectively: H460, H460-shCRIM1, H460-shNC, and H358, H358-shCRIM1, H358-shNC, where shCRIM1 indicates the knockdown of CRIM1 expression level by shRNA and shNC indicates the negative control. Small interfering RNA was used to knock down the expression of CRIM1 in H358 cells, and the cells were divided into two groups: H358-siNC and H358-siCRIM1. Clone formation assay (irradiation dose of 0, 1, 2, and 4 Gy), comet assay (irradiation dose of 8 Gy), and cellular immunofluorescence assay (irradiation dose of 6, 8, and 12 Gy) were used in observing the effect of CRIM1 on the radiosensitivity of H460 cells. Transwell and cell adhesion assays were used in observing the effect of CRIM1 on cell metastasis in vitro. A mouse in situ tumor model was constructed, and the metastasis of tumors inoculated in situ into nude mouse lungs was assessed using histopathological examination, and transcriptomic analysis was used in exploring the possible effects of CRIM1 on the mechanism of NSCLC cell metastasis. Independent samples t-test was used in comparing groups. Results Clone formation assay showed statistically significant differences between the clone formation rates of H460-shNC and H460-shCRIM1 after 1 and 2 Gy of irradiation ((1 Gy: (87.04±8.04)% vs. (58.01±4.39)%, t=4.48, P<0.05; 2 Gy: (48.23±1.22)% vs. (31.43±0.08)%, t=19.50, P<0.05)). The results of comet assay showed that the olive tail moment of H460-shCRIM1 cells after 8 Gy of irradiation was longer than that of H460-shNC cells, and the difference was statistically significant (1.27±0.54 vs. 1.05±0.42, t=2.14, P<0.05). The results of cell immunofluorescence experiments showed that the number of phosphorylated histone H2AX foci was higher in H460-shCRIM1 cells than in H460-shNC after irradiation (6 Gy: 14.33±2.81 vs. 11.00±3.92; 8 Gy: 34.00±11.14 vs. 21.17±6.15; 12 Gy: 25.80±3.96 vs. 20.17±3.31), and the difference was statistically significant (t=2.45, 5.52, 2.47; all P<0.05). Transwell assay showed that the mobility rates of H460-shCRIM1 and H358-shCRIM1 were significantly higher than those of H460-shNC and H358-shNC, respectively, and the differences were statistically significant (t=4.73, 10.19; both P<0.05). The results of cell adhesion assay showed that the adhesion ability of H460-shCRIM1 and H358-shCRIM1 decreased relative to that of H460-shNC and H358-shNC, respectively, and the difference was statistically significant (t=2.86, 3.66; both P<0.05). Histopathological examination results showed the in situ inoculation of H460-shCRIM1 into nude mice. Intrapulmonary metastases of H460-shCRIM1 were more extensive than those in H460-shNC. Transcriptomic analysis showed that the expression levels of the screened cell adhesion-related genes junctional adhesion molecule 2 (JAM2), nectin cell adhesion molecule 3 (NECTIN3), and claudin 4 (CLDN4) decreased in H460-shCRIM1 and H358-siCRIM1, and this result was verified in in vitro experiments. The expression levels in H460-shCRIM1 decreased by 86.66% (JAM2), 49.35% (NECTIN3), and 30.27% (CLDN4) compared with those in H460-shNC (t=47.52, 7.47, 18.98; all P<0.05), and in H358-siCRIM1 decreased by 36.60% (JAM2), 31.70% (NECTIN3), and 50.00% (CLDN4) compared with those in H358-siNC (t=7.40, 7.10, 16.56; all P<0.05). Conclusion The inhibition of CRIM1 enhances the radiosensitivity of NSCLC cells H460, and CRIM1 may influence NSCLC metastasis by affecting tumor cell junctions.
Identification of radiation injury mouse urine by Caenorhabditis elegans
Xueying Zhang, Tong Zhu, Saijun Fan
2021, 45(4): 224-230. doi: 10.3760/cma.j.cn121381-202103013-00049
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Objective To study the relationship between urine tendency of Caenorhabditis elegans (C. elegans) to irradiated mice and administration dose and time of radiation. Methods A total of 168 C57/BL6 mice were divided into control group and irradiation group by randomized block design. The irradiation group was treated with 137Cs γ total body irradiation with 0.84 Gy/min. Mice and wild-type C. elegans were used to perform experiments with the following treatments: (1) crawling test at different time points after irradiation; the mice were divided into 7.5 Gy irradiation group and control group (n=12). After 7.5 Gy total body irradiation, urine samples were collected at 0, 2, 4, 8, 24, 48, and 72 h. (2) Crawling test after different doses of irradiation; the mice were divided into 2, 4, and 6 Gy irradiation groups and control groups (n=12). Urine samples were collected at 24 h after irradiation. (3) Orthogonal experiment between irradiation time and dose; the mice was divided into 2, 4, and 6 Gy irradiation groups and control groups (n=12), and urine samples were collected at 4, 8, and 24 h after irradiation. (4) Fan test and heating test; the urine samples were collected from 7.5 Gy total body irradiation mice after 24 h, accompanied by a blow on one side of the petri dish or heating of the urine prior to crawling test. C. elegans were cultured to L3 larval stage, and the urine of each group was dripped to different areas of the culture dish. The percentage of C.elegans in each area was observed and calculated under stereomicroscope. Independent-sample t test and paired t test were used for comparison between groups. Results (1) Crawling test at different time points after irradiation: C. elegans began to gather at 8 h after 7.5 Gy irradiation. Compared with the control group, significant differences in the percentage of C. elegans were observed at 8, 12, 24, 48, and 72 h after irradiation in the irradiation group (t=4.073−67.518, all P<0.01). (2) Crawling test after different doses of irradiation: compared with the control group, the percentages of C. elegans in the urine area of the 2, 4, and 6 Gy irradiation groups were increased ((69.58±7.00)%, (84.42±5.55)%, and (88.58±3.45)%, respectively, and (29.33±5.79)%, (11.58±3.60)%, and (9.08±2.19)% in the control group), and the differences were statistically significant (t=11.955, 30.320, 51.463; all P<0.001). (3) Orthogonal experiment between irradiation time and dose: compared with the control group, the percentages of C. elegans in the urine of mice showed significant differences at 8, 24 h after 2, 4, and 6 Gy irradiation (t=17.628−133.349, all P<0.001). (4) After the fan test, approximately (3.17±1.37)% C. elegans were distributed in the irradiation group and (2.38±1.26)% in the control group, without significant difference (t=1.250, P>0.05). The results of heating test showed a significant difference in the overall weight of urine before and after heating ((1.060±0.028) g vs. (1.051±0.026) g, t=11.814, P<0.001). Approximately (17.46±11.00)% C. elegans were distributed in the irradiation group and (12.70±9.91)% in the control group, but no significant difference was found between the two groups (t=0.585, P>0.05). Conclusion C. elegans have a tendency of volatile metabolites in urine of irradiated mice and can distinguish low-dose irradiation.
Diagnostic value of 18F-FDG micro-PET/CT in rat models of intracerebral hemorrhage in vivo
Fanhui Yang, Chaoxian Yang, Chunyin Zhang
2021, 45(4): 231-236. doi: 10.3760/cma.j.cn121381-202003023-00045
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Objective To assess the diagnostic value of 18F-fluorodeoxyglucose (FDG) micro-PET/CT in evaluating an intracerebral hemorrhage (ICH) model in rats in vivo. Methods A simple random sampling method was used to select 32 healthy male adult SD rats, 4 of which were placed in the sham operation group and 28 rats were injected with 0.125 U/µL collagenase Ⅳ into the right basal ganglia to induce ICH (ICH model group). In the sham operation group, 0.9% saline was used instead of collagenase Ⅳ to make the sham model. The ICH model group was divided into seven groups by simple random sampling according to the time after ICH, which were 6, 24, 48 h and 3, 5, 7, 14 d (4 rats in each group). The sham operation and seven ICH model groups (6, 24, 48 h and 3, 5, 7, 14 d) underwent the neurological impairment scoring and 18F-FDG micro-PET/CT imaging. The hematoma volume at each time point in the ICH model group was calculated according to 18F-FDG micro-PET/CT imaging to delineate the region of interest (ROI) and Tada's formula. After imaging, the head was decapitated and the brain was obtained for hematoma observation and histopathological examination. The hematoma volume obtained by the two methods at the same time was compared by paired t-test and evaluated by Pearson correlation analysis. Results In the sham operation group: the neurological impairment scores were zero; and micro-PET/CT clearly showed homogeneous 18F-FDG uptake in the brain tissue. The ICH model group: the neurological impairment scores were (2.21±0.30), (3.51±0.66), (2.83±0.20), (2.12±0.50), (1.44±0.37), (1.02±0.25) and (0.51±0.12) at 6, 24, 48 h and 3, 5, 7, 14 d after ICH, respectively. At each time point, the 18F-FDG uptake decreased or became defective in the right basal ganglia of the rat brain. The cerebral hematoma volumes evaluated by 18F-FDG micro-PET/CT were (24.05±3.00), (27.19±1.25), (25.58±1.57), (21.94±0.98), (19.88±1.53), (18.35±2.11) and (16.29±1.53) mm3, respectively. The cerebral hematoma volumes evaluated by Tada's formula were (23.17±1.93), (26.09±1.35), (24.64±1.95), (21.31±1.32), (19.07±1.64), (17.29±1.38), and (15.63±1.98) mm3, respectively. No significant difference in the hematoma volume was found between two methods at each time point in the ICH model group (t=1.18−3.06, all P>0.05). The cerebral hematoma volume obtained by the two methods was significantly positively correlated (r=0.99, P<0.001). After the dissection of the ICH model group, irregular hematoma formation was seen in the right basal ganglia of the brain tissue, which was opposite to the radioactive sparse and defective areas shown by 18F-FDG micro-PET/CT. Conclusion 18F-FDG micro-PET/CT can accurately display the position, shape and size of the hematoma after ICH, and thus can be to verify the success of the rat ICH model in vivo.
Meta Analysis
Therapeutic efficacy of condyloma acuminata by using 90Sr applicator and CO2 laser: a meta-analysis
Long Zheng, Xiaojie Dou, Jingang An, Xiaoshuang Tang, Xianghong Zheng, Wei Qu
2021, 45(4): 237-241. doi: 10.3760/cma.j.cn121381-201912026-00028
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Objective To evaluate the therapeutic effects of 90Sr applicator and CO2 laser treatment on condyloma acuminata (CA). Methods Searched PubMed, China national knowledge infrastructure, Wanfang, cqvip, and other literature databases for Chinese and English articles related to the use of 90Sr applicator and CO2 laser treatment for patients with CA from 2000 to 2017. Eligible studies were collected according to the inclusion and exclusion criteria. The Jadad scal was used to evaluate the quality of the included articles. The standard used a 0–5 point scoring method. A score of ≤2 was regarded as low-quality evidence, and a score of ≥3 was regarded as high-quality evidence. Meta-analysis was performed on count data by using Stata 12.0 software to calculate pooled odds ratio (OR) and 95% confidence interval (CI). χ2 test was used to assess the heterogeneity of the articles, and Begg's test and funnel plot method were used to detect the publication bias of the included articles. Results This work included three eligible Chinese studies (a total of 228 patients) published from 2003 to 2011. The Jadad scores of the three articles were 4, 4, and 3 points, respectively. Heterogeneity was not detected among the included articles (cure rate: I2=0, P=0.685; recurrence rate: I2=0, P=0.954). The Begg's test (Z=0.045, P>0.05) and the funnel plot method showed no publication bias among the included articles. The merge OR of 90Sr applicator on the cure rate of CA was 1.05, with 95%CI of 0.72–1.54. The merge OR of 90Sr applicator on the recurrence rate of CA was 0.06, with 95%CI of 0.02–0.24. Conclusion 90Sr applicator is an effective clinical treatment that has similar therapeutic effects and lower recurrence rate than CO2 laser.
Trends in Deinococcus radiodurans research based on bibliometrics
Bibo Liu, Huixian Zeng, Yuting Xie, Le Tan, Yan Tang
2021, 45(4): 242-250. doi: 10.3760/cma.j.cn121381-202005027-00047
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Objective To analyze the research status of radiation-resistant abnormal cocci, Deinococcus radiodurans, at home and abroad; identify frontier and hot issues; and preliminarily evaluate future development and prospects in order to provide information and direction for further research. Methods Numerous publications from the Web of Science and China national knowledge infrastructure were examined. Advanced search was used to search for relevant literatures between 2009 and 2018 that contain the keyword "Deinococcus radiodurans". Literature research covered the full spectrum of major indicators, such as the number of literatures published, journals published, author information, keywords, and countries. CiteSpace V.5.5, an authoritative tool for the visual analysis of literatures at home and abroad, was used to analyze the above information. in a multi-dimensional, time-sharing and dynamic way, to explore the relationship among the indicators and analyze the development trends, hotspots, and frontier fields of research. Results A total of 1026 English literatures and 157 Chinese literatures were reviewed. Statistical analyses revealed that the number of English literatures is stable but there is a small fluctuation decline trend in the past 10 years. By contrast, the number of Chinese literatures has fluctuated during the same period. However, the citation of Chinese literatures is increasing year after year. Among Chinese literatures, Hua YJ (Hua Yuejin) ranked first with 48 English papers, and Chen Ming has published the most in Chinese literatures with 14 papers. The main international journals are Plos One and Journal of Biological Chemistry, and the most popular domestic journal is the Journal of Nuclear Agricultural Sciences. The main research institutions are universities and atomic research centers, and the top three countries are America, China and France. Their studies focused on the resistance genes of Deinococcus radiodurans, but their specific research directions are scattered. Conclusions Current research on Deinococcus radiodurans is focused on its resistance genes. Therefore, the mechanism of its radiation resistance will still be a research hotspot in the future, and its application in medical treatment, agriculture, and environmental governance has a lot of room for exploration.
Review Article
Progress of 99Tcm-3PRGD2 SPECT/CT molecular imaging in the diagnosis and treatment of breast cancer
Jingfen Kang, Haiyan Liu, Caihong Li, Zhiyong Shi
2021, 45(4): 251-256. doi: 10.3760/cma.j.cn121381-202012038-00040
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Breast cancer is the most common malignant tumor in women. 99Tcm-hydrazino-nicotinamide(HYNIC)-(poly-(ethylene glycol), PEG)4-Glu (cyclo(Arg-Gly-Asp-D-Phe-Lys(PEG4)))2 (99Tcm-3PRGD2) is a kind of artificial synthesized molecular tracer, which can be used to SPECT/CT for breast cancer imaging. 99Tcm-3PRGD2 SPECT/CT can be used for early diagnosis, accurate staging and molecular typing of the breast cancer. Selecting the treatment regimen according to the result of 99Tcm-3PRGD2 SPECT/CT is helpful to reduce the mortality of patients and improve the quality of life of patients. The application progress of 99Tcm-3PRGD2 SPECT/CT in the diagnosis of breast cancer is reviewed and prospected in this paper.
Application of brachytherapy in the treatment of esophageal cancer
Xin Guo, Dongmei Han, Hongfu Zhao, Guanghui Cheng
2021, 45(4): 257-263. doi: 10.3760/cma.j.cn121381-202003049-00031
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Esophageal cancer is a common digestive system tumor. Surgery and radiotherapy are the most important radical treatment options for esophageal cancer. Radiotherapy has good curative effects for all stages of esophageal cancer, and external beam radiotherapy is the main method. Brachytherapy (BT), as a branch of radiotherapy, plays an auxiliary role in the treatment of esophageal cancer. Since the esophagus is the natural lumen of human body, intracavitary BT is used to treat local esophageal tumors; interstitial BT is used to treat recurrent metastatic lesions. This paper reviews the application of BT in the treatment of esophageal cancer from the aspects of technique, source applicator, target area delineation and dosage regimen.
Case Report
Contrast-enhanced CT and 18F-FDG PET/CT imaging of multiple intrapulmonary solitary fibrous tumor: a case report
Huimin Li, Juzhen Liu
2021, 45(4): 264-266. doi: 10.3760/cma.j.cn121381-202005006-00037
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Most solitary fibrous tumors (SFT) originate from the visceral pleura, and some from the parietal pleura, and intrapulmonary SFT is very rare. Contrast-enhanced CT examination is of great value in the diagnosis and differentiation of intrapulmonary SFT. PET/CT is an important examination method to evaluate the tumor size, invasion range and distant metastasis. Although the imaging features of intrapulmonary SFT have certain characteristics, its diagnosis depends on histopathological examination. The authors reported a case of intrapulmonary SFT. The characteristics of the disease were analyzed on the basis of clinical symptoms, contrast-enhanced CT and 18F-FDG PET/CT imaging findings as well as pathological diagnosis and differential diagnosis, and through literature review, the understanding of the disease was improved.
MSCT diagnosis and differential diagnosis of rare greater omentum infarction in children: two cases report
Yan Sun, Chunxiang Wang, Zhibin Hou, Hong Yang, Bin Zhao
2021, 45(4): 267-270. doi: 10.3760/cma.j.cn121381-202005002-00039
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The authors reported 2 cases of multislice spiral CT (MSCT) imaging findings with the greater omentum infarction in children, and summarized the diagnostic value of MSCT for the disease. Greater omentum infarction in children is relatively rare, and the clinical manifestation of the disease is not specific, the onset is similar to acute appendicitis or cholecystitis. For diagnosing the disease of the omentum infarction, ultrasound shows limitations, whereas the MSCT is the major method and has the specificity in the diagnosis. In children with secondary omental torsion and infarction, the disease progresses rapidly, and it is easy to be complicated with diffuse peritonitis without timely and accurate diagnosis and treatment, which endangers the lives of children. MSCT is helpful for showing the degree, extent, and complications of this disease and can be the first method used to avoid missed or erroneous diagnosis.