2021 Vol. 45, No. 1

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2021, 45(1): -1--1.
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2021, 45(1): 0-0.
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2021, 45(1): 1-2. doi: 10.3760/cma.j.cn121381-202011038-00007
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Clinical Investigation
Diagnostic accuracy and correlation between cerebrospinal fluid biomarkers and 11C-PIB PET/CT imaging in Alzheimer disease
Xiaodan Wu, Ying Zhan, Jia Guo, Yufeng Chen, Shanhu Hao, Guoxu Zhang, Zhiguo Wang
2021, 45(1): 3-9. doi: 10.3760/cma.j.cn121381-202004019-00003
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Objective To investigate the diagnostic accuracy and correlation between cerebrospinal fluid biomarkers and 11C-Pittsburgh compound-B (PIB) PET/CT imaging in Alzheimer disease (AD). The optimal cut-off values of cerebrospinal fluid biomarkers are also determined. Methods The clinical data of 66 subjects who underwent 11C-PIB PET/CT imaging and lumbar puncture at the General Hospital of Northern Theater Command from January 2011 to March 2020 were retrospectively analyzed. The participants included 32 males and 34 females aged 61–82 (71.0±3.4) years and were divided into the AD patient group (n=50) and the healthy control group (n=16) according to established criteria. Enzyme-linked immunosorbent assay was used to detect levels of the cerebrospinal fluid biomarkers α-synuclein (α-syn), β-amyloid (Aβ) 40, Aβ42, t-tau and p-tau. The level ratios of t-tau to Aβ42 (t-tau/Aβ42) and Aβ42 to Aβ40 (Aβ42/Aβ40) were calculated. The receiver operator characteristic (ROC) curve was used to analyze the diagnostic optimal cut-off value, sensitivity, and specificity of the cerebrospinal fluid biomarkers. 11C-PIB PET/CT images were analyzed. The average Aβ deposition standardized uptake value ratio (SUVR) was calculated, and the accuracy and correlation between the two groups of cerebrospinal fluid biomarkers and 11C-PIB PET/CT imaging in the diagnosis of AD were analyzed. The levels of cerebrospinal fluid biomarkers between the two groups was compared by independent-sample t test, and the count data were compared by χ2 test. Pearson correlation coefficients were calculated for correlation analysis, and consistency was determined using the Kappa test. Results The levels of cerebrospinal fluid biomarkers α-syn, t-tau andp-tau as well as t-tau/Aβ42 in the AD patient group were higher than those in the healthy control group (t=2.315, 4.001, 2.336, 3.291, all P<0.01), while the Aβ42 level and Aβ42/Aβ40 were lower than those in the healthy control group (t=−5.443, −3.487, both P<0.05). T-tau/Aβ42 revealed the highest diagnostic accuracy for AD (AUC=0.892, P<0.001), followed by Aβ42/Aβ40 and α-syn (AUC=0.865, 0.795, both P<0.01). The optimal cut-off values of t-tau/Aβ42 and Aβ42/Aβ40 were 0.509 and 0.072, respectively, and the aptimal cut-off value of α-syn was 465 pg/mL. The sensitivities of t-tau/Aβ42, Aβ42/Aβ40, α-syn and 11C-PIB PET/CT imaging for predicting AD were 80.0% (40/50), 76.0% (38/50), 74.0% (37/50) and 78.0% (39/50), respectively. The sensitivities of the first three methods in combination with 11C-PIB PET/CT imaging for predicting AD were 96.0% (48/50), 94.0% (47/50) and 94.0% (47/50), respectively, which were all higher than a single method (χ2=5.316–7.440, all P<0.05). The combined diagnostic accuracy of t-tau/Aβ42 and 11C-PIB PET/CT imaging was greater than that of a single diagnostic method (93.9% vs. 80.3%, 93.9% vs. 77.2%), and the difference noted was statistically significant (χ2=5.469, 7.439, both P<0.05). T-tau/Aβ42, Aβ42/Aβ40 and α-syn level were significantly correlated with 11C-PIB PET/CT SUVR (r=0.555, −0.451, 0.445, all P<0.01). The Kappa value of diagnostic consistencies of t-tau/Aβ42, Aβ42/Aβ40 and α-syn with 11C-PIB PET/CT imaging were 0.769, 0.623 and 0.587, respectively (all P<0.001). Among the criteria considered, t-tau/Aβ42 demonstrated great diagnostic consistency with 11C-PIB PET/CT. Conclusions T-tau/Aβ42, Aβ42/Aβ40 and α-syn are ideal diagnostic criteria for AD. Combining these parameters with 11C-PIB PET/CT imaging could improve the accuracy of AD diagnosis.
Impact of 131I treatment on health-related quality of life in female patients with early stage papillary thyroid cancer
Min Zhao, Luyue Zhang, Lin Bai, Qiang Wen, Jie Zhao, Shi Gao, Qingjie Ma
2021, 45(1): 10-17. doi: 10.3760/cma.j.cn121381-202004010-00006
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Objective To analyze the effect of 131I treatment on health-related quality of life (HRQOL) in female patients with early stage thyroid papillary carcinoma (PTC). Methods The data of 356 female PTC patients (aged 21−65 (41.00±9.64) years) with pT1N1aM0 in China-Japan Union Hospital of Jilin University collected from June 2015 to June 2016 were retrospectively analyzed. A total of 400 healthy women (aged 21−65 (41.70±9.38) years) were selected as healthy controls. The HRQOL scores by the European Organization for Research and Treatment of Cancer (EORTC) quality of life questionnaire-core 30(QLQ-C30) between the controls and PTC patients at preoperative period and at 6 months after the operation were compared. Patients were divided into two groups according to whether or not they received 131I treatment (131I treatment group: n=205, non-131I treatment group: n=151). The levels of thyroid-stimulating hormone (TSH), thyroglobulin (Tg), and HRQOL scores at preoperative period and at 1, 3, and 6 months after the operation were compared between the two groups. Informed consent was obtained from all subjects. Non-parametric test of Mann-Whitney U was used to compare the groups with SPSS 19.0 software. Results Before the operation, the global quality of life (GQOL) score of all patients was significantly lower than that of the controls (59.11±21.12 vs. 83.08±14.62), functional domain scores in patients were lower than those in the controls except physical function, symptom domain scores were significantly higher except pain (Z=−6.958 to −4.673, all P<0.05). At 6 months after operation, the GQOL score in patients was still lower than that in the controls (73.88±18.04 vs. 83.08±14.62), but it was significantly higher than the preoperative score. Similar improvements were found in eight other domains other than physical function, cognitive function, social function, fatigue, pain and dyspnoea (Z=−5.790 to −2.876, all P<0.05). No significant difference was found in the preoperative all-domain scores between the 131I and non-131I treatment groups (Z=−0.876 to −0.001, all P>0.05). TSH and Tg in 131I treatment group were significantly higher than non-131I treatment group at 1 month after operation (Z=−6.159, −10.061, both P<0.01). At 1 month after operation, the GQOL score in the 131I treatment group was significantly lower than that in the non-131I treatment group (50.57±17.72 vs. 55.74±18.82). Functional domain scores of the 131I treatment group were significantly lower than those in the non-131I treatment group, symptom domain scores were significantly higher except pain, diarrhea, and financial impact (Z=−5.512 to −2.550, all P<0.05). At 3 months after operation, the GQOL score of the 131I treatment group was still lower than that in the non-131I treatment group (64.43±32.12 vs. 72.68±17.29), but the functional domain scores of the 131I treatment group were lower than that in the non-131I treatment group only in the role function, emotional function, social function, and symptom domain scores were higher only in the insomnia, appetite loss (Z=−2.939 to −0.984, all P<0.05). At 6 months after operation, no difference was found in the GQOL score and any other scores between the 131I treatment group and non-131I treatment group (Z=−2.550 to −0.008, all P>0.05). Conclusion 131I treatment had no impact on HRQOL in female patients with early stage PTC at 6 months after the operation or longer.
Characteristics of thyroid function change after 131I treatment of Graves hyperthyroidism and correlation with level of antibodies before treatment
Meiyan Chen, Xuena Li, Yaming Li
2021, 45(1): 18-23. doi: 10.3760/cma.j.cn121381-202003035-000015
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Objective To analyze the characteristics of thyroid function change at 1st, 3rd and 6th months after 131I treatment of Graves' hyperthyroidism and determine the correlation between level of antibodies before treatment and prognosis. Methods A prospective study was conducted in 80 patients with Graves' hyperthyroidism patients treated with 131I for the first time from March 2016 to May 2016 in the First Hospital of China Medical University. The patients consisted of 20 males and 60 females,with median age of 19−70 (40.5±12.8) years. The patients were followed up and reexamined at 1st, 3rd, and 6th months after treatment. According to the thyroid function change, the patients at 1st and 3rd months were separately divided into four groups (thyroid function increased, thyroid function improved, thyroid function normal and thyroid function decreased). Patients at 6th month were divided into four groups, including improved completely, improved partially, invalid (these 3 groups are called non-hypothyroidism group) and hypothyroidism. The cured group including improved completely and the hypothyroidism, and the non-cured group including the improved partially, invalid and the patients who have secondary treatment.The characteristics of thyroid function change at 1st, 3rd, and 6th months were reviewed, and the correlation between level of antibodies (anti thyroglobulin antibodies (TgAb), thyroid peroxidase antibody (TPOAb) and thyrotrophin receptor antibody (TRAb)) and prognosis was found. Chi-square test was used to compare the differences in the incidence of hypothyroidism at 3rd month between each group at 1st month. Kappa test was used to analyze the consistency between changes in thyroid function at 3rd month and the curative effect at 6th month. The relationship between antibody level before treatment and the curative effect was analyzed by Wilcoxon test. Results The incidence of hypothyroidism at 3rd month significant differed between thyroid function increased (15.00(3/20)) and “normal and thyroid function decreased” (including thyroid function normal and thyroid function decreased) (88.90% (8/9)) at 1st month (χ2=14.39, P<0.01). The incidence of hypothyroidism at 3rd month significantly differed between thyroid function improved (25.49% (3/51)) and “normal and thyroid function decreased” at 1st month (χ2=13.52, P<0.01). The incidence of hypothyroidism at 3rd month between thyroid function increased and thyroid function improved at 1st month had no statistical difference (χ2=0.91, P>0.05). The consistency analysis showed that the Kappa value was 0.812 in comparison between thyroid function decreased at 3rd month and hypothyroidism at 6th month (P<0.01).The Kappa value was 0.615 in comparison between thyroid function normal at 3rd month and improved completely at 6th month (P<0.01). The Kappa value was 0.519 in comparison between thyroid function improved at 3rd month and improved partially at 6th month (P<0.01). The levels of TgAb[51.53 (9.05, 781.19) U/mL vs.14.30 (3.33, 45.14) U/mL] and TPOAb[577.50 (197.89, 1000) U/mL vs.397.71 (98.41, 955.68) U/mL] before treatment between hypothyroidism and non-hypothyroidism at 6th month had no significant differences (u=249.00, 306.50, both P>0.05). The level of TRAb[11.43 (4.34, 32.42) IU/L vs.19.82 (7.95, 39.14) IU/L] before treatment in cure group and non-cure group at 6th month had significant differences (u=557.50, P<0.05). Conclusions The clinical outcome at 6th month after 131I treatment can be evaluated and predicted by closely observing the change trend of thyroid function at 1st and 3rd month after 131I treatment. There was no correlation between the level of TgAb and TPOAb before treatment and occurrence of hypothyroidism, and there was correlation between the level of TRAb before treatment and the cure of hyperthyrodism, and it had significant difference.
Effect of different optimization methods for the same beam angles on IMRT plan of central lung cancer
Lingxiang Liu, Zhaohui Chen, Xianhai Huang, Lan Yi
2021, 45(1): 24-30. doi: 10.3760/cma.j.cn121381-202001016-00002
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Objective To investigate the effect of different optimization methods in the same beam angles on the dose distribution of the target area and organ at risk (OAR) in intensity modulated radiotherapy (IMRT) for central lung cancer. Methods Six patients with central lung cancer and received IMRT in Panyu Central Hospital of Guangzhou from November 2017 to October 2019 were retrospectively analyzed, including 5 males and 1 female; the median age was 64 (53–73) years old. Six patients were treated with two plans, namely, F-plan and B-plan. Both plans adopted the same beam angles, and the given beam angle was optimized in accordance with the distance between the edge of the target area to the surface of the skin and the principle of the minimum penetration of field into lung. The F-plan was that part of the beam angles was designed to fix the jaw, and the B-plan was that part of the beam angles was designed to add a block in the incident path of the view. The target area coverage, OAR distribution, and monitor unit (MU) with two treatment plans were receptivity evaluated. Paired t-test was used to compare the differences. Results The two treatment plans could satisfy the clinical requirements, the dose distributions of the planning clinical target volume and the planning gross target volume (PGTV) were basically the same, and no significant difference was found between the parameters such as the conformal index and uniformity index of PGTV, machine MU under the two plans (t=−1.383−1.863, all P>0.05). The mean lung dose (MLD) ((1572.13±148.08) cGy)/V5 ((62.58±5.91)%)/V25 ((24.33±1.83)%)/V30 ((20.14±2.43)%) and V40 ((13.38±2.78)%) of the double lung (where Vx refers to the percentage of the volume exposed to x-Gy dose to the total volume) and the mean dose (Dmean) ((1246.63±485.12) cGy)/V5 ((58.46±24.31)%) and V40 ((6.38±2.67)%) of normal tissue (NT) in the B-plan were generally higher than in the F-plan (MLD ((1546.45±152.98) cGy)/V5 ((60.66±5.34)%)/V25 ((23.79±2.20)%)/V30 ((19.59±2.71)%) and V40 ((12.70±2.79)%) of the double lung and the Dmean ((1209.37±466.66) cGy)/V5 ((54.87±22.60)%) and V40 ((5.89±2.63)%) of NT). Their difference was statistically significant (t=−6.370 to −2.601, all P<0.05). For the heart and spinal cord, no significant differences were found between the two plans (t=−1.120−0.377, all P>0.05). However, B-plan cardiac V30 ((17.21±10.42)%) and V40 ((11.70±8.04)%) were higher than F-plan cardiac V30 ((14.67±5.82)%) and V40 ((9.42±4.19)%). In addition, spinal cord maximum dose (Dmax) ((4112.12±304.66) cGy) was slightly lower than F-plan spinal cord Dmax ((4128.73±254.72) cGy). Conclusions Both treatment plans can obtain satisfactory target dosimetric distribution, and each plan has its own advantages and disadvantages in the protection of OARs. In clinical application, they can be used selectively or in combination according to individual differences and target distribution.
Basic Science Investigation
Hypoxia-induced UCHL5 expression enhanced radioresistance of Hela cells in cervical cancer
Shengyuan Jiao, Qiaohui Gao, Fei Da, Li Guo, Jin Wang, Juan Guo, Jing Li, Junye Liu
2021, 45(1): 31-40. doi: 10.3760/cma.j.cn121381-202010021-000011
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Objective To investigate the role of hypoxia-induced ubiquitin carboxyl-terminal hydrolase isozyme L5 (UCHL5) in the regulation of radiosensitivity of Hela cells in cervical cancer. Methods UCHL5 levels were detected in Hela cells cultured under 1% O2 condition. Western blot and qRT-PCR analyses verified the efficiency of lentiviral vector infection on stable UCHL5 modulation in HeLa cells, including oe-vector, oe-UCHL5-1, oe-UCHL5-2, oe-UCHL5-3, oe-UCHL5-4 and sh-vector, sh-UCHL5-1 and sh-UCHL5-2. The cells used in the experiment were divided into the following groups: oe-vector, oe-UCHL5, sh-vector and sh-UCHL5. Cell colony-formation rate and radiosensitivity were detected by colony-formation assay combined with single-dose (0, 2, 4 and 6 Gy) γ-ray irradiation after culturing for 2 weeks. The effect of radiation on cell apoptosis was determined by flow cytometry after 48 h of 8 Gy γ-ray irradiation. 3-(4,5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide assay was used to detect the cell viability of down- or up-regulated UCHL5 cells before and after 0, 2, 4, 6, 8 and 10 Gy of γ-ray irradiation. Gene expression profiling interactive analysis was used to analyze the correlated expression between UCHL5 and hypoxia inducible factor-1α (HIF-1α). The transcriptional activation effect of UCHL5 by HIF-1α was detected using dual-luciferase reporter-gene assay. Differences between groups were compared by single-sample t test, and Pearson test was used for correlation analysis. Results UCHL5 was significantly induced by hypoxia after culturing at different time points. Hela cell lines with stably overexpressed and silenced UCHL5 were successfully constructed, with oe-UCHL5-2 and sh-UCHL5-2 having the highest regulatory efficiency. These two groups were selected for subsequent experiments. Compared with the control group that received the same dose of irradiation, significant differences existed at doses of 0, 2, 4 and 6 Gy (t=14.16, 19.22, 8.76, 6.79, all P<0.05), respectively. Knock-down of UCHL5 promoted apoptosis (t=10.29, P<0.05) and radiation-induced apoptosis (t=52.01, P<0.05). UCHL5 up-regulation promoted cell proliferation, and the proliferation rate was statistically significant on the third day (t=3.905, P<0.05). Furthermore, UCHL5 strengthened the viability (t=3.40, 4.06, 3.68, all P<0.05) of irradiated Hela cells, with significant differences at doses of 6, 8 and 10 Gy (t=3.40, 4.06, 3.68, all P<0.05), respectively. The expression levels of HIF-1α and UCHL5 in cervical cancer tissues were positively correlated (R=0.31, P<0.01). Additionally, HIF-1α was a potential transcriptional activator of UCHL5 in Hela cells, and its activity increased 2.5 times (t=30.47, P<0.05). Conclusions The induced expression of UHCL5 in cervical cancer Hela cells under hypoxia condition can reduce the radiation sensitivity of cells. The underlying mechanism may be related to the HIF-1α transcriptional activation of UCHL5 expression.
Review Article
Application of radionuclide imaging in the diagnosis of kidney neoplasms
Hongjing Zhu, Aisheng Dong, Changjing Zuo
2021, 45(1): 41-46. doi: 10.3760/cma.j.cn121381-202004035-00008
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Accurate qualitative diagnosis and staging are of great value for the formulation of treatment plans for kidney neoplasms with diverse pathological types and complex classification. Radionuclide imaging can perform in vivo imaging of tumors at the molecular or cellular level, thereby providing important information in the diagnosis, staging, restaging and efficacy evaluation of tumors. In this paper, the current clinical application and research progress of radionuclide imaging in the diagnosis of kidney neoplasms are reviewed.
Application progress of multiple imaging modalities in preoperative localization and diagnosis of hyperparathyroidism
Yujie Xie, Dianchao Yue
2021, 45(1): 47-53. doi: 10.3760/cma.j.cn121381-201911029-00004
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The best management of hyperparathyroidism (HPT) is surgical treatment, accurate preoperative imaging localization is very important for operation. At present, there are many common preoperative localization methods for parathyroid surgery, including ultrasound, parathyroid radionuclide imaging, CT and MRI. Ultrasound, CT and MRI can show the location and anatomical relationship of neck lesions. Parathyroid radionuclide imaging can locate the parathyroid gland relatively specifically, but there are some limitations. The parathyroid gland is small in size and varied in number and position. The application of SPECT/CT, PET/CT, contrast-enhanced ultrasound, four-dimensional CT and four-dimensional MRI can further improve the sensitivity, accuracy and success rate of preoperative localization of parathyroid gland. The purpose of this paper is to introduce and analyze the advantages and disadvantages of various imaging methods of parathyroid gland.
Research progress on the role of immune system in radiation-induced bystander effect
Yimeng Song, Yan Pan, Chunlin Shao
2021, 45(1): 54-60. doi: 10.3760/cma.j.cn121381-201911006-00001
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Radiation-induced bystander effect (RIBE) has been a research hotspot in the field of radiation biology since it was discovered. It has been demonstrated that RIBE can be mediated by gap junctional communication and soluble cell secretions. Recent studies show that the immune system plays an important role in the progress of RIBE, profoundly affecting the progress and results of biological effect of radiation. In this paper, the role of the immune system in the RIBE is briefly reviewed, with a view to providing a theoretical basis for the study of RIBE.
Research progress of targeting PARP-1 to regulate radiosensitivity of tumor cells
Xiaojun Yu, Daiying Zuo, Wenbin Hou, Yiliang Li
2021, 45(1): 61-66. doi: 10.3760/cma.j.cn121381-201910019-00009
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Radiotherapy is the main treatment for advanced tumor. However, due to the emergence of tumor tolerance and resistance, the treatment effect is not ideal. Therefore, it is urgent to correct the resistance or improve the sensitivity of radiotherapy. Poly (adenosine diphosphate-ribose) polymerase (PARP)1 is a member of a functionally rich nuclear protein. In view of its important role in cellular processes such as regulation of chromatin structure and repair of DNA damage, PARP-1 is considered to be the most potential target for radiosensitization. In this paper, the author reviews the research progress of targeting PARP-1 to regulate radiosensitization of tumor cells.