1.Effects of Exercise Training on The Behaviors and HPA Axis in Autism Spectrum Disorder Rats Through The Gut Microbiota
Xue-Mei CHEN ; Yin-Hua LI ; Jiu-Gen ZHONG ; Zhao-Ming YANG ; Xiao-Hui HOU
Progress in Biochemistry and Biophysics 2025;52(6):1511-1528
ObjectiveThe study explores the influence of voluntary wheel running on the behavioral abnormalities and the activation state of the hypothalamic-pituitary-adrenal (HPA) axis in autism spectrum disorder (ASD) rats through gut microbiota. MethodsSD female rats were selected and administered either400 mg/kg of valproic acid (VPA) solution or an equivalent volume of saline via intraperitoneal injection on day 12.5 of pregnancy. The resulting offspring were divided into 2 groups: the ASD model group (PASD, n=35) and the normal control group (PCON, n=16). Behavioral assessments, including the three-chamber social test, open field test, and Morris water maze, were conducted on postnatal day 23. After behavioral testing, 8 rats from each group (PCON, PASD) were randomly selected for serum analysis using enzyme-linked immunosorbent assay (ELISA) to measure corticotropin-releasing hormone (CRH), adrenocorticotropic hormone (ACTH), and corticosterone (CORT) concentration, to evaluate the functional state of the HPA axis in rats. On postnatal day 28, the remaining 8 rats in the PCON group were designated as the control group (CON, n=8), and the remaining 27 rats in the PASD group were randomly divided into 4 groups: ASD non-intervention group (ASD, n=6), ASD exercise group (ASDE, n=8), ASD fecal microbiota transplantation group (FMT, n=8), and ASD sham fecal microbiota transplantation group (sFMT, n=5). The rats in the ASD group and the CON group were kept under standard conditions, while the rats in the ASDE group performed 6 weeks of voluntary wheel running intervention starting on postnatal day 28. The rats in the FMT group were gavaged daily from postnatal day 42 with 1 ml/100 g fresh fecal suspension from ASDE rats which had undergone exercise for 2 weeks, 5 d per week, continuing for 4 weeks. The sFMT group received an equivalent volume of saline. After the interventions were completed, behavioral assessments and HPA axis markers were measured for all groups. ResultsBefore the intervention, the ASD model group exhibited significantly reduced social ability, social novelty preference, spontaneous activity, and exploratory interest, as well as impaired spatial learning, memory, and navigation abilities compared to the normal control group (P<0.05). Serum concentration of corticotropin-releasing hormone (CRH), adrenocorticotropic hormone (ACTH), and corticosterone (CORT) in the PASD group were significantly higher than those in the PCON group (P<0.05). Following 6 weeks of voluntary wheel running, the ASDE group showed significant improvements in social ability, social novelty preference, spontaneous activity, exploratory interest, spatial learning, memory, and navigation skills compared to the ASD group (P<0.05), with a significant decrease in serum CORT concentration (P<0.05), and a downward trend in CRH and ACTH concentration. After 4 weeks of fecal microbiota transplantation in the exercise group, the FMT group showed marked improvements in social ability, social novelty preference, spontaneous activity, exploratory interest, as well as spatial learning, memory, and navigation abilities compared to both the ASD and sFMT groups (P<0.05). In addition, serum ACTH and CORT concentration were significantly reduced (P<0.05), and CRH concentration also showed a decreasing trend. ConclusionExercise may improve ASD-related behaviors by suppressing the activation of the HPA axis, with the gut microbiota likely playing a crucial role in this process.
2.Influencing factors for recurrence after successful treatment in pulmonary tuberculosis patients with isoniazid resistance in Shaoxing City, Zhejiang Province
Jiamei SUN ; Laichao XU ; Zuokai YANG ; Huaqiang GAO ; Kaixuan ZHANG ; Qiaoling LU ; Haibin MENG
Shanghai Journal of Preventive Medicine 2025;37(7):616-619
ObjectiveTo analyze the influencing factors for recurrence in successfully treated pulmonary tuberculosis patients with isoniazid-resistant and rifampicin-sensitive in Shaoxing City, Zhejiang Province. MethodsData on general demographic information, treatment information and drug susceptibility test results for pulmonary tuberculosis patients admitted to the designated tuberculosis medical institutions and registered in the tuberculosis information management system was collected in Shaoxing City from January 2011 to August 2024. A total of 428 patients with isoniazid resistance (including isoniazid single resistance and multiple resistance) but who were successfully treated were included in the study. Information for the recurrence after successful treatment of the patients was analyzed. The Cox proportional hazards models were used to analyze the influencing factors of recurrence in patients. ResultsAmong the 428 successfully treated patients included in the study, 31 cases (accounting for 7.24%) had recurrence by the end of the observation period, with a recurrence rate density of 1.31 per 100 person-years and a median recurrence time of 0.99 (0.08, 8.27) years. Among the relapsed population, 51.61% of the patients relapsed within one year after successful treatment. 77.42% of the patients relapsed within two years after successful treatment. Multivariate Cox regression analysis showed that when isoniazid resistance was discovered, the diagnosis classification of relapse (HR=4.115, 95%CI: 1.734‒9.767) and positive 0-month sequence smear (HR=4.457, 95%CI: 1.053‒18.866) were risk factors for recurrence after successful treatment in patients. ConclusionRegular follow-up should be strengthened for at least two years after the successful treatment of isoniazid-resistant pulmonary tuberculosis patients. Special attention should be paid to the treatment effect and regular re-examination and monitoring after the end of the treatment course of isoniazid-resistant pulmonary tuberculosis patients who have been re-treated and were sputum smear positive at baseline, so as to prevent recurrence and disease progression in high-risk populations.
3. Mechanism of Dahuangtang pellets in regulating podocyte autophagy of diabetic nephropathy mice through AMPK/mTOR/ULK1 signaling pathway
Beibei SU ; Yonglin LIANG ; Chunxia XUE ; Pu ZHANG ; Xiaoli PEI ; Lixia YANG ; Xiangdong ZHU ; Xia YANG
Chinese Journal of Clinical Pharmacology and Therapeutics 2024;29(3):260-269
AIM: To explore the intervention effect of Dahuangtang pellets (DHT) on diabetic nephropathy (DN) based on the AMP-activated protein kinase/mammalian target of rapamycin/unc-51-like kinase 1 (AMPK/mTOR/ULK1) signaling pathway. METHODS: Eight mice were randomly assigned to the model group, the dapagliflozin group, and the DHT (high, medium, and low dosage) group out of a total of 40 C57BL/KSJ-db/db (hereafter referred to as db/db) mice; another 10 C57BL/KSJ-db/dm mice were used as the normal group, saline was provided to the normal and model groups, and the mice in the treatment group received the appropriate medications. The medications were given for 10 consecutive weeks, once per day, to the mice in the treatment group. At weeks 0, 4, 8, and 10 of administration, fasting blood glucose (FBG) was assessed by drawing blood at a predetermined time from the tail vein; Urine samples were taken at 0, 5, and 10 weeks after treatment to evaluate the levels of albumin and creatinine, and the urinary albumin-creatinine ratio (ACR) was computed. After 10 weeks, mice in each group were assayed for 24 h total urine protein, serum creatinine (Scr), urea nitrogen (BUN) levels; Western blotting analysis was conducted to detect the expression of p-AMPK, p-mTOR, and p-ULK1, as well as the expression of autophagy related proteins homolog of yeast Atg6 (Beclin-1), autophagy-related proteins microtubule-associated protein 1 light chain 3 (LC3), P62 in renal tissue; Immunohistochemistry was used to measure the expression of podocyte lacunar membrane proteins (Nephrin, Podocin) in renal tissues; The pathological morphology of renal tissue was observed by light microscopy and transmission electron microscopy. RESULTS: Compared with the model group, FBG, ACR, and 24 h total urine protein were reduced in the dapagliflozin group and DHT groups of mice, and there was no statistically significant difference in Scr and BUN; In renal tissues, there is increased expression of p-AMPK and p-ULK1, decreased expression of p-mTOR, increased expression of LC3II / LC3I and Beclin-1, and decreased expression of P62 (P<0.01, P< 0.05); differentially upregulated in glomeruli are the podocyte lacunar membrane proteins Nephrin and Podocin (P<0.01, P<0.05); renal pathologic damage was reduced to varying degrees; transmission electron microscopy showed an increase in the number of autophagic vesicles and autophagic lysosomes. CONCLUSION: DHT can delay the development of DN by regulating the AMPK / mTOR / ULK1 signaling pathway, enhancing podocyte autophagy, and protecting glomeruli.
4.Artery anatomy of localized renal cell carcinoma: an initial study based on 3D Slicer software
Ke GAO ; Ziyan WAN ; Ya ZHANG ; Hui ZHANG ; Xiaojie YANG ; Tie CHONG ; Delai FU
Journal of Modern Urology 2024;29(4):298-301
【Objective】 To analyze the position of the feeding artery entering the renal cell carcinoma (RCC) with 3D Slicer software, so as to explore the distribution pattern of the tumor artery and to provide an anatomical basis for the accurate surgical resection. 【Methods】 The clinical data of RCC patients who underwent partial nephrectomy in the Department of Urology, The Second Affiliated Hospital of Xi'an Jiaotong University during Jan.2021 and Jun.2022 were collected.The preoperative renal artery CT angiography data were imported into 3D Slicer software in DICOM format to construct the relative positions of tumor-feeding artery from horizontal, sagittal and coronary planes.The number and distribution of tumor feeding arteries in each plane were analyzed. 【Results】 A total of 112 patients (59 male and 53 female) with single tumor were involved.RENAL score was 4-10.The tumor stages were T1a in 58 cases, T1b in 48 cases, and T2a in 6 cases.Among them, 38 cases (33.93%) had 1 tumor artery, 53 cases (47.32%) had 2 tumor arteries, and 21 cases (18.75%) had 3 tumor arteries.Of these 207 tumor arteries, 22 (10.63%) entered the tumor through the superficial part of the tumor bed, and 185 (89.37%) through the deep part. 【Conclusion】 In localized RCC, nearly 90% of the feeding arteries enter the tumor from deep part of the tumor bed, which provides an anatomical basis for accurate tumor resection and wound suture in partial nephrectomy.
5.Effect of Modified Dahuang Huanglian Xiexintang on Oxidative Stress Injury of Liver in Type 2 Diabetes Mellitus Rats Based on Nrf2/HO-1 Axis
Chengjun MA ; Fengzhe YAN ; Lixia YANG ; Yonglin LIANG ; Xiangdong ZHU ; Dong AN ; Yankui GAO
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(24):121-130
ObjectiveTo explore the effects and mechanisms of modified Dahuang Huanglian Xiexintang on hepatic oxidative stress injury in type 2 diabetes mellitus (T2DM) rats based on the nuclear factor erythroid 2 related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) axis. MethodSix ZDF (fa/+) rats were as assigned to the blank group, and 30 ZDF (fa/fa) rats were used to induce the T2DM model by feeding a high-fat diet. After successful modeling, the rats were randomly divided into the model group, metformin group (0.18 g·kg-1), and low, medium, and high dose groups of modified Dahuang Huanglian Xiexintang (0.54, 1.08, 2.16 g·kg-1), with six rats in each group. After 12 weeks of drug intervention, the body mass, liver mass, fasting blood glucose (FBG), and oral glucose tolerance test (OGTT) levels were measured. Serum total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL), low-density lipoprotein cholesterol (LDL), alanine aminotransferase (ALT), and aspartate aminotransferase (AST) levels were detected using an automatic biochemical analyzer. The pathological changes of liver tissue were observed by hematoxylin-eosin (HE) staining. Enzyme-linked immunosorbent assay (ELISA) was used to detect the activity of superoxide dismutase (SOD), reactive oxygen species (ROS), glutathione peroxidase (GSH-Px), and the level of malondialdehyde (MDA) in liver tissues. Immunohistochemistry was used to detect the expression of Nrf2 in the liver. Real time quantitative polymerase chain reaction (Real-time PCR) and Western blot were used to detect the mRNA and protein expression levels of Nrf2 and HO-1 in liver tissues. ResultCompared with the normal group, the model group showed a significant increase in body mass, liver mass, and liver index (P<0.01). Compared with the model group, the metformin group and the medium and high dose groups of modified Dahuang Huanglian Xiexintang showed a significant decrease in body weight, liver mass, and liver index (P<0.01). Compared with the normal group, the model group showed significantly increased TC, TG, and LDL levels (P<0.01), and significantly decreased HDL levels (P<0.01). Compared with the model group, the metformin group and all doses of modified Dahuang Huanglian Xiexintang showed significantly reduced TC levels (P<0.01), and significantly reduced TG levels (P<0.05). The medium and high dose groups of modified Dahuang Huanglian Xiexintang showed significantly reduced LDL levels (P<0.05). The metformin group and all doses of modified Dahuang Huanglian Xiexintang showed significantly increased HDL levels (P<0.05). Compared with the normal group, the model group showed significantly increased ALT and AST activities (P<0.01). Compared with the model group, all doses of modified Dahuang Huanglian Xiexintang and the metformin group showed significantly reduced ALT activities (P<0.05) and significantly reduced AST activities (P<0.01). Compared with normal group, the model group showed significantly increased FBG at all time points (P<0.01). Compared with the model group, the metformin group and all doses of modified Dahuang Huanglian Xiexintang showed significantly reduced FBG at 8, 10, 12 weeks. The OGTT results showed that compared with the normal group, the model group had significantly increased blood glucose at all time points (P<0.01). Compared with the model group, the metformin group showed significantly reduced blood glucose at all time points (P<0.01), and the medium and high dose groups of modified Dahuang Huanglian Xiexintang showed significantly reduced blood glucose at 90, 120 min (P<0.01). HE pathology showed clear and regular liver cell structure in the normal group, while the model group showed disordered liver cell structure with visible fat vacuoles and a large number of deformed necrotic cells. The liver tissue structure improved in the metformin group and all doses of modified Dahuang Huanglian Xiexintang, with fewer necrotic cells. Compared with the normal group, the model group showed significantly reduced SOD and GSH-Px levels (P<0.01), and significantly increased ROS and MDA levels (P<0.01). Compared with the model group, the metformin group and all doses of modified Dahuang Huanglian Xiexintang showed significantly increased SOD and GSH-Px levels (P<0.01), and significantly reduced MDA levels (P<0.01). The medium and high dose groups of modified Dahuang Huanglian Xiexintang showed significantly reduced ROS levels (P<0.05). Compared with the normal group, the model group showed significantly reduced Nrf2 and HO-1 mRNA expression levels (P<0.01). Compared with the model group, the metformin group and the medium and high dose groups of modified Dahuang Huanglian Xiexintang showed significantly increased Nrf2 and HO-1 mRNA expression levels (P<0.05). Immunohistochemistry showed that compared with the normal group, the model group had significantly reduced positive expression of Nrf2 and HO-1 (P<0.05). Compared with the model group, the metformin group and all doses of modified Dahuang Huanglian Xiexintang showed increased positive expression of Nrf2 and HO-1, with a significant increase in brown-yellow granules around the cell nucleus (P<0.05). Western blot results showed that compared with the normal group, the model group had significantly reduced protein expression of Nrf2 and HO-1 (P<0.01). Compared with the model group, the metformin group and all doses of modified Dahuang Huanglian Xiexintang showed significantly increased protein expression of Nrf2 and HO-1 (P<0.01). ConclusionModified Dahuang Huanglian Xiexintang can significantly improve the general condition and pathological changes of liver tissues in T2DM model rats. This improvement is likely achieved through ameliorating hepatic oxidative stress injury via regulating the Nrf2/HO-1 axis.
6.Hypothalamic-Pituitary-Adrenal Axis and Epilepsy
Xueying BIAN ; Wenxian YANG ; Jiannan LIN ; Biao JIANG ; Xiaoli SHAO
Journal of Clinical Neurology 2024;20(2):131-139
Epilepsy is a recurrent, transient seizure disorder of the nervous system that affects the intellectual development, life and work, and psychological health of patients. People with epilepsy worldwide experience great suffering. Stressful stimuli such as infection, mental stress, and sleep deprivation are important triggers of epilepsy, and chronic stressful stimuli can lead to frequent seizures and comorbidities. The hypothalamic-pituitary-adrenal (HPA) axis is the most important system involved in the body’s stress response, and dysfunction thereof is thought to be associated with core epilepsy symptoms and related psychopathology. This article explores the intrinsic relationships of corticotropin-releasing hormone, adrenocorticotropic hormone, and glucocorticoids with epilepsy in order to reveal the role of the HPA axis in the pathogenesis of epilepsy. We hope that this information will yield future possible directions and ideas for fully understanding the pathogenesis of epilepsy and developing antiepileptic drugs.
7.Research and Design of Calibration Device for Medical Test Lung.
Tingting ZHANG ; Qiu HUANG ; Xuhui LIAO ; Chenggang HUANG ; Zhilong RUAN ; Yafei YANG ; Tao LIN ; Bo YANG
Chinese Journal of Medical Instrumentation 2023;47(5):528-532
In order to solve the problems of quality control and traceability of medical test lung for meeting the calibration conditions of JJF 1234-2018 Calibration Specification for Ventilators, the calibration device and method are researched for compliance and airway resistance of medical test lung in this paper. A calibration device for medical test lung is designed using constant volume active piston technology to simulate human breathing. Through comparison experiment, the deviation between this device and the similar foreign device can be found. The deviation is lower than 0.4% for lung compliance and lower than 0.7% for airway resistance. The calibration of lung compliance and airway resistance can be completed by this device. This device has a clear and complete traceability path to ensure quality control from the source. The calibration of ventilator is improved. This paper provides a reference for related metrology departments and medical institutions to study on quality inspection of respiratory medical instruments.
Humans
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Calibration
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Ventilators, Mechanical
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Respiration
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Quality Control
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Lung
8.Traditional Chinese Medicine excessive pattern correlation analysis of chronic obstructive pulmonary disease complicated acute exacerbation of chronic pulmonary heart disease
Yin OUYANG ; Yongning LI ; Qiang LI ; Zunyou KE ; Li CHEN ; Shaoxing YANG ; Chunxia ZHANG ; Huiqing YAO ; Yongxiang ZHAO ; Ye TAN
International Journal of Traditional Chinese Medicine 2022;44(2):138-144
Objective:To explore the correlation between Traditional Chinese Medicine (TCM) excessive patterns and clinical characteristics of acute exacerbation of chronic obstructive pulmonary disease (COPD) complicated with chronic pulmonary heart disease (CPHD) in high altitude environment.Methods:Patients with acute exacerbation of COPD complicated with CPHD admitted to the Pulmonology Department of Qinghai Provincial Hospital of Traditional Chinese Medicine from December 2016 to November 2017 were selected. Demographic data and clinical medical characteristics data of the patients were collected, and TCM patterns differentiation was conducted. The correlation between each pattern type and clinical characteristics and all collected laboratory indexes were analyzed by multivariate logistic regression.Results:Phlegm obstructing lung pattern showed a negative correlation relationship with mMRC score [ OR=0.419, 95% CI (0.219-0.802), P=0.009], PCT [ OR=8.132×10 -11, 95% CI (1.632×10 -16-4.1×10 -5), P<0.001], Hb [ OR=0.971, 95% CI (0.952-0.989), P=0.002] and PaCO 2[ OR=0.914, 95% CI (0.853-0.980), P=0.011]; turbid phlegm obstructing lung pattern showed a negative correlation relationship with gender(0 male, 1 female) [ OR=0.427, 95% CI (0.204-0.892), P=0.024], Hb [ OR=0.960, 95% CI (0.945-0.975), P<0.001], and there was a positive correlation relationship with LVEF [ OR=1.061, 95% CI (1.006-1.118), P=0.028]; phlegm-heat obstructing lung pattern showed a negative correlation relationship with Hb [ OR=0.950, 95% CI (0.927-0.974), P<0.001]and cardiac function grade [ OR=0.468, 95% CI (0.248,0.881), P=0.019], and there was a positive correlation relationship with PCT [ OR=1.118×10 8, 95% CI (1.466×10 4-8.523×10 11), P<0.001] and D-D [ OR=2.283, 95% CI (1.300-4.010), P=0.004]; there was a negative correlation between phlegm and stasis blocking lung pattern with cardiac function grade[ OR=0.309, 95% CI (0.167-0.570), P<0.001], and there was a positive correlation relationship with Hb[ OR=1.060, 95% CI (1.042-1.078), P<0.001]; there was a negative correlation between wet phlegm and blood stasis heat pattern with PCT [ OR=1.266×10 -13, 95% CI (1.658×10 -21-0.1×10 -4), P<0.001], SaO 2 [ OR=0.934, 95% CI (0.892-0.979), P=0.004], LVEF [ OR=0.896, 95% CI (0.826-0.971), P=0.008], D-D [ OR=0.030, 95% CI (0.002-0.508), P=0.015], and there was a positive correlation relationship with CRP [ OR=1.042, 95% CI (1.018-1.067), P<0.001], RBC [ OR=3.411, 95% CI (1.684-6.910), P<0.001], cardiac function grade [ OR=8.573, 95% CI (2.410-30.504), P<0.001], pulmonary arterial pressure difference [ OR=2.091, 95% CI (1.243-3.516), P=0.005]. Conclusions:Male patients are more prone to phlegm and turbidities than female patients. PCT and D-D were the main risk factors of phlegm-heat obstruction syndrome. Elevated hemoglobin is a risk factor for patients with phlegm stasis and lung syndrome. Heart function classification is the main risk factor of phlegm-dampness-stasis heat syndrome.
10.Performance of the Combined Model Based on Both Clinicopathological and CT Texture Features in Predicting Liver Metastasis of High-risk Gastrointestinal Stromal Tumors.
Jing ZHENG ; Xu WANG ; Yang XIA ; Hai-Tao JIANG
Acta Academiae Medicinae Sinicae 2022;44(1):53-59
Objective To investigate the performance of the combined model based on both clinicopathological features and CT texture features in predicting liver metastasis of high-risk gastrointestinal stromal tumors(GISTs). Methods The high-risk GISTs confirmed by pathology from January 2015 to December 2020 were analyzed retrospectively,including 153 cases from the Cancer Hospital of the University of Chinese Academy of Sciences and 51 cases from the Shaoxing Central Hospital.The cases were randomly assigned into a training set(n=142)and a test set(n=62)at a ratio of 7∶3.According to the results of operation or puncture,they were classified into a liver metastasis group(76 cases)and a non-metastasis group(128 cases).ITK-SNAP was employed to delineate the volume of interest of the stromal tumors.Least absolute shrinkage and selection operator(LASSO)was employed to screen out the effective features.Multivariate logistic regression was adopted to construct the models based on clinicopathological features,texture features extracted from CT scans,and the both(combined model),respectively.Receiver operating characteristic(ROC)curve and calibration curve were established to evaluate the predictive performance of the models.The area under the curve(AUC)was compared by Delong test. Results Body mass index(BMI),tumor size,Ki-67,tumor occurrence site,abdominal mass,gastrointestinal bleeding,and CA125 level showed statistical differences between groups(all P<0.05).A total of 107 texture features were extracted from CT images,from which 13 and 7 texture features were selected by LASSO from CT plain scans and CT enhanced scans,respectively.The AUC of the prediction with the training set and the test set respectively was 0.870 and 0.855 for the model based on clinicopathological features,0.918 and 0.836 for the model based on texture features extracted from CT plain scans,0.920 and 0.846 for the model based on texture features extracted from CT enhanced scans,and 0.930 and 0.889 for the combined model based on both clinicopathological features and texture features extracted from CT plain scans.Delong test demonstrated no significant difference in AUC between the models based on the texture features extracted from CT plain scans and CT enhanced scans(P=0.762),whereas the AUC of the combined model was significantly different from that of the clinicopathological feature-based model and texture feature-based model(P=0.001 and P=0.023,respectively). Conclusion Texture features extracted from CT plain scans can predict the liver metastasis of high-risk GISTs,and the model established with clinicopathological features combined with CT texture features has best prediction performance.
Gastrointestinal Stromal Tumors/diagnostic imaging*
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Humans
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Liver Neoplasms/diagnostic imaging*
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ROC Curve
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Retrospective Studies
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Tomography, X-Ray Computed/methods*

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