Predicting Breast Cancer Subtypes Using Magnetic Resonance Imaging Based Radiomics With Automatic Segmentation.

OBJECTIVE: The aim of the study is to demonstrate whether radiomics based on an automatic segmentation method is feasible for predicting molecular subtypes. METHODS: This retrospective study included 516 patients with confirmed breast cancer. An automatic segmentation-3-dimensional UNet-based Convolutional Neural Networks, trained on our in-house data set-was applied to segment the regions of interest. A set of 1316 radiomics features per region of interest was extracted. Eighteen cross-combination radiomics methods-with 6 feature selection methods and 3 classifiers-were used for model selection. Model classification performance was assessed using the area under the receiver operating characteristic curve (AUC), accuracy, sensitivity, and specificity. RESULTS: The average dice similarity coefficient value of the automatic segmentation was 0.89. The radiomics models were predictive of 4 molecular subtypes with the best average: AUC = 0.8623, accuracy = 0.6596, sensitivity = 0.6383, and specificity = 0.8775. For luminal versus nonluminal subtypes, AUC = 0.8788 (95% confidence interval [CI], 0.8505-0.9071), accuracy = 0.7756, sensitivity = 0.7973, and specificity = 0.7466. For human epidermal growth factor receptor 2 (HER2)-enriched versus non-HER2-enriched subtypes, AUC = 0.8676 (95% CI, 0.8370-0.8982), accuracy = 0.7737, sensitivity = 0.8859, and specificity = 0.7283. For triple-negative breast cancer versus non-triple-negative breast cancer subtypes, AUC = 0.9335 (95% CI, 0.9027-0.9643), accuracy = 0.9110, sensitivity = 0.4444, and specificity = 0.9865. CONCLUSIONS: Radiomics based on automatic segmentation of magnetic resonance imaging can predict breast cancer of 4 molecular subtypes noninvasively and is potentially applicable in large samples.

Computed tomography-based COVID-19 triage through a deep neural network using mask-weighted global average pooling.

Background: There is an urgent need to find an effective and accurate method for triaging coronavirus disease 2019 (COVID-19) patients from millions or billions of people. Therefore, this study aimed to develop a novel deep-learning approach for COVID-19 triage based on chest computed tomography (CT) images, including normal, pneumonia, and COVID-19 cases. Methods: A total of 2,809 chest CT scans (1,105 COVID-19, 854 normal, and 850 non-3COVID-19 pneumonia cases) were acquired for this study and classified into the training set (n = 2,329) and test set (n = 480). A U-net-based convolutional neural network was used for lung segmentation, and a mask-weighted global average pooling (GAP) method was proposed for the deep neural network to improve the performance of COVID-19 classification between COVID-19 and normal or common pneumonia cases. Results: The results for lung segmentation reached a dice value of 96.5% on 30 independent CT scans. The performance of the mask-weighted GAP method achieved the COVID-19 triage with a sensitivity of 96.5% and specificity of 87.8% using the testing dataset. The mask-weighted GAP method demonstrated 0.9% and 2% improvements in sensitivity and specificity, respectively, compared with the normal GAP. In addition, fusion images between the CT images and the highlighted area from the deep learning model using the Grad-CAM method, indicating the lesion region detected using the deep learning method, were drawn and could also be confirmed by radiologists. Conclusions: This study proposed a mask-weighted GAP-based deep learning method and obtained promising results for COVID-19 triage based on chest CT images. Furthermore, it can be considered a convenient tool to assist doctors in diagnosing COVID-19.

A comparison of carotid atherosclerosis in symptomatic patients between 2002-2005 and 2012-2015 cohorts using multi-contrast magnetic resonance vessel wall imaging.

OBJECTIVE: To compare the morphological and compositional characteristics of carotid plaques in two cohorts (2002-2005 and 2012-2015) of Chinese patients using magnetic resonance vessel wall imaging. METHODS: Symptomatic patients with carotid atherosclerotic plaques who underwent carotid vessel wall magnetic resonance imaging between 2002-2005 and 2012-2015 were retrospectively recruited. Plaque morphology [including mean wall area, wall thickness, and maximum normalized wall index (NWI)] and composition [including calcification, intraplaque hemorrhage, and lipid-rich necrotic core (LRNC)] in symptomatic carotid arteries were evaluated and compared between patients in these two time periods. RESULTS: A total of 258 patients, including 129 patients in the 2002-2005 cohort and 129 patients in the 2012-2015 cohort, were recruited. Statin use (49.6%vs. 32.6%, P = 0.004) and hypertension (76.0% vs. 62.8%, P = 0.015) were significantly more common in the 2012-2015 cohort than in the 2002-2005 cohort. Patients in the 2012-2015 cohort also exhibited significantly low plaque burden parameters (allP < 0.05), as well as a lower prevalence (68.2% vs. 89.9%, P < 0.001) and volume percentages of LRNC (11.2% ± 14.2% vs. 25.7% ± 17.7%, P < 0.001). These differences remained significant after adjustment for clinical factors. The differences in the volume percentages of LRNC also remained significant after an additional adjustment for maximum NWI ( P < 0.001). CONCLUSIONS: Patients in the 2012-2015 cohort had a lower plaque burden and volume percentages of LRNC in symptomatic carotid arteries than those in the 2002-2005 cohort. These findings indicate that carotid plaques in the recent cohort had a lower severity and vulnerability.

Establishment of a Large Animal Model for Eustachian Tube Functional Study in Miniature Pigs.

This study was performed to investigate whether miniature pigs are a suitable animal model for studies of the Eustachian tube (ET). Sixteen Chinese experimental miniature pigs were used in this investigation. Ten animals were used for anatomical and morphometric analyses to obtain qualitative and quantitative information regarding the ET. Three animals were used for histological analysis to determine the fine structure of ET cross-sections. Three animals were used to investigate the feasibility of balloon dilation of the Eustachian tube (BDET). The anatomical study indicated that the pharyngeal orifice and tympanic orifice of the miniature pig ET are located at the posterior end of the nasal lateral wall and anterior wall of the middle ear cavity, respectively. The cartilaginous tube was seen to pass through the whole length of the ET, the length of the cartilaginous part of the ET and the diameter of the isthmus were similar between humans and miniature pigs. The inclination of the ET in miniature pigs was larger than that in humans. The gross histology seemed to be slightly different between miniature pig and human, but the fine structures were essentially the same in both species. BDET experiments verified that the miniature pig model is suitable as a model for clinical operations. The miniature pig ET corresponds very well to that of humans. In addition, the miniature pig ET is suitable as a model for clinical operations. Therefore, the miniature pig is a valid animal model for ET study. Anat Rec, 302:1024-1038, 2019. © 2019 Wiley Periodicals, Inc.

[Relationship between Angiotensin Converting Enzyme Gene Polymorphism and Carotid Atherosclerotic Plaque: A Study Based on Vessel Wall Magnetic Resonance Imaging].

Objective To investigate the relationship between angiotensin converting enzyme(ACE) gene polymorphism and carotid plaque composition,vessel wall morphology,and clinical symptoms based on vessel wall magnetic resonance imaging. Methods Totally 75 hypertensive patients(75 internal carotid artery plaques) with maximum plaque thickness≥1.5 mm,according to the ACE insertion(I) or deletion(D) gene polymorphism,were divided into ACE 2 genotype group(n=37) and ACE ID/DD genotype group(n=38). The influences of plaque composition,vessel wall morphology,clinical symptoms,and use of ACE inhibitor or angiotensin receptor blocker(ACEI/ARB) on vessel wall morphology were analyzed. Results Compared with ACE 2 genotype group,the ACE ID/DD genotype group had significantly higher incidence of ischemic stroke(Χ2=3.921,P=0.048). The plaque composition and vessel wall morphology showed no significant difference between these two groups. Inside ACE ID/DD genotype group,the carotid remodeling index was significantly lower in users of ACEI/ARB than non-users of ACEI/ARB(1.85±0.60 vs. 2.48±0.40;t=3.854,P=0.001).Conclusion In primary hypertension,ACE ID/DD genotype may be associated with carotid atherosclerotic plaque.

CpG-oligodeoxynucleotides may be effective for preventing ionizing radiation induced pulmonary fibrosis.

Pulmonary fibrosis is a serious adverse effect of radiotherapy for thoracic tumor, which is believed to be a process that is tightly regulated by the phenotype of the developing Th response after radiation. Here, we will investigate whether CpG-oligodeoxynucleotides (ODN) prevent radiation-induced pulmonary fibrosis by shifting the imbalance of Th1 and Th2 response and summarizes the possible mechanism. In this study, female C57BL/6 mice were chosen to preform pulmonary fibrosis model, the whole-thorax of mice was exposed to a single radiation dose of 15 Gy. When irradiated mice were administrated with CpG-ODN, forming of pulmonary fibrosis was significantly prevented. Th2-related cytokines (IL-4 and IL-13) expression decreased, Th1 related-cytokine (IFN-γ and IL-12) expression increased. Alveolar macrophage accumulation was reduced in irradiated tissue. Profibrotic cytokine TGF-ß1 expression stayed at lower level. In TGF-ß1-Smad-dependent pathways, TGF-ß1, TßR and phosphor-Smad 2/3 were down regulated, and Smad 7 was up regulated. These suggested that CpG-ODN prevented pulmonary fibrosis after radiation. The mechanism might be associated with reduction of alveolar macrophages accumulation and profibrogenic cytokines secretion TGF-ß1 through stimulating the combination of Th1-promoting and Th2-limiting responses after radiation, and finally inhibited the fibrosis-related downstream TGF-ß1-Smad-dependent pathway.

Protective Effects of Myrtol Standardized Against Radiation-Induced Lung Injury.

BACKGROUND/AIMS: As a major complication after thoracic radiotherapy, radiation-induced lung injury (RILI) has great impact on long term quality of life and could result in fatal respiratory insufficiency The present study was aimed to evaluate the effects of Myrtol standardized on RILI, and to investigate the underlying mechanism. METHODS: A mouse model of radiation-induced lung injury was generated by using thoracic irradiation with a single dose of 16Gy. Mice were orally administrated with Myrtol (25 mg/kg/day) for 4 weeks after irradiation, while prednisone (5 mg/kg/day) was used as a positive control. After then, the body weight and lung coefficient were calculated. The severity of fibrosis was evaluated by observing pulmonary sections after radiation and collagen content in lung tissues was calculated following the hydroxyproline (HYP) assay. Pathological changes were observed in all the groups by using HE staining and Masson staining. The serum levels of TGF-ß1, TNF-α, IL-1ß, IL-6, and PGE2 were also measured with an ELISA assay. Western blot assay was used to measure the impact of Myrtol on AKT and its downstream signaling pathway, including MMP-2 and MMP-9. The levels of Vimentin and α-SMA were evaluated with an immunofluorescence assay. RESULTS: Treatment with Myrtol standardized, but not prednisone, reduced lung coefficient and collagen deposition in lung tissues, while attenuated histological damages induced by irradiation. Myrtol standardized also reduced the production of MDA, while increased the level of SOD. It was also observed that Myrtol standardized inhibited TGF-ß1 and a series of pro-inflammatory cytokines including TNF-α, IL-1ß, IL-6, PGE2. While in prednisone group, even though the early pneumonitis was ameliorated, the collagen disposition remained unchanged in latter times. Immunofluorescence analysis also revealed elevation of vimentin and α-SMA in the alveoli after a single dose of 16Gy. CONCLUSION: The present results suggest Myrtol standardized as an effective agent for attenuating the lung injury induced by irradiation.

[Magnetic resonance imaging characteristics of unilateral versus bilateral intraplaque hemorrhage in patients with carotid atherosclerotic plaques].

OBJECTIVE: To investigate the difference in the vulnerability of carotid atherosclerotic plaques in patients with unilateral and bilateral intraplaque hemorrhage (IPH). METHODS: A retrospective analysis was conducted among 44 patients with unilateral IPH (30 cases) or bilateral IPH (14 cases) in the carotid plaques detected by magnetic resonance imaging (MRI) in our hospital between December, 2009 and December, 2012. The age, maximum wall thickness and incidence of fibrous cap rupture were compared between the two groups. RESULTS: Compared with those with unilateral IPH, the patients with bilateral IPHs had a significantly younger age (66.6∓9.4 years vs 73.7∓9.0 years, P=0.027), a significantly greater maximum plaque thickness (6.3∓1.9 mm vs 5.0∓1.3 mm, P=0.035) and a higher incidence of ulcers (50% vs 13.3%, P=0.025). Logistic regression analysis revealed a significant association between bilateral IPHs and the occurrence of ulcer with an odd ratio (OR) of 6.5 (95% confidence interval [CI]: 1.5-28.7, P=0.014). After adjustment for gender in Model 1, bilateral IPHs were still significantly associated with presence of ulcer (OR=5.7, 95%CI: 1.1-29.2, P=0.036). But after adjustment for age (P=0.131) or maximum plaque thickness (P=0.139) in model 2, no significant correlation was found between bilateral IPHs and the presence of ulcer. CONCLUSION: Compared with patients with unilateral IPH, those with bilateral IPHs are at a younger age and have a greater plaque burden and a higher incidence of fibrous cap rupture, suggesting a greater vulnerability of the carotid plaques in patients with bilateral IPHs.

Gene expression changes in residual advanced cervical cancer after radiotherapy: indicators of poor prognosis and radioresistance?

BACKGROUND: Different sensitivity of advanced cervical cancer to irradiation can decrease effectiveness of radiotherapy in some cases. We attempted to identify the differentially expressed genes in residual cervical cancer after radiotherapy that might be associated with poor prognosis and radioresistance. MATERIAL/METHODS: Differential genes expression was identified by an oligonucleotide microarray in cervical cancer tissues before radiation and after a 50-Gy dose of radiation. The microarray results were validated by quantitative real-time PCR. CXCL12 was validated by immunohistochemistry in paraffin-embedded cervical cancer tissues before radiotherapy. The relationship between the differentiated gene and prognosis was validated by survival analysis. RESULTS: Hierarchic cluster analysis identified 238 differentiated genes that exhibited ≥3.0-fold change and p<0.05. We found 111 genes that were in persistent up-regulation and 127 in persistent down-regulation after a 50-Gy dose of radiation when compared with the control group. These genes were involved in processes such as cell growth and death, cell-apoptosis, cell cycle regulation, cell signaling, DNA synthesis and repair, and cell adhesion. High differential expression of CXCL12, CD74, FGF7, COL14A1, PRC1, and RAD54L genes was validated by quantitative PCR before and after radiotherapy. Survival analysis results showed that the high expression of CXCL12 was closely related to poor prognosis. CONCLUSIONS: The higher expression of CXCL12 might be informative regarding poor prognosis in patients undergoing radical radiotherapy. The differentially expressed genes identified in our study might provide a new method for diagnosis and treatment of radioresistance in cervical cancer.

Protective effect of CpG-oligodeoxynucleotides against low- and high-LET irradiation.

BACKGROUND/AIMS: CpG-oligodeoxynucleotides (ODNs) are synthetic DNA sequences containing unmethylated cytosine-guanine motifs with potent immunomodulatory effects. Previous reports showed a powerful protective effect of CpG-ODN against the damage induced by low-LET γ-rays. In this study, we explored whether CpG-ODN also protects against the damage induced by high-LET irradiation. Parallel experiments were performed with low-LET irradiation. METHODS: RAW264.7 cells were incubated with 1 µM of CpG-ODN after γ-ray or carbon-beam irradiation. Cell death was then measured by PI/DAPI double staining, cell survival was assessed by colony-formation assays, DNA damage was evaluated by comet assays, cell cycle was monitored by flow cytometry, and the levels of apoptosis-related proteins were detected by western blots. RESULTS: When irradiated cells were treated with the CpG-ODN, cell viability decreased, cell survival increased, DNA damage and G2/M-phase arrest were ameliorated, and apoptosis was inhibited. CONCLUSIONS: The CpG-ODN showed protective effects against low-LET γ-ray and high-LET carbon-beam irradiation. These effects might be associated with the repair of DNA damage and inhibition of apoptosis.

[The Chinese urban metabolisms based on the emergy theory].

By using emergy indices of urban metabolisms, this paper analyzed 31 Chinese urban metabolisms' systematic structures and characteristics in 2000 and 2010. The results showed that Chinese urban metabolisms were characterized as resource consumption and coastal external dependency. Non-renewable resource emergy accounted for a higher proportion of the total emergy in the inland cities' urban metabolisms. The emergy of imports and exports accounted for the vast majority of urban metabolic systems in metropolises and coastal cities such as Beijing and Shanghai, showing a significant externally-oriented metabolic characteristic. Based on that, the related policies were put forward: to develop the renewable resource and energy industry; to improve the non-renewable resource and energy utilization efficiencies; to optimize the import and export structure of services, cargo and fuel; and to establish the flexible management mechanism of urban metabolisms.

Inhibition of TBK1 attenuates radiation-induced epithelial-mesenchymal transition of A549 human lung cancer cells via activation of GSK-3ß and repression of ZEB1.

Radiotherapy is an effective treatment method for lung cancer, particularly when the disease is at an advanced stage. However, previous researchers have observed that the majority of patients with conventional radiation therapy develop distant metastases and succumb to the disease. Thus, identifying and understanding novel pathways for the development of new therapeutic targets is a major goal in research on pulmonary neoplasms. Recent studies suggest that epithelial-mesenchymal transition (EMT) is the most important contributor to cancer metastasis. Induction of this complex process requires endogenously produced microRNAs; specifically, downregulation of the miRNA-200c causes an induction of EMT. We recently identified the tank-binding kinase-1 (TBK1) as a downstream effector of the miR-200c-driven pathway, but the biological function of TBK1 in EMT remains unknown. In this study, we tested whether TBK1 has a role in radiation-induced EMT and identified associated potential mechanisms. Human alveolar type II epithelial carcinoma A549 cells were irradiated with (60)Co γ-rays. Western blotting revealed a time- and dose-dependent decrease in E-cadherin with a concomitant increase in vimentin after radiation, suggesting that the epithelial cells acquired a mesenchymal-like morphology. TBK1 siRNA significantly inhibited radiation-induced suppression of the epithelial marker E-cadherin and upregulation of the mesenchymal marker vimentin. The invasion and migratory potential of lung cancer cells upon radiation treatment was also reduced by TBK1 knockdown. Furthermore, radiation-induced EMT attenuated by TBK1 depletion was partially dependent on transcriptional factor ZEB1 expression. Finally, we found glycogen synthase kinase-3ß (GSK-3ß) is involved in regulation of radiation-induced EMT by TBK1. Thus, our findings reveal that TBK1 signaling regulates radiation-induced EMT by controlling GSK-3ß phosphorylation and ZEB1 expression. TBK1 may therefore constitute a useful target for treatment of radiotherapy-induced metastasis diseases.

CpG-Oligodeoxynucleotide Treatment Protects against Ionizing Radiation-Induced Intestine Injury.

BACKGROUND: the bone marrow and the intestine are the major sites of ionizing radiation (IR)-induced injury. Our previous study demonstrated that CpG-oligodeoxynucleotide (ODN) treatment mitigated IR-induced bone marrow injury, but its effect on the intestine is not known. In this study, we sought to determine if CpG-ODN have protective effect on IR-induced intestine injury, and if so, to determine the mechanism of its effect. METHODS AND FINDINGS: Mice were treated with CpG-ODN after IR. The body weight and survival were daily monitored for 30 days consecutively after exposure. The number of surviving intestinal crypt was assessed by the microcolony survival assay. The number and the distribution of proliferating cell in crypt were evaluated by TUNEL assay and BrdU assay. The expression of Bcl-2, Bax and caspase-3 in crypt were analyzed by Immunohistochemistry assay. The findings showed that the treatment for irradiated mice with CpG-ODN diminished body weight loss, improved 30 days survival, enhanced intestinal crypts survival and maintained proliferating cell population and regeneration in crypt. The reason might involve that CpG-ODN up-regulated the expression of Bcl-2 protein and down-regulated the expression of Bax protein and caspase-3 protein. CONCLUSION: CpG-ODN was effective in protection of IR-induced intestine injury by enhancing intestinal crypts survival and maintaining proliferating cell population and regeneration in crypt. The mechanism might be that CpG-ODN inhibits proliferating cell apoptosis through regulating the expression of apoptosis-related protein, such as Bax, Bcl-2 and caspase-3.

[Evaluation of atherosclerotic carotid plaque composition with magnetic resonance imaging using different sequences].

OBJECTIVE: To evaluate the capability of magnetic resonance imaging (MRI) using different sequences in displaying atherosclerotic carotid plaque composition. METHODS: Thirty-five patients received pre- and post-contrast carotid MRI examination on a 3.0T scanner. TOF, T(1)W, T(2)W, PDW and CE-T(1)W were used for identifying the positive and negative cases for the plaque composition (lipid-rich necrotic core, intraplaque hemorrhage and calcification), and their respective sensitivity, specificity and Cohens κ with 95% CI for displaying the components of the plaques were calculated. RESULTS: A total of 74 plaques were found in the 35 patients, and after exclusion of 6 plaques for a thickness below 3 mm, 68 plaques were included for the analysis. Lipid-rich necrotic core were found in 57 plaques, intraplaque hemorrhage in 30 plaques, and alcification in 43 plaques. CE-T(1)W was the optimal sequence for displaying lipid-rich necrotic core with a sensitivity of 100%, specificity of 90.9%, and κ value of 0.944. Both T(1)W and TOF reliably showed the intraplaque hemorrhage, but the former had a greater sensitivity (100%), specificity (92.1%), and κ value (0.911). Of all the 5 sequences, TOF was the best to show calcification with high sensitivity (100%), specificity (92%), and κ value (0.936). CONCLUSION: CE-T(1)W is the best sequence to show lipid-rich necrotic core with high sensitivity and specificity. T(1)W and TOF show a high level of agreement with the standard to show the intraplaque hemorrhage. TOF is more sensitive and accurate than the other sequences in displaying calcification. The combination of T(1)W, TOF and CE-T(1)W allows accurate evaluation of each component of the plaque.

[Oblique-sagittal black-blood contrast-enhanced magnetic resonance imaging in preoperative evaluation for carotid endarterectomy].

OBJECTIVE: To evaluate the value of oblique-sagittal black-blood contrast-enhanced magnetic resonance imaging (OB-CEMRI) in atherosclerotic carotid artery (CA) assessment before carotid endarterectomy (CEA). METHODS: Twenty-five patients with symptomatic atherosclerotic stenosis in the carotid artery (involving 26 arteries) were scheduled for CEA. OB-CEMRI and digital subtraction angiography (DSA) were conducted within 1 week prior to CEA, and two radiologists independently assessed the location of maximal lumen stenosis, plaque rupture, degree of maximal lumen stenosis and plaque involvement on DSA and OB-CEMRI images. The differences of DSA and the OB-CEMRI in analyzing the plaque conditions were assessed in comparison with matched histological sections of the excised specimens. RESULTS: Compared with the corresponding histological specimens, both DSA (κ=0.807) and OB-CEMRI (κ=0.812) showed a good consistency in defining the location of the maximal lumen stenosis. OB-CEMRI showed a better performance in detecting plaque rupture with higher sensitivity (90.0%) and specificity (83.3%) than DSA (40.0% and 66.7%, respectively). No significant difference was found between DSA and the OB-CEMRI in evaluating the degree of maximal lumen stenosis [(77.33∓3.79)% vs (76.02∓3.95)%, P=0.648]. Compared with the histological examination, OB-CEMRI appeared to underestimate the stenosis. The plaque extent on OB-CEMRI was larger than that on DSA (18.96∓4.96 mm vs 14.80∓3.78 mm, P=0.004), and similar to that by histological examination (18.13∓4.57 mm, P=0.506). CONCLUSIONS: OB-CEMRI allows noninvasive and objective detection of the location of the maximal lumen stenosis, plaque rupture, and plaque extent, though with a lower accuracy than DSA in the assessment of the maximal lumen stenosis. OB-CEMRI combined with DSA offers a more reliable means for preoperative evaluation of the carotid artery plaques for CEA.

[Atherosclerotic area measurement in the vascular wall of the carotid artery: comparison between 16-slice computed tomography angiography and high-resolution magnetic resonance imaging].

OBJECTIVE: To assess the accuracy of computed tomography angiography (CTA) in quantifying atherosclerotic area in the vascular wall of the carotid artery in comparison with high-resolution magnetic resonance imaging (MRI). METHODS: Eighteen subjects (15 males and 3 females aged 63-/+8 years) with >or=50% stenosis in at least one carotid artery were enrolled in this study. CTA and high-resolution MRI scans (in-plane pixel size of 0.25 mmx0.25 mm for both) were conducted within 1 week on a multi-slice spiral CT scanner and a 1.5T MR scanner (Signa, GE Medical Systems), respectively. CTA images were matched with MR images with the carotid bifurcation as the mark. For each patient, multiple matched slices with carotid atherosclerotic plaques in the bilateral carotid arteries were selected to measure the outer wall boundary (OWB) area, lumen area and wall area. Bland-Altman analysis and Pearson correlation coefficients were used to analyze the correlations of the area measurements between CTA and high-resolution MRI. RESULTS: A wide range of lesion size (vascular wall area) was found in these patients. Strong correlations were noted between CTA and high-resolution MRI with the correlation coefficients for OWB area, lumen area and wall area of 0.98, 0.98 and 0.96, respectively. The mean differences between CTA and high-resolution MRI were 0.16-/+5.71 mm(2), 4.47-/+1.44 mm(2) and -4.31-/+5.73 mm(2) for OWB area, lumen area and wall area, respectively. CONCLUSION: Compared to high-resolution MRI, CTA is also a reliable method to measure carotid vascular wall area. CTA might become an alternative modality to high-resolution MRI for follow-up examination of patients with carotid artery atherosclerosis, especially in uncooperative patients or patients with contra-indications for MRI.

[Proteomic analysis of proteins related to radiation-induced carcinogenesis].

BACKGROUND & OBJECTIVE: Carcinogenesis is the most serious late effect of radiation, but the mechanism of radiation-induced carcinogenesis remains unknown. This study was to compare the protein expression profiles between radiation-induced cancer cells and normal cells. METHODS: Immortalized human bronchia epithelial cell line BEAS-2B was irradiated by gamma-ray to prepare malignant BR22P50 cells. Protein profiles of BR22P50 cells and normal cell line BNP50 were detected by two-dimensional (2D) electrophoresis. The differentially expressed proteins were identified by mass spectrometry. The protein levels of ENO1, Prx I, Dyrk2, and GPX1 in different phases of radiation-induced carcinogenesis were detected by Western blot. RESULTS: A total of 59 proteins were differentially expressed between BR22 P50 and BNP50 cells. Of the 59 proteins, 14 were only expressed in BR22P50 cells, 15 were only expressed in BNP50, 7 were overexpressed and 23 were lowly expressed in BR22P50 cells. Using MALDI-TOF MS technology, 26 proteins were identified, including enzymes, structure proteins, cell signal proteins, binding proteins, metabolism-related proteins, some unknown functional proteins, and poly-peptides. The expression of ENO1 and Prx I was up-regulated and that of Dyrk2 and GPX1 was down-regulated with the advancement of radiation-induced carcinogenesis. CONCLUSIONS: The proteins related to radiation-induced carcinogenesis are identified by 2D electrophoresis. This study may provide a novel clue to probe the mechanism of radiation-induced carcinogenesis.

[Effects of STAT3 antisense oligonucleotide on proliferation and apoptosis of non-small cell lung cancer cell line A549].

BACKGROUND & OBJECTIVE: Signal transducer and activator of transcription 3 (STAT3) is highly expressed in various human tumor tissues and tumor cell lines, and may be involved in tumor genesis and development. This study was to design effective antisense oligonucleotide targeting STAT3 mRNA, and explore its effect on the proliferation and apoptosis of human non-small cell lung cancer cell line A549. METHODS: Ten sets of antisense sequences targeting STAT3 were designed with RNAstructure4.2 software and STAT3 mRNA total sequences, and transfected respectively into A549 cells (AS group). Cell proliferation inhibition was measured by Cell Count Kit (CCK-8) assay. Cell proliferation and apoptosis were observed under inverted phase contrast microscope. Cell apoptosis was determined by flow cytometry (FCM) with Hoechst33258 staining and Annexin V/PI double staining. The expression of STAT3, p-STAT3, and Bcl-x(L) were detected by Western blot. Cell cycle was detected by FCM. RESULTS: The 10 sets of designed sequences inhibited the proliferation of A549 cells. The inhibition rate of A549 cell proliferation reached 75.46% after transfection of AS10; the higher the concentration of the antisense oligonucleotide was, the heavier the inhibitory effect was displayed (P<0.01). Apoptotic cells were increased after transfection of antisense oligonucleotide. Antisense oligonucleotide induced early apoptosis in A549 cells: the early apoptosis rate was significantly higher in AS group than in control group (11.51% vs. 5.18%, P<0.01). The expression of STAT3, p-STAT3, and Bcl-x(L) were down-regulated after transfection of antisense oligonucleotide. The G1 phase proportion of A549 cells was significantly higher in AS group than in control group (63.96% vs. 44.47%, P<0.01). CONCLUSION: The antisense oligonucleotide sequences targeting STAT3 designed with computer could inhibit the proliferation and induce the apoptosis of A549 cells.

[Effects of STAT3 antisense oligodeoxynucleotides on apoptosis and proliferation of mouse melanoma cell line B16].

BACKGROUND & OBJECTIVE: STAT3 protein has been found constitutively activated in a wide variety of human tumor tissues and cell lines. It may be involved in tumorigenesis and development. This study was to observe the activation of STAT3 protein in mouse melanoma cell line B16, human liver cancer cell lines SMMC-7721 and HepG-2, human lung cancer cell line A549, and human cervical cancer cell line HeLa, and to investigate the effects of STAT3 antisense oligodeoxynucleotides (ASODN) on proliferation and apoptosis of B16 cells. METHODS: B16 cells were transfected with STAT3 ASODN or STAT3 sense oligodeoxynucleotides (STAT3 SODN), respectively. The expression and phosphorylation levels of STAT3 protein in all the tumor cells were measured by Western blot. The proliferation of B16 cells was detected by MTT assay. Cell apoptosis was determined by Hoechst33258 staining and Annexin V/PI using flow cytometry. RESULTS: STAT3 was highly expressed and phosphorylated in all the tumor cells. Transfection of STAT3 ASODN suppressed the expression and phosphorylation levels of STAT3 protein in B16 cells. Forty-eight hours after transfection, the proliferation of B16 cells was inhibited the higher the concentration (0-200 nmol/L) of STAT3 ASODN was, the heavier the inhibition was (P<0.01); when transfected with STAT3 SODN over 250 nmol/L, the proliferation of B16 cells was also inhibited (P<0.05). Inhibitory effects appeared 24 h later after transfection of STAT3 ASODN, and became more obvious 48 h later (P<0.01). The early apoptosis rate was significantly higher in 400, 800, 2,000 nmol/L STAT3 ASODN groups and 2,000 nmol/L STAT3 SODN group than in blank control group (8.22%, 9.99%, 16.97%, and 13.31% vs. 5.52%, P<0.01); no significant difference was found among 400 and 800 nmol/L STAT3 SODN groups and blank control group (5.87%, 5.36% and 5.52%, P>0.05). CONCLUSIONS: STAT3 is highly expressed and activated in all the tumor cells detected. STAT3 ASODN can abrogate the activity of STAT3 protein, inhibit proliferation and induce apoptosis of B16 cells, which support that STAT3 may be a potential molecular target for tumor therapy.

Classification of human carotid atherosclerotic lesions with in vivo multicontrast magnetic resonance imaging.

BACKGROUND: Recent studies demonstrated that in vivo and ex vivo MRI can characterize the components of the carotid atherosclerotic plaque, such as fibrous tissue, lipid/necrotic core, calcium, hemorrhage, and thrombus. The purpose of this study was to determine whether in vivo high-resolution multicontrast MRI could accurately classify human carotid atherosclerotic plaque according to the American Heart Association classification. METHODS AND RESULTS: Sixty consecutive patients (mean age 70 years; 54 males) scheduled for carotid endarterectomy were imaged with a 1.5-T scanner after informed consent was obtained. A standardized protocol was used to obtain 4 different contrast-weighted images (time of flight and T1-, PD-, and T2-weighted) of the carotid arteries. Best voxel size was 0.25x0.25x1 mm3. Carotid plaques were removed intact and processed for histological examination. Both MR images and histological sections were independently reviewed, categorized, and compared. Overall, the classification obtained by MRI and the American Heart Association classifications showed good agreement, with Cohen's kappa (95% CI) of 0.74 (0.67 to 0.82) and weighted kappa of 0.79. The sensitivity and specificity, respectively, of MRI classification were as follows: type I-II lesions, 67% and 100%; type III lesions, 81% and 98%; type IV-V lesions, 84% and 90%; type VI lesions, 82% and 91%; type VII lesions, 80% and 94%; and type VIII lesions, 56% and 100%. CONCLUSIONS: In vivo high-resolution multicontrast MRI is capable of classifying intermediate to advanced atherosclerotic lesions in the human carotid artery and is also capable of distinguishing advanced lesions from early and intermediate atherosclerotic plaque.