Radiomics model for distinguishing tuberculosis and lung cancer on computed tomography scans.

BACKGROUND: Pulmonary tuberculosis (TB) and lung cancer (LC) are common diseases with a high incidence and similar symptoms, which may be misdiagnosed by radiologists, thus delaying the best treatment opportunity for patients. AIM: To develop and validate radiomics methods for distinguishing pulmonary TB from LC based on computed tomography (CT) images. METHODS: We enrolled 478 patients (January 2012 to October 2018), who underwent preoperative CT screening. Radiomics features were extracted and selected from the CT data to establish a logistic regression model. A radiomics nomogram model was constructed, with the receiver operating characteristic, decision and calibration curves plotted to evaluate the discriminative performance. RESULTS: Radiomics features extracted from lesions with 4 mm radial dilation distances outside the lesion showed the best discriminative performance. The radiomics nomogram model exhibited good discrimination, with an area under the curve of 0.914 (sensitivity = 0.890, specificity = 0.796) in the training cohort, and 0.900 (sensitivity = 0.788, specificity = 0.907) in the validation cohort. The decision curve analysis revealed that the constructed nomogram had clinical usefulness. CONCLUSION: These proposed radiomic methods can be used as a noninvasive tool for differentiation of TB and LC based on preoperative CT data.

Clinical and epidemiologic factors associated with breast cancer and its subtypes among Northeast Chinese women.

The incidence of breast cancer has increased dramatically in China. We evaluated the clinical and epidemiologic factors associated with breast cancer, and its stage in a case-control study of Northeast Chinese women. We also examined whether these factors were differentially distributed among molecular subtypes of breast cancer in a case-only analysis. We identified 1118 breast cancer patients and 2284 healthy women from Cancer Hospital of Medical University between January 2014 and December 2017. Logistic regression models were used to calculate the odds ratios (ORs) and corresponding 95% confidence intervals (CIs). We found that postmenopausal women had a decreased risk of breast cancer (multivariate-adjusted OR = 0.33, 95% CI:0.25-0.43), and tended to have breast cancer of human epidermal growth factor receptor 2 (HER2)-overexpressing (multivariate-adjusted OR = 2.99, 95% CI: 1.49-5.97) and triple-negative (multivariate-adjusted OR = 2.16, 95% CI: 1.02-4.56) subtypes, compared with the luminal B subtype. Women with history of abortion had an increased risk of breast cancer (multivariate-adjusted OR = 4.70, 95% CI: 3.60-6.14). Women with high breast density and high Breast Imaging Reporting and Data System (BIRADS) scores of lesions tended to have breast cancer of advanced stage, but were not differentially distributed among its molecular subtypes. In conclusion, postmenopausal women had decreased risk of breast cancer, and tended to have nonluminal subtype, while women with history of abortion had increased risk of breast cancer. Women with high breast density and BIRADS scores of lesions tended to have advanced stage breast cancer. We provide evidence on the epidemiologic factors for breast cancer and its subtypes, which may help with breast cancer risk stratification.

Clinical efficacy of gemcitabine and cisplatin-based transcatheter arterial chemoembolization combined with radiotherapy in hilar cholangiocarcinoma.

BACKGROUND: Radical surgical resection is regarded as the best treatment for hepatic hilar cholangiocarcinoma. However, 60%-70% of patients have lost the chance of surgery at the time of diagnosis. Simple biliary stent or drainage tube placement may fail in a short time due to tumor invasion or overgrowth, bile accumulation, or biofilm formation. Effective palliative treatments to extend the effective drainage time are of great significance for improving the quality of life of patients and changing the prognosis of patients. AIM: To investigate the clinical efficacy of gemcitabine and cisplatin-based transcatheter arterial chemoembolization (TACE) combined with radiotherapy in hilar cholangiocarcinoma. METHODS: A retrospective analysis was conducted on patients clinically diagnosed with hilar cholangiocarcinoma from June 2014 to January 2017 at the Liaoning Provincial Cancer Hospital. Patients were evaluated by specialists, and those who were not suitable for surgery or unwilling to undergo surgery and met the inclusion criteria were included in the study. There were a total of 72 patients (34 males and 38 females) with an average age of 59.9 years (range, 40-72 years). According to percutaneous transhepatic biliary angiography and the patients' wishes, stent implantation or biliary drainage tube implantation was used to relieve biliary obstruction. The patients were divided into either a control group or a combined treatment group according to their follow-up treatment. The control group consisted of a total of 35 patients who received simple biliary drainage tube placement and biliary stent implantation (7 patients with bilateral stents and 6 with a unilateral stent) and 22 patients receiving biliary drainage tube placement alone. The combined treatment group received TACE and extracorporeal radiotherapy after biliary drainage or biliary stent implantation and consisted of a total of 37 patients, including 21 patients receiving combined treatment after biliary stent placement (14 patients with bilateral stents and 7 with a unilateral stent) and 16 undergoing combined therapy after implanting the biliary drainage tube. In the combination treatment group, the TACE chemotherapy regimen employed gemcitabine and cisplatin, and the embolic agent was iodized oil. A particular dose was determined according to the patient's body surface area and the tumor staining indicated by DSA. In vitro radiotherapy was performed with intensity-modulated radiotherapy or three-dimensional conformal radiotherapy at an average dose of 48.3 Gy. Both groups were followed from stent implantation or drainage tube implantation until the patient quitted or died. The median length of follow-up observation was 13 mo. The differences in overall survival time and the effect of different jaundice reducing methods (single stent, double stent, or biliary drainage) on the patency time and survival time of biliary stents were compared between the two groups; the related factors affecting overall survival time were analyzed. RESULTS: The median survival time of the control group was 10.5 mo; the median survival time of patients with biliary stent implantation and those with percutaneous biliary drainage was 9.6 mo and 11.4 mo, respectively, and there was no statistically significant difference between them. The median survival time of the combined treatment group was 20.0 mo, which was significantly higher than that of the control group (P < 0.05). Among patients in the combined treatment group, the median survival time of patients who underwent biliary stent implantation and those who accepted percutaneous biliary drainage before the combination therapy was 19.5 mo and 20.1 mo, respectively, and there was no significant difference between them. In the combination treatment group, the mean time of median stent patency was 15.6 mo, which was significantly higher than that of the control group (7.0 mo; P < 0.05). The independent factors affecting survival time included age, whether to receive combination therapy, percutaneous biliary drainage tube implantation, and Bismuth-Corlette classification as type IV. CONCLUSION: Gemcitabine and cisplatin-based TACE combined with radiotherapy can prolong the survival of patients with hilar cholangiocarcinoma. Independent predictors of survival include selection of combination therapy, Bismuth-Corlette classification as type IV, selection of percutaneous biliary drainage tube implantation, and age.

Feasibility of an ADC-based radiomics model for predicting pelvic lymph node metastases in patients with stage IB-IIA cervical squamous cell carcinoma.

OBJECTIVES: To investigate the prediction value of a radiomics model based on apparent diffusion coefficient (ADC) maps for pelvic lymph node metastasis (PLNM) in patients with stage IB-IIA cervical squamous cell carcinoma (CSCC). METHODS: A total of 153 stage IB-IIA CSCC patients who underwent preoperative MRI including DWI from January 2015 to October 2017 were retrospectively studied and divided into a training cohort ( n = 102) and a validation cohort ( n = 51). Radiomics features were extracted from the ADC maps. The one-way ANOVA method, Mann-Whitney U test and Pearson's correlation analysis were used for selecting radiomics features. Logistic regression analyses were used to develop the model. ROC analyses were used to evaluate the prediction performance of the model. RESULTS: Clinical stage, tumor diameter, and MR-reported lymph node (LN) status were significantly associated with LN status ( p < 0.05 for both the training and validation cohorts). The radiomics model, which incorporated clinical stage, MR-reported LN status, and grey-level non-uniformity, showed good predictive performance in the training group (AUC 0.864; 95% CI, 0.782 - 0.924) and the validation group (AUC 0.870; 95% CI, 0.747 - 0.948). The performance of the radiomics model was significantly better than that of each predictive factor alone. CONCLUSION: The presented radiomics model, a non-invasive preoperative prediction tool, has the potential to have more predictive efficacy than clinical and radiological factors for differentiating between metastatic and non-metastatic lymph nodes. ADVANCES IN KNOWLEDGE: A radiomics model derived from the ADC maps of primary lesions demonstrated good performance for predicting PLNM in stage IB-IIA CSCC patients and may help to improve clinical decision-making.

The relationship between calcium (water) density and age distribution in adult women with spectral CT: initial result compared to bone mineral density by dual-energy X-ray absorptiometry.

BACKGROUND: Calcium (water) density (DCa(Wa)) of gemstone spectral imaging by spectral computed tomography (CT) is a new method of evaluating bone structures. PURPOSE: To investigate age-related change of DCa(Wa) of a chosen lumbar vertebra in adult women with spectral CT and the correlation between the DCa(Wa) and bone mineral density (BMD) of dual-energy X-ray absorptiometry (DXA). MATERIAL AND METHODS: A total of 305 adult women underwent spectral CT, 127 of whom simultaneously underwent DXA. All the patients were divided into 11 subgroups based on age. DCa(Wa) and BMD were measured at the second lumbar vertebra on the calcium (water)-based material decomposition images of spectral CT and DXA, respectively. A one-way analysis of variance (ANOVA) was performed for the difference of the measurements among adjacent age subgroups. Pearson correlation was used to assess the association between age and DCa(Wa), age and BMD, as well as DCa(Wa) and BMD. RESULTS: There was a significant negative correlation between DCa(Wa) and age (r = -0.719) as well as BMD and age(r = -0.851). The mean DCa(Wa) of L2 vertebral body was significantly different between the 40-44- and 45-49-, 45-49- and 50-54-, 55-59- and 60-64-, 65-69- and 70-74-year-old age subgroups. BMD was significantly different between the 35-39- and 40-44-, 45-49- and 50-54-, and 65-69- and 70-74-year-old age subgroups. There was a significant positive correlation between DCa(Wa) and BMD. CONCLUSIONS: The DCa(Wa) of lumbar vertebra by spectral CT demonstrated similar age distribution as BMD of DXA and could be used as a method of measuring the vertebral bone mineral density in adult women.

Sensitivity and Specificity of Diffusion-Weighted Magnetic Resonance Imaging in Diagnosis of Bladder Cancers.

PURPOSE: Our study is designed to examine the diagnostic performance of diffusion-weighted magnetic resonance imaging (DW-MRI) for bladder cancers (BC), and to determine whether DW-MRI can differentiate muscle invasive bladder cancer (MIBC) from non-MIBC (NMIBC). METHODS: A meta-analysis was performed of published studies that investigated the performance of DW-MRI for BC. These studies were retrieved from scientific literature databases using sensitive electronic search strategies. The STATA 12.0 and Meta-disc software were employed for statistical analyses of data extracted from selected studies. RESULTS: Our search initially returned 230 articles, of which 11 met the inclusion criteria and were enrolled into the final meta-analysis. Five of the included studies reported the diagnostic performance of DW-MRI for BC with a cumulative total of 243 BC patients and 82 healthy subjects. Eight studies investigated the diagnostic performance of DW-MRI for differentiating MIBC from NMIBC, involving 259 MIBC lesions and 515 NMIBC lesions. Meta-analysis results were as follows: the diagnostic performance of DW-MRI for BC (sensitivity: 0.95 [0.75-0.99]; specificity: 0.85 [0.74-0.92]; positive likelihood ratio: 6.45 [3.64-11.42]; negative likelihood ratio: 0.055 [0.009-0.333]; diagnostic odds ratio: 117.11 [19.37-708.05]; area under the curve (AUC): 0.91); the diagnostic performance of DW-MRI to differentiate MIBC from NMIBC (sensitivity: 0.85 [0.76 - 0.91]; specificity: 0.90 [0.87 - 0.93]; positive likelihood ratio:8.81[6.43 - 12.07]; negative likelihood ratio: 0.16 [0.10 - 0.28]; diagnostic odds ratio: 53.95 [25.68 - 113.33]; AUC: 0.92). CONCLUSION: DW-MRI has an outstanding diagnostic performance, with advanced sensitivity and specificity, for imaging of bladder cancers and for differentiating MIBC from NMIBC.

AGEs Promote Oxidative Stress and Induce Apoptosis in Retinal Pigmented Epithelium Cells RAGE-dependently.

Advanced glycation end products (AGEs) are extremely accumulated in diabetes mellitus, particularly in retinal vascular and epithelium cells, and are confirmed to contribute to diabetic retinopathy (DR). In the present study, we determined the promotion by AGEs to the oxidative stress and mitochondrial dysfunction in retinal pigmented epithelium ARPE-19 cells and investigated the influence by the knockdown or the overexpression of receptor for AGEs (RAGE) on the AGE-promoted oxidative stress and mitochondrial dysfunction. Furthermore, we determined the induction by AGEs to the cell apoptosis and to the activation of B-cell lymphoma 2 (Bcl-2) families in the AGE-BSA-induced apoptosis, and examined the RAGE-dependence in such induction. Results demonstrated that AGE-BSA upregulated the hydrogen peroxide production and induced mitochondrial dysfunction in ARPE-19 cells, dose-dependently. And the further investigation indicated that the AGE-RAGE interaction was required for the induction of oxidative stress and mitochondrial dysfunction. Moreover, the AGE-BSA treatment promoted a significantly high level of apoptotic cells, and the Bcl-2 family was implicated in the AGE-BSA-induced apoptosis, there was a significant high level of Cyt c release, Bcl-2-associated X protein (Bax) induction, Bcl-2 reduction, and caspase 9 activation in the AGE-BSA-treated cells. In conclusion, the present study recognized the apoptosis induction by AGE-BSAs in the retinal epithelium ARPE-19 cells, RAGE-dependently. The mitochondrial dysfunction was induced, and the Bcl-2 family was deregulated during the AGE-BSA-induced ARPE-19 cell apoptosis.

Low-frequency microsatellite instability in genomic di-nucleotide sequences correlates with lymphatic invasion and poor prognosis in gastric cancer.

The clinical significance of low-frequency microsatellite instability (MSI-L) in gastric cancer (GC) has not been well established. The aim of this study was to evaluate the clinicopathological features of MSI-L in GC. We investigated microsatellite instability (MSI) in 5 di-nucleotide repeat sequences in 210 unselected GC patients. High-resolution fluorescent microsatellite analysis assay was utilized to detect MSI. Clinicopathological variables were compared among groups with different microsatellite statuses. The overall survival (OS) was analyzed by Kaplan-Meier method. Multivariable analysis was performed to identify prognostic factors and variables correlated with lymph node metastasis. High-frequency microsatellite instability (MSI-H), MSI-L, and microsatellite stable were identified, respectively, in 10.5, 10.0, and 79.5% of unselected GC cases. Tumors with MSI-H were less invasive, and these patients showed a better OS. MSI-L was correlated with more advanced tumor Node Metastasis stage, and more frequent lymph node metastasis. The unfavorable prognosis predicted by MSI-L was ascribed to its correlation with lymphatic invasion. MSI-L characterized by di-nucleotide markers represents a distinct subcategory of GC with aggressive clinicopathological features, which are particularly affiliated to lymphatic system and correlated with a poor prognosis. MSI-L could be beneficial for predicting the clinical outcome of GC.

[Molecular mechanism of chemosensitization to paclitaxel in human melanoma cells induced by targeting the EGFR signaling pathway].

OBJECTIVE: To study the molecular mechanism of epidermal growth factor receptor (EGFR) signaling pathway in mediating paclitaxel-resistance and improving paclitaxel sensitivity in human melanoma A375 cells. METHODS: Human melanoma cell line A375 cells were treated with different concentrations of paclitaxel with or without 20 µmol/L AG1478 (EGFR inhibitor), 40 µmol/L PD98059 (extracellular signal conditioning kinase (ERK) 1/2 blockers) or 10 µmol/L LY294002 (PI3K inhibitor). MTT method was used to measure the proliferation of A375 cells. Flow cytometry was used to detect cell cycle and apoptosis in the A375 cells. The expressions of P-EGFR, P-ERK and P-AKT proteins were determined by Western blot analysis. RESULTS: Paclitaxel (0.001 µmol/L to 0.1 µmol/L) inhibited the growth of A375 cells (P < 0.01) and induced apoptosis (P < 0.05) in a dose- and time-dependent manner. AG1478 (20 µmol/L) increased the 0.01 µmol/L paclitaxel-induced inhibition rate from 38.5% to 62.6% at 72 h. Different doses of paclitaxel induced apoptosis in A375 cells by different ways, in which G0/G1 phase cells were decreased and mitotic phase was prolonged at 0.01 µmol/L, and cell cycle arrest at G2/M phase by 0.1 µmol/L paclitaxel. When DNA damage occurred in A375 cells exposed to paclitaxel, expression of P-EGFR, P-ERK and P-AKT proteins was increased. When EGFR signaling pathway was blocked, paclitaxel did not activate MAPK signaling pathway or PI3K/AKT signaling pathway and did not change its effect on cell cycle in vitro. When EGFR was inhibited by 20 µmol/L tyrophostin AG1478, the 0.001 and 0.01 µmol/L paclitaxel-induced early apoptosis rate in A375 cells was increased by 1.73- and 1.80-fold, respectively. When the ERK signaling was blocked by 40 µmol/L PD98059, the 0.001 and 0.01 µmol/L paclitaxel-induced early apoptosis rate in A375 cells was increased by 2.73- and 2.25-fold, respectively. When the AKT signaling was blocked by 10 µmol/L LY294002, the 0.001 and 0.01 µmol/L paclitaxel-induced early apoptosis rate in A375 cells was increased by 2.02- and 1.46-fold, respectively. CONCLUSIONS: Human melanoma A375 cells produce resistance to paclitaxel (0.001 to 0.1 µmol/L) by activating MAPK signaling and PI3K/AKT signaling pathways. Targeting EGFR, ERK and AKT signaling pathways significantly enhances the cytotoxic effect of paclitaxel on human melanoma cells.

Measurement of retinal nerve fiber layer thickness in optic atrophy eyes of patients with optic neuritis using optical coherence tomography.

OBJECTIVE: To measure the retinal nerve fiber layer (RNFL) thickness using optical coherence tomography (OCT) in optic atrophy eyes of patients with optic neuritis and investigate the correlation between the RNFL thickness and the visual function. METHODS: To compare the RNFL thickness using StratusOCT, three groups of the subjects were enrolled, including 72 patients with optic atrophy with definite demyelinating optic neuritis history (the neuritis group), 47 patients with advanced POAG atrophic neuropathy (the POAG group), and 47 healthy subjects (the control group). The correlation between the RNFL thickness and visual function parameters were investigated in the neuritis group, including the best-corrected visual acuity (BCVA), the visual field mean deviation (MD), pattern standard deviation (PSD), and P(100) latency of visual evoked potentials (VEP). RESULTS: The average RNFL thickness, superior, nasal and inferior thicknesses were significantly thinner in both the neuritis group and the POAG group than those in the control group (p < 0.05), while they were higher in the neuritis group than the POAG group (p < 0.05). The significant correlations were found both between the average RNFL thickness and BCVA (r = 0.35, p < 0.05), MD (r = 0.43, p < 0.05), and PSD (r = 0.39, p < 0.05). CONCLUSION: In comparison to the advanced POAG and normal eyes, the RNFL thickness was decreased moderately in the optic atrophy eyes resulting from demyelinating optic neuritis and was quantitatively correlated with the visual function parameters.

Fibronectin and focal adhesion kinase small interfering RNA modulate rat retinal Müller cells adhesion and migration.

Retinal Müller cells (RMCs) hypertrophy and proliferation play a crucial role in epiretinal membrane formation. This study was designed to analyze the effects of Fibronectin and specific FAK siRNA in cell adhesion and migration in rat Müller cells. RMCs were cultured and identified by GFAP, Vimentin, and GLAST mAb, respectively. The cells were planted on dishes coated with Fibronectin at 0, 1, 5, 10, 50, and 100 microg/ml. The attachment and migration assay was applied to characterize the RMCs-Fibronectin interactions. Cell lysis and Western blotting were utilized to detect beta(1)-integrin, FAK, and GLAST protein expression. Then the cells were treated with FAK siRNA, non-targeting siRNA, and control medium. The cell cycle and apoptosis rate was determined by flow cytometry. The attachment, migration, and Western blotting assay were repeated. These data suggested that almost all the cells expressed GFAP, Vimentin, and GLAST, respectively, which ensured most of the harvested cells were RMCs. In attachment assay, the A570 values increased significantly with time (F = 1105.439, P < 0.001) and Fibronectin concentration (F = 424.683, P < 0.001). There were significant difference between each Fibronectin concentration in RMCs migration (F = 34.703, P < 0.000). The expression ratio of FAK, beta(1)-integrin, and GLAST elevated significantly as Fibronectin concentration increased (F = 54.755, P < 0.000; F = 119.962, P < 0.000; F = 39.287, P < 0.000). The Fibronectin pretreatment was settled on 50 microg/ml for siRNA inhibition assays. The specific FAK siRNA treatment significantly increased G(0)/G(1) percentage and apoptosis rate compared with NT siRNA and control group (F = 11.526, P = 0.009; F = 64.772, P < 0.000). The apoptotic rate was significantly suppressed by inhibitors of caspase-8 and 3 (F = 10.500, P = 0.011). The A570 values were significantly suppressed in FAK siRNA groups compared with NT siRNA and control group (F = 154.241, P < 0.000), and the mean migratory cells per view field were significantly decreased (F = 10.906, P = 0.001). FAK and GLAST expression ratio decreased significantly after FAK siRNA treatment (F = 5.315, P = 0.047; F = 5.985, P = 0.042). Take together, FAK is involved in beta(1)-integrin mediated adhesive signaling and play a critical role in regulating Müller cell adhesion, migration, and so far as to glutamate transportation functions.