Drug-drug interaction between danshensu and irbesartan and its potential mechanism.

To uncover the effect of danshensu on irbesartan pharmacokinetics and its underlying mechanisms.To investigate the effect of danshensu on the pharmacokinetics of irbesartan, Sprague-Dawley rats (n = 6) were orally administered 30 mg/kg irbesartan alone (control group) or pre-treated with 160 mg/kg danshensu (experimental group). The effect of danshensu on the metabolic stability of irbesartan in RLMs was examined by LC-MS/MS method. The effect of danshensu on CYP2C9 activity was also determined.Danshensu markedly increased the AUC(0-t) (9573 ± 441 vs. 16157 ± 559 µg/L*h) and Cmax (821 ± 24 vs. 1231 ± 44 µg/L) of irbesartan. Danshensu prolonged the t1/2 (13.39 ± 0.98 vs. 16.04 ± 1.21 h) and decreased the clearance rate (2.27 ± 0.14 vs. 1.19 ± 0.10 L/h/kg) of irbesartan. Danshensu enhanced the metabolic stability of irbesartan in vitro with prolonged t1/2 (36.34 ± 11.68 vs. 48.62 ± 12.03 min) and reduced intrinsic clearance (38.14 ± 10.24 vs. 28.51 ± 9.06 µL/min/mg protein). Additionally, the IC50 value for CYP2C9 inhibition by danshensu was 35.74 µM.Danshensu enhanced systemic exposure of irbesartan by suppressing CYP2C9. The finding can also serve as a guidance for further investigation of danshensu-irbesartan interaction in clinical practice.

Preoperative Local Staging of Colon Cancer by CT: Radiological Staging Criteria Based on Membrane Anatomy and Visceral Adipose Tissue.

BACKGROUND: Accuracy of preoperative T staging for colon cancer remains disappointing. OBJECTIVE: This study aimed to propose specially designed radiological staging criteria based on membrane anatomy and visceral adipose tissue and compare the staging performance with the routinely used method. DESIGN: This is a prospective observational study. SETTING: This study was conducted at a high-volume colorectal center. PARTICIPANTS: Consecutive patients with colonoscopy-proven colon carcinoma referred for clinical staging and elective resection were enrolled. INTERVENTION: The preoperative CT data were separately reviewed by 2 teams of radiologists for assigning T-stage categories (T1-2, T3, or T4) using the routine staging method or the newly proposed radiological criteria. MEASURES: Diagnostic performance for T staging was compared between the 2 criteria. RESULTS: Between October 2019 and August 2020, 190 patients were included. Compared with pathological results, T stage was correctly determined in 113 of 190 patients (59.5%) with the conventional CT criteria. With the newly developed criteria, 160 patients (84.2%) were found to be correctly staged. Accuracies between the 2 criteria significantly differed ( p < 0.001). For T1-2 staging, there were no significant differences between the sensitivities of conventional and new criteria (57.1% vs 61.9%; p = 0.990) or between their specificities (95.3% vs 98.2%; p = 0.131). However, for T3 and T4 staging, the newly developed CT criteria exhibited significantly higher sensitivity (T3: 85.2% vs 57.4%; p < 0.001; T4: 90.7% vs 64.8%; p < 0.001) and specificity (T3: 82.7% vs 64%; p = 0.006; T4: 89.7% vs 69.1%; p < 0.001) than the conventional criteria. Moreover, the new criteria (area under the curve = 0.902) performed significantly better than the conventional criteria (area under the curve = 0.670; p < 0.001), for identifying the T4-stage tumor. LIMITATIONS: The limitations are that it is a single-center study and there was no external validation. CONCLUSIONS: The specially designed radiological criteria can offer more accurate T staging than the routine method in colon cancer. See Video Abstract at http://links.lww.com/DCR/B992 . PREDICCIN DE LA MORTALIDAD A DAS POSTERIORES A LA PRIMERA CIRUGA EN PACIENTES CON CNCER DE COLON OBSTRUCTIVO DEL LADO IZQUIERDO: ANTECEDENTES:Se cree que la resección aguda para el carcinoma de colon obstructivo del lado izquierdo está asociada con un mayor riesgo de mortalidad que un enfoque puente a la cirugía que utiliza un estoma de descompresión o un stent metálico autoexpandible, pero faltan modelos de predicción.OBJETIVO:Determinar la influencia de la estrategia de tratamiento sobre la mortalidad dentro de los 90 días desde la primera intervención utilizando un modelo de predicción en pacientes que presentan carcinoma de colon obstructivo del lado izquierdo.DISEÑO:Un estudio de cohorte multicéntrico nacional, utilizando datos de una auditoría nacional prospectiva.ENTORNO CLINICO:El estudio se realizó en 75 hospitales holandeses.PACIENTES:Se incluyeron los pacientes que se sometieron a una resección con intención curativa de un carcinoma de colon obstructivo del lado izquierdo entre 2009 y 2016.INTERVENCIONES:La primera intervención fue resección aguda, puente a cirugía con stent metálico autoexpandible o puente a cirugía con estoma descompresor.PRINCIPALES MEDIDAS DE VALORACIÓN:La principal medida de resultado fue la mortalidad a los 90 días después de la primera intervención. Los factores de riesgo se identificaron mediante análisis logístico multivariable. Posteriormente se desarrolló un modelo de riesgo.RESULTADOS:En total se incluyeron 2395 pacientes, siendo la primera intervención resección aguda en 1848 (77%) pacientes, estoma como puente a la cirugía en 332 (14%) pacientes y stent como puente a la cirugía en 215 (9%) pacientes. En general, 152 pacientes (6,3%) fallecieron dentro de los 90 días posteriores a la primera intervención. Un estoma de descompresión se asoció de forma independiente con un menor riesgo de mortalidad a los 90 días (HR: 0,27, IC: 0,094-0,62). Otros predictores independientes de mortalidad fueron la edad, la clasificación ASA, la ubicación del tumor y los niveles índice de creatinina sérica y proteína C reactiva. El modelo de riesgo construido tuvo un área bajo la curva de 0,84 (IC: 0,81-0,87).LIMITACIONES:Solo se incluyeron pacientes que se sometieron a resección quirúrgica.CONCLUSIONES:La estrategia de tratamiento tuvo un impacto significativo en la mortalidad a los 90 días. Un estoma descompresor reduce considerablemente el riesgo de mortalidad, especialmente en pacientes mayores y frágiles. Se desarrolló un modelo de riesgo, que necesita una mayor validación externa. Consulte Video Resumen en http://links.lww.com/DCR/B992 . (Traducción-Dr. Ingrid Melo ).

Spatial dynamics of pH in the rhizosphere of Leersia hexandra Swartz at different chromium exposure.

The roots of hyperaccumulators can significantly alter soil pH and thus change the chromium (Cr) availability in the rhizosphere. The pH dynamics in the rhizosphere of Cr hyperaccumulator Leersia hexandra Swartz remains unknown. In this study, the spatial dynamics of pH in the rhizosphere of L. hexandra at different Cr exposure were examined using planar optode (PO). The effects of different Cr concentrations on the biomass, physiological parameters, and soil enzyme activity were investigated. The results showed that pH in the rhizosphere of L. hexandra was highly heterogeneous and followed the root shape. There were obvious soil acidification in all groups and the average pH values in the control, Cr50, and Cr100 groups decreased by 0.26, 0.27, and 0.35 pH unit, respectively. At a certain concentration (50 mg kg-1), Cr significantly increased the plant height and biomass of L. hexandra compared to the control (p < 0.05). The concentrations of chlorophyll a, chlorophyll b, and total chlorophyll in the leaves increased with increasing Cr concentrations. The acid phosphatase, urease, and catalase activities in the rhizosphere were higher than those in the bulk soil. These results provide new insights into elucidating the hyperaccumulating mechanism of Cr and improving the phytoremediation efficiency.

Heterogeneous Fenton system driven by iron-loaded sludge biochar for sulfamethoxazole-containing wastewater treatment.

In this study, the treatment performance of a heterogeneous Fenton system (Fe-BC + H2O2) driven by iron-loaded sludge biochar (Fe-BC) on wastewater containing sulfamethoxazole (SMX) was investigated using the CODcr removal efficiency (φ) as an indicator. The batch experimental results showed that the optimal operating conditions were as follow: initial pH 3, H2O2 concentration 20 mmol L-1, Fe-BC dose 1.2 g L-1, temperature 298 K. The corresponding φ was as high as 83.43%. The removal of CODcr was better described by BMG model and revised BMG (BMGL) model. According to the BMGL model, the φmax could be 98.37% (298 K). Moreover, the removal of CODcr was a diffusion-controlled process, while liquid film diffusion and intraparticle diffusion together determined its removal rate. The removal of CODcr should be a synergistic effect of adsorption and Fenton oxidation (real heterogeneous Fenton and homogeneous Fenton) and other pathways. Their contributions were 42.79%, 54.01% and 3.20%, respectively. For homogeneous Fenton, there seemed to be two simultaneous SMX degradation pathways: SMX→4-(pyrrolidine-11-sulfonyl)-aniline→N-(4-aminobenzenesulfonyl) acetamide/4-amino-N-ethyl benzene sulfonamides→4-amino-N-hydroxy benzene sulfonamides; SMX→N-ethyl-3-amino benzene sulfonamides→4-methanesulfonylaniline. In summary, Fe-BC had potential for practical application as a heterogeneous Fenton catalyst.

Facile preparation of activated carbon supported nano zero-valent iron for Cd(â ¡) removal in aqueous environment.

Activated carbon-supported nano-zero-valent iron (nZVI@AC) is considered to be one of the most promising materials for in-situ remediation of pollutants in aqueous environment, while liquid phase reduction (LPR) is one of the most commonly used preparation methods for nZVI@AC. However, the complex operation and the requirement of various agents limit the practical application of the traditional liquid-phase reduction (TLPR). In this study, an improved liquid phase reduction method (ILPR) was proposed, which was characterized by solid-state dosing of reducing agents. Compared with TLPR, ILPR simplified the preparation process, while there was no requirement of polyethylene glycol and ethanol. When the Cd(II) removal efficiency was used as the evaluation index, the preferred parameters of ILPR were as follows: AC/FeSO4·7H2O mass ratio was 15:1; NaBH4 dosage was 8 g; ultrasonic time was 1 h; stirring time was 20 min. Moreover, the Cd(II) removal efficiency of nZVI@AC prepared by ILPR (nZVI@AC-I) was greater than 92.00%, which was superior to that of nZVI@AC prepared by TLPR (nZVI@AC-T). The characterization results showed that the pore parameters, surface functional groups and iron contents of nZVI@AC-I and nZVI@AC-T were basically the same. However, the distribution of iron-containing particles on the surface of nZVI@AC-I was more uniform. Furthermore, the Fe0 in nZVI@AC-I had a smaller particle size and a higher content. Overall, this study provided a promising approach for nZVI@AC preparation.

Long noncoding RNA BCRP3 stimulates VPS34 and autophagy activities to promote protein homeostasis and cell survival.

BACKGROUND: Autophagy plays important roles in cell homeostasis and protein quality control. Long non-coding RNAs (lncRNAs) have been revealed as an emerging class of autophagy regulators, but the majority of them function in regulating the expression of autophagy-related genes. LncRNAs that directly act on the core autophagic proteins remain to be explored. METHODS: Immunofluorescence staining and Western blotting were used to evaluate the function of BCRP3 in autophagy and aggrephagy. RNA immunoprecipitation and in vitro RNA-protein binding assay were used to evaluate the interaction of BCRP3 with its target proteins. Phosphatidylinositol 3-phosphate ELISA assay was used to quantify the enzymatic activity of VPS34 complex. qRT-PCR analysis was used to determine BCRP3 expression under stresses, whereas mass spectrometry and Gene Ontology analyses were employed to evaluate the effect of BCRP3 deficiency on proteome changes. RESULTS: We identified lncRNA BCRP3 as a positive regulator of autophagy. BCRP3 was mainly localized in the cytoplasm and bound VPS34 complex to increase its enzymatic activity. In response to proteotoxicity induced by proteasome inhibition or oxidative stress, BCRP3 was upregulated to promote aggrephagy, thereby facilitating the clearance of ubiquitinated protein aggregates. Proteomics analysis revealed that BCRP3 deficiency under proteotoxicity resulted in a preferential accumulation of proteins acting in growth inhibition, cell death, apoptosis, and Smad signaling. Accordingly, BCRP3 deficiency in proteotoxic cells compromised cell proliferation and survival, which was mediated in part through the upregulation of TGF-ß/Smad2 pathway. CONCLUSIONS: Our study identifies BCRP3 as an RNA activator of the VPS34 complex and a key role of BCRP3-mediated aggrephagy in protein quality control and selective degradation of growth and survival inhibitors to maintain cell fitness.

Ultrashort time-to-echo T2* and T2* relaxometry for evaluation of lumbar disc degeneration: a comparative study.

BACKGROUND: To compare potential of ultrashort time-to-echo (UTE) T2* mapping and T2* values from T2*-weighted imaging for assessing lumbar intervertebral disc degeneration (IVDD),with Pfirrmann grading as a reference standard. METHODS: UTE-T2* and T2* values of 366 lumbar discs (L1/2-L5/S1) in 76 subjects were measured in 3 segmented regions: anterior annulus fibrosus, nucleus pulposus (NP), and posterior annulus fibrosus. Lumbar intervertebral discs were divided into 3 categories based on 5-level Pfirrmann grading: normal (Pfirrmann grade I),early disc degeneration (Pfirrmann grades II-III), and advanced disc degeneration (Pfirrmann grades IV-V). Regional differences between UTE-T2* and T2* relaxometry and correlation with degeneration were statistically analyzed. RESULTS: UTE-T2* and T2*value correlated negatively with Pfirrmann grades (P < 0.001). In NP, correlations with Pfirrmann grade were high with UTE-T2* values (r = - 0.733; P < 0.001) and moderate with T2* values (r = -0.654; P < 0.001). Diagnostic accuracy of detecting early IVDD was better with UTE-T2* mapping than T2* mapping (P < 0.05),with receiver operating characteristic analysis area under the curve of 0.715-0.876. CONCLUSIONS: UTE-T2* relaxometry provides another promising magnetic resonance imaging sequence for quantitatively evaluate lumbar IVDD and was more accurate than T2*mapping in the earlier stage degenerative process.

Identifying response in colorectal liver metastases treated with bevacizumab: development of RECIST by combining contrast-enhanced and diffusion-weighted MRI.

OBJECTIVES: Response evaluation criteria in solid tumors (RECIST) often fail to identify clinically meaningful response to bevacizumab-containing therapy in colorectal liver metastasis (CRLM). This study aimed to develop RECIST by combining contrast-enhanced and diffusion-weighted magnetic resonance imaging (MRI). METHODS: A total of 126 patients with CRLM who underwent hepatic resection after bevacizumab-containing chemotherapy were split into initial analyses cohort (N = 42, with 76 indexed liver metastases) and validation cohort (N = 84). In lesion-based analyses, percentage decrease of arterial enhancement area and percentage increase of apparent diffusion coefficient (ADC) value from baseline to post-chemotherapy were measured. Their optimal cutoff values for distinguishing pathology-confirmed major and minor response were determined. Then, the developed RECIST (D-RECIST) was established by combining functional and size-based items. Survival relevance of D-RECIST and RECIST was examined in the validation cohort. RESULTS: Percentage decrease of arterial enhancement area and increase of ADC value significantly differed between lesions of pathologic major or minor response, with optimal cutoffs of approximately 33% and 19%, respectively. Patients defined as responders by D-RECIST had a significantly longer median disease-free survival (DFS) than non-responders (p = 0.021; 12.9 versus 8.6 months). No significant difference was observed with RECIST (p = 0.524). In a Cox regression model, D-RECIST- but not RECIST-defined responses independently predicted the DFS (p = 0.034 and 0.811). CONCLUSIONS: D-RECIST-defined responses provided significant prognostic information, and thus may serve as a better response evaluation approach than RECIST in CRLM treated with bevacizumab-containing therapy. KEY POINTS: • Changes in arterial enhancement area and apparent diffusion coefficient value are associated with pathological response in colorectal liver metastases treated with bevacizumab. • The MRI-based response criteria developed by combining size-based and functional features can provide significant prognostic information.

CT-Based Hand-crafted Radiomic Signatures Can Predict PD-L1 Expression Levels in Non-small Cell Lung Cancer: a Two-Center Study.

Here, we used pre-treatment CT images to develop and evaluate a radiomic signature that can predict the expression of programmed death ligand 1 (PD-L1) in non-small cell lung cancer (NSCLC). We then verified its predictive performance by cross-referencing its results with clinical characteristics. This two-center retrospective analysis included 125 patients with histologically confirmed NSCLC. A total of 1287 hand-crafted radiomic features were observed from manually determined tumor regions. Valuable features were then selected with a ridge regression-based recursive feature elimination approach. Machine learning-based prediction models were then built from this and compared each other. The final radiomic signature was built using logistic regression in the primary cohort, and then tested in a validation cohort. Finally, we compared the efficacy of the radiomic signature to the clinical model and the radiomic-clinical nomogram. Among the 125 patients, 89 were classified as having PD-L1 positive expression. However, there was no significant difference in PD-L1 expression levels determined by clinical characteristics (P = 0.109-0.955). Upon selecting 9 radiomic features, we found that the logistic regression-based prediction model performed the best (AUC = 0.96, P < 0.001). In the external cohort, our radiomic signature showed an AUC of 0.85, which outperformed both the clinical model (AUC = 0.38, P < 0.001) and the radiomics-nomogram model (AUC = 0.61, P < 0.001). Our CT-based hand-crafted radiomic signature model can effectively predict PD-L1 expression levels, providing a noninvasive means of better understanding PD-L1 expression in patients with NSCLC.

Effect of substrate types on contaminant removals, electrochemical characteristics and microbial community in vertical flow constructed wetlands for treatment of urban sewage.

The purpose of this study was to investigate the influence of substrates (quartz sand and coke) on the removal of pollutants (COD, NH4+-N and TP), electrochemical characteristics and microbial communities of vertical flow constructed wetlands (VFCW) under high pollutant loads. During operation, the removal rates of COD, NH4+-N and TP by VFCW-C (coke as substrate) were higher than that of VFCW-Q (quartz sand as substrate) by 9.73-19.41%, 5.03%-13.15% and 8.83%-14.58%, respectively. And the resistances of the VFCW-Q and VFCW-C were increased by 1228.9 Ω and 38.3 Ω, while their potentials were dropped from 182.4 mV to 377.9 mV-85.6 mV and 222.0 mV, respectively. The dominant bacteria at the bottoms of VFCW-Q and VFCW-C were individually aerobic denitrifying bacteria (ADNB; 14.98%)/ammonia oxidizing bacteria (AOB; 5.73%) and organics aerobic degrading bacteria (OADB; 12.48%)/ammonia oxidizing bacteria (AOB; 7.24%), while the predominant bacteria at their tops were separately ADNB (11.36%)/OADB (10.52%)/AOB (4.69%) and ADNB (15.09%)/AOB (8.86%) and OADB (3.20%) The removal of pollutants by VFCW-Q and VFCW-C may be mainly attributed to substrate adsorption and microbial degradation.

Identification of enterobacteria in viscera of pigs afflicted with porcine reproductive and respiratory syndrome and other viral co-infections.

In order to investigate enterobacteria presence involved in the secondary infections in Porcine Reproductive and Respiratory Syndrome (PRRS) pigs with different viral co-infections, we identified enterobacteria for guiding clinical treatment. Twenty-one diseased pigs were diagnosed with the PRRS virus (PRRSV) and other 7 virus primers by PCR/RT-PCR in the lung and spleen samples. Enterobacteria were isolated using MacConkey agar from 5 visceral samples of PRRS pigs, and identified by 16S rDNA sequencing. PRRSV was positive in 100% of the lung samples and 81.0% of the spleen samples. Seven diseased pigs were diagnosed with only PRRSV infection (33.3%), 7 pigs with PRRSV and 1 or 2 other viruses (33.3%) and 7 pigs with PRRSV and more than 2 types of other viruses (33.3%). PRRSV was more inclined to co-infect pigs with porcine group A rotavirus (PARV) with the co-infection rate of 52.4% (11/21). Approximately 13 types of bacteria were successfully isolated from lung, spleen, liver, kidney and lymph node samples of different PRRS pigs. Enterobacteria were isolated in 100% of lung, liver and lymph samples from pigs infected with PRRSV alone. However, the isolation rates were significantly decreased in the more than 3 viruses co-infection group. Escherichia coli was the most prevalent bacterium, followed by Morganella, Proteus, Shigella, Salmonella, Klebsiella and Aeromonas. Most of the isolated enterobacteria were opportunistic pathogens. Therefore, timely combination with antimicrobial agents is necessary for effective treatment of PRRS-infected pigs.

Pre-treatment ADC image-based random forest classifier for identifying resistant rectal adenocarcinoma to neoadjuvant chemoradiotherapy.

OBJECTIVE: To develop a predicting model for tumor resistance to neoadjuvant chemoradiotherapy (NCRT) in locally advanced rectal cancer (LARC) by using pre-treatment apparent diffusion coefficient (ADC) image-derived radiomics features. METHOD: A total of 89 patients with LARC were randomly assigned into training (N = 66) and testing cohorts (N = 23) at the ratio of 3:1. Radiomics features were derived from manually determined tumor region of pre-treatment ADC images. Random forest algorithm was used to determine the most relevant features and then to construct a predicting model for identifying resistant tumor. Stability and diagnostic performance of the random forest model was evaluated with the testing cohort. RESULTS: The top 10 most relevant features (entropymean, inverse variance, energymean, small area emphasis, ADCmin, ADCmean, sdGa02, small gradient emphasis, age, and size) were determined from clinical characteristics and 133 radiomics features. In the prediction of resistant tumor of the testing cohort, the random forest model constructed based on these most relevant features achieved an area under the receiver operating characteristic curve of 0.83, with the highest accuracy of 91.3%, a sensitivity of 88.9%, and a specificity of 92.8%. CONCLUSION: The random forest classifier based on radiomics features derived from pre-treatment ADC images have the potential to predict tumor resistance to NCRT in patients with LARC, and the use of predicting model may facilitate individualized management of rectal cancer.

Effects of phosphorous fertilizers on growth, Cu phytoextraction and tolerance of Leersia hexandra swartz under different Cu stress levels.

In this study, the effects of Ca(H2PO4)2, KH2PO4 and (NH4)2HPO4 on growth, Cu phytoextraction and tolerance of Leersia hexandra swartz (L. hexandra) under different Cu stress levels were investigated. The results showed that KH2PO4 could most significantly increase the plant height of L. hexandra (p < 0.05), while (NH4)2HPO4 had the most significant promoting effect on its biomass (p < 0.05) by enhancing photosynthesis (chlorophyll content) (p < 0.01). The application of Ca(H2PO4)2 could most significantly improve the Cu contents in roots, stems and leaves of L. hexandra (p < 0.05). In addition, (NH4)2HPO4 could enhance the tolerance of L. hexandra to Cu by obviously reducing the content of MDA and increasing the contents of SP and MTs (p < 0.05), while Ca(H2PO4)2 could evidently improve the activity of antioxidant enzymes (SOD, POD, CAT and APX) to reduce the damage of Cu to L. hexandra (p < 0.05). Although KH2PO4 could increase the contents of SP and MTs, the L. hexandra in KH2PO4 treatment groups had the highest MDA contents, which was unfavorable to the resistance to Cu stress. These suggested that the application in combination of Ca(H2PO4)2 and (NH4)2HPO4 may be more advantageous for Cu phytoextraction by L. hexandra.

Gastric sub-epithelial tumors: identification of gastrointestinal stromal tumors using CT with a practical scoring method.

OBJECTIVES: To determine CT features that can identify gastrointestinal stromal tumors (GISTs) among gastric sub-epithelial tumors (SETs) and to explore a practical scoring method. METHODS: Sixty-four patients with gastric SETs (51 GISTs and 13 non-GISTs) from hospital I were included for primary analyses, and 92 (67 GISTs and 25 non-GISTs) from hospital II constituted a validation cohort. Pre-operative CT images were reviewed for imaging features: lesion location, growth pattern, lesion margin, enhancement pattern, dynamic pattern, attenuation at each phasic images and presence of necrosis, superficial ulcer, calcification, and peri-lesion enlarged lymph node (LN). Clinical and CT features were compared between the two groups (GISTs versus non-GISTs) and a GIST-risk scoring method was developed; then, its performance for identifying GISTs was tested in the validation cohort. RESULTS: Seven clinical and CT features were significantly suggestive of GISTs rather than non-GISTs: older age (> 49 years), non-cardial location, irregular margin, lower attenuation on unenhanced images (≤ 43 HU), heterogeneous enhancement, necrosis, and absence of enlarged LN (p < 0.05). At validation step, the established scoring method with cut-off score dichotomized into ≥ 4 versus < 4 for identifying GISTs revealed an AUC of 0.97 with an accuracy of 92%, a sensitivity of 100% and a negative predictive value (NPV) of 100%. CONCLUSIONS: Gastric GISTs have special CT and clinical features that differ from non-GISTs. With a simple and practical scoring method based on the significant features, GISTs can be accurately differentiated from non-GISTs.

Silencing Stem Cell Factor Gene in Fibroblasts to Regulate Paracrine Factor Productions and Enhance c-Kit Expression in Melanocytes on Melanogenesis.

Melanogenesis is a complex physiological mechanism involving various paracrine factors. Skin cells such as keratinocytes, fibroblasts, and melanocytes communicate with one another through secreted regulators, thereby regulating the melanocytes' bio-functions. The stem cell factor (SCF) is a paracrine factor produced by fibroblasts, and its receptor, c-kit, is expressed on melanocytes. Binding of SCF to c-kit activates autophosphorylation and tyrosine kinase to switch on its signal transmission. SCF inhibition does not suppress fibroblast proliferation in MTT assay, and SCF silencing induced mRNA expressions of paracrine factor genes, HGF, NRG-1, and CRH in qPCR results. Following UVB stimulation, gene expressions of HGF, NRG, and CRH were higher than homeostasis; in particular, HGF exhibited the highest correlation with SCF variations. We detected fibroblasts regulated SCF in an autocrine-dependent manner, and the conditioned medium obtained from fibroblast culture was applied to treat melanocytes. Melanogenesis-related genes, tyrosinase and pmel17, were upregulated under conditioned mediums with SCF silencing and exposed to UVB treatments. Melanin quantities in the melanocytes had clearly increased in the pigment content assay. In conclusion, SCF silencing causes variations in both fibroblast paracrine factors and melanocyte melanogenesis, and the differences in gene expressions were observed following UVB exposure.

Application of texture analysis based on apparent diffusion coefficient maps in discriminating different stages of rectal cancer.

PURPOSE: To explore the potential of texture analysis based on apparent diffusion coefficient (ADC) maps, as a predictor of local invasion depth (stage pT1-2 versus pT3-4) and nodal status (pN0 versus pN1-2) of rectal cancer. MATERIALS AND METHODS: Sixty-eight patients with rectal cancer underwent preoperative magnetic resonance (MR) imaging including diffusion weighted imaging (DWI) at a 3.0 Tesla system. Routine ADC variables (ADCmean , ADCmin , ADCmax ), histogram features (skewness, kurtosis) and gray level co-occurrence matrix features (entropy, contrast, correlation) were compared between pT1-2 and pT3-4 stages, between pN0 and pN1-2 stages. RESULTS: Skewness, entropy, and contrast were significantly lower in patients with pT1-2 as compared to those with pT3-4 tumors (0.166 versus 0.476, P = 0.015; 3.212 versus 3.441 P = 0.004; 10.773 versus 13.596, P = 0.017). Furthermore, skewness and entropy were identified as independent predictors for extramural invasion of tumors (stage pT3-4). Significant differences were observed between pN0 and pN1-2 tumors with respect to ADCmean (1.152 versus 1.044, P = 0.029), ADCmax (1.692 versus 1.460, P = 0.006) and entropy (3.299 versus 3.486, P = 0.015). ADCmax. and entropy were independent predictors of positive nodal status. CONCLUSION: Texture analysis on ADC maps could provide valuable information in identifying locally advanced rectal cancer. LEVEL OF EVIDENCE: 3 J. MAGN. RESON. IMAGING 2017;45:1798-1808.

Locally advanced rectal cancer: predicting non-responders to neoadjuvant chemoradiotherapy using apparent diffusion coefficient textures.

PURPOSE: The purpose of the study is to evaluate whether apparent diffusion coefficient (ADC) textures could identify patient with locally advanced rectal cancer (LARC) who would not respond to neoadjuvant chemoradiotherapy (NCRT). METHOD: Twenty-six patients who underwent MRI including diffusion-weighted imaging at a 3.0 T system before NCRT were enrolled. Texture analysis of pre-therapy ADC mapping was carried out, and a total of 133 ADC textures as well as routine mean ADC value of the primary tumor were extracted for each patient. Texture parameters and mean ADC were compared between responsive group and non-responsive group. Logistic regression was used to determine the independent predictors for non-responders. Receiver operating characteristic curve (ROC) was performed to evaluate the predictive performance of the significant parameters. RESULTS: Eighteen of the 133 texture parameters significantly differed between responsive and non-responsive groups (p < 0.05). Further, energy variance and SdGa47 were identified as independent predictors for non-responders to NCRT; this logistic model achieved an area under the curve (AUC) of 0.908. CONCLUSION: Texture analysis based on pre-therapy ADC mapping could potentially be helpful to identify patients with LARC who would not respond to NCRT.

Histogram analysis based on unenhanced CT for identifying thymoma and lymphoma among prevascular mediastinal incidentalomas.

OBJECTIVE: To determine whether histogram analysis based on unenhanced CT can play a role in the differential diagnosis of thymoma and lymphoma from thymic hyperplasia and cyst (mean CT attenuation > 10 HU). MATERIALS AND METHODS: This retrospective study included consecutive asymptomatic participants who have prevascular mediastinal lesions incidentally detected by unenhanced CT between December 2013 and August 2020, and with definitive diagnosis by pathology or additional radiologic work-ups. A total of thirteen histogram parameters on enhanced CT were calculated for each lesion, then were compared between tumor (thymoma + lymphoma) and non-tumor (hyperplasia + cyst). Receiver operating characteristic analysis was conducted to investigate the performance of histogram parameter for identifying tumor. RESULTS: The study population included 192 patients (106 men and 86 women) with a mean age of 50.5 years at the time of CT examination. Of them, 94 patients have tumor (87 thymomas and 7 lymphoma) and 98 have non-tumor (48 thymic hyperplasia and 50 cysts). Nine of the thirteen histogram parameters revealed significant difference between the two groups, including median, minimum, range, 10th percentile, 90th percentile, kurtosis, skewness, uniformity and entropy. No significant difference was observed in the mean CT attenuation between groups. Higher median was found to be independent predictors for distinguishing tumor from non-tumor, and can achieve an area under the curve (AUC) of 0.785 (95% confidence interval [95% IC], 0.720-0.841). CONCLUSIONS: Histogram analysis based on unenhanced CT may be able to provide some help in the differential diagnosis of incidental lesions in prevascular mediastinal. GRAND SUPPORT: This study was sponsored by Natural Science Foundation of Shanghai (No. 21ZR1459700).

Curcumin Supplementation Improves Growth Performance and Anticoccidial Index by Improving the Antioxidant Capacity, Inhibiting Inflammatory Responses, and Maintaining Intestinal Barrier Function in Eimeria tenella-Infected Broilers.

This study was conducted to investigate the effects of dietary curcumin supplementation on growth performance, anticoccidial index, antioxidant capacity, intestinal inflammation, and cecum microbiota in broilers infected with Eimeria tenella. A total of 234 one-day-old broilers were categorized into three treatments, with six replicates per treatment containing 13 broilers each. The three treatments included the control group, Eimeria tenella group, and Eimeria tenella + curcumin (200 mg/kg) group. The feeding trial lasted for 42 days, during which the broilers were orally administered with 0.9% saline or 5 × 104Eimeria tenella oocysts on day 14 of the study. On day 17 and day 21, one bird per replicate was selected for slaughtering. Results indicated an increased survival rate and anticoccidial index and improved productive performance in coccidia-infected broilers with curcumin supplementation. Furthermore, curcumin enhanced the serum antioxidant capacity in Eimeria tenella-infected broilers, evidenced by increased serum catalase activity (3d, 7d), as well as decreased malondialdehyde level (3d, 7d) and nitric oxide synthase activity (7d) (p < 0.05). Curcumin also improved intestinal inflammation and barrier function, evidenced by the downregulation of interleukin (IL)-1ß (3d, 7d), TNF-alpha (TNF-α) (3d, 7d), and IL-2 (7d) and the up-regulated mRNA levels of claudin-1 (7d), zonula occludens (ZO-1; 3d, 7d), and occludin (3d, 7d) in the ceca of infected broilers (p < 0.05). Eimeria tenella infection significantly disrupted cecum microbial balance, but curcumin did not alleviate cecum microbial disorder in broilers infected with Eimeria tenella. Collectively, curcumin supplementation enhanced growth performance and anticoccidial index in Eimeria tenella-infected broilers via improving antioxidant ability and cecum inflammation without affecting cecum microbiota.

Estimating Efficacy of Conversion Therapy on Patients with Initially Unresectable Colorectal Cancer Liver Metastases by using MRI: Development of a Predictive Score.

RATIONALE AND OBJECTIVES: The conversion success rate (CSR) has crucial implication for clinical outcomes of initially unresectable colorectal liver metastases (CRLM) following conversion therapy. This study aimed to develop a simple predictive scoring model for identifying CSR according to baseline magnetic resonance imaging (MRI) features, and confirm its performance and prognostic significance in a validation cohort. METHODS: A total of 155 consecutive patients with initially unresectable CRLM were retrospectively reviewed in the study. A simple MRI-based predictive scoring model for identifying CSR was developed in the development cohort (n = 104) by using multivariable logistic regression analyzes. The diagnostic performance was evaluated for the predictive score. Thereafter, patients in the validation cohort (n = 51) were stratified into groups with predicted high CSR or low CSR according to the score. The progression-free survival (PFS) and overall survival (OS) were compared between two groups using the log-rank test. RESULTS: The predictive score of CSR, named mrNISE, incorporated the number of CRLM ≥ 10, the largest size ≥ 50 mm, poorly defined tumor-liver interface, and peritumoral enhancement. The AUC of the mrNISE score was 0.845 for the development cohort and 0.776 for the validation cohort. According to the score, patients with predicted high CSR had better PFS and OS than those with low CSR in both development and validation cohorts. CONCLUSION: The predictive score demonstrated great performance for identifying CSR of initially unresectable CRLM. Stratifying patients by the score, personalized treatment goals can be formulated before conversion therapy to improve clinical prognosis and reduce adverse events caused by ineffective treatment.