Neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio as predictive markers in hepatoblastoma.

Background: The neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) have been presented to be a prognostic indicator in several cancers. We were supposed to evaluate the prognostic role of such inflammatory markers in hepatoblastoma (HB). Methods: Total of 101 children, diagnosed with hepatoblastoma between January 2010 and January 2018, were enrolled before treatment in the study. The clinicopathological parameters, and outcomes were collected through laboratory analyses and patient follow-up. The association between NLR, PLR, and clinicopathological characters were analyzed with Wilcoxon test, Chi-Squared test, Kaplan-Meier, Log-rank and Cox regression analyses. Results: NLR and PLR were significantly elevated in HB patients (P < 0.001), and related to age (P < 0.001), risk stratification system (P < 0.001), and pretreatment extent of disease (P < 0.0001). NLR was significantly related to alpha-fetoprotein (P = 0.034) and lactate dehydrogenase (P = 0.026). The 3-year overall survival (OS) and event-free survival (EFS) were poor in the high-NLR group (OS: 44.3% vs. 90.3%, P < 0.0001, EFS: 38.6% vs. 80.6%, P = 0.0001). The 3-year OS and EFS were poor in the high-PLR group (OS: 49.1% vs. 68.8%, P = 0.016, EFS: 39.6% vs. 64.6%, P = 0.0117). The multivariate analysis suggested that NLR (HR: 11.359, 95% CI: 1.218-105.947; P = 0.033) and risk stratification (HR: 44.905, 95% CI: 2.458-820.36; P = 0.01), were independent predictors of OS. Conclusion: Our research showed that elevated NLR and PLR were the poor prognostic factors in HB patients before treatment. The NLR was an independent prognostic factor for OS.

Pear xyloglucan endotransglucosylase/hydrolases PcBRU1 promotes stem growth through regulating cell wall elongation.

Brassinosteroids (BRs) play numerous important roles in plant growth and development. Previous studies reported that BRs could promote stem growth by regulating the expression of xyloglucan endotransglucosylase/hydrolases (XTHs). However, the mechanism of XTHs involved in stem growth remains unclear. In this study, PcBRU1, which belonged to the XTH family, was upregulated by exogenous BL treatment in Pyrus communis. The expression of PcBRU1 was highest in stems and lowest in leaves. Subcellular localization analysis indicated that PcBRU1 was located in the plasma membrane. Furthermore, overexpressing PcBRU1 in tobaccos promoted the plant height and internode length. Electron microscopy and anatomical structure analysis showed that the cell wall was significantly thinner and the cells were slenderer in transgenic tobacco lines overexpressing PcBRU1 than in wild-type tobaccos. PcBRU1 promoted stem growth as it loosened the cell wall, leading to the change in cell morphology. In addition, overexpressing PcBRU1 altered the root development and leaf shape of transgenic tobaccos. Taken together, the results could provide a theoretical basis for the XTH family in regulating cell-wall elongation and stem growth.

Design, synthesis, and biological evaluation of a novel dual peroxisome proliferator-activated receptor alpha/delta agonist for the treatment of diabetic kidney disease through anti-inflammatory mechanisms.

Diabetic kidney disease (DKD) is a major feature of the final stage of nearly all cause types of diabetes mellitus (DM). To date, few safe and effective drugs are available to treat. Peroxisome proliferator-activated receptors (PPARs), comprised of three members: PPAR-α, PPAR-δ and PPAR-γ, play a protective role in the DKD through glycemic control and lipid metabolism, whereas systemic activation of PPAR-γ causes serious side-effects in clinical trials. GFT505 is a dual PPAR-α/δ agonist, and the selectivity against PPAR-γ is still to be improved. Sulfuretin has been shown to suppress the expression of PPAR-γ and improve the pathogenesis of diabetic complications. In this study, by hybridizing the carboxylic acid of GFT505 and the parent nucleus of sulfuretin, we pioneeringly designed and synthetized a series of novel dual PPAR-α/δ agonists, expecting to provide a better benefit/risk ratio for PPARs. Of all the synthesized compounds, compound 12 was identified with highly activity on PPAR-α/δ and higher selectivity against PPAR-γ than that of GFT505 (EC50: hPPAR-α: 0.26 µM vs.0.76 µM; hPPAR-δ: 0.50 µM vs.0.73 µM; hPPAR-γ: 4.22 µM vs.2.79 µM). The molecular docking studies also depicted good binding affinity of compound 12 for PPAR-α and PPAR-δ compared to GFT505. Furthermore, compound 12 exhibited an evidently renoprotective effect on the DKD through inhibiting inflammatory process, which might at least partly via JNK/NF-κB pathways in vivo and in vitro. Overall, compound 12 hold therapeutic promise for DKD.

Intra-rectal use of epinephrine in radiotherapy of prostate cancer.

Purpose: The aim of the study was to evaluate the feasibility and toxicity of intra-rectal epinephrine during prostatic radiotherapy. Materials and methods: A total of 34 patients with prostate cancer were randomized to receive daily intra-rectal epinephrine (4 mg in 40 mL, n=16) or placebo (40 mL normal saline, n=18) 5 min before daily radiotherapy. Physical examination including systolic blood pressure (SBP) and heart rate (HR) was performed before, 5 min after, and 20 min after intra-rectal use. Toxicities were graded using the Radiation Therapy Oncology Group standard. A two-sided Fisher's exact test was used to compare proportions between groups. A mixed-effects model was used to analyze multiple measurements of SBP and HR. Survival curves were calculated using the Kaplan-Meier method and compared between groups using the log-rank test. Results: All patients completed the protocol treatment and reported no cardiovascular symptoms after intra-rectal administration. There were no differences in SBP and HR between these two groups at any time point (before, 5 min after, and 20 min after epinephrine). At 5 weeks after the start of radiotherapy, the incidence of rectal toxicity≥grade 2 was 27.8% (5/18) for the control group versus 12.5% (2/16) for the epinephrine group, but was not statistically significant (p=0.4). There was no rectal toxicity≥grade 2 in these two groups beyond 2-year follow-up. The 5-year biochemical relapse-free survival was 75.0% and 72.2% for the epinephrine and control group, respectively. Conclusion: Results of this pilot randomized trial have demonstrated that intra-rectal administration of epinephrine is feasible and safe in prostatic radiotherapy. Its radio-protective effect warrants further investigation.

WITHDRAWN: MicroRNA-18a promotes proliferation and metastasis in oral squamous cell carcinoma via targeting KLF4.

Ahead of Print article withdrawn by publisher.

3.0T MR-CAD: Clinical Value in Diagnosis of Breast Tumor Compared with Conventional MRI.

PURPOSE: to explore the clinical value of 3.0T magnetic resonance (MR) imaging compared with computer-aided MR diagnosis (MR-CAD) in differential diagnosis of benign and malignant breast tumors. MATERIALS AND METHODS: MRI method and MR-CAD method was used in the diagnosis of a total of 93 breast lesions of 78 patients, based on the morphological and time-intensity-curve (TIC) analysis. The accuracy of the two modalities in differentiating malignant and benign breast tumor was compared. RESULTS: MR-CAD method yielded a statistically better accuracy than MRI method. For 51 mass-like lesions, MRI and MR-CAD had no difference in diagnosing accuracy, but MR-CAD had better accuracy in 42 non-mass-like lesions. CONCLUSION: MR-CAD had a notable advantage over MRI in differential diagnosis of benign and malignant breast tumors, especially non-mass-like tumor.

Improved longitudinal length accuracy of gross tumor volume delineation with diffusion weighted magnetic resonance imaging for esophageal squamous cell carcinoma.

BACKGROUND: To analyze the longitudinal length accuracy of gross tumor volume (GTV) delineation with diffusion weighted magnetic resonance imaging for esophageal squamous cell carcinoma (SCC). METHODS: Forty-two patients from December 2011 to June 2012 with esophageal SCC who underwent radical surgery were analyzed. Routine computed tomography (CT) scan, T2-weighted MRI and diffusion weighted magnetic resonance imaging (DWI) were employed before surgery. Diffusion-sensitive gradient b-values were taken at 400, 600, and 800 s/mm2. Gross tumor volumes (GTV) were delineated using CT, T2-weighted MRI and DWI on different b-value images. GTV longitude length measured using the imaging modalities listed above was compared with pathologic lesion length to determine the most accurate imaging modality. CMS Xio radiotherapy planning system was used to fuse DWI scans and CT images to investigate the possibility of delineating GTV on fused images. RESULTS: The differences between the GTV length according to CT, T2-weighted MRI and pathology were 3.63 ± 12.06 mm and 3.46 ± 11.41 mm, respectively. When the diffusion-sensitive gradient b-value was 400, 600, and 800 s/mm2, the differences between the GTV length using DWI and pathology were 0.73 ± 6.09 mm, -0.54 ± 6.03 mm and -1.58 ± 5.71 mm, respectively. DWI scans and CT images were fused accurately using the radiotherapy planning system. GTV margins were depicted clearly on fused images. CONCLUSIONS: DWI displays esophageal SCC lengths most precisely when compared with CT or regular MRI. DWI scans fused with CT images can be used to improve accuracy to delineate GTV in esophageal SCC.

[CT and MRI image fusion in three-dimensional conformal radiotherapy for cranial carcinoma].

OBJECTIVE: To investigate the advantage of CT and MRI image fusion in determining the target precisely during 3-dimensional conformal radiotherapy for cranial carcinoma. METHODS: Twenty-five patients received CT and MRI examination simultaneously for localizing the tumor and defining target before 3-dimensional conformal radiotherapy. The target defined by MRI image was used as gross tumor volume, whereas CT value was used to calculate dose, making plan for radiotherapy. The difference between the target defined by CT and MRI was compared. RESULTS: All the 25 patients underwent CT and MRI image fusion for localizing the tumor and defining the target in order to make anatomic symbol and surface symbol superposed. The number of tumor nodual detected by CT was as same as that found by MRI in 23 cases except two. Compared with the GTV defined by MRI image, it was larger in 10 cases by CT image, whereas smaller in 15 cases. The response rate assessed by MRI image was 64.0% (CR + PR) at the end of radiotherapy. CONCLUSION: CT and MRI image fusion technique is more precise than either by CT or MRI alone in defining the GTV of 3-dimensional conformal radiotherapy for cranial carcinoma.