[Based on CT radiomics model for predicting the response to first-line chemotherapy of diffuse large B-cell lymphoma].

Objective: To investigate the potential value of CT Radiomics model in predicting the response to first-line chemotherapy in diffuse large B-cell lymphoma (DLBCL). Methods: Pre-treatment CT images and clinical data of DLBCL patients treated at Shanxi Cancer Hospital from January 2013 to May 2018 were retrospectively analyzed and divided into refractory patients (73 cases) and non-refractory patients (57 cases) according to the Lugano 2014 efficacy evaluation criteria. The least absolute shrinkage and selection operator (LASSO) regression algorithm, univariate and multivariate logistic regression analyses were used to screen out clinical factors and CT radiomics features associated with efficacy response, followed by radiomics model and nomogram model. Receiver operating characteristic (ROC) curve, calibration curve and clinical decision curve were used to evaluate the models in terms of the diagnostic efficacy, calibration and clinical value in predicting chemotherapy response. Results: Based on pre-chemotherapy CT images, 850 CT texture features were extracted from each patient, and 6 features highly correlated with the first-line chemotherapy effect of DLBCL were selected, including 1 first order feature, 1 gray level co-occurence matrix, 3 grey level dependence matrix, 1 neighboring grey tone difference matrix. Then, the corresponding radiomics model was established, whose ROC curves showed AUC values of 0.82 (95% CI: 0.76-0.89) and 0.73 (95% CI: 0.60-0.86) in the training and validation groups, respectively. The nomogram model, built by combining validated clinical factors (Ann Arbor stage, serum LDH level) and CT radiomics features, showed an AUC of 0.95 (95% CI: 0.90-0.99) and 0.91 (95% CI: 0.82-1.00) in the training group and the validation group, respectively, with significantly better diagnostic efficacy than that of the radiomics model. In addition, the calibration curve and clinical decision curve showed that the nomogram model had good consistency and high clinical value in the assessment of DLBCL efficacy. Conclusion: The nomogram model based on clinical factors and radiomics features shows potential clinical value in predicting the response to first-line chemotherapy of DLBCL patients.

Transcriptional activation of ENPP1 by osterix in osteoblasts and osteocytes.

Ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1) is the main source of extracellular pyrophosphate. Along with tissue-nonspecific alkaline phosphatase (TNAP), ENPP1 plays an important role in balancing bone mineralisation. Although well established in pre-osteoblasts, the regulating mechanisms of ENPP1 in osteoblasts and osteocytes remain largely unknown. Using bioinformatic methods, osterix (Osx), an essential transcription factor in osteoblast differentiation and osteocyte function, was found to have five predicted binding sites on the ENPP1 promoter. ENPP1 and Osx showed a similar expression profile both in vitro and in vivo. Over-expression of Osx in MC3T3-E1 and MLO-Y4 cells significantly up-regulated the expression of ENPP1 (p < 0.05). The consensus Sp1 sequences, located in the proximal ENPP1 promoter, were identified as Osx-regulating sites using promoter truncation experiments and chromatin immunoprecipitation (ChIP) assays. The p38-mitogen-activated protein kinase (MAPK) signalling pathway was demonstrated to be responsible for ENPP1 promoter activation by Osx. Runt-related transcription factor 2 (Runx2) was confirmed to have synergistic effects with Osx in activating ENPP1 promoter. Taken together, these results provided evidence of the regulating mechanisms of ENPP1 transcription in osteoblasts and osteocytes.

Expression of gicerin, a novel cell adhesion molecule, is upregulated in the astrocytes after hypoglossal nerve injury in rats.

Gicerin is an integral membrane glycoprotein which mediates cell-cell and cell-extracellular matrix (ECM) interactions in the nervous system. We studied gicerin expression in the hypoglossal nucleus post transection using in situ hybridization and immunocytochemistry. We found that hypoglossal nerve injury resulted in a significant increase in gicerin expression. Its expression levels reached peak values in reactive astrocytes surrounding axotomized motoneurons of the ipsilateral hypoglossal nucleus 14 days after hypoglossal nerve injury. The results indicate that gicerin is up-regulated during nerve regeneration, suggesting that gicerin expressed in the reactive astrocytes might be involved in the processes of nerve regeneration.

Differential display reveals transcriptional up-regulation of the motor molecules for both anterograde and retrograde axonal transport during nerve regeneration.

RNA fingerprinting using an arbitrary primed polymerase chain reaction was carried out to compare differences in expression of mRNAs between axotomized and normal hypoglossal motoneurons in the mouse. In this survey, the kinesin light chain (KLC) was identified as a nerve injury-associated molecule. This was also confirmed by in situ hybridization using hemihypoglossal nerve-transected brain sections. In order to identify the exact species of molecules belonging to the KLC family, in situ hybridization was carried out with oligonucleotide probes specific to rat KLC A, KLC B and KLC C, using the rat hypoglossal nerve injury model. In addition, expression of both ubiquitous and neuron-specific kinesin heavy chain and cytoplasmic dynein which is a retrograde motor, was also examined. Expression of all the members of the KLC (A-C) family and dynein was up-regulated during nerve regeneration, whereas the abundant expression of the neuron-specific KHC mRNA was not changed. The present results indicate that the molecules associated with both anterograde and retrograde axonal transport are up-regulated in their expression during efferent motor nerve regeneration, suggesting that the retrograde transport of growth factors and anterograde transport of vesicles, providing membrane material, could be increased during motor nerve regeneration.