Predictive Model and Precaution for Oral Mucositis During Chemo-Radiotherapy in Nasopharyngeal Carcinoma Patients.

PURPOSE: To explore risk factors for severe acute oral mucositis of nasopharyngeal carcinoma (NPC) patients receiving chemo-radiotherapy, build predictive models and determine preventive measures. METHODS AND MATERIALS: Two hundred and seventy NPC patients receiving radical chemo-radiotherapy were included. Oral mucosa structure was contoured by oral cavity contour (OCC) and mucosa surface contour (MSC) methods. Oral mucositis during treatment was prospectively evaluated and divided into severe mucositis group (grade ≥ 3) and non-severe mucositis group (grade < 3) according to RTOG Acute Reaction Scoring System. Nineteen clinical features and nineteen dosimetric parameters were included in analysis, least absolute shrinkage and selection operator (LASSO) logistic regression model was used to construct a risk score (RS) system. RESULTS: Two predictive models were built based on the two delineation methods. MSC based model is more simplified one, it includes body mass index (BMI) classification before radiation, retropharyngeal lymph node (RLN) area irradiation status and MSC V55%, RS = -1.480 + (0.021 × BMI classification before RT) + (0.126 × RLN irradiation) + (0.052 × MSC V55%). The cut-off of MSC based RS is -1.011, with an area under curve (AUC) of 0.737 (95%CI: 0.672-0.801), a specificity of 0.595 and a sensitivity of 0.786. OCC based model involved more variables, RS= -4.805+ (0.152 × BMI classification before RT) + (0.080 × RT Technique) + (0.097 × Concurrent Nimotuzumab) + (0.163 × RLN irradiation) + (0.028 × OCC V15%) + (0.120 × OCC V60%). The cut-off of OCC based RS is -0.950, with an AUC of 0.767 (95%CI: 0.702-0.831), a specificity of 0.602 and a sensitivity of 0.819. Analysis in testing set shown higher AUC of MSC based model than that of OCC based model (AUC: 0.782 vs 0.553). Analysis in entire set shown AUC in these two method-based models were close (AUC: 0.744 vs 0.717). CONCLUSION: We constructed two risk score predictive models for severe oral mucositis based on clinical features and dosimetric parameters of nasopharyngeal carcinoma patients receiving chemo-radiotherapy. These models might help to discriminate high risk population in clinical practice that susceptible to severe oral mucositis and individualize treatment plan to prevent it.

Evaluation of the value of plasma concentration of copeptin in the first prenatal visit to diagnose gestational diabetes mellitus.

AIMS: Gestational diabetes mellitus (GDM) is increasing worldwide. The aim of this study was to investigate whether copeptin concentrations, measured at the first prenatal visit, are associated with risk of GDM. METHODS: From July 2015 to June 2016, consecutive women who admitted to the obstetrics center of our hospital were included. Data for fasting plasma glucose and copeptin concentrations at the first prenatal visit and one-step GDM screening with 75-g oral glucose tolerance test performed between 24 and 28 weeks of gestation were collected and analyzed. The relationship between levels of copeptin and GDM were evaluated using univariate and multivariate regression analysis. RESULTS: In this study, 101 out of the 827 women developed GDM (12.2%). The GDM distribution across the copeptin quartiles ranged between 4.4% (first quartile) and 25.1% (fourth quartile). For each 1 log-unit increase in plasma concentration of copeptin, the unadjusted and adjusted risk of GDM increased by 1442% (odds ratio 15.42 [95% CI 3.35-54.25], P < 0.001) and 642% (7.42 [2.69-16.02], P < 0.001), respectively. In a multivariate model using the fourth quartiles of copeptin versus quartiles 1 through 3 together with the clinical variables, the marker displayed prognostic information (GDM: OR for fourth quartile, 3.11 [95% CI 1.95-5.24; P = 0.001]). The net reclassification improvement statistic showed that the addition of copeptin to established risk factors significantly increased the correct reclassification of GDM (P = 0.02). The integrated discrimination improvement statistic found that the copeptin level significantly increased discrimination between women with GDM and without GDM (P = 0.01). CONCLUSIONS: High copeptin concentrations at the first prenatal visit were associated with increased risk of GDM and might be useful in identifying women at risk of GDM for early prevention strategies.

PERK-eIF2α-ATF4 pathway mediated by endoplasmic reticulum stress response is involved in osteodifferentiation of human periodontal ligament cells under cyclic mechanical force.

To prevent excess accumulation of unfolded proteins in endoplasmic reticulum (ER), eukaryotic cells have signaling pathways from the ER to the cytosol or nucleus. These processes are known as the endoplasmic reticulum stress (ERS) response. Protein kinase R like endoplasmic reticulum kinase (PERK) is a major transducer of the ERS response and it directly phosphorylate α-subunit of eukaryotic initiation factor 2 (eIF2α), resulting in translational attenuation. Phosphorylated eIF2α specifically promoted the translation of the activating transcription factor 4 (ATF4). ATF4 is a known important transcription factor which plays a pivotal role in osteoblast differentiation and bone formation. Furthermore, ATF4 is a downstream target of PERK. Studies have shown that PERK-eIF2α-ATF4 signal pathway mediated by ERS was involved in osteoblastic differentiation of osteoblasts. We have known that orthodontic tooth movement is a process of periodontal ligament cells (PDLCs) osteodifferentiation and alveolar bone remodeling under mechanical force. However, the involvement of PERK-eIF2α-ATF4 signal pathway mediated by ERS in osteogenic differentiation of PDLCs under mechanical force has not been unclear. In our study, we applied the cyclic mechanical force at 10% elongation with 0.5Hz to mimic occlusal force, and explored whether PERK-eIF2α-ATF4 signaling pathway mediated by ERS involved in osteogenic differentiation of PDLCs under mechanical force. Firstly, cyclic mechanical force will induce ERS and intensify several osteoblast marker genes (ATF4, OCN, and BSP). Next, we found that PERK overexpression increased eIF2α phosphorylation and expression of ATF4, furthermore induced BSP, OCN expression, thus it will promote osteodifferentiation of hPDLCs; mechanical force could promote this effect. However, PERK(-/-) cells showed the opposite changes, which will inhibit osteodifferentiation of hPDLCs. Taken together, our study proved that PERK-eIF2α-ATF4 signaling pathway mediated by ERS involved in osteoblast differentiation of PDLCs under cyclic mechanical force.

Two different classes of vector beams that have the same paraxial approximation.

It is observed that there exist two different classes of vector light beams that have the same first-order paraxial approximation. They are characterized by the axial and transverse orientations of a constant unit vector that comes from the constraint of transversality condition. Their vectorial structures in the nonparaxial regime and angular momentum properties are compared.

Characterization of vector diffraction-free beams.

It is observed that a constant unit vector denoted by I is needed to characterize a complete orthonormal set of vector diffraction-free beams. The previously found diffraction-free beams are shown to be included as special cases. The I-dependence of the longitudinal component of diffraction-free beams is also discussed.