Development and Validation of a 18F-FDG PET-Based Radiomic Model for Evaluating Hypermetabolic Mediastinal-Hilar Lymph Nodes in Non-Small-Cell Lung Cancer.

BACKGROUND: Accurate evaluation of lymph node (LN) status is critical for determining the treatment options in patients with non-small cell lung cancer (NSCLC). This study aimed to develop and validate a 18F-FDG PET-based radiomic model for the identification of metastatic LNs from the hypermetabolic mediastinal-hilar LNs in NSCLC. METHODS: We retrospectively reviewed 259 patients with hypermetabolic LNs who underwent pretreatment 18F-FDG PET/CT and were pathologically confirmed as NSCLC from two centers. Two hundred twenty-eight LNs were allocated to a training cohort (LN = 159) and an internal validation cohort (LN = 69) from one center (7:3 ratio), and 60 LNs were enrolled to an external validation cohort from the other. Radiomic features were extracted from LNs of PET images. A PET radiomics signature was constructed by multivariable logistic regression after using the least absolute shrinkage and selection operator (LASSO) method with 10-fold cross-validation. The PET radiomics signature (model 1) and independent predictors from CT image features and clinical data (model 2) were incorporated into a combined model (model 3). A nomogram was plotted for the complex model, and the performance of the nomogram was assessed by its discrimination, calibration, and clinical usefulness. RESULTS: The area under the curve (AUC) values of model 1 were 0.820, 0.785, and 0.808 in the training, internal, and external validation cohorts, respectively, showing good diagnostic efficacy for lymph node metastasis (LNM). Furthermore, model 2 was able to discriminate metastatic LNs in the training (AUC 0.780), internal (AUC 0.794), and external validation cohorts (AUC 0.802), respectively. Model 3 showed optimal diagnostic performance among the three cohorts, with an AUC of 0.874, 0.845, and 0.841, respectively. The nomogram based on the model 3 showed good discrimination and calibration. CONCLUSIONS: Our study revealed that PET radiomics signature, especially when integrated with CT imaging features, showed the ability to identify true and false positives of mediastinal-hilar LNM detected by PET/CT in patients with NSCLC, which would help clinicians to make individual treatment decisions.

Amniotic Mesenchymal Stem Cells Decrease Aß Deposition and Improve Memory in APP/PS1 Transgenic Mice.

Transplantation of human amniotic mesenchymal stem cells (hAM-MSCs) seems to be a promising strategy for the treatment of neurodegenerative disorders, including Alzheimer's disease (AD). However, the clinical therapeutic effects of hAM-MSCs and their mechanisms of action in AD remain to be determined. Here, we used amyloid precursor protein (APP) and presenilin1 (PS1) double-transgenic mice to evaluate the effects of hAM-MSC transplantation on AD-related neuropathology and cognitive dysfunction. We found that hAM-MSC transplantation into the hippocampus dramatically reduced amyloid-ß peptide (Aß) deposition and rescued spatial learning and memory deficits in APP/PS1 mice. Interestingly, these effects were associated with increasing in Aß-degrading factors, elevations in activated microglia, and the modulation of neuroinflammation. Furthermore, enhanced hippocampal neurogenesis in the subgranular zone (SGZ) of the dentate gyrus (DG) and enhanced synaptic plasticity following hAM-MSC treatment could be another important factor in reversing the cognitive decline in APP/PS1 mice. Instead, the mechanism underlying the improved cognition apparently involves a robust increase in hippocampal synaptic density and neurogenesis that is mediated by brain-derived neurotrophic factor (BDNF). In conclusion, our data suggest that hAM-MSCs may be a new and effective therapy for the treatment of AD.

Disrupted-in-Schizophrenia-1 Attenuates Amyloid-ß Generation and Cognitive Deficits in APP/PS1 Transgenic Mice by Reduction of ß-Site APP-Cleaving Enzyme 1 Levels.

Disrupted-in-Schizophrenia-1 (DISC1) is a genetic risk factor for a wide range of major mental disorders, including schizophrenia, major depression, and bipolar disorders. Recent reports suggest a potential role of DISC1 in the pathogenesis of Alzheimer's disease (AD), by referring to an interaction between DISC1 and amyloid precursor protein (APP), and to an association of a single-nucleotide polymorphism in a DISC1 intron and late onset of AD. However, the function of DISC1 in AD remains unknown. In this study, decreased levels of DISC1 were observed in the cortex and hippocampus of 8-month-old APP/PS1 transgenic mice, an animal model of AD. Overexpression of DISC1 reduced, whereas knockdown of DISC1 increased protein levels, but not mRNA levels of ß-site APP-Cleaving Enzyme 1 (BACE1), a key enzyme in amyloid-ß (Aß) generation. Reduction of BACE1 protein levels by overexpression of DISC1 was accompanied by an accelerating decline rate of BACE1, and was blocked by the lysosomal inhibitor chloroquine, rather than proteasome inhibitor MG-132. Moreover, overexpression of DISC1 in the hippocampus with an adeno-associated virus reduced the levels of BACE1, soluble Aß40/42, amyloid plaque density, and rescued cognitive deficits of APP/PS1 transgenic mice. These results indicate that DISC1 attenuates Aß generation and cognitive deficits of APP/PS1 transgenic mice through promoting lysosomal degradation of BACE1. Our findings provide new insights into the role of DISC1 in AD pathogenesis and link a potential function of DISC1 to the psychiatric symptoms of AD.

[Vulvovaginal candidiasis in pregnant women with impaired tolerance for glucose].

OBJECTIVE: To evaluate whether incidence of 50 g glucose challenge test (GCT) and 75 g oral glucose tolerance test (OGTT) is higher in pregnant women with vulvovaginal candidiasis (VVC). METHODS: A retrospective study of pregnant women with IGGT or GDM who delivered at Peking University First Hospital from Jan 1, 2004 to June 30, 2005 was conducted. The prevalence of VVC and re-infected vulvovaginal candidiasis (RVVC) were determined, and blood glucose concentrations of GGT and OGTT in VVC, RVVC and NVVC groups were compared. RESULTS: Four hundred and one pregnant women were recruited, of whom 51 had VVC, and 16 had RVVC. The prevalence of VVC was greater among GDM women than among IGGT women (P = 0.014). Glucose concentrations were higher in VVC cases than in NVVC cases at GCT [(9.6 +/- 2.0) vs (9.3 +/- 1.6) mmol/L], OGTT 0 hour [(5.4 +/- 1.1) vs (5.3 +/- 0.9) mmol/L], 1 hour [(11.1 +/- 1.7) vs (11.0 +/- 1.5) mmol/L], 2 hours [(9.4 +/- 1.8) vs (9.2 +/- 1.6) mmol/L], however, there were no statistical differences (P > 0.05). Glucose concentrations were higher in RVVC cases than in NVVC cases at GCT [(10.4 +/- 1.2) vs (9.3 +/- 1.6) mmol/L]; OGTT 0 hour [(5.3 +/- 0.6) vs (5.3 +/- 0.9) mmol/L], 1 hour [(11.4 +/- 1.0) vs (11.0 +/- 1.5) mmol/L]; 2 hours [(9.4 +/- 1.4) vs (9.2 +/- 1.6) mmol/L], but there were no statistical differences (P > 0.05). CONCLUSION: The incidence of VVC is higher in pregnant women with GDM than in pregnant women with GIGT, however, GCT, and OGTT show no statistical differences between women with VVC and those without VVC.