Successful treatment of a pure red-cell aplasia patient with γδT cells and clonal TCR gene rearrangement: A case report

Pure red-cell aplasia (PRCA) is a syndrome associated with reduced erythroid precursors. This report presents the case of an elderly PRCA patient with significantly proliferated γδT cells and clonal T-cell receptor (TCR) gene rearrangement. The cause of this patient’s PRCA was confirmed to be an autoimmune disorder rather than malignancy on the basis of flow cytometry, TCR gene rearrangement, and positron emission tomography/computed tomography (PET/CT) findings. Moreover, the γδT cell group identified in this case was captured for the first time under the microscope; this CD4+/CD8− (extremely high CD4/CD8 ratio) population is rare in PRCA patients. Our patient with a monoclonal and polyclonal hybrid of TCR gene rearrangement was sensitive to cyclosporin A (CsA), despite previous reports suggesting that patients with TCR clonal rearrangement may respond poorly to this drug. Overall, this case presents valuable clinical findings for the future diagnosis and management of PRCA caused by autoimmune conditions and further research on γδT cells’ autoimmune pathophysiology and gene rearrangement

Genetic and non-genetic factors in prediction of early pubertal development in Chinese girls

ObjectiveThe objective of this study is to develop a combined predictive model for early pubertal development (EPD) in girls based on both non-genetic and genetic factors.MethodsThe case-control study encompassed 147 girls diagnosed with EPD and 256 girls who exhibited normal pubertal development. The non-genetic risk score (NGRS) was calculated based on 6 independent biochemical predictors screened by multivariate logistic regressions, and the genetic risk score (GRS) was constructed using 28 EPD related single-nucleotide polymorphisms (SNPs). Area under receiver operator characteristic curve (AROC), net reclassification optimization index (NRI) and integration differentiation index (IDI) were used to evaluate the improvement of adding genetic variants to the non-genetic risk model.ResultsOverweight (OR=2.74), longer electronic screen time (OR=1.79) and higher ratio of plastic bottled water (OR=1.01) were potential risk factors, and longer exercise time (OR=0.51) and longer day sleeping time (OR=0.97) were protective factors for EPD, and the AROC of NGRS model was 83.6% (79.3-87.9%). The GRS showed a significant association with EPD (OR=1.90), and the AROC of GRS model was 65.3% (59.7-70.8%). After adding GRS to the NGRS model, the AROC significantly increased to 85.7% (81.7-89.6%) (P=0.020), and the reclassification significantly improved, with NRI of 8.19% (P= 0.023) and IDI of 4.22% (P <0.001).ConclusionsWe established a combined prediction model of EPD in girls. Adding genetic variants to the non-genetic risk model brought modest improvement. However, the non-genetic factors such as overweight and living habits have higher predictive utility

Identifying optimal ranges of weight gain at the end of the second trimester result from a population-based cohort study

Abstract Objective: To identify the optimal weight gain at the end of the second trimester. Design: This was a population-based cohort study from the antenatal care system in Tianjin, China. We calculated gestational weight gain (GWG) based on the weight measured in the first trimester and the end of the second trimester. Restricted cubic spline analysis was performed to model the possible non-linear relationships between GWG and adverse outcomes. The optimal GWG was defined as the value of the lowest risk. Non-inferiority margins and the shape of the spline curves identified the recommended ranges in Chinese-specific BMI categories. Setting: Tianjin Maternal and Child Health Cohort. Participants: Singleton pregnant women aged 18–45 years. Results: In total, 69 859 pregnant women were included. Adverse outcome (including stillbirth, preterm birth, hypertensive disorders of pregnancy, gestational diabetes mellitus, small and large for gestational age) was significantly associated with GWG at the end of the second trimester. The risk score was non-linearly correlated with GWG in the underweight, normal weight and overweight groups. GWG at the end of the second trimester should not be 0 kg) in the first and second trimesters. Conclusions: According to the comprehensive adverse maternal and infant outcomes, we recommend the optimal GWG at the end of the second trimester. This study may provide a considerable reference for weight management

Collection of Epithelial Cells from Rodent Mammary Gland Via Laser Capture Microdissection Yielding High-Quality RNA Suitable for Microarray Analysis

Laser capture microdissection (LCM) enables collection of cell populations highly enriched for specific cell types that have the potential of yielding critical information about physiological and pathophysiological processes. One use of cells collected by LCM is for gene expression profiling. Samples intended for transcript analyses should be of the highest quality possible. RNA degradation is an ever-present concern in molecular biological assays, and LCM is no exception. This paper identifies issues related to preparation, collection, and processing in a lipid-rich tissue, rodent mammary gland, in which the epithelial to stromal cell ratio is low and the stromal component is primarily adipocytes, a situation that presents numerous technical challenges for high-quality RNA isolation. Our goal was to improve the procedure so that a greater probe set present call rate would be obtained when isolated RNA was evaluated using Affymetrix microarrays. The results showed that the quality of RNA isolated from epithelial cells of both mammary gland and mammary adenocarcinomas was high with a probe set present call rate of 65% and a high signal-to-noise ratio

Effect of a low fat versus a low carbohydrate weight loss dietary intervention on biomarkers of long term survival in breast cancer patients ('CHOICE'): study protocol

<p>Abstract</p> <p>Background</p> <p>Weight loss in overweight or obese breast cancer patients is associated with an improved prognosis for long term survival. However, it is not clear whether the macronutrient composition of the chosen weight loss dietary plan imparts further prognostic benefit. A study protocol is presented for a dietary intervention to investigate the effects of weight loss dietary patterns that vary markedly in fat and carbohydrate contents on biomarkers of exposure to metabolic processes that may promote tumorigenesis and that are predictive of long term survival. The study will also determine how much weight must be lost for biomarkers to change in a favorable direction.</p> <p>Methods/Design</p> <p>Approximately 370 overweight or obese postmenopausal breast cancer survivors (body mass index: 25.0 to 34.9 kg/m²) will be accrued and assigned to one of two weight loss intervention programs or a non-intervention control group. The dietary intervention is implemented in a free living population to test the two extremes of popular weight loss dietary patterns: a high carbohydrate, low fat diet versus a low carbohydrate, high fat diet. The effects of these dietary patterns on biomarkers for glucose homeostasis, chronic inflammation, cellular oxidation, and steroid sex hormone metabolism will be measured. Participants will attend 3 screening and dietary education visits, and 7 monthly one-on-one dietary counseling and clinical data measurement visits in addition to 5 group visits in the intervention arms. Participants in the control arm will attend two clinical data measurement visits at baseline and 6 months. The primary outcome is high sensitivity C-reactive protein. Secondary outcomes include interleukin-6, tumor necrosis factor-α, insulin-like growth factor-1 (IGF), IGF binding protein-3, 8-isoprostane-F2-alpha, estrone, estradiol, progesterone, sex hormone binding globulin, adiponectin, and leptin.</p> <p>Discussion</p> <p>While clinical data indicate that excess weight for height is associated with poor prognosis for long term survival, little attention is paid to weight control in the clinical management of breast cancer. This study will provide information that can be used to answer important patient questions about the effects of dietary pattern and magnitude of weight loss on long term survival following breast cancer treatment.</p> <p>Clinical Trial Registration</p> <p>CA125243</p

CDL-GAN: Contrastive Distance Learning Generative Adversarial Network for Image Generation

While Generative Adversarial Networks (GANs) have shown promising performance in image generation, they suffer from numerous issues such as mode collapse and training instability. To stabilize GAN training and improve image synthesis quality with diversity, we propose a simple yet effective approach as Contrastive Distance Learning GAN (CDL-GAN) in this paper. Specifically, we add Consistent Contrastive Distance (CoCD) and Characteristic Contrastive Distance (ChCD) into a principled framework to improve GAN performance. The CoCD explicitly maximizes the ratio of the distance between generated images and the increment between noise vectors to strengthen image feature learning for the generator. The ChCD measures the sampling distance of the encoded images in Euler space to boost feature representations for the discriminator. We model the framework by employing Siamese Network as a module into GANs without any modification on the backbone. Both qualitative and quantitative experiments conducted on three public datasets demonstrate the effectiveness of our method

Energetics and mammary carcinogenesis: effects of moderate-intensity running and energy intake on cellular processes and molecular mechanisms in rats

The objective of this experiment was to determine the effects on mammary carcinogenesis of similar limitations in energy availability either by energy expenditure due to moderate-intensity running (physical activity, PA) or by regulating dietary energy (RE) intake relative to a sedentary control (SC) group that ate ad libitum. A total of 90 female Sprague-Dawley rats were injected with 1-methyl-1-nitrosourea (50 mg/kg) and 7 days thereafter were randomized to either SC, a PA group given free access to a motorized running wheel, or a RE group whose food intake limited growth to the rate observed in PA. Compared with SC, mammary carcinogenesis was inhibited by RE or PA. Cancer incidence, 92.6%, 77.8%, and 66.7% (P = 0.06), and cancer multiplicity, 3.44, 2.11, and 1.62 cancers/rat (P = 0.006), in SC, RE, and PA, respectively, were reduced to a similar extent by RE and PA. Histological and Western blot analyses of mammary carcinomas provided evidence that RE and PA induced apoptosis via the mitochondrial pathway, that cell cycle progression was suppressed at the G1/S transition, and that intratumoral blood vessel density was reduced, although it remains to be determined whether PA and RE exert these effects via the same mechanisms