课程文献中心 更多>>

摘要： 355

关键词： beta‐   cell function   induction   intensive insulin therapy   intermittent insulin   maintenance   preservation  

摘要： Aim To test the hypothesis that the addition of periodic courses of short-term intensive insulin therapy (IIT) could enhance the effect of metformin (MET) maintenance therapy on preservation of beta-cell function following induction IIT. Methods In this multicentre, randomized controlled trial, 108 adults with type 2 diabetes (median 1.3 years' duration;HbA1c 6.6% +/- 0.6%) were randomized to 3 weeks of induction IIT (glargine, lispro) followed by MET maintenance, either with or without periodic 2-week courses of IIT every 3 months for 2 years. Beta-cell function was assessed by the Insulin Secretion Sensitivity Index-2 (ISSI-2) at an oral glucose tolerance test every 3 months. Results In both arms, induction IIT increased ISSI-2, improved whole-body insulin sensitivity and reduced hepatic insulin resistance (all P <= .0004). The primary outcome of baseline-adjusted ISSI-2 at 2 years was not improved by the addition of intermittent IIT (MET + IIT) and was slightly higher in the MET arm (baseline-adjusted difference -35 [95% CI: -66, -3]), with three additional beta-cell measures showing no significant differences. Baseline-adjusted HbA1c at 2 years did not differ between MET and MET + IIT (6.3% +/- 0.1% vs. 6.4% +/- 0.1%, P = .46), with 32.6% of participants in each arm maintaining HbA1c of 6.0% or less at 2 years. Conclusion Although initial induction IIT induces metabolic improvement, subsequent repeat courses of IIT every 3 months do not further enhance the effect of MET maintenance therapy on beta-cell function.

关键词： Endocannabinoids   Cannabinoid system   Granulosa cells   Fertility   Folliculogenesis   Apoptosis  

摘要： The endocannabinoid system (ECS) plays a crucial role in human reproduction. Changes in anandamide (AEA) levels affect reproductive events and has already been suggested as biomarker of reproductive potential of male and female gametes. Although cannabinoid-receptor 1 (CB1) was already identified in human granulosa cells (hGCs) the ECS was not characterized on granulosa cells line COV434 nor the effects of AEA on GCs viability and function depicted. Therefore, the aim of this study was to characterize the ECS elements and explore the effects of AEA on both COV434 and hGCs. Our results revealed that hGCs express the full enzymatic machinery responsible for AEA metabolism as well as cannabinoid receptors. In addition, AEA induced a reduction in both COV434 and hGCs viability in a concentration and time-dependent manner. Nevertheless, the effects of AEA in cell viability was independent of either CB1 or CB2 receptors. There was no ROS release in both cell models;however, AEA induced morphological changes, presenting chromatin condensation at 72 h, and variation on mitochondrial membrane potential. Moreover, AEA induced an increase in caspase-3/-7 activities in both cell models, but in hGCs there was also an increase in caspase 8 activity. This study supports the idea that ECS balance is crucial for folliculogenesis and oocyte quality as dysregulated AEA levels may compromise female fertility.

关键词： Lymphoid cell culture   Penaeus monodon   Immortalization   H-ras oncogene   Baculovirus expression system  

摘要： Cell line development from shrimp is not a novel venture as researchers across the globe have been trying to have crustacean cell lines over 30 years. The reason for not attaining a crustacean or precisely a shrimp cell line is believed to be the replicative senescence and the inability to maintain telomere length in vitro. Moreover, spontaneous in vitro transformations do not happen in shrimp cells. Oncogenic induction in primary cell culture is one of the ways to attain in vitro transformation by way of disrupting the mechanisms which involve cellular senescence. In this context, a recombinant baculovirus with shrimp viral promoter IHHNV-P2 was used for the transduction aimed at immortalization. An oncogene, H-ras, was successfully amplified and cloned in to the baculoviral vector, downstream to shrimp viral promoter IHHNV-P2 and upstream to GFP. Recombinant baculovirus with H-ras was generated and used for transduction into shrimp lymphoid cells during early dividing stage. Accordingly, fibroblast-like primary cell culture got developed, and H-ras and GFP expression could be confirmed. The study suggests that the simple method of incubating recombinant baculovirus with minced tissue enables in vitro transduction during early dividing stage of the cells, and the transduction efficiency gets enhanced by adding 5 mM sodium butyrate to the culture medium.

关键词： giant cells   lung   immunohistochemistry   sarcoma   carcinoma  

摘要： Three cases of primary giant cell tumors of the lung akin to those described in the soft tissues are presented. The patients are 3 men between the ages of 43 and 54 years who presented with nonspecific symptoms of cough, chest pain, and shortness of breath. None of the patients had any prior history of malignancy anywhere else. Diagnostic imaging disclosed the presence of an intrapulmonary mass. All the patients underwent lobectomy. Grossly, the tumors were described as solid, slightly hemorrhagic, and measuring between 1.8 and 2.4 cm in greatest diameter. Histologically, the tumors were characterized by a dual population of multinucleated giant cells admixed with a mononuclear proliferation. Nuclear atypia was mild to moderate, and mitotic activity varied but was under 5 mitotic figures per 10 high power fields. Immunohistochemical stains showed positive staining for vimentin, CD68, and cathepsin K, whereas the tumors were negative for keratin, TTF-1, p40, S-100 protein, and SABT-2. Clinical follow-up was obtained in 2 patients who have remained alive and without evidence of recurrence or metastasis up to 12 months after surgery. One patient was lost to follow-up. The current neoplasms represent a tumor that to the best of our knowledge has not been reported as a primary neoplasm of the lung. The cases herein described represent an unusual occurrence and should be maintained in the differential diagnosis of primary pulmonary tumors rich in multinucleated giant cells.

关键词： Large-eddy simulation (LES)   Facade geometrical details   Wind speed   Pressure coefficient   Balcony geometry   High-rise building  

摘要： The presence of building balconies can significantly modify the near-facade wind flow pattern and surface pressures. The present study evaluates the impact of building balcony geometry on mean wind speed on balcony spaces and wind-induced mean surface pressure for generic high-rise buildings. The focus is on balconies that extend along the entire width of the building facade. Large-eddy simulations (LES), validated with wind tunnel experiments, are conducted to investigate the impact of (i) balconies present or not, (ii) balcony depth, (iii) balcony parapet walls, (iv) balcony partition walls, and (v) density of balconies. The results indicate that the balcony geometry can greatly affect the mean wind speed on balcony spaces and the local and facade-averaged mean pressure coefficient (Cp). The presence of balconies can increase the facade-averaged Cp over the windward and leeward facades by 5.2% and 8.9%, respectively. These numbers rise to 23.5% and 23.3% when two partition walls are added at the lateral edges of the facades. Adding five partition walls can reduce the overall areaaveraged wind speed on balcony spaces by 68.0% compared to the case without partition walls. These findings can be useful in developing, designing and constructing buildings with facade geometrical details that improve building ventilation, air quality and wind comfort.

关键词： Glucagon‐   like peptide‐   1 receptor agonist   Lixisenatide   Pooled analysis  

摘要： Aims/Introduction The prevalence and pathophysiological background of type 2 diabetes mellitus vary across ethnicities, and can affect treatment responses. Adding lixisenatide to basal insulin (BI) in type 2 diabetes mellitus patients has shown improvements in glycated hemoglobin (HbA1c) and postprandial glycemic (PPG) excursions, without increasing hypoglycemic events. We aim to compare the efficacy of lixisenatide in Asian and white patients inadequately controlled with basal insulin. Materials and Methods An individual-level pooled analysis of two multi-national phase III studies, GetGoal-L and GetGoal-L-C, was carried out to assess the efficacy of lixisenatide versus placebo as an add-on treatment to BI +/- metformin in Asian and white patients with type 2 diabetes mellitus. Change in HbA1c, 2-h PPG and PPG excursion were analyzed, along with possible predictors of glycemic control. Results Pooled data showed that baseline characteristics were similar between Asian and white patients with the exception of bodyweight, body mass index and BI dose being higher in white patients. After 24 weeks, lixisenatide reduced HbA1c in both ethnic groups, with no statistically significant difference between the two groups (Asian patients least squares mean difference -0.49, 95% confidence interval -0.68 to - 0.30 and white patients least squares mean difference -0.45, 95% confidence interval -0.63 to - 0.26;P = 0.6287). Similarly, no significant difference was found in 2-h PPG reduction between both groups (least squares mean difference for Asian vs white patients: -3.37 vs -3.93;P = 0.3203). Treatment with lixisenatide contributed to HbA1c reduction of -0.56% after adjustment of baseline HbA1c level in Asian patients, and -0.41% in white patients. Conclusions Adding lixisenatide to BI significantly reduced HbA1c and 2-h PPG levels in both Asian and white participants with type 2 diabetes mellitus. No differences in treatment effect were observed between the two populations.

关键词： AMACR   p504s   SP116   Prostatic adenocarcinoma   Immunohistochemistry  

摘要： Alpha-methylacyl-coenzyme A-racemase (AMACR), also known as p504s, is overexpressed in prostatic adenocarcinoma and is frequently used in combination with basal cell markers to aid in diagnosing difficult prostate adenocarcinoma cases. In this retrospective method comparison study, we examined the sensitivity and specificity of the ready-to-use anti-p504s (SP116) Rabbit Monoclonal Primary Antibody compared to the monoclonal rabbit anti-human AMACR clone 13H4 in prostatic adenocarcinoma samples. De-identified prostatic adenocarcinoma tissue samples were stained with either the SP116 or 13H4 antibody clone in combination with the VENTANA Basal Cell Cocktail (34 beta E12+p63) and scored as positive or negative for prostatic adenocarcinoma. The scoring pathologist was blinded to the known historical diagnosis of each sample. The scoring pathologist correctly diagnosed each sample regardless of which p504s clone was used. Both assays using either clone were 100% concordant in their sensitivity and specificity. This study demonstrates that the ready-to-use anti-p504s (SP116) Rabbit Monoclonal Primary Antibody is equivalent to clone 13H4 concentrate when used according to package insert instructions in combination with the VENTANA Basal Cell Cocktail (34 beta E12+p63) to aid pathologists in the diagnosis of prostatic adenocarcinoma.

关键词： Gastrointestinal stromal tumors   Immunotherapy   Immune infiltrate   Programmed cell death-ligand 1  

摘要： Purpose To characterize the immune cell profile and expression of PD-1, PD-L1, and IDO in PDGFRA-mutant gastrointestinal stromal tumors (GISTs). Methods The clinicopathological data of PDGFRA-mutant GIST patients who received surgical resection in Zhongshan Hospital between January 2013 and August 2019 were reviewed retrospectively. The specimens of tissue chips were detected for immune cell infiltration and the expression of PD-1, PD-L1, and IDO by immunohistochemical staining. Results CD3(+), CD8(+), and CD68(+) cells were the main infiltrating immune cells in the 42 patients included in this study. In addition, CD4(+), CD56(+), Foxp3(+), and CD20(+) cells were also observed. A higher CD8(+) T cell count was associated with smaller tumor size and PDGFRA D842V mutation (P = 0.047, P = 0.005). A higher CD3(+) and CD68(+) cell count was associated with a higher mitotic index (P = 0.022, P = 0.006). CD4(+) and CD20(+) cell count was associated with tumor morphology (P = 0.002, P = 0.045). PD-1 expression was present in 37 (88%) samples. Eighteen samples were positive for PD-L1 expression, and it was higher in small vs. large tumors (P = 0.012) and epithelioid and mixed cell type vs. spindle cell type GISTs (P = 0.046). IDO expression was positive in all 42 patients. The number of CD4(+) cells was significantly greater in the specimens with high IDO expression (P = 0.012). Conclusion There were abundant infiltrating immune cells in PDGFRA-mutant GISTs. PD-L1 expression was negatively associated with tumor size. The immunotherapy targeting PD-1/PD-L1 checkpoint and IDO may be valuable.

关键词： Wheat kernels   Spectrogram   SPGAN-PNAS   Classification  

摘要： Quantity and quality of grain are both closely related to national development and social stability. Grain is lost during storage due to mildew and insects. Detection of damaged grain kernels not only can reduce the loss of grain, but also protect human beings from diseases caused by damaged grain. Therefore, research on the automatic detection of damaged grain is of continued urgency. In this paper, we propose a framework combining spectrogram generative adversarial network and progressive neural architecture search (SPGAN-PNAS) to detect and classify mildew-damaged wheat kernels (MDK), insect damaged wheat kernels (IDK) and undamaged wheat kernels (UDK). First, the spectrogram generative adversarial network (SPGAN) is designed to enlarge the data set. Second, we apply progressive neural architecture search (PNAS) to generate network structure to classify three types of wheat kernels. An F1 of 96.2% is obtained using the proposed method with 5-fold cross-validation. The results are superior to the classical neural networks for detection and classification of damaged wheat kernels. Experimental results show that the structure of SPGAN-PNAS is feasible and effective. (c) 2021 IAgrE. Published by Elsevier Ltd. All rights reserved.