Background: Tumor PD-L1 levels have predictive value in PD-1/PD-L1 checkpoint blockade therapies, yet biopsies can only provide baseline information. Whether PD-L1 expression on circulating tumor cells (CTCs) could serve as an alternative biomarker is of great interest.Design: We established an immunofluorescence assay for semi-quantitative assessment of the PD-L1 expression levels on CTCs with four categories (PD-L1negative, PD-L1low, PD-L1medium and PD-L1high). 35 patients with different advanced gastrointestinal tumors were enrolled in a phase 1 trial of a PD-1 inhibitor, IBI308. The CTC numeration and the PD-L1 expression levels were analyzed.Results: Prior the treatment of IBI308, 97% (34/35) patients had CTCs, ranging from1 to 70 (median 7). 74% (26/35) had PD-L1positive CTCs, and 60% (21/35) had at least one PD-L1high CTCs. The disease control (DC) rate in PD-L1high patients (48%) is much higher than the others (14%). The group with at least 20% abundance of PD-L1high CTCs had even higher DC rate of 64% (9/14), with only 14% DC rate for the rest (3/21). We also observed that the count changes of total CTC, PD-L1postive CTC and PD-L1high CTC correlate quite well with disease outcome (P<0.001, P = 0.002 and 0.007, respectively). In addition, the abundance of PD-L1high CTCs at baseline had predicative significance for progression free survival (PFS).Conclusions: We revealed that the abundance of PD-L1high CTCs at baseline might serve as a predictor to screen patients for PD-1/PD-L1 blockade therapies and measuring the dynamic changes of CTC could indicate the therapeutic response at early time.
Our objective was to explore the mechanism of cell-assisted adipose transplantation by using freshly isolated human stromal vascular fraction (SVF) cells and to observe the dynamic changes of the graft after transplantation. The SVF was isolated from human liposuction aspirates, and 0.5 ml adipose tissue was mixed with 1 × 10 6 SVF cells or culture medium then injected to nude mice subcutaneously. At 1,4,7,14,30, 60, and 90 days after transplantation, samples were harvested for 1) general observation and retention rate; 2) whole-mount stain; 3) H&E stain; 4) immunohistochemical staining for S100, CD68, and CD34; 5) ELISA for VEGF and bFGF; 6) peroxisome proliferator-activated receptor-g (PPARg) fluorescence in situ hybridization. The retention rate in the experiment group was markedly higher than that in the control group. Whole-mount stain shows most of the cells in the center of the graft could not survive the ischemia until day 14. Histology showed new vessels on the surface of the graft at 3 days. However, in the control group, fewer newly formed vessels were detected until day 7. In the late stage of transplantation, gradual fibrosis was found in the graft, and the tissue was divided into a grid-like structure. A large number of round neonatal adipocytes with big nuclei in the center were found surrounding the new vessels, which were S100 and CD34 positive and CD68 negative. In the late stage of transplantation, most of the neonatal adipocytes were human PPARg positive. Moreover, the SVF group showed a higher level of VEGF and bFGF. SVF assisting adipose transplantation could increase the retention rate of the graft through promoting adipose tissue regeneration via secretion of growth factors, promotion of angiogenesis, and increasing the density of mesenchymal stem cells.
The current operational World Weather Watch over the tropical latitudes exhibits large data gaps. This paper proposes a detailed physical initialization procedure where the combined use of the World Weather Watch and detailed 'satellite data sets are used to enhance the definition of initial surface fluxes of water vapor and sensible heat, the initial rainfall rates and the earth's radiation budget. The satellite radiances are used to unify the physical initializations of the fluxes, rainfall, and the clouds. This is carried out using a Newtonian relaxation during a•pre integration phase between day -1 and day 0 where the fluxes, the rainfall rates, and the cloud distributions provide a consistent humidity analysis and a spin up of the diabatic heating and the divergent circulations. A comparison of medium range forecasts from a control experiment (that utilizes the standard nonlinear normal mode initialization, with physics, at day 0) with an experiment based on the unified physical initialization is carried out to demonstrate the effective enhancement of the World Weather Watch over the tropics by the proposed method. These experiments are carried out with a global spectral model which is run at a resolution of 106 wave triangular truncation.
Based on the new-generation Global/Regional Assimilation and PrEdiction System (GRAPES) developed by the Numerical Prediction Research Center, China Meteorological Administration and the Chinese Unified Atmospheric Chemistry Environment for Dust Atmospheric Chemistry Module (CUACE/Dust) developed by the Centre for Atmosphere Watch and Services (CAWAS) of the Chinese Academy of Meteorological Sciences (CAMS), the China sand and dust storm forecasting system GRAPES /CUACE-Dust model has been established. The latest data of land desertification, optical properties of China sand and dust aerosols, daily soil moisture and snow cover over China main land was introduced in this system. The system showed good performance in mass conservation. The comparisons of real-time prediction outputs with surface observations and aerosol indices derived from TOMS ozone spectrophotometers (TOMS AI) indicate that the model can predict the outbreak, development, transport and depletion processes of sand and dust storms accurately over China and the East Asian region. The system makes real-time quantitative prediction of a series of elements including sand and dust injection from the surface, dry and wet deposition amount, dust concentration and optical depth. We selected 7 major dust storms occurring in April 2006 and analyzed the spatiotemporal distribution patterns of dust emission, dry and wet deposition and atmospheric load in this paper. The results showed that about 225 million tons of dust were emitted into the atmosphere from the deserts over east Asia in that month. The 3 major sand and dust sources were just as the following: The deserts in northern Inner Mongolia and the boundary area around China-Mongolia were the first dust sources with a contribution of 153 million tons accounting for 68% of the total emission. The Taklimakan Desert ranked second and contributed approximately 40 million tons accounting for 17% of the dust emission.The Onqin Daga Sandland emitted about 15 million tons or 7% of the total emission. The contributions from other deserts, sandy lands and abandoned farmlands were about only 8% of the total dust emission. The total deposition over the East Asian region in April 2006 was 136 million tons. The regional distribution of dust deposition showed that the 3 major sources were also the major deposition areas. The deposition amount in the 3 major sources accounted for 78% of the total with about 135 million tons falling back to the source regions. The secondary deposition area was the China mainland downriver, where more than 2 million tons deposited accounting for 16% of the total deposition. The deposition over the region east of 120°E including China off-shore regions, Korean Peninsula, Japan and the West Pacific took only 6% of the total deposition, which was about 850000 tons. The analysis on dry and wet deposition showed that dry deposition dominated in the process, accounting for 94% of the total sand and dust depositions in the period and wet deposition only was around for 6%, since it was general...
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