Search

In this research, we reveal the inter-connection between lightning strokes, reversal of the electric field, ionospheric disturbances, and a sodium layer (NaS), based on the joint observations by a temperature/wind (T/W, where the slash means “and”) lidar, an ionosonde, an atmospheric electric mill, a fluxgate magnetometer, and the World Wide Lightning Location Network (WWLLN). Our results suggest that lightning strokes could trigger or amplify the formation of an NaS layer in a descending sporadic E layer (ES), through a mechanism that involves the overturning of the electric field. A conjunction between the lower and upper atmospheres could be established as follows by these inter-connected phenomena, and the key processes could be suggested to be: lightning strokes → overturning of the electric field → ES generating NaS.

In recent years, the concept of multistatic meteor radar systems has attracted the attention of the atmospheric radar community, focusing on the mesosphere and lower thermosphere (MLT) region. Recently, there have been some notable experiments using such multistatic meteor radar systems. Good spatial resolution is vital for meteor radars because nearly all parameter inversion processes rely on the accurate location of the meteor trail specular point. It is timely then for a careful discussion focused on the error distribution of multistatic meteor radar systems. In this study, we discuss the measurement errors that affect the spatial resolution and obtain the spatial-resolution distribution in three-dimensional space for the first time. The spatial-resolution distribution can both help design a multistatic meteor radar system and improve the performance of existing radar systems. Moreover, the spatial-resolution distribution allows the accuracy of retrieved parameters such as the wind field to be determined.

Long-lived metallic ions in the Earth's atmosphere (ionosphere) have been investigated for many decades. Although the seasonal variation in ionospheric “sporadic E” layers was first observed in the 1960s, the mechanism driving the variation remains a long-standing mystery. Here, we report a study of ionospheric irregularities using scintillation data from COSMIC satellites and identify a large-scale horizontal transport of long-lived metallic ions, combining the simulations of the Whole Atmosphere Community Climate Model with the chemistry of metals and ground-based observations from two meridional chains of stations from 1975–2016. We find that the lower thermospheric meridional circulation influences the meridional transport and seasonal variations of metallic ions within sporadic E layers. The winter-to-summer meridional velocity of ions is estimated to vary between −1.08 and 7.45 m/s at altitudes of 107–118 km between 10–60∘ N. Our results not only provide strong support for the lower thermospheric meridional circulation predicted by a whole atmosphere chemistry–climate model, but also emphasize the influences of this winter-to-summer circulation on the large-scale interhemispheric transport of composition in the thermosphere–ionosphere.

For elective surgery of colorectal cancer, current evidence supports preoperative mechanical bowel preparation combined with oral antibiotics. Meanwhile, for patients with varied degrees of intestinal stenosis, individualized protocol is required to avoid adverse events. We hereby summarize recent high-quality evidences and updates of guidelines and consensus, and recommend stratified bowel preparation based on the clinical practice of our institute as follows. (1) For patients with unimpaired oral intake, whose tumor can be passed by colonoscopy, mechanical bowel preparation and oral antibiotics are given. (2) For patients without symptoms of bowel obstruction but with impaired oral intake or incomplete colonoscopy due to tumor-related stenosis, small-dosage laxative is given for several days before surgery, and oral antibiotics the day before surgery. (3) For patients with bowel obstruction, mechanical bowel preparation or enema is not indicated. We proposed this evidence-based, individualized protocol for preoperative bowel preparation for the reference of our colleagues, in the hope of improving perioperative outcomes and reducing adverse events.对于结直肠癌的择期手术，最新的循证医学证据支持术前机械性肠道准备联合口服抗生素。由于患者肠道通畅程度各异，需要实施个体化术前肠道准备方案，以避免不良事件。本文概要介绍相关高级别证据、指南和共识更新，并结合本中心的实践经验作出以下分层推荐：（1）无进食受限、肠镜可通过肿瘤的患者，可行机械性肠道准备和预防性口服抗生素；（2）无典型梗阻症状，但因肿瘤肠段狭窄导致进食受限或肠镜不可通过的患者，建议术前数日开始口服小剂量缓泻药至手术前夕，并在术前预防性口服抗生素；（3）梗阻患者无须术前机械性肠道准备或灌肠。.

Accurate assessment of anthropogenic carbon dioxide (CO2) emissions and their redistribution among the atmosphere, ocean, and terrestrial biosphere in a changing climate is critical to better understand the global carbon cycle, support the development of climate policies, and project future climate change. Here we describe and synthesize data sets and methodology to quantify the five major components of the global carbon budget and their uncertainties. Fossil CO2 emissions (EFOS) are based on energy statistics and cement production data, while emissions from land-use change (ELUC), mainly deforestation, are based on land-use and land-use change data and bookkeeping models. Atmospheric CO2 concentration is measured directly, and its growth rate (GATM) is computed from the annual changes in concentration. The ocean CO2 sink (SOCEAN) is estimated with global ocean biogeochemistry models and observation-based data-products. The terrestrial CO2 sink (SLAND) is estimated with dynamic global vegetation models. The resulting carbon budget imbalance (BIM), the difference between the estimated total emissions and the estimated changes in the atmosphere, ocean, and terrestrial biosphere, is a measure of imperfect data and understanding of the contemporary carbon cycle. All uncertainties are reported as ±1σ. For the first time, an approach is shown to reconcile the difference in our ELUC estimate with the one from national greenhouse gases inventories, supporting the assessment of collective countries’ climate progress. For the year 2020, EFOS declined by 5.4 % relative to 2019, with fossil emissions at 9.5 ± 0.5 GtC yr−1 (9.3 ± 0.5 GtC yr−1 when the cement carbonation sink is included), ELUC was 0.9 ± 0.7 GtC yr−1, for a total anthropogenic CO2 emission of 10.2 ± 0.8 GtC yr−1 (37.4 ± 2.9 GtCO2). Also, for 2020, GATM was 5.0 ± 0.2 GtC yr−1 (2.4 ± 0.1 ppm yr−1), SOCEAN was 3.0 ± 0.4 GtC yr−1 and SLAND was 2.9 ± 1 GtC yr−1, with a BIM of −0.8 GtC yr−1. The global atmospheric CO2 concentration averaged over 2020 reached 412.45 ± 0.1 ppm. Preliminary data for 2021, suggest a rebound in EFOS relative to 2020 of +4.9 % (4.1 % to 5.7 %) globally. Overall, the mean and trend in the components of the global carbon budget are consistently estimated over the period 1959–2020, but discrepancies of up to 1 GtC yr−1 persist for the representation of annual to semi-decadal variability in CO2 fluxes. Comparison of estimates from multiple approaches and observations shows: (1) a persistent large uncertainty in the estimate of land-use changes emissions, (2) a low agreement between the different methods on the magnitude of the land CO2 flux in the northern extra- tropics, and (3) a discrepancy between the different methods on the strength of the ocean sink over the last decade. This living data update documents changes in the methods and data sets used in this new global carbon budget and the progress in understanding of the global carbon cycle compared with previous publications of this data set (Friedlingstein et al., 2020; Friedlingstein et al., 2019; Le Quéré et al., 2018b, 2018a, 2016, 2015b, 2015a, 2014, 2013). The data presented in this work are available at https://doi.org/10.18160/gcp-2021 (Friedlingstein et al., 2021).

Background and Aims: Chronic hepatitis B virus (HBV) infection remains a major public health problem globally. Here, we describe the baseline characteristics and treatment profiles of HBV-infected patients recruited to the China Registry of Hepatitis B. Methods: Inclusion criteria were patients with different stages of chronic HBV infection and complete key data. Exclusion criteria were patients with hepatocellular carcinoma. The baseline clinical, laboratory and treatment profiles were analyzed. Results: Finally, 40,431 patients were included. The median age was 43 years, with 65.2% being men and 51.3% being positive for hepatitis B e antigen (HBeAg). The most common initial diagnosis was chronic hepatitis B (81.0%), followed by cirrhosis (9.3%), inactive carrier of hepatitis B surface antigen (HBsAg) (6.7%), and immune tolerant phase of hepatitis B infection (3.0%). Among the 21,228 patients who were on treatment, 88.0%, 10.0% and 2.0% received nucleos(t)ide analogues (NAs), interferon or combination of NAs and interferon, respectively. The proportion of patients who received preferred NAs (entecavir or tenofovir disoproxil fumarate) had increased from 13.5% in 2003 to 79.7% in 2016. Conclusions: We concluded that middle-aged men accounted for most of the patients with chronic hepatitis B in this cross-sectional study. About half of the patients were HBeAg-positive. NAs were the most commonly used therapy, and use of the preferred NAs had steadily increased in the past decade.

A long-lived gravity wave (GW) in the atmospheric boundary layer (ABL) is analysed during a field experiment in Anqing, China (30∘37′ N, 116∘58′ E). Persistent GWs with periods ranging from 10 to 30 min over 10 h in the ABL within a 2 km height are detected by a coherent Doppler lidar from 4 to 5 September 2018. The amplitudes of the vertical wind due to these GWs are approximately 0.15–0.2 m s−1. The lifetimes of these GWs are longer than 20 wave cycles. There is no apparent phase progression with altitude. The vertical and zonal perturbations in the GWs are 90∘ out of phase, with vertical perturbations generally leading to zonal ones. Based on experiments and simplified two-dimensional computational fluid dynamics (CFD) numerical simulations, a reasonable generation mechanism of this persistent wave is proposed. A westerly low-level jet of ∼5 m s−1 exists at an altitude of 1–2 km in the ABL. The wind shear around the low-level jet leads to wave generation under the condition of light horizontal wind. Furthermore, a combination of thermal and Doppler ducts occurs in the ABL. Thus, the ducted wave motions are trapped in the ABL and have long lifetimes.

The existing distribution of meteor radars located from high- to low-latitude regions provides a favorable temporal and spatial coverage for investigating the climatology of the global mesopause density. In this study, we report the climatology of the mesopause relative density estimated using multiyear observations from nine meteor radars, namely, the Davis Station (68.6∘ S, 77.9∘ E), Svalbard (78.3∘ N, 16∘ E) and Tromsø (69.6∘ N, 19.2∘ E) meteor radars located at high latitudes; the Mohe (53.5∘ N, 122.3∘ E), Beijing (40.3∘ N, 116.2∘ E), Mengcheng (33.4∘ N, 116.6∘ E) and Wuhan (30.5∘ N, 114.6∘ E) meteor radars located in the midlatitudes; and the Kunming (25.6∘ N, 103.8∘ E) and Darwin (12.3∘ S, 130.8∘ E) meteor radars located at low latitudes. The daily mean relative density was estimated using ambipolar diffusion coefficients derived from the meteor radars and temperatures from the Microwave Limb Sounder (MLS) on board the Aura satellite. The seasonal variations in the Davis Station meteor radar relative densities in the southern polar mesopause are mainly dominated by an annual oscillation (AO). The mesopause relative densities observed by the Svalbard and Tromsø meteor radars at high latitudes and the Mohe and Beijing meteor radars at high midlatitudes in the Northern Hemisphere show mainly an AO and a relatively weak semiannual oscillation (SAO). The mesopause relative densities observed by the Mengcheng and Wuhan meteor radars at lower midlatitudes and the Kunming and Darwin meteor radars at low latitudes show mainly an AO. The SAO is evident in the Northern Hemisphere, especially at high latitudes, and its largest amplitude, which is detected at the Tromsø meteor radar, is comparable to the AO amplitudes. These observations indicate that the mesopause relative densities over the southern and northern high latitudes exhibit a clear seasonal asymmetry. The maxima of the yearly variations in the mesopause relative densities display a clear latitudinal variation across the spring equinox as the latitude decreases; these latitudinal variation characteristics may be related to latitudinal changes influenced by gravity wave forcing. In addition to an AO, the mesopause relative densities over low latitudes also clearly show an intraseasonal variation with a periodicity of 30–60 d.

The atmospheric boundary layer height (BLH) is a key parameter in weather forecasting and air quality prediction. To investigate the relationship between BLH and air pollution under different conditions, a compact micro-pulse lidar integrating both direct-detection lidar (DDL) and coherent Doppler wind lidar (CDWL) has been built. This hybrid lidar is operated at 1.5 µm, which is eye-safe and made of all-fibre components. The BLH can be determined from aerosol density and vertical wind independently. During a 45 h continuous observation in June 2018, the stable boundary layer, residual layer and convective boundary layer are identified. The fine structure of the aerosol layers, drizzles and vertical wind near the cloud base are also detected. In comparison, the standard deviation between BLH values derived from DDL and CDWL is 0.06 km, indicating the accuracy of this work. The retrieved convective BLH is a little higher than that from ERA5 reanalysis due to different retrieval methods. Correlation between different BLH and PM2.5 is strongly negative before a precipitation event and becomes much weaker after the precipitation. Different relationships between PM2.5 and BLH may result from different BLH retrieval methods, pollutant sources and meteorological conditions.

On the basis of S4max data retrieved from COSMIC GPS radio occultation measurements, the long-term climatology of the intensity of Es layers is investigated for the period from December 2006 to January 2014. Global maps of Es intensity show the high-spatial-resolution geographical distribution and strong seasonal dependence of Es layers. The maximum intensity of Es occurs over the mid-latitudes, and its value in summer is 2–3 times larger than that in winter. A relatively strong Es layer is observed at the North Pole and South Pole, with a distinct boundary dividing the mid-latitudes and high latitudes along the 60–80∘ geomagnetic latitude band. The simulation results show that the convergence of vertical ion velocity could partially explain the seasonal dependence of Es intensity. Furthermore, some disagreements between the distributions of the calculated divergence of vertical ion velocity and the observed Es intensity indicate that other processes, such as the vertical motions of gravity waves, magnetic-field effects, meteoric mass influx into Earth's atmosphere, and the chemical processes of metallic ions, should also be considered as they may also play an important role in the spatial and seasonal variations in Es layers.

The University of Science and Technology of China narrowband sodium temperature and wind lidar, located in Hefei, China (32° N, 117° E), has made routine nighttime measurements since January 2012. A total of 154 nights (∼ 1400 h) of vertical profiles of temperature, sodium density, and zonal wind and 83 nights (∼ 800 h) of vertical flux of gravity wave (GW) zonal momentum in the mesopause region (80–105 km) were obtained during the period from 2012 to 2016. For temperature, it is most likely that the diurnal tide dominates below 100 km in spring, while the semidiurnal tide dominates above 100 km throughout the year. A clear semiannual variation in temperature is revealed near 90 km, in phase with the tropical mesospheric semiannual oscillation (MSAO). The variability in sodium density is positively correlated with temperature below 95 km, suggesting that in addition to dynamics, the chemistry also plays an important role in the formation of sodium atoms. The seasonal variability in sodium density observed by both lidar and satellite generally agrees well with a whole atmosphere model simulation using an updated meteoric input function which includes different cosmic dust sources. For zonal wind, the diurnal tide dominates in both spring and fall, while semidiurnal tide dominates in winter. The observed semiannual variation in zonal wind near 90 km is out of phase with that in temperature, consistent with the tropical MSAO. The lidar observations generally agree with satellite and meteor radar observations as well as model simulations at similar latitude. The 50–70 % of zonal momentum flux is induced by short-period (10 min–2 h) GWs. The large zonal momentum flux in summer and winter due to short-period GWs is clearly anticorrelated with eastward zonal wind maxima below 90 km, suggesting the filtering of short-period GWs by the SAO wind.

The electrical magnetic field plays an essential role in controlling the molten steel flow, heat transfer and migration of inclusions. Electromagnetic induction heating technology utilizes the force or heat effect of the electromagnetic field or simultaneously uses force and heat effect to control molten metal flow, heat transfer and the movement of non-metallic inclusion in the metallurgical process, to optimize the metallurgical process, improve production efficiency, quality, and performance. In this work, the development of IH in continuous casting tundish was outlined. The current theoretical and experimental research on electromagnetic induction heating for molten steel flow and heat transfer were introduced. Meanwhile, the electromagnetic purification mechanism and research progress of non-metallic inclusions in molten steel were analyzed. Finally, the prospects for the application of electromagnetic IH are proposed.

The waterway of Panjin Port is planning to be constructed in order to meet the requirement of the larger cargo ship. There are two layout schemes of the waterway and the back-silting under normal condition and storm surge is simulated by the numerical model. The results show that the construction of the waterway leads to the decrease of the sediment concentration within the waterway. For normal year without storm, the largest deposition occurs at 3km mileage then decreases along the seaward direction. The total deposition amount and average thickness of scheme 1 is larger than that of scheme 2. The SSW direction storm surge bring significant sediment deposition along the waterway. Under storm surge, the average deposition thickness of scheme 1 is smaller than that of scheme 2 because of the waterway direction. The one-week back-silting of 25-year return storm is larger than that of 10-year return storm. Different from other scenarios, in the case of a storm surge in 25 years, a sudden increase in siltation thickness at 10 km of the channel.

To investigate the appropriate time and computed tomography perfusion (CTP) parameters for predicting delayed cerebral ischaemia (DCI) following aneurysmal subarachnoid haemorrhage (aSAH).All patients underwent baseline CTP within 24 hours and follow-up CTP on day 4 and day 7 after aSAH. The quantitative and semi-quantitative parameters, cerebral blood volume (CBV), cerebral blood flow (CBF), mean transit time (MTT), time to peak (TTP), relative CBV and CBF (rCBV, rCBF), and MTT and TTP difference (ΔMTT, ΔTTP) were compared between the DCI and non-DCI (NDCI) groups at the three time points.Thirty-nine patients were included. Twelve patients developed DCI. CBF, rCBF, and ΔMTT were significantly different in the DCI group among all time points (p0.05), but these parameters did not significantly change from day 4 to day 7. CBF and rCBF in the DCI group were lower than in the NDCI group. ΔMTT in the DCI group was longer than in the NDCI group, but significant differences were only found in the two follow-up CTPs (both p0.05). The optimal threshold values distinguishing DCI and NDCI were 40.1 ml/100 g/min for CBF, 0.90 for rCBF and 0.33 seconds for ΔMTT. The follow-up CTP on day 4 was an appropriate time to predict DCI after aSAH.The follow-up CTP on day 4 after aSAH can be helpful for the early identification of DCI. CBF, rCBF, and ΔMTT were found to be the best prognosticators for the development of DCI.

The essence of low carbon economy development is a continuous evolution and innovation process of socio-economic system from traditional high carbon economy to new sustainable green low carbon economy to achieve a sustainable dynamic balance and benign interactive development of various elements between society, economy and natural ecosystem. At the current stage, China’s socio-economy is showing the feature of "three high" (high energy consumption, high emissions and high pollution). In this case, quickly to promote the development of green low carbon economy is necessary and urgent. This research indicates that, low carbon economy development is achieved by micro-economic agents such as households, businesses and social intermediary organizations through Government’s guidance and the role of market mechanism. In low carbon economy development, the state (government) is a leader and markets are core, while economic agents (e.g., households, businesses and social intermediary organizations) are basis. For this reason, it is necessary to build an effective cleaner development and incentive-compatible policy system oriented to end-users.

We compared dosimetry and clinical toxicity for 3-dimensional conformal radiotherapy (3D-crt), intensity-modulated radiotherapy (imrt), and RapidArc (Varian Medical Systems, Palo Alto, CA, U.S.A.) in locally advanced pancreatic cancer (lapcc). We hypothesized that the technique with better sparing of organs at risk (oars) and better target dose distributions could lead to decreased clinical toxicity. The study analyzed 280 patients with lapcc who had undergone radiotherapy. The dosimetry comparison was performed using 20 of those patients. Dose&ndash, volume histograms for the target volume and the oars were compared. The clinical toxicity comparison used the 280 patients who received radiation with 3D-crt, imrt, or RapidArc. Compared with 3D-crt, RapidArc and imrt both achieved a better conformal index, homogeneity index, V95%, and V110%. Compared with 3D-crt or imrt, RapidArc reduced the V10, V20, and mean dose to duodenum, the V20 of the right kidney, and the liver mean dose. Compared with 3D-crt, RapidArc reduced the V35, and V45 of duodenum, the mean dose to small bowel, and the V15 of right kidney. The incidences of grades 3 and 4 diarrhea (p = 0.037) and anorexia (p = 0.042) were lower with RapidArc than with 3D-crt, and the incidences of grades 3 and 4 diarrhea (p = 0.027) were lower with RapidArc than with imrt. Compared with 3D-crt or imrt, RapidArc showed better sparing of oars, especially duodenum, small bowel, and right kidney. Also, fewer acute grades 3 and 4 gastrointestinal toxicities were seen with RapidArc than with 3D-crt or imrt. A technique with better sparing of oars and better target dose distributions could result in decreased clinical toxicities during radiation treatment for lapcc.

We present a state-of-art 12LP FinFET technology with PPA (Performance, Power, and Area) improvement over 14LPP. 12LP enables >10% area reduction including a 7.5T library and 16% power reduction at fixed frequency or a 15% performance improvement at given leakage over 14LPP with comparable reliability and yield. In addition, SRAMs benefit from a 30% leakage reduction at the same Iread. 12LP extends the 14nm technology with compelling performance and area scaling.

Nucleotide-binding oligomerization domain-like receptor pyrin domain containing-3 (NLRP3) inflammasome is a type of multi-protein complex within the cell, the activation of which promotes the release of bioactive interleukin(IL)-1β and IL-18 and contributes to inflammatory progress. In recent years, the research on the role of NLRP3 inflammasome in the pathogenesis and development of ocular surface and fundus diseases has made considerable progress. This review summarizes current understanding in the structure, ocular expression, and mechanisms of activation of NLRP3 inflammasome, as well as the contribution of this protein complex to eye diseases, thereby revealing the theoretical possibility that NLRP3 inflammasome might serve as a novel therapeutic target for the related ocular diseases.NLRP3（nucleotide-binding oligomerization domain-like receptor pyrin domain containing-3）炎性小体是细胞内一类多蛋白复合体，活化后能促进具有生物学活性的白细胞介素1β和白细胞介素18释放，参与炎性反应的进程。近年关于NLRP3炎性小体在眼表和眼底疾病发生、发展中作用的研究取得一定进展。本文就NLRP3炎性小体的结构、在眼部的表达、在眼病中活化的机制及其对眼部疾病的作用进行总结和分析，以期在理论上揭示以NLRP3炎性小体作为相关眼病治疗靶点的可能性，为相关研究提供参考。

The ZY-3 is the civil high-resolution optical stereoscopic mapping satellite independently developed by China. The ZY-3 constellation of the twin satellites operates in a sun-synchronous, near-polar, circular 505 km orbit, with a descending location time of 10:30 AM and a 29-day revisiting period. The panchromatic triplet sensors, pointing forward, nadir, and backward with an angle of 22°, have excellent base-to-height ratio, which is beneficial to the extraction of DEM. In order to extract more detailed and highprecision DEM, the ZY-3 (02) satellite has been upgraded based on the ZY-3 (01), and the GSD of the stereo camera has been optimized from 3.5 to 2.5 meters. In the paper case studies using the ZY-3 01 and the 02 satellite data for block adjustment and DEM extraction have been carried out in Liaoning Province of China. The results show that the planimetric and altimetric accuracy can reach 3 meters, which meet the mapping requirements of 1 : 50,000 national topographic map and the design performance of the satellites. The normalized elevation accuracy index (NEAI) is adopted to evaluate the twin satellite stereoscopic performance, and the NEAIs of the twin ZY-3 satellites are good and the index of the ZY-3(02) is slightly better. The comparison of the overlapping DEMs from the twin ZY-3 satellites and SRTM is analysed. The bias and the standard deviation of all the DEMs are better than 5 meters. In addition, in the process of accuracy comparison, some gross errors of the DEM can be identified, and some elevation changes of the DEM can also be found. The differential DEM becomes a new tool and application.

Mother-to-child transmission of hepatitis B virus (HBV) is one of major public health issues. Difference is found on effect of preventions of mother to child transmission of HBV such as Hepatitis B vaccine, Hepatitis B immunoglobulin and antiretroviral drugs. Based on the risks of hepatitis B virus on children, influencing factors and interventions of HBV mother-to-child transmission were explored to improve prevention mother-to-child transmission of hepatitis B and to search appropriate strategies reducing mother-to-child transmission of HBV.HBV母婴传播已成为引起社会关注的重大公共卫生问题之一。目前，乙型肝炎疫苗、乙型肝炎免疫球蛋白和抗病毒药物等不同干预措施预防HBV母婴传播的效果存在差异。本文从儿童感染HBV的途径与危害、影响HBV母婴传播的因素以及HBV传播干预措施等3个方面进行综述，探讨不同因素和干预措施对HBV母婴传播的影响，为提高预防HBV母婴传播的效果，探讨进一步降低HBV母婴传播干预措施的研究方向。.

Here we report the extreme toxicity in vitro of Bi(OH)

Liver biopsy is not routinely performed in treated chronic hepatitis B. Liver stiffness measurement has been validated for non-invasive liver fibrosis assessment in pre-treatment chronic hepatitis B but has not been assessed for fibrosis monitoring during antiviral therapy. Liver stiffness was systemically monitored by Fibroscan® every 6 months in a cohort of patients with hepatitis B receiving antiviral therapy and compared with liver biopsies at baseline and week 104. A total of 534 hepatitis B e antigen positive treatment-naive patients receiving telbivudine based therapy with qualified liver stiffness measurement at baseline and week 104 were analyzed, 164 of which had adequate paired liver biopsies. Liver stiffness decreased rapidly (-2.2 kPa/24 weeks) in parallel with alanine aminotransferase (ALT) from 8.6 (2.6 - 49.5) kPa at baseline to 6.1 (2.2 - 37.4) kPa at week 24. Interestingly, liver stiffness decreased slowly (-0.3 kPa/24 weeks) but continually from week 24 to week 104 (6.1 vs. 5.3 kPa, P

Background Chemerin has been implicated to play opposing roles, either pro-inflammatory or anti-inflammatory, in various tissue inflammation processes primarily through the regulation of tissue recruitment of immune cells. However, the effect of chemerin in allergic asthma has not yet been explored. We sought to investigate the role of chemerin in the murine model of allergic asthma and explore the underlying mechanism. Methods We examined the effect of intranasal (i.n.) administration of chemerin during antigen challenge in murine models of asthma. Moreover, we examined whether administration of CCL2 or bone marrow-derived dendritic cells (BMDCs) transfer reversed the effects of chemerin on ovalbumin-induced asthma. We finally examined the effect of chemerin on CCL2 expression in activated lung epithelial cells in vitro. Results The administration of chemerin attenuated allergic airway inflammation and airway hyperreactivity during antigen challenge. Chemerin treatment caused significant decreases in BALF CD4(+) T-cell accumulation and mRNA expression of Th2-attracting chemokines, CCL17 and CCL22, which was accompanied by significantly decreased BALF CD11c(+) CD11b(+) inflammatory DC accumulation and CCL2 production. Furthermore, airway administration of exogenous CCL2 or adoptive transfer of CD11c(+) CD11b(+) BMDCs abrogated the suppressive effects of chemerin on allergic asthma. Finally, in vitro study showed that chemerin inhibited CCL2 secretion by low-dose LPS-stimulated lung epithelial cells, which led to decreased chemotaxis of BMDCs. Conclusions Our study demonstrates that chemerin plays a protective role in allergic asthma by suppressing airway recruitment of inflammatory CD11c(+) CD11b(+) DCs through the inhibition of CCL2 secretion by active lung epithelial cells.

Background: Bmi1, a polycomb-group protein, maintains stem cell self-renewal and is frequently overexpressed in cancers. Upregulation of Bmi1 by Twist1 can promote tumor-initiating capability and Epithelial-mesenchymal transition (EMT) by repressing E-cadherin expression. It has been demonstrated that Post-EMT breast cancer cells express cancer stem cell (CSC) markers including Bmi1, but display decreased ERα expression. ERα is a ligand-activated nuclear hormone receptor that regulates the transcription of E2-responsive genes in diverse target cells. It's reported that ligand-activated ERα could repress slug transcription by binding to the half-site ERE element in its promoter, and then regulate E-cadherin and EMT. Herein, we hypothesized that ERα signaling might regulate E-cadherin and EMT through Bmi1. Methods: First, we determined Bmi1 and ERα expression at both mRNA and protein levels by quantitative RT-PCR and Western blot in various breast cancer cell lines. Further, we quantitatively analyzed mRNA and protein levels of Bmi1 as well as its down-stream genes including E-cadherin after silencing ERα in T47D cells with siRNA, or after overexpressing ERα in BT549 cells. The chromatin immunoprecipitation (ChIP) and electrophoretic mobility shift assay (EMSA) were also performed to investigate whether ERα binds directly to Bmi1 promoter region. Luciferase assay with Bmi1 reporter was performed to ERα mediated regulation. To identify whether ERα regulates EMT, transwell and matrigel invasion, flow cytometry, mammosphere assay and wound healing assay were performed to invasion, metastases and characterize stem-cell properties of EMT. Finally, we analyzed the expression of ERα, Bmi1 and E-cadherin in human breast cancer specimens with immunohistochemistry. Results: The study showed that Bmi1 inversely correlated with ERα expression in different subtypes of breast cancer cells. We further confirmed that Bmi1 was upregulated at both mRNA and protein levels and E-cadherin was downregulated with siRNA against ERα in T47D cells, and Bmi1 was downregulated and E-cadherin was upregulated when overexpressing ERα in BT549 cells with qRT-PCR and western blot analyses. The present study also demonstrated that ERα could directly binds to the half-ERE region of the Bmi1 gene and repressing Bmi1 expression transcriptionally with CHIP/EMSA and reporter analyses. Overexpression of ERα in BT549 cell significantly decreased levels of migration of transwell and wounding healing, invasiveness, CD44high/CD24low population, and the capabilities of mammosphere formation. Conclusions: Our results demonstrated that ERα can suppress EMT through transcriptionally down-regulating Bmi-1 and its down-stream genes in human breast cancer cells. The inverse relationship between ERα and Bmi1 expression further supports the epithelial phenotype of ERα positive tumors or mesenchymal phenotype of ERα negative tumors. Our findings provide a novel mechanistic insight into how ERα regulates EMT, and is of valuable for developing biomarkers to predict prognosis and targeted therapies in breast cancers in the future. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P1-07-11.