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The paradigm of one drug against multiple targets, known as unimolecular polypharmacology, offers the potential to improve efficacy while overcoming some adverse events associated with the treatment. This approach is best exemplified by targeting two or three class B1 G protein-coupled receptors, namely, glucagon-like peptide-1 receptor (GLP-1R), glucagon receptor (GCGR) and glucose-dependent insulinotropic polypeptide receptor for treatment of type 2 diabetes and obesity. Some of the dual and triple agonists have already shown initial successes in clinical trials, although the molecular mechanisms underlying their multiplexed pharmacology remain elusive. In this study we employed structure-based site-directed mutagenesis together with pharmacological assays to compare agonist efficacy across two key signaling pathways, cAMP accumulation and ERK1/2 phosphorylation (pERK1/2). Three dual agonists (peptide 15, MEDI0382 and SAR425899) and one triple agonist (peptide 20) were evaluated at GLP-1R and GCGR, relative to the native peptidic ligands (GLP-1 and glucagon). Our results reveal the existence of residue networks crucial for unimolecular agonist-mediated receptor activation and their distinct signaling patterns, which might be useful to the rational design of biased drug leads.

Nonalcoholic steatohepatitis (NASH), as a severe form of nonalcoholic fatty liver disease (NAFLD), is characterized by liver steatosis, inflammation, hepatocellular injury and different degrees of fibrosis. The pathogenesis of NASH is complex and multifactorial, obesity and type 2 diabetes mellitus (T2DM) have been implicated as major risk factors. Glucagon-like peptide-1 receptor (GLP-1R) is one of the most successful drug targets of T2DM and obesity, and its peptidic ligands have been proposed as potential therapeutic agents for NASH. In this article we provide an overview of the pathophysiology and management of NASH, with a special focus on the pharmacological effects and possible mechanisms of GLP-1 mimetics in treating NAFLD/NASH, including dual and triple agonists at GLP-1R, glucose-dependent insulinotropic polypeptide receptor or glucagon receptor.

Inflammatory bowel disease (IBD) is a global health burden whose existing treatment is largely dependent on anti-inflammatory agents. Despite showing some therapeutic actions, their clinical efficacy and adverse events are unacceptable. Resolution as an active and orchestrated phase of inflammation involves improper inflammatory response with three key triggers, specialized pro-resolving mediators (SPMs), neutrophils and phagocyte efferocytosis. The formyl peptide receptor 2 (FPR2/ALX) is a human G protein-coupled receptor capable of binding SPMs and participates in the resolution process. This receptor has been implicated in several inflammatory diseases and its association with mouse model of IBD was established in some resolution-related studies. Here, we give an overview of three reported FPR2/ALX agonists highlighting their respective roles in pro-resolving strategies.

The growth of solid tumors depends on tumor vascularization and the endothelial cells (ECs) that line the lumen of blood vessels. ECs generate a large fraction of ATP through glycolysis, and elevation of their glycolytic activity is associated with angiogenic behavior in solid tumors. 6-Phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3 (PFKFB3) positively regulates glycolysis via fructose-2/6-bisphosphate, the product of its kinase activity. Partial inhibition of glycolysis in tumor ECs by targeting PFKFB3 normalizes the otherwise abnormal tumor vessels, thereby reducing metastasis and improving the outcome of chemotherapy. Although a limited number of tool compounds exist, orally available PFKFB3 inhibitors are unavailable. In this study we conducted a high-throughput screening campaign against the kinase activity of PFKFB3, involving 250,240 chemical compounds. A total of 507 initial hits showing50% inhibition at 20 µM were identified, 66 of them plus 1 analog from a similarity search consistently displayed low IC

Single-site laparoscopic percutaneous extraperitoneal ligation (SLPEL) for pediatric inguinal hernia gained popularity all over the world. However, complications associated with extraperitoneal knotting were not rare in the classical SLPEL(C-SLPEL) procedure. In order to overcome disadvantages, we herein developed the modified SLPEL (M-SLPEL) procedure, intact circuit ligation of the peritoneum around the internal ring using a homemade hernia needle with a single abdominal wall centesis. To evaluated the effectiveness of the M-SLPEL procedure to decrease adverse events associated with ligation knotting, a comparative study was carried out. A total of 3219 patients from multiple centers were divided into two groups according to the operative procedures: M-SLPEL group and C-SLPEL group. All patients were followed up. Data describing the clinical characteristics, operative time, postoperative hospital stay, and complications was collected and retrospectively analyzed. With equivalent operative time, postoperative hospital stay, there was statistically significant difference between two groups in terms of the overall complications incidence (2.6% in C-SLPEL Vs 0.11% in M-SLPEL, P=0.03), including pain in inguinal area, knot foreign body reaction, palpable knot, recurrence. Together, these findings suggest that the M-SLPEL procedure is an effective and safe approach, with unique advantage in reducing adverse events in the inguinal region.

Tight reservoirs in China’s Bohai Bay Basin has abundant oil and gas resources. Depletion drive can only achieve an oil recovery lower than 10% OOIP, and water flooding is not suitable for this kind of reservoir. Hydrocarbon gas flooding is considered as one of the most promising technologies for developing tight reservoirs. In this paper, the influences of hydrocarbon gas injected on oil properties at reservoir condition, the minimum miscibility pressure and the enhanced oil recovery performance of hydrocarbon gas flooding are investigated through PVT test experiment, slim tube experiment, core flooding experiment and reservoir numerical simulation method, the hydrocarbon gas injection pressure is predicted and a simple economic evaluation is conducted, using tight reservoir X Block in Dagang Oilfield as the research object. The experimental results indicate that hydrocarbon gas can increase the expansion coefficient of oil and decrease density and viscosity of oil. The minimum miscibility pressure (MMP) between oil from X Block and hydrocarbon gas from Y gas reservoir is about 45 MPa. High displacement pressure and low displacement rate are conducive to delaying gas breakthrough and improving sweep efficiency and oil recovery. Reservoir numerical simulation results demonstrate that gravity assisted hydrocarbon gas flooding can obtain the best development performance, with a cumulative oil production of 8.42 × 104 t and a final oil recovery of 33.48%, which is 21.96% points higher than that of depletion drive. In order to maintain the formation pressure to be above MMP, the hydrocarbon gas injection pressure (well-head pressure) should be higher than 37 MPa, thus hydrocarbon gas compressor, injection pipeline and wellhead and safety control system of 50 MPa grade are prerequisite for the hydrocarbon gas miscible flooding project considering formation pollution and other unfavorable factors.

Chemical genomics has been applied extensively to evaluate small molecules that modulate biological processes in Saccharomyces cerevisiae. Here, we use yeast as a surrogate system for studying compounds that are active against metazoan targets. Large-scale chemical-genetic profiling of thousands of synthetic and natural compounds from the Chinese National Compound Library identified those with high-confidence bioprocess target predictions. To discover compounds that have the potential to function like therapeutic agents with known targets, we also analyzed a reference library of approved drugs. Previously uncharacterized compounds with chemical-genetic profiles resembling existing drugs that modulate autophagy and Wnt/β-catenin signal transduction were further examined in mammalian cells, and new modulators with specific modes of action were validated. This analysis exploits yeast as a general platform for predicting compound bioactivity in mammalian cells.

For lots of scientific questions about lunar physics deep inside the Moon, in-situ observation on lunar physical libration is one of the most potential ways. In this paper, we propose a brand new optical telescope functioned with simultaneously observing multiple (here there are three) fields of view (FOVs) for in-situ observation of lunar physical libration. The telescope can be placed at any place with any attitude on the Moon and do not require manned install, control or operation. It passively, continuously and simultaneously observe stars in three FOVs along with rotation of the Moon. Libration is to be measured and studied from celestial motion of the directions of three FOVs from image processing. The concept and design of this telescope are firstly introduced in this paper. The principle and feasibility of the method of in-situ observation are also demonstrated. From simulation, precision of the determined lunar physical libration is expected to be several milliarcsecs, about two orders of magnitude better than the current precision of libration by lunar laser ranging observation. Libration data with milliarcsec precision level can play a valuable role in the study of the physics and dynamics of the interior of the Moon. This telescope can also be applied to observe the rotation of other terrestrial planets like Mars.

Chemical genomics has been applied extensively to evaluate small molecules that modulate biological processes in Saccharomyces cerevisiae. Here, we use yeast as a surrogate system for studying compounds that are active against metazoan targets. Large-scale chemical-genetic profiling of thousands of synthetic and natural compounds from the Chinese National Compound Library identified those with high-confidence bioprocess target predictions. To discover compounds that have the potential to function like therapeutic agents with known targets, we also analyzed a reference library of approved drugs. Previously uncharacterized compounds with chemical-genetic profiles resembling existing drugs that modulate autophagy and Wnt/β-catenin signal transduction were further examined in mammalian cells, and new modulators with specific modes of action were validated. This analysis exploits yeast as a general platform for predicting compound bioactivity in mammalian cells.

A new kind of 3-d.o.f. vibration platform is introduced, which may be used in active vibration control, presion manufacturing, and other precision positioning fields. The platform is mainly comprised of four parts: the top board of the platform, flexure hinges, amplification mechanisms and gaint magnetostrictive actuators (GMAs). Among them, finite element analysis is taken on flexure hinges; the constitutive model of GMA is described. Eventually, the dynamic model of the system is established. According to the model, a simulation system based on SIMULINK is carried out. The simulation results verify the model, and may serve for the active control analysis of the platform system.

The deformations of the 600mm aperture interferometer mirrors induced by gravity and supporting forces must be controlled strictly to ensure the accuracy of the large aperture interferometer to achieve 63nm. The mirror deformations induced by two types of forces and four axial distribution positions are analyzed respectively by finite element method. And the deformed interference wavefront are simulated by synthesizing deformations of reference flat and test flat mirrors. The maximum deformed interference wavefront formed by the cosine wave force at the middle of the mirrors and the minimum formed by the square wave force at the periphery of the mirrors. The peak to valley value varies 30nm and root mean square value varies 2.8nm between them. The measurement accuracy of large aperture interferometers can be improved by adjusting the force distributions and supporting positions of the mirrors according to the analysis.

A 30-m TeraHertz (THz) radio telescope is proposed to operate at 200μm with an active primary surface. This paper presents sensitivity analysis of active surface panel positioning errors with optical performance in terms of the Strehl ratio. Based on Ruze’s surface error theory and using a Monte Carlo simulation, the effects of six rigid panel positioning errors, such as piston, tip, tilt, radial, azimuthal and twist displacements, were directly derived. The optical performance of the telescope was then evaluated using the standard Strehl ratio. We graphically illustrated the various panel error effects by presenting simulations of complete ensembles of full reflector surface errors for the six different rigid panel positioning errors. Study of the panel error sensitivity analysis revealed that the piston error and tilt/tip errors are dominant while the other rigid errors are much less important. Furthermore, as indicated by the results, we conceived of an alternative Master-Slave Concept-based (MSC-based) active surface by implementating a special Series-Parallel Concept-based (SPC-based) hexapod as the active panel support mechanism. A new 30-m active reflector based on the two concepts was demonstrated to achieve correction for all the six rigid panel positioning errors in an economically feasible way.

This paper presents a finite element method (FEM) for the kinematic solution of parallel manipulators (PMs), and this approach is applied to analyze the kinematics of a parallel hip joint manipulator (PHJM). The analysis and simulation results indicate that FEM can get accurate results of the kinematics of the PHJM, and the solution process shows that using FEM can solve nonlinear and linear kinematic problems in the same mathematical framework, which provides a theory base for establishing integrated model among different parameter models of the PHJM.

Unified modeling for the kinematics analysis of a parallel hip joint manipulator (PHJM) is proposed, and structural parameters of the PHJM are optimized based on the unified model for obtaining low-velocity driving performance. Based on the finite element theory, a unified model for kinematics analysis is established, and the Monte Carlo method is subsequently proposed to solve the workspace for the PHJM. To optimize the workspace, a 6 surface-14 point (6 S-14 P) method is proposed to judge whether the workspace includes the task space. The structural parameters are further optimized to obtain low-velocity driving performance, and the motion performances of the PHJM with the optimal parameter are numerically simulated. The velocity simulation results demonstrate that the maximum relative velocity of the PHJM with the optimal parameter decreases by 23.2%. The unified kinematics analysis and low-velocity driving optimization effectively improve the performance for the PHJM and enrich the optimization theory for parallel manipulators with high velocities and given tasks.

The Large sky Area Multi-Object Spectroscopic Telescope (LAMOST) General Survey is a spectroscopic survey that will eventually cover approximately half of the celestial sphere and collect 10 million spectra of stars, galaxies and QSOs. Objects both in the pilot survey and the first year general survey are included in the LAMOST First Data Release (DR1). The pilot survey started in October 2011 and ended in June 2012, and the data have been released to the public as the LAMOST Pilot Data Release in August 2012. The general survey started in September 2012, and completed its first year of operation in June 2013. The LAMOST DR1 includes a total of 1202 plates containing 2,955,336 spectra, of which 1,790,879 spectra have observed signal-to-noise S/N >10. All data with S/N>2 are formally released as LAMOST DR1 under the LAMOST data policy. This data release contains a total of 2,204,696 spectra, of which 1,944,329 are stellar spectra, 12,082 are galaxy spectra and 5,017 are quasars. The DR1 includes not only spectra, but also three stellar catalogues with measured parameters: AFGK-type stars with high quality spectra (1,061,918 entries), A-type stars (100,073 entries), and M stars (121,522 entries). This paper introduces the survey design, the observational and instrumental limitations, data reduction and analysis, and some caveats. Description of the FITS structure of spectral files and parameter catalogues is also provided., 39 pages, 13 figures

A radio telescope of 50m in diameter, basically, for pulsar observation, is to work at multi-wave bands among which the shortest wavelength is 13 cm. Proposed is a fully steerable exposed truss structure scheme of the telescope. The design is essentially a wheel-on-track style radio telescope with 6 rollers in three bodies for azimuth drive and support, while two sets of gear wheel for elevation drive. The main reflector is a mesh with crimped stainless steel wire spanned on a ``bowl-like'' back-up truss structure which is supported by 6 points on its bottom. After discussion of structural design and related dead-load analysis, wind and thermal disturbances are estimated. Particularly, response spectrum seismic hazard is performed with response spectra analysis. The results confirm that the 50m radio telescope can meet the observational requirements and survive seismic hazard of acceleration of 0.1 gravity with a light and cost-effective structure.

RNA interference (RNAi) is triggered by the presence of a double-stranded RNA (dsRNA), and results in the silencing of homologous gene expression through the specific degradation of an mRNA containing the same sequence. dsRNA-mediated RNAi can be used in a wide variety of eucaryotes to induce the sequence-specific inhibition of gene expression. Synthetic 21-23 nucleotide (nt) small interfering RNA (siRNA) with 2 nt 3' overhangs was recently found to mediate efficient sequence-specific mRNA degradation in mammalian cells. Here, we studied the effects of synthetic siRNA duplexes targeted to SARS coronavirus structural proteins E, M, and N in a cell culture system. Among total 26 siRNA duplexes, we obtained 3 siRNA duplexes which could sequence-specifically reduce target genes expression over 80% at the concentration of 60 nM in Vero E6 cells. The downregulation effect was in correlation with the concentrations of the siRNA duplexes in a range of 0 approximately 60 nM. Our results also showed that many inactive siRNA duplexes may be brought to life simply by unpairing the 5'end of the antisense strands. Results suggest that siRNA is capable of inhibiting SARS coronavirus genes expression and thus may be a new therapeutic strategy for treatment of SARS.

To compare the the similarities and differences during the surrounding operation of endovascular repair (EVAR) and open surgical repair (OSR) for abdominal aortic aneurysm.112 patients with abdominal aortic aneurysms (AAA) were selected from 2004 to 2009: among them, 66 patients were treated with EVAR, 46 patients with OSR. Data of two groups were collected and analyzed during surrounding operation.Compared to OSR group, the mean blood lost, blood transfusion and intra-operative fluid in EVAR group were significantly less than OSR group (P0.05). The mean time of operation, observation period in ICU and being in hospital in EVAR group were shorter than OSR group (P0.05). But the cost of hospitalization in EVAR was far higher than that of OSR group (P0.05). In short term postoperative complications the OSR group was higher than the EVAR (P0.05), however, there was no statistically significant difference in death rate of the two groups during surrounding operation (P0.05).EVAR has the advantages of mild trauma, less blood loss, quicker recovery after operation, and less disturbance to internal environment. Especially, it is suitable for the patients who can not undergo open surgery repair, but its cost is still higher.

To analyze the death-related risk factors of type B aortic dissection treated medically during the acute phase (symptoms presenting within 14 d), and to determine the predictors of surgical indications for acute type B aortic dissection.Clinical data of 42 patients with acute type B aortic dissection admitted from January 2007 to May 2009 was retrospectively reviewed. There were 33 male and 9 female with a mean age of (50 +/- 12) years old. Therapy included analgesia, controlled hypotension and beta-receptor blocker, the mortality in acute phase was 33.3% (14/42). Univariate and multivariate logistic regression analyses were performed to identify the predictors of the death in acute phase.In univariate logistic regression analysis, the malperfusion of aortic branches (P = 0.018) and maximum aortic diameter (P = 0.002) were significant predictors of death. In the multivariate logistic regression model, the malperfusion of aortic branches (P = 0.041) and maximum aortic diameter (P = 0.005) were also considered as the significant death-related factors.Risk of death augmented significantly (P = 0.000) when the maximum aortic diameter over 40 mm.Malperfusion of aortic branches and the large maximum aortic diameter (40 mm) are the indications of surgery or endovascular therapy for acute type B aortic dissection.

To investigate the expression of proto-oncogene Wip1 in breast cancer tissue and its clinical significance.Through the uses of semi-RT-PCR, immunohistochemical technique and Western blot, the specimens from 70 patients of breast cancer and 20 normal controls were detected for Wip1 mRNA and protein expression. At the same time, the authors analyzed the relations between the expression of Wip1 in human breast cancer and different clinical pathologic parameters.RT-PCR: The values of gene expression of Wip1 mRNA in breast cancer tissue, pericancerous tissue and normal breast tissue were 0.715 +/- 0.087, 0.175 +/- 0.021 and 0.154 +/- 0.022 respectively. Thus the value of gene expression in breast cancer tissue was significantly higher than that in pericancerous tissue or normal breast tissue (P0.01). Immunohistochemistry: The high expression rates of Wip1 protein in breast cancer tissue, pericancerous tissue and normal breast tissue were 62.9% (44/70), 2.9% (2/70) and 0 (0/20) respectively and there was a significant difference among these three different tissues (P0.01). Western blot: The relative contents of Wip1 protein in breast cancer tissue, pericancerous tissue and normal breast tissue were 0.688 +/- 0.151, 0.251 +/- 0.043 and 0.234 +/- 0.044 respectively. The relative content of Wip1 protein in breast cancer tissue was significantly higher than that in pericancerous tissue or normal breast tissue (P0.01). The high expression of Wip1 protein was negatively correlated with the expression of p53, but it had nothing to do with tumor size, age, tumor staging, axillary lymph node metastasis and expressions of ER and PR.The high expression of Wip1 mRNA and its protein in breast cancer tissue may promote the growth of breast cancer. Wip1 may become a new target for therapy of breast cancer.

To investigate the effects of the different treatments of deep venous thrombosis (DVT) of lower extremities on the incidence of the pulmonary embolism (PE).201 patients (97 males and 104 females, mean age 60.4 years ranged from 24 to 83) from August 2002 to June 2008 with DVT were retrospectively reviewed and divided into 3 groups based on different treatment, including anticoagulants plus thrombolytics alone (group 1), thrombectomy plus anticoagulants plus thrombolytics (group 2) and anticoagulants plus thrombolytics after delivery of inferior vena cava (IVC) filter (group 3) respectively. One hundred and seventy-four cases had left lower limb DVT, 24 cases had right lower limb DVT and 3 cases had both sides of lower limb DVT. Different incidence of PE in different period (7-14 d in hospital and follow-up after discharge) were calculated. Effects of the three different treatment methods of DVT on the incidence of PE were studied.For in-patients, the prevalence of symptomatic PE was 2.8% (3/107) in the group of receiving anticoagulants plus thrombolytics alone, but in the other two groups, no symptomatic PE happened. There was no significant difference in incidence of symptomatic PE among the 3 groups (P=0.425). For patients discharged, after 6 to 72-month follow-up (mean 24-month), we found that no PE happened in group 1 and group 2, while in group 3, the incidence of PE was 2.4% (1/42). There was also no significant difference (P=0.656) among 3 groups.There is no significant difference in relation to the incidence of PE in these 3 groups. Therefore vena cava filter implantation should be restricted to optimal indication.

To construct RNA interference (RNAi) vector of mammalian target of rapamycin (mTOR) and study the effect on the proliferation of vascular smooth muscle cell (VSMC) and the intimal hyperplasia (IH).The sequence of short hairpin RNA (shRNA) targeting mTOR was designed and synthesized by chemical method and inserted into a retroviral vector pLXIN, then the vector was packaged in PT67 cells. The efficiency of inhibition was verified by Northern blot and Western blot after transfection to VSMC. The changes of p70s 6k and 4E-BP1 were also determined. The proliferation activity of VSMC was determined by flowcytometry and MTT. Autogenous vein graft model were established in 54 rats. Three groups were divided, including gene therapy group, control group and vein graft group. The grafted veins were harvested 7 days, 14 days and 28 days after transplanting respectively. The expression of mTOR was determined by immunohistochemistry stain and Western blot. IH was also observed. The apoptotic VSMC was determined by TUNEL.The shRNA fragments was inserted into pLXIN vector. The shRNA vector was successfully constructed. Additionally, the vector targeting mTOR gene could efficiently decrease the mRNA and protein expression of mTOR and p70s 6k in VSMC, while the expression of 4E-BP1 increased significantly. The cell cycle of VSMC was stunned in phase G(0)/G(1). The protein expression of mTOR in vein graft was inhibited by transfection of pLXIN-shRNA targeting mTOR (P0.01) and the IH was also inhibited (P0.01), but the apoptosis of VSMC increased significantly (P0.01).The mTOR RNAi retroviral vector has been constructed successfully, which can significantly inhibit the proliferation of VSMC and the IH, and promote apoptosis after vein grafting.

To investigate the effect of inhibition of nuclear factor kappa B on multiple organ injury following ruptured abdominal aortic aneurysm.Forty-five Wistar rats underwent catheterization to observe the intestinal microcirculation blood flow, and were randomly divided into 3 equal groups. Rats of the ruptured abdominal aortic aneurysm (RAAA) group underwent laparotomy and extraction of blood to cause hemorrhage shock for 1 h (hemorrhagic shock phase), by the end of this phase normal saline at the dose of 50 ml/kg was injected intravenously, after that the abdominal aorta and bilateral common iliac arteries were blocked with artery clamps for 45 min so as to cause lower torso ischemia, and then the extracted blood was reperfused. The lungs, small intestine were taken out to undergo histological examination, and examination of lung polymorphonuclear neutrophilic leukocyte (PMN) sequestration, lung wet tissues/dry (W/D) tissues ratio, and myeloperoxidase (MPO) activity. The rats of pyrrolidine dithiocarbamate (PDTC) group were perfused with PDTC, a specific inhibitor of nuclear factor kappa B (NF-kappaB), by the end of the hemorrhagic shock phase. And the rats of the sham operation group were perfused of normal saline. RT-PCR was used to detect the mRNA expression of NF-kappaB p65 and intercellular adhesion molecule (ICAM). Western blotting was used to detect the protein expression of NF-kappaB p65 and ICAM-1. Immunohistochemistry was used to detect the expression of NF-kappaB p65 and ICAM-1 in the lung and small intestine tissues.Histological examination showed that severe damage could be found in the lung and small intestine of the RAAA group, and damages were significantly mild in the PDTC group. Lung PMN sequestration, W/D ratio, MPO activity were significantly increased in the RAAA group and these changes were relatively mild in the PDTC group (all P0.01). The intestinal microcirculation blood flow was 0.25 +/- 0.04 mlxmin(-1)xg(-1) in the RAAA group, significantly less than that of the sham operation group (0.71 +/- 0.11 mlxmin(-1)xg(-1), P0.01), and was 0.64 +/- 0.06 mlxmin(-1)xg(-1) in the PDTC group, significantly higher than that of the RAAA group (P0.01). The mRNA expression of NF-kappaB p65 in the lung of the RAAA group was 0.68 +/- 0.22, significantly higher than that of the sham operation group (0.11 +/- 0.02, P0.01) and that of the PDTC group (0.23 +/- 0.07, P0.01). The mRNA expression of NF-kappaB p65 in the intestine of the RAAA group was 0.48 +/- 0.10, significantly higher than that of the sham operation group (0.20 +/- 0.05, P0.01) and that of the PDTC group (0.27 +/- 0.06, P0.01). The mRNA expression of ICAM-1 in the lung of the RAAA group was 0.92 +/- 0.31, significantly higher than that of the sham operation group (0.07 +/- 0.02, P0.01) and that of the PDTC group (0.21 +/- 0.04, P0.01). The mRNA expression of ICAM-1 in the intestine of the RAAA group was 0.74 +/- 0.15, significantly higher than that of the sham operation group (0.14 +/- 0.05, P0.01) and that of the PDTC group (0.25 +/- 0.08, P0.01). The protein expression of NF-kappaB p65 in the lung of the RAAA group was 1.04 +/- 0.26, significantly higher than that of the PDTC group (0.52 +/- 0.13, P0.01). The protein expression of NF-kappaB p65 in the intestine of the RAAA group was 1.20 +/- 0.30, significantly higher than that of the PDTC group (0.64 +/- 0.21, P0.01). The protein expression of ICAM-1 in the lung of the RAAA group was 0.40 +/- 0.12, significantly higher than that of the PDTC group (0.18 +/- 0.06, P0.01). The protein expression of ICAM-1 in the intestine of the RAAA group was 0.46 +/- 0.15, significantly higher than that of the PDTC group (0.22 +/- 0.05, P0.01). Immunohistochemistry showed that NF-kappaB p65 and ICAM-1 positive cells were widely distributed in the lungs and intestine of the RAAA group and were rarely distributed in the sham operation group.PDTC attenuates the multi-organ injury by inhibiting the expression of NF-kappaB p65, thus reducing the mRNA and protein expression of its downstream gene ICAM-1 gene.

ObjectivesAcute mesenteric venous thrombosis (AMVT) was first reported by Fagge and was recognised as a distinct clinical entity by Warreen in 1935. However, its pathogenesis is still unclear. Elevated plasma levels of homocysteine (Hcy) are associated with an increased risk of deep vein thrombosis. This case-control study examines the potential association among hyperhomocysteinaemia (hyper-Hcy), low serum folate and vitamin B12 levels and the common C677T mutation of the MTHFR gene in patients with AMVT.Materials and methodsSixty-three patients with AMVT and 75 sex- and age-matched healthy controls were recruited, and their plasma Hcy, folate and vitamin B12 levels were measured by high performance liquid chromatography (HPLC) and immunological assays. The polymorphism of MTHFR C677T was detected by PCR-RFLP.ResultsThe mean plasma Hcy levels were significantly higher in patients with AVMT compared with controls (23.5 standard deviation (S.D.) 8.8 vs. 12.6±6.6μmoll−1, P0.05).ConclusionsHyper-Hcy and low serum folate levels were associated with an increased risk of AMVT. The homozygous (TT) genotype of MTHFR gene mutation may be a crucial hereditary risk factor in the development of AMVT for a Chinese population.