Characteristics of amino acid metabolism in myeloid-derived suppressor cells in septic mice / 北京大学学报(医学版)

OBJECTIVE@#To explore the amino acid metabolomics characteristics of myeloid-derived suppressor cells (MDSCs) in mice with sepsis induced by the cecal ligation and puncture (CLP).@*METHODS@#The sepsis mouse model was prepared by CLP, and the mice were randomly divided into a sham operation group (sham group, n = 10) and a CLP model group (n = 10). On the 7th day after the operation, 5 mice were randomly selected from the surviving mice in each group, and the bone marrow MDSCs of the mice were isolated. Bone marrow MDSCs were separated to measure the oxygen consumption rate (OCR) by using Agilent Seahorse XF technology and to detect the contents of intracellular amino acids and oligopeptides through ultra-performance liquid chromatography/tandem mass spectrometry (UPLC-MS/MS) technology. Different metabolites and potential biomarkers were analyzed by univariate statistical analysis and multivariate statistical analysis. The major metabolic pathways were enriched using the small molecular pathway database (SMPDB).@*RESULTS@#The proportion of MDSCs in the bone marrow of CLP group mice (75.53% ± 6.02%) was significantly greater than that of the sham group (43.15%± 7.42%, t = 7.582, P < 0.001), and the basal respiratory rate [(50.03±1.20) pmol/min], maximum respiration rate [(78.07±2.57) pmol/min] and adenosine triphosphate (ATP) production [(25.30±1.21) pmol/min] of MDSCs in the bone marrow of CLP group mice were significantly greater than the basal respiration rate [(34.53±0.96) pmol/min, (t = 17.41, P < 0.001)], maximum respiration rate [(42.57±1.87) pmol/min, (t = 19.33, P < 0.001)], and ATP production [(12.63±0.96) pmol/min, (t = 14.18, P < 0.001)] of sham group. Leucine, threonine, glycine, etc. were potential biomarkers of septic MDSCs (all P < 0.05). The increased amino acids were mainly enriched in metabolic pathways, such as malate-aspartate shuttle, ammonia recovery, alanine metabolism, glutathione metabolism, phenylalanine and tyrosine metabolism, urea cycle, glycine and serine metabolism, β-alanine metabolism, glutamate metabolism, arginine and proline metabolism.@*CONCLUSION@#The enhanced mitochondrial oxidative phosphorylation, malate-aspartate shuttle and alanine metabolism in MDSCs of CLP mice may provide raw materials for mitochondrial aerobic respiration, thereby promoting the immunosuppressive function of MDSCs. Blocking the above metabolic pathways may reduce the risk of secondary infection in sepsis and improve the prognosis.

Protective Effect and Mechanism of Buzhong Yiqitang on Concanavalin A-induced Acute Liver Failure in Mice / 中国实验方剂学杂志

<b>Objective::To explore the hepatoprotective effect and the mechanism of Buzhong Yiqitang (BZYQT) on mice with acute liver failure induced by Concanavalin A (ConA). <b>Method::A total of 80 mice were randomly divided into normal group, model group, Cyclosporine A (CsA) group, BZYQT low and high dose group (10.5, 21 g·kg^-1), 16 mice per group. All the mice except for normal group were injected intravenously with 15 mg·kg^-1 ConA. The treatment group mice were orally administrated with BZYQT, or intravenously administrated with 50 mg·kg^-1 CsA 30 min post ConA injection, normal and model group mice were orally administrated with ddH₂O at the same time. Blood, liver and spleen were collected 3 and 10 h post ConA injection. Cytokine levels of tumor necrosis factor alpha (TNF-<italic>α</italic>), interleukin-6 (IL-6), interleukin-12 (IL-12), interferon-gamma (IFN-<italic>γ</italic>) and monocyte chemoattractant protein-1 (MCP-1) in the serum were detected with cytometric bead array. The alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels in the serum were analyzed with fully automatic biochemical analyzer. The pathological changes of liver tissues were observed by hematoxylin-eosin (HE) staining. The activation of splenic CD4⁺ T lymphocytes was analyzed by flow cytometry. The expression and phosphorylation of extracellular regulated protein kinase 1/2(ERK1/2) and p38 mitogen-activated protein kinase (p38 MAPK) was analyzed by Western blot. <b>Result::Compared with normal group, model group showed higher levels of ALT and AST in the serum (<italic>P</italic><0.01), obvious pathological damage of liver tissue, higher levels of TNF-<italic>α</italic>, IL-6, IL-12, IFN-<italic>γ</italic> and MCP-1 in the serum (<italic>P</italic><0.01), higher expression of IL-2, IFN-<italic>γ</italic> and IL-4 CD4⁺ T lymphocytes in the spleen (<italic>P</italic><0.01), and elevated levels of phosphorylation of ERK1/2 and p38 MAPK (<italic>P</italic><0.01). Compared with the model group, BZYQT high dose group showed decreased levels of ALT and AST (<italic>P</italic>< 0.05, <italic>P</italic><0.01), reduced liver injury, decreased levels of TNF-<italic>α</italic>, IL-6, IL-12, IFN-<italic>γ</italic> and MCP-1 in the serum (<italic>P</italic><0.05, <italic>P</italic><0.01), reduced level of IL-2 and IFN-<italic>γ</italic> CD4⁺ T lymphocytes in the spleen (<italic>P</italic><0.05, <italic>P</italic><0.01), and reduced levels of phosphorylation of ERK1/2 and p38 MAPK (<italic>P</italic><0.05, <italic>P</italic><0.01). <b>Conclusion::BZYQT has a protective effect on mice with acute liver failure induced by ConA. The mechanism may be through inhibiting ERK1/2 and p38 MAPK signaling pathways, thereby reducing T lymphocyte activation and inflammatory cytokine secretion.

Xijiao Dihuang Decoction () and Rehmannia glutinosa Libosch. protect mice against lipopolysaccharide and tumor necrosis factor alpha-induced acute liver failure / 中国结合医学杂志

OBJECTIVE@#To investigate the hepatoprotective effect of Xijiao Dihuang Decoction (, XJDHD) on lipopolysaccharide (LPS)- and tumor necrosis factor alpha (TNF-α)-induced acute liver failure (ALF) as well as the underlying mechanism of action, and to clarify the key herbs and components of XJDHD.@*METHODS@#LPS/D-galactosamine (D-GalN) or TNF-α/D-GalN were intraperitoneally injected into C57BL/6J mice to induce ALF. Simultaneously, XJDHD or its individual herbs and components were orally administered. Survival rates, transaminase levels in serum, and hepatic histology were examined to evaluate the effects of XJDHD. The terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay and real-time polymerase chain reaction were additionally performed to expound the mechanism underlying the anti-apoptotic activity of XJDHD.@*RESULTS@#Oral administration of XJDHD protected mice from lethal liver failure induced by LPS and TNF-α, with notable amelioration of liver injury in histology and a significant decrease in transaminase levels in serum. XJDHD significantly inhibited apoptosis of hepatocytes and enhanced expression of the antiapoptosis genes, c-Flip, Iap1, Gadd45b and A20. In addition, Rehmannia glutinosa Libosch. was identified as the key herb of XJDHD and galactose as the effective component of Rehmannia glutinosa Libosch. that protects against ALF.@*CONCLUSIONS@#XJDHD inhibits TNF-α-induced apoptosis of hepatocytes by promoting the expression of nuclear factor κ B-regulated anti-apoptotic genes. Rehmannia glutinosa Libosch. is the effective herb of XJDHD and galactose is an active component in this protection.

A second protein marker of caveolae: caveolin-2 / 中国医学科学杂志(英文版)

Caveolin-2, a protein about 20 kD, is a major component of the inner surface of caveolae, small invaginations of the plasma membrane. Similar with caveolin-1 and caveolin-3, it serves as a protein marker of caveolae. Caveolin-1 and -2 are located next to each other at 7q31.1 on human chromosome, the proteins encoded are co-localized and form a stable hetero-oligomeric complex, distributing similarly in tissue and cultured cells. Caveolin-3 is located on different chromosomes but confirmed to interact with caveolin-2. Caveolin-2 is similar to caveolin-1 in many respects but differs from the latter in functional domains, especially in G-protein binding domain and caveolin scaffolding domain. The mRNAs of both caveolin-1 and caveolin-2 are most abundantly expressed in white adipose tissue and are induced during differentiation of 3T3-L1 cells to adipocytes. Caveolin-2-deficient mice demonstrate clear pulmonary defects, with little or no change in caveolin-1 expression and caveolae formation, suggesting that caveolin-2 plays a selective role in lung functions. Caveolin-2 is also involved in lipid metabolism and human cancers.

Research advances in Sirt1 gene / 中国医学科学院学报

As the most homologic homologue of silent information regulator 2 of yeast, Sirt1 gene is extensively expressed in mature tissues, and is rich in early embryo and reproductive cells. It is involved in the regulation of gene transcription, energy metabolism and cell aging. It promotes fat mobilization in adipocytes and glucose production in liver and regulates insulin secretion in islet beta cell. Furthermore, Sirt1 gene is an essential endogenous apoptosis inhibitor. In future, it may be used as new drug targets or applied in other disease management modalities.

Current situation researching of methylation in tumor / 中国医学科学院学报

The disorders of DNA and histone methylation have a close relationship with the development and progression of tumors. Epigenetic regulation is critical in maintaining the stability and integrity of the expression profiles of different cell types by modifying DNA methylation and histone methylation. However, the abnormal changes of methylation often result in the development and progression of tumors. This review summarized the theory of tumor genomic and histone methylation, detection methods of methylation and their applications, and the clinical application of methylation as biological markers and drug targets.

Endoscopic radial artery harvest for coronary artery bypass grafting: applications and histologic assessment / 中华外科杂志

<p><b>OBJECTIVE</b>To observe the influence of endoscopic radial artery harvesting techniques on the prevalence of complications after coronary artery bypass grafting, and to assess the potential trauma to the radial artery through the histological changes.</p><p><b>METHODS</b>From August 2003 to June 2008, 87 patients undergoing CABG had radial artery harvested by endoscopic harvesting system. About 4 mm proximal and distal radial artery end segment of 10 patients undergoing endoscopic and conventional harvesting were examined with light and electro-microscope.</p><p><b>RESULTS</b>The endoscopic harvest time was 42 to 98 min, with a mean of (57.6 +/- 17.3) min. The harvested conduit length was 15 to 20 cm, with a mean of (17.5 +/- 1.6) cm. Objective dorsal thenar numbness remained in 7 patients, none complained of forearm numbness at 3-month follow-up. The result of light and electro-microscope had no differences in the intima, media, or adventitia between endoscopically and conventionally obtained radial artery segments.</p><p><b>CONCLUSION</b>The use of endoscopic radial artery harvesting in coronary artery bypass grafting can be performed safely with infrequent complications. This method results in excellent patient satisfaction, particularly regarding the cosmetic outcome.</p>

Research on a scanner for tilting orthogonal double prisms.

The original scanner for tilting orthogonal double prisms is studied to test the tracking performance in intersatellite laser communications. With a reduction ratio of more than 100 times from the change rate of the angle of beam deviation to that of the tilting angle of each prism, the theoretical analysis performed, as well as the verification experiment, indicates that the scanner can meet the requirements of the scanning accuracy superior to 0.5 microrad with the scanning range greater than 500 microrad and can facilitate the mechanical structure design.

Clinical effect of off-pump epicardial microwave ablation of atrial fibrillation / 中华心血管病杂志

<p><b>OBJECTIVE</b>To apply the off-pump epicardial microwave ablation (MW) to treat the permanent atrial fibrillation (PAF) and evaluate the clinical effect.</p><p><b>METHODS</b>From April 2003 to April 2005, a total of 46 patients with PAF underwent off-pump epicardial MW, including the patients with mitral valve disease (28 cases), mitral and aortic valve disease (5 cases), coronary artery disease (8 cases) and lone PAF (5 cases). FLEX 10 probe was placed around four pulmonary orifices and the access orifice of the inferior vena cava to tricuspid annulus. The microwave application was set 65 W, 90 s and a continuous ablation line was finished encircling the pulmonary veins. Subsequently, patients underwent either off-pump coronary artery bypass graft or valve surgery on-pump. Mean left atrial diameter was (52.5 +/- 15.3) mm, LVEF 42% - 70% before operation. All patients were followed up in the discharge, 3, 6, 12 months after surgery by standard 12-lead ECG, 24 h Holter, UCG and clinical examination.</p><p><b>RESULTS</b>All procedures were completed successful on the off-pump cardiac surgery and 46 patients were converted sinus rhythm when the operations were performed. Mean ablation time was (37.7 +/- 7.8) min, without any related complications. At discharge, 3, 6 and 12 months follow-up, 63.0%, 66.7%, 72.7% and 80.6% of the patients kept sinus rhythm and left atrial diameter of < 50 mm.</p><p><b>CONCLUSIONS</b>Using MW, electrical isolation of the pulmonary veins can be achieved epicardially without cardiopulmonary bypass support. Off-pump epicardial microwave ablation is an efficient option with an excellent benefit/risk ratio for the treatment of PAF with or without other cardio-surgical disease.</p>

ABCD matrix for reflection and refraction of Gaussian beams at the surface of a parabola of revolution.

We report the formulation of an ABCD matrix for reflection and refraction of Gaussian light beams at the surface of a parabola of revolution that separate media of different refractive indices based on optical phase matching. The equations for the spot sizes and wave-front radii of the beams are also obtained by using theABCD matrix. With these matrices, we can more conveniently design and evaluate some special optical systems, including these kinds of elements.

Wave-front analysis method of circular aperture sampling for collimation testing.

A new type of wave-front analysis method for the collimation testing of laser beams is proposed. A concept of wave-front height is defined, and, on this basis, the wave-front analysis method of circular aperture sampling is introduced. The wave-front height of the tested noncollimated wave can be estimated from the distance between two identical fiducial diffraction planes of the sampled wave, and then the divergence is determined. The design is detailed, and the experiment is demonstrated. The principle and experiment results of the method are presented. Owing to the simplicity of the method and its low cost, it is a promising method for checking the collimation of a laser beam with a large divergence.

Jamin double-shearing interferometer for diffraction-limited wave-front test.

A Jamin double-shearing interferometer with three changeable schemes is proposed for the measurement of diffraction-limited laser wave front. A concept of detectable wave-front height is thus defined, and on this basis the limits of detectable wave-front height from the suggested schemes of interferometer are analyzed. The design is detailed, the simulation for wave aberrations is given, and the experiment is demonstrated. One of the major features of this interferometer is that it is capable of visually testing a diffraction-limited wave front immediately by the fringes with the matched accuracy and minimum detectable wave-front height on the order of 0.1lambda.

Optimal switching from recording to fixing for high diffraction from a LiNbO3:Ce:Cu photorefractive nonvolatile hologram.

An oscillatory characteristic of diffraction is observed as a result of strong beam coupling in a weakly oxidized LiNbO3:Ce:Cu crystal during the recording step in the production of nonvolatile photorefractive holograms. On this basis the optimal switching time from the recording step to the fixing step for high diffraction of a fixed hologram is studied. It is shown that switching after the first diffraction maximum leads theoretically to fixed diffraction of as much as 100% with a suitable switching time. Both an experimental demonstration and a theoretical simulation are presented.

Uniform theory of the Talbot effect with partially coherent light illumination.

A uniform formulation for the self-imaging of gratings with any kind of partially coherent illumination is developed in terms of the cross mutual spectral density of the partial coherence theory. The formulation includes the time diffractive intensity distribution and the averaged diffractive intensity distribution at self-imaging distances and can be applied to both continuous and temporal illuminations with any kind of spectra. It is found that the averaged intensity distribution is related only to the intensity spectrum of illumination. The continuous polychromatic illumination and the ultrashort laser pulses with or without frequency chirp are then studied by a numerical stimulation. It is shown that the ultrashort laser pulse and the continuous polychromatic illuminations have similar averaged self-image distributions. Thus the Talbot effect may help in the study of the temporal and spectral characteristics of ultrashort laser pulses. An experiment with an LED is given, as well.

Nearly-off-axis transmissivity of Solc birefringent filters.

The characteristics of light propagating near the axis of a birefringent filter are studied. A generalized formulation to describe the nearly-off-axis transmissivity of a Solc birefringent filter is derived. On this basis, the polarization conoscopic figures of Solc filters with different numbers of birefringent plates are simulated. Furthermore the variation of spectral transmission with angle of incidence is analyzed, and the field-of-view transmissivity and the spectral transmissivity averaged with respect to the spread of incident light are given. Primary experiments for verification are also demonstrated.