影响因子（impact factor）

影响因子是美国科学信息情报研究所（Institute？for？Scientific？Information,ISI）的期刊引证报告（JCR）中的一项数据。指的是某一期刊的文章在特定年份或时期被引用的频率，是衡量学术期刊影响力的一个重要指标。是用该期刊前2年发表论文在当年被引用的次数除以该期刊前2年发表论文的总数所得到的值。可以用来评估同一研究领域不同期刊的相对重要性。这是一个国际上通行的期刊评价指标。     

Guanine-nucleotide exchange factor H1 mediates lipopolysaccharide-induced interleukin 6 and tumor necrosis factor α expression in endothelial cells via activation of nuclear factor κB

The development of sepsis is multifactorial. Tissue damage and organ dysfunction may be caused not only by the microorganisms but also by the inflammatory mediators released in response to the infection. Interleukin 6 (IL-6) and tumor necrosis factor α (TNF-α) levels in serum are well known to be upregulated in humans with sepsis and can be used to predict outcome. Using human umbilical vein endothelial cells, we analyzed the role of guanine-nucleotide exchange factor H1 (GEF-H1) on lipopolysaccharide (LPS)-dependent IL-6/TNF-α expression in endothelial cells. Lipopolysaccharide upregulated IL-6 secretion in a dose- and time-dependent manner. Specific inactivation of RhoA/Cdc42/Rac1 by Clostridium difficile toxin B-10463 (TcdB-10463) reduced LPS-induced nuclear factor κB (NF-κB) p65 phosphorylation, IL-6/TNF-α messenger RNA (mRNA), and IL-6/TNF-α protein productions. Guanine-nucleotide exchange factor H1 protein expression remained on a high level among 1 to 9 h in response to LPS challenge of endothelial cells. Inhibition of GEF-H1 by specific small interfering RNA or inactivation of Rho-associated kinase with Y-27632 not only significantly reduced LPS-induced p38 and extracellular signal-regulated kinase 1/2 (ERK1/2) activities but also blocked LPS-induced NF-κB translocation and activation, thereby inhibiting IL-6/TNF-α mRNA and protein productions. Furthermore, SB203580 (p38 inhibitor) but not PD98059 (ERK1/2 inhibitor) blocked LPS-induced NF-κB activation; however, both inhibitors significantly suppressed IL-6/TNF-α mRNA and protein expression. In summary, our data suggest that LPS rapidly upregulates GEF-H1 expression. Activated Rho-associated kinase by GEF-H1 subsequently activates p38 and ERK1/2, thereby increasing IL-6/TNF-α expression in endothelial cells. P38 and ERK1/2 regulate LPS-induced IL-6/TNF-α expression through an NF-κB-dependent manner and an NF-κB-independent manner, respectively.     

Experimental research of curing sciatic nerve injury using nerve growth factor and basic fibroblast growth factor combination

AIM:To explore the co-effect of nerve growth factor (NGF)and basic fibroblast growth factor(bFGF) on the sciatic nerve after injury.METHODS:96 rats were divided into normal saline group,NGF group,bFGF group and NGF bFGF group.Sciatic nerve function index(SFI),nerve conduction velocity,regeneration axon counting were detected in the 3rd,6th,9th,12th week postinjury.RESULTS:The end of SFI,nerve conduction velocity,regeneration axon counting in NGF bFGF group were higher than those in the other groups.CONCLUSION:The co-effect of NGF and bFGF on sciatic nerve is better than the effect of NGF or bFGF alone.     

Serum uric acid--a cardiovasular risk factor?

Serum uric acid represents an important, independent risk factor for cardiovascular and renal disease in patients with hypertension, heart failure, or diabetes. Elevated serum uric acid is highly predictive of mortality in patients with heart failure or coronary artery disease and of cardiovascular events in patients with diabetes. Although the mechanism(s) by which uric acid may play a pathogenetic role in cardiovascular disease is unclear, hyperuricemia is associated with deleterious effects on endothelial dysfunction, oxidative metabolism, platelet adhesiveness, hemrheology, and aggregation. Whether a reduction in uric acid impacts CV and renal disease remains to be determined. However, recent findings from LIFE in hypertensive patients with LVH suggest the possibility that a treatment-induced decrease in serum uric acid may indeed attenuate cardiovascular risk. Almost one third of the treatment benefit of a losartan-based versus atenolol-based therapy on the composite endpoint (death, myocardial infarction, or stroke) may be ascribed to differences in achieved serum uric acid levels. Clearly, randomized clinical trials are needed to investigate further the long-term cardioprotective benefits issue of reducing hyperuricemia in hypertensive patients.     

High concentrations of circulating macrophage migration inhibitory factor in patients with severe blunt trauma: Is serum macrophage migration inhibitory factor concentration a valuable prognostic factor?

OBJECTIVE: To determine serum concentrations of macrophage migration inhibitory factor and other cytokines in severe blunt trauma patients in critical settings and to evaluate their association with patient outcome. DESIGN: Prospective, observational study. SETTING: Emergency department and surgical intensive care unit of a university hospital. PATIENTS: Fifty-four severe blunt trauma patients with systemic inflammatory response syndrome requiring intensive care, emergency surgical intervention, or both were enrolled in the study. Forty-four patients with minor injuries were the controls. INTERVENTIONS: Serum macrophage migration inhibitory factor concentrations were measured in the emergency department <4 hrs postinjury (day 1) and the surgical intensive care unit 24 hrs later (day 2). Blood samples for determination of tumor necrosis factor-alpha, interleukin-6, interleukin-8, and interleukin-10 were measured both in patients with severe blunt trauma and in controls. The Acute Physiology and Chronic Health Evaluation II, Injury Severity Score, Revised Trauma Score, and Trauma Revised Injury Severity Score were used for clinical evaluation of trauma severity. MEASUREMENTS AND MAIN RESULTS: Serum macrophage migration inhibitory factor concentrations were higher in severe blunt trauma patients than in controls; were significantly correlated with Acute Physiology and Chronic Health Evaluation II, Revised Trauma Score, and Trauma Revised Injury Severity Score scores in severe blunt trauma patients but not in controls; and were higher in nonsurvivors than in survivors. CONCLUSIONS: Our data suggest that the serum macrophage migration inhibitory factor concentration is higher in severe blunt trauma and that it reflects the severity of trauma. The serum macrophage migration inhibitory factor concentration might be a valuable predictor for the outcome of severe blunt trauma.     

Tissue factor assays as diagnostic tools for cancer? Correlation between urinary and monocyte tissue factor activity

Monocyte and urinary tissue factors (mTF and uTF) are both elevated in a number of pathologic conditions, including cancer. This study validates the best available uTF and mTF assays as diagnostic tools for cancer and examines if uTF levels reflect monocyte activation. Using kinetic chromogenic assays for uTF and mTF (measured on fresh resting cells [baseline], unstimulated cells, and lipopolysaccharide [LPS]-stimulated cells), we assessed TF levels in normal individuals, surgical controls, and patients with benign and malignant diseases. Each benign disease group was stratified as inflammatory or noninflammatory. Controls and benign noninflammatory results were indistinguishable. The malignant and inflammatory groups showed raised uTF levels over controls (p < 0.001). mTF levels differ similarly. For mTF and uTF assays, there was no significant difference between the malignant and inflammatory groups. The relative operating characteristic (ROC) curve plots sensitivity against false positive rate (1-specificity) for all possible cutoff values of a diagnostic test. Assay performance is assessed as the area under the curve (AUC). The ROC curve for the uTF assay displayed both sensitivity and specificity for cancer, the AUC being 0.83. Of the three mTF levels, LPS-stimulated cells gave the optimum curve (AUC = 0.71). uTF showed a weak to moderate association with mTF levels but correlated best and was statistically significant when compared with levels in the LPS-stimulated cells. uTF represents an intrinsic, kidney-derived, physiologic concentration rather than that of preactivated or postactivated monocytes. In conclusion, both uTF and LPS-stimulated mTF levels showed sensitivity and specificity in detecting cancer and inflammatory diseases. However, the two forms of TF appear to be independently derived.     

Tissue factor and tissue factor pathway inhibitor: a potential role in pregnancy and obstetric vascular complications?

Tissue factor (TF) is the principal cellular initiator of normal blood coagulation. As a result it is considered to be a major regulator of haemostasis and thrombogenesis. In vivo TF activity is regulated by specific circulating inhibitor known as "tissue factor pathway inhibitor (TFPI)". TF is also essential for other cellular processes including embryogenesis and angiogenesis as well as in implantation where it is particularly important in the first trimester. TF is highly expressed in syncytiotrophoblasts (STB) while TFPI is expressed in human umbilical vein endothelial cells (HUVEC). TFPI may be internalized via an endocytic pathway and recycled to the cell surface. The procoagulant tendency of STB may reflect a physiological need for immediate inhibition of hemorrhage in the placental intervillous spaces. Furthermore, the haemostatic balance involving STB and HUVEC may be critical for normal placental function and pregnancy outcome. Homozygous knockouts of both TF and TFPI are generally lethal in fetal mice; heterozygotes survive but with altered coagulation parameters. Despite their apparent association with placental microcirculation-thrombi-formation only few studies have addressed the role of TF and TFPI in the pathogenesis of gestational vascular complications. In this context, detailed studies could provide clinically relevant information.     

Homocysteine: an emergent cardiovascular risk factor?

Cardiovascular disease is the leading cause of mortality and disability in the western world. In the last years, the accumulation of evidence coming from both retrospective and prospective clinical studies has led to an increased interest in the potential role of mild hyperhomocysteinemia as a major, independent risk factor for cardiovascular disease. The present paper reviews the position of homocysteine in metabolism to understand the pathogenesis of hyperhomocysteinemia, as well as the clinical data pointing to its proposed role as an independent cardiovascular disease risk factor.     

Krüppel-like factor 4 regulates macrophage polarization

Current paradigms suggest that two macrophage subsets, termed M1 and M2, are involved in inflammation and host defense. While the distinct functions of M1 and M2 macrophages have been intensively studied - the former are considered proinflammatory and the latter antiinflammatory - the determinants of their speciation are incompletely understood. Here we report our studies that identify Krüppel-like factor 4 (KLF4) as a critical regulator of macrophage polarization. Macrophage KLF4 expression was robustly induced in M2 macrophages and strongly reduced in M1 macrophages, observations that were recapitulated in human inflammatory paradigms in vivo. Mechanistically, KLF4 was found to cooperate with Stat6 to induce an M2 genetic program and inhibit M1 targets via sequestration of coactivators required for NF-κB activation. KLF4-deficient macrophages demonstrated increased proinflammatory gene expression, enhanced bactericidal activity, and altered metabolism. Furthermore, mice bearing myeloid-specific deletion of KLF4 exhibited delayed wound healing and were predisposed to developing diet-induced obesity, glucose intolerance, and insulin resistance. Collectively, these data identify KLF4 as what we believe to be a novel regulator of macrophage polarization.