股票市场不是融资的重要来源

本文对理论界这几年普遍流行的“股票发行是最佳的筹资方式，股票流通能实现资源配置优化重组，股票价格能评价和监督公司经营”的观点提出质疑。论证了无论在西方发达国家还是在我国，股票市场都仅仅是市场经济中的一个重要构架。

Molecular mechanism of TNF signaling and beyond

Tumor necrosis factor (TNF) is a proinflammatory cytokine that plays a critical role in diverse cellular events, including cell proliferation, differentiation and apoptosis. TNF is also involved in many types of diseases. In recent years, the molecular mechanisms of TNF functions have been intensively investigated. Studies from many laboratories have demonstrated that the TNF-mediated diverse biological responses are achieved through activating multiple signal- ing pathways. Especially the activation of transcription factors NF-κB and AP-1 plays a critical role in mediating these cellular responses. Several proteins, including FADD, the death domain kinase RIP and the TNF receptor associated factor TRAF2 have been identified as the key effectors of TNF signaling. Recently, we found that the effector mol- ecules of TNF signaling, such as RIP and TRAF2, are also involved in other cellular responses. These finding suggests that RIP and TRAF2 serve a broader role than as just an effector of TNF signaling.

Variation regularity of metal magnetic memory signals with inspecting time-interval and location

Influences of inspecting time-interval and location on varying behavior of metal magnetic memory (MMM) signals of defects were studied. Different areas in two precracked weldments were inspected at different time-intervals by type TSC-1M-4 stress-concentration magnetic inspector to obtain MMM signals. Mechanisms of MMM signals varying behavior with inspecting time and space were analyzed and discussed respectively. It is found that MMM signals don't change with inspecting time-interval, since stress field and magnetic leakage field maintain unchanged at any time after welding. On the other hand, MMM signals differ greatly for different inspecting locations, because stress field and magnetic leakage field are unevenly distributed in defective ferromagnetic materials.

Temporal and spatial profiling of nuclei-associated proteins upon TNF-α/NF-kB signaling

The tumor necrosis factor （TNF）-α/NF-kB-signaling pathway plays a pivotal role in various processes including apoptosis, cellular differentiation, host defense, inflammation, autoimmunity and organogenesis. The complexity of the TNF-α/NF-kB signaling is in part due to the dynamic protein behaviors of key players in this pathway. In this present work, a dynamic and global view of the signaling components in the nucleus at the early stages of TNF-a/ NF-KB signaling was obtained in HEK293 cells, by a combination of subcellular fractionation and stable isotope la- beling by amino acids in cell culture （SILAC）. The dynamic profile patterns of 547 TNF-α-induced nuclei-associated proteins were quantified in our studies. The functional characters of all the profiles were further analyzed using that Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway annotation. Additionally, many previously unknown effectors of TNF-α/NF-kB signaling were identified, quantified and clustered into differential activation profiles. In- terestingly, levels of Fanconi anemia group D2 protein （FANCD2）, one of the Fanconi anemia family proteins, was found to be increased in the nucleus by SILAC quantitation upon TNF-α stimulation, which was further verified by western blotting and immunofluorescence analysis. This indicates that FANCD2 might be involved in TNF-α/NF-kB signaling through its accumulation in the nucleus. In summary, the combination of subcellular proteomics with quan- titative analysis not only allowed for a dissection of the nuclear TNF-α/NF-kB-signaling pathway, but also provided a systematic strategy for monitoring temporal and spatial changes in cell signaling.

Omega-3 polyunsaturated fatty acids promote liver regeneration after 90% hepatectomy in rats

AIM:To evaluate the effectiveness of omega-3 polyunsaturated fatty acid(ω-3 PUFA) administration on liver regeneration after 90% partial hepatectomy(PH) in rats.METHODS:ω-3 PUFAs were intravenously injected in the ω-3 PUFA group before PH surgery.PH,sparing only the caudate lobe,was performed in both the control and the ω-3 PUFA group.Survival rates,liver weight/body weight ratios,liver weights,HE staining,transmission electron microscope imaging,nuclearassociated antigen Ki-67,enzyme-linked immunosorbent assay and signal transduction were evaluated to analyze liver regeneration.RESULTS:All rats in the control group died within 30 h after hepatectomy.Survival rates in the ω-3 PUFA group were 20/20 at 30 h and 4/20 1 wk after PH.Liver weight/body weight ratios and liver weights increased significantly in the ω-3 PUFA group.The structure of sinusoidal endothelial cells and space of Disse was greatly restored in the ω-3 PUFA group compared to the control group after PH.In the ω-3 PUFA group,interleukin(IL)-4 and IL-10 levels were significantly increased whereas IL-6 and tumor necrosis factor-levels were dramatically decreased.In addition,activation of protein kinase B(Akt) and of signal transducer and activator of transcription 3 signaling pathway were identified at an earlier time after PH in the ω-3 PUFA group.CONCLUSION:Omega-3 polyunsaturated fatty acids may prevent acute liver failure and promote liver regeneration after 90% hepatectomy in rats.

A Study on the Correlativity of MRI Signal Classifications with TCM Syndromes in Femoral Head Necrosis Patients

Objective:To probe into the relation between magnetic resonance imaging(MRI) signal classifications and TCM syndromes in femoral head necrosis patients,so as to provide reference for TCM diagnosis of this disease.Methods:Refering to the criteria for TCM syndrome types of necrosis of the femoral head described in "The Guiding Principles of Clinical Studies of New Chinese Drugs" and Shimizu and Mitchell's MRI signal classifications,MRI signal classifications between different TCM syndrome types were compared.Results:The Shimizu signal classification of different TCM syndrome types had statistically significant difference(P=0.04);Both T2WI+fs and Mitchell signal classifications of different TCM syndrome types had no statistical by significant differences(P=0.42 or P=0.15).Conclusion:There is a certain correlativity of TCM syndrome types of necrosis of the femoral head with T1WI signal classification of MRI.MRI signal classification may contribute to objectivity in TCM syndrome typing of this disease.

Electroacupuncture inhibits annulus fibrosis cell apoptosis in vivo via TNF-α-TNFR1-caspase-8 and integrin β1/Akt signaling pathways

OBJECTIVE: To examine whether electroacupuncture(EA) treatment inhibited cell apoptosis of intervertebral annulus fibrosis(AF) via tumor necrosis factor-α(TNF-α)-tumor necrosis factor receptor 1(TNFR1)-caspase-8 and integrin β1/Akt signaling pathways in a rat model of cervical intervertebral disc degeneration caused by unbalanced dynamic and static forces.METHODS: Thirty-two Sprague-Dawley rats were included in this study, of which 24 rats underwent surgery to induce cervical intervertebral disc degeneration, while eight rats received EA treatment at Dazhui(GV 14). Immunohistochemical staining was used to detect TNF-α, TNFR1, and caspase-8Apoptosis of AF cells was examined with terminal deoxynucleotidyl transferase-mediated d UTP-biotin nick end labeling(TUNEL) staining. The m RNA and protein expression levels of integrin β1 andAkt were evaluated with real-time polymerase chain reaction and western blot analysis, respectively.RESULTS: Treatment with EA decreased TUNEL-positive AF cells and lowered TNF-α, TNFR1 and caspase-8 positive cells compared with control groups. EA treatment also increased integrin β1and Akt m RNA and protein levels compared with controls.CONCLUSION: Treatment with EA inhibits AF cell apoptosis through suppression of the TNF-α-TNFR1-caspase-8 signal pathway and increases the expression of integrin β1 and Akt. EA may be a good alternative therapy for treating cervical spondylosis.

HuoguⅠformula prevents steroid-induced osteonecrosis in rats by down-regulating PPARγ expression and activating Wnt/LRP5/β-catenin signaling

OBJECTIVE： To investigate the effects of Huogu I formula on regulation of lipid metabolism in ste- roid-induced osteonecrosis of the femoral head （SONFH） rats and verify our hypothesis that Huogu I formula regulates lipid metabolism by down-regulating peroxisome proliferator-activated receptor gamma （PPARy） expression and activating Wnt signaling pathways. METHODS： Eighty-five rats were divided into four groups： control, model, Huogu 15 g/kg and Huogu 30 g/kg. Six weeks later, animals were anaesthe- tized, femora were dissected for histopathologicalexamination of the osteonecrotic changes and re- pair processes, micro computed tomography （Mi- cro-CT）-based micro-angiography was performed to assess vascularization. Serum lipid levels were detected by haematological examination. The ex- pressions of PPARy, Wnt3a, low density lipoprotein receptor-related protein 5 （LRP5） and 13-catenin were evaluated by immunohistochemistry, Western blot and quantitative real-time polymerase chain reaction analyses. RESULTS： The incidence of osteonecrosis, ratio of empty lacuna, adipose tissue area and adipocyte perimeter in the bone marrow were dramatically lower in the Huogu ~ formula treatment groups. By micro-CT quantification, Huogu ~ formula treat- ment dose-dependently increased vessel volume, vessel surface, percentage of vessel volume and vessel thickness of the femoral heads of SONFH rats. Levels of serum lipid in Huogu 15 g/kg and Huogu 30 g/kg groups reduced significantly. HuoguⅠformula treatment could suppress the ex- pression of PPARy and increase the expressions of Wnt3a, LRP5 and 13-catenin at both protein and mRNA levels. CONCLUSION： The results of our present study highlight the lipid-lowering potential of Huogu Ⅰ formula, and provide further evidence of the in- volvement of the PPARy inhibition and Wnt/LRPS/ 13-catenin signaling activation in the effects of Huogu Ⅰ formula.

Effects of electroacupuncture pretreatment on M1 polarization of alveolar macrophages in rats with acute lung injury

Objective:To observe the effects of electroacupuncture(EA)pretreatment on M1 polarization of alveolar macrophages(AMs)in rats with acute lung injury(ALI)induced by lipopolysaccharide(LPS),and to explore the potential protective mechanism of EA.Methods:Forty Sprague-Dawley rats were randomly divided into a normal group,a model group,and three groups of EA pretreatment[including a Chize(LU5)group,a Zusanli(ST36)group and a Chize(LU5)plus Zusanli(ST36)group],with eight rats in each group.The model rats of ALI were established by instilling LPS[2 mg/(kg·bw)]into the trachea of rats for 3 h.The rats in each EA pretreatment group were pretreated with EA for 30 min per day at the corresponding bilateral acupoints 6 d before instilling LPS.Three hours after modeling,the pulmonary function of the rats was tested,and the lung tissue was taken to calculate the ratio of lung wet weight to dry weight(W/D).The pathological lung changes and the injury score were observed by hematoxylin-eosin staining.The contents of tumor necrosis factor(TNF)-α,interleukin(IL)-1β,and myeloperoxidase(MPO)in rat's bronchoalveolar lavage fluid(BALF)were detected by enzyme-linked immunosorbent assay.The mRNA and protein expression levels of M1 macrophage markers clusters of differentiation 86(CD86),inducible nitric oxide synthase(iNOS),and its signaling pathway factor Toll-like receptor(TLR)4,and nuclear factor-κB(NF-κB)p65 in the alveoli were detected by fluorescence quantitative polymerase chain reaction and Western blot,respectively.Results:After being induced by LPS,the pulmonary function of the model rats showed that the forced expiratory volume in 0.1 s(FEV0.1),forced expiratory volume in 0.3 s(FEV0.3),and their respective ratios of FEV to forced vital capacity(FVC)(including FEV0.1/FVC and FEV0.3/FVC)were significantly decreased(P<0.01),while the W/D of lung tissue was increased(P<0.01).The score of lung injury was significantly higher(P<0.01).The contents of TNF-α,IL-1β,and MPO in the BALF and the mRNA and protein expression levels of CD86,iNOS,TLR4,and NF-κB p65 in the lung tissue were significantly increased(P<0.01).After EA pretreatment,the FEV0.1,FEV0.3,FEV0.1/FVC,and FEV0.3/FVC were significantly increased,the lung injury score decreased significantly,and the contents of TNF-α,IL-1β,and MPO in the BALF and the expression levels of CD86,iNOS,TLR4,and NF-κB p65 mRNAs and proteins in the alveoli decreased significantly(P<0.05 or P<0.01).Compared with the other two single acupoint groups,the contents of TNF-α,IL-1β,and MPO in the BALF and the expression levels of CD86,iNOS,TLR4,and NF-κB p65 mRNAs in the alveoli in the Chize(LU5)plus Zusanli(ST36)group were significantly lower(P<0.01).Conclusion:EA pretreatment at Chize(LU5)and Zusanli(ST36)can inhibit inflammation and reduce pulmonary injury in ALI rats induced by LPS.The effect of the combination of Chize(LU5)and Zusanli(ST36)is better than that of using these two acupoints separately,and its mechanism may be related to the inhibition of AMs'M1 polarization by down-regulation TLR4/NF-κB signaling pathway.

Advance in the Study of the Mechanisms Regulated by Sphingosine-1-Phosphate

Sphingosine-1-phosphate（S1P） is a bioactive lipid messenger in the cells that regulate gene expression and NF-κB signal pathway through unknown mechanisms.Recently,Cheng Luo,associate professor of DDDC in Shanghai Institute of Materia Medica,whose project was funded by the National Natural Science Foundation of China,joined in a research team led by Professor Sarah Spiegel of Virginia Commonwealth University.The team continuously made significant breakthroughs in understanding the regulation mechanism of Sphingosine-1- Phosphate.In September 2009,in a paper published on SCIENCE magazine（Science 2009, 325：1254-7）,they firstly demonstrated that S1P is a physiologically important regulator of histone deacetylases（HDACs）,HDACs are direct intracellular targets of S1P.Furthermore,they identified the mechanism that S1P regulates gene expression through regulating the activity of HDACs.In June 24th,2010,in another paper to be published on NATURE magazine（Nature 2010,June 24th,advance online publication,（doi：10.1038/ nature09128）） which reports the regulation of NF-κB signaling pathway by S1P.They demonstrate that S1P is the missing cofactor for TRAF2（tumour-necrosis factor receptor-associated factor 2） and indicate a new paradigm for the regulation of lysine-63- linked poly-ubiquitination.The study also highlight the key role of SphK1 and its product S1P in TNF-αsignalling and the canonical NF-κB activation pathway, and then play crucial role in inflammatory,antiapoptotic and immune processes.The identification of new mechanisms fay which S1P regulates gene expression and TNF and NF-κB signaling pathway will light up the road to develop novel inhibitors that might be useful for treatment of cancer and in- flammatory diseases.