TU-100 Antagonizes the M2 Polarization Phenotype of Macrophages in the Tumor Microenvironment by Suppressing the TLR4/NF-B/STAT3 Axis.

BACKGROUND/AIM: Macrophages are the most abundant immune cells in the tumor stroma, and their polarization states within the tumor microenvironment (TME) exert critical roles in tumorigenesis. TU-100 (Daikenchuto) is a commonly prescribed Japanese herbal medicine that has shown anti-cancer effects by regulating cancer-associated fibroblasts (CAFs) in the TME. However, its effects on tumor-associated macrophages (TAMs) remain unclear. MATERIALS AND METHODS: TAMs were generated by macrophage exposure to tumor-conditioned medium (CM), and their polarization states were evaluated after TU-100 treatment. The underlying mechanism was further studied. RESULTS: TU-100 exhibited little cytotoxicity over a range of doses in M0 macrophages and TAMs. However, it could antagonize the M2-like polarization of macrophages evoked by tumor-CM exposure. These effects might be caused by the inhibition of TLR4/NF-B/STAT3 signaling in the M2-like phenotype of macrophages. Interestingly, TU-100 antagonized the malignancy promoting effects of M2 macrophages on hepatocellular carcinoma cell lines in vitro. Mechanistically, the administration of TU-100 restrained the high expression of MMP-2, COX-2, and VEGF in TAMs. CONCLUSION: TU-100 may alleviate the progression of cancer by regulating the M2 polarization of macrophages within the TME, suggesting a viable therapeutic approach.

Remodeling of the osteoimmune microenvironment after biomaterials implantation in murine tibia: Single-cell transcriptome analysis.

Osseointegration seems to be a foreign body reaction equilibrium due to the complicated interactions between the immune and skeletal systems. The heterogeneity of the osteoimmune microenvironment in the osseointegration of implant materials remains elusive. Here, a single-cell study involving 40043 cells is conducted, and a total of 10 distinct cell clusters are identified from five different groups. A preliminary description of the osteoimmune microenvironment revealed the diverse cellular heterogeneity and dynamic changes modulated by implant properties. The increased immature neutrophils, Ly6C + CCR2hi monocytes, and S100a8hi macrophages induce an aggressive inflammatory response and eventually lead to the formation of fibrous capsule around the stainless steel implant. The enrichment of mature neutrophils, FcgR1hi and differentiated immunomodulatory macrophages around the titanium implant indicates favorable osseointegration under moderate immune response. Neutrophil-depletion mice are conducted to explore the role of neutrophils in osseointegration. Neutrophils may improve bone formation by enhancing the recruitment of BMSCs via the CXCL12/CXCR3 signal axis. These findings contribute to a better knowledge of osteoimmunology and are valuable for the design and modification of 'osteoimmune-smart' biomaterials in the bone regeneration field.

An overview of Charcot's neuroarthropathy.

Charcot's neuroarthropathy is a destructive complication of the joints, which is often found in people with diabetes with peripheral neuropathy. Despite the fact that its description was published almost 130 years ago, its pathophysiology, diagnosis, and treatment remain areas that need to be described. Thanks to the use of bone remodelling, new therapeutic classes have emerged, we hope that this review will shed light on the pathology from its discovery through to the current state of knowledge on its classification, diagnosis and treatment methods.

Modified Ginseng Extract Induces Apoptosis in HepG2 Cancer Cells by Blocking the CXCL8-Mediated Akt/Nuclear Factor-[Formula: see text]B Signaling Pathway.

The cytokine C-X-C motif chemokine ligand 8 (CXCL8) is produced in the tumor microenvironment and has an important role in cancer pathogenesis. CXCL8 activates the nuclear factor (NF)-[Formula: see text]B signaling. However, the role of NF-[Formula: see text]B inactivation in apoptosis induced by negative regulation of CXCL8 remains unclear. Here, we assessed the effects of MRGX on the transcriptional activity of NF-[Formula: see text]B and the expression of tumor necrosis factor (TNF)-[Formula: see text]-stimulated target genes in liver cancer cells. Furthermore, we found that modified regular ginseng extract (MRGX)-mediated inhibition of NF-[Formula: see text]B signaling induced apoptosis. Importantly, MRGX exerted strong activity, inhibiting TNF-[Formula: see text]-induced expression of Akt and NF-[Formula: see text]B in a concentration-dependent manner. Furthermore, MRGX inhibited the TNF-[Formula: see text]-induced expression of genes encoding CXCL8, CXCL1, inducible nitric oxide synthase and intercellular adhesion molecule 1. MRGX also dowregulated Akt activation, and there was a significant decrease in Akt activation in HepG2 cells treated with CXCL8 siRNA. Conversely, CXCL8 overexpression increased Akt activation in MRGX-treated HepG2 cells. When Akt was silenced, MRGX treatment of HepG2 cells overexpressing CXCL8 decreased nuclear translocation of NF-[Formula: see text]B, whereas Akt overexpression increased nuclear translocation of NF-[Formula: see text]B in MRGX-treated HepG2 cells. Moreover, MRGX negatively regulated the TNF-[Formula: see text]-mediated I[Formula: see text]B/NF-[Formula: see text]B pathway to promote Bax activation, resulting in caspase-3 activation and apoptosis. Taken together, these results indicated that MRGX inhibited CXCL8-mediated Akt/NF-[Formula: see text]B signaling, which upregulated Bax activation and consequently induced apoptosis in HepG2 cells.

Eclipta prostrata Improves DSS-Induced Colitis through Regulation of Inflammatory Response in Intestinal Epithelial Cells.

Eclipta prostrata (EP) and its compounds are known to have several pharmacological effects including anti-inflammatory effects. In the present study, we demonstrated that EP improves the dextran sulfate sodium (DSS)-induced colitis symptoms such as body weight loss, colon length shortening and disease activity index. In DSS-induced colitis tissue, EP controls the protein expressions of cyclooxygenase-2 (COX-2) and hypoxia inducible factor-1[Formula: see text] (HIF-1[Formula: see text]). In addition, the release of prostaglandin E2 and vascular endothelial growth factor-A were significantly reduced by EP administration. EP also inhibited COX-2 and HIF-1[Formula: see text] expressions in the tumor necrosis factor-[Formula: see text] stimulated HT-29 cells. These inhibitory effects of EP occurred by reducing the phosphorylation of I[Formula: see text]B and the translocation of the nuclear factor-[Formula: see text]B (NF-[Formula: see text]B). Additionally, we found through HPLC analysis that wedelolactone, which is an inhibitor of NF-[Formula: see text]B transcription, was contained in water extract of EP. These results indicate that EP can improve colitis symptoms through the modulation of immune function in intestinal epithelial cells and suggests that EP has the potential therapeutic effect to intestinal inflammation.

Effect of lifestyle interventions with or without metformin therapy on serum levels of osteoprotegerin and receptor activator of nuclear factor kappa B ligand in patients with prediabetes.

Osteoprotegerin has been shown to be increased in cardiovascular disorders and type 2 diabetes mellitus. Prediabetes represents a high risk condition for diabetes and diabetic complications. Therefore, we aimed to find the relationship between prediabetes and osteoprotegerin with nuclear factor-B ligand, carotid intima media thickness, and metabolic markers. A total of 54 participants with prediabetes including impaired fasting glucose (n = 21), impaired glucose tolerance (n = 8), impaired fasting glucose and impaired glucose tolerance (n = 25), and 60 healthy individuals as a control were admitted to the study. Metabolic and anthropometric parameters, insulin resistance variables, osteoprotegerin, and nuclear factor-B ligand markers, carotid intima media thickness were examined at baseline for all participants. To evaluate the effect of therapy we determined the same parameters after the end of the study. Measurements of waist circumference, body mass index, body fat percentage and levels of fasting blood glucose, fasting insulin, homeostatic model assessment of insulin resistance, triglyceride levels and hsCRP and carotid intima media thickness were significantly higher in patients with prediabetes (p < 0.05). We also found higher osteoprotegerin and lower nuclear factor-B ligand levels in patients than in controls however, the value was non-significant (p > 0.05). Patients with prediabetes were under lifestyle interventions with (group 1, n = 33) or without metformin (group 2, n = 21) therapy. Baseline anthropometric and metabolic characteristics were not found statistically different in group 1 and group 2. Mean follow up period of the patients were 7.9 ± 2.2 month (min-max: 6-12 months). After the follow up period we evaluated the same parameters and found significant differences between waist circumference, body mass index, body fat percentage, fasting insulin, homeostatic model assessment of insulin resistance, and osteoprotegerin levels (p < 0.05). However, carotid intima media thickness, and nuclear factor-B ligand levels significantly different only in the group treated with metformin (p < 0.05). We also compared the variables after the treatment period with the control group and found significantly lower levels in terms of fasting insulin, homeostatic model assessment of insulin resistance, waist circumference, body mass index, body fat percentage, carotid intima media thickness, osteoprotegerin, and nuclear factor-B ligand values (p < 0.05). Correlation analysis revealed a negative relationship between nuclear factor-B ligand and body mass index, and body fat percentage in group 1 (p = 0.05, r = -0.646, p = 0.01, r = -0.585). Therapy of prediabetes was associated with a significant decrease in osteoprotegerin and certain metabolic variables together with an increase in nuclear factor-B ligand levels particularly in patients with under metformin therapy.

Alpinia officinarum Stimulates Osteoblast Mineralization and Inhibits Osteoclast Differentiation.

Alpinia officinarum rhizome has been used as a traditional herbal remedy to treat inflammatory and internal diseases. Based on the previously observed inhibitory effect of A. officinarum rhizome in an arthritis model, we evaluated whether a water extract of A. officinarum rhizome (WEAO) would enhance in vitro osteoblast mineralization using calvarial osteoblast precursor cells or would inhibit in vitro osteoclast differentiation and bone resorption using bone marrow derived macrophages. In osteoblasts, WEAO enhanced the mRNA levels of transcription factor (runt-related transcription factor 2, smad1, smad5, and junB) and marker (bone morphogenetic protein-2, collagen type 1alpha1, and osteocalcin) genes related to osteoblast mineralization, consistent with increased alizarin red S staining intensity. WEAO markedly inhibited osteoclast differentiation by suppressing the receptor activator for nuclear factor-[Formula: see text]B ligand-induced downregulation of inhibitor of DNA binding 2 and V-maf musculoaponeurotic fibrosarcoma oncogene homolog B and the phosphorylation of c-Jun N-terminal kinase, p38, nuclear factor-[Formula: see text]B, c-Src, and Bruton's tyrosine kinase to induce nuclear factor of activated T cells cytoplasmic 1 expression. WEAO also suppressed the resorbing activity of mature osteoclasts by altering actin ring formation. Therefore, the results of this study demonstrate that WEAO stimulates osteoblast mineralization and inhibits osteoclast differentiation. Thus, WEAO may be a promising herbal candidate to treat or prevent pathological bone diseases by regulating the balance between osteoclast and osteoblast activity.

Astragalus saponins Inhibits Lipopolysaccharide-Induced Inflammation in Mouse Macrophages.

Excessive nitric oxide (NO) and pro-inflammatory cytokines are produced during the pathogenesis of inflammatory diseases and cancer. It has been demonstrated that anti-inflammation contributes Astragalus membranaceus saponins (AST)'s beneficial effects in combination of conventional anticancer drugs. However, the immunomodulating property of AST has not been well characterized. In this study, we found that AST suppressed lipopolysaccharide (LPS)-induced generation of NO without causing cytotoxicity in the mouse macrophage RAW264.7. The gene and protein overexpression of inducible NO synthase (iNOS) as well as the production of tumor necrosis factor-[Formula: see text], evoked by LPS, was consistently down-regulated by AST. AST also inhibited the phosphorylation of p38 mitogen-activated protein kinase (MAPK) and suppressed nuclear factor (NF)-[Formula: see text]B activation and the associated I[Formula: see text]B[Formula: see text] degradation during LPS insult. Furthermore, AST induced growth inhibition in promyelocytic leukemic HL-60 cells and T-lymphocyte leukemic Jurkat cells, but exerted no cytotoxic effects in normal human peripheral blood mononuclear cells (PBMC). It is known that the chemotherapeutic drug 5-FU can suppress the immune system, which can be identified by a reduced white blood cell count and decreased hematocrit, while the combination of AST and 5-FU can reverse the above hematologic toxicities. To summarize, non-cytotoxic concentrations of AST suppress LPS-induced inflammatory responses via the modulation of p38 MAPK signaling and the inhibition of NO and cytokine release. Importantly, AST can alleviate the hematologic side effects of current chemotherapeutic agents. These findings can facilitate the establishment of AST in the treatment of inflammatory diseases and inflammation-mediated tumor development.

The protective effect of piperine on dextran sulfate sodium induced inflammatory bowel disease and its relation with pregnane X receptor activation.

ETHNOPHARMACOLOGICAL RELEVANCE: Inflammatory bowel disease (IBD) is associated with chronic inflammation of the intestinal tract. Piperine (1-peperoylpiperidine), the primary lipophilic component in black pepper (Piper nigrum) and long pepper (Piper longum), has been reported to be effective for anti-inflammatory. Rencently, several ethnopharmacological purity compounds, such as baicalin and artemisinin, are reported to have potentially therapeutic role in treating IBD. In the present study, the effects of piperine on pregnane X receptor (PXR)-mediated CYP3A expression and its therapeutic role in IBD were investigated. MATERIALS AND METHODS: LS174T cells and C57BL/6J mice were treated by the piperine. Gene expressions were analyzed by real-time PCR, Western blot analysis, transient transfections assay and histological analysis. RESULTS: Data indicated that treatment of LS174T cells with piperine markedly increased both CYP3A4 and PXR mRNA and protein. Transient transfection experiments indicated that transcriptional activation of the CYP3A4 gene via piperine was PXR-dependent. Data show that pre-administration of piperine decreased clinical hallmarks of colitis in DSS-treated PXR mice as measured by body weight loss and assessment of diarrhea, rectal bleeding, colon length, and histology. Inflammatory mediators (CCR2, ICAM-1, IL-1ß, IL-6, IL-10, iNOS, MCP-1, and TNFα) after DSS treatment were significantly decreased in mice pretreated with piperine but corresponding conditions did not occur in mice with down-regulation of PXR by small interfering RNA (siRNA). CONCLUSION: Piperine is a potential agonist of PXR and an inducer of PXR, which may induce CYP3A4 gene expression at the mRNA and protein levels. These results establish that piperine may contribute to prevention or reduction of colonic inflammation.

Role of NF-?B in the mechanism of liver injury following intestinal perforations due to abdominal firearm wound in pigs / 中国现代普通外科进展

Objective:To study the role of NF- ?B in the mechanism of liver injury following intestinal perforations due to abdominal firearm wound. Methods:A total of 42 Chang-Bai piglets were assigned randomly into 7 groups: control group and wounded 1, 2, 4, 8, 12, 24 hours group.The model of intestinal perforations due to abdominal firearm wound was established in wounded groups. Hepatic NF-?B and TNF-? content was measured with immunohistochemical staining and image analysis in all groups. Hepatocyte apoptosis indexes and serum ALT levels were also determined at the same time. The alterations of hepatic tissue were observed under light microscope. Results: Levels of hepatic NF-?B activity in wounded groups were significantly elevated compared with control group, and two peaks appeared in 1 h group and 8 h group, respectively (P

Effects of lipopolysaccharide preconditioning on the activities of nuclear factor kappa-B and the expression of intercellular adhension molecule-1/lymphocyte function associated antigen-1 in rats graft with liver ischemia/reperfusion injury / 重庆医科大学学报

Objective: To study the effects and significances of lipopolysaccharide preconditioning on the activities of NF-?B and the expression of ICAM-1/LFA-1 in rats graft liver ischemia/reperfusion injury. Methods: Male Sprague-Dawley rats were divided into three groups: sham operation group(Sham group),orthotopic liver transplantation group (OLT group) and LPS preconditioning group (LPS group). Only dissecting hepatoduodenal ligament was perfomed in Sham group. Experiments of OLT were performed by two-cuff method in OLT group and LPS group. The activities of NF-?B and the expression of ICAM-1/LFA-1 in hepatic tissue ,the levels of ALT,AST in inferior caval vein blood were detected at 0,60,180 min after dissecting of hepatoduodenal ligament in Sham group and after portal vein reperfusion in OLT group and LPS group. Results: Compared with those in Sham group at the different time points respectively,the activities of NF-?B and the expression of ICAM-1/LFA-1 were higher in OLT group and LPS group(P0.05) at 0 min after reperfusion,they were evidently higher in OLT group than in LPS group (P

Combined Effect of Arsenite and Cigarette Smoke Solution on NF-?B in Lymphocytes of Rats / 环境与健康杂志

Objective To investigate the effect of sodium arsenite combined with cigarette smoke solution on NF-?B in rat lymphocytes. Methods Rat lymphocytes were divided into 4 groups: the arsenite treatment group, the CSS treatment group, the arsenite and CSS treatment group, and the control group. Electrophoretic mobility shift assays was used to detect levels of NF-?B DNA binding. Western blot was used to detect protein expression of I?B?. Results Levels of NF-?B DNA binding in the CSS treatment group and the arsenite treatment group were significantly increased (P

Atorvastatin Decreased Toll-Like Receptor 4 Expression and Downstream Signals in Human Endothelial Cells / 中华高血压杂志

Background The impact of statins on inflammation are independent of cholesterol-lowering effect.Recent studies showed that Toll-like receptor 4(TLR4),a mediator of innate immune responses,is involved in the initiation and progression of atherosclerosis.Objective To investigate the effects of atorvastatin on LPS-induced TLR4 expression and downstream signals and to explore the molecular mechanisms of anti-inflammation by statins.Methods Human umbilical vein endothelial cells(HUVEC)were pretreated with atorvastatin(1 or 10 ?mol/L)or NF-?B inhibitor CAPE for 30 min,then incubated by purified LPS for 24 hours.TLR4,ICAM-1 and E-selectin mRNA were measured by RT-PCR;the percentage of TLR4 positive cells were detected by flow cytometry.The activation of NF-?B(p65)were detected by Western blot.Results Atorvastatin(1-10 ?mol/L)prevented LPS-induced increases in TLR4,ICAM-1 and E-selectin expression [TLR4 mRNA(1.24?0.21)vs LPS(1.82?0.27),P

Effects of troglitazone on cytokines induced expression of ICAM-1 in human mesangial cell / 重庆医科大学学报

Objective:To investigate the effects of troglitazone on cell proliferation and expression of intercellular adhesion molecule-1(ICAM-1) induced by tumor necrosis factor-?(TNF-?) in human mesangial cells.Methods:Human mesangial cells were cultured in RPMI-1640 media containing TNF-? with or without troglitazone.Cell proliferation was assessed by MTT;the mRNA and protein expression of ICAM-1 were measured by RT-PCR and ELISA;the protein expression of NF-?B was measured by immunohistochemistry.Results:Troglitazone inhibited the proliferation of mesangial cell.The mRNA and protein expression of ICAM-1 of the cell induced by TNF-? increased significantly(P

Diallyl trisulfide inhibites interleukin-1? expression induced by lipopolysaccharide through inhibiting NF-?B activation in murine lung / 基础医学与临床

Objective To investigate the role of nuclear factor-kappa B(NF-?B)in the modulation of diallyl trisulfide(DATS)on interleukin-1?(IL-1?)expression induced by lipopolysaccharide(LPS)in mice with acute lung injury(ALI).Methods Mice were randomly divided into Control group,ALI group,DATS group,DATS prevention group and DATS treatment group.The expression of IL-1? mRNA in the lung tissue was detected by reverse transcription PCR(RT-PCR).NF-?B activity in the lung tissue was detected by electrophoresis mobility shift assay(EMSA).The expression of phospho-I?B and I?B were assayed by Western blot.Results The expression of IL-1? mRNA,NF-?B activity and the phospho-I?B expression in lung tissues increased significantly at ALI group(P

The significance of Inhibition of NF-?B by I?B? in Cerebral Ischemia / 国际脑血管病杂志

Nuclear factor-?B (NF-?B) is a nuclear transcription factor that regulates the expressions of multiple genes. It can be activated during cerebral ischemia; it is closely correlated with the inflammatory reaction and apoptosis during cerebral ischemia. NF-?B inhibitor ? (I?B?), an important inhibitor factor of NF-?B, can regulate the survival and death of neuron in the ischemia penumbra. Therefore, the inhibition of the degradation of I?B? and the prevention of the activation of NF-?B with drugs or molecular biological methods has become an important approach in study of the effect of NF-?B at present. Recent studies have indicated that I?B? itself may also participate in the regulation of apoptosis.

Effect of Buyang Huanwu decoction(补阳还五汤) on nuclear factor-kB and nitric oxide synthase expression in aged rats with focal cerebral ischemia/reperfusion injury / 中国中西医结合急救杂志

Objective To study the protective mechanism of Buyang Huanwu decoction(补阳还五汤) on brain damage after focal cerebral ischemia/reperfusion(I/R)in aged rats from the expression changes of nuclear factor-?B(NF-?B),heat shock protein 70(HSP70)and nitric oxide synthase(NOS).Methods A focal cerebral ischemia model was established by middle cerebral artery occlusion(MCAO),and the models were duplicated.Ninety-six aged rats were randomly divided into four groups:sham-operated group,model group,nimodipine group(6 mg?kg~(-1)?d~(-1)),Buyang Huanwu decoction group(0.9g?kg~(-1)?d~(-1)).The ischemia(I)was performed for 3 hours and reperfusion(R),for 1,3,6 and 12 days.The effects of Buyang Huanwu decoction on the nervous dysfunction score,the water content of cerebral constitution and the expressions of NF-?B,HSP70 and NOS were observed at different time points of reperfusion.Results The nervous dysfunction score,the water content of cerebral constitution,the expressions of NF-?B,HSP70, endothelial nitric oxide synthase(eNOS),neuronal nitric oxide synthase(nNOS),and inducible nitric oxide synthase(iNOS)in the model group were higher than those of the sham-operated group(P

Effects of panax notoginseng saponins(三七总皂苷)on activity of lung nuclear factor-?B and acute lung injury in rats with acute necrotizing pancreatitis / 中国中西医结合急救杂志

Objective To investigate whether panax notoginseng saponins(三七总皂苷,PNS) can inhibit the activity of lung nuclear factor-?B(NF-?B) and ameliorate the lung pathologic injury in rats with acute necrotizing pancreatitis(ANP).Methods Thirty Sprague-Dawley(SD) rats were randomly divided into three groups: sham operation group(group sham),ANP group(group ANP),PNS preconditioning group(group PNS).There were 10 rats in each group.Rat ANP model was induced by retrograde injection of 5% sodium taurocholate to pancreatic duct(1 ml/kg).The rats in the PNS preconditioning group were given by intraperitoneal injection of 50 g/L PNS(1 ml/kg) one hour before model establishment,and those in the other two groups were given 0.9% physiological saline(1 ml/kg) one hour before the operation.Put the rat in each group to death at 6 hours after the respective management was made,and the pulmonary tissues were taken to detect the activity of NF?B by immunohistochemistry and the wet/dry weight ratio of the lung tissue was measured.Results At 6 hours after the model was established in the ANP group,the NF-?B positive cell number(70%-100% positive cells,7 vs.0) and the positive unit((72.52?7.63)PU vs.(33.09?4.75)PU) in the lung tissue were remarkably increased in comparisons with those in the sham group(both P

Influence of tripterygium polyglycosid (雷公藤) on airway inflammation and remodeling in rats with allergic asthma / 中国中西医结合急救杂志

Objective: To observe the effect of tripterygium polyglycosid(TP,雷公藤) on airway inflammation and remodeling in rats with asthma.Methods: Forty rats were randomly divided evenly into negative control group,positive control group,normal dose TP group(TPⅠ group) and small dose TP group(TPⅡgroup).The experimental model was induced by ovalbumin sensitization.Number of cells in bronchoalveolar lavage fluid(BALF) was observed by immunocytochemical staining.The expressions of nuclear factor-?B(NF-?B),matrix metalloproteinases-9(MMP-9) and tissue of inhibitor of metalloproteinases-1(TIMP-1) were detected by immunohistochemistry method.Results: Compared with the negative control group,the counts of lymphocyte,neutrophilic leukocyte,macrophage and eosinocyte in BALF were elevated significantly,positive cell percentages of NF-?B, MMP-9 and TIMP-1 in lung tissues increased greatly in positive control group,the differences being significant(all P

Role and significance of nuclear factor-?B activity in systemic inflammtory response syndrome / 中国医师进修杂志

Objective To examine the change and role of nuclear factor-kappa B(NF-?B) activity and tumor necrosis factor-alpha(TNF-?) level in patients with systemic inflammatory response syndrome(SIRS).Methods Eighty patients with SIRS were studied.The NF-?B activity in monocytes and the level of TNF-? in serum was measured.The state of illness was estimated by APACHEⅡ score.Results There was significant difference for the activity of NF-?B in patients with SIRS compared with the control group.The NF-?B activity,TNF-? level and APACHEⅡ score are higher in both resuscitation multiple organ dysfunction syndrome(MODS) group and death group than the non-MODS group and survival group correspondingly(P