The Janus kinase/signal transducer and activator of transcription (JAK/STAT) are a major signal transduction pathway in controlling and regulating a number of cytokine-mediated responses, including interferon-?, interleukin-1 (IL-1), IL-6, IL-10 and IL-4. The JAK/STAT pathway is particularly elegant because of its very rapid and simple cytoplasm-to-nucleus signaling. Recently, it has been found that JAK/STAT pathway might also be involved in the regulation of high mobility group box-1 protein (HMGB1), which plays an important role as a potential late mediator of sepsis. Inhibition of the activation of JAK/STAT pathway can down-regulate the gene expression of HMGB1 in vital organs, especially in the liver and lungs. In addition, treatment with JAK/STAT pathway inhibitors can effectively prevent the occurrence and development of multiple organ dysfunction syndrome following sepsis, and the probable underlying mechanism of which involves a reduction of direct or indirect harmful effect of HMGB1. Over the past few years, numerous investigations have contributed to our knowledge of the JAK/STAT pathway and its role in cytokine-mediated abnormality of immune function as well as inflammatory response during sepsis, and it might be helpful in further identifying a potential strategy of intervention for posttraumatic or postburn sepsis. This review summarizes the salient features of JAK/STAT pathway and focuses on the pathophysiological role of JAK/STAT in regulating proinflammatory cytokine activity and HMGB1 expression in vivo.

The present study was performed to investigate the significance and potential role of signal transducers and activators of transcription 3 (STAT3) activation in postburn Staphylococcus aureus sepsis. Seventy one male Wistar rats were randomly divided into five groups: normal controls, scald control group, postburn sepsis group, AG490 (JAK2 inhibitor) treatment group, and rapamycin (RPM, STAT3 inhibitor) treatment group. Tissue samples from the liver and lung were collected to determine activation of STAT3, and interferon ? (IFN ?) mRNA as well as protein expression. The results showed that activation of STAT3 was quickly up regulated at 0 5～1 hour following thermal injury combined with Staphylococcus aureus challenge in the liver and lung, and it gradually weakened after 2 hours. Treatment with AG490 or RPM could inhibit activation of STAT3 at 0 5 hour in the liver and lung. Meanwhile, IFN ? mRNA expression markedly declined at 2 hours after treatment with AG490 or RPM in the liver and RPM in the lung ( P

Objective To investigate the effects of inhibition of nuclear factor-kappa B (NF-?B) by pyrrolidine dithiocarbamate (PDTC) on tissue pro- and anti-inflammatory cytokine expression in rats with postburn Staphylococcus aureus sepsis and its potential regulating mechanism. Methods Thirty-four male Wistar rats were randomly divided into normal control group (n=6), scald control group (n=6), postburn sepsis group (n=12),and PDTC treatment group (n=10). Tissue samples from the liver, kidneys and lungs were collected to determine tumor necrosis factor-? (TNF-?) and interleukin-10 (IL-10) mRNA expression as well as their protein levels. Results Both TNF-? mRNA and protein expressions in the liver, kidneys and lungs of postburn septic animals were up-regulated rapidly at 0.5-2 hours (P

Objective To investigate the effect of rapamycin(RPM)on hepatic interleukin-10(IL-10)gene and acute liver injury in rats with postburn Staphylococcus aureus sepsis.Methods Fifty male Wistar rats were randomly divided into four groups:normal control group,scald control group,postburn sepsis group,and RPM treatment group.Tissue samples from liver and plasma were collected to determine IL-10 mRNA and protein expressions,and liver function parameters were also measured.Results Compared to postburn Staphylococcus aureus sepsis group,in RPM treatment group hepatic IL-10 mRNA expression and plasma IL-10 were significantly increased at 0.5 hour after RPM treatment(P

Child ; Child, Preschool ; Female ; Humans ; Infant ; Intercellular Adhesion Molecule-1 ; blood ; Leukocytes, Mononuclear ; metabolism ; Lymphocyte Function-Associated Antigen-1 ; blood ; Male ; Seizures, Febrile ; blood

Abstract Sepsis and related syndromes are the major cause of multiple organ failure and death in patients with critical illnesses.Neuroendocrine dysfunction has long been thought to be an important event in sepsis.In clinic,optimal management of the hormones could alleviate severe complications in sepsis.In this article,we review the dysfunction of neuroendocrine system as well as autonomic nervous system in sepsis,and summarize the respective therapy strategies.

Objective To evaluate the methods and outcome of laparoscopic degradable bio-patch repair of umbilical hernia in adults. Methods From January 2003 to October 2008, 21 adult patients underwent elective laparoscopic patch repair of umbilical hernia. There were 15 women and 6 men. The mean age was 56 years old (range of 36-73). The diameter of hernia ring was from 3 to 7.5 cm averaging at 5.2 cm. All patients received general anesthesia. Preoperative bowel preparation routinely started one day before the operation. The patients received prophylaxis systemic antibiotics 30 minutes before the operation. An appropriate size of prosthetic patch (Composix E/X, Bard, USA) was that extended the defect margin for about 3-5 cm. The mesh was then inserted into the peritoneal cavity and spreaded flattening, with the polyplypylene side facing outside and it's center coinciding with that of the defect. The mesh was fixed to the abdominal wall with staple tacks in two rings, which was 3-5 cm along the hernia ring and 1-2 cm along the edge of the mesh. Results There was no conversion to open repair. The operative time was 30 to 96 rain and the average was 52 min. Two patients suffered from a transient postoperative tympanites and which subsided 2 to 3 days after the operation. One patient had a severe pain in the repair area around the umbilical and underwent oral medicine treatment, which disappeared one week after operation. There was no seroma and incision or mesh infection occurred. The postoperative hospital stay was 3 to 8 days and the average was 4. 2 days. The follow-up time was 3 months to 5 years and the average was 32 months. No ileus or hernia recurrence during the follow-up. Conclusion Laparoscopic patch repair of umbilical hernia in adults is a safe and effective procedure.

0.05).The level of interleukin-8 in the sputum showed a positive correlation with neutrophil proportion(r=0.544).Conclusion Neutrophil,IL-8 in the sputum are associated with respiratory tract inflammation in the healthy smokers,smoking is an important factor in the inflammation.

Systemic inflammatory response syndrome (SIRS) and its lethal sequela multiple organ dysfunction syndrome (MODS) are common complications in critical illness, such as severe trauma, shock, infection and major operations. During the past three decades, the evolution in our understanding of SIRS and/or MODS could be divided into three stages. Particularly in recent years, advances in molecular and cellular biology have provided new insights in the pathogenesis of this complex condition. The earlier emphasis on the pro inflammatory mediators involved in propagation of inflammatory response, has gradually been replaced by a realization that SIRS/MODS are the result of an imbalance of pro and anti inflammatory mediators to create the final status of excessive inflammation or immunoparalysis'. Though prognosis remains poor, the knowledge that now exists about SIRS/MODS gives great hope for the future. Progress has been made in new treatment modalities and re evaluation of current available measures. Nevertheless, improved techniques to monitor immunological or other markers of inflammatory and host defense responses will be important in assessing the effects of future therapies on central mechanisms contributing to SIRS/MODS.

Evidence-based medicine is also currently promoted and extolled as the best way to evaluate its various treatment and to draft clinical guidelines for the management of severe sepsis with aim to result in a reduction in mortality. There are several obvious factors in the design and conduct of clinical trials in sepsis to be observed, including case selection, end points, and sub-population evaluation, etc. In the past years, several scientific reports of evidence-based strategies for the treatment of sepsis were published, including recombinant human activated protein C, control of hyperglycemia in sepsis, and administration of low dose of corticosteroid in severe sepsis management.