Matrix metalloproteinase-8 regulates dendritic cell tolerance in late polymicrobial sepsis via the nuclear factor kappa-B p65/ß-catenin pathway.

Background: Tolerogenic dendritic cells (DCs) are associated with poor prognosis of sepsis. Matrix metalloproteinases (MMPs) have been shown to have immunomodulatory effects. However, whether MMPs are involved in the functional reprogramming of DCs is unknown. The study aims to investigate the role of MMPs in sepsis-induced DCs tolerance and the potential mechanisms. Methods: A murine model of late sepsis was induced by cecal ligation and puncture (CLP). The expression levels of members of the MMP family were detected in sepsis-induced tolerogenic DCs by using microarray assessment. The potential roles and mechanisms underlying MMP8 in the differentiation, maturation and functional reprogramming of DCs during late sepsis were assessed both in vitro and in vivo. Results: DCs from late septic mice expressed higher levels of MMP8, MMP9, MMP14, MMP19, MMP25 and MMP27, and MMP8 levels were the highest. MMP8 deficiency significantly alleviated sepsis-induced immune tolerance of DCs both in vivo and in vitro. Adoptive transfer of MMP8 knockdown post-septic bone marrow-derived DCs protected mice against sepsis-associated lethality and organ dysfunction, inhibited regulatory T-cell expansion and enhanced Th1 response. Furthermore, the effect of MMP8 on DC tolerance was found to be associated with the nuclear factor kappa-B p65/ß-catenin pathway. Conclusions: Increased MMP8 levels in septic DCs might serve as a negative feedback loop, thereby suppressing the proinflammatory response and inducing DC tolerance.

Partial Depletion of Regulatory T Cells Enhances Host Inflammatory Response Against Acute Pseudomonas aeruginosa Infection After Sepsis.

Immune dysfunction contributes to secondary infection and worse outcomes in sepsis. Regulatory T cells (Tregs) have been implicated in sepsis-induced immunosuppression. Nevertheless, the role of Tregs in secondary infection after sepsis remains to be determined. In the present study, a two-hit model which mimics clinical conditions was used and the potential role of Tregs in secondary Pseudomonas aeruginosa infection post-sepsis was investigated. Results showed that mice were susceptible to secondary P. aeruginosa infection 3 days, but not 7 days, post-cecal ligation and puncture (CLP). The levels of IL-17A, IL-1ß, and IL-6 remained low in CLP mice after P. aeruginosa infection, while the levels of IL-10 increased significantly. Additionally, increased number of Tregs in both lung and spleen was observed in "two-hit" mice. Injection with PC61 (anti-CD25) mAb reduced the number of Tregs by 50% in spleen and 60% in lung of septic mice. This partial depletion of Tregs elevated IL-17A, IL-1ß, and IL-6 production and decreased IL-10 levels in septic mice with P. aeruginosa infection, leading to lower bacterial load, attenuation of lung injury, and improvement of survival. The present findings demonstrate that Tregs play a crucial role in secondary P. aeruginosa infection after sepsis by modulating the inflammatory response.

[Progress on cervical anterior transpedicular screw fixators for lower cervical vertebrae].

Compared with the traditional anterior and posterior operation,anterior transpedicular screw fixation (ATPS) has many advantages of hiomechanics, relative safety. Both problems of decompression and reconstruction can be resolved only through an anterior approach. A rather peculiar anatomic channel was used in ATPS, but no special tools was used in system supporting for anterior pedicle screw to place,so the indications of ATPS of lower cervical vertebrae is relatively narrow,it cannot replace of traditional anterior and posterior surgery. Problems of accurately inserting screws and the development of internal fixation device about ATPS is a hot spot of current research and a future direction. In recent years,many scholars have systematically studied the technique, and applied it in clinic gradually and achieved good effects. In order to improve the level of application,recent articles were analyzed retrospectively in this paper,and the studies of anatomy,biomechanical and clinical application of ATPS were reviewed.

[Clinical research of HPV DNA detection and HPV RNA detection in single time].

OBJECTIVE: To research the application of the single time detection of HPV E6/E7 mRNA and HC2-HPV-DNA in cervical screening project. METHODS: We detected both HPV E6/E7 mRNA and HC2-HPV-DNA of each sample which collected from 130 cervical disease patients' cervix during Jan. 2008 and July. 2009. TCT results were taken as standard to evaluate the diagnostic accuracy of the above two test methods in detecting high-grade cervical disease. RESULTS: 82.3% (107/130)women were confirmed to infect HPV by HC2-HPV-DNA detection, and 40.0% (52/130) women were confirmed to infect HPV by HPV E6/E7 mRNA detection, there was no significant difference between the two results (chi2 = 24.5, P < 0.05). The sensitivity, specificity, positive predictive value, negative predictive value of HC2-HPV-DNA detection were 90.1%, 22.1%, 37.4% and 82.6%, respectively. The sensitivity, specificity, positive predictive value, negative predictive value of HPV E6/E7 mRNA detection were 65.9%, 73.3%, 55.8% and 80.8%, respectively. CONCLUSION: In clinical cervical screening project of single time, the combination of HC2-HPV-DNA detection and HPV E6/E7 mRNA detection wick take on more potential value than applying each of them alone. RNA;

[Pre-hospital systematic treatment for patients with severe acute organophosphorus pesticide poisoning].

OBJECTIVE: To evaluate the feasibility, safety and effectiveness of on-spot systematic treatment for the patients with severe acute organophosphorus pesticide poisoning (SAOPP). METHODS: Two hundred and twenty-three SAOPP patients were divided into two groups: pre-hospital treatment group (116 patients), in which rescue equipment and drugs were carried to the spot for the treatment of the patients; hospital treatment group (107 patients), in which the patients received emergency treatment after reaching the hospital. The pre-hospital group was sub-divided into group A and group B. In group A, gastric lavage was performed with aid of automatic lavage instrument, and in group B lavage was done by using suspending bucket. Antidotes including pralidoxime chloride and atropine were used simultaneously based on the patients' conditions. Cholinesterase (ChE) activity was dynamically monitored. When the symptoms disappeared, the length of atropinization, the total dosage of atropine and pralidoxime chloride, the recovery time of ChE, the mortality, hospital days, and the incidence of complications were analyzed. RESULTS: The therapeutic effect in pre-hospital group was better than that in in-patient group in terms of disappearance of the symptoms, length of atropinization, recovery time of ChE, the total dosage of atropine and pralidoxime chloride, hospital days, and the mortality rate in group A was markedly lower than in-patient group(P<0.05 or P<0.01). The incidence of respiratory failure, heart injury, brain injury, and atropine poisoning were also lower in pre-hospital group compared with in-patient group (all P<0.01). However, there were no significant differences in intermediate syndrome, relapse, liver injury (all P>0.05). On the other hand, there were no significant differences in mortality rate and hospital days between two subgroups of pre-hospital treatment group(P>0.05). CONCLUSION: Pre-hospital systematic treatment for SAOPP patients, due to its good effects, should be recommended as a safe and effective treatment strategy.