BackgroundStudies in murine models suggested that platelet desialylation was an important mechanism of thrombocytopenia during sepsis.MethodsFirst, we performed a prospective, multicenter, observational study that enrolled septic patients with or without thrombocytopenia to determine the association between platelet desialylation and thrombocytopenia in patients with sepsis, severe sepsis, and septic shock. Gender- and age-matched healthy adults were selected as normal controls in analysis of the platelet desialylation levels (study I). Next, we conducted an open-label randomized controlled trial (RCT) in which the patients who had severe sepsis with thrombocytopenia (platelet counts ≤50 × 109/L) were randomly assigned to receive antimicrobial therapy alone (control group) or antimicrobial therapy plus oseltamivir (oseltamivir group) in a 1:1 ratio (study II). The primary outcomes were platelet desialylation level at study entry, overall platelet response rate within 14 days post-randomization, and all-cause mortality within 28 days post-randomization. Secondary outcomes included platelet recovery time, the occurrence of bleeding events, and the amount of platelets transfused within 14 days post-randomization.ResultsThe platelet desialylation levels increased significantly in the 127 septic patients with thrombocytopenia compared to the 134 patients without thrombocytopenia. A platelet response was achieved in 45 of the 54 patients in the oseltamivir group (83.3%) compared with 34 of the 52 patients in the control group (65.4%; P = 0.045). The median platelet recovery time was 5 days (interquartile range 4–6) in the oseltamivir group compared with 7 days (interquartile range 5–10) in the control group (P = 0.003). The amount of platelets transfused decreased significantly in the oseltamivir group compared to the control group (P = 0.044). There was no difference in the overall 28-day mortality regardless of whether oseltamivir was used. The Sequential Organ Failure Assessment score and platelet recovery time were independent indicators of oseltamivir therapy. The main reason for all of the mortalities was multiple-organ failure.ConclusionsThrombocytopenia was associated with increased platelet desialylation in septic patients. The addition of oseltamivir could significantly increase the platelet response rate, shorten platelet recovery time, and reduce platelet transfusion.Trial registrationChinese Clinical Trial Registry, ChiCTR-IPR-16008542.Electronic supplementary materialThe online version of this article (doi:10.1186/s13045-017-0476-1) contains supplementary material, which is available to authorized users.
BackgroundHeme oxygenase-1 (HO-1) is an inducible defense gene which plays a significant role in inflammation. HO-1 protects cells and tissues through the mechanism of anti-oxidation, maintaining microcirculation and anti-inflammation. The aim of the current study is to investigate the role of HO-1 on systemic inflammatory response in severe acute pancreatitis (SAP).MethodsForty male Sprague-Dawley (SD) rats were randomly assigned into four groups: control group (n = 10); SAP group (n = 10), SAP model was induced by retrograde injection of 3% sodium taurocholate through pancreatic duct; HO-1 stimulation group (n = 10), SD rats were injected 75 μg/kg hemin intraperitoneally 30 min after induction of SAP; HO-1 inhibition group (n = 10), SD rats were injected 20 μg/kg Zinc porphyrin (Zn-PP) intraperitoneally 30 min after induction of SAP. After 24 h of SAP establishment, tissues were collected for HO-1, tumor necrosis factor-α (TNF-α) and interleukin-10 (IL-10) mRNA expression, and blood samples were collected for cytokines and biochemical measurements. Meanwhile, the histopathological changes of pancreas and liver tissues were observed.ResultsThe expression of HO-1 mRNA and protein were significantly induced by SAP in rat pancreas and liver. Hemin treatment significantly decreased oxidative stress and TNF-α in plasma and tissues, while the IL-10 was significantly increased. Pancreas and liver injury induced by SAP was markedly attenuated by Hemin treatment. Moreover, inhibition of HO-1 expression by Zn-PP administration aggravated the injury caused by SAP.ConclusionsInduction of HO-1 in early SAP may modulate systemic inflammatory response and prevent pancreas and nearby organs such as liver injury through inhibition of TNF-α and augmentation of IL-10.
SFI significantly improved hemodynamic indices such as CI, GEDI, MAP and HR in early volume resuscitation treated septic shock patients.
ABSTRACT. Spinal cord injury (SCI) is typically caused by trauma or disease, and it severely affects patients' motor function. The relationship between signal transducers and activators of transcription-1 (STAT1) and neuronal death after cerebral focal ischemia has been comprehensively studied, but its role in SCI remains largely unknown. This study investigated the protective effect of an STAT1 inhibitor on SCI. Thirty SD rats were SCIinduced and were then randomly divided into two groups (N = 15 each), either receiving STAT1 or the STAT1 inhibitor S1491 by intraperitoneal injection. The motor dysfunction of the rats was evaluated by behavioral scores, followed by the examination of SCI by hematoxylin and eosin staining. Apoptosis was also detected by Western blot and terminal deoxynucleotidyl transferase-mediated dUTP nick-end-labeling (TUNEL) assay. The motor functions of rats receiving STAT1 did not score as well as the STAT1 inhibitor group (P < 0.01). Further assays showed remarkable improvements in pathological damage to spinal code tissue in STAT1 inhibitor-treated rats, along with lower Bax and higher Bcl-2 expression. The STAT1 inhibitor also suppressed the occurrence of TUNEL-positive cells compared to the STAT1-treated group. In summary, we suggest that the STAT1 inhibitor alleviates SCI by decreasing apoptosis.
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