ABSTRACT
Aim This study aimed to assess the therapeutic potential of ACT001, a micheliolide derivative, in the treatment of acute lung injury ( ALI) induced by sepsis and investigate its pharmacological mechanisms. Methods At the animal level, an ALI model was established in mice through intraperitoneal injection of li-popolysaccharide (LPS). Subsequently, ACT001 was administered to the ALI-afflicted mice. The therapeutic effects of ACT001 were assessed by evaluating factors such as individual survival rate, lung inflammation, and pulmonary edema. At the cellular level, RAW264. 7 cells were stimulated with LPS to explore the pharmacological mechanism of ACT001. The study examined inflammatory response and oxidative stress levels, and proteomics analysis was conducted to investigate the underlying molecular mechanisms. Results At the animal level, ACT001 can improve the survival of mice with ALI, reduce lung inflammation, and reduce the levels of inflammatory cytokines in serum. At the cellular level, ACT001 promotes the polarization of RAW264. 7 cells toward an anti-inflammatory pheno-type by inhibiting MHC-II related pathways, inhibiting the production of NO and related inflammatory cytokines while increasing SOD content and scavenging ROS. Conclusions ACT001 exhibited the potential to alleviate ALI via its anti-inflammatory and antioxidative activity, mainly by inhibiting the STAT1/ CIITA/ MHC-II pathway. ACT001 holds promise as a novel therapeutic candidate for the treatment of ALI induced by sepsis.
ABSTRACT
With the serious aging of the population, the incidence of fragility fractures of the pelvis(FFPs) has gradually increased, which has become a public problem affecting the living quality of the elderly. When a surgical treatment is chosen, the procedure should be as minimal invasive as possible and avoid all surgical complications. In recent years, different techniques for percutaneous or less invasive fixation of the posterior pelvic ring have been developed. Their advantages and limitations are presented: sacroplasty, iliosacral screw osteosynthesis, cement augmentation, transiliac internal fixation, transsacral osteosynthesis, lumbopelvic fixation. The purpose of this paper is to review the classification and minimally invasive treatment of FFP.
Subject(s)
Aged , Humans , Bone Screws , Fracture Fixation, Internal , Fractures, Bone , General Surgery , Pelvic Bones , PelvisABSTRACT
<p><b>OBJECTIVE</b>To explore the changes of CD(14)(+) monocyte human leucocyte antigen DR (HLA-DR) and their relationship with multiple organ dysfunction syndrome (MODS) in severe sepsis.</p><p><b>METHODS</b>Ninety-one patients with a definite diagnosis of severe sepsis in the intensive care unit (ICU) were included. CD(14)(+) monocyte HLA-DR levels were detected by flow cytometry on the first, 4th and 7th days of the study, and Marshall scores and prognosis on day 28 were evaluated.</p><p><b>RESULTS</b>Thirty-four patients died within 28 days following the onset with a mortality rate of 37.4%. Persistently lowered levels of HLA-DR were detected and significantly increased Marshall scores were found in the fatal cases at all the time points (P<0.001). In the surviving patients, the levels of HLA-DR were significantly increased (P<0.01) and Marshall scores were gradually decreased (P<0.001). During the observation period, the levels of HLA-DR decreased significantly as the number of dysfunctional organs and Marshall scores increased (P<0.001). The levels of HLA-DR were significantly increased in severe sepsis patients with 2-4 dysfunctional organs and Marshall score of 5-12 (P<0.05 or P<0.001). No changes in HLA-DR levels in severe sepsis patients with 5-6 dysfunctional organs and Marshall scores of 13-22. The levels of HLA-DR showed a significant inverse correlation to Marshall scores (r=-0.368, P<0.001).</p><p><b>CONCLUSION</b>In patients with severe sepsis, persistent low CD(14)(+) monocyte HLA-DR levels predicts high mortality. The levels of HLA-DR are significantly correlated to the severity of organ dysfunction.</p>