Alzheimer's disease (AD) has been a major health issue for more than one century since it was first reported in 1906. As one of the most common neurodegenerative diseases, AD is characterized by the presence of senile plaques and neurofibrillary tangles (NFTs) in the affected brain area. Microglia are the major regulators of neuroinflammation in the brain, and neuroinflammation has become recognized as the core pathophysiological process of various neurodegenerative diseases. In the central nervous system (CNS), microglia play a dual role in AD development. For one thing, they degrade amyloid β (Aβ) to resist its deposition; for another, microglia release pro-inflammatory and inflammatory factors, contributing to neuroinflammation as well as the spreading of Aβ and tau pathology. Wnt pathways are important regulators of cell fate and cell activities. The dysregulation of Wnt pathways is responsible for both abnormal tau phosphorylation and synaptic loss in AD. Recent studies have also confirmed the regulatory effect of Wnt signaling on microglial inflammation. Thus, the study of microglia, Wnt pathways, and their possible interactions may open up a new direction for understanding the mechanisms of neuroinflammation in AD. In this review, we summarize the functions of microglia and Wnt pathways and their roles in AD in order to provide new ideas for understanding the pathogenesis of AD.
Hypothermic oxygenated machine perfusion (HOPE) is a safe and reliable method that could alleviate liver injury in donation after circulatory death (DCD). This study focuses on the role of autophagy in HOPE’s protective effect on DCD liver injury. A 30‐minute warm ischemic liver model was established in mice. After 4 hours of cold storage (CS), 1 hour of hypothermic machine perfusion (HMP) with 100% O2 or 100% N2 was employed. During 2 hours of reperfusion, liver tissue and perfusate were collected to evaluate liver function, oxidative stress level, apoptosis, and necrosis. Western blotting was used to explore the level of autophagy. When the liver experienced warm ischemic injury, LC3B‐II expression was significantly enhanced. Compared with the CS, HOPE induced lower release of AST and ALT, as well as lower oxidative stress levels, apoptosis, and necrosis cell numbers, and led to higher tissue ATP content. Meanwhile, expression of autophagy‐related proteins, such as ULK1, Atg5, and LC3B‐II, increased. When oxygen was completely replaced by nitrogen, the washout effect of HMP did not activate autophagy and did not relieve DCD liver injury. When the autophagy inhibitor 3‐methyladenine was used in HOPE, the protective effect of HOPE was attenuated. In conclusion, DCD liver injury activated autophagy compared with healthy liver, while HOPE alleviated DCD liver injury by increasing autophagy levels further in this mouse model. However, HMP with 100% of N2 had no beneficial effect on DCD liver injury or on autophagy levels compared with CS. The research on autophagy may provide a new strategy for alleviating DCD liver injury in clinical practice.
Background: Neutrophil lymphocyte Ratio (NLR) and Platelet lymphocyte Ratio (PLR) are an indicator of the status of inflammation. The objective of this study was to evaluate the relationship between recipient pre-operative Neutrophil lymphocyte Ratio (NLR) and Platelet lymphocyte Ratio (PLR) with delayed graft function in the kidney transplant patient.
Methods: The preoperative full blood count, data regarding patient demographics and postoperative graft function was retrospectively evaluated from the database of our institution. All statistical calculations were carried out using SPSS 20.0 version (SPSS Inc., Chicago, IL, USA). A p-value<0.05 was considered statistically significant.
Results: 289 patients were included in this study. DGF occurred in 33 cases. Elevated preoperative NLR had a sensitivity of 75.75% and specificity of 76.56% whereas elevated preoperative PLR had a sensitivity of 72.72% and specificity of 58.20% for predicting DGF. The area under the ROC curve was found to be 0.762 and 0.655 for NLR and PLR, respectively. Multivariate analysis showed NLR>3.5 and PLR>120 independently responsible for DGF.
Conclusion: Recipient preoperative NLR and PLR can predict the occurrence of DGF following DBD renal transplantation. In addition, NLR is better than PLR in predicting DGF. DGF prolongs the total ICU and in-hospital stay.
BackgroundThe optimal treatment for the rare subtype of non‐Hodgkin lymphoma, extranodal natural killer/T‐cell lymphoma (ENKTL), nasal‐type, has not been clearly defined. The purpose of the study was to investigate the efficacy of sequential and “Sandwich” chemotherapy and extended involved‐field intensity‐modulated radiotherapy (IMRT) in patients with stage IE/IIE extranodal ENKTL, nasal‐type.MethodsOne hundred and fifty‐five patients with stage IE/IIE nasal‐type ENKTL were enrolled in the study, including 99 patients treated with sequential chemotherapy and extended involved‐field IMRT (SCRT) and 56 patients with “Sandwich” chemotherapy and extended involved‐field IMRT and chemotherapy (SCRCT). All patients were treated with extended involved‐field IMRT with median dose of 54.6 Gy to the primary tumor and positive lymph nodes. Ninety‐four patients had Ann Arbor stage IE disease, and 61 patients had stage IIE disease.ResultsThe 5‐year rates of loco‐regional recurrence (LRR), progression‐free survival (PFS), and overall survival (OS) were 17.0%, 78.5%, and 84.7%, respectively. Univariate analysis revealed that EBV DNA copy after treatment (normal vs elevated level) was significant prognostic factor for LRR, PFS, and OS (P < 0.001); therapeutic method (SCRT vs SCRCT) was significant prognostic factor for PFS (71.0% vs 91.8%, P = 0.011), but there was no significant effect on 5‐year LRR and OS (22.2% vs 8.2%, P = 0.051 for LRR; 80.9% vs 91.8%, P = 0.199 for OS).ConclusionsCompared with SCRT, SCRCT was significantly associated with higher PFS rates and showed a trend toward improved loco‐regional control. EBV DNA copy after treatment is a good index for recurrence and prognosis for stage IE/IIE ENKTL patients.
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