ABSTRACT
Background: Interleukin-34 (IL-34) is an important immunomodulatory factor that plays a crucial role in a variety of autoimmune diseases. Aims: To investigate the expression of IL-34 in primary biliary cholangitis (PBC) and its influence on intrahepatic inflammation and bile duct damage. Methods: Liver tissues were obtained from 26 PBC patients and 10 hepatic hemangioma patients without PBC. Expression and localization of IL-34 were detected by immunohistochemistry. In animal experiment, Poly I:C intraperitoneal injection was used to construct PBC model in wild-type and IL-34-knockout C57BL/6 mice (WT-PBC group and IL-34KO-PBC group). Subsequently, the intrahepatic inflammation and bile duct damage were evaluated pathologically, and the expressions of IL-34 and associated cytokines in liver tissues were detected by real-time PCR and Western blotting. Results: Expression of IL-34 in liver tissues of PBC patients and PBC model mice was significantly higher as compared with those of the controls (all P<0.05). No morphological changes in hepatic pathological evaluation were observed in IL-34KO mice receiving intraperitoneal saline injection. In IL-34KO-PBC mice, the portal area inflammation and biliary epithelial cell damage were more severe than those in WT-PBC mice (all P<0.05). Expressions of proinflammatory cytokine interleukin-1β (IL-1β) and monocyte chemotactic protein-1 (MCP-1) in liver tissues of IL-34KO-PBC mice were significantly increased than those of WT-PBC mice, whereas expressions of antiinflammatory cytokine IL-10 and CD163, the surface marker of M2 macrophages, were significantly reduced (all P<0.05). Conclusions: IL-34 expression is increased in liver tissues of PBC patients and animals. It might reduce the portal area inflammation and bile duct damage via modulating cytokines expression and driving macrophages polarization to the M2 phenotype. IL-34 might act as a self-rescue factor which negatively regulates hepatic immune microenvironment and prevents disease progression.
ABSTRACT
Objective To assess the outcomes of ischemic stroke patients with atrial fibrillation (AF).Methods Six thousand six hundred and ninety-five patients with acute ischemic stroke,admitted to our hospital from May 2005 to December 2013,were recruited consecutively.These patients were divided into combined AF group (n=583) and non-combined AF group (n=6112).The clinical data,including stroke subtypes,stroke severity,risk factors of stroke,NIHSS scores and Barthel index,and outcomes,including mortality,unfavourable prognosis and recurrence at 3,12,and 36 months after stroke were analyzed.Results The prevalence rate of AF in the patients enrolled in this study was 8.7％ (583/6695).There was a higher frequency of AF in female than that in male,with significant difference (45.8％ vs.33.0％,P＜0.05).The patients from combined AF group were older than those without AF.The percentage of severe stroke in AF patients (34.8％) was significantly higher than that in non-combined AF group (8.3％,P＜0.05).The patients with AF were less likely than the patients without AF to have hypertension (63.8％ vs.73.3％),diabetes (24.9％ vs.32.3％),dyslipidemias (26.1％ vs.31.5％),artery stenosis (17.2％ vs.23.4％),current smoking (22.6％ vs.39.0％),and alcohol consumption (7.5 ％ vs.18.9％),with significant differences (P＜0.05).After adjusting age,gender,stroke subtype,and severity,and risk factors,multivariate analysis showed that there was a higher recurrence risk in combined AF group at 3 months after stroke than that in non-combined AF group (P＜0.05);patients with AF had significantly higher mortality,dependency,and recurrence rates at 12 and 36 months after stroke than those without AF (P＜0.05).Conclusion The long-term prognosis of patients with stroke complicated with AF is poor;therefore,normalized anticoagulant therapy should be taken to decrease the recurrence rate and burdens of stroke in China.