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Background and purpose Tirofiban administration after mechanical thrombectomy (MT) remains controversial. This study aimed to investigate the efficacy and safety of adjunct tirofiban treatment following MT for acute ischemic stroke (AIS) patients with large vessel occlusion (LVO) that resulted in successful reperfusion on digital subtraction angiography (DSA).Methods This retrospective study was conducted in Zhengzhou University University People's Hospital, an advanced stroke center in China. Consecutive patients with AIS who underwent endovascular therapy (EVT) were enrolled from June 2018 to January 2022. The safety endpoints were symptomatic intracerebral hemorrhage (sICH), total intracranial hemorrhage (ICH), and 3-month mortality. The efficacy endpoints were 3-month modified Rankin scale (mRS) score and 24-h neurological improvement.Results A total of 145 consecutive patients with AIS who underwent MT were analyzed, of whom 51 (35.2%) patients were in the tirofiban group. There were 30 (20.7%) patients with sICH, 50 (34.5%) patients suffered from ICH within 24-h post-MT, and 47 (32.4%) dead at 3-month. Besides, 31 (21.4%) patients achieved excellent clinical outcomes (mRS, 0-1), and 24-h neurological improvement was found in 29 (20.0%) patients. No statistically significant differences were found in safety outcomes on sICH, total ICH, and 3-month mortality, as well as efficacy outcomes on 3-month mRS scores (0-1) and 24-h neurological improvement between the two groups (P> 0.05 for all). Additionally, tirofiban was associated with 3-month mRS scores of 0-2 (adjusted odds ratio (OR), 3.75; 95% confidence interval (CI), 1.41–10.02, P= 0.008).Conclusion Adjunct tirofiban treatment following MT for AIS patients with LVO that resulted in successful reperfusion on DSA was not correlated with the increased risk of safety endpoints on sICH, ICH, and 3-month mortality, and it may be associated with a lower 3-month mRS score.

Background and aimsLiver fibrosis is a wound-healing response that disrupts the liver architecture and function by replacing functional parenchyma with scar tissue. Recent progress has advanced our knowledge of this scarring process, but the detailed mechanism of liver fibrosis is far from clear.MethodsThe fibrotic specimens of patients and HLF (hepatic leukemia factor)PB/PBmice were used to assess the expression and role of HLF in liver fibrosis. Primary murine hepatic stellate cells (HSCs) and human HSC line Lx2 were used to investigate the impact of HLF on HSC activation and the underlying mechanism.ResultsExpression of HLF was detected in fibrotic livers of patients, but it was absent in the livers of healthy individuals. Intriguingly, HLF expression was confined to activated HSCs rather than other cell types in the liver. The loss of HLF impaired primary HSC activation and attenuated liver fibrosis in HLFPB/PBmice. Consistently, ectopic HLF expression significantly facilitated the activation of human HSCs. Mechanistic studies revealed that upregulated HLF transcriptionally enhanced interleukin 6 (IL-6) expression and intensified signal transducer and activator of transcription 3 (STAT3) phosphorylation, thus promoting HSC activation. Coincidentally, IL-6/STAT3 signalling in turn activated HLF expression in HSCs, thus completing a feedforward regulatory circuit in HSC activation. Moreover, correlation between HLF expression and alpha-smooth muscle actin, IL-6 and p-STAT3 levels was observed in patient fibrotic livers, supporting the role of HLF/IL-6/STAT3 cascade in liver fibrosis.ConclusionsIn aggregate, we delineate a paradigm of HLF/IL-6/STAT3 regulatory circuit in liver fibrosis and propose that HLF is a novel biomarker for activated HSCs and a potential target for antifibrotic therapy.