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： background：As the priority drug for treating acute ischemic stroke, alteplase is a thrombolytic drug with strong fibrin specificity. It can obviously treat acute ischemic stroke with high safety. However, the validity of its time window is controversial. This study focus on the efficacy and safety of intravenous thrombolysis with alteplase for treating acute ischemic stroke at different time windows. Methods：Retrieval of English database（PubMed, Embase, Web of Science, the Cochrane Library）and Chinese database was conducted（CNKI, WAN FANG, VIP, CBMDISC) by computers. From the establishment of the database to October 2020, a retrospective study and case-control study on intravenous thrombolysis at different time windows for treating acute ischemic stroke were conducted. Two researchers independently conducted data extraction and quality evaluation of literature on the included studies, and RevMan5.3 was used for Meta-analysis on the included literature. Results：This study aims to evaluate the efficacy and safety of intravenous thrombolysis with alteplase at different time windows for treating acute ischemic stroke by NIHSS score, mRS rating scale, SICH incidence rate, All-cause mortality, and so on. Conclusions：This study will provide an evidence-based basis for the clinical efficacy of alteplase for treating acute ischemic stroke by thrombolytic therapy at different time windows.

Additional file 1: Table S1, Table S2, Table S3, Table S4, Table S5, and Fig S1, Fig S2 are shown in the file ���supporting information.

Additional file 1: Figure s1a. Star-port platform specific operation. Fig. s1b. Star-port platform before assembling. Fig. s1c. Star-port platform after assembling. Figure s2. Risk-adjusted cumulative sum (RA-CUSUM) curve for specimen quality.

Aging is a natural life process which leads to a gradual decline of essential physiological processes. For the liver, it leads to alterations in histomorphology (steatosis and fibrosis) and function (protein synthesis and energy generation) and affects central hepatocellular processes (autophagy, mitochondrial respiration, and hepatocyte proliferation). These alterations do not only impair the metabolic capacity of the liver but also represent important factors in the pathogenesis of malignant liver disease. Autophagy is a recycling process for eukaryotic cells to degrade dysfunctional intracellular components and to reuse the basic substances. It plays a crucial role in maintaining cell homeostasis and in resisting environmental stress. Emerging evidence shows that modulating autophagy seems to be effective in improving the age-related alterations of the liver. However, autophagy is a double-edged sword for the aged liver. Upregulating autophagy alleviates hepatic steatosis and ROS-induced cellular stress and promotes hepatocyte proliferation but may aggravate hepatic fibrosis. Therefore, a well-balanced autophagy modulation strategy might be suitable to alleviate age-related liver dysfunction. Conclusion. Modulation of autophagy is a promising strategy for “rejuvenation” of the aged liver. Detailed knowledge regarding the most devastating processes in the individual patient is needed to effectively counteract aging of the liver without causing obvious harm.

Studies have shown that liver fibrosis and some cases of early liver cirrhosis can be reversed, and thus a timely, accurate judgment of fibrosis degree has important clinical significance in prevention/treatment and prognostic evaluation of chronic liver diseases. In recent years, great achievements have been made in the application of serum markers and transient elastography for the evaluation of liver fibrosis. This article introduces the value of serological markers and related models in evaluating liver fibrosis, including CHI3L1, GP model, Forns, APRI, and FIB-4 index, and reviews the advances in the application of transient elastography in determining fibrosis stage in patients with chronic liver diseases. It is pointed out that a combination of these two methods has a high value in evaluating fibrosis degree.