The brain endothelium is an important therapeutic target for the inhibition of cerebrovascular dysfunction in ischemic stroke. Previously, we documented the important regulatory roles of microRNAs in the cerebral vasculature, in particular the cerebral vascular endothelium. However, the functional significance and molecular mechanisms of other classes of non-coding RNAs in the regulation of cerebrovascular endothelial pathophysiology after stroke are completely unknown. Using RNA sequencing (RNA-seq) technology, we profiled long non-coding RNA (lncRNA) expressional signatures in primary brain microvascular endothelial cells (BMECs) after oxygen-glucose deprivation (OGD), an in vitro mimic of ischemic stroke conditions. After 16h of OGD exposure, the expression levels for 362 of the 10,677 lncRNAs analyzed changed significantly, including a total of 147 lncRNAs increased and 70 lncRNAs decreased by more than 2-fold. Among them, the most highly upregulated lncRNAs include Snhg12, Malat1, and lnc-OGD 1006, whereas the most highly downregulated lncRNAs include 281008D09Rik, Peg13, and lnc-OGD 3916. Alteration of the most highly upregulated/downregulated ODG-responsive lncRNAs was further confirmed in cultured BMECs after OGD as well as isolated cerebral microvessels in mice following transient middle cerebral artery occlusion (MCAO) and 24h reperfusion by the quantitative real-time PCR approach. Moreover, promoter analysis of altered ODG-responsive endothelial lncRNA genes by bioinformatics showed substantial transcription factor binding sites on lncRNAs, implying potential transcriptional regulation of those lncRNAs. These findings are the first to identify OGD-responsive brain endothelial lncRNAs, which suggest potential pathological roles for these lncRNAs in mediating endothelial responses to ischemic stimuli. Endothelial-selective lncRNAs may function as a class of novel master regulators in cerebrovascular endothelial pathologies after ischemic stroke.

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PS of 0 (n¼39, 15.18%) or 1 (n¼203, 78.99%). The treatment of apatinib was mainly first-line treatment (n¼103, 40.08%), second-line treatment (n¼64, 24.90%), and adjuvant treatment (n¼42, 16.34%). The starting dose of apatinib was 250mg in 132 patients and 500mg in 125 patients. The treatment regimens were: apatinib combined with chemotherapy drugs (178/257), apatinib monotherapy (64/257), apatinib combined with chemotherapy drugs plus PD-1 antibody drug (8/275), and apatinib combined with PD-1 antibody drug (7/275). Thirty-three patients achieved partial response, 69 patients achieved stable disease, and 26 patients had progressive disease, and no CR was achieved, illustrating an ORR of 25.78% and a DCR of 79.69%. During the treatment, the overall incidence of adverse events was 70.82%. The most common adverse events were hypertension (32.68%), leukopenia (26.46%), hand-foot syndrome (25.29%), neutropenia (20.23%), etc.Conclusions: This real-world research showed current treatment status and provided preliminary evidence for the efficacy and safety of apatinib in the treatment of gastric cancer in China. More data would be analyzed and reported in future.[ChiCTR2000035597]Legal entity responsible for the study: The authors.

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