LncRNA Expression Profiling of Ischemic Stroke During the Transition From the Acute to Subacute Stage

Ischemic stroke induces profound effects on the peripheral immune system, which may participate the infectious complications. However, the exact function and mechanism of immune reaction in stroke development are not well-elucidated. Recently, several long non-coding RNAs (LncRNAs) are reported to affect ischemic stroke process, especially the immunological response after stroke. In the present study, we investigated the profile of LncRNAs in human ischemic stroke during the transition from the acute to subacute stage, when the state of the peripheral immune system changes from activation to systemic immunosuppression. In this study, we analyzed the RNA-sequencing (RNA-seq) datasets obtained at two time points (24 h and 7 days) from the peripheral blood mononuclear cells of ischemic patients. Vascular risk factor-matched healthy adults were enrolled as controls. A total of 3,009 LncRNAs and 3,982 mRNAs were identified as differentially expressed 24 h after stroke. Furthermore, 2,034 LncRNAs and 1,641 mRNAs were detected to be differentially expressed on day 7. Bioinformatics analyses, including GO, KEGG pathway enrichment analysis, and network analysis, were performed for the identified dysregulated genes. Our study reveals that ischemic stroke can influence the expression of LncRNAs and mRNAs in the peripheral blood at both the acute and subacute stages; the level of LncRNAs in the antigen processing and presentation pathway was clearly upregulated at 24 h and had recovered to normal levels on day 7 after stroke. Moreover, inflammatory mediator regulation of TRP channels and GABAergic synapses were two specifically downregulated pathways on day 7 after stroke. Our findings provide a valuable resource for further study of the role of LncRNAs in peripheral immune system changes following ischemic stroke

Association of hepatitis B virus infection status with outcomes of non-small cell lung cancer patients undergoing anti-PD-1/PD-L1 therapy

Background: The aim of this study was to evaluate the safety and survival outcomes of anti-programmed cell death (PD)-1/programmed cell death-ligand 1 (PD-L1) monotherapy in patients with advanced nonsmall cell lung cancer (NSCLC) and different hepatitis B virus (HBV) infection status. Methods: Patients with advanced NSCLC and both chronic and/or resolved HBV infection who were treated with anti-PD-(L)1 monotherapy were retrospectively enrolled. The primary endpoint was the safety of PD-1/PD-L1 monotherapy, while the secondary endpoints included the survival outcomes. Results: Of the 62 eligible patients, 10 (16.1%) were hepatitis B surface antigen (HBsAg) positive [chronic hepatitis B (CHB) infection] and 52 (83.9%) were HBsAg negative and HBcAb positive [resolved hepatitis B (RHB) infection]; 42 (67.7%) patients had at least 1 treatment-related adverse event (AE), with 4 patients (6.5%) developing grade 3 AEs and 6 (9.7%) developing hepatic AEs. One CHB patient experienced HBV reactivation during anti-PD-1 immunotherapy due to the interruption of antiviral prophylaxis. The objective response rate and durable clinical benefit (DCB) rate were 17.7% and 29.0%, respectively. Median overall survival (OS) and progression-free survival (PFS) were 23.6 months [95% confidence interval (CI): 14.432.8] and 2.1 months (95% CI: 1.2-3.0), respectively. The DCB rate was significantly higher in the CHB group than in the RHB group (60% vs. 23.1%; P=0.048). Patients with CHB experienced a longer PFS (8.3 vs. 2.0 months; P=0.103) and OS (35.0 vs. 18.2 months, P=0.119) than did RHB patients. Conclusions: Anti-PD-(L)1 monotherapy was safe and effective in patients with NSCLC and HBV infection. This population should not be excluded from receiving immunotherapy in routine clinical practice or within clinical trials if HBV biomarkers are monitored and antiviral prophylaxis is properly used