Background: The association between immune checkpoint inhibitors (ICIs) and Stevens-Johnsons syndrome (SJS) /toxic epidermal necrolysis (TEN) is unclear. We assessed the risk of SJS and TEN related to ICIs, via a systematic analysis of SJS/TEN cases reported in clinical trials and the FDA Adverse Event Reporting System (FAERS). Methods: We explored ICIs related SJS/TEN events in randomized control trials available in Clinical-Trials.gov and electronic databases (Pubmed, Embase, the Cochrane Central Register of Controlled Trials) up to 12 January 2021. Meta-analysis was performed by using Peto odds ratios (ORs) with 95% CIs. In a separate retrospective pharmacovigilance study of FAERs, cases of ICIs related SJS/TEN were extracted between the first quarter (Q1) of 2004 and Q4 of 2020. Disproportionality was analyzed using the proportional reports reporting odds ratio (ROR) and information components (IC). PROSPERO registration number: CRD42021232399. Findings: A total of 20 RCTs (11597 patients) were included. ICIs were associated with an increased risk of SJS/ TEN (OR= 4.33, 95%CI:1.90À9.87). FAERS pharmacovigilance data identified 411 cases of SJS (n = 253) or TEN (n = 184) related to ICIs therapy. ICIs were significantly associated with SJS/TEN (n = 411; ROR=2.88, 95%CI:2.61À3.17; IC=1.49, 95%CI:1.35À1.65). The median onset time of SJS/TEN was 25.5 days (SJS:21.5 days; TEN:32 days) (n = 190), 97.5% of patients discontinued use of ICIs when suffering from SJS/TEN (n = 201). Of 305 cases that reported outcomes, 113 (37%) resulted in death (SJS:19.9%, TEN:61.6%). Interpretation: These data suggest that ICIs were significantly associated with increased risk of SJS/TEN.

Curzerene is a sesquiterpene and component used in oriental medicine. It was originally isolated from the traditional Chinese herbal medicine rhizomes. In this study, anticancer activity of curzerene was examined in both and models. The result of the MTT assay showed that curzerene exhibited antiproliferative effects in SPC-A1 human lung adenocarcinoma cells in a time-dependent and dose-dependent manner. The anticancer ICs were 403.8, 154.8, and 47.0 µM for 24, 48, and 72 hours, respectively. The flow cytometry analysis indicated curzerene arrested the cells in the G2/M cell cycle and promoted or induced apoptosis of SPC-A1 cells. The percentage of cells arrested in the G2/M phase increased from 9.26 % in the control group cells to 17.57 % in the cells treated with the highest dose (100 µM) of curzerene. Western blot and RT-PCR analysis demonstrated that curzerene induced the downregulation of GSTA1 protein and mRNA expressions in SPC-A1 cells. Tumor growth was significantly inhibited in SPC-A1 cell-bearing nude mice by using curzerene (135 mg/kg daily), meanwhile, curzerene did not significantly affect body mass and the organs of the mice, which may indicate that curzerene has limited toxicity and side effects . In conclusion, curzerene could inhibit the proliferation of SPC-A1 human lung adenocarcinoma cells line in both and models. Focusing on its relationship with GSTA1, curzerene could induce the downregulation of GSTA1 protein and mRNA expressions in SPC-A1 cells. Curzerene might be used as an anti-lung adenocarcinoma drug candidate compound for further development.

UES and esophageal body pressure responses to low-volume ultraslow reflux and associated post-reflux residue are reduced in elderly individuals. This deterioration could have negative effects on airway protection for people in this age group.

In this paper, a novel small-molecular apoptotic PET imaging probe, 18F-ML-8 with a malonate motif structure, is presented and discussed. After study, the small tracer that belongs to a member of ApoSense family is proved to be capable of imaging merely apoptotic regions in the CTX treated tumor-bearing mice. The experimental result is further confirmed by in vitro cell binding assays and TUNEL staining assay. As a result, 18F-ML-8 could be used for noninvasive visualization of apoptosis induced by antitumor chemotherapy.