BackgroundHigh tumor mutational burden (TMB-H) is correlated with enhanced objective response rate (ORR) and progression-free survival (PFS) for certain cancers receiving immunotherapy. This study aimed to investigate the safety and efficacy of toripalimab, a humanized programmed death-1 (PD-1) antibody, in advanced gastric cancer (AGC), and the predictive survival benefit of TMB and PD-L1.Patients and methodsWe reported on the AGC cohort of phase Ib/II trial evaluating the safety and activity of toripalimab in patients with AGC, oesophageal squamous cell carcinoma, nasopharyngeal carcinoma and head and neck squamous cell carcinoma. In cohort 1, 58 chemo-refractory AGC patients received toripalimab (3 mg/kg d1, Q2W) as a monotherapy. In cohort 2, 18 chemotherapy-naive AGC patients received toripalimab (360 mg d1, Q3W) with oxaliplatin 130 mg/m2 qd, d1, capecitabine 1000 mg/m2 b.i.d., d1–d14, Q3W as first-line treatment. Primary end point was ORR. Biomarkers such as PD-L1 and TMB were evaluated for correlation with clinical efficacy.ResultsIn cohort 1, the ORR was 12.1% and the disease control rate (DCR) was 39.7%. Median PFS was 1.9 months and median OS was 4.8 months. The TMB-H group showed significant superior OS than the TMB-L group [14.6 versus 4.0 months, HR = 0.48 (96% CI 0.24–0.96), P = 0.038], while PD-L1 overexpression did not correlate with significant survival benefit. A 77.6% of patients experienced at least one treatment-related adverse event (TRAE), and 22.4% of patients experienced a grade 3 or higher TRAE. In cohort 2, the ORR was 66.7% and the DCR was 88.9%. A 94.4% of patients experienced at least one TRAE and 38.9% of patients experienced grade 3 or higher TRAEs.ConclusionsToripalimab has demonstrated a manageable safety profile and promising antitumor activity in AGC patients, especially in combination with XELOX. High TMB may be a predictive marker for OS of AGC patients receiving toripalimab as a single agent.Trial registrationClinicalTrials.gov NCT02915432.

Based on liquid crystal elastomer (LCE) materials, hierarchically structured soft actuators can meet some requirements for "human-friendly" working mode and execute complex tasks with intelligent adaptation to environmental changes. However, few researchers have paid much attention to the preparation methods of multicomponent/hierarchical LCE actuators. In this communication, we demonstrate the successful integration of an exchangeable diselenide chain extender for the preparation of dynamic LCEs, which could be reprogrammed on heating or under visible light illumination. Moreover, the rearrangeable polydiselenide networks could be applied to develop the self-welding technology toward fabricating hierarchically structured LCE actuators with sophisticated deformability without using any auxiliary reagent (adhesive, tape, catalysts or initiator) during the assembling process.

Background:A randomized controlled trial was performed to compare analgesic effects and adverse effects of oxycodone and sufentanil in patient-controlled intravenous analgesia (PCIA) after abdominal surgery under general anesthesia.Methods:Adult patients undergoing elective abdominal surgery were randomly allocated into oxycodone and sufentanil groups according to the randomization sequence. Study personnel, health-care team members, and patients were masked to the group assignment throughout the study period. Oxycodone (0.1 mg/kg for endoscopy; 0.15 mg/kg for laparotomy) or sufentanil (0.1 μg/kg for endoscopy; 0.15 μg/kg for laparotomy) was administrated at the end of surgeries. Postoperative pain was controlled using PCIA. Bolus dose was 2 mg and 2 μg for oxycodone and sufentanil group, respectively. The lockout time was 5 minutes for all patients, and there was no background infusion for oxycodone group, whereas 0.02 μg/kg/h background infusion was administrated in sufentanil group. The primary outcomes were the total analgesic doses in PCIA, effective bolus times, the length of first bolus since patients returning to ward from postanesthesia care unit (PACU), rescue analgesic rate in PACU, numeric rating scales, functional activity scores, and patients’ satisfaction scores.Results:A total of 200 patients were screened, and 175 patients were enrolled. Patients were randomly assigned to oxycodone (n = 87) and sufentanil (n = 88) groups. Both oxycodone and sufentanil PCIA provided adequate postoperative pain relief. Patients in oxycodone group showed a shorter consciousness recovery time after surgery. The major adverse effect in patients from oxycodone group was nausea/vomiting, whereas multiple adverse complications including nausea/vomiting, pruritus, and respiratory depression were observed in patients from sufentanil group. Patients from oxycodone group showed significantly reduced analgesic drug consumption (calculated as equivalent dose of morphine), functional activity scores, and patient satisfaction scores.Discussion:Compared with sufentanil PCIA, oxycodone PCIA showed better analgesic effects, lower incidence of adverse complications, and less analgesic drug consumption during postoperative pain management.