Graphical Abstract Highlights d CD19 + EVs through CD39 and CD73 hydrolyze ATP from tumor cells into adenosine d CD19 + EVs blunt post-chemotherapeutic CD8 T cell responses via adenosine d Tumor B cells produce more EVs by enhancing HIF-1a-mediated Rab27a transcription d IEBVs-Rab27a siRNA is a potential tool for improving chemotherapeutic effect SUMMARY Systemic immunosuppression greatly affects the chemotherapeutic antitumor effect. Here, we showed that CD19 + extracellular vesicles (EVs) from B cells through CD39 and CD73 vesicle-incorporated proteins hydrolyzed ATP from chemotherapy-treated tumor cells into adenosine, thus impairing CD8 + T cell responses. Serum CD19 + EVs were increased in tumor-bearing mice and patients. Patients with fewer serum CD19 + EVs had a better prognosis after chemotherapy. Upregulated hypoxia-inducible factor-1a (HIF-1a) promoted B cells to release CD19 + EVs by inducing Rab27a mRNA transcription. Rab27a or HIF-1a deficiency in B cells inhibited CD19 + EV production and improved the chemotherapeutic antitumor effect. Silencing of Rab27a in B cells by inactivated Epstein-Barr viruses carrying Rab27a siRNA greatly improved chemotherapeutic efficacy in humanized immunocompromised NOD Prkdc scid Il2rg À/À mice. Thus, decreasing CD19 + EVs holds high potential to improve the chemotherapeutic antitumor effect.

Background The aim of the study was to investigate whether simulation education (SE) and case management had any effect on glycemic control in type 2 diabetes (T2DM) patients. Methods In this single center pilot trial, 100 T2DM patients who received medication and basic diabetes self‐management education (DSME) were randomly divided into a control group ( n = 50) and an experimental group ( n = 50), who received SE and a case management program. Evaluation of biochemical indices was conducted at baseline and after 6 months. DSME consisted of 2‐hour group trainings weekly for 2 consecutive weeks followed by 2 × 30 minute education sessions after 3 and 6 months. The SE program comprised additional 50‐minute video sessions 3 times in the first week and twice in the second week. The experimental group was supervised by a nurse case manager, who followed up participants at least once a month, and who conducted group sessions once every 3 months, focusing on realistic aspects of physical activity and nutrition, with open discussions about setting goals and strategies to overcome barriers. Results After 6 months, HbA1c, fasting plasma glucose, and postprandial blood glucose level improvements were superior in the experimental group compared with the control group ( P < 0.05). Self‐care behavior adherence scores of healthy diet ( P = 0.001), physical activity ( P = 0.043), self‐monitoring of blood glucose ( P < 0.001), and reducing risks ( P < 0.001) were significantly increased in the experimental group compared with the control group. Conclusions Simulation education and case management added to routine DSME effectively improved glycemic control in T2DM patients.

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We investigate the robustness of complex communication networks on allocating redundancy links. The protecting key nodes (PKN) strategy is proposed to improve the robustness of complex communication networks against intentional attack. Our numerical simulations show that allocating a few redundant links among key nodes using the PKN strategy will significantly increase the robustness of scale-free complex networks. We have also theoretically proved and demonstrated the effectiveness of the PKN strategy. We expect that our work will help achieve a better understanding of communication networks.

Background: Pancreatic injury (pancreatitis, amylase/lipase elevation) is a rare adverse event of immune checkpoint inhibitors (ICIs). With the high number of clinical studies on ICIs, the incidence and characteristics of associated pancreatic injury (PI) need to be reevaluated.Methods: A systematic review and meta-analysis was conducted to assess the incidence of PI in cancer patients who received ICIs in randomized controlled trials (RCTs). PubMed, Embase, the ASCO, ESMO, and AACR conference proceedings before 1 April 2022, were investigated for relevant research.Results: 50 RCTs involving 35,223 patients were included. The incidence of ICIs-PI was 2.22% (95% CI = 1.94%–2.53%). The incidence of PI was 3.76% (95% CI = 1.84–7.67%) when combining two ICIs, which was higher than single ICIs [2.25% (95% CI = 1.91–2.65%)]. The ICIs were ranked from high to low based on PI incidence: PD-L1 inhibitors 3.01% (95% CI = 1.86–4.87%), CTLA-4 inhibitors 2.92% (95% CI = 0.99–8.65%) and PD-1 Inhibitor 2% (95% CI = 1.67–2.39%). The ICI with the highest rate of PI was pembrolizumab 7.23.% (95% CI = 1.69–30.89%). In addition, the incidence of severe ICIs-PI was 2.08% (95% CI = 1.76–2.46%); and the incidence of severe PI was 2.32% (95% CI = 1.76–3.06%) when combining two ICIs, which was higher than single ICI [1.95% (95% CI = 1.58–2.41%)]. The ICIs were ranked from high to low according to the incidence of severe PI: PD-L1 inhibitors 3.1% (95% CI = 1.7–5.64%), CTLA-4 inhibitors 2.69% (95% CI = 0.76–9.49%), PD-1 inhibitors 1.80% (95% CI = 1.41–2.29%).Conclusion: Treatment with multiple ICIs result in a higher incidence of PI compared to single ICIs, irrespective of the grade of pancreatic injury. The incidence of PI caused by PD-L1 inhibitors is higher than that of CTLA-4 inhibitors and PD-1 Inhibitor, and Pembrolizumab has the highest rate of ICIs-PI. Although the incidence of ICIs-PI is not high, they are usually severe (≥ grade 3 events).