Background and aims:Radiofrequency ablation(RFA)is the first-line treatment for early-stage hepato-cellular carcinoma(HCC).However,recurrence after curative RFA remains a significant challenge for HCC patients.Although RFA induces an immune response,the anti-tumor effect is often limited by the immunosuppressive tumor microenvironment.Enhancing anti-tumor immunity is essential to improve treatment efficacy and prevent recurrence.In this study,we explore the efficacy and underlying mechanisms of the combination of RFA and anti-PD-1 in suppressing abscopal and recurrent tumors.Methods:We established a bilateral subcutaneous HCC mouse model and performed complete RFA on the right-flank tumor.Anti-PD-1 or anti-IgG was administered post-RFA.Tumor growth,immune cell profiles,and molecular pathways were assessed using flow cytometry,immunohistochemistry staining,RNA-sequencing,and Western blot.Chemokines released by the tumor were detected by ELISA.An in vivo tumor rechallenge experiment was performed after a complete tumor regression to evaluate the immune memory induced by the RFA+anti-PD-1 treatment.Results:RFA combined with anti-PD-1 significantly suppressed abscopal tumor growth and prolonged survival.Compared with RFA monotherapy,the infiltration of CD8+T cells and dendritic cells was sig-nificantly increased in the combined treatment group,while PMN-MDSCs were markedly reduced.Mechanistically,the chemokine signaling pathway and JAK-STAT signaling pathway were activated in the tumor of the RFA+anti-PD-1 group with upregulation of CXCL10 to recruit CD8+T cells.In addition,the combination therapy induced durable immune memory that inhibited rechallenge tumor outgrowth.Conclusions:Our study discovered that RFA combined with anti-PD-1 induced anti-tumor immunity to inhibit abscopal tumors and durable immune memory to prevent recurrence,suggesting RFA+anti-PD-1 as a potential therapeutic strategy for multifocal HCC and preventing recurrence.

Hederin is a natural active component of triterpenoid saponins extracted from many medicinal herbs， such as Lithospermum erythrorhizon， Pulsatilla chinensis， and Clematis florida. It has attracted much attention from doctors for its anti-inflammatory， anti-convulsive， anti-oxidation and anti-leishmaniasis activities. Hederin has significant anti-tumor bioactivity and is expected to be a potential drug for the treatment of malignant tumors. The available studies have demonstrated that hederin can promote the apoptosis， inhibit the proliferation， metastasis， and invasion， and induce the autophagy of tumor cells， exhibiting a promising prospect in the treatment of breast cancer， lung cancer， liver cancer， and pancreatic cancer. Specifically， hederin can regulate the phosphoinositide 3-kinase/protein kinase B （PI3K/Akt） pathway， reactive oxygen species （ROS）， and microRNA （miRNA） to trigger tumor cell apoptosis. Its anti-proliferation activity is mainly reflected in the regulation of cyclin and cyclin-dependent kinase （CDK）. Hederin inhibits the metastasis and invasion of tumor cells by blocking epithelial-mesenchymal transformation （EMT）. In addition， hederin can influence metabolic reprogramming to induce tumor cell autophagy. Hederin is involved in a variety of pathways to exert its anti-tumor activity and may become a novel anti-tumor drug in the future， which give new sights into the study of hederin in the anti-tumor field. There are few studies about hederin and no systematic review of its anti-tumor mechanisms. Therefore， this study reviewed the studies about the anti-tumor mechanism of hederin， aiming to provide reference and information for researchers and clinical staff.

Objective To analyze related factors for pacemaker pocket infection in elderly patients after implantation of permanent pacemakers and to provide a theoretical basis for preventing pacemaker pocket infection.Methods Pacemaker pocket infection and related factors were analyzed for 412 patients who received implantation of permanent pacemakers from Apr.2010 to Jun.2013 in the Department of Cardiology.Results With 5 cases of pacemaker pocket infection,the rate of infection was 1.2％.The infected patients were older than the uninfected patients [(74.5±4.2) years vs.(60.3±6.6) years,t=4.781,P＜0.01].The rate of infection was higher in patients who had undergone operations twice or more than in patients who had undergone one operation [10.0％ (3/300) vs.0.5％ (2/382),x2=10.583,P＜0.01].The rate of infection was higher in patients with the operation lasting 2 hours or longer than in patients with the operation time shorter than 2 hours [(3.8％ (4/106) vs.0.3％ (1/306),x2=7.802,P＜0.01].The rate of infection was higher in patients with pocket hematoma than in patients without pocket hematoma [16.7％ (3/18) vs.0.5％(2/394),x2=37.492,P＜0.01].Independent risk factors for pacemaker pocket infection included pocket hematoma (OR=6.193),number of operations≥2 (OR=2.594),operating time≥2 hours (OR=2.265) and age of 75 years or older (OR =2.193).Conclusions Pocket infection after implantation of permanent pacemakers is related to pocket hematoma,number of operations,operating time and age.