Clinical Analysis of Transcatheter Arterial Chemoembolization Sequential Microwave Ablation Combined with Targeted Therapy and Immunotherapy in the Treatment of Large Hepatocellular Carcinoma

Objective: To investigate the safety and efficacy of Transcatheter Arterial Chemoembolization (TACE), sequential Microwave Ablation (MWA) combined with targeted therapy and immunotherapy versus TACE combined with targeted therapy and immunotherapy in the treatment of large hepatocellular carcinoma (defined as tumor diameter > 5 cm). Methods: The prospective cohort study was conducted, with 81 patients with large hepatocellular carcinoma who were admitted to Jingzhou Central Hospital from 2018 to 2022, they were divided into two groups, 41 patients received TACE sequential MWA combined with targeted therapy and immunotherapy (observation group), and 40 patients received single TACE combined with targeted therapy and immunotherapy (control group). The short-term efficacies after 3 months of treatment, the Disease Control Rate (DCR), the Overall Survival (OS), adverse drug reactions and complications were compared and analyzed between the two groups. Results: The Objective Response Rate (ORR) of the observation group was significantly higher than that of the control group (ORR: 85.4% vs 57.5%, P = 0.005), The median Progression-Free Survival (PFS) and median OS of the observation group were better than those of the control group (mPFS: 16 months vs 10 months, P = 0.004;mOS: 39 months. vs 24 months, P = 0.008). The 1-, 2- and 3-year progression-free survival rates of the observation group were 72.9%, 50.4%, and 25.6%, and those of the control group were 30.4%, 11.0%, and 3.7%. The 1-, 2- and 3-year overall survival rates of the observation group were 78.9%, 71.7%, and 65.2%, and those of the control group were 65.1%, versus 42.1% and 36.9%. There was no significant difference in the incidence of adverse drug reactions and complications between the two groups. In this study, the adverse drug reactions were mild in Grades 1 - 2. Conclusion: TACE sequential MWA combined with targeted therapy and immunotherapy has efficacy and safety.

Microbe-derived non-necrotic glycoside hydrolase family 12 proteins act as immunogenic signatures triggering plant defenses

Plant pattern recognition receptors(PRRs)are sentinels at the cell surface sensing microbial invasion and activating innate immune responses.During infection,certain microbial apoplastic effectors can be recognized by plant PRRs,culminating in immune responses accompanied by cell death.However,the intricated relationships between the activation of immune responses and cell death are unclear.Here,we studied the glycoside hydrolase family12(GH12)protein,Ps109281,secreted by Phytophthora sojae into the plant apoplast during infection.Ps109281 exhibits xyloglucanase activity,and promotes P.sojae infection in a manner dependent on the enzyme activity.Ps109281 is recognized by the membranelocalized receptor-like protein RXEG1 and triggers immune responses in various plant species.Unlike other characterized GH12 members,Ps109281 fails to trigger cell death in plants.The loss of cell death induction activity is closely linked to a sequence polymorphism at the Nterminus.This sequence polymorphism does not affect the in planta interaction of Ps109281 with the recognition receptor RXEG1,indicating that cell death and immune response activation are determined using different regions of the GH12 proteins.Such GH12 protein also exists in other Phytophthora and fungal pathogens.Taken together,these results unravel the evolution of effector sequences underpinning different immune outputs.