AIM:To explore whether angiotensin Ⅱtype 2 receptor antagonist EMA 401 decreases neuropathic pain and the expression of growth-associated protein-43 (GAP-43), protein kinase C (PKC) and calmodulin (CaM) in dorsal root ganglia (DRG) during chronic constriction injury (CCI) in rats.METHODS:SD rats were used to establish CCI model and randomly divided into 4 groups.The rats in model group were given equal volume of normal saline by intra-gastric administration .The rats in low dose ( LD) group were given 5 mg/kg EMA401 by intragastric administration .The rats in middle dose ( MD) group were given 10 mg/kg EMA401 by intragastric administration .The rats high dose ( HD) group were given 20 mg/kg EMA401 by intragastric administration .The rats in sham operation group received equal volume of normal saline by intragastric administration .Thermal withdrawal latency ( TWL ) and mechanical withdrawal threshold (MWT) were measured before operation and 7 d, 14 d and 28 d after CCI.After behavioral test, DRG of lumbar spinal was obtained from each group , and was used to determine Ca 2+concentration by o-cresolphthalein complexone microplating method, and the expression of GAP-43, PKC and CaM at mRNA and protein levels by Western blotting and RT-PCR.RE-SULTS:Compared with model group, EMA401 significantly increased the TWL and MWT (P <0.05).Meanwhile, EMA401 significantly reduced Ca 2+concentration and the expression of GAP-43, PKC and CaM at mRNA and protein levels in the DRG (P<0.05).CONCLUSION:EMA401 may attenuate neuropathic pain of CCI by inhibiting Ca 2+concentra-tion and the expression of GAP-43, PKC and CaM.

Amplifying "eat me signal" during tumor immunogenic cell death (ICD) cascade is crucial for tumor immunotherapy. Inspired by the indispensable role of adenosine triphosphate (ATP, a necessary "eat me signal" for ICD), a versatile ICD amplifier was developed for chemotherapy-sensitized immunotherapy. Doxorubicin (DOX), ATP and ferrous ions (Fe²⁺) were co-assembled into nanosized amplifier (ADO-Fe) through π‒π stacking and coordination effect. Meanwhile, phenylboric acid-polyethylene glycol-phenylboric acid (PBA-PEG-PBA) was modified on the surface of ADO-Fe (denoted as PADO-Fe) by the virtue of d-ribose unit of ATP. PADO-Fe could display active targetability against tumor cells via sialic acid/PBA interaction. In acidic microenvironment, PBA-PEG-PBA would dissociate from amplifier. Moreover, high H₂O₂ concentration would induce hydroxyl radical (·OH) and oxygen (O₂) generation through Fenton reaction by Fe²⁺. DOX and ATP would be released from the amplifier, which could induce ICD effect and "ICD adjuvant" to amplify this process. Together with programmed death ligands 1 (PD-L1) checkpoint blockade immunotherapy, PADO-Fe could not only activate immune response against primary tumor, but also strong abscopal effect against distant tumor. Our simple and multifunctional ICD amplifier opens a new window for enhancing ICD effect and immune checkpoint blockade therapy.