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Background: The combination of programmed cell death ligand-1 (PD-L1) immune checkpoint blockade (ICB) and immunogenic cell death (ICD)-inducing chemotherapy has shown promise in cancer immunotherapy. However, triple-negative breast cancer (TNBC) patients undergoing this treatment often face obstacles such as systemic toxicity and low response rates, primarily attributed to the immunosuppressive tumor microenvironment (TME). Methods and results: In this study, PD-L1-targeted theranostic systems were developed utilizing anti-PD-L1 peptide (APP) conjugated with a bio-orthogonal click chemistry group. Initially, TNBC was treated with azide-modified sugar to introduce azide groups onto tumor cell surfaces through metabolic glycoengineering. A PD-L1-targeted probe was developed to evaluate the PD-L1 status of TNBC using magnetic resonance/near-infrared fluorescence imaging. Subsequently, an acidic pH-responsive prodrug was employed to enhance tumor accumulation via bio-orthogonal click chemistry, which enhances PD-L1-targeted ICB, the pH-responsive DOX release and induction of pyroptosis-mediated ICD of TNBC. Combined PD-L1-targeted chemo-immunotherapy effectively reversed the immune-tolerant TME and elicited robust tumor-specific immune responses, resulting in significant inhibition of tumor progression. Conclusions: Our study has successfully engineered a bio-orthogonal multifunctional theranostic system, which employs bio-orthogonal click chemistry in conjunction with a PD-L1 targeting strategy. This innovative approach has been demonstrated to exhibit significant promise for both the targeted imaging and therapeutic intervention of TNBC. [ABSTRACT FROM AUTHOR]

Objective: Hypoglossal-facial nerve anastomosis (HFA) is the most commonly used surgical treatment for severe facial palsy that does not respond to conservative treatments. A major complication of HFA is the loss of tongue function. The authors aimed to evaluate whether anastomosing the transected hypoglossal nerve using the ramus descendens hypoglossi could prevent tongue deviation and dysfunction in patients undergoing HFA., Methods: In this randomized trial, adult patients with severe peripheral facial palsy (House-Brackmann grade V or VI) who did not respond to at least 6 months of conservative treatment were randomized at a 1:1 ratio to undergo either HFA alone (control group) or HFA plus anastomosis between the hypoglossal nerve and descendens hypoglossi (intervention group). The primary endpoint was tongue deviation angle at 12 months. Key secondary endpoints included tongue disability (chewing difficulty, swallowing defect, and articulation defect), tongue disability index (TDI; range 1-4, with a higher score indicating more severe disability), and facial nerve function., Results: Twenty patients were enrolled (10 in each group). At 12 months, the tongue deviation angle was significantly lower in the intervention group than in the control group (7.8° ± 5.1° vs 23.6° ± 9.6°, p < 0.001). Although not statistically significant, the intervention group had lower rates of chewing difficulty (1/10 vs 3/10, p = 0.58), swallowing defect (1/10 vs 5/10, p = 0.14), and articulation defect (2/10 vs 6/10, p = 0.17). TDI was significantly lower in the intervention group (1.5 ± 0.6 vs 2.5 ± 0.3, p < 0.001). The percentage of the patients achieving House-Brackmann grade II or III was 80% in each group., Conclusions: Anastomosis of the descendens hypoglossi to the transected hypoglossal nerve attenuated tongue deviation in patients undergoing HFA for facial palsy, without compromising facial nerve function. Clinical trial registration no: ChiCTR2000034372 (Chinese Clinical Trials Registry).