Yanyan Xu

Introduction: Psoriasis is an autoimmune disease characterized primarily by chronic inflammation, with suboptimal clinical therapeutic outcomes. Quercetin, a bio-safe plant secondary metabolite, exerts anti‐inflammatory effects by modulating multiple signaling pathways and holds promise as a therapeutic candidate for psoriasis. Methods: Our preliminary studies demonstrated that silk protein (SF) derived from silkworm cocoons exhibits excellent biocompatibility and can form hydrogels, serving as an ideal drug carrier for skin applications. We loaded quercetin into the SF hydrogel system and systematically investigated the therapeutic efficacy of this composite formulation (QSF) against imiquimod-induced psoriasis models through in vitro and in vivo experiments. Results: The hydrogel exhibited desirable enzyme-responsive properties. When exposed to an in vitro microenvironment containing 10 nM MMP‐9, the hydrogel network rapidly disintegrated, achieving a cumulative quercetin release of 58.26% ± 7.64% within 24 h. The enriched quercetin in lesion tissues markedly reduced the positive expression levels of IL‐17, TNF‐α, and IL‐1β, with inhibition rates of 32.14%, 20.25%, and 33.71%, respectively, which effectively interrupted the inflammatory cascade and obviously alleviated skin desquamation and pruritus. Discussion: Collectively, the fabricated QSF hydrogel presents anti‐inflammatory and symptomatic relief effects, providing a feasible strategy and experimental basis for the development of novel topical preparations for psoriasis treatment.

Background: Antibody–drug conjugates (ADCs) exhibit structurally driven and highly heterogeneous toxicities, yet most pharmacovigilance studies remain drug-centered and lack systematic component-level evaluation. This study provides a comprehensive real-world safety assessment of FDA-approved ADCs using a component-based analytical framework. Methods: All adverse event (AE) reports for 14 FDA-approved ADCs (2004–2024) were extracted from the Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS). ADCs and AEs were included when positive signals were simultaneously detected by four disproportionality methods (reporting odds ratio (ROR), proportional reporting ratio (PRR), information component (IC), and empirical Bayes geometric mean (EBGM)) under a multi-method consensus criterion (MCC). AEs were classified using MedDRA at the preferred term (PT) and system organ class (SOC) levels. Signal prioritization was performed by ranking ROR values within each key component type—antibody subtype, linker type, payload category, and drug-to-antibody ratio (DAR) value class, with the top 20 signals designated as “strong signals.” False discovery rate (FDR) correction was applied for sensitivity analysis. Results: A total of 52,699 positive PT-level AE signals were included across 13 ADCs. Distinct toxicity signatures were observed across component types: IgG1-based ADCs demonstrated prominent ocular and corneal toxicity and treatment-related secondary lymphoma, whereas IgG4-based ADCs were dominated by hepatobiliary injury, vascular toxicity, bone marrow suppression, and severe infections. ADCs with cleavable linkers showed toxicity patterns enriched for treatment-related secondary lymphoma, pulmonary toxicity, and infections, while non-cleavable linker ADCs showed a highly distinctive pattern dominated by ocular toxicity, particularly corneal epithelial and stromal injury. DNA-damaging payload ADCs exhibited severe systemic toxicities, including hepatobiliary toxicity, vascular injury, interstitial lung disease, serious infections, and bone marrow suppression. In contrast, microtubule inhibitor payloads mainly produced ocular and corneal toxicity, treatment-related secondary lymphoma, and local hemorrhagic events. DAR 3–5 ADCs were highly enriched for ocular toxicity and treatment-related secondary lymphoma; DAR < 3 ADCs were characterized by hepatobiliary injury and infection-dominant patterns, and DAR > 5 ADCs demonstrated a heterogeneous multi-organ toxicity profile spanning metabolic, hepatic, pulmonary, infectious, neurological, vascular, and ocular domains. All MCC-identified PT-level AE signals remained significant after FDR correction. Conclusion: This large-scale real-world evaluation reveals clear component type-specific toxicity signatures among ADCs, supporting more targeted safety monitoring and informing rational ADC design.

Objectives: This study aimed to evaluate the antiviral efficacy of lopinavir-ritonavir alone or combined with arbidol in the treatment of hospitalized patients with common coronavirus disease-19 (COVID-19). Materials and methods: In this retrospective observational study, hospitalized COVID-19 patients were identified and divided into two groups based on the antiviral agents during their hospitalization. Patients in group LR were treated with lopinavir-ritonavir 400 mg/100 mg, twice a day, while patients in group LR+Ar were treated with lopinavir-ritonavir 400 mg/100 mg twice a day and arbidol 200 mg three times a day for at least 3 days. Data from these patients were collected from electronic medical record management system. Results: 73 patients were divided into two groups: group LR (34 cases) and group LR+Ar (39 cases), according to the antiviral agents. The overall cure rate of COVID-19 in group LR+Ar and group LR were 92.3% and 97.1%, respectively, with no significant difference (p = 0.62). In a modified intention-to-treat analysis, lopinavir-ritonavir combined with arbidol led to a median time of hospital stay that was shorter by 1.5 days than in group LR (12.5 days vs. 14 days). The percentages of COVID-19 RNA clearance was 92.3 in group LR and 97.1 in group LR+Ar which was similar to the cure rate. The median time to nucleic acid turning negative = (date of first negative PCR test) - (date of last positive PCR test) was 8.0 days in both groups with no significant difference (p = 0.59). Treatment of lopinavir-ritonavir combined with arbidol did not significantly accelerate main symptom improvement and promote the image absorption of pulmonary inflammation. Conclusion: No benefit was observed in the antiviral effect of lopinavir-ritonavir combined with arbidol compared with lopinavir-ritonavir alone in the hospitalized patients with COVID-19. More clinical observations in COVID-19 patients may help to confirm or exclude the effect of antiviral agents.