Proteolysis-targeting chimeras (PROTACs) have emerged as a promising therapeutic strategy for targeted protein degradation. However, the clinical application of PROTACs may be hindered by off-target toxicity resulting from non-tissue-specific protein degradation and ingenious prodrug strategies may open new avenues to addressing this concern. Herein, we propose a light-induced positive feedback strategy to use photodynamic therapy (PDT) to improve the activation efficiency of PROTAC prodrugs, monitor PROTAC release, and combine PROTAC to induce tumor cell apoptosis. In the hypoxic tumor microenvironment, the azo bond in AZO-PRO selectively cleaves, triggering the release of the potent protein degrader PRO and the multifunctional photosensitizer. Once activated, the fluoresce signal of the photosensitizer dramatically recovers, allowing monitoring of prodrug activation. Additionally, upon irradicating the tumor site using near-infrared (NIR) laser, PDT exacerbates tumor hypoxia, further promoting AZO-PRO activation. Our work introduces a novel approach to efficiently track and activate PROTAC prodrugs, enhance their antitumor efficacy, and mitigate off-target systemic toxicity.

Objective:To explore the mechanism of the active compounds in Banxia Houpo Decoction treating tension type headache through network pharmacology and molecular docking.Methods:The potentially effective components and targets of Banxia Houpo Decoction were screened by TCMSP, and the action targets of tension type headache were obtained by GeneCards, PharmGKB, TTD, Drugbank and OMIM. The intersection target of "Banxia Houpo Decoction - tension type headache" was obtained by Perl software. The protein interaction network was uploaded to STRING database and topological analysis was carried out. With the help of Cytoscape 3.8.0 software, the visualization network of "Banxia Houpo Decoction - medicine ingredient-Target-tension type headache" was constructed, and the GO enrichment analysis and KEGG pathway enrichment analysis of the intersection targets were carried out by using R 4.1.0 language and related programs. The AutoDockTools-1.5.6 software was used to complete the molecular docking analysis.Results:There were 33 intersection targets in Banxia Houpo Decoction and tension type headache. Topological attribute analysis suggested that MAPK1, TP53, ESR1, PTGS2, MYC, CYP1A2, CYP3A4 and GSTP1 might be important potential targets of Banxia Houpo Decoction in the prevention and treatment of tension type headache. GO enrichment analysis showed 516 cell biological processes (BP), 62 cell components (CC) and 149 molecular functions (MF). KEGG pathway enrichment analysis showed that there were 94 related signal pathways, such as cGMP-PKG signaling pathway, Cholinergicsynapse, Serotonergic synapse and TNF signaling pathway.Conclusions:Banxia Houpo Decoction has multi-component, multi-target and multi-pathway characteristics in the prevention and treatment of tension-type headache. It mainly acts on 5-HT synaptic pathway, TNF signal pathway, cholinergic synaptic pathway, G protein coupled receptor pathway and other pathways through ESR1, TP53, PGTS2 and other multi target.

Objective:To explore the clinical value of autoantibodies in patients with liver disease.Methods:We retrospectively analyzed the data of 1 495 outpatients or inpatients with liver disease in Beijing Ditan Hospital of Capital Medical University from August 2020 to April 2021. Indirect immunofluorescence and Western blot were used to detect antinuclear antibody (ANA) and antinuclear antibodies (ANAs).Results:ANA and ANAs were positive in patients with liver diseases of various etiologies. Among 1 495 patients with liver disease, 494 cases were ANA positive, the positive rate was 33.04%; 573 cases were positive for ANAs, the positive rate was 38.33%. The positive rate of ANA in the immune liver disease group (63.37%) was higher than that in the viral, alcoholic, fatty liver, confounding factors and other liver disease groups, and the difference was statistically significant ( P<0.01). The ANA positive rate between the viral, alcoholic, fatty liver, and confounding factor groups was statistically significant ( χ2=19.823, P<0.01), the positive rate of ANAs in the immune liver disease group (80.23%) was higher than that in other liver disease groups, and the difference was statistically significant ( P<0.05). The antibody titer of immune liver disease group was mainly 1∶1000, and other liver disease etiology groups was mainly 1∶100. The two most common fluorescent karyotypes in liver disease groups of different etiologies are cytoplasmic and nuclear granular types. The most common specific antibody in the immune liver disease group was anti-mitochondrial antibody type 2 (anti-AMA-M2) antibody, the most common anti-Ro-52 antibody in viral, drug-induced, complex etiology, and other etiological groups, and the most common anti-SSA antibody in alcoholic liver disease. Anti-SSA antibody (17.44%), anti-SSB antibody (9.30%), anti-CENP-B antibody (22.09%), anti-Ro-52 antibody (41.28%), anti-AMA-M2 antibody (51.74%) were positive in immune liver disease group, The rate was higher than that of other liver disease etiology groups, and the difference was statistically significant ( P<0.01). When the ANA fluorescence karyotype is nuclear granule type, the positive rate of anti-CENP-B antibody, anti-Ro-52 antibody, and anti-AMA-M2 antibody in the immune liver disease group was higher than that in the viral liver disease group ( P<0.01), The positive rate of anti-Ro-52 antibody was higher than that of drug-induced liver disease group ( P<0.05). Conclusions:The ANA titer of autoimmune liver disease was mainly (1∶1 000). ANAs were mainly positive for anti-SSA antibody, anti-SSB antibody, anti-CENP-B antibody, anti-Ro-52 antibody, and anti-AMA-M2 antibody, especially anti-AMA-M2 antibody. When combined with ANA fluorescent karyotype and ANAs for analysis, if the fluorescent karyotype is nuclear particle type, the positive anti-Ro-52 antibody in ANAs is more valuable in distinguishing immunity from viral and drug-induced liver diseases.