BACKGROUND Endolymphatic hydrops (EH) has long been considered the primary pathological feature of Meniere's disease (MD). Consequently, most existing animal models of MD are EH models, yet they cannot fully reflect all the pathological features of MD. Moreover, the causal relationship between EH and MD remains controversial. The objective of this study is to develop an animal model of MD that accurately reflects the clinical and pathophysiological characteristics of the disease. METHODS Male C57BL/6J mice aged 6-8 weeks received daily injections of inflammatory soup (IS) at the middle of the right postauricular groove for 5 consecutive weeks. EH was assessed weekly using hematoxylin and eosin staining. Changes in auditory function were evaluated using auditory brainstem response testing and immunofluorescence staining. Vestibular function was assessed using the open-field test, balance beam test, vestibulo-ocular reflex, and immunofluorescence staining. RESULTS Morphological findings revealed EH in cochlear sections 2 weeks after IS injection. The auditory brainstem response results showed significantly higher thresholds by week 2 after IS injection. The I-wave amplitude decreased as early as week 1 after injection. Immunofluorescence analysis demonstrated reduced inner hair cell synaptic ribbon counts and decreased spiral ganglion cell density. Immediately after each IS injection, the mice exhibited circling behavior and transient agitation, lasting approximately 10 seconds. Decreased locomotor activity was observed in the open-field test at 1, 2, and 5 weeks after IS injection. Vestibular testing showed prolonged balance beam-crossing time at 2 and 5 weeks and reduced vestibulo-ocular reflex gain at 1, 2, and 5 weeks after IS injection. Morphological findings also revealed decreased stereocilia bundle density in the utricle and cristae of the semicircular canals. CONCLUSIONS This study established an animal model exhibiting several key features of MD, including EH, hearing loss, and vestibular dysfunction. This model may provide a useful experimental tool for investigating the pathogenesis of MD and exploring potential therapeutic strategies.
Abstract Background: Esophageal cancer (EC) is the eighth most common cancer and fifth leading cause of cancer death globally. Asia bears a disproportionate burden, accounting for approximately 80% of cases, yet comprehensive regional assessments remain limited. Methods: Using data from the Global Burden of Disease (GBD) 2023 study, we systematically analyzed EC incidence, mortality, and disability-adjusted life years (DALYs)—along with their corresponding 95% uncertainty intervals (UIs)—by sex and age groups across five Asian subregions and 33 countries and territories from 1990 to 2023. The quantification of trends was achieved through the utilization of age-standardized rates (ASRs) and estimated annual percentage change (EAPC). Additionally, risk attribution and decomposition analyses were conducted. Besides, we focused on China and analyzed the burden of EC there. Results: In 2023, East Asia remained the region with the heaviest burden of EC, with 261,367.96 (95% UI: 223,690.57, 299,941.44) deaths and an age-standardized mortality rate (ASMR) of 10.88 (95% UI: 9.34, 12.43) per 100,000 population. Central Asia demonstrated the most significant decline in burden (EAPC for ASMR = –3.67% [95% CI: –3.86%, –3.47%]), while South Asia was the only region with an increasing trend (EAPC for ASMR = 1.80% [95% CI: 1.34%, 2.27%]), primarily linked to chewing tobacco and diet low in vegetables. Smoking and high alcohol use remained the dominant risk factors in East Asia and the high-income Asia-Pacific region. The burden of EC among males was found to be considerably higher than among females. Decomposition analysis identified population aging and growth as key drivers of death increases, despite mitigating epidemiological improvements. China accounted for approximately 59.1% of Asia’s total incident cases (267,431.62 out of 452,378.59), approximately 59.8% of deaths (254,462.56 out of 425,429.23), and 55.7% of DALYs (5,734,333.60 out of 10,295,667.36) in 2023, making it the dominant contributor to the overall Asian EC burden. Although the EC burden remains substantial in China, the ASRs have shown a particularly pronounced reduction, with the EAPC values were –3.42% (95% CI: –3.75%, –3.09%) for ASIR, –3.58% (95% CI: –3.92%, –3.24%) for ASMR, and –3.96% (95% CI: –4.31%, –3.60%) for ASDR. Smoking and high alcohol use remained the two leading risk factors for EC in China. Conclusion: Disease burden of EC in Asia remains substantial and heterogeneous, with China contributing the largest share of cases, deaths, and DALYs in the region. Targeted prevention, lifestyle modification, and advanced screening for high-risk populations are crucial to reduce future burden.
Abstract Aptamers are single-stranded DNA or RNA molecules that fold into unique 3-dimensional structures and are selected through systematic evolution of ligands by exponential enrichment (SELEX) and its advanced variants. They provide high target specificity, low immunogenicity, easy synthesis and modification, reversible denaturation, and superior tissue penetration compared with monoclonal antibodies. The approvals by the Food and Drug Administration of pegaptanib in 2004 and avacincaptad pegol in 2023 established aptamers as clinically viable therapeutic platforms. Leukemia is a hematological malignancy characterized by the uncontrolled proliferation of abnormal white blood cells. Its genetic and molecular heterogeneity poses diagnostic and therapeutic challenges. Although the rapid development of novel therapies has improved outcomes for patients with leukemia, challenges such as high relapse rates (particularly in acute myeloid leukemia [AML]), tyrosine kinase inhibitor resistance in chronic myeloid leukemia (CML), and treatment toxicity persist. Diagnostically, aptamer-based biosensors are sensitive detectors of leukemia cells and minimal residual disease. Therapeutically, aptamer–drug conjugates and standalone aptamers enable targeted delivery of cytotoxic agents (methotrexate and doxorubicin) or modulate oncogenic pathways (nucleolin, protein tyrosine kinase 7, and C-X-C motif chemokine 12). This review details the clinical milestones (AS1411 in AML and NOX-A12 in chronic lymphocytic leukemia [CLL]) and preclinical successes across AML, ALL, CML, and CLL, additionally spotlighting the challenges in stability, scalability, and tumor penetration. Future research should focus on enhancing stability, advanced delivery systems, and synergistic immunotherapy combinations.
Abstract Lung cancer, the leading cause of cancer-related mortality worldwide, remains a formidable therapeutic challenge due to profound tumor heterogeneity and the emergence of drug resistance. Conventional small-molecule inhibitors that rely on an occupancy-driven mechanism are frequently undermined by acquired mutations. Proteolysis-targeting chimeras (PROTACs) represent an event-driven therapeutic strategy that enables catalytic degradation of disease-driving proteins. This review systematically summarizes recent advances in PROTAC technology for lung cancer, emphasizing its efficacy against key oncogenic drivers (e.g., EGFR, KRAS, ALK, MET ) and reactivating apoptosis (e.g., via B-cell lymphoma [BCL]-2/BCL-extra-large [BCL-2/BCL-xL] degrader 753b). We further highlight potential applications targeting epigenetic regulators such as bromodomain protein 4 (BRD4) to overcome immunosuppression via programmed death ligand-1 degradation. Despite promising preclinical results, the clinical translation of PROTACs faces challenges in pharmacokinetics, tissue specificity, and resistance. Finally, we discuss emerging innovations such as next-generation degraders and advanced delivery strategies, including antibody-PROTAC conjugates (Ab-PROTACs) and nano-PROTACs, underscoring PROTACs’ potential to redefine precision oncology in lung cancer.
