Cancer incidence is increasingly seen in younger individuals. Molecular distinctions between young and elderly patients at onset are understudied. This study used public databases to explore genomic, transcriptomic, and immune-related features across age groups in cervical cancer. Additionally, it aims to create a prognostic model applicable across diverse age cohorts, enabling precise patient stratification, and personalized therapies. Gene mutations, expression data, and clinicopathological information were obtained from 317 cervical cancer patients. These patients were divided into a young group and an old group based on the median age of onset. The characteristics of differential gene mutation, gene expression, and immune cells analysis were analyzed by R software. Finally, the prognostic model was constructed by univariate Cox, least absolute shrinkage and selection operator, and multivariate Cox regression analyses of angiogenic and immune gene sets. Its validity was further confirmed using an additional 300 cervical squamous cell carcinoma and endocervical adenocarcinoma tissues. Cervical cancer patients at elderly onset age exhibit a significantly higher frequency of NOTCH1 and TP53 driver mutations compared to young patients, along with a notably higher tumor mutational burden. However, there were no significant differences between the 2 groups in terms of genomic instability and age-related mutational signatures. Differential gene expression analysis revealed that the young group significantly upregulated interferon-alpha and gamma responses and exhibited significantly higher activity in multiple metabolic pathways. Immune microenvironment analysis indicated enrichment of dendritic cells and natural killer cells in the young group, while transforming growth factor-β signature was enriched in the elderly group, indicating a higher degree of immune exclusion. A multigene prognostic model based on angiogenesis and T cell immune gene sets showed excellent prognostic performance independent of clinical factors such as age. High-risk groups identified by the model exhibit significant activation of tumor-promoting processes, such as metastasis and angiogenesis. Our study reveals distinct patterns in cancer-driving mechanisms, biological processes, and immune system status between young and elderly patients at onset with cervical cancer. These findings shed light on the age-specific underlying mechanisms of carcinogenesis. Furthermore, an independent molecular prognostic model is constructed to provide valuable references for patient stratification and the development of potential drug targets.

Purpose: Immunotherapy as a neoadjuvant treatment approach has achieved certain therapeutic effects in various types of cancer. However, in the specific cancer type of hepatocellular carcinoma (HCC), standardized protocols for neoadjuvant immunotherapy remain to be defined. This systematic review and meta-analysis focus on evaluating the efficacy and safety of neoadjuvant immunotherapy in the treatment of HCC, aiming to provide a robust basis for clinical decision-making.Methods: This study systematically searched databases such as PubMed, EMBASE, the Cochrane Library, and conference proceedings to identify clinical trials focusing on patients with HCC undergoing neoadjuvant immunotherapy. The Review Manager 5.4 software was applied to estimate the odds ratio (OR) of effect sizes and their corresponding 95% confidence intervals (CI).Results: Immune checkpoint inhibitors (ICIs) demonstrate significant efficacy in improving pathological outcomes and safety profiles in patients with resectable hepatocellular carcinoma (HCC). Specifically, ICIs significantly increase the pathological complete response (pCR) rate (OR = 0.23, 95% CI [0.14, 0.37], p < 0.00001) and major pathological response (MPR) rate (OR = 0.47, 95% CI [0.32, 0.70], p = 0.0002). They also markedly enhance the objective response rate (ORR) (OR = 0.42, 95% CI [0.28, 0.63], p < 0.0001). Furthermore, ICIs potentially improve the surgical resection rate (OR = 3.91, 95% CI [2.05, 7.45], p < 0.0001) and reduce the incidence of grade 3–4 treatment-related adverse events (TRAEs) (OR = 0.27, 95% CI [0.17, 0.44], p < 0.00001), indicating both therapeutic benefits and acceptable toxicity profiles.Conclusion: Neoadjuvant immunotherapy shows promise in the treatment of resectable HCC. Nonetheless, to further validate its efficacy, more large-scale, well-designed clinical trials are necessary to provide conclusive evidence.Systematic review registration: This comprehensive review adheres to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) standards and has been carried out as per a preregistered protocol (PROSPERO registration number: CRD42024560660).

CIRI is characterized by severe oxidative stress and neuroinflammation, fundamentally driven by the pathological interplay between defective mitophagy and robust pyroptosis. While the natural isoflavonoid puerarin exhibits neuroprotective potential, its precise atomistic interactions with targeted biological macromolecules remain elusive. In this study, we employed an integrated computational biophysics and in vitro approach to explore the multiscale mechanisms by which puerarin modulates PINK1-mediated mitophagy and NLRP3/GSDMD-dependent pyroptosis. ADMET profiling and DFT calculations initially confirmed puerarin’s favorable pharmacokinetics and intrinsic reactive oxygen species (ROS) scavenging capacity (Bond Dissociation Energy = 89.68 kcal/mol). Extensive 100 ns MD simulations and MM/GBSA analyses suggested that puerarin could act as a structural modulator. It was computationally predicted to anchor stably within the functional cavities of the PINK1, NLRP3, and GSDMD monomers and act as a steric hindrance, theoretically attenuating the binding free energies of the native NLRP3-ASC and Caspase-3-GSDMD macromolecular assemblies. These thermodynamic predictions were empirically supported by an in vitro OGD/R model using HT22 cells, with nimodipine included as a reference comparator. At the protein level, puerarin significantly upregulated markers of PINK1/Parkin-mediated mitophagy while profoundly suppressing NLRP3 inflammasome activation and subsequent GSDMD cleavage. Furthermore, the application of the autophagy inhibitor 3-MA exacerbated OGD/R-induced pyroptotic marker expression, experimentally validating the intrinsic biological crosstalk between defective mitophagy and pyroptosis. Collectively, our findings propose that puerarin may mitigate CIRI through a dual-pronged mechanism: the computationally predicted thermodynamic destabilization of pyroptotic machineries, coupled with the in vitro modulation of mitophagy-related proteins to potentially clear upstream oxidative triggers.