The translation of genetic findings from genome-wide association studies into actionable therapeutics persists as a critical challenge in Alzheimer's disease (AD) research. Here, we present PI4AD, a computational medicine framework that integrates multi-omics data, systems biology, and artificial neural networks for therapeutic discovery. This framework leverages multi-omic and network evidence to deliver three core functionalities: clinical target prioritisation; self-organising prioritisation map construction, distinguishing AD-specific targets from those linked to neuropsychiatric disorders; and pathway crosstalk-informed therapeutic discovery. PI4AD successfully recovers clinically validated targets like APP and ESR1, confirming its prioritisation efficacy. Its artificial neural network component identifies disease-specific molecular signatures, while pathway crosstalk analysis reveals critical nodal genes (e.g., HRAS and MAPK1), drug repurposing candidates, and clinically relevant network modules. By validating targets, elucidating disease-specific therapeutic potentials, and exploring crosstalk mechanisms, PI4AD bridges genetic insights with pathway-level biology, establishing a systems genetics foundation for rational therapeutic development. Importantly, its emphasis on Ras-centred pathways-implicated in synaptic dysfunction and neuroinflammation-provides a strategy to disrupt AD progression, complementing conventional amyloid/tau-focused paradigms, with the future potential to redefine treatment strategies in conjunction with mRNA therapeutics and thereby advance translational medicine in neurodegeneration.

Pancreatic ductal adenocarcinoma (PDAC) is difficult to diagnose in its early stages. Most patients are diagnosed at a locally advanced or metastatic stage. Systemic therapy has become the key to improve survival. To bridge the differences in guidelines across Asian countries and address regional clinical practice needs, 14 leading experts in the Asia-Pacific region developed the “Asian Consensus on systemic therapy for pancreatic ductal adenocarcinoma” on the Delphi method. The consensus centers on 14 core recommendations (R1-R14) and proposes stratified management strategies based on disease stage. For resectable PDAC, adjuvant modified FOLFIRINOX (mFOLFIRINOX) is the preferred option, while for the patients with poor performance status gemcitabine plus capecitabine, S-1 monotherapy, and other regimens can be selected. For borderline resectable PDAC, neoadjuvant therapy is recommended, with GnP or FOLFIRINOX as the preferred regimens. For locally advanced PDAC, combination or monochemotherapy is selected based on their performance status. For metastatic PDAC, first-line options include GnP, NALIRIFOX, or mFOLFIRINOX, with second-line therapy the cross-use of gemcitabine-based and 5-FU-based regimens are emphasized. This consensus provides for the first time a comprehensive and standardized management framework for systemic therapy of PDAC in Asia, aiming to enhance regional homogeneity in clinical practice and improve patient outcomes. This article interpreted the consensus content with the goal of guiding clinical practice.

Objective:To study the effect of psoralen on the proliferation, invasion and migration of HTB-47 and CRL-1932 renal cancer cells cultured in vitro, and to further explore the internal mechanism of psoralen inhibiting renal cancer.Methods:The experimental group was HTB-47 and CRL-1932 renal cancer cells treated with dimethyl sulfoxide solution containing 30 μg/ml psoralen, and the control group was renal cancer cells treated with dimethyl sulfoxide. Scratch test, CCK8, Transwell, and Western blot were used to detect the effect of psoralen on renal cancer cells.Results:Compared with the control group, the proliferation, invasion and migration of renal cancer cells treated with psoralen in the experimental group were significantly inhibited. In the renal cancer cells treated with psoralen, the protein expression levels of MKI67, PCNA, MMP2 and MMP9 were significantly decreased (all P<0.05). Conclusions:Psoralen can significantly inhibit the proliferation, invasion and migration of HTB-47 and CRL-1932 renal cancer cells in vitro. The mechanism may be to inhibit the progression of renal cancer by regulating MKI67, PCNA, MMP2 and MMP9.