Co-cited reference clustering and temporal clustering analysis (Figures 7B, C) reveal various research hotspots over time, such as toll-like receptors (cluster 3), chronic allograft nephropathy (cluster 7) and ivig (cluster 8) in earlier periods, progressing to Netrin-1 (cluster 2), mesenchymal stem cell (cluster 9) and mesenchymal stromal cells (cluster 10), tlrs (cluster 11), screening (cluster 12), crossmath (cluster 13) as mid-term research hotspots. The gene discussed is NTN1; the disease is Crouzon syndrome-acanthosis nigricans syndrome.