161、PL-FIRE:癌症代谢—炎症状态的计算建模与12个月生存风险预测——元律医学的可证伪研究(PL-FIRE: Computational Modeling of Metabolic–Inflammatory States and 12-Month Survival Risk in Cancer—A Falsifiable Prim-Lex Medicine Study)

Routine cancer state assessment centers on TNM staging, histological grading, molecular subtyping, and performance status. While indispensable and mature in anatomic and molecular matching, this architecture integrates host systemic inflammatory burden, albumin-related systemic reserve, and glycolytic–tissue-injury load only in a fragmented manner. The theoretical core of Prim-Lex Medicine—the Animal-Life Prim-Fire, anchored in NADH/NAD⁺ redox regulation and the dynamic coupling between glycolysis and oxidative phosphorylation—cannot be directly measured in general hospitals due to equipment, cost, and standardization barriers associated with fluorescence lifetime imaging, lactate/pyruvate ratio determination, and mitochondrial function assays. This paper develops the PL-FIRE framework. Its core methodological shift is explicit: rather than “measuring the Prim-Fire” in general hospitals, the framework tests whether the Prim-Fire level has left reproducible incremental traces—independent of TNM and molecular subtyping—in routinely available hematological and clinical variables. The detection layer comprises six groups of routine information: complete blood count, C-reactive protein (CRP), albumin (ALB), serum lactate dehydrogenase (LDH), fasting plasma glucose (FPG), and standard clinical data. The computation layer simplifies the Five-Element structure into two candidate modules: Fire (F) , an equal-weight aggregation of standardized LDH and FPG, positioned as a “joint candidate proxy for glycolytic–tissue-injury–host glucose metabolic burden”; and Wood (W) , a direction-unified aggregation of NLR, CRP, and albumin, positioned as a “joint candidate proxy for systemic inflammatory–albumin-related burden.” The Fire–Wood interaction is the sole coupling structure entering formal testing. Two substantive methodological revisions are made to the prior framework. First, 12-month overall survival (OS) is frozen as the proposed primary prediction time point; all incremental judgments are anchored to time-dependent metrics at that horizon. Second, the “joint decision rule” is thoroughly revised: the mechanical three-item rule ( + calibration slope including 1 + any DCA advantage) is abandoned. Instead, comprehensive reporting of time-dependent AUC, IPCW-Brier score, predicted-probability calibration (calibration plot, calibration slope, calibration-in-the-large), and time-dependent decision curve analysis constitutes the core. serves only as an exploratory target difference, not a universal clinical-importance threshold. The model comparison hierarchy is expanded to: (standard clinical baseline), (), (), (baseline + five standardized raw variables), and (). versus compares the parsimony of fixed equal-weight aggregation; versus compares whether retains incremental predictive value after all raw-variable information is preserved. The framework explicitly states that is not a complete fair comparator against “all conventional interaction models”; if unique Prim-Lex interaction value is later claimed, comparably complex pre-specified conventional interaction models must be added in subsequent research. The anticipated contribution is strictly limited: a minimum viable validation version executable in general hospitals, with actually collectable data and honestly falsifiable hypotheses. It does not claim that Prim-Lex Medicine treats cancer, that LDH/NLR/CRP “measure NADH/NAD⁺,” or that Five-Element coupling has been biologically proven. Regardless of direction, the framework places Prim-Lex clinical claims under reproducible testing and establishes explicit criteria and boundaries for bridging studies.