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Furthermore, mitochondrial NADPH production is dependent on at least 5 mitochondrial enzymes including nicotinamide nucleotide transhydrogenase (NNT), isocitrate dehydrogenase 2 (IDH2), malic enzyme 3 (ME3), mitochondrial homolog of 10-formyltetrahydrofolate dehydrogenase (ALDH1L2) and methylenetetrahydrofolate dehydrogenase 1 like (MTHFD1L) ( Figure 1 The non-oxidative branch is composed of a series of reversible transfer reactions of chemical groups

Several studies have adopted composite indices such as the Systemic Immune-Inflammation Index (SII = platelet neutrophil/lymphocyte), which integrates PLR and NLR components and outperforms either marker alone in predicting postoperative outcomes and survival in ESCC cohorts (98, 99)

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