The Use of Peripheral Parenteral Nutrition in Hospitalized Patients: A Clinical Case Series.

Cancer-related fatigue (CRF) is a common and debilitating symptom throughout the cancer trajectory. Meta-analyses indicate that approximately 70–80% of patients experience clinically significant fatigue during or after treatment, with many survivors developing severe fatigue []. CRF substantially impairs health-related quality of life, employment, and daily functioning, imposing considerable psychosocial and economic burdens on patients, families, and society []. Current pharmacological and non-pharmacological interventions have limited efficacy; psychostimulants, antidepressants, corticosteroids, and other agents show inconsistent benefits and are often restricted by adverse effects or narrow indications []. Therefore, elucidating the biological basis of CRF is essential for developing mechanism-based therapies. CRF has been linked to systemic inflammation, neuroendocrine disruption, mitochondrial dysfunction, anemia, and psychosocial factors [,]. However, its complexity suggests that additional pathways may contribute to central and peripheral fatigue. Metal ion homeostasis is critical for cellular function, particularly in mitochondria, which regulate energy production and redox balance in high-demand tissues such as skeletal muscle and brain [,]. Ferroptosis is an iron-dependent regulated cell death characterized by lipid peroxide accumulation and plasma membrane damage []. Ferroptosis inducers (FINs) have shown therapeutic potential in ferroptosis-sensitive cancers and in overcoming resistance to radiotherapy, chemotherapy, and immunotherapy [,,]. For example, targeting induces ferroptosis by suppressing intracellular glutathione (GSH) synthesis and inhibiting -mediated antioxidant defense, showing efficacy in preclinical cancer models and lung cancer immunotherapy []. Cuproptosis is a copper-triggered cell death process driven by mitochondrial copper overload, aggregation of lipoylated TCA-cycle proteins, destabilization of iron–sulfur cluster proteins, and proteotoxic stress []. A PROTAC-based copper accumulation sensitizer has recently shown favorable therapeutic effects in lung cancer []. Although ferroptosis and cuproptosis are increasingly recognized in oncology, their roles in CRF remain poorly defined. FK506-binding protein 51, encoded by , is a stress-responsive immunophilin that regulates glucocorticoid receptor signaling []. Beyond endocrine functions, FKBP5 also regulates redox homeostasis and mitochondrial integrity [,]. overexpression reversed the effects of PRRX1 silencing on excessive mitophagy and cardiomyocyte ferroptosis in OGD/R-treated AC16 cells []. Although the relationship between FKBP5 and cuproptosis remains unclear, copper ionophores (CINs) can increase oxidative stress and impair mitochondrial function [], suggesting that FKBP5 may participate in cuproptosis regulation and contribute to CRF driven by ion-homeostasis imbalance.