Redox signaling acts as a critical mediator in the dynamic interactions between organisms and their external environment, profoundly influencing both the onset and progression of various diseases. Under physiological conditions, oxidative free radicals generated by the mitochondrial oxidative respiratory chain, endoplasmic reticulum, and NADPH oxidases can be effectively neutralized by NRF2-mediated antioxidant responses. These responses elevate the synthesis of superoxide dismutase (SOD), catalase, as well as key molecules like nicotinamide adenine dinucleotide phosphate (NADPH) and glutathione (GSH), thereby maintaining cellular redox homeostasis. Disruption of this finely tuned equilibrium is closely linked to the pathogenesis of a wide range of diseases. Recent advances have broadened our understanding of the molecular mechanisms underpinning this dysregulation, highlighting the pivotal roles of genomic instability, epigenetic modifications, protein degradation, and metabolic reprogramming. These findings provide a foundation for exploring redox regulation as a mechanistic basis for improving therapeutic strategies. While antioxidant-based therapies have shown early promise in conditions where oxidative stress plays a primary pathological role, their efficacy in diseases characterized by complex, multifactorial etiologies remains controversial. A deeper, context-specific understanding of redox signaling, particularly the roles of redox-sensitive proteins, is critical for designing targeted therapies aimed at re-establishing redox balance. Emerging small molecule inhibitors that target specific cysteine residues in redox-sensitive proteins have demonstrated promising preclinical outcomes, setting the stage for forthcoming clinical trials. In this review, we summarize our current understanding of the intricate relationship between oxidative stress and disease pathogenesis and also discuss how these insights can be leveraged to optimize therapeutic strategies in clinical practice.

Background: The gut-lung axis, the long-range communication between the intestinal microbiota and the lungs, has been shown to influence immunotherapy responses in non-small-cell lung cancer (NSCLC). Existing reviews, however, focus almost exclusively on the chemical signaling dimension of microbial metabolites. The relay function of enteroendocrine hormones and the integrative role of the nervous system have yet to be incorporated into a unified framework. Methods: We searched seven databases (PubMed, EMBASE, Web of Science, Cochrane Library, CNKI, Wanfang, and VIP) from inception to June 2026 for original studies and reviews addressing gut microbiota and lung-gut-brain axis mechanisms in the context of NSCLC or small-cell lung cancer. Two authors independently performed study selection, data extraction, and thematic classification. A narrative synthesis was conducted, with evidence organized along three signaling axes: soluble metabolites, the metabolic-endocrine axis, and neuroimmune integration. As a narrative review with a systematic search, this study was registered on PROSPERO (CRD420261425826), while formal risk-of-bias assessment and GRADE evaluation were not performed. Results: A total of 168 studies was included (only a subset of these included studies cited in the main text). The volume of evidence across the three axes formed a pronounced gradient. Soluble metabolites (short-chain fatty acids, tryptophan metabolites, and bile acids) have been cross-validated in clinical cohorts, animal models, and in vitro experiments; fecal microbiota transplantation and prebiotic strategies have entered clinical trials. The metabolic-endocrine axis rests on a solid foundation in normal physiology, but the key bridging nodes in the NSCLC disease context remain untested. Evidence for the neuroimmune integration axis is the sparsest: the only support for a direct transport function of the vagus nerve comes from a non-peer-reviewed preprint in a non-cancer model, and the full neuroendocrine signal transduction chain remains hypothetical. To address this gap, we outline a pathway model annotated with evidence levels at each node. Conclusions: Research on the lung-gut-brain axis is heavily concentrated in the chemical dimension. The mechanistic gaps in the endocrine and neural dimensions represent the principal barrier for the field’s transition from correlational description to causal mechanism studies.

With the advancement of minimally invasive techniques, uniportal video-assisted thoracoscopic surgery (VATS) for lobectomy has been increasingly adopted due to minimal trauma and faster recovery. Conventionally, chest drains are routinely placed to evacuate air/fluid and monitor complications, but they cause pain, restrict mobility, and prolong hospitalization. Recently, the safety of omitting drains has drawn attention. This retrospective study analyzed 200 patients undergoing uniportal VATS lobectomy, divided into a no-drain group (n = 100) and a drain group (n = 100). Intraoperative parameters, recovery, complications, imaging, pain scores, and satisfaction were compared. Baseline characteristics were comparable ( P > .05). Intraoperative blood loss showed no difference (15.2 ± 4.2 mL vs 20.4 ± 5.1 mL, P = .103). The no-drain group achieved earlier ambulation (1.2 ± 0.6 vs 2.3 ± 0.9 days, P < .001) and shorter hospital stay (3.6 ± 1.2 vs 5.2 ± 1.4 days, P < .001). Visual analog scale pain scores were significantly lower at all time points, persisting to day 30 ( P < .001). Complication (8% vs 15%, P = .048) and fever rates (12% vs 20%, P = .048) were reduced. Computed tomography on day 3 showed smaller pneumothorax and pleural effusion volumes ( P < .001). Suture removal occurred earlier (12.6 ± 2.2 vs 15.0 ± 2.4 days, P < .001). Satisfaction on day 7 was higher in the no-drain group (9.1 ± 0.7 vs 8.3 ± 0.9, P < .001). Omitting chest tubes after uniportal VATS lobectomy is safe and feasible with proper selection. It reduces pain, accelerates recovery, lowers complication rates, and improves satisfaction, supporting wider clinical use.

Trace elements including iron, copper, zinc, selenium, and manganese are indispensable for life, serving as enzyme cofactors, structural components, and signaling molecules that govern energy metabolism, redox balance, and genomic stability. Their physiological functions exhibit a characteristic dose–effect biphasicity, wherein homeostatic imbalance can both safeguard health and promote malignant transformation. This review systematically delineates the complete lifecycle of these five core trace elements under physiological conditions, emphasizing their extensive functional interconnections, and elucidates how tumor cells hijack this regulatory network through an element-addiction mechanism. We detail the emerging roles of iron-dependent ferroptosis and copper-dependent cuproptosis, alongside the context-dependent regulation of apoptosis and autophagy by trace elements, revealing tumor-specific metabolic vulnerabilities. Within the tumor immune microenvironment, we examine how zinc, iron, copper, selenium, and manganese function as molecular switches: zinc and selenium generally support antitumor immunity, whereas iron and copper dysregulation drives immunosuppressive polarization; manganese additionally emerges as a cGAS-STING agonist with immunotherapeutic potential. In tumor angiogenesis and metastasis, we explore the central roles of copper and iron in extracellular matrix remodeling, epithelial-mesenchymal transition, and angiogenic signaling. Extensive clinical evidence is integrated to establish systemic and local elemental imbalances as risk biomarkers across diverse cancer types. Therapeutic strategies are categorized into traditional nutritional and pharmacological interventions, element-metabolism-based synergistic sensitization with chemotherapy, radiotherapy, and immunotherapy, and interdisciplinary engineering approaches including element-responsive nanoplatforms and synthetic biology-engineered immune cells. Throughout, we emphasize that the majority of therapeutic evidence derives from preclinical models, underscoring that rigorous foundational research must precede clinical translation. We conclude by outlining knowledge gaps and priorities for future investigation, advocating a systems biology framework that acknowledges current limitations while guiding hypothesis-driven exploration.

Background: Thoracic radiotherapy is an option for some patients with extensive-stage small-cell lung cancer (ES-SCLC), but it is unclear how it should be used after first-line chemoimmunotherapy and whether its value differs with age. In two observational datasets that defined radiotherapy exposure differently, we asked whether age changed the association between radiotherapy and overall survival (OS). Methods: We studied a historical Surveillance, Epidemiology, and End Results (SEER) cohort diagnosed in 2010–2015 and re-analyzed a previously published multicenter cohort of 171 patients given first-line chemoimmunotherapy in Sichuan. In SEER the exposure was recorded first-course radiotherapy, which is not the same as consolidative thoracic radiotherapy (cTRT). The primary SEER cohort contained 13,676 patients with distant metastasis, and one global propensity-score match (PSM) produced 4,116 pairs. In the institutional cohort we fitted a time-varying Cox model for cTRT and OS; 33 patients with 33 deaths had complete data for the adjusted model. Age was treated as continuous, and we tested treatment-by-age interactions in both cohorts. Results: In SEER, recorded first-course radiotherapy was associated with lower all-cause mortality in the multivariable model [hazard ratio (HR) 0.75, 95% confidence interval (CI): 0.72–0.78; P<0.001]; the matched cohort gave a similar estimate (HR 0.72, 95% CI: 0.69–0.75; P<0.001). Age did not interact with radiotherapy (ratio of HRs per 10-year increase 1.02, 95% CI: 0.98–1.06; likelihood-ratio P=0.36). In the institutional time-varying Cox analysis, cTRT was associated with lower mortality (HR 0.40, 95% CI: 0.17–0.98; P=0.04), and here the interaction was apparent (ratio 0.27 per 10-year increase, 95% CI: 0.11–0.64; Wald P=0.003; likelihood-ratio P=0.01). At age 65 years, the model-derived cTRT HR was 0.35 (95% CI: 0.16–0.78; P=0.01). Conclusions: In the SEER cohort, recorded first-course radiotherapy was associated with OS, and the interaction with age was not statistically significant. In the Sichuan cohort, the time-varying model gave an overall cTRT HR of 0.40 and a significant continuous age-by-cTRT interaction. That model, however, rested on 33 complete cases and on covariates chosen by outcome screening, two of which were measured after treatment began. These findings establish neither a validated age threshold nor a causal age-specific treatment effect.

An accessory hemidiaphragm is a rare congenital intrathoracic malformation characterized by a fibromuscular diaphragm located superior to the normal diaphragm, typically featuring a central hiatus through which pulmonary vessels and bronchi traverse. This anomaly is often associated with scimitar syndrome. We present a unique case of an isolated accessory hemidiaphragm—devoid of the characteristic vascular anomalies typical of scimitar syndrome—discovered incidentally during thoracoscopic surgery performed for a pulmonary nodule. This report elaborates the rationale for performing a concurrent partial membranectomy and underscores the necessity of an individualized surgical strategy in such cases.