Construction of a Diagnostic Model for Small Cell Lung Cancer Combining Metabolomics and Integrated Machine Learning.

BACKGROUND: To date, no study has systematically explored the potential role of serum metabolites and lipids in the diagnosis of small cell lung cancer (SCLC). Therefore, we aimed to conduct a case-cohort study that included 191 cases of SCLC, 91 patients with lung adenocarcinoma, 82 patients with squamous cell carcinoma, and 97 healthy controls. METHODS: Metabolomics and lipidomics were applied to analyze different metabolites and lipids in the serum of these patients. The SCLC diagnosis model (d-model) was constructed using an integrated machine learning technology and a training cohort (n = 323) and was validated in a testing cohort (n=138). RESULTS: Eight metabolites, including 1-mristoyl-sn-glycero-3-phosphocholine, 16b-hydroxyestradiol, 3-phosphoserine, cholesteryl sulfate, D-lyxose, dioctyl phthalate, DL-lactate and Leu-Phe, were successfully selected to distinguish SCLC from controls. The d-model was constructed based on these 8 metabolites and showed improved diagnostic performance for SCLC, with the area under curve (AUC) of 0.933 in the training cohort and 0.922 in the testing cohort. Importantly, the d-model still had an excellent diagnostic performance after adjusting the stage and related clinical variables and, combined with the progastrin-releasing peptide (ProGRP), showed the best diagnostic performance with 0.975 of AUC for limited-stage patients. CONCLUSION: This study is the first to analyze the difference between metabolomics and lipidomics and to construct a d-model to detect SCLC using integrated machine learning. This study may be of great significance for the screening and early diagnosis of SCLC patients.

Effect of Nutritional Intervention on Energy Intake in Head and Neck Cancer Patients After Radiotherapy.

Objective: This study aimed to analyze the impact of nutritional intervention during radiotherapy for head and neck tumors and its effects on energy intake, consumption, and nutritional status. Methods: A comparative or observational study was conducted, and a total of 103 head and neck tumor patients undergoing radiotherapy were selected for this study and divided into two groups. The control group (n = 51) received routine nursing intervention, while the observation group (n = 52) received additional nutritional intervention. We compared the nutritional status, energy intake and consumption, and emotional well-being between the two groups. Results: After the intervention, the observation group exhibited significantly higher levels of BMI, serum prealbumin, hemoglobin, and albumin compared to the control group (P < .05). Energy intake during radiotherapy was significantly higher in the observation group than in the control group. Furthermore, the energy consumption in the observation group was significantly lower than in the control group (P < .05). After the intervention, the observation group reported lower scores on the Self-rating Anxiety Scale and Self-rating Depression Scale compared to the control group (P < .05). In a three-month follow-up after radiotherapy, the observation group's EORTC Cancer Quality of Life Scale score was also significantly higher than that of the control group (P < .05). Conclusions: Nutritional intervention proved effective in increasing energy intake and reducing energy consumption in patients undergoing radiotherapy for head and neck tumors. This improvement positively impacted the nutritional status and quality of life of the patients, emphasizing its significant research value.

Boosting immunotherapy of triple negative breast cancer through the synergy of mild PTT and Fe-loaded organosilica nanoparticles.

Triple negative breast cancer (TNBC) is associated with drug resistance, metastasis, and poor immune response. The development of novel strategies to evoke a robust immune response against TNBC is necessary. In this study, we propose a TNBC tumor immunotherapy modality by synergizing nanocatalytic medicine with mild photothermal therapy. Briefly, mesoporous organosilica nanoparticles (MONs) and an Fe3+-loaded MON (MOF) were prepared. Then, the MOF was modified by hyaluronic acid (HA) and loaded with indocyanine green (ICG) to obtain MOFH (IMOFH). The IMOFH was spherical with a uniform particle size and showed pH-dependent Fe3+ release behavior. In vitro experiments showed that IMOFH was effectively internalized by 4T1 cells, which resulted in Fe3+-mediated oxidative cell death in synergy with mild PTT. Furthermore, this synergistic therapy activated dendritic cells (DCs) through damage-associated molecular pattern (DAMP) exposure resulting from enhanced oxidative damage in tumor cells. In vivo experiments showed that the application of mild PTT promoted IMOFH-mediated maturation of DCs and infiltration of CD8+ T cells. The synergistic effects of IMOFH and mild PTT resulted in boosted activation of adaptive immunity. The pH responsive nanocatalytic medicine IMOFH promoted significant adaptive immunity through the exposure of tumor associated antigens via the Fe3+ mediated Fenton reaction in concert with mild PTT. These effects resulted in the elimination of TNBC tumors without obvious side effects. Therefore, such a synergistic modality of IMOFH + mild PTT is promising for TNBC therapy.

Metastases of basal-like breast invasive ductal carcinoma to the endometrium: A case report and review of the literature.

We present a case of single endometrial metastasis from breast invasive ductal cancer. This case was unique because the immunohistochemical staining was negative for human epidermal growth factor receptor 2/neu and estrogen and progesterone receptors, and positive for cytokeratin 5/6 and epidermal growth factor receptor in the primary and metastatic tumor cells. No gross evidence of tumor was observed in other sites. We identified 12 cases of metastases to the endometrium from breast carcinoma from series and case reports in the literature between 1985 and 2014. This review indicated that hormone receptor-positive invasive lobular breast cancer cells are more likely to metastasize to the endometrium than other cell types in patients over 50 years of age.

Mitochondria in traumatic brain injury and mitochondrial-targeted multipotential therapeutic strategies.

Traumatic brain injury (TBI) is a major health and socioeconomic problem throughout the world. It is a complicated pathological process that consists of primary insults and a secondary insult characterized by a set of biochemical cascades. The imbalance between a higher energy demand for repair of cell damage and decreased energy production led by mitochondrial dysfunction aggravates cell damage. At the cellular level, the main cause of the secondary deleterious cascades is cell damage that is centred in the mitochondria. Excitotoxicity, Ca(2+) overload, reactive oxygen species (ROS), Bcl-2 family, caspases and apoptosis inducing factor (AIF) are the main participants in mitochondria-centred cell damage following TBI. Some preclinical and clinical results of mitochondria-targeted therapy show promise. Mitochondria- targeted multipotential therapeutic strategies offer new hope for the successful treatment of TBI and other acute brain injuries.

The selective ablation of inflammation in an acute stage of ischemic stroke may be a new strategy to promote neurogenesis.

Ischemic stroke is one of the most common diseases in the world. Pre-clinical studies have proved that stem cell therapy is effective in treating ischemic stroke. But there is a "time window" for stem cell therapy that is only limited in acute/subacute stage after stroke. Meanwhile, ischemic stroke can elicit an immediate neuroinflammatory reaction in the brain, and an uncontrolled inflammatory process in acute/subacute stage will impair survival of stem cells and block repair processes. A selective ablation of harmful inflammation factors can greatly decrease a hostile environment and facilitate neurogenesis. If detrimental factors of inflammation in an acute/subacute stage after an ischemic stroke are suitably handled and more specific immunomodulatory interventions are adopted, neurogenesis in the "time window" will greatly enhanced.