Frailty, a common, multifaceted, and significant geriatric condition, involves crucial roles of inflammation and metabolic factors in its onset and progression. Nevertheless, the ambiguities and complexities in earlier observational studies make current research into their interactions somewhat insufficient. Our goals were to clarify the causal link between inflammatory cytokines and frailty and to explore the potential mediating effect of metabolites using Mendelian randomization (MR) analysis. Utilizing detailed summary-level data from genome-wide association studies, we conducted two-sample Mendelian randomization analyses to evaluate the potential causal connection between 91 inflammatory cytokines and the frailty index, along with the possible mediating pathways that involve 1400 metabolites. For our main analysis, we applied the inverse variance weighted method. To evaluate the potential mediating pathways of metabolites, a two-step MR analysis was utilized. We identified 8 inflammatory cytokines that were genetically associated with the frailty index, we subsequently identified 2 mediated relationships, with 2 metabolites acting as potential mediators between 2 inflammatory cytokines and frailty index. The 8 inflammatory cytokines were fractalkine (CX3CL1), interleukin-33 (IL-33), leukemia inhibitory factor receptor (LIF-R), monocyte chemoattractant protein-1 (CCL8), CC motif chemokine 4 (CCL4), C-X-C motif chemokine 10 (CXCL10), fibroblast growth factor 5 (FGF-5), and TNF-beta (TNFB) levels. The findings of this study demonstrate a direct connection between inflammatory cytokines and the frailty index, as well as two pathways mediated by metabolites. These biomarkers contribute valuable insights into the foundational mechanisms of frailty, presenting a novel research avenue for upcoming clinical studies.

Although observational studies have revealed a link between frailty and serum micronutrient levels, it remains unclear whether these 2 states are directly connected. Thus, Mendelian randomization (MR) was used to investigate the causal relationship between frailty and blood micronutrient levels. Summary-level data for 15 blood micronutrients (copper, selenium, zinc, calcium, iron, magnesium, potassium, folate, carotene, vitamin A, vitamin B6, vitamin B12, vitamin C, vitamin D, and vitamin E) were obtained from people of European ancestry from the Integrative Epidemiology Unit. Single nucleotide polymorphisms associated with the frailty index were extracted from a published meta-analysis study in the UK Biobank and Swedish TwinGene. We used the inverse variance weighted (IVW) method for the primary analysis. We employed pleiotropy residual sum and outlier (MR-PRESSO) tests, MR-Egger intercepts, Cochran Q tests, and leave-one-out analysis to assess causality validity and robustness. Reverse MR analysis was used to determine reverse causation. The IVW results revealed that vitamin D (odds ratio [OR] = 1.096; 95% confidence interval [CI]: 1.019–1.178; P = .014) increased the likelihood of a high risk of frailty, whereas the frailty index had a protective effect on selenium (OR = 0.622; 95% CI: 0.396–0.977; P = .039), carotene (OR = 0.916; 95% CI: 0.858–0.979; P = .009), vitamin C (OR = 0.895; 95% CI: 0.837–0.957; P = .001), iron (OR = 0.921; 95% CI: 0.859–0.988; P = .022), and vitamin E (OR = 0.907; 95% CI: 0.847–0.971; P = .005). The reverse IVW analysis revealed no significant correlation between micronutrient levels and frailty indices. The study revealed causal links between vitamin D and the risk of frailty. Notably, our findings highlight the necessity of adjuvant vitamin D in frailty management.

Osteosarcopenia is under-recognized in clinical practice and its specific prognostic value beyond sarcopenia has not been fully elucidated. This study aimed to identify osteosarcopenia using abdominal computed tomography (CT) scans and investigate its influence on survival outcomes in gastric cancer patients. We retrospectively analyzed 1,394 patients who underwent surgical resection for gastric cancer between 2019 and 2024. Of these patients, 838 were included in the study (exclusion rate 39.9%). Demographic data and clinical data were collected and compared. Osteosarcopenia was diagnosed by assessing the skeletal muscle index at the third lumbar vertebra level and bone mineral density at the first lumbar vertebra level on routine CT scans. With a median follow-up of 20 months, the associations between osteosarcopenia, baseline characteristics, and survival outcomes were analyzed. Osteosarcopenia was diagnosed in 142 (16.9%) patients. Compared with the non-osteosarcopenia group, the osteosarcopenia group had a higher proportion of males, older age, poorer nutritional status, and a lower rate of receiving chemotherapy (all P0.05). Multivariate Cox analysis revealed that cancer stage [II: hazard ratio (HR) =2.973, 95% confidence interval (CI): 1.274–6.937, P=0.01; III: HR =7.133, 95% CI: 3.300–15.415, P<0.001; IV: HR =10.390, 95% CI: 3.641–29.651, P<0.001], chemotherapy (HR =0.491, 95% CI: 0.311–0.776, P=0.002), carbohydrate antigen 199 (CA199) (HR =1.634, 95% CI: 1.020–2.617, P=0.041), patient-generated subjective global assessment (PG-SGA) (HR =1.939, 95% CI: 1.158–3.247, P=0.01), osteoporosis (HR =1.785, 95% CI: 1.019–3.126, P=0.043) and osteosarcopenia (HR =2.291, 95% CI: 1.238–4.239, P=0.008) were associated with poorer overall survival. Osteosarcopenia is associated with reduced overall survival in gastric cancer patients after surgical resection. Routine abdominal CT serves as a convenient tool for the opportunistic screening of osteosarcopenia, which could help in nutritional status assessment and intervention development.

Background: Cancer is one of the leading causes of pathological death in humans. Although CTHRC1 is a prooncogene highly expressed in a variety of tumor tissues, the specific biological mechanisms of CTHRC1 involvement in cancer development need to be elucidated. Methods: In the present study, nine online bioinformatics databases were employed to explore the potential prognostic and grading value of CTHRC1 in generalized cancer as well as its potential role in regulating tumor immunity. Results: Data from GEPIA2.0, Oncomine, TNMplot, Kaplan-Meier Plotter and TISIDB database had consistently demonstrated that CTHRC1 was associated with the expression, prognosis and typing in most cancer tissues. Cbioportal and SMART analysis revealed that genomic changes and methylation of CTHRC1 in most tumor tissues. Finally, Sangerbox and TIMER database analysis suggested that CTHRC1 was involved in the changes of immune cell components in tumor immune microenvironment, with certain heterogeneity. Meanwhile, CTHRC1 was correlated with TMB, MSI, neoantigen and tumor immune checkpoint, especially CD276. Conclusion: CTHRC1 had the potential as a prognostic and grading molecular marker for pan-cancer. And CTHRC1-related targeting agents may be a novel breakthrough in tumor immunotherapy.

Background: Gastric cancer (GC) remains one of the most common malignancies worldwide, highlighting the importance of characterizing microbial alterations associated with its development. Methods: This study analyzed changes in the gastric fluid microbiota of patients with GC and identified GC-related microbial signatures. Thirty patients with GC and 25 healthy volunteers undergoing routine physical examinations were included. Gastric fluid samples were subjected to absolute quantitative 16S ribosomal RNA (rRNA) gene sequencing. Differences in the microbial composition between groups were assessed using the linear discriminant analysis effect size (LEfSe). Results: The analysis revealed no significant differences in microbial diversity or richness between GC patients and healthy controls. However, the relative abundances of Neisseria and Haemophilus genera were markedly reduced in patients with GC, whereas Clostridiales bacterium canine oral taxon 162 and Prevotella 1 were increased. LEfSe identified 13 bacterial genera with linear discriminant analysis (LDA) scores ≥2.0 that discriminated between the cancer and healthy groups. Conclusions: The development of GC may be associated with alterations in the community structure of gastric fluid microbiota rather than changes in microbial diversity. LEfSe identified 13 bacterial genera with LDA scores≥2.0, which could effectively distinguish patients with GC and healthy controls.