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Abstract Objective We investigated the different life styles among the diet structures and exercise patterns of 100 patients with refractory gout and 79 healthy volunteers; of these, we selected 39 patients and 20 healthy volunteers for serum proton magnetic resonance (1H-NMR) metabolic network detection. We determined the potential biomarkers of refractory gout and attempted to explore the relation between potential biomarkers and diet structures and exercise patterns. Methods The study employed a questionnaire survey to analyze diet structures and exercise patterns from 100 patients of refractory gout and 79 healthy volunteers. At the same time, using 1H-NMR metabolic technology to analyze the metabolites present in the serum samples obtained from 39 patients of refractory gout (group B) and 20 healthy subjects (group A). Employing MestReNova (Version 8.0.1) to analyze the metabolites maps, collecting the NMR results, further importing into SIMCA-P+ 14.0 software (Umetrics, Sweden) for principal component analysis (PCA), partial least squares discriminant analysis (PLS-DA), and orthogonal partial least squares discriminant analysis (OPLS-DA) statistical analysis. Combining patterns recognition and multivariate statistics, potential biomarkers were searched. Other experimental data, including creatinine and adiponectin, were counted by the SPSS21.0. The measurement data were expressed by X ± S and t test. The counting data were expressed in percent and performed by X 2 test. Results Our results revealed that patients with gout tended to be obese, and there were differences in their lifestyle with exercise, sleep, and smoking, as well as in their preference for fructose drinks, alcohol, and total and structural distribution of meat, milk, eggs, and so on when compared with the healthy volunteers. Importantly, we found the adiponectin in the gout group was lower as compared to the healthy group. Further, metabolomics in combination with KEGG analysis revealed that the biosynthesis of aminoacyl tRNA, biosynthesis of valine, leucine, and isoleucine, metabolism of alanine, aspartic, and glutamate, metabolism of glycine, serine, and threonine, phenylalanine, glycolysis/gluconeogenesis, ketone body synthesis and degradation, metabolism of d‐glutamine, citric acid cycle (TCA cycle), triglyceride metabolism, and others could be used as specific biomarkers of this disease. Conclusion Recurrent refractory gout and formation of tophus may be related to the diet structures and lifestyles between the patients and the healthy people, and their abnormal metabolic network may be related to the disorder of mitochondrial energy metabolism, which further results in abnormal metabolism of glucose, lipids, amino acids, and deposition of uric acid in joints, peripheral connective tissue, and kidney, inducing an inflammatory response.

Objective: This study aimed to use proton nuclear magnetic resonance technology to analyze the metabolic pathways of invigorating the spleen and promoting Yang dehumidification and dredging collaterals (Cassia twig Peony Anemarrhenae and Rise Yang Dehumidification Decoction) in treating the acute attack of refractory gout and to find the target of traditional Chinese medicine (TCM). Method: Forty patients with acute refractory gout of spleen deficiency and dampness-heat type were recruited and randomly divided into TCM group and the Western medicine group, with 20 patients in each group. Serum samples were collected before and after 10 days of treatment for comparative analysis, and the metabolic pathways were identified. Combined with the results of TCM syndrome score, inflammatory indexes (C reactive protein, erythrocyte sedimentation rate), and creatinine, adiponectin, and cytokine (interleukin-6, tumor necrosis factor-α) levels before and after treatment, the mechanism of TCM action was analyzed. Results: Cassia twig Peony Anemarrhenae and Rise Yang Dehumidification Decoction were found to be better than Western medicine in alleviating joint swelling and pain, localized as well as systemic fever, and bitter and dry mouth. Furthermore, inflammatory indicators, cytokines, creatinine, and adiponectin levels were better in the TCM group than in the Western medicine group. In terms of metabolic pathways, the treatment of an acute attack of refractory gout with our TCM compounds resulted in better improvements in branched-chain amino acid (BCAA) metabolism, glycine, serine, and threonine metabolism, tyrosine metabolism, taurine, and low taurine metabolism, glycolysis/sugar dysplasia, synthesis and degradation of ketone body, D-glutamine metabolism, citric acid cycle (TCA cycle), glyceride metabolic pathways, etc., than the use of Western medicine. Conclusion: TCM compounds may improve the metabolic network of refractory acute gout by stimulating the above metabolic pathways to inhibit the inflammatory response, relieve joint pain, and augment glucose metabolism, energy metabolism, and lipid metabolism. These compounds are hence worthy of promotion.

Introduction: DNA ploidy (P), stroma fraction (S), and nucleotyping (N) collectively known as PSN, have proven prognostic accuracy in stage II colorectal cancer (CRC). However, few studies have reported on the prognostic value of the PSN panel in stage III colon cancer patients receiving capecitabine and oxaliplatin adjuvant chemotherapy. Objectives: This study aimed to validate PSN's prognostic impact on stage III colon cancer, identifying candidates for optimized adjuvant chemotherapy duration. Design: A retrospective analysis was conducted on a cohort of stage III colon cancer patients from April 2008 to June 2020. Methods: Postoperative pathological samples from stage III colon cancer patients who underwent radical surgery and postoperative adjuvant chemotherapy at Sun Yat-sen University Cancer Center were retrospectively collected. Automated digital imaging assessed PSN, categorizing risk groups. Kaplan–Meier, Cox regression, and time-dependent receiver operating characteristic analysis compared model validity. Results: Significant differences in 5-year disease-free survival (DFS) and overall survival (OS) were noted among PSN-based low-, moderate-, and high-risk groups (DFS: 92.10% versus 83.62% versus 79.80%, p = 0.029; OS: 96.69% versus 93.99% versus 90.12%, p = 0.016). PSN emerged as an independent prognostic factor for DFS [hazard ratio (HR) = 1.409, 95% confidence interval (CI): 1.002–1.981, p = 0.049] and OS (HR = 1.720, 95% CI: 1.127–2.624, p = 0.012). The PSN model, incorporating perineural invasion and tumor location, displayed superior area under the curve for 5-year (0.692 versus 0.553, p = 0.020) and 10-year (0.694 versus 0.532, p = 0.006) DFS than TNM stage. In the PSN high-risk group, completing eight cycles of adjuvant chemotherapy significantly improved 5-year DFS and OS compared to four to seven cycles (DFS: 89.43% versus 71.52%, p = 0.026; OS: 96.77% versus 85.46%, p = 0.007). Conclusion: The PSN panel effectively stratifies stage III colon cancer, aiding in optimized adjuvant chemotherapy duration determination. [ABSTRACT FROM AUTHOR]

Background: Liver metastasis is the leading cause of death in patients with colorectal cancer (CRC). Emerge evidence suggests that circular RNA (circRNA) is a pivotal player in cancer progression. However, its role in CRC liver metastasis remains largely unknown. Methods: Circ-YAP expression was detected by qRT-PCR and in situ hybridization. The function of circ-YAP was tested by wound healing, transwell and CCK-8 assays. RNA immunoprecipitation, pull-down, luciferase reporter, chromatin immunoprecipitation assays were used to investigate the mechanism underlying circ-YAP promoting CRC liver metastasis. CRC liver metastasis animal model was established to assess the effect of circ-YAP in vivo. Results: Circ-YAP was notably upregulated in CRC with liver metastasis, which was associated with dismal prognosis. Circ-YAP promoted CRC cell migration and invasion in vitro, and facilitated liver metastasis in patient-derived xenografts (PDX) models in vivo. Mechanistically, circ-YAP encoded a novel truncated protein containing 220 amino acids, termed as YAP-220aa, which competitively bound to LATS1, resulting in YAP dephosphorylation and nuclear translocation, thereby activating a cohort of metastasis-promoting genes. Importantly, N6-methyladenosine (m6A) modification orchestrated efficient initiation of circ-YAP translation, requiring m6A reader YTHDF3 and eIF4G2 translation initiation complex. Intriguingly, circ-YAP was transcriptionally enhanced by YAP/TEAD complex, thus forming a positive regulatory feed-forward loop. Conclusions: Our findings reveal a previously uncharacterized oncoprotein encoded by circ-YAP, implying a promising biomarker and therapeutic target for CRC patients with liver metastasis. [ABSTRACT FROM AUTHOR]