ABSTRACT
@#【Objective】 To investigate the correlations between intestinal flora, plasma metabolites, and blood stasis syndrome in coronary heart disease (CHD), and the mechanisms of Yangxin Tongmai Formula (养心通脉方, YXTMF) for blood stasis syndrome in CHD rats. 【Methods】 A total of 18 specific pathogen free (SPF) male Sqrague-Dawley (SD) rats were used to establish CHD rat models with blood stasis syndrome, which were then randomized into model, YXTMF, and atorvastatin calcium (AVT) groups, with six rats in each group, and were intervened through gavage for two weeks. Subsequently, additional six rats that received normal diet were included as normal group. The pathological changes in the CHD rat models were identified by hematoxylin-eosin (HE) staining. The electrocardiogram, hemodynamics, and lipid profiles of the rats were detected as well. The untargeted plasma metabolomics of rats were analyzed by liquid chromotography-tandem mass spectrometry (LC-MS/MS), their ileal mucosal flora by 16S rRNA sequencing, and the correlation between the two results were also analyzed. 【Results】 The whole blood viscosity, total cholesterol (TC), and low-density lipoprotein cholesterol (LDL-C) of rats in the model group increased compared with those in the control group (P < 0.05). In the model group, the proliferation of endothelial cells in the coronary artery of rats was damaged, with quite a few vacuolated pathological changes observed. However, the endothelial lesions in the coronary artery of rats were alleviated in the intervention groups (YXTMF and AVT groups). With the use of LC-MS/MS, a total of 33 potential endogenous metabolites were identified in plasma, among which 1-methylhistidine, N-acetylhistamine, progesterone, and deoxycorticosterone were expected to be the differential metabolites in CHD rats with blood stasis syndrome. The 16S rRNA sequencing results showed that improved diversity and abundance of intestinal flora were observed in the YXTMF group. The correlation analysis suggested that Hydrogenophaga, Limnohabitans, and Polaromonas, which were highly related to the formation of blood stasis syndrome in CHD patients, were positively correlated with plasma metabolites such as 5-hydroxyindole, N-acetylhistamine, and progesterone (P < 0.01), but were negatively correlated with plasma metabolites such as L-arginine, homoarginine, and Boc-beta-cyano-L-alanine (P < 0.01). After YXTMF intervention, Lactobacillus, Corynebacterium, and Candidatus Nitrososphaera were positively correlated with plasma metabolites such as Boc-β-cyano-L-alanine, stachydrine, and naringenin (P < 0.05), while negatively correlated with 5-hydroxyindole, N-acetylhistamine, and oleoylethanolamide (P < 0.05). 【Conclusion】 YXTMF could alleviate blood stasis syndrome in CHD rats through improving their plasma metabolisms achieved by regulating the intestinal flora.
ABSTRACT
Objective@#To investigate The Cancer Genome Atlas (TCGA) molecular classification of endometrial cancer (EC) and endometrial atypical hyperplasia (AH) treated with fertility-sparing therapy. @*Methods@#A total of 46 EC and AH patients who received fertility-sparing therapy and TCGA molecular classification tested by next generation sequencing, in Peking University People’s Hospital from June 2020 to December 2021, were retrospectively collected. We analyzed the relationship between molecular classification and clinicopathological factors and treatment outcomes. @*Results@#Of the 46 patients, including 40 EC and 6 AH patients, 70.5% (32 patients) had complete remission (CR) after treatment, with median CR time of 8 months. The cases were distributed as no specific molecular profile (NSMP; n=34, 73.9%) subtype mainly, microsatellite instability-high (MSI-H; n=7, 15.2%), POLE ultra‑mutated (n=3, 6.5%), and copy number high (CNH; n=2, 4.3%). Patients with MSI-H subtype had lower body mass index (24.0±5.5 kg/m2), more family history of tumor (6/7), more with loss of mismatch repair protein expression by immunohistochemical (7/7), and higher Ki67 expression level (3/3). Patients in MSI-H subgroup had the lowest CR rate at 6 months (0/6, p=0.019), and survival analysis showed that such patients were less likely to achieve CR than those with NSMP subtype (p=0.022). Subgroup analysis of patients with NSMP showed that, age ≥30 years and diabetes mellitus related with longer treatment time to CR (p=0.01 and p=0.059, respectively). In addition, CR was obtained in 2 (2/3) POLE ultra‑mutated cases and 1 (2/2) CNH case, respectively. @*Conclusion@#TCGA molecular classification relates with the treatment response in patients with EC and AH treated with fertility-sparing therapy. Patients with MSI-H subtype have poor treatment efficacy.