RESUMO
Astragaloside IV (AS-IV), a natural triterpenoid isolated from Astragalus membranaceus, has been used traditionally in Chinese medicine. Previous studies have highlighted its benefits against carcinoma, but its interaction with the gut microbiota and effects on adenomatous polyps are not well understood. This present study investigates the effects of AS-IV on colonic adenomatous polyp (CAP) development in high-fat-diet (HFD) fed [Formula: see text] mice. [Formula: see text] mice were fed an HFD with or without AS-IV or Naringin for 8 weeks. The study assessed CAP proliferation and employed 16S DNA-sequencing and untargeted metabolomics to explore correlations between microbiome and metabolome in CAP development. AS-IV was more effective than Naringin in reducing CAP development, inhibiting colonic proinflammatory cytokines (IL-1[Formula: see text], IL-6, and TNF-[Formula: see text]), tumor associated biomarkers (c-Myc, Cyclin D1), and Wnt/[Formula: see text]-catenin pathway proteins (Wnt3a, [Formula: see text]-catenin). AS-IV also inhibited the proliferative capabilities of human colon cancer cells (HT29, HCT116, and SW620). Multiomics analysis revealed AS-IV increased the abundance of beneficial genera such as Bifidobacterium pseudolongum and significantly modulated serum levels of certain metabolites including linoleate and 2-trans,6-trans-farnesal, which were significantly correlated with the number of CAP. Finally, the anti-adenoma efficacy of AS-IV alone was significantly suppressed post pseudoaseptic intervention in HFD-fed [Formula: see text] mice but could be reinstated following a combined with Bifidobacterium pseudolongum transplant. AS-IV attenuates CAP development in HFD-fed [Formula: see text] mice by regulating gut microbiota and metabolomics, impacting the Wnt3a/[Formula: see text]-catenin signaling pathway. This suggests a potential new strategy for the prevention of colorectal cancer, emphasizing the role of gut microbiota in AS-IV's antitumor effects.
RESUMO
BACKGROUND: Data on severe and extensive burns in China are limited, as is data on the prevalence of a range of related gastrointestinal (GI) disorders [such as stress ulcers, delayed defecation, opioid-related bowel immotility, and abdominal compartment syndrome (ACS)]. We present a multicentre analysis of coincident GI dysfunction and its effect on burn-related mortality. METHODS: This retrospective analysis was conducted on patients with severe [≥ 20% total burn surface area (TBSA)] and extensive (> 50% TBSA or > 25% full-thickness TBSA) burns admitted to three university teaching institutions in China between January 1, 2011 and December 31, 2020. Both 30- and 90-day mortality were assessed by collating demographic data, burn causes, admission TBSA, % full-thickness TBSA, Baux score, Abbreviated Burn Severity Index (ABSI) score, and Sequential Organ Failure Assessment (SOFA) score, shock at admission and the presence of an inhalation injury. GI dysfunction included abdominal distension, nausea/vomiting, diarrhoea/constipation, GI ulcer/haemorrhage, paralytic ileus, feeding intolerance and ACS. Surgeries, length of intensive care unit (ICU) stay, pain control [in morphine milligram equivalents (MME)] and overall length of hospital stay (LOHS) were recorded. RESULTS: We analyzed 328 patients [75.6% male, mean age: (41.6 ± 13.6) years] with a median TBSA of 62.0% (41.0-80.0%); 256 (78.0%) patients presented with extensive burns. The 90-day mortality was 23.2% (76/328), with 64 (84.2%) of these deaths occurring within 30 d and 25 (32.9%) occurring within 7 d. GI dysfunction was experienced by 45.4% of patients and had a significant effect on 90-day mortality [odds ratio (OR) = 14.070, 95% confidence interval (CI) 5.886-38.290, P < 0.001]. Multivariate analysis showed that GI dysfunction was associated with admission SOFA score and % full-thickness TBSA. Overall, 88.2% (67/76) of deceased patients had GI dysfunction [hazard ratio (HR) for death of GI dysfunction = 5.951], with a survival advantage for functional disorders (diarrhoea, constipation, or nausea/vomiting) over GI ulcer/haemorrhage (P < 0.001). CONCLUSION: Patients with severe burns have an unfavourable prognosis, as nearly one-fifth died within 90 d. Half of our patients had comorbidities related to GI dysfunction, among which GI ulcers and haemorrhages were independently correlated with 90-day mortality. More attention should be given to severe burn patients with GI dysfunction.
Assuntos
Queimaduras , Úlcera , Adulto , Queimaduras/complicações , Queimaduras/epidemiologia , Constipação Intestinal/complicações , Diarreia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Náusea/complicações , Estudos Retrospectivos , Úlcera/complicações , Vômito/complicaçõesRESUMO
OBJECTIVE: The World Health Organization (WHO) grading system for the stratification of G1 and G2 pancreatic neuroendocrine tumors (pNETs) using an optimal Ki-67 index cutoff is still controversial. The present study aimed at finding one optimal Ki-67 cutoff value that distinguishes G1 and G2 tumors by analyzing the prognosis of patients with pNET in our center. METHODS: Data from 84 patients with pNET undergoing surgical resection in The First Affiliated Hospital of Sun Yat-sen University between March 2003 and October 2015 were retrospectively analyzed. RESULTS: The 5-year overall survival rate was 74.2%. Univariate analysis revealed that functional secretion, WHO grade, and TNM stage were significantly associated with long-term survival (all P < 0.05). Multivariate analysis demonstrated that WHO grade (P = 0.023) and TNM stage (P = 0.040) were independent prognostic factors. The receiver operating characteristic curve showed that the Ki-67 index of 5% had the best predictive ability (76.7%) for 5-year survival with a hazard ratio of 44.7. The hazard ratio was only 8.14 when the Ki-67 index cutoff was 2%. CONCLUSIONS: TNM stage and WHO grade were independent prognostic factors of pNETs. A Ki-67 index of 5% is better than 2% in stratifying G1 and G2 pNET tumors.