Cervical cancer is the fourth most common malignant tumor globally in terms of morbidity and mortality. The presence of lymph node metastasis (LNM) is an independent prognostic factor for progression-free survival (PFS) and overall survival (OS) in cervical cancer patients. The International Federation of Gynecology and Obstetrics (FIGO) staging system was revised in 2018. An important revision designates patients with regional LNM as stage IIIC, pelvic LNM only as stage IIIC1, and para-aortic LNM as stage IIIC2. However, the current staging system is only based on the anatomical location of metastatic lymph nodes (LNs). It does not consider other LN status parameters, which may limit its prognostic significance to a certain extent and needs further exploration and confirmation in the future. The purpose of this review is to summarize the choice of treatment for stage IIIC cervical cancer and the effect of different LN status parameters on prognosis.
Objective The aim of this study was to investigate the value of multiparametric magnetic resonance imaging (MRI) in demonstrating the metastatic potential of primary tumor and differentiating metastatic lymph nodes (MLNs) from nonmetastatic lymph nodes (non-MLNs) in stage IB1–IIA1 cervical cancer. Methods Fifty-seven stage IB1–IIA1 subjects were included. The apparent diffusion coefficient (ADC) values and dynamic contrast-enhanced MRI (DCE-MRI) parameters of primary tumors and lymph nodes and the conventional imaging features of the lymph nodes were measured and analyzed. Mann-Whitney test and χ2 test were used to analyze statistically significant parameters, logistic regression was used for multivariate analysis, and receiver operating characteristic analysis was used to compare the diagnostic performance of the MLNs. Results Nineteen subjects had lymph node metastasis. A total of 94 lymph nodes were evaluated, including 30 MLNs and 64 non-MLNs. There were no significant difference in ADC and DCE-MRI parameters between metastatic and nonmetastatic primary tumors. The heterogeneous signal was more commonly seen in MLNs than in non-MLNs (P = 0.001). The values of ADCmean, ADCmin, and ADCmax of MLNs were lower than those of non-MLNs (P < 0.001). The values of short-axis diameter, K trans, K ep, and V e of MLNs were higher than those of non-MLNs (P < 0.05). Compared with individual MRI parameters, the combined evaluation of short-axis diameter, ADCmean, and K trans showed the highest area under the curve of 0.930. Conclusions Diffusion-weighted imaging and DCE-MRI could not demonstrate the metastatic potential of primary tumor in stage IB1–IIA1 cervical cancer. Compared with individual MRI parameters, the combination of multiparametric MRI could improve the diagnostic performance of lymph node metastasis.
BackgroundThe gut microbiome affects the occurrence and development of NAFLD, but its mechanism has not yet been fully elucidated. Chinese medicine is a new treatment strategy to improve NAFLD by regulating the gut microbiome. Tianhuang formula (TH) has been proved to have a lipid-lowering effect in which constituents of ginsenoside Rb1, ginsenoside Rg1, ginsenoside Rb, ginsenoside Re, and ginsenoside R1 from Panax notoginseng and berberine, palmatine, and coptisine from Coptis chinensis have low drug permeability, which results in poor intestinal absorption into the human body, and are thus able to come into contact with the gut microflora for a longer time. Therefore, it might be able to influence the gut microbial ecosystem, but it still needs to be investigated.MethodThe characteristics of the gut microbiome were represented by 16S rRNA sequencing, and the metabolites in intestinal contents and liver were discovered by non-targeted metabolomics. Correlation analysis and fermentation experiments revealed the relationship between the gut microbiome and metabolites. Blood biochemical indicators, liver function indicators, and oxidation-related indicators were assayed. H&E staining and Oil Red O staining were used to analyze the characteristics of hepatic steatosis. RT-qPCR and western blotting were used to detect the expression of genes and proteins in liver tissues, and fecal microbial transplantation (FMT) was performed to verify the role of the gut microbiome.ResultsGut microbiome especially Lactobacillus reduced, metabolites such as 5-Methoxyindoleacetate (5-MIAA) significantly reduced in the liver and intestinal contents, the level of hepatic GSH and SOD reduced, MDA increased, and the protein expression of Nrf2 also reduced in NAFLD mice induced by high-fat diet (HFD). The normal diet mice transplanted with NAFLD mice feces showed oxidative liver injury, indicating that the NAFLD was closely related to the gut microbiome. TH and TH-treated mice feces both can reshape the gut microbiome, increase the abundance of Lactobacillus and the content of 5-MIAA in intestinal contents and liver, and improve oxidative liver injury. This indicated that the effect of TH improving NAFLD was related to the gut microbiome, especially Lactobacillus. 5-MIAA, produced by Lactobacillus, was proved with fermentation experiments in vitro. Further experiments proved that 5-MIAA activated the Nrf2 pathway to improve oxidative stress in NAFLD mice induced by HFD. TH reshaped the gut microbiome, increased the abundance of Lactobacillus and its metabolite 5-MIAA to alleviate oxidative stress, and improved NAFLD.ConclusionThe study has demonstrated a mechanism by which the gut microbiome modulated oxidative stress in NAFLD mice induced by HFD. The traditional Chinese medicine TH improved NAFLD by regulating the gut microbiome, and its mechanism was related to the “Lactobacillus-5-MIAA-Nrf2” pathway. It provided a promising way for the intervention of NAFLD.
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