Comparative analysis of monocyte-derived dendritic cell phenotype and T cell stimulatory function in patients with acute-on-chronic liver failure with different clinical parameters.

Background: Acute-on-Chronic Liver Failure (ACLF) patients experience systemic inflammation as well as immune dysfunction and exhaustion. The phenotype and functionality of monocyte-derived dendritic cells in ACLF patients with different clinical parameters have not been elucidated. Methods: This study included 37 cases of ACLF, 20 cases of Chronic Hepatitis B (CHB) patients, and 12 healthy controls. Demographic and laboratory parameters were collected from the enrolled patients. Peripheral blood samples were obtained from the participants. Monocyte-derived dendritic cells were induced and cultured, followed by co-culturing with T cells from the patients. Cell surface markers and intracellular markers were analyzed using flow cytometry. The relationship between these markers and clinical parameters was compared. Results: Our study found that ACLF patients had lower expression levels of HLA-DR, CD86, and CD54 on monocyte-derived dendritic cells compared to both CHB patients and healthy controls. IL-4, GM-CSF, and alcohol were found to promote the expression of HLA-DR, CD86, and CD54 on monocyte-derived dendritic cells. In ACLF patients, higher levels of procalcitonin (PCT), lower levels of albumin, decreased prothrombin activity and deceased patients were associated with lower expression of HLA-DR, CD86, and CD54 on monocyte-derived dendritic cells. Peripheral blood mononuclear cells (PBMCs), after removing adherent cells, were co-cultured with monocyte-derived DC. Our study revealed that patients with infection and low albumin levels exhibited a decreased proportion of T cell subsets within PBMCs. Additionally, these patients' T cells showed lower levels of Ki-67 and interferon-gamma (IFN-γ) production. Conclusion: ACLF patients exhibit varying clinical states, with differences in the phenotype and the ability of monocyte-derived dendritic cells to stimulate T cells. Alcohol can stimulate the maturation of monocyte-derived dendritic cells.

Feasibility of Breast MRI as the Primary Imaging Modality in a Large Asian Cohort.

Purpose Contrast-enhanced MRI has repeatedly demonstrated significantly enhanced sensitivity compared to mammography and ultrasound in breast cancer detection. The purpose of this study was to evaluate the feasibility and outcomes of using breast MRI as the initial imaging study for screening and diagnosis.  Materials and methods In this retrospective review of a cohort of 10,374 breast MRI scans in 7967 patients in Taitung County, Taiwan, a total of 5619 participants met inclusion criteria and were included in our analysis. We reviewed all biopsies that were performed subsequent to MRI studies in women (screening vs. diagnostic). The primary outcomes were false-positive (FP) biopsy rates and positive predictive value (PPV) of MRI - parameters that have historically been associated with performance that restricts more widespread use of MRI. False-positive rate based on benign biopsies (FPR-3) and the positive predictive value (PPV-3) were calculated. Results Without complementary imaging or follow-up to identify false negatives, the study of performance characteristics was limited to false positives and PPV. There were 351 benign biopsies generated by MRI out of the cohort of 5555 participants (5619 minus the malignant biopsies), generating a false-positive rate of 6.3%. Sixty-four patients out of 415 biopsies were malignant, generating a PPV-3 of 15.4%. Conclusion In this Asian cohort, utilizing breast MRI as the initial study for screening and/or diagnosis appears to be limited more by practical considerations such as cost and patient flow efficiency than by feasibility based on performance characteristics. With well-established superior sensitivity, coupled with improved interpretive skills and techniques that allow for low false-positive rates, MRI should be further studied for its role as the primary imaging modality in breast screening and diagnosis.

Downregulation of SUMO2 inhibits hepatocellular carcinoma cell proliferation, migration and invasion.

This study aimed to evaluate the prognostic value and biological function of small ubiquitin-like modifier 2 (SUMO2) in hepatocellular carcinoma (HCC). SUMO2 expression in HCC tissues was markedly higher than that in normal liver tissues, and patients with high SUMO2 expression had significantly shorter median overall survival than those with low SUMO2 expression. Furthermore, SUMO2 expression was closely correlated with lymph node metastasis and vascular invasion and was a predictor of poor prognosis. The knockdown of SUMO2 in two HCC cell lines (SMMC-7721 and Bel-7404) dramatically suppressed their proliferation, migration and invasion. Western blot analysis showed that the downregulation of SUMO2 significantly reduced the expression of Ki-67, matrix metalloproteinase-9 (MMP-9) and vascular endothelial growth factor (VEGF) in SMMC-7721 and Bel-7404 cells. Similarly, quantitative reverse transcription-PCR revealed consistently decreased expression of MMP-9 and VEGF. Our data suggest that SUMO2 promotes proliferation, migration and invasion of HCC cells via mechanisms involving MMP-9 and VEGF. Therefore, SUMO2 may be a prognostic factor and a promising therapeutic target for patients with HCC.

A Prognostic 5-lncRNA Expression Signature for Head and Neck Squamous Cell Carcinoma.

Head and neck squamous cell carcinoma (HNSCC) is a common malignant cancer that accounts for 5-10% of all cancers. This study aimed to identify essential genes associated with the prognosis of HNSCC and construct a powerful prognostic model for the risk assessment of HNSCC. RNAseq expression profile data for the patients with HNSCC were obtained from the TCGA database (GEO). A total of 500 samples with full clinical following-up were randomly divided into a training set and a validation set. The training set was used to screen for differentially expressed lncRNAs. Single-factor survival analysis was performed to obtain lncRNAs that associated with prognosis. A robust likelihood-based survival model was constructed to identify the lncRNAs that are essential for the prognosis of HNSCC. A co-expression network between genes and lncRNAs was also constructed to identify lncRNAs co-expressed with genes to serve as the final signature lncRNAs for prognosis. Finally, the prognostic effect of the signature lncRNAs was tested by multi-factor survival analysis and a scoring model for the prognosis of HNSCC was constructed. Moreover, the results of the validation set and the relative expression levels of the signature lncRNAs in the tumour and the adjacent tissue were consistent with the results of the training set. The 5 lncRNAs were distributed among 3 expression modules. Further KEGG pathway enrichment analysis showed that these 3 co-expressed modules participate in different pathways, and many of these pathways are associated with the development and progression of disease. Therefore, we proposed that the 5 validated lncRNAs can be used to predict the prognosis of HNSCC patients and can be applied in postoperative treatment and follow-up.