Expression of immune related genes and possible regulatory mechanisms in different stages of non-alcoholic fatty liver disease.

Background: Non-alcoholic fatty liver disease (NAFLD), which includes simple steatosis (SS) and non-alcoholic steatohepatitis (NASH), is a significant contributor to liver disease on a global scale. The change of immunity-related genes (IRGs) expression level leads to different immune infiltrations. However, the expression of IRGs and possible regulatory mechanisms involved in NAFLD remain unclear. The objective of our research is to investigate crucial genes linked to the development of NAFLD and the transition from SS to NASH. Methods: Dataset GSE89632, which includes healthy controls, SS patients, and NASH patients, was obtained using the GEO database. To examine the correlation between sets of genes and clinical characteristics, we employed weighted gene co-expression network analysis (WGCNA) and differential expression analysis. Hub genes were extracted using a network of protein-protein interactions (PPI) and three different machine learning algorithms. To validate the findings, another dataset that is publicly accessible and mice that were subjected to a high-fat diet (HFD) or MCD diet were utilized. Furthermore, the ESTIMATE algorithm and ssGSEA were employed to investigate the immune landscape in the normal versus SS group and SS versus NASH group, additionally, the relationship between immune infiltration and the expression of hub genes was also examined. Results: A total of 28 immune related key genes were selected. Most of these genes expressed reverse patterns in the initial and progressive stages of NAFLD. GO and KEGG analyses showed that they were focused on the cytokine related pathways and immune cell activation and chemotaxis. After screening by various algorithms, we obtained two hub genes, including JUN and CCL20. Validation of these findings was confirmed by analyzing gene expression patterns in both the validation dataset and the mouse model. Ultimately, two hub genes were discovered to have a significant correlation with the infiltration of immune cells. Conclusion: We proposed that there were dynamic changes in the expression levels of IRGs in different stages of NAFLD disease, which led to different immune landscapes in SS and NASH. The findings of our research could serve as a guide for the accurate management of various phases of NAFLD.

Prevention of distal stent graft-induced new entry after endovascular repair for type B aortic dissection: A retrospective cohort study.

OBJECTIVES: Distal stent graft-induced new entry (dSINE) can occur after thoracic endovascular aortic repair (TEVAR) for type B aortic dissection (TBAD). In this study we aimed to compare the effectiveness of restrictive bare stent (RBS), tapered stent graft (TSG), and non-TSG in TEVAR in preventing dSINE after a midterm follow-up. METHODS: This retrospective cohort study included patients with TBAD who underwent TEVAR (June 2010 to December 2018). The occurrence of dSINE during follow-up was examined. Predictors of dSINE were determined using Fine-Gray regression with death as the competing event. Survival was evaluated using Cox proportional hazards regression. RESULTS: Finally, 364 patients were included: 111 with non-TSG TEVAR, 125 with TSG TEVAR, and 128 with TEVAR with RBS. After 54.5 months, incidences of dSINE in the 3 groups were 12.61%, 4.80%, and 1.56%, respectively (P = .002). On Fine-Gray regression adjusted for clinically relevant covariates, the expansion mismatch ratio (subdistribution hazard ratio, 1.09; 95% CI, 1.07-1.12; P < .001) and complete false lumen thrombosis (subdistribution hazard ratio, 0.35; 95% CI, 0.13-0.94; P = .037) were identified as predictors of dSINE. The Cox proportional hazards regression analysis revealed that dSINE was not only a risk factor for aortic-related mortality (hazard ratio, 17.90; 95% CI, 3.27-98.12; P = .001), but also a predominant risk factor for all-cause mortality (hazard ratio, 4.91; 95% CI, 1.66-14.52; P = .004). CONCLUSIONS: dSINE can happen in TBAD patients who undergo TEVAR. Thus, long-term surveillance is crucial. TSG and RBS had lower expansion mismatch ratios, which might help prevent dSINE.

Utilization of 3D printing technology in hepatopancreatobiliary surgery. / 3D打印技术在肝胆胰外科中的应用进展.

The technology of three-dimensional (3D) printing emerged in the late 1970s and has since undergone considerable development to find numerous applications in mechanical engineering, industrial design, and biomedicine. In biomedical science, several studies have initially found that 3D printing technology can play an important role in the treatment of diseases in hepatopancreatobiliary surgery. For example, 3D printing technology has been applied to create detailed anatomical models of disease organs for preoperative personalized surgical strategies, surgical simulation, intraoperative navigation, medical training, and patient education. Moreover, cancer models have been created using 3D printing technology for the research and selection of chemotherapy drugs. With the aim to clarify the development and application of 3D printing technology in hepatopancreatobiliary surgery, we introduce seven common types of 3D printing technology and review the status of research and application of 3D printing technology in the field of hepatopancreatobiliary surgery.

Advances in Drug Therapy for Metastatic Pancreatic Ductal Adenocarcinoma.

Pancreatic ductal adenocarcinoma (PDAC) is an aggressive disease with a notably poor prognosis. A large number of patients with PDAC develop metastases before they are diagnosed with metastatic pancreatic cancer (mPDAC). For mPDAC, FOLFIRINOX or gemcitabine plus nab-paclitaxel are the current first-line treatments. It is important to note, however, that many patients will fail chemotherapy because of drug resistance. ​Heterogeneous tumors and complex tumor microenvironments are key factors. As a result, clinical researchers are exploring a variety of alternative treatment modalities. Current understanding of the molecular signature and immune landscape of PDAC has motivated the emergence of different targeted and immune-based therapeutic approaches, some of which have shown promising results. The purpose of this review is to discuss the new targets and new drugs for mPDAC in terms of specific pathogenic factors such as metabolic vulnerability, DNA damage repair system, tumor microenvironment and immune system, in order to identify potential vulnerabilities in mPDAC patients and hopefully improve the prognosis of mPDAC patients.

Research progress and applications of epigenetic biomarkers in cancer.

Epigenetic changes are heritable changes in gene expression without changes in the nucleotide sequence of genes. Epigenetic changes play an important role in the development of cancer and in the process of malignancy metastasis. Previous studies have shown that abnormal epigenetic changes can be used as biomarkers for disease status and disease prediction. The reversibility and controllability of epigenetic modification changes also provide new strategies for early disease prevention and treatment. In addition, corresponding drug development has also reached the clinical stage. In this paper, we will discuss the recent progress and application status of tumor epigenetic biomarkers from three perspectives: DNA methylation, non-coding RNA, and histone modification, in order to provide new opportunities for additional tumor research and applications.