Transcutaneous Electrical Acustimulation Improved the Quality of Life in Patients With Diarrhea-Irritable Bowel Syndrome.

BACKGROUND AND AIM: Patients with diarrhea-dominant irritable bowel syndrome (IBS-D) experience abdominal pain and reduced quality of life and need effective treatments. This study aimed to evaluate whether transcutaneous electrical acustimulation (TEA) at two acupuncture points, LI4 and ST36, could improve pain and quality of life of patients with IBS-D. MATERIALS AND METHODS: A total of 42 patients with IBS-D who met the Rome IV criteria were randomly divided into two groups: TEA and sham-TEA. TEA was performed through acupoints Hegu (LI4) and Zusanli (ST36) for one hour twice daily for one month, using previously established parameters; sham-TEA was delivered in the same way as TEA but without actual electrical current stimulation. RESULTS: The sham-TEA group showed a significantly higher rate of drop-out than the TEA group (29% vs 0%, p = 0.021). TEA, but not sham-TEA, significantly improved quality of life (before: 78.55 ± 9.62, after: 85.97 ± 9.49, p < 0.0001). Both TEA and sham-TEA reduced abdominal pain; however, TEA was more potent than sham-TEA (p = 0.014). The IBS symptom severity scale score was reduced by both TEA and sham-TEA. Autonomic functions assessed by plasma norepinephrine and pancreatic polypeptide were not altered with TEA, nor was interleukin 10 or interleukin 6. CONCLUSIONS: TEA at LI4 and ST36 improves abdominal pain and quality of life of patients with IBS-D, probably mediated by mechanisms other than autonomic function or inflammatory cytokines.

Comprehensive analysis of prognostic immune-related genes in the tumor microenvironment of hepatocellular carcinoma (HCC).

ABSTRACT: Growing evidence supports that the tumor microenvironment plays a key role in the development and progression of tumors. But immune microenvironment of hepatocellular carcinoma (HCC) has not yet been fully explored. In the present investigation, the clinical value and prognostic significance of immune-related genes in HCC were investigated.The immune and stromal scores of HCC were calculated through the application of Estimation of Stromal and Immune cells in Malignant Tumor tissues using Expression data Algorithm based on the Cancer Genome Atlas database. Differentially expressed genes were identified using the "edgeR" package of the R software. Functional annotation and pathway enrichment were performed using "ggplots2" and "clusterProfiler" packages in R software. Protein-protein interaction network was constructed using STRING, and the hub genes were identified through the Cytoscape. Survival analysis was performed using Kaplan-Meier methods. Tumor Immune Estimation Resource algorithm was used to view the immune landscape of the microenvironment in HCC.Firstly, the immune and stromal scores of HCC were calculated and we found that the immune and stromal scores of HCC were closely related to the patients' prognosis. Then the differentially expressed genes were identified respectively stratified by the median value of the immune and stromal scores, and the immune-related genes that related to the prognosis in HCC patients were further identified. Functional enrichment analysis and protein-protein interaction networks further showed that these genes mainly participated in immune-related biological process. In addition, dendritic cells were found to be the most abundant in the microenvironment of HCC through Tumor Immune Estimation Resource algorithm and were significantly associated with the patients' prognosis. To robust the results, the immune-related genes were validated in an independent dataset from the Gene Expression Omnibus database.We arrived at a more comprehensive understanding of the microenvironment of HCC and extracted 7 immune-related genes that were significantly associated with the recurrence survival of HCC.

CYP3A suppression during diet-induced nonalcoholic fatty liver disease is independent of PXR regulation.

Cytochrome P450 3A (CYP3A) activity is inhibited, and its expression is suppressed during many diseases, including nonalcoholic fatty liver disease (NAFLD). However, the mechanism is controversial. Here, we report that PXR may not take part in the downregulation of CYP3A during NAFLD. Hepatic CYP3A11 (major subtype of mouse CYP3A) mRNA and protein expression was significantly decreased in both mice fed a high-fat diet (HFD) for 8 weeks and palmitate (PA)-treated mouse primary hepatocytes. Similarly, in HepG2 cells, PA treatment significantly suppressed the CYP3A4 (major subtype of human CYP3A) mRNA level and promoter transcription activity. However, Western blotting analysis found an induction of PXR nuclear translocation during NAFLD in both in vivo and in vitro models. Moreover, immunofluorescence determination also found nuclear translocation effect of PXR by PA stimulation in HepG2 cells. In addition, the siRNA knockdown of PXR did not affect the suppressive effects of PA on the CYP3A4 promoter transcription activity and mRNA levels in HepG2 cells. Similarly, PXR knockdown also did not affect the suppressive effects of PA on CYP3A11 mRNA and protein expression levels in mouse primary hepatoctyes. Taken together, the results showed that the suppressive effect of CYP3A transcription was independent of PXR regulation.

Increased admission serum cold-inducible RNA-binding protein concentration is associated with prognosis of severe acute pancreatitis.

BACKGROUND: Cold-inducible RNA-binding protein (CIRP) is a pro-inflammatory cytokine. This study assessed its relation to disease severity and major adverse events (namely local complications, organ failure and in-hospital mortality) of severe acute pancreatitis (SAP) and its discriminatory ability for SAP. METHODS: This prospective and observational study recruited a total of 102 SAP patients, 48 patients with mild acute pancreatitis and 102 healthy individuals. Serum CIRP concentrations were determined using enzyme-linked immunosorbent assay. RESULTS: Serum CIRP concentrations were significantly higher in patients compared to controls. Serum CIRP concentrations were highly correlated with the circulating concentrations of common inflammatory mediators (i.e., procalcitonin, C-reactive protein and white blood cell) and the traditional predictors of disease severity (namely Acute Physiology and Chronic Health Care Evaluation II score, Ranson score, multiple organ dysfunction score and sequential organ failure assessment score). CIRP in serum was an independent predictor for major adverse events. Serum CIRP concentrations showed high predictive value for major adverse events, and possessed high discriminatory performance for SAP. Moreover, its effects significantly exceeded those of the preceding inflammatory mediators. CONCLUSIONS: Increased serum CIRP concentrations clearly reflect SAP severity and prognosis and significantly distinguish SAP, substantializing CIRP as a potential SAP biomarker.

Long noncoding RNA linc00462 promotes hepatocellular carcinoma progression.

BACKGROUND: Hepatocellular carcinoma (HCC) represents one of the most common malignancies worldwide. In two pubic long noncoding RNA (lncRNA) profiling studies of HCC, linc00462 was consistently upregulated. We analyzed the clinical significance and biological role of linc00462 in HCC. METHODS: We performed quantitative real-time PCR analysis to determine the levels of linc00462 in HCC tissues from 49 patients. Functional analysis was performed in cell lines and in an animal model to support clinical findings. RESULTS: Our data showed that linc00462 was significantly upregulated in HCC tissues compared with matched normal tissues. The knockdown of linc00462 in HCC cells resulted in a much less aggressive oncogenic phenotype, and linc00462 downregulation contribute to the inactivation of the PI3K/AKT signaling pathway. CONCLUSIONS: linc00462 may be a potential therapeutic target in HCC.