A Histogram Model to Predict the Risk of Bleeding from Oesophageal and Gastric Variceal Rupture in Cirrhosis.

OBJECTIVE: To establish and verify a nomogram for individualized prediction of patients with oesophageal and gastric variceal rupture and haemorrhage in cirrhosis. STUDY DESIGN: Descriptive study. PLACE AND DURATION OF STUDY: Department of Digestive Internal Medicine, Funan County People's Hospital, Anhui, China, from June 2017 to June 2020. METHODOLOGY: Univariate and multivariate logistic regression analyses were used to identify the risk factors for oesophageal and gastric variceal bleeding in cirrhosis. An individualized risk prediction model was established, which was validated by the parallel bootstrap method and an external validation set. RESULTS: It was found that emotional stimuli (OR=4.591, 95% CI: 1.419-14.852), improper diet (OR=3.702, 95% CI: 1.606-8.526), overwork (OR=3.529, 95% CI: 1.331-9.366), lower temperature (OR=3.013, 95% CI: 1.242-7.308), and increased abdominal pressure (OR=2.416, 95% CI: 0.900-6.487) were independent risk factors for oesophageal and gastric variceal bleeding in cirrhosis. A risk prediction model was established based on the five risk factors, and the R equation test showed that the C-index of the modelling group and the verification group was 0.815 (95% CI: 0.794-0.836) and 0.812 (95% CI: 0.793-0.831), respectively. CONCLUSION: The results of the correction curve showed little difference, which indicated that the risk prediction model has good accuracy and differentiation. KEY WORDS: Cirrhosis, Oesophagus varices and gastric fundus varices, Bleeding, Risk factors, Risk model, Validation.

Rifaximin Improves Visceral Hyperalgesia via TRPV1 by Modulating Intestinal Flora in the Water Avoidance Stressed Rat.

BACKGROUND: Rifaximin is effective in relieving pain symptoms with IBS patients, although the mechanisms were not clear. The aims of the research were to investigate whether the visceral hyperalgesia was alleviated by rifaximin via TRPV1 channel in rats. METHODS: Rats were subjected to water avoidance stress (WAS) and were pretreated with rifaximin by oral gavage. The visceromotor response to colorectal distension was measured. The changes of TRPV1 in peripheral and central neurons of rats were detected by immunofluorescence, western blot method, and RT-PCR. Bacterial 16S ribosomal DNA in ileal contents was assessed using the Illumina MiSeq platform. The effect of intestinal flora on TRPV1 channel was observed by fecal microbiota transplantation (FMT) methods. RESULTS: Rifaximin could relieve the visceral hyperalgesia and reduce the TRPV1 expression of neurons and ileum mucosa in rats induced by WAS. The reduced relative abundance of intestinal flora induced by WAS could be partly prevented by rifaximin. The electromyographical activities and immunoreactivity of TRPV1 in rats could be changed after FMT. CONCLUSIONS: Rifaximin could improve visceral hyperalgesia via TRPV1 channels of peripheral and central neurons by modulating intestinal flora in rats.

Therapeutic effect of targeted Fas-expressing adenoviruses method combining γδ T cells in a mouse model of human ovarian carcinoma.

The present study aimed to investigate the therapeutic effect and safety of targeted use of Fas-expressing adenoviruses combined with γδ T cell-mediated killing to treat human ovarian cancer xenografts in BALB/c mice. Shuttle plasmids containing control elements of human telomerase reverse transcriptase promoter and two-step transcriptional amplification system were constructed and packaged into adenovirus-5 vectors to generate expression of an exogenous Fas gene. A mouse xenograft model of human ovarian carcinoma was constructed. A total of 35 BALB/c mice were randomly divided into five groups, which were injected with PBS, γδ T cells, Fas-expressing adenoviruses, taxol, or Fas-expressing adenovirus and γδ T cells. The weight and volume of tumors in mice in each group was monitored. Tissue sections of the various tissues of mice in the Fas-expressing adenovirus and γδ T cells group was compared with those in the PBS group to evaluate the safety of Fas-expressing adenovirus and γδ T cells in the treatment of human ovarian cancer xenograft tumors. The results of the present study indicated that mice in all treatment groups were alive at the end of the treatment course. Tumor weight and volume was the highest in the PBS group, followed successively by the adenovirus group, the γδ T cell group, the adenovirus and γδ T cell group, and the taxol group. The weight and volume inhibition rate in adenovirus and γδ T cell group were significantly higher compared with in the PBS group (P<0.05). Pathological observation of tissue samples revealed that none of vital organs in the adenovirus and γδ T cell group developed any evident morphological changes during treatment, when compared with healthy controls. In conclusion, the combined therapy with Fas-expressing adenoviruses and γδ T cells is efficient and safe for the treatment of mouse human ovarian carcinoma xenografts.

Gene therapy for human ovarian cancer cells using efficient expression of Fas gene combined with γδT cells.

Low tissue specificity and efficiency of exogenous gene expression are the two major obstacles in tumor­targeted gene therapy. The Fas cell surface death receptor (Fas)/Fas ligand pathway is one of the primary pathways responsible for the regulation of cell apoptosis. The aim of the present study was to explore whether the regulation of tumor specific promoters and a two­step transcriptional amplification system (TSTA) assured efficient, targeted expression of their downstream Fas gene in human ovarian cancer cells, and to assess the killing effect of γδT cells on these cells with high Fas expression. Three shuttle plasmids containing different control elements of the human telomerase reverse transcriptase (hTERT) promoter and/or TSTA were constructed and packaged into adenovirus 5 (Ad5) vectors for the expression of exogenous Fas gene. The human ovarian cancer cell line SKOV3 and a control human embryonic lung fibroblast cell line were transfected with Ad5­hTERT­Fas or Ad5­hTERT­TSTA­Fas. Fas mRNA and protein expression were examined by reverse transcription­quantitative polymerase chain reaction and western blot analysis. γδT lymphocytes were isolated, cultured and mixed at different ratios with SKOV3 cells with Fas expression in order to assess the killing effect of γδT cells. hTERT promoter induced the specific expression of FAS gene in SKOV3 cells, and the TSTA strategy increased FAS expression by 14.2­fold. The killing effect of γδT cells increased with the expression level of Fas and the effector­target cell ratio. The killing rate for SKOV3 cells with high FAS expression was 72.5% at an effector­target cell ratio of 40:1. The regulators of hTERT promoter and TSTA assure the efficient and targeted expression of their downstream Fas gene in SKOV3 cells. The killing effect of γδT cells for ovarian cancer cells with relatively high Fas expression was improved.