Intestinal HIF-1α deletion exacerbates alcoholic liver disease by inducing intestinal dysbiosis and barrier dysfunction.

BACKGROUND & AIMS: Alcoholic liver disease (ALD) is characterized by gut dysbiosis and increased gut permeability. Hypoxia inducible factor 1α (HIF-1α) has been implicated in transcriptional regulation of intestinal barrier integrity and inflammation. We aimed to test the hypothesis that HIF-1α plays a critical role in gut microbiota homeostasis and the maintenance of intestinal barrier integrity in a mouse model of ALD. METHODS: Wild-type (WT) and intestinal epithelial-specific Hif1a knockout mice (IEhif1α-/-) were pair-fed modified Lieber-DeCarli liquid diet containing 5% (w/v) alcohol or isocaloric maltose dextrin for 24 days. Serum levels of alanine aminotransferase and endotoxin were determined. Fecal microbiota were assessed. Liver steatosis and injury, and intestinal barrier integrity were evaluated. RESULTS: Alcohol feeding increased serum levels of alanine aminotransferase and lipopolysaccharide, hepatic triglyceride concentration, and liver injury in the WT mice. These deleterious effects were exaggerated in IEhif1α-/- mice. Alcohol exposure resulted in greater reduction of the expression of intestinal epithelial tight junction proteins, claudin-1 and occludin, in IEhif1α-/- mice. In addition, cathelicidin-related antimicrobial peptide and intestinal trefoil factor were further decreased by alcohol in IEhif1α-/- mice. Metagenomic analysis showed increased gut dysbiosis and significantly decreased Firmicutes/Bacteroidetes ratio in IEhif1α-/- mice compared to the WT mice exposed to alcohol. An increased abundance of Akkermansia and a decreased level of Lactobacillus in IEhif1α-/- mice were also observed. Non-absorbable antibiotic treatment reversed the liver steatosis in both WT and IEhif1α-/- mice. CONCLUSION: Intestinal HIF-1α is essential for the adaptative response to alcohol-induced changes in intestinal microbiota and barrier function associated with elevated endotoxemia and hepatic steatosis and injury. LAY SUMMARY: Alcohol consumption alters gut microbiota and multiple intestinal barrier protecting factors that are regulated by intestinal hypoxia-inducible factor 1α (HIF-1α). Absence of intestinal HIF-1α exacerbates gut leakiness leading to an increased translocation of bacteria and bacterial products to the liver, consequently causing alcoholic liver disease. Intestinal specific upregulation of HIF-1α could be developed as a novel approach for the treatment of alcoholic liver disease.

[Application of cryoablation in minimally invasive mitral valve surgery].

OBJECTIVE: To summarize the clinical data of patients who experienced cryoablation in minimally invasive mitral valve surgery and to explore safety and effectiveness of the surgery.
 METHODS: We retrospectively collected the clinical data of patients who experienced cryoablation in minimally invasive mitral valve surgery in Department of Cardiovascular of Second Xiangya Hospital from August 2013 to July 2015. Through a right side (4-6 cm) thoracotomy, femoral cannulation and aortic cross-clamp by Chitwood clamper was performed, left atrium was entered from interatrial groove. Modified left and right side cryomaze followed by valve surgery was finished. The left atrial appendage was excluded by oversewing from endocardial surface. The cardiopulmonary bypass time, cross-clamp time, duration in hospital were recorded. The heart rhythm of 3 consecutive post operation days, at 7th day, 3 months, 6 months, 12 months or 18 months after the surgery was monitered by 12-leads electrical cardiogram.
 RESULTS: No death was observed in this group. Reexploration for bleeding was conducted for one case. Operation time, CBP time and cross-clamp time was (197.4±27.2), (103.6±20.3)and (65.3±15.7) min, respectively. Duration in ICU and hospital was (1.2±0.4) and (9.2±1.6) d, respectively. The ratio of sinus rhythm restoration right after surgery was 97.1%. The ratio of sinus rhythm restoration at the time of hospital discharge was 94.3%. No motality was found in follow-up. The ratio of sinus rhythm restoration at 3, 6, 12,18 months after the surgery was 94.3%, 93.5%, 90.5%, 93.3%, respectively.
 CONCLUSION: Right minimal invasive thoracoscopic-assisted cryoablation in mitral valve surgery is quite effective in the treatment of atrial fibrillation, displaying the advantages of less complications, motality and hospitalization.