Objective To evaluate the role of hypoxia-inducible factor-1α (HIF-1α) in sevoflurane postconditioning-induced reduction of myocardial ischemia-reperfusion (I/R) injury in mice.Methods Forty pathogen-free healthy male C57 mice,aged 8 weeks,weighing 20-30 g,were assigned into 4 groups (n=10 each) using a random number table:sham operation group (group Sham),myocardial I/R group (group I/R),sevoflurane postconditioning group (group SPC) and HIF-1α inhibitor 2Me2 group (group 2Me2).Myocardial I/R was induced by occlusion of the left anterior descending branch of the coronary artery for 30 min followed by 120 min of reperfusion in pentobarbital sodium-anesthetized mice.In group SPC,3％ sevofiurane was inhaled for 15 min starting from the onset of reperfusion.In group 2Me2,30％ 2Me2 (30 mg/kg) was intraperitoneally injected at 30 min before ischemia.The mice were sacrificed at the end of reperfusion,and the hearts were removed for determination of the myocardial infarct size (using the Image J software) and expression of HIF-1α in thc nucleus of cardiomyocytes (by Western blot).Results Compared with group Sham,the myocardial infarct size was significantly increased in I/R,SPC and 2Me2 groups,the expression of HIF-1α was significantly up-regulated in I/R and SPC groups,and the expression of HIF-1α was significantly down-regulated in group 2Me2 (P＜ 0.05).Compared with group I/R,the myocardial infarct size was significantly decreased,and the expression of HIF-1α was up-regulated in group SPC,and the myocardial infarct size was significantly increased,and the expression of HIF-1α was down-regulated in group 2Me2 (P＜0.05).Compared with group SPC,the myocardial infarct size was significantly increased,and the expression of HIF-1α was down-regulated in group 2Me2 (P＜0.05).Conclusion The mechanism by which sevoflurane postconditioning reduces myocardial I/R injury is related to up-regulation of HIF-1α expression in mice.

Objective: To investigate if paclitaxel can enhance the protective effect of myocardial ischemia preconditioning on ischemia/reperfusion injury in aged ratand explore related mechanism. Methods: Primary cardiomyocytes of Sprague-Dawley rats were isolated by trypsin and divided into 5 groups(n=6 each): control group, hypoxia injury group, hypoxia preconditioning group, paclitaxel group,and paclitaxel+hypoxia preconditioning group. The structure of microtubules and the expression of hypoxia-inducible factor-1α(HIF-1α) were analyzed by immunofluorescence staining. The Langendorff isolated heart perfusion model was applied in 4 groups: hypoxia reperfusion injury group, hypoxia preconditioning group, paclitaxel group, and paclitaxel+hypoxia preconditioning group. Each group was further divided into elderly subgroup and adult subgroup (n=6 each). Left ventricular developed pressure and maximum rate of rise in left ventricular pressure were analyzed. Results: (1) Primary cardiomyocyte experiments showed that the myocardial tubular microtubule structure in control group was intact and evenly stained; most of the microtubules in the hypoxia-injured group were absent and the tubular tissue was broken; the hypoxia-induced damage on microtubule structure was smaller in the hypoxic preconditioning group compared with the hypoxic injury group (microtubule staining was not uniform, and the lattice structure was broken, but not that obvious as in the hypoxia group); the tubular structure of the microtubules of the paclitaxel group was basically complete, and the staining was basically uniform.The integrity of tubular structure was maintained to some extent, similar to a normal microtubule structure in paclitaxel+hypoxia preconditioning group. The expression of HIF-1α in the cytoplasm and nucleus was very low in the control group, which was evidenced in both cytoplasm and nucleus in the hypoxic injury group.The expression was further increased in hypoxic preconditioning group, significant nuclear HIF-1 expression was found in the paclitaxel group, the expression was aggregated in the nucleus in the Paclitaxel+ hypoxia preconditioning group. (2)In Langendorff isolated heart perfusion model, left ventricular developed pressure was similar between the elderly subgroup and the adult subgroup at the end of the infusion,after precondition, 5 minutes of reperfusion, 30 minutes of reperfusion, and 60 minutes of reperfusion in the hypoxic injury group (all P> 0.05).In the hypoxic injury group, both the elderly subgroup and the adult subgroup had lower left ventricular developed pressure at 30 minutes of reperfusion when compared with the end of the infusion((15.63±4.88) mmHg (1 mmHg=0.133 kPa) vs. (95.63±22.14)mmHg and (17.31±2.75)mmHg vs. (91.00±9.58)mmHg, respectively,all P<0.05). In the hypoxic preconditioning group, the adult subgroup had higher left ventricular developed pressure at 5 and 30 minutes of reperfusion when compared with the elderly subgroup((7.13±1.02) mmHg vs. (3.75±1.06)mmHg and (43.94±3.21)mmHg vs.(16.31±1.54)mmHg, respectively,all P<0.01). In the paclitaxel group, the adult subgroup had higher left ventricular developed pressure at 30 and 60 minutes of reperfusion when compared with the elderly subgroup((44.31±7.59)mmHg vs. (5.44±1.21)mmHg, (51.56±6.03)mmHg vs. (22.19±5.14)mmHg, respectively, all P<0.01). In the paclitaxel+hypoxia preconditioning group, both the elderly subgroup and the adult subgroup had lower left ventricular developed pressure at 30 minutes of reperfusion when compared with the end of the infusion((18.63±4.30)mmHg vs. (99.94±8.23) mmHg, P<0.01; (49.69±5.34)mmHg vs. (95.31±5.26)mmHg, P<0.05). Meanwhile, the adult subgroup had higher left ventricular developed pressure at 30 minutes of reperfusion when compared with the elderly subgroup((49.69±5.34)mmHg vs. (18.63±4.33)mmHg, P<0.01).The adult subgroup had higher change rate of maximum rate of rise in left ventricular pressure at 60 minutes of reperfusion when compared with the elderly subgroup in hypoxia preconditioning group, paclitaxel group, and paclitaxel combined hypoxia preconditioning group((62.83±3.92)% vs. (33.33±3.20)%, (44.17±2.32)% vs. (36.67±2.88)%, (72.50±2.66)% vs. (53.17±2.56)%, respectively,all P<0.01). Conclusion Paclitaxel can enhance the myocardial protective effect of myocardial ischemia preconditioning through stabilizing microtubules of cardiomyocytes and promoting HIF-1α localization in the nucleus.

Background/Aims: The risk factors of colorectal stricture associated with ulcerative colitis (UC) carcinogenesis in the long-term disease duration remain unclear. Methods: This study included all UC patients registered from a prospectively maintained database between June 1986 to July 2018. The demographic data, clinical features, and outcomes in patients with dysplasia and stricture were assessed using univariable analysis and multivariate logistic regression models. Results: A total of 246 eligible patients were in-cluded in the analysis. The median follow-up time was 13.0 years (interquartile range [IQR], 9.0 to 16.0). There were 35 cases (14.2%) of colorectal stricture. Patients with stricture had worse clinical outcomes. Stricture formation (odds ratio [OR], 9.350; 95% confidence interval [CI], 2.842 to 30.762), inflammatory polyps (OR, 5.464; 95% CI, 1.692 to 17.638), disease duration of more than 10 years (OR, 3.223; 95% CI, 1.040 to 9.985), and age >40 years at diagnosis (OR, 8.499; 95% CI, 1.903 to 37.956) were significantly associated with high-grade dysplasia or colorectal cancer. In addition, disease duration of more than 5 years (OR, 3.211; 95% CI, 1.168 to 8.881), moderated anemia (OR, 3.373; 95% CI, 1.472 to 7.731), and primary sclerosing cholangitis (OR, 5,842; 95% CI, 1.395 to 24.468) were contributing factors for the development of colorectal stricture. Conclusions Colorectal stricture had the highest risk for malignant transformation.Earlier initiation of colonoscopic surveillance in UC patients with risk factors for stricture should be considered to prevent stricture formation and further malignant transformation.