Portal hypertension develops along with liver cirrhosis then induces the formation of portal-systemic collaterals and lethal complications. Extrahepatic angiogenesis plays an important role. Glycyrrhizin has been found to exhibit anti-angiogenic features, which leads to its extensive use. However, the relevant effects of glycyrrhizin on liver cirrhosis and portal hypertension have not been evaluated. This study thus aimed to investigate the impact of glycyrrhizin on portal hypertension-related derangements in cirrhotic rats. Male Sprague-Dawley rats received bile duct ligation (BDL) to induce cirrhosis or sham operation as control. The rats were subdivided to receive glycyrrhizin (150 mg/kg/day, oral gavage) or vehicle beginning on the 15th day post operation, when BDL-induced liver fibrosis developed. The effects of glycyrrhizin were determined on the 28th day, the typical timing of BDL-induced cirrhosis. Glycyrrhizin significantly reduced portal pressure (p = 0.004). The splanchnic inflow as measured by superior mesenteric arterial flow decreased by 22% (p = 0.029). The portal-systemic collateral shunting degree reduced by 30% (p = 0.024). The mesenteric angiogenesis and phospho-VEGFR2 protein expression were also downregulated (p = 0.038 and 0.031, respectively). Glycyrrhizin did not significantly influence the liver biochemistry data. Although glycyrrhizin tended to reverse liver fibrosis, statistical significance was not reached (p = 0.069). Consistently, hepatic inflow from portal side, hepatic vascular resistance, and liver fibrosis-related protein expressions were not affected. Glycyrrhizin treatment at the stage of hepatic fibrosis still effectively attenuated portal hypertension and portosystemic collateral shunting. These beneficial effects were attributed to, at least in part, the suppression of mesenteric angiogenesis by VEGF signaling pathway downregulation.

Liver fibrosis causes portal hypertension which dilates collateral vasculature and enhances extra-hepatic angiogenesis including intrapulmonary shunts, which subsequently complicates with hepatopulmonary syndrome. Metformin is an anti-diabetic agent which possesses anti-inflammation and anti-angiogenesis properties. This study evaluated the effect of metformin treatment on liver and lung in a non-diabetic rat model with biliary cirrhosis induced via common bile duct ligation (CBDL). CBDL rats were fed with metformin 150 mg/kg/day during the 8th-28th day post operation. The hemodynamic and biochemistry parameters were tested, and blood gas analysis was performed. The liver and lung were dissected for protein analysis and immuno-histochemical stains. Intrapulmonary shunting degree was determined using color microsphere method. Metformin treatment neither induced obvious hypoglycemic event nor altered hemodynamics in cirrhotic rats. The plasma levels of alanine aminotransferase were significantly reduced by metformin (control vs. metformin: 269 ± 56 vs. 199 ± 21 IU/L, P = 0.02). Sirius Red stains and CD-68 stains showed that metformin reduced intrahepatic fibrosis and CD-68-positive macrophages. Metformin did not influence hypoxia and intrapulmonary angiogenesis; however, it significantly reduced intrapulmonary shunts (31.7 ± 10.1 vs. 15.0 ± 6.6%, P = 0.006.). Furthermore, metformin reduced the protein expressions of COX-2 and PI3K in liver and COX-1 in lung. Metformin reduced liver injury and improved hepatic fibrosis in cirrhotic rats. It also attenuated the intrapulmonary shunts. However, the effects of metformin on pulmonary angiogenesis and hypoxia were insignificant.

Background: This study aimed to evaluate whether the role-play (RP) of real patients by medical students as part of interactive clinical reasoning training can improve medical students’ clinical performance. Methods: A total of 26 medical students volunteered to portray real patients within this program and were treated as the RP group while the other 72 students as the non-RP group. In the interactive morning meeting, the medical students practiced how to approach the RP student as if they were encountering a real patient. All students were evaluated by mini-clinical evaluation exercises (mini-CEX) before and after this training program. Results: We found that all students had an increased total mini-CEX score after 4-week training, especially for interviewing skills. Notably, after training, the RP students had significantly elevated total mini-CEX scores (51.23 ± 1.06 vs 53.12 ± 1.11, p = 0.028), and for counselling (7.15 ± 0.14 vs 7.54 ± 0.18, p = 0.015) and overall clinical competence (7.27 ± 0.15 vs 7.65 ± 0.16, p = 0.030). In contrast, the non-RP students had lower scores compared with the RP group, as revealed by both the pre- and post-training tests. Moreover, their mini-CEX scores were not improved after training. Conclusion: Medical students who were motivated to RP real patients had better performance scores than those who did not. In addition, RP can enhance their counselling skills and clinical competences.

Background: Liver cirrhosis is characterized by liver fibrosis and pathological angiogenesis, which results in hyperdynamic circulation, portal-systemic collateral vascular formation, and abnormal angiogenesis. Lycopene is a nutrient mostly found in tomatoes. The beneficial effects of lycopene include anti-inflammation, anti-oxidation, anti-fibrosis, and anti-angiogenesis; however, the association between liver cirrhosis and pathological angiogenesis has yet to be studied. This study aimed to investigate the effects of lycopene on biliary cirrhotic rats. Methods: The efficacy of lycopene treatment in common bile duct ligation (BDL)-induced biliary cirrhotic rats was evaluated. Sham-operated rats served as surgical controls. Lycopene (20 mg/kg/day, oral gavage) or vehicle was administered to BDL or sham-operated rats for 4 weeks, after which the hemodynamics, liver biochemistry, portal-systemic shunting, liver and mesenteric angiogenesis, and hepatic angiogenesis-related protein expressions were examined. Results: Lycopene alleviated hyperdynamic circulation as evidenced by decreased cardiac index and increased peripheral vascular resistance (p < 0.05), but it did not affect portal pressure or liver biochemistry in the BDL rats (p > 0.05). Lycopene significantly diminished the shunting degree of portal-systemic collaterals (p = 0.04) and mesenteric vascular density (p = 0.01), and also ameliorated intrahepatic angiogenesis and liver fibrosis. In addition, lycopene upregulated endothelial nitric oxide synthase, protein kinase B (Akt) and phosphatidylinositol 3-kinases (PI3K), and downregulated vascular endothelial growth factor receptor 2 (VEGFR-2) protein expressions (p < 0.05) in the livers of the BDL rats. Conclusion: Lycopene ameliorated liver fibrosis, hyperdynamic circulation, and pathological angiogenesis in biliary cirrhotic rats, possibly through the modulation of intrahepatic Akt/PI3K/eNOS and VEGFR-2 pathways.

Background: Non-alcoholic fatty liver disease (NAFLD) is linked with metabolic syndrome. Previous studies showed that obesity may disrupt adrenal function and adversely affect its counter-regulations against shock. This study hence evaluated adrenal function abnormalities in NAFLD with shock. Methods: Sprague-Dawley rats were fed with regular chow-diet (control) or high fat diet (HFD, 60% energy derived from fat). Blood tests were performed at the end of the 4th, 6th and 8th week, respectively. Experiments were performed at the end of the 8th week. Results: HFD rats developed NAFLD. HFD rats had 27% and 51% increase in plasma corticosterone at the 6th and 8th week in usual status. However, HFD rats had 5 times more reduction of mean arterial pressure in response to lipopolysaccharide-induced sepsis as compared to control rats. The corticosterone increment ratio was also lower in HFD rats, even after ACTH administration. 11β-HSD system tended to generate more corticosterone in HFD rats under hemodynamic stable status without shock and the trend was lost in HFD rats with septic shock. Conclusion: Rats with NAFLD had profound septic shock due to inadequate corticosterone response. This is, at least partly, due to 11β-HSDs dysregulation in sepsis.