Serum ammonia variation predicts mortality in patients with hepatitis B virus-related acute-on-chronic liver failure.

Background: Hyperammonemia is critical to the development of hepatic encephalopathy (HE) and is associated with mortality in end-stage liver disease. This study investigated the clinical value of ammonia variation in hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF) patients. Methods: A total of 276 patients with HBV-ACLF were retrospectively recruited. Patients' ammonia levels were serially documented. Baseline ammonia, Peak ammonia (highest level), and Trough ammonia (lowest level) were particularly corrected to the upper limit of normal (AMM-ULN). The primary endpoint was 28-day mortality. Results: The 28-day, 3-month, and 12-month mortality rates were 19.2, 25.7, and 28.2%, respectively. A total of 51 (18.4%) patients had overt HE (grade 2/3/4). Peak AMM-ULN was significantly higher in patients with overt HE and non-survivors compared with their counterparts (P < 0.001). Following adjustment for significant confounders, high Peak AMM-ULN was an independent predictor of overt HE (hazard ratio, 1.031, P < 0.001) and 28-day mortality (hazard ratio, 1.026, P < 0.001). The cut-off of Peak AMM-ULN was 1.8, determined by using the X-tile. Patients with Peak AMM-ULN appearing on days 1-3 after admission had a higher proportion of overt HE and mortality compared to other groups. Patients with decreased ammonia levels within 7 days had better clinical outcomes than those with increased ammonia. Conclusion: Serum Peak ammonia was independently associated with overt HE and mortality in HBV-ACLF patients. Serial serum ammonia may have prognostic value.

Effects of enhanced external counterpulsation on exercise capacity and quality of life in patients with chronic heart failure: A meta-analysis.

BACKGROUND: This meta-analysis aimed to synthesize randomized controlled trials to evaluate the effects of enhanced external counterpulsation (EECP) on exercise capacity and quality of life in patients with chronic heart failure (CHF). METHODS: Both English and Chinese databases were searched from their inception to June 30, 2020 (PubMed, EMBASE, Cochrane Library, CINAHL (EBSCO), Web of Science for English publications and Chinese Biomedical Database, China National Knowledge Infrastructure, Wanfang Data for Chinese publication). Titles, abstracts, and full-text articles were screened against study inclusion criteria: randomized controlled trials studying EECP intervention for patients with CHF. The meta-analysis was conducted with Revman 5.3 or STATA 16.0. RESULTS: Eight randomized controlled trials were included. EECP induced significant improvement in 6-min walking distance (WMD=84.79 m; 95% CI, 47.64 to 121.95; P < .00001). Moreover, EECP was beneficial for left ventricular ejection fraction (SMD = 0.64; 95% CI,0.29 to 1.00; P = .0004), and N-terminal pro brain natriuretic peptide (SMD = -0.61; 95%CI, -1.20 to -0.01; P = 0.04).However, compared with the control groups, EECP did not significantly reduce the Minnesota Living with Heart Failure Questionnaire scores(WMD, -9.28; 95% CI, -19.30 to 0.75; P = 0.07). CONCLUSIONS: Despite heterogeneity and risk of bias, this meta-analysis confirms that EECP can improve exercise capacity in CHF patients, especially the elderly. However, the evidence that EECP improves the quality of life in patients with CHF is still insufficient. More and larger well-designed randomized controlled trials are still warranted. REGISTRATION INFORMATION: PROSPERO registration no. CRD 42020188848.

Curcumol induces cell cycle arrest in colon cancer cells via reactive oxygen species and Akt/ GSK3ß/cyclin D1 pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Curcuma kwangsiensis S. G. Lee & C. F. Liang (Guangxi ezhu, in Chinese) belongs to the Zingiberaceae family, has been used as a traditionally Chinese medicine nearly 2000 year. Curcumol is one of the guaiane-type sesquiterpenoid hemiketal isolated from medicine plant Curcuma kwangsiensis S. G. Lee & C. F. Liang, which has been reported possesses anti-cancer effects. Our previous study found that the most contribution to inhibit nasopharyngeal carcinoma cell growth was curcumol. AIM OF THE STUDY: To assess the effect of curcumol on cell cycle arrest against human colon cancer cells (CRC) cells (LoVo and SW480) and explore its mechanism in vitro and in vivo. MATERIALS AND METHODS: Curcumol was dissolved in absolute ethyl alcohol. The concentration of absolute ethyl alcohol in the control group or in experimental samples was always 1/500 (v/v) of the final medium volume. LoVo and SW480 cells were treated with different concentrations of curcumol (0, 53, 106, 212 and 424µM). And then the cell cycle of each group was examined by flow cytometry. The protein levels of PI3K, p-Akt, cyclin D1, cyclin E, CDK2, CDK4 and GSK3ß were determined by Western blot. The mRNA expression of PI3K, Akt, cyclin D1, CDK4, P27, p21, and P16 in the treated cells were analyzed by real-time RT-PCR. In addition, the antitumor activity of curcumol was evaluated in nude mice bearing orthotopic tumor implants. RESULTS: Curcumol induced cell cycle arrest in G1/S phase. RT-qPCR and Western blot data showed that curcumol enhanced the expression of GSK3ß, P27, p21 and P16, and decreased the levels of PI3K, phosphorylated Akt (p-Akt), cyclin D1, CDK4, cyclin E and CDK2. Furthermore, curcumol induced reactive oxygen species (ROS) generation in LoVo cells, and ROS scavenger N-acetylcysteine (NAC) significantly reversed curcumol-induced cell growth inhibition. Besides, curcumol also prevented the growth of human colon cancer cells xenografts in nude mouse, accompanied by the reduction of PI3K, Akt, cyclin D1, CDK4, cycln E and significant increase of GSK3ß. CONCLUSIONS: Curcumol caused cell cycle arrest at the G0/G1 phase by ROS production and Akt/ GSK3ß/cyclin D1 pathways inactivation, indicating the potential of curcumol in the prevention of colon cancer carcinogenesis.

Constituents of Gnetum montanum.

A new stilbene, gnetifolin M (1), was isolated from the lianas of Gnetum montanum, together with seven known compounds, resveratrol (2), gnetol (3), 4', 5,7-trihydroxy-3'-methoxyflavone, beta-sitosterol, daucosterol, ursolic acid, and tetracosanoic acid. The structure of 1 was determined to be 2-(5'-methoxy-3'-hydroxyphenyl)-4-hydroxybenzofuran on the basis of spectroscopic evidence.