The effect of metformin on esophageal cancer risk in patients with type 2 diabetes mellitus: a systematic review and meta ‑ analysis

Objective Recently, numerous studies have yielded inconsistent results regarding the effect of metformin on esophageal cancer risk in type 2 diabetes mellitus patients. The purpose of this study is to systematically assess this effect using meta-analysis. Methods We searched clinical studies on metformin and esophageal cancer risk in PubMed, Embase, and the Cochrane Library. After literature screening, a series of meta-analyses were conducted using RevMan 5.3 software. The pooled hazard ratio (HR) and the corresponding 95% confidence interval (CI) were used as the effect size. Results Five eligible studies (four cohort studies and one case–control study) were included for our meta-analysis using a random-effect model. The analysis showed that metformin could not reduce esophageal cancer risk in type 2 diabetes mellitus patients (HR 0.88, 95% CI 0.60–1.28, P > 0.05). Subgroup analyses by geographic location showed that metformin significantly reduced esophageal cancer risk in Asian patients with type 2 diabetes mellitus (HR 0.59, 95% CI 0.39–0.91, P = 0.02), without heterogeneity between studies (P = 0.80 and I2 = 0%). Conclusions Overall, our systematic review and meta-analysis demonstrate that metformin does not reduce esophageal cancer risk in type 2 diabetes mellitus patients. However, a significant reduction in esophageal cancer risk in Asian populations remains to be clarified (AU)

The effect of metformin on esophageal cancer risk in patients with type 2 diabetes mellitus: a systematic review and meta­analysis.

OBJECTIVE: Recently, numerous studies have yielded inconsistent results regarding the effect of metformin on esophageal cancer risk in type 2 diabetes mellitus patients. The purpose of this study is to systematically assess this effect using meta-analysis. METHODS: We searched clinical studies on metformin and esophageal cancer risk in PubMed, Embase, and the Cochrane Library. After literature screening, a series of meta-analyses were conducted using RevMan 5.3 software. The pooled hazard ratio (HR) and the corresponding 95% confidence interval (CI) were used as the effect size. RESULTS: Five eligible studies (four cohort studies and one case-control study) were included for our meta-analysis using a random-effect model. The analysis showed that metformin could not reduce esophageal cancer risk in type 2 diabetes mellitus patients (HR 0.88, 95% CI 0.60-1.28, P > 0.05). Subgroup analyses by geographic location showed that metformin significantly reduced esophageal cancer risk in Asian patients with type 2 diabetes mellitus (HR 0.59, 95% CI 0.39-0.91, P = 0.02), without heterogeneity between studies (P = 0.80 and I2 = 0%). CONCLUSIONS: Overall, our systematic review and meta-analysis demonstrate that metformin does not reduce esophageal cancer risk in type 2 diabetes mellitus patients. However, a significant reduction in esophageal cancer risk in Asian populations remains to be clarified.

Intervention effects of four exercise modalities on nonalcoholic fatty liver disease: a systematic review and Bayesian network meta-analysis.

OBJECTIVE: This study aimed to evaluate the effect of four exercise modalities on patients with nonalcoholic fatty liver disease (NAFLD). MATERIALS AND METHODS: Databases of CNKI, Wanfang, VIP, Web of Science, PubMed, Cochrane Library, Medline, and Embase were searched for relevant studies. The literature search was restricted to those published between January 2010 and June 2021. Randomized controlled trials of exercise interventions on NAFLD were collected. Data were presented as statistical graphics using ADDIS 1.16.5 and R-Studio 4.1. RESULTS: Seventeen controlled studies analyzing 1627 patients with NAFLD were included. Patients were divided into the control group (n=688), aerobic training group (AT, n=554), resistance training group (RT, n=232), high-intensity interval training group (HIIT, n=53), and aerobic training with resistance training group (AT+RT, n=100). Results of the statistical analysis showed that the combined exercise intervention had the most significant effect on the total serum cholesterol of patients' mean difference [MD=0.47(0.23, 0.73), p<0.05]. Levels of alanine aminotransferase and aspartate aminotransferase were improved, but no significant difference was found in their levels in the four groups of exercise intervention. The intervention effect of the four exercises on blood lipid and liver enzymes in patients with NAFLD was in the order of AT+RT > HIIT > RT > AT > control. CONCLUSIONS: Exercise interventions are recommended as stand-alone or adjunctive therapy. For patients with NAFLD who can tolerate various exercises, priority should be given to AT+RT exercise 4-5 times per week. The exercise intensity should be 50%-70% of the maximum heart rate and performed for >3 months to improve the effectiveness of the exercise supervision intervention.

Oxidative stress and metallothionein expression in the liver of rats with severe thermal injury.

The aim of this work was to study oxidative stress and the compensating mechanisms implicated in severe thermal injury using the burned rat model. Results showed that after thermal injury glutathione (GSH) level was decreased, oxidized glutathione (GSSG) and the ratio of GSSG/GSH increased both at 24 and 48 h in the liver. The activities of GSH-reductase (GSH-Rx) in the liver and GSH-peroxidase (GSH-Px) both in the liver and erythrocytes increased at 24 h and then decreased at 48 h. The level of alpha-tocopherol in plasma was reduced at 24 h. Lipid peroxide levels increased both at 24 and 48 h in the liver. The serum zinc level decreased, reaching a minimum at 12h, whereas liver zinc level was elevated and reached the maximum at 12 h. After severe thermal injury enhancement of metallothionein (MT) expression has been discovered for the first time. MT content in the liver increased both at 24 and 48 h. Expression of MT-I mRNA was activated at 3 h and reached the top at 24 h postburn. The conclusion is that severe thermal injury gives rise to oxidative stress and dramatic enhancement of MT expression could be one of the important compensative mechanisms of natural defense system postburn.

Effects of m-nisoldipine on contraction and 45Ca influx in isolated rat aorta.

m-Nisoldipine caused a concentration-dependent depression of the contractile response and 45Ca influx evoked by KCl in isolated rat thoracic aorta. The IC50 value for contraction and 45Ca influx were 0.69 (95% confidence limits 0.32-1.5) nmol.L-1 and 0.35 (95% confidence limits 0.06-2.0) nmol.L-1, respectively. There was a positive correlation between the inhibition of KCl-evoked contraction and 45Ca influx (r = 0.996). m-Nisoldipine (0.1-10 mumol.L-1) did not influence the 45Ca influx into resting cells and failed to inhibit noradrenaline (1.0 mumol.L-1)-evoked contraction and 45Ca influx. The results suggest that the relaxant effect of m-nisoldipine on rat aorta may be closely related to the blockade of Ca2+ entry through a potential-dependent calcium channel.