Background: Limited data exist on the association of glucagon‐like peptide 1 receptor agonists (GLP‐1RAs) with the risk of venous thromboembolism. This meta‐analysis aimed to investigate the association between GLP‐1RAs and the risk of venous thromboembolism including deep vein thrombosis (DVT) and pulmonary embolism. Methods and Results: A systematic search of PubMed, Web of Science, EMBASE, and Cochrane library was conducted from inception until July 3, 2024, to identify randomized controlled trials comparing GLP‐1RAs with placebo or other anti‐iabetic drugs, with reported data on DVT and pulmonary embolism. The primary outcome was venous thromboembolism, and secondary outcomes included DVT and pulmonary embolism. Pooled odds ratios (ORs) were calculated using fixed‐effects models with Mantel–Haenszel method and treatment arm continuity correction for zero‐event trials. A total of 39 randomized controlled trials involving 70 499 participants were included. A nonsignificant upward trend in the risk of venous thromboembolism was observed among participants using GLP‐1RAs (OR, 1.19 [95% CI, 0.94–1.50]). GLP‐1RAs were significantly associated with an increased risk of DVT (OR, 1.64 [95% CI, 1.14–2.36]); risk difference 25 (5–52) more events per 10 000 person‐years). Subgroup analyses revealed that increased risk of DVT was particularly prominent in randomized controlled trials with treatment duration >1.5 years (OR, 2.32 [95% CI, 1.49–3.60]) and in cardiovascular outcome trials (OR, 2.18 [95% CI, 1.36–3.49]). No significant association was observed between GLP‐1RAs and risk of pulmonary embolism. Conclusions: GLP‐1RAs might increase the risk of DVT, especially for long‐term use of GLP‐1RAs. Clinicians should be aware of this potential risk when prescribing GLP‐1RAs.

Mounting evidence suggests a causal relationship between specific bacterial infections and the development of certain malignancies. In this study, we examined the presence of Porphyromonas gingivalis (P. gingivalis) in oral-digestive tract tumors by immunohistochemistry (IHC) and PCR and analyzed the correlation between P. gingivalis detection and clinicopathological characteristics and prognosis of oral and esophageal carcinoma. The IHC results showed that the positive rates of P. gingivalis were 60.00, 46.00, 20.00, 6.67, and 2.86% in oral, esophagus, cardiac, stomach, and colorectal cancer tissues, respectively. Likewise, PCR results showed rates of 56.00, 42.00, 16.67, 3.33, and 2.86%, respectively. The two methods were consistent, and the kappa value was 0.806, P < 0.001. In addition, P. gingivalis expression was significantly correlated with lymph node metastasis and the clinical stages of oral and esophageal cancer (P < 0.05). The overall survival rate of the P. gingivalis undetected group (86, 50%) was significantly higher than that of the P. gingivalis detected group (57, 14%) for oral and esophageal cancer, respectively. In conclusion, the detection rate of P. gingivalis showed a decreasing trend in oral-digestive tract tumors. Detection with P. gingivalis was associated with poor prognosis for oral and esophageal cancer.

The interplays of cellular aging and oxidative stress (OS) markers form a complex network, which has been reported to be interrelated with numerous age-related and metabolic diseases, including metabolic syndrome (MS). However, given the multifactorial mechanisms of MS, several important confounders such as dietary factors and the reciprocal effect among these markers have not been considered and adjusted in previous investigations regarding the associations of cellular aging and OS markers with MS and its related metabolic abnormalities. To explicate this, we conducted a cross-sectional study among 533 Chinese adults. All the participants underwent a 75 g oral glucose tolerance test. Dietary data were collected via a 24-hour dietary recall and subsequently analyzed by a registered dietitian using nutrition calculation software. Clinical diagnosis of MS was made according to the revised National Cholesterol Education Program Adult Treatment Panel III criteria (2004) with waist circumference cutoff modified for an Asian population. The leukocyte telomere length, mitochondrial DNA copy number, 8-hydroxy-2-deoxyguanosine, superoxide dismutase (SOD) activity, and glutathione reductase were examined. SOD activity was significantly decreased in MS subjects (62.06±16.89 U/mL vs. 56.25±22.61 U/mL, P=0.001) and exhibited a descending trend across sequential increase of MS component number (Pfortrend=0.031). SOD activity is modestly correlated with glucose indicators and insulin sensitivity and β-cell function indices and was independently and negatively correlated with the level of triglyceride. An independent association between SOD activity and MS was observed after adjusting for metabolic indicators, dietary factors, cellular aging, and OS markers, as well as insulin sensitivity and β-cell function indices. However, the statistical significance of the association between SOD activity and MS was attenuated after adjusting for the Matsuda insulin sensitivity index (ISIM) and insulin secretion-sensitivity index-2 (ISSI-2), suggesting a possible mediating effect. Therefore, we conducted a mediation model analysis, which showed that decreased ISIM and ISSI-2 partially and synergistically mediated the contribution of decreased SOD activity to MS. In conclusion, decreased SOD activity is an independent predictor for increased risk of MS, and insulin resistance and β-cell dysfunction partially mediate the relationship between decreased SOD activity and MS.

Background: Alterations in mitochondrial DNA are potentially associated with oxidative stress and may be involved in the pathogenesis of non-alcoholic fatty liver disease (NAFLD). However, the association between mitochondrial DNA copy number (mtDNAcn) and NAFLD was not consistent. In addition, the association between inflammation and NAFLD has not been established yet. The present study, based on a Chinese population of individuals with different glucose statuses, aimed to explore the association between leukocyte mtDNAcn, markers of oxidative stress, and inflammation and NAFLD. Methods: A total of 318 participants from a diabetes project were included. NAFLD was diagnosed by ultrasonography. Leukocyte mtDNAcn was determined by PCR assay. The levels of the inflammation markers tumor necrosis factor α (TNF-α) and interleukin 6 (IL-6) and the oxidative stress markers glutathione reductase (GR), superoxide dismutase (SOD), and 8-oxo-2′-deoxyguanosine (8-oxo-dG) were also measured. Results: Participants with NAFLD (n = 105) exhibited significantly higher leukocyte mtDNAcn, IL-6, and 8-oxo-dG (all P < 0.05). Pearson correlation analysis indicated mtDNAcn was negatively associated with age, uric acid, SOD, and TNF-α, but was positively associated with 8-oxo-dG (all P < 0.05). Univariate logistic regression analysis revealed that mtDNAcn was positively associated with NAFLD [odds ratio (OR) = 1.617, 95% confidence interval (CI) = 1.036–2.525; P = 0.034]. However, after adjustment for 8-oxo-dG, this association was no longer statistically significant (OR = 1.534, 95% CI = 0.979–2.403, P = 0.062). Moreover, the stress marker 8-oxo-dG was independently associated with NAFLD after adjustment for mtDNAcn, IL-6, glucose tolerance status, and other conventional NAFLD risk factors (OR = 1.707, 95% CI =1.142–2.550, P = 0.009). Mediation analysis indicated that 8-oxo-dG fully mediated the effect of mtDNAcn on the incidence of NAFLD (direct effect β = 0.5221, 95% CI = −0.0648 to 1.2504; indirect effect β = 0.0946, 95% CI = 0.0049–0.2463). Conclusions: In a Chinese population, the association between leukocyte mtDNAcn and NAFLD was fully mediated by high levels of 8-oxo-dG. Thus, oxidative stress may be an important driver of NAFLD, and clinical interventions aimed at decreasing oxidative stress to improve NAFLD warrant further research.

Objectives. In this study, we assessed the effects of dietary magnesium on leukocyte telomere length (LTL). Designs. The current cross-sectional analysis was based on data collected within a type 2 diabetes project. Settings. Dietary magnesium intake is associated with peripheral blood leukocyte telomere length (LTL). However, few epidemiological studies have evaluated the effects of magnesium on LTL in the clinical setting. Participants. This cross-sectional analysis included 467 participants (34.8% men). Measurements. Serum blood lipid profile, HbA1c, oxidative stress, and proinflammatory mediator levels were measured. Detailed dietary data were obtained using a 24 h food recall. LTL was assessed using a real-time PCR assay. Regression models and simple regulatory models were used for data analysis. Results. There was an inverse relationship between dietary magnesium and LTL (P<0.001), with a between-extreme-quarter difference of -0.55. Conversely, there was a positive relationship between dietary magnesium and serum tumor necrosis factor (TNF) α, with an interquarter difference of 3.79 pmol/mL (Pfortrend=0.006). Multivariate regression analysis revealed that the odds ratios (ORs) for shorter LTL and higher serum TNFα increased with magnesium intake, and the ORs of the differences between extreme quartiles were 2.60 (95% confidence interval (CI): 1.31–5.36; P=0.003) and 1.98 (95% CI: 1.09–3.59; P=0.008). There was a direct negative effect of dietary magnesium intake on LTL (B=−0.002; P=0.001), which appeared to be indirectly influenced by TNFα (-0.002 to -0.0005). Conclusions. Dietary magnesium intake may be a critical component of the cellular aging process, and its effect could be partly mediated by TNFα.

We aimed to explore the association between antioxidant vitamin intake, oxidative stress related markers and non-alcoholic fatty liver disease (NAFLD) by a cross-sectional analysis. A total of 241 non-diabetic participants from a Chinese rural cohort were included. NAFLD was diagnosed by abdominal ultrasound (NAFLD, n = 71; Non-NAFLD, n = 171). Dietary intake was assessed by a 24-h food recall. Plasma oxidative stress related markers superoxide dismutase (SOD), glutathione reductase (GR) and 8-oxo-2′-deoxyguanosine(8-oxo-dG) were measured. The association between dietary antioxidant vitamin intake, oxidative stress related markers and NAFLD were analysed by Spearman correlation analysis and multiple logistic regression analysis. Mediation models were established to examine whether SOD mediated the association between dietary vitamin A or α-tocopherol intake and NAFLD. Spearman correlation analysis indicated that dietary vitamin A and α-tocopherol intake were positively correlated with SOD (p < .05). Multiple logistic regression analysis found plasma SOD, dietary vitamin A and α-tocopherol intake were inversely associated with NAFLD (all p < .05). Mediation analysis indicated that SOD significantly mediated the indirect effect of dietary α-tocopherol (mediated effect = 13.21% total effect) or vitamin A (mediated effect = 3.12% total effect) intake on NAFLD. Our study indicated that dietary vitamin A and α-tocopherol intake may contribute to protect from NAFLD in Chinese non-diabetics, and the associations were partly mediated by SOD. However, SOD only accounted for a minor percentage of the association between vitamin A intake and NAFLD. Thus, other mechanisms underlying antioxidant vitamin’ protective effect on NAFLD need further exploration.