Aim: We aimed to assess the association between the use of Glucagon-like peptide-1 receptor agonists and the risk of 12 respiratory diseases in patients with type 2 diabetes, obesity, or overweight. Method: The PubMed (MEDLINE), EMBASE, Cochrane Library, and ClinicalTrials.gov databases were searched from the establishment of the database to December 24, 2022. Dichotomous outcomes were analyzed using RR and 95% CI calculated from fixed-effects models. Results: Twenty-eight RCTs were ultimately included for analysis, involving a total of 77,485 participants. Compared to controls, patients with GLP-1RAs have a 14% lower risk of respiratory disease (RR 0.86, 95% CI 0.81–0.93 p < 0.0001), with Semaglutid (RR 0.82, 95% CI 0.68–0.97, p = 0.02), Liraglutide (RR 0.86. 95% CI 0.75–0.98, p = 0.03), Dulaglutide (RR 0.82, 95% CI 0.70–0.96, p = 0.02), Albiglutide (RR 0.93,95% CI 0.79–1.10, p = 0.40), Exenatide (RR 0.93, 95% CI 0.74–1.18, p = 0.55), Lixisenatide (RR 0.83, 95% CI 0.62–1.12, p = 0.22), and Efpeglenatide (RR 0.76, 95% CI 0.46–1.24, p = 0.27). Semaglutide, Liraglutide and Dulaglutide reduce the risk of respiratory diseases by 18%, 14% and 18%, respectively.Trial duration, control type, and indication were not associated with the impact of GLP-1 receptor agonists on overall respiratory disease. Among secondary outcomes, the risk of Pulmonary edema (RR 0.66, 95% CI 0.44–0.98, p = 0.04), and Bronchitis (RR 0.86, 95% CI 0.74–1.00, p = 0.04) was reduced. Conclusion: In conclusion, GLP-1RAs were linked to a lower risk of overall respiratory diseases, especially Pulmonary edema and Bronchitis. In the future, physicians should pay attention to the relationship between GLP-1 RA and the risk of respiratory diseases and evaluate the efficacy of GLP-1RAs in the primary and secondary prevention of respiratory diseases. Trial registration CRD42023396138. Graphical

Purpose: An update of a systematic review and meta-analysis of the risk of arrhythmias and their subtypes in type 2 diabetic patients receiving glucagon-like peptide 1 receptor agonist (GLP-1RA) medication according to data from the Cardiovascular Outcome Trial(CVOT).Methods: Randomized controlled trials (RCT) on GLP-1RA therapy and cardiovascular outcomes in type 2 diabetes mellitus patients published in full-text journal databases such as MEDLINE (via PubMed), Embase, Clinical Trials.gov, and the Cochrane Library from establishment to March 1, 2022 were searched. We assessed the quality of individual studies by the Cochrane risk-of-bias algorithm. RevMan 5.4.1 software was use for calculating meta-analysis.Results: A total of 60,081 randomized participants were included in the data of these 8 GLP-1RA cardiovascular outcomes trials. Pooled analysis reported no significant effect on total arrhythmia [RR=0.96, 95% CI (0.96, 1.05), p =0.36], and its subtypes such as atrial fibrillation [RR=0.96, 95% CI (0.86, 1.07), p =0.43], atrial flutter [RR= 0.82, 95% CI (0.57, 1.19), p =0.30], atrial tachycardia [RR=0.64, 95% CI (0.20, 2.01), p =0.44)], sinoatrial node dysfunction [RR=0.74, 95% CI (0.44, 1.25), p =0.26], ventricular preterm systole [RR=1.42, 95% CI (0.62, 3.26), p =0.41], second degree AV block [RR=0.96, 95% CI (0.53, 1.72), p =0.88], complete AV block [RR=0.75, 95% CI (0.49, 1.17), p =0.21], ventricular fibrillation [RR=1.00, 95% CI (0.50, 2.02), p =1.00], ventricular tachycardia [RR=1.37, 95% CI (0.91, 2.08), p =0.13] from treatment with GLP-1RA versus placebo. However, the risk of hypoglycemia was reduced by about 30% [RR=0.70, 95% CI (0.57, 0.87), p=0.001] and the risk of pneumonia by about 25% [RR=0.85, 95% CI (0.75, 0.97), p=0.01], both statistically significant differences.Conclusion: In type 2 diabetic patients, treatment with GLP-1RA has no significant effect on the risk of major arrhythmias but significantly reduces the risk of hypoglycemia and pneumonia.

Summary: Background: Fatty liver disease (FLD) is the most common cause of liver dysfunction in developed countries. There is great interest in developing clinically valid and minimally invasive biomarkers to enhance early diagnosis of FLD.Aim: To investigate the potential of circulatory microRNAs (miRNAs) as biomarkers of FLD at the population level.Methods: Plasma levels of 2083 miRNAs were measured by RNA sequencing in 1999 participants from the prospective population‐based Rotterdam Study cohort. The Hounsfield Unit (HU) attenuation of liver was measured using non‐enhanced computed tomography (CT) scan. Logistic and linear regression models adjusting for potential confounders were used to examine the association of circulatory miRNAs with liver enzymes (n = 1991) and CT‐based FLD (n = 954). Moreover, the association of miRNAs with hepatic steatosis and liver fibrosis was assessed longitudinally in individuals who underwent abdominal ultrasound (n = 1211) and transient elastography (n = 777) after a median follow‐up of >6 years.Results: Cross‐sectional analysis showed 61 miRNAs significantly associated with serum gamma‐glutamyl transferase and/or alkaline phosphatase levels (Bonferroni‐corrected P < 8.46 × 10⁻⁵). Moreover, 17 miRNAs were significantly associated with CT‐based FLD (P < 8.46 × 10⁻⁵); 14 were among miRNAs associated with liver enzymes. Longitudinal analysis showed that 4 of these 14 miRNAs (miR‐193a‐5p, miR‐122‐5p, miR‐378d and miR‐187‐3p) were significantly associated with hepatic steatosis (P < 3.57 × 10⁻³) and three (miR‐193a‐5p, miR‐122‐5p and miR‐193b‐3p) were nominally associated with liver fibrosis (P < 0.05). Nine of the 14 identified miRNAs were involved in pathways underlying liver diseases.Conclusions: Plasma levels of several miRNAs can be used as biomarkers of FLD, laying the groundwork for future clinical applications.

Background: Prior studies have reported inconsistent results or less well-explored associations between sex hormones and non-alcoholic fatty liver disease (NAFLD). Here, we aimed to investigate the associations of NAFLD with sex steroids and sex hormone-binding globulin (SHBG) in the population-based study and conduct a comprehensive systematic review and meta-analysis of all published observational studies. Methods: Analyses included 755 men and 1109 women with available data on sex steroids, SHBG, and ultrasound-based NAFLD from the Rotterdam Study. Multivariable regression models were used to examine the associations. Additionally, we searched five databases from inception to 1 April 2022 and performed a systematic review and meta-analysis. Random-effects (DerSimonian-Laird) method was used for meta-analysis, odds ratios (ORs) were calculated for the effect estimate, subgroup and leave-one-out sensitivity analyses were conducted, and meta-regression was performed to explore the pooled statistics with high heterogeneity. Results: In the Rotterdam Study, lower levels of SHBG were associated with NAFLD in both sexes, while lower testosterone was associated with NAFLD only among women. Similarly, the meta-analysis of 16 studies indicated no sex-specific association between SHBG and NAFLD (men: OR = 0.37, 95%CI 0.21–0.53; women: OR = 0.40, 95%CI 0.21–0.60), yet there was a sex-specific association between testosterone and NAFLD (men: OR = 0.59, 95%CI 0.42–0.76; women: OR = 1.06, 95%CI 0.68–1.44). Moreover, men with NAFLD had lower estradiol levels than those without NAFLD. Conclusions: Lower SHBG levels were associated with NAFLD in both sexes, but testosterone levels were associated in a sex-specific manner. In addition, our results showed estradiol with the potential as a protective factor for NAFLD in healthy men.

Background: Fatty liver disease (FLD), primarily nonalcoholic fatty liver disease (NAFLD), is the most common liver disorder that affects a quarter of the global population. NAFLD is a spectrum of disease ranging from simple steatosis to nonalcoholic steatohepatitis, which is associated with increased risk of developing liver cancer. Given that the pathogenic mechanisms of fatty liver remain largely elusive, it is important to further investigate potential underlying mechanisms including epigenetic modifications. Here, we performed a systematic review of human epigenetic studies on FLD presence. Methods: Five bibliographic databases were screened until 28 August 2020. We included cross‐sectional, case‐control and cohort studies in humans that examined the association of epigenetic modifications including global, candidate or epigenome‐wide methylation of DNA, noncoding RNAs and histone modifications with FLD. Results: In total 36 articles, based on 33 unique studies, consisting of 12 112 participants met the inclusion criteria. Among these, two recent epigenome‐wide association studies conducted among large population‐based cohorts have reported the association between cg06690548 ( SLC7A11 ) and FLD. Moreover, several studies have demonstrated the association between microRNAs (miRNAs) and FLD, in which miR‐122, miR‐34a and miR‐192 were recognized as the most relevant miRNAs as biomarkers for FLD. We did not find any studies examining histone modifications in relation to FLD. Conclusions: Cumulative evidence suggests a link between epigenetic mechanisms, specifically DNA methylation and miRNAs, and FLD. Further efforts should investigate the molecular pathways by which these epigenetic markers may regulate FLD and also the potential role of histone modifications in FLD.

Objective: To analyze the therapeutic effect of uterine artery embolisation (UAE) in patients with cesarean section pregnancy (CSP) delivered by cesarean section and the effect on serum human chorionic gonadotrophin (β-HCG) levels and reproductive function.Methods: In total 142 patients with CSP, The control group (n = 71) received Methotrexate (MTX) with ultrasound monitoring after admission and the research group (n = 71) was treated with UAE on basic of the control group. The two groups were compared in terms of treatment outcome, intraoperative bleeding, bed activity, vaginal bleeding and length of hospital stay, and serum follicle stimulating hormone (FSH), oestradiol (E2), luteinising hormone (LH) and β-HCG levels at 1 month postoperatively. The clinical symptoms (normalization of β-HCG and return of menstruation) and clinical outcomes (normal pregnancy, recurrent scar pregnancy) were compared between the two groups, as well as the occurrence of post-operative complications in both groups.Results: Compared with the control group, the research group had a higher overall near-term effective rate, a lower recurrence rate of CSP in pregnancy, and a lower complication rate (P < 0.05); meanwhile, the time to get out of bed, postoperative vaginal bleeding, length of hospital stay, normalization of serum β-HCG, and return to menstruation were shorter in the research group than in the control group (P < 0.05); In addition, serum FSH, E2, LH and β-HCG levels improved better in the research group compared with the control group 1 month after surgery (P < 0.05).Conclusion: The treatment of CSP patients with UAE can reduce the amount of intraoperative bleeding and the duration of vaginal bleeding, promote the improvement of patients' clinical symptoms, have less impact on the disruption of patients' sex hormone balance, reduce patients' surgical risks to a greater extent, preserve patients' normal fertility, and have better application.