Objective: Investigating the causal relationship between rheumatoid arthritis (RA) and atlantoaxial subluxation (AAS) and identifying and quantifying the role of C-reactive protein (CRP) as a potential mediator.Methods: Using summary-level data from a genome-wide association study (GWAS), a two-sample Mendelian randomization (MR) analysis of genetically predicted rheumatoid arthritis (14,361 cases, and 43,923 controls) and AAS (141 cases, 227,388 controls) was performed. Furthermore, we used two-step MR to quantitate the proportion of the effect of c-reactive protein-mediated RA on AAS.Results: MR analysis identified higher genetically predicted rheumatoid arthritis (primary MR analysis odds ratio (OR) 0.61/SD increase, 95% confidence interval (CI) 1.36-1.90) increased risk of AAS. There was no strong evidence that genetically predicted AAS had an effect on rheumatoid arthritis risk (OR 1.001, 95% CI 0.97-1.03). The proportion of genetically predicted rheumatoid arthritis mediated by C-reactive protein was 3.7% (95%CI 0.1%−7.3%).Conclusion: In conclusion, our study identified a causal relationship between RA and AAS, with a small proportion of the effect mediated by CRP, but a majority of the effect of RA on AAS remains unclear. Further research is needed on additional risk factors as potential mediators. In clinical practice, lesions of the upper cervical spine in RA patients need to be given more attention.

The association between non-alcoholic fatty liver disease (NAFLD) and cardiovascular disease (CVD) is well studied. Liver fibrosis is the main histopathologic manifestations of NAFLD. However, whether concomitant NAFLD influence the association of non-invasive liver fibrosis scores with CVD remains unclear. We systematically searched PubMed, Cochrane Library, and Embase databases for cohort studies exploring the association between liver fibrosis score (LFS)and CVD events up to June 10, 2025. Random-effects model was used to pool results. CVD events were defined as cardiovascular mortality, myocardial infarction, and coronary heart disease. Nineteen cohorts involving 1,481,875 adults were included with an average age of 54.8 years old, and 50.2% males. Fibrosis 4 score (FIB-4), nonalcoholic fatty liver disease fibrosis score (NFS) and APRI (Aspartate transaminase/platelet ratio index) were associated with increased risks of CVD events (FIB-4: odds ratio [OR] 1.77, 95% confidence interval [CI] 1.58–1.99, low certainty; NFS: OR 2.40, 95% CI 1.83–3.14, low certainty; APRI: OR 1.61, 95% CI 1.17–2.21, low certainty). Each one-unit increment in FIB-4, NFS scores was associated with CVD events (FIB-4: OR 1.21, 95% CI 1.12–1.31; NFS: OR 1.38, 95% CI: 1.17–1.62). A positive linear relationship was observed between FIB-4 (P-nonlinearity = 0.000), NFS (P-nonlinearity = 0.7145) and CVD events. Risk estimates for cardiovascular events were similar in patients with NAFLD (FIB-4: OR 1.87, 95% CI 1.53–2.28; NFS: OR 2.59, 95% CI 1.55–4.33) and without NAFLD (FIB-4: OR 1.74, 95% CI 1.51-2.00; NFS: OR 2.26, 95% CI 1.64–3.11) (P for difference: FIB-4 = 0.56; NFS = 0.66). FIB-4 and NFS were associated with an increased risk of CVD events in patients with and without NAFLD. FIB-4 and NFS risk estimates for cardiovascular events were not influenced by concomitant NAFLD. URL: http://www.crd.york.ac.uk/prospero/ PROSPERO (registration number: CRD42023421092). The online version contains supplementary material available at 10.1186/s12889-025-23883-x.

Background: Perioperative acute kidney injury (AKI) is common in surgical patients and is associated with high morbidity and mortality. There are currently few options for AKI prevention and treatment. Due to its complex pathophysiology, there is no efficient medication therapy to stop the onset of the injury or repair the damage already done. Certain anesthetics, however, have been demonstrated to affect the risk of perioperative AKI in some studies. The impact of anesthetics on renal function is particularly important as it is closely related to the prognosis of patients. Some anesthetics can induce anti-inflammatory, anti-necrotic, and anti-apoptotic effects. Propofol, sevoflurane, and dexmedetomidine are a few examples of anesthetics that have protective association with AKI in the perioperative period. Summary: In this study, we reviewed the clinical characteristics, risk factors, and pathogenesis of AKI. Subsequently, the protective effects of various anesthetic agents against perioperative AKI and the latest research are introduced. Key Message: This work demonstrates that a thorough understanding of the reciprocal effects of anesthetic drugs and AKI is crucial for safe perioperative care and prognosis of patients. However, more complete mechanisms and pathophysiological processes still need to be further studied.

Aim: Observational studies have reported that levels of vitamin D were associated with the incidence of chronic obstructive pulmonary disease (COPD), but the relationship between them may have been confounded in previous studies. In this study, we aimed to determine the relationship between the levels of 25-hydroxyvitamin D (25OHD) and the risk of COPD by two-sample Mendelian randomization (MR) analysis.Methods: Summary statistics for 25OHD and COPD in this study were obtained from the EBI (n = 496,946) consortium and Finn (n = 187,754) consortium. MR was adopted to explore the effect of the genetically predicted levels of 25OHD on the risk of COPD. Based on three assumptions of MR analysis, inverse variance weighting was used as the main analysis. To make our results more robust and reliable, MR Egger’s intercept test, Cochran’s Q test, funnel plot, and “leave-one-out” sensitivity analysis were used to assess the potential pleiotropy and heterogeneity in this study. Then, colocalization analysis and MR Steiger approaches were used to estimate the possible directions of estimates between them. Finally, we analyzed the causal associations between the four core genes (DHCR7, GC, CYP2R1, and CYP24A1) of vitamin D and the levels of 25OHD or the risk of COPD.Results: Our results showed that each 1 standard deviation (SD) increase in the genetically predicted 25OHD level was associated with a 57.2% lower relative risk of COPD [odds ratio (OR): 0.428, 95% Cl: 0.279–0.657, p = 1.041 × 10⁻⁴], and the above association was also verified by maximum likelihood (OR: 0.427, 95% Cl: 0.277–0.657, p = 1.084 × 10⁻⁴), MR–Egger (OR: 0.271, 95% CI: 0.176–0.416, p = 2.466 × 10⁻⁴), MR-PRESSO (OR: 0.428, 95% Cl: 0.281–0.652, p = 1.421 × 10⁻⁴) and MR-RAPS (OR: 0.457, 95% Cl: 0.293–0.712, p = 5.450 × 10⁻⁴). Furthermore, colocalization analyses (rs3829251, PP.H4 = 0.99) and MR Steiger (“TRUE”) also showed a reverse association between them. Besides, the core genes of vitamin D also showed similar results except for CYP24A1.Conclusion: Our findings provide evidence for a reverse association between genetically predicted 25OHD levels and COPD risk. Taking measures to supplement 25OHD may help reduce the incidence of COPD.

Objectives: Although it has long been reported that high levels of cystatin C could contribute to the development of osteoporosis in some studies, no evidence has established a causal association between them thus far.Methods: A Mendelian randomization (MR) study was conducted to determine the causal effect of cystatin C on osteoporosis based on public databases obtained from separately published genome-wide association studies (GWASs). The single-nucleotide polymorphisms (SNPs) for cystatin C were extracted from the MR-Base (CKDGen, 33,152 participants), and the SNPs for osteoporosis were extracted from the United Kingdom Biobank project (United Kingdom Biobank, including 5,266 osteoporosis cases and 331,893 controls). We defined the odds ratio (OR) of IVW methods as the primary outcome. In addition, weighted median and MR–Egger regressions were used in the sensitivity analysis.Results: In IVW, we found that genetically predicted cystatin C was causally associated with the risk of osteoporosis with an OR of 1.02 [95% confidence interval (CI) = 1.003–1.025, p = 0.01]. In the further sensitivity analysis, weighted median regression also showed directionally similar estimates (OR = 1.02, 95% CI = 1.005–1.03, p = 0.005), and MR–Egger regression (OR = 1.02, 95% CI = 1.000–1.036, p = 0.15) revealed similar estimates but with lower precision. The funnel plot, MR–Egger intercept, and MR-PRESSO all indicate that no directional pleiotropic effect was observed.Conclusion: In conclusion, our MR study showed evidence of a causal association between serum cystatin C levels and osteoporosis, which also needs to be verified by studies with larger sample sizes in the future. Early monitoring of cystatin C may enable us to prevent osteoporosis-related diseases.