Observational studies have shown that educational attainment is associated with the risk of myopia, but the causality of this relationship is unclear. The aim of the present study was to investigate the causal association between educational attainment and myopia.

Using publicly available data from genome-wide association studies, single nucleotide polymorphisms associated with educational attainment (college/university completion and years of education) were selected as instrumental variables. Causal associations with myopia risk were examined using two-sample Mendelian randomization (MR) analyses. Sensitivity analyses were conducted to assess the robustness of the results in terms of violations of MR assumptions.

The inverse variance–weighted analysis revealed potential causal associations of college/university completion (odds ratio (OR) = 1.102; 95% confidence interval (CI): 1.085–1.119; P < 0.001) and years of education (OR = 1.009; 95% CI: 1.007–1.010; P < 0.001) with myopia risk. MR-Egger and weighted median methods yielded similar results for both educational attainment measures.

MR evidence supports a potential causal association between educational attainment and myopia. This evidence highlights the need for careful management of myopia risk in individuals with higher educational attainment.

Observational studies indicate frequent associations between systemic lupus erythematosus (SLE) and various hematologic disorders, yet causal inferences are limited by confounding and reverse causality. We therefore applied a bidirectional Mendelian randomization (MR) design to assess potential genetic causal associations of SLE with specific hematologic conditions.

We used European-ancestry GWAS summary statistics for SLE (5,201 cases, 9,066 controls) and five hematologic outcomes (vitamin B12 deficiency anemia (B12DA), myelodysplastic syndrome (MDS), immune thrombocytopenia (ITP), agranulocytosis (AGC), iron deficiency anemia (IDA)) from FinnGen. The primary analysis used inverse-variance weighting, supplemented by MR-Egger and weighted median methods, with comprehensive sensitivity analyses, including heterogeneity tests, pleiotropy assessment, and leave-one-out analysis.

Bidirectional MR analysis revealed that genetically predicted SLE increased the risk of B12DA (odds ratio (OR) = 1.08, P < 0.001), and genetically predicted B12DA was associated with an increased risk of SLE (OR = 2.22, P = 1.6 × 10−29). The MDS → SLE association was nominally significant (P = 0.023) but did not survive Bonferroni correction (P < 0.005) and was inconsistent across MR methods. No significant genetic associations were found between SLE and ITP, AGC, or IDA in either direction (all P > 0.005).

This bidirectional MR study provides genetic evidence that SLE increases the risk of B12DA, whereas the reverse direction (B12DA → SLE) should be interpreted cautiously because it was based on only five instruments and was not supported by the Steiger directionality test. No robust genetic associations were found for ITP, AGC, IDA, or MDS. Clinically, monitoring B12DA in SLE patients may be warranted, although screening recommendations await prospective validation.

Metabolic dysfunction-associated steatotic liver disease affects roughly 38% of adults, yet approved agents do not correct the upstream redox-metabolic perturbations—a depressed nicotinamide adenine dinucleotide (NAD+/NADH) ratio, saturated lipid excess, and endoplasmic reticulum (ER) stress—that drive hepatocyte injury. Cytochrome b5 reductase 3 (CYB5R3) couples NADH oxidation to fatty acid desaturation, nuclear factor erythroid 2-related factor 2 (NRF2)-linked antioxidant and cholesterol-handling pathways, NAD+/sirtuin signaling, and ER-phagy, and is the sole electron input to mitochondrial amidoxime-reducing component 1 (mARC1). This review grades every link in the axis across the steatosis–cirrhosis–hepatocellular carcinoma spectrum, reporting effect estimates with sample sizes and test statistics alongside a study-level appraisal of clinical relevance. The common MTARC1 p.A165T variant protects against all-cause cirrhosis (odds ratio, 0.91; 95% CI, 0.89–0.94; P = 2.3 × 10−11; 12,361 cases, 790,095 controls), with lower hepatic fat, liver enzyme levels, and low-density lipoprotein cholesterol levels. Germline mARC1 deletion reduces picrosirius red fibrosis area by 24%–50% depending on diet, without altering histological disease activity, whereas partial protein reduction confers no protection. Critically, therapeutic hepatocyte-directed knockdown loses its anti-fibrotic effect when started at higher disease burden and in the choline-deficient model: efficacy depends on the depth, compartment, and timing of inhibition. Deep, hepatocyte-restricted mARC1 inhibition by GalNAc-conjugated oligonucleotides—which also avoids a male-predominant cardiac liability—is therefore the most credible near-term strategy, only in pre-cirrhotic F2–F3 disease. CYB5R3 activation, and its combination with mARC1 inhibition, remain unproven, and no clinical trial of this axis has been reported. Falsifiable in vivo and pharmacodynamic biomarker roadmaps are proposed, together with the efficacy, delivery, and safety uncertainties specific to advanced cirrhosis and a non-invasive pharmacodynamic framework.

Hepatic stellate cell (HSC) activation has traditionally been described as a binary transition from vitamin A-rich quiescent cells to alpha-smooth muscle actin-positive, collagen-producing myofibroblast-like cells. Advances in single-cell RNA sequencing, single-nucleus RNA sequencing, spatial transcriptomics, and chromatin-accessibility profiling now reveal a more complex and dynamic landscape. During chronic liver injury, HSCs can adopt five overlapping activation-associated states characterized by injury sensing, inflammatory signaling, proliferation, extracellular matrix production and contractility, together with a senescent state that represents a possible fate of activated HSCs. These states differ in their molecular markers, spatial distribution, regulatory pathways, and interactions with hepatocytes, liver sinusoidal endothelial cells, macrophages, natural killer cells, and cholangiocytes. Importantly, they are not fixed lineages and may coexist or interconvert during fibrosis progression and regression. This review revisits the classical quiescent-activated framework and proposes a state-based approach for interpreting HSC heterogeneity. We summarize the defining features and translational relevance of six major HSC functional states, discuss their multicellular niches, and highlight the opportunities and limitations of function-selective therapeutic targeting. A reproducible classification that integrates molecular identity, spatial context, and causal function may help refine antifibrotic treatment strategies.

This study aimed to evaluate the predictive value of cholesterol, high-density lipoprotein, and glucose index (CHG index) alone and combined with the monocyte-to-high-density lipoprotein cholesterol ratio (MHR) or triglyceride-to-high-density lipoprotein cholesterol ratio (TG/HDL-C) for NSTE-ACS.

This cross-sectional diagnostic study included 150 patients with NSTE-ACS and 76 healthy controls. Based on the median Gensini score, patients were divided into high-risk (Gensini score ≥51, n = 75) and low-risk groups (Gensini score <51, n = 75). MHR, TG/HDL-C, and CHG index were compared between patients and controls and between high- and low-risk groups. Their correlations with Gensini scores were assessed. Univariate and Multivariate binary logistic regression analysis was performed to identify factors independently associated with high-risk coronary lesions among patients with NSTE-ACS. The predictive performance of individual indicators (MHR, TG/HDL-C, and CHG index) and their combinations was evaluated using receiver operating characteristic curve analysis.

MHR, TG/HDL-C, and CHG index were significantly higher in the patient group than in the control group (all P < 0.001) and the high-risk group than the low-risk group. Those indicators positively correlated with Gensini scores and were independently associated with high-risk coronary lesions among patients with NSTE-ACS (odds ratio (OR) = 16.051, 95% confidence interval (CI): 13.677-99.650 for MHR; OR = 3.562, 95% CI: 1.868-6.793 for TG/HDL-C; and OR = 2.455, 95% CI: 1.040-5.791 for CHG index). The areas under the curve (AUCs) were 0.803 (95% CI: 0.730-0.876) for MHR, 0.746 (95% CI: 0.666-0.826) for TG/HDL-C, and 0.659 (95% CI: 0.573-0.746) for CHG index. The combination of CHG index and TG/HDL-C achieved an AUC of 0.821 (95% CI: 0.755-0.887), while the combination of CHG index and MHR achieved the higher AUC of 0.872 (95% CI: 0.815-0.929).

MHR, TG/HDL-C, and CHG index are independently associated with high-risk coronary lesions among patients with NSTE-ACS. Combining CHG index with MHR or TG/HDL-C shows numerically higher AUCs for identifying high-risk coronary lesions.