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Background: The associations between platelet-to-lymphocyte ratio (PLR) and non-alcoholic fatty liver disease (NAFLD) and cirrhosis are unclear, and there are still no effective means for diagnosing or monitoring disease progression., Methods: Data from the National Health and Nutrition Examination Surveys were collected for analysis. Logistic regression and restricted cubic splines were used to evaluate the associations between PLR and NAFLD and cirrhosis in different populations. The Area Under Curve Receiver Operating Characteristic (AUCROC) was used to distinguish the models. Threshold analysis was performed by constructing a two-piecewise linear regression. Correlation analysis was performed separately on either side of the inflection point., Results: A total of 5724 adults were included. Logistic regression analysis revealed that the PLR was associated with NAFLD and cirrhosis (AUCROC of NAFLD: 0.803; AUCROC of cirrhosis: 0.851). The AUCROC of the PLR for predicting NAFLD incidence was 0.762 in the diabetic population and 0.804 in the nondiabetic population. High PLR predicted cirrhosis in the diabetic population, with an AUCROC of 0.824, whereas a high PLR was not associated with cirrhosis in the nondiabetic population. The restricted cubic spline revealed a negative linear correlation between the PLR and NAFLD incidence. The inflection point of the PLR for NAFLD was 180.74. A PLR ≤180.74 was statistically significant (odds ratio=0.997, 95% confidence interval=0.995-0.999). In the NAFLD population, the PLR was negatively correlated with cirrhosis at a PLR ≤130.5 (odds ratio=0.987, 95% confidence interval=0.977-0.996) and positively correlated with cirrhosis at a PLR > 130.5 (odds ratio=1.006, 95% confidence interval=1.001-1.012)., Conclusions: The PLR and NAFLD were negatively correlated in the U.S. population. The PLR had a U-shaped relationship with cirrhosis in the NAFLD population. The PLR has potential value in monitoring NAFLD patient progression to cirrhosis., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Yan, Zhang, Xiao, Sun, Peng and Cai.)

Arteriovenous fistulae (AVF) fail to mature more frequently in female patients compared with male patients, leading to inferior outcomes and decreased utilization. Since our mouse AVF model recapitulates sex differences in human AVF maturation, we hypothesized that sex hormones mediate these differences during AVF maturation. C57BL/6 mice (9-11 wk) were treated with aortocaval AVF surgery and/or gonadectomy. AVF hemodynamics were measured via ultrasound ( days 0-21 ). Blood was collected for FACS and tissue for immunofluorescence and ELISA ( days 3 and 7 ); wall thickness was assessed by histology ( day 21 ). Inferior vena cava shear stress was higher in male mice ( P = 0.0028) after gonadectomy, and they had increased wall thickness (22.0 ± 1.8 vs. 12.7 ± 1.2 µm; P < 0.0001). Conversely, female mice had decreased wall thickness (6.8 ± 0.6 vs. 15.3 ± 0.9 µm; P = 0.0002). Intact female mice had higher proportions of circulating CD3 + T cells on day 3 ( P = 0.0043), CD4 + ( P = 0.0003) and CD8 + T cells ( P = 0.005) on day 7 , and CD11b + monocytes on day 3 ( P = 0.0046). After gonadectomy, these differences disappeared. In intact female mice, CD3 + T cells ( P = 0.025), CD4 + T cells ( P = 0.0178), CD8 + T cells ( P = 0.0571), and CD68 + macrophages ( P = 0.0078) increased in the fistula wall on days 3 and 7. This disappeared after gonadectomy. Furthermore, female mice had higher IL-10 ( P = 0.0217) and TNF-α ( P = 0.0417) levels in their AVF walls than male mice. Sex hormones mediate AVF maturation, suggesting that hormone receptor signaling may be a target to improve AVF maturation. NEW & NOTEWORTHY After arteriovenous fistula creation, females have lower rates of maturation and higher rates of failure than males. In a mouse model of venous adaptation that recapitulates human fistula maturation, sex hormones may be mechanisms of the sexual dimorphism: testosterone is associated with reduced shear stress, whereas estrogen is associated with increased immune cell recruitment. Modulating sex hormones or downstream effectors suggests sex-specific therapies and could address disparities in sex differences in clinical outcomes.

Background: Pericardial patches are frequently used in vascular surgery to close arteriotomies. The early healing of these patches is mediated by attraction of CD34 and ephrinB2-positive cells. Atorvastatin is a commonly used statin drug that promotes healing of cardiovascular injury. We hypothesized that atorvastatin attracts ephrinB2-positive cells by regulating the microRNA140-ADAM10-ephrinB2 pathway during patch healing in the arterial environment. Methods: Pericardial patches were used to close an infra-renal aortic arteriotomy in Wistar rats (male, 200-400 g). Atorvastatin was given to rats at a daily dose of 0 mg, 2.5 mg, 5 mg or 10 mg. Patches were harvested at 1 or 4 weeks and analyzed by histology, immunohistochemistry, immunofluorescence, western blot and qPCR. Result: Animals treated with atorvastatin showed a higher number of infiltrating cells and a thicker patch neointima than the control animals. Furthermore, ADAM10 protein expression decreased (P<0.01) and ephrinB2 expression increased (P<0.01) in time- and atorvastatin dose-dependent manner. Similarly, ADAM10 mRNA expression decreased (P<0.01), while the expression of ephrinB2 mRNA and miR-140 mRNA expression increased (P<0.01; P<0.01) in a time- and dose-dependent manner. Conclusion: Atorvastatin regulates neointimal growth after pericardial patch angioplasty; atorvastatin is associated with infiltration of ephrinB2-positive cells, diminished ADAM10 expression, and increased ephrinB2 and miR-140 expression. These results suggest new mechanisms for regulating neointimal formation after vascular procedures. Clinical relevance: This study may help physicians to know more healing mechanism after pericardial patch angioplasty. Further, it may reveal some mechanism that how atorvastatin play roles in endothelium repair of the cardiovascular system., Competing Interests: None.