Establishment of Reference Intervals for SII, NLR, PLR, and LMR in Healthy Adults in Jiangsu Region in Eastern China.

BACKGROUND: We preliminarily established the reference intervals for the systemic immune-inflammation index (SII), neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), and lymphocyte to monocyte ratio (LMR) in healthy adults in Jiangsu region in Eastern China to guide the interpretation and application of these indicators in clinical practice. METHODS: In total, 29,947 ostensibly healthy subjects from December 2020 to March 2021 were included in this study. The distributions of the SII, NLR, PLR, and LMR were analyzed using the Kolmogorov-Smirnov test. According to the C28-A3 guidelines, the 2.5th and 97.5th percentiles (P2.5 to P97.5) of the SII, NLR, PLR, and LMR were used to establish the reference intervals based on nonparametric methods. RESULTS: All SII, NLR, PLR, and LMR data were non-normally distributed. The levels of the SII, NLR, PLR, and LMR in healthy adults were significantly different between males and females (all p < 0.05). However, there were no significant differences in the SII, NLR, PLR or LMR among the different age groups, regardless of gender (all p > 0.05). Therefore, the reference intervals for the SII, NLR, PLR, and LMR were established based on the Sysmex testing platform for males (162 × 109/L - 811 × 109/L; 0.89 - 3.26; 63.15 - 191.34; 3.18 - 9.61) and females (165 × 109/L - 792 × 109/L; 0.87 - 3.16; 69.04 - 205.62; 3.46 - 10.96). CONCLUSIONS: We have established the reference intervals for SII, NLR, PLR, and LMR in healthy adults based on the Sysmex detection platform and large sample size, which may provide important guidance for its clinical application.

Reference interval for urinary neutrophil gelatinase-associated lipocalin in healthy adults in Jiangsu region in Eastern China: a multicenter study.

Aim: We explored the concentrations of urinary neutrophil gelatinase-associated lipocalin (NGAL) in healthy adults in the Jiangsu region in Eastern China and established a reference interval using latex-enhanced immunoturbidimetry to provide important guidelines for the interpretation and application of urinary NGAL in clinical practice. Methods: In total, 1970 eligible subjects from four regions were included in this study. The urinary NGAL levels were measured using an AU5800 automatic biochemical analyzer with its matched reagents. The urinary NGAL reference interval was established using the one-sided percentile method (95th percentile). Results: The urinary NGAL data were non-normally distributed. The urinary NGAL levels were not significantly different by sex or age. Therefore, the urinary NGAL reference interval in healthy adults in the Jiangsu region in Eastern China was <87.5 ng/ml (95th percentile of the upper limit). Conclusion: Urinary NGAL reference interval will play an important role in promoting the clinical value of urinary NGAL.

Acetylcholine attenuated TNF-α-induced intracellular Ca2+ overload by inhibiting the formation of the NCX1-TRPC3-IP3R1 complex in human umbilical vein endothelial cells.

The endoplasmic reticulum (ER) forms discrete junctions with the plasma membrane (PM) that play a critical role in the regulation of Ca2+ signaling during cellular bioenergetics, apoptosis and autophagy. We have previously confirmed that acetylcholine can inhibit ER stress and apoptosis after inflammatory injury. However, limited research has focused on the effects of acetylcholine on ER-PM junctions. In this work, we evaluated the structure and function of the supramolecular sodium-calcium exchanger 1 (NCX1)-transient receptor potential canonical 3 (TRPC3)-inositol 1,4,5-trisphosphate receptor 1 (IP3R1) complex, which is involved in regulating Ca2+ homeostasis during inflammatory injury. The width of the ER-PM junctions of human umbilical vein endothelial cells (HUVECs) was measured in nanometres using transmission electron microscopy and a fluorescent probe for Ca2+. Protein-protein interactions were assessed by immunoprecipitation. Ca2+ concentration was measured using a confocal microscope. An siRNA assay was employed to silence specific proteins. Our results demonstrated that the peripheral ER was translocated to PM junction sites when induced by tumour necrosis factor-alpha (TNF-α) and that NCX1-TRPC3-IP3R1 complexes formed at these sites. After down-regulating the protein expression of NCX1 or IP3R1, we found that the NCX1-mediated inflow of Ca2+ and the release of intracellular Ca2+ stores were reduced in TNF-α-treated cells. We also observed that acetylcholine attenuated the formation of NCX1-TRPC3-IP3R1 complexes and maintained calcium homeostasis in cells treated with TNF-α. Interestingly, the positive effects of acetylcholine were abolished by the selective M3AChR antagonist darifenacin and by AMPK siRNAs. These results indicate that acetylcholine protects endothelial cells from TNF-alpha-induced injury, [Ca2+]cyt overload and ER-PM interactions, which depend on the muscarinic 3 receptor/AMPK pathway, and that acetylcholine may be a new inhibitor for suppressing [Ca2+]cyt overload.

[Role of endoplasmic reticulum-plasma membrane junctions in intracellular calcium homeostasis and cardiovascular disease].

Calcium overload is one of the important mechanisms of cardiovascular disease. Endoplasmic reticulum is an important organelle which regulates intracellular calcium homeostasis by uptake, storage and mobilization of calcium. So it plays a critical role in regulation of intracellular calcium homeostasis. Endoplasmic reticulum, which is widely distributed in cytoplasm, has a large number of membrane junction sites. Recent studies have reported that these junction sites are distributed on plasma membrane and organelle membranes (mitochondria, lysosomes, Golgi apparatus, etc.), separately. They could form complexes to regulate calcium transport. In this review, we briefly outlined the recent research progresses of endoplasmic reticulum-plasma membrane junctions in intracellular calcium homeostasis and cardiovascular disease, which may offer a new strategy for prevention and treatment of cardiovascular disease.

Role of endoplasmic reticulum-plasma membrane junctions in intracellular calcium homeostasis and cardiovascular disease / 生理学报

Calcium overload is one of the important mechanisms of cardiovascular disease. Endoplasmic reticulum is an important organelle which regulates intracellular calcium homeostasis by uptake, storage and mobilization of calcium. So it plays a critical role in regulation of intracellular calcium homeostasis. Endoplasmic reticulum, which is widely distributed in cytoplasm, has a large number of membrane junction sites. Recent studies have reported that these junction sites are distributed on plasma membrane and organelle membranes (mitochondria, lysosomes, Golgi apparatus, etc.), separately. They could form complexes to regulate calcium transport. In this review, we briefly outlined the recent research progresses of endoplasmic reticulum-plasma membrane junctions in intracellular calcium homeostasis and cardiovascular disease, which may offer a new strategy for prevention and treatment of cardiovascular disease.