Objective:To investigate the associations between thyroid homeostasis and risk of carotid plaque in healthy euthyroid individuals.Methods:In this retrospective cohort study, 4 726 healthy euthyroid adults who received health examination two times or more in the Health Promotion Center of the First Affiliated Hospital with Nanjing Medical University from January 2018 to December 2024 and had no carotid artery plaques at the baseline were selected. Data encompassed demographics, physical and laboratory tests, carotid ultrasound, and calculated thyroid sensitivity indices [thyroid feedback quantile-based index (TFQI), thyroid hormone resistance index (TT4RI), thyroid-stimulating hormone index (TSHI), and free triiodothyronine (FT3)/free thyroxine (FT4) ratio] were recorded. The participants were divided into two groups based on whether they had newly-developed carotid plaques. The associations between thyroid homeostasis indices and risk of carotid plaque were analyzed using Cox proportional hazards regression and restricted cubic splines.Results:During 11 459 person-years of follow-up, the cumulative incidence of carotid plaque was 16.84%, with an incidence density of 6.95 cases per 100 person-years. After multivariable adjustment, FT3 ( HR=0.79, 95% CI: 0.68-0.93) and FT4 ( HR=0.95, 95% CI: 0.91-0.98) were inversely associated with risk of carotid plaque. TSH and thyroid hormone sensitivity showed no significant association with the occurrence of carotid plaques. Subgroup analysis showed that there was no significant interaction between thyroid function indicators and risk of carotid plaque among different subgroups, but the decreased FT3 and FT4 levels significantly increased the risk of new-onset carotid plaques in individuals aged<60 years, without diabetes, without hypertension, or without lipid-lowering medication use. Restricted cubic spline analysis indicated that when TFQI (nonlinear P=0.028, node value was 0.29) and TT4RI (nonlinear P=0.014, node value was 54.95) exceeded specific thresholds, their increase were associated with a reduced risk of carotid plaque. Conclusions:The reduction of FT3 and FT4 in healthy euthyroid adults is associated with an increased risk of carotid plaque. When TFQI and TT4RI are higher than specific thresholds, their increase are associated with a reduced risk of new-onset plaques.

Objective:To investigate the associations between thyroid homeostasis and risk of carotid plaque in healthy euthyroid individuals.Methods:In this retrospective cohort study, 4 726 healthy euthyroid adults who received health examination two times or more in the Health Promotion Center of the First Affiliated Hospital with Nanjing Medical University from January 2018 to December 2024 and had no carotid artery plaques at the baseline were selected. Data encompassed demographics, physical and laboratory tests, carotid ultrasound, and calculated thyroid sensitivity indices [thyroid feedback quantile-based index (TFQI), thyroid hormone resistance index (TT4RI), thyroid-stimulating hormone index (TSHI), and free triiodothyronine (FT3)/free thyroxine (FT4) ratio] were recorded. The participants were divided into two groups based on whether they had newly-developed carotid plaques. The associations between thyroid homeostasis indices and risk of carotid plaque were analyzed using Cox proportional hazards regression and restricted cubic splines.Results:During 11 459 person-years of follow-up, the cumulative incidence of carotid plaque was 16.84%, with an incidence density of 6.95 cases per 100 person-years. After multivariable adjustment, FT3 ( HR=0.79, 95% CI: 0.68-0.93) and FT4 ( HR=0.95, 95% CI: 0.91-0.98) were inversely associated with risk of carotid plaque. TSH and thyroid hormone sensitivity showed no significant association with the occurrence of carotid plaques. Subgroup analysis showed that there was no significant interaction between thyroid function indicators and risk of carotid plaque among different subgroups, but the decreased FT3 and FT4 levels significantly increased the risk of new-onset carotid plaques in individuals aged<60 years, without diabetes, without hypertension, or without lipid-lowering medication use. Restricted cubic spline analysis indicated that when TFQI (nonlinear P=0.028, node value was 0.29) and TT4RI (nonlinear P=0.014, node value was 54.95) exceeded specific thresholds, their increase were associated with a reduced risk of carotid plaque. Conclusions:The reduction of FT3 and FT4 in healthy euthyroid adults is associated with an increased risk of carotid plaque. When TFQI and TT4RI are higher than specific thresholds, their increase are associated with a reduced risk of new-onset plaques.

Ocular diseases pose a significant challenge to global health. The field of metabolomics, which involves the systematic identification and quantification of metabolites within a biological system, has emerged as a promising research approach for unraveling disease mechanisms and discovering novel biomarkers. Through its application, metabolomics has yielded valuable knowledge pertaining to the initiation and advancement of various ocular diseases. This review presents an overview of metabolomics and examines recent research progess in four ocular diseases, specifically diabetic retinopathy, age-related macular degeneration, glaucoma, and dry eye, summarizing potential biomarkers and metabolic pathways associated with these diseases. Additionally, this review offers insights into the future prospects of utilizing metabolomics for the management and treatment of ocular diseases.

OBJECTIVE To study the vasorelaxant effects and mechanism of polyphenol compound 2，4′，5′-trihydroxy-5，2′- dibromo-diphenyl-methanone（LM49）on isolated aortic rings of rats. METHODS Thoracic aortic vascular rings of rats were collected. Using the diastolic rate as index ， the effects of different concentrations of LM 49 on endothelium-intact and endothelium-denuded aortic rings pre-contracted by norepinephrine （NE，1×10－6 mol/L）or KCl （60 mmol/L）were investigated. After pre-culturing vascular rings by nitric oxide synthase inhibitor L-nitro-arginine methyl ester （L-NAME，0.1 mmol/L） and cyclooxygenase inhibitor indomethacin （1×10－5 mol/L），as well as pre-culturing vascular rings by 4 potassium channel blockers [BaCl 2（0.1 mmol/L），tetraethylammonium（TEA，5 mmol/L），4-aminopyridine（4-AP，0.1 mmol/L）and glibenclamide （1×10－5 mol/L）]，the vasorelaxant effect of different concentrations of LM 49 on the vascular rings were investigated by using the same method. With the percentage of vasoconstriction as the index ，using KCl （60 mmol/L），NE（1×10－6 mol/L），calcium channel blocker verapamil （1×10－6 mol/L）and sarcoplasmic Δ 基金项目 重大新药创制国家科技重大专项 （No.2018ZX097- reticulum Ca 2 +-adenosine triphosphate （ATP） enzyme pump inhibitor thacarotene （TG，1×10－6 mol/L）to induce the release of calcium in vascular rings in the absence of calcium. CaCl was added cumulatively ，and the effect of LM 49 on the cxyw06，vasoconstriction caused by calcium influx induced by CaCl 2 was investigated. RESULTS 3×10－6，5×10－6，1×10－5 mol/L LM49 had a significant relaxation effect on NE and KCl precontracted vascular rings （P＜0.01）； whether the endothelium was removed or not had no significant effect on the vasodilation of LM 49（P＞0.05）. After L-NAME ，indomethacin， TEA and 4-AP was pre-incubated ，different concentrations of LM 49 had no significant effects on aortic rings precontracted by NE （P＞0.05）. Glibenclamide and BaCl 2 could inhibit the vasorelaxant effects of LM 49 on aortic rings precontracted by NE （P＜0.01）. In the absence of calcium ，LM49 could inhibit the contraction caused by calcium influx induced by accumulated CaCl 2 after pre-incubation with KCl ，NE，verapamil and TG （P＜0.01）. CONCLUSIONS LM49 evokes significant relaxation of isolated aortic vascular rings without endothelium dependence ；the mechanism of which is inducing ATP-sensitive potassium channel ， inward rectifier potassium channel open and restraining extracellular Ca 2 + influx via voltage-gated calcium channel ， receptor-operated calcium channel and store-operated calcium channel.

Objective:To investigate the role of Caveolin (Cav-3)/extracellular signal-regulated kinase (ERK) signaling pathway in reduction of myocardial ischemia-reperfusion (I/R) injury by morphine preconditioning in rats with chronic heart failure.Methods:Clean-grade healthy adult male Sprague-Dawley rats, weighing 200-250 g, were used in this study.Chronic heart failure was induced by ligating the left anterior descending coronary artery for 6 weeks.Thirty-six Langendorff-perfused hearts with chronic heart failure were divided into 4 groups ( n=9 each) by a random number table method: myocardial I/R group (group IR), morphine preconditioning group (group MP), morphine preconditioning plus methyl-β-cyclodextrin group (group MP+ MβCD), and methyl-β-cyclodextrin group (group MβCD). Global myocardial I/R was induced by 30 min ischemia followed by 120 min reperfusion.In group MP, after 15 min of equilibration, hearts were subjected to 3 cycles of 5 min perfusion with K-H solution containing 1 μmol/L morphine for preconditioning followed by 5 min perfusion with K-H solution, 30 min in total, and after the end of treatment, hearts were subjected to 30 min ischemia followed by 120 min reperfusion.In group MP+ MβCD, hearts were perfused with K-H solution containing 200 μmol/L methyl-β-cyclodextrin at 10 min before preconditioning with morphine, and the other treatments were similar to those previously described in group MP.In group MβCD, hearts were perfused with K-H solution containing 200 μmol/L methyl-β-cyclodextrin at 40 min before ischemia, and the other treatments were similar to those previously described in group IR.At the end of 15 min of equilibration (T 0) and 5 and 10 min of reperfusion (T 1, 2), coronary outflow was collected for determination of actate dehydrogenase (LDH) activity by chemical colorimetry.Myocardial infarct size (IS) and area at risk (AAR) were measured, and IS/AAR was calculated at the end of 120 min reperfusion.Myocardial tissues of left ventricle were taken to detect the expression of Cav-3, ERK1/2 and phosphorylated ERK1/2 (p-ERK1/2) by Western blot, and p-ERK1/2/ERK1/2 ratio was calculated. Results:Compared with group IR, IS, IS/AAR and LDH activity in coronary outflow were significantly decreased, the expression of Cav-3 was up-regulated, and p-ERK1/2/ERK1/2 ratio was increased in group MP ( P<0.05). Compared with group MP, IS, IS/AAR and LDH activity in coronary outflow were significantly increased, the expression of Cav-3 was down-regulated, and p-ERK1/2/ERK1/2 ratio was decreased in group MP+ MβCD ( P<0.05). Conclusions:The mechanism by which morphine preconditioning reduces I/R injury may be related to activation of Cav-3/ERK signaling pathway in rats with chronic heart failure.

Electrogenerated chemiluminescence (electrochemiluminescence, ECL) generates species at electrode surfaces, which undergoes electron-transfer reactions and forms excited states to emit light. It has be-come a very powerful analytical technique and has been widely used in such as clinical testing, bio-warfare agent detection, and pharmaceutical analysis. This review focuses on the current trends of molecular recognition-based biosensing methods for pharmaceutical analysis since 2010. It introduces a background of ECL and presents the recent ECL developments in ECL immunoassay (ECLIA), im-munosensors, enzyme-based biosensors, aptamer-based biosensors, and molecularly imprinted poly-mers (MIP)-based sensors. At last, the future perspective for these analytical methods is briefly discussed.

A novel electrogenerated chemiluminescence (ECL) sensor for the determination of metoclopramide was developed by employing ruthenium complex as an ECL signal producer and an ordered mesoporous carbon (OMC) material as modified material. The ECL sensor was fabricated by adsorption ruthenium complex into a mixture of OMC and Nafion, which showed good electrochemical and ECL behaviors. It was found that the ECL intensity of the sensor fabricated was greatly enhanced in the presence of metoclopramide. Based on this finding, a highly sensitive and reproducible ECL method was developed for the determination of metoclopramide. The result showed that the ECL intensity was linear with the concentration of metoclopramide in the range from 1.0×10-10 to 5.0×10-7M and the detection limit was 3×10-11M. The ECL sensor exhibited a long-term stability and a fine reproducibility with relative standard deviation of 1.0 % for 1.0×10-10M metoclopramide in 18 continuous determinations. The developed method has been applied to the determination of metoclopramide in tablet samples with satisfactory results.

To evaluate the feasibility of using human embryonic fibroblast(HEF) as feeder layer in the culture of human embryonic stem(ES) cells in vitro, we investigated the morphology, the sensitivity to 0.25% trypsin, the growth curve and cell cycle of HEF with DMEM(low glucose) +10% FBS used as culture medium, and then we compared HEF with mouse embryonic fibroblast (MEF). The results showed that both HEF and MEF are adherent cells in vitro, and HEF has longer life span and better growth ability than MEF. In room temperature, HEF is more sensitive to 0.25% trypsin. Our research suggested that HEF can be used as feeder layer in culture of ES cells. HEF has longer service life than MEF and is worthy to be studied further.
Animals ; Cell Cycle ; Cell Differentiation ; Cell Division ; Cells, Cultured ; Embryo, Mammalian ; cytology ; Fibroblasts ; cytology ; physiology ; Humans ; Mice