Objective To explore the the detection of MMP-2,-7,-9,and-12 enzymatic activity using the CEACAM1-derived fluorescent peptide substrate Site 84,investigating the application of substrate Site 84 to distinguishing between MMP-2 and MMP-9 in the gelatinase spectrum of MMPs.Methods The fluorescent enzymatic method was employed to observe the detection of MMP-2,-7,-9,and-12 enzymatic activity using substrate Site 84;further observations were made on the sensitivity and specificity of substrate Site 84 to enzymatic activity of MMP-2 and MMP-9 within the gelatinase spectrum;the kinetic parameters(Km and Kcat)of the enzymatic reaction between substrate Site 84 and MMP-2 were obtained.Results Using Site 84 as a substrate,enzymic kinetics curves for MMP-12,-7,-2 were obtained,but no enzymatic activity curve for MMP-9 was observed.Furthermore,Site 84 specifically detected the enzymatic activity of MMP-2 within the gelatinase spectrum,capable of detecting low concentration(0.6 μM)of MMP-2 enzymatic activity,but no obvious enzymatic reaction was observed for high concentration(6 μM)of MMP-9;the kinetics parameters for the enzymatic reaction between Site 84 and MMP-2 were Km=315 μM,Kcat/Km=2 565/MS.Conclusion The CEACAM1-derived substrate Site 84 serves as a novel fluorescent peptide substrate,enabling the acquisition of enzymatic activity curves for MMP-12,-7 and-2,and specifically detecting the enzymatic activity of MMP-2 within the MMP gelatinase spectrum.

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.

Lactic acid bacteria(LAB)were isolated and cultivated from the intestinal contents of rabbits by MRS-CaCO3 solid medium.Identification was achieved through morphological observa-tion,Gram staining,physiological and biochemical characterisation,16S rDNA sequence analysis,and ERIC-PCR analysis.Strains displaying typical Lactobacilli characteristics were exanimated for their biological characteristics,resistance properties,adherence capacity in vitro,colonization abili-ty in vivo,and safety profile.In this study,a total of four strains of Lactobacillus reuteri were iso-lated from rabbits,all of which exhibited typical biological characteristics of LAB.These strains demonstrated inhibitory effects on common pathogenic bacteria in the gastrointestinal tract,with the primary inhibitory substance being bacteriocin.Furthermore,they showed sensitivity to chlor-amphenicol,rifampicin,and erythromycin,and displayed a degree of tolerance to gastrointestinal conditions and high temperature.These stains were capable of successful colonization in rabbits with a higher degree of safety.This study lays a foundation for the development of LAB prepara-tions for the prevention and treatment of rabbit intestinal diseases.

OBJECTIVE To provide reference for clinically safe and rational drug use through mining and analyzing adverse drug event （AE） signals induced by valproic acid （VPA）. METHODS Reporting Odds Ratio （ROR） and Bayesian Confidence Propagation Neural Network （BCPNN） methods of Measures of Disproportionality were performed to mine and analyze the data of VPA-related AE reports in the US FDA Adverse Event Reporting System （FAERS） database from the first quarter of 2013 to the fourth quarter of 2022. RESULTS A total of 1 253 （ROR） and 1 109 （BCPNN） valid signals of preferred terms （PT） were obtained after data processing by the two analysis methods， involving 27 system organs （SOC）， mainly focusing on nervous system disorders， psychiatric disorders， general disorders and administration site conditions. Signals that did not appear in the instruction were associated with 2 SOCs： ear and labyrinth disorders， infections and infestations. CONCLUSIONS As a first-line broad-spectrum anti-epileptic drug， attention should also be paid to eye toxicity and infection risk in the clinical application in addition to paying attention to common adverse events in the instruction.

Objective:To analyze the influence of lifestyle changes on body weight and metabolic parameters during the early stage of corona virus disease 2019 (COVID-19) epidemic and regular epidemic prevention period in physical examination population.Methods:A total of 801 subjects from Nanjing enterprises and institutions who underwent physical examination in the Department of Health Promotion Center, the First Affiliated Hospital of Nanjing Medical University in May of 2019 to 2021 were included in this study. The basic information and data of body mass index, fasting blood glucose, total cholesterol, low density lipoprotein cholesterol (LDL-C), triglyceride and uric acid were collected. Information about dietary and exercise habits was obtained through pre-examination questionnaires. The data of 2019 was set as baseline data, data of 2020 represented information during the early stage of COVID-19 epidemic and data of 2021 represented information in regular epidemic prevention period. The subjects were divided into underweight group, normal weight group, overweight group, and obese group according to the body mass index at baseline. The Friedman test was applied to compare changes in body mass index and metabolic parameters across the population. Chi-square test was used to compare changes in dietary and exercise habits. Multivariate logistic regression analysis was adopted to explore the influencing factors of body mass index changes.Results:During the early stage of COVID-19 epidemic, the proportion of weight gain was the highest in the underweight group (42.9%), the proportion of weight loss was the highest in the overweight group (24.2%), and the obese group has the most stable body weight (70.6%) ( P=0.004). Men ( OR=0.56, 95% CI: 0.36-0.87) were less likely to gain weight than women ( P=0.010). There was no significant differences in weight change among all groups in the regular epidemic prevention period ( P=0.380). During the early stage of COVID-19 epidemic, the levels of fasting blood glucose, total cholesterol and LDL-C were significantly lower than those of baseline [4.98 (4.66, 5.42) vs 5.23 (4.91, 5.66) mmol/L, 4.98 (4.36, 5.67) vs 5.11 (4.54, 5.77) mmol/L, 2.90 (2.45, 3.33) vs 3.23 (2.77, 3.74) mmol/L], and the uric acid level was higher [333.0 (275.5, 397.0) vs 311.0 (257.5, 368.0) μmol/L] (all P<0.001). In regular epidemic prevention period, the levels of body mass index, fasting blood glucose, total cholesterol and LDL-C were significantly higher than those in the early stage of the epidemic [24.0 (21.9, 26.3) vs 23.8 (21.7, 26.1) kg/m 2, 5.18 (4.85, 5.62) vs 4.98 (4.66, 5.42) mmol/L, 5.12 (4.42, 5.76) vs 4.98 (4.36, 5.67) mmol/L, 3.06 (2.59, 3.57) vs 2.90 (2.45, 3.33) mmol/L], while the uric acid was significantly lower [319.0 (265.0, 377.0) vs 333.0 (275.5, 397.0) μmol/L] (all P<0.001). During the early stage of the epidemic, the reduction proportion of unhealthy diet in the home group was significantly higher than that in the outing group (19.5% vs 11.4%), and the increment proportion of exercise in the outing group was significantly higher than that in the home group (5.1% vs 1.6%) (both P<0.05). In regular epidemic prevention period, the increase rate of unhealthy diet in the home group was significantly higher than that in the outing group (26.8% vs 13.0%) ( P<0.001), and there was no significant difference in exercise between the two groups ( P=0.325). During the early stage of COVID-19 epidemic and in the regular epidemic prevention period, unhealthy diet>3 times per week ( OR=3.85, 3.01, 95% CI: 1.74-8.51, 1.41-6.39) was positively correlated with weight gain, and regular exercise ( OR=4.35, 2.61, 95% CI: 2.05-9.23, 1.15-5.91) was positively correlated with weight loss (all P<0.05). Conclusions:During the early stage of COVID-19 epidemic and in the regular epidemic prevention period, the lifestyle in the physical examination population has an impact on body weight and metabolic indicators. In the early stage of the epidemic, unhealthy diet and exercise decreased, and metabolic indicators such as blood glucose and lipids decreased. People with low body weight tend to gain weight. In the regular epidemic prevention period, the subjects′ exercise increased but unhealthy diet also increased, and blood glucose, lipid and body weight elevated significantly.

To investigate the application value of slanted gel pads in carotid ultrasonography by comparing the parameters obtained by slanted gel pads with different angles. Methods The right common carotid artery was examined by ultrasonography in 50 adult patients with negative carotid artery ultrasonography. The peak systolic velocity （PSV，cm /s） and Doppler Angle of the common carotid artery were measured without and with the use of slanted gel pads of 18°，25° and 32°. Results The PSV of common carotid artery was 90.10±8.12 cm/s，84.42 ±7.91 cm/s，78.30 ±7.88 cm/s，（72.25 ±7.62）cm/s without and with the use of slanted gel pads of 18°，25° and 32°，the differences were statistically significant（P<0.01）；The Doppler angle correction were（59.78±0.51）°，（54.92±1.51）°，（50.78± 2.48）° and （46.22±2.82）°，respectively. The differences were statistically significant（P<0.01），and the CV were 0.008，0.027，0.049 and 0.061，respectively.Conclusion Increasing the angle of slanted gel pads can significantly reduce the carotid artery PSV and Doppler angle，potentially improve the accuracy of ultrasonic evaluation of carotid artery flow velocity，and has no obvious effect on the coefficient of variation of PSV.

Objective:To investigate the effects of three different luteal phase support protocols on pregnancy outcomes in hormone replacement therapy frozen-thawed embryo transfer(HRT-FET).Methods:The clinical data of 3288 HRT-FET cycles in Reproductive Center of the Third Affiliated Hospital of Zhengzhou University from January 2016 to February 2019 were retrospective cohort study analyzed. The cycles were divided into three groups according to luteal phase support protocols. The patients received a combination of progesterone soft capsule and dydrogesterone in group A (478 cycles), the patients received a combination of progesterone vaginal sustained-release gel and dydrogesterone in group B (1293 cycles), the patients received a combination of progesterone injection and dydrogesterone in group C (887 cycles). Pregnancy outcomes and neonatal outcomes in group A, group B and group C were compared.Results:The clinical pregnancy rate, the 12-week pregnancy rate and the live birth rate had no significant difference among the three groups ( P>0.05). The rates of premature delivery and twin delivery [19.90% (78/392), 30.61% (120/392)] in group C were higher than those in group B [13.61% (109/801), P=0.011; 20.47% (164/801), P<0.001]. The birth weight [(3 178.60±635.38) g] in group B was significantly higher than that in group C [(3 033.01±682.54) g, P<0.001] . There was no significant difference in the incidence of birth defects among the three groups ( P>0.05). Logistic regression analysis showed that three different luteal phase support regimens were not associated with 12-week pregnancy rate. Conclusion:In HRT-FET cycle, progesterone soft capsule or progesterone vaginal sustained-release gel combined with dydrogesterone can achieve the same pregnancy outcome as progesterone injection combined with dydrogesterone, but a large-scale prospective study is needed.

Objective:To investigate the effects of three different luteal phase support protocols on pregnancy outcomes in hormone replacement therapy frozen-thawed embryo transfer(HRT-FET).Methods:The clinical data of 3288 HRT-FET cycles in Reproductive Center of the Third Affiliated Hospital of Zhengzhou University from January 2016 to February 2019 were retrospective cohort study analyzed. The cycles were divided into three groups according to luteal phase support protocols. The patients received a combination of progesterone soft capsule and dydrogesterone in group A (478 cycles), the patients received a combination of progesterone vaginal sustained-release gel and dydrogesterone in group B (1293 cycles), the patients received a combination of progesterone injection and dydrogesterone in group C (887 cycles). Pregnancy outcomes and neonatal outcomes in group A, group B and group C were compared.Results:The clinical pregnancy rate, the 12-week pregnancy rate and the live birth rate had no significant difference among the three groups ( P>0.05). The rates of premature delivery and twin delivery [19.90% (78/392), 30.61% (120/392)] in group C were higher than those in group B [13.61% (109/801), P=0.011; 20.47% (164/801), P<0.001]. The birth weight [(3 178.60±635.38) g] in group B was significantly higher than that in group C [(3 033.01±682.54) g, P<0.001] . There was no significant difference in the incidence of birth defects among the three groups ( P>0.05). Logistic regression analysis showed that three different luteal phase support regimens were not associated with 12-week pregnancy rate. Conclusion:In HRT-FET cycle, progesterone soft capsule or progesterone vaginal sustained-release gel combined with dydrogesterone can achieve the same pregnancy outcome as progesterone injection combined with dydrogesterone, but a large-scale prospective study is needed.

Objective: To explore the association between screen time and autistic behavior in infants and young children, and to provide clues to the mechanism for further research. Methods: The primary caregivers of 22 586 children in the district of Longhua in Shenzhen were surveyed. Demographic data and screen time were collected using a selfdisigned questionnaire, and children’s autistic behavior was assessed using the child Autism Behavior Checklist(ABC).The chisquare test was used to analyze the correlation between demographic data and screen time, demographic data and autistic behavior, and screen time and autistic behavior. Unconditioned Logistic regression model was used to study the effect of electronic screen exposure on autistic behavior. Results: The amount of screen time spent in infancy increased with age. For children ages 0-,1- and 2-3 years, 60.1%, 35.0% and 20.2% respectively did not watch TV, and 74.0%, 52.6% and 26.8% respectively did not watch the new generation of electronic products. The positive rate of ABC scale screening was 5.3%, including 6.0% male and 4.4% female, OR(95%CI)=1.37 (1.23-1.54).There was correlations between screen time and autistic behavior in infants at all ages (P<0.05).Screen time increased the risk of autistic behavior in younger age groups than in older age groups. For 1 year olds with moderate screen exposure, increased screen exposure at 2 to 3 years of age was associated with an increased risk of autistic behaviors, while reduced screen exposure at 2 to 3 years of age was associated with a lower risk of autistic behaviors(OR=2.14, 2.77, P<0.05). The higher daily screen time at 0-3 years old was, the greater risk of autistic behaviors. Compared with the noncontact electronic screen group, the OR values of the daily TV screens in the ≥1 h/d group and the ＜1 h/d group were 2.01 and 2.45, respectively (P＜0.05).Compared with the non-contact electronic screen group, the OR values of the screens exposed to the new generation of electronic products in the ≥1 h/d group and the ＜1 h/d group were 2.01 and 2.33, respectively(P<0.05).The higher the time of single exposure to electronic screen between 0 and 3 years old, the greater the risk of autistic behaviors. The OR values were 2.50, 1.79 and 1.47 when ≥1 h/time, 0.5-1 h/time and 15-30 min/time compared with <15 min/time（P<0.05）. Conclusion Early exposure to electronic screens in infants, excessive total daily exposure to electronic screens, and excessive screen time each time are all likely to increase autistic behavior. Therefore, it is suggested that children under 2 years old should not be exposed to electronic screens every day. Children aged 2-3 years old who are exposed to electronic screens＜0.5 h/d and whose screen time <15 min might not significantly increase autistic behaviors.