Objective:To explore the association between glutamyl transpeptidase (GGT) trajectories and new-onset metabolic syndrome to provide insights for the prevention and treatment of metabolic syndrome.Methods:A total of 3 209 subjects who met the inclusion criteria were enrolled in the study cohort of physical examination population. The GGT levels before follow-up were classified by R LCTMtools program into 3 GGT trajectory groups: low-stable group, medium-stable group and high-stable group. Cox proportional hazards regression model was used to analyze the correlation between different GGT trajectories and new-onset metabolic syndrome.Results:At the end of follow-up in 2020, the cumulative incidence of metabolic syndrome was 7.0%, and the incidence of metabolic syndrome in the low-stable group, medium-stable group and high-stable group were 3.9%, 11.4%, and 15.0%, respectively, showing a growth trend ( P<0.001). After adjusting for multiple confounding factors by Cox proportional hazards regression model, the risk of metabolic syndrome in medium-stable group and high-stable group increased in the total population. The hazard ratios (95% CI)for the high stable group in males and the medium-stable group in females were 1.67(1.07-2.60) and 3.29(1.14-9.53), respectively, compared with their respective low-stable group. Conclusion:Elevated longitudinal trajectory of GGT is a risk factor for new-onset metabolic syndrome, the risk of metabolic syndrome in the total population increased with the increase of long-term GGT level. It is recommended to maintain the long-term level of GGT at about 28 U/L in males and 14 U/L in females, respectively, to achieve the goal of early prevention of metabolic syndrome.

Objective:To investigate the correlation between the trajectory of triglyceride-glucose index multiplied by body mass index (TyG×BMI) and the incidence of new-onset non-alcoholic fatty liver disease (NAFLD).Methods:It was a retrospective cohort study. A total of 2 304 subjects who underwent health examinations at the Health Management Center of the First Affiliated Hospital of Zhengzhou University from 2017 to 2019 were included as the study population. Based on the TyG×BMI values from the health examinations, a latent class modeling approach was used to determine four distinct TyG×BMI trajectory groups: low-stable, moderate-stable, high-stable, and extremely high-stable group. The incidence of NAFLD was followed-up during the 2020 and 2021 health examinations for each group. The differences in NAFLD incidence among different TyG×BMI trajectory groups were compared using the log-rank test, and the correlation between different TyG×BMI trajectories and the incidence of new-onset NAFLD was analyzed using Cox proportional hazards regression models.Results:The incidence of NAFLD increased with the elevation of TyG×BMI trajectories. The cumulative incidence rates of NAFLD for the low-stable, moderate-stable, high-stable, and extremely high-stable groups was 13.00%, 16.70%, 20.10% and 26.60%, respectively, with statistically significant differences ( χ2=35.155, P<0.01). Compared with the low-stable group, the high-stable and extremely high-stable groups had higher risks of NAFLD (HRs for high-stable group was 1.564, 1.428, 1.426, 1.289, respectively; HRs for extremely high-stable group was 2.121, 1.670, 1.659, 1.607, respectively; all P<0.05). After adjusting for various confounding factors such as gender, waist circumference, BMI, blood glucose, blood lipids and liver function in model 4, the risks of NAFLD for the high-stable and extremely high-stable groups were still 1.389 and 1.607 times higher than that in the low-stable group (95% CIs: 1.035-1.864, 1.207-2.140). Conclusion:The risk of NAFLD increases with the elevation of TyG×BMI trajectories, suggesting that TyG×BMI can serve as a predictive index for NAFLD.

Objective:To investigate the mediation effect of triglyceride glucose index(TyG) on the relation between thyroid nodules and visceral fat area.Methods:A total of 9 324 individuals at the Health Management Center of the First Affiliated Hospital of Zhengzhou University from January 2017 to December 2021 were selected, and the basic information, biochemical indicators, color ultrasound of thyroid were also collected. According to the cut-off value of visceral fat area(VFA) of 100 cm 2 and body mass index(BMI) of 24 kg/m 2, they were divided into four groups: VFA(-)BMI(-), VFA(-)BMI(+ ), VFA(+ )BMI(-), and VFA(+ )BMI(+ ). Chi-square test was used to compare the incidence rate among the four groups, and multivariate logistic regression analysis to indentify influencing factors. TyG and VFA were quartiled, and multivariate logistic regression analysis was used to explore the effects of TyG and VFA on thyroid nodules. The regression coefficient test was used to analyze whether TyG mediated the association between VFA and thyroid nodules. Results:Multivariate logistic regression analysis revealed that compared with VFA(-)BMI(-) group, the VFA(+ )BMI(-) group had the highest risk of thyroid nodules( OR=1.283, 95% CI 1.064-1.546, P=0.009), followed by VFA(+ )BMI(+ ) group( OR=1.245, 95% CI 1.028-1.508, P=0.025). When using TyG and VFA Q1 group as reference, the Q4 group showed an increased risk of thyroid nodule by 1.584 times(95% CI 1.208-2.077, P=0.001) and 1.573 times(95% CI 1.249-1.982, P<0.001), respectively. Mediation analysis indicated that VFA had a direct impact on the incidence rate of thyroid nodules( β=0.162, 95% CI 0.140-0.186, P<0.001). TyG partially mediated the effect of VFA on the incidence rate of thyroid nodules( β=0.103, 95% CI 0.087-0.121, P<0.001), accounting for 38.87% of the total effect. Conclusions:VFA is an independent risk factor for thyroid nodules regardless of BMI. Among individuals with visceral obesity but normal BMI, the incidence rate of thyroid nodules was the highest. In addition, TyG partially mediates the risk of thyroid nodules in patients with visceral obesity. The evaluation of visceral obesity might be of great significance in the early screening and prevention of thyroid nodules.

Objective: To explore the association between urinary metals and lung function among college students, and to provide a theoretical basis for related research on metal exposure and lung function injury. Methods: A total of 45 healthy college students were recruited from North China University of Science and Technology in Caofeidian between 2017-2018. During the four seasons, information was obtained from questionnaires and physical examinations, lung function parameters were assessed, including FVC, FEV1, PEF, FEV1/FVC and FEF 25-75 , and morning urine samples were collected simultaneously. The urinary levels of 15 metals were measured by inductively coupled plasma mass spectrometry (ICP/MS); a Kruskal Wallis H test was used to compare differences in urinary metals during the four seasons; and a mixed effect model was used to assess correlations between urinary metals and lung function. Results: There were significant differences in the levels of urinary chromium, iron, nickel, copper, zinc, arsenic, selenium, selenium, molybdenum, cadmium, antimony and lead from 15 metals over the four seasons ( H =9.79- 20.61 , P <0.05). The differences observed in five lung function parameters over the four seasons were statistically significant ( F =61.72, 45.30, 47.61, 25.47, 35.13, P <0.05). The linear mixed effect model analysis showed that urinary concentrations of vanadium, manganese, iron, cobalt, nickel and antimony were negatively correlated with FEV1( B =0.202, 0.192, 0.181, 0.154, 0.131 , 0.283); urinary concentrations of aluminum, vanadium, manganese, iron, cobalt, nickel, zinc, cadmium, and antimony were negatively correlated with FVC ( B =0.252, 0.290, 0.292, 0.271, 0.201, 0.180, 0.171, 0.163, 0.381); urinary concentrations of manganese and antimony were negatively correlated with PEF ( B =0.291, 0.354)( P <0.05). Conclusion The increase of multiple metal concentrations among college students was related to lung function decline, the long term metal exposure might lead to lung function damage. So environmental metal pollution should be controlled.

Objective:To investigate the correlation between fasting plasma glucose (FPG) and new-onset carotid plaque through latent class trajectory models.Methods:A total of 953 observation objects came from the first affiliated hospital of Zhengzhou University in accordance with the inclusion criteria. According to the FPG values of the observed subjects during the annual physical examination from January 2017 to December 2019, the following four different FPG trajectories groups were determined by latent class trajectory modelling tools: the low-stable group, the medium stable group, the medium-high stable group, and the high stable group. Carotid plaque incidence in each group was followed up in 2020 to compare the differences of the cumulative incidences of the four groups. The Cox proportional risk regression model was used to analyze the correlation between different FPG trajectories and new-onset carotid plaque.Results:The incidence of carotid plaque increased with the increase of FPG trajectories by 11.13%, 19.70%, 23.44%, 23.81%, respectively, with significance ( P<0.001). After adjusting gender, age, BMI and other confounding factors with the cox proportional risk regression model, the risk of carotid plaque in the FPG medium stable group, medium and high stable group, high-stable group was still 1.895 (95% CI: 1.296-2.769), 2.273 (95% CI: 1.241-4.161), 2.527 (95% CI: 1.219-5.241) times of the low stable group (all P<0.05). Conclusion:The long-term high FPG levels are independent risk factors for the incidence of carotid plaque, and controlling FPG at a low level steadily can reduce the risk of carotid plaque.

Objective To investigate the incidence and risk factors of neonatal asphyxia in Hubei Enshi Tujia and Miao Autonomous Prefecture. Methods Live born infants, including those diagnosed with neonatal asphyxia, were recruited from 16 different hospitals in Hubei Enshi Tujia and Miao Autonomous Prefecture from January to December of 2016. The 16 hospitals included four grade A tertiary hospitals (three general hospitals and one traditional Chinese medicine hospital) and 12 grade A secondary hospitals (eight general hospitals, one maternal and child health hospital and three traditional Chinese medicine hospitals). A retrospective investigation was conducted using questionnaire to analyze the basic information, perinatal risk factors and prognosis of those infants. Chi-square test was used for statistical analysis. Results Among 22 294 recruited live born infants, 733 (3.29%) were diagnosed with neonatal asphyxia on discharge, including 627 (85.54%) mild cases and 106 (14.46%) severe cases. And neonatal asphyxia resulted in deaths of 27 cases (3.68%). The risk factors for neonatal asphyxia included multiple pregnancy, pregnancy conceived with assisted reproductive technology, premature infant, low birth weight infant, fetal malposition, congenital malformation, male infant, born during transfer, mother of Tujia nationality, low educational level (primary school or lower), living in rural area, the number of antenatal visits ≤3, history of early threatened abortion, anemia in pregnancy, hypertensive disorders of pregnancy, chorioamnionitis, abnormal pregnancy history and abnormality of umbilical cord, amniotic fluid or placenta. Conclusions The incidence of neonatal asphyxia in Enshi area is obviously higher than the national average. The main risk factors for neonatal asphyxia in this area are related to maternal background and the living condition of the mother during pregnancy, delivery as well as the newborn at birth.

Objective To analyze the prognostic impact of Ikaros family zinc finger 1(IKZF1)mutation on adult Philadelphia chromosome (Ph1) positive acute lymphoblastic leukemia (ALL) patients.Methods IKZF1 mutation was detected in 63 adult Phi positive ALL patients at diagnosis using capillary electrophoresis.Recruited patients were treated in our center and other three hospitals in Ningbo from January 2014 to January 2017.Clinical data were collected and retrospectively analyzed.Results Thirty-nine (61.9％) patients were positive IKZF1 mutation in this cohort.The white blood cell (WBC) count in IKZF1 mutation group was significantly higher than that of mutation negative group [(64.6±11.3)× 109/L vs.(33.7±5.6)×109/L,P＜0.05].Patients with WBC count over 30×109/L accounted for 56.4％ in IKZF1 mutation group.Complete remission (CR) rate in the IKZF1 mutation group was also lower than that of negative group after induction chemotherapy (64.1％ vs.75.0％,P＞0.05).IKZF1 was a negative prognostic factor but not independent factor for survival by univariate and multivariate analyses.Patients were divided into chemotherapy and allogeneic transplantation groups.The 3-year overall survival (OS) rate and 3-year leukemia-free survival (LFS) rate in IKZF1 mutation group were significantly lower than those of negative group in both transplantation group (42.3％ vs.59.3％;31.2％ vs.50.0％;respectively,both P＜0.05) and chemotherapy group (24.8％ vs.40.0％;19.0％ vs.34.3％;respectively,both P＜0.05).Conclusion IKZF1 mutation is a poor prognostic factor for adult Ph1 positive ALL patients.

Objective: To develop an LC-MS/MS method for the determination of donepezil and rivastigmine in human serum. Methods: After protein precipitation with 600μl acetonitrile, the serum samples were analyzed by LC-MS/MS. Using loratadine as the internal standard, a Waters Xselect CSH C18(150 mm×3 mm, 2. 5 μm) column was used with the mobile phase consisting of water (containing 10 mmol·L-1ammonium acetate)-acetonitrile(20 ∶ 80)at a flow rate of 0. 4 ml·min-1with the column temperature at 40 ℃. The ion transitions were performed in a positive electrospray ionization multiple reaction-monitoring mode regarding [M+H] +as the molecular ion peak of donepezil and rivastigmine monitored with m/z 380. 1→m/z 91. 1 and m/z 251→m/z 206. 5, respectively. The internal standard was monitored with m/z 383. 1→m/z 337. 1. Results: The linear range of donepezil and rivastigmine was 0. 5-400 ng·ml-1(r>0. 99) and the lowest quantification limit was 0. 5 ng·ml-1. For donepezil, the intra-day and inter-day RSD was 2. 06% to 12. 51% , the relative error was -6. 60% to 4. 20% , and the relative recovery was ranged from 80. 76% to 96. 17% (RSD<15% ). For rivastigmine, the intra-day and inter-day RSD was 1. 69% to 9. 31% , the relative error was -5. 58% to 5. 20% , and the mean relative recovery was ranged from 96. 69% to 100. 15% (RSD<15% ). For the two compounds, the serum samples were stable at -40℃ for 75 d and kept stable after three repeated freeze-thaw cycles. The prepared samples were stable in the automatic sample injector (4℃) for 5 h (RSD<15% ). Conclusion: The developed assay method can be applied in the therapeutic monitoring and pharmacokinetic study of donepezil and rivastigmine in human serum.

Objective: To develop a method for the determination of lacidipine (LAC) in human plasma.Methods: After liquid-liquid extraction with tert-butyl methyl ether, the plasma samples were analyzed by LC-MS/MS.Using lacidipine-13C8 as the internal standard, a Agilent ZORBAX Eclipse XDB C18 column (150 mm×2.1 mm, 5 μm) was used with the mobile phase consisting of water(containing 5 mmol·L-1 ammonium formate)-acetonitrile(15∶85,v/v)at a flow rate of 0.3 ml·min-1 and with the column temperature at 40 ℃.The ion transitions were performed in a positive electrospray ionization multiple reaction-monitoring mode regarding + as the molecular ion peak of lacidipine and monitoring with m/z 473.5→m/z 410.3, m/z 473.5→m/z 400.1 and m/z 473.5→m/z 354.3.The internal standard was monitored with m/z 481.4→m/z 362.3.Results: The linear range of lacidipine was 0.1-10 ng·ml-1 (r＞0.99) and the lower quantification limit was 0.1 ng·ml-1.The intra-and inter-day RSDs were 3.15%-7.04% and the relative error was from-8.58% to 12.71%.The mean relative recovery of lacidipine was from 107% to 118% (RSD＜15%).The plasma samples were stable at-20℃ for 40 d and kept stable after three repeated freeze-thaw cycles.The prepared samples were stable at room temperature for 24 h and in the automatic sample injector (4℃) for 24 h(RSD＜15%).Conclusion: The developed assay method can be applied in the bioequivalence evaluation and pharmacokinetic studies of lacidipine in human.

OBJECTIVE: To investigate the role and mechanism of the endoplasmic reticulum stress(ERS) pathway of apoptosis mediated by inositol-requiring enzyme-1(IRE1) in the intervention of silicosis fibrosis in rats using polyguanylic acid(PolyG).METHODS: The specific pathogen free adult male SD rats were randomly divided into control group(24rats),silicosis model group(24 rats),PolyG intervention group(16 rats) and PolyG treatment group(16 rats).The silicosis fibrosis rat model was constructed using the single inhalable intratracheal instillation method.The rats in the control group were injected with 1 mL of 0.9% sodium chloride solution.The other 3 groups were given 1 mL of silica suspension at 50.0 g/L mass concentration.The rats in PolyG intervention group on the day of model construction and rats in PolyG treatment group on the 28 th day after model construction were all given PolyG with 2.5 mg/kg body weight by one time tail vein intravenous injection.Eight rats in the PolyG intervention group and PolyG treatment group were sacrificed respectively on day 28 and day 56 after injection.The pathological changes of lung tissue in each group were observed.The expression of glucose regulated protein-78(GRP78),IRE1,CCAAT/enhancer-binding protein homologous protein(CHOP),Casepase-3,Casepase-12,type Ⅰ collagen and type Ⅲ collagen in lung tissue was detected by the Western blot.RESULTS: The histopathology examination results showed that the structure of lung tissue in control group was normal.The alveolar structure of the lung tissue of the silicosis model group was severe,and the fibrous nodules and a large amount of collagen deposition appeared.The silicosis nodules and collagen deposition in PolyG intervention group and PolyG treatment group were less than those in silicosis model group.The expression of GRP78,IRE1,CHOP,Casepase-3,Casepase-12,type Ⅰ collagen and type Ⅲ collagen in silicosis model group was higher than that of control group(P <0.05).The expression of the above 7 proteins in the PolyG intervention group and PolyG treatment group was lower than that of silicosis model group(P<0.05),higher than that of control group(P<0.05),except IRE1 and CHOP in PolyG intervention group.On day 56 after model construction,the expression of GRP78,IRE1,Casepase-3,Casepase-12,typeⅠ collagen and type Ⅲ collagen in PolyG intervention group were lower than that of PolyG treatment group(P<0.05).CONCLUSION: The unfolded protein response of ERS mediated by IRE1 may participate in the process of PolyG the intervention on silicosis fibrosis in rats.PolyG can effectively prevent and treat silicosis fibrosis.Prophylactic administration is recommended.