Objective To establish a UPLC-MS/MS method for the determination of dexmedetomidine in human plasma and investigate the effect of obstructive jaundice on pharmacokinetics of dexmedetomidine in vivo. Methods Samples were obtained by liquid-liquid extraction. Agilent Eclipse Plus C₁₈ column was used for chromatograph with methanol and 0.1% formic acid-water solution as mobile phase. Flow rate was 0.2 ml/min. The column temperature was 35 ℃, and the MS detection was selected in MRM mode. Results The calibration curves of dexmedetomidine showed good linearity in the ranges of 0.01−10.00 ng/ml. The results of intra and inter-day precisions were both within 15%. The recovery rate was 85.5%−93.1%. Matrix effect was 91.2%−95.6%. Samples remained stable during analysis. Compared with the control group, c_max、AUC_(0−t)、AUC_(0−∞) and V_z of dexmedetomidine in the patients with obstructive jaundice were increased by 63.4%, 78.9, 66.4%, 82.5%, respectively (P<0.01). CLz was decreased by 42.1%. Conclusion This method is accurate, sensitive and reproducible. It is suitable for dexmedetomidine assay in human plasma. The elimination rate of dexmedetomidine is slower in obstructive jaundice.

Objective: The study aimed to explore sex differences in the growth and physical development of Beijing school-aged children and adolescents. Methods: Data obtained from regular health examinations of 94 122 school-aged children and adolescents aged 6-18 years old were collected from primary and high schools in Shunyi District from 2009 to 2018, and a longitudinal dataset was compiled with complete anthropometric parameters including height, weight, and BMI levels after linkage of individuallevel information. The age-specific growth rate was calculated and a linear mixed-effects model was used to identify sex differences according to chronological or relative age to peak height velocity (PHA). Results: Height, weight, and BMI levels increased with age in both boys and girls. Girls were taller than boys in the 10-11 year-old age group, catch-up growth in height was observed in boys at age 12, whose height surpassed that of girls thereafter. Boys had a higher weight and BMI than girls in all age groups (P<0.01). Sex differences were found in the growth rates of height, weight, and BMI levels(t=-67.56，-47.46，3.22，P<0.01), which was demonstrated by the interaction effect of sex and age in the linear mixed-effects model. The PHA in boys was 12 years old, which was two years later than the PHA in girls. Boys reached peak weight velocity at 12 years old, lagging one year behind girls who reached their peak at 11 years old. The curves of the BMI growth rate with age showed double peaks in boys and the first peak appeared at 10 years, which was one year earlier than girls. The change in weight was highly synchronized in time with the increase in height, after adjusting for the growth rate of weight by PHA. Weight velocity increased with age before the onset of puberty until PHA, and then it declined; boys presented with obvious fat accumulation before the onset of puberty. Conclusion Sex differences in the growth and physical development of school-aged children and adolescents were persistent and apparent, and the change in weight was highly synchronized in time with the increase in height.

Objective: To explore sex differences between weight and systolic blood pressure (SBP) changes among school-age children and adolescents in Beijing, and to provide a basis for priority intervention to control the rapid growth of body weight and blood pressure. Methods: Anthropometric measurement data of 70 288 children and adolescents from primary and high schools in Shunyi District were collected from 2009 to 2018, and a longitudinal dataset with complete data related to weight and BP after individual data linkage was compiled. The age-specific weight and SBP growth rates were calculated, and a linear mixed-effects model was used to identify sex differences in chronological growth rates. Results: Weight and SBP increased with age in both boys and girls, and the mean weight and SBP were higher in boys than in girls across all age groups. The result of the linear mixed-effects model indicated apparent sex differences in weight and SBP growth rates, with an age and sex interaction term(β=-0.35, -0.40, P<0.01). The age at peak weight velocity (PWA) was 12 years old and the age at peak SBP velocity was 13 years old in boys, which occurred one and three years later than for girls, respectively. In addition, the peak weight and SBP velocity were higher in boys than in girls. The curves of the SBP growth rate adjusted for the PWA, showed that the peak SBP velocity occurred two years before PWA and the second peak SBP velocity occurred at the PWA, which indicated "double peaks" in both boys and girls. The SBP growth rate was always higher in boys than in girls, and the rates declined after PWA. Conclusion Sex differences in weight and SBP growth rates were persistent and obvious in school-age children and adolescents in Beijing and the change in SBP was highly time synchronized with the increase in weight.

Objective: To explore differences in the detection rate of elevated blood pressure (BP) in children aged 6-8 years old, and to verify the apparent existence of white-coat hypertension (BP) in children. Methods: Based on census data(PROC), and three subsequent BP readings were taken during follow-ups which were carried out from October 2018 to June 2019. A total of 1 785 children were included in the present study. Using updating blood pressure reference for Chinese children aged 3-17 years, compared the BP detection rate at baseline, at the first follow-up, and the average value of the last two BP readings. Fluctuations in the detection rate of elevated BP in children at different time-points were analyzed. Results: The detection rates of the three elevated BP measurements of 6-8-year-old children were 57.65%, 25.88% and 15.46%, respectively, and the detection rate was higher among boys than girls. The detection rate of baseline BP was higher than that of the first follow-up BP measurements and the average of the last two BP measurements(P<0.01). Given the agreement in the diagnosis of high SBP, high DBP, high BP at baseline, and the average of the last two follow-up BP measurements, elevated BP at baseline was the lowest among the three groups and SBP was higher than DBP. Conclusion Blood Pressure fluctuations might be caused by transient tension that was experienced during the baseline BP measurement and during the first of the three follow-ups. Therefore, the average value of last two BP measurements may better reflect the real BP level in children.

Objective: To examine the association between the visceral adiposity index (VAI) and nonalcoholic fatty liver disease (NAFLD) in the pediatric population in order to improve risk stratification and prevention systems for chronic liver disease. Methods: A total of 510 overweight/obese children aged 6-8 years old were enrolled from the child cohort which was designed to study puberty, obesity, and cardiovascular risk (PROC), and complete data from liver ultrasounds and the VAI were obtained. Used Spearman s rank correlation coefficient, Chi-square tests, and Logistic regression analyses to explore the association between the VAI and NAFLD. Results: The detection rates of NAFLD for boys and girls were 25.9% and 11.1%, respectively. VAI for normal group and the NAFLD group were 0.43(0.31, 0.61) and 0.61(0.44, 0.87) in boys, and 0.74(0.56, 1.07) and 1.08(0.67, 1.51) in girls, respectively. Spearman s correlation coefficient analysis showed that triglycerides(TG), VAI, and the third quintile VAI group were positively correlated with NAFLD in both boys and girls(r=0.19,0.26,0.29;0.16,0.16,1.18,P<0.05), and high-density lipoprotein-cholesterol (HDL-C) was negatively correlated with NAFLD in boys (r=-0.21, P<0.05). With advancing tertiles of VAI, the increasing trend in the NAFLD detection rate was statistically significant in boys and girls(Chi-square for trend were 21.77,7.66, P<0.01). The results of univariate and multivariable Logistic regression showed that, by taking the first tertile of VAI as a reference, the risk of NAFLD among boys was higher in the second tertile (cOR=2.59, 95%CI=1.15-5.86; aOR=2.33, 95%CI=1.01-5.36) and in the third tertile(cOR=5.73, 95%CI=2.62-12.53; aOR=4.87, 95%CI=2.15-11.03), where as the risk among girls was higher in the third tertile(cOR=4.43, 95%CI=1.40-14.00). Conclusion VAI is positively correlated with pediatric NAFLD. Higher tertiles of VAI were associated with an increased risk of NAFLD in overweight and obese children, which indicates that VAI can be used as an early predictor of NAFLD.

Objective:To investigate the clinical characteristics and influencing factors of mortality in patients with intra-abdominal candidiasis (IAC).Methods:The retrospective case-control study was conducted. The clinicopathological data of 203 IAC patients who were admitted to 7 medical centers from June 2018 to June 2020 were collected, including 54 cases in Sir Run Run Shaw Hospital of Zhejiang University School of Medicine, 31 cases in Fujian Medical University Union Hospital, 25 cases in Beijing Hospital, 25 cases in the First Affiliated Hospital of Xi'an Jiaotong University, 24 cases in China-Japan Friendship Hospital, 22 cases in General Hospital of Eastern Theater Command of Chinese PLA and 22 cases in Chongqing University Cancer Hospital. There were 130 males and 73 females, aged (64±15)years. Observation indicators: (1) candida infection and treatment of IAC patients; (2) analysis of influencing factors for mortality of IAC patients. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was analyzed using the t test. Measurement data with skewed distribution were represented as M(range), and comparison between groups was analyzed using the Mann-Whitney U test. Count data were expressed as absolute numbers or percentages, and comparison between groups was analyzed using the chi-square test. Univariate and multivariate analyses were performed by Logistic regression model. Results:(1) Candida infection and treatment of IAC patients: 134 cases of candida albicans were cultured in the initial abdominal drainage fluid or intraoperative abdominal specimens of 203 patients, and 49 cases were treated with fluconazole. Of 69 cases infected with non candida albicans, 13 cases were treated with fluconazole. The resistance rate of candida albicans to fluconazole was 5.91%(12/203). Of 203 patients, there were 68 cases with infections shock, 53 cases with renal failure, 84 cases with respiratory failure and 63 cases with multiple organ failure, respectively. There were 148 of 203 patients admitted to intensive care unit for 9 days(range, 3-20 days), and the total hospital stay was 28 days(range, 17-50 days). Of 203 patients, 86 cases were cured and discharged, 50 cases were improved and transferred to local hospitals, 32 cases gave up treatment and discharged automatically, 19 cases died, 16 cases had no follow-up data. The mortality was 25.12%(51/203). (2) Analysis of influencing factors for mortality of IAC patients. Results of univariate analysis showed that acute physiology and chronic health evaluation score, sequential organ failure assessment score, the Cr, bilirubin, albumin, procalcitonin, and PLT on the first day of candida positive culture, of the lowest value in a week and the highest in a week, heart disease, diabetes, infections shock, renal failure, respiratory failure, multiple organ failure, anti-fungal therapy were the related factors for mortality of IAC patients ( t=-2.322, Z=-2.550, -2.262, -4.361, t=2.085, Z=-3.734, -5.226, -2.394, -5.542, t=3.462, Z=-4.957, -5.632, 3.670, -5.805, t=3.966, Z=-3.734, -5.727, χ2=4.071, 4.638, 27.353, 18.818, 13.199, 26.251, 13.388, P<0.05). Multivariate analysis showed that the bilirubin, procalcitonin on the first day of candida positive culture and infections shock were independent risk factors for mortality of IAC patients ( odds ratio=1.021, 1.022, 6.864, 95% confidence interval as 1.010-1.033, 1.001-1.044, 1.858-25.353, P<0.05). Conclusions:The common fungus of IAC was candida albicans, and fluconazole can be used as the initial empirical treatment. The prognosis of patients with abdominal candidiasis is poor. Bilirubin, procalcitonin on the first day of candida positive culture and infections shock are indepen-dent risk factors for mortality of IAC patients.

Objective: To identify the association of carotid intima-media thickness (cIMT) and visceral fat area (VFA) to inform prevention of cardiovascular disease in later life. Methods: All the grade one students of six non-boarding primary schools in Shunyi District, Beijing were enrolled, based on population-based survey design, to establish the child cohort on sensitization, puberty, obesity and cardiovascular risk (PROC). Socio-demographic information survey and anthropometric measure, blood and urine test were carried out. Robust linear regression was used to determine the relationship between cIMT and other factors. Results: Among 1 711 participants, a significant difference were observed between normal, overweight and obesity children on cIMT [(0.35±0.02)(0.36±0.02)(0.37±0.03)mm] (F=41.4, P<0.01) and VFA [16.2(13.6-19.3), 22.7(18.6-27.3), 51.5(33.9-73.0)cm2] (χ2=854.5, P<0.01). After adjusting age and sex, univariate robust linear regression showed that cIMT was associated with height, SBP, DBP, HDL-C, VFA (P<0.05) and TG (P=0.055). Multivariable robust linear regression indicated that in total and boys only included models, cIMT was associated with VFA and SBP(β=0.000 2, 0.000 2, 0.000 2, 0.000 2, P<0.05); while in girls only included model cIMT was associated with VFA and TG (β=0.000 2, 0.006 2, P<0.05). Conclusion VFA is stable to predict the increase of cIMT in children. We can use VFA to simplify the classification management of children and inform targeted early prevention of cardiovascular disease in adulthood.

Objective:To explore sex difference in height growth and blood pressure (BP) change among Beijing school-age children and adolescents.Methods:Using physical examination data of 70 769 school-age children and adolescents from primary to high school during 2009-2018 in Shunyi District, a longitudinal dataset was formed with completed anthropometrical measurements of height and blood pressure (BP) after individual information linkage. Age-specific height, BP, growth rate of height and BP as well BP growth rate based on age at peak height velocity (PHA) were calculated. Linear mixed-effects model was used to identify sex disparity in the growth rates of height and BP.Results:Height and BP increased with age in both boys and girls, and the mean height and BP of boys were always higher than those of girls, except age group from 10 to 11 years. Sex disparity existed in growth rates of height and BP ( P<0.001), which was demonstrated by the interaction item of"sex ?×?age"in linear mixed-effects model. The PHA of boys was 12 years old, which was 2 years later than that of girls, about 10 years old. The curves of BP growth rate with age showed double peaks in both boys and girls. Boys reached the peak BP velocity at 13 years old, 3 years lagging behind that of girls who reached the peak at 10 years old. However, the peak of height and BP velocity of boys were higher than that of girls. The change of BP was highly synchronized in time with the increase of height, after adjusting for the growth rate of height by PHA. BP velocity increased with age before onset of puberty till PHA and then declined. Conclusion:Sex disparity in height growth and BP change among school-age children and adolescents is persistent and significant and the change of BP is highly synchronized in time with the increase of height.

Objective:The study is to explore the association between trunk fat index (TFI) and carotid intima-media thickness (cIMT) among children aged 6-8 years old in Shunyi District, Beijing.Methods:The participants were enrolled from the child cohort on sensitization, puberty, obesity and cardiovascular risk (PROC) conducted in Shunyi District, Beijing from October 2018 to June 2019. The PROC used a community-based census-like design, and all eligible first-grade children from six public non-boarding primary schools in urban area were approached. Finally, a total of 1 503 children with written informed consent from parents and had complete data of TFI and cIMT were included for the present study. Sequential baseline surveys including anthropometric measurements, laboratory testing and ultrasonography measurement were conducted to collect the data on height, weight, body composition, blood pressure, serum lipids and cIMT. Linear regression was used to determine the predictors of cIMT, receiver operating characteristic (ROC) curve analysis was used to determine the cut-off value of TFI to identify children with high cIMT, and analysis of covariance was used to evaluate the post-consistency classification of cIMT by TFI.Results:The age of 1 503 participants was (6.7±0.3) years, and 752 boys accounted for 50.0%. The average cIMT was (0.358±0.024) and (0.355±0.023) mm, and the M( P25, P75) of TFI was 0.70 (0.22, 1.78) and 0.74 (0.23, 1.52) kg/m 2 for boys and girls, respectively. The detection rates for boys and girls of high cIMT were 2.1% and 3.3%, respectively. Linear regression analysis showed that height, systolic blood pressure (SBP), diastolic blood pressure (DBP), TFI were positively correlated with cIMT in boys ( P values<0.05). And height, SBP, triglyceride (TG), TFI were positively correlated with cIMT, and high-density lipoprotein cholesterol (HDL-C) was negatively correlated with cIMT in girls ( P values<0.05). ROC curve analysis indicated that the best cut-off values for TFI to identify children with high cIMT were 1.78 and 1.14 kg/m 2, at P75 and P66 for boys and girls, respectively. After grouped with the cut-off value of TFI and adjusted for age, height, SBP, DBP, TG, HDL-C, multivariable covariance analysis showed a consistent cut-off of inter-group cIMT mean by TFI groups ( P values<0.005). Conclusion:TFI is associated with cIMT, which underscore its application potential in identifying early vascular structural damage.

Objective:To explore the association between blood pressure (BP) and the left ventricular mass (LVM) in children aged 6-8 years.Methods:The participants were from the community-based census-like design child cohort on sensitization, puberty, obesity and cardiovascular risk (PROC) conducted in six public non-boarding primary schools in Shunyi District, Beijing. Repeated three measurements on anthropometrical, M-mode and 2-dimensional (2D) echocardiographic imaging (2D/M ECHO) and blood biochemical assay, and BP measurements were carried out at baseline and follow-up from October 2018 to June 2019. A total of 1 659 children who had repeated BP measurements and cardiac structure information were included in this study. The average value of last two measurements of BP was determined as BP value for analysis. Formula recommended by Devereux was used to calculate the mass of left ventricle. Robust linear regression models were used to explore the association between BP and LVM in different groups.Results:The average age of all patients was (7.10±0.29) years old, including 832 boys (50.15%). Of all, 83.54% (1 386/1 659) were grouped as normal BP with average LVM (58.54±13.33) g, and 16.46% (273/1 659) as elevated BP group with LVM (63.84±15.78) g ( P<0.001). The LVM of the normal BP group was lower than elevated BP group in overall participants, boys and girls ( P<0.005). Univariate analysis showed that systolic BP was associated with LVM in overall, boys and girls ( P<0.001) respectively. While diastolic BP was associated with LVM in overall and girls ( P<0.03). Multivariable analysis indicated that the associations between systolic BP and LVM were observed in overall, boys and girls ( P<0.05) with the β (95% CI)=0.14 (0.08, 0.21), 0.18 (0.08, 0.27) and 0.12 (0.03, 0.22), respectively. However, the associations of diastolic BP and LVM were not significant. Conclusion:Systolic BP is highly associated with LVM and elevated BP could increase the LVM in children. Boys with elevated BP present a larger LVM and might indicate higher risk of left ventricular hypertrophy in adulthood.