Objective:To understand the current status of pubertal sexual characteristics development of girls aged 6-18 years in Tongzhou District of Beijing and to compare the differences in sexual characteristics development among girls characterized as thin, normal, overweight, and obese.Methods:A cross-sectional survey was conducted among 2 844 girls aged 6-18 years in Tongzhou District of Beijing from September 2022 to July 2023. The developmental stages of breast and pubic hair were assessed on site, and menarche status was inquired. Weight and height were measured. The girls were subsequently characterized into thin, normal, overweight and obese groups. Basic information (including family and personal history) was obtained through questionnaires. Probit probability unit regression was applied to calculate the age of each Tanner stage of sexual characteristics development and the age of menarche. The χ 2 test was applied to compare the counting data between two or multiple groups. Results:A total of 2 844 girls were surveyed and 2 704 girls met the inclusion criteria, resulting in a valid response rate of 95.1%. Among these girls, 1 105 (40.9%) were aged 6-9 years, 1 053 (38.9%) were aged 10-13 years, and 546 (20.2%) were aged 14-18 years. The of height-for-age Z-score (HAZ), weight-for-age Z-score (WAZ), and body mass index-for-age Z-score (BAZ) were 0.46(-0.23,1.16), 0.69(-0.16,1.67), and 0.67(-0.27,1.73) respectively. The prevalences of thin, overweight, and obesity were respectively 1.7% (45/2 704), 17.3% (467/2 704), and 19.9% (538/2 704), respectively. There were 45 girls in the thin group, 1 654 girls in the normal weight group, 1 005 girls in the overweight and obesity group. The age of Tanner stage breast 2 (B2), Tanner stage pubic hair 2 (P2), and menarche was 9.0 (95% CI 8.9-9.1), 10.5 (95% CI 10.4-10.6), and 11.4 (95% CI 11.3-1.5) years, respectively. The current status of breast and pubic hair maturity in girls with pubertal development shows that 64.6% (1 211/1 874) of these girls had breast development preceding pubic hair development, 32.4% (607/1 874) had concurrent breast and pubic hair development, and 3.0% (56/1 874) had pubic hairs development preceding breast development. The interval age between B2 and B5 was 4.7 (95% CI 4.6-4.8) years, between P2 and P5 was 4.5 (95% CI 4.4-4.6) years, and between B2 and menarche was 2.4 (95% CI 2.3-2.5) years. The ages of sexual characteristics development in overweight and obese groups were earlier than that in normal and thin groups. The ages of B2 in thin, normal, overweight, and obese groups were 10.0 (95% CI 9.5-10.6), 9.3 (95% CI 9.2-9.4), and 8.6 (95% CI 8.4-8.7) years, respectively. The age of menarche in thin, normal, overweight, and obese groups were 13.1 (95% CI 12.4-13.7), 11.6 (95% CI 11.4-11.7), and 11.1 (95% CI 11.0-11.2) years, respectively. The interval ages between B2 and B5 and between P2 and P5 was 4.5 and 4.1 years, respectively in the overweight and obese groups, and those in normal group and thin group was 4.7 and 4.5 years, 4.6 and 4.7 years, respectively. Conclusions:The ages of sexual characteristics development and menarche tend in Tongzhou District of Beijing to be earlier than that being reported of Beijing's survey 20 years ago. Girls characterized as overweight and obese not only start puberty at an earlier age than girls of normal weight, but also have a shorter developmental process.

Objective:To investigate the variation of reference ranges of hemodynamic parameters in normal pregnancy and their relation to maternal basic characteristics.Methods:A total of 598 healthy pregnant women who underwent regular prenatal examination at the Third Affiliated Hospital of Guangzhou Medical University from January to December 2023 were prospectively enrolled, and noninvasive hemodynamic monitors were used to detect changes in hemodynamic parameters of the pregnant women with the week of gestation, including cardiac output (CO), stroke volume (SV), thoracic fluid content (TFC), systemic vascular resistance (SVR), mean arterial pressure (MAP), and heart rate (HR). Relationships between hemodynamic parameters and maternal basic characteristics, including age, height, and weight, were analyzed using restricted cubic spline.Results:(1) CO ( r=0.155, P<0.001), TFC ( r=0.338, P<0.001), MAP ( r=0.204, P<0.001), and HR ( r=0.352, P<0.001) were positively correlated with the week of gestation, and SV was negatively correlated with the week of gestation ( r=-0.158, P<0.001). There was no significant correlation between SVR and gestational age ( r=-0.051, P=0.258). (2) CO exhibited a positive correlation with maternal height and weight (all P<0.001). The taller and heavier of pregnant women, the higher their CO. A linear relationship was observed between maternal weight and SV, MAP and HR (all P<0.01). As maternal weight increased, SV, MAP and HR showed an upward trend. Furthermore, there was an inverse association between maternal age and SVR ( P<0.001). (3) There was a significant nonlinear association observed between TFC and body mass index during pregnancy ( P<0.05). Additionally, a nonlinear relationship was found between SVR and MAP in relation to maternal age (all P<0.05). Notably, when the age exceeded 31 years old, there was an evident upward trend observed in both SVR and MAP. Conclusions:The hemodynamic parameters of normal pregnant women are influenced by their height, body weight, and age. It is advisable to maintain a reasonable weight during pregnancy and give birth at an appropriate age.

In this study, we presented the isolation and characterization of eight novel seco-guaianolide sesquiterpenoids (1-8) and two known guaianolide derivatives (9 and 10), from the aerial part of Achillea alpina L.. Compounds 1-3 were identified as guaianolides bearing an oxygen insertion at the 2, 3 position, while compounds 4-8 belonged to a group of special 3-nor guaianolide sesquiterpenoids. The structural elucidation of 1-8, including their absolute configurations, were accomplished by a combination of spectroscopic data analysis and quantum electronic circular dichroism (ECD) calculations. To evaluate the potential antidiabetic activity of compounds 1-10, we investigated their effects on glucose consumption in palmitic acid (PA)-mediated HepG2-insulin resistance (IR) cells. Among the tested compounds, compound 7 demonstrated the most pronounced ability to reverse IR. Moreover, a mechanistic investigation revealed that compound 7 exerted its antidiabetic effect by reducing the production of the pro-inflammatory cytokine IL-1β, which was achieved through the suppression of the NLRP3 pathway.
Humans ; Hypoglycemic Agents/pharmacology* ; Circular Dichroism ; Cytokines ; Glucose ; Hep G2 Cells ; Insulin Resistance

BackgroundHome-based intervention occupies a prominent place in the treatment of autism spectrum disorder （ASD） in children， whereas previous studies on the effect of home-based early intensive behavioral intervention on verbal ability of children with ASD are somewhat inadequate. ObjectiveTo study the effects of intensive family behavioral of intervention based on Verbal Behavior Milestones Assessment and Placement Program （VB-MAPP） on the language ability of children with ASD， so as to provide references for the development of family intervention strategies for children with ASD. MethodsChildren aged 2 to 3 years old who attended the Children's Rehabilitation Department of the Second Affiliated Hospital of Shantou University Medical College from September 2020 to December 2021 and met the Diagnostic and Statistical Manual of Mental Disorders， fifth edition （DSM-5） diagnostic criteria for ASD were selected as the study objects. A non-randomized concurrent control trial was conducted to compare a study group （n=24） receiving home-based early intensive behavioral intervention using VB-MAPP with a control group （n=14） receiving training from other special institutions or early childhood education institutions. The intervention lasted for 6 months in both groups. Before and after the intervention， the VB-MAPP milestone assessment was performed in the two groups， and the VB-MAPP milestone score， mand， trac and listener responds were selected as the study indicators. Then the intervention effect was compared between two groups， and the multiple linear regression was performed to screen the related influencing factors. ResultsAfter intervention， the total milestone assessment score， mand， tact and listener responds scores of study group were higher than those of control group， with statistical difference （Z=-4.339~-2.195， P<0.05 or 0.01）. Multiple linear regression analysis denoted that the average weekly hours of home-based intervention in the first three months had certain effect on listener responds （β=1.029， P<0.05）. ConclusionApplication of home-based early intensive behavior intervention using VB-MAPP may contribute to the improvement of verbal abilities such as mand， tact and listener responds in children with ASD. ［Funded by 2020 Guangdong Provincial Science and Technology Innovation Strategy Special Fund （number， 20200601）］

Background Global warming may increase the frequency of compound hot extreme (CHE).However, there is still a lack of studies assessing the associations between CHE and preterm birth (PTB), and the underlying biological mechanisms remain unclear. Objective To estimate the association of exposure to CHE during pregnancy with PTB, and to explore the roles of inflammatory, endothelial dysfunction, and oxidative stress in the association between CHE and PTB. Methods All participants were selected from the Prenatal Environments and Offspring Health (PEOH), a prospective birth cohort conducted in Guangzhou. In this study, a total of 2449 participants who gave birth from May to October in 2014 to 2017 were enrolled, and among them blood samples were collected from 311 preterm (n=43) and full-term (n=268) pregnant women at the time of delivery. A hot day/night was identified as a day when the daily maximum temperature/minimum temperature was higher than its 90th percentile in the study period, and a CHE was defined as having both a hot night and a following hot day. The meteorological data were obtained from the China Meteorological Data Sharing Service System. Anusplin was used to assess the daily maximum temperature, daily minimum temperature, and relative humidity of the participant residence. Enzyme-linked immunosorbent assay (ELISA) was used to measure C reactive protein (CRP), endothelin-1 (ET-1), and malondialdehyde (MDA) levels in maternal serum, and their results were transformed by natural logarithm. A distributed lag nonlinear model was used to investigate the associations of exposures to hot day, hot night, and CHE during pregnancy with PTB at different lag days, and a logistic regression model was used to investigate the associations of CRP, ET-1, and MDA with PTB. Results The incidence rate of PTB was 6.2% in all selected participants. Compared with the non-hot day, the RRs (95%CIs) of CHE in lag 3, 7, and 14 days on PTB were 1.43 (1.12-1.84), 1.24 (1.08-1.43), and 1.17 (1.05-1.30), respectively, and the cumulative effects (% difference) (95%CI) of CHE in lag 14 days on maternal serum CRP, ET-1, and MDA were 0.33% (−0.45%-1.12%), 0.59% (0.11%-1.07%), and 0.57% (0.09%-1.05%), respectively. Compared with the Q1 (lowest quartile) for CRP, ET-1 and MDA, the RRs (95%CIs) of Q4 (highest quartile) for PTB were 1.27 (0.50-3.22), 1.51 (0.61-3.72), and 2.07(0.81-5.27), respectively. Conclusion Maternal exposure to CHE during pregnancy might be associated with an increased risk of PTB. Prenatal exposure to CHE is positively associated with maternal serum CRP, ET-1, and MDA, and the three biochemical indicators are also positively associated with PTB. However, the above conclusions still need further confirmation.

Objective: To explore the relationship between prepregnancy body mass index, weight gain during pregnancy with preschool obesity and body composition in offspring, so as to provide evidence for gestational weight gain and childhood obesity prevention. Methods: A total of 1 333 preschool children were recruited from 3 kindergartens in Tianjin from September to December 2020. Structured questionnaire was used to collect children s lifestyle information. Height, weight and body fat mass of children were assessed, and body fat percentage (FM%), fat mass index (FMI) and non fat mass index (FFMI) were calculated. Maternal medical records were collected and the mothers were grouped according to their prepregnancy weight status and weight gain during pregnancy. χ 2 test, t test, linear regression model and Logistic regression were used to analyze the differences of obesity and body composition among different groups. Results: The prevalence of overweight and obesity in preschoolers was 12.7% and 7.7%. After adjusting maternal age and delivery, gestational age, gender, age and lifestyle of children, the correlation between maternal pre pregnancy BMI,gestational weight gain with obesity and body composition indexes of children in preschool age was statistically significant ( P <0.05). For mothers with normal weight before pregnancy, excessive weight gain during pregnancy increased risk of high FM% and high FMI in offspring ( OR=1.81, 1.68, P <0.05). There was no significant correlation between maternal weight gain during pregnancy with offspring obesity and body composition among mothers with prepregnant overweight or obesity. Conclusion Maternal weight status before pregnancy and weight gain during pregnancy are correlated with obesity and body composition in the preschool age of offspring. It is suggested that mothers should maintain appropriate weight status before and during pregnancy.

p-coumaric acid is one of the aromatic compounds that are widely used in food, cosmetics and medicine due to its properties of antibacterium, antioxidation and cardiovascular disease prevention. Tyrosine ammonia-lyase (TAL) catalyzes the deamination of tyrosine to p-coumaric acid. However, the lack of highly active and specific tyrosine ammonia lyase limits cost-effective microbial production of p-coumaric acid. In order to improve biosynthesis efficiency of p-coumaric acid, two tyrosine ammonia-lyases, namely Fc-TAL2 derived from Flavobacterium columnare and Fs-TAL derived from Flavobacterium suncheonense, were selected and characterized. The optimum temperature (55 ℃) and pH (9.5) for Fs-TAL and Fc-TAL2 are the same. Under optimal conditions, the specific enzyme activity of Fs-TAL and Fc-TAL2 were 82.47 U/mg and 13.27 U/mg, respectively. Structural simulation and alignment analysis showed that the orientation of the phenolic hydroxyl group of the conserved Y50 residue on the inner lid loop and its distance to the substrate were the main reasons accounting for the higher activity of Fs-TAL than that of Fc-TAL2. The higher activity and specificity of Fs-TAL were further confirmed via whole-cell catalysis using recombinant Escherichia coli, which could convert 10 g/L tyrosine into 6.2 g/L p-coumaric acid with a yield of 67.9%. This study provides alternative tyrosine ammonia-lyases and may facilitate the microbial production of p-coumaric acid and its derivatives.
Ammonia-Lyases/chemistry* ; Coumaric Acids ; Escherichia coli/genetics* ; Tyrosine

Objective:To evaluate the immunogenicity of recombinant factor H binding protein(fHBP) by detecting serum antibody titer and serum bactericidal antibody test (SBA).Methods:fHBP sequence was selected and synthesized, connected to plasmid pET43.1a, transformed to Escherichia coli BL21(DE3), and expressed two recombinant fHBP proteins, included two subfamilies, fHBPA and fHBPB. After purification, the recombinant fHBP proteins were immunized to rabbits and mice. The immune antiserum titer and the bactericidal titer to epidemic strains of meningococcal bacteria group B were measured by ELISA and SBA respectively. Results:The antiserum titer of fHBP immunized rabbits was greater than 2.0×10 6, and that of immunized mice was not less than 1.0×10 6. fHBP immunized rabbit serum had bactericidal titer more than 1∶128 to 41 strains A subfamily and 20 strains B subfamily in the SBA against 69 endemic strains, and there was no cross-protection between the subfamily bacteria. The bactericidal titers of mouse serum immunized fHBPA to strains A subfamily such as Nm210902 Nm211009、Nm450522 were 1∶1 024, 1∶608、1∶861, to Nm510703、Nm311304、Nm431002 were 1∶234、1∶861、1∶430 respectively, and mouse serum immunized fHBP B to strains B subfamily Nm311302、Nm311304、Nm431002 were 1∶876、1∶274、1∶1858, all of three strains were positive in bactericidal titers. Conclusions:the titer of fHBP antiserum was higher than 1.0×10 6, the bactericidal titer was no less than 1∶128 to 61 epidemic strains, and it has a 94.2% protective effect on 69 meningococcal epidemic strains group B.

Objective:To analyze the influence of obesity status on the development of cardiometabolic disorders in school-age children.Methods:Information about children's body weight, body height and cardiovascular risk factors were collected in baseline survey in 2017 and follow-up survey in 2019. The school-age children were divided into four groups based on their baseline and follow-up obesity status, i.e. sustained non-obesity group, restored obesity group, newly classified obesity group, and persistent obesity group. Analysis of covariance was used to compare the difference of change in levels of cardiometabolic factors among the four groups. The multivariate logistic regression model was used to analyze the relationship between obesity status and the incidence risk of cardiometabolic disorders.Results:The present study included 11 379 school-age children (boys accounting for 49.6%). During the 2 years, the incidence of obesity was 3.2% (95% CI: 2.9%-3.5%) with the restoration ratio of obesity of 4.4% (95% CI: 4.0%-4.8%). Compared with the sustained non-obesity group, increases in SBP, DBP, TG, LDL-C and non-HDL-C were much higher in newly classified obesity group and persistent obesity group, but lower in restored obesity groups except for DBP (all P<0.05). In addition, the incidence risk of hypertension, high glucose, dyslipidemia and cardiometabolic disorders (≥2 risks) were much higher in newly classified and persistent obese children than in sustained non-obese children. No difference was found in incidence risks of most cardiovascular disorders between restored obese children and sustained non-obese children, except for hypertension and cardiometabolic risks. Conclusion:Both newly classified obesity and persistent obesity increased the incidence risks for multi cardiovascular disorders, while these risks could be reduced when non-obese status restore.

MTUS1 (microtubule-associated tumor suppressor 1) has been identified that can function as a tumor suppressor gene in many malignant tumors. However, the function and mechanisms underlying the regulation of MTUS1 are unclear. In the present study, we reported that miR-19a and miR-19b (miR-19a/b) promote proliferation and migration of lung cancer cells by targeting MTUS1. First, MTUS1 was proved to function as a tumor suppressor in lung cancer and was linked to cell proliferation and migration promotion. Second, an inverse correlation between miR-19a/b expression and MTUS1 mRNA/protein expression was noted in human lung cancer tissues. Third, MTUS1 was appraised as a direct target of miR-19a/b by bioinformatics analysis. Fourth, direct MTUS1 regulation by miR-19a/b in lung cancer cells was experimentally affirmed by cell transfection assay and luciferase reporter assay. Finally, miR-19a/b were shown to cooperatively repress MTUS1 expression and synergistically regulate MTUS1 expression to promote lung cancer cell proliferation and migration. In conclusion, our findings have provided the first clues regarding the roles of miR-19a/b, which appear to function as oncomirs in lung cancer by downregulating MTUS1.
A549 Cells ; Cell Movement ; Cell Proliferation ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Lung Neoplasms ; genetics ; metabolism ; pathology ; Male ; MicroRNAs ; genetics ; metabolism ; RNA, Neoplasm ; genetics ; metabolism ; Tumor Suppressor Proteins ; biosynthesis ; genetics