[Effect of abdominal obesity in childhood on abdominal obesity in adulthood].

Objective: To examine the effect of childhood abdominal obesity on abdominal obesity in adulthood. Methods: Based on data from the "China Health and Nutrition Survey (CHNS)" 1993-2011, the participants who were followed up at least once in childhood (7-17 years old) and adulthood (≥18 years old) were the potential eligible ones for the inclusion. The first follow- up data in childhood and the last follow-up data in adulthood were finally included in this study, and there were 1 366 participants (males: 61.4%). Partial correlation analysis was used to examine the correlation of waist circumference in childhood with adult waist circumference. Cox regression model was used to examine the effect of abdominal obesity in childhood on abdominal obesity in adulthood. Results: The median follow-up of this cohort was 10.4 years. 36.4% (28/77) of children with abdominal obesity remained abdominally obese in adulthood. The coefficient of partial correlation was moderate for association of childhood waist circumference with adult waist circumference (r=0.32, P<0.001). The risk of abdominal obesity in adulthood was significantly increased in abdominal obese children (HR=7.54, 95%CI: 4.91-11.58) compared with children with normal waist circumference. Conclusion: Children with abdominal obesity significantly increases the risk of abdominal obesity in adulthood.

[The joint effect of abdominal obesity in childhood and adulthood on adult hypertension].

Objective: To investigate the joint effect of abdominal obesity in childhood and adulthood on adult hypertension. Methods: Based on the data from the China Health and Nutrition Survey (CHNS, 1993-2011), a total of 1 431 subjects who were investigated in both childhood (6 to17 years old) and young adulthood (18 to 35 years old) were selected for the analysis. According to waist circumference (WC) status (normal WC or abdominal obesity) in childhood and adulthood, all subjects were categorized into 4 groups. The multinomial logistic regression model was used to analyze the joint effect of abdominal obesity in childhood and adulthood on adult hypertension and pre-hypertension. Results: Compared to the subjects (n=1 057) who had normal WC in both childhood and adulthood, subjects with abdominal obesity in childhood but with normal WC (n=45) in adulthood didn't have significantly increased risk of hypertension (OR=1.52, 95%CI: 0.19-12.06). In contrast, those who had normal WC in childhood and abdominal obesity in adulthood (n=289) had increased risk of hypertension (OR=6.48, 95%CI: 3.60-11.66). In addition, subjects with persistent abdominal obesity from childhood to adulthood (n=40) had the highest risk of hypertension (OR=15.98, 95%CI: 5.39-47.35). There was a similar trend for the association of abdominal obesity in childhood and adulthood with adult pre-hypertension, with the corresponding OR (95%CI) of 1.28 (0.66-2.49), 2.90 (2.17-3.89) and 3.49 (1.65-7.40), respectively. Conclusion: The joint effect of abdominal obesity in childhood and adulthood increased the risk of adult hypertension and pre-hypertension. There was no statistical significance for subjects who had abdominal obesity in childhood but had normal WC in adulthood when compared to those with normal WC in both childhood and adulthood.

[The preliminary development of reference values of carotid artery intima-media thickness in children aged 6-11 years].

Objective: To develop the reference values of carotid intima-media thickness (cIMT) in Chinese children aged 6-11 years. Methods: A convenient cluster sampling method was used to conduct a cross-sectional survey from November 2017 to January 2018 in a primary school in Huantai County, Zibo City, Shandong Province. A total of 1 033 children aged 6-11 years (excluding children with obesity or hypertension) were included. Percentile curves for cIMT were drawn using the lambda, mu and sigma (LMS) method. Results: This study developed the cIMT reference values (P(90) and P(95)) for sex and age aged 6-11 years, including P(90) and P(95) reference values of mean cIMT, left cIMT and right cIMT, respectively. With the increase of age, the cIMT percentile values also increased. For the same age and the same percentile, the cIMT values of boys were higher than those of girls. Conclusion: This study developed sex-specific and age-specific cIMT percentile reference values in children aged 6-11 years.

[Development and validation of a simplified height-specific blood pressure cutoffs table for screening hypertension in Chinese children and adolescents].

Objective: To develop and validate a simplified height-specific blood pressure cutoffs table for screening hypertension in Chinese children and adolescents. Methods: We developed a simplified height-specific blood pressure cut offs table according to Chinese Blood Pressure Reference for Children and Adolescents aged 7-18 years (WS/T 610-2018) (hereafter referred to as "complex definition"). Populations from Early Warning, Diagnosis and Treatment of Children Cardiovascular Disease Project ("Ji'nan sample") and Shandong Children Cardiovascular Cohort Study Project ("Zibo sample") were used as validation populations for evaluating the screening effect of the simplified table for elevated blood pressure and hypertension in children and adolescents. Results: We developed simplified height-specific blood pressure cutoffs table including 7 height groups and 28 cutoffs. Both Ji'nan and Zibo samples were selected by convenient sampling method, and the former included 7 233 participants aged 7 to 17 years, among whom 3 790 (52.4%) were boys. Latter population included 1 277 participants aged 7 to 11 years, among whom 681 (53.3%) were boys. The simplified table performed well for identifying elevated blood pressure in Ji'nan sample, with values of area under the receiver operating curve (AUC) (95%CI), sensitivity, specificity, and Kappa statistic as 0.96 (0.95-0.97), 93.0%, 98.5% and 0.91, respectively, which were similar with results in Zibo sample [the values were 0.92 (0.90-0.95), 87.0%, 98.0% and 0.85, respectively]. The simplified table also performed well for identifying hypertension in Ji'nan sample with values of AUC (95%CI), sensitivity, specificity, and Kappa statistic as 0.92 (0.91-0.94), 86.9%, 98.1% and 0.85, respectively, which were similar with results in Zibo sample [the values were 0.94 (0.91-0.96), 88.2%, 98.9% and 0.88, respectively]. Conclusion: Screening for elevated and high blood pressure based on simplified height-specific blood pressure cutoffs table is easy to use and it shows satisfying effect.

Application Prospect of Massively Parallel Sequencing in Mixed Stain Detection.

Mixed stains is the common biological sample in sexual crime cases. Its analysis and DNA profiles interpretation are one of the difficulties in forensic examination. The current genetic marking of mixed stain detection mainly rely on capillary electrophoresis （CE） separation technology, and the analysis methods of the results are mainly inclusion rate and likelihood methods. Because CE has limited resolution and is not able to exploit the efficacy of each genetic marker, its ability to split mixed stain is limited. In recent years, the emerging massively parallel sequencing （MPS） technique not only can obtain the base sequence information of genetic markers, but also is capable of detecting multiple genetic markers simultaneously, and thus derives new analytical methods, bringing new opportunities for forensic detection and analysis of mixed stain. This paper intends to review the application prospects of conventional mixed stain analyses and MPS technique, therefore to provide references for later research and practice.

[Progress on Molecular Biology for Forensic Ancestry Inference].

Forensic ancestry inference refers to the application of ancestry inference of population genetics in forensic practice, which aims to assist police investigation and judicial trial. With the rapid development and extensive use of genomics, DNA as a direct carrier of genetic information, has soon replaced various phenotypic markers and become the main research topics of forensic ancestry inference. This paper reviews different kinds of genetic markers used for forensic ancestry inference, the statistical analysis methods applied, and the prospects of the development in this field.

Calcium-sensing receptor (CASR) is involved in porcine in vitro fertilisation and early embryo development.

It has been demonstrated that extracellular calcium is necessary in fertilisation and embryo development but the mechanism is still not well understood. The present study mainly focussed on the extracellular calcium effector called the calcium-sensing receptor (CASR) and examined its expression in porcine gametes and embryos and its function during fertilisation and early embryo development. By using reverse transcription polymerase chain reaction, CASR was found to be expressed in porcine oocytes, spermatozoa and embryos at different developmental stages. Functionally, medium supplementation with a CASR agonist or an antagonist during in vitro fertilisation (IVF) and in vitro culture (IVC) was tested. During fertilisation, the presence of a CASR agonist increased sperm penetration rate and decreased polyspermy rate leading to an increased normal fertilisation rate. During embryo development, for the IVF embryos, agonist treatment during IVC significantly increased cleavage rate and blastocyst formation rate compared with the control group. Furthermore, parthenogenetically activated embryos showed similar results with lower cleavage and blastocyst formation rates in the antagonist group than in the other groups. It was concluded that CASR, as the effector of extracellular calcium, modulates porcine fertilisation and early embryo development.

[Application of SNP-STR Composed by D18S51 and Three SNPs of Its Flanking Region in Paternity Testing].

OBJECTIVES: To develop a SNP-STR haplotype by consisting of the SNP and STR genetic markers, both of which locate in a haplotype block. To investigate its distribution in Han population from Chengdu, and explore its application in some special cases of paternity testing. METHODS: D18S51, one of the high mutation rate STR markers in combined DNA index system （CODIS）, and three SNP loci rs8089331, rs8094489 and rs7236090 in its flanking region, were chosen to establish SNP-STR. Its haplotype was obtained by nested allele-specific polymerase chain reaction, and the relevant distribution of 75 unrelated individuals were investigated in Han population from Chengdu. The SNP-STR haplotype was tentatively applied in duo paternity testing cases with D18S51 incompatibility. RESULTS: The SNP-STR typing method was established and a total of 43 haplotypes were obtained successfully in Han population from Chengdu. Its polymorphism was 0.948 6, and duo paternity testing cases were resolved by this method. CONCLUSIONS: SNP-STR shows high diversity and can be applied in the identifications of some special paternity testing cases.

Origin of ultralow Young׳s modulus in a metastable ß-type Ti-33Nb-4Sn alloy.

Although there is difficulty in growing a Ti-33Nb-4Sn single crystal due to its ultralow ß-phase stability, the single-crystal elastic constants of metastable ß-type Ti-33Nb-4Sn (wt%) alloy were extracted successfully from its polycrystal by in-situ synchrotron X-ray diffraction technique, to clarify the origin of the ultralow Young's modulus in its polycrystal. It is indicated that compared to binary TiCr, TiV and TiNb alloys, the Ti-33Nb-4Sn alloy possesses slightly lower ß-phase stability with respect to {110}<110>(-)shear (i.e., C׳) but much lower ß-phase stability regarding to {001}〈100〉 shear (i.e., C44). An analysis by the Hill approximation suggests that the ultralow isotropic polycrystalline Young׳s modulus (EH) of Ti-33Nb-4Sn alloy originates from the extremely low shear modulus C44 as well as the relatively low C׳. This indicates that in addition to C׳, C44 has a significant contribution to the Young's modulus of polycrystal, which challenges a conventional understanding that the Young's modulus of ß-type Ti alloys is predominantly determined by C׳.

Neuropeptide S promotes wakefulness through activation of the posterior hypothalamic histaminergic and orexinergic neurons.

In spite of the initial and pivotal findings that the newly identified neuropeptide S (NPS) promotes arousal associated with locomotor and anxiolytic-like effects, the mechanisms through which NPS acts to modulate sleep-waking states remain unclear. The present study was undertaken to investigate in the rat the effects of i.c.v. injection of NPS on the EEG, sleep-wake cycle, and brain c-Fos expression. NPS at 0.1 and 1 nmol increased significantly wakefulness (W) during the first 2 h (54.7 ± 3.2 and 64.9 ± 2.1 min, respectively, vs. 41.4 ± 2.5 min seen with saline injections, P<0.01 and P<0.001), accompanied by an increase in EEG high frequency activities (14.5-60 Hz). In the meanwhile, slow wave sleep (SWS) and paradoxical sleep (PS) decreased significantly. Ex-vivo Fos immunohistochemistry in the posterior hypothalamus revealed that, as compared with saline-treated rats, NPS enhanced c-Fos expression in histaminergic neurons by 76.0% in the ventral tuberomammillary nucleus (TMN) and 57.8% in the dorsal TMN, and in orexinergic neurons by 28.2% in the perifornical nucleus (PeF), 24.3% in the dorsomedial hypothalamic nucleus (DMH), and 13.7% in the lateral hypothalamic area (LH) of the posterior hypothalamus. The NPS-induced c-Fos expression in histaminergic neurons and orexinergic neurons where NPS receptor (NPSR) mRNA is highly expressed, suggests that NPS activates histaminergic and orexinergic neurons to promote W.

Exploration of chemical space based on 4-anilinoquinazoline.

Chemical space is defined as all possible small organic molecules, including those present in biological systems, which is so vast that so far only a tiny fraction of it has been explored. Indeed, a thorough examination of all "chemical space" is practically impossible. The success of three EGFR inhibitors (Gefitnib, Erlotinib, Lapatinib) suggests that 4-anilinoquinazoline scaffold is still worth developing in the future. To date hundreds of this sort of derivatives have been synthesized and show potent anticancer activities. Most of the compounds have been proved to be EGFR/HER2 kinase inhibitors, binding at the hinge region of the ATP site and some lead compounds have been optimized against a number of different kinases, including VEGFR-2, Src, Aurora A/B, Tpl, Clk and PDE10A. Now there is now a rich pipeline of novel anticancer agents based on 4-anilinoquinazoline in early phase clinical trials. This review will highlight the exploration of chemical space of 4-anilinoquinazoline in the past ten years and we hope that increasing knowledge of the SAR and cellular processes underlying the antitumor-activity of anilinoquinazoline derivatives will be beneficial to the rational design of new generation of small molecule anticancer drugs.

L-carnitine enhances oocyte maturation and development of parthenogenetic embryos in pigs.

The objective was to determine whether adding L-carnitine in IVM/IVC medium enhanced maturation and developmental competence of porcine oocytes in vitro. Oocyte maturation rates did not differ significantly among groups supplemented with 0, 0.25, 0.5, or 1 mg/mL of L-carnitine added during IVM (although 2 mg/mL of L-carnitine reduced maturation rate). Compared with control oocytes, those treated with 0.5 mg/mL of L-carnitine during IVM had greater (P < 0.05) rates of blastocyst formation after parthenogenetic activation, and these blastocysts had less (P < 0.05) apoptosis. Adding 0.5 mg/mL of L-carnitine during IVM also significantly reduced intracellular reactive oxygen species (ROS), and increased glutathione (GSH) concentrations. With or without glucose supplementation, 0.5 mg/mL of L-carnitine in the IVM medium significantly hastened nuclear maturation of oocytes. Moreover, supplementing the IVM medium with either glucose or L-carnitine increased (P < 0.05) percentages of oocytes that reached the metaphase II (MII) stage, relative to a control group. Final maturation rates in IVM medium containing either glucose or L-carnitine were not significantly different. Adding L-carnitine (0 to 2 mg/mL) to IVC medium for activated porcine oocytes did not significantly affect development. However, 0.5 mg/mL of L-carnitine in IVC medium significantly reduced reactive oxygen species levels and apoptosis in activated blastocysts, although glutathione concentrations were not significantly altered. In conclusion, adding L-carnitine during IVM/IVC improved developmental potential of porcine oocytes, and also the quality of parthenogenetic embryos, probably by accelerating nuclear maturation, and preventing oxidative damage and apoptosis.

The characteristics of placental transfer and tissue concentrations of nickel in late gestational rats and fetuses.

The dynamics of nickel (Ni) uptake, transfer, retention and clearance in fetuses and late gestational rats were investigated by assessing its distributions in placenta, maternal and fetal organs and tissues during the 24 h period after a single dose of (63)Ni intraperitoneal injection on gestational day 20. Peak (63)Ni radioactivity was detected at 0.5 h in maternal blood, at 3 h in placenta, fetal membranes, fetal blood, fetal heart, maternal kidney, lung, stomach, liver and brain, at 9 h in fetal kidney, stomach, liver and brain, and lastly at 24 h in fetal lung and amniotic fluid. The maximal (63)Ni radioactivity among all samples was detected consistently in the fetal membranes and placenta. The (63)Ni radioactivity in fetal blood was higher than that in maternal blood from 3 to 24 h. The fetal liver, heart, stomach and brain exhibited higher (63)Ni radioactivity than the corresponding maternal organs from 6 to 24 h. However, maternal kidney consistently exhibited significantly higher (63)Ni radioactivity than the fetal kidney. The (63)Ni in fetal lung and amniotic fluid increased throughout the period of experimental observation. These observations corroborated previous finding that nickel is actively transferred across the blood-placenta-barrier into fetus, but hardly from fetus to mother. Moreover, these results suggest that the placenta has a high affinity for nickel and its barrier does not protect the fetus from nickel exposure. The fact that nickel concentrations are higher in most fetal organs and tissues than in corresponding maternal organs and tissues in late gestation indicates that, unlike the dam, fetuses lack effective means for getting rid of excessive nickel due to its confined environment and relatively weak kidney functions. The situation is exacerbated by mother-to-fetus unidirectional transfer. Consequently, the fetuses are particularly vulnerable to the damaging effects of nickel.

Gestational age and dose influence on placental transfer of 63Ni in rats.

The effects of gestational age and dose of nickel exposure on regulating and influencing placental transfer were investigated. Pregnant rats on gestational day (GD) 12, 15 or 20 were injected intraperitoneally with saline, 64,320 or 640 kBq/kg body weight of (63)Ni. Twenty-four hours after administration, samples were harvested from each for measurement of radioactivity by liquid scintillation counting and for autoradiography. In placenta, amniotic fluid and fetal membrane, (63)Ni concentrations increased with increasing doses and gestational age. In fetus, (63)Ni concentrations reached a maximum on GD 15 and then declined on GD 20 although they maintained a dose-dependency for each GD group. In fetal blood on GD 20, (63)Ni concentration increased dose-dependently and was higher than in maternal blood. The autoradiographs demonstrated that (63)Ni radioactivity was located within placental basal lamina, fetal bones and most organs. These findings suggest that the nickel uptake, retention and transport in placenta increase dose- and gestation age-dependently, and nickel transfer through placental barrier is primarily from mother into the fetus, but hardly from fetus to mother.

Improved parthenogenetic development of vitrified-warmed bovine oocytes activated with 9% ethanol plus 6-DMAP.

The objective was to compare various activation protocols on developmental potential of vitrified bovine oocytes. Bovine oocytes matured in vitro for 23 h were vitrified with EDFSF30 in open pulled straws. After warming, they were cultured in vitro for 1h, followed by parthenogenetic activation. Vitrified-warmed oocytes had a morphologically normal rate similar to that of controls (nonvitrified oocytes cultured in vitro for 24h; 98.6% vs. 100%, P>0.05). When vitrified-warmed oocytes were first activated with 7% ethanol for 5 min and then incubated in 6-dimethylaminopurin (6-DMAP) for 4h, cleavage and blastocyst rates were 41.2% and 23.2%, respectively, which were lower than those of controls (77.5% and 42.0%, P < 0.05). Subsequently, we varied the ethanol concentration to increase the effectiveness of parthenogenetic activation. When either 5%, 6%, 7%, 8%, 9%, 10%, or 11% ethanol alone (for 5 min) or in combination with 6-DMAP (4h) was used to activate vitrified-warmed oocytes, cleavage rates ranged from 22.3% to 61.1% and blastocyst rates ranged from 1.1% to 30.6%. These rates were optimized when oocytes were treated with 9% ethanol plus 6-DMAP; this was verified in experiments evaluating other activation protocols with 9% ethanol, calcium ionophore A23187, or ionomycin alone, or in combination with DMAP or cycloheximide (CHX). In conclusion, the oocyte activation protocol affected developmental capacity of vitrified bovine oocytes; 9% ethanol (5 min) followed by 6-DMAP (4h) promoted optimal parthenogenetic activation.

Forensic DNA typing in China.

In the field of forensic genetics, essential developmental impulses come from the advances of the molecular biology and human genome projects. This paper overviews existing technologies for forensic genetics in China and gives a perspective of forensic DNA analysis. In China, work has been done in the development of blood group serology of the conventional markers. Forensic scientists in China also contributed to the progress of DNA analysis by the validation of numerous test methods and by optimization of these methods. During these years, forensic DNA analysis in China has experienced tremendous progress towards development of robust, efficient and precise protocols, including the development of short tandem repeat analysis, mitochondrial DNA and Y-chromosome analysis. Forensic scientists are constantly looking for new methods to further improve DNA typing. Therefore, this paper also focuses on emerging new technologies in China, which represent an interest for forensic genetics.

Tracking kidney volume in mice with polycystic kidney disease by magnetic resonance imaging.

Polycystic kidney disease is characterized by the progressive enlargement of kidneys due to expanding fluid-filled cysts with the rate of renal volume increase held to be a marker of disease progression. Magnetic resonance imaging (MRI) is used to monitor changes in renal volume in patients with polycystic kidney disease; however, it has not been effectively used in mice to monitor changes in kidney volume during drug treatment studies. We used a powerful 9.4-T horizontal bore magnetic resonance scanner to track changes in kidney volume in pcy/pcy mice, an ortholog of nephronophthisis type 3. Mice were sequentially scanned from 4 to 30 weeks of age and kidney volumes determined from high-resolution images. Kidney volume and maximal cross-sectional surface area correlated positively with kidney weight and the histologic determination of surface area. The increase in kidney volume was exponential up to 20 weeks of age, after which there was a plateau consistent with the replacement of normal parenchyma by fibrotic tissue. Our study demonstrates that MRI accurately determines the rate of kidney volume increase in mice with polycystic kidney disease and hence may be useful in assessing the effectiveness of therapeutic agents to slow disease progression.