[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.

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.

[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.

[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.

[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.

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.

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׳.

Immunostaining of cholinergic pontomesencephalic neurons for alpha 1 versus alpha 2 adrenergic receptors suggests different sleep-wake state activities and roles.

Cholinergic neurons of the pontomesencephalic tegmentum play a critical role in paradoxical sleep, when, according to single unit recording of 'possibly' cholinergic neurons, they fire maximally. The profile of activity of the cholinergic neurons may be determined by noradrenergic locus coeruleus neurons that are active during waking and silent during paradoxical sleep. Indeed, a permissive role of the noradrenergic neurons in paradoxical sleep has been proposed based upon an inhibitory action of noradrenaline through alpha(2) adrenergic receptors on the cholinergic cells. Yet some 'possibly' cholinergic neurons are purportedly maximally active during waking and excited by noradrenaline through alpha(1) receptors. In the present study, we examined by fluorescent dual-immunostaining in the laterodorsal and pedunculopontine tegmental nuclei of the rat whether choline acetyltransferase-immunopositive neurons are stained for alpha(2A) or alpha(1A) adrenergic receptors. For comparison, we examined immunostaining for these receptors on tyrosine hydroxylase-immunopositive locus coeruleus neurons, which are known to bear alpha(2A) autoreceptors. Whereas virtually all the noradrenergic neurons were labeled for the alpha(2A) and none for the alpha(1A), approximately half the cholinergic neurons were labeled for the alpha(2A) and one third for the alpha(1A) adrenergic receptors in adjacent sections. These results suggest that different groups of cholinergic neurons bear alpha(2) versus alpha(1) adrenergic receptors and would accordingly have different sleep-wake state activities and roles. The alpha(2)-bearing group would be inhibited by noradrenaline during waking to become disinhibited and maximally active while promoting paradoxical sleep, whereas the alpha(1)-bearing group would be excited by noradrenaline during waking to become maximally active while promoting features of that state.

Allele sequences of six new Y-STR loci and haplotypes in the Chinese Han population.

Human chromosome Y-specific short tandem repeat (Y-specific STR) markers have useful properties for forensic applications. However, there is a need to develop more Y-specific STR markers, because the discriminating power of each STR locus is limited. In the present study, we describe our results on six new Y-specific STR markers that were initially located using sequence database information by Ayub et al. and were named DYS434, DYS435, DYS436, DYS437, DYS438 and DYS439. Our studies focused on the analysis of the DNA sequence for each allele at all six Y-specific STR loci in order to understand their structures in the human genome and to construct human allelic ladders, which are necessary for forensic DNA typing. In addition, the haplotype distribution for all six analyzed loci was studied in a Chinese Han population sample. The results indicate that DYS434, DYS435, DYS436, DYS437, DYS438 and DYS439 are useful Y-specific STR markers for forensic sciences.

Characterization and haplotype analysis of 10 novel Y-STR loci in Chinese Han population.

In this study, we analyzed allelic sequences of 10 novel Y-specific STR loci, DYS454, DYS510, DYS513, DYS520, DYS542, DYS544, DYS552, DYS561, DYS587 and DYS593, surveyed the distribution of haplotypes in a Chinese Han population. Extracted DNA was amplified with PCR, followed by a horizontal non-denaturing polyacrylamide gel electrophoresis with discontinuous buffer system. Purified alleles were sequenced on DNA sequencer (ABI Model 377) to verify the number of motif repeats. The number of alleles observed at each locus ranged from 3 to 8, yielding 102 haplotypes in 103 unrelated males samples. The allele diversity values for each locus ranged from 0.2099 (DYS544) to 0.7523 (DYS552). The haplotype diversity using all these loci was 0.9998. Our study revealed that they were valuable Y-specific markers for forensic applications.

Further characterization and population data for the pentanucleotide STR polymorphism D10S2325.

Pentanucleotide tandem repeat markers are interesting for forensic sciences, because they may present less stutter on the electrophoretic pattern. We focused on the analysis of the DNA sequence for each allele at the pentanucleotide STR locus D10S2325 in order to understand their structures in the human genome and to construct human allelic ladder, which is necessary for forensic DNA typing. In order to evaluate the forensic applicability of D10S2325 and to construct a preliminary database, the genotype distributions and allele frequencies in three major ethnic groups were investigated. The population samples included Caucasians (Germans), Africans (African Americans), and Asians (Chinese). A total of 520 samples from unrelated individuals was analyzed by Amp-FLP. An example of each allele and new alleles were sequenced. Allele determination was carried out by comparison with a sequenced human allelic ladder made in-house. This pentanucleotide STR provided easily interpretable results. A total of 15 alleles was found in our population samples. Three new alleles were observed and named as alleles 19 and 21 based on the number of repeat motifs, while allele 19 can be divided further into two alleles, 19a and 19 according to analysis of the sequence. No evidence of deviation from Hardy-Weinberg equilibrium was observed. In 64 confirmed father/mother/child triplets no mutation event was observed. Using a maximum likelihood method, the mutation rate was indirectly estimated as 2.5 x 10(-5). These results suggest that D10S2325 is a useful marker for forensic casework and paternity analysis.

Frequencies of D8S384 alleles and genotypes in European, African-American, Chinese, and Japanese populations.

D8S384 is a tetranucleotide tandem repeat locus. In order to evaluate the forensic validation of D8S384, the genotype distributions and allele frequencies in ten populations from three main ethnic groups were investigated, including Germans, Slovakians, African Americans, Japanese, and Chinese (Jilin, Guangzhou, Nanning, Hailaer, Dali, and Chengdu). A total of 1011 unrelated individuals, 41 pedigrees, 30 disputed paternity trios and three personal identification cases were analyzed for D8S384 by Amp-FLP technique. Many kinds of tissues, body fluids, secreta and stains have been tested. The alleles were determined by comparison with a human allele ladder. The results showed that D8S384 typing was both precise and reliable. There were eight alleles in these populations. The genotype distributions conformed to Hardy-Weinberg equilibrium predictions. No mutation events were observed. With a maximum likelihood method, the mutation rate was indirectly estimated as 2.14 x 10(-5). The heterozygosity was 0.704 +/- 0.014 at D8S384 locus. All these results suggest that D8S384 locus is a useful marker for forensic identification and paternity analysis.

[Allele and genotype frequency distribution of D19S400 locus in several populations].

Using polymerase chain reaction and PAG electrophoresis, D19S400 Locus was investigated in the populations of Chinese, Germany, Slovakian, and American Black Population. 620 samples collected from the four populations were tested and a total of 11 alleles (*7 to *17) and 47 genotypes were found. The heterozygosity was observed between 0.78 and 0.88, and the discriminating power was between 0.9385 and 0.9664. The distributions of genotypes in the four populations were in accordance with Hardy-Weinberg equilibrium. Significant differences were observed in the distribution of allele frequencies among the three major racial populations (Mongoloid, Caucasian, Negroid). According to the results obtained in this study, D19S400 locus is a robust STR for forensic and genetic purposes.

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.

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.

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.