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BackgroundHigh altitude de-acclimatization (HADA) is gradually becoming a public health concern as millions of individuals of different occupations migrate to high-altitude areas for work due to economic growth in plateau areas. HADA affects people who return to lower elevations after exposure to high altitudes. It causes significant physiological and functional changes that can negatively impact health and even endanger life. However, uncertainties persist about the detailed mechanisms underlying HADA.MethodsWe established a population cohort of individuals with HADA and assessed variations in metabolite composition. Plasm samples of four groups, including subjects staying at plain (P) and high altitude (H) as well as subjects suffering from HADA syndrome with almost no reaction (r3) and mild-to-moderate reaction (R3) after returning to plain from high altitude, were collected and analyzed by Liquid Chromatography-Mass Spectrometry metabolomic. Multivariate statistical analyses were used to explore significant differences and potential clinical prospect of metabolites.ResultAlthough significantly different on current HADAS diagnostic symptom score, there were no differences in 17 usual clinical indices between r3 and R3. Further multivariate analyses showed isolated clustering distribution of the metabolites among the four groups, suggesting significant differences in their metabolic characteristics. Through K-means clustering analysis, we identified 235 metabolites that exhibited patterns of abundance change consistent with phenotype of HADA syndrome. Pathway enrichment analysis indicated a high influence of polyunsaturated fatty acids under high-altitude conditions. We compared the metabolites between R3 and r3 and found 107 metabolites with differential abundance involved in lipid metabolism and oxidation, suggesting their potential role in the regulation of oxidative stress homeostasis. Among them, four metabolites might play a key role in the occurrence of HADA, including 11-beta-hydroxyandrosterone-3-glucuronide, 5-methoxyindoleacetate, 9,10-epoxyoctadecenoic acid, and PysoPC (20:5).ConclusionWe observed the dynamic variation in the metabolic process of HADA. Levels of four metabolites, which might be provoking HADA mediated through lipid metabolism and oxidation, were expected to be explore prospective indices for HADA. Additionally, metabolomics was more efficient in identifying environmental risk factors than clinical examination when dramatic metabolic disturbances underlying the difference in symptoms were detected, providing new insights into the molecular mechanisms of HADAS.

Aim: To evaluate the 23 autosomal short tandem repeat (STR) loci included in GoldenEye™ 25 A kit using forensic human identification and paternity testing. Subjects and methods: In total, 3751 unrelated individuals from the Southern Chinese Han population were genotyped with the 5-dye GoldenEye™ 25 A multiplex amplification system. PCR products were separated using arrayed capillary electrophoresis. Allele frequencies and forensic parameters for the 23 autosomal STR loci were statistically analysed. Results: A total of 344 alleles were observed, with corresponding allelic frequencies ranging from 0.0001–0.5519 for the 23 STR loci. No significant deviation from the Hardy-Weinberg equilibrium and linkage disequilibrium was observed. The combined power of discrimination (CPD) was 1–1.6290 × 10−28 and the combined power of exclusion (CPE) was 0.999 999 999 89 and 0.999 999 286 93 for trio and duo cases, respectively. From 3865 meioses, 87 mutation events were discovered. The mutation rate varied from 0–0.00285 for each locus. One-step mutation accounted for 94.25% of total mutations. The ratio of paternal vs maternal mutation was 3.76:1.13 kinds of n/(n + 1) heterozygote genotypes were observed. Conclusions: The results show that 23 STR loci of GoldenEye™ 25 A kit are highly polymorphic in the Southern Chinese Han population, indicating the kit is suitable for forensic application.

The present study uses a method to address microvibrations effects on an optical satellite by combining simulations and experiments based on high-precision acceleration sensors. The displacement and angular displacement of each optical component can be obtained by introducing flywheel perturbation data from a six-component test bench to the finite element model of the optical satellite. Combined with an optical amplification factor inferred from the linear optical model, the pixel offset of the whole optical system is calculated. A high accuracy and broad frequency range for a new microvibration measurement experimental system is established to validate the simulation. The pixel offset of the whole optical system can be measured by testing the acceleration signals of each optical component and calculating optical amplification factors. The results are consistent with optical imaging test results, indicating correctness of the experimental scheme and the effectiveness of the simulation. The results suggest that the effect of microvibrations on a camera can be verified by using mechanical simulators instead of a whole optical camera for the experiment scheme, which is demonstrated to be an effective way for increasing efficiency in jitter measurements.

Intercalated disk (ID), which electromechanically couples cardiomyocytes into a functional syncitium, is closely related to normal morphology and function of engineered heart tissues (EHTs), but the development mode of ID in the three-dimensional (3D) EHTs is still unclear. In this study, we focused on the spatiotemporal development of the ID in the EHTs constructed by mixing neonatal rat cardiomyocytes with collagen/Matrigel, and investigated the effect of 3D microenvironment provided by collagen/Matrigel matrix on the formation of ID. By histological and immmunofluorescent staining, the spatiotemporal distribution of ID-related junctions was detected. Furthermore, the ultra-structures of the ID in different developmental stages were observed under transmission electron microscope. In addition, the expression of the related proteins was quantitatively analyzed. The results indicate that accompanying the re-organization of cardiomyocytes in collagen/Matrigel matrix, the proteins of adherens junctions, desmosomes and gap junctions redistributed from diffused distribution to intercellular regions to form an integrated ID. The adherens junction and desmosome which are related with mechanical connection appeared earlier than gap junction which is essential for electrochemical coupling. These findings suggest that the 3D microenvironment based on collagen/Matrigel matrix could support the ordered assembly of the ID in EHTs and have implications for comprehending the ordered and coordinated development of ID during the functional organization of EHTs.

The age-related decline of signal joint T-cell receptor rearrangement excision circles (sjTRECs) in human peripheral blood has been demonstrated in our previous study and other reports. Until now, only a few studies on sjTREC detection in bloodstain samples were reported, which were based on a small sample of subjects of a limited age range, although bloodstains are much more frequently encountered in forensic practice. In this present study, we adopted the sensitive Taqman real-time quantitative polymerase chain reaction (qPCR) method to perform sjTREC quantification in bloodstains from individuals ranging from 0-86 years old (n = 264). The results revealed that sjTREC contents in human bloodstains were declined in an age-dependent manner (r = -0.8712). The formula of age estimation was Age = -7.1815Y-42.458 ± 9.42 (Y dCt(TBP-sjTREC); 9.42 standard error). Furthermore, we tested for the influence of short- or long- storage time by analyzing fresh and stored bloodstains from the same individuals. Remarkably, no statistically significant difference in sjTREC contents was found between the fresh and old DNA samples over a 4-week of storage time. However, significant loss (0.16-1.93 dCt) in sjTREC contents was detected after 1.5 years of storage in 31 samples. Moreover, preliminary sjTREC quantification from up to 20-year-old bloodstains showed that though the sjTREC contents were detectable in all samples and highly correlated with donor age, a time-dependent decrease in the correlation coefficient r was found, suggesting the predicting accuracy of this described assay would be deteriorated in aged samples. Our findings show that sjTREC quantification might be also suitable for age prediction in bloodstains, and future researches into the time-dependent or other potential impacts on sjTREC quantification might allow further improvement of the predicting accuracy.

Background/Aims: We tried to investigate the expression characteristics of KAI1, a suppressor of wide-spectrum tumor metastasis, and vascular endothelial growth factor (VEGF), the most common angiogenesis factor, and then to analyze their diagnostic value for hepatocellular carcinoma (HCC). Methods: The protein and mRNA expression levels of KAI1 or VEGF in HCC tissues and in self-controlled paracarcinoma tissues were analyzed by Western blot and realtime polymerase chain reaction, respectively. Serum levels of KAI1 and VEGF in the patients with HCC, benign liver disease or in healthy controls were quantitatively detected by enzyme-linked immunosorbent assay. Results: The expression level of KAI1 was downregulated, while the expression level of VEGF was upregulated in the tissues or serum of the patients with HCC. The expression level of serum KAI1 in HCC patients was correlated with TNM staging, intrahepatic metastasis, lymph node or peritoneal metastasis, and portal vein thrombus. In addition to the factors that were correlated with KAI1 expression, VEGF expression was also closely related to the α-fetoprotein level of the patients. The area under the receiver operating characteristic curve for the diagnosis of HCC was 0.907 for KAI1 and 0.779 for VEGF. The sensitivity of serum KAI1 levels in the diagnosis of HCC was 86.96%; the accuracy was 83.06%, while the sensitivity, the accuracy and the negative predictive value were improved to 91.86%, 84.68%, and 78.79% according to the combined detection of KAI1 and VEGF, respectively. Conclusions: A combined detection of KAI1 and VEGF may greatly improve the efficiency of diagnosis and form a reliable panel of diagnostic markers for HCC. [ABSTRACT FROM AUTHOR]

Abstract  We investigated the polymorphism of five X-chromosomal short tandem repeat markers (ChrX STRs) loci (DXS7132, DXS981, DXS6803, DXS6809, and DXS6789) and their value for forensic applications. A fluorescent multiplex polymerase chain reaction (PCR) for amplifying five ChrX STRs loci in the same PCR reaction was set up. A total of 827 unrelated individuals of the Han nationality in China were tested. The results show that the five loci in the multiplex system provide high polymorphism information for forensic identification and paternity testing, particularly for difficult paternity-deficient cases. [ABSTRACT FROM AUTHOR]

Methods & Results In southern China, the average carrier rates of alpha-thalassemia and beta-thalassemia in the population are as high as 10.3% and 2.8%, respectively. Because of the high rates, they are known as 'social diseases' in some regions. In this study, the fluorescent gap PCR, which can detect the alpha-thalassemia Southeast Asia deletion (SEA deletion), was applied in four clinical applications of preimplantation genetic diagnosis (PGD) on four couples, among whom both partners were alpha-thalassemia carriers. Two patients became pregnant and two healthy babies were born, which confirmed the PGD results. The single cell multiplex nested PCR followed by reverse dot blot (RDB), which can simultaneously detect the 16 beta-thalassemia mutations in the Chinese population, was applied in four clinical PGD cycles on four couples among whom both partners were beta-thalassemia carriers. One pregnancy was achieved and it resulted in a live healthy birth, which confirmed the results of PGD. The amplification efficiencies of the two protocols described above were 89.5% and 93.9%, respectively. The allele drop-out (ADO) rates of these two protocols were 5.9% and 10.9%, respectively. Conclusion These studies represent the successful applications of PGD protocols that can detect more than 95% of alpha- and beta -thalassemia mutations in the Chinese population. Copyright © 2006 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Objective To study the detection efficiency of trio full sibling with another known full sibling reference added under different number of autosomal STR typing systems. Methods Based on 43 detection systems consisting of 13 to 55 representative autosomal STR loci，10 000 true families （full sibling group） and 10 000 false families （unrelated individual group） were randomly simulated. The full sibling index （FSI） was calculated based on the method of family reconstruction. The cumulative sibling relationship index （CFSI） of 0.000 1 and 10 000 were used as the evaluation thresholds, and the detection efficiency parameters were calculated and compared with the identification of the duo full sibling testing. Results With the increasing number of STR loci， the error rate and inability of judgement rate gradually decreased; the sensitivity， specificity, correct rate of judgment and other parameters gradually increased, and the system efficiency gradually improved. Under the same detection system， trio full sibling testing showed higher sensitivity， specificity， system efficiency and lower inability of judgement rate compared with duo full sibling testing. When the system efficiency was higher than 0.85 and inability of judgement rate was less than 0.01%， at least 20 STRs should be detected for trio full sibling testing， which was less than 29 STRs required by duo full sibling testing. Conclusion The detection efficiency of trio full sibling testing is superior to that of duo full sibling testing with the same detection system， which is an effective identification scheme for laboratories with inadequate detection systems or for materials with limited conditions.

Objective To establish an analytical method for half sibling testing involving common three relatives’ participation. Methods Based on the half sibling testing scenarios with the known biological mother, grandfather or uncle, and two unidentified controversial half siblings participating， two opposing hypotheses were set. Lineage reconstruction according to Mendel’s law of heredity was carried out, and the calculation formula of the half sibling kinship index was derived. Verification of actual cases was carried out and the results were compared with duo half sibling testing. Results In the scenarios of the known biological mother， grandfather and uncle participating in half sibling testing, the kinship calculation formulae of 54， 91 and 99 genotype combinations for kinship index calculation were deduced respectively. The actual cases showed higher kinship indexes in trio half sibling testing compared with duo half sibling testing. Conclusion It is beneficial to obtain more genetic information for family reconstruction and improvement of the strength of genetic evidence for half sibling testing by adding known relatives.

Kinship testing is widely needed in forensic science practice. This paper reviews the definitions of common concepts, and summarizes the basic principles, advantages and disadvantages, and application scope of kinship analysis methods, including identity by state （IBS） method， likelihood ratio （LR） method， method of moment （MoM）， and identity by descent （IBD） segment method. This paper also discusses the research hotspots of challenging kinship testing, complex kinship testing, forensic genetic genealogy analysis, and non-human biological samples.

Tri-allelic pattern in autosomal STR is a common abnormal typing phenomenon in forensic DNA analysis, which brings difficulties and uncertainties to the evaluation of the evidence weight in actual cases. This paper reviews the types, formation mechanism, occurrence frequency, genetic pattern and quantitative evaluation of evidence of the tri-allelic pattern in autosomal STR in forensic DNA analysis. This paper mainly explains the formation mechanism and genetic patterns based on different types of tri-allelic pattern. This paper also discusses the determination of tri-allelic pattern and the quantitative method of evidence evaluation in paternity testing and individual identification. This paper aims to provide references for scientific and standardized analysis of this abnormal typing phenomenon in forensic DNA analysis.