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OBJECTIVE: To investigate the effects of systemic lupus erythematosus (SLE) on health-related quality of life (HRQOL), the relationship between disease activity and HRQOL, and potential factors affecting HRQOL in Chinese SLE patients. METHODS: This study recruited 1568 patients and 2610 controls to explore the effects of SLE on HRQOL. The association between disease activity and HRQOL, and the influencing factors of HRQOL were determined in 1568 patients. Then, we prospectively followed 1096 patients to explore the association between reduced disease activity and improved HRQOL, and the influencing factors of improved HRQOL. The Short-Form 36 (SF-36) and SLE disease activity index (SLEDAI) were used to evaluate HRQOL and disease activity. RESULTS: Chinese SLE patients had lower HRQOL than controls in all domains (P < 0.001), especially in role-physical (RP) and role-emotional (RE). Compared with SLE patients from outside China, the HRQOL of Chinese patients appeared to be higher in mental component summary (MCS) but lower in RP and RE. SLEDAI was negatively correlated with HRQOL, which was validated using the results of a follow-up study, where SLEDAI reduction was positively associated with HRQOL improvements (P < 0.05). Furthermore, personality, life nervous and experiences of adverse life events may influence HRQOL and HRQOL improvements. CONCLUSION: SLE significantly affected the HRQOL of Chinese patients, especially in RP and RE. Disease activity was negatively correlated with HRQOL. We also found for the first time some factors affecting HRQOL, which can be regarded as the basis for improving the HRQOL of SLE patients.
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Lupus Eritematoso Sistémico , Calidad de Vida , Humanos , Calidad de Vida/psicología , Estudios de Seguimiento , Índice de Severidad de la Enfermedad , Encuestas y Cuestionarios , Lupus Eritematoso Sistémico/psicología , ChinaRESUMEN
Objective: To explore the protective effect of placenta-derived mesenchymal stem cells (P-MSCs) transplantation on intestinal injury in septic mice and its mechanism. Methods: A total of 24 mice were randomly assigned to 3 groups, a sham operation group, a sepsis group that underwent cecal ligation and puncture (CLP) procedure, and a group that received CLP and P-MSCs treatment. Hereinafter, the three groups are referred to as the Sham group, the CLP group, and the CLP+P-MSCs group. For the mice in the Sham group, the abdomen was cut open and the cecum was exposed and then placed back in the abdomen. CLP was performed in the other two groups to establish the sepsis model. Mice in the Sham and the CLP groups received 0.1 mL of 0.9% NaCl injection in the tail vein 1 hour after operation, while mice in the CLP+P-MSCs group received 2×10 5 P-MSCs infusion 1 hour after operation. Intestinal and blood specimens were collected from the mice in each group 24 hours after P-MSCs transplantation. Hematoxylin and eosin (HE) staining of the intestinal tissue was performed for pathological evaluation. The serum concentrations of D-lactic acid, diamine oxidase (DAO), endotoxin, interleukin (IL)-1ß, tumor necrosis factor (TNF)-α, IL-6, IL-10, and transforming growth factor (TGF)-ß were determined by enzyme linked immunosorbent assay (ELISA). The gene expression of the relevant inflammatory factors in the small intestinal tissue was determined by real-time fluorescence polymerase chain reaction. The expression of zonula occludens protein-1 (ZO-1) and occludin protein in the intestine was determined by Western blot, the infiltration of intestinal macrophages was determined by immunohistochemical method, and the polarization of macrophages was determined by immunofluorescence. Results: The exogenous transplantation of P-MSCs could form colonies in the injured intestines of septic mice. Compared with those of the CLP group, the intestinal injury of the CLP+P-MSCs group was significantly alleviated, the serum concentrations of D-lactic acid, DAO, endotoxin, IL-1ß, IL-6, and TNF-α were significantly decreased ( P<0.05), while the serum concentrations of IL-10 and TGF-ß were significantly increased ( P<0.05), the expression levels of IL-1 ß, TNF-α and IL-6 genes in the intestinal tissue were significantly decreased ( P<0.05), while the expression levels of IL-10 and TGF-ß genes were significantly increased ( P<0.05), and the expression of ZO-1 and occludin proteins in the intestine was also significantly increased ( P<0.05). In addition, the distribution of macrophages in the intestinal tissue of the CLP+P-MSCs group decreased significantly and the macrophages showed a tendency for M2 polarization. Conclusion: Exogenous transplantation of P-MSCs can significantly reduce inflammatory injury and improve the intestinal barrier function in septic mice with intestinal injury. Reduction in the infiltration of macrophages and promotion of the polarization of macrophages from M1 to M2 may be the mechanisms underlying the reduction of inflammation.
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Trasplante de Células Madre Mesenquimatosas , Sepsis , Ratones , Animales , Factor de Necrosis Tumoral alfa , Interleucina-10 , Interleucina-6 , Ocludina , Factor de Crecimiento Transformador beta , Sepsis/terapia , Ácido LácticoRESUMEN
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.
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Dermatoglifia del ADN , Genética Forense , Genética Forense/métodos , Ciencias Forenses , Linaje , HumanosRESUMEN
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.
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Medicina Legal , Repeticiones de Microsatélite , Alelos , ADN/genética , Frecuencia de los Genes , HumanosRESUMEN
OBJECTIVES: 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. CONCLUSIONS: 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.
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Madres , Hermanos , Femenino , Humanos , Genotipo , Repeticiones de MicrosatéliteRESUMEN
OBJECTIVES: 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. CONCLUSIONS: 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.
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Repeticiones de Microsatélite , Hermanos , Humanos , Repeticiones de Microsatélite/genética , Dermatoglifia del ADN , Frecuencia de los GenesRESUMEN
To describe the knowledge and attitude of Chinese patients with advanced cancer towards advanced care planning (ACP), a convenience sample of 275 patients with advanced cancer was recruited from a tertiary cancer hospital in Beijing, China, between February and December 2017. The multi-item questionnaire focused on patients' demographics, disease characteristics and knowledge about and attitude towards ACP and was administered to eligible patients. Descriptive statistics were performed. Most patients had never heard about ACP (82.2%) and had never talked about ACP (83.0%), but only a few (18.3%) were not willing to talk about ACP. A total of 67.8% patients chose to refuse resuscitation attempts or life-sustaining medical interventions, and 70.8% of patients hoped to have surrogate decision makers when they became unconscious. By binary logistic regression analysis, patients who were of greater age, female and living in urban areas preferred to refuse resuscitation attempts or life-sustaining medical interventions (OR = 1.023, P = 0.042; OR = 2.011, P = 0.020; OR = 0.254, P < 0.01); patients who had very rich or rich family economic status preferred to involve surrogate decision makers compared with patients of very poor family economic status (OR = 0.250, P = 0.011). There is a large gap between the knowledge about ACP and the expectation of implementing ACP in Chinese patients with advanced cancer. To develop culturally appropriate and individualized programmes to promote knowledge and implementation in practice of ACP among Chinese patients with advanced cancer and their relatives is still a significant challenge.
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Planificación Anticipada de Atención , Neoplasias , Pueblo Asiatico , China , Femenino , Humanos , Neoplasias/terapia , Encuestas y CuestionariosRESUMEN
Forensic genetics mainly uses human biological samples as the objects, solves the identification of biological materials related to law by detecting genetic information, provides clues for investigation and evidences for trial, thus facing many ethical issues. This paper put forward the ethical principles in forensic genetics research and practice, and discussed the ethical issues in sample collection, forensic DNA phenotyping, forensic genetic genealogy analysis, forensic DNA database development, paternity and kinship testing, and research data sharing. We suggest that specific ethical requirements should be formulated, the ethical review system should be established for forensic genetics and ethical training for practitioners should be strengthened.
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Bases de Datos de Ácidos Nucleicos , Genética Forense , ADN , HumanosRESUMEN
Short tandem repeat (STR) markers have been widely used in forensic paternity testing and individual identification, but the STR mutation might impact on the forensic result interpretation. Importantly, the STR mutation rate was underestimated due to ignoring the "hidden" mutation phenomenon in most similar studies. Considering this, we use Slooten and Ricciardi's restricted mutation model based on big data to obtain more accurate mutation rates for each marker. In this paper, the mutations of 20 autosomal STRs loci (D3S1358, D1S1656, D13S317, Penta E, D16S539, D18S51, D2S1338, CSF1PO, Penta D, TH01, vWA, D21S11, D6S1043, D7S820, D5S818, TPOX, D8S1179, D12S391, D19S433, and FGA; The restricted model does not include the correction factor of D6S1043, this paper calculates remaining 19 STR loci mutation rates) were investigated in 28,313 (Total: 78,739 individuals) confirmed parentage-testing cases in Chinese Han population. As a result, total 1665 mutations were found in all loci, including 1614 one-steps, 34 two-steps, 8 three-steps, and 9 nonintegral mutations. The loci-specific average mutation rates ranged from 0.00007700 (TPOX) to 0.00459050 (FGA) in trio's and 0.00000000 (TPOX) to 0.00344850 (FGA) in duo's. We analyzed the relationship between mutation rates of the apparent and actual, the trio's and duo's, the paternal and maternal, respectively. The results demonstrated that the actual mutation rates are more than the apparent mostly, and the values of µ1"/µ2"(apparent) are also greater than µ1/µ2 (actual) commonly (µ1", µ1; µ2", µ2 are the mutation rates of one-step and two-step). Therefore, the "hidden" mutations are identified. In addition, the mutations rates of trio's and duo's, the paternal and maternal, exhibit significant difference. Next, those mutation data are used to do a comparison with the studies of other Han populations in China, which present the temporal and regional disparities. Due to the large sample size, some rare mutation events, such as monozygotic (MZ) mutation and "fake four-step mutation", are also reported in this study. In conclusion, the estimation values of actual mutations are obtained based on big data, they can not only provide basic data for the Chinese forensic DNA and population genetics databases, but also have important significance for the development of forensic individual identification, paternity testing and genetics research.
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Macrodatos , Repeticiones de Microsatélite , Frecuencia de los Genes , Genética de Población , Humanos , Repeticiones de Microsatélite/genética , Mutación , Tasa de MutaciónRESUMEN
We had previously demonstrated that the calcitonin gene-related peptide (CGRP) suppresses the oxidative stress and vascular smooth muscle cell (VSMC) proliferation induced by vascular injury. A recent study also indicated that CGRP protects against the onset and development of angiotensin II (Ang II)-induced hypertension, vascular hypertrophy and oxidative stress. However, the mechanism behind the effects of CGRP on Ang II-induced oxidative stress is unclear. CGRP significantly suppressed the level of reactive oxygen species (ROS) generated by NADPH oxidase in Ang II-induced VSMCs. The Ang II-stimulated activation of both Src and the downstream transcription factor, STAT3, was abrogated by CGRP. However, the antioxidative effect of CGRP was lost following the expression of constitutively activated Src or STAT3. Pre-treatment with H-89 or CGRP8-37 also blocked the CGRP inhibitory effects against Ang II-induced oxidative stress. Additionally, both in vitro and in vivo analyses show that CGRP treatment inhibited Ang II-induced VSMC proliferation and hypertrophy, accompanied by a reduction in ROS generation. Collectively, these results demonstrate that CGRP exhibits its antioxidative effect by blocking the Src/STAT3 signalling pathway that is associated with Ang II-induced VSMC hypertrophy and hyperplasia.
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Angiotensina II/farmacología , Péptido Relacionado con Gen de Calcitonina/metabolismo , NADPH Oxidasas/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Factor de Transcripción STAT3/metabolismo , Transducción de Señal/fisiología , Familia-src Quinasas/metabolismo , Animales , Antioxidantes/metabolismo , Calcitonina/metabolismo , Humanos , Masculino , Ratones , Ratones Endogámicos C57BL , Músculo Liso Vascular/metabolismo , Miocitos del Músculo Liso/metabolismo , Oxidación-Reducción/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos , Estrés Oxidativo/fisiología , Ratas , Ratas Sprague-Dawley , Transducción de Señal/efectos de los fármacosRESUMEN
Apoptosis is associated with various cardiovascular diseases. CGRP exerts a variety of effects within the cardiovascular system, and protects against the onset and development of angiotensin (Ang) II-induced vascular dysfunction and remodelling. However, it is not known whether CGRP has a direct effect on Ang II-induced apoptosis in vascular smooth muscle cells (VSMCs), and the mechanism underlying the anti-apoptotic role remains unclear. In this study, CGRP significantly suppressed reactive oxygen species (ROS) and apoptosis in Ang II-induced VSMCs. In VSMCs pre-treated with a CGRP receptor antagonist (CGRP8-37), the CGRP-mediated inhibition of Ang II-induced ROS and apoptosis was completely abolished. Moreover, pre-treatment with N-acetyl-L cysteine (NAC), an ROS scavenger, blocked the effects of CGRP on Ang II-induced apoptosis. In addition, the activation of CaMKII and the downstream transcription factor CREB stimulated by Ang II was abrogated by CGRP. Importantly, in both CGRP and NAC-treated VSMCs, CGRP failed to further attenuate CaMKII and CREB activation. The results demonstrate that CGRP attenuated Ang II-induced ROS-dependent apoptosis in VSMCs by inhibiting the CaMKII/CREB signalling pathway.
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Angiotensina II/farmacología , Apoptosis , Péptido Relacionado con Gen de Calcitonina/fisiología , Músculo Liso Vascular/citología , Especies Reactivas de Oxígeno/metabolismo , Transducción de Señal/efectos de los fármacos , Animales , Proteína Quinasa Tipo 2 Dependiente de Calcio Calmodulina/antagonistas & inhibidores , Proteína Quinasa Tipo 2 Dependiente de Calcio Calmodulina/metabolismo , Células Cultivadas , Proteína de Unión a Elemento de Respuesta al AMP Cíclico/metabolismo , HumanosRESUMEN
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.
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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.
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Frecuencia de los Genes , Repeticiones de Microsatélite/genética , Mutación , Polimorfismo Genético , China , HumanosRESUMEN
Controlling the surface structure of Pt nanocrystals (NCs), especially creating high-index facets with abundant active step sites, is an effective approach to enhance catalytic performances. However, the available high-index faceted Pt NCs have large particle sizes, which severely impedes their practical applications. In this study, we reported a new electrochemically seed-mediated method, by which sub-10 nm tetrahexahedral Pt NCs (THH Pt NCs) enclosed with {210} high-index facets supported on graphene were synthesized. Pt nanoparticles of â¼3 nm in size as high-density crystal seeds play a key role in the small-sized control. The obtained THH Pt NCs exhibited a higher mass activity than commercial Pt/C catalyst for ethanol electrooxidation. We further demonstrated that this method is also valid for reshaping commercial Pt/C, to create high-index facets on surfaces and thus to improve both mass activity and stability.
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In this study, we investigated the genetic polymorphisms of 24 Y-chromosomal short tandem repeat (Y-STR) loci in 885 unrelated Chinese Han male individuals from Guangdong Province, using a domestic AGCU Y24 STR kit. A total of 878 different haplotypes were observed at the 24 Y-STR loci; among them, 871 haplotypes were unique and 7 haplotypes occurred twice. The overall haplotype diversity was 0.99998 and the discrimination capacity was 99.2%. The gene diversity values ranged from 0.4354 at DYS438 to 0.9606 at DYS385a/b. Population relationships between the Guangdong Han population and seven other published Chinese populations were evaluated by Rst values and visualized in a two multi-dimensional scaling plot. The results showed the 24 Y-STR loci are highly polymorphic in Guangdong Han population and of great value in forensic application.
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Cromosomas Humanos Y , Etnicidad/genética , Genética de Población , Haplotipos , Repeticiones de Microsatélite , Pueblo Asiatico/genética , China/etnología , Dermatoglifia del ADN , Humanos , Masculino , Reacción en Cadena de la Polimerasa , Polimorfismo GenéticoRESUMEN
To investigate genetic diversity in Chinese populations, 706 unrelated male individuals from five ethnic groups (Han, Korean, Hui, Mongolian, and Tibetan, respectively) were analyzed with 17 Y-chromosomal STRs. The haplotype diversity was 0.99985 in the combined data. A total of 675 distinct haplotypes were observed, of which 649 were unique. Y-chromosome haplogroups in the five groups were also predicted with Y-STR haplotypes. Genetic distance between the five studied ethnic groups and other published groups was analyzed by analysis of molecular variance and visualized in a multidimensional scaling plot. In conclusion, the 17 Y-STR loci are highly polymorphic markers in the five groups and hence are very useful in forensic application, population genetics, and human evolution studies.
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Pueblo Asiatico/genética , Cromosomas Humanos Y/genética , Etnicidad/genética , Haplotipos/genética , Repeticiones de Microsatélite/genética , China , Humanos , Masculino , FilogeniaRESUMEN
OBJECTIVE: To explore the mutation of Y-STR loci in meiotic allelic transmission in a large pedigree. METHODS: The oral swabs of 163 male individuals were collected from a Lin pedigree. Twenty-two Y-STR genetic markers were typed with AGCU Y24 fluorescent detection kit (AGCU Y24 system), which also contained 16 Y-STR markers included in Yfiler multiple amplification kit (Yfiler system). The genotyping results of Y-STR loci were compared between each two males in the pedigree. RESULTS: There were 20 and 30 kinds of haplotypes obtained with Yfiler and AGCU Y24 systems in 163 male individuals from the Lin pedigree, respectively. The rates referred to haplotype differences (RRHD) of these two typing systems between male pairs were 0.910 5 and 0.922 7, respectively. The average number of marker differences were 6.582 1 and 9.824 8, respectively. The RRHD increased along with the incidents of meiosis. CONCLUSION: Y-STR mutation leads to different Y-STR haplotypes among the male members in a paternal pedigree and the rate of difference increases along with the incidents of meiosis.
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Cromosomas Humanos Y/genética , Marcadores Genéticos/fisiología , Mutación/genética , Linaje , Alelos , Dermatoglifia del ADN , Ligamiento Genético , Genotipo , Haplotipos , Humanos , MasculinoRESUMEN
Background: High 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. Methods: We 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. Result: Although 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). Conclusion: We 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.
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OBJECTIVE: To identify potential mutation in a Chinese family featuring X-linked alpha thalassemia/mental retardation syndrome (ATR-X). METHODS: Based on clinical symptoms and inheritance pattern, linkage analysis of X chromosome short tandem repeats (X-STR) loci was carried out to locate the candidate gene. Subsequently, sequences of exons and exon-intron boundaries of the candidate gene were amplified with polymerase chain reaction (PCR). Potential mutations were detected by direct DNA sequencing. All patients were also analyzed for the trait of thalassemia. RESULTS: Linkage analysis indicated the candidate gene to be ATRX. Subsequently, a homozygous missense mutation c.736C>T (p.R246C) was found in exon 9 of ATRX in all of the 3 patients. And a heterozygous mutation c.736C>T (p.R246C) was also identified in the patient's mother and grandmother. Similar mutations were not detected in other members of the family. Alpha thalassemia was detected in the proband and another patient, whose genotypes were determined as -α(3.7)/αα and --(sea)/αα, respectively. CONCLUSION: Missense mutation of c.736C>T in ATRX gene is a mutation hotspot, and p.R246C may disturb the function of ATRX-DNMT3-DNMT3L domain (ADD), which may be responsible for the disease in this family.
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Pueblo Asiatico/genética , Discapacidad Intelectual Ligada al Cromosoma X/genética , Mutación Missense , Talasemia alfa/genética , Preescolar , ADN Helicasas/genética , Análisis Mutacional de ADN/métodos , Femenino , Humanos , Masculino , Proteínas Nucleares/genética , Linaje , Proteína Nuclear Ligada al Cromosoma XRESUMEN
OBJECTIVE: To deduce the calculation formulae of likelihood ratio for kinship testing with X-short tandem repeat (X-STR) typing. METHODS: With the identity by decent coefficient of different relationships, the joint genotypic probability of two individuals with specific genotypes was calculated as X value, and then the joint genotypic probability of two unrelated individuals was calculated as Y value; therefore, the likelihood ratio value (X/Y) was obtained. RESULTS: The calculation formulae of the likelihood ratio for different genotype combinations of the female-female, female-male and male-male genetic relationships were derived and verified by real cases. CONCLUSION: The calculation formulae are simple and accurate to evaluate the likelihood ratio for two individuals' genetic relationship with X-STR typing. The formulae provide the basic potential value for the difficult kinship testing with X-STR loci.