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1.
Hum Mol Genet ; 33(7): 583-593, 2024 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-38142287

RESUMO

To control genetic background and early life milieu in genome-wide DNA methylation analysis for blood lipids, we recruited Chinese discordant monozygotic twins to explore the relationships between DNA methylations and total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and triglycerides (TG). 132 monozygotic (MZ) twins were included with discordant lipid levels and completed data. A linear mixed model was conducted in Epigenome-wide association study (EWAS). Generalized estimating equation model was for gene expression analysis. We conducted Weighted correlation network analysis (WGCNA) to build co-methylated interconnected network. Additional Qingdao citizens were recruited for validation. Inference about Causation through Examination of Familial Confounding (ICE FALCON) was used to infer the possible direction of these relationships. A total of 476 top CpGs reached suggestively significant level (P < 10-4), of which, 192 CpGs were significantly associated with TG (FDR < 0.05). They were used to build interconnected network and highlight crucial genes from WGCNA. Finally, four CpGs in GATA4 were validated as risk factors for TC; six CpGs at ITFG2-AS1 were negatively associated with TG; two CpGs in PLXND1 played protective roles in HDL-C. ICE FALCON indicated abnormal TC was regarded as the consequence of DNA methylation in CpGs at GATA4, rather than vice versa. Four CpGs in ITFG2-AS1 were both causes and consequences of modified TG levels. Our results indicated that DNA methylation levels of 12 CpGs in GATA4, ITFG2-AS1, and PLXND1 were relevant to TC, TG, and HDL-C, respectively, which might provide new epigenetic insights into potential clinical treatment of dyslipidemia.


Assuntos
Epigênese Genética , Gêmeos Monozigóticos , Humanos , Epigênese Genética/genética , Gêmeos Monozigóticos/genética , Metilação de DNA/genética , Lipídeos/genética , Triglicerídeos/genética , LDL-Colesterol/genética , China
2.
Int J Obes (Lond) ; 2024 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-38773251

RESUMO

OBJECTIVES: Central obesity poses significant health risks because it increases susceptibility to multiple chronic diseases. Epigenetic features such as DNA methylation may be associated with specific obesity traits, which could help us understand how genetic and environmental factors interact to influence the development of obesity. This study aims to identify DNA methylation sites associated with the waist circumference (WC) in Northern Han Chinese population, and to elucidate potential causal relationships. METHODS: A total of 59 pairs of WC discordant monozygotic twins (ΔWC >0) were selected from the Qingdao Twin Registry in China. Generalized estimated equation model was employed to estimate the methylation levels of CpG sites on WC. Causal relationships between methylation and WC were assessed through the examination of family confounding factors using FAmiliaL CONfounding (ICE FALCON). Additionally, the findings of the epigenome-wide analysis were corroborated in the validation stage. RESULTS: We identified 26 CpG sites with differential methylation reached false discovery rate (FDR) < 0.05 and 22 differentially methylated regions (slk-corrected p < 0.05) strongly linked to WC. These findings provided annotations for 26 genes, with notable emphasis on MMP17, ITGA11, COL23A1, TFPI, A2ML1-AS1, MRGPRE, C2orf82, and NINJ2. ICE FALCON analysis indicated the DNA methylation of ITGA11 and TFPI had a causal effect on WC and vice versa (p < 0.05). Subsequent validation analysis successfully replicated 10 (p < 0.05) out of the 26 identified sites. CONCLUSIONS: Our research has ascertained an association between specific epigenetic variations and WC in the Northern Han Chinese population. These DNA methylation features can offer fresh insights into the epigenetic regulation of obesity and WC as well as hints to plausible biological mechanisms.

3.
J Hum Genet ; 2024 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-38649436

RESUMO

Handgrip strength is a crucial indicator to monitor the change of cognitive function over time, but its mechanism still needs to be further explored. We sampled 59 monozygotic twin pairs to explore the potential mediating effect of DNA methylation (DNAm) on the association between handgrip strength and cognitive function. The initial step was the implementation of an epigenome-wide association analysis (EWAS) in the study participants, with the aim of identifying DNAm variations that are associated with handgrip strength. Following that, we conducted an assessment of the mediated effect of DNAm by the use of mediation analysis. In order to do an ontology enrichment study for CpGs, the GREAT program was used. There was a significant positive association between handgrip strength and cognitive function (ß = 0.194, P < 0.001). The association between handgrip strength and DNAm of 124 CpGs was found to be statistically significant at a significance level of P < 1 × 10-4. Fifteen differentially methylated regions (DMRs) related to handgrip strength were found in genes such as SNTG2, KLB, CDH11, and PANX2. Of the 124 CpGs, 4 within KRBA1, and TRAK1 mediated the association between handgrip strength and cognitive function: each 1 kg increase in handgrip strength was associated with a potential decrease of 0.050 points in cognitive function scores, mediated by modifications in DNAm. The parallel mediating effect of these 4 CpGs was -0.081. The presence of DNAm variation associated with handgrip strength may play a mediated role in the association between handgrip strength and cognitive function.

4.
Sensors (Basel) ; 24(5)2024 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-38474965

RESUMO

Deep learning promotes the breakthrough of emotion recognition in many fields, especially speech emotion recognition (SER). As an important part of speech emotion recognition, the most relevant acoustic feature extraction has always attracted the attention of existing researchers. Aiming at the problem that the emotional information contained in the current speech signals is distributed dispersedly and cannot comprehensively integrate local and global information, this paper presents a network model based on a gated recurrent unit (GRU) and multi-head attention. We evaluate our proposed emotion model on the IEMOCAP and Emo-DB corpora. The experimental results show that the network model based on Bi-GRU and multi-head attention is significantly better than the traditional network model at detecting multiple evaluation indicators. At the same time, we also apply the model to a speech sentiment analysis task. On the CH-SIMS and MOSI datasets, the model shows excellent generalization performance.


Assuntos
Percepção , Fala , Acústica , Emoções , Reconhecimento Psicológico
5.
Twin Res Hum Genet ; 26(3): 219-222, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-37170793

RESUMO

Almost all creatinine is excreted by the kidney in individuals. Serum creatinine concentration, a widely used renal function index in clinical practice, can be affected by both genetic and environmental factors, as evidenced by current research exploring the relationship between these factors and kidney function. However, few studies have explored the heritability of serum creatinine in Asian populations. Therefore, we explored the genetic and environmental factors that affect the serum creatinine level in Asian populations. Participants in this study came from the Qingdao Twin Registry in China, and 374 pairs of twins were included, of which 139 pairs were dizygotic twins, whose ages ranged from 40 to 80 years old, and the serum creatinine level ranged from 10 to 126 µmol/L. Structural equation models were constructed using Mx software to calculate heritability, with adjusted covariates being age, sex, and body mass index. The results of heritability analysis showed that ACE was the best fit model. Serum creatinine level is influenced by genetic and environmental factors. The result of heritability was 35.44%, and the influence of shared environmental factors accounted for 52.13%. This study provided the relevant basis for future research on genetic and environmental factors affecting serum creatinine levels in Asian populations.


Assuntos
População do Leste Asiático , Gêmeos Dizigóticos , Humanos , Adulto , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Creatinina , Gêmeos Dizigóticos/genética , Povo Asiático/genética , Sistema de Registros , Gêmeos Monozigóticos/genética
6.
Twin Res Hum Genet ; 26(1): 26-30, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36852647

RESUMO

An abnormal alanine aminotransferase (ALT) level is predictive of disease and all-cause mortality and may indicate liver injury. Using twin modeling, the genetic and environmental factors that affect human serum ALT levels have been well studied for the populations in the different countries, and the results showed moderate-to-high heritability. However, the heritability of ALT level has not been explored in Chinese population. Thus, we recruited 369 pairs of twins (233 monozygotic and 136 dizygotic) from the Qingdao Twin Registry in China with a median age of 50 years (40-80 years). Correlation analysis and a structural equation model (SEM) were conducted to evaluate the heritability of ALT level. The data for age, gender, body mass index and alcohol consumption were set as covariates. Intrapair correlation in monozygotic twins was 0.64 (95%CI [.56, .71]) and 0.42 (95% CI [.28, .55]) in dizygotic twins. The SEM analysis indicated that 65% (95% CI [57%, 71%]) of the variation in ALT levels can be explained by additive genetics and 35% (95% CI [29%, 44%]) of the variation is attributed to unique environmental factors or residuals. Shared environmental influences were not significant. In conclusion, serum ALT variations exhibited strong genetic effects. The variation could also be explained by unique environmental factors. However, shared environmental factors have a minor impact on the serum ALT level.


Assuntos
População do Leste Asiático , Gêmeos Monozigóticos , Humanos , Pessoa de Meia-Idade , Alanina Transaminase/genética , Gêmeos Monozigóticos/genética , Gêmeos Dizigóticos/genética , Consumo de Bebidas Alcoólicas
7.
Appl Opt ; 62(23): 6212-6217, 2023 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-37707090

RESUMO

In this study, we demonstrate the optical induction of ferroelectric domain inversion on the -z surface of lithium niobate crystals using a 1035 nm femtosecond fiber laser. We investigate the effects of laser power and focusing parameters on domain morphology. The results revealed that domains exhibit an irregular random distribution at low power, whereas regularly arranged domains were formed near the crystal damage threshold. Furthermore, with sufficiently high power, lens focusing enables the fabrication of uniformly sized domains exceeding 100 µm. The results suggest potential applications for controlling domain morphology and the duty cycle, and fabricating ferroelectric functional devices.

8.
Cancer Cell Int ; 22(1): 28, 2022 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-35033083

RESUMO

BACKGROUND: Liver is the most common metastatic site of colorectal cancer (CRC) and liver metastasis (LM) determines subsequent treatment as well as prognosis of patients, especially in T1 patients. T1 CRC patients with LM are recommended to adopt surgery and systematic treatments rather than endoscopic therapy alone. Nevertheless, there is still no effective model to predict the risk of LM in T1 CRC patients. Hence, we aim to construct an accurate predictive model and an easy-to-use tool clinically. METHODS: We integrated two independent CRC cohorts from Surveillance Epidemiology and End Results database (SEER, training dataset) and Xijing hospital (testing dataset). Artificial intelligence (AI) and machine learning (ML) methods were adopted to establish the predictive model. RESULTS: A total of 16,785 and 326 T1 CRC patients from SEER database and Xijing hospital were incorporated respectively into the study. Every single ML model demonstrated great predictive capability, with an area under the curve (AUC) close to 0.95 and a stacking bagging model displaying the best performance (AUC = 0.9631). Expectedly, the stacking model exhibited a favorable discriminative ability and precisely screened out all eight LM cases from 326 T1 patients in the outer validation cohort. In the subgroup analysis, the stacking model also demonstrated a splendid predictive ability for patients with tumor size ranging from one to50mm (AUC = 0.956). CONCLUSION: We successfully established an innovative and convenient AI model for predicting LM in T1 CRC patients, which was further verified in the external dataset. Ultimately, we designed a novel and easy-to-use decision tree, which only incorporated four fundamental parameters and could be successfully applied in clinical practice.

9.
Aging Ment Health ; 26(3): 493-498, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33295797

RESUMO

OBJECTIVE: Leisure activity has been shown to be beneficial to mental health and cognitive aging. The biological basis of the correlation is, however, poorly understood. This study aimed at exploring the genetic and environmental impacts on correlation between leisure activities and cognitive function in the Chinese middle- and old-aged twins. METHODS: Cognition measured using a screening test (Montreal Cognitive Assessment, MoCA) and leisure activities including intellectual and social activity were investigated on 379 complete twin pairs of middle- and old-aged twins. Univariate and bivariate twin models were fitted to estimate the genetic and environmental components in their variance and covariance. RESULTS: Moderate heritability was estimated for leisure activities and cognition (0.44-0.53) but insignificant for social activity. Common environmental factors accounted for about 0.36 of the total variance to social activity with no significant contribution to leisure activity, intellectual activity and cognition. Unique environmental factors displayed moderate contributions (0.47-0.64) to leisure activities and cognition. Bivariate analysis showed highly and positively genetic correlations between leisure activities and cognition (rG=0.80-0.96). Besides, intellectual activity and cognition presented low but significant unique environmental correlation (rE=0.12). CONCLUSIONS: Genetic factor had the moderate contribution to leisure activities and cognition. Cognitive function was highly genetically related to leisure activities. Intellectual activity and cognitive function may share some unique environmental basis.


Assuntos
Envelhecimento , Envelhecimento Cognitivo , Idoso , Envelhecimento/genética , Envelhecimento/psicologia , China , Cognição , Humanos , Atividades de Lazer , Pessoa de Meia-Idade
10.
J Sci Food Agric ; 102(10): 4373-4383, 2022 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-35066866

RESUMO

BACKGROUND: Probiotics exhibit antibiotic properties and are capable of treating certain bacterial infections, including diarrhea. Therefore, the aim of this study is to investigate the effects of dietary supplementation with multispecies probiotic (MSP) on diarrhea, average daily gain (ADG) and intestinal development of neonatal calves challenged with Escherichia coli K99. RESULTS: Thirty-six neonatal Holstein calves were randomly assigned to three treatment groups. After E. coli K99 challenge, calves in the control (C) and MSP treatment groups had significantly higher ADG and feed efficiency, and significantly lower fecal scores than those of calves in the diarrhea (D) group. The mean time of diarrhea resolution was 4.5 and 3.1 days for calves in the D and MSP treatment groups, respectively. Furthermore, the structures of the various segments (duodenum, jejunum and ileum) of the small intestine of the calves, activities of several small intestinal enzymes, and expression of several energy metabolism-related genes in the small intestine segments were significantly affected by MSP treatments. CONCLUSION: Dietary supplementation of MSP had a positive effect in treating calf diarrhea; it improved ADG and feed efficiency and promoted development of the small intestine. © 2022 The Authors. Journal of The Science of Food and Agriculture published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.


Assuntos
Escherichia coli , Probióticos , Ração Animal/análise , Animais , Bovinos , Diarreia/microbiologia , Diarreia/veterinária , Dieta/veterinária , Crescimento e Desenvolvimento , Probióticos/farmacologia , Desmame
11.
Respir Res ; 22(1): 300, 2021 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-34809630

RESUMO

BACKGROUND: Previous studies have determined the epigenetic association between DNA methylation and pulmonary function among various ethnics, whereas this association is largely unknown in Chinese adults. Thus, we aimed to explore epigenetic relationships between genome-wide DNA methylation levels and pulmonary function among middle-aged Chinese monozygotic twins. METHODS: The monozygotic twin sample was drawn from the Qingdao Twin Registry. Pulmonary function was measured by three parameters including forced expiratory volume the first second (FEV1), forced vital capacity (FVC), and FEV1/FVC ratio. Linear mixed effect model was used to regress the methylation level of CpG sites on pulmonary function. After that, we applied Genomic Regions Enrichment of Annotations Tool (GREAT) to predict the genomic regions enrichment, and used comb-p python library to detect differentially methylated regions (DMRs). Gene expression analysis was conducted to validate the results of differentially methylated analyses. RESULTS: We identified 112 CpG sites with the level of P < 1 × 10-4 which were annotated to 40 genes. We identified 12 common enriched pathways of three pulmonary function parameters. We detected 39 DMRs located at 23 genes, of which PRDM1 was related to decreased pulmonary function, and MPL, LTB4R2, and EPHB3 were related to increased pulmonary function. The gene expression analyses validated DIP2C, ASB2, SLC6A5, and GAS6 related to decreased pulmonary function. CONCLUSION: Our DNA methylation sequencing analysis on identical twins provides new references for the epigenetic regulation on pulmonary function. Several CpG sites, genes, biological pathways and DMRs are considered as possible crucial to pulmonary function.


Assuntos
Doenças Cardiovasculares/genética , Doenças em Gêmeos/genética , Volume Expiratório Forçado/fisiologia , Regulação da Expressão Gênica , Estudo de Associação Genômica Ampla/métodos , Fator 1 de Ligação ao Domínio I Regulador Positivo/genética , Gêmeos Monozigóticos/genética , Idoso , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/metabolismo , China/epidemiologia , Metilação de DNA , Doenças em Gêmeos/epidemiologia , Feminino , Humanos , Incidência , Pulmão/fisiopatologia , Masculino , Pessoa de Meia-Idade , Fator 1 de Ligação ao Domínio I Regulador Positivo/biossíntese , Regiões Promotoras Genéticas , Sistema de Registros , Capacidade Vital/fisiologia , Dedos de Zinco
12.
BMC Genomics ; 21(1): 491, 2020 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-32682390

RESUMO

BACKGROUND: Currently, diabetes has become one of the leading causes of death worldwide. Fasting plasma glucose (FPG) levels that are higher than optimal, even if below the diagnostic threshold of diabetes, can also lead to increased morbidity and mortality. Here we intend to study the magnitude of the genetic influence on FPG variation by conducting structural equation modelling analysis and to further identify specific genetic variants potentially related to FPG levels by performing a genome-wide association study (GWAS) in Chinese twins. RESULTS: The final sample included 382 twin pairs: 139 dizygotic (DZ) pairs and 243 monozygotic (MZ) pairs. The DZ twin correlation for the FPG level (rDZ = 0.20, 95% CI: 0.04-0.36) was much lower than half that of the MZ twin correlation (rMZ = 0.68, 95% CI: 0.62-0.74). For the variation in FPG level, the AE model was the better fitting model, with additive genetic parameters (A) accounting for 67.66% (95% CI: 60.50-73.62%) and unique environmental or residual parameters (E) accounting for 32.34% (95% CI: 26.38-39.55%), respectively. In the GWAS, although no genetic variants reached the genome-wide significance level (P < 5 × 10- 8), 28 SNPs exceeded the level of a suggestive association (P < 1 × 10- 5). One promising genetic region (2q33.1) around rs10931893 (P = 1.53 × 10- 7) was found. After imputing untyped SNPs, we found that rs60106404 (P = 2.38 × 10- 8) located at SPATS2L reached the genome-wide significance level, and 216 SNPs exceeded the level of a suggestive association. We found 1007 genes nominally associated with the FPG level (P < 0.05), including SPATS2L, KCNK5, ADCY5, PCSK1, PTPRA, and SLC26A11. Moreover, C1orf74 (P = 0.014) and SLC26A11 (P = 0.021) were differentially expressed between patients with impaired fasting glucose and healthy controls. Some important enriched biological pathways, such as ß-alanine metabolism, regulation of insulin secretion, glucagon signaling in metabolic regulation, IL-1 receptor pathway, signaling by platelet derived growth factor, cysteine and methionine metabolism pathway, were identified. CONCLUSIONS: The FPG level is highly heritable in the Chinese population, and genetic variants are significantly involved in regulatory domains, functional genes and biological pathways that mediate FPG levels. This study provides important clues for further elucidating the molecular mechanism of glucose homeostasis and discovering new diagnostic biomarkers and therapeutic targets for diabetes.


Assuntos
Glicemia/genética , Povo Asiático/genética , China , Jejum , Estudo de Associação Genômica Ampla , Humanos , Padrões de Herança , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único
13.
Ear Hear ; 40(2): 253-259, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-29794565

RESUMO

OBJECTIVES: The heritability of age-related hearing loss has been studied mostly in developed countries. The authors aimed to estimate the heritability of better ear hearing level (BEHL), defined as hearing level of the better ear at a given frequency, and pure-tone averages at the middle (0.5, 1.0, and 2.0 kHz) and high (4.0, 8.0, and 12.5 kHz) frequencies among middle-aged and elderly Chinese twins, and to explore their genetic correlations. DESIGN: This population-based twin study included 226 monozygotic and 132 dizygotic twin-pairs and 1 triplet (age range, 33 to 80 years; mean age, 51.55 years). Pure-tone air-conducted hearing thresholds in each ear were measured at the frequencies of 0.5, 1.0, 2.0, 4.0, 8.0, and 12.5 kHz with a diagnostic audiometer. Univariate and multivariate twin models were fitted to evaluate heritability and genetic correlations. RESULTS: Our data showed a reverse J-shaped pattern of BEHLs at six frequencies by age and sex. Univariate analysis showed that the heritability of BEHLs at the frequencies between 2.0 and 12.5 kHz ranged from 47.08 to 54.20%, but the heritability at the frequencies of 0.5 and 1.0 kHz was 1.65% and 18.68%, respectively. The heritability of pure-tone average at the middle and high frequencies was 34.77% and 43.26%, respectively. Multivariate analysis showed significant genetic correlations among BEHLs at all six frequencies, with the correlation coefficients ranging from 0.48 to 0.83 at middle frequencies, and from 0.46 to 0.75 at high frequencies. CONCLUSIONS: This population-based twin study suggests that genetic factors are associated with age-related hearing loss at middle and high frequencies among middle-aged and elderly Chinese.


Assuntos
Presbiacusia/genética , Gêmeos Dizigóticos/genética , Gêmeos Monozigóticos/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Povo Asiático/genética , Audiometria de Tons Puros , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fenótipo , Presbiacusia/fisiopatologia
14.
Biol Reprod ; 99(2): 461-472, 2018 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-29272345

RESUMO

Immunocastration via vaccination against gonadotropin-releasing hormone (GnRH) is an effective alternative to surgical castration in livestock. In this study, male mice were immunized with eight GnRH peptide derivatives. Two, which exhibited highly significant effects in mice, and one which exhibited the least significant effects were selected for active immunization of 13-month-old bulls. The effects of these GnRH vaccines on sexual development and meat quality in bulls were evaluated by examining testis length, serum hormone and GnRH antibody concentrations, observation of sexual behavior and testicular tissue sections, and evaluation of meat quality indexes. The results indicated that anti-GnRH titers increased rapidly (P < 0.05) and serum follicle stimulating hormone, luteinizing hormone, and testosterone concentrations decreased sharply after booster immunization (P < 0.05), while testis volumes were lower (P < 0.01), testicular growth was arrested and spermatogenesis inhibited in group C GnRH-treated versus control bull groups. Meat quality was not significantly different in immunocastrates relative to bulls in the control group. Our collective results provide a scientific basis to further clarify the mechanisms underlying GnRH-mediated regulation of livestock reproduction, and contribute to the development of an efficient, safe, and reversible immune castration vaccine.


Assuntos
Hormônio Liberador de Gonadotropina/administração & dosagem , Hormônio Liberador de Gonadotropina/imunologia , Espermatogênese/efeitos dos fármacos , Testículo/efeitos dos fármacos , Animais , Anticorpos , Bovinos , Hormônio Foliculoestimulante/sangue , Hormônio Luteinizante/sangue , Masculino , Carne , Camundongos , Testosterona/sangue , Vacinação
15.
Pak J Pharm Sci ; 31(5(Special)): 2191-2195, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30463811

RESUMO

At present, the drugs used in the field of postoperative analgesia are mainly opioids. The three analgesics selected in this study are opioid receptor agonists, but opioids are easy to produce adverse reactions. In this study, the visual analogue score of resting pain and dynamic pain at two time points of 4 hours and 12 hours was observed in group B and group C were higher than that in group A (P<0.05), indicating that the analgesic effect of dezocine was better. Follow up observation of adverse reactions, dezocine group patients had fewer adverse reactions (P<0.05). It can be seen that although there are certain differences in the mechanism of these three drugs, there are some relevant evidence that all three drugs can be used safely and effectively for postoperative obstetric analgesia.


Assuntos
Analgésicos/uso terapêutico , Compostos Bicíclicos Heterocíclicos com Pontes/uso terapêutico , Butorfanol/uso terapêutico , Dor Pós-Operatória/tratamento farmacológico , Tetra-Hidronaftalenos/uso terapêutico , Tramadol/uso terapêutico , Adulto , Analgésicos Opioides/uso terapêutico , Cesárea/métodos , Feminino , Humanos , Masculino , Medição da Dor/métodos , Gravidez
16.
BMC Genomics ; 18(1): 872, 2017 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-29132311

RESUMO

BACKGROUND: The therapeutic management of obesity is challenging, hence further elucidating the underlying mechanisms of obesity development and identifying new diagnostic biomarkers and therapeutic targets are urgent and necessary. Here, we performed differential gene expression analysis and weighted gene co-expression network analysis (WGCNA) to identify significant genes and specific modules related to BMI based on gene expression profile data of 7 discordant monozygotic twins. RESULTS: In the differential gene expression analysis, it appeared that 32 differentially expressed genes (DEGs) were with a trend of up-regulation in twins with higher BMI when compared to their siblings. Categories of positive regulation of nitric-oxide synthase biosynthetic process, positive regulation of NF-kappa B import into nucleus, and peroxidase activity were significantly enriched within GO database and NF-kappa B signaling pathway within KEGG database. DEGs of NAMPT, TLR9, PTGS2, HBD, and PCSK1N might be associated with obesity. In the WGCNA, among the total 20 distinct co-expression modules identified, coral1 module (68 genes) had the strongest positive correlation with BMI (r = 0.56, P = 0.04) and disease status (r = 0.56, P = 0.04). Categories of positive regulation of phospholipase activity, high-density lipoprotein particle clearance, chylomicron remnant clearance, reverse cholesterol transport, intermediate-density lipoprotein particle, chylomicron, low-density lipoprotein particle, very-low-density lipoprotein particle, voltage-gated potassium channel complex, cholesterol transporter activity, and neuropeptide hormone activity were significantly enriched within GO database for this module. And alcoholism and cell adhesion molecules pathways were significantly enriched within KEGG database. Several hub genes, such as GAL, ASB9, NPPB, TBX2, IL17C, APOE, ABCG4, and APOC2 were also identified. The module eigengene of saddlebrown module (212 genes) was also significantly correlated with BMI (r = 0.56, P = 0.04), and hub genes of KCNN1 and AQP10 were differentially expressed. CONCLUSION: We identified significant genes and specific modules potentially related to BMI based on the gene expression profile data of monozygotic twins. The findings may help further elucidate the underlying mechanisms of obesity development and provide novel insights to research potential gene biomarkers and signaling pathways for obesity treatment. Further analysis and validation of the findings reported here are important and necessary when more sample size is acquired.


Assuntos
Índice de Massa Corporal , Redes Reguladoras de Genes , Gêmeos Monozigóticos/genética , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Obesidade/genética , Obesidade/patologia , Transdução de Sinais/genética
17.
Biogerontology ; 18(5): 811-819, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28808816

RESUMO

Multiple loci or genes have been identified using genome-wide association studies mainly in western countries but with inconsistent results. No similar studies have been conducted in the world's largest and rapidly aging Chinese population. The paper aimed to identify the specific genetic variants associated with cognitive function in middle and old-aged Chinese dizygotic twins (DZ). Cognitive function was measured on 139 pairs of DZ by Montreal Cognitive Assessment. The subjects were genotyped at 1048575 SNP positions. Regression-based mixed-effect kinship model of GWAS was conducted to test the SNPs. Gene-based analysis was performed on VEGAS2. The statistically significant genes were then subject to gene set enrichment analysis to further identify the specific biological pathways associated with cognitive function. No SNPs reached genome-wide significance although there were 13 SNPs of suggestive significance (P < 10-5). Gene-based analysis found 823 significant genes topped by TNRC18P1 (P = 1.00 × 10-6), FGFR1OP2 (P = 6.00 × 10-6), and AKR1D1 (P = 2.30 × 10-5). Enrichment analysis identified 46 biological pathways, mainly involving in signaling transmission, metabolic process and Alzheimer's disease. Analysis of SNPs involved in the regulatory motif detected cell-type specific enhancers involving aorta and colon smooth muscle both have been reported to implicate in cognition. We conclude that genetic variations are significantly involved in functional genes, biological pathways and the regulatory domain that mediate cognitive performances.


Assuntos
Cognição , Estudo de Associação Genômica Ampla , Adulto , China , Humanos , Polimorfismo de Nucleotídeo Único
18.
Twin Res Hum Genet ; 20(1): 60-65, 2017 02.
Artigo em Inglês | MEDLINE | ID: mdl-28105965

RESUMO

Although the correlation between cognition and physical function has been well studied in the general population, the genetic and environmental nature of the correlation has been rarely investigated. We conducted a classical twin analysis on cognitive and physical function, including forced expiratory volume in one second (FEV1), forced vital capacity (FVC), handgrip strength, five-times-sit-to-stand test (FTSST), near visual acuity, and number of teeth lost in 379 complete twin pairs. Bivariate twin models were fitted to estimate the genetic and environmental correlation between physical and cognitive function. Bivariate analysis showed mildly positively genetic correlations between cognition and FEV1, r G = 0.23 [95% CI: 0.03, 0.62], as well as FVC, r G = 0.35 [95% CI: 0.06, 1.00]. We found that FTSST and cognition presented very high common environmental correlation, r C = -1.00 [95% CI: -1.00, -0.57], and low but significant unique environmental correlation, r E = -0.11 [95% CI: -0.22, -0.01], all in the negative direction. Meanwhile, near visual acuity and cognition also showed unique environmental correlation, r E = 0.16 [95% CI: 0.03, 0.27]. We found no significantly genetic correlation for cognition with handgrip strength, FTSST, near visual acuity, and number of teeth lost. Cognitive function was genetically related to pulmonary function. The FTSST and cognition shared almost the same common environmental factors but only part of the unique environmental factors, both with negative correlation. In contrast, near visual acuity and cognition may positively share part of the unique environmental factors.


Assuntos
Envelhecimento/genética , Cognição/fisiologia , Gêmeos Dizigóticos/genética , Gêmeos Monozigóticos/genética , Adulto , Idoso , Envelhecimento/fisiologia , Povo Asiático/genética , China , Feminino , Volume Expiratório Forçado/genética , Interação Gene-Ambiente , Força da Mão/fisiologia , Humanos , Pulmão/fisiologia , Masculino , Pessoa de Meia-Idade , Força Muscular/genética , Força Muscular/fisiologia , Acuidade Visual/genética , Acuidade Visual/fisiologia , Capacidade Vital/genética
19.
Twin Res Hum Genet ; 20(5): 374-379, 2017 10.
Artigo em Inglês | MEDLINE | ID: mdl-28803591

RESUMO

The genetic and environmental impacts on correlations between hearing and cognitive functions have not been well studied. Cognitive function was evaluated by the Montreal Cognitive Assessment (MoCA). Hearing function was assessed by audiometric pure-tone hearing thresholds at different frequencies, including 0.5 kHz, 1 kHz, 2 kHz, 4 kHz, 8 kHz, and 12.5 kHz, with the lower hearing thresholds indicating better hearing function. Cognitive and hearing functions were measured on 379 complete twin pairs (240 monozygotic and 139 dizygotic pairs) with a median age of 50 years (range: 40-80 years). Bivariate twin models were fitted to quantify the genetic and environmental components of the correlations between hearing and cognitive functions. The analysis showed significantly high genetic correlation between 2 kHz of hearing and cognition (r G = -1.00, 95% CI [-1.00, -0.46]) and moderate genetic correlation between 4 kHz of hearing and cognition (r G = -0.62, 95% CI [-1.00, -0.14]). We found no significant genetic correlations between low as well as high frequencies of hearing and cognition. Low to moderate common and unique environmental correlations were shown between low frequencies of hearing and cognition (-0.13 to -0.39) and the common environmental correlation between 8 kHz, one of the high frequencies of hearing, and cognition (-0.22). The middle frequencies of hearing and cognitive functions may have a shared genetic basis. Low frequencies of hearing and cognition may share similar common and unique environmental factors. At 8 kHz, the high frequency of hearing and cognition may share similar common environment. This twin study detected a significant genetic and environmental basis in the phenotype correlation between cognition and hearing, which differed across frequencies.


Assuntos
Cognição/fisiologia , Interação Gene-Ambiente , Percepção da Altura Sonora/fisiologia , Gêmeos Dizigóticos , Gêmeos Monozigóticos , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
20.
Twin Res Hum Genet ; 20(1): 53-59, 2017 02.
Artigo em Inglês | MEDLINE | ID: mdl-28105962

RESUMO

Genetic and environmental influences on predictors of decline in daily functioning, including forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC), handgrip, and five-times-sit-to-stand test (FTSST), have not been addressed in the aging Chinese population. We performed classical twin modeling on FEV1, FVC, handgrip, and FTSST in 379 twin pairs (240 MZ and 139 DZ) with median age of 50 years (40-80 years). Data were analyzed by fitting univariate and bivariate twin models to estimate the genetic and environmental influences on these measures of physical function. Heritability was moderate for FEV1, handgrip, and FTSST (55-60%) but insignificant for FVC. Only FVC showed moderate control, with shared environmental factors accounting for about 50% of the total variance. In contrast, all measures of pulmonary function and muscle strength showed modest influences from the unique environment (40-50%). Bivariate analysis showed highly positive genetic correlations between FEV1 and FVC (r G = 1.00), and moderately negative genetic correlations between FTSST and FEV1 (r G = -0.33) and FVC (r G = -0.42). FEV1 and FVC, as well as FEV1 and handgrip, displayed high common environmental correlations (r C = 1.00), and there were moderate correlations between FVC and handgrip (r C = 0.44). FEV1 and FVC showed high unique environmental correlations (r E = 0.76) and low correlations between handgrip and FEV1 (r E = 0.17), FVC (r E = 0.14), and FTSST (r E = -0.13) with positive or negative direction. We conclude that genetic factors contribute significantly to the individual differences in common indicators of daily functioning (FEV1, handgrip, and FTSST). FEV1 and FVC were genetically and environmentally correlated. Pulmonary function and FTSST may share similar sets of genes but in the negative direction. Pulmonary function and muscle strength may have a shared environmental background.


Assuntos
Envelhecimento/genética , Interação Gene-Ambiente , Gêmeos Dizigóticos/genética , Gêmeos Monozigóticos/genética , Adulto , Idoso , Envelhecimento/fisiologia , Povo Asiático/genética , China , Feminino , Volume Expiratório Forçado/genética , Força da Mão/fisiologia , Humanos , Masculino , Pessoa de Meia-Idade , Força Muscular/genética , Força Muscular/fisiologia , Capacidade Vital/genética
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