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Objective: To anlysis the efficacy and safety of cut-umbilical cord milking (C-UCM) compared with immediate cord clamping in preventing anemia and iron deficiency among term cesarean-delivered newborns. Methods: A total of 485 pregnant women planning to deliver by cesarean section were recruited in this randomized controlled trial in Hunan Maternal and Child Health Hospital and Liuyang Maternal and Child Health Care Hospital from July 2016 to April 2019. A block randomization was conducted to evenly allocate them to the controlled group and the C-UCM group. In the controlled group, the cord was clamped within 30 seconds as routine. In the C-UCM group, the cord was first clamped at 25 cm from the newborn's navel, and then the blood in the cord was gently squeezed into the newborn's body until the cord became white and shriveled. The cord was clamped twice at 2-3 cm from the newborn's navel subsequently. Neonatal jaundice, hyperbilirubinemia and polycythemia were monitored before discharge. After the newborns discharged, their hemoglobin, red blood cell count, hematocrit (at the age of 1, 6 and 12 months) and serum ferritin (at the age of 6 and 12 months) were followed up; body length and weight were measured; and information about their feeding and iron supplementation were collected (at the age of 1, 6, 12 and 18 months). The two groups were compared by t test, Mann-Whitney U test, χ² test, or Fisher exact probability method. The hospital was set as a random item, and the mixed effects regression model was used to evaluate the effect of C-UCM on relevant indicators of cesarean-delivered newborns. Results: There were 244 women in the C-UCM group with an average age of (31.9±4.4) years, and 241 in the control group with an average age of (31.8±4.2) years (P>0.05). There was no statistically significant difference between the C-UCM group and the control group at 1, 6 and 12 months of age in hemoglobin [(123.6±14.5) vs (122.2±14.5) g/L, (115.3±9.4) vs (114.1±8.5) g/L, (115.6±9.6) vs (116.1±12.6) g/L] or anemia incidence rate [15.2% (17/112) vs 18.4% (19/103), 22.7% (34/150) vs 26.8% (44/164), 22.3% (25/112) vs 19.5% (22/113)] (all P>0.05). There was no statistically significant difference between the two groups at 6 and 12 months of age in serum ferritin [M (Q1, Q3), 39.9 (24.9, 61.8) vs 43.6 (25.2, 100.9) µg/L, 40.3 (25.4, 259.2) vs 40.3 (26.4, 167.6) µg/L)] or iron deficiency incidence rate [6.1% (5/82) vs 4.2% (3/72), 6.7% (5/75) vs 3.8% (3/80)] (all P>0.05). There were also no significant difference between the two groups in other indicators, such as the Z-score of weight-for-length, the incidence of neonatal jaundice, and the incidence of neonatal hyperbilirubinemia (all P>0.05). After adjusting for the relevant covariates, there were still no significant effects of C-UCM on these outcomes above. Conclusions: Compared to immediate cord clamping, the intervention of gently squeezing 25 cm of the cord does not significantly reduce the risk of anemia or iron deficiency in term cesarean-delivered newborns, nor does it have a significant impact on infant growth and development. Yet this intervention does not increase the risk of jaundice or hyperbilirubinemia in newborns as well.
Assuntos
Anemia Ferropriva , Cesárea , Cordão Umbilical , Humanos , Feminino , Recém-Nascido , Gravidez , Anemia Ferropriva/prevenção & controle , Adulto , Sangue FetalAssuntos
Linfonodos , Neoplasias , Humanos , Linfonodos/patologia , Excisão de Linfonodo , Neoplasias/patologia , DissecaçãoRESUMO
Objective: To investigate the prevalence of albuminuria in Chinese residents aged >35 years and its potential association with cardiovascular disease (CVD). Methods: A total of 34 647 Chinese subjects aged ≥35 years were selected by stratified multi-stage random sampling from 2012 to 2015. Data were collected through questionnaires, physical examinations, and laboratory tests. Albuminuria was categorized into 3 types according to urinary albumin-to- creatinine ratio: normal (<30 mg/g), microalbuminuria (MAU, 30-300 mg/g), and macroalbuminuria (≥300 mg/g). Measurement data were expressed as x¯±s, and t-tests were used for comparisons between indicators. Qualitative data were expressed as rate or constituent ratio, and the χ2 test or Kruskal-Wallis test was used to examine differences. Logistic regression was used for multivariate analyses. SAS 9.4 software was used for statistical analyses, and P<0.05 was considered statistically significant. Results: The prevalence of abnormal albuminuria was 19.1%; the prevalence was 17.2% for MAU and lower in males (13.8%) than females (20.1%, P<0.01). The risk of CVD was higher among subjects with MAU (OR=1.23, 95%CI 1.12-1.35) and macroalbuminuria (OR=1.86, 95%CI 1.50-2.32). When MAU was complicated by hypertension and diabetes mellitus, the CVD risk was 1.76 times higher. Conclusions: The prevalence of MAU is high among Chinese subjects aged 35 years and over. Those with MAU have higher CVD risk, especially those with hypertension and diabetes mellitus.
Assuntos
Albuminúria , Doenças Cardiovasculares , Feminino , Humanos , Masculino , Albuminúria/epidemiologia , Doenças Cardiovasculares/epidemiologia , Diabetes Mellitus/epidemiologia , População do Leste Asiático , Hipertensão/epidemiologia , Prevalência , Fatores de Risco , AdultoRESUMO
Gut microbiota (GM) dysbiosis has been increasingly associated with Alzheimer's disease (AD). However, the association between APOE4, the most common genetic risk factor for sporadic AD, and GM in AD remains unclear. In this study, we conducted a comparative analysis of the GM of participants from China and the USA, with and without APOE4 genes and with or without AD (67 AD cases, 67 control cases). Our results revealed that the GM alpha diversity was not different between groups (AD_APOE4, Control_APOE4, AD_non-APOE4, and Control_non-APOE4) (419.031 ± 143.631 vs 391.091 ± 126.081, 351.086 ± 169.174 and 386.089 ± 177.200, respectively. P > 0.05). Interestingly, individuals in the AD_APOE4 group had different bacterial compositions and bacterial biomarkers. The Kruskal-Wallis rank sum test indicated that the abundances of many bacterial species in the AD_APOE4 patients differed from those in control individuals, including decreases in unclassified_g__Escherichia-Shigella (1.763 ± 6.73, 4.429 ± 11.13, 8.245 ± 16.55, and 5.69 ± 13.91 in four groups, respectively; P < 0.05), and unclassified_g_Clostridium_sensu_stricto_1 (0.1519 ± 0.348, 2.502 ± 5.913, 0.5146 ± 0.9487, 1.063 ± 3.428 in four groups, respectively; P < 0.05), and increases in gut_metagenome_g_Faecalibacterium (2.885 ± 4.47, 2.174 ± 3.957, 0.5765 ± 1.784, 1.582 ± 2.92 in four groups, respectively. P < 0.01) and unclassified_g_Bacteroides (3.875 ± 3.738, 2.47 ± 2.748, 2.046 ± 3.674, 3.206 ± 3.446 in four groups, respectively; P < 0.05). In the KEGG pathway level 2 analysis, we identified three significant differences in relative abundances of predicted functions between AD_APOE4 and AD_non-APOE4_carrier groups: neurodegenerative diseases (0.0007 ± 0.0005 vs 0.0009 ± 0.0004; P < 0.01), metabolism (0.0240 ± 0.0003 vs 0.0250 ± 0.0003; P < 0.05), and biosynthesis of other secondary metabolites (0.0094 ± 0.0002 vs 0.0090 ± 0.0002; P < 0.05). Receiver operating characteristic curves further demonstrated an area under the curve (AUC) of 0.74 for the discrimination of AD_APOE4_carrier and AD_non-APOE4_carrier individuals.
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Doença de Alzheimer , Apolipoproteína E4 , Bactérias , Microbioma Gastrointestinal , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Doença de Alzheimer/microbiologia , Doença de Alzheimer/genética , Apolipoproteína E4/genética , Bactérias/genética , Bactérias/classificação , Bactérias/isolamento & purificação , Estudos de Casos e Controles , China , Disbiose/microbiologia , Fezes/microbiologia , Estados UnidosRESUMO
Objective: To estimate the prevalence, awareness, treatment and control rate of hypertension among young and middle-aged population in China. Methods: The analysis was based on the results of 2012-2015 China Hypertension Survey, which was a cross-sectional stratified multistage random sampling survey. A total of 229 593 subjects were included in the final analysis. The data including sex, age, living in urban and rural areas, prevalence of hypertension, history of stroke, family history of coronary heart disease and drinking, physical examination, heart rate were collected. Hypertension was defined as mean systolic blood pressure (SBP) ≥140 mmHg (1 mmHg=0.133 kPa), and (or) diastolic blood pressure (DBP) ≥90 mmHg, and (or) self-report a history of hypertension, and (or) use of antihypertensive medicine within 2 weeks before survey. Prehypertension was defined as SBP between 120-139 mmHg, and (or) DBP between 80-89 mmHg. Control of hypertension was considered for hypertensive individuals with SBP<140 mmHg and DBP<90 mmHg. The prevalence of prehypertension, hypertension, awareness, treatment, control rate were calculated, and the control rate among those with antihypertensive medication was also calculated. Results: The prevalence of prehypertension and hypertension was 43.8% (95%CI: 42.3%-45.4%), and 22.1% (95%CI: 20.8%-23.3%), respectively. The prevalence of prehypertension and hypertension was significantly higher among male than female across different age groups. The awareness, treatment, control rate of hypertension and control rate among treated hypertensive participants were 43.8%, 33.2%, 16.7%, and 40.2%, respectively. The prevalence was higher, and the control rate was lower among individuals with higher heart rate. Conclusion: The prevalence of prehypertension and hypertension among young and middle-aged population is high, the awareness, treatment and control rate need to be further improved in this population. The prevention and treatment of hypertension should be strengthened in the future to improve the control rate of hypertension in China.
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Hipertensão , Pré-Hipertensão , Pessoa de Meia-Idade , Masculino , Feminino , Humanos , Anti-Hipertensivos/uso terapêutico , Pré-Hipertensão/tratamento farmacológico , Pré-Hipertensão/epidemiologia , Prevalência , Estudos Transversais , Hipertensão/epidemiologia , Hipertensão/tratamento farmacológico , Pressão Sanguínea , China/epidemiologiaRESUMO
OBJECTIVE: This study aimed to evaluate the effect of resistance exercise on peripheral inflammatory biomarkers in healthy adults. MATERIALS AND METHODS: Four databases, including PubMed, Web of Science, Cochrane Library, and SPORTDiscus, were searched from inception until April 1st, 2022. A meta-analysis was conducted using a random-effects model, followed by sensitivity analysis, subgroup analysis, meta-regression analysis, and publication bias analysis. RESULTS: 15 randomized controlled trials were included in the meta-analysis. The pooled results showed that resistance exercise significantly decreased TNF-α levels (SMD = -0.81, 95% CI: -1.42 to -0.20, p = 0.009) but did not affect IL-6 and CRP levels. Individuals with BMI 18.5-24.9 exhibited significantly decreased IL-6 levels, while moderate strength resistance exercise could significantly decrease TNF-α levels. Finally, age might be a confounding factor influencing the effect of resistance exercise on IL-6. CONCLUSIONS: Resistance exercise could reduce TNF-α levels in healthy adults, and resistance exercise with moderate intensity could reduce TNF-α levels more effectively.
Assuntos
Treinamento Resistido , Fator de Necrose Tumoral alfa , Humanos , Interleucina-6 , Ensaios Clínicos Controlados Aleatórios como Assunto , BiomarcadoresRESUMO
Objective: To investigate the prevalence, awareness, treatment and control status of dyslipidemia among females aged ≥35 years old across China. Methods: Participants were selected by stratified multistage random sampling method in the "Twelfth Five-Year Plan" National Science and Technology Support Project "Survey on the Prevalence of Important Cardiovascular Diseases and Key Technology Research in China" project. This study is a retrospective, cross-sectional study. A total of 17 418 females aged 35 years and over were included in the current study. The basic information such as age, medical history and menopause was collected by questionnaire. The blood lipid parameters were derived from clinical laboratory examinations. The prevalence of dyslipidemia and the rate of awareness, treatment, and control of dyslipidemia were analyzed in females aged 35 years and over. Results: The age of participants was (56.2±13.0) years old, and the prevalence of dyslipidemia was 33.1% (5 765/17 418). The prevalence rates of high total cholesterol, hypertriglyceridemia, low HDL-C and high LDL-C were 9.7% (1 695/17 418), 11.1% (1 925/17 418), 10.9% (1 889/17 418) and 7.3% (1 262/17 418), respectively. The prevalence of dyslipidemia increased with age and the prevalence of dyslipidemia in women who were not married, Han, menarche age>16 years, obesity, central obesity, alcohol consumption, diabetes, hypertension and family history of cardiovascular disease were higher than those without such characteristics (P<0.05). There were 10 432 (59.9%) menopausal females in this cohort and prevalence of dyslipidemia of these participants was 38.8% (4 048/10 432), which was higher than that of non-postmenopausal females (24.6%, 1 717/6 986) (P<0.05). The awareness rates, treatment rates and control rates of dyslipidemia were 33.9% (1 953/5 765), 15.1% (870/5 765) and 2.5% (143/5 765) respectively among females aged 35 years and over in China. Conclusion: The prevalence of dyslipidemia in Chinese females aged 35 years and over is high, and its awareness, treatment, and control rates need to be optimized.
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Doenças Cardiovasculares , Dislipidemias , Adulto , Idoso , China/epidemiologia , Estudos Transversais , Dislipidemias/tratamento farmacológico , Dislipidemias/epidemiologia , Feminino , Humanos , Pessoa de Meia-Idade , Obesidade/epidemiologia , Prevalência , Estudos Retrospectivos , Fatores de RiscoRESUMO
Objective: To investigate pathogenic genes related to the phenotype of fetus with severely short limbs in the first and second trimester by whole exome sequencing (WES). Methods: Thirteen fetuses with severely short limbs detected by ultrasonography in the first and second trimester admitted in Chinese PLA General Hospital from September 2016 to June 2018 were collected. All cases were performed induced abortion, 6 of which were carried out karyotype analysis of amniotic fluid at the same time. WES and copy number variations (CNV) were performed on specimens from fetal tissues after labor induction. The suspected pathogenic mutations were validated by Sanger sequencing reactions. Results: No abnormal karyotypes or pathological CNV were found. In 10 fetuses, pathogenic or possibly pathogenic mutations were detected in the following genes: COL2A1, FGFR3, COL1A1, COL1A2, DYNC2LI1 and TRIP11, all of which were essential to skeletal development. The diagnostic yield of WES in the fetuses with severe short limbs was 10/13. Conclusions: In the first and second trimester, most of the fetuses with extremely short limbs suffer from monogenic diseases. WES is likely to be a valuable diagnostic testing option for the fetuses with severe short limbs.
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Anormalidades Congênitas/genética , Dineínas do Citoplasma , Variações do Número de Cópias de DNA , Sequenciamento do Exoma/métodos , Desenvolvimento Fetal/genética , Feto/anormalidades , Anormalidades Congênitas/diagnóstico , Variações do Número de Cópias de DNA/genética , Feminino , Feto/diagnóstico por imagem , Humanos , Cariotipagem , Gravidez , Primeiro Trimestre da Gravidez , Segundo Trimestre da Gravidez , Ultrassonografia Pré-NatalRESUMO
Objective: To analyze the efficiency and safety of navigation guided extraction of impacted supernumerary tooth. Methods: Twenty-five cases of navigation guided supernumerary tooth extraction and 25 cases of non-navigation guided supernumerary tooth extraction (control group) were included in the study. Each group had 3 cases with one impacted supernumerary tooth and 22 cases with two impacted teeth. Results: Preoperative navigation system designing time was (45.0±8.0) min in average. Navigation system installation time was (15.0±2.8) min. The average operation time was (0.64±0.08) hour in navigation group and (0.91±0.09) hour in control group. Conclusions: Navigation guided extraction of impacted supernumerary tooth takes less time for operation but more time for the preoperative navigation system design.
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Duração da Cirurgia , Extração Dentária/métodos , Dente Impactado/cirurgia , Dente Supranumerário/cirurgia , Estudos de Casos e Controles , Humanos , Maxila , Estudos RetrospectivosRESUMO
Wnt signaling regulates a broad variety of processes in both embryonic development and various diseases. Recent studies indicated that some genetic variants in Wnt signaling pathway may serve as predictors of diseases. Low-density lipoprotein receptor protein 6 (LRP6) is a Wnt co-receptor with essential functions in the Wnt/ß-catenin pathway, and mutations in LRP6 gene are linked to many complex human diseases, including metabolic syndrome, cancer, Alzheimer's disease and osteoporosis. Therefore, we focus on the role of LRP6 genetic polymorphisms and Wnt signaling in complex diseases, and the mechanisms from mouse models and cell lines. It is also highly anticipated that LRP6 variants will be applied clinically in the future. The brief review provided here could be a useful resource for future research and may contribute to a more accurate diagnosis in complex diseases.
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Proteína-6 Relacionada a Receptor de Lipoproteína de Baixa Densidade/genética , Síndrome Metabólica/genética , Mutação/genética , Polimorfismo Genético , Doença de Alzheimer/diagnóstico , Doença de Alzheimer/genética , Doença de Alzheimer/patologia , Humanos , Síndrome Metabólica/diagnóstico , Síndrome Metabólica/patologia , Neoplasias/diagnóstico , Neoplasias/genética , Neoplasias/patologia , Osteoporose/diagnóstico , Osteoporose/genética , Osteoporose/patologia , Via de Sinalização Wnt/genéticaAssuntos
Alopurinol/efeitos adversos , Toxidermias/genética , Supressores da Gota/efeitos adversos , Proteínas/genética , RNA Longo não Codificante/genética , Alelos , Povo Asiático/genética , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Polimorfismo de Nucleotídeo Único/genética , Estudos RetrospectivosRESUMO
WHAT IS KNOWN AND OBJECTIVE: Warfarin is a widely used anticoagulant with a narrow therapeutic index. Polymorphisms in the VKORC1, CYP2C9 and CYP4F2 genes have been verified to correlate with warfarin stable dosage (WSD). Whether any other genes or variants affect the dosage is unknown. The aim of our study was to investigate the relationship between GGCX, miR-133 variants and the WSD in Han Chinese patients with mechanical heart valve replacement (MHVR). METHODS: A total of 231 patients were enrolled in the study. Blood samples were collected for genotyping. The average WSD among subjects with different GGCX or miR-133 genotypes was compared. Regression analyses were performed to test for any association of genetic polymorphisms with WSD. RESULTS AND DISCUSSION: The warfarin dosage in patients with the GGCX rs699664 TT and rs12714145 TT genotypes was 3.77±0.93 (95% CI: 3.35-4.19) mg/d and 3.70±1.00 (95% CI: 3.32-4.09) mg/d, respectively. The GGCX rs699664 and rs12714145 genotypes were significantly associated with WSD (P<.05). But they were ruled out in the multivariate regression analysis. There were no significant differences in the average warfarin stable dosage between subjects with MIR133B rs142410335 wild-type and variant genotypes (P>.05). WHAT IS NEW AND CONCLUSION: The genotypes of GGCX rs699644 and rs12714145 were significantly associated with WSD (P<.05), but their contributions were not significant after accounting for other factors. MIR133B rs142410335 makes no significant contributions to warfarin stable dosage in Han Chinese patients with MHVR neither in univariate regression nor in multivariate regression analyses.
Assuntos
Carbono-Carbono Ligases/genética , Implante de Prótese de Valva Cardíaca , MicroRNAs/genética , Varfarina/administração & dosagem , Adolescente , Adulto , Idoso , Anticoagulantes/administração & dosagem , Povo Asiático/genética , China , Relação Dose-Resposta a Droga , Feminino , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Polimorfismo Genético , Análise de Regressão , Adulto JovemRESUMO
Objective: To analyze the clinical features and to explore the etiology of short fetal femur during the third trimester. Methods: From January 2010 to June 2016, 21 singleton pregnancies with short fetal femur detected by ultrasonography during the third trimester were referred to the Chinese PLA General Hospital. Clinical data were collected, karyotype or single nucleotide polymorphism microarray was carried out to detect chromosomal abnormalities, and FGFR3 c.1138G>A mutation detection was carried out to detect achondroplasia (ACH) via invasive procedure, respectively. The deviation of femur length from the mean value of the gestational age in ultrasonography was expressed as the Z-score. The difference between ACH and isolated short femur (ISF, in the absence of associated structure abnormality or genetic abnormality) was then explored. Results: In the 21 fetuses, 11 had abnormal genetic test results(52%, 11/21), including 9 cases of ACH, 1 case of Ellis-van Creveld Syndrome and 1 case of Pallister-Killian syndrome. In the 10 ISF fetuses (48%, 10/21), 3 cases were fetal growth restriction, 1 was normal small for gestational age infant and 6 cases were unexplained. The median Z-scores for 9 cases of ACH and 10 cases of ISF in the third trimester were -5.04, -3.20, respectively. The short femur in ACH was more severe than in ISF (P=0.005) in the third trimester. Conclusions: The etiology of short fetal femur is complicated, including skeletal dysplasia, chromosomal abnormality, fetal growth restriction, as well as normal variants during fetal development. Genetic test should be considered during the antenatal consultation.
Assuntos
Doenças do Desenvolvimento Ósseo/diagnóstico por imagem , Fêmur/anormalidades , Fêmur/diagnóstico por imagem , Retardo do Crescimento Fetal/diagnóstico por imagem , Ultrassonografia Pré-Natal , Acondroplasia , Doenças do Desenvolvimento Ósseo/genética , Aberrações Cromossômicas , Transtornos Cromossômicos , Cromossomos Humanos Par 12 , Feminino , Fêmur/embriologia , Desenvolvimento Fetal , Retardo do Crescimento Fetal/etiologia , Feto , Idade Gestacional , Humanos , Cariotipagem , Análise em Microsséries , Polimorfismo de Nucleotídeo Único , Gravidez , Segundo Trimestre da Gravidez , Terceiro Trimestre da Gravidez , Receptor Tipo 3 de Fator de Crescimento de Fibroblastos/metabolismoRESUMO
Nano nickel oxide (NiO), widely used in industry, has recently been discovered to have pulmonary toxicity. However, no subchronic exposure studies about nano NiO-induced pulmonary fibrosis have been reported. The objective of this study was to investigate pulmonary fibrosis induced by nano NiO and its potential mechanism in rats. Male Wistar rats ( n = 40, 200-240 g) were randomized into control group, nano NiO groups (0.015, 0.06, and 0.24 mg/kg), and micro NiO group (0.024 mg/kg). All rats were killed to collect lung tissue after intratracheal instillation of NiO particles twice a week for 6 weeks. To identify pulmonary fibrosis, Masson trichrome staining, hydroxyproline content, and collagen protein expression were performed. The results showed widespread lung fibrotic injury in histological examination and increased content of hydroxyproline, collagen types I and III in rat lung tissue exposed to nano NiO. To explore the potential pulmonary fibrosis mechanism, transforming growth factor beta 1 (TGF- ß1) content was measured by enzyme-linked immunosorbent assay, and the messenger RNA expression of key indicators was detected by reverse transcription-quantitative polymerase chain reaction (RT-qPCR). The TGF- ß1 content was increased in nano NiO exposure groups, as well as the upregulated gene expression of TGF- ß1, Smad2, Smad4, matrix metalloproteinase, and tissue inhibitor of metalloproteinase. The findings indicated that nano NiO could induce pulmonary fibrosis, which may be related to TGF- ß1 activation.
Assuntos
Regulação da Expressão Gênica/efeitos dos fármacos , Nanopartículas Metálicas/toxicidade , Níquel/toxicidade , Fibrose Pulmonar/induzido quimicamente , Fator de Crescimento Transformador beta1/metabolismo , Animais , Masculino , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Ratos , Ratos Wistar , Fator de Crescimento Transformador beta1/genéticaRESUMO
The adverse reactions of warfarin that were found mainly occurred in the first month. This study was carried out to observe the effect of gene polymorphisms on the warfarin therapy at the initial stage. Four-hundred and sixty Chinese patients began warfarin treatment with daily 2.5 mg after heart valve replacement operations were enrolled. The daily international normalized ratio (INR) for anticoagulation were recorded till the seventh day. Blood samples were collected and used to detect genotypes for VKORC1 rs7294, CYP2C9 rs1057910, CYP4F2 rs2108622 and ORM1 rs17650. INR and their changes were compared among genotypes. INR was partially correlated with the VKORC1 rs7294, CYP2C9 rs1057910, CYP4F2 rs2108622 and ORM1 rs17650 polymorphisms from the third, fourth and sixth day on, respectively. VKORC1 rs7294 and CYP4F2 rs2108622 carriers responded lower than the wild genotype, whereas CYP2C9 rs1057910 and ORM1 rs17650 carriers responded higher, respectively. Fifty percent of AA/*1*3/CC/*S*S patients and 16% of AA/*1*1/CC/*S*S patients were over anticoagulation treated with INR >4.0 at the third day. Ninety percent of VKORC1 rs7294 carrier patients have INR <1.63, a mark of the 25% of lower responders of the wild genotype. Our study provided another kind of evidence that VKORC1 rs7294, CYP2C9 rs1057910, CYP4F2 rs2108622 and ORM1 rs17650 affected the action of warfarin in different styles. Patients with AA/*1*1/CC/*S*S, AA/*1*3/CC/*S*S should use a less initial dosage to avoid over anticoagulation, and patients with VKORC1 rs7294 should use larger initial dose to proof an effective therapy.
Assuntos
Anticoagulantes/efeitos adversos , Implante de Prótese de Valva Cardíaca/efeitos adversos , Variantes Farmacogenômicos , Trombose/prevenção & controle , Varfarina/efeitos adversos , Administração Oral , Adolescente , Adulto , Idoso , Anticoagulantes/administração & dosagem , Coagulação Sanguínea/efeitos dos fármacos , Coagulação Sanguínea/genética , China , Citocromo P-450 CYP2C9/genética , Família 4 do Citocromo P450/genética , Cálculos da Dosagem de Medicamento , Monitoramento de Medicamentos/métodos , Feminino , Frequência do Gene , Genótipo , Humanos , Coeficiente Internacional Normatizado , Pessoa de Meia-Idade , Orosomucoide/genética , Farmacogenética , Testes Farmacogenômicos , Fenótipo , Trombose/sangue , Trombose/etiologia , Trombose/genética , Fatores de Tempo , Resultado do Tratamento , Vitamina K Epóxido Redutases/genética , Varfarina/administração & dosagem , Adulto JovemRESUMO
AIM: Several factors have been implicated in the pathogenesis of colorectal cancer (CRC) associated with ulcerative colitis (UC). We investigated markers of cancer cell pluripotency, including CD44 and CD166, microRNA-21 (miR-21) and microRNA-215 (miR-215), and APC, K-ras and DCC mutations in biopsy specimens from patients with UC to evaluate any correlations with clinical risk factors. METHOD: We observed 18 patients with UC and collected two biopsy specimens from each patient at diagnosis and at a follow-up end-point. We examined the expression of CD44, CD166, miR-21 and miR-215, and APC, K-ras and DCC mutations. We compared these markers at the two time points and assessed their associations with clinical characteristics, including the duration of colitis, histological alterations and the age of the patient at the onset of UC. RESULTS: Most (16/18) patients had alleviation of mucosal inflammation or remained stable during follow-up; one patient developed dysplasia and one had severe aggravation of the lesion during follow-up. Enhanced expression of CD44, CD166 and miR-21 with miR-215 was found in the specimens obtained at follow-up, despite alleviation of mucosal lesions. Coherence of cancer stem cell markers and miRNAs was seen in patients who had significant worsening of inflammation, dysplasia and a long duration of colitis. APC mutation occurred in only one patient; this patient had the longest duration of UC (23 years). CONCLUSION: Enhanced markers of CRC in follow-up colonic mucosal samples support the conclusion that the duration of UC plays the most important role in UC-related carcinogenesis.
Assuntos
Biomarcadores Tumorais/genética , Colite Ulcerativa/genética , Neoplasias Colorretais/genética , MicroRNAs/genética , Células-Tronco Neoplásicas/fisiologia , Lesões Pré-Cancerosas/genética , Adulto , Biópsia , Colite Ulcerativa/complicações , Colite Ulcerativa/patologia , Colite Ulcerativa/fisiopatologia , Neoplasias Colorretais/fisiopatologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mutação , Células-Tronco Neoplásicas/patologia , Células-Tronco Pluripotentes/fisiologia , Fatores de Risco , Fatores de Tempo , Adulto JovemRESUMO
WHAT IS KNOWN AND OBJECTIVE: Identification of biomarkers that could predict high-dose cytarabine (Ara-C) efficacy and toxicity is a key issue in individualized therapy. The aim of our study was to evaluate the influence of cytidine deaminase (CDA) single nucleotide polymorphisms (SNPs) -451G>A (rs532545), 435C>T (rs1048977) and -33delC (rs3215400) on treatment outcome in patients with relapsed acute myeloid leukaemia (AML) after high-dose Ara-C chemotherapy. METHODS: In total, 173 patients with relapsed AML, treated with high-dose Ara-C chemotherapy, were genotyped for three polymorphisms in CDA gene using the allele-specific matrix-assisted laser desorption/ionization time-of-flight mass spectrometry assays. Binary logistic regression was used to evaluate the influence of selected polymorphisms on tumour response and occurrence of treatment-related toxicity. RESULTS AND DISCUSSION: The CC genotype at -33delC, a promoter polymorphism, increased the odds of overall response rate (odds ratio [OR] = 5·125; 95% confidence intervals (CI) = 2·446-10·74; P = 0·0008) and grade ≥3 infection toxicity incidence rate (OR = 3·572; 95% CI = 1·68-7·594; P = 0·003). In multivariable analysis, this polymorphism was a potential independent prognostic marker for the risk of overall response (P = 0·011), but not grade ≥3 infection toxicity incidence rate (P = 0·49). Two other polymorphisms, -451G>A and 435C>T, did not influence treatment outcome, including overall response rate, infection toxicity and nausea/vomiting, in patients with relapsed AML (P > 0·05). WHAT IS NEW AND CONCLUSION: The findings suggest that CDA -33delC variant might be a potential marker for predicting treatment outcome in Chinese patients with relapsed AML given high-dose cytarabine chemotherapy.
Assuntos
Alopurinol/efeitos adversos , Síndrome de Hipersensibilidade a Medicamentos/genética , Supressores da Gota/efeitos adversos , Antígenos HLA-B/genética , Síndrome de Stevens-Johnson/genética , Povo Asiático/genética , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos RetrospectivosRESUMO
The objective of this study was to assess the associations of presenilin 1 (PS1) 1/2, angiotensin I-converting enzyme (ACE) insertion/deletion (I/D), and low-density lipoprotein receptor-related protein (LRP) C/T polymorphisms with the risk of Alzheimer's disease (AD) in the Chinese population. PS1 1/2, ACE I/D, and LRP C/T, which are commonly investigated polymorphisms, were evaluated to obtain summary estimates regarding their associations with AD. In total, the data from 24 studies (2611 patients with AD and 2822 control subjects from 23 provinces and special districts in China) that were obtained from the Chinese Biomedicine Database, China National Knowledge Infrastructure, PubMed, and Medline were included. Different models (i.e., dominant, recessive, etc.) of these polymorphisms were analyzed using the Cochrane Review Manager. Statistically significant associations among patients with AD for the 1/1 genotype of the PS1 1/2 polymorphism [odds ratio (OR) = 1.77, 95% confidence interval (CI) = 1.03-3.04; P = 0.04] and the I/I genotype of the ACE I/D polymorphism (OR = 2.44, 95%CI = 1.78-3.35; P < 0.01) were identified. Statistically significant associations were also found for the PS1 1/2 polymorphism in both the dominant and recessive genetic models, whereas no association was found for the LRP C/T polymorphism. All studies exhibited heterogeneity (P < 0.05). This meta-analysis suggests that the 1/1 genotype of the PS1 1/2 polymorphism and the I/I genotype of the ACE I/D polymorphism are significantly associated with an increased risk of AD in the Chinese population.
Assuntos
Doença de Alzheimer/genética , Predisposição Genética para Doença , Proteína-1 Relacionada a Receptor de Lipoproteína de Baixa Densidade/genética , Peptidil Dipeptidase A/genética , Presenilina-1/genética , Idoso , Idoso de 80 Anos ou mais , Alelos , Doença de Alzheimer/patologia , Povo Asiático , China , Feminino , Estudos de Associação Genética , Humanos , Mutação INDEL/genética , Polimorfismo de Nucleotídeo Único/genéticaRESUMO
WHAT IS KNOWN AND OBJECTIVE: Variation in the expression of drug-response-related genes contributes significantly to interindividual differences in drug response. DNA methylation is one of the most common epigenetic modifications that control gene expression. DNA methylation may occur in genes encoding drug metabolizing enzymes (DMEs), drug transporters and drug targets, and can thereby alter the pharmacokinetics and pharmacodynamics of drugs. In this review, we discuss recent advances in pharmacoepigenetics with a focus on DNA methylation. METHODS: The literature search focusing on DNA methylation of drug-response-related genes and DNA methylation-related SNPs in pharmacogenomics was carried out using the PUBMED database and a combination of keywords including DNA methylation, drug response, DMEs, drug transporters, drug target and SNPs. RESULTS AND DISCUSSION: An extensive range of research has contributed to our understanding of how DNA methylation of drug-response-related genes alters their function. This is particularly well studied in cancer chemotherapy and drug resistance. The impact of polymorphisms of miRNAs in these processes requires further study. WHAT IS NEW AND CONCLUSION: DNA methylation-related genetic variation is an increasingly recognized mechanism for altered drug-response and disease susceptibility. These new discoveries require assimilation into the practice of personalized medicine.