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BACKGROUND: Breast cancer (BC) patients tend to suffer from distant metastasis, especially bone metastasis. METHODS: All the analysis based on open-accessed data was performed in R software, dependent on multiple algorithms and packages. The RNA levels of specific genes were detected using quantitative Real-time PCR as a method of detecting the RNA levels. To assess the ability of BC cells to proliferate, we utilized the CCK8 test, colony formation, and the 5-Ethynyl-20-deoxyuridine assay. BC cells were evaluated for invasion and migration by using Transwell assays and wound healing assays. RESULTS: In our study, we identified the molecules involved in BC bone metastasis based on the data from multiple BC cohorts. Then, we comprehensively investigated the effect pattern and underlying biological role of these molecules. We found that in the identified molecules, the EMP1, ACKR3, ITGA10, MMP13, COL11A1, and THY1 were significantly correlated with patient prognosis and mainly expressed in CAFs. Therefore, we explored the CAFs in the BC microenvironment. Results showed that CAFs could activate multiple carcinogenic pathways and most of these pathways play an important role in cancer metastasis. Meanwhile, we noticed the interaction between CAFs and malignant, endothelial, and M2 macrophage cells. Moreover, we found that CAFs could induce the remodeling of the BC microenvironment and promote the malignant behavior of BC cells. Then, we identified MMP13 for further analysis. It was found that MMP13 can enhance the malignant phenotype of BC cells. Meanwhile, biological enrichment and immune infiltration analysis were conducted to present the effect pattern of MMP13 in BC. CONCLUSIONS: Our result can improve the understanding of researchers on the underlying mechanisms of BC bone metastasis.
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Neoplasias da Mama , MicroRNAs , Humanos , Feminino , Neoplasias da Mama/patologia , MicroRNAs/genética , Metaloproteinase 13 da Matriz , Movimento Celular/genética , Mama/patologia , Microambiente TumoralRESUMO
The aims of this study are to estimate the contributions of genetic factors to the variation of tea drinking and cigarette smoking, to examine the roles of genetic factors in their correlation and further to investigate underlying causation between them. We included 11 625 male twin pairs from the Chinese National Twin Registry (CNTR). Bivariate genetic modelling was fitted to explore the genetic influences on tea drinking, cigarette smoking and their correlation. Inference about Causation through Examination of FAmiliaL CONfounding (ICE FALCON) was further used to explore the causal relationship between them. We found that genetic factors explained 17% and 23% of the variation in tea drinking and cigarette smoking, respectively. A low phenotypic association between them was reported (rph = 0.21, 95% confidence interval [CI]: [0.19, 0.24]), which was partly attributed to common genetic factors (rA = 0.45, 95% CI [0.19, 1.00]). In the ICE FALCON analysis with current smoking as the exposure, tea drinking was associated with his own (ßself = 0.39, 95% CI [0.23, 0.55]) and his co-twin's smoking status (ßco-twin = 0.25, 95% CI [0.10, 0.41]). Their association attenuated with borderline significance conditioning on his own smoking status (p = 0.045), indicating a suggestive causal effect of smoking status on tea drinking. On the contrary, when we used tea drinking as the predictor, we found familial confounding between them only. In conclusion, both tea drinking and cigarette smoking were influenced by genetic factors, and their correlation was partly explained by common genetic factors. In addition, our finding suggests that familial confounders account for the relationship between tea drinking and cigarette smoking. And current smoking might have a causal effect on weekly tea drinking, but not vice versa.
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Fumar Cigarros , Fumar , Adulto , Consumo de Bebidas Alcoólicas/genética , China , Fumar Cigarros/epidemiologia , Fumar Cigarros/genética , Humanos , Masculino , Fatores de Risco , Fumar/genética , Chá , Gêmeos/genéticaRESUMO
OBJECTIVES: Studies of the prevalence and risk factors for behavioral and psychological symptoms of dementia (BPSD) have primarily been conducted in nursing home and clinic populations. Few population-based studies have been conducted in community-living persons with dementia. METHODS: In this cross-sectional study, persons aged 65 and above who were living in the community were screened for dementia with the Chinese version of Mini-Mental State Examination (CMMSE) and Ability of Daily Living (ADL-14) scale. Participants with a diagnosis of dementia according to DSM-IV criteria made by trained neuropsychiatrists s were with the Neuropsychiatric Inventory assessed for BPSD by informant interview. RESULTS: Among 1271 persons with dementia, 50.1% had at least one BPSD. Sleep disturbance was the most common symptom (21.9%), followed by irritability (19.6%), and apathy (15.7%). About 40% (N = 501) of these problems were clinically significant (NPI score > 4). The NPI score was significantly associated with the CMMSE score, ADL score and education. CONCLUSION: BPSD are common among community living Chinese people with dementia, but the relatively lower prevalence rate and different pattern of symptoms from those reported in the USA, UK and Japan suggest the possible influence of cultural background and psychosocial environment.
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Demência/psicologia , Transtornos Mentais/epidemiologia , Idoso , Idoso de 80 Anos ou mais , China/epidemiologia , Estudos Transversais , Cultura , Feminino , Humanos , Masculino , Transtornos Mentais/classificação , Transtornos Mentais/etiologia , Testes Neuropsicológicos , Prevalência , Características de Residência , Índice de Gravidade de DoençaRESUMO
Hepatocellular carcinoma (HCC) is characterized by a poor prognosis. Our previous work suggested that Protocadherin 20 (PCDH20) promoted ferroptosis in HCC. Nevertheless, the underlying mechanism remains elusive. Recently, we found that both the mRNA and protein levels of PCDH20 were upregulated in erastin- or sorafenib-treated HCC cells. Meanwhile, data showed that Sirtuin 1 (SIRT1) was markedly downregulated in PCDH20-SNU-449 cells. Additionally, overexpression of PCDH20 or erastin-treated cells dramatically decreased cell viability and colony-forming capacity of HCC cells, whereas blocking PCDH20 reversed these effects. Moreover, PCDH20 overexpression or treatment with erastin significantly downregulated the expression of SIRT1, Solute carrier family 7 member 11 (SLC7A11), as well as the ferroptosis-related protein glutathione peroxidase 4 (GPX4) and glutathione (GSH), while elevated malondialdehyde (MDA), 2'- 7'-dichlorofluorescein (DCF) and intercellular iron levels. Conversely, knockdown of PCDH20 upregulated SIRT1 and SLC7A11. Immunoprecipitation assay demonstrated that PCDH20 or erastin increased the amount of acetylated nuclear factor erythroid 2-related factor-2 (NRF2). This reducing effect of NRF2 deacetylation by PCDH20 was counteracted by restoring the expression of SIRT1. In addition, PCDH20 lowered the levels of GPX4, GSH, and cell viability, as well as resulted in an elevation in intercellular iron level, MDA, and DCF. These effects were reversed by SIRT1 expression. Besides, PCDH20 could promote ferroptosis by inhibiting SIRT1 from deacetylating NRF2, which led to the downregulation of SLC7A11, GPX4, and GSH both in vivo and in vitro. Our results signals that PCDH20 promotes ferroptosis by suppressing the expression of SIRT1 and thus, promoting the acetylation of NRF2in HCC.
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Carcinoma Hepatocelular , Ferroptose , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/genética , Acetilação , Sirtuína 1/genética , Protocaderinas , Fator 2 Relacionado a NF-E2/genética , Neoplasias Hepáticas/genética , Glutationa , FerroRESUMO
Background: Conventionally, the judgment of whether small pulmonary nodules are invasive is mainly made by thoracic surgeons according to the chest computed tomography (CT) features of patients. However, there are limits to how much useful information can be obtained from this approach. A large number of feature information was extracted from CT images by CT radiomics. The machine learning algorithm was used to construct models based on radiomic characteristics to predict the invasiveness of lung adenocarcinoma (LUAD) with a good prediction accuracy. Methods: A total of 416 patients with pathologically confirmed preinvasive lesions and LUAD after video-assisted thoracoscopic surgery (VATS) in the Department of Thoracic Surgery of the First People's Hospital of Yunnan Province from February 2020 to February 2022 were retrospectively analyzed. According to random classification, patients were divided into 2 groups. The RadCloud platform was used to extract radiomics features, and the most relevant radiomics features were selected by continuous dimension reduction method. Then, 6 machine learning algorithms were used to establish and verify the prediction model of small lung nodular adenocarcinoma invasiveness. Receiver operating characteristic (ROC) curve and area under curve (AUC) were used to evaluate the predictive performance. Results: There were 78 cases of pre-invasive lesions and 226 cases of invasive lesions in the training group, and 34 cases of pre-invasive lesions and 78 cases of invasive lesions in the validation group. In the training group, the AUC values of the 6 models were all more than 0.914, the 95% confidence interval (CI) was 0.857-1.00, the sensitivity was equal or more than 0.87, and the specificity was equal or more than 0.85. In the validation group, the AUC values of the 6 models were all equal or more than 0.732, the 95% CI was 0.651-1.00, the sensitivity was equal or more than 0.7, and the specificity was more than 0.77. Conclusions: Machine learning algorithms were used to construct models to predict the invasiveness of small nodular LUAD based on radiomics features, which it could provide more evidence for doctors to make diagnoses and more personalized treatment plans for patients.
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Aim: Alcohol intake alters DNA methylation profiles and methylation might mediate the association between alcohol and disease, but limited number of positive CpG sites repeatedly replicated. Materials & methods: In total, 57 monozygotic (MZ) twin pairs discordant for alcohol drinking from the Chinese National Twin Registry and 158 MZ and dizygotic twin pairs in the Swedish Adoption/Twin Study of Aging were evaluated. DNA methylation was detected using the Infinium HumanMethylation450 BeadChip. Results: Among candidate CpG sites, cg07326074 was significantly correlated with drinking after adjusting for covariates in MZ twins in both datasets but not in the entire sample or dizygotic twins. Conclusion: The hypermethylation of cg07326074, located in the tumor-promoting gene C16orf59, was associated with alcohol consumption.
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Consumo de Bebidas Alcoólicas , Biomarcadores , Ácidos Nucleicos Livres , Metilação de DNA , Estudo de Associação Genômica Ampla , Adulto , Biomarcadores/sangue , Biologia Computacional/métodos , Ilhas de CpG , Epigênese Genética , Epigenômica/métodos , Feminino , Perfilação da Expressão Gênica , Humanos , Masculino , Pessoa de Meia-Idade , SuéciaRESUMO
Objective:This study aims to analyze the threshold changes in distortion product otoacoustic emissions(DPOAE) and auditory brainstem response(ABR) in adult Otof-/- mice before and after gene therapy, evaluating its effectiveness and exploring methods for assessing hearing recovery post-treatment. Methods:At the age of 4 weeks, adult Otof-/- mice received an inner ear injection of a therapeutic agent containing intein-mediated recombination of the OTOF gene, delivered via dual AAV vectors through the round window membrane(RWM). Immunofluorescence staining assessed the proportion of inner ear hair cells with restored otoferlin expression and the number of synapses.Statistical analysis was performed to compare the DPOAE and ABR thresholds before and after the treatment. Results:AAV-PHP. eB demonstrates high transduction efficiency in inner ear hair cells. The therapeutic regimen corrected hearing loss in adult Otof-/- mice without impacting auditory function in wild-type mice. The changes in DPOAE and ABR thresholds after gene therapy are significantly correlated at 16 kHz. Post-treatment,a slight increase in DPOAE was observeds,followed by a recovery trend at 2 months post-treatment. Conclusion:Gene therapy significantly restored hearing in adult Otof-/- mice, though the surgical delivery may cause transient hearing damage. Precise and gentle surgical techniques are essential to maximize gene therapy's efficacy.
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Camundongos , Animais , Emissões Otoacústicas Espontâneas/fisiologia , Audição/fisiologia , Orelha Interna , Perda Auditiva/terapia , Terapia Genética , Limiar Auditivo/fisiologia , Potenciais Evocados Auditivos do Tronco Encefálico/fisiologia , Proteínas de MembranaRESUMO
Objective:To evaluate the effectiveness of the artificial intelligence-assisted diagnosis and treatment system in distinguishing benign and malignant lung nodules.Methods:Clinical data of 1 650 patients with pulmonary nodules admitted to the Tianjin Chest Hospital Affiliated to Tianjin University from January 2015 to October 2022 were retrospectively analyzed, which included a total of 1 650 nodules. The malignant probability was compared to and analyzedpredict the benign and malignant nodules.Results:A total of 1 650 nodules were included, which were divided into a malignant tumor group(n=1 391, 84.3%) and a benign lesion group(n=259, 15.7%). Between the malignant tumor group and the benign lesion group, the malignant probability was significantly different, and the malignant probability could better distinguish malignant nodules and benign lesions[(78.85±22.91)% vs.(54.91±28.68)%, P<0.001]. The area under the curve( AUC) was 0.768. The critical value of malignant probability for diagnosis of lung cancer was 81.3% with a sensitivity of 0.620 and specificity of 0.815. Stratified analysis results showed that the accuracy of the AI intelligent system for diagnosing pulmonary nodules with the sizes of 0-1 cm, 1-2 cm and 2-3 cm was also increased, and the areas under ROC curve were 0.717, 0.769 and 0.804, respectively. Conclusion:The malignant probability of lung nodules calculated by the artificial intelligence-assisted diagnosis and treatment system can be used in the assessment of the preoperative benign and malignant lung nodules.
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BACKGROUND@#Severe liver disease (SLD), including cirrhosis and liver cancer, constitutes a major disease burden in China. We aimed to examine the association of genetic and healthy lifestyle factors with the incidence and prognosis of SLD.@*METHODS@#The study population included 504,009 participants from the prospective China Kadoorie Biobank aged 30-79 years. The individuals were from 10 diverse areas in China without a history of cancer or liver disease at baseline. Cox regression was used to estimate adjusted hazard ratios (HRs) for incident SLD and death after SLD diagnosis associated with healthy lifestyle factors (smoking, alcohol, physical activity, and central adiposity). Additionally, the contribution of genetic risk for hepatitis B virus (HBV, assessed by genetic variants in major histocompatibility complex, class II, DP/DQ [ HLA - DP / DQ ] genes) was also estimated.@*RESULTS@#Compared with those with 0-1 healthy lifestyle factor, participants with 2, 3, and 4 factors had 12% (HR 0.88 [95% confidence interval [CI] 0.85, 0.92]), 26% (HR 0.74 [95%CI: 0.69, 0.79]), and 44% (HR 0.56 [95%CI: 0.48, 0.65]) lower risks of SLD, respectively. Inverse associations were observed among participants with both low and high genetic risks (HR per 1-point increase 0.83 [95%CI: 0.74, 0.94] and 0.91 [95%CI: 0.82, 1.02], respectively; Pinteraction = 0.51), although with a non-significant trend among those with a high genetic risk. Inverse associations were also observed between healthy lifestyle factors and liver biomarkers regardless of the genetic risk. Despite the limited power, healthy lifestyle factors were associated with a lower risk of death after incident SLD among participants with a low genetic risk (HR 0.59 [95%CI: 0.37, 0.96]).@*CONCLUSIONS@#Lifestyle modification may be beneficial in terms of lowering the risk of SLD regardless of the genetic risk. Moreover, it is also important for improving the prognosis of SLD in individuals with a low genetic risk. Future studies are warranted to examine the impact of healthy lifestyles on SLD prognosis, particularly among individuals with a high genetic risk.
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Humanos , Estudos Prospectivos , Incidência , População do Leste Asiático , Estilo de Vida Saudável , Fatores de Risco , Neoplasias Hepáticas , Prognóstico , China/epidemiologiaRESUMO
BACKGROUND@#Several studies have reported that polygenic risk scores (PRSs) can enhance risk prediction of coronary artery disease (CAD) in European populations. However, research on this topic is far from sufficient in non-European countries, including China. We aimed to evaluate the potential of PRS for predicting CAD for primary prevention in the Chinese population.@*METHODS@#Participants with genome-wide genotypic data from the China Kadoorie Biobank were divided into training ( n = 28,490) and testing sets ( n = 72,150). Ten previously developed PRSs were evaluated, and new ones were developed using clumping and thresholding or LDpred method. The PRS showing the strongest association with CAD in the training set was selected to further evaluate its effects on improving the traditional CAD risk-prediction model in the testing set. Genetic risk was computed by summing the product of the weights and allele dosages across genome-wide single-nucleotide polymorphisms. Prediction of the 10-year first CAD events was assessed using hazard ratios (HRs) and measures of model discrimination, calibration, and net reclassification improvement (NRI). Hard CAD (nonfatal I21-I23 and fatal I20-I25) and soft CAD (all fatal or nonfatal I20-I25) were analyzed separately.@*RESULTS@#In the testing set, 1214 hard and 7201 soft CAD cases were documented during a mean follow-up of 11.2 years. The HR per standard deviation of the optimal PRS was 1.26 (95% CI:1.19-1.33) for hard CAD. Based on a traditional CAD risk prediction model containing only non-laboratory-based information, the addition of PRS for hard CAD increased Harrell's C index by 0.001 (-0.001 to 0.003) in women and 0.003 (0.001 to 0.005) in men. Among the different high-risk thresholds ranging from 1% to 10%, the highest categorical NRI was 3.2% (95% CI: 0.4-6.0%) at a high-risk threshold of 10.0% in women. The association of the PRS with soft CAD was much weaker than with hard CAD, leading to minimal or no improvement in the soft CAD model.@*CONCLUSIONS@#In this Chinese population sample, the current PRSs minimally changed risk discrimination and offered little improvement in risk stratification for soft CAD. Therefore, this may not be suitable for promoting genetic screening in the general Chinese population to improve CAD risk prediction.
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Masculino , Humanos , Feminino , Doença da Artéria Coronariana/genética , Bancos de Espécimes Biológicos , População do Leste Asiático , Medição de Risco/métodos , Predisposição Genética para Doença/genética , Fatores de Risco , Estudo de Associação Genômica AmplaRESUMO
BACKGROUND@#Evidence on the relations of the American Heart Association's ideal cardiovascular health (ICH) with mortality in Asians is sparse, and the interaction between behavioral and medical metrics remained unclear. We aimed to fill the gaps.@*METHODS@#A total of 198,164 participants without cancer and cardiovascular disease (CVD) were included from the China Kadoorie Biobank study (2004-2018), Dongfeng-Tongji cohort (2008-2018), and Kailuan study (2006-2019). Four behaviors (i.e., smoking, physical activity, diet, body mass index) and three medical factors (i.e., blood pressure, blood glucose, and blood lipid) were classified into poor, intermediate, and ideal levels (0, 1, and 2 points), which constituted 8-point behavioral, 6-point medical, and 14-point ICH scores. Results of Cox regression from three cohorts were pooled using random-effects models of meta-analysis.@*RESULTS@#During about 2 million person-years, 20,176 deaths were recorded. After controlling for demographic characteristics and alcohol drinking, hazard ratios (95% confidence intervals) comparing ICH scores of 10-14 vs. 0-6 were 0.52 (0.41-0.67), 0.44 (0.37-0.53), 0.54 (0.45-0.66), and 0.86 (0.64-1.14) for all-cause, CVD, respiratory, and cancer mortality. A higher behavioral or medical score was independently associated with lower all-cause and CVD mortality among the total population and populations with different levels of behavioral or medical health equally, and no interaction was observed.@*CONCLUSIONS@#ICH was associated with lower all-cause, CVD, and respiratory mortality among Chinese adults. Both behavioral and medical health should be improved to prevent premature deaths.
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Adulto , Humanos , Doenças Cardiovasculares/prevenção & controle , População do Leste Asiático , Estudos Prospectivos , Fatores de Risco , FumarRESUMO
@#Objective To systematically analyze the World Health Organization Rehabilitation Competency Framework (RCF) theoretical framework, methodology and its application in the field of rehabilitation.Methods We systematically analyzed RCF conceptual framework and key characteristics, and discussed how to apply the RCF in the fields of human resource planning, education program and curriculum system, and vocational competency standards and certification criteria for rehabilitation human resources.Results The RCF encompasses five domains, naming practice, professionalism, learning and development, management and leadership, and research. Rehabilitation professionals' performance is the result of the interaction of their core values and beliefs, competencies, activities, knowledge, and skills. The RCF can be used to plan rehabilitation human resources, establish competency-based rehabilitation education programs and curriculum systems, and develop competency certification standards and licensure accreditation standards.Conclusion This study analyzed background, content and implementation framework of RCF, and systematically discussed the theories and methods related to how to use the RCF to construct national rehabilitation human resources development plans, develop rehabilitation education programs and curriculum systems based on the RCF, and establish certification and assessment standards for rehabilitation human resources.
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Accumulating evidence indicated that microRNAs (miRNA) play an important role in tumor invasion and metastasis by regulating their target genes.However, whether the miRNA-216b-5p(miR-216b-5p ) and their target genes butyrophilin subfamily 3 member A2(BTN3A2) promote glioma invasion and metastasis is unclear.This study aims to study whether miR-216b-5p promoted migration and invasion in glioma cells by negatively regulating BTN3A2.The differential expression analysis of GSE15824 and GSE4290 was analyzed by GEO2R.We found that only BTN3A2 is up-regulated in both GSE15824 and GSE4290 (P<0.05).The gene set enrichment analysis (GSEA) analysis indicated BTN3A2 was related to many cancer-related pathways (P<0.05).The results of survival curves showed that the overall survival of patients with high expression of BTN3A2 decreased significantly (P <0.001).The expression of BTN3A2 was increased with the increase of WHO grade (P<0.05), while the expression of BTN3A2 was increased in 1p/19q uncombined deletion and IDH mutant patients (P<0.001).Western blotting results showed that BTN3A2 was up-regulated in seven glioma tissues and glioma cell lines U87, U251 and LN-229 and downregulated in the miR-216b-5p mimics group; Transwell results showed that transfection with BTN3A2 silencing plasmids(si-BTN3A2) or miR-216b-5p mimics plasmids could inhibit the ability of migration and invasion in LN-229 cells in vitro (P<0.05).The online websites predicted miR-216b-5p as a potential target gene of BTN3A2.The survival curve results show that compared with patients with low expression of miR-216b-5p , the survival rate of patients with high expression was significantly increased (P=0.025).The relative expression of miR-216b-5p was decreased in U87, U251 and LN229 cells was detected by real time quantitative PCR (P<0.05).The results of dual luciferase assay showed that BTN3A2 could bind to miR-216b-5p (P<0.05).Transwell experiment results showed that overexpression of miR-216b-5p can inhibit the migration and invasion ability of LN229 cells (P<0.05).In summary, miR-216b-5p promotes the migration and invasion by targeting BTN3A2 of LN-229 glioma cells.
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Background: Cardiopulmonary resuscitation (CPR) strategies in COVID-19 patients differ from those in patients suffering from cardiogenic cardiac arrest. During CPR, both healthcare and non-healthcare workers who provide resuscitation are at risk of infection. The Working Group for Expert Consensus on Prevention and Cardiopulmonary Resuscitation for Cardiac Arrest in COVID-19 has developed this Chinese Expert Consensus to guide clinical practice of CPR in COVID-19 patients. Main recommendations: 1) A medical team should be assigned to evaluate severe and critical COVID-19 for early monitoring of cardiac-arrest warning signs. 2) Psychological counseling and treatment are highly recommended, since sympathetic and vagal abnormalities induced by psychological stress from the COVID-19 pandemic can induce cardiac arrest. 3) Healthcare workers should wear personal protective equipment (PPE). 4) Mouth-to-mouth ventilation should be avoided on patients suspected of having or diagnosed with COVID-19. 5) Hands-only chest compression and mechanical chest compression are recommended. 6) Tracheal-intubation procedures should be optimized and tracheal-intubation strategies should be implemented early. 7) CPR should be provided for 20-30 min. 8) Various factors should be taken into consideration such as the interests of patients and family members, ethics, transmission risks, and laws and regulations governing infectious disease control. Changes in management: The following changes or modifications to CPR strategy in COVID-19 patients are proposed: 1) Healthcare workers should wear PPE. 2) Hands-only chest compression and mechanical chest compression can be implemented to reduce or avoid the spread of viruses by aerosols. 3) Both the benefits to patients and the risk of infection should be considered. 4) Hhealthcare workers should be fully aware of and trained in CPR strategies and procedures specifically for patients with COVID-19.
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OBJECTIVE@#To explore the cytidine-phosphate-guanosine (CPG) sites associated with fas-ting plasma glucose (FPG) and glycated haemoglobin (HbA1c) in twins.@*METHODS@#In the study, 169 pairs of monozygotic twins were recruited in Qingdao, Zhejiang, Jiangsu, Sichuan and Heilongjiang in June to December of 2013 and June 2017 to October 2018. The methylation was detected by Illumina Infinium HumanMethylation450 BeadChip and Illumina Infinium MethylationEPIC BeadChip. According to the Linear Mixed Effect model (LME model), fasting plasma glucose and HbA1c were taken as the main effects, the methylation level (β value) was taken as the dependent variable, continuous variables, such as age, body mass index (BMI), blood pressure, components of blood cells, surrogate variables generated by SVA, and categorical variables, such as gender, smoking and drinking status, hypoglycemic drugs taking, were included in the fixed effect model as covariates, and the identity numbers (ID) of the twins was included in the random effect model. The intercept was set as a random. Regression analysis was carried out to find out the CpG sites related to fasting blood glucose or HbA1c, respectively.@*RESULTS@#In this study, 338 monozygotic twins (169 pairs) were included, with 412 459 CpG loci. Among them, 114 pairs were male, and 55 pairs were female, with an average age of (48.2±11.9) years. After adjustment of age, gender, BMI, blood pressure, smoking, drinking, blood cell composition, and other covariates, and multiple comparison test, 7 CpG sites (cg19693031, cg01538969, cg08501915, cg04816311, ch.8.1820050F, cg06721411, cg26608667) were found related to fasting blood glucose, 3 of which (cg08501915, ch.8.1820050f, cg26608667) were the newly found sites in this study; whereas 10 CpG sites (cg19693031, cg04816311, cg01538969, cg01339781, cg01676795, cg24667115, cg09029192, cg20697417, ch.4.1528651F, cg16097041) were found related to HbA1c, and 4 of which(cg01339781, cg24667115, cg20697417, and ch.4.1528651f) were new. We found that cg19693031 in TXNIP gene was the lowest P-value site in the association analysis between DNA methylation and fas-ting plasma glucose and HbA1c (PFPG=2.42×10-19, FDRFPG<0.001; PHbA1c=1.72×10-19, FDRHbA1c<0.001).@*CONCLUSION@#In this twin study, we found new CpG sites related to fasting blood glucose and HbA1c, and provided some clues that partly revealed the potential mechanism of blood glucose metabolism in terms of DNA methylation, but it needed further verification in external larger samples.
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Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Glicemia , Ilhas de CpG , Metilação de DNA , Epigênese Genética , Jejum , Hemoglobinas Glicadas , Gêmeos MonozigóticosRESUMO
OBJECTIVE@#To estimate the univariate heritability of resting heart rate and common chronic disease such as hypertension, diabetes, and dyslipidemia based on extended pedigrees in Fujian Tulou area and to explore bivariate heritability to test for the genetic correlation between resting heart rate and other relative phenotypes.@*METHODS@#The study was conducted in Tulou area of Nanjing County, Fujian Province from August 2015 to December 2017. The participants were residents with Zhang surname and their relatives from Taxia Village, Qujiang Village, and Nanou Village or residents with Chen surname and their relatives from Caoban Village, Tumei Village, and Beiling Village. The baseline survey recruited 1 563 family members from 452 extended pedigrees. The pedigree reconstruction was based on the family information registration and the genealogy booklet. Univariate and bivariate heritability was estimated using variance component models for continuous variables, and susceptibility-threshold model for binary variables.@*RESULTS@#The pedigree reconstruction identified 1 seven-generation pedigree, 2 five-generation pedigrees, 23 four-generation pedigrees, 186 three-generation pedigrees, and 240 two-generation pedigrees. The mean age of the participants was 57.2 years and the males accounted for 39.4%. The prevalence of hypertension, diabetes, dyslipidemia in this population was 49.2%, 10.0%, and 45.2%, respectively. The univariate heritability estimation of resting heart rate, hypertension, and dyslipidemia was 0.263 (95%CI: 0.120-0.407), 0.404 (95%CI: 0.135-0.673), and 0.799 (95%CI: 0.590-1), respectively. The heritability of systolic blood pressure, diastolic blood pressure, fasting glucose, total cholesterol, triglyceride, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol was 0.379, 0.306, 0.393, 0.452, 0.568, 0.852, and 0.387, respectively. In bivariate analysis, there were phenotypic correlations between resting heart rate with hypertension, diabetes, diastolic blood pressure, fasting glucose, and triglyceride. After taking resting heart rate into account, there were strong genetic correlations between resting heart rate with fasting glucose (genetic correlation 0.485, 95%CI: 0.120-1, P<0.05) and diabetes (genetic correlation 0.795, 95%CI: 0.181-0.788, P<0.05).@*CONCLUSION@#Resting heart rate was a heritable trait and correlated with several common chronic diseases and related traits. There was strong genetic correlation between resting heart rate with fasting glucose and diabetes, suggesting that they may share common genetic risk factors.
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Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pressão Sanguínea , Doença Crônica , Frequência Cardíaca , Hipertensão , LinhagemRESUMO
The cohort study provides the strongest evidence of causality among observational epidemiological study design. One of the most important reasons is that cohort study more clearly indicates the temporal sequence between exposure and outcome. Effective and efficient follow-up is the fundamental necessity for research quality. This review briefly introduces the requirements for the observation period of the cohort study, the two most common ways for follow-up and their advantages and disadvantages.
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Platelet activation plays an important role in the occurrence and development of sepsis. During sepsis stage, platelet activation can cause endothelial cell damage, promote the formation of neutrophil extracellular traps (NETs) and microthrombosis, aggravate coagulation dysfunction and inflammatory response disorder, and ultimately lead to multiple organ dysfunction syndrome (MODS) in septic patients. During the infection, platelets also participate in the process of congenital immune response and acquired immune response, through the interaction with immune mediators, platelets can actively defend the invasion and spread of pathogens, but also may aggravate the disease and even cause septic shock due to overactive immune response. This paper mainly introduces the role of platelet activation in the occurrence and development of sepsis, and highlights the role of platelet-mediated immune response in anti-infection of human body.
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OBJECTIVE@#To investigate the methylation status of CHD5 gene promoter in bone marrow from acute myeloid leukemia (AML) patients, and the underlying mechanism for initiating the pathogenesis of AML via p19/p53/p21 pathway.@*METHODS@#Methylation status of the CHD5 gene promoter was detected by using methylation-specific polymerase chain reaction (MSPCR) in bone marrow from AML patients, and the iron-deficiency anemia (IDA) samples were served as control. The expression of CHD5, p19, p53 and p21 was determined by real-time quantitative reverse transcriptase PCR and Western blot.@*RESULTS@#The methylation of CHD5 gene in bone marrow from AML patients increased significantly (39.06%) as compared with control group (6.67%). The methylation of CHD5 gene significantly correlated with chromosome karyotype differentiation (P<0.01), but did not correlate with the patient's sex, age and clinical classification (P>0.05). The mRNA expression of CHD5 gene in AML decreased, compared with control group, the mRNA and protein expression of p19, p53 and p21 in AML with CHD5 methylation promoter decreased.@*CONCLUSION@#The hypermeltylation of CHD5 gene promoter in AML patients can lead to decrease of CHD5, p19, p53 and p21 expression levels which may reduce the inhibitory effect on proliferation of leukemia cells through the regulation of p19, p53 and p21 pathway, thus promotes the occurence of AML.