Study on gene therapy for DPOAE and ABR threshold changes in adult Otof-/- mice / 临床耳鼻咽喉头颈外科杂志

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.

Ideal cardiovascular health and mortality: pooled results of three prospective cohorts in Chinese adults / 中华医学杂志(英文版)

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.

Minimal improvement in coronary artery disease risk prediction in Chinese population using polygenic risk scores: evidence from the China Kadoorie Biobank / 中华医学杂志(英文版)

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.

Genetic and healthy lifestyle factors in relation to the incidence and prognosis of severe liver disease in the Chinese population / 中华医学杂志(英文版)

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.

Systematic implementation of World Health Organization rehabilitation competency framework in rehabilitation: conceptual framework, approaches and application / 中国康复理论与实践

@#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.

Expert consensus on prevention and cardiopulmonary resuscitation for cardiac arrest in COVID-19

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.

miR-216b-5p Promotes the Migration and Invasion of LN-229 Glioma Cells by Targeting BTN3A2 / 中国生物化学与分子生物学报

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.

Bivariate heritability estimation of resting heart rate and common chronic disease based on extended pedigrees / 北京大学学报(医学版)

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.

Correlation between fasting plasma glucose, HbA1c and DNA methylation in adult twins / 北京大学学报(医学版)

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.

The role of platelet activation and related immune response in sepsis / 中国感染控制杂志

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.

Follow up in cohort study / 中华疾病控制杂志

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.

Methylation of CHD5 Gene Promoter Regulates p19/p53/p21 Pathway to Facilitate Pathogenesis of Acute Myeloid Leukemia / 中国实验血液学杂志

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.

Family History, Tobacco Smoking, and Risk of Ischemic Stroke / 대한뇌졸중학회지

BACKGROUND AND PURPOSE: Both genetic factors and smoking are associated with ischemic stroke (IS) risk. However, little is known about the potential interaction of these factors. We aimed to assess whether smoking and a positive family history interact to increase the risk of IS. METHODS: The nationwide prospective study recruited 210,000 men and 300,000 women in 2004 to 2008 at ages 30 to 79 years. During 9.7 years of follow-up, we documented 16,923 and 20,656 incident IS cases in men and women without major chronic diseases at baseline, respectively. Multivariable Cox regression models were used to examine associations between family history and IS. Likelihood ratio tests were used to test the smoking-family history interactions on IS. RESULTS: About 67.8% (n=135,168) of men ever smoked regularly compared with 2.7% (n=7,775) of women. Among men, a significant interaction between family history and smoking on IS was observed (P for interaction=0.03), with more pronounced association between family history and IS among ever-regular smokers (hazard ratio [HR], 1.21; 95% confidence interval [CI], 1.16 to 1.27) than among never-smokers (HR, 1.11; 95% CI, 1.01 to 1.23). The association between family history and IS among ex-smokers after more than 10 years of cessation (HR, 1.01; 95% CI, 0.85 to 1.20) appeared similar to that among never-smokers. Among women, a similar but not significant interaction between family history and smoking on IS was observed. Ever-regular smokers who had a family history of stroke had the highest risk of IS. CONCLUSIONS: Among Chinese men, the association of family history with IS was accentuated by smoking, and such accentuation tended to be lowered by cessation.

Effects of low level laser irradiation on the osteogenic capacity of sodium alginate/gelatin/human adipose-derived stem cells 3D bio-printing construct / 北京大学学报(医学版)

OBJECTIVE@#To explore the effects of low level laser irradiation (LLLI) on the osteogenic capacity of three-dimensional (3D) structure by 3D bio-printing construct used human adipose-derived stem cells (hASCs) as seed cells.@*METHODS@#Using hASCs as seed cells, we prepared sodium alginate/gelatin/hASCs 3D bio-printing construct, and divided them into four groups: PM (proliferative medium), PM+LLLI, OM (osteogenic medium) and OM+LLLI, and the total doses of LLLI was 4 J/cm². Immunofluorescence microscopy was used to observe the viability of the cells, and analyze the expression of the osteogenesis-related protein Runt-related transcription factor 2 (Runx2) and osteocalcin (OCN).@*RESULTS@#The 3D constructs obtained by printing were examined by microscope. The sizes of these 3D constructs were 10 mm×10 mm×1.5 mm. The wall thickness of the printed gelatin mold was approximately 1 mm, and the pores were round and had a diameter of about 700 μm. The cell viability of sodium alginate/gelatin/hASCs 3D bio-printing construct was high, and the difference among the four groups was not significant. On day 7, the expression of OCN from high to low was group OM+LLLI, PM+LLLI, OM and PM. There were significant differences among these groups (P<0.01), but there was no significant difference between group PM+LLLI and OM. On day 14, the expression of OCN in each group was higher than that on day 7, and there was no significant difference between group OM+LLLI and OM. The expression of Runx2 in group OM+LLLI was more than 90%, significantly higher than that in group OM (P<0.01). But the expression of Runx2 in group PM+LLLI and OM+LLLI were significantly lower than that in the non-irradiated groups. The expression of osteogenesis-related protein Runx2 and OCN were higher in OM groups than in PM groups. Furthermore, the irradiated groups were significantly higher than the non-irradiated groups.@*CONCLUSION@#LLLI does not affect the cell viability of sodium alginate/gelatin/hASCs 3D bio-printing construct, and may promote the osteogenic differentiation of hASCs.

Correlation between blood pressure and DNA methylation in adult twins / 北京大学学报(医学版)

OBJECTIVE@#To explore the DNA methylation sites correlated with blood pressure (systolic blood pressure, diastolic blood pressure, mean arterial pressure, pulse pressure) in adult twin population.@*METHODS@#A total of 476 twins from the Chinese National Twin Registry were selected as the research population. Questionnaires were used to collect demographic characteristics, lifestyle, disease status and other information, and blood pressure, height, weight and other anthropometric indicators were measured. The genome-wide DNA methylation of whole blood samples was detected by using Infinium HumanMethylation450 BeadChip. The DNA methylation sites correlated with blood pressure were analyzed by constructing mixed effect model with adjusting potential confounding factors, and the significant level was false discovery rate <0.05.@*RESULTS@#After data quality control, 465 twins (122 pairs of monozygotic twins, 104 pairs of dizygotic twins, 13 individuals from 13 pairs of twins) aged (44.8±13.2) years were finally enrolled. There were more males and more monozygotic twins, and the current smokers and current regular drinkers both accounted for more than 30%. No significant CpG site was found after multiple testing in the correlation study between genome-wide DNA methylation and blood pressure by using the collected twins. However, the cg07761116 located on chromosome 10 had low P value in the correlation analysis of 3 blood pressure indices (systolic blood pressure, diastolic blood pressure, mean arterial pressure), suggesting that this site might be correlated with blood pressure. The other 7 sites had low P value in the correlation analysis of the two blood pressure indices, respectively, which pointed to genes involved in neurological development, protein homeostasis, inflammatory reaction and other pathways.@*CONCLUSION@#There is no sufficient evidence to support any DNA methylation site correlated with blood pressure, which may be caused by insufficient sample size and other reasons. This study could provide a reference for subsequent similar twin studies, and subsequent studies can focus on the cg07761116 located on chromosome 10 and other sites with low P values.

Astragalus polysaccharides downregulates apoptosis in HepG2 cell through Wnt/β-catenin signaling pathway / 中草药

Objective To investigate the effects of Astragalus polysaccharides (APS) on HepG2 cell proliferation and apoptosis through Wnt/β-catenin signaling pathway. Methods Cell proliferation ability and cell viability was measured by MTT assay. Annexin V-FITC/PI stain and Caspase-3 activity assay were used to detect cell apoptosis. The changes of Wnt/β-catenin signaling pathway activity after treated by APS (100 and 200 mg/L) was measured by luciferase assay. The expression levels of β-catenin, c-myc, and Cyclin D1 were detected by qRT-PCR and Western blotting. Results As the concentration of APS increases, the cell viability of HepG2 cells decreased significantly (P < 0.05). Compared with control group, the cells apoptosis rates of in APS 100 and 200 mg/L groups were increased remarkably (P < 0.05); The relative activities of Caspase-3 in APS 100 and 200 mg/L groups increased significantly (P < 0.05); Meanwhile, the activity of luciferase in APS 100 and 200 mg/L groups decreased significantly (P < 0.05). The expression level of cleaved Caspase-3 was increased significantly. The mRNA 1evel of β-catenin, Cyclin D1, and c-myc in APS 100 and 200 mg/L groups were decreased significantly (P < 0.05), and the expression levels of Bcl-2, β-catenin, c-myc, and Cyclin D1 protein in APS 100 and 200 mg/L groups were decreased significantly (P < 0.05, 0.01). Conclusion APS promote the apoptosis of HepG2 cells through the down-regulation of Wnt/β-catenin signaling pathway, which leads to the inhibition of apoptosis-related gene Bcl-2 expression.

Advance in Contents and Standard of Disability-related Data / 中国康复理论与实践

@#This paper reviewed international documents of disability statistics. The results showed that all disability measurements had been adopted International Classification of Functioning, Disability and Health (ICF) terminology and approach. Disability statistics in US tailored to ICF framework and classification. Disability statistics in China had partially adopted ICF approach.

Construction of Framework and Indicators of Disability-related Service Data in China Using ICF / 中国康复理论与实践

@#Objective To develop a framework and indicators system for disability-related service data in China. Methods Using International Classification of Functioning, Disability and Health (ICF) framework and approach, the framework and indicators system were developed using content analysis, logical reasoning and expert consultation. Results A system with nine aspects, 35 dimensions and 115 indicators was established. Eleven experts with disability-related background all accepted the system, and satisfied in the importance and operability.Conclusion A data framework and indicators system with nine aspects, 35 dimensions and 115 indicators has been established for disability-related service, which can be used in further data collection.

Self-Rated Health Status and Risk of Incident Stroke in 0.5 Million Chinese Adults: The China Kadoorie Biobank Study / 대한뇌졸중학회지

BACKGROUND AND PURPOSE: Self-rated health (SRH) is a consistent and strong predictor of all-cause and cardiovascular mortality in various populations. However, the associations between SRH measures and risk of first-ever or recurrent stroke were rarely explored. We thus aim to prospectively investigate the associations between SRH measures and risk of total and subtypes of stroke in Chinese population. METHODS: A total of 494,113 participants from the China Kadoorie Biobank without prior heart diseases or cancer (486,541 without stroke and 7,572 with stroke) were followed from baseline (2004 to 2008) until December 31, 2013. General and age-comparative SRH were obtained from baseline questionnaires. First-ever stroke or recurrent events were ascertained through linkage to disease registry system and health insurance data. RESULTS: We identified 27,662 first-ever stroke and 2,909 recurrent events during an average of 7.0 years of follow-up. Compared with excellent general SRH, the hazard ratios (HRs) and 95% confidence intervals (CIs) for first-ever stroke associated with good, fair, and poor general SRH were 1.04 (1.00 to 1.08), 1.19 (1.15 to 1.23), and 1.49 (1.42 to 1.56) in the multivariate model, respectively. Compared with better age-comparative SRH, the HRs (95% CIs) of same and worse age-comparative SRH were 1.13 (1.10 to 1.17) and 1.51 (1.45 to 1.58), respectively. The relations of SRH measures with ischemic stroke, hemorrhagic stroke, and recurrent stroke were similar to that with total first-ever stroke. However, the magnitude of associations was much stronger for fatal stroke than for non-fatal stroke. CONCLUSIONS: This large-scale prospective cohort suggests that self-perceived health status is associated with incident stroke, regardless of stroke subtype.

Role of vitamin K-dependent protein Gas6 in the expression of endothelial cell adhesion molecule-1 and chemokines induced by Porphyromonas gingivalis lipopolysaccharide / 北京大学学报(医学版)

OBJECTIVE@#Growth-arrest-specific protein 6 (Gas6) is a vitamin K-dependent protein and involved in cell proliferation, survival, adhesion and migration . Also it has been shown to play an important role in the inflammatory response .The aim of present study was to investigate the role of Gas6 in the process of the expression of adhesion molecules and chemokines of human umbilical vein endothelial cells (HUVECs) induced by Porphyromonas gingivalis lipopolysaccharide(P.g-LPS).@*METHODS@#After up-regulation and down-regulation of the expression of Gas6, the vascular endothelial cells were stimulated with 1 mg/L P.g-LPS for 3 h and 24 h. Real-time quantitative polymerase chain reaction(real-time PCR) was taken to detect the expression of the cell adhesion molecules:intercellular adhesion molecule-1 (ICAM-1) and E-selectin, as well as chemokines:interleukin-8 (IL-8) and monocyte chemoattractant protein 1 (MCP-1). Wound healing assay was taken to observe the migration ability of endothelium cells in different groups.@*RESULTS@#After 3 h of P.g-LPS stimulation, the expression of adhesion molecules and chemokine in the down-regulation group was not significantly different from that in the control group,while in the up-regulation group the decrease of E-selectin, ICAM-1, IL-8 and MCP-1 was 81%±0%, 47%±3%, 76% ± 3%, 26% ± 6% respectively. After 24 h of P.g-LPS stimulation, the expression of adhesion molecules and chemokine in down-regulation group was significantly higher than that in control group (2.06±0.07, 1.99±0.11, 3.14±0.15, 1.84±0.03 flod), while these molecules in the down-regulation group was significantly lower than in the control group (29%±1%, 62%±3%, 69%±1%, 41%±2%). Differences were statistically significant (P<0.01). Wounding healing assay showed that down-regulation of Gas6 enhanced migration ability of endothelial cells while up-regulation of Gas6 weakened this ability,which was consistent with the trend of real-time PCR result.@*CONCLUSION@#Down-regulation of the Gas6 gene enhanced the expression of ICAM-1, E-selectin, IL-8 and MCP-1 in HUVECs after P.g- LPS stimulating, while up-regulaiton of the Gas6 gene weakened the expression of ICAM-1, E-selectin, IL-8 and MCP-1 in HUVECs after P.g-LPS stimulating,suggesting that Gas6 may play a role in the process of endothelial cell adhesion.