Incidence and risk factors of ischemic stroke in patients with type 2 diabetes among urban workers in Beijing, China / 北京大学学报(医学版)

OBJECTIVE@#To explore the incidence of ischemic stroke after the onset of type 2 diabetes, and further analyze the risk factors, so as to provide a basis for further research.@*METHODS@#The data were obtained from the database of the Beijing Urban Employee Basic Medical Insurance Database. The study used a prospective design to describe the incidence of ischemic stroke in patients with type 2 diabetes. In our study, these patients were followed up for seven years. Multivariate Logistic regression models were used to analyze the risk factors of ischemic stroke in patients with type 2 diabetes.@*RESULTS@#A total of 185 813 newly diagnosed type 2 diabetes patients were enrolled, with an average age of (58.5±13.2) years, and 49.0% of them were males. A total of 10 393 patients with newly diagnosed ischemic stroke occurred in 7 years, with a cumulative incidence of 5.6% and an incidence density of 8.1/1 000 person-years. Ischemic stroke occurred in all age groups in patients with type 2 diabetes. The cumulative incidence was 1.5% (95%CI: 1.3%-1.6%) in group ≤44 years old, 3.6% (95%CI: 3.4%-3.7%) in group 45-54 years old, 5.4% (95%CI: 5.2%-5.5%) in group 55-64 years old, and 9.2% (95%CI: 9.0%-9.4%) in group ≥65 years old, and the cumulative incidence increased with age (P < 0.05). Cumulative incidence rate of the males (6.8%, 95%CI: 6.7%-7.0%) was higher than the females (4.4%, 95%CI: 4.3%-4.6%). Among the patients < 80 years old, the cumulative incidence rate of the males was higher than that of the females in all the age groups. In the patients ≥80 years of age, the cumulative incidence was higher in the females (9.2%) than in the males (7.9%). Further analysis revealed that complications, such as coronary heart disease (OR=3.18, 95%CI: 2.72-3.72), heart failure (OR=1.53, 95%CI: 1.32-1.79) and kidney failure (OR=1.45, 95%CI: 1.20-1.75) were associated with ischemic stroke in the patients with type 2 diabetes.@*CONCLUSION@#The incidence level of ischemic stroke in patients with type 2 diabetes is high. It is necessary to strengthen the management of risk factors in elderly patients, screen the complications of type 2 diabetes as early as possible, and take active preventive and control measures.

Summary of tools for assessment of public health emergency response capability / 中华流行病学杂志

With the progress of globalization, the public health emergencies represented by major infectious diseases have become a major challenge for the public health management in China. The article briefly describes the emergency response capability assessment tools in China, and introduces two emergency response assessment tools with complete content structure and wide application in the world. Then the advantages and disadvantages of the tools are compared and discussed in order to provide reference for improvement of the assessment tools for public health emergency response capability in China.

Relationship between obesity and death by multi-morbidity status in older adults in China / 中华流行病学杂志

Objective: To explore the relationship between obesity status and death stratified by different multi-morbidity status in older adults in China. Methods: Data for older Chinese adults aged ≥65 years were from Chinese Longitudinal Healthy Longevity Survey (CLHLS). Multi-morbidity patterns based on 13 chronic conditions were explored using exploratory factor analysis. Cox models were used to examine relationships between obesity status and death stratified by disease count and multi-morbidity patterns at baseline, respectively. Besides, obesity status was defined by baseline body mass index and waist circumference. Results: A total of 6 272 participants were included in the analyses. Multi-morbidity including cardio-metabolic, sensory perception and other patterns were identified. For those without any chronic condition, compared with those without central obesity, central obesity was associated with a higher risk for death (HR=1.66, 95%CI:1.04-2.66). For those only with one chronic condition, compared with normal weight, underweight was associated with a higher risk for death (HR=1.41, 95%CI: 1.10-1.80). For those with multi-morbidity, compared with normal weight, underweight increased the risk for death (HR=1.19, 95%CI:1.05-1.34). Compared with those without central obesity, central obesity decreased the risk for death (HR=0.88, 95%CI:0.78-0.99). Conclusions: Relationships between obesity status and death varied by multi-morbidity status in older adults in China. Underweight and non-central obesity were associated with increased risks for death in older adults with only one chronic disease or multi-morbidity. Therefore, it is necessary to pay attention to multi-morbidity status in the management of obesity in older adults and provide effective targeted body weight management plan.

Interaction between ischemic stroke risk loci identified by genome-wide association studies and sleep habits / 北京大学学报(医学版)

OBJECTIVE@#To explore the relationship between sleep habits (sleep duration, sleep efficiency, sleep onset timing) and ischemic stroke, and whether there is an interaction between sleep habits and ischemic stroke susceptibility gene loci.@*METHODS@#A questionnaire survey, physical examination, blood biochemical testing and genotyping were conducted among rural residents in Beijing, and the gene loci of ischemic stroke suggested by previous genome-wide association studies (GWAS) were screened. Multivariable generalized linear model was used to analyze the correlation between sleep habits, sleep-gene interaction and ischemic stroke.@*RESULTS@#A total of 4 648 subjects with an average age of (58.5±8.7) years were enrolled, including 1 316 patients with ischemic stroke. Compared with non-stroke patients, stroke patients with sleep duration ≥9 hours, sleep efficiency < 80%, and sleep onset timing earlier than 22:00 accounted for a higher proportion (P < 0.05). There was no significant association between sleep duration and risk of ischemic stroke (OR=1.04, 95%CI: 0.99-1.10, P=0.085). Sleep efficiency was inversely associated with the risk of ischemic stroke (OR=0.18, 95%CI: 0.06-0.53, P=0.002). The risk of ischemic stroke in the subjects with sleep efficiency < 80% was 1.47-fold (95%CI: 1.03-2.10, P=0.033) of that in the subjects with sleep efficiency ≥80%. Falling asleep earlier than 22:00 was associated with 1.26 times greater risk of stroke than falling asleep between 22:00 and 22:59 (95%CI: 1.04-1.52, P=0.017). Multifactorial adjustment model showed that rs579459 on ABO gene had an interaction with sleep time (P for interaction =0.040). When there were two T alleles for rs579459 on the ABO gene, those who fell asleep before 22:00 had 1.56 times (95%CI: 1.20-2.04, P=0.001) the risk of stroke compared with those who fell asleep between 22:00 and 22:59, and there was no significant difference when the number of pathogenic alleles was 0 or 1. In the model adjusted only for gender, age and family structure, sleep duration and the number of T allele rs2634074 on PITX2 gene had an interaction with ischemic stroke (P for interaction=0.033).@*CONCLUSION@#Decreased sleep efficiency is associated with increased risk of ischemic stroke, and falling asleep earlier than 22:00 is associated with higher risk of ischemic stroke. Sleep onset timing interacted with rs579459 in ABO gene and the risk of ischemic stroke. Sleep duration and PITX2 rs2634074 may have a potential interaction with ischemic stroke risk.

Association study between haplotypes of WNT signaling pathway genes and nonsyndromic oral clefts among Chinese Han populations / 北京大学学报(医学版)

OBJECTIVE@#To explore whether WNT signaling pathway genes were associated with non-syndromic oral clefts (NSOC) based on haplotypes analyses among 1 008 Chinese NSOC case-parent trios.@*METHODS@#The genome-wide association study (GWAS) data of 806 Chinese non-syndromic cleft lip with or without cleft palate (NSCL/P) trios and 202 Chinese non-syndromic cleft palate (NSCP) case-parent trios were drawn from the International Consortium to Identify Genes and Interactions Controlling Oral Clefts (ICOCs) study GWAS data set, whose Chinese study population were recruited from four provinces in China, namely Taiwan, Shandong, Hubei, and Sichuan provinces. The process of DNA genotyping was conducted by the Center for Inherited Disease Research in the Johns Hopkins University, using Illumina Human610-Quad v.1_B Bead Chip. The method of sliding windows was used to determine the haplotypes for analyses, including 2 SNPs haplotypes and 3 SNPs haplotypes. Haplotypes with a frequency lower than 1% were excluded for further analyses. To further assess the association between haplotypes and NSOC risks, and the transmission disequilibrium test (TDT) was performed. The Bonferroni method was adopted to correct multiple tests in the study, with which the threshold of statistical significance level was set as P < 0.05 divided by the number of tests, e.g P < 3.47×10-4 in the current stu-dy. All the statistical analyses were performed by using plink (v1.07).@*RESULTS@#After quality control, a total of 144 single nucleotide polymorphisms (SNPs) mapped in seven genes in WNT signaling pathway were included for the analyses among the 806 Chinese NSCL/P trios and 202 Chinese NSCP trios. A total of 1 042 haplotypes with frequency higher than 1% were included for NSCL/P analyses and another 1 057 haplotypes with frequency higher than 1% were included for NSCP analyses. Results from the TDT analyses showed that a total of 69 haplotypes were nominally associated with the NSCL/P risk among Chinese (P < 0.05). Another 34 haplotypes showed nominal significant association with the NSCP risk among Chinese (P < 0.05). However, none of these haplotypes reached pre-defined statistical significance level after Bonferroni correction (P>3.47×10-4).@*CONCLUSION@#This study failed to observe any statistically significant associations between haplotypes of seven WNT signaling pathway genes and the risk of NSOC among Chinese. Further studies are warranted to replicate the findings here.

Exploring the association between de novo mutations and non-syndromic cleft lip with or without palate based on whole exome sequencing of case-parent trios / 北京大学学报(医学版)

OBJECTIVE@#To explore the association between de novo mutations (DNM) and non-syndromic cleft lip with or without palate (NSCL/P) using case-parent trio design.@*METHODS@#Whole-exome sequencing was conducted for twenty-two NSCL/P trios and Genome Analysis ToolKit (GATK) was used to identify DNM by comparing the alleles of the cases and their parents. Information of predictable functions was annotated to the locus with SnpEff. Enrichment analysis for DNM was conducted to test the difference between the actual number and the expected number of DNM, and to explore whether there were genes with more DNM than expected. NSCL/P-related genes indicated by previous studies with solid evidence were selected by literature reviewing. Protein-protein interactions analysis was conducted among the genes with protein-altering DNM and NSCL/P-related genes. R package "denovolyzeR" was used for the enrichment analysis (Bonferroni correction: P=0.05/n, n is the number of genes in the whole genome range). Protein-protein interactions among genes with DNM and genes with solid evidence on the risk factors of NSCL/P were predicted depending on the information provided by STRING database.@*RESULTS@#A total of 339 908 SNPs were qualified for the subsequent analysis after quality control. The number of high confident DNM identified by GATK was 345. Among those DNM, forty-four DNM were missense mutations, one DNM was nonsense mutation, two DNM were splicing site mutations, twenty DNM were synonymous mutations and others were located in intron or intergenic regions. The results of enrichment analysis showed that the number of protein-altering DNM on the exome regions was larger than expected (P < 0.05), and five genes (KRTCAP2, HMCN2, ANKRD36C, ADGRL2 and DIPK2A) had more DNM than expected (P < 0.05/(2×19 618)). Protein-protein interaction analysis was conducted among forty-six genes with protein-altering DNM and thirteen genes associated with NSCL/P selected by literature reviewing. Six pairs of interactions occurred between the genes with DNM and known NSCL/P-related genes. The score measuring the confidence level of the predicted interaction between RGPD4 and SUMO1 was 0.868, which was higher than the scores for other pairs of genes.@*CONCLUSION@#Our study provided novel insights into the development of NSCL/P and demonstrated that functional analyses of genes carrying DNM were warranted to understand the genetic architecture of complex diseases.

Predicting prolonged length of intensive care unit stay via machine learning / 北京大学学报(医学版)

OBJECTIVE@#To construct length of intensive care unit (ICU) stay (LOS-ICU) prediction models for ICU patients, based on three machine learning models support vector machine (SVM), classification and regression tree (CART), and random forest (RF), and to compare the prediction perfor-mance of the three machine learning models with the customized simplified acute physiology score Ⅱ(SAPS-Ⅱ) model.@*METHODS@#We used medical information mart for intensive care (MIMIC)-Ⅲ database for model development and validation. The primary outcome was prolonged LOS-ICU(pLOS-ICU), defined as longer than the third quartile of patients' LOS-ICU in the studied dataset. The recursive feature elimination method was used to do feature selection for three machine learning models. We utilized 5-fold cross validation to evaluate model prediction performance. The Brier value, area under the receiver operation characteristic curve (AUROC), and estimated calibration index (ECI) were used as perfor-mance measures. Performances of the four models were compared, and performance differences between the models were assessed using two-sided t test. The model with the best prediction performance was employed to generate variable importance ranking, and the identified top five important predictors were pre-sented.@*RESULTS@#The final cohort in our study consisted of 40 200 eligible ICU patients, of whom 23.7% were with pLOS-ICU. The proportion of the male patients was 57.6%, and the age of all the ICU patients was (61.9±16.5) years.Results showed that the three machine learning models outperformed the customized SAPS-Ⅱ model in terms of all the performance measures with statistical significance (P < 0.01). Among the three machine learning models, the RF model achieved the best overall performance (Brier value, 0.145), discrimination (AUROC, 0.770) and calibration (ECI, 7.259). The calibration curve showed that the RF model slightly overestimated the risk of pLOS-ICU in high-risk ICU patients, but underestimated the risk of pLOS-ICU in low-risk ICU patients. Top five important predictors for pLOS-ICU identified by the RF model included age, heart rate, systolic blood pressure, body tempe-rature, and ratio of arterial oxygen tension to the fraction of inspired oxygen(PaO2/FiO2).@*CONCLUSION@#The RF algorithm-based pLOS-ICU prediction model had a best prediction performance in this study. It lays a foundation for future application of the RF-based pLOS-ICU prediction model in ICU clinical practice.

Prediction of intensive care unit readmission for critically ill patients based on ensemble learning / 北京大学学报(医学版)

OBJECTIVE@#To develop machine learning models for predicting intensive care unit (ICU) readmission using ensemble learning algorithms.@*METHODS@#A publicly accessible American ICU database, medical information mart for intensive care (MIMIC)-Ⅲ as the data source was used, and the patients were selected by the inclusion and exclusion criteria. A set of variables that had the predictive ability of outcome including demographics, vital signs, laboratory tests, and comorbidities of patients were extracted from the dataset. We built the ICU readmission prediction models based on ensemble learning methods including random forest, adaptive boosting (AdaBoost), and gradient boosting decision tree (GBDT), and compared the prediction performance of the machine learning models with a conventional Logistic regression model. Five-fold cross validation was used to train and validate the prediction models. Average sensitivity, positive prediction value, negative prediction value, false positive rate, false negative rate, area under the receiver operating characteristic curve (AUROC) and Brier score were used as performance measures. After constructing the prediction models, top 10 predictive variables based on importance ranking were identified by the model with the best discrimination.@*RESULTS@#Among these ICU readmission prediction models, GBDT (AUROC=0.858) had better performance than random forest (AUROC=0.827), and was slightly superior to AdaBoost (AUROC=0.851) in terms of AUROC. Compared with Logistic regression (AUROC=0.810), the discrimination of the three ensemble learning models was much better. The feature importance provided by GBDT showed that the top ranking variables included vital signs and laboratory tests. The patients with ICU readmission had higher mean arterial pressure, systolic blood pressure, diastolic blood pressure, and heart rate than the patients without ICU readmission. Meanwhile, the patients readmitted to ICU experienced lower urine output and higher serum creatinine. Overall, the patients having repeated admissions during their hospitalization showed worse heart function and renal function compared with the patients without ICU readmission.@*CONCLUSION@#The ensemble learning based ICU readmission prediction models had better performance than Logistic regression model. Such ensemble learning models have the potential to aid ICU physicians in identifying those patients with high risk of ICU readmission and thus help improve overall clinical outcomes.

Prevalence and risk factors of osteoarthritis in patients with type 2 diabetes in Beijing, China from 2015 to 2017 / 北京大学学报(医学版)

OBJECTIVE@#To explore the prevalence and related factors of osteoarthritis in patients with type 2 diabetes mellitus, and provided a scientific basis for the prevention of the comorbidity.@*METHODS@#The data were obtained from the database of all designated medical institutions in Beijing from 2015 to 2017. Data of the adult patients with type 2 diabetes mellitus were collected for descriptive analysis, and a Logistic regression model was used to explore the related factors of osteoarthritis in the patients with type 2 diabetes mellitus.@*RESULTS@#A total of 1 046 264 diagnosed type 2 diabetes mellitus adult patients were included in our study, with an average age of 63.07 years, and 50.78% were males. Among the patients with type 2 diabetes mellitus, there were 341 561 cases with osteoarthritis, and the prevalence of osteoarthritis was 32.65%. The prevalence of females (38.05%) was higher than that of males (27.41%), and the difference was statistically significant (P < 0.05). Osteoarthritis occurred in all age groups among the patients with type 2 diabetes mellitus, with the highest prevalence of osteoarthritis in the age group of 65-69 years (36.76%), and the lowest prevalence in the age group ≤44 years (14.3%). Before the age of 70, the prevalence increased with age. Further analysis of related factors for osteoarthritis in the patients with type 2 diabetes mellitus showed that female (OR=1.62, 95%CI: 1.61-1.63), age (OR=1.01, 95%CI: 1.01-1.01), had other comorbidities (OR=1.19, 95%CI: 1.18-1.21), used hypoglycemic drugs (OR=0.79, 95%CI: 0.78-0.80), having the cardiovascular disease (OR=1.13, 95%CI: 1.11-1.15), having cerebrovascular disease (OR=1.25, 95%CI: 1.23-1.28), and having nephropathy (OR=1.61, 95%CI: 1.51-1.71) were associated with the osteoarthritis in the type 2 diabetic mellitus patients.@*CONCLUSION@#Our study revealed that the prevalence of osteoarthritis in patients with type 2 diabetes mellitus is high in Beijing area. Health education and disease monitoring should be strengthened in middle-aged and elderly patients. Screening for comorbidities should be carried out as soon as possible, with the focus on menopausal women.

Evaluating the effect of WNT pathway genes considering interactions on the risk of non-syndromic oral clefts among Chinese populations / 北京大学学报(医学版)

OBJECTIVE@#In this study, we used genome-wide association study (GWAS) data to explore whether WNT pathway genes were associated with non-syndromic oral clefts (NSOC) considering gene-gene interaction and gene-environment interaction.@*METHODS@#We conducted the analysis using 806 non-syndromic cleft lip with or without cleft palate (NSCL/P) case-parent trios and 202 non-syndromic cleft palate (NSCP) case-parent trios among Chinese populations selected from an international consortium established for a GWAS of non-syndromic oral clefts. Genotype data and maternal environmental exposures were collected through DNA samples and questionnaires. Conditional Logistic regression models were adopted to explore gene-gene interaction and gene-environment in teraction using trio package in R software. The threshold of significance level was set as 3.47×10-4 using Bonferroni correction.@*RESULTS@#A total of 144 single nucleotide polymorphisms (SNPs) in seven genes passed the quality control process in NSCL/P trios and NSCP trios, respectively. Totally six pairs of SNPs interactions showed statistically significant SNP-SNP interaction (P < 3.47×10-4) after Bonferroni correction, which were rs7618735 (WNT5A) and rs10848543 (WNT5B), rs631948 (WNT11) and rs556874 (WNT5A), and rs631948 (WNT11) and rs472631 (WNT5A) among NSCL/P trios; rs589149 (WNT11) and rs4765834 (WNT5B), rs1402704 (WNT11) and rs358792 (WNT5A), and rs1402704 (WNT11) and rs358793 (WNT5A) among NSCP trios, respectively. In addition, no significant result was found for gene-environment interaction analysis in both of the NSCL/P trios and NSCP trios.@*CONCLUSION@#Though this study failed to detect significant association based on gene-environment interactions of seven WNT pathway genes and the risk of NSOC, WNT pathway genes may influence the risk of NSOC through potential gene-gene interaction.

Application of the China-PAR stroke risk equations in a rural northern Chinese population / 北京大学学报(医学版)

OBJECTIVE@#To validate five-year risk prediction models for stroke in a contemporary rural Northern Chinese population.@*METHODS@#Totally 6 483 rural adults aged 40 to 79 years without cardiovascular diseases were enrolled at baseline between June and August 2010, and followed up through January 2017. Expected prediction risk using the China-PAR (prediction for atherosclerotic cardiovascular disease risk in China) stroke risk equations were compared with the new Framingham stroke risk profile (FSRP). The recalibrated models were applied by adjusting the five-year baseline survival rate and the mean score to our rural northern Chinese population, while keeping other coefficient parameters the same as the original models. Kaplan-Meier analysis was used to obtain the observed event (nonfatal or fatal stroke) rate for the five years, and the expected-observed ratios were calculated to evaluate overestimation or underestimation in the cohort. The models were assessed by discrimination C statistic, calibration χ2, and calibration charts and plots for illustration as well.@*RESULTS@#Over an average of (5.83 ± 1.14) years of the follow-up in this validation cohort with 6 483 rural Chinese participants, 438 subjects deve-loped a first stroke event. Recalibrated China-PAR stroke risk equations and FSRP well-performed for predicting five-year stroke risk in men, and had C statistics of 0.709 (95%CI, 0.675 - 0.743) and 0.721 (95%CI, 0.688 - 0.754), with calibration χ2 values being 5.7 (P = 0.770) and 13.6 (P = 0.137), respectively. However, both China-PAR and FSRP overestimated stroke events by 11.6% and 30.0% in women, and had C statistics of 0.713 (95%CI, 0.684-0.743) and 0.710 (95%CI, 0.679-0.740), respectively. Calibration χ2 values in women were 12.5 (P = 0.188) for China-PAR and 24.0 (P = 0.004) for FSRP. In addition, the calibration charts and plots illustrated good agreement between the observations and the predictions only in the China-PAR stroke risk equations, especially for men.@*CONCLUSION@#In this validation cohort of rural northern Chinese adults, the China-PAR models had better performance of five-year stroke risk prediction than the FSRP, indicating that recalibrated China-PAR stroke risk equations might be appropriate tools for risk assessment and primary prevention of stroke in China.

Association of obesity and brachial-ankle pulse wave velocity among type 2 diabetes patients / 中华疾病控制杂志

Objective The aim of this study was to investigate associations of overall obesity (OO) and abdominal obesity (AO) with brachial-ankle pulse wave velocity (baPWV) among type 2 diabetes(T2DM) patients. Methods A community-based study for T2DM patients was conducted in rural communities in Beijing．Every patient completed a questionnaire to collect demography, lifestyle and diseases history, and underwent physical examinations, baPWV assessments and blood biochemical tests. Multivariate linear regression was used to assess the relationship between obesity index and baPWV. Abnormal baPWV was defined as patients with baPWV≥1,700 cm/s. Logistic regression model was performed to explore the risk of abnormal baPWV after adjusting for poetential confounders step by step. Results A total of 2 048 T2DM patients were recruited. The average age was (59.2±8.3) years and total prevalence of abnormal baPWV was 49.7%. After multivariable adjustment, linear regression showed that there was a negative correlation between body mass index(BMI) and baPWV and a positive correlation between waist-to-hip ratio (WHR) and baPWV. Compared to normal weight group, those with BMI≥28 kg/m2 had lower risk of abnormal baPWV (OR=0.59, 95% CI: 0.44-0.78，P<0.001), but there was an increased risk of 46% among patients with obesity in WHR (OR=1.46, 95% CI:1.07-2.00，P=0.018). Compared to those without OO and AO, patients without OO but with AO had a 1.67-fold increasesd risk of abnormal baPWV (OR=1.67, 95% CI: 1.19-2.35，P=0.003). Conclusions Abdominal obesity is related with arterial stiffnening among T2DM patients, and it is critical to evaluate arterial stiffness of T2DM patients with abdmonal obesity and normal BMI in order to reduce future risk of cardiovascular diseases.

Associations between sleep duration and different ischemic stroke subtypes / 中华疾病控制杂志

Objective To explore the relationship between sleep duration and different ischemic stroke (IS) subtypes. Methods Participants in the study were recruited from rural communities in Beijing. The survey questionnaires, physical examination and biochemical tests were performed. Sleep duration was categorized into 5 groups, namely ≤5 hours/day, 6 hours/day (5.5-6.5 h/d), 7 hours/day (6.5-7.5 h/d), 8 hours/day (7.5-8.5 h/d) and ≥9 hours/day(≥8.5 h/d). Classification of ischemic stroke was based on Trial of org 10172 in acute stroke treatment(TOAST)classification. Logistic models were used to evaluate the associations between sleep duration and different IS subtypes. Results A total of 6 370 participants were recruited. The average age was (58.34±9.37) years old. Logistic regression analysis showed that after adjusting for age, sex, behavioral lifestyle, socioeconomic status and health status, compared to subjects with 7 hours/day, subjects with sleep duration ≤5 hours/day was significantly associated with increased risk of IS (OR=1.75, 95% CI: 1.42-2.15, P<0.001), large-artery atherosclerosis (OR=1.98, 95% CI:1.46-2.70, P<0.001), small-artery occlusion lacunar (OR=5.73, 95% CI:3.34-9.83, P<0.001) and stroke of undetermined etiology (OR=4.43, 95% CI:1.86-10.53, P=0.001). Subjects with sleep duration 8 hours/day and ≥9 hours/day was only found to be significantly associated with IS and large-artery atherosclerosis (P<0.05). Conclusions Short sleep duration is associated with increased risk of IS, large-artery atherosclerosis, small-artery occlusion lacunar and stroke of undetermined etiology. But long sleep duration is only associated with increased risk of IS and large-artery atherosclerosis.

Effectiveness of different screening strategies for primary prevention of cardiovascular diseases in a rural northern Chinese population / 北京大学学报(医学版)

OBJECTIVE@#To estimate the potential health benefit of screening strategies for cardiovascular diseases primary prevention in a rural northern Chinese population.@*METHODS@#A total of 6 221 adults aged 40-74 years old, from rural Beijing, China and free from cardiovascular diseases at baseline were included. The following screening strategies were compared: Strategy 1, the strategy based on numbers of risk factors recommended by the Chinese Guideline for Prevention of Cardiovascular Diseases in people aged 40-74; Strategy 2, screening people aged 40-74 based on the Prediction for Atherosclerotic Cardiovascular Disease Risk in China (China-PAR) risk prediction model; Strategy 3, screening people aged 50-74 using the China-PAR risk prediction model. Participates who were classified into medium- or high-risk by the corresponding strategies would be introduced to lifestyle intervention, while high risk population would take medication in addition. Markov model was used to compare the potential health benefits within 10 years in each scenario, which applied the parameters from this rural northern Chinese cohort, published literatures, meta-analyses and systematic reviews, clinical trials and other cohort studies of Chinese population. Quality-adjusted life year (QALY) gained, cardiovascular diseases (CVD) events/deaths could be prevented and number needed to be screened (NNS) per QALY gained/per CVD event prevented/per CVD death prevented were calculated to compare the effectiveness. One-way sensitivity analysis concerning uncertainty of cardiovascular disease incidence rate and probabilistic sensitivity analysis about the uncertainty of hazard ratios were conducted.@*RESULTS@#Compared with non-screening strategy, the potential health benefits of each strategy were: Strategy 1 would gain QALY of 498 (95%CI: 103-894) and prevent 298 (95%CI: 155-441) CVD events; Strategy 2 would gain QALY of 691 (95%CI: 233-1 149) and prevent CVD events of 374 (95%CI: 181-567); Strategy 3 would gain QALY of 654 (95%CI: 199-1 108) and prevent CVD events of 346 (95%CI: 154-538). Screening strategy based on ChinaPAR risk prediction model (strategy 2 or 3) would be generally better in terms of QALY gained, CVD events/deaths prevented and NNS than the strategy based on numbers of CVD risk factors (all P<0.05 except NNS per QALY gained and NNS per CVD event prevented in 40-74 years). Similar benefits were obtained for the strategy 2 and 3. The results were consistent in the sensitivity analyses on the parameters of incidence rates and hazard ratios.@*CONCLUSION@#Screening people to target increased risks of cardiovascular diseases in this rural northern Chinese population is necessary. Screening strategy based on China-PAR risk prediction model could gain more health benefits than that based on numbers of CVD risk factors.

Application of support vector machine in predicting in-hospital mortality risk of patients with acute kidney injury in ICU / 北京大学学报(医学版)

OBJECTIVE@#To construct an in-hospital mortality prediction model for patients with acute kidney injury (AKI) in intensive care unit (ICU) by using support vector machine (SVM), and compare it with the simplified acute physiology score II (SAPS-II) which is commonly used in the ICU.@*METHODS@#We used Medical Information Mart for Intensive Care III (MIMIC-III) database as data source. The AKI patients in the MIMIC-III database were selected according to the 2012 Kidney Disease: Improving Global Outcomes (KDIGO) definition of AKI. We employed the same predictor variable set as used in SAPS-II to construct an SVM model. Meanwhile, we also developed a customized SAPS-II model using MIMIC-III database, and compared performances between the SVM model and the customized SAPS-II model. The performance of each model was evaluated via area under the receiver operation characteristic curve (AUROC), root mean squared error (RMSE), sensitivity, specificity, Youden's index and accuracy based on 5-fold cross-validation. The agreement of the results between the SVM model and the customized SAPS-II model was illustrated using Bland-Altman plots.@*RESULTS@#A total number of 19 044 patients with AKI were included. The observed in-hospital mortality of the AKI patients was 13.58% in MIMIC-III. The results based on the 5-fold cross validation showed that the average AUROC of the SVM model and the customized SAPS-II model was 0.86 and 0.81, respectively (The difference between the two models was statistically significant with t=13.0, P<0.001). The average RMSE of the SVM model and the customized SAPS-II model was 0.29 and 0.31, respectively (The difference was statistically significant with t=-9.6, P<0.001). The SVM model also outperformed the customized SAPS-II model in terms of sensitivity and Youden's index with significant statistical differences (P=0.002 and <0.001, respectively).The Bland-Altman plot showed that the SVM model and the customized SAPS-II model had similar mortality prediction results when the mortality of a patient was certain, but the consistency between the mortality prediction results of the two models was poor when the mortality of a patient was with high uncertainty.@*CONCLUSION@#Compared with the SAPS-II model, the SVM model has a better performance, especially when the mortality of a patient is with high uncertainty. The SVM model is more suitable for predicting the mortality of patients with AKI in ICU and early intervention in patients with AKI in ICU. The SVM model can effectively help ICU clinicians improve the quality of medical treatment, which has high clinical value.

CDH13 Genetic Polymorphisms, Adiponectin and Ischemic Stroke: a Chinese Family-based Sib-pair Study / 生物医学与环境科学（英文）

<p><b>OBJECTIVE</b>To understand the relationships between CDH13 (T-cadherin) genetic polymorphisms, adiponectin levels and ischemic stroke, and possible interactions between CDH13 polymorphisms and other risk factors.</p><p><b>METHODS</b>We recruited 342 Chinese ischemic stroke sib pairs. We genotyped rs4783244 and rs7193788 on CDH13 using time-of-flight mass spectrometry genotyping technology and measured total and high-molecular weight (HMW) adiponectin levels. We investigated associations between SNPs and ischemic stroke, and interactions between SNPs and other risk factors using multi-level mixed-effects regression model.</p><p><b>RESULTS</b>In individuals without ischemic stroke, CDH13 rs4783244 was associated with total adiponectin levels (per T: Coef = -0.257, P = 0.001). CDH13 rs7193788 was associated with total adiponectin levels (per A: Coef = -0.221, P = 0.001) and HMW adiponectin levels (per A: Coef = -0.163, P = 0.003). rs7193788 was significantly associated with ischemic stroke (GA/AA vs. GG: OR = 1.55, 95% CI: 1.07 to 2.24, P = 0.020) after Bonferroni correction (α = 0.025). There was an interaction between rs7193788 and diabetes (P = 0.036). Compared to diabetes-free individuals with rs7193788 GG genotype, diabetes patients with rs7193788 GA/AA genotypes had higher risks for ischemic stroke (OR = 2.64, 95% CI: 1.58-4.40, P < 0.001).</p><p><b>CONCLUSION</b>CDH13 genetic polymorphisms are associated with adiponectin levels and ischemic stroke. An interaction is found between CDH13 SNP and diabetes for ischemic stroke.</p>

Application of prism alternate cover test and perimeter strabismometry in strabismic operation / 国际眼科杂志(Guoji Yanke Zazhi)

AlM:To discuss the application of prism alternate cover test ( PACT) and perimeter strabismometry in strabismic operation.METHODS: A total of 145 patients with concomitant esotropia or exotropia, aging 2 ~ 50 years old, were included. They were examined by PACT and perimeter strabismometry before operation. The strabismic operations were performed, the orthotropia rate of postoperation was assessed.RESULTS:Using PACT and perimeter strabismometry, there was a significantly difference of deviating angle ( P0. 05) in moderate strabismic group. The functional cure rate of postoperation was respectively 70. 83%, 67. 01%; the clinical cure rate was 20. 84%, 24. 74%; invalid rate was 8. 33%, 8. 25% .CONCLUSlON: The application of PACT and perimeter strabismometry in strabismic operation design, referring to the eye axial length, this can be helpful of improving the cure rate postoperation and decreasing the danger of reopreation.

Profile and Correlates of Health-related Quality of Life in Chinese Patients with Coronary Heart Disease / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Although coronary heart disease (CHD) is one of the major cardiovascular diseases, risk factors associated with the health-related quality of life (HRQoL) of CHD patients remain unclear. The present study was designed to determine the profile and significant factors of the HRQoL in CHD patients.</p><p><b>METHODS</b>A cross-sectional study was conducted in rural communities of Fangshan District, Beijing, China. Socio-demographic, lifestyle, and comorbidity information of CHD patients were collected by a structured questionnaire and medical records. HRQoL was measured using European Quality of Life 5-dimensions (EQ-5D) scale and EQ Visual Analog Scale (EQ-VAS). Multiple linear and logistic regressions were performed to explore the association of potential risk factors with HRQoL scores and each EQ-5D, respectively.</p><p><b>RESULTS</b>Totally, 1928 CHD patients (mean age 61.64 ± 9.24 years; female:male = 2.4:1) were enrolled in the study. The mean score of EQ-5D index and EQ-VAS were 0.889 ± 0.172 and 71.56 ± 17.65, respectively. Multiple linear regression revealed that marital status, physical activity, moderate alcohol drinking, and family's population were positive independent correlates of EQ-VAS, whereas diabetes mellitus and stroke were negative independent correlates (all P < 0.05). Age and stroke were negatively while physical activity, moderate alcohol drinking, family's population and household income were positively correlated with EQ-5D index (all P < 0.05) independently. In addition, each of the five HRQoL dimensions had various specific determinants, including obesity, underweight, smoking or education.</p><p><b>CONCLUSIONS</b>Findings of the study highlight certain socio-demographic, lifestyle factors, and comorbid stroke or diabetes mellitus as correlates of HRQoL in Chinese CHD patients. Large-scale cohort studies should be carried out to confirm our results in the future.</p>

The impact of lipid-metabolizing genetic polymorphisms on body mass index and their interactions with soybean food intake: a study in a Chinese population / 生物医学与环境科学（英文）

<p><b>OBJECTIVE</b>To evaluate the association of known polymorphisms in the lipid metabolic pathway with body mass index (BMI), and estimate their interactions with soybean food intake.</p><p><b>METHODS</b>A community-based cross-sectional survey was conducted in a Chinese Han population. BMI, soybean food intake, and single nucleotide polymorphisms of rs599839, rs3846662, rs3846663, rs12916, rs174547, rs174570, rs4938303, and rs1558861 were measured in 944 subjects. A multivariate logistic regression was used to analyze the association of the studied polymorphisms with BMIs. The expectation-maximization algorithm was employed to evaluate the extent of linkage disequilibrium between pairwise polymorphisms. The gene-environment interaction was assessed in the general multifactor dimensionality reduction model.</p><p><b>RESULTS</b>The polymorphisms of rs3846662 and rs3846663 were associated with 10% highest BMIs when comparing to the 10% lowest values both in individuals and haplotype-based association tests. Although no statistically significant gene-environment interactions were found, people with the haplotype composed of C allele in rs3846662 and T allele in rs3846663 and low frequency of soybean intake had significantly higher risk to overweight and obesity as compared with those with the haplotype consisting of T allele in rs3846662 and C allele in rs3846663 and highly frequent soybean food intake, with an odds ratio of 1.64 (95% confidence interval: 1.15-2.34, P<0.01) after adjusting for the common confounders.</p><p><b>CONCLUSION</b>Our study has suggested that rs3846662 and rs3846663 may be the potential candidate polymorphisms for obesity, and their effect on the pathogenesis could be mediated by the frequency of soybean food intake.</p>

Methodological quality of Meta-analyses regarding studies related to genetic association on papers published in Chinese journals / 中华流行病学杂志

Objective To assess the methodological quality of Meta-analyses on papers published in Chinese journals regarding studies on genetic association.Methods Meta-analyses of genetic association study published in Chinese journals up to December 2012 had been searched through on 4 Chinese electronic databases (China biomedicine database,CNKI,Wanfang database and VIP Information).Articles independently selected by both two researchers under definite inclusion and exclusion criteria were included in this study (with consultation on a third researcher if inconsistent opinions existed).A Measurement Tool for the Assessment of Multiple Systematic Reviews (AMSTAR) checklist was used to evaluate the methodological quality together with the methodological quality score being calculated.Results Totally,440 articles were included in this study,with mean score of the methodological quality score (maximum score is 11) as 5.77.Among the 440 articles,none had met the requirement of total 11 items in AMSTAR,with 89.5％ and 38.6％ of them had a priori design or duplicate study selection and data extraction.72.7％ of them performed a comprehensive literature search and 14.8％ included studies regardless of their publication status.10.9％ and 92.5％ of them provided a list of including or excluding studies or stated characteristics of the included ones.32.0％ of them assessed the scientific quality of those included studies,with 50.0％ of them mentioned their qualities when formulating the conclusions.93.2％ of them used appropriate methods to combine data while 82.3％ assessed the likelihood of publication bias.0.5％ of them declared the conflict of interests.Conclusion Our results from Meta-analyses showed an acceptable quality regarding their methodology related to genetic association on papers being published in Chinese journals.Improvement is needed especially on aspects as:selection of studies,data extraction,publication status with list of inclusion and exclusion,quality assessment and declaration on conflict of interests,etc.