Objectives To assess the associations of sensitisation to common allergens with atopic dermatitis, allergic rhinitis and allergic asthma in adults. Design Case–control study. Setting Data were collected from the First Affiliated Hospital of Harbin Medical University in Harbin, China. Participants Cases were 5111 patients with physician-diagnosed atopic dermatitis (n=2631), allergic asthma (n=1320) and allergic rhinitis (n=1160) recruited from the department of allergy from March 2009 to December 2017. Controls were 2576 healthy adults who underwent physical examination at the same hospital during the same period. Main outcome measures Specific IgE levels to 16 common food, indoor and outdoor allergens were assessed in all participants. Adjusted ORs and 95% CIs for the association between allergen sensitisation and allergic diseases were estimated using multivariate logistic regression. Results The prevalence of allergen sensitisation was higher in patients with atopic dermatitis (indoor=17.14%, outdoor=12.85%, food=21.44%), allergic rhinitis (indoor=23.18%, outdoor=26.81%, food=8.94%) and allergic asthma (indoor=24.65%, outdoor=16.46%, food=14.31%) compared with controls (indoor=11.03%, outdoor=6.84%, food=5.83%). After adjustment for potential confounding variables, there was a dose–response relevance between the levels of allergen-specific IgE and allergic diseases (p trend <0.0001). The number of allergens to which a patient was sensitised increased the risk of allergic diseases (atopic dermatitis: highest adjusted OR=4.28, 95% CI 2.57 to 7.11; allergic rhinitis: highest adjusted OR=13.00, 95% CI 3.76 to 45.00; allergic asthma: OR=2.37, 95% CI 1.67 to 3.37). Conclusion There was a dose–response relevance between levels of allergen-specific IgE and allergic diseases’ prevalence, and multiple sensitisations increased the risk of allergic diseases. This study provides evidence for the prophylaxis of allergic diseases.

BACKGROUND:Although Henoch-Schönlein purpura nephritis (HSPN) is characterized by glomerular deposition of aberrantly glycosylated immunoglobulin A1 (IgA1), the underlying mechanism of HSPN progression has not yet been completely elucidated. In this study, we integrated transcriptomic and proteomic analyses to explore the underlying mechanism of HSPN progression.METHODS:RNA sequencing and tandem mass tag- (TMT-) based quantitative proteomics were used to gain serum transcriptomic and proteomic profiles of patients with different types of HSPN (3 × type 1, 3 × type 2, and 3 × type 3). Student's t-tests were performed to obtain the significance of the differential gene expression. The clusterProfiler package was used to conduct the functional annotation of the DEGs for both Gene Ontology terms and Kyoto Encyclopedia of Genes and Genomes pathways.RESULTS:A total of 2315 mRNAs and 30 proteins were differentially expressed between the different types of HSPN. 58 mRNAs and one protein changed continuously during HSPN development and are potential biomarkers for HSPN progression. The validation cohort (another 9 patients) confirmed the high-throughput results of the transcriptomic and proteomic analyses. A total of 385 significant pathways were related to HSPN progression, and four of them were closely related to clinical biochemical indicators and may play an important role in the progression of HSPN. Those pathways reveal that HSPN progression may be related to the inhibition of inflammation, promotion of apoptosis, and repair of renal injury.CONCLUSIONS:Four pathways were found to be closely related to HSPN progression, and it seems that HSPN progression is mainly due to the inhibition of inflammation, promotion of apoptosis, and repair of renal injury.

目的 探索基于压缩感知理论变量筛选方法在小样本量蛋白质组学研究中应用的效果和特点,为小样本量的蛋白质组学的变量筛选提供更灵敏、可靠的方法.方法 模拟实验比较基于CS理论的变量筛选方法与偏最小二乘(PLS)及随机森林(RF)筛选变量的能力,通过灵敏度、特异度及平衡准确度评价其变量筛选效果;利用CS变量筛选方法筛选非小细胞肺癌两亚型组(腺癌和鳞状细胞癌)的差异蛋白.结果 模拟实验表明,CS理论的变量筛选方法在样本量较小时具有较好的变量筛选效果,灵敏度、特异度及平衡准确度均较高;利用基于CS理论的变量筛选方法筛选,获得肺腺癌和鳞状细胞癌间差异表达蛋白22种,被证明是肺腺癌和鳞状细胞癌间有差异的蛋白为:Cytokeratin 6A、Cytokeratin 6B、Cytokeratin 6C、PKP1、P63、MCT1.结论 基于CS理论的变量筛选方法在样本量特别少时,筛选变量的效果优于PLS和RF,更适用于小样本蛋白质组学数据变量筛选研究.

目的 建立权重概率主成分分析模型,通过模拟实验进行模型评价,选择最优模型进行代谢组学数据分析,为代谢组学数据分析提供降噪优化的分析方法.方法 使用折刀抽样法计算变量载荷的置信区间和变异系数,利用变量载荷的变异信息设计倒数式、开根式、对数式三种加权方式进行原始数据中的变量加权,结合概率主成分分析模型建立权重概率主成分分析模型;通过模拟实验从第一主成分载荷的估计和预测效能进行模型评价,选择最优权重概率主成分分析模型;绘制代谢组学数据主成分得分图,利用中心距离比较权重概率主成分分析模型与概率主成分分析模型在可视化分组效果.结果 倒数式加权概率模型在第一主成分载荷的估计和模型预测方面优于另外两种权重概率模型.在可视化方面,权重概率主成分分析不仅缩小了模型估计的不确定性,而且增大组间的中心距离.结论 构建了权重概率主成分分析模型,不仅结果解释和可视化优于概率主成分分析模型,而且为差异变量的筛选提供了一个较小的参考范围.

Objective This paper aims to identify differentially expressed metabolites between patients of purpura ne-phritis and those with anaphylactoid purpura.Methods Four ranked lists from Student’s t test,Wilcoxon rank sum test,partial least square,and the random forest,respectively,are aggregated to get a combined single ranking list for identifying differentially expressed variables between groups.The ranking aggregation model was cross-validated and compared with the Least absolute shrinkage and selection operator(LASSO)model using simulation,and then applied to an real dataset,in which the ability of i-dentifying differentially expressed metabolites between patients of purpura nephritis and those with anaphylactoid purpura were compared between these two methods.Results The simulation experiment shows that:(1)when the number of observations and differential variables are small,the average area under the curve(AUC)value from the rank aggregation model is greater than that from LASSO;(2)when the number of observations and differential variables are larger,two AUCs are similar to each other;(3) no matter how the parametersare set,the number of differential variables selected by the rank aggregation model is basically less than that selected by LASSO.The real dataset analysis finds that 12 differential variables in patients with purpura nephritis are i-dentified to be differentially expressed as compared with patients with anaphylactoid purpurausing the rank aggregation model, with the AUC reaching its highest value of 0. 96.Conclusion Comparing with the LASSO model,the rank aggregation model is more reliable and accurate when being used to select differentially expressed variables,which may provide us with a new idea in metabolomics data analysis.

Objective To evaluate the trend of catastrophic health expenses (CHE) for inpatient care in relation to the commencement of the New Cooperative Medical Scheme (NCMS) in rural China from 2003 to 2013, and the roles of NCMS in protecting affected households from CHE. Methods We assessed the 10-year trend of the incidence and severity of CHE in rural households with hospitalised members using data from the Chinese National Health Services Survey. Generalised estimating equations were used to estimate the OR and 95% CI of the association between incidence rates of CHE (RCHE) and NCMS reimbursement. Results The incidence and severity of CHE after NCMS reimbursement both decreased and their changes increased rapidly from 2003 to 2013. After adjustment of the covariates, RCHE before reimbursement was significantly higher than that after reimbursement, and the OR (95% CI) was 1.50 (1.24 to 1.81), 1.79 (1.69 to 1.90) and 2.94 (2.77 to 3.11) in 2003, 2008 and 2013, respectively. Conclusion The incidence and severity of CHE both reduced after NCMS reimbursements in each year. Excluding some confounding factors, RCHE was significantly associated with NCMS reimbursement. NCMS partly protected the rural households with hospitalised members from CHE. However, the inequalities between different income groups still existed. RCHE in rural households with hospitalised members was still rather high in 2003, 2008 and 2013 even though they were covered by NCMS. This study will provide suggestions for further reforms in China and guidance for other low-income/middle-income countries.

To assess the associations of obesity with newly diagnosed and previously known atopic disorders in Chinese adults. 4,629 adults aged 18 years or older were recruited in Harbin, China. Among them, 1,114 were previously diagnosed atopic cases, 1,298 were newly diagnosed cases, and 2,217 non-atopic controls. Obesity and overweight are defined according to the criteria established by the Working Group on Obesity in China. The associations of obesity with known and newly diagnosed atopic disorders were assessed using logistic regressions. Obesity was significantly associated with known atopic disorders (adjusted OR =2.41 (95% CI:1.81, 3.22)). The association of obesity with newly diagnosed atopic cases was not as strong as that with known cases, and was not statistically significant (adjusted OR=1.27 (95% CI: 0.94, 1.72)). The similar pattern was observed in different allergic diseases, gender and age stratifications. The association between overweight and atopic diseases were not significant. Obesity is strongly associated with previously diagnosed atopic cases but not so with newly diagnosed atopic cases in Chinese adults. It is likely that people with atopic disorders have a higher risk of developing obesity. Our findings are important for the management of atopic disorders and chronic disease prevention among atopic disease patients.

代谢组学的概念自20世纪90年代被正式提出[1],已被广泛应用于医学研究领域,其一般研究流程包括样本采集、样本检测、数据预处理、数据分析和生物学解释等.常用的样本检测技术有核磁共振(nuclear magnetic resonance,NMR)和高分辨率色谱-质谱联用技术[2],本文所述方法针对后者.经色谱-质谱联用平台检测的数据具有以下特点:高维度,小样本,变量间高度相关,高噪声,高缺失,以及高度变异性.基于以上数据特征,在代谢组学数据分析之前需要对数据进行预处理[3],以消除或减小数据中高噪声、高缺失和高度变异性对统计分析结果的干扰.数据预处理是数据分析的前提,有利于统计分析过程的多变量模型构建;若数据未经过充分预处理而直接用于统计分析,可能会掩盖数据中某些真实特征(如组间差异),使研究结果模糊化.数据预处理包括缺失数据处理,数据标准化,以及数据的中心化、标度化和转换等内容.本文将全面介绍基于色谱-质谱联用平台的代谢组学数据预处理方法,并进行各方法比较,为研究者选择合适的数据预处理方法提供思路.

Background: The relationship between physical activity (PA) and bone health is well known, but the role of lean mass (LM) and fat mass (FM) in this relationship remains uncertain. Therefore, the aim of this study was to examine the mediating effect of LM and FM on the relationship between PA and bone mineral density (BMD) in postmenopausal women. Materials and Methods: This cross-sectional study involved 282 postmenopausal women aged between 50 and 65 year, who were randomly selected from Hongqi community of Harbin City in China. PA was measured using an International PA Questionnaire. Body composition, BMD of the lumbar spine, hip, and total body were measured using dual-energy X-ray absorptiometry. Mediation analysis was performed to investigate the mediating effect of LM and FM on the relationship between PA and BMD. Results: In partial correlation analysis, PA, LM, and FM were positively related to BMD. Positive correlation was found between PA and LM. There were significant differences in BMD between different categories of PA, but the differences disappeared after adjusting for LM. Mediation analysis showed that LM and FM played a mediating role in the relationship between PA and BMD. LM appeared to mediate the effect of BMD in the spine, hip, and total body by 26.91%, 19.55% and 47.98%, respectively; and FM was 22.23%, 27.97%, and 33.02%, respectively. Conclusion: LM and FM affected the relationship between PA and BMD as mediator. Postmenopausal women with high LM and FM had more BMD.

Objective To compare the effect of one cross-validation and multiple cross-validations on PLSDA optimal model and discuss the effect of multiple cross-validations on stability of the optimal model when a few individuals are wrong grouped and when all individuals are right grouped,respectively.Methods The order of individuals in one dataset was disor-ganized to perform multiple cross-validations.Simulative data and real data were analyzed using one cross-validation and multiple cross-validations.The variation and stability of the models were tested using parameters like principal component number and MSEP.Results For simulative data,the principal component number of one cross-validation is 3 and MSEP is 0.3792;for re-sult of 5000 cross-validations when the data is not disordered,the range of principal component number is 2~6 and the range of MSEP is 0.2569~0.5794;for result of 5000 cross-validations when the data is 5%disordered,the range of principal component number is 1 ~8 and the range of MSEP is 0.2061 ~0.6463;for result of 10000 times cross-validation of real data,the range of principal component number is 4~10 and the range of MSEP is 0.0802 ~0.3761.Conclusion PLSDA models built by one cross-validation are not stable whereas multiple cross-validations can help build PLSDA models more stably when a few individ-uals are wrong grouped.So multiple cross-validation is recommended to ensure the stability of PLSDA model.

Background In children with Henoch-Schonlein purpura (HSP), the severity of Henoch-Schonlein purpura nephritis (HSPN) is considered responsible for the prognosis of HSP. The pathological process from HSP to HSPN is not clear yet and current diagnostic tools have shortcomings in accurate diagnosis of HSPN. This study aims to assess clinical characteristics of HSP and HSPN, to identify metabolic perturbations involved in HSP progress, and to combine metabolic biomarkers and clinical features into a better prediction for HSPN. Methods A total of 162 children were recruited, including 109 HSP patients and 53 healthy children (HC). The clinical characteristics were compared between HSPN and HSP without nephritis (HSPWN). The serum metabonomics analysis was performed to determine the metabolic differences in HSP and HC. Results Among 109 HSP children, 57 progressed to HSPN. The increased D-dimer level was significantly associated with renal damage in HSP. The metabonomic profiles revealed alterations between various subgroups of HSP and HC, making it possible to investigate small-molecule metabolites related to the pathological process of HSP. In total, we identified 9 biomarkers for HSP vs. HC, 7 for HSPWN vs. HC, 9 for HSPN vs. HC, and 3 for HSPN vs. HSPWN. Conclusions (S)-3-hydroxyisobutyric acid, p-Cresol sulfate, and 3-carboxy-4-methyl-5-pentyl-2-furanpropanoic acid were found associated with the progress of HSP to HSPN. Moreover, resulting biomarkers, when combined with D-dimer, allowed improving the HSPN prediction with high sensitivity (94.7%) and specificity (80.8%). Together these findings highlighted the strength of the combination of metabonomics and clinical analysis in the research of HSP.

The objective of this study is to examine the effect of milk powder supplementation with different calcium contents on bone mineral density (BMD) in postmenopausal Chinese women, and to determine a more appropriate dose of calcium supplementation. A 2-year, randomized controlled double-blind trial. Postmenopausal women (n = 210) aged 50-65 years were recruited and assigned randomly into three calcium supplementation groups. All participants received milk powder supplementation with different calcium contents (300, 600, and 900 mg per day for groups A, B, and C, respectively) and all groups received 800 IU of vitamin D per day. During the follow-up period, BMD of the left hip and lumbar spine (as the main indicator) was measured using dual-energy X-ray absorptiometry at the baseline, 1 and 2 years. Both three BMD measures and the changes of BMD over 2 years were used to analyze. Before adjusting for covariates, BMD in group A of the lumbar spine and groups A and B of greater trochanter decreased significantly from the baseline over time but increased significantly in the rest groups of the lumbar spine and greater trochanter and in three groups of Ward's triangle. There were significant differences across the three groups for changes of BMD in the greater trochanter and Ward's triangle. When adjusting for covariates, there were significant decreases with time in group A of the spine (P = 0.001), groups A and B of greater trochanter (P = 0.0002 and P = 0.04, respectively) and increases in groups B and C of Ward's triangle (P = 0.03 and P = 0.004, respectively). BMD change in the greater trochanter was significantly different among three groups. For healthy postmenopausal women, high calcium milk powder supplementation was better in retarding bone loss than medium and low calcium in the greater trochanter. Considering the dietary calcium intake of postmenopausal women in north of China, a dose of 900 mg/day is considered as the most appropriate calcium supplementation for greater trochanter but not for other sites.

Objective The aim of this study is to assess the associated factors of Henoch-Schonlein purpura( HSP) in Chinese children. This study has important public implications for developing strategies of preventing HSP. Methods In this hospital-based, case-control study, we recruited 353 HSP cases and 61 control participants during 2012 and 2015. We collected related information of 414 HSP in children and the control group through questionnaires. Student's t-test, Pearson Chi-square test and Wilcoxon test were used respectively to compare the difference between the case and control group; We applied logistic re-gression model to analyze the associated factors of HSP in children. Results Univariate analysis revealed that the differences in age, mother and father's level of education were significant between the case and control group. Univariate analysis also revealed that the differences in diet regularity, eating cold, fried and spicy food, meat, drinks, milk and dairy products, fruits and vege-tables between the two groups were statistically significant. Similarly, the differences in way of birth, breast-feeding, mixed feed-ing and mother contacting harmful substances before becoming pregnant between the two groups were statistically significant. After the adjustment of age, sex and mother's level of education, multivariate Logistic regression demonstrated that living in rural are-as, the enough sleep time, consumption frequencies of fruit, sweet and meat and mother's level of education were protective fac-tors for HSP in children. Multivariate Logistic regression also demonstrated that mixed feeding, feeding after chewing, illness during pregnancy, and consumption frequencies of cold, spicy food and nuts were the risky factors for HSP. Conclusion Suffi-cient sleep time, less cold and spicy food and plenty of meat and fruit can reduce the risk of HSP in children. Advocating breast-feeding, avoid feeding after chewing can also prevent children from HSP.

Background: It is unclear whether the relationship between cigarette smoking and atopy is mediated by body fat mass, such as the Body Mass Index (BMI). We assessed the mediating role of BMI on the relationship between smoking and atopy in Chinese adults. Methods: A hospital-based case-control study of 786 atopic cases and 2771 controls was conducted in adults aged 18 years or older from March 2010 to September 2014 in Harbin, China. Mediation models were used to estimate the indirect effects of smoking on atopic sensitization through BMI. Results: Compared to non-smokers, light smokers and moderate smokers had a lower risk of inhalant allergen sensitization. The indirect effect of smoking and sensitization to aeroallergens were only observed in light smokers (point estimate, −0.026; 95% CI, −0.062 to −0.004). The mediating roles of BMI on the relationships between smoking and other types of allergic sensitization were not statistically significant. Conclusion: BMI appeared to partially mediate the effect of light smoking on sensitization to aeroallergens. However, considering the other harmful health effects of cigarette smoking, the effective method to lower the incidence of atopy would be to decrease body fat mass by physical exercise and employing other more healthy ways of living rather than smoking.