Screening of key genes and pathway and analytical research of traditional Chinese medicines for primary immune thrombocytopenia based on bioinformatics analysis / 中国免疫学杂志

Objective:To preliminarily screen the key genes of primary immune thrombocytopenia(ITP)by bioinformatics method and explore the pathogenesis,so as to predict the potential traditional Chinese medicine(TCM)for the treatment of ITP.Methods:Based on the original microarray data set GSE80401 under the National Center for Biotechnology Information(NCBI),the differential miRNA of ITP were obtained by analyzing the adjusted P<0.05 and |logFC|≥1 as the screening criteria for differential miRNA.miRTarBase,miRDB and TargetScan were used to predict miRNA target genes.The target of ITP was searched in Genecards database,and the predicted up-regulated target genes and down-regulated target genes were intersected with disease targets.On this basis,the mapped target genes were respectively constructed into PPI network through String database and Cytoscape to screen core target genes,and the core target genes were enriched and analyzed in DAVID and Omicsbean databases for GO and KEGG pathways.The key genes were imported into the Coremine Medical database to analyze the TCM for the treatment of key genes.Results:Total of 422 differential genes and 17 key genes were finally screened,including BCL2L1,CCND1,CD44,CDKN1A,CREB1,GRB2,MAPK1,MAPK8,PIK3R1,CDK2,CAV1,FGF2,IGF1,SMAD2,SMAD4,TLR4 and VEGFA,mainly involving proteoglycan,FoXO,PI3K-Akt,human T cell leukemia virus 1 infection,endocrine resistance,focal adhesion and other signal pathways.A total of 12 TCM for ITP prevention and treatment,including ginseng,Radix Paeoniae Rubra,Angelica sinensis,bee venom,cobra,Psoralea corylifolia,Rehmannia glutinosa,buffalo horn,hemp seed,dodder seed,Wulingzhi and Jinji NaPi were screened.TLR4 maps the most TCM,followed by CCND1 and VEGFA.Among many TCM,ginseng acts on 17 targets at the same time,Radix Paeoniae Rubra,Angelica sinensis and bee venom act on 11 targets at the same time,cobra and Psoralea corylifolia act on 9 and 8 targets at the same time,Rehmannia glutinosa and buffalo horn act on 7 targets at the same time,hemp seed act on 4 targets at the same time,dodder seed act on 3 targets at the same time,and wulingzhi act on 2 targets at the same time.It is suggested that these drugs had the potential of multi-target prevention and treatment of ITP.Conclusion:The key pathogenic genes of ITP and the TCM with preventive and thera-peutic effects could be preliminarily predicted based on the analysis of genetic information,which can provide targets and research ideas for the development of related TCM.

iTRAQ-based Proteomic Analysis of Serum Differential Proteins from Henoch-Schönlein Purpura Patients Before and After Qishun Baolier Treatment / 中国实验方剂学杂志

ObjectiveHenoch-Schönlein purpura（HSP） is one of the dominant diseases in Mongolian medicine. Qishun Baolier（QSBLE）， as the main prescription for the treatment of HSP， has significant clinical effect， but its mechanism is not yet clear. Baed on this， this study is intended to screen the differentially expressed proteins before and after treatment， and preliminarily explore the molecular mechanism of QSBLE in the treatment of HSP. MethodTaking oneself as the control， 30 HSP patients aged 6-45 years were collected， and QSBLE was taken orally at 12：00 and 24：00， respectively. The dose was adjusted according to age and the course of treatment was one week. The distribution of proteinuria， hematuria and skin purpura of all patients were determined before and after treatment. The serum samples of 10 patients with clinically significant remission after QSBLE treatment were randomly selected for proteomics. Isobaric tags for relative and absolute quantification（iTRAQ） combined with liquid chromatography tandem mass spectrometry（LC-MS/MS） was used to analyze the proteins in serum of HSP patients before and after treatment， and differential proteins were analyzed bioinformatically and the protein-protein interaction（PPI） networks were constructed. ResultA total of 378 proteins were identified from serum， including 18 differentially expressed proteins， of which 15 proteins were up-regulated and 3 proteins were down regulated. Bioinformatics showed that the differential proteins were mainly involved in biological processes such as immune response， immunoglobulin production， phagocytosis， adaptive immune response before and after treatment. Biological processes， pathways and proteins were used to construct the PPI network， the proteins represented by immunoglobulin heavy constant γ1（IGHG1）， immunoglobulin λ-chain 7-43（IGLV7-43）， gelsolin（GSN） and 60 kDa heat shock protein（HSPD1） were involved in biological processes and related pathways such as adaptive immune response， immunoglobulin production， leukocyte-mediated immunity， regulation of stress response， regulation of immune system processes， regulation of trauma response， and these proteins were at the center of the PPI network. ConclusionQSBLE may play a role in the treatment of HSP by regulating the expression of IGHG1， IGLV7-43， GSN， HSPD1 and other key proteins to affect immune-related biological processes.

Combined Effects of Family History of Cardiovascular Disease and Serum C-reactive Protein Level on the Risk of Stroke: A 9.2-year Prospective Study among Mongolians in China / 生物医学与环境科学（英文）

<p><b>OBJECTIVE</b>We aimed to evaluate the combined effect of a family history of cardiovascular disease (CVD) and high serum C-reactive protein (CRP) on the stroke incidence in an Inner Mongolian population in China.</p><p><b>METHODS</b>A prospective cohort study was conducted from June 2002 to July 2012, with 2,544 participants aged 20 years and over from Inner Mongolia, China. We categorized participants into four groups based on the family history of CVD and CRP levels.</p><p><b>RESULTS</b>We adjusted for age; sex; smoking; drinking; hypertension; body mass index; waist circumference; and blood glucose, triglycerides, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol levels. Compared with the group with no family history of CVD/low CRP levels, the group with family history of CVD/high CRP levels had a hazard ratio (HR) of 1.78 [95% confidence interval (CI), 1.03-3.07; P = 0.039] of stroke, and an HR of 2.14 (95% CI, 1.09-4.20; P = 0.027) of ischemic stroke. The HRs of hemorrhagic stroke for the other three groups were not statistically significant (all P > 0.05).</p><p><b>CONCLUSION</b>Participants with both a family history of CVD and high CRP levels had the highest stroke incidence, suggesting that high CRP levels may increase stroke risk, especially of ischemic stroke, among individuals with a family history of CVD.</p>

Combined effects of both cardiovascular disease family history and smoking on the incidence of ischemic stroke / 中华流行病学杂志

<p><b>OBJECTIVE</b>To investigate the cumulative effect regarding the family history of cardiovascular disease and smoking on ischemic stroke events in population with Mongolian ethnicity.</p><p><b>METHODS</b>Based on data gathered from the baseline investigation, a 10-year prospective cohort follow-up project was conducted among 2 589 participants with Mongolian ethnicity. Ischemic stroke events were defined as the outcomes of the study. All the 2 589 participants were categorized into four subgroups: without family history of cardiovascular disease/nonsmokers, without family history of cardiovascular disease/smokers, with family history of cardiovascular disease/nonsmokers and with family history of cardiovascular disease/smokers, according to family history of cardiovascular disease and smoking status. Cumlative incidence rates of events among the four subgroups was described with Kaplan-Meier curves. Cox proportional hazards model was used to estimate the hazard ratios (HRs) and 95% confidence intervals (95%CI) of ischemic stroke events among the four subgroups.</p><p><b>RESULTS</b>Data from the Kaplan-Meier curves showed that the cumulative incidence rates of ischemic stroke were 1.17% (15/1 278), 3.83% (37/967), 5.70% (9/158) and 8.33% (15/180) for the groups of no family history of cardiovascular disease/nonsmokers, no family history of cardiovascular disease/smokers, with family history of cardiovascular disease/nonsmokers and with family history of cardiovascular disease/smokers, respectively. By cox proportional hazards model, after adjusting for age, male, drinking status, systolic and diastolic blood pressure, body mass index, fasting glucose, total cholesterol, triglycerides, LDL cholesterol factors, the HRs (95% CI) of ischemic stroke were 2.26 (1.19-4.28) and 2.45 (1.13-5.33) in the no family history of cardiovascular disease/smokers group, with family history of cardiovascular disease/smokers group when compared to the no family history of cardiovascular disease/nonsmokers group, respectively. The risk of ischemic stroke appeared the highest in the group with family history of cardiovascular disease/smokers (all P<0.05).</p><p><b>CONCLUSION</b>Smoking may increase the risk of ischemic stroke events among the population with family history of cardiovascular disease.</p>

C-reactive Protein Level, Apolipoprotein B-to-apolipoprotein A-1 Ratio, and Risks of Ischemic Stroke and Coronary Heart Disease among Inner Mongolians in China / 生物医学与环境科学（英文）

<p><b>OBJECTIVE</b>We aimed to investigate the cumulative effect of high CRP level and apolipoprotein B-to-apolipoprotein A-1 (ApoB/ApoA-1) ratio on the incidence of ischemic stroke (IS) or coronary heart disease (CHD) in a Mongolian population in China.</p><p><b>METHODS</b>From June 2003 to July 2012, 2589 Mongolian participants were followed up for IS and CHD events based on baseline investigation. All the participants were divided into four subgroups according to C-reactive protein (CRP) level and ApoB/ApoA-1 ratio. Cox proportional hazard models were used to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs) for the IS and CHD events in all the subgroups.</p><p><b>RESULTS</b>The HRs (95% CI) for IS and CHD were 1.33 (0.84-2.12), 1.14 (0.69-1.88), and 1.91 (1.17-3.11) in the 'low CRP level with high ApoB/ApoA-1', 'high CRP level with low ApoB/ApoA-1', and 'high CRP level with high ApoB/ApoA-1' subgroups, respectively, in comparison with the 'low CRP level with low ApoB/ApoA-1' subgroup. The risks of IS and CHD events was highest in the 'high CRP level with high ApoB/ApoA-1' subgroup, with statistical significance.</p><p><b>CONCLUSION</b>High CRP level with high ApoB/ApoA-1 ratio was associated with the highest risks of IS and CHD in the Mongolian population. This study suggests that the combination of high CRP and ApoB/ApoA-1 ratio may improve the assessment of future risk of developing IS and CHD in the general population.</p>

Interaction and relationship between angiotensin converting enzyme gene and environmental factors predisposing to essential hypertension in Mongolian population of China / 生物医学与环境科学（英文）

<p><b>OBJECTIVE</b>To investigate the association of specific functional gene ACE (I/D) variants of the renin-angiotensin system with essential hypertension (EH) and interaction between ACE (I/D) gene and risk factors for EH in a genetically homogenous Mongolia rural population of China.</p><p><b>METHODS</b>Individuals (n=1099) were recruited from general population of Kezuohouqi Banner in Inner Mongolian Autonomous Region.</p><p><b>RESULTS</b>The association was found between ACE genotype DD plus ID and EH, with an interaction between ACE genotype DD plus ID and cigarette smoking in an additive model. Cigarette smoking index and ACE gene showed a low exposure-gene (LEG) effect on EH, with interaction indices from 7.10 to 1.16. Interaction between ACE genotype DD plus ID and alcohol drinking on EH appeared an additive model. Alcohol drinking index and ACE gene showed a low exposure-gene (LEG) effect on EH, with interaction indices from 1.66 to 1.09. BMI and ACE gene showed a low exposure-gene (LEG) effect on EH, with interaction indices from 6.15 to 2.49. Interactions between ACE genotype and WHR on EH showed a multiplicative model. In a short,there was an interaction between ACE gene and cigarette smoking, alcohol drinking and BMI on EH, especially in a low dose-exposure effect</p><p><b>CONCLUSION</b>It is important for individuals who carry ACE D allele gene to prevent EH, and furthermore, to prevent and control coronary heart disease, in a view of population-based prevention.</p>