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Background Cyclophilin B (CypB) has been found overexpressed in various malignant tumors. To date, there are few studies on CypB in colon cancer. In this study, we aimed to analyze the CypB expression pattern and to further evaluate its clinical significance, especially its prognostic value for colon cancer. Methods CypB expression was investigated in colon cancer tissue microarrays (TMA) by RNAscope in situ hybridization and immunohistochemical (IHC) staining. The correlation between CypB and clinicopathological characteristics was analyzed. The Cancer Genome Atlas (TCGA) RNA-seq dataset of colon adenocarcinoma (COAD) was further analyzed to validate our main findings. Gene Set Enrichment Analysis (GSEA) and Search Tool for the Retrieval of Interacting Genes (STRING) analysis were performed to enrich CypB related biological pathways. In vitro experiments by knockdown of CypB in colon cancer cell HCT116 were performed to verify the bioinformatics results and analyze its role in the metastatic pathways in colon cancer. Results We found that CypB expression was highly upregulated in colon cancer tissues (P

Background The serum isocitrate dehydrogenase 1(IDH1) level is significantly elevated in patients with non-small cell lung cancer (NSCLC) and has important clinical value as a marker for early diagnosis. This study examined the dynamic changes of serum IDH1 levels of patients with NSCLC undergoing surgery or medical treatment, to evaluate its potential prognostic value. Methods The study cohort included 83 NSCLC patients who underwent surgery, 37 NSCLC patients who underwent medical treatment, 50 healthy controls, and 52 disease controls. Serum levels of IDH1 were assayed by enzyme-linked immunoassay. Tumor biomarkers including carcinoembryonic antigen, squamous cell carcinoma, neuron-specific enolase, CYFRA21-1, and pro-gastrin-releasing peptide—which are currently used in clinical practice—were measured by automatic immunoanalyzers. Results Serum IDH1 was significantly higher in patients with NSCLC compared with healthy people or patients with benign lung diseases ( p < 0.001). The area under the receiver operating characteristic curve for diagnosis and differential diagnosis were 0.897 and 0.879, respectively, which were superior to the five tumor markers. Serum IDH1 levels decreased in most patients after surgery, with the most dramatic changes in patients with stage I tumors compared with stage II and III. Analyses of changes in the serum IDH1 level of patients after receiving chemotherapy or targeted therapy revealed that for patients with progressive disease, serum IDH1 increased significantly after treatment; for patients with partial response or stable disease, it decreased steadily. Conclusion IDH1 has potential prognostic value and may be used as a marker for the monitoring of treatment efficacy.

BackgroundYoung lung cancer as a small subgroup of lung cancer has not been fully studied. Most of the previous studies focused on the clinicopathological features, but studies of molecular characteristics are still few and limited. Here, we explore the characteristics of prognosis and variation in young lung cancer patients with NSCLC.MethodsA total of 5639 young lung cancer samples (NSCLC, age ≤40) were screened from the SEER and the same number of the old (NSCLC, age ≥60) were screened by propensity score matching to evaluate the prognosis of two groups. 165 treatment-naïve patients diagnosed with NSCLC were enrolled to explore the molecular feature difference between two age-varying groups. CCLE cell line expression data was used to verify the finding from the cohort of 165 patients.ResultsThe overall survival of the young lung cancer group was significantly better than the old. Germline analysis showed a trend that the young group contained a higher incidence of germline alterations. The TMB of the young group was lower. Meanwhile, the heterogeneity and evolutionary degrees of the young lung cancer group were also lower than the old. The mutation spectrums of two groups exhibited variance with LRP1B, SMARCA4, STK11, FAT2, RBM10, FANCM mutations, EGFR L858R more recurrent in the old group and EML4-ALK fusions, BCL2L11 deletion polymorphism, EGFR 19DEL, 20IN more recurrent in the young group. For the base substitution, the young showed a lower fraction of transversion. Further, we performed a pathway analysis and found the EGFR tyrosine kinase inhibitor resistance pathway enriched in the young lung cancer group, which was validated in gene expression data later.ConclusionsThere were significantly different molecular features of the young lung cancer group. The young lung cancer group had a more simple alteration structure. Alteration spectrums and base substitution types varied between two groups, implying the different pathogenesis. The young lung cancer group had more potential treatment choices. Although young lung patients had better outcomes, there were still adverse factors of them, suggesting that the young group still needs more caution for treatment choice and monitoring after the treatment to further improve the prognosis.

AZD9291 (osimertinib) is the third-generation EGFR-TKI treat for EGFR mutated NSCLC patients. Despite its encouraging efficacy in clinical, acquired resistance is still inevitable. The mechanism of drug resistance needs to be further explored. In a previous study, we established an AZD9291-resistant cell strain named HCC827/AZDR. We found that insulin-like growth factor binding protein 7 (IGFBP7) expression was markedly increased in HCC827/AZDR cells and AZD9291-resistant patients by RNA sequencing and immunohistochemical analysis, respectively. Reduced IGFBP7 in HCC827/AZDR cells by si-RNA interference recovered the sensitivity to AZD9291 partially and increased AZD9291-induced cell apoptosis. Enhancing IGFBP7 expression in EGFR-mutated non-small cell lung cancer (NSCLC) cells using lentiviruses infection reduced their sensitivity to AZD9291. This study is the first to discover that high IGFBP7 expression could occur following treatment with AZD9291. This might be one of the mechanisms underlying AZD9291 resistance and a potential therapeutic target following AZD9291 resistance.

The number of service offerings in cloud manufacturing continues to grow, so that service level agreement (SLA) within cloud manufacturing is increasingly used to ensure the coordination of the cro...

Background Multiple meta-analyses have reported inflammatory bowel diseases (IBD) are associated with an increased risk of diverse diseases, but the evidence quality remains unclear. Objectives We aimed to summarize and evaluate this existing evidence on the associations between IBD and a range of diseases a-crossed from meta-analyses. Methods PubMed, the Cochrane Library Database, Embase, Web of Science, CNKI Databases, Wanfang Databases and VIP Database were searched to obtain eligible literatures from inception to November 1, 2019. We appraised the methodological quality of the included meta-analyses using AMSTAR 2 tool, and evaluated the quality of evidence for each outcome using the GRADE approach. Results Nineteen articles covering associations between IBD and 28 types of health outcomes were included. The methodological quality of meta-analyses was rated moderate for 5.26%, low for 21.05%, and critically low for 73.68%. Overall, summary effect estimates were significant in 26 meta-analyses. The evidence quality was rated high for 3.57%, moderate for 21.43%, low for 28.57%, and very low for 46.43%. Evidence quality was high for association between IBD and an increased periodontitis risk (OR = 4.55; 95% CI, 3.00-6.19). Evidence quality was moderate for associations between IBD and an increased thyroid cancer risk (OR = 1.75; 95% CI, 1.48–2.07), myocardial infarction incidence (RR = 1.12; 95% CI, 1.05–1.21), preterm birth incidence (OR = 1.85; 95% CI, 1.67–2.05), stillbirth incidence (OR = 1.57; 95% CI, 1.03–2.38), gallstone disease prevalence (OR = 1.72; 95% CI, 1.40–2.12), and vitamin D deficiency prevalence (OR = 1.64; 95% CI, 1.30–2.08). Conclusions Though, associations between IBD and diverse diseases have been extensively studied, few of the reported associations have robust support. Further well-designed studies are essential to determine whether IBD increases the risk of other diseases.

ObjectiveNumerous meta-analyses have revealed the association between gastro-oesophageal reflux disease (GORD) and a range of diseases; however, the certainty of the evidence remains unclear. This study aimed to summarise and assess the certainty of evidence derived from meta-analyses.MethodsEmbase, PubMed, Web of Science, Cochrane Databases of Systematic Reviews, CNKI and Wangfang databases from their inception to 22 February 2020 were queried for systematic reviews and meta-analyses on the association between GORD and various diseases. The methodological quality of the included studies was assessed using A Measurement Tool to Assess Systematic Reviews 2 (AMSTAR 2), and evidence certainty was evaluated using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) system. Statistical analysis was conducted using Stata V.15.ResultsTen publications with associations between GORD and different types of diseases were included. There was high heterogeneity (I2 >75%) among seven independent meta-analyses. Evidence for publication bias in two independent meta-analyses was also observed. According to the AMSTAR 2 approach, the methodological quality was high for 20% of meta-analyses, moderate for 10%, low for 40% and critically low for 30%. Based on GRADE approach, the certainty of evidence was high for the association between GORD and higher risk of chronic obstructive pulmonary disease (COPD) exacerbation (OR 5.37; 95% CI 2.71 to 10.64) and higher prevalence of oesophageal adenocarcinoma (OR 4.57; 95% CI 3.89 to 5.36), and it was moderate for the association between GORD and higher chronic rhinosinusitis prevalence (OR 2.16; 95% CI 1.37 to 3.48).ConclusionThe association between GORD and a range of diseases was extensively studied, and our findings revealed a high certainty of evidence of the association between GORD and an increased risk of COPD exacerbation as well as increased prevalence of oesophageal adenocarcinoma. Further investigations using systematic reviews and meta-analyses of high methodological quality that include prospective large cohort studies and adjusted confounders are warranted.PROSPERO registration numberCRD42019122264.

Objective Systematic reviews and meta-analyses have revealed the associations between H. pylori infection and various health outcomes. We aimed to evaluate the strength and breadth of evidence on the associations. Design Umbrella review of systematic reviews and meta-analyses. Setting No settings. Participants No patients involved. Data sources Embase, PubMed, Web of Science, Cochrane Library Databases, CNKI, VIP database and Wangfang database from inception to February 1, 2019. Outcomes measures Diverse diseases (such as cancer and ischaemic heart disease). Results Sixty articles reporting 88 unique outcomes met the eligible criteria. 74 unique outcomes had nominal significance (p75%). Moreover, 20% exhibited publication bias (p

Due to high fuel efficiency and environmental friendliness combined cooling, heating and power (CCHP)-based microgrids (MGs) become much more popular. To reduce the total operating costs of CCHP-based MG cluster, an incentive-based multi-energy trading mechanism is proposed to facilitate multi-energy trading among independent CCHP-based MG operators (CMGOs). Motivated by the mechanism, multi-energy trading is carried out among a number of neighboring CMGOs. In practice, CMGOs may belong to different economic entities. Besides, there is usually no coordination center. Therefore, a fully decentralized distributed solution based on the alternating direction method of multipliers decomposition technique is proposed. Especially, to achieve fair benefit allocation, a novel index termed as contribution rate is first proposed to identify CMGO’s contributions to multi-energy trading. Then, asymmetric Nash bargaining theory is used to determine the benefits obtained by each CMGO. Besides, a payment chain is designed to implement the benefit allocation mechanism proposed in this paper. Each CMGO gets the corresponding benefits according to their contribution rates. The simulation results demonstrate the effectiveness of the proposed mechanism.

Many studies reported that toll-like receptors (TLRs) played an important role in the process of ischemic stroke (IS). However, the impact of TLR5 rs5744174 on stroke risk, gene expression and on inflammatory cytokines, and lipid levels in ischemic stroke patients has not yet been reported and was therefore the subject of this study. In this case-control study, a total of 816 ischemic stroke patients and 816 healthy controls were genotyped using Sequenom MassArray technology. The mRNA expression of TLR5 was detected through quantitative real-time PCR among 52 ischemic stroke patients. The levels of IL-1b, IL-6, IL-8, and TNFα were measured by ELISA among 62 IS patients. Total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) were determined among 816 IS patients using a Hitachi 7600 Automatic Biochemistry Analyzer. Our result showed TLR5 rs5744174 polymorphism was not associated with stroke risk, TLR5 mRNA expression and inflammatory cytokines of IS patients (P > 0.050), but was significantly associated with HDL-C (recessive model: β = - 0.14, 95 % CI: -0.24 to -0.03, P = 0.009). TLR5 rs5744174 polymorphism may have no impact on the stroke risk, gene expression and inflammatory cytokines, but may influence the HDL-C serum level of IS patients in Chinese Han population.

ObjectiveSystematic reviews and meta-analyses have revealed the associations betweenH. pyloriinfection and various health outcomes. We aimed to evaluate the strength and breadth of evidence on the associations.DesignUmbrella review of systematic reviews and meta-analyses.SettingNo settings.ParticipantsNo patients involved.Data sourcesEmbase, PubMed, Web of Science, Cochrane Library Databases, CNKI, VIP database and Wangfang database from inception to February 1, 2019.Outcomes measuresDiverse diseases (such as cancer and ischaemic heart disease).ResultsSixty articles reporting 88 unique outcomes met the eligible criteria. 74 unique outcomes had nominal significance (p2=50%–75%) and 24 had high heterogeneity (I2>75%). Moreover, 20% exhibited publication bias (pH. pyloriinfection may be associated with an increased risk of five diseases and a decreased risk of irritable bowel syndrome.ConclusionAlthough 60 meta-analyses explored 88 unique outcomes, moderate quality evidence only existed for six outcomes with statistical significance.H. pyloriinfection may be associated with a decreased risk of irritable bowel syndrome and an increased risk of hypertriglyceridemia, chronic cholecystitis and cholelithiasis, gestational diabetes mellitus, gastric cancer and systemic sclerosis.Trial registrationCRD42019124680.

Long noncoding RNAs (LncRNAs) have been reported to play vital roles in non-small cell lung cancer (NSCLC). Recently, LncRNA/VPS9D1-AS1 has been reported to be overexpressed in various cancers. In this study, we aimed to investigate its expression pattern and clinical significance and further evaluate its prognostic value for NSCLC. VPS9D1-AS1 expression was examined in 184 NSCLC patients using a highly sensitive in situ hybridization protocol (RNAscope), and the expression values were correlated with the clinicopathological features. Another cohort including 12 NSCLC patients was used to validate the differential expression of VPS9D1-AS1 by qRT-PCR. TCGA datasets were further used to validate the main findings. We found that the levels of VPS9D1-AS1 were significantly higher in cancer tissues than in paired normal tissues from both lung squamous cell carcinoma (SCC) and adenocarcinoma (ADC) (P 0.001). Importantly, the levels of VPS9D1-AS1 in patients with lung SCC were significantly higher than those in patients with lung ADC. The high levels of VPS9D1-AS1 were found to be associated with cancer lymph node metastasis (P = 0.020). Prognostic analysis revealed that the survival time for SCC patients with high levels of VPS9D1-AS1 was significantly shorter than that of patients with low levels of VPS9D1-AS1 (P = 0.007). Therefore, our findings suggest that the overexpression of VPS9D1-AS1 serves as a promising biomarker to predict the prognosis of NSCLC.

Background Serological antibodies tests for tuberculosis (TB) are widely used in developing countries. They appear to have some advantages- faster, simple and could be used for extrapulmonary TB. However, most of current commercial TB serological tests are failed to provide sufficient sensitivity and specificity. Improved serological biomarkers were essential. In this study, we present an approach using peptide array to discover new immunodiagnostic biomarkers based on immunodominant epitopes of TB antigens. Results The Probable conserved lipoprotein LppZ, which is difficult to express and purify in vivo was selected as the model antigen. We use two-step screening for dominant epitope selection. Based on peptide array data from 170 TB patients and 41 control samples, two dominant epitopes were identified to have diagnostic value for TB patients. Truncation assay was used to identify the core reactive sequence. Peptide- based ELISA was used to evaluate the diagnostic ability of pep-LppZ-1 and pep-LppZ-13. Pep-LppZ-1 has a sensitivity of 49.2% and a specificity of 83.3% in TB diagnose. Pep-LppZ-13 has a sensitivity of 43.3% and a specificity of 88.5% in TB diagnose. Conclusions Our result demonstrated that peptide array screening would be an advantage strategy of screening TB diagnostic peptides. Electronic supplementary material The online version of this article (10.1186/s12865-018-0243-2) contains supplementary material, which is available to authorized users.

The Supplementary Data. (DOCX 1919Â kb)

Advances in multiplex immunohistochemistry (IHC) techniques and digital pathology platforms allow quantification of multiple proteins at same tissue section and produce continuous data. TGF-β signaling plays crucial and complex roles in colorectal cancer (CRC). We here aimed to investigate clinical pathological relevant of proteins involved in TGF-β signaling at CRC tissues. Multiplex fluorescent IHC was used to quantitative analysis. The levels of eight proteins (TGF-β1, TGFBRI, TGFBRII, SMAD4, SMAD2/3, p-SMAD2/3, SMAD1/5/9, and p-SMAD1/5/9) were determined in TMA sections. Quantitative analysis was carried out by a scoring system by InForm software. It revealed that TGF-β signaling was hyper active. The levels of TGF-β1, TGFBRI, TGFBRII, SMAD4, SMAD1/5/9 and p-SMAD2/3 were significantly increased in cancer tissues when compared their levels in normal tissues. Furthermore, the levels of eight proteins in stroma were significantly lower than the levels that in cancer tissues. Clinical pathological relevant analysis exhibited that TGF-β signaling inclined to suppress the progression of tumor. SMAD1/5/9, TGFBRII, SMAD2/3 were confirmed as significant predictors for overall survival. In conclusion, we established a method based on multispectral imaging to extensively explore the clinical relevant of TGF-β signaling proteins. These results provided an opportunity to consider the novel application for proteins involving TGF-β signaling that used as diagnostic or prognostic biomarkers to conduct tumor therapy.

The tumor necrosis factor receptor-associated factor 6 (TRAF6) gene encodes a protein that acts downstream of the Toll-like receptor (TLR) pathway. TLRs activate inflammatory cascades and mediate inflammatory injury after cerebral ischemia. However, the role of TFAR6 gene polymorphisms in ischemic stroke (IS) remains unknown. This study aims to investigate the associations of TRAF6 gene polymorphisms with susceptibility to IS and IS-related quantitative traits in Southern Chinese Han population. A total of 816 IS cases and 816 age- and gender-matched controls were included. Two variants of the TRAF6 gene (rs5030411 and rs5030416) were genotyped using the Sequenom MassARRAY iPLEX platform. Our study showed that rs5030416 was significantly associated with increased susceptibility to IS in the additive model [ORadj 1.25(1.04–1.51), P adj = 0.019, P Bc = 0.038] and dominant model [ORadj 1.23(1.04–1.60), P adj = 0.021, P Bc = 0.042] after adjusting by age and sex and applying a Bonferroni correction. No significant association was found between rs5030411 and IS susceptibility (all P > 0.05). The haplotype rs5030416 (allele C)-rs5030411 (allele C) was significantly associated with IS susceptibility (P adj = 0.015). Moreover, a significant association of rs5030411 with TC levels in IS patients under the additive model [β 0.16(0.01–0.30), P adj = 0.034] and recessive model [β 0.45(0.12–0.78), P adj = 0.007] was observed after adjustment by age and sex. This association remained statistically significant under the recessive model (P Bc = 0.042) after Bonferroni correction. Our results suggest that TRAF6 gene polymorphisms may be involved in the pathogenesis of IS.

Lei Shen,1,* Xiaoguang Wu,2,* Jinjing Tan,1 Meng Gu,1 Yu Teng,1 Zitong Wang,3 Wentao Yue1,4 1Department of Cellular and Molecular Biology, Beijing Tuberculosis and Thoracic Tumor Research Institute, 2Department of Ward 2, 3Department of Thoracic Surgery, Beijing Chest Hospital, Beijing, 4Central Laboratory, Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Chaoyang, Beijing, People’s Republic of China *These authors contributed equally tothis work Purpose: This study aims to identify the clinical significance of serum autoantibodies against dickkopf-1 (DKK1) and evaluate their feasibility in the immunodiagnosis and prognosis of non-small cell lung cancer (NSCLC).Experimental design: Epitope mapping by peptide microarray-based serum screening of NSCLC patients (n=72) and healthy controls (n=16) was performed. Indirect ELISA with peptides was used to measure the serum levels of autoantibodies in 206 NSCLC patients and 99 healthy controls. A 3-year follow-up was monitored to evaluate the correlation between serological levels of autoantibodies and overall survival (OS) and progression-free survival (PFS).Results: Four highly reactive epitopes were identified, which included peptides 67–84 (PepA), 37–54 (Pep B), 145–156 (Pep C) and 247–261 (Pep D). The autoantibodies levels were considerably higher in sera of NSCLC patients compared with controls (P

A number of studies have assessed a relationship between the T102C polymorphism in the HTR2A gene with an increased risk of major depressive disorder (MDD), bipolar disorder (BPD), and schizophrenia (SCZ). However, the results have been inconsistent. Hence, we performed this study to further evaluate potential associations between the T102C polymorphism and MDD, BPD, and SCZ. The strength of separate associations between the T102C polymorphism and the risk of MDD, BPD, or SCZ was measured by ORs and 95% confidence intervals (CIs) in six genetic models. Cochran's chi-square-based Q-statistic and I(2) were used to evaluate the heterogeneity between studies. The funnel plot and the Egger's test were used to assess the publication bias. Cumulative meta-analysis was also performed to evaluate the trend in OR over time. No significant association was found in the overall analysis of MDD, BPD and SCZ with a sample size of 17,178 cases and 20,855 control subjects. In a further analysis by ethnicity, the OR and 95% CIs indicated the T102C polymorphism was not associated with MDD, BPD, or SCZ in Caucasian, Asian or Chinese populations. No publication bias was observed in the meta-analysis, and the cumulative analyses indicated the robust stability of the results. Thus, the results of our study indicate that the T102C polymorphism is not associates with increased susceptibility to MDD, BPD, and SCZ.

ObjectiveSchizophrenia (SCZ) and bipolar disorder (BD) are common psychotic disorders, which show some overlaps in genetic aetiology. Researchers have conducted a number of studies to investigate the relationship between SCZ and the 1354C/T genetic polymorphism of 5-hydroxytryptamine receptor 2A (HTR2A–1354C/T), as well as the associations between BD and the HTR2A–1354C/T polymorphism. However, the results were conflicting. To provide a more robust estimate about the effects of the HTR2A–1354C/T polymorphism on the risk of these two psychotic disorders, we performed this meta-analysis.MethodsWe used the pooled odds ratios (ORs) with 95% confidence intervals (95% CIs) to investigate the relationships between SCZ and the 1354C/T polymorphism of HTR2A, as well as the associations between BD and HTR2A–1354C/T. Publication bias was tested by Begg's test and inverted funnel plot, and heterogeneity was checked by Cochran's Q statistic and the inconsistency index (I2).ResultsEight studies were concerned with SCZ, analysing a cumulative total of 2953 cases and 3153 controls; six papers studied BD, using a total of 923 cases and 928 controls. There was no significant association found between HTR2A–1354C/T and SCZ in the overall population (T allele vs. C allele, OR = 1.035, 95% CI 0.912–1.175, p = 0.596) or in the subgroups Caucasian population and Asian population. Moreover, there was no significant association between the HTR2A–1354C/T polymorphism and BD in the overall population (T allele vs. C allele, OR = 1.038, 95% CI = 0.607–1.772, p = 0.892).ConclusionOn the basis of these results, the HTR2A–1354C/T polymorphism is unlikely to be a risk factor for SCZ and BD.

Ischemic stroke (IS) is a complex multifactorial inherited disease. Many studies have focused on the potential genetic effects of apolipoprotein E (ApoE) gene polymorphism on IS. However, inconsistencies still exist in the association of ApoE gene polymorphism with IS. The aim of this study was to investigate the ApoE gene polymorphism in relation to IS in the Guangxi Han populations and assess the risk of various ApoE genotypes associated with IS in Chinese populations. We conducted a case-control study involving a total of 166 IS cases and 192 healthy controls to investigate the association of ApoE gene polymorphism with IS in the Guangxi Han populations. Furthermore, we performed a meta-analysis to investigate whether the ApoE gene polymorphism is associated with IS in Chinese populations. There was no evidence for a significant association between ApoE gene polymorphism and IS in the Guangxi Han populations (ɛ2/ɛ2 vs. ɛ3/ɛ3: OR=1.25, 95% CI=0.08-20.17; ɛ2/ɛ3 vs. ɛ3/ɛ3: OR=1.49, 95% CI=0.79-2.79; ɛ2/ɛ4 vs. ɛ3/ɛ3: OR=1.25, 95% CI=0.17-9.00; ɛ3/ɛ4 vs. ɛ3/ɛ3: OR=1.10, 95% CI=0.60-2.04; ɛ4/ɛ4 vs. ɛ3/ɛ3: OR=2.50, 95% CI=0.22-27.87; allele ɛ2 vs. allele ɛ3: OR=1.39, 95% CI=0.80-2.44; allele ɛ4 vs. allele ɛ3: OR=1.16, 95% CI=0.68-1.98). In our meta-analysis, a significant association of ApoE gene polymorphism with IS was found in the genetic model of ɛ2/ɛ4 vs. ɛ3/ɛ3 (OR=2.04, 95% CI=1.45-2.85), ɛ3/ɛ4 vs. ɛ3/ɛ3 (OR=1.93, 95% CI=1.42-2.62), ɛ4/ɛ4 vs. ɛ3/ɛ3 (OR=3.41, 95% CI=2.17-5.34) and allele ɛ4 vs. allele ɛ3 (OR=2.34, 95% CI=1.91-2.86). However, no clear associations were found in the model of ɛ2/ɛ2 vs. ɛ3/ɛ3 (OR=1.56, 95% CI=0.90-2.71), ɛ2/ɛ3 vs. ɛ3/ɛ3 (OR=0.93, 95% CI=0.79-1.09) and allele ɛ2 vs. allele ɛ3 (OR=1.10, 95% CI=0.97-1.25). In conclusion, no association was found between ApoE gene polymorphism and IS in the Guangxi Han populations, while the results of the meta-analysis indicate that the ApoE mutation allele ɛ4 increases the risk of IS in Chinese populations.

Stroke is a multi-factorial disorder that has become the leading cause of death and disability worldwide. Previous studies reported that TLR7 mRNA expression is associated with poor outcome of ischemic stroke (IS). This study aimed to assess whether TLR7 mRNA expression affects IS occurrence, as well as the association of TLR7 rs2897827 with susceptibility to IS and TLR7 mRNA expression and serum apolipoprotein and lipid levels in a Chinese Han population. A total of 816 stroke patients and 816 healthy controls were included in this study. mRNA expression was determined by quantitative real-time PCR. The Sequenom MassARRAY iPLEX platform was used to genotype the TLR7 rs2897827 polymorphism. TLR7 mRNA expression of the IS cases was statistically significantly higher than that of the controls in the male or female group (male, P = 0.014; female, P = 0.025). In the male IS cases, TLR7 mRNA expression of the T allele carriers was statistically significantly higher than that of the C allele carriers (P = 0.018). However, a significant difference was not observed in the female cases (P = 0.545). In either the male or female group, the distribution of genotype or allele had no statistical significance (P > 0.050). The ApoA1 level of the T carriers was statistically significantly higher than the C carriers in males (t = -2.383, P = 0.020); however, the ApoB and lipid levels were not associated with rs2897827 (P > 0.050). In female patients, no significant difference was observed between different genotypic/allelic carriers in serum apolipoprotein and lipid levels (all P > 0.050). The expression of the TLR7 gene may affect IS occurrence. TLR7 gene rs2897827 may influence TLR7 mRNA expression and the plasma ApoA1 level in male IS patients.

Stroke is the second highest cause of morbidity and functional disability around the world. In addition, it is the second most common cause of death worldwide [ 1 ]. However, the genetic pathology of stroke is still unclear. Published data on the association between TNF-a 238G/A polymorphisms and ischemic stroke risk are inconsistent and controversial. To provide a more robust estimate about TNF-a 238G/A polymorphisms on the risk of ischemic stroke, we conducted this meta-analysis.We used the pooled odds ratios (ORs) with 95% confidence intervals (95%CIs) to investigate the relationship between TNF-α238G/A polymorphisms and ischemic stroke. Publication bias was tested by Begg's test and inverted funnel plot, and Heterogeneity was checked by Cochran's Q statistic and the inconsistency index (I(2)).There are 7 studies that include 1,766 cases and 1,560 controls in this meta-analysis. The results indicated a significant association between TNF-α238G/A polymorphisms and ischemic stroke in overall analysis, Caucasian and Adult. However, statistical association was not observed in Juvenile and Asian.This meta-analysis suggests that TNF-α238G/A polymorphisms increases the risk of ischemic stroke in Adult, Caucasian, and overall analysis. However, in Juvenile and Asian analysis, significant associations between TNF-α238G/A and ischemic stroke were not found.

Background Mitogen-activated protein kinase kinase 4 ( MAP2K4 ) gene acts as the direct upstream activator of c-Jun NH 2 -terminal kinase pathway, which plays an important role in regulating neuron survival and apoptosis in response to cerebral ischemia. However, the association between MAP2K4 gene polymorphisms and ischemic stroke (IS) has not yet been published. Therefore, this study investigates the association between MAP2K4 gene polymorphism rs3826392 and IS susceptibility, as well as its quantitative traits in Southern Chinese Han population. Methods A total of 816 Chinese patients with IS and 816 age- and sex-matched controls were recruited. Rs3826392 was genotyped using Sequenom MassARRAY iPLEX platform (Sequenom, San Diego, CA, USA). The mRNA expression of MAP2K4 gene in peripheral blood mononuclear cells was detected using reverse transcription-polymerase chain reaction. The levels of serum cytokines, including IL-1b, IL-6, IL-8, IL-12, and tumor necrosis factor-α (TNF-α), were measured by enzyme-linked immunosorbent assay. Results Significant association was not observed between MAP2K4 gene polymorphism rs3826392 and IS susceptibility in all genetic models ( P > .05). A significant difference was found in IL-1b, IL-6, IL-8, and TNF-α serum levels between patients with IS and control groups. MAP2K4 gene polymorphism rs3826392 C/A genotype carriers showed significantly higher IL-1b serum levels compared with AA genotype carriers ( P = .029) in patients with IS. Conclusion MAP2K4 gene polymorphism rs3826392 did not contribute to IS susceptibility, but rs3826392 C/A genotype carriers showed significantly higher IL-1b serum levels. This result suggests that rs3826392 may play a potential role in the IS inflammatory process.

Inflammatory response and lipid metabolism influence the development of ischemic stroke (IS). TLRs have an important function in inflammation and lipid metabolism. To investigate association of TLR8 rs3764880 polymorphism with susceptibility of IS and the relationship between rs3764880 with inflammation response- and lipid metabolism-related quantitative traits, we conducted a case–control study in a Han Chinese population comprising 816 cases and 816 controls being matched for age and gender. The distribution of allele of TLR8 rs3764880 had statistical significance in male group ( P = 0.017). The G allele carrier had a higher level of IL-8 ( P = 0.001, P Bc = 0.004) than the A allele carrier in male cases. Moreover, the rs3764880 genotype was significantly associated with TC ( P = 0.001, P Bc = 0.004) and LDL level ( P = 0.0002, P Bc = 0.0008) in the allele model, and the GG carrier had a higher LDL level ( P = 0.009, P Bc = 0.036) than the AA carrier in male patients. However, no statistically significant association was found between rs3764880 and any IS-related quantitative traits in female patients. Our study also revealed that IL-1b was associated with HDL ( P = 0.006, P Bc = 0.012) in IS patients. Therefore, TLR8 gene rs3764880 polymorphism might be associated with susceptibility and involved in the inflammatory reaction and lipid metabolism of IS in southern Chinese Han.

The common and major pathological change in ischemic stroke is atherosclerosis in the artery. Tumor necrosis factor-a (TNF-a) is closely related to the pathogenesis of atherosclerosis. The aim of our study was to investigate whether TNF-a gene variants (-238G/A and -308G/A) are associated with ischemic stroke.A total of 619 ischemic stroke patients and 612 controls were recruited to estimate the frequencies of two TNF-a (-238G/A and -308G/A) single nucleotide polymorphisms using a Sequenom MassARRAY time-of-flight mass spectrometer. The association between TNF-a gene polymorphisms and ischemic stroke risk was evaluated by computing the odds ratio (OR) and 95% Confidence Interval with multivariate unconditional logistic regression analyses.The OR results indicated that no significant associations were found between TNF-a gene (-238G/A and -308G/A) polymorphisms and the risk of ischemic stroke using five genetic models, including the allele model (A vs. G), co-dominant model 1 (GA vs. GG), co-dominant model 2 (AA vs. GG), the dominant model (AA+GA vs. GG), and the recessive model (GG+GA vs. AA).The TNF-a (-238G/A and -308G/A) gene polymorphisms may not be a susceptible predictor of ischemic stroke in Chinese populations.