The interaction effects of coke oven emissions exposure and metabolic enzyme Gene variants on total antioxidant capacity of workers

ObjectivesThe aim of this study was to investigate the association between coke oven emissions (COEs) exposure and total antioxidant capacity (T-AOC), and to explore whether genetic variations in metabolic enzyme genes GSTT1, GSTM1, GSTP1, and CYP2E1 can affect these associations in coke oven workers.Methods536 coke oven workers and 238 healthy controls were recruited. T-AOC of plasma was determined with kit. Five polymorphic loci of GSTT1 (+/-), GSTM1 (+/-), GSTP1 rs1695, CYP2E1 rs6413432 and CYP2E1 rs3813867 were detected by polymerase chain reaction and restriction fragment length polymorphism.ResultsThis study shows that the T-AOC in exposure group (12.02 ± 4.72) was significantly lower than that in control group (15.32 ± 7.19) (P < 0.01), and the COEs exposure could decrease the T-AOC of coke oven workers significantly [β(95% CI) = -2.663 (-4.538,-0.787), P < 0.001]. The T-AOC of female was lower than that of male in exposed and control groups (P < 0.001). The T-AOC was higher in GSTM1 (-) individuals than in GSTM1 (+) individuals in the control group (P = 0.037). The T-AOC with the AG genotype in GSTP1 rs1695 polymorphism was higher than that of the GG genotype in the control group (P = 0.043). The generalized linear model results showed that the risk factors for the decrease of T-AOC include GSTT1 (+) (b = -0.999, P = 0.009), female (b = -2.875, P < 0.01), COEs-exposed (b = -2.712, P = 0.004), GSTM1 (+) (b = -1.814, P = 0.008), and interactions of GSTM1 (+) and COEs-exposed (b = 1.872, P=0.024).ConclusionsThe risk factors for the decrease of T-AOC include GSTT1 (+), female, COEs-exposed, GSTM1 (+), and interactions of GSTM1 (+) and COEs-exposed.     

Genetic variations of CYP2B6 gene were associated with plasma BPDE-Alb adducts and DNA damage levels in coke oven workers

Polycyclic aromatic hydrocarbons (PAHs), the main components of coke oven emissions, can induce activation of cytochrome P450 (CYP) enzymes, which metabolize PAHs and result in DNA damage by forming adducts. This study was designed to know whether genetic variants of CYP genes are associated with plasma benzo[a]pyrene-7,8-diol-9,10-epoxide-albumin (BPDE-Alb) adducts and DNA damage in coke oven workers. In this study, 298 workers were divided into four groups according to the environmental PAHs exposure levels. The concentrations of plasma BPDE-Alb adducts were detected by reverse-phase high-performance liquid chromatography and the DNA damage levels were measured using comet assay. Twelve tag single nucleotide polymorphisms (tagSNPs) of 4 CYP genes were selected and genotyped by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. In the top group, workers with CYP2B6 rs3760657GA genotype have lower BPDE-Alb adducts and DNA damage levels than those with rs3760657GG genotype (P < 0.05). In the control group, the DNA damage levels of subjects with CYP1A1 rs4646421AA or GA + AA genotypes were lower than those with GG genotype (P < 0.05). However, no such effects were shown for the other tagSNPs. These results suggested that genetic variations of CYP2B6 might be associated with low BPDE-Alb adducts and DNA damage levels in worker with high exposure to PAHs.     

Association between genetic polymorphisms of telomere pathway genes and hydrogen peroxide level in omethoate exposure workers

ObjectiveThe aim of this study was to explore the association between genetic variations in telomere pathway genes and the level of hydrogen peroxide (H₂O₂) in omethoate exposure workers.MethodsA total of 180 omethoate exposure workers and 115 healthy controls were recruited. The level of H₂O₂ in plasma was determined with molybdenic acid colorimetry. Polymerase chain reaction and restriction fragment length was used to detect polymorphisms in POT1 rs1034794, POT1 rs10250202, TERF1 rs3863242, and TERT rs2736098.ResultsThe level of H₂O₂ in exposure group (4.26 ± 0.71) was significantly higher than that in control group (3.29 ± 0.46). Generalized linear models indicated that risk factors for the increase H₂O₂ level were exposure [β(95 % CI) = 0.951 (0.806, 1.096), P < 0.001] and AA + AT genotype in POT1 rs034794 [β(95 % CI) = 0.397 (0.049, 0.745), P = 0.025].ConclusionThe increase H₂O₂ level was associated with omethoate exposure and AA + AT genotypes in POT1 gene rs1034794. It provided a new idea that polymorphisms in telomere pathway genes may indirectly regulate telomere length by influencing oxidative stress.     

MicroRNA expression profiling of Chinese follicular lymphoma by microarray: A preliminary study

BackgroundMicroRNAs (miRNAs) have been widely regarded as crucial regulators in various biological processes involved in carcinogenesis. However, the comprehensive miRNA profiles of Chinese follicular lymphoma (FL) remains completely unknown.MethodsThe Exiqon miRCURY LNA™ microRNA Array (v.18.0) was used to detect the miRNA expression profiles of three Chinese FL samples, and compared to three reactive lymphatic nodes (RLN). Quantitative real-time polymerase chain reaction (qRT-PCR) was used to confirm the selected miRNAs in different series. Three databases (miRAnda, miRBase and TargetScan) were used to predict the putative target genes. Bioinformatic analysis (gene ontology analysis and pathway analysis) was performed for further evaluation.ResultsThe microarray assay demonstrated that 1643 miRNAs were expressed; in which 103 miRNAs were upregulated and 68 miRNAs were downregulated, according to P-value (< 0.05) and fold change (FC > 2-fold). Furthermore, qRT-PCR was used to confirm that miR-17-5p, miR-20a-5p and miR-19a-3p were upregulated, and miR-3615 was downregulated (P < 0.05). Bioinformatic analysis (gene ontology analysis and pathway analysis) was used for further evaluation. Pathway analysis indicated that 25 pathways corresponded to differentially expressed miRNAs (P-value cut-off is 0.05). Furthermore, miR-17-5p, miR-20a-5p and miR-19a-3p were validated by qRT-PCR in an independent series including five FL3a and five RLN cases. Data analysis revealed that the changing trend of miR-19a-3p and miR-17-5p expression in the independent series was basically identical with that of the microarray data.ConclusionsOur results are the first to reveal the miRNA expression profiling of Chinese FL and three upregulated miRNAs. Furthermore, the expression of miR-19a-3p and miR-17-5p were found to be significantly upregulated in FL3a. Further study needs to be urgently performed to reveal its potential role in the pathogenesis of FL in the near future.     

Association of omentin-1, adiponectin,and resistin genetic polymorphisms with systemic lupus erythematosus in a Chinese population

ObjectiveAn increasing number of studies have demonstrated the roles of adipokines in systemic lupus erythematosus (SLE). We aimed to investigate the association of genetic variations of omentin-1, adiponectin, and resistin with SLE susceptibility.MethodsWe selected 623 SLE patients and 665 normal controls in the present study. Genotyping of omentin-1 rs2274907, rs35779394, rs79209815, and rs13376023; adiponectin rs16861194 and rs266729; and resistin rs1862513, rs3745368, and rs3745367 was conducted by TaqMan SNP genotyping assays.ResultsOverall, we found no significant differences in the allele or genotype frequencies of the nine studied SNPs between the SLE patients and controls. However, an increased frequency of the resistin rs3745368 variant was observed in the SLE patients under the dominant model (P = 0.024). In omentin-1, the rs13376023 A allele was found to be related to oral ulcers in SLE patients (P = 0.013), and the rs35779394 C and rs13376023 A allele frequencies were significantly lower in SLE patients with BMI ≥ 24 kg/m² (P = 0.019, P = 0.033, respectively). For resistin, the frequencies of the rs3745368 AA genotype and A allele were lower in SLE patients with discoid rash (P = 0.036, P = 0.011), and the rs3745368 A allele frequency was higher in SLE patients with lupus nephritis (P = 0.018). The resistin rs3745367 AA genotype and A allele frequencies were related to the occurrence of renal disorder in SLE patients (P = 0.024, P = 0.009). The haplotype analysis showed that the CGA haplotype of resistin was associated with susceptibility to SLE (P = 0.005). No significant associations of plasma omentin-1, adiponectin or resistin levels with their respective genotypes were found in SLE patients.ConclusionsIn summary, omentin-1, adiponectin and resistin SNPs are not associated with the genetic background of SLE in Chinese patients. However, omentin-1 and resistin genetic variations might contribute to several clinical phenotypes of SLE.     

Circulating CTLA-4 levels and CTLA4 polymorphisms associate with disease condition and progression and hepatocellular carcinoma patients' survival in chronic hepatitis B virus infection

BackgroundCTLA-4 is involved in the immune dysfunction of hepatitis B virus (HBV) infection and hepatocellular carcinoma (HCC). This study analyzed the association of circulating CTLA-4 levels and CTLA4 polymorphisms with disease condition and progression in chronic HBV infection.MethodsSerum CTLA-4 levels and CTLA4 rs231775 and rs5742909 polymorphisms were determined in patients with various HBV-related diseases [53 asymptomatic HBV carrier status (ASC), 147 chronic hepatitis, 130 cirrhosis and 102 HCC] and nearly a 10-year follow-up.ResultsSerum CTLA-4 levels were stepwisely increased from ASC, chronic hepatitis, cirrhosis to HCC and independently associated with HCC (OR 2.628, P < 0.001). HCC patients had lower frequencies of rs231775 genotype GA, genotype AA and allele A than ASC, chronic hepatitis and cirrhosis patients. Rs231775 genotype GG was independently associated with HCC (OR 2.324, P = 0.010) and higher CTLA-4 levels in patients with HBV infection. In the follow-up, higher baseline CTLA-4 levels and CTLA4 rs231775 genotype GG significantly associated with disease progression from chronic hepatitis to cirrhosis (OR 2.561, P = 0.011 and OR 2.799, P = 0.015, respectively) or from cirrhosis to HCC (OR 2.673, P = 0.008 and OR 2.097, P = 0.023, respectively) and with a shorter overall survival in HCC patients (HR 0.317, P = 0.018 and HR 0.682, P = 0.026, respectively). Rs5742909 had no significant association with CTLA-4 levels and disease progression.ConclusionCTLA-4 levels and CTLA4 rs231775 polymorphism associate with the disease condition and progression and HCC development in chronic HBV infection and their determination may be used for monitoring disease progression and predicting patient prognosis.     

IL-7R gene variants are associated with breast cancer susceptibility in Chinese Han women

BackgroundInterleukin 7 receptor (IL-7R) is a member of the type I cytokine receptor family, which affects the occurrence of various tumors by forming a signaling complex with its ligand Interleukin 7 (IL-7). This study aimed to explore the potential relationships of IL-7R polymorphisms with breast cancer susceptibility in the Chinese Han women.MethodsFive polymorphisms of IL-7R gene (rs969129, rs10213865, rs10053847, rs118137916, and rs6451231) form 553 patients and 550 healthy individuals among the Chinese Han women were genotyped using Agena MassARRAY platform. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated to evaluate the relationship.ResultsThe resulted of this study showed that rs10213865 was related to an increased breast cancer risk in allele (P = 0.045), dominant (P = 0.040), and log-additive (P = 0.029) models. As for rs969129, an increased risk of breast cancer was found in the allele (P = 0.018), co-dominant (P = 0.017), recessive (P = 0.034), and additive (P = 0.019) models. Rs6451231 was related to an increased risk of breast cancer under allele (P = 0.018), co-dominant (P = 0.021), and log-additive (P = 0.019) models. Age stratified analysis revealed that rs6451231 could enhance risk of breast cancer among the individuals older than 52 years. Furthermore, there was a significant correlation between haplotype C_rs969129G_rs10213865A_rs10053847G_rs118137916 and the decreased risk of breast cancer (P = 0.010).ConclusionsThis study firstly proved that IL-7R polymorphisms were significantly correlated with an increased susceptibility of breast cancer in the Chinese Han women.     

MMP9基因rs2274755多态性与云南汉族人群冠心病的相关性研究

目的 研究基质金属蛋白酶9（MMP9）基因多态性与中国云南汉族人群冠心病（CHD）的相关性。方法 采用Sequenom MassARRAY^®对云南省第二人民医院2012年9月至2015年9月收集的198例正常人（对照组）和514例冠心病患者（冠心病组）MMP9基因rs2274755单核苷多肽（SNP）位点的多态性进行基因分型,分析该基因多态性与冠心病的相关性。结果 正常对照组和冠心病组rs2274755位点基因型频率分别为GG 0.67/0.76,GT 0.31/0.22,TT 0.02/0.02,差异有统计学意义（P<0.05）,两组等位基因频率分别为G 0.82/0.87,T 0.18/0.13,差异有统计学意义（P<0.05）。校正年龄、性别、体质量指数等logistic回归分析显示,rs2274755位点携带T等位基因者患冠心病风险降低[加性模型（T vs G）：OR=0.72,95%CI（0.52～0.99）,P=0.046;显性模型（TT/GT vs GG）：OR＝0.96,95%CI（0.93～1.00）,P=0.028]。结论 MMP9基因多态性与云南汉族人群冠心病发生风险相关。     

Association of CD40 − 1C/T polymorphism with cerebral infarction susceptibility and its effect on sCD40L in Chinese population

This study aims to determine whether functional polymorphism of CD40 is associated with the cerebral infarction (CI) susceptibility, and to investigate the effect of CD40 gene polymorphism on CD40 mRNA expression in PBMCs and plasma sCD40L concentration. A case–control study was performed in 402 CI patients and 693 controls. Genotyping was performed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). The expressions of CD40 mRNA and plasma sCD40L concentration were determined. The distribution of TT genotype and the frequency of T allele in CI patients were significantly higher than those in the controls (P < 0.05). The frequency of T allele was also significantly higher in the male subjects and the elder subjects (P < 0.05) when stratified analysis was carried out. The PBMCs from CI patients showed significantly higher CD40 mRNA expression than controls (P < 0.01), the CD40 mRNA expression from TT genotype was higher than other genotypes (P < 0.05). TT genotype subjects also showed the highest plasma sCD40L concentration in the male CI patients (P < 0.01). CD40 − 1C/T polymorphism may interfere CI susceptibility, and the T allele may be associated with increased risk of CI. The CD40 − 1C/T polymorphism is also a regulator of CD40 expression and plasma sCD40L concentration.     

Genetic variations in cytotoxic T-lymphocyte antigen-4 and susceptibility to cervical cancer

Cytotoxic T-lymphocyte antigen-4 (CTLA-4), a molecule expressed predominantly on activated T cells, plays an important role in the down-regulation of T-cell activation. To evaluate the potential effects of CTLA-4 gene polymorphisms on susceptibility to cervical cancer, we genotyped polymorphisms in CTLA-4 (− 318 T/C, CT60 G/A, + 49 G/A, − 658 T/C, and − 1661 G/A) and calculated odds ratios for the genotype and allele distributions between patients and controls. We then examined the functional relevance of the polymorphisms using enzyme-linked immunosorbent assays (ELISAs), in vitro lymphocyte proliferation assay, and cytotoxic assay. The CTLA-4 − 318 CC, CT60 AA, and + 49 GG genotype frequencies were lower in patients than in controls (p < 0.05). The frequencies of CTLA-4 − 318 T allele and CT60G allele carriers were significantly higher in patients than in controls (p < 0.05). Upon stimulation, peripheral blood mononuclear cells (PBMCs) carrying the − 318TT and CT60GG genotypes exhibited significantly lower proliferation, IL-2, and IL-4 levels; fewer cytolytic activities; and higher TGF-β levels compared with PBMCs carrying the − 318 CC/CT or CT60 AA/AG genotypes. We also found that CTLA-4 − 318 T/C and CT60 G/A single nucleotide polymorphisms were associated with the severity of cervical cancer. These results indicate that CTLA-4 − 318 T/C and CT60 G/A can affect cervical cancer susceptibility by altering the immune status of an individual.     

KCNA5基因多态性与特发性房颤的关系

目的 探讨KCNA5基因单核苷酸多态性（SNP）与特发性房颤（IAF）的关系。方法 选取2015年1月至2018年12月海南医学院第二附属医院收治的204例IAF患者（IAF组）作为研究对象,并以性别、年龄作为匹配因子收集200例体检健康者作为对照组。采用基因测序法检测两组研究对象KCNA5 SNP（rs3741930、rs1056468）的分布,基于不同基因型（rs3741930、rs1056468）将IAF患者分为两组,比较IAF患者不同基因型相关临床指标的差异。结果 ①KCNA5基因rs3741930位点CC、CT、TT在IAF组、对照组中实际分布与预期分布对比,差异均无统计学意义（P>0.05）,KCNA5基因rs1056468位点AA、AT、TT在IAF组、对照组中实际分布与预期分布对比,差异均无统计学意义（P>0.05）;②IAF组rs3741930位点CC基因型和等位基因C分布频率高于对照组,差异有统计学意义（P<0.05）,两组研究对象CT、TT基因型频率对比,差异无统计学意义（P>0.05）;IAF组rs1056468位点AA、AT、TT和等位基因A分布频率与对照组对比差异均无统计学意义（P>0.05）;③IAF患者rs3741930位点CC与CT+TT基因型年龄、舒张压、收缩压、心率、左心房内径、射血分数对比,差异均无统计学意义（P>0.05）,CC基因型患者体质量指数（BMI）高于CT+TT基因型,差异有统计学意义（P<0.05）;IAF患者rs1056468位点AA与AT+TT基因型年龄、舒张压、收缩压、心率、左心房内径、射血分数对比,差异均无统计学意义（P>0.05）,AA基因型患者BMI低于AT+TT基因型,差异有统计学意义（P<0.05）。结论 KCNA5基因SNP rs3741930与IAF发病有关,C等位基因携带人群更易患病。     

How well do randomized controlled trial data generalize to ‘real-world’ clinical practice settings? A comparison of two generalized anxiety disorder studies

The aim of this post-hoc comparison is to compare efficacy and tolerability results from two generalized anxiety disorder (GAD) studies: a placebo-controlled, randomized controlled trial (RCT) and a study conducted in the clinical practice setting, and to evaluate the extent to which results from RCTs in GAD patients can be generalized to clinical practice. In the clinical practice study, GAD outpatients (n=578) were treated with 4 weeks of pregabalin 150–600 mg/day. In the double-blind placebo-controlled RCT, GAD outpatients (n=249) were randomized to 8 weeks of pregabalin (300–600 mg/day), or placebo (only the first 4 weeks are included in the current analysis). Efficacy measures included the Hospital Anxiety and Depression Scale – Anxiety and Depression subscales (HADS-A; HADS-D), a visual analogue anxiety scale (VAS-Anxiety), and the Medical Outcomes Study Sleep Problems Index (MOS-SPI). Baseline HADS-A and HADS-D scores were both higher in the clinical practice study vs. the RCT. In the RCT, treatment with pregabalin resulted in significantly greater Week 4 change vs. placebo in the HADS-A (−5.3 vs. −3.9; P<0.005), VAS-Anxiety (−24.0 vs. −13.3; P<0.02), MOS-SPI (−19.1 vs. −9.5; P<0.01), and HADS-D (−2.7 vs. −1.4; P<0.05). The magnitude of Week 4 improvement on pregabalin in the clinical practice study was numerically larger on the HADS-A (−5.9), VAS-Anxiety (−36.0), MOS-SPI (−22.7), and HADS-D (−5.1), despite use of lower doses. These results suggest that clinical practice patients with GAD may achieve comparable efficacy on lower doses of pregabalin than tested in RCTs, despite having comparable levels of anxiety symptom severity at baseline. The current exploratory comparison also suggests that results from RCTs in patients with GAD may not be directly generalizable to clinical practice.     

Association study of IL10 gene polymorphisms (rs1800872 and rs1800896) with cervical cancer in the Bangladeshi women

ObjectiveCervical cancer is one of the most destructive diseases among females worldwide, especially in developing countries. Interleukin-10 (IL10) is a multifunctional cytokine, and polymorphisms in the IL10 gene have been identified in multiple malignancies. However, no prior studies were conducted to determine the association of IL10 polymorphisms (rs1800872 and rs1800896) with cervical cancer patients in Bangladesh.MethodsThis case-control study was carried out on 240 cervical cancer patients and 204 healthy volunteers. Genotyping was performed using the tetra-primer amplification refractory mutation system polymerase chain reaction (ARMS-PCR).ResultsIn the case of rs1800872, CA and AA genotypes significantly increased the risk of cervical cancer (OR = 1.59, 95% CI = 1.01–2.49, p = 0.043; OR = 2.75, 95% CI = 1.53–4.93, p = 0.0007, respectively) but the significance did not exist for CA genotype after Bonferroni correction (p < 0.025). An increased risk was also observed for the dominant model, recessive model, and allele model (A vs. C) of rs1800872 (dominant model: OR = 1.83, 95% CI = 1.18–2.80, p = 0.006; recessive model: OR = 2.00, 95% CI = 1.22–3.29, p = 0.006; allele model: OR = 1.55, 95% CI = 1.19–2.03, p = 0.001) which remained significant after the correction of Bonferroni. For rs1800896, only GG genotype and recessive model showed increased risk for cervical cancer (GG vs. AA: OR = 3.48, 95% CI = 1.46–8.31, p = 0.005; recessive model: OR = 3.57, 95% CI = 1.52–8.38, p = 0.003). These associations were statistically significant, and the significance existed after Bonferroni correction. Haplotype analysis revealed that AA haplotype significantly increased the risk (OR = 1.56, p = 0.001) whereas, CA haplotype significantly lowered the risk (OR = 0.42, p = 2.42x10^-8), and both rs1800872 and rs1800896 are strongly in linkage disequilibrium (D’=1, r² = 0.333). Moreover, the IL10 mRNA level was found up-regulated in silico in cervical squamous cell carcinoma tissues compared to healthy tissues (p = 1.11x10^-16).ConclusionOur study suggests that rs1800872 and rs1800896 polymorphisms of IL10 gene are associated with cervical cancer in Bangladeshi females.     

Host interleukin-28B genetic variants versus viral kinetics in determining responses to standard-of-care for Asians with hepatitis C genotype 1

Background

Both interleukin-28B genetic variants and on-treatment virological responses are factors predictive of treatment outcome in hepatitis C virus genotype 1 (HCV-1) patients. We aimed to compare the clinical significance of the two factors.

Methods

Rs8099917 genotype and on-treatment responses were determined in 182 HCV-1 patients with 48-week peginterferon/ribavirin.

Results

Comparing to patients with rs8099917 TG/GG genotype, those with TT genotype had significantly higher rapid virological response (RVR, 46.2% vs. 19.2%, P = 0.01) and sustained virological response (SVR, 85.3% vs. 42.3%, P < 0.001) rates. Logistic regression analysis revealed that the strongest factor predictive of a RVR was the carriage of rs8099917 TT genotype (odds ratio/95% confidence intervals [OR/CI]: 4.25/1.39-13.01). The most important factor predictive of an SVR was the attainment of a RVR (OR/CI: 57.22/6.23-525.37), followed by the carriage of rs8099917 TT genotype (OR/CI: 10.06/3.12-32.44). However, while on-treatment factors were taken into account, the cEVR was the most important determinant to an SVR (OR/CI:54.98/9.07-333.38), whereas the influence of rs8099917 genotype became non-significant in non-RVR patients.

Conclusions

Rs8099917 TT genotype is significantly independently predictive of on-treatment virological responses, which were the major determinants of an SVR, in Asian HCV-1 patients.     

Contribution of IL-7/7R genetic polymorphisms in coronary heart disease in Chinese Han population

BackgroundCoronary heart disease (CHD) is a common chronic inflammatory disease. Interleukin (IL)-7/IL-7R has been reported to be involved in the development of CHD. However, the relationship between IL-7/7R genetic polymorphisms and CHD among the Han Chinese population remains unclear.MethodsTo examine whether IL-7/7R variants contributed to CHD, six single-nucleotide polymorphisms (SNPs) were genotyped by using the Agena MassARRAY platform in 499 CHD patients and 496 controls. Logistic regression was used to calculate the odds ratios (ORs) and 95% confidence intervals (CIs). The linkage disequilibrium was analyzed using Haploview software. The association between clinical parameters and IL-7/7R polymorphisms was determined by a one-way ANOVA.ResultsIL-7R rs969129 G (OR = 1.20, 95% CI: 1.00–1.43, p = 0.047) allele and GG (OR = 1.45, 95% CI: 1.01–2.08, p = 0.044) genotype carriers had a higher risk for CHD. IL-7R haplotype “ACAG” (OR = 1.43, 95% CI: 1.09–1.87, p = 0.010) conferred an increased CHD risk. Rs969129, rs6451231, and rs117173992 were related to CHD susceptibility in males and/or the subgroup of individuals aged >61 years. IL-7R rs969129, rs10053847, rs6451231, and rs118137916 variants were associated with diabetes in patients with CHD. Moreover, rs969129, rs6451231, and rs117173992 were associated with high-density lipoprotein cholesterol (HDL-C) concentrations, whereas rs118137916 and rs10053847 were associated with low-density lipoprotein cholesterol (LDL-C) levels (p < 0.05).ConclusionIL-7/7R variants were related to the genetic predisposition of CHD in the Chinese Han population. These findings increase our knowledge regarding the effect of IL-7/7R on CHD.     

TSH-β gene polymorphism in Saudi patients with thyroid cancer: A case-control study

BackgroundThe role of thyroid-stimulating hormone in the pathogenesis of thyroid cancer is not yet fully explored. This study aimed to evaluate the role of the TSH-β polymorphism in thyroid cancer in a Saudi cohort.MethodsA prospective case-control study was conducted on 507 patients with differentiated thyroid carcinoma and compared them with 560 controls of Saudi origin. The association of two variants, the rs201857310, and rs7530810, in the TSH-β gene with thyroid cancer risk as well as thyroxine dose, were evaluated.ResultsThe rs201857310_A > G [OR: 0.50 (95 % CI: 0.35–0.71); P < 0.0001] was strongly associated with thyroid cancer. The multivariable analysis adjusted the effect of possible confounders (age, sex, body mass index, and smoking). Multivariable analysis elucidated that the rs201857310 maintained its significant association with the disease [OR: 0.47 (95 % CI: 0.32–0.68); P < 0.0001]. There was no significant association between the other rs7530810 variant and the disease. There was no association between any of the variants and the thyroxine dose requirement (P = 0.79 and 0.73).ConclusionsOur findings indicate that the TSH-β gene could have a role in the pathogenesis of differentiated thyroid carcinoma in the Saudi population.     

The effect of oseltamivir use in critically ill patients with COVID-19: A multicenter propensity score-matched study

BackgroundOseltamivir has been used as adjunctive therapy in the management of patients with COVID-19. However, the evidence about using oseltamivir in critically ill patients with severe COVID-19 remains scarce. This study aims to evaluate the effectiveness and safety of oseltamivir in critically ill patients with COVID-19.MethodsThis multicenter, retrospective cohort study includes critically ill adult patients with COVID-19 admitted to the intensive care unit (ICU). Patients were categorized into two groups based on oseltamivir use within 48 hours of ICU admission (Oseltamivir vs. Control). The primary endpoint was viral load clearance.ResultsA total of 226 patients were matched into two groups based on their propensity score. The time to COVID-19 viral load clearance was shorter in patients who received oseltamivir (11 vs. 16 days, p = 0.042; beta coefficient: −0.84, 95%CI: (−1.33, 0.34), p = 0.0009). Mechanical ventilation (MV) duration was also shorter in patients who received oseltamivir (6.5 vs. 8.5 days, p = 0.02; beta coefficient: −0.27, 95% CI: [−0.55,0.02], P = 0.06). In addition, patients who received oseltamivir had lower odds of hospital/ventilator-acquired pneumonia (OR:0.49, 95% CI:(0.283,0.861), p = 0.01). On the other hand, there were no significant differences between the groups in the 30-day and in-hospital mortality.ConclusionOseltamivir was associated with faster viral clearance and shorter MV duration without safety concerns in critically ill COVID-19 patients.     

Effect of c-fos gene silence on PM2.5-induced miRNA alteration in human bronchial epithelial cells

Human bronchial epithelial (HBE) cells and c-fos-silenced HBE cells were first exposed to fine particulate matter (PM_2.5) and the resulting miRNA sequenced. Thereafter, a weighted gene co-expression network analysis was performed using Cytoscape software to visualize the interactions between identified hub miRNAs and their target genes. Nine differentially expressed miRNAs in hub miRNAs were identified in the different treatment groups, of which miR-25−3p, miR-215−5p, and miR-145−5p were selected for further study. Following qPCR validation, both miR-25−3p and miR-215−5p were found to be significantly up-regulated whilst, miR-145−5p was significantly down-regulated (p < 0.05) in the PM_2.5 group. Furthermore, miR-25−3p and miR-145−5p were also significantly down-regulated in the untreated group of c-fos silenced HBE cells. However, miR-215−5p was significantly down-regulated in both the untreated and PM_2.5-treated groups of c-fos silenced HBE cells. Subsequent analysis of their target genes also illustrated differential gene expression when comparing the treatment groups of the two cell types. The present data indicated that the c-fos gene has an important effect on the miRNA expression profiles and the related signaling pathways in PM_2.5-treated HBE cells. Therefore, each of miR-25−3p, miR-145−5p, and miR-215−5p may potentially provide future research information for additional exploration of a PM_2.5-induced carcinogenesis mechanism.     

Effect of donor STAT4 polymorphism rs7574865 on clinical outcomes of pediatric acute leukemia patients after hematopoietic stem cell transplant

STAT4 polymorphism, rs7574865 is linked to various autoimmune diseases such as systemic lupus erythematosus and rheumatoid arthritis. Its T minor allele is associated with higher STAT4 mRNA and protein expression, indicating a stronger skewed immune response than the norm. Although widely studied in autoimmune disease patients and the general population, its effect on immunocompromised subjects is still unknown. Especially in situations, i.e. post-hematopoietic stem cell transplantation (post-HSCT), where control of the immune response is crucial. Hence, this study investigates if the presence of the T minor allele in donors would affect immunological response and clinical outcomes post-HSCT. Samples from 161 pediatric patients who underwent allogeneic HSCT for acute leukemia and showed complete chimerism by donor cells were obtained. Six clinical outcomes were investigated; hepatic veno-occlusive disease, acute graft-vs-host disease, chronic graft-vs-host disease, cytomegalovirus (CMV) infection, relapse and overall survival. The TT genotype was found to be significant in the occurrence of CMV infection (P = 0.049), showing higher incidence of CMV infection compared to the others. Multivariate analysis confirmed that association of the TT genotype is independent from other variables in CMV infection occurrence (P = 0.010). This is the first study on STAT4 polymorphism rs7574865 in allogeneic HSCT as well as immunocompromised patients. As the TT genotype is associated with autoimmune diseases, our results seem at a paradox with current evidence hinting at a different role of STAT4 in normal circumstances versus immunocompromised patients. Further investigation is needed to elicit the reason behind this and discover novel applications for better post-transplant outcomes.     

Spatial and sociodemographic correlates of gambling participation and disorder among female Filipino migrant workers in Macao,People's Republic of China

Background and aimsCorrelates and risk factors for gambling disorder among vulnerable or transient populations such as transnational migrant workers are unknown. The current study examined sociodemographic and spatial correlates of gambling disorder among female Filipino domestic workers in Macao (SAR), China.DesignSurvey-based, respondent-driven sampling study administered from November 2016 to August 2017.SettingMacao (SAR), which encompassed 38 casinos within its 30.4 km² area at the time of this study.ParticipantsRepresentative sample of N = 1194 female Filipino domestic workers in Macao.MeasurementsSymptoms of gambling disorder based on Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5). Correlates evaluated included sociodemographic information, proximity to venues, perceived social support, and symptoms of depression and anxiety.FindingsPrevalence of gambling disorder was 5.1%. Multivariable regression analyses indicated that likelihood of gambling participation (i.e., ever gambling) was associated with current indebtedness (RR = 1.56, 95%CI = 1.08–2.25, p = .017) and worse self-reported health (RR = 1.31, 95%CI = 1.04–1.65, p = .02). Increased symptoms of gambling disorder were independently associated with lower perceived social support (RR = 0.92, 95%CI = 0.87–0.98, p = .006), increased dependents relying upon monthly remittances (RR = 1.10, 95%CI = 1.06–1.16, p < .001), increased depression severity (RR = 1.16, 95%CI = 1.07–1.25, p < .001), decreased salary quintile (RR = 0.97, 95%CI = 0.94–1.00, p = .04), and proximity to the nearest Mocha Club gaming venues (RR = 1.04, 95%CI = 1.02–1.07, p = .005). The association between proximity to casinos and increased symptoms of gambling disorder was significant only for domestic workers living apart from employers (RR = 1.07, 95%CI = 1.00–1.14, p = .04).ConclusionsIncreased spatial proximity to gambling venues and greater financial and psychosocial burdens are associated with gambling disorder among domestic workers in Macao.