Genetic polymorphisms in the Toll-like receptor signalling pathway in Helicobacter pylori infection and related gastric cancer

Background

Gastric cancer (GC) is a progressive process initiated by Helicobacter pylori-induced inflammation. Initial recognition of H. pylori involves Toll-like receptors (TLRs), central molecules in the host inflammatory response. Here, we investigated the association between novel polymorphisms in genes involved in the TLR signalling pathway, including TLR2, TLR4, LBP, MD-2, CD14 and TIRAP, and risk of H. pylori infection and related GC.

Methods

A case-control study comprising 310 ethnic Chinese individuals (87 non-cardia GC cases and 223 controls with functional dyspepsia) was conducted. Twenty-five polymorphisms were detected by MALDI-TOF mass spectrometry, PCR, PCR–RFLP and real-time PCR.

Results

Seven polymorphisms showed significant associations with GC (TLR4 rs11536889, TLR4 rs10759931, TLR4 rs1927911, TLR4 rs10116253, TLR4 rs10759932, TLR4 rs2149356 and CD14 −260 C/T). In multivariate analyses, TLR4 rs11536889 remained a risk factor for GC (OR: 3.58, 95% CI: 1.20–10.65). TLR4 rs10759932 decreased the risk of H. pylori infection (OR: 0.59, 95% CI: 0.41–0.86). Statistical analyses assessing the joint effect of H. pylori infection and the selected polymorphisms revealed strong associations with GC (TLR2, TLR4, MD-2, LBP and TIRAP polymorphisms).

Conclusions

Novel polymorphisms in TLR2, TLR4, MD-2, LBP, CD14 and TIRAP, genes encoding important molecules of the TLR signalling pathway, showed clear associations with H. pylori-related GC in Chinese.     

Association of STAT6 variants with asthma risk: A systematic review and meta-analysis

A large number of studies have reported that the genetic variants in STAT6 gene may be implicated in susceptibility to asthma, but with inconsistent results. Therefore, the aim of this meta-analysis was to determine the likelihood of developing asthma for the individuals with different STAT6 variants. The database including Pubmed, Embase and CNKI (Chinese National Knowledge Infrastructure) were searched to find the relevant papers. Data were extracted by two independent reviewers and the odds radios (ORs) were pooled with 95% confidence intervals (CIs), using random effect or fixed effect models as appropriate, to indicate the risk of asthma for different STAT6 variants. The heterogeneity and bias were tested for each pooled result. Data from 19 studies were pooled that reported associations of rs324015, rs71802646 and rs324011 in STAT6 gene with asthma risk. The results demonstrated that 13GT and short GT in rs71802646 were both associated with increased risk of asthma in overall analysis (OR = 1.26 for 13GT and 1.30 for short GT). Further, subgroup analysis showed an increased risk of asthma in Asian population with 13GT (OR = 1.21), 14GT (OR = 1.97) and short GT (OR = 1.27). Besides, 13GT, 14GT and short GT all contributed to higher risk of atopic asthma, with OR 1.50, 2.21 and 1.65 respectively. However, rs324015 (G>A) appeared to be associated with decreased risk for atopic asthma (with OR = 0.83, 0.68 and 0.79 for A, AA and AA+AG respectively). Both overall and subgroup analyses indicated no effect of rs324011 on asthma risk. In conclusion, our meta-analyses suggest that short GT repeats of rs71802646 in STAT6 contribute to higher risk for asthma, while rs324015 may have a protective effect on atopic asthma.     

Hemodynamic effects of pindolol and atenolol at rest and during isometric exercise: A noninvasive study with healthy volunteers

Summary Hemodynamic effects of intravenous and oral pindolol and atenolol were assessed in ten healthy volunteers by left ventricular echocardiography and systolic time intervals. Measurements were made at rest and during hand-grip-induced isometric exercise. Drug doses were pindolol 0.015 mg/kg intravenously and 10 mg/day orally, atenolol 0.1 mg/kg intravenously, and 50 mg/day orally.Heart rate at rest was reduced by both drugs. The reduction caused by atenolol during oral treatment was significantly greater (p<0.01). Intravenously only pindolol reduced mean arterial pressure. During oral treatment atenolol reduced the mean arterial pressure nonsignificantly. Both drugs lowered heart rate during isometric exercise, atenolol being significantly more effective. During oral treatment atenolol blunted the heart-rate reaction to exercise. Mean arterial pressure during isometric exercise rose slightly with both drugs after intravenous administration. During oral treatment only atenolol reduced the mean arterial pressure significantly. Intravenous atenolol reduced cardiac contractility at rest, indicated by significant decreases in fractional shortening, ejection fraction, and the mean velocity of circumferential fiber shortening. In contrast, intravenous pindolol and oral therapy with either drug did not change contractility. Intravenous atenolol raised total peripheral resistance. The preejection period/left ventricular ejection time ratio decreased with intravenous pindolol, while atenolol increased it.In conclusion, atenolol had more negative inotropic and chronotropic effects, especially after acute intravenous administration. Only atenolol reduced cardiac output and increased peripheral resistance. After repeated oral administration, these effects were less apparent.     

Hormone Replacement Therapy Shortens QT Dispersion in Healthy Postmenopausal Women

Background: The aim of the study was to investigate the effects of hormone replacement therapy (HRT) on myocardial repolarization characteristics in postmenopausal women without coronary artery disease. Methods: Fifty‐one consecutive healthy postmenopausal women (age 48 ±; 5) with negative exercise stress testing were prospectively enrolled into the study. Standard 12‐lead electrocardiograms were obtained to evaluate the effects of 6 months of HRT on QT intervals, corrected QT intervals (QTcmax and QTcmin), QT dispersion (QTd), and corrected QTd (QTcd). Hormone regimens were continuous 0.625 mg/day conjugated equine estrogen (CEE) plus 2.5 mg/day medroxyprogesterone acetate (MPA) or 0.625 mg/day CEE alone depending on the hysterectomy status. Results: Although not statistically significant, CEE alone or in combination with MPA increased QTmax and QTmin values. However, the increase in QTmin was greater than the increase in QTmax, which resulted in statistically significant shortening of QTd (P = 0.007 in CEE and P < 0.001 in CEE + MPA groups). There was a significant prolongation of QTcmin values after 6 months in patients assigned to the CEE group (P = 0.001). The QTcd values were significantly shortened by HRT with both regimens (for CEE group 49 ±; 13 ms vs 38 ±; 13 ms, P = 0.01; for CEE + MPA group 49 ±; 14 ms vs 36 ±; 13, P < 0.001). Conclusion: HRT significantly decreased the QTd and QTcd in postmenopausal women without coronary artery disease, independent of the addition of MPA to the regimen. This improvement in myocardial repolarization may be one of the mechanisms of the favorable effects of HRT on cardiovascular system. However, the clinical implications of the shortening of QTd in postmenopausal women with HRT must be clarified. A.N.E. 2001; 6(3):193–197     

Is asthma a protective factor for dengue fever? In vitro experiment and nationwide population-based cohort analysis

BackgroundDengue fever (DF) is the most rapidly spreading mosquito-borne viral disease. Practical vaccines or specific therapeutics are still expected. Environmental factors and genetic factors affect the susceptibility of Dengue virus (DV) infection. Asthma is a common allergic disease, with house dust mites (HDMs) being the most important allergens. Asthmatic patients are susceptible to several microorganism infections.MethodsA nationwide population-based cohort analysis was designed to assess whether to determine whether asthma can be a risk factor for DF.ResultsUnexpectedly, our data from a nationwide population-based cohort revealed asthmatic patients are at a decreased risk of DF. Compared to patients without asthma, the hazard ratio (HR) for DF in patients with asthma was 0.166 (95% CI: 0.118–0.233) after adjustment for possible confounding factors. In the age stratification, the adjusted HR for DF in young adult patients with asthma was 0.063. Dendritic cell-specific intercellular adhesion molecule 3-grabbing non-integrin (DC-SIGN) of dendritic cells (DCs) is an important entry for DV. Through another in vitro experiment, we found that HDM can diminish surface expression of DC-SIGN in monocyte-derived DCs and further decrease the cellular entry of DV.ConclusionsDecreased DC-SIGN expression in DCs of allergic asthmatic patient may be one of many factors for them to be protected against DF. This could implicate the potential for DC-SIGN modulation as a candidate target for designing therapeutic strategies for DF.     

美托洛尔对扩张型心肌病QT间期离散度及室性心律失常变化的研究

目的:探讨美托洛尔治疗对扩张型心肌病(DCM)患者心电图QT间期离散度(QTd)及室性心律失常的影响。方法:80例DCM患者分为基础治疗组(A组,40例)及基础治疗加美托洛尔治疗组(B组,40例),给予B组在基础治疗上加服美托洛尔25mg/tid,疗程9个月。治疗前后应用24h动态心电图和多普勒超声心动图,观测QTd、QTcd、HR、室性心律失常(VA)如室性早搏(PVC)、非持续性室性心动过速(NSVT))的发生情况、左心室射血分数(LVEF)。结果:B组QTd、QTcd及室性心律失常(VA)发生率均较A组显著降低(P均<0.01),左室射血分数(LVEF)较A组明显提高(P<0.01),而HR、血压无明显变化(P>0.05)。提示B组疗效明显优于A组。结论:DCM患者长期应用美托洛尔可显著降低QTd、QTcd及VA的发生率,改善心功能,改善预后。     

杭州地区2～6岁健康儿童血清垂体-甲状腺轴激素正常参考范围调查

用化学发光法检测592名杭州地区2～6岁健康儿童的血清TSH、T3、T4、FT3、FT4浓度并作统计分析,得出总人群的正常参考范围为:TSH 1.09～4.60 mIU/L,T3 1.17～1.95μg/L,T4 57.43～99.60μg/L,FT3 5.35～7.50 pmol/L,FT4 13.96～19.70 pmol/L.不同年龄、不同性别间比较,差异无统计学意义(P＞0.05).

Abstract：

Serum concentrations of TSH, total and free thyroxine, and total and free triiodothyronine in 592 healthy children aged 2-6 years were determined by means of ADVIA Centaur. The normal reference ranges were calculated. The reference ranges of TSH, T3, T4, FT3, and FT4 were 1.09-4.60 mIU/L, 1.17-1.95 μg/L,57.43-99.60 μg/L, 5.35-7.50 pmol/L, 13.96-19.70 pmol/L, respectively. There was no significant difference in the interval of thyroid hormones between males and females as well as among different age groups.     

Diagnostic value of RASSF1A hypermethylation in colorectal cancer: a meta-analysis

Purpose

Ras association domain family 1 isoform A (RASSF1A), a member of Ras association domain family, plays an important role in tumorigenesis. The goal of our meta-analysis was to assess the diagnostic value of RASSF1A hypermethylation in colorectal cancer (CRC).

长沙市成人血细胞分析参考值范围的验证和建立

目的验证长沙地区引用WS/T 405-2012行业标准血细胞分析报告指标参考值范围并建立适宜该地区的研究参数的参考值范围。方法按照《临床实验室检验项目参考区间的制定》程序分析3 138例参考人群的血细胞分析结果,并与WS/T405-2012行业标准比较。结果报告参数中WBC、Neu#、Mon%、MCHC、PLT、MPV、PCT、P-LCC、P-LCR、InR‰和研究参数中的WBC-D、PDW-SD在男性和女性间差异不具有统计学意义(P0.050);WBC、Neu#、Mon%、MCHC和PLT等5项性别间无差异,指标较标准中的参考值范围变窄;男性血细胞分析指标中的Neu%、RBC、HGB、MCV和MCH等5项指标参考值范围变窄,Bas%、Lym#、Mon#和HCT等4项指标参考值范围下限升高,Bas%、Lym#、Mon#和HCT等4项指标参考值范围上限升高,Eos#和Eos%指标参考值范围上限减低,Lym%下限减低;女性血细胞分析指标中的Neu%、Lym#、Mon#和RBC指标变窄,Bas#和Bas%下限升高,Eos%、Lym%、HGB、MCV和MCH下限减低,Eos#、Eos%、Lym%、HGB、MCV和MCH上限减低而HCT上限升高。结论长沙地区应该有选择性的引用标准的参考值范围,并根据需要建立适用于该地区或本实验室的参考值范围。     

Age‐dependent biochemical quantities: An approach for calculating reference intervals

Objective. A parametric method is often preferred when calculating reference intervals for biochemical quantities, as non‐parametric methods are less efficient and require more observations/study subjects. Parametric methods are complicated, however, because of three commonly encountered features. First, biochemical quantities seldom display a Gaussian distribution, and there must either be a transformation procedure to obtain such a distribution or a more complex distribution has to be used. Second, biochemical quantities are often dependent on a continuous covariate, exemplified by rising serum concentrations of MUC1 (episialin, CA15.3) with increasing age. Third, outliers often exert substantial influence on parametric estimations and therefore need to be excluded before calculations are made. Material and methods. The International Federation of Clinical Chemistry (IFCC) currently recommends that confidence intervals be calculated for the reference centiles obtained. However, common statistical packages allowing for the adjustment of a continuous covariate do not make this calculation. Results. In the method described in the current study, Tukey's fence is used to eliminate outliers and two‐stage transformations (modulus‐exponential‐normal) in order to render Gaussian distributions. Fractional polynomials are employed to model functions for mean and standard deviations dependent on a covariate, and the model is selected by maximum likelihood. Confidence intervals are calculated for the fitted centiles by combining parameter estimation and sampling uncertainties. Finally, the elimination of outliers was made dependent on covariates by reiteration. Conclusions. Though a good knowledge of statistical theory is needed when performing the analysis, the current method is rewarding because the results are of practical use in patient care.