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.     

如何正确运用χ2检验——队列设计四格表资料的χ2检验

本文目的是介绍队列设计四格表资料的χ²检验、相对危险度的假设检验和区间估计、SAS以及R软件的实现。针对队列设计的特点,重点介绍相对危险度的概念、假设检验和区间估计方法。对SAS与R软件计算的结果作出解释,并给出统计和专业结论。     

Study on developmental abnormalities in hypospadiac male rats induced by maternal exposure to di-n-butyl phthalate (DBP)

The objective of this study was to establish a hypospadiac rat model by maternal exposure to di-n-butyl phthalate (DBP) and to evaluate the developmental abnormalities of hypospadiac male rats. Timed-pregnant rats were given DBP by gastric intubation at doses of 0, 250, 500, 750 or 1000 mg/kg body weight (bw)/day from gestation day (GD) 14 to 18 to establish a hypospadiac rat model. The hypospadias was observed in the 500 and 750 mg/kg bw/day groups, the incidence of which was 6.8 and 41.3%, respectively. Transverse serial histological analysis of genitalia of hypospadiac male rats confirmed the malformation. With exposed dose increasing, the serum testosterone (T) levels of male rats inversely decreased, and in the same dosage group the serum T levels of hypospadiac rats were significantly lower than the levels of nonhypospadiac counterparts. The other reproductive lesions such as cryptorchidism and decreased ratio of anogenital distance/body weight (AGD/bw) were also observed. Autopsy analysis revealed the development of reproductive organs (prostate, testes, epididymis, pituitary gland) and nonreproductive organs (adrenal gland, liver, kidney, heart, spleen) of hypospadiac rats and nonhypospadiac counterparts. The results indicated that the reproductive system and developmental condition of hypospadiac male offspring were damaged severely by DBP.     

Mice with deleted multimerin 1 and α-synuclein genes have impaired platelet adhesion and impaired thrombus formation that is corrected by multimerin 1

Background

Multimerin 1 is a stored platelet and endothelial cell adhesive protein that shows significant conservation. In vitro, multimerin 1 supports platelet adhesion and it also binds to collagen and enhances von Willebrand factor-dependent platelet adhesion to collagen. As selective, multimerin 1 deficient mice have not been generated, we investigated multimerin 1 effects on platelet adhesion using a subpopulation of C57BL/6J mice with tandem deletion of the genes for multimerin 1 and α-synuclein, a protein that inhibits α-granule release in vitro. We postulated that multimerin 1/α-synuclein deficient mice might show impaired platelet adhesive function from multimerin 1 deficiency and increased α-granule release from α-synuclein deficiency.

Methods

Platelet function was assessed by intravital microscopy, after ferric chloride injury, using untreated and human multimerin 1-transfused multimerin 1/α-synuclein deficient mice, and by in vitro assays of adhesion, aggregation and thrombin-induced P-selectin release.

Results

Multimerin 1/α-synuclein deficient mice showed impaired platelet adhesion and their defective thrombus formation at sites of vessel injury improved with multimerin 1 transfusion. Although multimerin 1/α-synuclein deficient platelets showed increased P-selectin release at low thrombin concentrations, they also showed impaired adhesion to collagen, and attenuated aggregation with thrombin, that improved with added multimerin 1.

Conclusions

Our data suggest that multimerin 1 supports platelet adhesive functions and thrombus formation, which will be important to verify by generating and testing selective multimerin 1 deficient mice.     

A genetic schizophrenia-susceptibility region located between the ANKK1 and DRD2 genes

Background

The gene coding for the D2 dopamine receptor (DRD2) is considered to be one of the most pertinent candidate genes in schizophrenia. However, genetic studies have yielded conflicting results whereas the promising TaqIA variant/rs1800497 has been mapped in a novel gene, ANKK1.

Methods

We investigated eleven single nucleotide polymorphisms (SNPs) spanning the DRD2 and ANKK1 genes, using both a case–control association study comparing 144 independent patients to 142 matched healthy subjects, and a transmission disequilibrium test in 108 trios. This classical genetic study was coupled with a cladistic phylogeny-based association test of human variants, and with an interspecies evolution study of ANKK1.

Results

Case–control study, followed by a 108 trios family-based association analysis for replication, revealed an association between schizophrenia and the ANKK1 rs1800497 (p = 0.01, Odds Ratio = 1.5, 95% Confidence Interval = 1.1–2.2), and the intergenic rs2242592 (p = 2 · 10^− 4, OR = 1.8, 95%CI = 1.3–2.5). A significant SNP–SNP interaction was also found (p < 10^− 5, OR = 2.0, 95%CI = 1.6–2.5). The phylogeny-based association test also identified an association between both these polymorphisms and schizophrenia. Finally, interspecies comparison of the sequences from chimpanzee, orangutan, rhesus macaque and human species suggested specific involvement of ANKK1 in the human lineage.

Conclusions

Intergenic rs2242592 appears to be involved in the genetic vulnerability to schizophrenia, whereas the ANKK1 rs1800497 appears to have a modifying rather than causative effect. Finally, ANKK1 may be a specific human lineage-trait involved in a specific human disease, schizophrenia.     

肺内孤立性结节 CT 动态增强扫描诊断价值的探讨

目的：分析肺内孤立性结节（ SPN）的CT动态增强特点,为临床进一步治疗提供重要帮助。方法回顾分析肺内29个孤立性结节,从病变强化特点、血供模式进行分析其影像学表现。结果本组29例患者中,20例肺癌结节增强后均有不同程度强化,增强峰值位于1～3 min,大部分时间－密度曲线呈速升缓降型,增强后净增CT值15～78 HU;5例炎性结节均出现明显强化,增强后净增CT值均在40～70 HU之间,其中3例炎性结节中心可见低密度区,延迟后未见进一步强化征象,增强曲线呈速升型,达峰后仍有上升趋势;1例肺良性结节增强后净增CT值24 HU,但动态增强曲线呈平台型;3例结核球病灶,1例内部未见强化,1例边缘部呈轻度薄壁环状强化,1例呈轻度不均匀强化。结论动态增强CT扫描可提供结节血液动力学特点及增强模式等功能信息,对良恶性结节的诊断具有较高的应用价值,可协助良恶性结节的鉴别诊断。     

Pulmonary disease among inpatient decedents: Impact of schizophrenia

OBJECTIVES: Determine the risk associated with schizophrenia for common pulmonary illness (pneumonia and chronic obstructive pulmonary disorder (COPD)) during the last year of life. METHODS: Inpatient decedents in Veterans (VA) hospitals in 2002 (N=27,798) were identified. Logistic regression modeled diagnosis of pulmonary illness in either the final year or final admission as a function of schizophrenia, smoking history and other covariates. RESULTS: Among decedents, 943 (3%) had schizophrenia, 3% were women, most were white (76%) or African-American (18%), and average age at death was 72.4 years (SD 11.5). Three-fifths received VA outpatient care in the year prior to death. Among those with schizophrenia, only two-fifths had outpatient care. Pneumonia was more common among schizophrenia patients (38% vs 31%) as was COPD (46% vs 38%). In models controlling for history of smoking and other covariates, schizophrenia was a risk factor for pulmonary disease in the last year of life (OR=1.9, 95% CI 1.6-2.2) but less so for final-stay pulmonary disease (OR=1.5, 95% CI 1.3-1.7). CONCLUSIONS: VA inpatient decedents with schizophrenia were at increased risk for pneumonia and COPD, independent of smoking indicators. Clinicians treating schizophrenia patients need to be especially alert to potential comorbid medical conditions and ensure vulnerable patients receive appropriate care.     

如何正确运用χ2检验——横断面设计四格表资料的χ2检验

本文目的是介绍横断面设计四格表资料的χ²检验及SAS和R软件实现。具体介绍了3种方法,即“Pearson?sχ²检验”“校正的Pearson?sχ²检验”和“似然比χ²检验”。内容涉及前述提及的3种统计分析方法的检验假设、计算原理与公式、前提条件、SAS与R软件的实现、结果解释以及结论陈述。     

Suicide verdicts as opposed to accidental deaths in substance-related fatalities (UK, 2001-2007)

Background

Substance-related deaths account for a great number of suicides.

Aim

To investigate levels and characteristics of suicide verdicts, as opposed to accidental deaths, in substance misusers.

Methods

Psychological autopsy study of cases from the UK National Programme on Substance Abuse Deaths (np-SAD) during the period 2001-2007.

Results

Between January 2001 and December 2007, 2108 suicides were reported to the np-SAD. Typical suicide victims were White and older than 50 (respectively 95% and 41% of cases). Medications, especially antidepressants (44%), were prescribed to 87% of victims. Significantly fewer suicide victims than controls presented positive blood toxicological results for illicit drugs (namely: cocaine, heroin, amphetamines, ecstasy-type drugs, cannabis, and GHB/GBL) and alcohol.

Conclusions

Suicide prevention programmes should devote specific attention to deaths among substance misusers who are at high risk of fatal intentional self-harm. Specific characteristics distinguish those at risk; caregivers should be better educated as to what these factors are. Limitations of the current study included lack of provision of comprehensive information relating to the victims' psychosocial variables. Furthermore, no differentiation between different classes of antidepressants in terms of involvement in suicide was here provided.