前列腺源性ETS因子在哮喘及鼻黏膜炎性疾病中的研究进展

含SAM尖端结构域的E26转化特异性因子(SPDEF)是ETS转录因子家族的最新成员之一, SPDEF又称为前列腺源性ETS因子(PDEF),首次发现其在前列腺癌中高度表达,参与肿瘤细胞的增殖分化、迁移凋亡和血管形成。近年来研究发现SPDEF与杯状细胞增生和分化密切相关,是调控呼吸道黏液高分泌的核心因子。对SPDEF调控黏液高分泌的机制及其在呼吸道慢性炎性疾病中的研究进展做一综述,以期为呼吸道黏液高分泌疾病的发病机制和诊治提供新思路。     

A review of the evidence on smoking bans and incidence of heart disease

We update an earlier review of smoking bans and heart disease, restricting attention to admissions for acute myocardial infarction. Forty-five studies are considered. New features of our update include consideration of non-linear trends in the underlying rate, a modified trend adjustment method where there are multiple time periods post-ban, comparison of estimates based on changes in rates and numbers of cases, and comparison of effect estimates according to post-ban changes in smoking restrictiveness. Using a consistent approach to derive ban effect estimates, taking account of linear time trends and control data, the reduction in risk following a ban was estimated as 4.2% (95% confidence interval 1.8–6.5%). Excluding regional estimates where national estimates are available, and studies where trend adjustment was not possible, the estimate reduced to 2.6% (1.1–4.0%). Estimates were little affected by non-linear trend adjustment, where possible, or by basing estimates on changes in rates. Ban effect estimates tended to be greater in smaller studies, and studies with greater post-ban changes in smoking restrictiveness. Though the findings suggest a true effect of smoking bans, uncertainties remain, due to the weakness of much of the evidence, the small estimated effect, and various possibilities of bias.     

Relationship between 18F-FDG PET/CT Semi-Quantitative Parameters and International Association for the Study of Lung Cancer,American Thoracic Society/European Respiratory Society Classification in Lung Adenocarcinomas

ObjectiveTo investigate the relationship between ¹⁸F-FDG PET/CT semi-quantitative parameters and the International Association for the Study of Lung Cancer, American Thoracic Society/European Respiratory Society (IASLC/ATS/ERS) histopathologic classification, including histological subtypes, proliferation activity, and somatic mutations.Materials and MethodsThis retrospective study included 419 patients (150 males, 269 females; median age, 59.0 years; age range, 23.0–84.0 years) who had undergone surgical removal of stage IA–IIIA lung adenocarcinoma and had preoperative PET/CT data of lung tumors. The maximum standardized uptake values (SUVmax), background-subtracted volume (BSV), and background-subtracted lesion activity (BSL) derived from PET/CT were measured. The IASLC/ATS/ERS subtypes, Ki67 score, and epidermal growth factor/anaplastic lymphoma kinase (EGFR/ALK) mutation status were evaluated. The PET/CT semi-quantitative parameters were compared between the tumor subtypes using the Mann–Whitney U test or the Kruskal–Wallis test. The optimum cutoff values of the PET/CT semi-quantitative parameters for distinguishing the IASLC/ATS/ERS subtypes were calculated using receiver operating characteristic curve analysis. The correlation between the PET/CT semi-quantitative parameters and pathological parameters was analyzed using Spearman’s correlation. Statistical significance was set at p < 0.05.ResultsSUVmax, BSV, and BSL values were significantly higher in invasive adenocarcinoma (IA) than in minimally IA (MIA), and the values were higher in MIA than in adenocarcinoma in situ (AIS) (all p < 0.05). Remarkably, an SUVmax of 0.90 and a BSL of 3.62 were shown to be the optimal cutoff values for differentiating MIA from AIS, manifesting as pure ground-glass nodules with 100% sensitivity and specificity. Metabolic-volumetric parameters (BSV and BSL) were better potential independent factors than metabolic parameters (SUVmax) in differentiating growth patterns. SUVmax and BSL, rather than BSV, were strongly or moderately correlated with Ki67 in most subtypes, except for the micropapillary and solid predominant groups. PET/CT parameters were not correlated with EGFR/ALK mutation status.ConclusionAs noninvasive surrogates, preoperative PET/CT semi-quantitative parameters could imply IASLC/ATS/ERS subtypes and Ki67 index and thus may contribute to improved management of precise surgery and postoperative adjuvant therapy.     

Perinatal exposure to environmental tobacco smoke induces adenylyl cyclase and alters receptor-mediated cell signaling in brain and heart of neonatal rats

Perinatal exposure to environmental tobacco smoke (ETS) has adverse effects on neurobehavioral development. In the current study, rats were exposed to ETS during gestation, during the early neonatal period, or both. Brains and hearts were examined for alterations in adenylyl cyclase (AC) activity and for changes in beta-adrenergic and m2-muscarinic cholinergic receptors and their linkage to AC. ETS exposure elicited induction of total AC activity as monitored with the direct enzymatic stimulant, forskolin. In the brain, the specific coupling of beta-adrenergic receptors to AC was inhibited in the ETS groups, despite a normal complement of beta-receptor binding sites. In the heart, ETS evoked a decrease in m2-receptor expression. In both tissues, the effects of postnatal ETS, mimicking passive smoking, were equivalent to (AC) or greater than (m2-receptors) those seen with prenatal ETS mimicking active smoking; the effects of combined prenatal and postnatal exposure were equivalent to those seen with postnatal exposure alone. These data indicate that ETS exposure evokes changes in cell signaling that recapitulate those caused by developmental nicotine treatment. Since alterations in AC signaling are known to affect cardiorespiratory function, the present results provide a mechanistic link reinforcing the participation of ETS exposure, including postnatal ETS, in disturbances culminating in events like Sudden Infant Death Syndrome.     

Nicotine and surface of particulates as indicators of exposure to environmental tobacco smoke in public places in Austria

As part of a Europe-wide project the amount of exposure to environmental tobacco smoke (ETS) in public places like schools, restaurants, and public transport facilities was investigated. Three methods were applied: nicotine passive samplers (with a filter treated with sodium bisulphate), the same filters with an active sampling device, and the measurement of fine particles' active surface by unipolar diffusion charging. Settings were selected where either high or low ETS concentrations were expected and where non-smokers would have to stay or at least to pass by. Highest ETS concentrations were found in discos (mean nicotine concentration 154.4 maximum 487.1 microg/m3) and intermediate concentrations in restaurants with no significant difference between smoking (21.3 +/- 6.1 microg/m3) and non-smoking areas (23.3 +/- 15.9 microg/m3) but on average higher values in restaurants with no separation between smoking and non-smoking areas (38.0 +/- 60.6 microg/m3). Concentrations usually below 10 microg/m3 were found in transport facilities (8.9 +/- 8.0 microg/m3, maximum 20.6 in the restaurant section of a railway station's waiting room) and in schools (3.0 +/- 4.6 microg/m3). In hospitals "problem spots" were sought and so concentrations from very low to as high as 45.1 microg/m3 next to a smoking area with no physical barrier or separation and 47.7 microg/m3 inside a smoking room could be documented (21.4 +/- 39.3 microg/m3). The fine particle's surface correlated well with the nicotine concentration (r = 0.8; p < 0.001). Only in one instance (in a pizza restaurant on a busy road with heavy duty diesel traffic and the sampling spot next to the pizza stove) high concentration of fine particles was detected without high nicotine. Tobacco smoke is a key source of indoor fine particles. Health policy must intervene to change the situation found at present in many public places in Austria.     

The interpersonal management of environmental tobacco smoke in the home–a qualitative study

The home is a significant source of environmental tobacco smoke (ETS) exposure for many children and, therefore, increasingly a focus of intervention, although evidence of effectiveness remains equivocal. However, little is known about the nature, genesis, and micro-social context of self-imposed restrictions on smoking in the home. In this exploratory study, interviews were conducted in 15 diverse households that had resident children in Toronto, Canada. The results suggest that households cluster into three distinctive groups, from a high degree of restrictions to a lack of consistent measures. Attempts to control ETS exposures in homes often emerge as a result of protracted negotiations and must be understood in the context of situated relationships within the family. Implications for policy and practice, as well as recommendations for future research, are addressed.     

What is new in HIV/AIDS research in developing countries?

HIV epidemic has had greatest impact in sub‐Saharan Africa (SSA) and mainly in East and Southern Africa with HIV prevalence in some parts going up to 30%. In the recent years, considerable HIV research on prevention, treatment and care, and vaccine has been conducted in many developing countries and provided evidence‐based knowledge to control the epidemic. However, there have also been disappointing results in HIV prevention trials such as in HIV vaccine and microbicide trials. Despite these outcomes, important lessons have been learnt that help in designing future trials. This article examines the recent advances in HIV research in developing countries. The most recent HIV prevention research has demonstrated the effect of male circumcision on HIV acquisition, and lack of impact of HSV‐2 treatment on HIV transmission and acquisition. Use of HIV antiretroviral drugs (ARVs) for HIV prevention is a new area that has attracted interest and a number of trials are examining the effect of oral Pre‐Exposure Prophylaxis on HIV acquisition and also looking at the potential of ARVs in reducing infectiousness. Progress has been made in HIV treatment, monitoring treatment efficacy and toxicity as well as evaluation of different models of ART delivery. HIV vaccine research has, however, faced most challenges despite many efforts that have been put in. Looking into the future, there are ongoing trials that will hopefully generate important information to strengthen HIV policies in the next few years. There are, however, many other gaps in HIV research that need to be urgently addressed.