铅对雄性生殖毒性的研究进展

从铅对睾丸与附睾形态、精子生成和发育以及生殖内分泌功能等三方面的影响综述了铅对雄性生殖毒性的研究进展;并从铅对睾丸的脂质过氧化损伤,对睾丸标志酶活性的影响,对染色体、DNA及基因的影响以及对CaM、Ca2 -ATP酶活性的影响等方面探讨了铅对雄性生殖毒性作用机理。同时,提出了铅对雄性生殖毒性的研究中存在的若干问题和发展方向。     

丙烯酰胺对雄性小鼠生殖细胞遗传损伤的研究

以雄性小鼠的生殖细胞为研究对象,经腹腔注射丙烯酰胺建立动物模型,采用生殖细胞早期精细胞微核和初级精母细胞染色体制作技术联合评价丙烯酰胺对雄性小鼠的生殖毒性及遗传毒性,观察染毒后精子发育的不同阶段对丙烯酰胺的损伤反应,为丙烯酰胺的生殖损伤提供一定依据。     

丙烯酰胺神经系统毒性机制

丙烯酰胺(acrylamide,ACR)是公认的神经、致癌、遗传和雄性生殖毒物。高温(120 oC)烹饪富含淀粉食物会产生ACR及致癌性已在近年引起世界卫生组织(WHO)和联合国粮农组织(FAO)的关注,本文就ACR的性质、危害、代谢、对神经行为的影响和神经毒性机制的研究状况方面进行综述,以期为ACR对神经系统毒性作用的特点、机制及危险度评定和防治提供科学依据。     

蛇毒心脏毒素对动物细胞的遗传损伤和生殖毒性研究

目的 应用眼镜蛇毒心脏毒素（ＣＴＸ）作用于小鼠的骨髓细胞和生殖细胞,以探讨ＣＴＸ对动物体的生殖毒性和遗传毒性。方法 对小鼠腹腔注射不同剂量ＣＴＸ,通过生殖毒性实验和致突变实验,分析孕鼠的胚胎存活率,骨髓细胞和精母细胞的染色体畸变率。结果：ＣＴＸ能影响胎鼠的生长发育,使孕鼠的增重和活胎率均明显地降低（Ｐ〈０．００１）,染色体畸变实验显示ＣＴＸ０．４ｍｇ／ｋｇ剂量上精母细胞多倍体和非整倍体细胞数目增高     

康脂口服液毒理学的研究

通过大、小鼠的急性毒性试验和大鼠的急性毒性试验和大鼠蓄积毒性试验及遗传毒性试验表明,康脂口服液的ＬＤ５０大于１０．００ｇ／ｋｇ．ｂｗ,实属无毒物质;蓄积毒性试验３表明,本品蓄积系数Ｋ〉５,为弱蓄积;遗传毒性试验得知,Ａｍｅｓ试验无遗传毒性,对小鼠骨髓嗜多染红细胞微核及小鼠精子畸形试验也均未产生影响,说明本品长期服用比较安全。     

不同温度下氯对水生生物的毒性及制订渔业水质标准的探讨

研究氯对鱼类、蚤类及藻类的急性及亚致死毒性,从急性试验结果看,氯的性随温度的上升而提高。亚致死毒性研究了氯对大型蚤的生殖,白鲢幼鱼的鳃组织学,血液学的变化,白鲢幼鱼的迥避反应及对鲤鱼吸收的影响等,结果说明,氯对水生生物的亚致死死效应不尽相同,不同的生物种,不同的生理指标,氯的亚致死效率与温度的关系也不同,反映出这种毒性效应的复杂性,两者之间并没有固定的相关关系。在亚致死效应中大型蚤的生殖及白链的血液指标对氯最为敏感,据此作者对我国保护水生生物的氯的水质标准提出了一些建议。     

粪便提取液毒性检测方法的建立及应用

目的建立检测人体粪便提取液对肠上皮细胞毒性的方法。方法以Caco-2细胞为体外模型,应用建立好的毒性检测方法：用MTT法（四甲基偶氮唑盐微量酶反应比色法）检测细胞毒性,用单细胞凝胶电泳技术检测遗传毒性,对糖尿患者和健康人的粪便提取液进行分析。结果糖尿病患者粪便提取液的细胞毒性显著高于健康人（n=30,P〈0.05）;其遗传毒性显著高于阴性对照PBS（P〈0.05）,与健康人相比有升高趋势,但差异无统计学意义。结论粪便提取液的毒性检测方法可以简便、有效地检测人体粪便中毒性物质对肠上皮细胞的影响,因此可作为评价肠道菌群状态的方法。     

遗传毒性检测的新标准

简单来讲,遗传毒性是指某种物质（如药物研发中的先导化合物）能直接或间接杀伤细胞DNA的性质。例如,化合物中的铅含量可以致动物组织DNA的损伤。许多抗癌冶疗的不良反应也是遗传毒性药物对正常细胞的影响所致。因此,美国食品与药物管理局要求美国的制药行业,针对药物产品业制定遗传毒性检测标准,以保证新药品的安全性。     

用SOS显色法检测金属化合物的遗传毒性

用SOS显色法对12种金属化合物的遗传毒性进行了检测,发现多种金属化合物具有遗传毒性,在 SOS显色法中呈阳性反应,其中已知具有致癌作用的镍和钻化合物在Ames沙门氏菌／微粒体测试法 检测中呈阴性结果,镍化合物在枯草杆菌的Rec测试法中也呈阴性。uvrA基因的存在对SOS显色法 检测某些金属化合物的遗传毒性有重要的影响。     

Cu2+对泥鳅精子运动的影响

以泥鳅精子为受试材料,应用计算机辅助精子分析(CASA),研究不同浓度Cu2+暴露对运动型精子和静止型精子的毒性.结果 显示,运动型精子和静止型精子暴露在10 μM的Cu2+中,两者运动能力均受到明显抑制;在30 μM及以下浓度中运动型精子受影响程度较静止型精子大,而在更高浓度中出现相反结果.表明泥鳅精子对Cu2+毒性较敏感,不同能量代谢状态时其敏感性不同;Cu2+对泥鳅精子运动能力有较大影响,对淡水鱼具有潜在生殖毒性.     

吸烟、自由基与健康

吸烟有害健康,其中,吸烟过程中产生的大量自由基是损害健康的重要因素。研究吸烟产生的自由基及其损害健康的机理,以及减少乃至祛除吸烟危害、保护人类健康的策略,具有重要的社会意义。从学术角度来看,吸烟产生多种自由基,也是研究自由基的一个好模型。本文综述了吸烟、自由基与健康关系方面的研究进展,特别总结了我们实验室20多年在这方面的研究工作,供读者和同行参考。     

Socioeconomic Inequalities in Smoking and Smoking Cessation Due to a Smoking Ban: General Population-Based Cross-Sectional Study in Luxembourg

This study aimed to measure changes in socioeconomic inequalities in smoking and smoking cessation due to the 2006 smoking ban in Luxembourg. Data were derived from the PSELL3/EU-SILC (Panel Socio-Economique Liewen Zu Letzebuerg/European Union—Statistic on Income and Living Conditions) survey, which was a representative survey of the general population aged ≥16 years conducted in Luxembourg in 2005, 2007, and 2008. Smoking prevalence and smoking cessation due to the 2006 smoking ban were used as the main smoking outcomes. Two inequality measures were calculated to assess the magnitude and temporal trends of socioeconomic inequalities in smoking: the prevalence ratio and the disparity index. Smoking cessation due to the smoking ban was considered as a positive outcome. Three multiple logistic regression models were used to assess social inequalities in smoking cessation due to the 2006 smoking ban. Education level, income, and employment status served as proxies for socioeconomic status. The prevalence of smoking decreased by 22.5% between 2005 and 2008 (from 23.1% in 2005 to 17.9% in 2008), but socioeconomic inequalities in smoking persisted. Smoking prevalence decreased by 24.2% and 20.2% in men and women, respectively; this difference was not statistically significant. Smoking cessation in daily smokers due to the 2006 smoking ban was associated with education level, employment status, and income, with higher percentages of quitters among those with a lower socioeconomic status. The decrease in smoking prevalence after the 2006 law was also associated with a reduction in socioeconomic inequalities, including differences in education level, income, and employment status. Although the smoking ban contributed to a reduction of such inequalities, they still persist, indicating the need for a more targeted approach of smoke-free policies directed toward lower socioeconomic groups.     

Passive exposure to tobacco smoke: saliva cotinine concentrations in a representative population sample of non-smoking schoolchildren.

Saliva cotinine concentrations in 569 non-smoking schoolchildren were strongly related to the smoking habits of their parents. When neither parent smoked the mean concentration was 0.44 ng/ml, rising to 3.38 ng/ml when both parents were cigarette smokers. Mothers'' smoking had a stronger influence than did fathers'' (p less than 0.01). In addition, there was a small independent effect of number of siblings who smoked (p less than 0.01). The dose of nicotine received from fathers'' smoking was estimated as equivalent to the active smoking of 30 cigarettes a year, that from mothers'' smoking as equivalent to smoking 50 cigarettes a year, and that from both parents smoking as equivalent to smoking 80 cigarettes a year. This unsolicited burden may be prolonged throughout childhood and poses a definite risk to health.     

Smoking status of parents, siblings and friends: predictors of regular smoking? Findings from a longitudinal twin-family study.

The relationship between regular smoking behavior and the smoking behavior of parents, siblings and friends was investigated using data from the Netherlands Twin Register. Cross-sectional analyses of data of 3906 twins showed significant associations between smoking behavior of the participant and smoking behavior of co-twin, additional brothers, parents of the same sex as the participant and friends. Those variables, together with age, explained 47% of the variance in smoking behavior. Longitudinal analyses of data from 2397 twins, who, in 1993, reported never to have smoked (regularly), showed that uptake of regular smoking two years later was predicted by having a smoking co-twin, smoking same-sex siblings, smoking mother and smoking friends. Males are, in contrast to females, at a later age still vulnerable to taking up regular smoking. The variables explained 21% of the variance. Sport participation, alcohol use, boredom susceptibility and neuroticism significantly added to the predictive value of this model. Including those additional factors increased the explained variance to 30%, and subsequently adding experimental smoking behavior further increased the explained variance to almost 50%. In summary, having smoking family members and friends, as well as lifestyle and personality factors are important predictors for the uptake of regular smoking. However, the experimental smoking behavior of the participant is equally important.     

What Are the Major Determinants in the Success of Smoking Cessation: Results from the Health Examinees Study

Understanding mechanisms underlying smoking-related factors should be prioritized in establishing smoking prevention and cessation policy. The aim of this study was to identify factors significantly associated with smoking initiation and/or smoking cessation as well as the most important determinants of successful smoking cessation in a developed non-Western setting. Based on multiple logistic regression models, the odds ratios (ORs) for smoking initiation and cessation were estimated among males (N = 24,490) who had participated in the Health Examinees (HEXA) study. The Cox proportional hazards regression model was used to assess the association between selected predictors of smoking cessation and the likelihood of reaching this goal. Finally, Kaplan–Meier curves were constructed to illustrate the distribution of time from age at smoking initiation to age at smoking cessation. We found that the ORs for successfully quitting smoking increased with age, married status, educational achievement, having a non-manual job, drinking cessation and disease morbidity. Those exposed to secondhand smoking showed less likelihood of quitting smoking. A continual decrease in the ORs for successfully quitting smoking was observed according to increased smoking duration, smoking dose per day and lifetime tobacco exposure (p _trend <0.001). Among the selected predictors, lifetime tobacco exposure, educational attainment, alcohol drinking status and birth cohort were the major determinants in the success of smoking cessation. Our findings suggest that lifetime tobacco exposure, educational attainment, alcohol drinking status and birth cohort can determine success in smoking cessation. Public interventions promoting a smoke-free environment are needed to reinforce discouraging the initiation of, reducing, and quitting cigarette smoking.     

Variation in size at birth and cigarette smoking during pregnancy

The influence of cigarette smoking during pregnancy and other familial factors on size at birth and gestation length is investigated among 458 births to 227 mothers living in a suburban community in the U.S. In this sample, 56% of the births were to mothers who reported not smoking during the pregnancy and 35% were to mothers who reported smoking 20 cigarettes or less. Multiple stepwise regression analysis was employed to examine the influence of cigarette smoking after statistical adjustment for such social and biological characteristics of the family as parents' sizes, education, income, and aspects of mother's reproductive history. After correction for significant social and biological characteristics, smoking status was a significant contributor to birth weight variation. In fact, cigarette smoking had the next-largest partial correlation coefficient (r = -0.26) second to gestation length. Birth length is also negatively associated with cigarette smoking, though not so strongly as is birth weight. The reduction in birth lengths can be attributed to the reduction in birth weights. Gestation length was not associated with cigarette smoking in this sample. The analysis of collinearity between smoking status and the other independent variables indicates that the effect of smoking appears to be independent of interrelationships among the independent variables.     

Determinants of Smoking and Quitting in HIV-Infected Individuals

BackgroundCigarette smoking is widespread among HIV-infected patients, who confront increased risk of smoking-related co-morbidities. The effects of HIV infection and HIV-related variables on smoking and smoking cessation are incompletely understood. We investigated the correlates of smoking and quitting in an HIV-infected cohort using a validated natural language processor to determine smoking status.MethodWe developed and validated an algorithm using natural language processing (NLP) to ascertain smoking status from electronic health record data. The algorithm was applied to records for a cohort of 3487 HIV-infected from a large health care system in Boston, USA, and 9446 uninfected control patients matched 3:1 on age, gender, race and clinical encounters. NLP was used to identify and classify smoking-related portions of free-text notes. These classifications were combined into patient-year smoking status and used to classify patients as ever versus never smokers and current smokers versus non-smokers. Generalized linear models were used to assess associations of HIV with 3 outcomes, ever smoking, current smoking, and current smoking in analyses limited to ever smokers (persistent smoking), while adjusting for demographics, cardiovascular risk factors, and psychiatric illness. Analyses were repeated within the HIV cohort, with the addition of CD4 cell count and HIV viral load to assess associations of these HIV-related factors with the smoking outcomes.ResultsUsing the natural language processing algorithm to assign annual smoking status yielded sensitivity of 92.4, specificity of 86.2, and AUC of 0.89 (95% confidence interval [CI] 0.88–0.91). Ever and current smoking were more common in HIV-infected patients than controls (54% vs. 44% and 42% vs. 30%, respectively, both P<0.001). In multivariate models HIV was independently associated with ever smoking (adjusted rate ratio [ARR] 1.18, 95% CI 1.13–1.24, P <0.001), current smoking (ARR 1.33, 95% CI 1.25–1.40, P<0.001), and persistent smoking (ARR 1.11, 95% CI 1.07–1.15, P<0.001). Within the HIV cohort, having a detectable HIV RNA was significantly associated with all three smoking outcomes.ConclusionsHIV was independently associated with both smoking and not quitting smoking, using a novel algorithm to ascertain smoking status from electronic health record data and accounting for multiple confounding clinical factors. Further research is needed to identify HIV-related barriers to smoking cessation and develop aggressive interventions specific to HIV-infected patients.     

Tomotherapy-based moderate hypofractionation for localized prostate cancer: a mono-institutional analysis

BackgroundTo date, few studies have been published on image-guided helical tomotherapy (HT) in a moderate hypofractionation of localized PCa. We report outcome and toxicity of localized PCa patients treated with HT-based moderate hypofractionated radiotherapy.Materials and methods76 patients were retrospectively analyzed. A total dose of 60 Gy (20 × 3 Gy) or 67.5 Gy (25 × 2.7 Gy) was prescribed. The χ² test was used to analyze associations between toxicity and dosimetric and clinical parameters. The Cox proportional hazard regression model was used for multivariate analysis. Kaplan-Meier method was used for survival analysis.Resultsmedian follow-up was 42.26 months [interquartile (IQR), 23–76). At 4-year, overall survival (OS) and metastasis-free survival (MFS) were 91% and 89%, respectively. At multivariate analysis, smoking habitude was associated with MFS [hazard ratio (HR) 7.32, 95% CI: 1.57–34.16, p = 0.011]. Acute and late grade ≥ 2 gastro-intestinal (GI) toxicity was observed in 6.5% and 2.6% of patients, respectively. Acute and late grade ≥ 2 genito-urinary (GU) toxicity were 31.5% and 3.9%. Four-year late GI and GU grade ≥ 2 toxicity were 3% and 7%, respectively. Acute GI toxicity was associated with statins medication (p = 0.04) and androgen deprivation therapy (p = 0.013). Acute GU toxicity was associated with the use of anticoagulants (p = 0.029) and antiaggregants (p = 0.013).ConclusionsHT-based moderate hypofractionation shows very low rates of toxicity. Smoking habitude is associated with the risk of developing metastases after radical treatment for localized PCa.     

Effect of Exposure to Smoking in Movies on Young Adult Smoking in New Zealand

Onscreen Smoking Is a Form of Tobacco Marketing

Tobacco advertising has been prohibited in New Zealand since 1990, and the government has set a goal of becoming a smokefree nation by 2025. However, tobacco marketing persists indirectly through smoking in motion pictures, and there is strong evidence that exposure to onscreen smoking causes young people to start smoking. We investigated the relationship between exposure to smoking in movies and youth smoking initiation among New Zealand young adults. Data from an online survey of 419 smokers and non-smokers aged 18 to 25 were used to estimate respondents’ exposure to smoking occurrences in 50 randomly-selected movies from the 423 US top box office movies released between 2008 and 2012. Analyses involved calculating movie smoking exposure (MSE) for each respondent, using logistic regression to analyse the relationship between MSE and current smoking behaviour, and estimating the attributable fraction due to smoking in movies.

Effect of Smoking in Movies on New Zealand Youth

Exposure to smoking occurrences in movies was associated with current smoking status. After allowing for the influence of family, friends and co-workers, age and rebelliousness, respondents’ likelihood of smoking increased by 11% for every 100-incident increase in exposure to smoking incidents, (aOR1.11; p< .05). The estimated attributable fraction due to smoking in movies was 54%; this risk could be substantially reduced by eliminating smoking from movies currently rated as appropriate for youth. We conclude that exposure to smoking in movies remains a potent risk factor associated with smoking among young adults, even in a progressive tobacco control setting such as New Zealand. Harmonising the age of legal tobacco purchase (18) with the age at which it is legal to view smoking in movies would support New Zealand’s smokefree 2025 goal.     

Cigarette smoking and risk of second primary cancer: a systematic review and meta-analysis

Approximately 5% of the population are living with a diagnosis of cancer. Recent improvements in survival following a diagnosis of cancer have led to an increase in second primary cancers (SPCs) worldwide. Their aetiology remains largely unknown with a large proportion believed to be related to modifiable lifestyle factors. We conducted a systematic review and meta-analysis of published data that evaluated an association between cigarette smoking and risk of SPC. Studies were identified by searching Medline, Web of Science, CINAHL (Cumulative Index to Nursing and Allied Health Literature) and Scopus databases through March 2021 using broad search criteria. A meta-analysis was performed to derive pooled relative risks (RRs) for SPC defined a priori as smoking-related based on current evidence (lung, upper aero-digestive tract, stomach, pancreas, colorectum, liver, kidney, ureter, bladder and acute myeloid leukaemia). Eleven cohort studies and ten case-control studies met the eligibility criteria for review. There was marked heterogeneity in methods used in terms of classification and timing of smoking, confounders adjusted for and duration of follow-up across the studies. Nine cohort and seven case-control studies classified smoking habits prior to diagnosis of first cancer while the remaining studies classified post-first cancer smoking habits. In a meta-analysis using six studies, an increased risk of smoking-related SPC was observed for both former (RR=1.42; 95% confidence interval (CI) 1.20–1.67) and current smoking (RR=2.76; 95% CI 2.29–3.33), compared with never smoking. The pooled RRs changed only slightly when studies which measured post-first cancer smoking were excluded. A two-fold increase in risk was observed for ever smoking compared with never smoking. In conclusion, there was evidence that smoking might increase the risk of SPC in cancer survivors. For better informed cancer survivorship practice guidelines, more studies are needed particularly of post-cancer smoking and for cancers not known to be caused by smoking.