Inhibitory effects of cigarette smoke extracts on neural differentiation of mouse embryonic stem cells

Maternal smoking during the perinatal period is linked to adverse neonatal outcomes such as low birth weight and birth defects. Numerous studies have shown that cigarette smoke or nicotine exposure has a widespread effect on fetal nerve development. However, there exists a lack of understanding of what specific changes occur at the cellular level on persistent exposure to cigarette smoke during the differentiation of embryonic stem cells (ESCs) into neural cells. We previously investigated the effects of cigarette smoke extract (CSE) and its major component, nicotine, on the neural differentiation of mouse embryonic stem cells (mESCs). Differentiation of mESCs into neural progenitor cells (NPCs) or neural crest cells (NCCs) was induced with chemically defined media, and the cells were continuously exposed to CSE or nicotine during neural differentiation and development. Disturbed balance of the pluripotency state was observed in the NPCs, with consequent inhibition of neurite outgrowth and glial fibrillary acidic protein (Gfap) expression. These inhibitions correlated with the altered expression of proteins involved in the Notch-1 signaling pathways. The migration ability of NCCs was significantly decreased by CSE or nicotine exposure, which was associated with reduced protein expression of migration-related proteins. Taken together, we concluded that CSE and nicotine inhibit differentiation of mESCs into NPCs or NCCs, and may disrupt functional development of neural cells. These results imply that cigarette smoking during the perinatal period potentially inhibits neural differentiation and development of ESCs cells, leading to neonatal abnormal brain development and behavioral abnormalities.     

两种灸法治疗轻中度膝骨关节炎的疗效对照研究

目的:观察雷火-热敏灸与单纯雷火灸治疗轻中度膝骨关节炎的临床疗效差异。方法:将60例轻中度KOA患者随机分为治疗组和对照组,每组30例,治疗组采用雷火灸条施以热敏灸法治疗,对照组采用单纯雷火灸条悬灸治疗。分别于治疗后2周及治疗4周后,观察两组疼痛VAS评分及骨关节炎指数(WOMAC评分),并比较两组临床疗效。结果:治疗后2周,两组VAS评分及WOMAC各项评分与治疗前比较,差异均具有统计学意义(P0.01);治疗组与对照组比较,VAS评分差异显著(P0.05),WOMAC疼痛评分、WOMAC身体功能评分、WOMAC总分差异极显著(P0.01)。治疗后4周,两组WOMAC僵硬评分与治疗后2周比较,差异显著(P0.05);两组VAS评分、WOMAC疼痛评分、WOMAC身体功能评分及WOMAC总分与治疗后2周比较,差异极显著(P0.01);治疗组与对照组比较,WOMAC身体功能评分、WOMAC总分差异显著(P0.05)。治疗后4周,治疗组与对照组总有效率分别为96.67%和93.33%,两组比较差异具有统计学意义(P0.01);治疗后3个月随访,治疗组与对照组总有效率分别为96.55%和96.30%,两组比较差异具有统计学意义(P0.05)。结论:雷火-热敏灸较单纯雷火灸治疗KOA在短期内疗效更优,且疗效稳定。     

艾灸督脉对肾精亏虚型卒中后轻度认知障碍患者认知功能和中医症状的临床疗效研究

背景 卒中后轻度认知障碍（PSMCI）是卒中后患者常见并发症,影响患者全面康复的同时也给其家庭带来了经济和精神方面的压力。 目的 观察艾灸督脉对肾精亏虚型PSMCI患者认知功能及中医症状的临床疗效。 方法 选取2020年7月至2021年7月河南中医药大学第一附属医院康复中心收治的符合纳入标准的PSMCI患者60例为研究对象,采用随机数字表法将其分为艾灸组和对照组,每组30例。对照组患者给予常规基础治疗及常规认知功能康复训练,艾灸组患者在对照组基础上进行艾灸督脉治疗,1次/d,5次/周,持续4周。比较治疗前后两组患者简易智能精神状态量表（MMSE）、蒙特利尔认知评估量表（MoCA）、血管性痴呆中医辨证量表（SDSVD）中肾精亏虚型和脑卒中专用生活质量量表（SS-QOL）评分,并评定两组治疗的临床疗效和安全性。 结果 艾灸组患者治疗前后MMSE、MoCA、SDSVD、SS-QOL评分差值大于对照组（P<0.05）。艾灸组患者治疗后临床疗效优于对照组（P<0.05）。两组患者治疗安全性比较,差异无统计学意义（P>0.05）。 结论 艾灸督脉可以改善PSMCI患者的认知功能和中医症状,临床疗效佳,且安全性较好。     

Analysis of electrocautery smoke released from the tissues frequently cut in orthopedic surgeries

BACKGROUND Electrosurgical smoke could be different by the device of cutting or the type of tissue that is being cut.AIM To analyze the electrocautery smoke released from the tissues that are frequently cut in orthopedic surgeries.METHODS The released smoke from electrocautery of five different tissue types(meniscus,ligament,adipose,muscle,and synovium) of five patients who underwent total knee arthroplasty were collected and analyzed for volatile organic compounds(VOCs) and 27 candidate polycyclic aromatic hydrocarbons(n = 25).Surgical smoke was produced with an electrocautery device for 4 min.RESULTS None of the 27 evaluated polycyclic aromatic hydrocarbons compounds were detectable in electrocautery smoke collected from the surgical cutting of the different tissues.The number and identity of detected VOCs were similar between the patients but not between tissue types.The number of detected VOCs was the highest in synovial tissue(n = 21) and the lowest in the meniscus and adipose tissue(n = 12).The number of toxic and/or carcinogenic VOCs were the most in the muscle and meniscus tissues(Toluene,Ethylbenzene,and Styrene).No toxic and/or carcinogenic VOCs were identified in the ligament and adipose tissue.CONCLUSION Meniscus and muscle tissue are associated with the highest number of toxic and/or carcinogenic VOCs.Therefore,we recommend that surgeons avoiding the electrocautery of these tissues.     

环境烟草烟雾对小鼠泪膜功能和角膜上皮组织结构的影响

目的　探讨环境烟草烟雾（enviromental tobacco smoke,ETS）对小鼠泪膜功能和角膜上皮组织结构的影响。方法　选取SPF级c57BL雄性小鼠12只,随机分为对照组和ETS干预组,每组6只。对照组不进行ETS干预,ETS干预组进行ETS干预,每天2次,一次30 min,干预12周。在干预前及干预后对各组小鼠进行泪膜功能检测,包括泪膜破裂时间、荧光素染色(FL)评分;干预后摘取小鼠角膜组织,行HE染色,在光学显微镜下观察小鼠角膜上皮结构变化情况。结果　干预12周后,对照组泪膜破裂时间和FL评分与干预前相比,差异均无统计学意义(均为P>0.05);而ETS干预组泪膜破裂时间较干预前明显缩短,FL评分较干预前明显增加,差异均有统计学意义（均为P<0.05)。ETS干预组干预12周后泪膜破裂时间较对照组明显缩短,FL评分较对照组明显增加,差异均有统计学意义(均为P<0.05);两组干预前泪膜破裂时间和FL评分差异均不明显（均为P>0.05）。FL染色结果显示:干预12周后,对照组小鼠角膜上皮完整,角膜染色呈阴性;ETS干预组整个角膜上皮荧光素着染区域明显增加,呈点片状。HE染色结果显示:干预12周后,对照组未见角膜上皮层数的改变,厚度也基本未变,基底细胞仍为单层柱状上皮细胞,表层上皮较完整;ETS干预组可见角膜上皮细胞层数增多,厚度增加,细胞排列紊乱,表层上皮细胞有损失及脱落,角膜表面不光滑。干预前对照组小鼠上皮细胞为（5±1）层,干预后基本不变;ETS干预组干预后为（7±1）层;干预后两组上皮细胞层数比较差异有统计学意义（P＜0.05）。结论　ETS会影响小鼠泪膜功能,损伤小鼠角膜上皮的组织结构。     

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 cigarette format and mouth-level exposure to tar and nicotine in smokers of Russian king-size cigarettes

Differences in length and circumference of cigarettes may influence smoker behaviour and exposure to smoke constituents. Superslim king-size (KSSS) cigarettes (17 mm circumference versus 25 mm circumference of conventional king-size [KS] cigarettes), have gained popularity in several countries, including Russia. Some smoke constituents are lower in machine-smoked KSSS versus KS cigarettes, but few data exist on actual exposure in smokers. We investigated mouth-level exposure (MLE) to tar and nicotine in Russian smokers of KSSS versus KS cigarettes and measured smoke constituents under machine-smoking conditions. MLE to tar was similar for smokers of 1 mg ISO tar yield products, but lower for smokers of 4 mg and 7 mg KSSS versus KS cigarettes. MLE to nicotine was lower in smokers of 4 mg KSSS versus KS cigarettes, but not for other tar bands. No gender differences were observed for nicotine or tar MLE. Under International Organization for Standardization, Health Canada Intense and Massachusetts regimes, KSSS cigarettes tended to yield less carbon monoxide, acetaldehyde, nitric oxide, acrylonitrile, benzene, 1,3-butadiene and tobacco-specific nitrosamines, but more formaldehyde, than KS cigarettes. In summary, differences in MLE were observed between cigarette formats, but not systematically across pack tar bands.     

Oxidative stress and innate immunity responses in cigarette smoke stimulated nasal epithelial cells

Cigarette smoke extracts (CSE) may play a significant role in diseases of the upper airway including chronic rhinosinusitis. Even short term exposure of cigarette smoke has adverse effects on mitochondrial functions and redox homeostasis in tissues which may progress to further complications associated with chronic smoking. Cigarette smoke alters toll-like receptor 4 (TLR4) expression and activation in bronchial epithelial cells. Carbocysteine is an anti-oxidant and mucolytic agent. The effects of carbocysteine on CSE induced oxidative stress and on associated innate immune and inflammatory responses in nasal epithelial cells are largely unknown. The present study was aimed to assess in CSE stimulated nasal epithelial cells (RPMI 2650) the effects of carbocysteine (10⁻⁴ M) on: cell survival, intracellular reactive oxygen species (ROS) production, TLR4 expression, LPS binding and neutrophil chemotaxis (actin reorganization). We found that CSE increased ROS production, TLR4 expression, LPS binding and neutrophil chemotaxis and all these events were counteracted by pre-incubating CSE stimulated RPMI 2650 cells with carbocysteine. In conclusion, the present study provides compelling evidence that carbocysteine may be considered a promising therapeutic strategy in chronic inflammatory nasal diseases.     

Brief exposure to cigarette smoke impairs airway epithelial cell innate anti-viral defence

BackgroundHuman rhinovirus (hRV) infections commonly cause acute upper respiratory infections and asthma exacerbations. Environmental cigarette smoke exposure is associated with a significant increase in the risk for these infections in children.ObjectiveTo determine the impact of short-term exposure to cigarette smoke on innate immune responses of airway epithelial cells infected with hRV.MethodsA human bronchial epithelial cell line (HBEC-3KT) was exposed to cigarette smoke extract (CSE) for 30 min and subsequently infected with hRV serotype 1B. Viral-induced cytokine release was measured with AlphaLISA and viral replication quantified by shed viral titer and intracellular viral copy number 24 h post-infection.ResultsCSE induced a concentration-dependent decrease in CXCL10 (p < 0.001) and IFN-β (p < 0.001), with a 79% reduction at the highest dose with an associated 3-fold increase in shed virus. These effects were maintained when infection was delayed up to 24 h post CSE exposure. Exogenous IFN-β treatment at t = 0 after infection blunts the effects of CSE on viral replication (p < 0.05).ConclusionA single exposure of 30 min to cigarette smoke has a lasting impact on epithelial innate defence providing a plausible mechanism for the increase in respiratory infections seen in children exposed to second-hand tobacco smoke.