- 作者列表："Huang CC","Chen TH","Ho CH","Chen YC","Hsu CC","Lin HJ","Wang JJ","Chang CP","Guo HR
BACKGROUND:Carbon monoxide poisoning (COP) is an important public health issue around the world. It may increase the risk of myocardial injury, but the association between COP and congestive heart failure (CHF) remains unclear. We conducted a study incorporating data from epidemiological and animal studies to clarify this issue. METHODS:Using the National Health Insurance Database of Taiwan, we identified patients with COP diagnosed between 1999 and 2012 and compared them with patients without COP (non-COP cohort) matched by age and the index date at a 1:3 ratio. The comparison for the risk of CHF between the COP and non-COP cohorts was made using Cox proportional hazards regression. We also established a rat model to evaluate cardiac function using echocardiography and studied the pathological changes following COP. RESULTS:The 20 942 patients in the COP cohort had a higher risk for CHF than the 62 826 members in the non-COP cohort after adjusting for sex and underlying comorbidities (adjusted hazard ratio, 2.01 [95% CI, 1.74-2.32]). The increased risk of CHF persisted even after 2 years of follow-up (adjusted hazard ratio, 1.85 [95% CI, 1.55-2.21]). In the animal model, COP led to a decreased left ventricular ejection fraction on echocardiography and damage to cardiac cells with remarkable fibrotic changes. CONCLUSIONS:Our epidemiological data showed an increased risk of CHF was associated with COP, which was supported by the animal study. We suggest close follow-up of cardiac function for patients with COP to facilitate early intervention and further studies to identify other long-term effects that have not been reported in the literature.
背景: 一氧化碳中毒是世界范围内的重要公共卫生问题。它可能增加心肌损伤的风险，但COP与充血性心力衰竭 (CHF) 之间的关系仍不清楚。我们进行了一项纳入流行病学和动物研究数据的研究，以澄清这一问题。 方法: 使用台湾国家健康保险数据库，我们确定了1999年至2012年间诊断为COP的患者，并将其与年龄和指数日期1:3匹配的无COP患者 (非COP队列) 进行比较。使用Cox比例风险回归对COP和非COP队列之间的CHF风险进行比较。我们还利用超声心动图建立了评价心功能的大鼠模型，并研究了COP后的病理变化。 结果: 在调整了性别和基础合并症后，COP队列中的20-942例患者比非COP队列中的62-826例患者患CHF的风险更高 (调整后的风险比，2.01 [95% CI，1.74-2.32])。即使在2年的随访后，CHF的风险仍然增加 (校正风险比，1.85 [95% CI，1.55-2.21])。在动物模型中，COP导致超声心动图上的左心室射血分数降低和心脏细胞损伤，具有显著的纤维化变化。 结论: 我们的流行病学数据显示CHF的风险增加与COP相关，这得到了动物研究的支持。我们建议对COP患者的心功能进行密切随访，以促进早期干预，并进一步研究以确定文献中尚未报道的其他长期影响。
METHODS::The ATP binding-cassette superfamily corresponds the mostly transmembrane transporters family found in humans. These proteins actively transport endogenous and exogenous substrates through biological membranes in body tissues, so they have an important role in the regulation of many physiological functions necessary for human homeostasis, as well as in response regulation to several pharmacological substrates. The development of multidrug resistance has become one of the main troubles in conventional chemotherapy in different illnesses including cancer, being the increased efflux of antineoplastic drugs the main reason for this multidrug resistance, with a key role of the ABC superfamily. Likely, the interindividual variability in the pharmacological response among patients is well known, and may be due to intrinsically factors of the disease, genetic and environmental ones. Thus, the understanding of this variability, especially the genetic variability associated with the efficacy and toxicity of drugs, can provide a safer and more effective pharmacological treatment, so ABC genes are considered as important regulators due to their relationship with the reduction in pharmacological response. In this review, updated information about transporters belonging to this superfamily was collected, the possible role of these transporters in cancer, the role of genetic variability in their genes, as well as some therapeutic tools that have been tried to raise against main transporters associated with chemoresistance in cancer.
METHODS:BACKGROUND:Cholinergic neurotransmission regulates neuroinflammation in Parkinson disease (PD). RESEARCH DESIGN AND METHODS:The authors conducted a delayed-start study of donepezil for cognitive decline in non-demented PD patients. The study consisted of a 96-week randomized placebo-controlled double-blind phase 1, followed by a 24-week donepezil extension phase 2. The primary outcome measure was a change in the Mini-Mental State Examination (MMSE) at week 120. RESULTS:A total of 98 patients were randomly allocated to the early-start (donepezil-to-donepezil) and delayed-start (placebo-to-donepezil) groups. Mean (SD) of the baseline MMSE was 27.6 (2.0) and 28.0 (2.1), respectively. MMSE change at week 120 was better in the early-start group than in the delayed-start group, but the difference was not significant. The MMSE declined in apolipoprotein ε4 carriers, but not in non-carriers, and the factor interaction (intervention × ε4 genotype) was highly significant (P < 0.001). Analyzed with the interaction, the difference was significant (group difference 1.95 [0.33 to 3.57], P = 0.018). The MMSE decline slope in phase 1 was significantly better in the early-start group than in the delayed-start group (P = 0.048). CONCLUSIONS:Cognitive function deteriorated in ε4 carriers, but not in non-carriers, and early-start donepezil may postpone cognitive decline in the former.
METHODS::Since the discovery of dental pulp stem cells, a lot of teams have expressed an interest in dental pulp regeneration. Many approaches, experimental models and biological explorations have been developed, each including the use of stem cells and scaffolds with the final goal being clinical application in humans. In this review, the authors' objective was to compare the experimental models and strategies used for the development of biomaterials for tissue engineering of dental pulp with stem cells. Electronic queries were conducted on PubMed using the following terms: pulp regeneration, scaffold, stem cells, tissue engineering and biomaterial. The extracted data included the following information: the strategy envisaged, the type of stem cells, the experimental models, the exploration or analysis methods, the cytotoxicity or viability or proliferation cellular tests, the tests of scaffold antibacterial properties and take into account the vascularization of the regenerated dental pulp. From the 71 selected articles, 59% focused on the "cell-transplantation" strategy, 82% used in vitro experimentation, 58% in vivo animal models and only one described an in vivo in situ human clinical study. 87% used dental pulp stem cells. A majority of the studies reported histology (75%) and immunohistochemistry explorations (66%). 73% mentioned the use of cytotoxicity, proliferation or viability tests. 48% took vascularization into account but only 6% studied the antibacterial properties of the scaffolds. This article gives an overview of the methods used to regenerate dental pulp from stem cells and should help researchers create the best development strategies for research in this field.